Wednesday, November 2, 2005

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Nov 2, 2005 - sity of Missouri-Kansas City, Kansas City, MO ..... years age group coming to outdoor of Department of Pulmonary Medi ...... Johns Hopkins Bayview Medical Center, Baltimore, MD .... coordinating pressurized metered-dose inhaler (pMDI) use, ... washing in water containing a mild ionic detergent, rinsed and ...
Wednesday, November 2, 2005 Acute Lung Injury and ARDS 12:30 PM - 2:00 PM INTERLEUKIN 2 INCREASES ALVEOLAR FLUID CLEARANCE IN ISOLATED RAT LUNGS Makoto Sugita MD* Zheng Wang MD Sumiko Maeda MD Motoyasu Sagawa MD Jin Xu MD Toshishige Shibamoto MD Tsutomu Sakuma MD Kanazawa Medical University, Ishikawa, Japan

LONG PENTRAXIN 3, A NEW INFLAMMATORY MEDIATOR IN ACUTE LUNG INJURY Daisuke Okutani MD* Bing Han MD Marco Mura MD Thomas K. Waddell MD Shaf Keshavjee MD Mingyao Liu MD Thoracic Surgery Research Laboratory, Toronto General Hospital, U of Toronto, Toronto, ON, Canada PURPOSE: Acute respiratory distress syndrome (ARDS) is a serious form of acute lung injury (ALI), and has a high mortality of 30-50%. Understanding of ALI at molecular level may provide insights and lead to new therapies. PTX3 is a newly identified acute-phase protein, which can be induced from a variety of tissue cells on pro-inflammatory stimulations, such as LPS, IL1␤ and TNF␣. In this study we sought to define the PTX3 expression patterns in multiple ALI models in rats and its relationship with the lung injury. METHODS: Rats were randomized to receive hemorrhagic (HS) or endotoxic shock (LPS) followed by resuscitation, or sham operation. Then the animals were subjected to either high (HV) or low (LV) volume ventilation for 4 hours. Blood gas, lung elastance, and wet/dry ratio were measured. PTX3, IL1␤, and TNF␣ were assayed by quantitative real time PCR and ELISA. Distribution of PTX3 in the lung tissue was determined by immunohistochemistry. RESULTS: After 4 hours of mechanical ventilation, the PTX3 expression in both mRNA and protein levels in the lung tissues were significantly enhanced by HS, or LPS, which is further increased by HV. In fact, HV alone also increased PTX3 expression significantly. In contrast, the serum level of PTX3 was found no obviously increase by HV and HS, but only slightly enhanced by LPS. Immunohistochemistry showed a profound positive staining of PTX3 on the epithelial layer of alveolar walls, indicating a major local response of PTX3 during ALI. The local PTX3 expression was well correlated with IL-1␤ and TNF␣. Furthermore, the PTX3 expression was highly correlated with changes in wet/dry lung ratios, elastance, and PaO2, respectively (p ⬍ 0.0001). CONCLUSION: PTX3 is an important inflammatory mediator whose expression can be increased by the inflammatory responses in the pathogenesis of ALI. CLINICAL IMPLICATIONS: PTX3 might serve as a sensitive biomarker for local inflammatory responses during ALI. DISCLOSURE: Daisuke Okutani, None.

PURPOSE: Two previous studies showed that ARDS patients fed an enteral diet containing EPA⫹GLA and elevated antioxidants (Oxepa) had significantly increased oxygenation, and improved clinical outcomes. We investigated the potential benefits of the same diet in patients with ARDS in addition to Multiple Organ Dysfunction (MOD) which correlates strongly with the risk of intensive care unit (ICU) mortality. METHODS: We enrolled 16 ICU patients with ARDS (as defined by the American-European Consensus Conference) as a prospective, multicenter, double-blind, randomized controlled trial. Patients meeting entry criteria were randomized and continuously tube-fed EPA⫹GLA or an isonitrogenous, isocaloric standard diet at a minimum caloric delivery of 90% of basal energy expenditure for at least 4 days. RESULTS: Ventilator settings were recorded and arterial blood gases were measured, at baseline and study days 4 and 7 to enable calculation of PaO2/FIO2, a marker for gas exchange and part of the Modified Lung Injury Score (LIS). Significant improvements in oxygenation (PaO2/ FIO2) from baseline to study day 4 with lower ventilation variables (FIO2, positive end-expiratory pressure, and minute ventilation) occurred in patients with higher APACHE scoring at enrollment who were fed EPA⫹GLA compared with controls (p⬍.01). In addition, patients fed EPA⫹GLA had a decrease in their APACHE score 4 days after initiation of the enteral nutrition with decreased in length of stay in the intensive care unit (12.8 vs. 17.5 days; p ⫽ .016) compared with controls. Over all, patients fed EPA⫹GLA had a significant decrease in MOD score at 28 days after initiation of their tube feeding (p⬍.05). CONCLUSION: This preliminary report support the previously reported benefits of EPA⫹GLA diet on gas exchange, and length of ICU stay. In addition, patients fed EPA⫹GLA had reduction of their APACHE score within 4days of initiating of the enteral nutrition with decreased MOD scores 28 days after initiation of their tube feeding. CLINICAL IMPLICATIONS: Enteral nutrition of ARDS patients with EPA⫹GLA diet can improve their gas exchange, in addition to decrease length of ICU stay and 28 days mortality. DISCLOSURE: Elamin Elamin, None. OPTIMIZATION OF VENTILATION-PERFUSION MATCHING DURING PROTECTIVE LUNG VENTILATION Chin-Pyng Wu PhD* Kun-Lun Huang PhD Wann-Cherng Perng MD Hung Chang PhD Chien-Wen Chen MD Chien-Ling Su MA Hsien-Liang Chuang MA Horng-Chin Yan PhD Yuh-Chin Huang MPH Department of Critical Care Medicine, Tri-Service General Hospital, Taipei, Taiwan ROC PURPOSE: The primary purpose of this study was to determine the effects of different positive end-expiratory pressure in the lung protective strategy on ventilation-perfusion distribution measured by the multiple inert gas elimination technique. METHODS: All patients were on pressure-controlled mode with the inspiratory pressure, FiO2 and PEEP adjusted to provide a tidal volume of 6-8 ml/kg, an oxygen saturation ⬎ 90% and a plateau pressure ⱕ 35 cm H2O. Six levels of PEEP were studied in an incremental manner: 0 cmH2O (ZEEP), PLIP-4, -1 ,⫹2 ,⫹5 ,⫹8 cmH2O. All physiological parameters were measured at the end of each 30-min PEEP trial. If the patient showed signs of hemodynamic instability or desaturation to ⬍ 88% during trials at lower PEEP, that trial was terminated and PEEP was increased to the next higher level. RESULTS: Eleven patients were ventilated with low tidal volume and PEEP from 0 to 8 cmH2O above the lower inflection point pressure. These patients had a large intrapulmonary shunt and dead space with an additional mode at the high ventilation-perfusion regions. Intrapulmonary shunt and dead space improved with increasing positive end-expiratory pressure up to 2-5 cmH2O above the lower inflection point pressure. Higher positive end-expiratory pressure increased dead space without further reduction in intrapulmonary shunt. CONCLUSION: The dispersion of ventilation and perfusion also followed a similar trend. Other endpoints commonly used for titrating positive end-expiratory pressure, such as oxygenation, alveolar recruitCHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: Clinical and basic studies have suggested that interleukin 2 (IL-2) plays an important role for the development of pulmonary edema. However, its precise mechanism is still undetermined. For the resolution of pulmonary edema, alveolar fluid clearance is essential, and this clearance is known to be dependent of ion transport ability of alveolar epithelial cells. In this study, we determined the effects of IL-2 on alveolar fluid clearance. METHODS: Isotonic 5% albumin solutions with pharmacological treatments were instilled into the distal airways in the isolated rat lungs. The lungs were inflated with 100% oxygen at 8cm H2O and placed in a humid incubator at 37°C. Alveolar fluid clearance was estimated by the progressive increase in the albumin concentration over 1h. RESULTS: Seven male S-D rats were used in each group. IL-2 stimulation caused dose-dependent increase in alveolar fluid clearance (Control, IL-2 (50U/ml), IL-2 (5000U/ml), vs. IL-2 (10000U/ml): 15.8⫾1.8%, 15.3⫾1.5%, 21.8⫾1.0%, vs. 24.6⫾1.7: P⬍0.05). Terbutaline (␤ adrenergic receptor agonist) caused significant increase in alveolar fluid clearance (27.8⫾1.1%), and this increase was inhibited by propranolol (␤ adrenergic receptor blocker). In contrast, propronolol did not inhibit the IL-2 stimulation. CONCLUSION: This study indicates that IL-2 increases alveolar fluid clearance in the isolated rat lungs. Because the stimulatory effect by IL-2 is not inhibited by propranolol, IL-2 may increase alveolar fluid clearance via non-␤ adrenergic receptor mediated pathway. CLINICAL IMPLICATIONS: Intravenous administration of IL-2 has been shown to cause pulmonary edema. However, our results suggest that IL-2 stimulates transalveolar fluid transport for clearance of excess edema fluid. This study was supported by Grant for Promoted Research from Kanazawa Medical University (S2003-8). DISCLOSURE: Makoto Sugita, None.

EFFECT OF ENTERAL NUTRITION WITH EICOSAPENTAENOIC ACID (EPA), GAMMA-LINOLENIC ACID (GLA), AND ANTIOXIDANTS REDUCES ALVEOLAR INFLAMMATORY MEDIATORS AND PROTEIN INFLUX IN PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) Elamin M. Elamin MD* Larry F. Hughes PhD Diane Drew RN University of South Florida, Tampa, FL

Wednesday, November 2, 2005 Acute Lung Injury and ARDS, continued ment and lung compliance, all increased with increasing positive endexpiratory pressure while hemodynamic parameters were unaffected. Thus based on ventilation-perfusion matching, positive end-expiratory pressure of 2-5 cmH2O above the lower inflection point pressure appears optimalduring protective lung ventilation. CLINICAL IMPLICATIONS: We determined PEEP effects during protective lung ventilation using ventilation-perfusion (VA/Q) distribution as an endpoint.This method of adjusting PEEP was used because it has been shown that the recruiting potential of lung tissues with PEEP varied significantly among individual ARDS patients. Our goal was to determine if there was a PEEP level that gave the most optimal VA/Q distribution. DISCLOSURE: Chin-Pyng Wu, None. RISK FACTORS FOR FAILURE OF NON-INVASIVE VENTILATION IN PATIENTS WITH ACUTE LUNG INJURY Sameer Rana MD* Milie M. Tolentino MD Rolf D. Hubmayr MD Peter C. Gay MD Ognjen Gajic MD Mayo Clinic, Rochester, MN PURPOSE: Non Invasive Positive Pressure Ventilation (NIPPV) is the accepted initial treatment for exacerbation of chronic obstructive lung disease and cardiogenic pulmonary edema. Its role in Acute Lung Injury (ALI) is controversial. We sought to assess the outcome of ALI initially treated with NIPPV and to identify specific risk factors for NIPPV failure in this patient population. METHODS: In this observational cohort study,consecutive patients with ALI initially treated with NIPPV were identified. ALI was defined according to standard American European Consensus Conference Definition. Patients with do not resuscitate orders were excluded. NIPPV failure was defined as the need to intubation or death while on NIPPV. Data on demographics, APACHE III scores, degree of hypoxemia (PaO2/FIO2), presence of shock, sepsis, aspiration, transfusion, metabolic acidosis, time to intubation, as well as NIPPV parameters (tidal volume, minute volume, inspiratory and expiratory pressure) were recorded. Univariate and multivariate regression analysis was performed to identify risk factors for NIPPV failure. RESULTS: 79 patients met the inclusion criteria. 23 were excluded because of do not resuscitate order and 2 denied research authorization. 34 of the remaining 54 patients (62.9%) had a primary diagnosis of pneumonia. 38 (70.3%) patients failed NIPPV, including all 19 patients with shock. ALI patients successfully treated with NIPPV had lower Apache-3 scores (55.5 vs 81.5; p⫽0.004), were less likely to have metabolic acidosis (base deficit: 0.52 vs -4.01; p⫽0.017) and severe hypoxemia (PaO2/FIO2: 147 vs 112; p⫽0.020). Multivariate logistic regression analysis identified higher base deficit (p⫽ 0.04) and lower PaO2/FIO2 ratio (p⫽0.008) but not APACHE III scores (p⫽0.105) as significant predictors of NIPPV failure. In patients who failed NIPPV the observed mortality was higher than APACHE predicted mortality (68.4% vs 38.6 %). CONCLUSION: The presence of septic shock, low PaO2/FIO2 ratio and metabolic acidosis in patients with Acute Lung Injury predicts failure of NIPPV . CLINICAL IMPLICATIONS: NIPPV should not be used in patients with Acute Lung Injury who have shock, metabolic acidosis or profound hypoxemia. DISCLOSURE: Sameer Rana, None.

RESULTS: 21/71 patients were enrolled before the landmark and 50/71 after the landmark. Vt normalized to real or IBWs were reduced after Nov 2000 (7.8 ⫹/- 0.2 vs 6.8 ⫹/- 0.1 p⬍0.0001 and 9.3 ⫹/- 0.2 vs 8.1 ⫹/- 0.1 p⬍0.0001 respectively). There was no significant difference of mortality between the two groups (48% vs 36%, NS). PEEP (10.6 ⫹/- 0.4 vs 13.9 ⫹/- 0.2 p⫽0.02), respiratory rate (20 ⫹/- 1.2 vs 29 ⫹/- 0.6 p⬍0.0001), PaCO2 (47 ⫹/- 1.4 vs 50 ⫹/- 0.7 p⫽0.02) significantly changed. A trend towards higher number of days without organ dysfunction was found after November 2000 (all organs: 14.8 vs 20.5; p⫽0.08, renal: 19.5 vs 24.4; p⫽0.06, cardiovascular: 15.4 vs 22.4; p⫽0.07, hepatic 18.8 vs 22.4, p⫽0.2, coagulation; 18.4 vs 24.1; p⫽0.07). CONCLUSION: Knowledge translation regarding on ventilation setting of ARDS patients has moved nearer standard practice in Quebec ICUs after the 2000 ARDS Net release. Morbidity was affected in this small cohort of patients. CLINICAL IMPLICATIONS: Standard practice regarding on mechanical ventilation of ARDS patients has changed with time following the ARDS Net release, with trends toward lower secondary organ dysfunction rate. DISCLOSURE: Yannick POULIN, None. LOW VS HIGH TIDAL VOLUME THROUGH EXTRA-TRACHEAL CONTINUOUS GAS INSUFFLATION ⴙ NITRIC OXIDE IN PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME AND REFRACTORY HIPOXEMIA Santiago M. Herrero PhD* Joseph Varon MD Robert E. Fromm MPH Hospital Cabuen˜es, Gijon, Spain PURPOSE: Mechanical ventilation (NCMV) using extra-tracheal continuous gas insufflation (ETCGI) and nitric oxide (NO) has been used for patients with ALI(1).The purpose of this preliminary study was to compare the conventional mechanical ventilation (CMV) through lung protective ventilation versus the effect of ETCGI using NO mixture, on oxygenation and ventilation parameters in patients with ARDS and refractory hypoxemia. METHODS: Five patients (four women) with severe systemic inflammatory response syndrome, multiple organ system failure (ApacheII: 26,88,5⫾2,99) and ARDS (LIS:3,75⫾0,3) with refractory hipoxemia (PaO2/FiO2:52,06⫾2,14 torr and SatO2:65,2⫾4,20 cmH2O) were studies. The sequential ventilatory support protocol was: 1.Protocol CMV: Initial PRVC:Pressure regulated volume control or PCV: Pressure controlled ventilation to 6,28⫾0,38 ml/kg tidal volume (protective ventilation), optimizing best Peep (17,4⫾1,81 cmH2O) and NO. 2.Protocol NCMV: Subsequently changes ventilation mode to PRVC or PCV, with Peep (2,4⫾0,54 cmH2O), ETCGI (9,0⫾2,64 liters/minute) and Nitric Oxide (3,92⫾0,83 ppm). The tidal volume, finaly was: 11,97⫾1,89 ml/kg and the volume minute was 15654⫾3050 ml/minute (range:12400-19600). The peak pressure (PIP) values in ETCGI mode, were obtained through tracheal level monitoring. All patients, the informed consent was obtained, less in two patients that was obtained differed. RESULTS: See table: t-Student for comparative samples (95% CI).

A MULTICENTER RETROSPECTIVE STUDY OF THE IMPACT OF THE 2000 ARDS NETWORK TRIAL ON MECHANICAL VENTILATOR SETTING IN QUEBEC ICUS Yannick Poulin MD* Marc-Andre LeClair MD Olivier Lesur MD MICU CHUS, CHU Sherbrooke, PQ, Canada PURPOSE: Mechanical ventilation (MV) with low tidal volumes (Vt: 8-6 cc/kg of IBW) has become a standard of care for patients with ARDS since mid-2000 (NEJM 2000, 342: 1301). To analyze MV setting’s habits for ARDS patients by Quebec ICU physicians, before and after the ARDS network report. METHODS: i) files of 71 ARDS patients from 5 Quebec ICUs studied from January 2000 to March 2002, ii) 2 groups arbitrarily defined to compare the period up to 6 months (i.e November 2000) following the ARDS network report, with the period after this landmark.Outcomes primary: the change of Vt over-time between the groups, secondary: mortality, number of days without organ failure, PEEP level, respiratory rate, PaCO2 .

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CONCLUSION: 1.- NO⫹ETCGI optimal application appears to improve oxygenation and ventilation substantially. 2.- All patients survived the refractory hypoxemia. 3.-One patient died due to refractory septic shock, after a new episode of sepsis. 4.- No high levels of NO2 (⬍1,0 ppm). 5.- No barotrauma episodes, in spite use high tidal volume (two patients development barotrauma previous and were treated with NO⫹ETCGI without ventilatory problems). REFERENCE: 1.Herrero S, CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Acute Lung Injury and ARDS, continued Varon J, Fromm RE. “Nitric Oxide and Extratracheal continuous gas flow in the acute respiratory distress syndrome. Crit Care Med. December 2004. Vol. 32, No. 12 (Suppl.) P400. CLINICAL IMPLICATIONS: 1.- In life-threatening ARDS with refractory hypoxemia, it is possible to maintain an adequate PaO2 with the application of NO and ETCGi (considered as ”rescue treatment“) 2.ETCGi can be performed even in presence of previous barotrauma. DISCLOSURE: Santiago Herrero, None. LACTATE DEHYDROGENASE ISOZYMES AS A MARKER OF VENTILATOR-RELATED LUNG INJURY Gregory H. Howell MD* Mark Yagan MD Betty Herndon PhD University of Missouri-Kansas City, Kansas City, MO

FACTORS AFFECTING SUCCESSFUL TRANSITION FROM HIGH FREQUENCY OSCILLATION TO CONVENTIONAL MECHANICAL VENTILATION IN ADULT PATIENTS Satomi Shiota MD* Stephen E. Lapinsky MB, BCh Rod MacDonald RRT Robert Fowler MD Sangeeta Mehta MD Thomas E. Stewart MD Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada PURPOSE: High frequency oscillation (HFO) is increasingly used to support adults with ARDS. Little data are available to guide the transition to conventional mechanical ventilation (CMV); commonly this occurs when mean airway pressure has been weaned below 24 cmH2O. This study aimed to identify predictive factors for successful transition from HFO to CMV. METHODS: Retrospective chart review of all patients receiving HFO in our institutions from 2000 to 2005. Data are presented as mean ⫾ SD. Student’s t-test was used for comparisons. RESULTS: 117 patients received HFO, with a mean age 50.9 ⫾ 18.8 years. We excluded from analysis patients who died on HFO (n⫽10), or who were transitioned for withdrawal of care (n⫽25) or other reasons (e.g. hemodynamic compromise or deterioration on HFO, n⫽17). The remaining 65 patients were transitioned to CMV with a view to weaning. Of these, 24 (37%) died a mean of 19.1 ⫾ 24.1 days after transition (“non-survivors”) and 41 (63%) survived to discharge (“survivors”). Com-

THE EFFECTS OF INOS ON PULMONARY CHEMOKINE PRODUCTION AND POLYMORPHONUCLEAR LEUKOCYTE SURFACE EXPRESSION OF ADHESION MOLECULES DURING SEPSIS Cedrin S. Law BSc* Ravi Taneja MD Lefeng Wang PhD El-Bdaoui Haddad PhD George De Sanctis PhD David G. McCormack MD Sanjay Mehta MD Lawson Health Research Institute, London, ON, Canada PURPOSE: Previous work has shown that inducible nitric oxide synthase (iNOS) derived from inflammatory cells plays a particularly important role in the development of high-protein pulmonary edema and increased oxidative stress in sepsis-induced acute lung injury (ALI). Interestingly, iNOS-/- animals show increased pulmonary polymorphonuclear leukocyte (PMN) infiltration despite decreased lung injury. The purpose of this study was to test the hypothesis that iNOS reduces pulmonary production of CXC chemokines and increases surface expression of adhesion molecules on PMN. METHODS: Experiments were performed using iNOS⫹/⫹ and iNOS-/- C57BL/6 mice. Sepsis was induced via cecal ligation and perforation (CLP), the lungs were removed and homogenized for analysis of the CXC chemokine macrophage inflammatory protein-2 (MIP-2). Alveolar macrophages (AM) were cultured, stimulated with LPS⫹IFN-␥ and the culture medium was analyzed for MIP-2 production. Surface expression of CD11b and CD62L was measured via flow cytometry in bone marrow PMN after LPS⫹IFN-␥ stimulation. RESULTS: MIP-2 levels in lung homogenate were increased in septic mice vs control and were significantly lower in septic iNOS⫹/⫹ vs iNOS-/- mice (35.8⫾12.3 vs 67.4⫾14.2 ng/mL). AM MIP-2 production increased following LPS⫹IFN-␥ stimulation but there was no difference between iNOS⫹/⫹ and iNOS-/- AM. Bone marrow PMN stimulated with LPS⫹IFN-␥ showed increased expression of CD11b and decreased expression of CD62L vs control but there was no difference between iNOS⫹/⫹ and iNOS⫹/⫹ PMN. CONCLUSION: iNOS inhibits septic pulmonary, but not AM production of MIP-2. PMN iNOS has no apparent effect septic PMN surface expression of CD11b and CD62L on PMN. CLINICAL IMPLICATIONS: A better understanding of the mechanisms by which iNOS affects PMN infiltration and sequestration may lead to new therapeutic options for patients with ALI. DISCLOSURE: Cedrin Law, None. APPLICATION OF LUNG PROTECTIVE MECHANICAL VENTILATION (USING LOWER TIDAL VOLUMES) MANDATES THE USE OF PREDICTED BODY WEIGHT INSTEAD OF ACTUAL BODY WEIGHT Esther K. Wolthuis MD Rogier M. Determann MD Marcus J. Schultz PhD* Academic Medical Center, Amsterdam, Netherlands PURPOSE: Use of lower tidal volumes (VT) is recommended for patients suffering from ALI/ARDS. We previously reported on a simple ’intervention’ aiming at lowering VT in our institution (goal: VT 6-8 ml/kg): this intervention existed of feedback and education on the use of lower VT, during which special attention was paid to the importance of closely adjusting VT to predicted body weight (PBW) in stead of actual bodyweight (Wolthuis, Intensive Care Med 2005). CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: Mechanical ventilation as a life-sustaining procedure is a benefit to medicine and usually safe for the patient. When performed over extended periods, it is known to cause lung injury. Various methods of assessing lung injury have been utilized. An objective measure, lactate dehydrogenase (LDH) isozyme profiles, changed significantly after ventilation in lung-healthy rats. Human studies using LDH 4/5 ratio in bronchoalveolar lavage (BAL) have assisted in diagnosing pulmonary infection. We hypothesized that BAL LDH isozymes would relate to lung changes induced by mechanical ventilation. METHODS: With IRB approval and individual signed consent, 30 patients with healthy lungs undergoing elective surgery were enrolled in a prospective non-randomized trial to determine levels of LDH isozymes in BAL fluid, and to correlate these levels to time on mechanical ventilation. Bronchoscopy was performed and a BAL was obtained at intubation. After surgery a second BAL was done in the contralateral lung. Total LDH and LDH isozymes were measured by protein electrophoresis on BAL concentrates. Using pre-surgical BAL LDH isozymes as individual baseline, change in each LDH isozyme as a function of time on mechanical ventilation was plotted. RESULTS: Mechanical ventilation averaged 2 hr 20 minutes (range: 15-509 minutes). All 5 LDH isozymes increased in the post-surgical BAL, isozyme 4 significantly so (p⫽0.05). Ventilator time was compared with the change in each LDH isozyme; no statistical significance was found. CONCLUSION: This study demonstrated an elevated LDH isoenzyme 4 in BAL fluid during surgical mechanical ventilation with an average time of approximately 2 hours. LDH isozyme measurements, which have historically emphasized cardiac and skeletal muscle metabolism, showed that isozyme 4 is usually remarkably stable, with exercise and training affecting the other isozymes. CLINICAL IMPLICATIONS: The significant increase in BAL isozyme 4 in the present study suggests a potential target for investigating lung injury in patients who are subjected to prolonged mechanical ventilation. DISCLOSURE: Gregory Howell, University grant monies We work for the University of Missouri-Kansas City. The study was funded by the University.

paring non-survivors with survivors, no differences were noted in illness severity when HFO was initiated (APACHE II 19.1 ⫾ 6.8 and 21.1 ⫾ 8.3, p⫽0.20; PaO2/FiO2 ratio 105 ⫾ 43.3 and 120 ⫾ 74.0, p⫽0.49; oxygenation index 32.1 ⫾ 13.6 and 34.4 ⫾ 16.4, p⫽0.39). At the time of transition to CMV, no difference was noted between non-survivors and survivors in mean airway pressure (23.6 ⫾ 2.6 cmH2O and 24.6 ⫾ 3.9 cmH2O, p⫽0.062) or ventilator frequency (4.90 ⫾ 1.59 Hz and 4.93 ⫾ 1.84 Hz, p⫽0.43). However, non-survivors had significantly worse oxygenation at transition than survivors (PaO2/FiO2 ratio 191 ⫾ 74.3 and 224 ⫾ 72.3, p⬍0.05; OI 14.4 ⫾ 6.1 and 12.0 ⫾ 3.3, p⬍0.05). CONCLUSION: Despite similar severity of illness and oxygenation at initiation of HFO, patients who did not survive following successful transition to CMV demonstrated worse oxygenation parameters at the time of transition. CLINICAL IMPLICATIONS: These finding may suggest a role for oxygenation indices in the decision to transition from HFO to CMV. DISCLOSURE: Satomi Shiota, Consultant fee, speaker bureau, advisory committee, etc. Speakers fees

Wednesday, November 2, 2005 Acute Lung Injury and ARDS, continued METHODS: To determine the longstanding effects of the above-mentioned intervention, we (a) compared data on VT-settings of mechanically ventilated patients before feedback and education (June 2003, N ⫽ 30) with VT-settings 15 months later (September 2004, N ⫽ 103); in addition, we (b) collected data on VT-settings of patients recruited in two consecutive randomized controlled ALI/ARDS- trials: the first trial was performed in 10-month period before the intervention (March 2002 – December 2002, N ⫽ 12), the second was performed in a 10-month period after the intervention (July 2003 – May 2004, N ⫽ 8). Statistical analysis: Mann-Whitney U test. P-value ⬍ 0.05 was considered to represent a significant difference. RESULTS: (a) Before intervention, VT was 9.6 ⫾ 1.8 ml/kg PBW; VT declined shortly after the intervention (8.0 ⫾ 1.8 ml/kg PBW), and remained low (7.8 ⫾ 1.3 ml/kg PBW) 15 months after the intervention. (b) VT in the second randomized controlled trial was significantly lower as compared with VT in the first study on ALI/ARDS-patients: while in the majority of patients in the first study VT was ⬎ 10 ml/kg at all times, in the second study almost all VT were between 6 and 8 ml/kg. CONCLUSION: Feedback and education caused a sustained decline in VT in mechanically ventilated patients in our institution. CLINICAL IMPLICATIONS: These results possibly underscore the importance of the use of PBW, instead of actual bodyweight, to adjust VT. DISCLOSURE: Marcus Schultz, None. SHORT TERM ANALYSIS OF PULMONARY MECHANICS DURING MECHANICAL VENTILATION FOR ARDS William D. Marino MD* Mary O’Connell-Szaniszlo MS Our Lady of Mercy Medical Center, Mount Kisco, NY PURPOSE: Current practice employs low tidal volumes (Vt) in the ventilation of patients with ARDS. Studies supporting this approach also suggest that plateau alveolar pressures (Pplat) associated with such tidal volumes (25 cmH2O) are much lower than Pplat values (⬍35 cmH2O) previously demonstrated to be safe. These studies assume that Pplat during mechanical ventilation remains constant. We have observed fluctuating airway pressures during positive pressure ventilation of patients with ARDS. The “snapshot” measurements of mechanics in the above studies could thus misrepresent the actual Pplat, explaining the studies’ discrepancies. We have measured serial pulmonary mechanics and pressures during short periods of ventilation of patients with ARDS in order to evaluate this possibility. METHODS: In each of 20 patients using mechanical ventilation for ARDS, clinical and ventilator data were extracted from the chart. Subsequently compliance, airway resistance (Raw), peak airway pressure (Ppeak) and Pplat were measured every 30 minutes for 6 hours. These measurements were performed in the absence of any spontaneous breathing effort or change in ventilator settings. Mean values and the range of values of each parameter were measured in each patient. RESULTS: 7 males and 13 females, aged 72⫹/-17 years were studied. All utilized volume ventilation with a Vt of 9⫹/-2.6ml/kg and inspired oxygen concentration of 48⫹/-21%. Compliance was 32⫹/-10ml/cm with an intraindividual variation of 12⫹/-6ml/cm. Raw was 18⫹/-6.6l/s/cm with a variation of 12⫹/-6.6l/s/cm. Pplat was 23.8⫹/-8.9cmH2O with ranges of values from 5 to 18 cmH2O. Ppeak was 32 ⫹/-11cmH2O with ranges from 7 to 17. CONCLUSION: There is substantial short term variation in airway and alveolar pressures during mechanical ventilation of lungs with ARDS. This may expose such lungs to barotrauma if initial ventilator settings cause alveolar pressures at the high end of the safe pressure range, since these pressures may be exceeded during continued mechanical ventilation. CLINICAL IMPLICATIONS: When optimizing ventilation and lung expansion of patients with ARDS, Pplat should be monitored serially to prevent exposure of the lung to traumatic pressures. DISCLOSURE: William Marino, None.

Advances in Obstructive Sleep Apnea 12:30 PM - 2:00 PM REPETITIVE INSPIRATORY OCCLUSIONS ACUTELY IMPAIR MYOCARDIAL CONTRACTILITY Colleen Lynch BSc* Jeremy Simpson PhD Steve Iscoe PhD Queen’s University, Kingston, ON, Canada PURPOSE: Obstructive sleep apnea (OSA) adversely affects ventricular function, increasing the incidence of nocturnal death of cardiac origin

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and contributing to the pathogenesis of congestive heart failure. The large swings in intrathoracic pressure caused by airway occlusion increase cardiac transmural pressure, decrease preload, and increase afterload, augmenting metabolic demand at the same time as arterial oxygen content decreases. We hypothesized that repeated inspiratory occlusions, mimicking OSA, cause myocardial dysfunction and injury. METHODS: We subjected anesthetized male Sprague-Dawley rats to 3 h of repeated airway occlusion (30 s occlusion every 2 min); results were compared to sham rats. RESULTS: Following occlusions, left ventricular function decreased; the peak rates of pressure generation (⫹dP/dt) and relaxation (-dP/dt) fell from 7820 ⫾ 271 (SEM) to 6310 ⫾ 623 and from -8851 ⫾ 502 to -7121 ⫾ 381 mmHg/s (p ⬍ 0.05), respectively. Myofibril proteins were isolated from the left ventricle for determination of Ca2⫹-activated myosin ATPase activity. Compared to shams, inspiratory occlusion significantly reduced maximum (97 ⫾ 5 vs. 137 ⫾ 9, p ⬍ 0.01) and minimum (35 ⫾ 6 vs. 76 ⫾ 9 nmol/min/mg, p ⬍ 0.01) ATPase activity. We detected release of cTnT into the blood in 4 of 9 occluded rats but none of the shams. CONCLUSION: These results demonstrate for the first time that repeated inspiratory occlusions acutely impair left ventricular contractility, reduce ATPase activity of myofibril proteins, and, in some rats, cause myocardial necrosis. The mechanism(s) underlying the decrease in ATPase activity is unknown but probably reflects a post-translational modification(s) to one or more myofibril proteins. CLINICAL IMPLICATIONS: Collectively, these results may account for the acute pathological effects of OSA. DISCLOSURE: Colleen Lynch, None.

FUNDAMENTAL FREQUENCY MEASURES WITH MORPHEUS OF HUMAN SLEEP ELECTROENCEPHALOGRAPHY(EEG) IN SEVERE SLEEP APNEA WITH EARLY INTERVENTION OF CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP) Richard K. Bogan MD* Jo Anne Turner MSN Alex Novodvorets MS Koby Todros BS Baruch Levy BS SleepMed, Columbia, SC PURPOSE: To evaluate a new measure of EEG synchrony or stability using fundamental frequency analysis provided by Morpheus in subjects with severe obstructive sleep apnea (OSA) adequately treated with CPAP using a split night protocol. METHODS: A total of 27 adults were selected with a primary diagnosis of obstructive sleep apnea and who were treated with CPAP during their initial study. Each individual had a baseline and treatment period. Only those individuals with a respiratory disturbance index (RDI) ⬍ 10 episodes per hour and oxygen saturation greater than 85% during the ideal CPAP titration period were selected. When there was more than one CPAP level that this occurred, the multiple levels were included. Fundamental frequency values below 4 Hz are believed to represent increased EEG synchrony. The percentage of fundamental frequency below 4 Hz was calculated during the baseline period and ideal CPAP titration period (total sleep time). RESULTS: Means with standard deviations are reported. There were 24 males (ages 25-77) and 3 females (ages 46-52). Body mass index was 35(7); Epworth Sleepiness Scale 12(5), and SleepMed Insomnia Index 16(8). Low oxygen saturation at baseline was 81%(6); oxygen saturation at ideal CPAP level 91%(2); RDI at baseline 71(26); and RDI at ideal CPAP level 3(3). Fundamental frequency under 4Hz during the baseline period was 12%(13) and at the ideal CPAP pressure 31%(13). Independent t-tests comparing % of fundamental frequency below 4Hz at the baseline period with the ideal CPAP period were significant p⬍0.001. CONCLUSION: Early intervention with CPAP in OSA improves sleep quality. Automated analysis that calculates modal frequency of adaptive segmentation and fuzzy logic segments in sleep EEG demonstrates EEG synchrony that is believed to reflect improvement in sleep quality. CLINICAL IMPLICATIONS: Enhanced resolution by automated analysis offers improved efficiencies, reproducibility, and insights into sleep states and processes. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Advances in Obstructive Sleep Apnea, continued as the number of respiratory events. We conclude that bioelectric signals are not necessary for the diagnosis of OSA. CLINICAL IMPLICATIONS: Because PSGs are much simpler to perform without bioelectric signals, this simplified approach should improve access to and cost/benefit of diagnosis and treatment of OSA. DISCLOSURE: Pierre Mayer, None. EVALUATION OF ANATOMIC BREATHING PATTERNS RELATED TO OBSTRUCTION AT NASOPHARYNX AND OROPHARYNX Florence M. Sekito MS* Lucas N. Lemes MD State University of Rio de Janeiro, Rio de Janeiro, Brazil

CLINICAL UTILITY OF BIOELECTRIC SIGNALS IN THE DIAGNOSIS OF OBSTRUCTIVE SLEEP APNEA (OSA) IN UNATTENDED SETTINGS Pierre Mayer MD* Vincent Jobin MD Franc¸ois Bellemare PhD HoˆtelDieu of CHUM, Montreal, PQ, Canada PURPOSE: The standard diagnostic test of OSA, i.e. overnight polysomnography (PSG), is complex and difficult to perform outside the sleep laboratory. However, the value of electrophysiological and respiratory monitoring has not been assessed critically in unattended settings. In this study we evaluated whether full PSG is necessary to establish a diagnosis of OSA in unattended studies. METHODS: Full unattended PSG studies were conducted in the home place (25 tetraplegic patients)or in the hospital (25 surgical patients studied preoperatively)using a standard montage. Installation of the biosensors was performed by a trained sleep technician. Recording was initiated at a preset time and all signals stored on a digital storage media (Flash card) and subsequently downloaded to a desktop computer for analysis. No overnight monitoring was possible. The PSGs were first scored using standard criterions by one of 3 trained sleep technicians and an apnea/hypopnea index (AHI) calculated as the number of respiratory events per hour of sleep as determined by sleep staging. The analysis was then repeated on a separate day and in a blind fashion using respiratory variables only (i.e. without EEG and EMG signals) and a respiratory disturbance index (RDI) calculated as the number of respiratory events per hour of recording time. RESULTS: Sleep efficiency was 77.1⫾13.8%. Recording time exceeded sleep time by 117⫾79 minutes (p⬍.03) but RDI (20.5⫾21.3) was not ⱖsignificantly different from AHI (22.9⫾24.2; p⫽.116). Both were highly correlated (r2⫽.82). Using a AHI diagnostic cutoff value ⱖ15 events/h, the diagnostic sensitivity and specificity of RDI were both 86%. If a RDI cutoff value of ⱖ10 events/h was adopted instead, sensitivity would be 100%. CONCLUSION: Because of frequent arousal, the Rechtschaffen and Kales method for scoring sleep markedly underestimate sleep time as well

Evaluation of the Clinical Concepts of Normal Breathing, Types of Breathing and the Obstruction in Nasopharynx and Oropharynx Frequency % No obstruction

n

Nasopharynx obstruction Oropharynx obstruction Naso and Oropharynx obstruction Total

n n n

NasalBreathing

OralBreathing

MixedBreathing

61 68.54% 15 16.85% 6 6.74% 7 7.87% 89

1 11.11% 4 44.44% 3 33.33% 1 11.11% 9

25 53.19% 8 17.02% 10 21.28% 4 8. 51% 47

Total 87 27 19 12 145

DISCLOSURE: Florence Sekito, None. A STUDY ON PREVALENCE ESTIMATES OF OBSTRUCTIVE SLEEP APNEA IN INDIAN POPULATION Rajendra Prasad MD* Rajiv Garg MD Ram K. Verma MD S. P. Agarwal MS R. C. Ahuja MD King George’s Medical University, Lucknow, India PURPOSE: To know prevalence estimates for key symptoms and features that can indicate the presence of obstructive sleep apnea(OSA) in Indian population. METHODS: Single centre cross sectional study done from August 2003 to July 2004 in consecutive apparently healthy attendants of 25-64 years age group coming to outdoor of Department of Pulmonary Medicine, King George’s Medical University, Lucknow, India. We recorded CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

DISCLOSURE: Richard Bogan, Shareholder SleepMed Inc.

PURPOSE: The objective was to evaluate the clinical prevalence of nasal breathing mode, the most frequent one, and the presence of nasal obstruction. The obstruction sites (naso and oropharynx) and frequency in the oral-breathing mode and mixed-breathing mode were also evaluated. METHODS: The study design was transversal, analyzing 145 consecutive healthy patients enrolled at UERJ Faculty of Dentistry, without any previous history of smoking or respiratory disease. They were classified by clinical examination in 3 groups according their mode of breathing: nasal-breathing, oral-breathing, mixed-breathing (turns nasal or oral mode). Their respiratory airflow were measured by the Forced Oscillation Technique (FOT), Oscilab-version 2.0, from nose and from mouth at a frequency of 5 Hz, to determine the obstruction in naso and oropharynx. RESULTS: The Fisher exact test was used, with significant association between breathing mode and the obstruction level (p ⫽ 0,003). The oral-breathing occurred when there were obstruction (p⫽0,001) in nasopharynx (33.33%), and/or oropharynx (44.44%). The nasal and mixed mode were more frequent with the obstruction absence (68.54% and 53.19%, respectively). CONCLUSION: The breathing pattern had positive correlation with the obstruction site. The nasal and the mixed-breathing, may occur with some obstruction degree. The naso or oropharynx obstruction contributed significantly to oral-breathing mode. CLINICAL IMPLICATIONS: In the literature review, there wasn’t any reference about quantitative or qualitative methods to verify the relationship between the type of breathing and obstruction. This technique could testify this correlation significantly.

Wednesday, November 2, 2005 Advances in Obstructive Sleep Apnea, continued data on a pre-designed proforma and took interview on the basis of pre-tested Berlin Questionnaire with some relevant modifications. RESULTS: Out of 816 subjects approached, 702 responded. Out of 702, 452(64.4%)were males. Mean age was 42.7 ⫾ 10.4 years; mean neck circumference was 13.6 ⫾ 1.2 inch, mean BMI was 23.8 ⫾ 4.2 kg/m2. 31.1%(218/702) were snorers. The loud snorers were17.4%, and 60.5% of them were at high risk for OSA. Among snorers 22.9% bothered other people and 46.0% of them were at high risk for OSA. Out of 702, 6.0% had morning tiredness or sleepy awakening (ⱖ 3-4 times /wk) and 52.4% of them were at high risk for OSA, 5.1% had wake time tiredness and 61.1% of them were at high risk for OSA. Out of 702, 45.3% either did not know to drive or never needed driving and only 54.7 % used to drive. Among persons who use to drive 2.1% had drowsiness behind the wheel (ⱖ 3-4 times/wk) and 75% of them were at high risk for OSA. Out of 702, 13.0% were obese and 19.8% of them were at high risk for OSA. Overall there were 3.7% (26/702) were at high risk for OSA(qualified for 2 or more category symptoms of Berlin questionnaire) . CONCLUSION: Obstructive sleep apnea is a common disease and there is high demand of its awareness, evaluation, diagnosis and management in countries like India. CLINICAL IMPLICATIONS: There is need of relevant modification of Berlin Questionnaire for countries like India as half of our population either do not know to drive ored not to drive. DISCLOSURE: Rajendra Prasad, University grant monies Received no grants; Grant monies (from sources other than industry) Nil; Grant monies (from industry related sources) Nil

SLEEP APNEA IN SARCOIDOSIS Majid M. Mughal MD* Joseph Golish MD Mani Kavuru MD Oluranti Aladesanmi MD Nancy Ivansek Daniel A. Culver DO Cleveland Clinic Foundation, Cleveland, OH PURPOSE: The main purpose of this study is to estimate the prevalence of sleep related breathing disorders in patients with sarcoidosis by using Sleep Apnea/Sleep Disorders Questionnaire (SA/SDQ) and Epworth Sleepiness Scale (ESS). METHODS: 70 consecutive patients with diagnosis of biopsy proven sarcoidosis seen at the sarcoid clinic were screened for sleep related breathing disorders using SA/SDQ and ESS. The SA/SDQ consists of 8 questions and 4 other items related to weight, smoking status, age, and body mass index, which are calculated to generate a raw score. Total scores range from 0-60. To suspect sleep apnea, cutoffs of 32 for women and 36 for men were used as a criteria for sleep study referral. RESULTS: 70 patients with sarcoidosis completed the questionnaires. There were 42 females and 28 males with a mean age of 48 ⫾ 10 years. 34% of pateints were African American. Mean duration of diagnosis was 78 months. 60% of patients had 2 or more organs involved. Approximately 2/3rd of patients were actively treated with steroids or other immunosupressive agents (mean prednisone dose was 7 mg/day). 39 patients had positive questionnaires (25 with positive SA/SDQ while 14 with positive ESS). Considering the reported 81% specificity of SA/SDQ for sleep apnea in general population, 39% of patients will most likely have sleep apnae syndrome by polysomnography. CONCLUSION: The prevalence of sleep apnea syndrome in patients with sarcoidosis is significantly high. In this study, we persented our experience with SA/SDQ as a screening instrument for sleep disordered breathing in a sample of patients with sarcoidosis. CLINICAL IMPLICATIONS: Screening tools such as the SA/SDQ are gaining increasing importance because of high prevalence of sleep disordered breathing in chronic diseases and the high cost of polysomnography. Sleep disordered breathing is highly prevalent in our sarcoid population and SA/SDQ may be a useful test in identifying patients at risk for sleep apnea syndrome. DISCLOSURE: Majid Mughal, None.

THE ACCURACY OF NON-RESTRICTIVE SENSING SYSTEM FOR EVALUATING SLEEP APNEA SYNDROME UNDER THREE-DIMENSIONAL FIBER-GRATING SENSORS Hisashi Takaya MD* Toranomon Hospital, Tokyo, Japan PURPOSE: Nasal flow sensors are utilized for diagnosis of sleep apnea syndrome (SAS). Discomfort and fluctuation in sensitivity caused by body movements are problems when patients wear nasal flow sensors during polysomnography (PSG) tests. The aim of this study was to clarify the

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accuracy of non-restrictive sensing system for diagnosing SAS using three-dimensional Fiber-Grating (FG) sensors. METHODS: Twenty patients with SAS were enrolled in the study [M:F⫽19:1, age 50.0⫾26 years old, BMI 26.2kg/m2, apnea-hypopnea index (AHI): 25.6]. Three-dimensional FG measurement and PSG tests were conducted simultaneously. AHI determined by using pressure flow, and the movement of thoracic and abdominal walls during PSG were compared to those by FG sensors in the supine and lateral positions. RESULTS: AHI determined by FG sensors and PSG tests were well correlated (r⫽0.973, P⬍0.0001; supine position: r⫽0.974, P⬍0.0001, lateral position: r⫽0.965, P⬍0.0001, respectively). All twenty patients underwent these tests with no trouble and good compliance. CONCLUSION: The accuracy of non-restrictive sensing system for diagnosing SAS was clarified. CLINICAL IMPLICATIONS: Since the non-restrictive system using FG sensors is more comfortable and convenient for making diagnosis of SAS than the conventional one, it may be widely introduced. DISCLOSURE: Hisashi Takaya, None.

THE INCIDENCE OF POSSIBLE OBSTRUCTIVE SLEEP APNEA SYNDROME IN SUBJECTS WITH ACUTE MYOCARDIAL INFARCTION AND NORMAL CORONARY ANGIOGRAPHY Michael Chalhoub MD* Marwan Elia MD Mohammed Zgheib MD Theodore Maniatis MD Staten Island University Hospital, Staten Island, NY PURPOSE: The purpose of this study is to compare the incidence of possible obstructive sleep apnea syndrome (OSAS) in patients with acute myocardial infarction (AMI) and normal coronary angiography to the incidence of possible OSAS in patients with MI and abnormal coronary angiography. METHODS: All patients admitted to a university hospital with the diagnosis of AMI were evaluated. AMI was defined as having 2 out of 3 criteria: Chest pain, ST elevation of ⬎ 1 mm in two contiguous leads, or elevated cardiac enzymes. Patients who underwent coronary angiography were included in the study. The subjects were asked a set of questions. The questions were scored from 1 to 3. The questions addressed the following: Epworth sleepiness scale (ESS). ESS⬎10 (score 1), ESS⬎18 (score 2), snoring (score 1), witnessed apneas (score 3), falling asleep in inappropriate situations (score 2), unrefreshed sleep (score 1), and history of OSA diagnosed by NPSG. The subjects were then classified into five classes. Class I highly unlikely to have OSA (score ⱕ 1), class II unlikely to have OSA (score 2), class III likely to have OSA (score 3), class IV highly likely to have OSA (score ⱖ3), and class V definite OSA (OSA diagnosed by nocturnal polysomnography (NPSG)). The subjects were divided into two groups. Group I included patients with normal coronaries, whereas group II included patients with abnormal coronaries on angiography. RESULTS: A total of 55 patients were included in the final data analysis. 22 subject in group I, and 33 in group II.The results are summarized in the following table. CONCLUSION: The incidence of possible OSAS was significantly higher in patients with AMI and normal coronaries compared to patients with AMI and abnormal coronaries on angiography. 28.5% compared to 6% p value 0.035. CLINICAL IMPLICATIONS: Patients with AMI and normal coronary angiography should be investigated for the possibility of OSAS. Those found to have high likelihood of having OSAS should be sent for NPSG and adequate treatment offered.

Group1 n⫽22 Group 2 n⫽33 P value

Age (years)

BMI (Kg/m2)

Male (%)

57.1⫾13.1

39.6⫾10

41

59

28.6

66.2⫾11.8

31.1⫾8

69

31

6

NS

NS

0.029

Female (%)

0.029

Class III/IV (%)

0.035

Results are mean⫹standard deviations unless otherwise specified. BMI⫽ Body Mass Index. DISCLOSURE: Michael Chalhoub, None. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Advances in Obstructive Sleep Apnea, continued THE IMPACT OF SLEEP DISORDERS ON THE ATTENTION DEFICIT DISORDER IN THE ADULT PART I: THE PATIENT WITH OBSTRUCTIVE SLEEP APNEA Clifford G. Risk MD* Clifford Risk, MD, Marlborough, MA

IS OBSTRUCTIVE SLEEP APNEA (OSA) IN NON-OBESE PATIENTS A LESS SERIOUS DISEASE THAN IN OBESE PATIENTS? Ammar Ghanem MD* Syed Mahmood MD Marshall University, Huntington, WV PURPOSE: OSA occurs in non-obese patients,but they may exhibit different characteristics than obese patients with OSA. To elucidate this point,we investigated several physiological and clinical parameters among non-obese and obese OSA patients. METHODS: Of 254 patients referred to sleep clinic,we identified 102 patients with OSA(Apnea Hypopnea Indexⱖ5). We classified OSA patients with Body Mass Index(BMI)⬍30 as non-obese and those with a BMIⱖ30 as obese. We conducted a retrospective evaluation that included demographic,physiological and clinical data and compared the non obese and obese groups. For statistical comparisons, continuous variables were analyzed by student’s t-test and categorical variables by chi-square. Fisher’s exact test was used for analysis when a variable contained less than 5 observations. RESULTS: Of 102 patients with OSA,17(16.7%)were non-obese and 85(83.3%)were obese. The groups of non-obese and obese OSA patients differed significantly in four parameters. Mean AHI was 13.5 in the non-obese group and 27.6 in the obese group(P⫽ 0.03). Non-obese patients were older(average age 57.1 years compared to 48.3 years among obese patients)(t-test,p⫽ 0.01);used more sedatives(usage of one or more sedatives by 52.9% in non-obese group compared to 24.7% in the obese group)(Chi-square,p⫽ 0.02);and,exhibited less upper airway narrowing(23.5% of the non-obese group compared to 55.1% in the obese group)(Chi-square,p⫽ 0.02). Only one non-obese patient(5.9%) was younger than 50,compared to 48 patients(56%)in the obese group(Chisquare,p⬍0.0001). There were no significant differences between nonobese and obese OSA patients in gender,family history of OSA,facial

OBESITY HYPOVENTILATION SYNDROME: AN UNDERRECOGNIZED ENTITY Farooq Sattar MD* Alex Duarte MD Luigi Terminella MD Gulshan Sharma MBBS University of Texas Medical Branch, Galveston, TX PURPOSE: Obesity is epidemic in the United States and is a major cause of morbidity and mortality. In addition to obstructive sleep apnea, obesity is associated with obesity hypoventilation syndrome (OHS), characterized by daytime hypercapnia. OHS is associated with significant morbidity and mortality. In order to initiate therapy with non invasive positive pressure ventilation (NIPPV), a sleep study is required. We perrformed a study to determine the prevalence of daytime hypercapnia in morbidly obese patients referred for evaluation of dyspnea and to evaluate if body mass index or pulmonary function test help distinguish simple obesity from OHS. METHODS: All subjects who underwent pulmonary function test (PFT) at our institution from January 2003 to December 2004 were screened. Inclusion criteria was a BMI ⱖ 35 kg/m2, ⱕ 20 pack years history of smoking, an FEV1 ⬎ 50%, an FEV1 / FVC ⬎70, and absence of neuromuscular disorder. Simple Obesity (SO) was defined as a BMI ⱖ 35 kg/m2 in the absence of daytime hypercapnea. OHS was defined as a BMI ⱖ 35 Kg/m2 and daytime hypercapnia (arterial PaCO2 ⱖ 45 mm Hg). Data on subjects age, gender, height, weight, smoking history, pulmonary function tests (PFT’s), arterial blood gas (ABG), polysomnography and use of NIPPV were collected by chart review. RESULTS: 1904 PFT’s were performed during the study period. 122 patients met the inclusion criteria. Seventy six (62%) patients had complete PFT’s and an ABG available for review. Twelve (16%) subjects had daytime hypercapnia. CONCLUSION: OHS is common in morbidly obese patients. Clinical parameters such as BMI and pulmonary function test do not help distinguish OHS from SO. Arterial blood gas measurements are necessary to establish a diagnosis of OHS. CLINICAL IMPLICATIONS: Morbidly obese individuals with unexplained dyspnea should have arterial blood gas measurements to exclude daytime hypercapnia. Polysomnography should be considered in patients with daytime hypercapnia to determine the presence of sleep disordered breathing and to initiate noninvasive positive pressure ventilation. DISCLOSURE: Farooq Sattar, None. USE OF A SIX POINT QUESTIONNAIRE TO CATEGORIZE STABLE HEART FAILURE PATIENTS TO HIGH AND LOW RISK FOR SLEEP DISORDERED BREATHING John D. Roehrs MD* Anselmo Garcia MD Cynthia K. Scott RN Carl T. Hayden VA Medical Center, Phoenix, AZ PURPOSE: We evaluated the efficacy of an abbreviated sleep questionnaire, desgined to recognize sleep disordered breathing (SDB)in a cohort of patients assigned to a VA heart failure clinic. METHODS: A 6 point data set consisting of (1)Excessive Daytime Sleepiness,(2) Snoring, (3)Observed Apneas,(4) Non-restorative sleep, (5)BMI, (6)and Neck Circumference were collected. Each positive response was given one point. BMI⬎30 and Neck Circumference⬎17.5 in were given one point each. Scores of 3 or more points were placed in the high probability category and were assigned high priority for SDB evaluation. Two or less point scores were assigned to the Low probability. All were scheduled for Attended Polysomnography. RESULTS: Of the 40 heart failure clinic patients evaluated 25 had scores of 3 or more points on the screening questionnaire. 15 patients had 2 or less points and were referred to the VA sleep clinic for confirmatory examination. Four of those 15 patients were referred for polysomnography while the remainder were felt unlikely to have significant SDB. All CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

PURPOSE: Patients with obstructive sleep apnea (OSA) report excessive daytime sleepiness and attention impairment. This study assesses the impact of continuous positive airway pressures (CPAP) treatment of attention deficit. METHODS: We studied 41 adult patients who presented at a nationally accredited sleep center for evaluation of OSA. Severity of OSA is evaluated using the Epworth Sleepiness Scale (ESS) a self report questionnaire designed to assess daytime sleepiness on a scale of 0 to 24; and by the respiratory disturbance index (RDI) measured during their sleep study. Attention impairment was evaluated using the adult selfreport scale (ASRS) symptom checklist, a validated scale assessing attention impairment on a scale of 0 to 36. A score of 17 or greater indicates possible or probable attention deficit. Patients completed both questionnaires at baseline and following CPAP treatment; the RDI was measured during their baseline sleep study and during a subsequent CPAP titration study. RESULTS: The average baseline score on ESS was 11.6 (4.2) and 2.7 (3.3) at 3 months post-treatment (t⫽11.8,p⬍.0001). The average RDI on the baseline PSG was 29.9 (16.8) and 2.2 (3.6) on the subsequent CPAP study (t⫽10.5,p⬍.0001). The ASRS score was 16 (8) at baseline and 11 (8) at 3 months post-treatment (t⫽6.0,p⬍.0001). Of 41 patients at baseline, 19 demonstrated an ASRS score of 17 or greater; at 3 months posttreatment, 11 showed an ASRS that had decreased to the normal range, while 8 did not. These patients were subsequently diagnosed with ADD due to a comorbid psychological or neuromuscular diagnosis, hearing or reading deficit, or memory or executive function impairment. Most suffered from concurrent insomnia and non-restorative sleep. CONCLUSION: This study demonstrated a high comorbidity between ADD and OSA. Forty-six percent showed significant attention impairment at baseline; with treatments, 58% reported substantial improvement, but 42% reported persistent serious attention deficit, and required further evaluation and treatment. CLINICAL IMPLICATIONS: OSA is a significant factor contributing to ADD. In patients with persisting deficits after CPAP treatment, further evaluation and treatment is required. DISCLOSURE: Clifford Risk, None.

malformations,adenoid or tonsillar enlargement,smoking,co-morbid conditions and use of narcotics. CONCLUSION: In our study,about 1 in 5 patients with OSA was non-obese,suggesting OSA is not limited to obese persons. Non-obese persons differed from obese persons in several important characteristics. We report for the first time that excess use of sedatives occurred in non-obese OSA patients compared to obese patients. CLINICAL IMPLICATIONS: OSA is milder in non-obese patients and is unlikely in non-obese patients who are less than 50 years old. DISCLOSURE: Ammar Ghanem, None.

Wednesday, November 2, 2005 Advances in Obstructive Sleep Apnea, continued

Variable (mean ⫾ SD) Age Body mass index (kg/m2) Pulmonary Function (% predicted) FEV-1 FVC FEV-1/ FVC TLC ERV DLCO FEV-1 FVC FEV-1/FVC TLC ERV DLCO Arterial blood gases pH PaO2 PaCO2 Polysomnogram n (%) Apnea-hypopnea index ⱖ 5 (n)

Simple Obesity (n⫽64)

Obesity Hypoventilation Syndrome (n⫽12)

54.2⫾12.9 43.5⫾9.3

52.5⫾13.4 48.3⫾10.2

81⫾16 82⫾15 80⫾5 88⫾12 48⫾37 85⫾22

77⫾15 77⫿15 81⫾5 87⫾13 37⫾21 85⫾14

7.41⫾0.03 76⫾9 39.5⫾3 20 (31) 13

7.39⫾0.02* 69⫾12* 48.4⫾6.6* 1 (8) 1

*p-value ⬍ 0.05 high probablity patients were scheduled for polyomnography. Sleep Disordered Breathing was identified in 70 per cent of those patients. CONCLUSION: The 6 point screening questionnaire appeared to delineate a higher risk group for sleep disordered breathing in this cohort of patients with known heart failure. Less than 30 per cent of the low probability cohort were ultimately studied. CLINICAL IMPLICATIONS: SDB is present in approximately 50 percent of patients with known stable CHF. A short simplified 6 point data set appeared to be sensitive in selecting patients with a high probability for SDB. Use of the questionnaire should identify patients at risk for SDB earlier, and could prioritize their early evaluation and should result in earlier treatment. DISCLOSURE: John Roehrs, None.

health. It is of note that there was no significant correlation between apnea-hypoanea index (AHI), arousal index, nocturnal oxygen desaturation (NOD) and the SF-36 physical and mental health scores. CONCLUSION: AHI factor that define OSA may not determine the severity of disease outcome with respect to health related QOL.The study showed the significant impact of obesity on QOL in patients with OSA. CLINICAL IMPLICATIONS: weight reduction measures should aggressively be incorporated in management of OSA to improve their QOL. The positive association in sleep efficiency and QOL may indicate possible mechanism of improvement of QOL with CPAP. DISCLOSURE: Asegid Kebede, None. EFFECTS OF A HEATED TUBE ON SLEEP QUALITY, WITH ACTIVE HEATED HUMIDIFICATION DURING CPAP THERAPY IN A COOL SLEEPING ENVIRONMENT Georg Nilius MD* Ulrike Domanski PhD Karl-Josef Franke MD KralHeinz Ruhle MD Klinik-Ambrock, Hagen, Germany PURPOSE: Active heated humidification improves the side-effects of CPAP therapy for patients with sleep-breathing disorder (SAS) in the upper airways.In a cool ambience temperature, however, condensation will form and the patients feel disturbed in their sleep.The object of this study was to examine the effects of condensation on sleep quality during continuous CPAP. Furthermore, a comparison of sleep quality achieved with an active heating breathing tube versus conventional heated humidification was intended to be gained in a prospectively random study. METHODS: 19 patients with a first diagnosis of obstructive sleep apnoea syndrome, median age 55.2 (⫹/- 10.4) years, median BMI 32.8 (⫹/- 6.3) kg/m2 and median ESS score 10.8 (⫹/- 5.0) were treated with CPAP (HC 602, Fisher & Paykel) with conventional heated humidification (integrated humidifier and tube heater turned off, humidification via HC100, temperature 32°C) and on another night with an active heated breathing tube (level 8, heating humidifier 32°C) in the sleep lab. RESULTS: The results of the poysomnography data. CONCLUSION: If condensation forms in the CPAP tubing system, sleep quality is considerably reduced. This can be eliminated almost entirely by a heated breathing tube. CLINICAL IMPLICATIONS: We suggest that patients needing active heated humidification during CPAP, who wish to sleep in a cold bedroom ambience, should use a system with a heated breathing tube.

THE IMPACT OF PHYSICAL CHARACTERISTICS AND POLYSOMNOGRAPHIC FINDINGS TO HEALTH RELATED QUALITY OF LIFE (QOL) IN A PATIENT WITH OBSTRUCTIVE SLEEP APNEA (OSA) Asegid M. Kebede MD* Amao Olusegun MD Samir Fahmy MD SUNY Downstate Medical Center, Brooklyn, NY PURPOSE: OSA is a relatively common condition with a prevalence of 5%. Significant reduction in QOL is the major complication OSA.Continuous positive airway pressure (CPAP) titrated to eliminate Apnea and Hypoapnea significantly improve quality of life. Previous study indicates there is no correlation between QOL and severity of sleep apnea. There are various physical and polysomnographic finding that associated with the decrease in health related QOL in this cohort study. The purpose of this study is to evaluate the impact of polysomnographic features and physical characteristics to health related QOL in a patient with OSA. METHODS: The Study was conducted in sleep laboratory of Kings County medical center, Brooklyn, New York. We studied 34 adult (22 male and 12 female) patients with mean age of 45 (19-72), a body mass index (BMI) of 41.99 and diagnosis of OSA (apnea-hypoapnea index more than 5). Patients with major medical and psychiatric illness were excluded. Baseline physical and polysomnographic characteristics were obtained. The health related QOL was assessed by administering medical outcomes short-form ( MOS SF-36), a 36-item questionnaire that summarizes health related QOL using eight subscales and two summary scores. The results were analyzed using Pearson correlation statistics. RESULTS: The was significant negative correlation between BMI and SF-36 physical score ( p⬍0.001). Subclass analysis also showed significant correlation between BMI and all components. There was also positive correlation between sleep efficiency and physical functioning and mental

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DISCLOSURE: Georg Nilius, Grant monies (from industry related sources) The study was fianced by gift from fisher and Paykel healthcare A RANDOMISED SINGLE-BLINDED CROSS-OVER TRIAL OF SESAME OIL (“NOZOIL™”) FOR THE TREATMENT OF NASAL SYMPTOMS ASSOCIATED WITH CPAP John F. Feenstra MBBS* Kelli Rixon BSc Craig Hukins MBBS Sleep Disorders Centre, Princess Alexandra Hospital, Brisbane, Australia PURPOSE: Nasal symptoms are a common side effect of CPAP therapy. Although most patients experience self-limiting nasal congestion, at least 10% complain of persistent nasal problems to some degree after 6 months of therapy. Nasal symptoms can be treated in a variety of ways (inhaled nasal steroids, antihistamines, topical saline sprays and heated humidification); there is limited trial data of their effectiveness. The ideal and best treatment is heated humidification. Unfortunately heated huCHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Advances in Obstructive Sleep Apnea, continued

DETERMINANTS OF THE EFFECTIVE LEVEL OF CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP) IN OBSTRUCTIVE SLEEP APNEA (OSA) Octavian C. Ioachimescu MD* Joseph Lamont RRT Charles Bae MD Nancy Foldvary-Schaefer DO Joseph Golish MD Cleveland Clinic Foundation, Cleveland, OH PURPOSE: CPAP is the established treatment of moderate/severe OSA. The parameters capable to influence the level of effective CPAP in these patients are yet unknown. Previous predictive equations for CPAP (hereafter called eCPAP) included body mass index (BMI), neck circumference (NC) and baseline apnea-hypopnea index (AHI. None of these equations included arousal index (AI) or desaturation index (DI). METHODS: Fifty consecutive patients (20 females and 30 males) with moderate/severe OSA, who underwent a split-night or a CPAP titration polysomnographic study in our Sleep Center, were retrospectively analyzed. We used multiple regression analysis to compute a predictive equation of the effective level of CPAP and we analyzed the correlation between eCPAP and the prescribed CPAP (pCPAP). RESULTS: The derived predictive equation for pCPAP was: pCPAP ⫽ 6.8 ⫹ 0.001AHI ⫹ 0.10BMI - 0.08NC ⫹ 0.06AI - 1.14DI (p⬍0.0001, R2⫽0.45, SD⫽2.0). The mean pCPAP was 10 (⫾2.6 SD); the mean eCPAP was 8 (⫾2.3 SD); mean difference was 2 cmH2O. The mean difference was slightly smaller in split-night vs. titration studies (2.0 vs. 2.6), in males vs. females (2.0 vs. 2.8), and in severe OSA vs. moderate OSA (2.0 vs. 3.0) cmH2O. The derived equation is distinct from previously published equations, which estimated eCPAP. There was a weak correlation between pCPAP and eCPAP [R2⫽0.48, p⬍0.0001]. This could be explained by the fact that our CPAP prescription protocol takes into account not only normalization of AHI, but also near-normalization of AI and DI. CONCLUSION: We determined an equation for pCPAP based on several clinical parameters. The correlation between eCPAP and the pCPAP was weak, warranting new studies to explore the lack of correlation and the role of additional predictive parameters. CLINICAL IMPLICATIONS: This is a pilot phase of a larger study for derivation and validation of the best predictive equation for effective CPAP in OSA. The predictive value of OSA severity parameters such as AHI, AI, DI, and body habitus characteristics such as NC and BMI will be evaluated extensively in the main study. DISCLOSURE: Octavian Ioachimescu, None.

PREDICTORS OF IMPROVEMENT WITH CONTINUOUS POSITIVE AIRWAY PRESSURE (CPAP) IN PATIENTS WITH CHRONIC FATIGUE SYNDROME AND OBSTRUCTIVE SLEEP APNEA Marcel A. Baltzan MD* Osama Elkhouli MD Laura Creti PhD Sally Bailes PhD Catherine Fichten PhD Norman Wolkove MD Eva Libman PhD Mount Sinai Hospital Center, Montreal, PQ, Canada PURPOSE: Patients with chronic fatigue syndrome (CFS), as defined by Centers of Disease Control criteria, often have a potentially treatable sleep disorder. However, even when obstructive sleep apnea (OSA) is identified in these patients, improvement with treatment is not predictable. We sought to determine whether any parameters of the diagnostic or titration sleep study were associated with improvement in symptoms of CFS after a subsequent trial of home CPAP. METHODS: We reviewed the clinical and polysomnographic (PSG) findings of 78 patients with CFS. Thirty-nine (50%) were found to have OSA and underwent a CPAP titration night. Thirty-seven pts subsequently agreed to a therapeutic CPAP trial lasting up to 6 months. They then rated their CFS symptoms as “improved” or “not-improved”. RESULTS: In the diagnostic PSG, patients with CFS who reported improvement to later CPAP had a higher mean arousal index 67.6 (70.1) vs. 26.1 (12.1) in those who did not improve (p ⫽ 0.037). The following table compares several PSG variables in patients who improved with the CPAP trial compared with those who did not. Each value represents the change between the diagnostic and CPAP titration nights (mean and standard deviation). CONCLUSION: Patients with CFS and OSA are more likely to improve with CPAP if they have higher arousal indices in the diagnostic PSG and show improved sleep efficiency during CPAP titration. Changes in REM latency and stage 1 and 2 sleep may also predict improvement. CLINICAL IMPLICATIONS: The above mentioned PSG variables may be clinically useful in predicting which patients with CFS and OSA are more likely to improve with CPAP use.

Diagnostic vs. Titration Change in Sleep Efficiency (%) Change in Latency to REM-sleep (min) Change in Stage 1 Sleep (%) Change in Stage 2 Sleep (%) Change in Apnea-hypopnea index (per hour)

Improvement No Improvement with CPAP with CPAP p Value 13.1 (27.8)

⫺9.6 (14.2)

0.010

⫺40.8 (108)

48.9 (75.8)

0.023

⫺4.8 (8.9)

2.9 (12.1)

0.050

5.0 (10.3)

⫺7.5 (18.2).

0.023

⫺21.7 (50.7)

3.3 (19.5)

0.094

DISCLOSURE: Marcel Baltzan, None. COMPLIANCE IN CHINESE PATIENTS WITH OBSTRUCTIVE SLEEP APNEA SYNDROME (OSAS): A SINGLE NURSE-CONDUCTED EDUCATIONAL SESSION WOULD MAKE A DIFFERENCE Maggie P. Lit RN* C.K. Ng MBBS W.H. O MBBS H.W. She MBBS W.L. Law MBBS Samuel Lee MBBS Johnny W. Chan MBBS Queen Elizabeth Hospital, Kowloon, Hong Kong PRC PURPOSE: CPAP is the cornerstone treatment for OSAS, yet its compliance was unsatisfactory. Attempt is made to look at the factors associated with compliance. METHODS: A retrospective study evaluating CPAP compliance in a group of newly diagnosed OSAS Chinese patients in a regional hospital over a 6-month period (August 2003 - February 2004). Objective and self-reported compliance was obtained 6 months after commencing CPAP. Acceptable compliance was defined as CPAP usage for at least 4 hours/day in at least 70% of the night. Suboptimal treatment was defined CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

midification is expensive and many patients cannot afford this treatment. Nasal sesame oil (“Nozoil™”) has been shown to be superior to Normal Saline when used in patients with nasal symptoms associated with dry winter months in the northern hemisphere. The aim of the study was to assess the effect of “Nozoil™” on nasal symptoms and objective compliance. METHODS: Randomised, single-blinded, cross-over trial of subjects with obstructive sleep apnoea on CPAP with nasal symptoms, recruited from a tertiary referral Sleep Disorders Centre. Subjects were assessed with visual analogue scales of nasal symptoms, anterior rhinomanometry, and objective compliance at enrolment and at the end of each 2 week intervention period. Patients were randomised to normal saline (NS) or “Nozoil™” for 2 weeks then crossed over for a further 2 weeks. RESULTS: 17 subjects have completed the protocol. Compliance significantly improved on “Nozoil™” from baseline (5.50⫾2.05 hours/day improving to 6.50⫾1.35, p⫽0.007) and also when compared to NS (6.50⫾1.35 vs. 5.97⫾1.55, p⫽0.002). There was no statistically significant difference with nasal resistance between the baseline and intervention measurements. Significant subjective improvements in nasal crustiness (p⬍0.05), nasal and sinus discomfort on CPAP (p⬍0.001) and CPAP tolerance (p⬍0.001) were seen with the use of “Nozoil™”. Subjects also reported “Nozoil™” was superior to NS in making it easier to breathe through the nose (p⬍0.001). CONCLUSION: The use of “Nozoil™” in subjects with nasal side effects with CPAP results in improvements in objective compliance with CPAP and subjective improvement in nasal symptoms. CLINICAL IMPLICATIONS: “Nozoil™” is a potential alternative treatment for patients with nasal symptoms on CPAP. DISCLOSURE: John Feenstra, None.

Wednesday, November 2, 2005 Advances in Obstructive Sleep Apnea, continued as either refusal of CPAP treatment or unsatisfactory CPAP compliance. Newly diagnosed patients are invited to attend a specialty-nurse conducted educational session on OSAS before physician assessment. RESULTS: One hundred and six subjects were diagnosed to have OSAS. Only 58 patients (54.7%) accepted CPAP treatment. Fifty patients (86.2%) fulfilled the criteria of acceptable compliance (mean5.9⫾1.3 hours/day) and 8 had unsatisfactory compliance (mean 3.0⫾1.7 hours/ day). Attendance of the education class (p⫽0.007) and number of side effects experienced by patients (p⫽0.007) were independent predictors of satisfactory compliance. Fifty-six (52.8%) either declined or failed to comply to CPAP satisfactorily. There were no significant differences in age, sex distribution, presenting symptoms, degree of sleepiness, level of CPAP pressure, and type of side effects experienced between the 2 groups. Univariate analysis suggested associations of optimal treatment with greater body weight (p⬍0.05) and body mass index (p⬍ 0.01), higher respiratory disturbance index (p⬍ 0.05), higher desaturation index (p⬍0.01), higher arousal index (p⬍ 0.05), having hypertension (p⬍ 0.01), attendance of an education session (p⬍ 0.001). Using logistic regression, CPAP education was the only independent predictor of both good acceptance and compliance (p⬍ 0.001). CONCLUSION: CPAP acceptance rate was fair (54.7%). A single educational session could improve CPAP acceptance and compliance in newly diagnosed OSAS patients. CLINICAL IMPLICATIONS: Since augmented CPAP education has not been shown to offer additional benefits (Hui DSC et al. Chest 2000), basic education appears a cost-effective intervention in improving acceptance and compliance rate. DISCLOSURE: Maggie Lit, None. EFFECT OF TREATMENT BY UVULOPALATOPHARYNGOPLASTY ON CARDIOPULMONARY EXERCISE TEST IN OBSTRUCTIVE SLEEP APNEA SYNDROME Ching C. Lin MD* Chest Division, Mackay Memorial Hospital, Taipei, Taiwan ROC PURPOSE: To evaluate the effects of successful uvulopalatopharyngoplasty (UPPP) on cardiopulmonary exercise testing (CPET) in patients with obstructive sleep apnea syndrome (OSAS). METHODS: 25 subjects with moderately severe or severe OSAS who desired UPPP were enrolled. All patients had an overnight sleep study and CPET before and 3 months after LAUP. Patients were divided into 2 groups based on the success (group I) or failure (group II) of UPPP to improve their sleep apnea. RESULTS: The results showed that successful UPPP in group I was followed by improvement in right ventricular ejection fraction, maximal work rate (WRmax), VO2max/kg, anaerobic threshold, oxygen pulse and a lower breathing reserve. CPET results were unchanged after UPPP in group II subjects. CONCLUSION: Patients with OSAS before UPPP had abnormal CPET as reflected by low VO2peak/kg, WRmax, anaerobic threshold and oxygen pulse. All of these variables improved after UPPP that successfully ameliorated OSAS. CLINICAL IMPLICATIONS: Patients with OSAS before UPPP had abnormal CPET. CPET improved after UPPP that successfully ameliorated OSAS. DISCLOSURE: Ching Lin, None. ORAL APPLIANCE THERAPY FOR OBSTRUCTIVE SLEEP APNEA Vidya Krishnan MD* Steven C. Scherr Nancy A. Collop MD Johns Hopkins University, Baltimore, MD PURPOSE: Oral appliance therapy (OAT) is an alternative therapy for obstructive sleep apnea (OSA). It is most often recommended for patients who have mild OSA, or who have moderate-severe OSA and are unwilling or unable to comply with continuous positive airway pressure. We sought to identify the subset of patients most likely to benefit from OAT. METHODS: Patients of a sleep disordered breathing dental clinic with nocturnal polysomnography date before OAT initiation and during OAT titration. The main outcome variable was success of OAT (post-treatment AHI⬍10/hr). Secondary outcome measures included average nocturnal oxygen saturation (SpO2) and subjective symptoms. Independent variables available for analysis included patient demographics (age, sex), body anthropomorphic measurements (body-mass index (BMI), neck circum-

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ference, canine classification, facial skeletal classification), sleep characteristics (apnea-hypopnea index, average nocturnal oxygen saturation), and intervention (type of oral appliance, posture change during PSG and overall). Comparisons of patients by treatment success were performed using Student’s t-tests and chi-squared tests. RESULTS: Twenty-nine patients were identified for analysis, with age 54.7⫾13.3years, 62.1% male, and BMI 30.1 kg/m2. Most patients (76%) had moderate to severe OSA (AHI⬎20/hr) at baseline. OAT resulted in total posture change of 6.5⫾3.1mm, with 66.8⫾32.7% reduction in AHI (p⬍0.001), 6.8⫾7.5% absolute increase in SpO2 (p⬍0.001), improvement of subjective symptoms of 86%, and overall success of 69.0%. In the bivariate analysis, patients with post-treatment success were no different by age, sex, anthropomorphic measurements, or intervention characteristics compared to patients with post-treatment failure, but had higher average baseline SpO2 (82.4% vs. 76.2%, p⫽0.061). SpO2 remained significantly different after therapy (89.1% vs. 82.1%, p⬍0.001). CONCLUSION: OAT improves AHI, SpO2, and subjective symptoms in most patients with OSA, regardless of severity. Baseline hypoxia may predict failure of OAT monotherapy. CLINICAL IMPLICATIONS: OAT may be appropriate for treatment of OSA patients without baseline hypoxemia. Further studies are needed to evaluate the role for OAT in adjuvant therapy with CPAP and to determine the degree of baseline oxygen saturation that will predict OAT success. DISCLOSURE: Vidya Krishnan, None. LONG-TERM EFFECTS OF BILEVEL NONINVASIVE POSITIVE PRESSURE VENTILATION ON SLEEP APNEA AND HEART RATE VARIABILITY IN STABLE CONGESTIVE HEART FAILURE Hitoshi Koito MD* Keiko Kohna MD Satoshi Morita MD Hiroshi Yutaka MD Kansai Medical University, Otokoyama Hospital, Yawata, Japan PURPOSE: The purpose of this study is to evaluate the long-term effects of domiciliary bilevel noninvasive positive pressure ventilation (NPPV) on sleep apnea, cardiac function, sympathetic nervous activity and heart rate variability in stable congestive heart failure. METHODS: We examined 6 patients with stable congestive heart failure who completed 1 year of domiciliary NPPV with pulsed oxymeter, chest and abdominal wall motion sensor, nasal air flow sensor and electrocardiographic monitoring system (TEIJIN, Morpheus C) during sleep at night under a room air and NPPV before (Control; C) and after 1 month (1M), 4 month (4M) and 1 year (1Y) of NPPV. Urinary noradrenaline level at night and next morning mood index were also examined. Chest rentogenogram, electrocardiography, doppler echocardiography and serum noradrenaline level were measured befor and after 1M, 4M and 1Y of domiciliary NPPV. RESULTS: Apnea hypopnea index (/h) improved from 23 (C; Air) to 9 (C; NPPV), 9 (1M; NPPV), 10 (4M; NPPV) and 10 (1Y; NPPV). Centrl apnea index (/h) improved from 11 (C; Air) to 2 (C; NPPV), 2 (1M; NPPV), 3 (4M; NPPV) and 1 (1Y; NPPV). The left ventricular systolic dimension (mm) by echocardiography decreased from 50 (C) to 46 (1M), 43 (4M) and 43 (1Y). Percent fractional shortening (%) of the left ventricle increased from 21 (C) to 28 (1M), 29 (4M) and 32 (1Y), and the left ventricular ejection fraction (%) increased from 42 (C) to 51 (1M), 53 (4M) and 56 (1Y). Heart rate (bpm) decreased from 65 (C) to 59 (4M), and SDNN increased from 86 (C) to 98 (4M) and 108 (1Y). Serum noradrenaline level had decreased tendency in 1M and 1Y. CONCLUSION: The long-term domiciliary bilevel NPPV improved a sleep apnea, cardiac function, sympathetic nervous activity, heart rate and heart rate variability in patients with stable congestive heart failure. CLINICAL IMPLICATIONS: The long-term domiciliary bilevel NPPV might be a useful complementary therapy for stable congestive heart failure. DISCLOSURE: Hitoshi Koito, None. EFFECT OF OBSTRUCTIVE SLEEP APNEA ON LIPID PROFILE IN CHINESE SUBJECTS Jamie C. Lam MBBS* Sidney C. Tam MD Clara S. Yan MBBS Agnes Lai Karen S. Lam MD Mary S. Ip MD The University of Hong Kong, Hong Kong, PRC PURPOSE: Dyslipidemia has been reported to be common in subjects with obstructive sleep apnea (OSA), but this may be comorbid with CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Advances in Obstructive Sleep Apnea, continued

SUBJECTIVE SLEEP PERCEPTIONS FROM POST-TEST QUESTIONNAIRE AND OBJECTIVE SLEEP PARAMETERS AMONG AFRICAN AMERICAN AND CAUCASIAN POPULATION WITH OBSTRUCTIVE SLEEP APNEA Cynthia R. Crowder MD* Houman Dahi MD Narong Simakajornboon MD Denise Sharon Tulane University Health Sciences Center, New Orleans, LA PURPOSE: Currently, there are controversies about the relationship between OSA and subjective sleepiness. Recent study has shown the correlation between subjective sleep complaints and respiratory arousal. However, there is limited information on the relationship between subjective sleep perceptions and objective sleep parameters in different patient populations. METHODS: A retrospective study was performed in patients with obstructive sleep apnea. All patients completed post-test questionnaire after sleep study as part of our routine procedure. Any patients with significant neurological diseases, psychiatric disorder, central sleep apnea, severe periodic leg movements (PLMI⬎50) or incomplete records were excluded from the study. RESULTS: 79 patients met the criteria for entry into analysis; 41 African American (B) and 38 Caucasian (W). The average age is 47.5⫾10.1 years and the mean apnea-hypopnea index (AHI) is 25.9⫾19.5 per hour. There was no difference between age, sex, BMI or AHI between two groups. The subjective feeling upon awakening (Question 15 (Q15); scale 1-6) correlated with the arousal index (r⫽0.27, P⫽0.019), AHI (r⫽0.3, P⫽0.008), and apnea-hypopnea related arousal (r⫽0.24, P⫽0.038). There is a tendency toward significant correlation between subjective sleep quality (Question 7 (Q7), scale 1-4) and arousal index (r⫽0.22, P⫽0.054) as well as between Q7 and AHI (r⫽0.22, P⫽0.056). The subgroup analysis revealed a significant correlation between Q15 and arousal index only in African American population (r⫽0.36, P⫽0.02 [B] versus r⫽0.17, P⫽NS [W]). However, Q15 correlated with AHI only with Caucasian population (r⫽0.20, P⫽NS [B] versus r⫽0.46 P⬍0.01 [W]). CONCLUSION: It is concluded that subjective perception from post-sleep questionnaire correlates significantly with severity of apnea and frequency of arousals especially respiratory arousals. The subjective perception correlates only with the frequency of arousals in African American population, while subjective perception of Caucasian population correlates directly with severity of apnea.

CLINICAL IMPLICATIONS: It is speculated that other factors in addition to apnea may play a role in sleep disruption in African American population with sleep apnea. However, more studies are needed.

DISCLOSURE: Cynthia Crowder, None. EFFECT OF ZOLPIDEM ON THE EFFICACY OF NASAL CONTINUOUS POSITIVE AIRWAY PRESSURE AS TREATMENT OF OBSTRUCTIVE SLEEP APNEA Prakash B. Patel MD* Richard B. Berry MD University of Florida, Gainesville, FL PURPOSE: Obstructive sleep apnea (OSA) patients using CPAP (Continuous Positive Airway Pressure) are frequently prescribed BZRA(Benzodiazepine receptor agonist) hypnotics. However, no prior studies have evaluated the effect of BZRAs on the efficacy of CPAP. CPAP works as a pneumatic splint so upper airway muscle tone is much reduced. Therefore, further reduction in muscle tone by BZRAs should be minimal. For this reason, we hypothesize that Zolpidem (selective BZRA with greater hypnotic than muscle relaxant properties)should not cause a change in the level of required CPAP to maintain an open airway. METHODS: To test this hypothesis, we conducted a double blind placebo controlled cross-over study in patients with OSA currently being treated with CPAP. Patients were studied on three nights in the sleep laboratory over three consecutive weeks (one night per week). On night one, the pressure level required to prevent apnea, hypopnea, and snoring was determined (optimal pressure). On the second night and third nights, either Placebo or Zolpidem 10 mg was given and subjects slept on the CPAP level determined by first night (optimal pressure). RESULTS: For our initial four patients, there was no significant difference in Total Sleep Time (TST), REM sleep, AHI overall, or AHI NREM sleep (see table). CONCLUSION: Study of a limited number of OSA patients suggests Zolpidem 10 mg does not significantly increase the AHI in a patient treated with an appropriate level of CPAP. We plan to study at least 20 patients to confirm this preliminary result. CLINICAL IMPLICATIONS: If further study confirms our preliminary findings this would suggests Zolpidem can be used safely in OSA patients with insomnia who are on CPAP. This may improve tolerance of CPAP in these patients. DISCLOSURE: Prakash Patel, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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obesity or visceral obesity which are highly prevalent in those with OSA. This prospective cohort study investigated the relationship of OSA to lipid profile in Chinese subjects. METHODS: Consecutive Chinese subjects of male sex, with no history of cardiovascular disease, diabetes mellitus, hyperlipidemia or significant chronic illness or medications, were recruited from our sleep laboratory. Their demographic and anthropometric data, fasting lipid profile (cholesterol, triglycerides, low density lipoprotein-cholesterol (LDL-cholesterol) & high density lipoprotein-cholesterol (HDLcholesterol), apolipoproteins A1 & B (Apo A1 & B), and polysomnographic findings were collected. The relationships between apneahypoapnea index (AHI) and each lipid parameter were examined with multiple linear regression, adjusted for obesity (body mass index or waist circumference). RESULTS: 98 subjects were recruited, aged between 21 and 65. OSA was defined as AHIⱖ5. 73 subjects had OSA. Significant linear relationships were present between AHI and waist circumference, body mass index (BMI), LDL-cholesterol, HDL-cholesterol, Apo B, LDL-cholesterol:HDL-cholesterol and Apo B:Apo A1 (all p⬍0.05). On multiple linear regression analysis, with lipid parameters as dependent variables, adjusted for BMI, AHI was associated with Apo B (p⬍0.05), total cholesterol: HDL-cholesterol (p⬍ 0.01), LDL-cholesterol:HDL cholesterol (p⬍ 0.05)and Apo B:Apo A1 (p⬍0.05). CONCLUSION: In this cohort of Chinese subjects, AHI was associated with apolipoprotein B, apolipoprotein and cholesterol fraction ratios, controlled for obesity. CLINICAL IMPLICATIONS: OSA may have an independent effect on adverse lipid profile, and thus confer independently to cardiovascular risks. DISCLOSURE: Jamie Lam, University grant monies This project was supported by the Hong Kong Research Grants Council, The University of Hong Kong, HKU7307/00M

Wednesday, November 2, 2005 Asthma Evaluation I 12:30 PM - 2:00 PM COMPARISON OF MEDICAL UTILIZATION IN THE YEAR PRECEDING AND ANTECEDING LARYNGOSCOPIC DIAGNOSIS OF VOCAL CORD DYSFUNCTION Jeffrey A. Mikita MD* Joseph Parker MD Walter Reed Army Medical Center, Washington, DC PURPOSE: Patients with vocal cord dysfunction (VCD) have high medical utilization. This has been attributed to somatization, but may reflect a lack of understanding and recognition of the VCD disease process. The effect of laryngoscopic diagnosis of VCD on medical utilization has never been evaluated and results from this study will add insight into the benefit of laryngoscopy evaluation and treatment of VCD. Furthermore, the role of somatization in the pathogenesis of VCD may be better understood. METHODS: Subjects were obtained thru retrospective review of all laryngoscopies conducted in our clinic from January 2002 to March 2004. Patients with laryngoscopy confirmed VCD had their medical utilization evaluated. Inclusion required subjects to have evidence of medical utilization one year predating and one year postdating diagnosis and exclusion occurred if their diagnosis could not be confirmed by chart review. Medical utilization information for the preceding year and anteceding year were compiled from a computerized medical record. t-test analyses was utilized to compare differences between the group’s medical utilization before and after diagnosis of VCD. This study was approved by the Institutional Review Board. RESULTS: Forty three ambulatory patients with VCD with a mean age of 45 (range 21-81) yearsmet inclusion criteria. Total physician visits and primary care visits were found to reduce significantly after diagnosis of VCD. These patients were also found to have comparable frequency of hospitalizations, urgent care visits, and prescriptions. CONCLUSION: Total physician visits and primary care visits among ambulatory VCD patients are significantly reduced after diagnosis of VCD by laryngoscopic criteria. CLINICAL IMPLICATIONS: Aggressive diagnosis of ambulatory VCD patients has a significant impact on healthcare utilization.

Year preceding Year anteceding VCD diagnosis VCD diagnosis Health Care Measure n⫽43 n⫽43 Total Physician Visits Primary Care Visits Urgent Care Visits Hospitalizations Total Prescriptions

796 265 77 12 767

603 137 49 5 767

NO via REMPI, we found a concentration profile in agreement with that of research groups using different techniques (chemiluminescence and LMRS). Sampling the breath from a person without respiratory ailments, we found a dead-space air NO concentration of 20 ppbV and an alveolar ventilation concentration of 5 ppbV. In contrast to the chemical-based technique chemiluminescence, MPLI-MS can also selectively measure isotopically-labeled NO, as demonstrated with REMPI of 14N16O, 15N16O and 14N18O. Further, MPLI-MS can be used to measure other biologically-significant molecules, such as the aldehydes. In forthcoming studies, we will explore the application of MPLI-MS for the measurement of other biologically-significant molecules. CLINICAL IMPLICATIONS: (1) ppbV mixing ratios of NO can be measured on a sub-second time scale, (2) other biologically significant gas molecules can be measured on a similar time scale and (3) since the technique operates optically as well as mass-resolved, isotopomers of NO are discernable, permitting the use of isotopic tracing.

p 0.049* 0.0005* 0.084 0.068 ns

DISCLOSURE: Jeffrey Mikita, None. DISCLOSURE: Luke Short, None. REAL-TIME ANALYSIS OF EXHALED BREATH WITH MPLIMS: OBSERVED NITRIC OXIDE PROFILE Luke C. Short PhD* Thorsten Benter PhD Bergische Universita¨t Wuppertal, Wuppertal, Germany PURPOSE: An elevated concentration of nitric oxide (NO) in alveolar ventilation indicates inflammatory stress within the lung. Trace-gas analysis using mass spectrometers (MS) have been used extensively within the atmospheric community with great success. We present here the first description of time-resolved NO measurement in breath using photoionization MS, providing new capabilities for the medical investigator, such as isotopic tracing. METHODS: For NO measurement, we use resonance enhanced multiphoton ionization (REMPI) coupled with a time-of-flight MS with a medium pressure laser ion source. A single male subject breathes NO-free air for several minutes, and then the exhaled breath is monitored for NO. RESULTS: The ability of REMPI to differentiate among three different isotopomers of NO is demonstrated, and then the concentration profile of NO in exhaled breath is measured. A similar time-dependence concentration is found as observed by previous techniques. CONCLUSION: This study presents MPLI-MS as a new technique available for the time-resolved measurement of NO in breath. The resulting system can be made portable and brought into the medical setting using newer-generation, broad-bandwidth lasers. When measuring

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HIGH RESOLUTION COMPUTED TOMOGRAPHY EVALUATION OF AIRWAY DISTENSIBILITY IN ASTHMATIC AND HEALTHY SUBJECTS Antonio Castagnaro MD* Alfredo Chetta MD Emilio Marangio MD Panagiota Tzani MD Marina Aiello MD Raffaele D’ippolito MD Nicola Sverzellati MD Maurizio Zompatori MD Dario Olivieri MD Dept of Clinical Sciences, Respiratory Disease Section, University of Parma, Parma, Italy PURPOSE: In bronchial asthma, airway wall remodeling may result in reduced airway distensibility. In this study, we assessed in asthmatic patients both the baseline airway caliber and distensibility by means of High Resolution Computed Tomography (HRCT). METHODS: We studied 7 patients (2 M, age range: 36-69 yrs) affected by chronic asthma (FEV1 range: 30-87 % of predicted; FEV1/VC range: 48-75 % of predicted) in stable clinical conditions and 6 healthy subjects (3 M, age range: 29-50 yrs), as a control group. In all subjects, HRCT scanning, obtained at suspended end-espiratory volume, was performed at rest and during ventilation with 6 and 12 cmH2O by nCPAP, both at baseline and after the inhalation of 200 mcg oxitropium bromide MDI.. External and lumen diameter (mm) of the right apical upper lobe bronchus were measured in all HRCT scans. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Asthma Evaluation I, continued RESULTS: Results (means⫾SD) are listed in the table. CONCLUSION: Our results showed that in asthmatic patients the airway distensibility, assessed by HRCT, could differ as compared to that of healthy controls. CLINICAL IMPLICATIONS: HRCT can provide useful information on airway distensibility.

Asthmatics Patients Baseline

After Oxitropium

At rest

6 cmH2O 12 cmH2O

At rest

6 cmH2O 12 cmH2O

external Ø (mm)

6.2⫾0.9

6.3⫾0.9

6.7⫾0.8*

7.3⫾1

6.9⫾0.7

7.1⫾0.9

lumen Ø (mm)

3.3⫾0.7

3.5⫾0.6

3.8⫾0.6*

4.4⫾0.6

3.8⫾0.4

4⫾0.4

Healthy Controls external Ø (mm)

7.3⫾1.8

7.9⫾1.7

7.8⫾2

8⫾1.6

8⫾1.8

9⫾1.7

lumen Ø (mm)

4.0⫾1.6

4.8⫾1.6*

4.7⫾1.7*

5⫾1.5

5⫾1.4*

6⫾1.6*

* p⬍ 0.05 vs at rest DISCLOSURE: Antonio Castagnaro, None.

PURPOSE: Nitric oxide in exhaled air (FENO) is a marker of airway inflammation in asthma. This study was undertaken to determine whether FENO increases as a result of stress. METHODS: This study was a prospective, unblinded study in an office setting. 20 adult asthmatics were recruited to participate. Subjects were initially put into a relaxed state using a progressive relaxation technique. They were then put into a stressful state by asking them to complete complicated mathematical problems. RESULTS: FENO was measured using standard techniques after relaxation and after stress. Pulse was monitored during the stressful intervention. FENO significantly increased after stress. Mean ⫹/-Standard Deviation (SD) for baseline FENO was 2.9 ⫹/- 2.1. After stress, mean ⫹/- SD FENO rose to 3.1 ⫹/- 2.1. This was significant by paired test. (p⫽ 0.03). CONCLUSION: A stressful situation can cause an immediate increase in the inflammatory state of the airways in adult asthmatics, as measured by FENO. CLINICAL IMPLICATIONS: This study provides insight into the mechanism in which a psychological stress could lead to worsening asthma. DISCLOSURE: Jonathan Ilowite, None. THE DIFFERENCES IN ASTHMA SEVERITY BETWEEN PREMENOPAUSAL AND POSTMENOPAUSAL AFRICAN AMERICAN WOMEN Celia Maxwell MD Reverly M. John MBBS* Alicia Thomas MBBS Howard University Hopsital, Washington, DC PURPOSE: Prolonged hormonal exposure has been linked to an increased severity of asthma among Caucasian women. Our aim is to determine if the same is true or are there differences in the severity of asthma among premenopausal(PREM) vs postmenopausal(PM)African American(AA)women. METHODS: We enrolled 37 women ages 18-82, who were admitted through the emergency department over a 2-year period with asthma exacerbation. In this retrospective chart review, asthma severity was defined by the National Heart Lung and Blood Institute guidelines. Menopause was defined as cessation of the menstrual cycle by natural or surgical means.Additionally, body mass index (BMI), age of onset of menarche and number of cigarette pack years (CPY) of smoking were recorded. RESULTS: Twenty (58.5%)of the women were PM, and 17 (41.5%)were PREM. The mean ages were 35⫹/-8.2 for PREM and 60⫹/-10 for PM women. There was no significant difference in population

DOES BODY MASS INDEX OF PATIENTS EFFECTS SEVERITY OF DISEASE IN HOSPITALIZED ASTHMATICS? Esra Uzaslan MD* Oktay Gozu MD Funda Coskun MD Dane Ediger MD Mehmet Karadag MD Ercument Ege MD Uludag University Medical Faculty, Bursa, Turkey PURPOSE: In this study, we aimed to analyze the effects of obesity to the severity of the disease, by investigating the correlation between body mass index (BMI) and characteristics of asthma in hospitalized asthma patients. METHODS: Characteristics of asthma related factors and BMI of patients analyzed retrospectively from the data obtained from the clinic files of 160 hospitalized patients (41male,119female, mean age 46.5⫾1.1years)who were followed in our department.Body mass index was calculated as body weight/ height (kg/m2).Patients were divided and evaluated in three groups according to their BMI; Group1: BMI⬍22.5 thin, Group2: 22.5ⱕ BMI⬍30 normal or overweight,Group3: BMIⱖ30 obese. RESULTS: The mean BMI of the whole patients was 28.3⫾0.5, whilst the mean BMI of patients in Group 1 was 32.9⫾2.9,in Group 2 was 46.6 ⫾ 1.6,and in Group 3 was 49.2 ⫾ 1.5. The 20% of patients in Group 1, 47% of patients in Group2 and 33% of patients in Group3 were atopic The 33%of the asthmatic patients was also diagnosed to have allergic rhinites.The 8.4% of patients (n:13)had a history of childhood asthma (54% in Group1, 31% in Group2 and 15% in Group3).The percentage of patients with the history of childhood asthma was significantly higher in Group1 than in Group2 and Group 3.Although there was not any significant difference in the mean eosinophiles counts and mean serum ECP levels of patients, those values were lower in Group3 than in other groups.There was not any significant difference in mean outdoor and indoor allergen sensitivity scores of patients among groups. Mean medication score (number of controller drugs) of patients in Group1 was significantly lower than in Group2 and Group3.The lung function parameters of FEV1 and PEF were not significantly different among groups, but predicted value of FVC was significantly higher in Group1 than Group2 and Group3 . CONCLUSION: According these results we came to the conclusion that obesity was a severity factor in hospitalized asthmatic patients. CLINICAL IMPLICATIONS: Asthma outcomes was effected badly with increasing body weight in asthmatics. DISCLOSURE: Esra Uzaslan, None. RHINOSINUSITIS CONTROL DECREASES SEVERITY OF ASTHMA Ramon Figueroa -Lebron MD* Asthma Management Center, San Juan, PR PURPOSE: Chronic non allergenic Rhinosinusitis accounts for 1/3 of visits to physicians offices.In many of our asthmatics, cough is the presenting symptom. This study is to evaluate benefits of daily nasal steroids and HT1 blockers in decreasing severity of bronchial inflamation, improvement of disease control and quality of life. METHODS: Study is a retrospective observational based on Blue Shield Puerto Rico expenditures of all services and medications paid in 2004 for the population of this study and the control patients. The subject were 358 patients referred to center because of refractioness to management. Control population consisted of 12,070 asthmatics treated by the CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

EXHALED NITRIC OXIDE IS INCREASED IN RESPONSE TO STRESS IN ADULT ASTHMATICS Jonathan S. Ilowite MD* Mary Bartlett RN Winthrop University Hospital, Mineola, NY

demographics except for CPY, that was statistically greater in PM women P⫽0.003. Multivariate analysis was used to control for BMI, CPY, number of pregnancies, highest educational level and onset of menarche. Eighty percent of PM and 55.8% of PREM women had a BMI ⬎30, (40% of PM vs 29%of PREM had BMI’S ⬎ 40). P ⫽ 0.68 between the groups. Average onset of menarche in the PREM vs PM group was 11.2⫹/-2.8 and 13.4 ⫹/-2.7, P ⫽ 0.9. Chi-Square test was used in the analysis of the asthma severity. Although there was a percentage trend to more severe asthma in the PM group, it was not statistically significant P ⫽ 0.189. CONCLUSION: Women in the PM group had shorter duration of hormonal exposure, however an increased severity of asthma. While not explained by population characteristics except CYP and BMI that were not statistically significant , nonetheless, severe obesity rather than hormonal changes may be the primary factor in asthma severity among PREM and PM AA women. CLINICAL IMPLICATIONS: Asthma severity in PREM vs PM AA women may need to be evaluated using different parameters. Further studies are required. DISCLOSURE: Reverly John, None.

Wednesday, November 2, 2005 Asthma Evaluation I, continued neumologists in the community. Inclussion criteria were: an age of 12-70 years, presence of Rhinosinusitis, cough as prominent symptons, severe airway obstruction shown by spirometry and low peak flow (PEF)readings, prior visits to emergency department and or hospital admissions in 2003.Upon entry patients received instructions in the use of PEF and logging, nasal steroids, inhaled bronchial medication, emergency albuterol inhalations.The use of daily nasal steroids was continous for 4 weeks. RESULTS: Asthma complex with Bronchial Obstruction decreased as evidenced by peak flow redings and controller medications and by dollars paid for them.The shift in cost occurs in favor use of nasal steroids and HT1 blockers .The emergency dept visits and admissions decreased to the lowest levels. In 2004 2 out of 176 ptswere admitted for 0.4% lower than in 2003that was 1 %. CONCLUSION: The study showed dramatical improvement in severity of airway obstructions and symptoms complex with 88% less hpspital admissions and a dramatic decrease in the use and cost of controller medications. Use of daily nasal steroids is of great benefit in the majority of patients. CLINICAL IMPLICATIONS: Daily nasal steroids and HT1 blockers should be part of the management of moderately severe and severe asthmatic. Study showed the benefit of this practice for patients and for the economy. This study may improved the asthma management. DISCLOSURE: Ramon Figueroa -Lebron, None. TOTAL IGE AND STIMULATED T CELL CYTOKINE PRODUCTION IN A COHORT OF ETHNICALLY DIVERSE PREGNANT WOMEN BY ASTHMA HISTORY Christine C. Johnson* M Maliarik SL Haystad DR Ownby EL Peterson G Wegienka LK Williams M McCabe EM Zoratti CL Joseph Henry Ford Health Systems, Detroit, MI PURPOSE: Little is known about the relationships between total IgE as a marker for Th2 phenotype, T cell production of interferon _ (IFN-_) and IL4 as markers of Th1 and Th2 phenotypes, respectively, and IL10 as a marker of immune regulation, in a population of racially diverse females categorized by history of asthma diagnosis. METHODS: We analyzed blood samples taken during pregnancy from the mothers of urban and suburban African American and Caucasian children in a geographically defined Detroit area birth cohort (WHEALS). Total IgE was measured using the Pharmacia CAP low range with a detection limit of 0.1 IU/ml. IFN-_, IL4 and IL10 production by PMA stimulated lymphocytes was detected by antibody staining and flow cytometry. Results are expressed as the percentage of CD4⫹ cells positive for these cytokines. Wilcoxon rank sum tests were used to compare mean IgE and mean IFN-_, IL4 and IL10 percentages by history of physician diagnosed asthma and race. RESULTS: Blood samples from 443 women were tested; 65% were African American and 21.0% had a history of asthma. Total IgE was higher in women with asthma (155.7 vs 71.2 IU/mL, p⬍ .001) and higher in African American women vs Caucasian women with asthma (185.8 vs 114.7 IU/mL, p⬍ .001). IFN-_ positive cells tended to be lower in women with an asthma history (8.0% vs 9.4%, p⬍0.065), and lower in African American vs Caucasian asthmatics (7.4% vs 9.2%, p⬍0.097). There were no differences in IL4 or IL10. CONCLUSION: Total IgE is higher in women with a history of asthma and African American women, while IFN-_ was lower, following the Th1-Th2 paradigm. NIAID. CLINICAL IMPLICATIONS: Total IgE is higher in women with a history of asthma and African American women, while IFN-_ was lower, following the Th1-Th2 paradigm. NIAID. DISCLOSURE: Christine Johnson, None.

Asthma Evaluation II 12:30 PM - 2:00 PM CHARACTERISTICS OF PATIENTS WITH REPEAT ATTENDANCE AT EMERGENCY DEPARTMENT FOR ASTHMA EXACERBATIONS Lee Lan Phoa MBBS* Lathy Prabhakaran RN Wee Yang Pek MBBS Seow Yian Tay MBBS Eillyne Seow MBBS Alan W. Ng MBBS Tan Tock Seng Hospital, Singapore, Singapore PURPOSE: To identify demographic characteristics of patients with repeat Emergency Department (ED) attendance for asthma exacerbation. METHODS: Analysis of computer database records of all patients that were treated and discharged from the ED of a tertiary hospital over 6

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months in year 2004 for asthma. Data analyzed included demographic characteristics such as age, sex, ethnicity and ED attendance in the past 40 days and past 24hrs for acute asthma. RESULTS: 750 patients with Male: Female of 1:1 was seen at the ED for asthma exacerbation and 195 had previous attendances. Out of these 195 patients, 132 had past attendance within 40 days, 64 had past attendance within last 24 hrs and 1 had past attendance in the last 40 days and within last 24 hrs. The median age for our patients was 32 years (range 2 to 92 years). 42% of the patients were Chinese, 29% were Malays, 23% were Indians and 7% were of other ethnicity. Male patients had a significantly higher repeat ED attendance compared to female patients (34.3% vs 13.8%, p ⬍ 0.0001).There was also a significantly higher proportion of Malay patients with repeat attendance when compared to Chinese, Indians and other ethnicity (35.3% vs 23.3% vs 22.2% vs 16.4% respectively, p ⫽ 0.002).Patients of age 21 years and below were also found to have higher repeat attendance for asthma when compared to those above 21 years of age (39.3% vs 21.3%, p ⬍ 0.0001). Multivariate analysis showed that male sex (OR 3.03, p ⬍ 0.0001), Malay ethnicity (OR 2.30, p ⫽ 0.04) and age 21 years and below (OR 1.61, p ⫽ 0.015) were associated with increased risk of repeat ED attendance. CONCLUSION: Male sex, Malay ethnicity and young age of 21 years and below were associated with higher risk of repeat ED attendance in our asthmatic patients. CLINICAL IMPLICATIONS: Further studies should be conducted on this high risk group to identify factors which contribute to their frequent ED visits in order to optimise their asthma control. DISCLOSURE: Lee Lan Phoa, None. DOES OBESITY EFFECTS ASTHMA OUTCOMES IN FEMALE ASTHMATIC PATIENTS? Esra Uzaslan MD* Funda Coskun MD Dane Ediger MD Mehmet Karadag MD Oktay Gozu MD Uludag University Medical Faculty, Bursa, Turkey PURPOSE: In this study we aimed to investigate the correlation between body mass index and characteristics of asthma in female asthmatic patients of our clinic. METHODS: Characteristics of asthma related factors and body mass index (BMI) analyzed from the data obtained out-patients files of 900 female patients, who were followed in our department between the years of 1992-2004.Patients were divided and evaluated in four groups according to their BMI; Group1: BMI⬍18.5 thin,Group2:18.5ⱕBMI⬍25 normal, Group3: 25ⱕBMI⬍30 overweight, Group4: BMI ⱖ30 obese. RESULTS: The number of patients in Group1 was 23, was 336 in Group 2, was 302 in Group3, and was 239 in Group4. The mean BMI of patients was 26.9⫾0.2. The mean age of patients was 37.4⫾ 0.4 and the patients in Group4 was significantly older than patients in other groups. The 42.6% of patients were atopic and 50.9 % was also diagnosed to have allergic rhinites. The 53.8 % of patients in Group1, 72.9 % of patients in Group2, 63.5 % of patients in Group3, 58.2 % of patients in Group4 were atopic . The mean serum IgE levels of patients in Group4 was significantly lower than others. Although there was not any significant difference in the mean eosinophiles count of patients, those values were lower in Group4 than in other groups. The mean asthmatic years of patients in Group4 was significantly longer than others. The mean and predicted values of lung function parameters of Group4 were generally lower than other groups, especially the means FEV1 and FVC values was significantly lower in Group4 than Group1, Group2 and Group3. The mean medication score (number of controller drugs) of patients in Group4 was significantly higher than in patients of other groups.The hospitalization rate of patients in Group4 (19%) was significantly higher than patients in patients Group2 (9%) and Group3 (12) (p⬍0.05). CONCLUSION: In conclusion, obesity was a severity factor for asthmatic female patients. CLINICAL IMPLICATIONS: Asthma outcomes are effected badly due to obesity in females. DISCLOSURE: Esra Uzaslan, None. GENDER AND ASTHMA: WHAT DO WE KNOW? (A SURVEY) Wendy A. Lopez BSc* Sunnybrook & Women’s College Health Sciences Centre, Toronto, ON, Canada PURPOSE: There appear to be gender differences in the prevalence, morbidity and severity of asthma, with variations across the lifespan. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Asthma Evaluation II, continued Asthma is a chronic obstructive airway disease that occurrs more frequently in adult females. The objective of the survey was to determine whether respiratory therapy students (SRT) and registered respiratory therapists (RRT) who may deal with adult asthmatic patients are aware of the sex and gender differences that exist in this disease. METHODS: A survey was conducted with 175 subjects. Four different groups were surveyed: first-year, second-year, and third-year SRTs from the Michener Institute for Applied Health Sciences and RRTs from hospitals in Toronto. RESULTS: There was a 78% response rate. Out of all the respondents, 25.3% thought that asthma was the same in males and females, 24.7% thought that more males had asthma, 21.4% thought that more females had asthma, and 28.6% did not know. The second year SRTs and RRTs had the majority choosing males as having asthma more than females. The third year SRTs were the only group that identified women as having asthma more than males. CONCLUSION: Sex and gender differences of asthma in adulthood are still relatively new areas of research. SRTs and RRTs may not be aware of these differences, which may lead to misdiagnosis, and sub-optimal treatment and management plans for the female asthmatic population. CLINICAL IMPLICATIONS: More research in this area is needed. Updated school curricula should reflect emerging issues to provide the best treatment possible. DISCLOSURE: Wendy Lopez, None.

PURPOSE: Increased levels of fraction exhaled nitric oxide (FENO) have been found among individuals with atopic asthma and are believed to reflect on going airway inflammation. However, routine use of FENO in health care diagnosis and treatment is limited by the expense of the required equipment. Two offline methods are currently available for obtaining FENO namely, the American Thoracic Society (ATS) FENO 350cc/sec recommended method and the Dead Space Discard (DSD) FENO 50cc/sec kit method. However, there have not been published studies comparing the two techniques in the field. In the current study we sought to compare the FENO levels obtained by the ATS method and the DSD method and to investigate the utility of FENO levels in detecting inflammation is persons with diagnosed asthma. METHODS: Cross-sectional study. A convenient sample of 45 subjects ages 17 to 82 years, mean age 44.26 ⫾ 16.71 years. There were 19 females and 26 males. Paired exhaled samples were collected from the subjects in triplicate using ATS and DSD techniques and analyzed offline using Sievers 280i Nitric Oxide Analyzer. RESULTS: Comparison of the two methods was performed using correlations, regression analysis and ANOVA. 33.3% had health care provider diagnosed asthma, 8.9% had other respiratory problems, the remainders were healthy individuals with no known respiratory conditions; 11.1% were current cigarette smokers. FENO levels obtained by DSD technique were consistently higher than those obtained by the ATS technique. The two techniques were highly correlated r⫽ 0.691, p⬍0.000, 2df and r2 ⫽ 0.48. CONCLUSION: FENO levels obtained by the ATS and DSD technique are highly and positively correlated. CLINICAL IMPLICATIONS: The DSD technique is well suited for field studies when replicate samples are to be collected from many subjects. Furthermore, the smaller bags are more cost efficient and easier to transport than the high flow bags. DISCLOSURE: Jamson Lwebuga-Mukasa, None. COAL-DUST EXPOSURE AND THE PREVALENCE OF ASTHMA, ALLERGIC DISEASES AND ATOPY Zdenka Hajdukova´ MD* Daniela Pelclova´ MD Milena Menzlova´ MD Clinic of Occupational Diseases, University Hospital of Ostrava1, Czech Republic PURPOSE: Find out whether workplace exposures to coal mine dust contribute to the development of allergic diseases and if atopy in miners is more frequent than in general population. Atopy is an important risk factor for asthma. Latest epidemiological studies in Czech Republic

MORPHOLOGY OF TISSUES USED FOR CILIARY STUDIES Thorsten Stein MD* Mohamed Abdel-Aziz MD Inge Wissen-Siegert MD Christine Eidner MD Hans L. Hahn MD Deutsche Klinik fu¨r Diagnostik, Wiesbaden, Germany PURPOSE: We have shown previously that the allergic reaction does not change the beat frequency of nasal cilia (Europ. Respir. J., Vol. 22, Suppl. 45, 291s). Increasing allergen dose and length of exposure did not change this (CHEST, Vol. 124, Suppl. 4, 140s). It might be argued that significant components of the allergic reaction were lacking in our biopsy specimens. METHODS: We obtained surgical specimens during turbinate surgery. All patients (n ⫽ 17, 10M, 7F, age 35 ⫾ 14) had allergic rhinitis (allergy testing and clinical history). From each specimen we obtained at least five biopsies with a bronchoscopy forceps. We processed these biopsies histologically and stained them with H.E. and Giemsa. The sections were 3 ␮ thick with a distance of 10 ␮ in between; we analyzed a total of 8 sections. We overlaid them with a grid (integration plate I, Zeiss) and counted hits over the different tissue structures. We also counted single cells (mast cells, eosinophils, and polymorphonuclear leukocytes attached to the vessel wall [marginating PMN]) and expressed them per total grid area. RESULTS: Tissue composition derived from percent hits over each structure was as follows: epithelium 20,65%, blood vessels 10,32%, connective tissue 55,59%, serous glands 10,34%, mucous glands 3,10%, mast cells 47/mm2, marginating PMN 210/mm2, eosinophils 13/mm2. CONCLUSION: We conclude that all tissue components of the allergic reaction were contained in even the smallest of our biopsy specimens. Similarly, isolated blood or tissue cells that are known to be involved in the allergic reaction were present in our specimens in sufficient numbers. CLINICAL IMPLICATIONS: We suggest that a full blown allergic response with mediator release and mucosecretion was possible in our specimens and must have taken place following allergen challenge. Equivalence of mediator release from specimens challenged in vivo and in vitro has been shown (Nakamura et al., J. Allergy Clin. Immunol. 2000;105:1146-52). Nevertheless ciliary beating was unchanged and thus appears to be remarkably resistant to effects of the allergic reaction. DISCLOSURE: Thorsten Stein, None. GENETIC POLYMORPHISM OF GLUTATHIONE-S-TRANSFERASE M1,T1 AND SUSCEPTIBILITY TO PREMENSTRUAL ASTHMA IN UKRAINIAN POPULATION Natalia Gorovenko MD* Mohammad Ebrahimi MD Svetlana Podolskaya PhD Kiev Medical Academy of Post-Graduate Education, Kiev, Ukraine PURPOSE: About one-third of women with asthma (A) have an increase in asthma symptoms during in menstrual period. Patients CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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COMPARISON BETWEEN 3.5 LITER SINGLE BREATH COLLECTIONAND DEAD-SPACE DISCARD TECHNIQUES IN MEASUREMENT OF EXHALED NITRIC OXIDE IN ADULTS Jamson S. Lwebuga-Mukasa MD* Paulette M. Wydro MPH Tiffany Kolniak BS SUNY at Buffalo, Buffalo, NY

estimate, that prevalence of allergic diseases in Czech population is 24 %, the prevalence of asthma 5 % and atopy 40-50 %. METHODS: In the cross-sectional study (2004/2005) we studied the frequency distribution of airway diseases(spirometry including non-specific bronchoprovocation test, if indicated, examination by physician), allergic disease in personal history (mucosal and cutaneous) and atopy (presence of specific IgE to common inhalation allergens in blood by Phadiatop) in 548 coal miners (mean age 49) and 315 subjects of control group (mean age 43). Controls where recruited from men, who have never been exposed to dust in their occupational environment. Subjects where divided into cohorts according to age and lengh of exposure; statistical analysis was by x-square testing using contingency tables. RESULTS: Atopy and allergic diseases after mean exposure to coal dust lasting 3 years, 14 years, and 29 years was 38 % and 22 %; 31 % and 26 %, and 17 % and 19 %, respectively. Atopy and allergic diseases in miners age 27-31 years, 32-40 years, and 54-65 years was 37 % and 25 %; 30 % and 23 %, and 22 % and 20 %, respectively. Controls ind the same age group had atopy and allergic diseases in 48 % and 51 %; 37 % and 40 %, and 22 % and 19 %, respectively. Statistical analysis has shown, no influence of either coal-mine dust or of smoking status on the prevalence of atopy, rhinitis and asthma. Prevalence of chronic bronchitis and COPD increased with age and exposure to coal-dust. CONCLUSION: Coal mining does not seem to represent a risk factor of atopy and respiratory allergic disorders. CLINICAL IMPLICATIONS: In occupational medical care atopy in miners should not represent contra-indication for mining occupation. DISCLOSURE: Zdenka Hajdukova´, None.

Wednesday, November 2, 2005 Asthma Evaluation II, continued affected by premenstrual asthma (PA) in comparison to asthmatic women without premenstrual asthma (WPA), generally have more sever symptoms and more frequently hospitalization. Hormonal fluctuations and changes during the menstrual cycle may be responsible for PA occurring. GSTT1, GSTM1 genes take part in detoxification and excretion of xenobiotics from organism, and also in metabolism of prostaglandins, leukotreine and sexual hormones. Allergy also is a major risk factor for asthma. To evaluate the role of GSTT1 and GSTM1 genotypes and allergy in susceptibility to PA, we conducted the given study. METHODS: We survey 74 asthmatic women, 9 (12.16%) with PA, average age 44.95⫾1.50 years and 65 (87.84%) WPA, average age 44.47⫾1.22 years. All subjects were interviewed using a special questionnaire, which allowed taking into account presence or absence of symptoms of asthma related to menstrual cycle and allergy. Allergy is also assessed by skin prick test. GSTT1 and GSTM1 genotypes were identified by multiplex polymerase chain reaction. RESULTS: We found that the frequency of GSTT1 functional allele in women with PA was 100% and in asthmatic women WPA was 68.96% (p⫽0.0001).The frequency of allergy in patients WPA was 83.07% and in women with PA was 44.45% (␹2 ⫽4.37, P⫽0.027). CONCLUSION: We concluded that:1) The patients with PA have a significantly higher frequency of GSTT1 functional genotype as compared to those WPA.2) The frequency of allergy in patients WPA is significantly higher, then in cases with PA. CLINICAL IMPLICATIONS: The diagnosis of premenstrual asthma as one form of sever asthma in related to GSTM1 and GSTT1 genotypes in women. DISCLOSURE: Natalia Gorovenko, None.

Asthma Guidelines 12:30 PM - 2:00 PM DO RESTRICTIVE REIMBURSEMENT PROCESSES INHIBIT PHYSICIANS FROM ADOPTING AND IMPLEMENTING GUIDELINES INTO THEIR PRACTICE: THE CANADIAN ASTHMA EXPERIENCE Andrew R. Mc Ivor MD* Laureen Rance PharmD Dalhousie University, Bedford, NS, Canada PURPOSE: Provincial drug programs are increasingly listing pharmaceutical products with restrictions. This may be to ensure appropriate use of a drug or serve as a cost containment strategy to control the provincial formulary budget. To determine if physicians treat asthma patients who are beneficiaries of the provincial drug plan differently than patients who have private drug plan. METHODS: On-line market research was conducted using a structured questionnaire with 284 general practitioners (GPs) from across Canada. The sample was weighted by province. Physicians were provided scenario-based questions to determine their preferences for treating patients. They were presented with two scenarios for patients uncontrolled on moderate doses of inhaled corticosteroids (ICS), provincial plan beneficiary vs. private drug plan beneficiary. These asked whether they would increase the dose of ICS or add additional therapy. RESULTS: Physicians ranked asthma symptoms, treatment guidelines and insurance coverage (public versus private) as the three most important factors impacting drug therapy choice. Eighty percent of physicians (80%) reported that they ask patients about drug coverage (private vs. public) before making a prescribing decision. 37% of physicians reported that they would increase the dose of ICS for public versus 22% for privately insured patients uncontrolled on moderate doses of ICS. This trend remained consistent across the regions, however in Atlantic Canada there was no difference at 35%.For provincial drug plan patients, the majority reported adding a long acting beta agonist (LABA) via a separate inhaler vs. those with private drug plans where the physicians opted for a combination of ICS ⫹ LABA in one inhaler. CONCLUSION: Asthma treatment approaches differ for patients with public vs. private drug plans. Patients uncontrolled on ICS alone with public drug coverage, physicians continue to increase the dose of ICS, despite the fact that this approach is misaligned with current guideline recommendations. CLINICAL IMPLICATIONS: Patients with private drug coverage are treated more closely to national guidelines developed to improve outcomes. The market research used to prepare this document was performed by PSL Inc.,Toronto, Ontario, Canada. DISCLOSURE: Andrew Mc Ivor, None.

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THE 2005 ASTHMA ACTION STUDY IN CANADA Andrew R. Mc Ivor MD* Mark Greenwald MD Melva Bellefountaine Meyer Balter MD Dalhousie University, Bedford, NS, Canada PURPOSE: To obtain current 2005 information to determine the unmet needs of Canadians with asthma. METHODS: Telephone survey of patients with physician diagnosed asthma was performed during March 2005 in Canada. The authors developed a study questionnaire and ethics approval was obtained. The telephone interview was performed by a prominent Canadian Market Research Firm. The sample was weighted to obtain a representative sample of adult patients with asthma in Canada with respect to age, gender and geographical location (10 Provinces and 1 Canadian Territory). RESULTS: 997 patients with physician diagnosed asthma responded to the complete survey. Age ranges 18% (18-34 years old), 52% (35-54 years old), and 39% (55⫹ years old). 60% of the respondents were female. 10% of patients had been treated in the emergency room in the last year and 12% missed work or school; 97% of patients said that asthma effected their work or school performance over the previous year. 28% were experiencing daily daytime symptoms and 67% reported daytime symptoms at least weekly. 6% experienced nocturnal wakening from their asthma on a daily basis with 29% wakening at least once a week with asthma.Only 50% of the sample had objective tests of pulmonary function performed (peak flow/spirometry). 70% of patients stated that they had not had their inhaler technique checked. Only 15% had been referred for asthma education. Significant misconceptions of medications were identified including 39% of patients using short acting bronchodilators as their most often used “controller” medications and a further 11% were unsure as to which of their medications were “controller” medications. CONCLUSION: This March 2005, nationwide Canadian survey identifies significant asthma care gaps, patient and physician misconceptions around knowledge transfer of asthma guidelines to patient care. These have not reduced from previous surveys. CLINICAL IMPLICATIONS: Guideline groups should integrate methods of dissemination and implementation strategies to change practice, reduce care gaps and improve asthma outcomes.Funding via unrestricted grant from Novartis through the Asthma Society of Canada. Telephone survey conducted by Pollara Inc., Toronto, Canada. DISCLOSURE: Andrew Mc Ivor, None.

ASTHMA CARE PERCEPTIONS AND PRACTICES AMONG ASTHMA SPECIALISTS IN LEBANON Hani M. Lababidi MD* Mazen AbuAkl MD Makassed General Hospital, Beirut, Lebanon PURPOSE: Asthma is a common chronic condition. Despite published guidelines for the diagnosis and treatment of asthma, the real medical practices for this condition vary among different care providers. The purpose of this study is to evaluate the current perceptions and practices of asthma among asthma specialists in Lebanon. METHODS: A cross sectional survey was conducted on asthma specialists in Lebanon in November 2004. The studied parameters included asthma diagnosis, follow-up, treatment, patient education, use of asthma guidelines, demographic characteristics of providers and their involvement in continuous medical education. RESULTS: Out of 125 practicing pulmonolgists and allergists registered in Lebanon, 70 filled out the questionnaire (56%). These were 20 females (29%) and 50 males (71%). The average age was 42.6⫹8.5 years. There were 55 pulmonolgists (78.5%), 5 allergists (7.1%) and 10 with double specialty in pulmonary and allergy (14.3%). 81.4% of responders performed spirometry on newly diagnosed subjects with asthma, while 74.3% monitored peak flows. The frequency of use of different treatment modalities for asthma was 94.1% for inhaled steroids, 95.4% for long acting beta-agonists (LABA), 60.6% for Leukotriene antagonists, 32.8% for theophylline, 25.8% for oral anti-histamines and 5.2% for cromolyn sodium. The inhaler technique is often monitored by 65.2% and sometimes by 24.6%, while peak flow diary is often reviewed by 29.9% and sometimes by 34.3%. About 87.9% of the responders indicated that they follow asthma practice guidelines, 84.6% of them reported using the GINA guidelines. Around 92.6% of asthma specialists in Lebanon attended continuous medical education (CME) program on asthma in the past year. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Asthma Guidelines, continued CONCLUSION: This survey characterizes the pattern of asthma treatment by specialists in Lebanon. The overall performance of the responders meets the international guidelines. CLINICAL IMPLICATIONS: This study provides data for improving the performance of asthma treatment in Lebanon. DISCLOSURE: Hani Lababidi, None.

(59.7 SEM 12.3). The physicians performed least in asthma assessment, education, prevention, severity classification and therapy. Significant differences were noted in physician understanding of the guidelines concerning:diagnosis(p⫽ .001),pathology(p⬍.001), pharmacology (p ⬍ .001), severity (p ⬍ .001) and therapy(p⬍ .001). Across different specialties,pulmonary specialists got the highest mean score (61.7 SEM 11.6).Significant differences in understanding of the guidelines were observed in asthma diagnosis (p ⬍ .001), assessment (p ⬍ .026), pathology (p ⬍ .001), pharmacology (p ⬍ .001), prevention (p ⬍.001) and therapy (p ⬍ .001).

DOES ASTHMA KNOWLEDGE OF INTERNSHIP YEAR STUDENTS DIFFER THAN PHYSICIANS IN SPECIALIZATION TRAINING? Esra Uzaslan MD* Esref Erdem Funda Coskun MD Beril Erdogan MD Dane Ediger MD Mehmet Karadag MD Oktay Gozu MD Uludag University Medical Faculty, Bursa, Turkey

CONCLUSION: The results of the study showed that there is a need for further improvement in the knowledge and understanding of the NHLBI Global Initiative for Asthma among physicians at the VMMC.Subject areas that should be emphasized in asthma guidelines dissemination are proper assessment, asthma education, prevention of asthma triggers, proper severity classification and choice of appropriate therapy. CLINICAL IMPLICATIONS: Proper diagnosis and management of asthma will reduce its fatal consequences. This can be achieved by ensuring physicians’ understanding of existing guidelines through continuing medical education.

HOSPITAL-BASED PHYSICIAN ASSESSMENT OF KNOWLEDGE, ATTITUDES AND PRACTICE IN THE DIAGNOSIS AND MANAGEMENT OF ASTHMA GUIDELINES Ogee Mer A. Panlaqui MD* Eloisa S. De Guia MD Veterans Memorial Medical Center, Quezon City, Philippines PURPOSE: To determine the knowledge, attitude and practice of hospital based physicians in the diagnosis, management and prevention of asthma. METHODS: The study was conducted in a tertiary government hospital involving physicians in practice of Family Medicine, Internal Medicine, Pediatrics and Pulmonary Medicine. A 31 point questionnaire was distributed consisting eight subject areas: assessment, asthma diagnosis, education, pathology, prevention, pharmacology, severity and therapy. The score for each of the subjects and the total score were calculated and grouped according to the level of training of the physicians and specialties. The mean score for each group of physicians were compared using the one way analysis of variance with level of significance set at p⬍ 0.05 with 95% CI. RESULTS: A total of 144 (75.8%) physicians out of the 190 responded.The mean score is 45.8 ⫹/- 13.4 (mean, SEM) performing best in asthma diagnosis and scored poorly in prevention of asthma triggers. The pulmonary fellows in training got the highest mean score

DISCLOSURE: Ogee Mer Panlaqui, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: The goal of this survey was to assess the knowledge, attitudes and beliefs of interns (students in internship year of medical faculty)about asthma and its management and to compare the correct response rate of interns with physicians in specialization training (PST) in teaching hospitals. METHODS: An asthma questionnaire including 33 items was applied to interns (n:209,40% female and 60 % male) and PST (n:202,49% female and 51% male)of Uludag Medical Faculty in July 2004. RESULTS: The 89% of interns believed that asthma can be cured, whilst 84 % of PST believed so(p⬎0.05).The 13% of interns thought that when acute asthma attacks resolved, the disease can be cured, whilst 15% of thought so (p⬎0.05).The 76% of interns believed that asthma runs in families whilst 53% of PST believed so (p⬍0.001).The 99% of interns and 97% of PST knew that animal feathers were one of the triggers of asthma ((p⬎0.05).The 76% of interns and 47% of PST knew that cockroach was one of the triggers of asthma (p⬍0.001). The 57% of interns and 46% of PST thought that nutritional conditions can trigger asthma (p⬍0.05).There was not any significant difference on correct response rate to questions on about asthma signs. The 97% of interns believed that asthmatics can be treated without hospitalization, whilst 96% of PST believed so (p⬎0.05).The 19% of interns and 18% of PST thought that asthma medication should be sold without prescription (p⬎0.05).The 9% of interns and 9% of PST believed that asthma medication was addictive (p⬎0.05). The 90% of interns and 85% of PST thought that inhaler (vaporizer) was a good treatment (p⬎0.05).The 64 % of interns and 61% of PST believed that asthma care was expensive (p⬎0.05). CONCLUSION: The interns knowledge about asthma was generally better than the PST, but by the time passing this compact knowledge may decrease as we observed in PST. CLINICAL IMPLICATIONS: Postgraduate education about asthma should be offered every physician whatever their specialization is, when planning to improve asthma outcomes in society. DISCLOSURE: Esra Uzaslan, None.

Wednesday, November 2, 2005 Asthma Guidelines, continued A CLINCAL DIAGNOSIS OF ASTHMA DOES NOT CORRELATE WELL WITH ATS FEV1 BRONCHODILATOR CRITERA John A. Gjevre MD* Thomas S. Hurst DVM Regina M. Taylor-Gjevre MD Donald W. Cockcroft MD University of Saskatchewan, Saskatoon, SK, Canada PURPOSE: The ATS has developed criteria suggesting that a significant post-bronchodilator FEV1 response is 200 ml and 12% improvement. To our knowledge, the ATS criteria never been validated versus the clinical diagnosis of asthma. METHODS: All spirometry tests done from Sept 1999 to Sept 2004 were analyzed for meeting the ATS criteria for FEV1 improvement There were a total of 1862 tests meeting the ATS FEV1 criteria with a total of 644 individual non-duplicate records. A total of 311 individual patient records were analyzed for staff respirologists. RESULTS: 311 patients were found who met ATS FEV1 criteria and whose complete physician records were available. There were 170 men and 141 women with a median age of 62.8 years. Of the 311 patients meeting a 12% FEV1 change, there were 170 (54.7%) diagnosed by the staff respirologist with asthma. Of the 208 patients meeting a 15% FEV1 improvement, there were 120 (57.7%) diagnosed with asthma. Of the 98 patients meeting a 20% FEV1 improvement, there were 62 (63.3%) patients diagnosed by the staff respirologist with asthma. For the diagnosis of asthma versus not asthma, there was a statistically significant difference in the post-bronchodilator FEV1 % improvement with p⫽0.02 (CI 0.256-3.02). Of the 170 patients with asthma (for 12% FEV1 response), there was a mean improvement in FEV1 of 19.4% (SD 6.87), while the 140 not asthma patients had a mean improvement in FEV1 of 17.8% (SD 5.53). CONCLUSION: While the ATS FEV1 criteria are a help in asthma diagnosis, relying on spirometric criteria alone is inadequate in asthma diagnosis. Only 170 patients (54.7%) meeting ATS bronchodilator improvement criteria were felt to clinically have asthma. CLINICAL IMPLICATIONS: The diagnosis of asthma requires a clinical history and physical examination. Spirometry changes are helpful but the level of bronchodilator significance remains unclear. DISCLOSURE: John Gjevre, None. CLASSIFICATION OF ASTHMA SEVERITY AMONG STEROIDNAIVE ADULT SUBJECTS PREVIOUSLY RECEIVING SHORTACTING BETA2-AGONISTS: IS MILD REALLY MILD? Paul M. Dorinsky MD* Steve Yancey MS John Stauffer MD Amanda Emmett MS Laura Sutton PharmD GlaxoSmithKline, Research Triangle Park, NC PURPOSE: Current guideline criteria for mild asthma are based on symptomatology or rescue use which are quite broad, suggesting that they may not define a distinct group of patients. Furthermore, the results of a recent study suggested that patients with mild persistent asthma may not require regular maintenance treatment with an inhaled corticosteroid (ICS).1. METHODS: This analysis evaluated subjects (n⫽85) previously receiving short-acting beta2-agonists alone from two completed 12-wk trials in which subjects received placebo. Subjects were initially stratified by baseline PEF ⱖ80% or ⬍80% predicted and further stratified by symptoms and/or albuterol use on ⱕ2 days/wk, 3-6 days/wk or 7 days/wk. RESULTS: For subjects with PEF ⱖ80% and symptoms/albuterol use on ⱕ2 days/wk, the majority of weeks (78%) were spent in the intermittent or mild categories. However, for subjects with PEF ⱖ80% and symptoms/albuterol use on 3-6 days/wk, subjects who could be guidelineclassified as having mild persistent asthma, approximately 54% of weeks were spent in the moderate or severe categories. In addition, for subjects with PEF ⱖ80% and daily symptoms or albuterol use (i.e., the type of subject often recruited into mild asthma studies1), 77% of weeks were spent in the moderate category. Furthermore, when only those pts with PEF ⬍80% and symptoms/albuterol use on ⱕ2 days/wk were considered, approximately 67% of weeks were spent in the moderate or severe categories. CONCLUSION: This analysis clearly demonstrates that asthma severity cannot be determined in many patients by discrete, point-in-time assessments of lung function, albuterol use or symptoms. More importantly, these observations suggest that the current classification system for persistent asthma needs to be re-evaluated as many patients who meet current guideline criteria for mild persistent asthma would appear to be more appropriately classified as having moderate or severe disease.

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CLINICAL IMPLICATIONS: Using current guidelines to define mild asthma may underestimate the true severity of the underlying disease. In light of recent publications, this underestimation may lead to inadequate therapy for patients with mild asthma. 1. Boushey, et al. NEJM 2005;352:1519-28. DISCLOSURE: Paul Dorinsky, Shareholder I am a GSK shareholder; Employee I am a GSK employee RELATIONSHIP BETWEEN MEASURED LUNG FUNCTION AND SELF-REPORTED SYMPTOMS Jamson S. Lwebuga-Mukasa MD* Tiffany Kolniak BS Paulette M. Wydro MPH SUNY at Buffalo, Buffalo, NY PURPOSE: This study investigates the relationship between responses to a lung health questionnaire and measured pulmonary function using spirometry. METHODS: Community-based, cross-sectional study design using a convenient sample of adults. A total of 567 adults, ages from 18 to 86 years, mean age of 45 ⫾ 15.48; 36.5% males and 63.5% females; 24.3% African American, 53.8% Caucasian, 14.6% Latino/Hispanic, and 5.5% of other race/ethnicity. Lung function was measured by spirometry; an 18-item questionnaire was administered to adults attending health fairs in Western New York State over a period of two years (2003-2005). RESULTS: Asthma prevalence was 19.6%. Persons who reported three or four symptoms, namely: wheeze, night cough, wheezing with exercise, and long-lasting colds, in the preceding 12 months had a lower percent predicted value for the forced expiratory volume in the first second (FEV1) (F⫽5.92, p⫽.015 and p⫽.001, respectively) than persons who did not report any symptoms of asthma. Persons who had health care utilization for asthma in the preceding 12 months had lower percent predicted FEV1 values (⬍75%) than persons who had not (p⫽.000, OR⫽3.62, CI⫽2.18-6.02). The same relationship was seen for midexpiratory flow rate (MEFR 25/75) (p⫽.000, OR⫽2.62, CI⫽1.66-4.15). As the frequency of self-reported health care utilization increased, abnormal FEV1 measurements increased (B⫽-1.250, p⫽.001), and the ratio of FEV1 to the forced vital capacity (FEV1/FVC) decreased by -.131 standard deviations, S.E.⫽.001, p⫽.017. CONCLUSION: These results indicate that self-reported symptoms of asthma in thelung health questionnaire are associated with decreased pulmonary function and increased health care utilization. CLINICAL IMPLICATIONS: The results demonstrate that selfreported symptoms may be used as a cost-effective method for actual pulmonary function where spirometry is unavailable. DISCLOSURE: Jamson Lwebuga-Mukasa, None. A SECONDARY CARE PERSPECTIVE ON THE STEPPINGDOWN OF INHALED CORTICOSTEROID THERAPY IN PATIENTS WITH STABLE ASTHMA Daniel K. Lee MD* Prashant S. Borade MD Graeme P. Currie MD D. A. Promnitz MD Department of Respiratory Medicine, Ipswich Hospital, Ipswich, Suffolk, England, United Kingdom PURPOSE: Current guidelines advocate stepping-down inhaled corticosteroid (ICS) therapy at 3-monthly intervals once asthma control has been achieved. Despite this, there are no data describing how widespread the practice of reducing ICS therapy is, especially in secondary care. METHODS: We assessed patients with asthma being followed up in a secondary care respiratory clinic for a minimum period of 6 months. Patients who were actively receiving or had received either oral or parenteral corticosteroids, or immunosuppressive therapy within a 12month period were excluded. Patients were also required to be exacerbation-free during this period. A retrospective study was performed over the preceding 12 months in order to evaluate whether ICS therapy had been reduced or not following a prolonged period of stability. RESULTS: 60 consecutive patients with asthma were assessed in clinic. 12 patients with mean age of 56 years and forced expiratory volume in 1 second of 1.97L (73% predicted) completed the study. The mean beclomethasone dipropionate (BDP) equivalent ICS daily dose was 1267␮g and patients had either moderate (n ⫽ 6) or severe (n ⫽ 6) asthma. Only two patients had step-down in ICS therapy. One patient had a 33% reduction in ICS dose from an initial daily dose of BDP 1500␮g, having had stable asthma for 11 months. The other patient had a 50% reduction in ICS dose from an initial daily dose of fluticasone propionate 1000␮g, having had stable asthma for 8 months. The remaining 10 CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Asthma Guidelines, continued patients continued on the same dose of ICS despite having had stable asthma during the preceding 12 months. There were no significant differences in any outcomes according to whether patients had ICS therapy reduced or not. CONCLUSION: Our preliminary data have shown that stepping-down ICS therapy in patients with stable asthma is being poorly implemented. CLINICAL IMPLICATIONS: If this is reflective of practices throughout the United Kingdom, many patients with stable asthma may be exposed to unnecessary high doses of ICS. DISCLOSURE: Daniel Lee, None. NO HISPANIC ASTHMATIC LEFT BEHIND Ramon E. Figueroa-Lebron MD* Asthma Management Center, San Juan, PR

Asthma Treatment 12:30 PM - 2:00 PM OMALIZUMAB IMPROVES SYMPTOMS AND REDUCES RESCUE BETA-AGONIST USE IN OLDER PATIENTS WITH UNCONTROLLED ASTHMA Robert J. Maykut MD* Marc Massanari PharmD Farid Kianifard PhD Yamo Deniz MD Colin Reisner MD Robert Zeldin MD Gregory P. Geba MD Novartis Pharmaceuticals Corporation, East Hanover, NJ PURPOSE: Asthma in older adults is under-diagnosed, under-treated, and the role of immunoglobulin E (IgE) in asthma is under-appreciated in this population . Therapy with omalizumab (OMA), an anti-IgE antibody, is indicated in patients with moderate to severe IgE-mediated asthma whose remain symptomatic despite inhaled corticosteroids. We conducted a pooled analysis of all double-blind placebo-controlled trials to evaluate the effect of OMA on asthma symptom score and rescue beta-agonist use in patients 50 years and older.

PILOT STUDY OF ANTI-IGE ANTIBODY IN THE TREATMENT OF SEVERE OBSTRUCTIVE PULMONARY DISEASE: UPDATE AFTER ONE YEAR Clifford G. Risk MD* John L. Ohman, Jr. MD Clifford Risk, MD, Marlborough, MA PURPOSE: To report on the continued experience with the use of omalizumab in patients with obstructive lung disease who may also have a comorbid asthmatic component mediated by IgE antibody. METHODS: All patients were drawn from the original pool of 250 patients in a pulmonary practice who had asthma or chronic bronchitis and qualifying levels of IgE (⬎30 IU/ml). Seventeen patients have been studied. Eleven completed 12 months of therapy (4 completed 4 to 9 months of therapy). Age range was 48 to 82 years. Nine were females. Fifteen have heavy primary or secondary cigarette exposure. Sixteen had positive skin tests to relevant indoor allergens. Baseline FEV1 was below 60% predicted in 11 patients. IgE ranged from 32 to 496 IU/ml. End points were reduction in number of acute exacerbations requiring hospitalizations or unscheduled office visits, reduction in inhaler use and improvement in dyspnea or cough indices. A 12 month baseline period was compared was compared with treatment intervals after the first month of omalizumab therapy. RESULTS: Comparing the year before therapy to the treatment period, the average monthly exacerbation rate decreased from 0.20 to 0.11. Comparing the month before therapy with the final treatment month, the average daily number of inhalations of asthma inhalers decreased from 13.5 to 7.4. The average daily Fletcher dyspnea score decreased from 1.35 to 0.53. The average daily cough severity scale decreased from 1.12 to 0.59. Of the six patients that were prednisone dependent at baseline the average daily prednisone requirement decreased from 37 to 10 mg. CONCLUSION: Continued experience with the use of omalizumab in patients with severe chronic obstructive lund disease confirms the initial impression of effectiveness. The role of IgE in these patients may be significant in disease severity. This pilot study suggests that further controlled studies in this group of patients would be warranted. CLINICAL IMPLICATIONS: A patient population with chronic obstructive lung disease should be screened for the use of omalizumab therapy. Skin test reactivity to indoor allergens was common. DISCLOSURE: Clifford Risk, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

PURPOSE: Medical literature and government (Federal & State) reports that Hispanics suffer greater morbidity and mortality from asthma than the general population. This study compares the efficacy between a goal oriented management with the current NAEPP guidelines in this population since there is not a Spanish version of them and are inaccesible to patients. METHODS: A retrospective observational study based on expenditures paid by Blue Shield Puerto Rico for the years 2003-04 for services provided for the treatment of asthma. The services compared were office visits, ED admissions, ICU admissions, medications,readmissions and all diagnostic & therapeutic procedures per patient/year.Population was divided in two groups:A- 24,320 patients treated by 108 pneumologists with presumed knowledge of NAEPP guidelines in private offices.B1,094 patients treated by a team of a physician, therapist, nurse, and assistant. The management followed faithfully the Asthma Patient Bill of Rights (APBOR)Spanish version. Each person received a copy of the document.Patients were of low middle and middle class and Spanish was their principal language. On February Blue Shield provided the expenses paid for the previous year in U.S. dollars. RESULTS: Data showed huge differences between groups. The goal oriented had lowest expenses when compared to the standard therapy group saving $3 millions. No deaths in the goal oriented group and many in the standard group. Deaths occurred more at home or in route to hospital than in the ICU admissions. Readmissions were 20% within 15 days after discharge in the standard therapy group.There were no readmissions in the goal oriented group. CONCLUSION: Results were positive beyond expectations. No mortality and less morbidity in the goal oriented treatment group with great savings in resources. Current NAEPP guidelines are ignored by physicians creating inadequate prescriptions patterns and no patient education and support. CLINICAL IMPLICATIONS: A goal oriented management based on Spanish language guidelines (APBOR) generate commitment in patients, relatives, physicians with an unexpected positive outcome in Hispanics asthmatics. DISCLOSURE: Ramon Figueroa-Lebron, None.

METHODS: Data were combined from 5 randomized double blind placebo-controlled (PBO) trials of patients with moderate to severe IgE-mediated asthma; 4 were of 28 weeks and 1 was 32 weeks in duration. From the pooled study population comprised of 2236 patients, 601 were ⱖ 50 years of age (296 OMA, 305 PBO). The change from baseline in mean total asthma symptom score [range 0 (symptom free) to 9], and in mean beta-agonist rescue puffs was assessed using an analysis of covariance. Least-squares mean treatment differences were calculated and 95% confidence intervals were constructed. RESULTS: The mean age of the older subgroup was 58 years; 61% were female; median IgE level was 132 IU/dl; mean percent predicted FEV1 64.6% ⫾ 17.0%; baseline mean total asthma symptom score was 3.35 (OMA) and 3.40 (PBO), and baseline mean daily rescue beta-agonist use was 4.48 puffs (OMA) and 4.37 puffs (PBO). In this subpopulation, least-squares mean difference (OMA-PBO) for change from baseline in mean asthma symptom score was -0.26 (95% CI -0.51, -0.01; p⫽0.0411) and least-squares mean difference for change from baseline in rescue beta-agonist puffs was -0.47 (95% CI -0.92, -0.02; p⫽0.0414). The tolerability profile of OMA in the ⱖ 50 year age subgroup was generally similar to that of the overall study population. CONCLUSION: Treatment with omalizumab significantly improved asthma symptoms and reduced beta-agonist use in older patients with moderate to severe persistent IgE-mediated asthma. CLINICAL IMPLICATIONS: IgE-mediated asthma is important to recognize and manage in older patients. DISCLOSURE: Robert Maykut, Employee I am an employee of Novartis Pharmaceuticals Corporation.

Wednesday, November 2, 2005 Asthma Treatment, continued THE VIRTUAL ASTHMA CLINIC: MANAGING ASTHMA PATIENTS ONLINE Irvin Mayers MD* Arto Ohinmaa PhD Dilini Vethanayagam MD Heather M. Sharpe MSN Cindy O’Hara RN Carina Majaesic MD Philip Jacobs PhD University of Alberta, Edmonton, AB, Canada PURPOSE: Asthma continues to be a major health concern internationally despite improvements in treatment and the introduction of international asthma guidelines. Asthma education and action plans are essential to enhancing asthma knowledge, adherance, quality of life, and control of asthma and these form the basis for all treatment strategies recommended. There are over 90 Internet websites that provide asthma education. These sites did not provide interactive asthma management and the majority did not even meet acceptable educational standards. This study aimed to assess the impact of providing asthma management by a Certified Asthma Educator (CAE) to patients with asthma via the Internet. METHODS: The Virtual Asthma Clinic (VAC) was created to allow a CAE to communicate with patients, and assist patients with asthma management. Patients initially had spirometry testing, an asthma education session, and completed Asthma Quality of Life Questionnaire (AQLQ), symptoms questionnaire and SF-36. The site provided access to their personalized action plan, and asthma information. Data was compared between those who actively participated in the program and those who dropped-out. RESULTS: A total of 16 physicians referred 63 patients to the clinic. The active participants have taken part for a mean of 107.4 days (ongoing), while the dropouts participated for a mean of 140.6 days. The dropouts were younger (p⬍0.01) and both groups were predominantly female (60.5% active participants, 75.0% dropouts, NS). There were no differences in history of smoking. Participants had a mean of 41.4 hits to the website, compared to 14.8 for the dropouts (p⬍0.01). Participants were more likely to email the nurse (p⬍0.01), enter peak flow data (p⬍0.01), complete the weekly survey (p⬍0.05), the AQLQ (p⬍0.01), the SF-36 (p⬍0.01). CONCLUSION: Active participants in the VAC were older and while they were enrolled for fewer days, participated more actively. CLINICAL IMPLICATIONS: It is feasible to provide asthma management to patients online. Through this study we are able to identify a specific demographic of older patients who appear to participate more readily in the program than young adults. DISCLOSURE: Irvin Mayers, Grant monies (from sources other than industry) Capital Health Regional Telehealth, Alberta Health & Wellness; and The Alberta Strategy to Help Manage Asthma; Grant monies (from industry related sources) AstraZeneca Canada Inc. THE EFFECTS OF ADDITIONAL CARE BY A PULMONARY NURSE FOR ASTHMA AND COPD PATIENTS AT AN OUTPATIENT CLINIC: RESULTS FROM A DOUBLE BLIND, RANDOMIZED TRIAL Geert N. Rootmensen MD* Anton R. van Keimpema PhD Elske E. Looysen Letty van der Schaaf RN Rob J. de Haan PhD Henk M. Jansen PhD Academic Medical Center, Amsterdam, Netherlands PURPOSE: To determine the effects of additional nursing care in the treatment of asthma and COPD patients at a pulmonary outpatient clinic. METHODS: In a randomized, double blind clinical trial, 191 patients were allocated to an additional care (ACG) or control group (CG). Patients were masked for the trial objectives. Patients in the ACG group received an extra education program on individual basis provided by a pulmonary nurse. Between initial and final assessments was a six months interval. RESULTS: 97 patients were randomized to the additional care group and 94 to the control group of which 157 finished the trial. Small albeit significant differences were found for the outcomes knowledge and exacerbation rate in favour of the additional care group. No differences were found for self-management scores, inhalation technique, healthrelated quality of life and satisfaction with provided care. CONCLUSION: for the outcomes knowledge and exacerbation rate patients in the additional care group had significant better results. No differences were found for the outcomes self-management scores, inhalation technique, health-related quality of life and satisfaction with provided care. CLINICAL IMPLICATIONS: additional care by a pulmonary nurse is easy to implement, provides patient tailored care, is easy accessible and might reduce the workload of the pulmonary physician. Since we found that some aspects were effective we conclude that it is worthwhile to

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consider providing additional nursing care to asthma and COPD patients in a pulmonary outpatient clinic.

Primary outcomes: knowledge, self management, inhalation technique and exacerbation frequency incidences. Differerences between additional care (ACG) and control group (CG)

knowledge*

CG (n⫽77)

median#

median#

initial

55 (33-73)

final

64 (38-77)

change score inhalation

ACG (n⫽80)

p-value 55 (41-73)

59 (45-70)

5 (-5-14)

0 (-5-9)

initial

78 (68-83)

70 (63-80)

final

83 (68-90)

72 (63-83)

0,02

technique** change score self management

exacerbation

0 (-5-10)

0 (-8-12)

initial

36 (25-56)

36 (25-48)

0,84

final

38 (25-63)

38 (25-53)

change score

3 (-12-19)

6 (-10-13)

0,85

incidence rate‡

1,46

3,65

0,40 (0,24-0,67)

⫽ exacerbation*?

11%

24%

0,68 (0,49-0,94)

frequency?

DISCLOSURE: Geert Rootmensen, None.

CLINICAL EFFICACY OF AEROSOLIZED FLUTICASONE THERAPY IN THE EARLY MANAGEMENT OF ACUTE MODERATE EXACERBATIONS OF ASTHMA BY PMDI AND ZERO STAT ‘V’ SPACER Sudhir K. Agarwal MD* Institute of Medical Sciences, Banaras Hindu University, Varanasi, India PURPOSE: To assess the utility of inhaled corticosteroids for the early management of acute exacerbations of asthma in the emergency room. METHODS: This randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy of high dose inhaled fluticasone with frequent beta-2-agonist therapy in patients of acute moderate exacerbations of asthma. Eighty patients between 15 and 45 years of age with acute moderate exacerbations of asthma were put on aerosolized 500 ␮g of fluticasone at half hourly intervals for three doses with metered dose inhaler and zero stat ‘V’ spacer. All patients received humidified oxygen and nebulized salbutamol (0.15 mg/kg in 3 ml saline) prior to fluticasone administration. The control group received placebo instead of inhaled fluticasone. Patients who had received corticosteroids in the preceding 72 h were excluded from the study. If there was an inadequate response or no response to treatment at the end of 2 hour, oxygen and salbutamol therapy were continued and given one dose of intravenous hydrocortisone and was started on an aminophylline infusion. RESULTS: Both fluticasone and control group showed a significant improvement in respiratory status at the end of 2 h. However, patients in the fluticasone group showed greater improvement in PEFR (P ⬍ 0.05) and significantly lower proportion of patients required oxygen improvement in PEFR (P ⬍ 0.01). The length of stay was significantly shorter in the fluticasone group than in the placebo group (P ⬍ 0.01). CONCLUSION: Aerosolized fluticasone therapy with MDI and spacer together with salbutamol in the treatment of acute exacerbations of asthma helped in early recovery and decreased hospital stay. CLINICAL IMPLICATIONS: Inhaled fluticasone may be given with MDI and spacer in the treatment of acute exacerbations of asthma. DISCLOSURE: Sudhir Agarwal, None.

CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Asthma Treatment, continued ZILEUTON PROVIDED SIGNIFICANT IMPROVEMENT IN PULMONARY FUNCTION COMPARED TO PLACEBO IN MODERATE AND SEVERE ASTHMATICS William Berger MD* Daniel J. Stechschulte MD Karen Walton-Bowen Allergy and Asthma Associates, Mission Viejo, CA

Difference From Placebo in Mean Change From

Difference From Placebo in

BL to Post-Dose in FEV1 (L) Month 3

Mean Change From BL in

Month 6

A.M. PEFR (L/Min)

Severity

30

60

120

30

60

120

Group

Mins

Mins

Mins

Mins

Mins

Mins

Days 2-22

Days 163-190

Moderate

0.19* 0.26** 0.16䉬␮ 0.11

0.12 0.18䉬␮

17.76**

11.47

Severe

0.35* 0.30* 0.28䉬␮ 0.27䉬␮

0.33* 0.32䉬␮

15.93*

30.24*

**pⱕ0.010; *pⱕ0.050; 䉬␮pⱕ0.100; Mins⫽Minutes DISCLOSURE: William Berger, None. ZILEUTON PROVIDED CLINICALLY RELEVANT REDUCTIONS IN THE NEED FOR RESCUE MEDICATION AND ORAL CORTICOSTEROIDS COMPARED TO PLACEBO IN MODERATE AND SEVERE ASTHMATICS Mark C. Liu MD* Malcolm N. Blumenthal MD Karen Walton-Bowen Johns Hopkins Bayview Medical Center, Baltimore, MD PURPOSE: Zileuton Provided Clinically Relevant Reductions in the Need for Rescue Medication and Oral Corticosteroids Compared to Placebo in Moderate and Severe Asthmatics. METHODS: This was a previously published, randomized, placebocontrolled, double-blind, parallel, multi-center six-month study of the safety and efficacy of zileuton (400 or 600 mg QID) in 373 patients with asthma on no chronic asthma treatment other than beta-agonists (J Allergy Clin Immunol 1996; 98(5):859-71). Assessments included beta-agonist use, acute asthma exacerbations requiring alternative treatment or oral corticosteroids, and daily and nocturnal symptoms, as well as mean FEV1 and other pulmonary function tests.In an exploratory secondary analysis of patients in the high dose zileuton 600 mg QID group, patients were stratified by baseline (BL) percent predicted FEV1 into two subgroups of asthma severity: moderate (⬎60%-⬍80%) and severe (ⱕ60%). RESULTS: Moderate and severe zileuton patients reported reduced daily number of occasions of beta-agonist use. Fewer zileuton patients experienced asthma exacerbations requiring alternative treatment and oral corticosteroid treatment. Improvements in daily and nocturnal symptoms were also reported. These differences were sustained throughout the six-month study.

Mean Change From BL to Days 163-

Patients With Exacerbations

Patients Requiring

190 in Beta-Agonist Use

Requiring Alternative

Oral Corticosteroids

(Number of Occasions/Day)

Treatment (%)

(%)

Severity Group Moderate

Zileuton -0.70

Placebo

Zileuton

Placebo

Zileuton

Placebo

-0.40

13.6%⫹

26.5%

9.1%

17.7%

⫹0.16

7.8%*

23.4%

5.9%**

25.5%

(n⫽133) Severe

-0.85**

(n⫽98)

DISCLOSURE: Mark Liu, None.

EVALUATION OF POST-TREATMENT EFFECTS OF LEUKOTRIENE RECEPTOR ANTAGONISTS Esra Uzaslan MD* Funda N. Coskun MD Dane Ediger MD Erkan Rodoplu MD Mehmet Karadag MD Ercument Ege MD Oktay Gozu MD Uludag University Medical Faculty Chest Disease Department, Bursa, Turkey PURPOSE: The aim of this study to evaluate the of post-treatment effects of Leukotriene Receptor Antagonists (LTRA) in persistent asthmatic patients who have been treated with inhaler steroid and LTRA, by investigating clinical and laboratory parameters before addition of LTRA, end of treatment with LTRA and at least three months after ending of LTRA treatment. METHODS: We retrospectively investigated clinical data of 19 asthmatic patients (16 females, 3 males, mean age 33.3⫾2.5 years) before LTRA treatment,last day of LTRA treatment and at least three months after ending of LTRA treatment and compared symptom score, medication score (number of controller drugs for asthma), total dose of inhaler steroid and lung function tests of patients for each visits. RESULTS: We found decreases in symptom score (p⬍0.01), medication score (p⬎0.05), total dose of inhaler steroid (p⬎0.05),and increases lung function tests (p⬎0.05) at the end of the treatment.When we evaluated same parameters at least three months after the ending of LTRA treament, we observed continuation of increases in FEV1 and PEF values (p⬎0.05) comparing to beginning and ending of treatment and also a significant decrease in total dose of inhaler steroid comparing to beginning of treatment (p⬍0.05). CONCLUSION: We come to the conclusion that in persistent asthmatic who use LTRA in addition to inhaler steroids,the improvement in lung function tests, symptom scores and medication scores are protected and the total dose of inhaler steroids needed for control of asthma is decreased,even 3 months after the ending of treatment. CLINICAL IMPLICATIONS: The post-treatment effects of LTRA continues three months after the discontinuation of the treatment in asthmatics.

Symptom score Medication score Inhaled steroid dose (mcg) FEV1 (L) PEF (L/sec)

Baseline

Post-treatment

3 months later

1.3⫾0.8 1.4⫾0.9 875⫾583

0.5⫾0.6 1.2⫾0.7 695⫾391

0.9⫾0.8 1.3⫾0.2 445⫾216

2.62⫾0.9 5.68⫾1.7

2.66⫾0.9 6.27⫾1.8

2.75⫾0.8 6.77⫾1.8

DISCLOSURE: Esra Uzaslan, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: Zileuton Provided Significant Improvement in Pulmonary Function Compared to Placebo in Moderate and Severe Asthmatics. METHODS: This was a randomized, placebo-controlled, double-blind, parallel, multicenter study of the safety and efficacy of zileuton in patients with asthma. Asthma patients on no chronic asthma treatment other than inhaled beta-agonists were randomized to one of three treatment groups: zileuton, 600 mg QID, zileuton, 400 mg QID, or placebo for six months. Efficacy assessments included forced expiratory volume (FEV1) and peak expiratory flow rate (PEFR).In an exploratory secondary analysis, 231 asthma patients randomized to treatment were stratified by baseline (BL) percent predicted normal FEV1 into two subgroups: moderate (⬎60%-⬍80%; n⫽133) and severe (ⱕ60%; n⫽98). Pulmonary function measurements were obtained on asthmatics on 600 mg zileuton and compared to placebo. RESULTS: Moderate and severe patients on zileuton experienced significant improvement in FEV1 and A.M. PEFR. This difference was demonstrated as early as 30 minutes post-dose and was sustained throughout the duration of the study. Improvements in P.M. PEFR were also demonstrated. CONCLUSION: Zileuton, 600 mg QID, provided rapid and sustained improvement in pulmonary function in moderate and severe asthmatic patients versus placebo. CLINICAL IMPLICATIONS: Zileuton, a 5-lipoyxgenase inhibitor approved for chronic asthma, may improve pulmonary function via its mechanism of action in moderate and severe asthmatics.

CONCLUSION: In severe asthmatic patients, Zileuton, 600 mg QID, provided significant improvement versus placebo in markers of asthma control including reductions in daily number of occasions of beta-agonist use, asthma exacerbations. CLINICAL IMPLICATIONS: Zileuton, a 5-lipoyxgenase inhibitor approved for the treatment of chronic asthma, may reduce the need for beta-agonists and oral corticosteroids and improve other markers of asthma control, especially in severe asthmatics.

Wednesday, November 2, 2005 Asthma Treatment, continued ELECTROLYTES DISTURBANCE: THE EFFECT OF DIFFERENT FORMS OF B-STIMULANTS Emad H. Ibrahim MD* Ahmed Yousery MD Alexandria Faculty of Medicine, Alexandria, Egypt PURPOSE: To determine the electrolyte disturbances in chronic stable asthma patients receiving outpatient therapy including different forms of beta stimulants. METHODS: Consecutive out patients with chronic, stable airway obstruction of bronchial asthma. Once diagnosed patients were subjective full clinical data collection including: age, gender, duration of asthma, severity of illness, details of therapy, and serum levels of potassium, sodium, calcium, and magnesium were measured. RESULTS: Sixty consecutive patients with chronic, stable airway obstruction of bronchial asthma were included in the study.Age 37.7⫾12.8 and females were 53.3% of patients. Electrolyte disturbances were found in 58.3% of patients; of those patients 51.4% had one electrolyte disturbance, 31.4% had two electrolytes disturbance, and 17.1% had three electrolyte disturbance. The majority (45%) had lower potassium levels, followed by magnesium in 31.7% of patients. Lower incidence of hyponatremia was found in 18.3% of patients. We did not found hypocalcemia in those patients. Logistic regression analysis showed statistically significant correlation between inhaled steroids and the presence of electrolyte disturbance. Beta long acting inhalers were associated with significant correlation for hypokalemia whereas the use of theophyline was significant for the presence of hypomagnesmia. CONCLUSION: Hypokalemia and hypomagnesemia were the most common electrolyte disturbance in patients with chronic, stable bronchial asthma. Inhaled steroids and long acting beta agonist seems to have an effect on the electrolytes serum levels. Mechanisms are needed to be clarified. CLINICAL IMPLICATIONS: The use of different inhalers should be carefully monitored in patients with long term therapy. Especially, if those patients are relectant to consult their doctors about their illness. DISCLOSURE: Emad Ibrahim, None. HOSPITAL ECONOMIC IMPACT IN THE TREATMENT OF ACUTE ASTHMA: A COMPARISON OF RACEMIC ALBUTEROL VERSUS LEVALBUTEROL David M. Schreck MD* Stephen Babin RN Summit Medical Group, Summit, NJ PURPOSE: To quantify the hospital economic impact comparing racemic albuterol (ALB) versus levalbuterol (LEV) in the emergency department (ED) treatment of patients presenting with acute asthma. METHODS: ED patients with acute asthma were retrospectively reviewed over a 9 month consecutive period. Outcome measures included ED admission rate, length of stay (LOS), arrival acuity, payer status, and treatment costs. Patients were excluded for age less than 1 year or if no treatment for acute asthma was rendered. RESULTS: A total of 736 consecutive cases were reviewed, including 608 patients treated with ALB and 128 patients treated with LEV. The indigency rate was approximately 25%. There were 92 (15.1%) admitted patients treated with ALB and 6 (4.7%) admitted patients treated with LEV(p⫽0.0016; Chi-square). The number-needed-to-treat (NNT) to achieve ED discharge benefit was 9.58 patients. No significant differences in age, gender, LOS in ED, or arrival acuity were noted between the groups (p⫽NS; ANOVA). The drug costs were $0.25 and $1.50 per dose for ALB and LEV respectively. The average ED charge for discharged patients receiving ALB was $422.30 ⫾ 230.61 and $404.56 ⫾ 192.56 for those patients receiving LEV. The average LOS for admitted patients was 3.8 days. The per diem rate for admitted patients was $945 and the per diem cost of care was $780. Based on these data, a financial risk:benefit ratio of approximately 1:80 favoring LEV was determined for ED treatment. The hospital revenue loss for admitted patients was $40,600 for RAC and $13,500 for LEV. CONCLUSION: Patients treated with LEV had a better pharmacoeconomic outcome and ED discharge rate. The hospital sustained less of a financial loss for admitted patients using levalbuterol. This study may indicate beneficial economic and clinical effects of levalbuterol in patients with acute asthma. CLINICAL IMPLICATIONS: Levalbuterol use is controversial due to its perceived negative financial impact. This study demonstrates in large retrospective series that there are both financial and clinical benefits to using levalbuterol in patients presenting to the ED with acute asthma.

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DISCLOSURE: David Schreck, None. COMPARATIVE EVALUATION OF CARDBOARD VERSUS RIGID SMALL VOLUME VALVED HOLDING CHAMBERS FOR THE DELIVERY OF A BETA-2 AGONIST FORMULATION: DELIVERY TO THE UNCOORDINATED USER Dominic Coppolo RRT* Jolyon Mitchell PhD Kimberly Wiersema BA Valentina Avvakoumova BSc Mark Nagel BSc Monaghan Medical Corp., Syracuse, NY PURPOSE: VHCs are prescribed for patients that have difficulty coordinating pressurized metered-dose inhaler (pMDI) use, frequently resulting in delayed inhalation following inhaler actuation. Our study introduced a realistic 2-second delay, comparing delivery of a beta-2 agonist via VHCs of similar size (n⫽5/group), one manufactured from cardboard (LiteAire™, Thayer Medical, Tucson, AZ – 160-ml) the other from rigid polymer (AeroChamber Plus®, Monaghan Medical Corp., Syracuse, NY – 150-ml). METHODS: The AeroChamber Plus® VHCs were pretreated by washing in water containing a mild ionic detergent, rinsed and drip-dried, as recommended prior to use. The LiteAire™ VHCs were assembled and used in accordance with manufacturer’s instructions. Each VHC was tested using an Andersen 8-stage impactor with USP Induction Port operated at 28.3⫾0.5 L/min, representative of flow rates seen with adult patients. A shutter that interfaced between the VHC mouthpiece and induction port entrance was used to simulate a 2-s delay interval between pMDI actuation and the onset of sampling. The shutter moved to allow flow from the VHC to the impactor only after the defined delay. 5-actuations of albuterol (Ratiopharm, Mississauga, Canada, 100 ␮g/dose albuterol base equivalent ex metering valve) were delivered from a pre-primed and shaken pMDI canister at 30-s intervals. The induction port and stages of the impactor were subsequently assayed for albuterol by HPLC-UV spectrophotometry. Benchmark measurements were also made with the pMDI alone. RESULTS: Fine particle mass/actuation ((FPM) ⬍4.7 ␮m aerodynamic diameter (mean (95% CI)) was 27.8 (4.2) ␮g (pMDI alone), 21.7 (5.0) ␮g (AeroChamber Plus® VHC) and 13.9 (4.2) ␮g (LiteAire™ VHC). CONCLUSION: FPM(pMDI-alone) represents delivery with perfect inhaler technique. The AeroChamber Plus® VHC delivered nearly 80% FPM(pMDI-alone) with a 2-s delay, but the corresponding delivery via the LiteAire™ VHC was only 50% FPM(pMDI-alone). CLINICAL IMPLICATIONS: Dosing may have to be adjusted to take into account the poorer efficiency of the cardboard VHC, considering the likelihood of imperfect coordination. DISCLOSURE: Dominic Coppolo, Employee All of the authors are employees of companies in the Trudell Medical Group. These companies manufacture the AeroChamber Plus® VHC A SINGLE DOSE OF FORADIL PROVIDES SIGNIFICANTLY GREATER BRONCHODILATION THAT MULTIPLE DOSES OF ALBUTEROL OVER 12 HOURS IN OLDER ASTHMATICS Umit Yegen MD* Denise Till MS Gregory P. Geba MD Novartis Pharmaceuticals Corporation, East Hanover, NJ PURPOSE: The efficacy of beta-agonists in elderly patients has not been extensively studied. We conducted a pooled analysis conducted across two 12-week, randomized, double-blind, double-dummy multicenter clinical trials to assess the efficacy of Foradil® (FOR) in an elderly subgroup population. METHODS: Forty patients ⱖ65 years of age with mild to moderate asthma had been randomized to receive formoterol (Foradil® dry powder inhalation capsules) 12␮g b.i.d. (FOR12) or 24␮g b.i.d. (FOR24) via the AerolizerTM, albuterol MDI 180␮g q.i.d. (ALB) or placebo. FEV1 measurements were performed pre-dose, and 5, 15, 30 and 60 minutes and hourly through 12 hours post AM dose on the first day and every 4 weeks up to 12 weeks of treatment. RESULTS: Effect on FEV1 in the elderly subgroup receiving 12 or 24␮g formoterol b.i.d. were similar to the general population, showing clinically significant bronchodilation (⬎ 15% increase in FEV1) throughout the 12-hour interval, [area under the FEV1 curve (AUC; primary endpoint)]. CONCLUSION: These results show that elderly patients with asthma achieved significantly greater and sustained bronchodilitation (⬎12 hours) with FOR than with multiple doses of ALB. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Asthma Treatment, continued CLINICAL IMPLICATIONS: The elderly population is a growing subgroup of patients that need to be further studied. This small sample of data investigates the efficacy and safety of formoterol in an elderly subgroup.

AUC of FEV1 (L x hours)

After first dose After 12 weeks

FOR12 v Placebo

FOR24 v Placebo

FOR12 v 24

ALB v Placebo

4.50* 4.02

4.71* 4.17

-0.21 -0.15

2.53 1.54

* Indicates statistical significance at the 0.05 level DISCLOSURE: Umit Yegen, Employee

COPD Evaluation 12:30 PM - 2:00 PM

PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation of the respiratory tract. Thus, Th1/Th2 cytokines could be a useful tool to monitor exacerbations of COPD. The aim of the present study was to investigate Th1 and Th2 cytokines in exhaled breath condensate (EBC) of exacerbated COPD patients. METHODS: The study population consisted of 20 patients with exacerbated COPD. The inclusion criteria were as follows: FEV1/vital capacity ⬍70%, FEV1 ⬍80% predicted value and stage 3 or 4 of GOLD. EBC samples were collected within 24 hours after admittance to hospital and three months later. Cytokines were measured simultaneously in a single EBC sample of exacerbated COPD patients by using a Human Cytokine kit II BD. This kit allowed us to quantitatively measure IL-2, IL-4, IL-6, IL-10, IFN␥ and TNF␣ protein levels. RESULTS: The concentration of cytokines in the EBC of patients was close to the detection limits of the assay. The mean concentration of IFN␥, TNF␣, IL-10, IL-6, IL-4 and IL-2 at admittance to hospital was 40⫾5.1, 15⫾0.5, 23⫾1.0, 24⫾0.6, 34⫾1.1 and 15⫾0.4 respectively; while the concentration at three months after admittance was 39⫾2.5, 18⫾1.7, 27⫾1.6, 30⫾3.3, 44⫾6.2; 20⫾2.7 respectively. Although the parameters did not change significantly two months after admittance, there was a tendency to increase the concentration of IL-10(p⬍0.06) and IL-2(p⬍0.08). Remarkably, by analyzing mainly IFN␥ and IL-4, two clearly differentiated groups of patients appeared: those whose EBC concentration of cytokines had increased (Figure A) and those whose EBC concentration of cytokines had decreased (Figure B) two months after admittance. CONCLUSION: Considering the sample population as a whole, this study showed no significant changes in cytokine concentration in EBC three months after admittance to hospital. However, two different groups of patients could be identified based on the pattern of cytokine. CLINICAL IMPLICATIONS: Perhaps the presence of two group of patients may correlate with outcome of patients and will define a new perspective in the treatment of these patients.

DISCLOSURE: Juan Mazzei, None.

PURPOSE: Peripheral skeletal muscle dysfunction is observed in many patients with chronic obstructive pulmonary disease(COPD).A significant number of patients with normal weight also suffer muscle wasting.Furthermore,some investigators have found an association between reduced muscle mass and survival in COPD patients,independent of a reduction of FEV1.The molecular mechanisms of muscle wasting remains as yet unknown.Our study was to explore the role of ubiquitin-proteasome pathway(UPP) in the loss of muscle mass. METHODS: 11 consecutive COPD patients(aged 67.7⫾8.1 years,FEV1 percentage of predicted of 49.6⫾10.2%) and 6 healthy agematched control subjects were enrolled in the study.All subjects were underwent 6 minute walk test.Health-related quality of life(HRQL) was measured using St. George’s Respiratory Questionnaire(SGRQ).Wholebody and extremity fat free mass(FFM) were assessed by dual-energy X-ray absorptiometry.Samples of peripheral muscle were collected from the quadriceps by microbiopsy procedure(Bard,USA.).The extent of ubiquitin expression in skeletal muscle was determined by immunohistochemistry. RESULTS: Whole-body and extremity FFM were significantly lower in the COPD patients than in healthy control(whole body 50.1⫾8.4kg vs 53.9⫾10.5kg,p⬍0.05;extremities 21.4⫾4.6kg vs 25.2⫾5.2kg,p⬍0.01).The intensity of ubiquitin immunostaining in quadriceps muscle fibers in COPD patients was significantly higher than in control(110.1⫾2.0 density units vs 85.8⫾0.4 density units,p⬍0.01).Whole-body FFM was positively correlated with 6 minute walk distance(r⫽0.63,p⬍0.05).There was significantly negative correlation between extremity FFM and expression levels of ubiquitin(r⫽-0.78,p⬍0.05),SGRQ total score(r⫽-0.54,p⬍0.05). CONCLUSION: Depletion of FFM is associated with a decline in HRQL and exercise capacity in COPD patients.The ubiquitin expresion levels is up-regulated in these patients.Therefore,the UPP might be involved in peripheral skeletal muscle wasting of COPD patients. CLINICAL IMPLICATIONS: Drug development targeting UPP may provide novel strategies for treating skeletal muscle abnormalities in COPD. DISCLOSURE: Yi Ming Yuan, None.

SINGLE MEASUREMENTS OF INSPIRATORY CAPACITY ARE NOT BETTER THAN FEV1 IN PREDICTING SYMPTOM SCORES IN COPD Shirley F. Jones MD* John A. Cooper MD Mark T. Dransfield MD Birmingham VA Medical Center, Birmingham, AL PURPOSE: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States. Although the forced expiratory volume (FEV1) is an accurate marker of mortality in population studies it has only shown a weak correlation with dyspnea and quality of life. It has been shown that changes in inspiratory capacity (IC), a measure of hyperinflation, correlate well with improvements in these outcomes. The aim of this study is to determine whether a single, baseline measurement of IC is a better predictor of measures of dyspnea and quality of life than FEV1. METHODS: We enrolled veterans with COPD from two pulmonary clinics. Demographic data was obtained and enrollees completed three questionnaires, the Medical Research Council Dyspnea Scale (MRC), the University of California San Diego (UCSD) Shortness of Breath Questionnaire and the St. George’s Hospital Respiratory Questionnaire (SGRQ). Spirometry was performed according to ATS standards and FEV1 and IC measurements were recorded. Correlation coefficients between FEV1, IC, and questionnaire scores were then determined and compared. RESULTS: 36 patients were enrolled. The mean age of our participants was 66 with the majority being Caucasian males (95%). The mean number of pack-years smoked was 71. The mean IC among enrollees was 68% predicted. The mean FEV1 was 40% predicted indicating severe airflow obstruction. The mean scores for the MRC, UCSD and SGRQ were 3.3, 67.5, and 46.5 respectively. Both FEV1 (r⫽-0.58, p⬍0.001) and IC (r⫽-0.47, p⫽0.004) correlated with the UCSD score though neither measure was superior (p⫽0.53). Neither FEV1 (r⫽-0.24, p⫽0.15) nor IC CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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ANALYSIS OF TH1 AND TH2 CYTOKINES IN EXHALED BREATH CONDENSATE OF EXACERBATED CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS Juan A. Mazzei MD* Nancy Tateosian Paulo Maffia BS Catalina K. Wilson MD Eduardo Chuluyan PhD Hospital de Clinicas, Buenos Aires, Argentina

UBIQUITIN EXPRESSION IS UP-REGULATED IN PERIPERAL MUSCLE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE Yi Ming Yuan MD* Yang Hu Jiang MD Xiao Jing Liu PhD West China Hospital of Sichuan University, Chengdu, Peoples Rep of China

Wednesday, November 2, 2005 COPD Evaluation, continued (r⫽-0.28, p⫽0.10) correlated with the MRC. FEV1 correlated with the SGRQ (r⫽-0.37, p⫽0.02) while IC (r⫽-0.24, p⫽0.15) did not. CONCLUSION: In patients with severe COPD, a single baseline measurement of IC does not appear to be better predictor of dyspnea or quality of life scores than FEV1. CLINICAL IMPLICATIONS: Clinicians should be mindful that no spirometric measure is reliably predictive of symptoms and quality of life in COPD. DISCLOSURE: Shirley Jones, None. DETECTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE BY SPIROMETRIC SCREENING Ashok K. Janmeja MD* Kiran Jit MBBS Government Medical College Chandigarh, Chandigarh, India PURPOSE: COPD is a progressive disease but its advanced stages can be averted if noxious agents are removed early. Often, patients seek advice when they become dyspneic, but by then half of their ventilation is irreparably lost. By far smoking cessation is most rewarding intervention in prevention of COPD. If harnessed adequately for control of COPD, it would prevent alarming future predictions. COPD currently ranks 6th in global impact scale and is predicted to number 3 by 2020. Recent studies indicate that COPD could be detected early by spirometry. High prevalence, morbidity and cost involved prompt early identification of such cases to obviate progression. So far no such study has been conducted in India. Present study evaluated role of spirometric screening in early detection of COPD in smokers. METHODS: Study was conducted at Medical College Hospital since 2003 to 2005. Initially for 3 months, a COPD awareness campaign was enacted through mass media viz. articles in papers, radio and television interviews, posters in hospital etc. Thus, smokers with smoking index [SI] above 100 were motivated for spirometry. Finally, 307 subjects were enrolled. Spirometry performed comprised estimation of FVC, FEV1 and FEV1 / FVC ratio. COPD was diagnosed and staged as per GOLD guidelines. Non- COPD pulmonary cases were excluded through clinical examination and investigations. RESULTS: Of 60 asymptomatic smokers 12% had COPD while 47% of 240 symptomatic subjects suffered COPD. Incidence of COPD in subjects with SI of 100-200, 200-400, and above 400 was 33, 38 and 42 % respectively. Incidence of severe disease i.e. stage III and IV was higher [14%] in subjects with SI above 400 than the incidence [9%] in subjects with SI below 400, [P⬍0.01]. CONCLUSION: COPD detected in 40% of all smokers and 12% of asymptomatic smokers. Positive association existed between amount of smoking with incidence and severity of COPD, [P⬍0.01]. CLINICAL IMPLICATIONS: The preliminary data thus generated will make useful contribution towards concept of spirometric screening for early detection and prevention of COPD in country. DISCLOSURE: Ashok Janmeja, None. USE OF SPIROMETRY IN CLINICAL PRACTICE FOR OBSTRUCTIVE AIRWAYS DISEASE IN INDIA Sundeep S. Salvi MD* Liesel D’Silva MD Sushmeeta Chhowala MS Bill Brashier MBBS Trupti Bal MS Jaideep Gogtay MD Chest Research Foundation, Pune, India PURPOSE: Office Spirometry is essential for the diagnosis and management of asthma and COPD. However, it remains an underutilized tool in clinical practice. In this study we aimed to investigate the use of Spirometry by General Practitioners, General Physicians, Chest Physicians and Pediatricians from different cities across India. METHODS: 3750 doctors from 20 centers across India were randomly selected and invited to fill in a one-page questionnaire. RESULTS: 1715 doctors returned the completed questionnaire (256 general practitioners, 717 general physicians, 458 chest physicians, 209 pediatricians and 74 others) (response rate: 45.7%). The mean duration of clinical practice was 15.2 years and on average 32 asthma patients and 17.5 COPD patients were seen per week by each clinician. The table shows the use of spirometry by different groups of clinicians in their practice. The commonest cause for not using Spirometry was lack of access to Spirometry (41.6%), and non-affordability of the test by the patients (36.2%). CONCLUSION: Spirometry is underutilized by clinicians in India. CLINICAL IMPLICATIONS: Clinicians in India need to be motivated to perform spirometry in clinical practice.

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% Of patients asked to perform Spirometry Category

Asthma

COPD

General Practitioner General Physician Chest Physician Pediatrician

9.36 19.99 54.92 5.42

11.11 22.83 56.70 Not applicable

DISCLOSURE: Sundeep Salvi, Grant monies (from industry related sources) Cipla Ltd. COMPARISON OF BRONCHODILATOR RESPONSE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND BRONCHIAL ASTHMA G. Gandev MD* K. Gupta MD J. Williams MD K. Kanagarajan MD Coney Island Hospital, Brooklyn, NY PURPOSE: The response to bronchodilators is often used to distinguish chronic obstructive pulmonary disease (COPD) and bronchial asthma (BA). Numerous studies have shown that many patients with COPD exhibit significant bronchodilator response while some patients with BA may not. Our study compares the bronchodialator response in patients with COPD and BA. METHODS: Retrospective analysis of PFT’s in patients referred with diagnosis of COPD and BA was done. Positive bronchodialator response using ATS criteria were noted in both groups. The patients were further stratified into those under the age of 55 and those over 55. The data was analyzed using independent t-test for the mean and chi square test for any variables with percentage. RESULTS: 78 patients with COPD and 76 patients with BA were identified. In the group younger than 55 years, there were 6 patients with COPD and 47 patients with BA. 20 patients with COPD had significant bronchodilator response (25.6%), and 34 patients with BA had significant bronchodilator response (44.7%). The overall difference in bronchodilator response between the two groups was statistically significantly (p⫽0.01). In the group younger than 55, 50% (n⫽3) of patients with COPD had significant bronchodilator response versus 42.6% (n⫽20) of patient with BA. For the age above 55, 23.6% (n⫽17) of patient with COPD had significant bronchodilator response versus 48.3% (n⫽14) of patient with BA and the difference in bronchodilator response for this age group was statistically significant (p⫽0.01). CONCLUSION: Even though patients with BA were more likely to have bronchodilator response a significant number of patients with COPD, exhibit the same. Bronchodilator response was observed in the older cohort of COPD patients as well. CLINICAL IMPLICATIONS: Bronchodialator response cannot reliably distinguish between BA and COPD. DISCLOSURE: G. Gandev, None. CHANGES OF DIFFUSION CAPACITY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASES (COPD) Yaling Zhu MD* Haoyan Wang MD Xiaohong Chang Chaoyang Hospital, Beijing, Peoples Rep of China PURPOSE: To assess the changes of diffusion capacity in different stages of COPD patients. METHODS: 95 stable COPD patients were divided into 4 groups: Stage I, II, III and IV according to EFV1/FVC% and FEV1% values, each with 8, 47, 34, 6 patients respectively. The transfer factor of the lung for carbon monoxide (TLco), pulmonary membrane diffusion capacity (Dm) and pulmonary capillary blood volume (Vc) were measured with single breathing method. RESULTS: TLco,Dm and Vc were decreased in all COPD groups, significant differences were found in stage II to Stage IV groups in comparison with those of the normal subject group. TLco and Dm were progressively decreased from stage I to stage IV while Vc were comparable among all stage groups. CONCLUSION: Diffusion capacity was progressively impaired with the severity of COPD. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 COPD Evaluation, continued CLINICAL IMPLICATIONS: Diffusion capacity measurement is also a valuable approach for further understanding the entity of COPD.

Group

n ml/min/ mm Hg

Normal subject COPD stage I COPD stage II COPD stage III COPD stage IV Normal subject

43 8 47 34 6 43

Dm

TLco Pred

Vc ml

13.82⫾4.92 100.25⫾16.26 79.40⫾28.44 11.97⫾4.01 99.32⫾23.48 56.68⫾16.54 9.76⫾4.54** 69.39⫾19.43** 52.38⫾20.76** 8.26⫾3.27** 62.29⫾13.62** 45.13⫾18.29** 4.74⫾1.66** 43.60⫾10.24** 53.62⫾34.64* 13.82⫾4.92 100.25⫾16.26 79.40⫾28.44

* P⬍0.05 ** P⬍0.01 compared with normal subject group DISCLOSURE: Yaling Zhu, None.

retrosternal air (n⫽31; 46%). Patients with a CXR score ⱖ1 were older (63.5⫾10.3 vs. 58.1⫾11.1 years, p⫽0.01) and had more pack-years (48.5⫾20.8 vs. 36.7⫾18.9; p⬍0.01). Hyperinflation (increased TLC%), air-trapping (decreased FVC% and increased RV%) and gas exchange (decreased DLCO%) were all worse with increasing CXR scores as indicated in Table 1. A normal CXR score ⫽ 0 virtually excluded the possibility of hyperinflation (negative predictive value ⫽ 0.98). In contrast, a CXR score ⱖ1 was a good marker of functional hyperinflation (increased TLC% sensitivity ⫽ 0.96) and air trapping (increased RV/TLC% sensitivity ⫽ 0.81) while a score ⱖ2 was highly specific indicator of air trapping and decreased DLCO% (positive predictive values of 0.93 and 0.83 respectively). CONCLUSION: The CXR score is an accurate predictor of the degree of functional impairment in patients with COPD. A normal CXR score obviates the need to measure lung volumes. CLINICAL IMPLICATIONS: Disagreement between the CXR score and results of PFTs in the patient with COPD should prompt a search for technical errors in measurement.

Table 1

PURPOSE: To assess the true prevalence of COPD in the community in South India and to estimate the burden of disease. METHODS: Three year retrospective analysis of all subjects who underwent Pulmonary Function Tests between January 1999 to December 2001. The cohort included individuals who underwent spirometry as part of routine health checkup and patients attending hospital for elective surgery or for non-respiratory medical problems and those patients referred from the chest clinic for Spirometry. History of more than 10 pack years of smoking was noted in all relevant cases. RESULTS: Out of 13,860 patients who underwent pulmonary function testing during the 3 years period, there were 9702 males and 4164 females. 946 patients (6.8%) were diagnosed to have COPD according to GOLD guidelines of which 811 were males (86%) & 135 were females (14%). More than 10 pack years of smoking was seen in 830 patients (87.7%) & 116 patients were non-smokers (12.3%). Mean age was 44.65 ⫹ 4.15 years. Out of 946 patients, 284 had mild COPD (30%),286 had moderate disease (30%) and the remaining 387 patients (40%) had severe COPD. The overall prevalence of COPD in the present study was 6.85% with prevalence of disease in males being 7.4% and in females 4.64%. CONCLUSION: There is a significant burden of COPD as a disease in the community with overall prevalence of 6.85% in South India. CLINICAL IMPLICATIONS: The burden of COPD in south India is huge as shown by our study there is an urgent need to reconize this in field conditions so as to treat them appropriately. DISCLOSURE: Arul Vigg, None. RADIOGRAPHIC ABNORMALITIES PREDICT FUNCTIONAL IMPAIRMENT IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE Tarek A. Dernaika MD* Jean I. Keddissi MD Walid G. Younis MD Gary T. Kinasewitz MD University of Oklahoma Health Sciences Center, Oklahoma City, OK PURPOSE: To examine the hypothesis that abnormalities on chest roentogram (CXR) will predict physiologic impairment on pulmonary function tests (PFTs) in patients with chronic obstructive pulmonary disease (COPD). METHODS: The CXRs of 108 consecutive patients with COPD were scored 0-4 with 1 point being awarded for the presence of each of the following: 1) flattening of the diaphragm, 2) increased retrosternal air, 3) hyperlucency, and 4) bullous changes. Demographic characteristics, absolute and percent of predicted (%) values of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), residual volume (RV), single breath carbon monoxide diffusing capacity (DLCO) and corrected for alveolar volume (DLCO/VA) were correlated with the CXR score. Data are presented as mean ⫾ SD. RESULTS: Radiographic signs of emphysema (CXR score ⱖ1) were seen in 67 patients (62%). Diaphragmatic flattening was the most common (n⫽46; 68%), followed by bullous disease (n⫽40; 59%) and

CXR Score

FEV1 % FVC % TLC % RV % RV/TLC % DLCO %

0 (n⫽41)

1 (n⫽27)

2 (n⫽22)

ⱖ 3 (n⫽18)

65⫾12a 75⫾13.5c 96⫾10a 125⫾25a 44⫾8a 80⫾26a

51⫾8b 70⫾13 111⫾12 179⫾46 54⫾14d 73⫾29e

43⫾14 64⫾16 112⫾15 187⫾34 60⫾9 58⫾22

45⫾15 60⫾18 118⫾21 200⫾58 65⫾8 49⫾19

a⫽ p ⬍ 0.05; 0 vs. 1, 2, 3; b⫽ p ⬍ 0.05; 1 vs. 2; c⫽ p ⬍ 0.05; 0 vs. 2, 3; d⫽ p ⬍ 0.05; 1 vs. 3; e⫽ p⬍ 0.05; 1 vs. 2,3 DISCLOSURE: Tarek Dernaika, None.

PATIENT-REPORTED SYMPTOMS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) IN CLINICAL TRIALS Steven Kesten MD* Shailendra Menjoge PhD Boehringer Ingelheim, Ridgefield, CT PURPOSE: Several respiratory symptoms are associated with COPD. We sought to determine the symptom most frequently perceived by patients to be the first symptom and the most troublesome of COPD and to identify patient characteristics associated with these perceptions. METHODS: An evaluation of pooled data was conducted from three clinical trials of tiotropium in COPD (205.264, 205.266, 205.284) in which patients reported the features of their disease at baseline. The trials had common inclusion criteria (age ⱖ40 years, diagnosis of COPD, no history of asthma, FEV1/FVC ⱕ70%, FEV1 ⱕ60 to 65% predicted, smoking ⱖ10 pack-years). Data are expressed descriptively as means or proportions. RESULTS: There were 2,678 patients. Dyspnea was the most commonly reported first and most troublesome COPD symptom. In patients also reporting chronic bronchitis, the first symptom and most troublesome symptom was dyspnea (71% and 86%, respectively) followed by cough (19% and 8%, respectively). In patients also reporting emphysema, the first symptom and most troublesome symptom was dyspnea (77% and 90%, respectively) followed by cough (14% and 5%, respectively). Baseline data are displayed below according to the patient-reported first or most troublesome symptom:. CONCLUSION: Dyspnea is the first symptom and the most troublesome symptom of COPD and is reported as such irrespective of demographics and diagnoses of either chronic bronchitis and/or emphysema. In general, baseline demographic characteristics are unable to adequately distinguish which symptom patients will report as their most troublesome. CLINICAL IMPLICATIONS: The focus of clinical research in COPD should include evaluations of dyspnea as this appears to be the first and most troublesome symptom to COPD patients with differing demographic features. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PREVALENCE OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE IN PATIENTS ATTENDING CHEST CLINIC IN A TERTIARY CARE HOSPITAL Arul Vigg MBBS* Ajit Vigg MD Avanti Vigg MBBS Sumanth Mantri MD Chest Clinic-Hyderabad, Hyderabad, India

Wednesday, November 2, 2005 COPD Evaluation, continued First Symptom Dyspnea Cough Wheeze Sputum N⫽2033 N⫽400 N⫽113 N⫽43 1.6% 4.2% 14.9% 75.9%

% of total % women/% men FEV1 (L) FEV1 predicted (%) COPD duration (yrs) Former smoker (%) Smoking history (pack-yrs)

12/88 1.03 36.0 10.9 69.7 65.2

17/83 1.06 37.9 12.4 63.0 66.6

12/89 1.04 36.6 12.6 65.5 58.9

7/93 1.06 12.0 12.9 67.4 58.4

Other N⫽89 3.3%

tion for reasons other than a COPD exacerbation have a significantly increased risk of death. CLINICAL IMPLICATIONS: Pre-morbid spirometry data does not appear to aide in discussions of advance directives or prognosis regarding the use of MV in patients with COPD.

12/88 1.04 13.1 13.2 73.0 68.5

Most Troublesome Symptom

% of total % women / % men FEV1 (L) FEV1 predicted (%) COPD duration (yrs) Former smoker (%) Smoking history (pack-yrs)

Dyspnea Cough Wheeze Sputum Other N⫽2376 N⫽168 N⫽46 N⫽60 N⫽28 88.7% 6.3% 1.7% 2.2% 1.0% 12/88 1.02 35.7 11.3 70.0 65.5

16/84 1.19 42.1 11.0 54.2 62.2

15/85 1.21 42.0 14.1 50.0 69.1

10/90 1.22 42.8 11.5 66.7 67.8

25/75 1.07 37.9 9.6 67.9 57.8

DISCLOSURE: Steven Kesten, Employee S. Kesten and S. Menjoge are employees of Boehringer Ingelheim.; Grant monies (from industry related sources) Study 205.264 and 205.266 were funded by Boehringer Ingelheim and Pfizer. Study 205.284 was funded by Boehringer Ingelheim.

RELATIONSHIP OF SPIROMETRY RESULTS AND REASON FOR MECHANICAL VENTILATION (MV) TO HOSPITAL SURVIVAL IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) Thomas B. Zanders DO* David G. Bell MD Ethan E. Emmons MD Brooke Army Medical Center, San Antonio, TX PURPOSE: In general, the mortality of COPD patients requiring hospital admission and MV is high. Many physicians rely on a patient’s spirometry results in guiding advance directive discussions and determining prognosis. There is unclear data to support that pre-morbid spirometry helps predict outcomes in mechanically ventilated COPD patients. METHODS: We conducted a retrospective chart review of 33 admissions of 29 patients with COPD requiring MV for acute respiratory failure (ARF) for whom preadmission spirometry data was available. Additional data obtained included age, sex, comorbidities, outpatient therapies, and reason for MV. The primary outcome was in-hospital mortality. RESULTS: Nineteen (58%) of the patients were male. The mean age was 69.2 years (range 56-85). There were 16 (49%) current smokers and 18 (55%) patients on home oxygen. The mean percent predicted forced expiratory volume in one second (FEV1) was 44.1% and percent predicted forced vital capacity (FVC) was 53.6%. A COPD exacerbation necessitated MV in 51.5% of the admissions, pneumonia in 21.2%, cardiac reasons in 12.1%, and other etiologies in 15.2%. Overall in-hospital mortality was 21.2% (7 of 33). Survivors and non-survivors had no statistically significant difference in preadmission FEV1, FVC, or FEV1/FVC ratio values (Table 1). Multivariate analysis demonstrated significantly lower in-hospital mortality for patients intubated due to COPD exacerbations as compared to other etiologies of ARF (Figure 1). CONCLUSION: We conclude that pre-morbid spirometry data does not correlate to in-hospital mortality in COPD patients requiring MV for ARF. It appears that patients with COPD requiring mechanical ventila-

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DISCLOSURE: Thomas Zanders, None.

MECHANISM OF EXPIRATORY CRACKLES Raymond L. Murphy MD* Andrey Vyshedskiy PhD Ruqayyah M. Alhashem BS Rozanne Paciej BS Margo Ebril Brigham and Women’s / Faulkner Hospitals, Boston, MA PURPOSE: Crackles are intermittent explosive sounds that are associated with a number of pulmonary disorders including Interstitial Pulmonary Fibrosis (IPF), Congestive Heart Failure (CHF), and Pneumonia (Pn). The mechanism underlying expiratory crackles generation is not very well understood. Some authors think that airway closing is responsible for expiratory crackles. Others claim that intermittent airway reopening during expiration is responsible for the crackling sounds. The goal of this research was to gain insights into crackle generation mechanism by systematic examination of the relationship between inspiratory and expiratory crackle characteristics and by testing the crackle patterns, as recorded by multiple microphones, against the predictions of the stress-relaxation quadrupole crackle generation model as developed by Fredberg and Holford. METHODS: Fifty five patients with over 2 inspiratory crackles per breath and over 2 expiratory crackles per breath were selected for this study from a pool of nearly 1000 patients who were examined using a multichannel lung sound analyzer (Stethographics, STG1602). Crackle characteristics such as frequency, amplitude, transmission coefficient, and polarity were calculated for each crackle. RESULTS: The frequency, amplitude, and transmission coefficients of expiratory crackles were very similar to those of inspiratory crackles. The majority of patients had predominantly positive polarity of inspiratory crackles (98% of patients) and predominantly negative polarity of expiratory crackles (81% of patients). Crackle polarity was also found to be dependent on the observation angle, consistent with predictions by the stress-relaxation quadrupole crackle generation model. CONCLUSION: The reported findings are consistent with the hypothesis that expiratory crackles are caused by events that are identical in mechanism and opposite in direction to that of inspiratory crackles. The expiratory crackle data can be explained by the closing of airways during expiration in accordance with the stress-relaxation quadrupole crackle generation model. CLINICAL IMPLICATIONS: While there are no immediate clinical benefits to knowing the mechanism of crackles, a clearer understanding of the mechanism of production of lung sounds offers the promise of improving noninvasive diagnosis of lung disorders. DISCLOSURE: Raymond Murphy, Grant monies (from industry related sources) The research was supported in part by a grant from Stethographics, Inc.; Shareholder Dr. Murphy is founder and CMO of Stethographics, Inc. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 COPD Evaluation, continued PROLONGATION OF THE EXPIRATORY PHASE IN CHRONIC OBSTRUCTIVE LUNG DISEASE Raymond L. Murphy MD* Andrey Vyshedskiy PhD Rozanne Paciej BS Anna Wong-Tse RN Dhirendra Bana MD Brigham and Women’s / Faulkner Hospitals, Boston, MA

DISCLOSURE: Raymond Murphy, Grant monies (from industry related sources) The research was supported in part by a grant from Stethographics, Inc.; Shareholder Dr. Murphy is founder and CMO of Stethographics, Inc. USING DISTRIBUTION-BASED STANDARD ERROR OF MEASUREMENT (SEM) METHOD TO DETERMINE MINIMAL IMPORTANT DIFFERENCE (MID) FOR THE SYMPTOM STATUS INDEX (SSI) Rohit D. Borker PhD* Michael Watkins PharmD Kate Knobil MD Amanda Emmett MS Chris Kalberg PhD GlaxoSmithKline, Research Triangle Park, NC PURPOSE: To assess the minimal important difference (MID) of the Symptom Status Index (SSI) using the distribution-based standard error of measurement (SEM) method. METHODS: The SSI is a diary-based index comprised of 4 VAS items: shortness of breath, tiredness, activity limitation, and frustration with symptoms. It has been shown to be a reliable, valid, and a responsive tool in COPD population. Individual item scores are summed to obtain the SSI total score. Patients record the severity of their symptom status on a 0mm (none/not at all) to 100mm (worst it has ever been/as bad as it can be) VAS. The SEM method was used to determine the MID because of its sample independent properties. This results from simultaneous incorporation of sample reliability and variability in its determination. The

Study Sets

SSI Mean (SD)

rxx (Cronbach’s ␣)

1-SEM

Study set A (SCO40011 & 12) Study set B (SMS40314 & 15) Study set C (SMS40320 & 21)

50.82(16.93) 58.07(14.08) 52.10(17.01)

0.910 0.858 0.906

5.08 5.31 5.21

DISCLOSURE: Rohit Borker, Employee GlaxoSmithKline

FACTORS THAT REFLECT CLINICAL STABILITY OF COPD PATIENTS Jee-Hong Yoo MD* Myung Jae Park MD Hong Mo Kang MD Kyung Hee University Medical Center, Seoul, South Korea PURPOSE: Chronic obstructive pulmonary diseases (COPD) is one of the leading cause of death and is increasing in incidence. The forced expiratory volume in one second (FEV1) is usually used to grade the clinical severity of COPD. However, assessment of functional capacity is also important to understand clinical state of patients. The aim of this study was thus to retrospectively examine what factors reflects clinical stability in patients with COPD. METHODS: Twenty-six patients with COPD volunteered and completed the test sequence, which included pulmonary function tests, 6-minute walk distance (6-MWD), complete blood count, blood chemistry, blood pressure, and body mass index. The patients were divided into two groups, stable and unstable group, according to the presence of acute exacerbation history during last one year. After dividing, we retrospectively validated factors that reflect clinical stability of patients. RESULTS: At presentation, Mean age of 26 patients was 65.3 ⫾ 9.0 years (mean ⫾ SD). Sixteen patients were included in stable group and 10 patients in unstable group. FEV1 was 63.3 ⫾ 20.6% for stable group and 46.9 ⫾ 9.4 for unstable group (p⫽0.02). Mean 6-MWD was 461.9 ⫾ 88.3 meter and 298.0 ⫾ 72.1 meter respectively (p⬍0.01). The number of patients in each stage based on Global Initiative of Obstructive Lung Diseases (GOLD) showed significant difference between two groups (p⫽0.03) and number of patients who walked more than 400 meter was 13 out of 16 for stable group and no one for unstable group (p⬍0.001). 6-MWD and stage of COPD showed significant correlation (p⬍0.01). CONCLUSION: 6-MWD, a simple test to evaluate clinical status, showed significant correlation with GOLD stage of COPD. Multidimensional approach should be done to evaluate clinical stability. CLINICAL IMPLICATIONS: For the evaluation of severity of COPD, not only the degree of airflow limitation but also functional status such as 6-MWD should be included. DISCLOSURE: Jee-Hong Yoo, None.

WORLD COPD DAY EXPERIENCE IN ZONGULDAK PROVINCE OF TURKEY Meltem M. Tor MD* Tacettin Ornek MD Hakan Tanriverdi MD Muhammed E. Akkoyunlu MD Yalcin Dutkun MD Zonguldak Karaelmas University Hospital Department of Pulmonary Medicine, Zonguldak, Turkey PURPOSE: Chronic Obstructive Pulmonary Disease (COPD) is an important public health problem both in developed and developing countries. In Turkey too, COPD is an important lung health burden. Public education and early diagnosis are crucial in the prevention of COPD.We hereby present the results of our “World COPD Day” CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

PURPOSE: The expiratory phase of respiration is commonly described as prolonged in patients with Chronic Obstructive Pulmonary Disease (COPD). The goal of this study was to quantify the degree of this expiratory sound prolongation in patients with COPD as compared to normals. METHODS: We studied 38 patients with COPD and 43 normals using a multichannel lung sound analyzer (Stethographics, STG1602) as previously reported. The ratio of the duration of inspiration to expiration (R1) was measured on the time-amplitude plots from the microphone placed over the trachea. RESULTS: R1 averaged 0.67⫾0.16 in the COPD patients and 0.83⫾0.16 in the normals (p⬍0.0001). The frequency distribution of R1 is shown in Figure 1. R1 equal to or less than 0.6 was observed in 39% of COPD patients, but only in 9% of normals. R1 equal to or less than 0.5 was observed in 18% of COPD patients, but only in 2% of normals. The sensitivity of R1 equal to or less than 0.6 was 0.39, the specificity was 0.91, and the positive predictive value was 0.79. CONCLUSION: As expected a relatively prolonged expiratory phase was more common in COPD than normals. Values of R1 less than 0.6 were particularly more common in COPD than normals. However, low R1 values were seen in some normals and relatively high values were seen in some COPD patients. CLINICAL IMPLICATIONS: A simple test using a lung sound analyzer that requires little patient cooperation can identify the presence of prolonged expiration consistent with COPD. Although the test has relatively low sensitivity, the relatively high specificity can help guide the selection of patients for further evaluation.

one-SEM criterion has been shown to represent MID and was used in this analysis as MID criterion. Data from 3 sets of twin trials (Study sets A, B, & C) in patients with COPD was used in this analysis. Internal consistency reliability (Cronbach’s ␣) and the standard deviation of the summated SSI scores, which are required for computation of the SEM, were determined for the SSI. RESULTS: SEM based MID for SSI based on 3 study sets are illustrated in the Table. CONCLUSION: Consistent results across the 3 sets of trials point to about 5 to 6 unit change on the SSI (0 to 100 scale) as MID. CLINICAL IMPLICATIONS: Once this MID has been validated using different approaches, it can serve as an useful anchor to assess meaningful changes in patient’s symptom status.

Wednesday, November 2, 2005 COPD Evaluation, continued experience in the spirometry tent built in Zonguldak city center (population: 115000)on this occasion on 17 November 2004. METHODS: On World COPD Day, 305 persons over 18 years of age ( 197 males and 108 females, mean age 41.7⫾11.97(18-82), %38.7 smokers, %17.4 exsmokers, %43.9 nonsmokers) underwent spirometric analysis. RESULTS: Of 305 persons, 28 (9.2%) had FEV1/FVC below 70%, and 26 of 28 had %pred FEV1 below 80%. Overall, 52 (17%) had %pred FEV1 below 80%. Of 174 persons who were above 40 years of age, 14 (8%) had FEV1/FVC below 70%, and 13(7,4%) had %pred FEV1 below 80%. Of 14 with diagnosed with airway obstruction , spirometric analysis revealed %pred FEV1 ⬎80% in one(7%), between 50 and 80% in nine(%64), and below 50% in four(%29). At the end of this activity, 9.2% of adult population tested (age⬎18) and 8% of tested population above 40 years of age had airway obstruction.Tested population with a confirmed COPD had been referred to hospitals. CONCLUSION: In conclusion, obstructive pulmonary diseases including COPD are prevalent in central Zonguldak province. CLINICAL IMPLICATIONS: Wide scale epidemiologic studies are needed to reveal the real problem in this polluted region of Turkey. DISCLOSURE: Meltem Tor, None.

COPD Non-Pharmacologic Treatment and Outcomes 12:30 PM - 2:00 PM UTILITY OF A HIGH-FREQUENCY CHEST WALL OSCILLATION (HFCWO) TRIAL PERIOD TO ASSESS TREATMENT SATISFACTION, ADHERENCE AND BENEFIT IN PATIENTS WITH COPD Diane L. Kachel BA* Cynthia S. Davey MS Timothy C. Kennedy MD Victor L. Marchione MD Mark W. Rolfe MD Mark J. Rumbak MD Hill-Rom, St Paul, MN PURPOSE: To evaluate the utility of a short-term therapy trial to assess individual use and potential benefit of HFCWO in patients with COPD prior to extending therapy for long-term use. METHODS: Consenting patients with COPD, FEV1%⬍70%, retained secretions, dyspnea and reduced physical functioning were trained to use an HFCWO airway clearance device twice daily at home (N⫽94, 3 centers). Medical history, physical exam, spirometry, dyspnea, functional capacity, and quality of life (QOL) assessments were taken at baseline and after 90-days of therapy. Periodic symptom assessments and treatment satisfaction/adherence data were also collected. RESULTS: Patients with moderate to severe COPD that completed the trial demonstrated improvements in symptoms, 6-min walk distance (6-MWD, p⬍0.001) and role-physical domain (SF-36, p⬍0.004). Analysis of inter-group differences between patients who continued or discontinued HFCWO after trial completion indicated a higher, sustained level of treatment satisfaction and adherence within the group that continued HFCWO long-term. Improvements in dyspnea (Borg, p⬍0.009; BDI/ TDI, p⬍0.003), 6-MWD (p⬍0.001) and QOL (general health, vitality and physical functioning, p⬍0.05) were also significantly higher. Compared to baseline, a clinically significant improvement in 6-MWD (182⫾34 ft further) was demonstrated. Patients with moderate COPD demonstrated greater improvements in functional capacity after 90 days of HFCWO therapy than those with severe disease. Baseline predictors of success for specific outcomes are being assessed. CONCLUSION: In this prospective, cohort study, COPD patients completing a 90-day trial of HFCWO demonstrated improvements in symptoms, functional capacity and QOL. Patients who did not perceive treatment benefit were less adherent and more likely to discontinue. Patients who reported a higher level of treatment tolerance and effectiveness within the first week were more likely to demonstrate significant improvements after 90 days of therapy. CLINICAL IMPLICATIONS: Select patients with COPD adhere well to daily HFCWO therapy and may benefit from regular airway clearance therapy. A HFCWO therapy trial can help identify patients who are more likely to be adherent and satisfied with this therapy. Improve-

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ments in functional capacity and QOL may warrant consideration for long-term use. DISCLOSURE: Diane Kachel, None.

CHEST PHYSIOTHERAPY CHANGED VENTILATORY MECHANICS IN PATIENTS WITH SEVERE COPD Kayomi Matsumoto MS* Hajime Kurosawa MD Yuko Sano MS Naoki Mori MS Yoko Goto PhD Masahiro Kohzuki MD Tohoku. Univ. Grad. Sch. of Med. Dep. of Int. Med. and Rehab., Sendai, Miyagi, Japan PURPOSE: As one of chest physiotherapy (CPT) techniques, manual stretching of intercostal and other respiration related muscles to mobilize thoracic cage had been frequently performed in patients with airflow limitation, especially in Japan. Purpose of those techniques is supposed to improve chest flexibility and alleviate dyspnea. To examine hypothesis that CPT techniques in patients with chronic obstructive pulmonary disease (COPD) may change the mechanical properties of the chest. METHODS: Eight patients with COPD (mean age: 67.0 ⫾ 4.4 years, M:F⫽8:0) were studied. We performed physiological measurements including spirometry, oxygen consumption during quiet breathing at sitting position (VO2), maximal voluntary ventilation (MVV), and maximal inspiratory and expiratory pressures (MIP, MEP). Thoracic gas volume and specific airway conductance (sGaw) were also measured using body plethysmography. After those baseline measurements, the CPT described above including manual breathing support techniques were performed for about total 40 minutes. Immediately after the CPT, pulmonary function tests were repeated. RESULTS: Inspiratory capacity (IC) and vital capacity (VC) significantly increased (p⬍0.05, p⬍0.01). Forced expiratory volume in 1 second (FEV1) was unchanged. Functional residual capacity (FRC) and residual volume (RV) significantly decreased (p⬍0.01) after CPT. Both sGaw and VO2 were tended to decrease, but it could not reach to the statistic significance. MEP, MIP, and MVV were not significantly change. CONCLUSION: After CPT, lung volume decreased, and IC increased in patients with COPD. CLINICAL IMPLICATIONS: Decreased lung volume and increased IC by CPT possibly contribute to improve breathlessness in patients with COPD. Further research is needed to elucidate how long this effects last. DISCLOSURE: Kayomi Matsumoto, None.

SELF-MANAGEMENT EDUCATION PROGRAM FOR PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE HAS LONG TERM EFFECT ON QUALITY OF LIFE IMPROVEMENT Manon Labrecque MD* Khalil Raby PhD Marcel Julien MD Hoˆpital Sacre´-Coeur, Montreal, PQ, Canada PURPOSE: Purpose of this study was to investigate the effects on health related quality of life (HRQoL), and disease knowledge’s of a Self-management education programme(SMEP) for patients with chronic obstructive pulmonary disease (COPD). METHODS: The programme lasted 4 weeks (3 hours/week) and included teaching of how to use an action plan for self-treatment of exacerbations.Patients were evaluated at time 0 , at 3 months and 12 months. 61 COPD with a mean age of 70(53-84)and FEV1 48.8% of the predicted(SD:18.2%) that was stable on a standard medical regimen. OUTCOME MEASURES: The SF-36 Quality of Life Questionnaire (SF-36), St George’s Respiratory Questionnaire (SGRQ) and a Disease Knowledge’s Questionnaire (DKQ) based on the teaching programme . RESULTS: SGRQ total scores and domain scores were all lower (indicating a better HRQoL) 3 months, and 12 months after the programme comparing to before. These differences reach clinical significance for the SGRQ impact domain who was at (35.2⫾17.2) at time 0 , (28.2⫾19) at 3 months (P⫽ .001) and (24.2⫾17.8) at 12 months (P⫽.001). For the SGRQ total score the value was (44.1⫾17.0) before, (39.8⫾15.3) at 3 months (p⫽ 0.006) and (35⫾17.4) at 12 months (p⫽.001). For the SF-36, physical activity domain showed no significant difference; (33.8⫾8.6) before , (35.7⫾9.4) at 3 months and (36.8⫾11.3) at 12 months (NS). Psychological domain resulted in a score of (45.3⫾11.6) before , ( 50.8 ⫾10.7) at 3 months ( P⫽.003) and (49.5⫾11.3) at 12 months (P⫽.03) Concerning the DKQ, the pre- programme score was (59.4 %⫾11.4), (73.6%⫾13.4)(P⫽0.0001) at one month and 74.5⫾15.5 at 12 months,(P⫽0.0001). CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 COPD Non-Pharmacologic Treatment and Outcomes, continued CONCLUSION: A(SMEP) significantly improved HRQoL in COPD patients probably by increasing patients’ knowledge of disease and hence their ability to manage themselves. The Improvement in HRQoL last at least one year. CLINICAL IMPLICATIONS: This approach of care is interesting because it does not require specialized resources and could easily be implemented within normal practice by health professionals.The present study supports its use as an integral part of the long-terme care of patients with COPD. DISCLOSURE: Manon Labrecque, None. EFFECTIVENESS OF A REHABILITATION PROGRAM IN MORBIDLY OBESE SUBJECTS WITH SLEEP DISTURBANCIES Sasa Lucic MD Francesco Prato MD Daniela Lugli BSc Barbara Serri RRT Giuseppe Cirelli MD Manuela Nobile BSc Enrico M. Clini MD* Fondazione Villa Pineta, University of Modena, Pavullo (MO), Italy

DOES COPD DISEASE STATE EDUCATION BY A HOMECARE PROVIDER [RESPIRATORY THERAPIST] AND EARLY IDENTIFICATION OF NEED FOR LONG-TERM OXYGEN THERAPY (LTOT) REDUCE RELAPSES OF EARLY STAGE COPD PATIENTS? A MEASUREMENT OF SHORT-TERM CHANGES IN DYSPNEA AND DISEASE Vernon R. Pertelle RRT* James Dudley RRT Apria Healthcare, Lake Forrest, CA PURPOSE: We evaluated patients with COPD who were prescribed aerosolized respiratory medications; administered by homecare provider to determine if assessment and education by homecare respiratory therapist (RT)could decrease emergency room (ER) visits and hospitalization by identifying their need for LTOT before a relapse. METHODS: Patients were evaluated retrospectively following winter months from April 2003 to April 2004. Inclusion criteria: (1) diagnosis of COPD, (2) chronic airflow obstruction (evidenced by COPD diagnosis), (3) age ⬎/⫽ 65, (4) education by homecare RT (5) receiving LTOT. Patients recieved oximetry at rest, activity, noctur-

IMPROVEMENT IN PHYSICAL PERFORMANCE COINCIDES WITH IMPROVEMENT IN ACTIVITIES OF DAILY LIVING PERFORMANCE FOLLOWING PULMONARY REHABILITATION Mary K. Hart RRT* Cheri A. Duncan RRT Lucy A. Aguirre-Kelley BS Ana M. Lotshaw MS Mark W. Millard MD Baylor Universtiy Medical Center, Dallas, TX PURPOSE: Pulmonary rehabilitation (PR) has traditionally focused on improving patient endurance and strength, in which outcomes are easily measured. However, documenting objective improvement in an individual’s ability to perform activities of daily living (ADL) following PR has not been well established, despite the obvious utility of such a demonstration. We developed an observational functional assessment tool with three progressively more difficult levels of ADL tasks to evaluate ADL performance in patients with chronic lung disease. The purpose of this study was to determine if improvements found in ADL performance following PR coincided with concurrent improvements in physical performance. METHODS: A retrospective chart review was performed for PR participants from 2003-2004. Thirty six patients who had participated in either a land or water-based PR program and in whom data was completely available were included in this study. Charts were reviewed for data on physical performance and observed ADL performance. The data was analyzed with repeated measures, MANOVA, univariate analysis and a Wilcoxin Signed Ranks test. RESULTS: Both land and water-based exercise PR participants demonstrated similar improvements in physical performance as measured by changes in six minute walk test distance and six repetition maximum strength tests for the shoulder, knee, and hip (p⬍.05). These improvements were mirrored by significant increases in observed ADL task performance measured across all three levels of tasks (p⬍.05). CONCLUSION: The assessment tool developed at our facility was found to be effective in measuring changes in patient ADL performance following PR. Both physical and ADL performance can now be demonstrated to improve after PR. CLINICAL IMPLICATIONS: Usually, ADL function is obtained through self-reporting patient questionnaires. The ADL assessment tool developed by our facility provides an objective measurement of ADL performance. DISCLOSURE: Mary Hart, None. TOLERANCE AND QUALITY OF LIFE IMPROVEMENT FOLLOWING AEROBIC AND STRENGTH TRAINING EXERCISE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE Ogee Mer A. Panlaqui MD* Teresita O. Aquino MD Celestino S. Dalisay MD Veterans Memorial Medical Center, Quezon City, Philippines PURPOSE: To determine the efficacy of aerobic combined with strength training exercise in the improvement of exercise tolerance and CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

PURPOSE: To assess the clinical effectiveness of a hospital-based multidisciplinary rehabilitation program (MRP), in a selected population of morbidly obese subjects. METHODS: An observational study was undertaken in a population of 59 morbidly obese patients (18 M, 60⫾10 years, BMI 47⫾8) with disability and sleep disturbancies (Epworth scale score ⱖ6). Assessment and correction of OSAS, improvement of exercise tolerance, body weigth and associated psychological features were aims of this MRP. Calibrated dietary intake, twice daily sessions of moderate intensity exercising, twice weekly sessions of psychotherapy have been carried out over 1 month. Polisomnographic assessment and correction of apnea/hypopnea index (AHI) have been performed according to the current guidelines. Lung functions, AHI, 6-minute walked distance (6MWD), boby weight (BW), serum metabolic data (cholesterol, triglicerides, uric acid and glicate haemoglobin), and the quality of life by means of the Sat-P questionnaire have been recorded baseline (T0), at the end (T1) and 6 months after (T2) the MRP. RESULTS: Overall, PaO2 improved over time (p⬍0.01), whereas AHI reduced at T1 and then remained stable at T2; in particular, the percentage of patients with AHIⱖ10 declined (from 65% at T0 to 20% at T1 and T2), despite 14 obese with AHIⱖ20 were prescribed to have nCPAP at T1. At T1, 6MWD and BW significantly improved (p⬍0.005) and then maintained at T2; a significant relationship (r⫽ 0.379, p⬍0.01) has been found between changes of BW and 6MWD (recorded in between T0 and T2). Sat-P item scores dealing with sleep efficiency, problem solving, and social interactions improved (p⬍0.01) at T1 and then maintained at T2. CONCLUSION: This conservative intervention provides useful short and long-term benefits in morbidly obese subjects with disability and sleep disturbancies. CLINICAL IMPLICATIONS: Comprehensive and multidisciplinary rehabilitation could be a useful medical approach in the long-term management of severely disabled morbidly obese subjects. DISCLOSURE: Enrico Clini, None.

nally; nutritional status and activities of daily living assessed; LTOT based on qualification by an independent testing facility (IDTF). A total of N⫽56 from a database of N⫽238 completed the chronic respiratory disease index questionnaire (CRQ) and the transitional dyspnea index (TDI) via phone interview upon entry into the program and again within 6 months to determine if they experienced a relapse (urgent hospital revisit within 6 months because of an acute exacerbation). RESULTS: Patients who did not relapse (n ⫽ 49) showed moderateto-large improvements in disease-specific QOL across all four CRQ domains (p ⬍ 0.001) large positive changes in TDI (p ⫽ 0.0001). Patients with a relapse (n ⫽ 7) did not have improved CRQ or TDI scores (p ⫽ 0.02). Changes in the CRQ dyspnea score and TDI correlated with each other (r ⫽ 0.78; p ⫽ 0.0001). A control of N⫽5 with COPD who participated in the program and not prescribed LTOT showed no changes in the CRQ or TDI over 6 months. CONCLUSION: The outcomes and magnitude of change in CRQ and TDI scores were correlated. Outpatients treated for a COPD exacerbation with aerosolized medications and education with early identification of need for LTOT by a homecare RT experience significant short-term improvements in QOL and dyspnea. CLINICAL IMPLICATIONS: The use of a homecare RT for outpatient assessment and education of COPD patients can aid to identify the need for LTOT early to prevent rehospitalization following acute exacerbation. DISCLOSURE: Vernon Pertelle, None.

Wednesday, November 2, 2005 COPD Non-Pharmacologic Treatment and Outcomes, continued quality of life of mild and moderate chronic obstructive pulmonary diseases (COPD) patients. METHODS: The study was conducted at the Pulmonary Rehabilitation Unit of Veterans Memorial Medical Center. Inclusions are (1) physician diagnosed COPD based on smoking history, cough of 3 months in 2 consecutive years (2) pulmonary function test compatible with COPD (i.e. FEV 1/FVC ratio of less than 70% and bronchodilator response less than 15%) (3) stable patients at the time of entry (4) patients having exercise limitation manifested as shortness of breath or general fatigue. Exclusion criteria are clinical evidence of cardiovascular or neuromuscular diseases. RESULTS: Nine patients completed the exercise program. Mean age is 71 ⫹/- 7, with seven males and 2 females. Pre-training lung function studies showed mild to moderate airflow obstruction. Anthropometric measurements revealed normal body mass indexes. There were significant increase in the right arm and left thigh circumference with mean difference of 1.3cm ⫹/- 0.32cm and 1.14 cm ⫹/- 0.28 respectively. There was marginal improvement in lung function which is not significant. Six minute walk test improved to 631 m ⫹/- 148 m with significant mean difference of 218 meters post exercise training. Improvement in the quality of life showed significant change in the grading of patients from moderate grade to no impairment at all in performing their activities of daily living. CONCLUSION: Aerobic combined with strength training exercise improved patients exercise capacity and tolerance as shown by the change in the six minute walk test and increase in the upper arm extremity circumference. No improvement seen in the pulmonary function test.The greatest benefit is the improvement in the baseline dyspnea index of patients during and after the exercise program. CLINICAL IMPLICATIONS: Chronic obstructive pulmonary disease patients can benefit from this combined exercise program. Patients could perform daily activities and even help their households which is a significant reversal from their dependency for care. DISCLOSURE: Ogee Mer Panlaqui, None.

EFFECTS OF PULMONARY REHABILITATION ON EXACERBATION RATE, HOSPITALIZATIONS, LENGTH OF HOSPITAL STAY AND PUBLIC HEALTH ECONOMICS IN PATIENTS WITH MODERATE-TO-SEVERE CHRONIC OBSTRUCTIVE PULMONARY DISEASE Epaminondas N. Kosmas MD* Helen Vey RPh Maria-Konstantina Fraggou MD Irene Papaneofytou MD Zoi Athanassa MD Antonia Koutsoukou MD Ioannis Vogiatzis PhD Olga Georgiadou MS Nikolaos Koulouris MD Dora Orfanidou MD Charis Roussos MD Pulmonary Rehabilitation Unit, Sotiria Chest Diseases Hospital, Athens, Greece PURPOSE: Chronic obstructive pulmonary disease (COPD) exacerbations are a significant cause of morbidity and mortality and with a substantially high cost worldwide. The objective of this study was to evaluate the impact of pulmonary rehabilitation (PR) on the exacerbation rate and on the frequency and duration of hospitalizations in patients with COPD. A secondary aim was to estimate the annual cost savings/patient of PR with respect to hospitalizations. METHODS: We studied 32 ex-smoking patients (age 62⫾7 years) with moderate-to-severe COPD (FEV1 38⫾6 %pred). Patients participated in a 12-week (36-session) program of PR consisting of education, nutritional intervention, physiotherapy, exercise and psychologic support. They completed a questionnaire for the previous year to assess the exacerbations while their emergency visits, admissions and length of hospital stay were found from the hospital records. Patients were followed for the year after PR with both scheduled and emergency visits and with telephone contacts. RESULTS: The total annual number of exacerbations reduced from 112 pre-PR (3.5/patient) to 88 post-PR (2.8/patient)while the emergency visits decreased from 89 (2.8/patient) to 70 (2.2/patient). The significant decreases were found in hospitalizations (from 54 or 1.7/patient to 35 or 1.1/patient; p⬍0.05) and in hospital stay (from 648 days or 20.2/patient to 357 days or 11.2/patient; p⬍0.01). Considering the costs of PR program and of hospital days, the overall result is that the cost-savings for the 32 patients amounted to 9627 € (300 €/patient in approximation). CONCLUSION: A comprehensive pulmonary rehabilitation program results to a significant reduction in frequency and duration of hospitalizations in patients with moderate-to-severe COPD. There is also a trend

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towards reducing the annual number of exacerbations and the emergency hospital visits. CLINICAL IMPLICATIONS: These effects of pulmonary rehabilitation are very important, given that hospitalizations, among other detrimental effects, are an important factor of impairment in health-related quality of life and the principal source of increasing direct costs of COPD. Our results justify the need for reimbursement of rehabilitation programs for COPD patients by our National Public Health System. DISCLOSURE: Epaminondas Kosmas, None.

A RANDOMIZED TRIAL OF STRATEGIES FOR ASSESSING ELIGIBILITY FOR LONG-TERM DOMICILIARY OXYGEN THERAPY Gordon H. Guyatt MD Mika L. Nonoyama RRT* Christina Lacchetti Ron Goeree MA Diane Heels-Ansdell MS Roger Goldstein MB, ChB Respiratory Diagnostics & Evaluation Service, West Park Healthcare Centre, Toronto, ON, Canada PURPOSE: To determine the impact of alternative strategies for assessing eligibility for domiciliary oxygen on funded oxygen use, quality of life, and costs. METHODS: Randomized controlled trial involving applicants for a Government sponsored home oxygen program (HOP). Comparisons were an assessment system that relied on data collected and submitted by oxygen providers at the time of application and judgements by HOP personnel (conventional assessment) versus a system of data collection by a respiratory therapist that included, in patients unstable at the time of initial assessment, a repeat assessment after two months of stability, with judgements by the RT and a respiratory specialist (alternative assessment). Main outcome measures included use of funded domiciliary oxygen; quality of life; mortality; costs to the health care system. RESULTS: 276 applicants were allocated to the conventional arm and 270 to the alternative assessment. In the year following application, oxygen use was appreciably lower in the alternative arm with no between group differences in mortality, quality of life or resource use in the community. Although alternative assessment applicants had on average higher assessment costs by $155 per applicant, these costs were more than offset by decreased HOP costs of $596 per applicant.

CONCLUSION: Reassessment of applicants for domiciliary oxygen after several months of stability identifies an appreciable portion of initially eligible patients who are no longer eligible, thus reducing program costs to public funders without adverse consequences on quality of life, mortality, or other resource use. CLINICAL IMPLICATIONS: Limiting assessment of patients for eligibility for long-term oxygen to the period immediately following an exacerbation will lead to many patients receiving long-term oxygen in whom the benefit is uncertain. Many patients improve, physiologically and with respect to their quality of life, over the first three months following an exacerbation, and an appreciable additional group improve further between 3 months and one year. Optimizing oxygen use requires that the patients be reassessed, both at 3 months and at approximately one year after commencing oxygen. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 COPD Non-Pharmacologic Treatment and Outcomes, continued Table: Cost analysis comparing alternative and conventional assessment process, by type of health care expense, Canadian costing.

Assessment and

Alternative

Conventional

Assessment

Assessment

Difference

$168

$13

$155

Appeal Costs ● HOP Coordinator

n/a

4

● Respirologist

20

n/a

● Resp. Therapist

126

n/a

● Secretary

⬍1

n/a

6

n/a

● Travel Blood Gas HOP Oxygen Costs

16

9

$2,501

$3,097

($596) 95% CI (-903,-291) p⫽0.0002

Health Care Follow-up Costs

$2,871

$87

2090

2158

95% CI

● GP visits

263

273

(-1477, 1651)

● Specialist Visits

136

118

p⫽0.94

● Emergency Room

44

36

● Clinic Visits

10

5

● Tests/procedures

193

121

● Other Professionals Total Cost

222

160

$5,627

$5,982

($355) 95% CI (-1968, 1259) p⫽.66

DISCLOSURE: Mika Nonoyama, None.

VOLUME-REDUCING SURGERY FOR DIFFUSE EMPHYSEMA: EFFECT OF WAITING WITH OPERATION Gunnar N. Hillerdal MD* Kerstin Strom MD Karolinska Hospital, Stockholm, Sweden PURPOSE: Volume-reducing surgery for diffuse emphysema: effect of waiting with operation. METHODS: A Swedish study on Volume-reducing Surgery in diffuse Emphysema(EVRS)was performed during 1997 to 2000. Patients fulfilling strict criteria and having participated in a training program were randomized to either operation (Surgical Group, SG) or to continued training for one year (TG). After this year, patients in TG were offered surgery provided they were still fulfilling the criteria. 53 patients were randomized to each group, and the results showed a significant improvement in Health-related Quality of Life (QoL) and also lung function in the surgical group (Article in Press). In the TG, after the first year, surgery was performed in 32 patients. We compared the results with those who were operated in the SG. RESULTS: The QoL and Lung function was the same in both SG and TG at start (Total Score St Georges Respiratory Questionnaire 59; SF-36 Physical function 22.2 and 22.9, respectively; FEV1 per cent predicted 26 and 27, respectively, and RV % predicted 255 and 267, respectively). There were large improvements in the SG in these figures after 3 and 6 months which then had a tendency to worsen again but at 1 year there were still significant differences between the groups. After surgery in the training group, these patients also improved , but no to the same extent as had those in the SG after their operation; and at two years after randomization, the patients in the SG and those in the TG who had been operated one year later had only non-significant differences both in QoL and lung function, but with a tendency to worse figures in the TG. CONCLUSION: It seems that surgery should be performed early once the patient fulfills the criteria since this gives the patient a longer relief. CLINICAL IMPLICATIONS: Of importance when deciding on operation or postponing possible surgery. DISCLOSURE: Gunnar Hillerdal, None.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation leading to disability. Patients with severe COPD suffer from dyspnea, which can subsequently cause a difficulty in performing routine activities of daily living and affect their quality of life (QOL). Lung volume reduction surgery (LVRS) has been reported to be an effective treatment modality for selected patients with advanced COPD to improve pulmonary function, lung mechanics, exercise tolerance, and dyspnea. However, the long-term effects of LVRS on QOL and psychological states such as anxiety and depression have not been fully elucidated. We evaluated QOL and psychological state before and after LVRS in patients with severe COPD for 5 years. METHODS: Eleven patients with severe COPD (Age: 66.1⫾5.9, VC: 2.3⫾0.7L, FEV1: 0.75⫾0.21L, RV:4.5⫾1.0L) who underwent LVRS were studied. QOL was assessed by Sickness Impact Profile (SIP). Psychological states (anxiety, depression) were measured by using the State Trait Anxiety (STAI) and the Self-Rating Questionnaire for Depression (SRQD). Serial measurements of QOL and psychological state were done before and 3, 12, 24, 36 and 60 months after LVRS. RESULTS: The best scores in SIP were obtained at 36 months after LVRS. Especially, physical-SIP scores at 12, 24, 36 months reached to normal range. However, psychosocial-SIP score at 60 months was worse than pre-LVRS. As for psychological state scores, STAI scores did not show significant changes during 36 months, and indicated in the range of high anxiety at 60 months after LVRS. The SRQ-D scores have been in the suspected level of depression for 60 months. CONCLUSION: It is difficult to maintain the beneficial effect of LVRS on psychosocial QOL and psychological states up to 5 years. CLINICAL IMPLICATIONS: It is important to evaluate not only physiological functions but also psychological changes, when the total outcome should be assessed to determine the long-term benefit of LVRS. DISCLOSURE: Yoko Goto, None. COPARATIVE STUDY OF MANAGEMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AS PER GLOBAL INITIATIVE ON OBSTUVTIVE LUNG DISEASE (GOLD) GUIDELINES AND ALTERNATE SYMPTOMS/DYSPNEA BASED STRATEGY Jai Kishan MD* Ashish Chawla MBBS Bal K. Kapoor MD TB & Chest Dept/Hospital Govt. Medical College, Patiala, India PURPOSE: GOLD guidelines emphasize the need of spirometery for diagnosis and management of COPD.However, in developing countries who share the major burden of COPD spirometery is not universally available hence an alternate strategy avoiding spirometery need to be developed. METHODS: 50 patients each in Group A & B were studied. Group A were classified on spirometery and managed managed as per GOLD guidelines and Group B graded on symptoms/dyspnea based approach. A comparision made of outcome measures like exacerbations,hospital visits/ hosptallizaion.Group B was classified acording to no dyspnea, dyspnea on unaccustomed exercise, on accustomed exercise,on normal routines of life or on lying in the bed and also on basis of cyanosis, oedema feet or CCF. RESULTS: Exacerbtion were equal (16%)in both the groups.12% of Group A & 16% of Group B patients were lost to folow up.Time for symptomatic imrovement was delayed in Group B but was not statitically significant.Patients when classified according to alternate strategy were falling in lower grade of spirometery based Gold guidelines and thus received lower grade of treatment. CONCLUSION: COPD can be graded and managed according to symptoms/dyspnea based approach. Even GOLD guidelines based management shoul be validated thoroughly. CLINICAL IMPLICATIONS: In resource poor countries symptoms/ dyspnea based COPD management can be employed. DISCLOSURE: Jai Kishan, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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$2,958

● Hospitalizations

QUALITY OF LIFE FOR 5 YEARS AFTER LUNG VOLUME REDUCTION SURGERY IN PATIENTS WITH SEVERE COPD Yoko Goto PhD* Hajime Kurosawa MD Nobuyoshi Mori MD Masahiro Kohzuki MD Department of Occupational Therapy, School of Health Sciences, Sapporo Medical U, Sapporo, Japan

Wednesday, November 2, 2005 COPD Non-Pharmacologic Treatment and Outcomes, continued GASTRO ESOPHAGEAL REFLUX SYMPTOMS IN PATIENTS WITH CHRONIC RESPIRATORY FAILURE DUE TO CHRONIC OBSTRUCTIVE PULMONARY DISEASE Snezana V. Raljevic MD* Marija M. Mitic-Milikic PhD Ljudmila Nagorni-Obradovic PhD Institute for Pulmonary Diseases and TB, Belgrade, Serbia PURPOSE: Gastro Esophageal Reflux (GER) is well described in patients with Asthma and Chronic Obstructive Pulmonary Disease (COPD). The purpose of this study was to determine prevalence of GER symptoms among patients with Chronic Respiratory failure (CRF) due to COPD. METHODS: The study included two groups of patients: Group I: 70 patients with COPD and CRF and Group II: 50 patients with COPD and Acute Respiratory Failure (ARF). All patients were treated for exacerbation at Institute for pulmonary diseases in Belgrade. Pulmonary function tests (PFT) and blood gas analysis (BGA) were performed in all patients. After collecting basic demographic and habit information, all patients filled out Mayo Clinic Gastro Esophageal Reflux Questionnaire. RESULTS: In group I was 48 male and 22 female mean age 61⫾5 years. PFT results were: FEV1 36⫾10%, FEV1/FVC 42⫾8%. BGA analysis: PO2 6.8⫾10 Kpa, PCO2 8.1 ⫾4Kpa, Sat 85⫾8%. In group II was 35 male and 15 female, mean age 54 ⫾ 8 years. PFT results were FEV1 49⫾3.2%, FEV1/FVC 48⫾10%. BGA analysis were: PO2 7.1⫾5.5Kpa, PCO2 6.9⫾2Kpa, Sat 89⫾11%. GER symptoms in group I vs. group II were: acid regurgitation (68% vs. 55%), dysphagia (30% vs.19%), heartburn (81% vs.70%), chronic cough (71% vs. 67%) and hoarseness (15% vs. 8%). Both groups have significant GER symptoms, but difference did not reach statistical significance (p⬎0.05). Heartburn and acid regurgitation occurs daily and it was described as hard or very hard. Average duration of heartburn and acid regurgitation was 10⫾4 years. All patients occasionally take anti reflux drugs mostly during exacerbation of disease. CONCLUSION: GER symptoms are significantly present in patients with CRF due to COPD. There was a trend toward higher prevalence of GER symptoms among patients with CRF comparing to patients with ARF, but the difference did not reach statistical significance. CLINICAL IMPLICATIONS: Patients with respiratory failure due to COPD (both acute and chronic) require further medical investigation and appropriate therapy with anti reflux drugs. DISCLOSURE: Snezana Raljevic, None. CLINICAL OUTCOME OF PATIENTS ADMITED WITH ACUTE EXACERBATION OF COPD Avanti Vigg MBBS* Ajit Vigg MD Arul Vigg MBBS Sumanth Mantri MD Royal Preston Hospital, Preston, United Kingdom PURPOSE: To identify risk factors related to Acute Exacerbation of Chronic Obstructive Pulmonary disease ( COPD ) in hospitalized patients as a retrospective nested case control study. METHODS: From Jan 2002 to June 2004, a total of 162 patients were admitted who satisfied the criteria for Acute Exacerbation of COPD. Of these, 26 patients died. They were compared with 136 discharged patients (controls)Acute Exacerbation of COPD was defined using the criteria of Anthonisen et al : increased dyspnoea /sputum volume & sputum purulence. Severity of lung disease was stratified based on FEV1 % predicted using GOLD guidelines (StageI:FEV1/ FVC ⬍ 70% with FEV1 ⬎ 80%, Stage IIa:FEV1 50-80% stage IIb:FEV1 30 – 50% & stage III FEV1 ⬍30%): Clinical outcomes were recorded in all patients. RESULTS: Sixteen percent of deaths occurred in hospitalized patients due to acute exacerbation. The main risk factors with odds ratios (OR) were: use of ventilator OR ⫽ 3.46 ( 95% CI :1.22-9.28, P⫽ 0.02), increased stage of severity OR ⫽ 4.35 (95% CI : 1.01-18.86, P⫽ 0.05) prolonged length of stay in ICU OR 9.32 (95%,CI:4.27-87.3) (P⫽0.0001) prolonged length of stay in hospital OR ⫽2.76 (95% CI : 1.02-7.51, P⫽0.04). Interestingly age, sex, type of respiratory failure, sputum culture /sensitivity and presence of one or more co-morbidities did not affect the ultimate outcome. CONCLUSION: The results of our study suggest that use of ventilator, prolonged length of ICU stay, hospital stay,decreased FEV1 determine treatment outcomes. Prospective studies in appropriately stratified patients are needed to validate these findings in Indian setup loco regionally. CLINICAL IMPLICATIONS: Treatment outcomes in acute exacerbations of COPD are determined by variable factors which need to be ascertained in each center. DISCLOSURE: Avanti Vigg, None.

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OUTCOME AND SURVIVAL IN HYPERCARBIC RESPIRATORY FAILURE FROM COPD TREATED WITH NON-INVASIVE VENTILATION (NIV) Kwok Yim MS En-chia J. Liu MD Robert A. Fleming MD* Terence Brady MD NYHQ, Manhasset, NY PURPOSE: Objective: NIV in properly selected patients (non-obtunded with a pH⬎7.19) can result in improved tidal breath, minute ventilation and prevent endotracheal intubation in COPD patients with hypercarbic respiratory failure. This study explores the efficacy of NIV in avoiding endotracheal intubation and surviving to discharge. METHODS: Method: a retrospective chart review was conducted on 30 consecutive deployments of NIV in hypercarbic COPD patients in the year 2003. Arterial blood gas. (ABG) Pre-NIV, post NIV, endotracheal intubation and survival to discharge were recorded. RESULTS: Results: Demographics revealed 14 males, and 16 females; mean age was 74.4 years. ABG’s were all obtained within 24 hours of deployment. There were 25/30 (83%) responders with pre-NIV ABG of pH 7.29, PCO2 63.3 mmHg. and mean post –NIV ABG’s were pH 7.38, PCO2 52.6mmHg,ŒpH was 0.0796, ŒPCO2 was10.7mmHg. Of the non-responders 5/30 (17%) mean ABG’s pre-NIV were pH 7.29, PCO2 53.0mmHg, post-NIV mean ABG’s pH were 7.24, PCO2 60.6 mmHg ŒpH -0.058 and ŒPCO2 0.7.6 mmHg. NIV success in avoiding EI was 22/25 (88%) Patients surviving to discharge 22/25 in the responder group. CONCLUSION: The non-responding group had a pre-NIV ABG revealing a primary respiratory acidosis with no metabolic compensation or a concomitant metabolic acidosis that was predicted of failure on initial presentation. This has not been previously reported. We demonstated the high rate of success of NIV at avoiding endotracheal intubation with low mortality and high rate of discharge back to the community. CLINICAL IMPLICATIONS: Further study is required to validate the predictive value of NIV failure in uncompensated respiratory acidosis on the initial arterial blood gas. DISCLOSURE: Robert Fleming, None. PREDICTORS OF SUCCESS AND OUTCOME OF NONINVASIVE VENTILATION IN ACUTE EXACERBATIONS OF COPD AT A UNIVERSITY HOSPITAL IN TURKEY Meltem M. Tor MD* Suna Akbulut MD Levent Kart MD Remzi Altin MD Figen Atalay MD Muhammed E. Akkoyunlu MD Zonguldak Karaelmas University Hospital Department of Pulmonary Medicine, Zonguldak, Turkey PURPOSE: Non-invasive ventilation (NIV) is being used more frequently in the management of acute exacerbations of chronic obstructive pulmonary disease (COPD ). We hereby present our experience at a university hospital setting in Turkey. METHODS: Twenty-two patients with a COPD exacerbation whom were treated with NIV in the first place were enrolled in the study. Of 22 patients(82% males, mean age of 63.4), eight (36%) had a mild , 10(46%) had a moderate and four(18%) had a severe exacerbation. Comorbidities were present in 82% of them, and 68% had previous hospitalizations for exacerbation. APACHE II score (mean⫹/-SD) was 18.09⫹/-4.02. RESULTS: NIV was initiated in the emergency department in 9% of patients, in an ICU setting in 77% , on a general ward in 14% . The mean baseline pH, pO2 and pCO2 at baseline were 7.39(9% with a pH of ⬍ 7.30), 57⫹/-17 mmHg(63%with pO2⬍60mmHg),and 56⫹/-14 mmHg (87% with pCO2⬎45mmHg) respectively. Mean duration of NIV and total length of hospital stay were 9 and 18 days respectively. On follow-up, two patients (9%) required endotracheal intubation (ETI), and there was only one death (4.5%). Success of NIV was not correlated with APACHE score, age, severity of exacerbation, number of previous hospitalizations, pCO2 and pH, although one failed patient had a pH⬍7.30. Baseline pO2 (k⫽-0.470, p⫽0.027) and spO2 ( k⫽-0.491, p⫽0.020) were found as negative predictors of NIV success. On discharge, home ventilators were prescribed to three(13,5%) patients. CONCLUSION: We have found that NIV was iniatiated and used mostly inside of a critical care setting in our institution. Our outcomes of ETI and death were lower than those reported previously because less severe exacerbations were present in our series. Hypoxemia was found as the main predictor of NIV success. CLINICAL IMPLICATIONS: NIV should be considered early in the course of acute exacerbations of COPD and before severe hypoxemia ensues, in order to reduce the likelihood of ETI, treatment failure and mortality. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 COPD Non-Pharmacologic Treatment and Outcomes, continued DISCLOSURE: Meltem Tor, None.

SYSTEMATIC REVIEW OF DISEASE MANAGEMENT IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE Sandra G. Adams MD* Paulla K. Smith RRT John E. Cornell PhD Antonio Anzueto MD Jacqueline A. Pugh MD University of Texas Health Science Center at San Antonio and The South Texas Vet, San Antonio, TX

EVALUATION OF HEALTHCARE RESOURCE UTILIZATION (HRU) AND COSTS OF ANEMIA AMONG CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) PATIENTS Michael T. Halpern MD* Jordana K. Schmier MA Marya Zilberberg MD Edmund Lau MS Exponent, Alexandria, VA PURPOSE: Anemia has been reported in 13-30% of patients diagnosed with COPD1,2,3. However, little information is available on the incremental economic burden resulting from concomitant anemia. We evaluated the impact of anemia on HRU and costs among COPD patients. METHODS: Retrospective data analysis of the Medicare 5% beneficiary encrypted files (BEF) was performed. All individuals with a COPD diagnosis code in the 1997-2001 BEF data were identified. COPD patients with anemia (A⫹) were identified using ICD-9 diagnosis codes or receipt of transfusion(s) in the absence of major GI bleeding, trauma, or surgery. A 6-month control period preceding the 1st COPD diagnosis (index date) served to compare disease severity. RESULTS: Of the 132,424 patients with COPD identified, 27,932 (21%) had an anemia code. A⫹ patients were more likely to be older, female and non-Caucasian (p⬍0.0001). Except for pre-dialysis chronic kidney disease (22% A⫹ vs. 9% without anemia [A-], p⬍0.0001), comorbidity burden was similar between the 2 groups. Average total annual Medicare reimbursement was $855 for A⫹ and $437 for A- before the index date; after the index date it increased by 71% to $1466 in the A⫹ group vs. 49% to $649 in the A- group. In both groups, the greatest cost driver before and after the index date was hospitalizations, accounting for ⬎50% of the average payments. In regression models controlling for demographics, disease severity, and comorbidities, anemia maintained an independent and significant association with increased payments.

COPD Pharmacologic Therapy 12:30 PM - 2:00 PM RISK OF HOSPITALIZATION/EMERGENCY VISIT IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE BY INITIAL MEDICATION REGIMEN Rohit D. Borker PhD* Cortney Hayflinger MS Richard Stanford MS GlaxoSmithKline, Research Triangle Park, NC PURPOSE: To compare risk of all-cause & COPD-related emergency department (ED) visit/hospitalization in patients with COPD receiving initial maintenance therapy. METHODS: Retrospective observational analysis was conducted using data from a large managed care database ( ⬎ 30 managed care plans). Patients ⱖ 40 years with a primary diagnosis of COPD within 1 year prior to initial treatment and at least 18 months of continuous eligibility were identified. Following cohorts were identified: ipratropium (IP), salmeterol (SL), inhaled corticosteroid (ICS), ICS plus SL in the same inhaler (FS), and IPR and albuterol (AL) in the same inhaler (IP/AL). Logistic regression analysis was performed that determined risk of all cause and COPD-related hosp/emergency room (ER) visit. The model adjusted for baseline differences in age, comorbities, COPD sub type, baseline oral corticosteroid, theophylline and albuterol use. RESULTS: In all, 14,368 patients were identified, 2122 IP, 1099 SL, 3940 ICS, 3819 FS and 3388 IP/AL. Compared with IP, FS reduced the risk of all-cause ER/hosp by 46 % (OR 0.539, CI: 0.467 to 0.622). In addition, ICS and SL reduced the risk by 41 %, (OR 0.594, CI: 0.516 to 0.683) and 36% (OR 0.640, CI: 0.529 to 0.774), respectively. IP/AL cohort was associated with a 12% risk reduction (OR 0.877, CI: 0.770 to 0.999). FS was also associated with a 69% lower risk (OR 0.309, CI: 0.200 to 0.475) of having a COPD related ER/hosp, while ICS and SL had 58%, (OR 0.419, CI: 0.287 to 0.611) and 61% (OR 0.387, CI: 0.216 to 0.694) lower risk, respectively. A 13% risk reduction, which was not statistically significant, was also observed in the IP/AL cohort (OR 0.868, CI: 0.645 to 1.167). CONCLUSION: Treatment of COPD with SL or ICS containing medications, especially when ICS and SL are used in combination (FS), may significantly decrease the risk of all-cause and COPD related ED/hosp compared to treatment with IP alone. CLINICAL IMPLICATIONS: These findings provide further evidence of clinical benefits for FSC in patients with COPD. DISCLOSURE: Rohit Borker, Employee GlaxoSmithKline

POOLED CLINICAL TRIAL ANALYSIS OF THE SAFETY OF TIOTROPIUM Steven Kesten MD* Michele Jara PhD Charles Wentworth MS Stephan Lanes PhD Boehringer Ingelheim, Ridgefield, CT PURPOSE: Marketing approval of pharmaceutical products is often based on efficacy and safety data from several thousand subjects. After approval, information may be obtained from larger numbers of patients from Phase IV clinical trials enhancing the ability to detect rare adverse events. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: The chronic illness care model (CICM) has been shown to improve outcomes in diabetes mellitus and congestive heart failure, but data regarding the effectiveness of a comprehensive model in patients with chronic obstructive pulmonary disease (COPD) are lacking. A systematic review of the literature was undertaken to determine the effectiveness of the components of the CICM in patients with COPD. METHODS: MEDLINE, CINAHL, and COCHRANE databases were searched from the earliest date available to January of 2005 to identify English-language articles that evaluated outcomes of adults with an intervention of at least one of the components of the CICM in patients with COPD. RESULTS: A total of 514 abstracts were screened, but only 32 articles were suitable for full abstraction and review. These studies were heterogeneous (different interventions and outcomes) and only a few met standard criteria for high quality. Outcomes such as symptoms, quality of life, lung function, and functional status were not significantly different between the intervention and control groups. However, the pooled relative risk (RR) and 95% confidence intervals (CI) for the emergency/ unscheduled visits for the group who received at least 2 components of the CICM was 0.575 (0.418, 0.790) and for the length of hospital stay was -0.522 (-0.721, -0.322). There was no significant change in healthcare utilization in the control groups or in patients who received only one component (such as self-management alone) of the CICM. CONCLUSION: Only limited data are available in the literature evaluating interventions of any of the components of the CICM in patients with COPD. However, the pooled data from the available studies demonstrated that patients with COPD who received interventions including 2 or more components of the CICM had lower rates of emergency/unscheduled visits and an overall shorter length of hospital stay than patients who received only one component or those who were in the control groups. CLINICAL IMPLICATIONS: Implementation of multiple components of the CICM in patients with COPD has the potential to significantly reduce healthcare utilization. DISCLOSURE: Sandra Adams, None.

CONCLUSION: Presence of anemia is associated with a substantial increase in resource utilization and costs among Medicare enrollees with COPD, independent of demographic differences, higher disease severity, and comorbidity burden. CLINICAL IMPLICATIONS: Prospective studies are needed to evaluate the effect of anemia correction on HRU in the COPD population.1John M, et al. Chest. 2005;127:825-829.2Cote C, et al. Anemia Is Associated with Increased Breathlessness and Decreased 6-Minute Walk Distance in COPD Patients. Proc Am Thorac Soc 2005;2: A498.3Cote C, et al. Anemia Is a Predictor of Mortality in Patients with COPD. Proc Am Thorac Soc 2005;2:A890. DISCLOSURE: Michael Halpern, Grant monies (from industry related sources) Supported by a grant from Ortho Biotech Clinical Affairs, LLC.; Employee Marya Zilberberg, MD is an employee of Ortho Biotech Clinical Affairs, LLC.

Wednesday, November 2, 2005 COPD Pharmacologic Therapy, continued METHODS: We pooled data on adverse events from 19 randomized, double-blind, placebo-controlled trials with tiotropium in patients with COPD (17 studies) and asthma (2 studies) using data available in project database as of May 2004. Heterogeneity of incidence rate ratios was examined by trial prior to pooling. We computed incidence rates of selected adverse events and Maentel-Haenszel incidence rate ratio estimates, and used 95% confidence intervals for precision of effect estimates. Patients were included while in the study until 30 days post-treatment (tiotropium, placebo) or until they had the event of interest, whichever came first. RESULTS: Pooled population includes 7,819 patients (4,435 tiotropium; 3,384 placebo), contributing 2,159 person-years of exposure to tiotropium; 1,662 person-years of exposure to placebo. Dyspnea, dry mouth, COPD exacerbation and upper respiratory tract infection were the most common events. There was decreased relative risk of dyspnea (RR⫽0.64, 95%CI⫽0.05, 0.81) and COPD exacerbation (RR⫽0.72, 95%CI⫽0.64, 0.82) with tiotropium compared with placebo. Among heart rate and rhythm disorders, risk of tachycardia was slightly elevated with tiotropium (RR⫽1.68, 95%CI⫽0.69, 4.11). Serious cardiac conditions, such as cardiac arrest and myocardial infarction did not occur more frequently with tiotropium. There was an elevated risk of urinary retention (RR⫽10.93, 95%CI⫽1.26, 94.88) with tiotropium. There was lower risk of all cause mortality (RR⫽0.76, 95%CI⫽0.50, 1.16), cardiovascular mortality (RR⫽0.57, 95%⫽0.26, 1.26) and respiratory mortality (RR⫽0.71, 95%CI⫽0.29, 1.74) with tiotropium. CONCLUSION: The benefit/risk profile of tiotropium is characterized by decreased risk of dyspnea and COPD exacerbation and increased risk of dry mouth and urinary retention. Pooling of adverse event data from tiotropium clinical trials supports the present safety profile of tiotropium. CLINICAL IMPLICATIONS: Pooling of adverse event data from pre- and post-registration clinical trials has value in understanding the safety of recently approved medications. DISCLOSURE: Steven Kesten, Grant monies (from industry related sources) Funded by Boehringer Ingelheim and Pfizer.; Employee S. Kesten and S. Lanes are employees of Boehringer Ingelheim.; Consultant fee, speaker bureau, advisory committee, etc. M. Jara and C. Wentworth are consultants for Boehringer Ingelheim.

ADDITION OF FORMOTEROL TO TIOTROPIUM PRODUCES BETTER FEV1 AND FVC RESPONSES WHEN MEASURED OVER 24 HOURS FOLLOWING SINGLE-DOSE ADMINISTRATION IN SUBJECTS WITH MODERATE-TO-SEVERE COPD Bill Brashier MBBS Ashwini Jantikar MBBS Manisha Maganji MBBS Anchala Raghupathy MBBS Sapna Valsa MS Partha Gokhale MD Purnima Mahadik MS Jaideep Gogtay MD Sundeep S. Salvi MD* Chest Research Foundation, Pune, India PURPOSE: Tiotropium, a new long-acting anticholinergic drug is recommended as first-line bronchodilator in the management of COPD. The aim of this study was to investigate whether addition of Formoterol, a long-acting b2-agonist produces a superior bronchodilator response when compared to Tiotropium alone in subjects with moderate-to-severe stable COPD. METHODS: 23 male subjects (mean age: 59.6 ⫾ 7.6 yrs) diagnosed with COPD and no histories of exacerbation over the previous 4 weeks, were recruited into this study. Single doses of Tiotropium (18mcg) and a combination of Tiotropium plus Formoterol [18 and 12 mcg respectively) administered through a single ihaler, were given with a pMDI plus non-static spacer on two separate study days, 4-7 days apart, in a randomized, double-blind, cross-over manner. FEV1 and FVC were measured at baseline and 5min, 15min, 30min, 60min, 2hr, 3hr, 4hr, 6hr, 8hr, 12hr and 24hr following the study drug administration with a Vitalograph Gold Standard dry bellows Spirometer. RESULTS: The mean baseline FEV1 value in this study population was 40.6 ⫾ 14.1% predicted. Tiotropium plus Formoterol produced a significantly better mean difference in area under the curve change from baseline to 24 hrs for both FEV1 (p ⫽ 0.001) and FVC (p ⫽ 0.02). Also, the mean difference in trough (24 hr) values from baseline were significantly better with the combination than Tiotropium alone [(FEV1 – 289.6mL vs 185.7mL; p ⫽ 0.001)(FVC – 503.5mL vs 297mL; p ⫽ 0.007). The combination showed a faster onset of action for FVC, defined as an increase of at least 150mL from baseline (5.0 mins vs 12.1 mins; p ⫽ 0.02) and tended to show a longer duration of action when compared to Tiotropium alone (FEV1: p ⫽ 0.06; FVC: p ⫽ 0.05).

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CONCLUSION: In patients with moderate-to-severe COPD, addition of Formoterol to Tiotropium (in a single inhaler) produces better FEV1 and FVC responses than Tiotropium alone when measured over 24 hrs. CLINICAL IMPLICATIONS: Combination of Tiotropium and Formoterol may produce better clinical response in patients with moderateto-severe COPD. DISCLOSURE: Sundeep Salvi, Grant monies (from industry related sources) Cipla Ltd.

HANDLING PERFORMANCE AND PATIENT SATISFACTION OF A METERED DOSE INHALER(MDI) WITH INTEGRATED DOSE COUNTER IN PATIENTS WITH COPD Courtney Crim MD* William R. Lincourt BS Nickolas W. Locantore PhD J. R. Carranza-Rosenzweig PharmD GlaxoSmithKline Inc., Raleigh, NC PURPOSE: Current methods that require patients to track inhaler doses are unreliable and can lead to circumstances where medication is unavailable. This study examined patient satisfaction and handling performance of an MDI fitted with an integrated dose counter in 219 patients with COPD. METHODS: Data were collected using self-report questionnaires that assessed previous MDI experience and overall satisfaction with the MDI with counter. Counter performance was assessed during a 30 or 50 day treatment period by measuring the discrepancies between the counter readings and the actuations reported on a subject recorded diary card. RESULTS: At baseline 65% of the patients reported feeling anxious not knowing the amount of medication left in their inhaler. Fifty-seven percent reported assessing the remaining quantity by shaking the inhaler and 43% reported waiting until it was completely empty. After using fluticasone propionate/salmeterol HFA or albuterol HFA MDI with Counter, 93% of patients were satisfied with it based on its ease of use and convenience. Ninety-one percent felt that it would allow them to monitor their medication use while 93% agreed that the counter would help them avoid running out of medication. A total of 308 discrepancies between subject-reported use and counter readings occurred in 15,835 device handlings (31,667 MDI actuations), constituting a discrepancy rate of 0.97 discrepancies per 100 actuations. Fifty-two percent of the subjects reported no discrepancies. For subjects reporting a discrepancy, the majority (90%) were of 1 or 2 actuations. CONCLUSION: These data support the need for a reliable, MDI actuation counting device and document the favorable patient perceptions of the MDI with Counter. The results showed a high level of concordance between the MDI with Counter and the subject-recorded diary card. CLINICAL IMPLICATIONS: The addition of an integrated dose counter to an MDI will provide patients with a reliable indication of remaining actuations in their inhalers and increase clinicians’ assurance that patients are not using their inhalers beyond the recommended number of labeled doses, a situation that clearly impacts patient health. DISCLOSURE: Courtney Crim, Grant monies (from industry related sources) Study supported by a grant from GlaxoSmithkline; Employee All authors are employees of GlaxoSmithKline Inc.; Product/procedure/ technique that is considered research and is NOT yet approved for any purpose. MDI dose counter is approved for Ventolin HFA in the US and for Seretide in the UK

IMPROVEMENT OF DYSPNEA IN COPD PATIENTS BY COMBINATION THERAPY WITH TIOTROPIUM PLUS SALMETEROL (TⴙS) IN RESPONDERS AS WELL AS POOR RESPONDERS TO SALBUTAMOL J.A. van Noord MD* J-L Aumann MD E. Janssens MD J.J. Smeets A. Mueller P.J.G. Cornelissen PhD Atrium Medisch Centrum, Heerlen, Netherlands PURPOSE: Recommended mono- or combination therapy of longacting bronchodilators in COPD is successful if relief of dyspnea is provided. METHODS: A retrospective analysis was conducted in 93 patients (FEV1: 1.09 L / 39% pred) who completed a 4-way, double-blind, crossover study of tiotropium 18 mcg (qd), salmeterol 50 mcg (bid), T (qd) ⫹ S (qd) or T (qd) ⫹ S (bid). Patients were characterized as responder (R, ⬎ 12% increase in FEV1 45 min after 400 mcg salbutamol) or poor responder (PR, ⱕ 12%) on the basis of a single test. Effects on dyspnea (TDI, ⱖ 1 unit is clinically relevant), FEV1, FVC and need for CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 COPD Pharmacologic Therapy, continued reliever medication were compared at the end of 6-week treatment periods. RESULTS: Mean FEV1 at screening was 1.05 L (37% pred, N ⫽ 57) in the R-group and 1.16 L (40% pred, N ⫽ 36) in the PR group. CONCLUSION: Treatment responses showed the same rank order in the R and PR groups, with combination therapies superior to single agent therapy. CLINICAL IMPLICATIONS: Data confirm guidelines regarding patient benefit of combination therapy of long-acting agents tiotropium plus salmeterol over mono-therapy in moderate to severe COPD, even in patients who fail to reach a pre-defined threshold response to salbutamol.

Mean*

TDI (focal score) FEV1 (0-12h) - ml FVC (0-12h) - ml Puffs salb (0-12h) *

in breakthrough requirements. Ipratropium showed a significant benefit in breakthrough reduction for the Alb group. Lev 0.63 mg MP performed as well as Lev 1.25 mg via mask. CLINICAL IMPLICATIONS: The efficiencies gained by decreasing the daily frequency of aerosol administration can have a significant impact on resource utilization. The conversion to Lev allows for decreased respiratory therapy time or the re-allocating of workforce needs while maintaining, or improving, quality of aerosol administration, as evidenced by the decrease in breakthrough requirements. Smaller doses in the BAN lead to shorter administration times. DISCLOSURE: Robert Pikarsky, None.

Tio (qd) Salm (bid) T(qd) ⫹ S(qd) T(qd) ⫹ S(bid) R 1.52 142 230 1.55

PR R PR R # 0.65 1.18 0.67 2.97 86 97 32 250 185 133 66 411 2.26 1.47 2.21 1.00

PR R PR ⬎1.93# ⬎3.15# ⬎2.08# 152 262 164 301 407 294 1.50 1.12 1.38

Means are adjusted for centre, patient within centre and period.

BREAKTHROUGH TREATMENTS RATES DURING A CONVERSION TO LEVALBUTEROL, TIOTROPIUM AND BREATH ACTUATED NEBULIZERS Robert S. Pikarsky RRT* Russell A. Acevedo MD Tracey Farrell RRT Wendy Fascia RRT Crouse Hospital, Syracuse, NY PURPOSE: In order to maximize therapist time, an auto-conversion to Levalbuterol (Lev) Q8h, Tiotropium (Tio) QD and AeroEclipse Breath Actuated Nebulizer (BAN) usage in mouthpiece (MP) mode was evaluated. METHODS: All patients assessed by Respiratory Therapists with the ability to perform aerosol treatments by mouthpiece were converted to Lev 0.63 mg Q8h by BAN MP. If ordered, Ipratropium (Ipra) 0.5 mg was converted to Tio 18 mcg QD. If unable to perform the MP treatment patients were converted to Lev 1.25 mg Q8h delivered by mask. If ordered, Ipra 0.5 mg was converted to Ipra 0.25 mg Q8h. All protocol treatments, including breakthrough treatments delivered between 10/04 and 4/05 were recorded. Treatment refusals and omitted treatments were recorded. The breakthrough data for Racemic Albuterol (Alb)was from our previous studies. RESULTS: The table shows the number of treatments(tx), the number of prn breakthrough treatments and the per-treatment and daily rates of breakthroughs per 100 treatments. Lev 0.63 mg Q8h MP had significantly lower breakthroughs rates than the Alb 2.5 mg Q4h, both in per-treatment and daily rates (p⬍0.05)* Alb/Ipra Q4h had significantly lower pertreatment rates when compared with Lev/Tio Q8h and Lev/Ipra Q8h (p⬍0.01)**; the daily breakthrough rates were not significantly different. Omitted treatments decreased from 2.28% to 1.95%. Patients refused 3.81% of scheduled treatments. Breakthroughs per 100 tx

Treatment per day

Daily Breakthroughs per 100 tx

Order

Count

Breakthroughs

Lev 0.63 mg Q8h (MP) Lev 0.63 mg Q8h/Tio 18 mcg Qday (MP) Lev 1.25 mg Q8h (Mask)

3541

58

*1.64

3

*4.91

1130

22

**1.95

3

3092

74

2.39

3

PURPOSE: Crouse Hospital approved an automatic conversion from Racemic Albuterol (Alb) 2.5mg Q4h to either Levalbuterol (Lev) 0.63 mg Q6h or Lev 1.25 mg Q8h. To further maximize Respiratory Therapist time we took the next step of automatic conversion of all Lev Q6h to Lev Q8h. METHODS: All protocol treatments delivered between 10/04 and 4/05 were recorded. Pre-conversion estimates for Alb Q4h were twice the current Lev Q8h protocol. The ratio of Lev Q6h to Q8h delivered between 1/04 and 4/04 (prior protocol) was 85%:15%. The cost for unit dose Alb was $0.22. The cost for unit dose Lev was $1.85. We used the 0.26 hour per treatment time as reported in the AARC Uniform Reporting Manual. The FTE average cost (salary/benefits) ⫽ $23.80/hr. All aerosol therapy was provided with the use of the AeroEclipse Breath Actuated Nebulizer (BAN). RESULTS: The table shows the drug and labor cost for the current protocol and the estimated number of treatments, with their respective costs, for the prior protocol and pre-conversion periods. For the current protocol, the drug cost of $16,482 is lower than the prior protocol and considerably higher than the pre-conversion period. Labor costs decreased with each protocol as the number of treatments dropped. The drop in labor cost more than offset the increase drug costs in each protocol. The largest savings was seen with the current Lev Q8h protocol. The Respiratory Care Department’s total expenses for the first 3 months of this year was 8.6% under budget and 7.9% below the same time period in 2004. CONCLUSION: Hospital-wide conversion to Lev is cost-effective when administered on both a Q6h and Q8h frequency with the maximum benefit at the Q8h frequency. Therapist availability was enhanced with fewer scheduled treatments. CLINICAL IMPLICATIONS: The conversion to Lev allows the ability to meet our patient care demands and for the reallocation of workforce needs in an economically advantageous manner.

Prior Protocol

Current Protocol

17,818

9,642 1,678 11,320

8,909 8,909

Pre-conversion Treatments Alb Q4h Treatments Lev Q6h Treatments Lev Q8h Total treatments

17,818

Drug cost (dollars)

$

3,920

$20,942

$16,482

5.84

Labor (hours) Labor cost (dollars)

4,633 $110,258

2,943 $70,048

2,316 $55,129

7.18

Total cost (dollars) Savings compared with current protocol

$114,178 $ 42,567

$90,990 $19,380

$71,611

CONCLUSION: The conversion from Alb Q4h to Lev Q8h allowed for a decreased frequency of daily medication administrations and a decrease

DISCLOSURE: Robert Pikarsky, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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DISCLOSURE: JA van Noord, Grant monies (from industry related sources) First three authors received honorarium to conduct clinical research

ECONOMIC IMPACT RESULTING FROM A CONVERSION TO LEVALBUTEROL EVERY SIX TO EIGHT HOURS Robert S. Pikarsky RRT* Russell A. Acevedo MD Tracey Farrell RRT Wendy Fascia RRT Crouse Hospital, Syracuse, NY

Wednesday, November 2, 2005 COPD Pharmacologic Therapy, continued LEVALBUTEROL IN THE TREATMENT OF PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE James F. Donohue MD* Merdad Parsey MD Charles Andrews MD Tony D. D’Urzo MD Satyendra Sharma MD Kendyl Schaefer MS Raymond Claus MS Rudolf Baumgartner MD University of North Carolina at Chapel Hill, Chapel Hill, NC PURPOSE: GOLD guidelines recommend short-acting ␤2-agonists (SABAs) for symptom control across all severities of chronic obstructive pulmonary disease (COPD) and state that exacerbations affect quality of life and decrease health status. This study assessed the efficacy and safety of levalbuterol in treatment of patients with COPD. METHODS: This double-blind, placebo-controlled study evaluated patients with COPD who were ⱖ35 years of age, had FEV1 ⱕ65% predicted and ⬎0.70 L, a ⱖ15 pack-year smoking history, and a medical research council dyspnea scale score of ⱖ2. Stable doses of inhaled corticosteroids were allowed. Patients were randomized to nebulized levalbuterol 1.25mg (n⫽49), levalbuterol 0.63mg (n⫽53), racemic albuterol (RAC) 2.5mg (n⫽52), or placebo (n⫽55) TID for 6 weeks. Patients returned to clinic every 2 weeks for serial spirometry and assessment of dyspnea and rescue medication use (MDI SABA and ipratropium). COPD symptoms and exacerbations, adverse events (AEs), and dropouts were monitored throughout. At the 4-week visit only, response to study drug added to ipratropium bromide was assessed. RESULTS: Mean time-normalized AUC percent change FEV1 (AUC %⌬ FEV1) was significantly greater (p⬍0.001) following all active treatments relative to placebo. Concomitant administration of levalbuterol 1.25mg with ipratropium resulted in significantly greater (p⫽0.009) AUC %⌬ FEV1 than ipratropium with placebo. Rescue medication use increased in the RAC and placebo groups, was unchanged in the levalbuterol 0.63mg group, and significantly decreased in the levalbuterol 1.25mg group (p⫽0.02 vs RAC). RACtreated patients had the most COPD exacerbations and significantly more study withdrawals due to COPD exacerbations when compared with placebo (p⫽0.01). AE rates and beta-mediated side effects were lowest in the levalbuterol 0.63mg group, although all active treatments were well tolerated. CONCLUSION: In this study, levalbuterol was well tolerated, produced significant bronchodilation, and reduced rescue medication use. RAC was associated with significantly more study withdrawals due to COPD exacerbations compared with placebo. CLINICAL IMPLICATIONS: Levalbuterol may offer advantages in the treatment of patients with COPD. DISCLOSURE: James Donohue, Consultant fee, speaker bureau, advisory committee, etc. I am a paid consultant for Sepracor and serve on their Advisory Board. I have also participated as an investigator in several clinical trials for Sepracor, including the one presented here.

BRONCHODILATION IN ELDERLY PATIENTS WITH COPD: A SUB-GROUP ANALYSIS OF TWO RANDOMIZED CLINICAL TRIALS Umit Yegen MD* Denise Till MS Gregory P. Geba MD Novartis Pharmaceuticals Corporation, East Hanover, NJ PURPOSE: The efficacy of beta-agonists in elderly patients has received little attention to date. We performed an analysis based on pooled data from 2 large randomized, double-blind, multicenter clinical trials comparing Foradil® dry powder inhalation capsules 12␮g b.i.d. (FOR12) and 24␮g bid (FOR24) with placebo. METHODS: Of a total of 1634 COPD patients randomized, 598 were ⱖ65 years of age, comprising the elderly subgroup. Serial measurements of FEV1 were performed pre-dose, and 5, 15, 30 and 60 minutes and hourly through 12 hours post AM dose on the first day and after 3 months of treatment. RESULTS: Elderly patients tended to have slightly lower FEV1 at baseline. Clinically and statistically significant bronchodilation (⬎ 15% increase in FEV1) with both FOR doses compared to placebo was achieved throughout the 12 hour interval as shown by the area under the FEV1 curve (AUC; primary endpoint). These results were similar to the total study population (shown below). The incidence of adverse events (AEs) were also similar in the elderly subgroup compared to the full study population. CONCLUSION: FOR provided clinically significant and sustained increases in airflow in elderly patients with COPD that was similar in magnitude to the total study population with a similar tolerability profile.

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CLINICAL IMPLICATIONS: The elderly is a growing patient population that will have to studied carefully in the future, especially in the area of COPD. This study will give insight as to the efficacy and safety of formoterol in this subgroup.

AUC of FEV1 (L x hours)

Contrast FOR24 vs Placebo FOR12 vs Placebo FOR24 vs FOR12

Elderly Patients Trial 1

Elderly Patients Trial 2

Elderly Patients Pooled

N⫽394 1.701*

N⫽397 2.753*

N⫽598 2.251*

2.127*

2.459*

2.358*

-0.426

0.294

-0.108

All Age Groups Pooled N⫽1158** 2.430* 2.475* -0.045

* Indicates statistical significance at the 0.05 level DISCLOSURE: Umit Yegen, Employee

HIGH SATISFACTION WITH FLUTICASONE PROPIONATE/ SALMETEROL VIA DISKUS REPORTED DURING EXPERIENCE PROGRAM IN PATIENTS WITH COPD Stuart Stoloff MD* Steven Samuels MD Sidney Braman MD Christy Brown PharmD Donna Kerney PhD Michael Cicale MD University of Nevada School of Medicine, Reno, NV PURPOSE: An initial experience program was conducted in patients with COPD to collect patient reported feedback about newly initiated therapy with fluticasone propionate/salmeterol 250/50 (FSC). METHODS: Patients completed 2 surveys; one at baseline (before initiating therapy with FSC 250/50) and one targeted for 30 days after starting therapy with FSC 250/50). The first survey collected patient demographics, duration of COPD diagnosis, smoking history, and satisfaction with prior treatment. The second survey assessed patient perceived impact of FSC 250/50 on breathing, and convenience and satisfaction with FSC therapy. RESULTS: A total of 973 patients completed both surveys. Completers were mostly female (62%), and 87% were ⱖ 45 years of age. Two-thirds of the completers had been diagnosed with COPD for ⱖ 1 year. At baseline, 58% of the population used prescription medications prior to starting FSC 250/50. The most common medications were ipratropium/albuterol (37%) and salmeterol (27%). Patients reported satisfaction with their prior therapy (5.52 on a 9 point scale), but 22% of patients were quite dissatisfied (1-3 on a 9 point scale). The second survey, completed an average of 51 days after starting FSC 250/50, showed that patients perceived improvement in their breathing overall (6.82 on a 9 point scale) and had a high level of satisfaction with FSC 250/50 (7.76 on a 9 point scale). Less than 4% of patients were quite dissatisfied (⬍3 on a 9 point scale). FSC 250/50 was regarded as a very convenient medication (8.12 on a 9 point scale). CONCLUSION: Patients with COPD reported a high level of satisfaction with their treatment an average of 51 days after initiating therapy with FSC 250/50. CLINICAL IMPLICATIONS: High patient satisfaction with therapy may encourage increased compliance with therapy and therefore may result in improved outcomes. DISCLOSURE: Stuart Stoloff, Grant monies (from industry related sources) Received research grants from GlaxoSmithKline; Consultant fee, speaker bureau, advisory committee, etc. Received consultant fees from GlaxoSmithKline and serve on speaker bureau and advisory board for GlaxoSmithKline CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 COPD Pharmacologic Therapy, continued EFFECT OF THE BRONCHODILATOR INHALATION ON DIFFUSION CAPACITY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASES (COPD) Yaling Zhu MD* Haoyan Wang MD Xiaohong Chang Chaoyang Hospital, Beijing, Peoples Rep of China

CLINICAL IMPLICATIONS: Z intravenous augmentation therapy is associated with reconstitution of lower respiratory protease-anti-protease homeostasis similar to P. Median (range)

Bronchodilator inhalation Positive group Baseline After Negative group Baseline After

N

Dm ml/min/mm Hg

TLco %Pred

Vc ml

40 11.10⫾5.34

9.87⫾4.71 67.87⫾20.02

67.49⫾19.47 50.71⫾24.32

50.08⫾20.82

18 18

8.05⫾4.34 7.47⫾3.77

61.99⫾21.10 58.62⫾18.25

47.46⫾18.18 53.10⫾25.41

DISCLOSURE: Yaling Zhu, None.

LOWER RESPIRATORY TRACT BIOCHEMICAL EFFICACY OF INTRAVENOUS ADMINISTRATION OF A NEW FORM OF HIGHLY PURIFIED ALPHA1-ANTITRYPSIN L T. Spencer MD* David P. Pollock MD James M. Stocks MD Mark L. Brantly MD University of Florida College of Medicine, Gainesville, FL PURPOSE: To evaluate the biochemical efficacy and safety of a new source of highly purified, plasma derived alpha1-proteinase inhibitor (A1-PI) in individuals with alpha1-antitrypsin (AAT) deficiency. METHODS: A randomized, double-blind study compared Zemaira® (ZLB Behring LLC) [Z] with Prolastin® (Bayer Corporation) [P]. Patients received either Z or P (randomized 2:1) for 10 weeks by intravenous infusion (60 mg/kg functionally active A1-PI weekly). The P group was then crossed over to an open-label phase where all subjects received Z for 14 weeks. A subset of 15 patients with forced expiratory volume in 1 second ⱖ50% predicted underwent bronchoalveolar lavage. Antigenic AAT levels and AAT:neutrophil elastase (AAT:NE) complexes in the epithelial lining fluid (ELF) between baseline and Week 11 were measured by ELISA. RESULTS: Increases in ELF AAT levels were statistically significant in both treatment groups. Subjects receiving Z A1-PI had ELF values of 197.1 nM at baseline, increasing to 1125.5 nM after 10 weeks of treatment (p⬍0.0001), and those receiving P increased from 261.5 nM to 1192.5 nM (p⫽0.0121). Z A1-PI remained functionally active when delivered to the lung from the systemic circulation, as indicated by significant increases in ELF AAT:NE complexes from baseline to 11 weeks [2.8 nM to 66.8 nM (p⫽0.0012)]. Both Z and P were safely tolerated. CONCLUSION: The results indicate that both protein preparations are delivered to the lung in an equivalent manner after intravenous administration and that the exogenous protein is in a functional state capable of forming complexes with NE in the lung.

AUC variable (␮M*day) AUD0-21 AUD0-⬁

Z(A1-PI)

P(A1-PI)

129 (93 – 171) 140 (101 – 194) 134 (96 – 190) 147 (104 - 214)

Ratio of Z(A1-PI): P(A1-PI)

90% CI

92.4% 92.0%

88.5% - 96.5% 84.9% - 99.7%

DISCLOSURE: L Spencer, Consultant fee, speaker bureau, advisory committee, etc. LTS and MB have been scientific advisors to Aventis Berhing and Bayer Healthcare.; Other DPP and JMS have no financial disclosures.

COMPARABLE PHARMACOKINETIC PROPERTIES OF TWO ALPHA1-PROTEINASE INHIBITORS AFTER SINGLE THERAPEUTIC DOSES James M. Stocks MD* Mark Brantly MD Alan Barker MD Friedrich Kueppers MD Charlie Strange MD James F. Donohue MD Robert Sandhaus MD University of Texas Health Center at Tyler, Tyler, TX PURPOSE: This study evaluated the bioavailability of a new preparation of alpha1-proteinase inhibitor (A1-PI), Zemaira® (ZLB Behring LLC, [Z(A1-PI)]), with that of Prolastin® (Bayer Corporation, [P(A1-PI)]) after single intravenous infusions. METHODS: This was a double-blind, randomized, controlled, 2x2 crossover study comparing a single dose of Z(A1-PI) and P(A1-PI) (60 mg per kg bodyweight). Patients with AATD were randomized (n⫽9 per group) to Z(A1-PI) followed by P(A1-PI), or P(A1-PI) followed by Z(A1-PI), with a washout period between infusions of 35 days. Bioavailability was measured by two baseline-adjusted area-under-the-curve (AUC) variables: area-under-the observed data up to Day 21 (AUD0-21) and AUD0-⬁. The ratio of mean AUC variables (Z(A1-PI):P(A1-PI)) with 90% confidence intervals (CI) was calculated. Standard pharmacokinetic (PK) parameters Cmax, tmax, terminal t1⁄2, mean residence time, total clearance, and steady-state volume of distribution were also compared. RESULTS: The bioavailability of Z(A1-PI) was statistically non-inferior to P(A1-PI) as shown by the lower limit of the 90% CI for the mean AUC ratio (Z(A1-PI):P(A1-PI)) being greater than 80% for AUD0-21 and also for AUD0-⬁ (Table). Furthermore, the PK profile of functional A1-PI levels following Z(A1-PI) and P(A1-PI) administration showed no clinically relevant differences in terms of mean (SD) Cmax (39.9⫾5.3 vs. 41.6⫾8.0 ␮M), tmax (0.7⫾0.3 vs. 1.5⫾1.4 hours), terminal t1⁄2 (4.5⫾3.1 vs. 4.8⫾1.2 days), mean residence time (5.9⫾3.3 vs. 6.1⫾1.3 days), total clearance (636⫾115 vs. 583⫾108 mL/day) or steady-state volume of distribution (3.6⫾1.3 vs. 3.5⫾0.8 L). The PK profile was reflected by that of antigenic A1-PI levels. CONCLUSION: A single therapeutic dose of Z(A1-PI) was comparable and statistically not inferior to P(A1-PI) in bioavailability. There were no differences between Z(A1-PI) and P(A1-PI) in standard pharmacokinetic parameters. CLINICAL IMPLICATIONS: Since Z(A1-PI) is statistically not inferior to P(A1-PI) in bioavailability, a weekly infusion of Z(A1-PI) 60 mg per kg body weight is expected to augment and maintain A1-PI serum levels above the protective threshold of 11 ␮M, and increase A1-PI levels in the lower lung, to a similar extent to that reported with P(A1-PI). DISCLOSURE: James Stocks, None.

HEALTH-RELATED QUALITY OF LIFE (HRQOL) IN PATIENTS WITH ALPHA1-ANTITRYPSIN (AAT) DEFICIENCY AND EFFECT OF AUGMENTATION THERAPY: PRELIMINARY RESULTS Karen C. Chung PharmD Matthew E. Borrego PhD Jennifer Short BS* Loretta Kristofek RN Nancye Buelow David M. Gelmont MD University of New Mexico Health Sciences Center, Albuquerque, NM PURPOSE: AAT deficiency (AATD), a common genetic disorder which predisposes subjects to early onset emphysema, has been associated CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: To evaluate the effect of bronchodilator inhalation on the diffusion capacity in patients with COPD. METHODS: 58 COPD patients were tested with bronchodilator inhalation (Albuterol 200ug) and divided into 2 groups according to the response of FEV1 : Positive if FEV1 increase ⱖ15% and ⬎200ml, Negative if FEV1 increase ⬍15% and ⬍200ml. The transfer factor of the lung for carbon monoxide (TLco), pulmonary membrane diffusion capacity (Dm) and pulmonary capillary blood volume (Vc) were measured in baseline and after Albuterol inhalation and compared subsequently in each group. RESULTS: 40 COPD patients were found positive and 18 were negative in the Albuterol inhalation test. No significant differences were found in Dm, TLco and Vc between baseline and after Albuterol inhalation in either group. CONCLUSION: Bronchodilator inhalation did not affect diffusion capacity in COPD patients. CLINICAL IMPLICATIONS: Bronchodilator inhalation improves symptoms of COPD patients mainly by way of the improvement of ventilation rather than the improvement of diffusion capacity.

Wednesday, November 2, 2005 COPD Pharmacologic Therapy, continued with significant decrease in HRQoL over time. Chronic AAT augmentation therapy slows the progression of emphysema, however, its effect on HRQoL has not been clearly delineated. The purpose of our study is to evaluate HRQoL in AAT deficient patients receiving augmentation therapy and to compare the HRQoL scores of AAT deficient patients to the general population. METHODS: To date, 68 patients with AATD receiving AAT augmentation therapy have been enrolled in this longitudinal observational patient outcomes study. Interviewer-administered questionnaires, which collected demographic, clinical outcomes, healthcare resource utilization, and HRQoL [Short Form-36 Health Survey version 2 (SF-36)] data were administered at baseline (start of augmentation therapy), and at 6-month intervals. Six-month data has been collected on 36 patients. RESULTS: Analysis of 6-month HRQoL scores indicate no clinically important differences in the eight SF-36 scales and Physical and Mental Component Scores (Figure). Patients with AATD demonstrated clinically important decreases in HRQoL Physical Functioning scores compared to the general population, changes in HRQoL mental health scale scores were not clinically important. CONCLUSION: SF-36 scale scores remain stable from baseline to 6-month follow-up indicating a lack of significant disease progression during that timeframe. Trends toward improved HRQoL mental health scores from baseline to 6 months may be indicative of satisfaction with AAT augmentation therapy, resilience in this group of patients with regard to coping strategies and their disease, and/or Hawthorne effect. Overall, AAT deficient patients are disproportionately affected with regard to HRQoL Physical Functioning compared to the general population. CLINICAL IMPLICATIONS: Results suggest patients with AATD have significantly compromised physical health. Although HRQoL appeared stable from baseline to 6-month follow-up, additional longitudinal data are needed to assess the long-term stability of the HRQoL scores. HRQoL assessment can be used as an additional measure of disease severity and progression in AAT deficient patients.

DISCLOSURE: Jennifer Short, Grant monies (from industry related sources) MEB and JS received a grant from Baxter BioScience to conduct data entry and analysis.; Employee KCC and DMG - Baxter BioScience.

DIFFERENCES IN MICROHETEROGENEITY AND NONTHERAPEUTIC PROTEIN CONTENT OF THREE COMMERCIAL PREPARATIONS OF PURIFIED HUMAN ALPHA1-PROTEINASE INHIBITOR Friedrich Kueppers MD* Utpal Patel MS Temple University School of Medicine, Philadelphia, PA PURPOSE: Three commercially available preparations of alpha1proteinase inhibitor (A1-PI) are derived from human plasma but differ in the purification steps employed during manufacture, leading to differences in purity. As little is known about the effect of purification on biochemical composition of the final active substance, we compared their microheterogeneity and non-therapeutic protein content. METHODS: Zemaira® (ZLB Behring LLC) [Z], Prolastin® (Bayer Corporation) [P] and Aralast® (Baxter Inc) [A] were evaluated. Isoelectric focusing (Am J Hum Genet 1978; 30: 359-65) was performed to evaluate the relative proportion of different isoforms (M2, M4, M6) of A1-PI relative to historical values for normal serum (Scand J Clin Lab Invest 1969; 23: 97-103). Double diffusion experiments were performed to detect non-therapeutic serum proteins.

262S

RESULTS: The relative protein concentrations (SD) of the M2, M4 and M6 isoforms of Z were: 31.1 (4.2), 40.0 (5.0) and 19.8 (3.3) compared with 11 (2.3), 48.7 (1.5) and 40.4 (2.4) for normal serum. The corresponding values for P were: 12.6 (2.3), 39.1 (4.8), 48.3 (5.5) and those for A were: 13.0 (3.1), 48.0 (5.2) and 38.5 (4.2). Non-therapeutic serum proteins in all three preparations included alpha1-antichymotrypsin and antithrombin III. Albumin and transferrin were detected in A and P but not Z. Alpha1-acid glycoprotein was detected in Z but not A or P. CONCLUSION: Different purification processes appear to affect the microheterogeneity of A1-PI preparations: Z and P, but not A, displayed similar isoform content to that in normal serum. The absence of albumin in Z may account for its known high purity and solubility. CLINICAL IMPLICATIONS: The biochemical difference between isoforms of A1-PI is thought to reside in the carbohydrate portion, but other unidentified biochemical differences may lead to changes in isoelectric point. A1-PI glycoforms contain side chains with varying ratios of terminal moieties that could affect A1-PI tissue distribution and half-life. Long-term exposure to non-therapeutic proteins in A1-PI preparations may induce immune-mediated adverse events, as suggested by a previous study (Chest 2003; 123: 1425-34). Both findings warrant further investigation. DISCLOSURE: Friedrich Kueppers, Grant monies (from industry related sources) FK and UP have received funding from the Arlene Meth Fund, Baxter and ZLB Behring. EFFICACY AND ANTI-INFLAMMATION ACTIVITY OF A SELECTIVE PHOSPHODIESTERASE-4 INHIBITOR CILOMILAST IN TREATMENT OF COPD Changzheng Wang PhD* Yunxi Song PhD Xuiqing Liao BA Qi Li PhD Jingping Wang Zhiqiang Zhao Xinqiao Hospital,, Chongqing, Peoples Rep of China PURPOSE: To study the efficacy and anti-inflammation action of a selective phosphodiesterase-4 inhibitor cilomilast in treatment of COPD. METHODS: 38 patients were randomized into a double-blind, placebo-controlled, parallel-group trial. Twenty-four patients were randomized to treat by cilomilast 15mg b.i.d., for 24 weekd, and fourteen patients to placebo b.i.d.. Pulmonary function tests and symptoms such as cough, sputum, breathlessness were assessed at every visit. The levels of IL-8, TNF-␣, LTB4 and IL-6 induced sputum were assessed using ELISA. RESULTS: After treatment, the score of dyspnea, cough and sputum in the cilomilast group improved significantly, but there no difference in the control group.Though there was no significant change in FEV1 and FEV1% predicted after treatment in the cilomilast group. But compared with baseline, significant decrease in FEV1 was observed in the control group after 24 weeks of treatment (p⬍0.01). Also, no significant change in RV and FRC was observed in the control group after treatment. However, RV and FRC was significantly improved in the cilomilast group (p⬍0.01). After the treatment, significant decrease was observed for the level of IL-8, TNF-␣, LTB4 and IL-6 in induced sputum in cilomilast group (p⬍0.01) and there was no significant difference in control group. CONCLUSION: Cilomilast has clinical efficacy on COPD and could modify decline of pulmonary function for COPD, which effects may be due to its anti-inflammation activity. CLINICAL IMPLICATIONS: Cilomilast as a new selective phosphodiesterase-4 inhibitor might be an effective long-term treatment for COPD. DISCLOSURE: Changzheng Wang, Grant monies (from industry related sources).

COPD: Assessment of Comorbidity 12:30 PM - 2:00 PM NOSOCOMIAL INFECTIONS AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE Prashant S. Borade MD* Daniel K. Lee MD Department of Respiratory Medicine, Ipswich Hospital, Ipswich, Suffolk, England, United Kingdom PURPOSE: Chronic obstructive pulmonary disease (COPD) predisposes an individual to community-acquired infections. However, the relationship between COPD and nosocomial infections is less clear. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 COPD: Assessment of Comorbidity, continued METHODS: A prospective study was conducted in 499 consecutive patients admitted to the intensive care unit without clinical or laboratory evidence of community-acquired infections over a 6-month period. RESULTS: The incidence of nosocomial infections was not significantly different comparing patients with COPD (26%) and without COPD (20%). Mortality was 47% in ventilated patients. CONCLUSION: Patients with COPD are no more susceptible to develop nosocomial infections than patients without COPD. CLINICAL IMPLICATIONS: The acquisition of nosocomial infections is independent of COPD. DISCLOSURE: Prashant Borade, None.

DOPPLER TISSUE IMAGING IN THE EVALUATION OF RIGHT VENTRICULAR FAILURE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE Vasiliy Pyankov MD* Yulia Chuyasova MD Kirov Medical Academy, Kirov, Russia

CHRONIC OBSTRUCTIVE PULMONARY DISEASE INDUCED RIGHT VENTRICULAR DIASTOLIC DYSFUNCTION AND/OR FAILURE: FACT, FICTION OR A DILEMMA FOR NEW THERAPEUTIC INTERVENTIONS? Nestor J. Angomachalelis MD* Eva Serasli MD Alex Hourzamanis MD John N. Angomachalelis MD Nikos Salem MD Aristotle University of Thessaloniki, “George Papanikolaou” General Hospital, Thessaloniki, Greece PURPOSE: Up-to-date right ventricular diastolic function in Chronic Obstructive Pulmonary Disease (COPD) patients (pts)has not been thoroughly investigated. Thus, there is always a great dilemma to be recognised, whether right ventricular diastolic dysfunction (RVVD)and/or failure, related to COPD pathophysiology, is, indeed, a fact, fiction or a dilemma for new therapeutic interventions. METHODS: Fourty three consecutive pts with COPD and 14 age and heart rate-matched controls underwent M-Mode and Acoustic Quantification (AQ) echocardiographic evaluation of right ventricular systolic (RVS) and diastolic function, Doppler transtricuspid flow estimation and lung function tests (spirometry and blood gases analysis), as well as radionuclide ventriculography with Technetium-99m-pyrophosphate (Multigated Acquisition, MUGA).Pts were classified in three groups:

PREVALENCE AND RISK FACTORS OF LEFT VENTRICULAR DIASTOLIC DYSFUNCTION IN COPD PATIENTS Parthasarathi Bhattacharyya MD* Sushmita RoyChowdhury MD Dipabali Ghosh (Acharya) PhD Saikat Nag MD Dipankar Sarkar MD Institute of Pulmocare and Research, Kolkata, India PURPOSE: Left ventricular diastolic dysfunction, though known in COPD patients, is quite frequent in advanced COPD sufferers to our experience. We studied the presence of diastolic dysfunction in 43 (GOLD stage IIb and III) patients and its association with several clinical variables that appeared important from our experience in an OPD based study. METHODS: This was a cross sectional survey of patients in a tartiary clinic using the following variables: easy fatiguability, disproportionate tachycardia, poor clinical response to treatment, poor exercise tolerence, FEV1, cardiothoracic ratio, and cardiomegaly. The known predisposing factors for diastolic dysfunction as ischemic heart disease and hypertension were recorded. Thereafter, the patients underwent 2D doppler echocardiography to detect the presence of diastolic dysfunction. Finally, the association of diastolic dysfunction was evaluated with the variables of interest. RESULTS: Cardiothoracic ratio greater than 0.4, cardiomegaly and subjective easy fatiguability were found to be significantly associated with diastolic dysfunction. Low FEV1 (less than 35% predicted) and disproportionate tachycardia were the other two risk factors though they could not achieve statistical significance in explaining diastolic dysfunction. CONCLUSION: Diastolic dysfunction appear in about 70 % of advanced COPD patients independent of the presence of ischemia or hypertension. Cardiothoracic ratio greater than 0.4 and easy faiguability are the two independent predictors of diastolic dysfunction in advanced COPD sufferers. However, further evaluation is necessary to unveil the COPD-diastolic dysfunction association. CLINICAL IMPLICATIONS: Intervention of diastolic dysfunction in advanced COPD patients may help in ameliorating symptoms as dyspnoea or easy fatiguability with improvement in the functional ability. DISCLOSURE: Parthasarathi Bhattacharyya, None. INTENSIVISTS’ PERCEPTIONS OF ANEMIA IN INTENSIVE CARE UNIT (ICU) PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD): A SURVEY Marya Zilberberg MD* Michele Pisano PharmD Ortho Biotech Clinical Affairs, LLC, Bridgewater, NJ PURPOSE: To understand the hemoglobin (Hb) thresholds US Intensivists (ICUMDs) use to assess and manage anemia in critically ill COPD patients (ICU-COPD). METHODS: A survey was conducted to identify Hb thresholds representing presence and severity of anemia in ICU-COPD. RESULTS: Ninety-nine ICUMDs, who care almost exclusively for adult patients, completed the survey at a specialty society meeting in 2005. All were either certified or eligible in Critical Care, with the specialty of Pulmonology in 31%, Internal Medicine 45%, Surgery/Trauma 20%, CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: Right ventricular (RV) failure associated with pulmonary artery hypertension (PAH) in patients with chronic obstructive pulmonary disease (COPD) has important prognostic implications. The noninvasive evaluation of the RV failure in patients with COPD still represents a problem. The purpose of this study was to evaluate RV failure in patients with COPD using pulsed wave Doppler tissue imaging (DTI). METHODS: 46 males with COPD (mean age 57⫾8 years; mean FEV1 30⫾8%) were studied. All patients underwent clinical and laboratory examinations. RV wall thickness, RV end-diastolic diameter, RV systolic and diastolic functions were evaluated with two-dimensional echocardiography. The tricuspid inflow profile (E, A, E/A, DT) and hepatic vein flow velocity (S, D, A) were measured with pulsed Doppler. Peak velocities of the tricuspid annular motion (Sa, Ea, Aa, Ea/Aa) were derived from pulsed DTI. RESULTS: RV systolic dysfunction (RV ejection fraction ⬍ 45% and Sa ⬍ 11.5 sm/s) was detected in 13% of cases. RV diastolic dysfunction was detected in 100% of cases. Impaired relaxation pattern of tricuspid inflow (E/A⬍1.0 and Ea/Aa⬍1.0) was detected in 69.6%, pseudonormal pattern - in 17.4% (2.0⬍E/A⬎1.0 and Ea/Aa⬍1.0), restrictive pattern - in 13% (E/A⬎2.0). There were significant correlations between tricuspid annular motion (Ea/Aa) and tricuspid inflow profile (E/A) (r⫽-0.56; p⫽0.019), RV wall thickness (r⫽0.72; p⫽0.001), RV end-diastolic diameter (r⫽0.70; p⫽0.001) and RV ejection fraction (r⫽0.70; p⫽0.001); between systolic pulmonary artery pressure and hepatic vein flow velocity (retrograde A velocity) (r⫽0.60; p⫽0.007). CONCLUSION: Our study confirmed high prevalence of RV systolic and diastolic dysfunction in patients with COPD. Physicians should detect RV failure in patients with COPD. CLINICAL IMPLICATIONS: The complex echocardiography evaluation with DTI provides a simple, rapid and noninvasive tool for diagnosis of RV failure in patients with COPD. DISCLOSURE: Vasiliy Pyankov, None.

Group A (mean FEV1⬎70% predicted), Group B (50%⬍FEV1⬍69%), Group C (FEV1⬍50%), according to the ERS Consensus Statement. RESULTS: It was resulted that right ventricular systolic dysfucntion (RVSD)in COPD pts was found in 16/43 pts(37.2%) by AQ (FAC⬍39%)and in 13/43 pts (30.23%) by MUGA(RVEF⬍45%).Transtricuspid diastolic flow evaluation by Dopper showed diastolic abnormalities of relaxation type in 23 pts (53.4%), whereas AQ diastolic indices indicated the same pattern of RVDD in 20 pts (43.5%).Correlations of diastolic AQ and Doppler indices with lung function tests and blood gases abnormalities as well as with M-Mode indices of cor pulmonale were statistically significant. CONCLUSION: We conclude, that, altough RVS function remains normal in the first two stages of COPD, RVDD becomes evident earlier in the progress of the second and mainly the third stage of the disease in conjunction with the development of respiratory impairment and chronic cor pulmonale, followed very frequently by clinical symptoms and signs of right ventricular failure. Furthermore, RVDD is statistically proven to play an important role in the pathophysiology of right ventricular failure. CLINICAL IMPLICATIONS: Is it consequently the time for establishing new therapeutic interventions targeting the early asymptomatic and symptomatic stages of the disease, including the RVDD itself?. DISCLOSURE: Nestor Angomachalelis, None.

Wednesday, November 2, 2005 COPD: Assessment of Comorbidity, continued Anesthesia 18%, and other 8%. 30% have been in practice for ⬍5 years, with 41% and 29% in practice for 5-15 years and ⬎15 years, respectively. 48% work in a university-affiliated hospital, and 42% and 34% are affiliated with hospitals with ⬎500 total and ⬎50 ICU beds, respectively. Over 70% of responders see ⬎80% of their patients in a hospital setting, and ⬎1/3 spend ⬎80% of their time in the ICU. Of the mean 36⫾27 ICU pts seen/week, on the average 13⫾14 (36%) are estimated to have COPD, with 9⫾9 (69%) on mechanical ventilation (MV). Over 2/3 of the responders didn’t consider even mild anemia to be present above an Hb threshold of 10g/dL, and nearly 3/4 deemed severe anemia to be present only at Hbⱕ7g/dL. Despite this, over 50% utilize Hbⱖ8g/dL as a transfusion threshold for ICU-COPD, regardless of their MV status. Interestingly, 58% and 59% of the responders identified Hbⱖ10g/dL as the optimal Hb level in these patients off and on MV, respectively. CONCLUSION: Despite the accepted WHO definition of anemia (men, Hb⬍13g/dL; women, Hb⬍12g/dL), the majority of ICUMDs surveyed do not consider anemia to be present in ICU-COPD until the Hb is ⱕ10g/dL, and consider severe anemia to be present only at Hbⱕ7g/dL. CLINICAL IMPLICATIONS: Consistent with the findings of the recent Canadian survey by Hebert et al (Crit Care Med 2005), in the US much like in Canada, utilization of 7g/dL as the transfusion threshold (Hebert et al, NEJM 1999) is far from ubiquitous. DISCLOSURE: Marya Zilberberg, Employee Marya Zilberberg, MD is an employee of Ortho Biotech Clinical Affairs, LLC. Michele Pisano, PharmD, is an employee of Ortho Biotech Products, LP. ANEMIA IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD): ASSOCIATION WITH SUPPLEMENTAL O2 USE AND HOSPITALIZATIONS Marya Zilberberg MD* Claudia Cote MD Samir H. Mody PharmD Bartolome Celli MD Ortho Biotech Clinical Affairs, LLC, Bridgewater, NJ PURPOSE: We recently demonstrated that anemia in COPD patients is associated with diminished 6MWD and increased breathlessness and mortality1,2. A substantial percentage of annual expenditure in COPD is due to O2 utilization and hospitalizations. It is not known if anemia is associated with increased O2 utilization or hospitalization. We characterized the association of anemia with O2 utilization and hospitalization rate and duration in COPD. METHODS: A retrospective analysis of data collected prospectively on 683 patients between 1/97 and 6/02 in a VA Pulmonary clinic for BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index validation3 was conducted. Anemia was defined as Hb ⬍13g/dL. All values are expressed as mean (SD). P values were derived using a 2-sided Student’s t-test or Chi-square statistic where appropriate. RESULTS: In this sample of 677 patients with known Hb values, anemia (A⫹) was present in 116 (17%) patients. The Table below

Age (yrs) FEV1%predicted PaO2 (torr) BMI (kg/m2) Charlson Comorbidity index, points BODE index, points Supplemental O2 % on any Flow (L/min) Hospitalizations % hospitalized # hospitalizations/pt Days hospitalized/pt Follow-up (mos)

THE PREVALENCE OF POLYCYTHEMIA IN A CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) COHORT Claudia Cote MD* Marya Zilberberg MD Samir H. Mody PharmD Bartolome Celli MD Bay Pines VAMC, Bay Pines, FL PURPOSE: Although thought to occur frequently, the actual prevalence of polycythemia among patients with COPD and its effect on outcomes in the current treatment environment is unknown. We characterized polycythemia prevalence and its association with outcomes in COPD. METHODS: We retrospectively analyzed data collected prospectively on 683 patients between 1/97 and 6/02 in a VA Pulmonary clinic for BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index validation1. Polycythemia (P⫹) was defined as Hbⱖ17 g/dL in men and ⱖ15 g/dL in women2. All values are expressed as percentages or mean (SD). P values were derived using a 2-sided Student’s t-test or Chi-square statistic where appropriate. RESULTS: In this sample of 677 patients with known Hb values, polycythemia was present in 36 (5.3%) patients. The Table below compares P⫹ to non-polycythemic (P-) patients. CONCLUSION: Polycythemia is uncommon in COPD, occurring in ⬃5% of patients, and is not associated with greater hypoxemia or any other important clinical expression of the disease. CLINICAL IMPLICATIONS: Additional studies are warranted to evaluate the prevalence and effects on outcomes of polycythemia in COPD patients.1Celli BR et al. N Engl J Med 2004;350:1005-12 2Harrison’s online, accessed 11-12-04 http://www3.accessmedicine.com/ content.aspx?aID⫽58150&searchStr⫽polycythemia.

A⫹ (n⫽116)

A(n⫽561)

p Value

P⫹ (n⫽36) P- (n⫽641) p Value

72.8 (9.3) 43.17 (16.95) 72.1 (13.3) 27.1 (6.7) 6.5 (3.5)

69.5 (8.8) 42.07 (17.26) 71.9 (11.9) 26.3 (5.8) 4.8 (2.4)

0.0003 0.5 0.9 0.2 ⬍0.0001

5.3 (2.6)

4.7 (2.4)

0.0128

38 2.6 (0.7)

34 2.6 (0.9)

0.37 0.97

47 1.3 (2.2) 13.4 (30.3) 33.9 (21.7)

38 0.9 (1.7) 7.8 (21.7) 37.2 (22.1)

Hb (g/dL) 17.5 (0.8) 14.3 (1.5) ⬍0.0001 On supplemental O2 (%) 31 34 0.62 Age (yrs) 68.7 (9.5) 70.2 (9.0) 0.35 F/U time (mos) 34.3 (20.4) 36.7 (22.2) 0.52 FEV1% 42.7 (18.3) 42.2 (17.2) 0.88 Room air PaO2 (torr) 70.4 (11.3) 72.0 (12.2) 0.44 6MWD (m) 339.1 (131.1) 313.5 (125.6) 0.24 MRC dyspnea 2.4 (0.8) 2.6 (0.9) 0.21 Charlson co-morbidity 4.8 (2.1) 5.1 (2.7) 0.56 27.8 (4.6) 26.4 (6.0) 0.16 BMI (kg/m2) BODE index 4.4 (2.4) 4.9 (2.5) 0.30 2-year respiratory mortality (%) 31 27 0.82 2-year all-cause mortality (%) 36 35 0.93

0.06 0.03 0.02 0.1511

compares A⫹ to non-anemic (A-) patients. There was no difference between the groups with regard to the prevalence of O2 utilization or the

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mean O2 flow. There was a trend toward increased incidence of hospitalizations in the A⫹ group, and A⫹ patients had statistically significantly more hospitalizations per patient, as well as a longer hospitalization time over similar follow-up period. CONCLUSION: Although there was no difference between the groups in their supplemental O2 utilization, hospital utilization was significantly higher in the A⫹ than the A- group. CLINICAL IMPLICATIONS: Economic impact of anemia in COPD patients needs to be evaluated. 1Cote C, et al. Anemia Is Associated with Increased Breathlessness and Decreased 6-Minute Walk Distance in COPD Patients. Proc Am Thorac Soc 2005;2:A498. 2Cote C, et al. Anemia Is a Predictor of Mortality in Patients with COPD. Proc Am Thorac Soc 2005;2:A890. 3Celli BR, et al. N Engl J Med. 2004;350:1005-1012. DISCLOSURE: Marya Zilberberg, Grant monies (from industry related sources) These analyses were supported by Ortho Biotech Clinical Affairs, LLC.; Employee Marya Zilberberg, MD and Samir H. Mody, PharmD are employees of Ortho Biotech Clinical Affairs, LLC.

DISCLOSURE: Claudia Cote, Grant monies (from industry related sources) These analyses were supported by Ortho Biotech Clinical Affairs, LLC.; Employee Marya Zilberberg, MD and Samir H. Mody, PharmD are employees of Ortho Biotech Clinical Affairs, LLC. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 COPD: Assessment of Comorbidity, continued THE PENETRATION/ASPIRATION RISK IN PATIENTS PRESENTING WITH AN ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) Laura J. Carney MA Suzanne Sheppard PhD Karen F. Laframboise MD* University of Saskatchewan, Saskatoon, SK, Canada

SEX DIFFERENCES IN THE PREVALENCE OF PSYCHIATRIC DISORDERS AND PSYCHOLOGICAL DISTRESS IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE IN A CANADIAN SAMPLE Catherine Laurin BSc* Kim L. Lavoie PhD Simon Bacon PhD Philippe R. Ste´benne BSc Gilles Dupuis PhD Andre´ Cartier MD Guillaume Lacoste BA M Julien MD Manon Labrecque MD Sacre´-Coeur Hospital, Pneumology Research, Montreal, PQ, Canada PURPOSE: Research has documented a high prevalence of psychiatric disorders in patients with chronic obstructive pulmonary disease (COPD). In general, psychiatric disorders are more common in women than in men. However, few studies have evaluated sex differences in the prevalence of psychiatric disorders in COPD patients. The present study evaluated the prevalence of mood and anxiety disorders in 62 women and 54 men with documented, stable COPD. METHODS: Patients (n⫽116) underwent a sociodemographic and medical history interview, followed by a structured psychiatric interview (ADIS-IV). All patients underwent spirometry and completed a battery of questionnaires measuring psychological distress and quality of life. RESULTS: A total of 57% of women vs. 35% of men met criteria for one or more anxiety disorder (Chi-Square⫽5.70, p⬍.01), and 31% of women vs. 14% of men met criteria for one or more mood disorder (Chi-Square ⫽4.03, p⬍.05). The most common anxiety disorder among patients was panic disorder, affecting 27% of women and 11% of men (Chi-Square ⫽4.83, p⬍.05). The most common mood disorder was major depression, affecting 18% of women and 6% of men (Chi-Square ⫽6.70, p⬍.05). Women had significantly higher anxiety sensitivity and depression scores compared to men (p’s ⬍.01). Women also reported being less confident in their ability to control respiratory symptoms compared to men (p⬍.05) and perceiving themselves as more limited in their activities as a result of their disease (p⬍.01), despite having comparable dyspnea scores (p⫽.08).There were no differences in exacerbation rates (last year)

INDEPENDENT CONTRIBUTIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND ABDOMINAL AORTIC ANEURYSM TO MORTALITY RISK Dmitry Lvovsky MD* Ashok Fulambarker MD Mark E. Cohen PhD Sinan A. Copur MD Sunita Kumar MD Rosalind Franklin University of Medicine and Science, Chicago Medical School, North Chicago, IL PURPOSE: To determine mortality in patients with aortic abdominal aneurysm (AAA) and chronic obstructive pulmonary disease (COPD) as compared to patients with only AAA. METHODS: A retrospective cross-sectional study evaluated mortality for the four combinations of AAA (⫹ or -) and COPD (⫹ or -), using patient hospital records identified by ICD-9 codes. Other factors recorded and considered for predictive modeling included: coronary artery disease, peripheral arterial occlusive disease, hypertension, smoking, pulmonary function tests, hypercholesteremia, size and repair status of AAA. RESULTS: Data were available for 460 subjects (455 males), with 115 subjects in each of four groups defined by the presence or absence of COPD and AAA. Mean ages (SD) were 75.12 (6.41), 76.49 (6.61), 77.70 (5.64), and 76.60 (5.92) for COPD-/AAA-, COPD⫹/AAA-, COPD-/AAA⫹, and COPD⫹/AAA⫹ groups, respectively (P⫽0.018, ANOVA, with only the oldest and youngest groups being significantly different, Tukey). Among these groups, mortality rates were 6.96, 66.96, 34.78, and 69.57 percent, respectively.Preliminary analysis, using logistic regression, found that COPD and AAA (P⬍0.0001) and their interaction (P⫽0.0002) were significant predictors of the binary mortality outcome. These effects were consistent when other factors were included in the model. The Table shows odds ratios for various grouping arrangements. The group-wise comparisons suggest that COPD had a significant effect on mortality in the absence (OR⫽27.10) or presence of AAA (OR⫽4.29), while AAA had a significant effect on mortality in the absence of COPD (OR⫽7.13) but not in its presence (OR⫽1.13). CONCLUSION: Among patients positive for AAA, the risk of death is significantly greater when COPD is present. Among patients positive for COPD, the risk of death is not significantly raised by AAA. This outcome might due to a mortality ceiling effect observed for COPD but not for AAA. CLINICAL IMPLICATIONS: Patients with AAA should be screened for COPD, because of the latter’s profound effect on mortality. Future studies on recognition and management of concurrent COPD and AAA seem warranted, with a potential to extend survival in this high-risk population.

DISCLOSURE: Dmitry Lvovsky, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

PURPOSE: To determine the incidence of penetration/aspiration in patients presenting with a COPD exacerbation. Is there a relationship between the severity of tracheal penetration or aspiration and spirometry in patients with a COPD exacerbation?. METHODS: Prospective study of twenty-one consecutive and eligible patients with the diagnosis of an acute COPD exacerbation admitted to a university based tertiary care hospital. Patients underwent a videofluroscopic evaluation of swallowing and spirometry. consistencies were administered, for purposes of diet recommendation only, analysis was done only with thin liquid consistency (100 mls total volume swallowed). Spirometry and the swallowing assessment were carried out during the acute hospital admission. An eight-point Penetration/Aspiration Scale developed by Rosenbek et al (1996) was used to quantify the presence and severity of tracheal penetration or aspiration. Spirometry measures included FEV1, FVC and the FEV1/ FVC, all values met ATS standards. RESULTS: Penetration (contrast entering the trachea but not passing the vocal cords) was seen in 10/21 patients. Aspiration or silent aspiration occurred in 10/21 patients. One patient had no contrast enter the trachea. There was no obvious relationship between the severity ratings of penetration/aspiration and the severity of the airflow obstruction seen on spirometry. CONCLUSION: The incidence of penetration/aspiration in patients presenting with COPD exacerbation is of significance. There does not appear to be a correlation between the severity of the airflow obstruction and the degree degree of penetration or aspiration of thin fluids in the population. CLINICAL IMPLICATIONS: This study implies that a significant number of patients presenting with a COPD exacerbation have evidence of unrecognized penetration/aspiration. Consideration of the implications on dietary recommendations may need to be considered in this patient population. DISCLOSURE: Karen Laframboise, None.

or forced expiratory volume in 1 second (FEV1, % predicted) between women and men. CONCLUSION: Compared to prevalence rates in the general population (1-13%), results indicate that psychiatric disorders are at least three times higher in COPD patients, and that rates are nearly three times as high in women than in men. Women also show greater psychological distress, worse perceived control of symptoms and worse disease-related quality of life. CLINICAL IMPLICATIONS: Greater efforts should be made to identify and treat psychiatric disorders in COPD patients, particularly in women. DISCLOSURE: Catherine Laurin, None.

Wednesday, November 2, 2005 Cardiac Surgery 12:30 PM - 2:00 PM NITRIC OXIDE DONOR-INDUCED, PERSISTENT INHIBITION OF CELL ADHESION MOLECULE EXPRESSION AND NUCLEAR FACTOR KAPPAB ACTIVATION IN ENDOTHELIAL CELLS Thomas Waldow MD* Wolfgang Witt PhD Elvis Weber Michael Knaut MD Klaus Matschke MD Herzzentrum Dresden, Dresden, Germany PURPOSE: Our previous studies using a porcine model have shown that inhalation of NO for a brief period just before the onset of ischemia can protect the lung against ischemia/reperfusion (I/R) injury later on. The protection persisted throughout 90 min ischemia of the left lung and a reperfusion phase of up to 5 h. Here we present first results of the attempt to investigate the underlying mechanisms of “NO preconditioning” by an in vitro approach using endothelial cells. Since NO pretreatment was especially effective in blocking I/R-induced inflammation, the study aims at the cytokine-dependent and NFkappaB-mediated expression of cell adhesion molecules (CAM). METHODS: Human umbilical vein endothelial cells (HUVEC) were exposed to the NO donor, SNAP, for 5 min to 60 min. After washout, cells were cultured in reagent-free medium for up to 16 h before the CAM ICAM, VCAM, and E-selectin - were induced by exposure to TNFalpha or IL-1beta. The CAM on the cell surface were quantified by cell ELISA, and the level of the inhibitor of NFkappaB activation, IkappaBalpha, by Western blotting. The relevance of the cGMP pathway was tested by using the guanylyl cyclase inhibitor, ODQ, and the cGMP analogue, 8-BrcGMP. The dependence on NFkappaB was verified by the inhibitor of NFkappaB activation, BAY 11-7082. RESULTS: Preincubation with SNAP (1 mM) for 30 min was sufficient to reduce the cytokine-induced expression of CAM to less than 10 % of controls. This “refractory” state persisted for 6 h after washout of the NO donor in the combination TNFalpha/VCAM. The SNAP effect was not mediated by the cGMP pathway. The TNFalpha-dependent induction of CAM was strictly dependent on the activation of NFkappaB. After TNFalpha exposure, a high level of IkappaBalpha was persistently detected in SNAP-treated HUVEC, while the inhibitor was immediately degraded in controls. CONCLUSION: Persistent blocking of NFkappaB-dependent CAM expression by SNAP pretreatment in endothelial cells may be causally related to the stabilization of IkappaBalpha. CLINICAL IMPLICATIONS: Results may be relevant to clinical situations of I/R-induced inflammation. DISCLOSURE: Thomas Waldow, None.

OFF-PUMP CORONARY ARTERY BYPASS SURGERY IN A LOW CASE LOAD CENTER: MID-TERM FOLLOW-UP OF THE FIRST 107 PATIENTS Parwis Massoudy MD* Matthias Thielmann MD Julia Scha¨fer MS Eva Assenmacher MD Christian Lo¨sch Axel Schmermund MD Ivan Aleksic MD Jarowit A. Piotrowski MD Walter O. Schu¨ler MD Peter Kienbaum MD Raimund Erbel MD Heinz Jakob MD West German Heart Center, Department of Thoracic and Cardiovascular Surgery, Essen, Germany PURPOSE: Off pump coronary artery bypass (OPCAB) grafting is still discussed controversially in the cardiac surgical community. Early perioperative results are encouraging. Only few reports have focused on mid-term recurrence of angina and freedom from death or re-intervention. METHODS: 107 OPCAB patients (mean age 63⫾1 years, 77 male, mean additive EuroScore 4.1⫾0.3, mean logistic EuroScore 5.6⫾0.7%, number of distal anastomoses 2.0⫾0.1), operated on between January 1999 and December 2003, were systematically followed up comparing pre- and post-operative NYHA- and CCS-classifications and assessing freedom from death and re-intervention. 52 of 107 patients underwent postoperative angiography or multi-slice computed tomography (MSCT). 24 of the latter 52 patients were symptomatic, 21 with stable angina, 3 with unstable angina, the others underwent follow-up studies having given their informed consent. RESULTS: Perioperative 30 day mortality was 3%. Freedom from death or re-intervention at 5.5 years was 91% and 80%, respectively. Only three patients required re-intervention in an OPCAB-related vessel. CCS classification was 2.8⫾0.1 before surgery and 1.8⫾0.2 (p⬍0.01) at follow-up (3.3⫾0.3 years). NYHA classification was 2.7⫾0.1 and 2.2⫾0.1 (p⬍0.01), respectively. 52 patients (24 for cardiac symptoms) underwent coronary angiography or MSCT at a mean follow-up of 2.2⫾0.3 years. Left

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internal thoracic artery was patent in 91%, venous graft patency rate was 83%. CONCLUSION: In this small but consecutive OPCAB population with a considerable perioperative risk according to the EuroScore, freedom from death and re-intervention at 5.5 years is acceptable and graft patency rate at 2.2⫾0.3 years is in the expected range. Significant reduction in both CCS and NYHA classification indicate sustained clinical improvement at mid-term. CLINICAL IMPLICATIONS: Even with a low case load, reserving OPCAB to selected indications, surgery can be performed at low operative mortality and acceptable mid-term results. DISCLOSURE: Parwis Massoudy, None. CORONARY ARTERY BYPASS GRAFTING USING SKELETONIZATION OF THE RADIAL ARTERY: EXPERIENCE OF 500 CASES Hitoshi Hirose MD* Atsushi Amano MD Juntendo University Hospital, Tokyo, Japan PURPOSE: To optimize graft flow and graft patency of arterial graft, all arterial conduits including the internal mammary artery (since January 1999), radial artery (since September 1999) and gastroepiploic artery (since September 2002) have been harvested in skeletonized technique. Currently, in Japan, the “standard” technique of radial artery harvesting has been completely changed from pedicle harvesting technique (the artery, associated veins, adventitia, and surrounding fascia harvested as an en-block using an electrocautery) to skeletonized harvesting technique (removal of all adventitia from the main trunk of the radial artery using a ultrasonic scalpel). Here we report our experience of more than 500 cases of skeletonized radial artery grafting. METHODS: Between September, 1999 and April, 2004, isolated coronary artery bypass grafting (CABG) was performed in a total of 893 patients at Shin-Tokyo – Juntendo Hospital Group. Of these, 557 patients underwent skeletonized radial artery grafting, and their perioperative, early angiographic, and follow-up results were analyzed. RESULTS: Study group was consisted of 417 male and 138 female with mean age of 66.2 ⫾ 9.1, and preoperative EuroSCORE of 3.7 ⫾ 2.7. The details of the perioperative data are shown in Table 1. No perioperative myocardial infarction, bleeding related to the radial artery graft or graft harvesting site complication was observed. Early angiography within 3 month after surgery was performed in 291 patients demonstrated radial artery anastomosis patency rate of 97.0% (458/472) and stenosis-free anastomosis patency rate of 92.8% (458/ 472). Distant angiography beyond 6 months after surgery performed in additional 37 patients, revealed stenosis-free anastomosis patency rate of 92.4% (61/66). Follow-up was completed all hospital survivors with a mean follow-up of 1.0 ⫾ 0.5 years and found 3 patients (0.5%) developed radial artery related cardiac events. CONCLUSION: The early clinical outcome and angiographical results of radial artery grafting using “new standard” skeletonized harvested technique were excellent and comparable to previous reports of those with “classical” pedicle harvesting technique. CLINICAL IMPLICATIONS: This new standard skeletonization technique may replace the classical pedicle harvesting technique. DISCLOSURE: Hitoshi Hirose, None. POSTOPERATIVE CREATINE KINASE MB LEVEL IS ASSOCIATED WITH IN-HOSPITAL MORTALITY AFTER CORONARY SURGERY Li Zhang MD Kathleen Petro MD Peter Hill MD* Elizabeth Haile MS Jorge Garcia MD Ammar Bafi MD Steven Boyce MD Paul Corso MD Washington Hospital Center, Washington, DC PURPOSE: Cardiac enzymes are widely used for evaluation of perioperative myocardial injury. This study was to investigate the potential relationship between postoperative creatine kinase MB (CKMB) level and clinical outcomes in the patients after isolated coronary artery bypass grafting (CABG). METHODS: Seven thousand and ninety-five patients who underwent isolated CABG between January 2000 and June 2004 at the Washington Hospital Center were included in this study. CKMB level was measured in the morning of the first post-operative day. Three groups were created according to CKMB level: Group I: CKMB ⱕ 5.2 CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Cardiac Surgery, continued Table 1. Univariate Comparisons of Demographic and Clinical Characteristics Between the Three Groups.

Age (y)

Group I

Group II

Group III

Group I

Group II

Group III

(CKMB ⬍5.2

(5.2⬍CKMB

(CKMB⬎13

(CKMB ⬍5.2

(5.2 ⬍CKMB ⬍13

(CKMB ⬎13

ng/ml)

⬍13ng/ml)

ng/ml)

(N⫽3,531)

(N⫽2,197)

(N⫽1,367)

p value

65.1⫾10.7

0.05*

64.4⫾10.6

Female Gender

1020(28.9)

Diabetes Hypertension Congestive Heart

64.6⫾10.6

Carotid Artery Disease

0.19

Stroke

46 (1.3)

40 (1.8)

36 (2.6)

977 (71.5)

0.12

Myocardial Infarction

13 (0.4)

36 (1.6)

90 (6.6)

⬍0.01

281 (8.0)

215 (9.8)

98 (7.2)

0.92

Prolonged Ventilation

126 (3.6)

142 (6.5)

146 (10.7)

⬍0.01

Need of Hemodialysis

3 (0.1)

6 (0.3)

3 (0.2)

0.17

6 (0.2)

11 (0.5)

28 (2.1)

⬍0.01

Length of Hospital

4 (4–6)

5 (4–7)

5 (4–7)

⬍0.01*

891 (40.6)

633 (46.3)

⬍0.01

*Values are expressed as N (%) or median (25th – 75th percentile).

Stay (day) 1259 (35.7)

4 (0.1)

7 (0.3)

1 (0.1)

0.81

60 (1.7)

32 (1.5)

28 (2.1)

0.58 0.08

62 (4.5) 35 (2.6)

0.08

COPD

18 (0.5)

20 (0.9)

9 (0.7)

0.31

458 (13.0)

336 (15.3)

224 (16.4)

1951 (55.3)

1055 (48.0)

579 (42.4)

35% - 45%

945 (26.8)

623 (28.4)

445 (32.6)

25% - 34%

506 (14.3)

388 (17.7)

276 (20.2)

ⱕ 25%

129 (3.7)

131 (6.0)

67 (4.9)

38 (1.1)

42 (1.9)

33 (2.4)

397 (11.2)

288 (13.1)

188 (13.8)

11.0 (6.0–17.0)

12.0 (6.5–19.0)

13.5 (9.0–20.5)

⬍0.01*

1.1 (0.7–1.9)

1.5 (0.7–2.8)

1.5 (0.7–2.8)

⬍0.01*

⬍0.01 ⬍0.01*

Ejection Fraction

⬍0.01

Insertion 0.01

Disease

Northern New England

⬍0.01

482 (35.3)

44 (2.0)

Parsonnet Risk Score

⬍0.01

783 (35.6)

87 (4.0)

Peripheral Vascular

24 (1.8)

1587 (72.2)

62 (1.8)

Preoperative IABP

27 (1.2)

2465 (69.8)

123 (3.5)

⬎ 45%

13 (0.4)

Mortality

1308 (37.0)

Preoperative Hemodialysis

Left Main Disease

p Value

limit), in terms of in-hospital mortality, postoperative MI, and prolonged hospitalization (p ⬍ 0.01). CONCLUSION: This is the largest retrospective study on the prognostic value of postoperative CKMB level in patients undergoing CABG. We conclude that an extremely high CKMB level is an indicator of in-hospital mortality and morbidities. CLINICAL IMPLICATIONS: CKMB levels should be measured routinely after CABG, to identify high-risk patients. DISCLOSURE: Peter Hill, None.

C1-ESTERASE INHIBITOR TREATMENT DURING EMERGENCY CORONARY ARTERY BYPASS SURGERY IN PATIENTS WITH ACUTE ST-ELEVATION MYOCARDIAL INFARCTION Matthias Thielmann MD* Guenter Marggraf MD Parwis Massoudy MD Markus Neuha¨user PhD Stephan Knipp MD Markus Kamler MD Jarowit Piotrowski MD Heinz Jakob MD Thoracic and Cardiovascular Surgery, West-German Heart Center Essen, University, Essen, Germany

CVA Risk Score 2864 (81.1)

798 (36.3)

545 (39.9)

⬍0.01

82 (2.3)

110 (5.0)

122 (8.9)

⬍0.01

763 (21.6)

559 (25.4)

405 (29.6)

⬍0.01

221 (6.3)

42 (1.9)

32 (2.3)

2

704 (19.9)

192 (8.7)

147 (10.8)

3

1254 (35.5)

656 (29.9)

391 (28.6)

4

924 (26.2)

793 (36.1)

505 (36.9)

5

357 (10.1)

414 (18.8)

241 (17.6)

6

57 (1.6)

81 (3.7)

41 (3.0)

7

13 (0.4)

17 (0.8)

9 (0.7)

Off-pump CABG Redo CABG Urgent CABG

⬍0.01*

Number of Grafts 1

8

1 (0.03)

1 (0.1)

1 (0.1)

9

0(0.0)

1(0.1)

0(0.0)

*Values are expressed as N (%), mean ⫾ std or median (25th – 75th percentile). ng/ml; Group II: 5.2 ⬍ CKMB ⱕ 13 ng/ml; Group III: CKMB ⬎ 13 ng/ml. RESULTS: CKMB level above normal upper limit was relatively common after isolated CABG. Patient with CKMB ⬎ 13 ng/ml (5 times of normal upper limit) were more frequently those with history of myocardial infarction (MI), left main disease and poor left ventricular function (EF ⬍ 35%), preoperative IABP support, having a repeated procedure (Table 1). Difference of in-hospital mortality, morbidities (stroke, MI) and length of hospital stay was statistically significant between the three groups (Table 2). Based on multivariable analysis, patients with CKMB ⬎ 13 ng/ml were more likely at risk for isolated CABG than those with CKMB ⱕ 5.2 ng/ml (2 times of normal upper

PURPOSE: Myocardial inflammatory response including complement activation was demonstrated as an important mechanism of ischemiareperfusion injury and complement inhibition by C1-esterase-inhibitor (C1-INH) has recently shown cardioprotective effects in experimental and clinical settings. METHODS: The effects of C1-INH on complement activation, perioperative myocardial cellular damage and patients outcome were studied in patients undergoing emergency CABG due to acute ST-elevation myocardial infarction (STEMI) with (group 1,n⫽25) and without (group 2,n⫽25) bolus administration of C1-INH (40 IU.kg -1) during reperfusion and 6 hours (hrs) postoperatively (20 IU.kg-1) besides the same study protocol. Complement activation fragments (C4), C1-INH, and cardiac troponin I (cTnI) were measured preoperatively, and at 6, 12, 24, and 48 hrs postoperatively. Clinical data, adverse events and patients outcome were recorded prospectively. RESULTS: Patient characteristics were not different between groups. No drug-related adverse events could be observed in group 1. Constant plasma levels of C1-INH and a reduction of C4 fragments were found in group 1. Preoperative cTnI levels were elevated but not different between the groups. The postoperative release of cTnI was significantly lower (P⬍0.05;ANOVA) in group 1 with ⱕ6hrs between symptom onset and reperfusion compared to group 2 at 12 (38.5⫾22.1 versus 75.7⫾24.6 ng/mL), 24 (65.5⫾24.5 versus 95.2⫾28.3 ng/mL), and 48hrs (58.3⫾37.5 versus 87.5⫾41.2 ng/mL) after surgery, but remained unchanged between the groups among patients with a treatment delay of more than 6hrs. Adverse events, ICU and hospital stay, and in-hospital mortality (13.4% versus 14.3%) were not different between the groups. CONCLUSION: The present study is the first to evaluate the effects of complement inhibition during emergency CABG with STEMI. C1INH effectively inhibited complement activation and did not cause adverse effects. The reduced release of cTnI was only observed in CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

Renal Failure

ng/ml) (N ⫽ 1,367)

0.23

Infarction Previous CVA

ng/ml) (N ⫽ 2,197)

434 (31.8)

within 24 hrs History of Myocardial

In-Hospital Operative

ng/ml) (N ⫽ 3,531)

583 (26.5)

Failure Myocardial Infarction

Table 2. Univariate Comparisons of Postoperative Outcomes Between the Three Groups.

Wednesday, November 2, 2005 Cardiac Surgery, continued patients, who were treated within the first 6hrs from symptom onset to reperfusion. CLINICAL IMPLICATIONS: C1-INH administration during emergency CABG with acute STEMI is safe and effective to inhibit complement activation and may reduce myocardial ischemia-reperfusion injury in patients undergoing CABG within 6hrs between symptom onset and reperfusion. DISCLOSURE: Matthias Thielmann, None. RISK STRATIFICATION AND CLINICAL OUTCOME IN PATIENTS WITH ACUTE ST-ELEVATION MYOCARDIAL INFARCTION UNDERGOING CORONARY ARTERY BYPASS SURGERY Matthias Thielmann MD* Parwis Massoudy MD Guenter Marggraf MD Ivan Aleksic MD Markus Kamler MD Ulf Herold MD Jarowit Piotrowski MD Heinz Jakob MD Thoracic and Cardiovascular Surgery, WestGerman Heart Center Essen, University, Essen, Germany PURPOSE: Treatment strategies for ST-elevation myocardial infarction (STEMI) have undergone great evolution since introduction of acute percutaneous coronary intervention (PCI) therapy. The purpose was therefore to evaluate in-hospital mortality, clinical outcomes, and predictors of survival among patients who underwent surgical revascularization with coronary artery bypass grafting (CABG) due to STEMI unresponsive to maximal non-surgical therapy. METHODS: Between 01/2000 and 01/2005 eighty-four patients underwent CABG due to STEMI at our institution. Preoperative, intraoperative and postoperative data were recorded prospectively. In-hospital mortality, major adverse cardiac events (MACE), and other clinical outcomes were investigated retrospectively. RESULTS: Thirty-four, 22, 10, and 18 among 84 patients with STEMI underwent CABG within 6 hours (hrs), 7-24 hrs, 1-3 days, and 4-7 days from onset of symptoms to surgery, respectively. Thirty-two among 84 (38%) patients were admitted to surgery complicated by preoperative cardiogenic schock. Thus, preoperative and/or intraoperative intraaortic balloon counterpulsation was performed in 15 and 45 patients, whereas preoperative extracorporeal membrane oxygenation was necessary in 2 patients. Mean number of grafts per patient was 3.1⫾0.9. Aortic crossclamp time, cardiopulmonary bypass time, and reperfusion time were 67⫾21 min and 126⫾45 min, and 46⫾22 min, respectively. Ventilation time, ICU and hospial stay were 54⫾53 hrs (mean⫾SD), 6.3⫾6.4 hrs and 21⫾24 days, respectively. Overall in-hospital mortality was 13.1%. On multivariate logistic regression analysis, gender (Odds ratio [OR]: 8.7, 95% confidence interval [CI]: 1.2-62.5), the level extent of preoperative cardiac troponin I (OR: 1.2,CI: 1.1-1.4), and time from onset of symptoms to surgery (OR: 1.1,CI: 1.1-2.8) were independent predictors of in-hospital death. CONCLUSION: Emergency CABG in STEMI patients unresponsive to maximal non-surgical therapy can be performed with acceptable risk incorporating adequate management strategies. CLINICAL IMPLICATIONS: The extent of acute myocardial damage and time period from symptoms to surgery are major variables predicting mortality results and thus, may help the surgeon to decide about the appropriate timing of surgical revascularization in patients with acute STEMI. DISCLOSURE: Matthias Thielmann, None. IMPACT OF MYOCARDIAL HYPERTROPHY AND PREOPERATIVE LEFT VENTRICULAR EJECTION FRACTION ON POST OPERATIVE COMPLICATIONS AFTER AORTIC VALVE REPLACEMENT FOR AORTIC STENOSIS Jean-Louis Mariage MD* Pierre Bulpa MD Isabelle Michaux MD Manuel Gonzalez MD Jacques Jamart MD Etienne Installe´ MD Patrick Evrard MD Mont-Godinne Hospital, Cliniques Universitaires de MontGodinne, Yvoir, Belgium PURPOSE: Patients (pts) with aortic stenosis (AS) have a good prognosis after aortic valve replacement (AVR). Morbidity and mortality of AS pts with severe septal hypertrophy (SSH,ⱖ16mm) or supranormal (ⱖ70%) left ventricular ejection fraction (LVEF) have been poorly investigated. We retrospectively analysed complications and outcome of such pts after surgery. METHODS: Between 10/98 and 03/03, 280 pts underwent AVR. Only pure AS pts were included; excluding aortic regurgitation,

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ischaemic cardiomyopathy, associated coronary or thoracic aortic surgery, or mitral disease. Eighty seven pts met the criteria. Analysis was performed on 2 criteria: preoperative LVEF and septal thickness (ST). For LVEF analysis, pts were divided in 2 groups: GA: LVEF 50 to 69% (n⫽29) and GB: LVEF ⱖ70% (n⫽44); and in 3 for the ST criteria: G1: ST⬍13mm (n⫽18); G2: 13ⱕST⬍16mm (n⫽31); and G3: STⱖ16mm (n⫽11). We analysed length of ICU and hospital stay; duration of ventilation; use of vasoactive drugs, calcium channel’s blockers or b-blockers; arrhythmia events, occurrence of renal failure or need for haemodialysis, and mortality. Usually pts after AVR stay at least 2 nights in our ICU. RESULTS: In LVEF analysis, 17% of pts in GB were ventilated ⱖ24 hours in comparison with 0% in GA [p⫽0.036]. In ST analysis, 27.8% of pts in G1, 35.5% in G2, and 54.5% in G3 stayed ⬎2 nights in the ICU (NS). Two pts from G3 required haemodialysis [p⫽0.032]. There were no difference in the length of ICU and hospital stay, use of vasoactive or vasodilator drugs, and occurrence of arrhythmia in group GA vs. GB, or in group G1 vs. G2 vs. G3. No patient died during hospital stay. CONCLUSION: Using selective criteria, pure AS pts have an excellent prognosis after AVR; however pts with LVEF ⱖ70% have a higher risk of prolonged ventilation, and SSH pts have a higher incidence of haemodialysis. CLINICAL IMPLICATIONS: Diastolic dysfunction consecutive to SSH or supranormal LVEF pts could be improved by pharmacological intervention. Further studies are necessary to confirm this hypothesis. DISCLOSURE: Jean-Louis Mariage, None.

SURGICAL OUTCOMES FOR THE MANAGEMENT OF CHRONIC PULMONARY THROMBOEMBOLIC DISEASE Gonzalo V. Gonzalez-Stawinski MD* Arash Salemi MD Albert S. Chang MD Delos M. Cosgrove MD Bruce W. Lytle MD Nicholas G. Smedira MD The Cleveland Clinic Foundation, Cleveland, OH PURPOSE: Chronic pulmonary thromboembolic disease (cPE) results in significant morbidity and mortality. Surgical therapy is aimed at alleviating the effects of the thrombus on oxygen saturation, pulmonary hypertension, and improving outcomes. This study was conducted to determine our experience with pulmonary thromboembolectomy as a therapy for cPE. METHODS: A retrospective chart review identified patients undergoing pulmonary endarterectomy for chronic pulmonary thromboembolism. We obtained demographics, symptoms prior to surgical therapy, operative procedures, and outcomes. RESULTS: Between December 1994 and December 2003 a total of 30 patients were surgically treated for chronic pulmonary embolism. There were 13 males and 17 females. Average age was 49.2 yrs (range 21- 76 yrs). The most common presenting symptom was SOB in 26 (96.7%) patients. Half the patients (50%) had a past medical history of venous thromboembolic disease, 20% had a documented hypercoagulable state, but 93.3% of the patients had a vena cava filter placed preoperatively. Mean preoperative systolic pulmonary artery presssures (PAP) was 77.9 mmHg (range 53 –107 mmHg). Surgical approaches included bilateral thromboembolectomies in 25 (83.3%) patients. Circulatory arrest was used in 29 (97%. Mean arrest time of 33.2 minutes (range 6 – 60 minutes). Postoperatively there was a decrease in mean systolic PAP to 41.4 mmHg (range 26-73 mmHg, p ⬍ 0.001). While mean saturations (SAT) increased following surgical intervention (pre op SAT 94.2% vs. post op SAT 96.1%, p ⫽ 0.014) this did not result in a decrease in supplemental oxygen use. The 30 day survival was 93.3 % with an overall survival of 80.3% (mean follow-up of 3.5 yrs, range 7d - 10.3 years). CONCLUSION: Pulmonary thromboembolectomy under circulatory arrest is a safe and effective intervention which significantly improves pulmonary artery pressures, oxygen saturation and is associated with good mid-term outcomes. CLINICAL IMPLICATIONS: Pulmonary thromboembolectomy is an effective means of therapy for patients suffering of disabiling pulmonary symptoms as a result of chronic pulmonary thromboembolic disease. DISCLOSURE: Gonzalo Gonzalez-Stawinski, None. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Cardiac Surgery, continued SHORT TERM OUTCOMES FOR THE ST. JUDE AORTIC CONNECTORS: A REVIEW OF 348 IMPLANTS Douglas C. Miller MD* Timothy H. Trotter MD Mary Lane PhD University of Oklahoma, Section of Thoracic and Cardiovascular Surgery, Oklahoma City, OK

FACTORS INFLUENCING THE OUTCOME OF RESUSCITATION AFTER POSTOPERATIVE ARREST IN CARDIAC SURGERY PATIENTS Prashant C. Shah MD* Mikhail Vaynblat MD Murali Pagala PhD Dinesh Bhaskaran MD Joseph N. Cunningham, Jr MD Maimonides Medical Center, Brooklyn, NY PURPOSE: Cardiopulmonary arrest is an unexpected event in cardiac surgery patients in the postoperative period. Most studies have always advocated an expeditious conversion from closed-chest to open-chest CPR for cardiac arrest after cardiac surgery. The present study was designed to characterize the outcome of closed-chest compared with open-chest CPR, to define potential factors associated with unresponsiveness to closed-chest CPR, and to evaluate the need for open-chest CPR for this subgroup of patients. METHODS: A retrospective review was conducted for all cardiac surgical patients who underwent CPR for postoperative arrest between March 1995 and April 2002. Extensive data pertaining to preoperative, intraoperative characteristics, postoperative complications, and periarrest factors were collected. All data were analyzed using various statistical models. RESULTS: Of the 6,094 patients, 45 (0.74%) patients had a cardiac arrest within seven postoperative days and required CPR. Twenty-four (53%) patients underwent only closed-chest CPR, whereas 21 (47%) patients underwent a conversion from closed-chest to open-chest CPR. Within the closed-chest CPR group, 17 (71%) were successfully resuscitated, while 7 (29%) died. Within the open-chest CPR group, only 3 (14%) were successfully resuscitated, while 18 (86%) died. A chi-squared test showed that the difference in the proportion of successful outcome between closed and open CPR was significant (p⬍0.001). The 17 patients who were successfully revived with closed-chest CPR were compared against the other 28 patients as a whole who did not respond to closed-chest CPR. Univariate predictors of failed closed-chest CPR included the presence of preoperative hypertension (p⬍0.001), the presence of severe angina (p⫽0.06), and urgent/emergent nature of surgery (p⬍0.005). Univariate predictors of successful closed-chest CPR included elective nature of surgery (p⬍0.05) and shorter aortic crossclamp times (p⬍0.05).

RIGHT VENTRICULAR BLEEDING ASSOCIATED WITH MEDIASTINITIS: A NEW RISK FACTOR Xavier M. Mueller MD* David Greentree MD Dominique Dorion MD Marcel Martin MD Raymond Duperval MD Dominique Be´rard MD Michel Nguyen MD Serge Lepage MD CHUS, Sherbrooke, PQ, Canada PURPOSE: Mediastinitis-related right ventricular (RV) rupture is a potentially life-threatening complication of cardiac surgery. Our experience with this complication is analyzed. METHODS: All the cases of mediastinitis recorded since the introduction of a prospective database for our cardiac surgery program were reviewed. All the patients with bleeding from the anterior surface of the heart during this interval were analyzed. RESULTS: Among the 953 consecutive patients who underwent heart surgery between January 2003 and May 2005, mediastinitis occurred in 20 cases (2.1%). All 20 patients had coronary artery surgery, three of them combined with aortic valve replacement. Four patients developed RV bleeding while waiting for their secondary chest closure. In the four cases, bleeding occurred between 1 and 6 days after sternal debridement. One patient died immediately of exsanguination. The other three had limited bleeding which could be repaired at bedside with direct sutures. All 3 patients had subsequent successful closure with pectoral flaps, but one eventually died of multiple cerebral emboli. Notably, the four bleedings occurred among the 12 patients (33%) who had their pericardium left open at the time of the initial cardiac operation, while no rupture occurred among the 8 patients (0%) who had their pericardium closed. CONCLUSION: In this series, RV bleeding developed exclusively among patients who had their pericardium left opened during their initial cardiac operation. The RV tear likely resulted from the distraction of the sternal edges which was transmitted directly to the fragile RV wall. CLINICAL IMPLICATIONS: In order to prevent this severe complication, we recommend systematic closure of the pericardium at the primary operation. When the pericardium has been left open, we recommend that the RV should be widely freed from the sternal edges during the debridement and that the chest should be closed as soon as possible. DISCLOSURE: Xavier Mueller, None. COMPARISON BETWEEN “SWAN-GANZ” DERIVED AND ECHOCARDIOGRAPHIC VARIABLES IN THE PREDICTION OF HEMODYNAMIC COMPLICATIONS FOLLOWING CARDIAC SURGERY Pierre-Marc Chagnon MD* Andre´-Yves Denault MD Pierre Couture MD Sylvie Le´vesque MS Jean-Claude Tardif MD Michel Carrier MD Montreal Heart Institute, Longueuil, PQ, Canada PURPOSE: To compare hemodynamic and echocardiographic variables in their ability to predict hemodynamic complications following cardiac surgery. METHODS: We conducted a retrospective analysis of 243 consecutive patients having undergone a cardiac surgical procedure in our center. Demographic, perioperative variables, “Swan-Ganz” derived hemodynamic profile and a standard sequence of cardiac images to evaluate systolic and diastolic function (using a multiplane TEE) were obtained after the induction of anaesthesia but before sternotomy. The primary end point consisted of a composite index of death, resuscitated cardiac arrest, the use of vasoactive support for more than 24 hours postoperatively, or the use of an intra-aortic balloon pump that was not present preoperatively. RESULTS: 49 patients (20%) experienced hemodynamic complications, defined by the composite index. These patients had higher Parsonnet scores and body mass index, more complex surgeries and left ventricular dilatation, longer bypass and clamping time, more frequent difficult separation from bypass (DSB), lower mean arterial pressure/ mean pulmonary arterial pressure ratio (MAP/MPAP), lower fractional area change and higher regional wall motion score index (RWMSI). In the univariate analysis, the only significant hemodynamic and echocardiographic variables were the MAP/MPAP ratio (3.38 ⫾ 1.51 vs. 3.76 ⫾ 1.17; OR 0.75, CI 0.56-1.00, p ⫽ 0.0524) and the RWMSI (OR 2.26, CI CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: The use of aortic connectors for the performance of proximal anastomosis in beating heart surgery was initially embraced as a result of the ease of performance and the ability to avoid the placement of clamps on the aorta. Concerns regarding the failure rates of these devices have prompted most surgeons to abandon their use. We review the early clinical course of the 348 proximal anastamoses performed with the St. Jude Symmetry Aortic Conector (SJAC) device in our beating heart CABG program. METHODS: A review of the medical records of all patients who underwent placement of SJAC was undertaken to evaluate for the presence of recurrent angina, myocardial infarction, other cardiac event, or intervention in the cardiac catheterization lab. RESULTS: Proximal anastamotic failure occurred in 13/124 (10.48%) patients with 22/348 (6.3%) of the grafts requiring intervention in the catheterization lab at a mean interval of 9.2 months (range 0.5-18months). Overall mortality for the group of patients was 3/124 (2.42%) patients and the operative mortality was 2/124 (1.6%). There were no deaths directly attributable to SJAC failure. There were no strokes in any of the SJAC patients. CONCLUSION: There is a risk of early graft failure with the use of the SJAC. These failures can frequently be managed in the cardiac catheterization lab with standard catheter-based interventions. The late failure rate of these devices remains poorly defined and further study of those patients with implanted SJAC should occur. CLINICAL IMPLICATIONS: The introduction of SJAC allowed for performance of beating heart CABG with a lower incidence of stroke; however, this benefit appears to have been achieved at the cost of an increased early proximal anastamotic failure rate. The fate of spahenous vein grafts that have undergone intervention is known to be less satisfactory than unintervened grafts and it is anticipated that the higher than expected early graft failure rate will translate to poorer long term saphenous vein graft patencies. DISCLOSURE: Douglas Miller, None.

CONCLUSION: The above results confirm that open-chest CPR has a poor overall outcome and may not be worthwhile for all cases unresponsive to closed-chest CPR. CLINICAL IMPLICATIONS: Using the above outcome-associated factors may help the clinician determine which group of patients for whom it may be futile or worthwhile to convert to open-chest CPR. DISCLOSURE: Prashant Shah, None.

Wednesday, November 2, 2005 Cardiac Surgery, continued 1.17-4.35, p ⫽ 0.0153). A multiple stepwise logistic regression showed that the only 3 independent predictors of postoperative hemodynamic complications were the duration of cardiopulmonary bypass time (128 ⫾ 57 vs. 90 ⫾ 42 min; OR 1.02, CI 1.01-1.02, p ⬍ 0.0001), aortic cross-clamp time (87 ⫾ 44 vs. 60 ⫾ 40 min, OR 1.02, CI 1.01-1.02, p ⬍ 0.0002) and DSB (82% vs. 45%, OR 5.47, CI 2.52-11.9, p ⬍ 0.0001). CONCLUSION: No “Swan-Ganz” derived or echocardiographic variables were found to be independent predictors of complications after cardiac surgery. The duration of the procedure and DSB are the most important independent predictors of hemodynamic complications following cardiac surgery. CLINICAL IMPLICATIONS: Prevention of DSB could represent a potential strategy to reduce hemodynamic complications after cardiac surgery. DISCLOSURE: Pierre-Marc Chagnon, None. PERIOPERATIVE PHYSICAL THERAPY MANAGEMENT FOLLOWING CARDIAC SURGERY: A SYSTEMATIC REVIEW Tom J. Overend PhD* Cathy M. Anderson MS Jennifer Jackson-Lee BSc S Deborah Lucy PhD Monique Prendergast MS Susanne Sinclair BSc School of Physical Therapy, University of Western Ontario, London, ON, Canada PURPOSE: Two local hospitals were amalgamating cardiac surgery services. There was a disparity in the perioperative physiotherapy care provided following cardiac surgery at the two sites. Thus our purpose was to carry out a systematic review of the evidence to determine the optimal perioperative physiotherapy management of cardiac surgery patients following CABG and/or cardiac valve surgery. METHODS: Medline, CINAHL and EMBASE data bases were searched from inception until April 2005, using key terms including physiotherapy, coronary artery bypass, cardiac surgery, valve surgery, postoperative complications, atelectasis, breathing exercises, mobility, and education. A secondary search of the reference lists of all identified articles was also carried out. A form was developed to standardize critical appraisal. Each study was reviewed independently by one of three pairs of reviewers. The pair then met to reach consensus before presenting the study to the entire research team for final agreement. Accepted papers were graded for strength of evidence and recommendations were extracted for physiotherapy practice. RESULTS: The search strategy yielded 138 articles. Seventy-four studies dealing with physiotherapy management of the CABG and/or cardiac valve surgery patient in the perioperative period were accepted and critically appraised; 33 of these were rejected for methodological flaws. Evidence-based conclusions relating to physiotherapy practice were extracted from 37 papers and combined into 13 recommendations: perioperative cardiorespiratory therapy (5), education (6), anxiety (1) and pain control (1). There was insufficient evidence to support recommendations for exercise, positioning, shoulder range of motion, and acute effects of cardiorespiratory treatment in the perioperative period. CONCLUSION: Virtually all of the reviewed literature dealt with low-risk patients. High-risk cardiac surgery patients thus require individually determined, perioperative physiotherapy management. While perioperative education and mobility remain important for routine patients, the evidence does not support other traditional postoperative cardiorespiratory physiotherapy treatment approaches. CLINICAL IMPLICATIONS: The routine, low-risk cardiac surgery patient requires little in the way of perioperative cardiorespiratory physiotherapy save for ensuring initial mobility assistance and provision of education regarding breathing exercises and other self-treatments during the postoperative course. DISCLOSURE: Tom Overend, None.

Cardiac Surgery: Congenital 12:30 PM - 2:00 PM SURGICAL TREATMENT IN NEONATES WITH AORTIC ARCH OBSTRUCTION OR INTERRUPTION WITH FUNCTIONAL SINGLE VENTRICLE Mark Ruzmetov MD* Palasniswamy Vijay PhD Mark D. Rodefeld MD Mark W. Turrentine MD John W. Brown MD Indiana University School of Medicine, Indianapolis, IN PURPOSE: The neonate with a functional single ventricle (FSV) and aortic arch obstruction or interruption other than hypoplastic left heart

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syndrome (HLHS) poses a uniquely difficult challenge because of the stimulus for myocardial hypertrophy and failure from impedance to systemic outflow and pulmonary vascular disease from pulmonary overcirculation. METHODS: Among the patients with FSV and excessive pulmonary blood flow, who underwent palliative surgery since 1990, 36 neonates had aortic coarctation (n⫽32) or interruption (n⫽4). Patients with HLHS were excluded. The median age at operation was 7.5 days (range 2 to 84 days) and the median weight was 3.3 kg (range 2.7 to 5 kg). 28 children have undergone a pulmonary artery banding (PAB) and aortic coarctation or interruption repair (78%), and 8 children (22%;8/36) underwent a modified Norwood procedure. RESULTS: There were four early deaths and two late deaths after the initial surgical palliation. The overall survival at 10 years was 78%. Follow-up has ranged from 6 months to 13 years (average 5.2 years). Of the 32 survivors, 19 have undergone a bidirectional cavopulmonary anastomosis and 20 a Fontan procedure with no deaths. Twelve infants have required Damus-Kaye-Stansel procedure (DKS) and three infants have required bulboventricular foramen (BVF) enlargement for subaortic obstruction (two early deaths). In all survivors patients who underwent DKS or BVF enlargement (42%;15/36) regular sinus rhythm was maintained postoperatively. CONCLUSION: Our experience suggests that this high-risk subgroup of neonates with FSV and aortic arch obstruction or interruption is safely managed by initial palliation procedures (PAB with repair of aortic obstruction or modified Norwood procedure). This strategy, careful surveillance, and early relief of subaortic stenosis can maintain acceptable anatomy and hemodynamics for later bidirectional Glenn and Fontan procedures. CLINICAL IMPLICATIONS: Our experience suggests that this high-risk subgroup of neonates with FSV and aortic arch obstruction or interruption is safely managed by initial palliation procedures (PAB with repair of aortic obstruction or modified Norwood procedure). DISCLOSURE: Mark Ruzmetov, None.

SURGICAL MANAGEMENT OF SUBAORTIC OBSTRUCTION IN CHILDREN WITH SINGLE VENTRICLE PHYSIOLOGY Mark Ruzmetov MD* Palaniswamy Vijay PhD Mark D. Rodefeld MD Mark W. Turrentine MD John W. Brown MD Indiana University School of Medicine, Indianapolis, IN PURPOSE: Optimal prevention and treatment of subaortic stenosis (SAS) in the univentricular heart (UH) and high pulmonary blood flow remains controversial, especially when complicated by aortic arch obstruction. Several surgical techniques have been used in infancy to palliate this group of patients. METHODS: From January 1980 to December 2004, 43 children with UH and systemic ventricular outflow obstruction underwent relief of SAS subsequent to pulmonary artery banding (PAB;n⫽34) and modified Norwood procedure (MNP;n⫽9). Median age at operation was 20 days (range; 2 to 298 days; 79% were less than 1 month) and the average preoperative pressure gradient across the ascending aorta and systemic ventricle was 72⫾17 mmHg (range 31 to 135 mmHg). Three techniques to relief SAS were performed: (1) the Damus-Kaye-Stansel (DKS) procedure (including MNP patients;n⫽32); (2) subaortic resection or ventricular septal defect enlargement (n⫽7); and (3) apical aortic conduit (AAC;n⫽4). RESULTS: Four patients (9%) died in the early postoperative period: three infants after DNP (33%), and one after PAB (3%;p⬍0.001). The overall survival at 1 and 10 years was 79% and 70%, respectively. Complete heart block requiring insertion of a pacemaker occurred in five patients (12%). Completion Fontan, hemi-Fontan and heart transplantation have been performed in 25, 21 and 1 patient, respectively. Follow-up was complete in all survivors at a mean time of 7.2⫾6.6 years (range; 3 months to 23 years). Outcome was significantly worse in patients with associated aortic arch obstruction (p⫽0.002), and with the presence of AAC (p⫽0.006) or DNP (p⫽0.02). CONCLUSION: Surgical relief of subaortic obstruction in patients with UH and high pulmonary blood flow can be effectively palliated with PAB or DNP. DKS construction and ventricular septal defect enlargement provide good long-term relief of SAS in select patients. SAS surgery should precede completion Fontan in most patients. CLINICAL IMPLICATIONS: Surgical relief of subaortic obstruction in patients with UH and high pulmonary blood flow can be effectively CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Cardiac Surgery: Congenital, continued palliated with PAB or DNP. DKS construction and VSD enlargement provide good long-term relief of SAS in select patients. DISCLOSURE: Mark Ruzmetov, None. DYNAMIC ATRIODIAPHRAGMOPLASTY WITH AUTOLOGICAL BIOLOGICAL VALVE: A NEW METHOD FOR FONTAN REPAIR Pavel Karakozov MD Iscander Baibekov PhD Valeri Chekanov MD* Milwaukee Heart Institute, Milwaukee, WI

MANAGEMENT OF ANOMALOUS LEFT CORONARY ARTERY ARISING FROM THE PULMONARY ARTERY IN THE ADULT: CASE REPORT AND REVIEW OF THE LITERATURE Frank Manetta MD* Darren I. Rohan MD L M. Graver MD Long Island Jewish Medical Center, New Hyde Park, NY PURPOSE: Anomalous origin of the left coronary artery (ALCAPA) is a rare congenital defect with an incidence of 1:300,000. These patients often present in infancy with anterior myocardial infarction, CHF or death. Adult type ALCAPA patients often present with symptomatic lesions, and therapy is aimed to restore a two coronary system. We present a 52 year old female who presented with severe mitral insufficiency who underwent preoperative cardiac catheterization and was found to have an anomalous left coronary artery arising from the main pulmonary artery. The patient underwent a mitral valve replacement along with re-establishment of a dual coronary system with bypass grafting and ligation. The patient recovered without incident. A review of the literature was undertaken to determine the optimum management of these asymptomatic lesions in adults. METHODS: We conducted a Medline review of the English literature from 1966 through September of 2004. Fifteen articles containing 41 patients ⬎11 years old were identified. The patient data was tabulated and analyzed. RESULTS: The mean age at diagnosis was 34 (16-72). The male to female ratio was 1:2. 86% of the patients underwent surgical therapy. Of

CARDIAC RELEASE OF B-TYPE NATRIURETIC PEPTIDE, CYTOKINES, AND INFLAMMATORY MARKERS IN CONGENITAL HEART DISEASE: PERIOPERATIVE SETTING UNDERGOING CARDIAC SURGERY WITH CARDIOPULMONARY BYPASS Pao-Hsien Chu MD* Yu-Sheng Chang MD Jaw-Ji Chu MD Chang Gung Memorial Hospital and Chang Gung University, Taipei, Taiwan ROC PURPOSE: BB-type Natriuretic Peptide (BNP) is a cardiac neurohormone specifically secreted by the cardiac ventricles in response to volume expansion, pressure overload, and resultant increased wall tension. This study was designed to explore whether it was possible to evaluate the perioperative setting of ventricular septum defect (VSD) and tetralogy of Fallot (TOF) by measuring BNP levels, cytokines and inflammatory markers. METHODS: A prospective study conducted between June 2004 and February 2005 included 16 consecutive patients who had been surgically corrected, including TOF (n⫽7; 44%), and VSD (n⫽9; 56%). Detailed clinical parameters were reviewed. The blood level of BNP, lactase, inflammatory marker (while blood cells, WBC; high-sensitive C-reaction protein, hs-CRP), and cytokines (interleukine-6, IL-6; -8, IL-8; and tumor necrotizing factor-␣;, TNF-␣;) had been evaluated before and the day after operation. RESULTS: The patient population was comprised of 4 (25%) women and 12 (75%) men. The mean age of patients’ participants was 18 months, with an age range of 6 to 59 months. BNP levels showed lower in VSD compared with TOF perioperation. In the TOF patients, BNP levels rose from 63 ⫹/- 80 pg/ml before operation to 592 ⫹/- 279 pg/ml 24 hours after operation (P⬍0.000); in VSD changed from 12.8 ⫹/- 7 pg/ml to 140 ⫹/72 pg/ml perioperation (P⬍0.000). In VSD and TOF patients, BNP levels correlated significantly with Qp/Qs, and peak RVP/LVP. BNP levels were well-correlated with the severity of the disease. The levels of lactase, hc-CRP, IL-6, IL-8 and TNF-;␣ were elevated significantly after postoperation in VSD patients (P⬍0.000); but not WBC, IL-8 or TNF-␣; in TOF. CONCLUSION: We conclude that BNP is a useful diagnostic tool in the identification of the condition and residual VSD for the patients with VSD and TOF. Levels of IL-6, and hs-CRP also increased significantly after surgery. CLINICAL IMPLICATIONS: BNP is a useful diagnostic tool for perioperative evaluation. DISCLOSURE: Pao-Hsien Chu, None. OUTCOME OF PALLIATIVE SURGICAL CORRECTION FOR SINGLE VENTRICLE PHYSIOLOGY WITH ECHOCARDIOGRAPHY AS THE ONLY PREOPERATIVE ASSESSMENT TOOL Annette Santiago MD* Enrique Carrion MD Cid Quintana MD University of Puerto Rico, San Juan, Puerto Rico PURPOSE: Single ventricle physiology occurs when one of the two ventricles is sufficiently small that a series circuit is incompatible with survival. Traditionally, all patients with single ventricle physiology undergo cardiac catheterization before palliative surgical correction . Cardiac catheterization carries small but appreciable risks, including arrhythmias, vascular damage, radiation exposure, patient discomfort, and parental anxiety. Additionally, in the current atmosphere of cost containment, the role of preoperative cardiac catheterization versus echocardiography assessment should be reevaluated. We postulate that by solely using commonly acquired echocardiographic information, patients with single ventricle physiology can undergo palliative surgical correction with biCHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: To ascertain whether atriomyoplasty, using the diaphragmatic muscle flap as the front wall of the atrio-pulmonary tunnel, results in successful Fontan repair. METHODS: Fontan operation, was performed on four adult mongrel dogs. Autological biological valves were created in the superior and inferior vena cava openings. The tendinous-muscle flap of the diaphragm, along with the diaphragmatic nerve, was inserted as the front wall of the atrio-pulmonary tunnel. The flap was either directly inserted into the circulatory system (2 cases) or applied externally onto the atrium wall (2 cases) and was stimulated through the diaphragmatic nerve with 7 burst impulses, at 6 volts each. Ventricular flap contraction was synchronized with contraction of the atrium. RESULTS: Immediately after the operation, a sharp decrease was registered in cardiac output (2–2.5 L/min), arterial pressure (60 –70 mmHg), pulmonary pressure (12–15 mmHg) and capillary saturation (SO2 ⬍60 – 65. Central vein pressure increased (13–15 mmHg). Signs of right heart failure disappeared after beginning diaphragmatic flap stimulation. Before diaphragmatic flap stimulation began, pressure in the created neo chamber or right atrium was between 10/0 –12/2 mmHg. Following initiation of flap stimulation, pressure in the neo chamber or right atrium was tracked for 3 hours and registered between 25/1–35/3 mmHg. Central vein pressure ranged from 6 –7.6 mmHg and arterial pressure from 100/50 –120/70 mmHg. The created autological valves functioned quite adequately with good locking function. Intraoperative echocardiogram measured blood flow through the caval veins at 8-12 mm/sec and the pulmonary artery at 70 – 80 mm/sec. The gradient in the created valves did not exceed 1–2 mmHg. CONCLUSION: The stimulated, diaphragmatic flap plays the part of the actively contracting heart wall adequately without preliminary training. Autobiological valves, created in caval vein openings, perform the locking function properly, maintaining an adequate pressure level in the neo chamber or right atrium, comparable to the pressure in the right ventricle. CLINICAL IMPLICATIONS: This new variant of the Fontan procedure could be used in the repair of several complex congenital cardiac defects. DISCLOSURE: Valeri Chekanov, University grant monies Tashkent Center of Surgery Grant

these patients, 69% had a dual coronary system re-established either by direct reimplantation of the left coronary artery or by grafting with either the IMA or SVG. There were 2 perioperative deaths (5.7%). In the five patients reported with nonoperative therapy, there was a 40% incidence of cardiac arrest in follow up. CONCLUSION: Adult survival appears to be improved with surgical therapy for ALCAPA. Re-establishment of a dual coronary system with closure of the fistula is the most common surgical therapy for adult type ALCAPA. Interestingly, the male to female ratio (1:2) in adults is reversed to that found in infants and children (2:1); suggesting men are more susceptible to death as a result of this disorder if left untreated. CLINICAL IMPLICATIONS: Asymptomatic adult patient with ALCAPA are at increased risk for myocardial infarction and sudden death. DISCLOSURE: Frank Manetta, None.

Wednesday, November 2, 2005 Cardiac Surgery: Congenital, continued Glenn or Fontan procedure and safely avoid preoperative cardiac catheterization. METHODS: We retrospectively reviewed the medical records of all the patients who underwent biGlenn and Fontan procedure from April 1995 through June 2003 at the Intensive Care Unit of the Centro Cardiovascular de Puerto Rico y del Caribe. Inclusion criteria included all children with univentricular physiology who had a complete preoperative echocardiogram performed within two weeks of surgery and who underwent palliative surgical corrections in the selected study period. RESULTS: A total of 37 patients were identified to meet the criteria. The most common preoperative diagnosis was Tricuspid Atresia (n⫽15), followed by Single Ventricle (n⫽13) and Pulmonary Atresia (n⫽9). There was no discordance between echocardiography and surgical findings. Bi-Glenn was performed in thirty-two patients. One patient of the biGlenn group died for an overall group survival of 96.8% . Twenty patients underwent Fontan procedure. Seventeen patients had undergone prior Glenn shunt. The overall group survival was 100%. CONCLUSION: Echocardiography is a valuable diagnostic tool if performed after a careful physical examination. It can provide the information needed for a complete and accurate diagnosis of congenital heart diseases. CLINICAL IMPLICATIONS: We conclude that morbidity and mortality after single ventricle palliative correction is not affected by echocardiography as the only preoperative assessment tool and that routine use of cardiac catheterism with its implicated complications and higher costs may be avoided. DISCLOSURE: Annette Santiago, None.

Cardiac Surgery: Interventions and Predictors 12:30 PM - 2:00 PM SAFETY AND EFFICACY OF IMMEDIATE POSTOPERATIVE ASPIRIN IN OFF PUMP CORONARY ARTERY BYPASS GRAFTING PATIENTS Yatin Mehta MD* Satish Kumar MD Altaf Bukhari MD Mayank Vats MD Naresh Trehan MD Escorts Heart Institute and Research Center, New Delhi, India PURPOSE: Preoperative aspirin administration, which is continued during the postoperative period in Coronary Artery Bypass Grafting (CABG) patients, has resulted in improvement in early as-well-as late graft patency. However the precise complication rate as a result of immediate (i.e. within 24-hours) postoperative administration of aspirin has not been fully evaluated especially in Off-Pump-CABG(OPCAB) patients and the existing data has conflicting results.The aim of this study was to evaluate safety and efficacy of immediate postoperative aspirin (i.e. ⬍24 hours) in OPCABG. METHODS: Out of 887 patients, who underwent OPCAB, only 750 patients fulfilled the inclusion criteria and randomized into group-A (aspirin with-in first 24 hrs) and group-B (placebo till chest-tubes removal & then aspirin). Complete preoperative evaluation was done and surgical/ anesthetic techniques were same in both group. Primary end-points of study were:-Inhospital mortality, perioperative Myocardial Infarction (PMI), stroke, cerebral hemorrhage, reexploration and gastrointestinal ischemia and hemorrhage. Seondary end-points were-amount of mediastinal bleeding, blood/blood product transfusion and length of ICU/ hospital stay. RESULTS: Both groups were statistically similar regarding demographic, comorbidities, preoperative anti platelet/anticoagulation and other cardiac-medications and total platelet-count. Outcome measures in group A & B respectively were:Mortality–1.6% v/s 0.5% p-0.286, PMI2.7% v/s2.5% p-0.125,GI bleeding–1.1%v/s0.8% p-0.699, stroke 0.3% v/s0.3% p-1,Renal failure-3.5% v/s2.7%,p0.525, mediastinal drainage 307.7⫾30.5ml v/s298.3⫾ 29.3 ml p-001, reexploration3.5% v/s1.1% p-0.5, ICU stay 2.3⫾0.9v/s2.09 ⫾.0.8days, p-0.001. Blood/blood products transfusion requirement in group A&B were: whole blood 0.76⫾1.23v/ s0.60⫾0.90Units p0.04, platelet concentrate 1.2⫾0.8 v/s0.6⫾0.31Units p⬍ 0.001, Fresh Frozen Plasma2.67⫾ 0.21v/s1.33⫾0.14 Units P⬍ 0.001, PRBC 3.8⫾ 1.9 v/s1.7 ⫾ 1.2Units P⬍ 0.001.

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CONCLUSION: We conclude that early aspirin therapy i.e within 24 hours after OPCAB may not be beneficial in prevention of postoperative inflammatory injury rather it may increase the incidence of bleeding, blood/blood product requirement and re-exploration and other adverse outcome. CLINICAL IMPLICATIONS: Immediate postoperative administration of aspirin in OPCAB patients should be avoided and the risk benefit ratio of early aspirin therapy in OPCAB should be evaluated in doubleblinded, Randomised-Controlled-Trials. DISCLOSURE: Yatin Mehta, None.

CAN B-TYPE NATRIURETIC PEPTIDE LEVELS PREDICT THE OCCURRENCE OF ATRIAL FIBRILLATION IN THE POSTOPERATIVE PERIOD OF CARDIAC SURGERY? Alexandre R. Felipe MD* Renato V. Gomes MD Pedro M. Nogueira MD Marco Aure´lio d. Fernandes MD Jorge Sabino MD Fernando G. Aranha MD Luiz Antonio d. Campos MD Hans Fernando d. Dohmann MD Hospital Pro´-Cardı´aco, Rio De Janeiro, Brazil PURPOSE: The usefulness of measuring B-type natriuretic peptide (BNP) levels in the postoperative (PO) period of cardiac surgery (CS) has been frequently assessed.The objective this study is to correlate BNP levels and occurrence of Atrial Fibrillation (AF) in the PO period of CS. METHODS: Prospective study with a classic cohort of 77 patients (pts) undergoing CS and consecutively selected between August/2003 and January/ 2005. Their mean age was 66.9⫾9.89 years, 22 (28.5%) were females, and the mean Euroscore was 4.26. The BNP level was measured in the preoperative period (BNPPre), and in the first (BNP1) and sixth (BNP6) PO hours. The BNP level was quantitatively measured by use of immunofluorescence (Biosite Triage BNP Test). The occurrence of AF in the PO period was correlated with the following variables: Euroscore; age; sex; preoperative creatinine level and ventricular function; duration of ECC; SOFA on the first PO day; and BNP (Pre, 1, and 6) levels. The statistical analysis comprised the following tests: Student t; Chi-Square; Mann-Whitney followed by ROC curve construction; and principal component analysis. RESULTS: In the sample studied, 13 pts (16.8%) had AF in the PO period. A significant correlation was observed between the BNP levels [BNPPre (0.01), BNP1 (0.011), and BNP6 (0.03)] and the occurrence of AF. None of the other variables tested correlated with the occurrence of AF. After the principal component analysis, the 3 BNP levels maintained the correlation with the occurrence of AF. BNPPre had a better AUC (ROC) (0.727), in which values greater than 100 pg/dL correlated with the occurrence of AF. CONCLUSION: In the population studied, the occurrence of AF showed a correlation with the 3 BNP levels measured, and all of them were independently associated with the outcome. A BNPPre level greater than 100 pg/dL correlated with the occurrence of AF in the PO period of CS. CLINICAL IMPLICATIONS: The BNP showed to be a useful risk marker for the occurence of FA.

DISCLOSURE: Alexandre Felipe, None. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Cardiac Surgery: Interventions and Predictors, continued EFFECTS OF CLOPIDOGREL IN OFF-PUMP BEATING HEART SURGERY Simon Maltais MD* Karine Tetreault MS Quoc-Bao Do MD Notre Dame Hospital, Montreal, PQ, Canada

USE OF A NEGATIVE PRESSURE CUIRASS TO IMPROVE HEMODYNAMICS FOLLOWING CARDIAC SURGERY Rakesh K. Chaturvedi MD* McGill University, Montreal, PQ, Canada PURPOSE: In most cases in patients with normal lungs, positive pressure ventilation (PPV) with positive end expiratory pressure (PEEP) reduces cardiac output by decreasing venous return. We hypothesized that in patients receiving PPV, continuous negative pressure (CNP) applied to the chest via a cuirass would counter the negative effects of positive pressure in the chest, yet result in lung expansion similar to PEEP. METHODS: 20 patients with normal ejection fractions were studied 2 hours post coronary artery bypass graft (CABG) surgery with the pericardium left open. The patients were ventilated on pressure support ventilation (PSV) and synchronized intermittent mandatory ventilation (SIMV) with PEEP. Parameters were studied during 4 modes: A (baseline-1)⫽ SIMV, PSV and PEEP, B⫽SIMV & PSV without PEEP, C⫽SIMV & PSV without PEEP and with CNP applied to the thorax at -20 cm H2O for 15 minutes, D (baseline-2)⫽ SIMV, PSV and PEEP. Hemodynamic measurements were performed in the supine position after a 15 minutes period of equilibration between each mode using a standard pulmonary artery catheter and arterial line. No patient was treated with additional fluids or inotropes during the study. All comparisons were done using repeated ANOVA and the results of the 2 baselines were averaged, mean baseline (MB). RESULTS: All patients were hemodynamically stable during the trial; HR, BP and gas exchange were not affected. The removal of PEEP (5 cm H2O) did not affect CVP, WP or CO significantly MB vs B and B vs C. However, CNP significantly lowered both wedge and CVP (p⬍ .05) compared to before and after CNP MB vs C. The cardiac index (CI) and stroke volume index (SVI) also improved significantly with CNP compared to baselines MB vs C. CONCLUSION: The use of CNP applied to the thorax in the postoperative period appears to improve cardiovascular hemodynamics possibly by increased venous return or by improving the contractility of the myocardium. CLINICAL IMPLICATIONS: CNP may be beneficial as a novel treatment modality for postoperative low output syndrome.

LOW EXTUBATION TIMES IN CARDIAC SURGERY PATIENTS USING THE RAPID SHALLOW BREATHING INDEX Charles E. Oribabor MD* Naim Mansuroglu MD Felix Khusid RRT Anthony Patten Mary Suleiman Jessica Primiano Leonard Lee MD Anthony Tortolani MD New York Methodist Hospital: Affiliate Weill College of Cornell University, Brooklyn, NY PURPOSE: To utilize the Rapid Shallow Breathing Index (RSBI) to lower extubation times in open heart surgery patients. METHODS: We studied 167 open heart surgery patients prospectively between April 1st 2004 and March 30th 2005.This included 33 valve surgery patients,122 coronary artery bypass graft (CABG),5 Stanford A Aneurysm patients,1 aortic dissection,1 combined valve/aneurysm patient,4 off pump CABG patients and 1 pericardial stripping. No patients were excluded.EXTUBATION CRITERIA: Rapid shallow breathing indexⱕ105. EXTUBATION HALTING CRITERIA:(1)Medisatinal Hemorrhageⱖ 200cc/hour(2)Ramsay Sedation scaleⱖ4(3)Metabolic or respiratory acidosis on continuous positive airway ventilation.(4)Postoperative cardiogenic shock EXTUBATION TIME : defined as time from arrival in the intensive care unit to time extubated.REINTUBATION: was defined as any patient reintubated within 24 hours of extubation.Narcotic analgesia with morphine was used for postoperative pain.The patients cardiac anesthesiologists were informed of the weaning criteria with the RSBI that was going to be used.Drager ventilators; model EVITA XL; which calculate and display the RSBI continuously were used.All patients were placed in a semi recumbent position once the immediate postoperative blood samples had been taken.The head of the bed was raised to at least 45 degrees. Patients with intra-aortic balloon pumps were paced in a reversed trendelenburg position for weaning.Bedside physical therapy with incentive spirometers was commenced immediately post-extubation. RESULTS: The overall mean extubation time was 2hours 40 minutes. The mean extubation time was unaffected by outliers who did not meet the weaning criteria for extubation. This included a total of 6 patients who remained intubated forⱖ 18 hours. Zero reintubations. Overall mean extubation times were unaffected by the age,hemodynamic status,comorbidity, or ejection fraction. CONCLUSION: The utilization of the rapid shallow breathing index as the sole criteria for weaning has lead to significantly low mean extubation times in cardiac surgery patients.No increased rates of reintubation were observed.Postoperative narcotic analgesia did not increase mean extubation times. CLINICAL IMPLICATIONS: (1)Significant reductions in resource utilization of the respiratory department and ventilatory equipment.(2)Patient and family satisfaction at early extubation times. (3)Reduced length of stay in the intensive care unit. DISCLOSURE: Charles Oribabor, None.

DIFFERENT HEART-LUNG MACHINE CONCEPTS INFLUENCE PLATELET AND MONOCYTE SURFACE-MARKER EXPRESSION DURING CORONARY ARTERY SURGERY Thomas Waldow MD* Gunter Schumann MD Volker Schmidt Oliver Tiebel MD Gabriele Siegert MD Michael Knaut MD Klaus Matschke MD Herzzentrum Dresden, Dresden, Germany PURPOSE: Function of various cellular blood components is altered under conditions of cardiopulmonary bypass (CPB) which can lead to activation of pro- and anticoagulant systems. In the present study, the effects of two different heart-lung-machine (HLM) concepts on the expression of surface markers on monocytes and platelets are compared. METHODS: In a prospective, randomized and single-blinded study sixty patients with elective coronary artery bypass surgery were recruited into three groups. A standard system (group 1) was compared with a modified HLM containing of a Deltastream pump, surface-modified tubing, and reduced priming volume (Optimized Mini-Circulation Cardiopulmonary Bypass System (OMCPB)) (group 2). In group 3 patients were operated on without extracorporeal circulation (OPCAB). Blood was collected at different time points before, during, and until 48 hours after surgical intervention. Platelets were incubated with either CD42b-FITC-/ CD62P-PE- or Factor Va-FITC-/ Tissue Factor-PE-labeled antibodies. EDTA-anticoagulated blood was incubated with CD11b-FITC- / CD18PE- labelled antibodies. Samples were analysed applying flow cytometry. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: Platelet-rich intracoronary thrombus is central to the pathogenesis of acute coronary syndrome, and patients scheduled for coronary artery bypass graft (CABG) surgery today are receiving more antiplatelet drugs. The use of such drugs, especially the Clopidogrel, before the surgery creates a major dilemma for cardiac surgeons. Our primary objective was to evaluate the role of Clopidogrel on operative bleeding and the timing of discontinuing the medication before surgery. Secondary objectives were to assess the incidence of blood and platelet transfusions following its use. METHODS: We retrospectively analysed 453 patients undergoing off-pump CABG surgery which received or not Clopidogrel in the last 3 years, looking at the mean operative bleeding (per, post and total) and determining risks factors for blood or platelet transfusions using a multivariate analysis. RESULTS: Clopidogrel in off-pump CABG surgery is associated with higher operative and post-operative bleeding (702 vs 554 cc, p⫽0.03 and 864 vs 603 cc, p⫽0.03). Stopping Clopidogrel 72 hours before surgery significantly reduces mean operative blood loss (554 vs 802 cc, p⬍0.0001). Patients off Clopidogrel for more than 72 hours don’t seem to bleed more than the control group (p⫽NS). The use of Clopidogrel is associated with more platelet transfusions (OR⫽11.79, [1.48; 93.86]), but blood transfusions seems similar in all group studied (p⫽NS). CONCLUSION: Mean operative blood loss is higher in patients who used Clopidogrel before surgery. Clopidogrel is associated with more platelet, but not blood transfusions after off-pump CABG surgery. Stopping Clopidogrel 72 hours before surgery shows similar mean operative blood loss compared to control group. CLINICAL IMPLICATIONS: Stopping Clopidogrel 72 hours before surgery shows similar mean operative blood loss compared to control group. DISCLOSURE: Simon Maltais, None.

DISCLOSURE: Rakesh Chaturvedi, None.

Wednesday, November 2, 2005 Cardiac Surgery: Interventions and Predictors, continued RESULTS: CD42b-expression decreased significantly at the end of the observation period in group 1 disclosing significant differences to groups 2 and 3. Platelet Factor Va-expression was significantly elevated in group 1 during bypass compared to groups 2 and 3. Tissue Factor- and CD62P-expression showed no significant differences between groups. CD11b-expression on neutrophiles and monocytes increased significantly under bypass and until 30 minutes after bypass in groups 1 and 2 compared to group 3 with higher values in group 1. CONCLUSION: Activation of Factor X through monocyte CD11b expression and Factor Va expression on platelet surfaces are synergistic conditions in thrombin generation under CPB. This procoagulant stimulus could be significantly reduced using OMCPB. CLINICAL IMPLICATIONS: Dysfunction of cellular blood components has a major influence on clinical outcome after use of CPB through parameters like blood loss, systemic inflammation and micro-clot formation. Use of an optimized HLM may influence some of these factors. DISCLOSURE: Thomas Waldow, None.

CIRCADIAN RHYTHM HAS NO EFFECT ON MORTALITY IN CORONARY ARTERY BYPASS SURGERY Ajay K. Dhadwal MD* Mikhail Vaynblat MD Shyama Balasubramanya MD Murali Pagala PhD Nancy Schulhoff RN Joshua H. Burack MD Joseph N. Cunningham Jr MD Maimonides Medical Center, New York, NY PURPOSE: Circadian variation affects atherosclerosis at many levels, including a circadian outcome in the treatment of myocardial infarction by angioplasty and thrombolysis.This has not been studied in the surgical patient. The circadian variation in mortality dependant on the time of surgery was examined in patients undergoing coronary artery bypass surgery (CABG). METHODS: A 4 year retrospective review of all CABG patients (n⫽3140) from 1999 to 2002 at a single institution with an accreditated training program was undertaken. The patients were divided into elective, urgent and emergency cases. The cases were subdivided according to the start time of the operation as morning (7am-2pm ⫽AM), afternoon (2pm-8pm⫽AF) and night (8pm-7am ⫽NT) and as weekday (Monday to Friday ⫽WD) or weekend (WE) cases. The outcome was mortality within 30 days and compared for 4 different time frames: (1) AM vs. AF (2) AM vs. NT (3) AF vs. NT (4) WD vs. WE for each prioritized group. Risk factors and number of anastamoses were compared for each group. Sigma Statistical package and z-test for 2 group comparison were used for analysis. T-test was used to compare age and ejection fraction. RESULTS: No statistically significant difference in mortality was observed for the elective and urgent groups for each of the time periods compared (Table). The emergency cases had significantly increased deaths in the AM and NT compared to the AF (p⬍0.01 and p⬍0.05 respectively). There was no statistically significant difference with respect to age, gender, number of anastamoses performed, ejection fraction and preoperative risk factors between groups. CONCLUSION: The mortality for non-emergent CABG is independent of the timing of surgery. Circadian variation does not influence the outcome in cardiac surgical patients. CLINICAL IMPLICATIONS: This study demonstrates that the biological effect of circadian variation and environmental factors (eg. surgeon fatigue) has no effect on mortality in cardiac surgery. This reassures surgeons and patients alike that the outcome is independant of the time of the procedure.This should be noted prior to further work hour legislation being introduced. Mortality (Deaths/Cases) Elective CABG Urgent CABG Emergency CABG

AM 16/637 2.51% 48/1512 3.17% 6/23 26.09%

AF

NT

2/201 0/10 0.995% 0% 23/674 0/31 3.41% 0% 1/37 5/18 AM vs AF: p⬍0.01 2.70% 27.78% AF vs NT: p⬍0.05

DISCLOSURE: Ajay Dhadwal, None.

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WD

WE

18/835 0/13 2.16% 0% 66/2060 5/152 3.20% 3.29% 10/69 2/9 14.49% 22.22%

RESCUE PERCUTANEOUS CORONARY INTERVENTION, REOPERATION, OR CONSERVATIVE TREATMENT IN ACUTE PERIOPERATIVE GRAFT FAILURE AFTER CORONARY ARTERY BYPASS SURGERY Matthias Thielmann MD* Parwis Massoudy MD Guenter Marggraf MD Beate Jaeger MD Stefan Sack MD Raimund Erbel MD Heinz Jakob MD Thoracic and Cardiovascular Surgery, West-German Heart Center Essen, University, Essen, Germany PURPOSE: Perioperative graft failure after coronary artery bypass surgery (CABG) results in acute myocardial infarction (PMI), which necessitates acute re-revascularization to salvage myocardium, thus preserving ventricular function and improving patient outcome. Whether rescue percutaneous coronary intervention (PCI), emergency reoperation, or conservative intensive care treatment should be applied is currenly unknown. METHODS: Perioperative graft failure after coronary artery bypass surgery (CABG) results in acute myocardial ischemia/infarction (PMI), which necessitates acute re-revascularization to salvage myocardium, thus preserving ventricular function and improving patient outcome. Whether rescue percutaneous coronary intervention (PCI), emergency reoperation, or conservative intensive care treatment should be applied is currenly unknown. RESULTS: Repeat coronary angiography 4 (1-10) hrs (median and range) after the onset of symptoms revealed acute perioperative bypass graft failure in 73 patients and 98 out of 258 bypass grafts after CABG. The number and type of failing grafts were comparable between groups 1 and 2, but significantly different to group3 (P⬍0.001). Acute PCI was applied in 27 patients, reoperation in 18 patients, and conservative intensive care treatment in 28 patients. Maximum postoperative cTnI levels were significantly different between groups 1 and 2 (92⫾16 versus 205⫾42 ng/mL; P⬍0.001). Left ventricular ejection fraction was reduced during the acute event compared to preoperative values (P⬍0.01) and significantly improved during follow-up within each group (P⬍0.02), but did not differ between the groups. In-hospital and 1-year mortality were 14.8% and 22.2% in group 1, 27.8% and 33.3% in group 2, and 14.3% and 28.6% in group 3, respectively (P⫽NS). CONCLUSION: Re-revascularization with rescue PCI was succesfull to relieve acute myocardial ischemia and decreased the extent of myocardial cellular damage. However, no statistically significant difference could be observed between different re-revascularization strategies in terms of left ventricular function and short- and mid-term outcome. CLINICAL IMPLICATIONS: The cardiac cathlab should routinely be available to identify the underlying mechanism of PMI after CABG and to reintervene immediately in case of acute graft failure. DISCLOSURE: Matthias Thielmann, None. SURGICAL INTERVENTION FOR ACUTE PULMONARY EMBOLISM A. Salemi MD* G. Gonzalez-Stawinski MD B. W. Lytle MD D. M. Cosgrove MD G. Pettersson MD N. G. Smedira MD Cleveland Clinic Foundation, Cleveland, OH PURPOSE: Acute massive pulmonary embolism (APE) resulting in hemodynamic instability is a fatal condition. Pulmonary embolectomy serves as definitive therapy for those in whom catheter embolectomy and thrombolysis are either contraindicated or unsuccessful. METHODS: This study was performed to determine our experience with pulmonary embolectomy for APE. We performed a retrospective chart review of patients undergoing pulmonary embolectomy for APE from October 1994 to August 2003. Charts provided demography, symptomatology, operative procedures, and short term outcomes. RESULTS: A total of 13 patients underwent pulmonary embolectomy between October 1994 and August 2003. Average age was 52 years (range 32 to 65). Symptoms were present in all patients and 63% of patients had hemodynamic instability at the time of operation. Diagnosis was established by either spiral computerized tomography or transesophageal echocardiography. Emergent surgery was undertaken in 70% of patients. Cardiopulmonary bypass was established in all patients with 30% requiring circulatory arrest. Overall survival was 63%. When comparing survivors to non-survivors, the latter group was more likely to be operated on emergently. Of those who survived, all are well at a mean follow-up of 12.3 months. CONCLUSION: Pulmonary embolectomy utilizing cardiopulmonary bypass and circulatory arrest is effective treatment in patients with massive embolism and is associated with good short term outcomes. Operative mortality is increased when surgery is performed under emergent conditions. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Cardiac Surgery: Interventions and Predictors, continued CLINICAL IMPLICATIONS: Pulmonary embolectomy for acute massive pulmonary embolism serves as definitive therapy and should be utilized in patients refractory to other therapeutic modalities. DISCLOSURE: A Salemi, None. INFLUENCE OF THE USE OF VASOACTIVE AMINES ON BTYPE NATRIURETIC PEPTIDE LEVELS MEASURED IN PATIENTS UNDERGOING CARDIAC SURGERY Alexandre R. Felipe MD* Renato V. Gomes MD Pedro M. Nogueira MD Marco Aurelio d. Fernandes MD Gustavo Rodrigues MD Fernando G. Aranha MD Luiz Antonio d. Campos MD Hans Fernando d. Dohmann MD Hospital Pro´-cardı´aco, Rio De Janeiro, Brazil

IN-HOSPITAL EVOLUTION OF PATIENTS WITH AN CENTRAL VENOUS OXYGEN SATURATION GREATER THAN OR EQUAL TO 70% IN THE POSTOPERATIVE PERIOD OF CARDIAC SURGERY Pedro Miguel d. Nogueira MD* Alexandre R. Felipe MD Renato V. Gomes MD Marco Aure´lio d. Fernandes MD Leonardo d. Pinto MD Luiz Antonio d. Campos MD Jose´ Rodolfo Rocco PhD Hans Fernando d. Dohmann MD Hospital Pro´-Cardı´aco, Rio de Janeiro, Brazil PURPOSE: Central venous oxygen saturation (ScVO2) has been considered an important parameter for follow-up, prognostic estimate, and therapeutic target in the management of critically ill patients (pts).The objective this study is to assess the evolution of pts with an ScVO2 ⱖ 70% in the postoperative (PO) period of cardiac surgery, and to correlate that finding with in-hospital mortality. METHODS: A classic cohort of 128 consecutive pts was selected from January 2004 to August 2004. Blood samples were collected through a central venous catheter properly positioned in the right atrium according to a previously validated method. The ScVO2 measurements were taken in the postoperative period as follows: immediately (SV0), after 6 hours (SV1), and after 24 hours (SV2). The pts were divided into 4 groups as follows: GI (60 pts), none of the 3 measurements was ⱖ 70%; GII (33 pts), at least one of the 3 measurements was ⱖ 70%; GIII (22 pts), 2 of the 3 measurements were ⱖ 70%; and GIV (13 pts), all measurements were ⱖ 70%. The chi-square test was used for statistical analysis. In-hospital mortality was defined as the occurrence of death during hospitalization. RESULTS: In-hospital mortality in our sample was 8.6% and, in the groups, it was as follows: GI, 16.7%; GII, 3.0%; and GIII and GIV, 0%, as shown in the annexed table. After applying the chi-square test, the differences in mortality rate were significant (P ⫽ 0.023).

Groups GI GII GIII GIV TOTAL

Alive

Death

83,3% 97% 100% 100% 91,4%

16,7% 3% 0% 0% 0%

DISCLOSURE: Pedro Miguel Nogueira, None. MANAGING LIFE THREATENING VIRAL MYOCARDITIS WITH DILATED CARDIOMYOPATHY BY DROTRECOGIN ALFA AND CIRCULATORY ASSISTED DEVICES Tsung P. Tsai PhD* Shyh M. Tsao MD Yi L. Wu MD Jung M. Yu MD Kuei C. Chan MD Kwo C. Ueng MD Chung Shan Medical University Hospital, Taichung, Taiwan ROC PURPOSE: Acute fulminant myocarditis with dilated cardiomyopathy caused by Parvovirus B19 may present with cardiogenic shock refractory to the maximum dose of inotropics and intra-aortic balloon pumping (IABP). The benefits of extracorporeal membrane oxygenation (ECMO) support for patients with life-threatening myocarditis has been established. Drotrecogin alfa, recombinant human activated protein C, has antithrombotic, anti-inflammatory and profibrinolytic properties. The effectiveness from the circulatory support (ECOM or IABP) and activated protein C use in managing acute myocarditis with dilated cardiomyopathy caused by Parvovirus B19 has to be defined. METHODS: Four patients( 2 male, 2 female, mean age 37.2 years) presented with congestive heart failure 3 to 4 days after flu-like symptoms (intermittent fever 38⬃39°C, dyspnea and chest tightness). Chest roentgenograms showed cardiomegaly and bilateral pulmonary infiltrates. EKG revealed non-specific ST wave changes. 2-D echocardiograms demonstrated severe myocardial dysfunction with LVEF, measured between 18.4 to 22% (mean, 19.5%). Coronary angiography was performed in each patient and excluded ischemic heart disease. Acute decompensation with more than 2 organ failure (heart and lungs) and unresponsive to more than 2 inotropics and acute respiratory therapy were indications for the use of circulatory support by IABP (3pts) and/or ECMO (3pts) as well as activated protein C (3pts). Serological test and myocardial biopsy for Parvovirus B19 was positive in 3 pts and one pt, respectively. RESULTS: All three pts with ECMO and IABP support were weaned. Follow-up LVEF measured were 53%, 53%, 55% and 60%, respectively. However one pt died one month later because the deterioration of her SLE condition and repeated infection. There were no neurologic sequelae in survivors. CONCLUSION: Use of circulatory support and activated protein C is an effective alternative for treating life-threatening viral myocarditis with dilated cardiomyopathy, especially caused by Parvovirus B19 virus. CLINICAL IMPLICATIONS: Parvovirus B19virus can cause severe myocarditis with dilated cardiomyopathy and circulatory collapse. Combined use of Drotrecogin alfa and ECMO and/or IABP is an effective novel therapy for this cohort of patients. DISCLOSURE: Tsung Tsai, None.

Cardiology: Arrhythmias 12:30 PM - 2:00 PM COMPLAINCE TO ANTIPLATELET THERAPY AFTER SIROLIMUS-ELUTING STENT IMPLANTATION IN VARIOUS SOCIOECONOMIC POPULATION Vimesh K. Mithani MD Padmaja Akkineni MD Anuj Agarwal MD* Mahesh Bikkina MD St Joseph’s Hospital and Medical Center, Paterson, NJ PURPOSE: It has been shown that there are differences in outcomes in acute coronary syndromes due to income disparities. Antiplatelet CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: To establish the kinetics of BNP levels measured in the PO period of CS, and to correlate the BNP levels with the use of vasoactive amines (VA) in the first PO hour (PO1H). METHODS: Prospective study with a cohort of 77 patients (pts) undergoing CS, between August/2003 and January/2005. Mean age 66.9⫾9.89 years, 22 (28.5%) females, mean Euroscore 4.26. The BNP level was measured in the preoperative period (BNPPre), and in the first (BNP1) and sixth (BNP6) PO hours. Patients receiving VA [(dobutamine (DBT) and/or noradrenaline (NAD)] at any dosage in the first PO hour were assessed and the use of VA was correlated with the BNP1 and BNP6 levels. Statistical analysis: Wilcoxon Matched Pairs Test and Mann-Whitney test. RESULTS: In the total of sample the mean BNP levels found were as follows: BNPPre ⫽ 159.4 pg/mL ⫾ 217.9 (MED ⫽ 79.4); BNP1 ⫽ 150.2 ⫾ 203.3 (MED ⫽ 77.1); and BNP6 ⫽ 243.0 ⫾ 237.0 (MED ⫽ 168.5), between BNPPre and BNP6, the difference was statistically significant (p ⫽ 0.0004). About the use of amines in our sample, 22 pts received VA in the PO1H as follows: 7 pts, NAD ⫹ DBT; 12 pts, NAD; and 3 pts, DBT. A significant correlation was observed between the use of DBT and the BNPPre (p ⫽ 0.004), BNP1 (0.024), and BNP6 (0.05) levels. The use of NAD did not correlate with the BNP levels. The DBT group had greater mean BNPPre, BNP1, and BNP6 levels than those in the NAD group (790x159, 1004x243, and 609x203pg/dL, respectively). CONCLUSION: Was observed the difference between BNPPre and BNP6, this result cans establish a curve of the BNP kinetics in the PO of CS. In the patients using DBT had greater BNP levels than those receiving only NAD, this may correlate with a worse degree of ventricular dysfunction among those pts. CLINICAL IMPLICATIONS: This study showed the curve of the BNP kinetics in the PO period of CS. DISCLOSURE: Alexandre Felipe, None.

CONCLUSION: In the population studied, at least one ScVO2 ⱖ 70% in the first 24 PO hours of cardiac surgery seems to have an impact on in-hospital mortality. CLINICAL IMPLICATIONS: This study showed the importance of a ScVO2 to idendificate the patients with greather risk of death.

Wednesday, November 2, 2005 Cardiology: Arrhythmias, continued therapy (aspirin and clopidogrel) is essential for preventing adverse outcomes after stent implantation. The cost of this treatment particularly clopidogrel may pose hindrance to compliance in low-income and uninsured population. It has been recommended that with the sirolimuseluting stents the length of treatment with these antiplatelet agents is longer than conventional bare-metal stents. We looked at the compliance in different income populations who received sirolimus-eluting stents at a single-center registry. METHODS: The purpose of the study was to assess the noncompliance rate with the antiplatelet regimen in the insured population compared to uninsured low-income population and whether it was associated with recurrent hospitalizations, myocardial infarctions, or death. There are a total of 100 patients, who underwent sirolimus-eluting stent implantation, from April 2003 to October 2003 were followed at three months. It comprised of 50 patients in each socioeconomic arms from the registry of a single medical center. RESULTS: The non-complaince rate with the antiplatelet therapy in insured versus uninsured low-income population is 2 patients (4%) versus 12 patients (24%) respectively at three months. All these patients were non-complaint to clopidogrel and one patient from the uninsured lowincome population was non-complaint to aspirin as well. None of the patients from of the insured population were hospitalized or had myocardial infarction or death. One patient (2%) from the uninsured population had ST elevation myocardial infarction with stent thrombosis at 8 days and underwent successful revascularization. This patient was non-complaint to clopidogrel. CONCLUSION: There is a significant incidence of non-complaince rate with antiplatelet regimen particularly clopidogrel among the low socioeconomic population due to cost issues. CLINICAL IMPLICATIONS: Non-complaince to antiplatelet regimen is an important factor to consider prior to coronary intervention since stent thrombosis secondary to inadequate antiplatelet therapy has significant morbidity and mortality. DISCLOSURE: Anuj Agarwal, None.

REDUCED EJECTION FRACTION AFTER MYOCARDIAL INFARCTION: IS IT SUFFICIENT TO JUSTIFY IMPLANTATION OF A DEFIBRILLATOR? Patrizio Pascale MD* Patrick Taffe PhD Claude Regamey MD Lukas Kappenberger MD Martin Fromer MD University Hospital, Division of Cardiology, Lausanne, Switzerland PURPOSE: Improved survival after prophylactic implantation of a defibrillator in patients with reduced left ventricular ejection fraction (EF) after myocardial infarction (MI) has been demonstrated in patients with remote MI experienced in the 1990’s. The absolute survival benefit conferred by this recommended strategy must be related to the current risk of arrhythmic death which is evolving. This study evaluates the mortality rate in survivors of MI with impaired left ventricular function and its relation to pre-discharge baseline characteristics. METHODS: Clinical records of patients who had sustained acute MI from 1999 to 2000 and were discharged with an EF ⱕ 0䡠40 were included. Baseline characteristics, drug prescriptions and invasive procedures were recorded. Bivariate and multivariate analyses were performed using a primary endpoint of total mortality. RESULTS: 165 patients were included. During a median follow-up of 30 months (interquartile range 22-36) 18 patients died. One and two-year mortality rates were 6䡠7% and 8䡠6%, respectively. Variables reflecting coronary artery disease and its management (prior MI, acute reperfusion, complete revascularization) had a greater impact on mortality than variables reflecting mechanical dysfunction (EF, Killip class). CONCLUSION: Mortality in survivors of MI with reduced EF is substantially lower than reported in the 1990’s. CLINICAL IMPLICATIONS: This decreased absolute mortality implies a proportional increase in the number of patients needed to treat with a prophylactic defibrillator. The risk of event may even be sufficiently low to limit the detectable benefit of defibrillators in patients with the prognostic features identified in our study. This argues for additional risk stratification prior to the prophylactic implantation of a defibrillator.

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Multivariate analysis of the associations between selected variables and all-cause mortality All-cause death Age Male sex Left ventricular EF Previous MI Acute reperfusion Documented complete revascularization (acute or not)

Hazard ratio (95% CI) 1䡠067 2䡠076 1䡠020 3䡠632 0䡠267 0䡠279

(0䡠997-1䡠142) (0䡠652-6䡠610) (0䡠939-1䡠108) (1䡠356-9䡠728) (0䡠072-0䡠992) (0䡠074-1䡠050)

p Value 0䡠059 0䡠216 0䡠634 0䡠010 0䡠049 0䡠059

DISCLOSURE: Patrizio Pascale, None.

PERMANENT RIGHT PHRENIC NERVE PARALYSIS FOLLOWING CATHETER RADIOFREQUENCY (RF) ABLATION FOR PAROXYSMAL ATRIAL FIBRILLATION (PAF) Long X. Le MD* Patricia J. Sime MD University of Rochester School of Medicine, Rochester, NY PURPOSE: Introduction: Transcatheter radiofrequency ablation has emerged as an important treatment modality for PAF [1]. The risk of thromboembolism, pulmonary vein stenosis, and cardiac perforation has been documented. However, only one case of transient right phrenic nerve injury during pulmonary vein (PV) RF ablation has been reported [2]. We document a case of permanent right phrenic nerve paralysis following PV-RF ablation. METHODS: Case Report: A 61-year-old man with a 6-year history of PAF was admitted for PV-RF. His physical examination was unremarkable. An echocardiogram showed normal cardiac chamber size and function and four pulmonary veins. Electrophysiology studies revealed idiopathic AF with multiple pulmonary vein foci. PV-RF ablation was performed as described by Haissaguerre [1,3]. A total of 41 RF pulses for duration of 2080 seconds was required to ablate the arrhythmogenic foci. On post-procedure day one, he complained of dyspnea and orthopnea. A ventilation/perfusion scan was negative for pulmonary thromboembolism. A chest X-ray revealed elevation of the right hemidiaphragm (Figure I). Fluoroscopy confirmed paralysis of the right hemidiaphragm. Pulmonary function tests (PFT) revealed moderate restrictive pulmonary physiology (Table I). On postprocedure day six, his symptoms improved but right hemidiaphragm elevation persisted. Five months later, he was asymptomatic. However, the chest X-ray, fluoroscopy, and PFT revealed persistent right hemidiaphragm paralysis and restrictive pulmonary physiology. RESULTS: Discussion: Phrenic nerve paresis is an uncommon but potentially disabling complication of PV-RF ablation. Three mechanisms of injury have been implicated: 1. heat from the catheter contact site to the nerve [4]; 2. injury from the high intensity electromagnetic field generated at the catheter tip [5]; and 3. generation of a resonance current around the heart [6]. In this patient, the second mechanism seems most likely to induce direct nerve injury secondary to electroporation from locally generated electromagnetic field. CONCLUSION: Conclusion: This case report demonstrated that PV-RF ablation can induce significant nerve injury around the heart. CLINICAL IMPLICATIONS: Implication: Careful preventive precautions during the PV-RF ablation procedure are recommended. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Cardiology: Arrhythmias, continued

PFT on three days and five months post-procedure, showing restrictive physiology.* Three-days post-procedure

Five-months post-procedure

Predicted

Observed

%Predicted

Predicted

Observed

%Predicted

FVC

4.90L

2.53L

52%

4.59L

2.72L

59%

FEV1

3.41L

2.22L

65%

3.67L

2.27L

62%

70

88

126%

79

83

105%

7.28L

4.48L

62%

6.88

4.53L

66%

FEV1/FVC TLC

*FVC, forced vital capacity; FEV1, forced expiratory volume-1 second; TLC, total lung

DOFETILIDE THERAPY: IN PATIENTS WITH ATRIAL FIBRILLATION AND PACEMAKERS/DEFIBRILLATORS Pramod M. Deshmukh MD* Vera Hackett Sharad Chandrika MD Elizabeth Miller Guthrie Healthcare System, Sayre, PA PURPOSE: Dofetilide (Tikosyn) treatment for atrial arrhythmias requires initiation of the drug in the hospital, careful attention to multiple QTc intervals, and adherence to standard guidelines. Ventricular pacing, by widening the QRS interval, can prolong the QTc interval. As no data exists regarding monitoring of the QTc interval in patients with ventricular pacing, our objective was to assess the effect of ventricular pacing on QTc intervals in patients receiving dofetilide. METHODS: Over a two year period, 119 patients including 50 patients with implanted device (ID), [permanent pacemaker (PPM), ⫾ internal cardioverter defibrillator (ICD)] and 69 patients without ID were admitted for initiation of dofetilide using institutional protocol. Baseline and serial QRS intervals and QTC intervals (with manual correction) were utilized to guide drug therapy. In patients with ID (PPM ⫾ ICD), longer QTC intervals were accepted (in patients with PPM due to QRS widening; in the ICD group due to perceived safety) to achieve therapeutic drug effect. RESULTS: Fifty patients with ID (mean age 71.7 yrs), 68% with a history of antiarrhythmic therapy (AAR), were compared to 69 patients without ID (mean age 61.7 yrs), 50% of whom also had history of AAR. Their ECG parameters are shown in Table 1. Within the group with ID, QRS (duration) and QTc intervals were significantly longer than in PPM category. In each group, 96% of the patients were discharged to home in sinus rhythm and 4% of the patients required dofetilide to be discontinued due to torsade de pointes. After mean follow-up of 65 ⫾ 30 weeks in the ICD group, only one patient required discontinuation of dofetilide treatment due to torsade de pointes. None of the patients experienced a fatal outcome. CONCLUSION: Ventricular pacing is associated with significant QRS widening and, therefore, prolongation of QTc interval. CLINICAL IMPLICATIONS: Maximum limit of 500 msc. for QTc interval used for patients without ID may be safely extended by an additional 30 msc. in patients with ID and dofetilide therapy.

THE IMPACT OF STRESS ON HEART RATE VARIABILITY OF ON-CALL PHYSICIANS Stavros E. Mountantonakis MD* Dimitrios A. Moutzouris MD Craig McPherson MD Yale University - Bridgeport Hospital, Bridgeport, CT PURPOSE: The analysis of heart rate variability (HRV) has been recommended for the study of the impact of work-stress on the autonomic cardiac control. The literature related to the effect of work stress on physicians on-call is extremely limited. Our study aimed to evaluate the role of stress on the HRV of on-call physicians. METHODS: Twenty six healthy physicians (11 men,15 women) undertook a 24-hour Holter-ECG recording while being on-call, as well as on a normal work-day at least 3 days after the day on-call. The mean age was 34⫾7,49 years (range: 25-51 years). All recordings started at 3 p.m. and lasted 24 hours. RESULTS: The physicians presented decreased values of Standard Deviation of all filtered RR intervals over the length of the analysis(SDNN) during the day-on call in comparison with a normal workday (SDNN: 89.9 and 110.9 respectively, p⬍0.05). The rhythm disturbances during the day on-call were clearly more (p⬍0.05) and included sinus tachycardia and bradycardia, sinus pauses, supraventricular tachycardia, as well as premature atrial and ventricular systoles. CONCLUSION: Psychological and physical stress at working environment as well as sleep deprivation may result in adrenergic surge that predisposes to cardiac arrhythmias. In our study, the on-call physicians presented decreased SDNN. Although it is already known that decreased HRV correlates with increased morbidity and mortality, the studies about the clinical use of this marker in healthy subjects are few. CLINICAL IMPLICATIONS: Our findings demonstrated a negative impact of stress on the cardiac rhythm during an on-call day. It would be interesting to further investigate the significance of occupational stress in arrhythmogenesis in healthy and non-healthy individuals as well as the prognostic value of decreased HRV seen in our study. DISCLOSURE: Stavros Mountantonakis, None. INCORPORATION OF MEDICAL ADVANCES IN CLINICAL PRACTICE WITHIN GUTHRIE HEALTHCARE SYSTEM Pramod M. Deshmukh MD* Sailatha Padmanabhan MD Sudhakar Sattur MD Mary Romanyshyn Steven Alexander Guthrie Medical Center, Sayre, PA PURPOSE: Despite a large body of scientific evidence, primary prevention of sudden cardiac arrest remains a clinical challenge. The extent of incorporation of medical advances in practice remains unknown. We sought to evaluate how MADIT II (the second Multi-center Automatic Defibrillator Implantation Trial) findings were utilized in retrospective manner. METHODS: Guthrie Healthcare System is a large multidisplinary organization serving 500,000 patients in a primary service area of seven counties and comprises of 228 physicians. We evaluated all echocardiograms performed between October 2003 (beginning of reimbursement by CMS for MADIT II criteria) to October 2004. Using ICD codes, patients with cardiomyopathy, ischemic heart disease, and heart failure were identified. This group was further stratified for MADIT II criteria. Medical records were evaluated for presence/absence of heart failure, presentation with clinical arrhythmias, events leading to implantation of devices, QRS morphology and duration, screening by individual physicians (including holter monitors, event monitors), and clinical referrals to electrophysiology services. RESULTS: A total of 3538 echocardiograms were performed between October 2003 and October 2004. Of these, 591 patients were identified to have cardiomyopathy and heart failure, 109 patients met MADIT II criteria. Thirty-one patients (28.4%) received ICD implant. Of these, 27 patients received biventricular ICD and 4 patients received biventricular pacemaker. Twenty-nine patients had either spontaneous or inducible ventricular tachycardia. Solely based on MADIT II criteria, only 2 patients CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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DISCLOSURE: Long Le, None.

DISCLOSURE: Pramod Deshmukh, None.

Wednesday, November 2, 2005 Cardiology: Arrhythmias, continued were referred for procedure as an out-patient by their primary care physician; 29 patients were identified during routine follow-up or hospitalization. CONCLUSION: Despite widely published findings and efforts to educate primary care physicians, only a small percentage of patients who fulfill MADIT II criteria were referred for ICD implantation. CLINICAL IMPLICATIONS: In the light of recently published guidelines by CMS for implantation of defibrillator without electrophysiology studies, further education for primary care physicians is necessary. DISCLOSURE: Pramod Deshmukh, None. ANXIETY AND P-WAVE DISPERSION IN HEALTHY YOUNG POPULATION Huseyin Uyarel MD* Sennur Unal MD Hulya Kasikcioglu MD Zeynep Tartan MD Bulent Uzunlar MD Hasan Samur MD Ahmet Karabulut MD Ertan Okmen MD Nese Cam MD Siyami Ersek Cardiovascular and Thoracic Surgery Center, Istanbul, Turkey PURPOSE: P-wave dispersion (Pd), defined as the difference between the maximum and the minimum P-wave duration (Pmin) and maximum P-wave duration (Pmax) are electrocardiographic (ECG) markers that have been used to evaluate the discontinuous propagation of sinus impulses and the prolongation of atrial conduction time, respectively. Pd in normal subjects has been reported to be influenced by the autonomic tone, which induces changes in atrial size and the velocity of impulse propagation. However, the association between Pd and anxiety has not been studied in normal subjects. METHODS: Pmax, Pmin and Pd were measured in 726 physically and mentally young healthy male volunteers, aged 21.23 ⫾ 1.25 years (range 20-26). The Spielberger State-Trait Anxiety Inventory (STAI) was scored concomitantly. RESULTS: Blinded intra- and interobserver reproducibility of the P-wave duration and Pd measurement were evaluated, and comparision revealed a Pearson correlation coefficient of 0.87 and 0.89 for the P-wave duration, 0.93 and 0.90 for Pd, respectively (p⬍0.001). Pmax and Pd were significantly correlated with the STAI-1 subscale (State Anxiety Scale) (r ⫽ 0.662, p⬍0.001; r ⫽ 0.540, p⬍0.001, respectively) and STAI-2 subscale (Trait Anxiety Scale) (r ⫽ 0.583, p⬍0.001; r ⫽ 0.479, p⬍0.001, respectively). Pmin didn’t show any significant correlation with anxiety. Across 3 variables included in a multiple linear regression analysis, STAI-1 and STAI-2 were the significant independent determinants of Pmax and Pd. Beta coefficients indicated that the contribution of STAI-1 was much more than STAI-2 on Pmax (66.3%, 33.7%, respectively) and Pd (65%, 35%, respectively). CONCLUSION: The State Anxiety Scale and The Trait Anxiety Scale is associated with an increase in Pmax and Pd. Association of Pd resulted from augmentation of Pmax. This is the first study to show relation between Pmax, Pd and anxiety. CLINICAL IMPLICATIONS: The stimulation of sympathetic nervous system during anxiety may be the underlying mechanism of prolonged of Pmax and Pd. Extrapolating from these findings, our results point to a cardiac autonomic imbalance in patients with anxiety. DISCLOSURE: Huseyin Uyarel, None.

Cardiology: Diagnosis and Treatment of Coronary Disease 12:30 PM - 2:00 PM NUCLEAR STRESS TESTS IN ISOLATED AND SIGNIFICANT LEFT MAIN CORONARY ARTERY DISEASE: THERE IS NO UNIQUE PATTERN OF PERFUSION DEFICIT AND ABSENCE OF PERFUSION DEFICITS DOES NOT RULE OUT THE DIAGNOSIS Vijay Shetty MD* Nitin Mahajan MD Deepak Thekkoott MD Jacob Shani MD Gerald Hollander MD Edgar Lichstein MD Alvin Greengart MD Joshua Kerstein MD Bilal Malik MD Maimonides Medical Center, Brooklyn, NY PURPOSE: Left main coronary artery (LMCA) obstruction is the most potentially dangerous coronary disease. There is limited data on use of

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nuclear stress test to identify patients with Isolated And Significant Left Main Coronary Artery Disease (ILMCAD). METHODS: We compared nuclear stress test results for patients with ILMCAD (n⫽25; Group I) with stress results of patients with isolated LAD disease (n⫽25; Group II). Group I was selected over a period of 10 years. We compared electrocardiographic portion and perfusion deficits in the study groups. RESULTS: Electrocardiography portion of stress tests was non-revealing. In group I, perfusion deficits were absent in 4 (16%) patients. The different patterns are compared in figure 1. Inferolateral and inferior wall ischemia were commonly seen in group I as compared to significantly higher proportion (p⫽0.02) of anterior wall ischemia in Group II. The perfusion deficits in group I were independent of site of LMCA stenosis, coronary artery dominance, electrocardiogram changes, and severity of symptoms. CONCLUSION: This is the largest series of nuclear stress test results analysis involving ILMCAD. There is no unique pattern of ischemia associated with ILMCAD. Nuclear stress test may vary from being normal to diffuse ischemia in 3 vessel distribution. Its role may be limited to being an adjunct to clinical parameters including electrocardiography for diagnosing ILMCAD. CLINICAL IMPLICATIONS: Nuclear stress tests in diagnosing ILMCAD may be limited to being an adjunct to clinical parameters including electrocardiography.

DISCLOSURE: Vijay Shetty, None. TECHNICAL FEASIBILITY BASED ON LMCA STENOSIS CLASSIFICATION AND SHORT TERM CLINICAL OUTCOMES AFTER UNPROTECTED LMCA PERCUTANEOUS INTERVENTIONS WITH DRUG ELUTING STENTS: A SINGLE CENTER EXPERIENCE Narpinder Singh MD* Abdul Kani MD Augustin DeLago MD Albany Medical Center, Albany, NY PURPOSE: We sought to evaluate procedural technical feasibility; MACE including cardiac mortality at hospital discharge and thirty day follow up after stenting unprotected LMCA stenosis with DES stents. We also sought to classify and define the various anatomical variations of LMCA stenosis. METHODS: Total of forty one consecutive patients with LMCA stenosis underwent stenting in our institution. To define the location and complexity of LMCA disease lesions, we devised the classification of LMCA. DeLago’s LMCA stenosis classification includes 4 types and three classes (Figure 1). Different stenting techniques were used based on location of lesions. Patients were followed for the first three months. A repeat coronary angiogram was requested routinely after six months. RESULTS: Mean age was 67⫹14 with range of 28 to 90. Forty-four percent were males; 28% were smoker; 72% had HTN; 75 % had DM; and 68 hypercholestremia. Fifty- six percent presented as UA, 8% as recent acute MI and 36 % had abnormal stress test. Initial procedural success rate was 100%. At 30 days follow-up was 0%. MI (Non Q wave) 4.8%. At 30-day follow-up, CVA, TVR, CABG and death outcomes were 0%. Mortality at three months was 2.4%. CONCLUSION: Conclusion: Stenting of the unprotected LMCA stenosis provided excellent immediate result. Unprotected LMCA stenosis can be treated safely and effectively with DES coated stent and may be CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Cardiology: Diagnosis and Treatment of Coronary Disease, continued an effective strategy for treatment of LMCA disease in certain subset patient. CLINICAL IMPLICATIONS: Our classification of LMCA stenosis helps to understand the complexity of the lesions and based on that various stenting technique like direct stenting, stent into the branch with osteal lesion and dilation of the other branch if needed, kissing stents, Culottes stenting and V stent technique can be used. Certainly Type 1 and Type 2 lesion are technically easy to stent and Type 3AC, Type 4 AC are very challenging and technically complex to do.

META-ANAYLSIS OF TRANSIENT LEFT VENTRICULAR APICAL BALLOONING SYNDROME BASED ON GENDER AND RACE Daniel Donohue MD* Mohammad-Reza Movahed MD University of California, Irvine Medical Center, Orange, CA PURPOSE: Transient Left Ventricular Apical Ballooning (LVAB) was first described in Japan in the early 1990’s. Since then it has been reported in many countries worldwide. It typically presents after physical or emotional stress with chest pain, ECG changes, positive cardiac markers and marked akinesia of mid to apical left ventricular wall with ballooning appearance despite normal coronaries. The goal of this study was to perform meta-analysis of the published cases in regards to race and gender. METHODS: Using pubmed, we searched all published manuscripts relevant to left ventricular apical ballooning syndrome. We included case series and individual case reports in this study. We evaluated the effect of gender and race on the presentation of LVAB using uni and multi-variate analysis. RESULTS: A total of 185 patient cases were identified that were included in the analysis. Most cases were females, totaling 173 patients (93.5%). Asians and Caucasian were the majority of the reported races. Asians on average were older (70 ⫹/- 9.5 yo vs 64 ⫹/- 12.7 yo), less likely to have; their syndrome precipitated by emotional stress (26.5% vs 51.7%), positive cardiac markers (77.1% vs 97.6%), present with chest pain (55.4% vs 81.0%), or with T wave inversion (67.3% vs 95.8%), but were more likely to have ST elevation on EKG (97.1% vs 83.3%). There were no differences in regards to complications or death. CONCLUSION: LVAB is becoming more recognized in different races. While predominantly effecting females, the presentation is similar to men. However, there are significant differences in the presentation of LVAB between Asians and Caucasians. CLINICAL IMPLICATIONS: Clinical presentation of LVAB differs between Caucasians and Asian which needs to be considered in patient presenting with LVAB. DISCLOSURE: Daniel Donohue, None.

PURPOSE: Acute myocardial infarction (MI) is invariably caused by near total or total occlusion of epicardial coronary arteries by a thrombus superimposed on an unstable atheromatous plaque. However, normal coronary arteries on angiograms performed in patients with acute myocardial infarction have been described. The aim of our study was to see if and how often myocardial infarction occurs in the setting of normal coronary arteries visualized by angiography in patients seen in a community hospital. METHODS: All coronary angiograms done in Coney Island hospital from January 1995 to July 2002 were reviewed. 1699 patients with normal coronary arteries were identified. These charts were reviewed for evidence of acute myocardial infarction based on EKG findings and presence of elevated cardiac enzymes. Potential causative factors for myocardial infarction and incidence of ST elevation MI (STEMI) versus non-ST elevation MI (NSTEMI) were also studied. RESULTS: We identified 17/1699 (1%) patients who presented with acute myocardial infarction with normal coronary arteries by angiography. Mean age - 52.75; Age range - 24 to 81; Male - 10, Female 7, M/F - 1.5:1. 6/17 (35.3%) had STEMI. 5/6 (83.3%) had potential causative factors (3/5 had cocaine abuse, 1/5 had hyperviscosity due to polycythemia, 1/5 had hypercoaguable state due to lupus anticoagulant). 11/17 (64.7%) had NSTEMI. Only one of these 11 patients (9.1%) had an identifiable cause (cocaine abuse). CONCLUSION: Normal coronary arteries on angiography essentially excludes acute myocardial infarction. In rare instances when it occurs, potential causative factors include cocaine abuse, hypercoaguable disorders and hyperviscosity states. CLINICAL IMPLICATIONS: Patients with acute myocardial infarction and normal coronary angiogram must be evaluated for potential causative factors, such as cocaine abuse, hypercoaguable disorders and hyperviscosity states, specially in patients with STEMI. DISCLOSURE: Muhammad Rehman, None. PREVALENCE OF MODERATE OR SEVERE LEFT VENTRICULAR DIASTOLIC DYSFUNCTION IN PERSONS WITH SUSPECTED MYOCARDIAL ISCHEMIA WITH AND WITHOUT AN ABNORMAL ADENOSINE OR EXERCISE SESTAMIBI STRESS TEST OR PRIOR CORONARY REVASCULARIZATION Gautham Ravipati MD* Wilbert S. Aronow MD Albert J. De Luca MD Tamana Walia MD John A. McClung MD Robert N. Belkin MD New York Medical College, Valhalla, NY PURPOSE: To determine the prevalence of moderate or severe left ventricular diastolic dysfunction (LVDD) in patients with suspected myocardial ischemia with and without an abnormal adenosine or exercise sestamibi stress test (SST) or prior coronary revascularization. METHODS: The patients included 171 men and 164 women, mean age 63 years, with suspected myocardial ischemia who underwent a SST and Doppler and tissue Doppler interrogation of the mitral inflow and mitral annulus, respectively. Moderate LVDD was diagnosed if the peak early diastolic transmitral flow velocity (E)/peak late diastolic transmitral flow velocity (A) was 0.75-1.50 and one or both of the following were present: the E/peak early diastolic myocardial velocity (Ea) was ⱖ10 or the peak systolic pulmonary vein flow velocity (S)/ peak diastolic pulmonary vein flow velocity (D) was ⬍1. Severe LVDD was diagnosed if the E/A was ⬎1.5 and one or both of the following were present: the E/Ea was ⱖ10 or the S/D was ⬍1. LVDD was evaluated blindly by a single experienced echocardiographer without knowledge of the clinical characteristics or whether the SST was normal or abnormal. A left ventricular ejection fraction (LVEF) of ⬍50% was considered abnormal. RESULTS: Moderate or severe LVDD was present in 117 of 142 patients (82%) with an abnormal SST or prior coronary revascularization and in 11 of 193 patients (58%) with a normal SST and no prior coronary revascularization (p⬍0.001). Moderate or severe LVDD was present in 34 of 38 patients (89%) with an abnormal SST or prior coronary revascularization and an abnormal LVEF and in 4 of 8 patients (50%) with a normal SST and no prior coronary revascularization and an abnormal LVEF (p⬍0.01). CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

DISCLOSURE: Narpinder Singh, None.

ACUTE MYOCARDIAL INFARCTION WITH NORMAL EPICARDIAL CORONARY ARTERIES ON ANGIOGRAM: HOW REAL IS IT? Muhammad U. Rehman MD* Vijay Rupanagudi MD Umang Patel MD Raju Ailiani MD Javeria Shakil MBBS S. Banuru MD S. Niranjan MD P. Krishnan MD Coney Island Hospital, Brooklyn, NY

Wednesday, November 2, 2005 Cardiology: Diagnosis and Treatment of Coronary Disease, continued CONCLUSION: There is a very high prevalence of moderate or severe LVDD in patients with suspected myocardial ischemia, especially if there is an abnormal SST or prior coronary revascularization. CLINICAL IMPLICATIONS: There is a very high prevalence of moderate or severe LVDD in patients with ischemic heart disease, especially in those with an abnormal LVEF. DISCLOSURE: Gautham Ravipati, None.

STRESS-INDUCED APICAL BALLOONING SYNDROME CAN BE SUSPECTED BASED ON CLASSIC ECHOCARDIOGRAPHIC FINDINGS AND CLINICAL PRESENTATION Daniel Donohue MD* Chowdhury Ahsan MD Mohammad-Reza Movahed MD University of California, Irvine Medical Center, Orange, CA PURPOSE: Stress induced apical ballooning has been described as a reversible condition involving the apical left ventricular wall, sparing the base, and causing a ballooning appearance of the left ventricular during systole despite normal coronaries. However, there are no data about early diagnosis of Apical ballooning syndrome using echocardiography. METHODS: We are presenting four cases of apical ballooning seen at our institution with echocardiographic correlation. We compared angiogram with echocardiographic finding prior to angiogram. RESULTS: All Echocardiograms showed similar anatomical apical ballooning of the left ventricular apex. The diagnosis of apical ballooning syndrome was suspected based on echocardiography in conjunction with clinical data before cardiac catheterization was performed. In one case, in addition to classic left ventricular apical ballooning, marked right ventricular apical akinesia was present on the initial echocardiographic examination Subsequent angiograms in all patients showed classic apical ballooning and normal coronaries. CONCLUSION: Apical ballooning syndrome can be suspected based on classic echocardiographic findings and clinical data prior to angiography. CLINICAL IMPLICATIONS: Therefore, we suggest that echocardiography should be utilized more for the early diagnosis of this disease based on careful anatomical evaluation in conjunction with clinical data. Wall motion analysis should reveal apical ballooning appearance involving many coronary territories with discrepancy to electrocardiogram and cardiac enzyme elevation. Furthermore, the additional presence of right ventricular apical akinesia during echocardiographic examination makes the diagnosis of this syndrome more likely.

ISOLATED AND SIGNIFICANT LEFT MAIN CORONARY ARTERY DISEASE: DEMOGRAPHICS, HEMODYNAMICS AND ANGIOGRAPHIC FEATURES Nitin Mahajan MD* Deepak Thekkoott MD Gerald Hollander MD Bilal Malik MD Sunil Abrol MD Jacob Shani MD Edgar Lichstein MD Maimonides Medical Center, Brooklyn, NY PURPOSE: This paper describes the demographic, angiographic and hemodynamic characteristics of forty-six patients with isolated and significant LMCA disease (ILMCAD)in an attempt to determine the etiology of ILMCAD. METHODS: We identified 46 patients with ILMCAD from our database over 10 years (Group I) and compared them with 83 consecutive patients that underwent catheterization in our lab (Group II). We also compared ostial vs. distal ILMCAD. RESULTS: Group I represents 0.1% of catheterization patients. Unstable angina was the commonest presentation followed by non ST elevation myocardial infarction, elective catheterization, syncope and dyspnea on exertion. The comparison of study groups is shown in table 1 and figure 1.Mean left ventricular ejection fraction is similar in both sub-groups (ostial disease-49%, distal disease-50%). About half the patients with ILMCA (n⫽24/46:52%) disease had the classical “jet streaming” of contrast and was seen more commonly in patients with ostial and mid ILMCA disease. About one-fifths of ILMCA patients (9/46:20%) demonstrated retrograde filling from right coronary artery. Ventricularization was seen in only 4 patients. The majority of patients (23/44:52%) had normal segmental wall motion. An inverse relation was seen between the severity of LMCA stenosis and left ventricular ejection fraction. The left ventricular end diastolic pressure had no correlation with left ventricular ejection fraction or severity of LMCA stenosis.

Table 1. Comparison of Demographic Profile of Patients With ILMCA Disease (Group I) With General Population Seen in Cardiac Catheterization Center (Group II). Risk Factors Age (in years) Sex Male Female Race White Non-White Hypertension Hypercholesterolemia Diabetes Mellitus Smoking Family history Indication of Catheterization Angina Myocardial Infarction Elective Others (syncope, dyspnea on exertion, and others)

Group I (n⫽46)

Group II (n⫽83)

P value

65⫾13

65⫾14

Nsd*

22 (48%) 24 (52%)

57 (69%) 26 (31%)

0.02 0.02

44 (96%) 2 (4%) 33(72%) 30(65%) 20(43%) 12(26%) 18(39%)

75 (90%) 8 (10%) 59 (71%) 58 (70%) 24 (29%) 18 (22%) 36(43%)

Nsd Nsd Nsd Nsd Nsd Nsd Nsd

20 (43%) 9 (20%) 13 (28%) 4 (9%)

28 (34%) 23 (28%) 22 (26%) 8 (10%)

Nsd Nsd Nsd Nsd

* Nsd- No statistically significant difference.

DISCLOSURE: Daniel Donohue, None.

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CONCLUSION: This is the largest study of patients with ILMCAD. Risk factors for atherosclerosis were commonly seen. Non-atherosclerotic causes of ILMCAD were not seen. ILMCAD is more common in women. Diabetes is more commonly associated with distal lesion. There is a trend suggesting ostial lesion is more common in smokers and women. CLINICAL IMPLICATIONS: This study provides evidence in favour of atherosclerosis being the cause of ILMCAD. It is hoped that aggressive treatment of atherosclerotic risk factors will reduce the prevalence of ILMCAD. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Cardiology: Diagnosis and Treatment of Coronary Disease, continued

DISCLOSURE: Nitin Mahajan, None.

Cardiology: Diagnosis and Treatment of Heart Failure 12:30 PM - 2:00 PM

PURPOSE: High sensitivity C-reactive protein (hsCRP) assay has been found to be a useful biomarker for cardiovascular risk stratification. Little information exists regarding its prognostic impact in outpatients with heart failure (HF) as well as its correlation to other biomarkers or outcomes. METHODS: Serum levels of hsCRP were obtained in 89 patients with stage C HF. All patients were followed in a specialized HF management center for 2-24 months (average 13.5⫾6.06). The primary end point was major adverse cardiovascular events defined as cardiac hospitalization or cardiac death. RESULTS: The average age of the subjects was 62.8⫾14.2 years (range19-88). The etiology of HF was ischemic in 36 patients (40.45%) and non-ischemic in 53 patients (59.55%). There were 46 men and 43 women, 72 patients with systolic dysfunction and 17 patients with diastolic dysfunction defined as LVEF ⬎ 50%. The baseline hsCRP ranged from 0.03 to 8.4 mg/dl and averaged 0.86⫾1.39 mg/dl. HsCRP levels were ⬍ 0.1 mg/dl in 14 patients (15.8 %), 0.1-0.3 mg/dl in 25 patients (28%), and ⬎ 0.3 mg/dl in 50 patients (56.2%) (p⬍0.0001). Adverse cardiovascular events were significantly higher in patients with increased hsCRP (88.23% vs. 19%, p ⫽ 0.006, using hsCRP level of 0.2 mg/dl as a cutoff). Patients with systolic dysfunction had higher levels of hsCRP compared to patients with diastolic dysfunction (0.95 mg/dl vs. 0.46 mg/dl, respectively, p ⫽ 0.030). There was no significant difference in hsCRP levels in ischemic HF compared to non- ischemic HF (0.92 mg/dl vs. 0.81 mg/dl, respectively, p ⫽ 0.72). There was no significant correlation between baseline hsCRP levels and baseline BNP levels. CONCLUSION: Our findings establish that hsCRP is elevated in patients with stable Stage C HF independent of the etiology. Increased hsCRP levels were associated with significantly higher adverse cardiovascular events. The elevations in hsCRP and the cardiovascular outcomes are independent of other important biomarkers. CLINICAL IMPLICATIONS: In conclusion, our data suggests that elevated hsCRP is an independent prognostic marker for risk stratification in patients with chronic HF. DISCLOSURE: Marc Silver, None. HYPERKALEMIA AND RENAL DYSFUNCTION IN CONGESTIVE HEART FAILURE PATIENTS WITH CONCOMITANT USE OF SPIRONOLACTONE AND FUROSEMIDE Nobuyuki Anzai MD* Hiroko Anzai MD Rieko Mitobe MD Makiko Anzai MD Sadako Furuya MD Anzai Furuya Clinic, Oyama, Japan PURPOSE: This study aimed to identify predictors of hyperkalemia and renal impairment in congestive heart failure (CHF) patients taking spironolactone and furosemide.

IMPACT OF LEFT VENTRICULAR ASSIST DEVICE DESTINATION THERAPY ON VENTRICULAR RE-SYNCHRONIZATION Smitha G. Agadi MD* Helen Lonergan-Thomas RN Sharon Brennan RN Pamela Cianci MSN Mark Slaughter MD Marc Silver MD Advocate Christ Medical Center, Oak Lawn, IL PURPOSE: Heart failure (HF) is a lethal disease process that involves progressive ventricular remodeling and symptom worsening. Two strategies applied to HF populations include biventricular resynchronization pacing (BiVP) and left ventricular assist as destination therapy (DT). While there may be some overlap in these populations the therapies are generally thought of separately. Among the benefits of BiVP are ventricular resynchronization and improved oxygen consumption. Little information is known about the impact of DT on cardiac desynchronization and its impact on ventricular electromechanical recovery. METHODS: We analyzed the ECG intervals of 16 patients who received DT with a Heartmate XVE (Thoratec) secondary to end stage HF. Patients whose baseline ECG was paced (7) were excluded from analysis. The remaining 9 patients (8 men) were aged 50-79 (mean 64.8) years. The patients were supported from 1-180 days at the time of analysis. RESULTS: The mean patients were supported from 1-180 days at the time of analysis. Heart baseline and follow-up intervals are shown in the table below. CONCLUSION: While none of the intervals changed significantly during DT support, there was a trend towards improvement in QRS duration; of patients supported, the average improvement in QRSD was 15.4 msec (10.5%) whereas for patients supported ⬎ 20 days the improvement was 37.5 msec (21%). The only 2 patients to improve QTc were those supported 180 days. On the other hand PR did not improve in any patient. CLINICAL IMPLICATIONS: In summary, DT allows for long-term ventricular support and recovery. Improvement in cardiac desynchronization without BiVP may also occur after ventricular support. Longer observation needs to be applied to this phenomenon and to consider the potential for LVAD support to restore normal ventricular resynchronization. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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THE PROGNOSTIC VALUE OF HIGH SENSITIVITY C-REACTIVE PROTEIN LEVEL IN PATIENTS WITH CHRONIC HEART FAILURE Ghaith M. Mulki MD Pamela Cianci MSN Marc A. Silver MD* University of Illinois at Chicago/Advocate Christ Medical Center, Oak Lawn, IL

METHODS: Ninety (90) consecutive patients with CHF, 46M/44F, mean age 73.8 (range 56.4 -91.2 yrs) were studied. We started 26 patients while 20 patients were already taking spironolactone and furosemide when the study started. We measured blood electrolytes every two months. The study started from April 2003 and lasted two years. Mean observation duration was 489 days for 124 patient years with a mean 19 visits and a mean 25 days between visits. RESULTS: Baseline characteristics: Mean(SD) left ventricular ejection fraction (LVEF): 39.5%(15.1); mean(SD) creatinine concentration(mg/ dl): 0.91(0.25); mean serum potassium(mEq/dl): 4.3(0.4); mean(SD) dosage (mg/day): spironolactone: 14.9(7.3), furosemide: 30.3(14.1); patients needing angiotensin converting enzymes (ACE) inhibitors or angiotensin receptor blockers (ARB): n⫽50(50%), ␤ blockers: 48(53%); mean peak creatinine concentration: 1.07(SD 0.34) mg/dl; mean peak potassium: 5.0(SD 0.5)mEq/dl. A total of 45(50%) had creatinine ⬎ 1.04 mEq/dl, 16(18%) ⬎ 1.30, 9(10%) ⬎ 1.50. Relative to baseline, 24(27%) patients had creatine increase by 20%, 15(17%) by 30%, 8(9%) by 50%, 2(2%) by 100%. A total of 39(43%) patients had potassium ⬎ 5.0 mEq/dl, 9(10%) ⬎5.5, 2(2%) ⬎ 6.0. Patients taking spironolactone and furosemide before study started did not differ significantly from patients we started in terms of hyperkalemia (potassium ⬎5.5)(11.5% vs. 15.2%, p⫽0.54) and azotemia (creatinine ⬎ 1.30)(15.3% vs. 14.1%, p⫽0.82). We logistically regressed (30% increase in serum creatinine concentrations) with age, sex, use of ACE inihibitors, ARBs, ␤ blockers, and dosage of spironolactone and furosemide. Age (odds ratio 1.24(95% confidence index interval 1.01-2.54)for each ten years)) was an independent risk factor for azotemia.For hyperkalemia (potassium ⬎ 5.5), we added to the model baseline creatinine concentrations and found that age (1.03(0.84-2.86)) was a predictive factor. CONCLUSION: Age was a predictor of hyperkalemia and azotemia for patients taking spironolactone and furosemide with moderately decreased LVEF. CLINICAL IMPLICATIONS: Caution should be taken while dose adjustment and continuous monitoring may be needed in elderly patients. DISCLOSURE: Nobuyuki Anzai, None.

Wednesday, November 2, 2005 Cardiology: Diagnosis and Treatment of Heart Failure, continued Interval

Baseline

Follow-Up

PR (msec) QRS (msec) QTc (msec)

173.8 146.2 460.6

185.2 130.8 463.7

DISCLOSURE: Smitha Agadi, None. CHEST RADIOGRAPHIC CORRELATES OF SERUM BNP LEVELS Shahnaz Begum MD Xiaoqian Zhang MD Louis Salciccioli MD Arash Gohari MD Jason M. Lazar MD* SUNY Downstate Medical Center, Brooklyn, NY PURPOSE: Beta natriuretic peptide (BNP)is a biomarker of intravscular volume and serum levels correlate with left ventricular filling pressures. The relationship between BNP levels and radiographicic findings has not been well studied. Accordingly, the purpose of this study was to determine the relationships between chest radiographic findings and serum BNP levels. METHODS: We studied 88 consecutive patients hospitalized with cardiac and/or pulmonary symptoms who had chest xrays and BNP levels determined within 24 hours. Chest radiographs were evaluated for the following findings: left atrial enlargement (LAE), pleural effusions, pulmonary vascular congestion (PVC), cardiothoracic (CT) ratio, and the vascular pedicle width (WPW). Pulmonary vascular congestion was noted to be absent, mild, or greater than mild. The VPW was measure was measured according to previously published methods (Ely). RESULTS: The duration of time between BNP levels and chest xrays was 80⫹/-20minutes. There was a direct correlation between serum BNP levels and CT ratio (r⫽.29,p⫽0.03). There were no relationships between BNP levels and either VPW (r⫽-.12, p⫽.16) or age (r⫽.10,p⫽.50). BNP levels were unrelated to the presence of PVC (p⫽.17),but were higher in patients with LAE (p⫽.04)and pleural effusions (r⫽.04). On multivariate analysis analysis, CT ratio was the only independent correlate of BNP levels (r2⫽.09, p⫽.02). Log transformation of BNP levels improved the correlation with CT ratio (r⫽.40, p⫽.001), but did not alter other univariate or multivariate findings. CONCLUSION: In an unselected group of patients hospitalized with cardiac and/or pulmonary symptoms, serum BNP levels are chiefly related to the CT ratio but not to other radigraphic findings. CLINICAL IMPLICATIONS: Although the majority of studies focus on the diagnostic and prognostic value of BNP levels,a direct comparison to standard clinical evaluation is essential in understanding the clinical utility of serum BNP levle determination. DISCLOSURE: Jason Lazar, None. DETERMINANTS OF EXERCISE CAPACITY AND PERCEIVED EXERTION IN PATIENTS WITH PRESERVED LEFT VENTRICULAR SYSTOLIC FUNCTION Tanya Menard Louis Salciccioli MD Luther Clark MD Jason M. Lazar MD* SUNY Downstate Meidcal Center, Brooklyn, NY PURPOSE: Exercise capacity is known to be an important prognostic factor in patients with cardiovascular disease and in healthy subjects. While structural heart disease is found in a relatively small proportion, other factors are likely responsible for reduced exercise tolerance in these patients. Indices of left ventricular (LV) diastolic filling variably correlated with exercise time in select patient populations including hypertensives and the elderly. Moreover, no study has specifically addressed the contribution of LV systolic and diastolic functional abnormalities to both exercise duration and perceived effort. The objectives of the study were to determine echocardiographic correlates of exercise capacity and of perceived exertion in patients without structural heart disease. METHODS: We studied 111 consecutive patients, age 53⫹/-13 years, who were referred for echocardiographic stress testing. Patients underwent symptom limited treadmill exercise testing according to Bruce protocol in all cases. Standard blood pressures and 12 channel electrocardiograms were performed. Baseline 2 dimensional and Doppler echocardiographic images were recorded immediately prior to exercise. The primary end points were maximal exercise tolerance defined by mets and peak RPE.

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RESULTS: Age was directly correlated with mets (r⫽.38, p⫽.⬍.001) but not with RPE (r⫽.21,p⫽.51). On univariate analysis, mets also correlated with: hemoglobin (r⫽.39, p⫽.001), E/A (r⫽.33, p⫽.019) E/Vp (r⫽-.41, p⫽.004) and E/E’ (r⫽-.41, p⫽.004). Multiple regression analysis showed that independent predictors of mets were: age and gender (r2⫽.58,p⬍.001). There was a direct correlation between RPE and LA size (r⫽.35, p⫽.013) and a trend towards a correlation between RPE and LV mass index (r⫽.24, p⫽.09). On multivariate analysis, LA size remained the sole independent predictor of RPE (r2⫽.17, p⫽.021). CONCLUSION: This study showed reduced exercise capacity measured by metabolic equivalents (mets) is related to advanced age and female gender whereas perceived exertion is related to left atrial size. CLINICAL IMPLICATIONS: There are age and gender related differences in functional capacity but not in preceived exertion. The specific mechanism by which LA size modulates perceived exertion is unknown but merits further study. DISCLOSURE: Jason Lazar, None.

Cardiology: Diagnosis of Cardiovascular Disease 12:30 PM - 2:00 PM POOR AEROBIC FITNESS PREDICTS COMPLICATIONS ASSOCIATED WITH BARIATRIC SURGERY Justin E. Trivax MD* Michael J. Gallagher MD Daniel V. Alexander MD Adam T. deJong MA Gopi Kasturi MD Keisha R. Sandberg MPH Syed M. Jafri Kevin R. Krause MD David L. Chengelis MD Jason Moy MD Barry A. Franklin PhD Peter A. McCullough MD William Beaumont Hospital, Royal Oak, MI PURPOSE: Bariatric surgery provides substantial and prolonged weight reductions. Complications associated with bariatric surgery have been well-defined; although, the risk of developing these complications is unclear. Maximal oxygen consumption (VO2max), determined by cardiopulmonary exercise testing (CPX), is a measure of aerobic fitness. The aim of this study was to assess the association between VO2max and complications encountered with bariatric surgery. METHODS: CPX was performed on 109 consecutive patients with morbid obesity undergoing laparoscopic Roux-en-Y gastric bypass surgery. Chart review was performed by reviewers blinded to the CPX results. RESULTS: Mean age was 46.0⫾10.4 years and 82 (75.2%) were female. Mean body mass index (BMI) was 48.1⫾7.5 kg/m2 and 50.4⫾6.0 kg/m2 for women and men, respectively p⫽0.17. VO2max measurements ranged from 6.8 to 27.7 ml/kg/min. Patients were stratified by tertile of VO2max. Mean VO2max in the first tertile was 13.7⫾2.1, second tertile was 17.1⫾0.8, and third tertile was 21.3⫾2.1. Patients in the first tertile experienced longer operative room times, p⫽0.04, and greater number of ICU days, p⫽0.05. Composite complication rate, defined as death, unstable angina, myocardial infarction, venous thromboembolism, infection, gastrointestinal bleeding, renal failure or stroke, occurred in 2/72 (2.8%) and 6/37 (16.2%) above and below a peak oxygen consumption of 15.8 ml/kg/min (lowest tertile) respectively, p⫽0.02. No complications occurred in patients with both VO2max ⱖ 15.8 ml/kg/min and BMI ⬍ 45 kg/m2. In comparison to other cardiorespiratory parameters, the area under the receiver operating characteristic curve was highest for VO2max in predicting complications (AUC⫽0.72, p⬍0.0001.) Multivariate analysis found the first tertile of VO2max to have an odds ratio of 10.9 (95% CI 1.01-73.80, p⫽0.04) for the prediction of postoperative complications. CONCLUSION: Poor aerobic fitness, determined by a low VO2max, predicted complications associated with bariatric surgery. CLINICAL IMPLICATIONS: VO2max should be determined prior to bariatric surgery to assess the risk of surgical complications. Cardiorespiratory fitness is potentially modifiable and should be optimized prior to elective surgery with the goal of reducing surgical complications. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Cardiology: Diagnosis of Cardiovascular Disease, continued DOES MITRAL REGURGITATION PROVIDE PROTECTION AGAINST THE FORMATION OF LEFT ATRIAL THROMBUS AND EMBOLIC CEREBRAL VASCULAR ACCIDENT IN PATIENTS WITH ATRIAL FIBRILLATION? Xuedong Shen MD* Chandra K. Nair MD Huagui Li MD Tom Hee MD Dhanunjay Lakkireddy MD Mark J. Holmberg MD David Cloutier BS Karen Rovang MD Aryan N. Mooss MD Syed M. Mohiuddin MD The Cardiac Center of Creighton University, Omaha, NE

DOES THE AORTIC ATHEROSCLEROTIC PLAQUES SEVERITY CORELLATE WITH EMBOLIC EVENTS? Chandra K. Nair MD* Xuedong Shen MD Huagui Li MD Dhanunjay Lakkireddy MD Senthil Thambidorai MD David Cloutier BS Mark J. Holmberg MD Aryan N. Mooss MD Syed M. Mohiuddin MD The Cardiac Center of Creighton University, Omaha, NE PURPOSE: The impact of aortic atherosclerotic plaques (ASP) demonstrated by transesophageal echocardiography (TEE) is controversial. It is also unclear whether the severity of ASP correlate with embolic events. The purpose of this study was to investigate the incidence of embolic events in different grades of ASP. METHODS: We studied 277 consecutive patients (male/female⫽153/ 124, age 66.2⫾13.4 years) without left atrial thrombus by TEE. The thoracic aortic plaque severity was classified as Grade I (normal or minimal intimal thickening) in 86; Grade II (extensive intimal thickening) in 105; Grade III (atheroma ⬍ 5mm) in 70; Grade IV (atheroma ⱖ 5mm) in 11; and Grade V (mobile lesion) in 5 patients. The incidence of embolic events, mortality and clinical characteristics were evaluated in patients with different grades of ASP. RESULTS: The incidence of embolic events was increased with the severity of ASP (Grade II, 12%, Grade III, 16%, Grade IV, 27% and Grade V, 60%). Grade ⱖ IV had the highest incidence of embolic events (6/16, 38%) compared to grade I (11/86, 13%) (p⫽0.038). There was no significant difference in age, left atrial diameter, spontaneous contrast echo in left atrium, left ventricular ejection fraction and the prevalence of coronary artery disease, old myocardial infarction, aortic stenosis, aortic valve calcification, mitral annulus calcification and left ventricular hypertrophy between the groups (p⬎0.05). There was no significant difference in the percentage of patients with therapuetic anticoagulation or antiplatelets between the ASP groups. During the follow-up of 38.7⫾32 months, there was no significant difference in cardiac mortality between the groups (p⬎0.05). CONCLUSION: The incidence of the embolic events is related to the severity of ASP. There was significant increase in the embolic events in patients with grade ⱖIV ASP. CLINICAL IMPLICATIONS: ASP detected by TEE is associated with embolic events and there is significant increase in the embolic events in patients with grade ⱖ IV ASP. DISCLOSURE: Chandra Nair, None.

RIGHT VENTRICULAR MECHANICAL DELAY AND GLOBAL VENTRICULAR DYSFUNCTION Angel Lopez-Candales MD* Kaoru Dohi MD Raveen Bazaz MD Kathy Edelman University of Pittsburgh Medical Center, Pittsburgh, PA PURPOSE: Several abnormalities in both right ventricular (RV) size and function tend to occur in patients with pulmonary hypertension (PAH). However, there is no data regarding the effect of PAH on RV free wall mechanical activation in these patients that can contribute to global dysfunction. METHODS: We studied several well-established echocardiographic parameters used to assess RV performance in a heterogeneous group of patients with varying degrees of PAH as well as in a group of healthy volunteers and then used tissue Doppler imaging (TDI) to investigate if abnormalities in RV free wall mechanical activation occur with RV dysfunction. RESULTS: Prospective data collected in 20 patients with varying degrees of PAH (mean age 51 ⫾ 13 years, WHO class average 2.8 and mean pulmonary systolic pressure 78 ⫾ 24 mmHg) were compared to similar data retrospectively obtained from 20 healthy volunteers (mean age 45 ⫾ 15 years). Patients with varying degrees of PAH had worse RV performance parameters than healthy volunteers (RV fractional area change 37 ⫾ 13% versus 52 ⫾ 5%, p ⬍0.0001; RV myocardial performance index 0.76 ⫾ 0.31 versus 0.29 ⫾ 0.11, p ⬍0.0001; and Eccentricity Index 1.41 ⫾ 0.57 versus 0.98 ⫾ 0.06, p⬍0.005). Similarly, in these patients with an abnormal RV performance, TDI showed a statistically significant lower peak longitudinal RV free wall strain (-21.5 ⫾ 9.0% versus -28.0 ⫾ 4.1%, p⬍ 0.01) and a significantly delayed time-to-peak strain (459 ⫾ 76 msec versus 388 ⫾ 29 msec, p⬍0.0005) values than healthy volunteers; a very strong correlation between RV mechanical delay and RV fractional area change (r ⫽ -0.89) was noted. CONCLUSION: RV free wall mechanical delay, as documented by TDI, was identified in patients with varying degrees of PAH. Furthermore, there is strong correlation between RV free wall mechanical delay and overall global RV performance in these patients. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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DISCLOSURE: Justin Trivax, None.

PURPOSE: Previous studies suggest that patients with mitral regurgitation (MR) have a reduced incidence of embolic cerebral vascular accident (CVA), assuming that the regurgitating jet “washes out” and prevents the formation of left atrial thrombus (LAT). However, the incidence of MR in patients with LAT is largely unknown. The purpose of the study was to evaluate the incidence of MR in atrial fibrillation (AF) patients with LAT and its impact on embolic events. METHODS: 69 consecutive patients (male/female⫽36/33, age 70.2⫾11.7 years) with AF and documented LAT on transesophageal echocardiogram (TEE) prior to contemplated cardioversion were evaluated for MR. The thrombus was located in the left atrial appendage in 67 and the left atrial body in 2 patients. The severity of MR by color flow imaging was classified into four grades, trivial (1⫹), mild (2⫹), moderate (3⫹) and severe (4⫹). RESULTS: All but 2 (67/69, 97%) patients demonstrated MR. MR severity was 1⫹ in 20 (29%), 2⫹ in 27 (39%), 3⫹ in 17 (26%), and 4⫹ in 3 (5%) patients. During the follow-up of 29.1⫾27.5 months after TEE, 3 patients (4.3%) with LAT in left atrial appendage had embolic CVA. Their INR at time of CVA was 2.9, 3.84 and 2.5. The CVA incidence had no significant difference between patients with MR ⱖ 3⫹ (1/18, 5.6%) compared to ⬍3⫹ (2/51, 3.9%) (p⫽NS). However, the incidence of spontaneous echo contrast in left atrium was higher in patients with MR ⬍ 3⫹ (47/51, 92.2%) than MR ⱖ 3⫹ (14/18, 77.8%, p⫽0.034). CONCLUSION: MR is very common in AF patients with LAT, suggesting that MR may not protect against the formation of left atrial clot. The occurrence of embolic CVA also was not decreased by the presence or severity of MR although the incidence of spontaneous echo contrast in left atrium was lower in patients with ⱖ 3⫹ MR. CLINICAL IMPLICATIONS: The embolic events are not related to the severity of MR. Further studies with larger number of patients and longer follow-up seems indicated. DISCLOSURE: Xuedong Shen, None.

Wednesday, November 2, 2005 Cardiology: Diagnosis of Cardiovascular Disease, continued CLINICAL IMPLICATIONS: This novel echocardiographic technique has the potential for identifying patients with subclinical RV dysfunction.

plished using non-invasive strategies, such as carotid ultrasound to reduce the overall burden of disease. DISCLOSURE: Ana Schaper, None. THE EIGENVALUES OF THE ELECTROCARDIOGRAM: A NEW ELECTRICAL CARDIAC MARKER FOR ACUTE MYOCARDIAL INFARCTION David M. Schreck MD* Summit Medical Group, Summit, NJ

DISCLOSURE: Angel Lopez-Candales, None. SCREENING FOR ATHEROSCLEROSIS: INITIATING SECONDARY PREVENTION FOR HIGH-RISK YOUNG TO MIDDLE-AGED ADULTS Ana M. Schaper PhD* Vicki L. McHugh MS Sharon I. Barnhart RN Michelle A. Mathiason MS Kwame O. Akosah MD Gundersen Lutheran Health Systems, La Crosse, WI PURPOSE: The Framingham risk score is recommended for identifying individuals at high risk for a future event. However, the burden of cardiovascular disease resides in patients stratified as low and intermediate risk simply because of the large number of people receiving this classification. We propose the need to move beyond risk stratification for cardiovascular disease to identifying the presence of atherosclerosis in young to middle-aged adults who are truly at risk. The purpose of this analysis is to compare and contrast the role of Framingham risk stratification in the identification of atherosclerosis and risk for future events in a young to middle-aged population. METHODS: Men (ⱕ 55 years) and women (ⱕ65 years) without prior coronary heart disease scheduled for elective cardiac catheterization were studied. Subjects underwent coronary angiogram, carotid ultrasound and fasting lipid testing on the same day. Framingham risk scores were calculated. Endpoints included the presences of atherosclerosis (carotid or coronary disease) and one-year outcomes (hard events and future revascularization). RESULTS: Men (n⫽110) and women (n⫽136) were studied. Atherosclerosis was present in 170 subjects (carotid disease n⫽149, coronary disease n⫽124). Per Framingham risk classification, 73%, 8%, 19% of subjects presented as low, intermediate and high risk, respectively. Median follow-up was 19 months. 25 subjects developed 35 events that included death (n⫽2), stroke (n⫽5), MI (n⫽5), and revascularization (n⫽23). Neither lipid testing nor Framingham risk scores predicted the presence of atherosclerosis or future events. Overall, 16% of subjects with atherosclerosis who were classified as low or intermediate risk had events compared to 14% of those at high risk. No future events occurred in subjects without documented atherosclerosis. CONCLUSION: Many young to middle-aged adults classified as low or intermediate-risk have atherosclerosis and develop cardiovascular events. Framingham risk scores were not predictive of either. CLINICAL IMPLICATIONS: By shifting to a focus on identifying and aggressively treating atherosclerosis, screening can easily be accom-

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PURPOSE: To derive a 12-lead standard ECG from 3 measured leads using a universal patient coefficient matrix and to detect the presence of acute MI from an EV index calculated for both the measured and derived ECGs. METHODS: Twenty training ECGs of varying pathology were acquired and digitized resulting in a 300x12 voltage-time data array for mathematical processing. The simplex optimization (SOP) technique was used to derive a 12x3 universal patient coefficient matrix from the 20 case ECG training set. A different set of 55 test cases, including 37 normal and 18 acute infarction ECGs, were similarly acquired and digitized, from which leads I, aVF, and V2 were chosen as the measured 3 lead-vector basis factor space. The SOP coefficient 12x3 matrix was then multiplied by the [I, aVF, V2} measured lead-vector 3x300 matrix yielding the derived 12-lead ECG 300x12 matrix. The 55 measured and derived test case ECGs were graphically compared for diagnostic and morphologic correlation. RESULTS: All 55 test case ECGs were predicted correctly. No significant morphologic or diagnostic changes were noted in the derived ECGs. Significant differences between normal and acute MI were detected at EV3% (p ⬍ 0.05) for both measured and derived ECGs and the EV index predicted pathology in all cases correctly. The reduction of the measured 12-lead ECG data set to 3 leads allowed the display of a vector plot of the movement of the electrical forces resulting in a 3-dimensioanl spatial ECG curve. CONCLUSION: A universal patient coefficient matrix has been derived to allow 12-lead standard ECG derivations from 3 measured leads acquired using the SOP technique. This study also demonstrated that an EV index may differentiate normal from acute MI pathology. CLINICAL IMPLICATIONS: Using this new technology, it is now possible to perform instantaneous, real-time, point of service, costefficient 3-lead rhythm processing using bed-side cardiac monitoring systems to produce a derived 12-lead ECG. Continuous monitoring of the EV index provides a dynamic electrical marker for acute MI. DISCLOSURE: David Schreck, None. TYPE II DIABETES MELLITUS IS INDEPENDENTLY ASSOCIATED WITH NON-RHEUMATIC AORTIC VALVE STENOSIS OR REGURGITATION Mohammad-Reza Movahed MD* Mehrtash Hashemzadeh BS M. Mazen Jamal MD Department of Medicine, Division of Cardiology, University of California, Irvine, Orange, CA PURPOSE: Diabetes mellitus (DM) is a major risk for cardiovascular disease and mortality. There is a recent study that found DM was associated with aortic stenosis in univariate but not in multivariate analysis. The goal of this study was to evaluate any association between DM and non-rheumatic aortic valve stenosis or regurgitation using ICD-9 codes in a very large database. METHODS: We used PTF documents containing discharge diagnoses using ICD-9 codes of inpatient treatment from all Veterans Health Administration hospitals. The data were stratified using ICD-9 code for DM (n⫽293,124), and a control group with hypertension (HTN) but no DM (n⫽552,623), and the ICD-9 code for non-rheumatic aortic valve disorder(424.1). We performed multivariate analysis adjusting for coronary artery disease, congestive heart failure, smoking and hyperlipidemia. Continuous and binary variables were analyzed using c2 and Fisher’s Exact tests. RESULTS: Non-rheumatic aortic valve disease diagnosis was present in 7,322 (2.5%) of DM patients vs. 10906 (2.0%) in the control group. Using multivariate analysis, DM remained strongly associated with nonrheumatic aortic valve disease: (odds ratio (OR): 2.23, 95%; confidential interval (CI): 2.16 to 2.30 p⬍0. 000). CONCLUSION: Type II diabetes mellitus is independently associated with non-rheumatic aortic valve disorders (regurgitation and stenosis) suggesting the direct negative effect of DM on aortic valve structure. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Cardiology: Diagnosis of Cardiovascular Disease, continued CLINICAL IMPLICATIONS: Patient with DM may need close follow-up for the occurence of aortic valve stenosis or regurgitation. DISCLOSURE: Mohammad-Reza Movahed, None. ANATOMICAL BASIS OF CARDIOTHORACIC NEUROSTIMULATION Anselmo De La Fuente MD* Maria Jose Saez MD Ana Insausti MD Ignacio Pascual MD Ricardo Insausti MD Hospital de Navarra, Pamplona, Spain

COAGULATION STUDIES IN PATIENTS WITH THROMBOSED PROSTHETIC HEART VALVES AND INTRACARDIAC CLOTS Layla A. Mammo PhD Tanya M. Saou’r Atia W. Sheereen PhD M Shoukri PhD Jalal N. Saour MD* King Faisal Specialist Hospital, Riyadh, Saudi Arabia PURPOSE: To investigate the association of FVL, prothrombin G20210A and MTHFR C677T mutations in patients with thrombosed Prosthetic Heart Valves and intracardiac clots. METHODS: Blood from consenting healthy donors serving as the Control population (610 males and 111 females) and thirty one (31)patients with thrombosed PHV, left ventricular clot and left Atrial clot was collected. The DNA was extracted and stored at -70°C until needed . Testing for the mutations was done by the Polymerase Chain reaction using restriction enzymes and by the Roche Light Cycler. RESULTS: Nine subjects from the Control population tested positive for FVL (1.25%); two for prothrombin G20210A (0.28%); and 180 (25.4%) for MTHFR C677T. Thirty-one patients were tested.Twenty-four with thrombosed PHV, five with left ventricular clot and two with left atrial clot. Two patients tested positive for FVL (6.4%), one for prothrombin G20210A (3.2%) and twelve for MTHFR C 677T (38.7%) mutations. CONCLUSION: Our data suggest an association between FVL, prothrombin G20210A and MTHFR C677T mutations in patients with thrombosed PHV and intracardiac clots. However, upon comparing the patient population to the normal population no significant difference was found for FVL(P Value⫽ 0.11)and no significant difference for prothrombin G20210A (P value ⫽ 0.27) whereas for MTHFR C677T the difference was significant(P value ⫽⬍0.01). More data is needed to confirm this observation. CLINICAL IMPLICATIONS: Valve thrombosis and systemic thromboembolism continue to be the most serious complication in patients with

THE USE OF RADIOLOGICAL IMAGING IN THE INITIAL WORKUP OF SYNCOPE M. Shubair MD N. Jallad MD H. Aziz MD M. Ismail MD* M.A. Khan MD St. Joseph’s Regional Medical Center, Paterson, NJ PURPOSE: To evaluate the workup of patients admitted to the hospital with syncope and to evaluate that clinical practice guidelines for syncope were followed. METHODS: We retrospectively reviewed medical records of 104 patients (50 males, 54 females, age range 23-93; mean age 63.8 yrs) with the principal diagnosis of syncope over a period of 6 months and examined their initial diagnostic workup including CT-head and carotid Doppler ultrasound. RESULTS: Only one patient had focal neurological deficit on initial presentation. Both his carotid ultrasound and CT-head were abnormal. 55 (52.8%) patients had carotid doppler ultrasound and 62 (59.6%) patients had CT-head despite normal physical examination; both tests were normal. CONCLUSION: These data suggest that the use of imaging studies in the evaluation of syncope has a low diagnostic yield. Careful history, and physical examination should help guide diagnostic testing. CLINICAL IMPLICATIONS: The use of published clinical guidelines for syncope is a good tool for the diagnostic workup. Patients with no focal neurologic deficit on physical examination are unlikely to benefit from radiological imaging. DISCLOSURE: M. Ismail, None.

CORRELATION OF CARDIOVASCULAR RISK SCORES WITH MYOCARDIAL HIGH-ENERGY PHOSPHATE METABOLISM Ralf H. Zwick MD* Gert Klug MD Matthias Frick MD Michael Schocke MD Christian Wolf MD Werner Jaschke MD Otmar Pachinger MD Bernhard Metzler MD Cardiology, Innsbruck University, Innsbruck, Austria PURPOSE: Our preliminary data suggested a decrease of human myocardial, high-energy, phosphate metabolism in patients with hypercholesterolemia. Therefore we intended to prove its association with established cardiovascular risk scores. METHODS: Our study included 99 healthy, asymptomatic male patients (mean age 52.2 ⫹/- 8.8) with normal ejection fraction. All underwent echocardiography and cycle ergometry to exclude a latent coronary insufficiency. Blood was taken to evaluate cardiovascular risk scores: ESC cardiovascular (CV) risk, ESC coronary heart disease (CHD) risk, Procam and Framingham CHD score. Then Phosphorus-31, twodimensional chemical shift imaging (31P 2D CSI) of the heart was performed in all subjects using a 1.5 Tesla whole-body magnetic resonance (MR) scanner. The ratios (R) between phosphocreatine (PCr) and beta-adenosine-triphosphate (beta-ATP) were calculated for the left ventricular myocardium and divided into tertiles (R1-R3). RESULTS: There was a significant effect regarding differences across tertiles (R1-R3) within the cardiovascular risk scores (Kruskal Wallis ANOVA for ESC CV, p⬍0.001; ESC CHD, p⬍0.001; Procam, p⫽0.003; Framingham CHD, p⬍0.001). Bivariat analysis revealed an association between myocardial PCr-beta-ATP ratios and the ESC CV (p⬍0.001, r⫽ -0.444), ESC CHD (p⬍0.001, r⫽ -0.434), Procam (p ⫽ 0.027, r ⫽ -0.222), Framingham CHD (p⬍0.001, r ⫽ -0.380) score and patients with low R had a significant higher risk of cardiovascular events than those in the higher tertiles. CONCLUSION: We are the first to show a correlation between the myocardial high-energy, phosphate metabolism and cardiovascular risk scores. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: Our objectives are to determine in rodents, (a) the levels at which sensory afferents to heart and lungs enter the spinal cord and (b) the termination of cardiothoracic afferent fibers in spinal gray matter. Such information is required to understand neurostimulation and to progress development of rodent experimental models. METHODS: Under general anaesthesia and mechanical ventilation, 50 young Wistar rats were subjected to thoracotomy such that a neuroanatomical retrograde tracer (horseradish peroxidase or Fast Blue) could be injected with precision into either the pericardium, left atrium, root of the left lung, or the left lung parenchyma.After appropriate survival times animals were sacrificed and perfused with the adequate fixatives. Spinal ganglia and segments were identified, and those between C4 and Th12 were removed individually and cryoprotected. Segments were sectioned at 50␮m and studied under the microscope to create a “map” of the column and the distribution of tracer deposit within it. RESULTS: Segments C8 through T4 contained retrogradely labeled dorsal root neurons projecting to the heart, while C8-T6 were labeled after depositing tracer in the lung.Central branches of dorsal root ganglion cells entered laminae I and II. CONCLUSION: Information from the heart is collected in the four upper segments of the thoracic cord, but some information from the lungs also arrives in these segments. Neurostimulation of spinal segments C8-T4 will block afferents entering laminae I and II, including pain afferents from the heart. The blocking of pain afferents from the heart may explain the clinical improvement observed in angina patients under neurostimulation. CLINICAL IMPLICATIONS: The description of the anatomical basis of cardiothoracic neurostimulation provides a long-awaited scientific explanation of clinical findings. The experimental model developed and described here provides a way to further investigate cardiac neurostimulation. DISCLOSURE: Anselmo De La Fuente, None.

prosthetic heart valve (PHV) on long-term anticoagulation therapy. While under treatment with oral anticoagulants is a recognized cause for these complication, other factors possibly play a role as not all patients under-treated develop a coagulation problem.Factor V Leiden (FVL) prothrombin G20210A and the 5,10-methylenterahydrofolate-reductase (MTHFR)C677T mutations have been associated with venous & possibly arterial thrombosis. No studies as to whether or not these factors are associated with valve thrombosis or intracardiac clots in patients with PHV are available to date. DISCLOSURE: Jalal Saour, None.

Wednesday, November 2, 2005 Cardiology: Diagnosis of Cardiovascular Disease, continued CLINICAL IMPLICATIONS: Myocardial high-energy, phosphate metabolism may be of relevance in primary prevention of cardiovascular disease. DISCLOSURE: Ralf Zwick, None.

AN ABNORMAL RIGHT VENTRICULAR APICAL ANGLE IS INDICATIVE OF COMPROMISED RIGHT VENTRICULAR FUNCTION Angel Lopez-Candales MD* Kaoru Dohi MD Anca Iliescu MD Ross C. Peterson MD Kathy Edelman Raveen Bazaz MD University of Pittsburgh Medical Center, Pittsburgh, PA PURPOSE: Presence of right ventricular (RV) dysfunction is an adverse prognostic indicator but current echocardiographic methods have some limitations. METHODS: RV apical angles in systole and diastole were correlated with known parameters of RV function in patients without pulmonary hypertension (Group 1) and in patients with pulmonary hypertension (Group 2). RV apical angles were significantly smaller in both systole (22 ⫹ 7 degrees) and diastole (33 ⫹ 6 degrees) in Group 1 patients when compared to Group 2 (54 ⫹ 18 degrees, p⬍0.0001 and 59 ⫹ 17 degrees, p⬍0.0001, respectively). RESULTS: Group 2 patients had statistically larger RV systolic and diastolic areas (19⫾ 9 versus 8 ⫾ 3 and 27⫾ 9 versus 17 ⫾ 3, p⬍0.0001; respectively) and smaller maximal TV annular excursion (2.5 ⫾ 0.44 versus 1.5 ⫾ 0.66, p⬍ 0.00001; respectively) than Group 1. Group 2 had statistically larger RV apical angles in both systole and diastole when compared to Group 1 (54 ⫾ 18 and 59 ⫾ 17 versus 22 ⫾ 7 and 33 ⫾ 6, p⬍ 0.00001, respectively). The peak pulmonary systolic pressures were not only inversely correlated with RVFAC (R ⫽ -0.62; p⬍0.001) but also with maximal TV annular excursion (R ⫽ -0.69; p⬍0.001). A very strong linear correlation was noted between the RVEDA and RV diastolic apical angle (R ⫽ 0.81, p⬍0.0001) and between the RVESA and RV systolic apical angle (R ⫽ 0.89, p⬍0.0001). RV apical angle also had a statistically significant inverse correlation with measures of RV function. A representative end diastolic four chamber still frame image of a normal and a patient with an abnormal RV apical angle is shown. CONCLUSION: Therefore, we conclude that this new measurement of RV apical angle is simple and useful to quantify RV apical structural and functional abnormalities that are well correlated with global RV impairment in patients with chronic pulmonary hypertension. CLINICAL IMPLICATIONS: Ease of data acquisition, reproducibility, and lack of cumbersome geometric analyses allow for easy clinical application.

DISCLOSURE: Angel Lopez-Candales, None.

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TEACHING CARDIAC AUSCULTATION VIA THE INTERNET: THEORY BECOMES REALITY Michael J. Barrett MD* Katherine A. Thomas MS Maryann Kuzma MD Drexel University College of Medicine, Blue Bell, PA PURPOSE: The ability of medical students to recognize heart sounds is alarmingly low (⬃21%). We previously demonstrated students who listened to intensive repetition of abnormal heart sounds in a classroom setting achieved a proficiency score of 85%. This followup study investigated if similar results could be obtained using the Internet. METHODS: 64 third year medical students were randomized to either an intervention (I) group (N⫽50) or control (C) group (N⫽14). The intervention students were instructed to download a digital audio file (mp3) from a web page. This file contained auditory recognition exercises of 4 basic cardiac murmurs (Aortic Stenosis, Aortic Regurgitation, Mital Regurgitation, Mitral Stenosis) and 2 extra heart sounds (S3, S4). Each heart sound was repeated 400 times interspersed with clinically relevant comments. The 14 control students downloaded a sham file with no auditory instruction. Two tests of auscultatory proficiency were administered: a pretest before the intervention and a posttest after the intervention. At both tests, all subjects listened to prerecorded heart sounds in a randomized sequence and wrote the name of the sound on blank answer sheets. RESULTS: For the intervention students, the pretest proficiency score was 29.6 ⫹ 15.7% (Mean ⫹SD) and increased significantly to 82.0 ⫹ 16.9% on the posttest (p⬍0.001). The average improvement was 52 points. No significant improvement was seen in controls: pretest 38.8 ⫹/17.3% and posttest 44.6 ⫹/- 17.6% p⫽0.15. CONCLUSION: Third year medical students demonstrated dramatic improvement in cardiac auscultation after listening to a digital audio file downloaded via the internet. These improvements were equal to that obtained with classroom instruction using a similar approach of intensive repetition of abnormal sounds. CLINICAL IMPLICATIONS: This study confirms to importance of intensive repetition in learning cardiac auscultation and demonstrates that this type of learning can be effectively communicated via the internet. This method of instruction is associated with significant cost savings and expanded geographic reach. DISCLOSURE: Michael Barrett, Shareholder Michael Barrett, MD has an ownership interest in MED-Ed Consulting, Inc.

INTERVENTRICULAR SEPTAL FLATTENING OBSERVED ON THE MYOCARDIAL PERFUSION IMAGES STRONGLY CORRELATE WITH RIGHT VENTRICULAR OVERLOAD Mohammad-Reza Movahed MD* Absalam Hepner MD Paul Lazotte DO Norah Milne MD University of California, Irvine Medical Center, Orange, CA PURPOSE: Background: Flattening of the interventricular septum (D-shaped Septum) detected during echocardiographic examination is correlated with significant right ventricular (RV) overload. There are no reports of this finding with cardiac gated SPECT imaging. We report an observational study correlating this finding with the presence of RV overload. METHODS: Method: Retrospectively we compared eight cases with flattening of the interventricular septum on cardiac gated SPECT imaging of which echocardiographic correlations and clinical data were available for the presence of RV overload. RESULTS: Results: All patients but one had pulmonary hypertension ranging from 42 to 52 mmHg measured by echocardiographic doppler studies. Except one all patients had reasons for RV overload (chronic obstructive pulmonary disease in three, history of atrial septal defect in three, pulmonary embolism in one and obstructive sleep apnea in one). Septal flattening present on gated SPECT images was seen in 50% of the cases by echocardiography. Other signs of RV overload (RV enlargement, RV hypertrophy) were observed by echocardiography in five patients and by the gated SPECT in seven patients. CONCLUSION: Conclusion: The presence of interventricular septal flattening on gated SPECT studies correlates with right ventricular overload and should be routinely assessed during interpretation of gated SPECT studies. CLINICAL IMPLICATIONS: We suggest that more attention should be given to the shape of the interventricular septum during interpretation of gated SPECT studies and the term of septal flattening should be CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Cardiology: Diagnosis of Cardiovascular Disease, continued routinely used and reported similar to echocardiographic descriptions of the septum in patients with suspected RV overload.

LISTENING TO THE AORTIC VALVE: NOVEL ACOUSTIC ANALYSIS PREDICTS AORTIC VALVE CALCIFICATION AND CARDIOVASCULAR EVENTS Kian Keong Poh MB, BCh* Mark Y. Chan MBBS Hong Yang MD Lieng H. Ling MBBS National University Hospital, Singapore, Singapore PURPOSE: Aortic valve calcification (AVC) measured by multislice computed tomography (MSCT) has previously been shown to be of prognostic importance. We aimed to determine if a novel acoustic method of evaluating heart sounds in pts with valvular aortic stenosis (AS) or sclerosis is a useful alternative. METHODS: ECG-gated acoustic data recorded from the precordial aortic area using an electronic stethoscope were subjected to energybased continuous wavelet transformation by a laptop software program, which extract the dominant systolic frequency (DF). These were compared to AVC quantified in Agatston units (AU) by MSCT and echocardiographic indices of AS severity, determined independently. Patients were prospectively followed up for occurrence of cardiac death and symptom-driven aortic valve replacement. RESULTS: Of 50 pts (age 68⫾11 yrs, 58% males), 35 had lone AS of varying severity and 15 with aortic valve sclerosis. Mean aortic valve area indexed to body surface area (AVAI), AVC, DF and left ventricular ejection fraction (EF) were 0.94⫾0.50 cm2/m2, 1037⫾1476 AU, 103⫾69 Hz and 62⫾14% respectively. DF correlated significantly with AVC, maximal pressure gradient across the aortic valve (Pmax), AVAI and aortic valve resistance (r⫽0.62, 0.61, -0.51 and 0.60 respectively, all P⬍0.001). In a multivariate linear regression model incorporating AVC, AVAI and Pmax, the only independent predictor of DF was AVC (␤⫽0.37, P⫽0.03). Over 15⫾7 months, 7 pts reached the composite endpoint. Pts with events had higher DF (170⫾65 vs 93⫾64 Hz, P⫽0.005). For prediction of the endpoint, the areas under receiver characteristic curves for DF, AVC, AVAI, age and EF were 0.82(P⫽0.007), 0.79(P⫽0.013), 0.88(P⫽0.001), 0.50(P⫽NS) and 0.65(P⫽NS) respectively. A threshold of 145 Hz for DF provided optimal sensitivity of 86% and specificity of 81% of predicting an event. CONCLUSION: DF derived from novel acoustic analysis of aortic valve stenosis or sclerosis correlates well with AVC by MSCT and offers prognostic information in these patients. CLINICAL IMPLICATIONS: Acoustic analysis of heart sound may provide a simple and useful non-invasive adjunct in the management of patients with aortic valve calcification. DISCLOSURE: Kian Keong Poh, Grant monies (from sources other than industry) National Healthcare Group (Singapore) and Singapore Heart Foundation grants.

PURPOSE: Oxygen desaturations and sleep fragmentations are frequently seen during sleep in OSA. These events provoke heightened sympathetic activity and may impair vascular function. We investigated flow and nitroglycerin-mediated (FMD and NMD, respectively) vascular dilation in middle-aged (⬍65) and elderly (⬎ 65) patients with moderate to severe OSA. METHODS: We recorded polysomnograms from 18 male subjects (mean age ⫽ 55 ⫹10.99]) with symptomatic OSA and measured FMD and NMD in brachial artery using high-resolution vascular ultrasound with a 10-MHz linear-array transducer. The right brachial artery diameter (BAD) was measured at baseline, and then a pneumatic tourniquet was placed around the forearm and inflated to a pressure of 200 mm Hg for 5 minutes. BAD measurements were repeated at 15 seconds, then at every minute for 5 minutes following cuff deflation and following administration of 0.4 mg of sublingual NTG. The FMD was expressed as a percentage change of diameter after reactive hyperemia relative to the baseline scan. Likewise, the NMD was expressed as a percentage change of diameter after NTG administration relative to the baseline scan. RESULTS: Mean [SD] ESS was 14 [7], mean [SD] AI and AHI were 30[34] and 50 [33] respectively, and lowest and mean O2 saturations were 75% [22%] and 93%[3%] respectively. Brachial artery diameter (mm) at baseline, 1 minute post hyperemia, and 3 minutes post NTG were 0.45 [0.09], 0.48 [0.06], and 0.49 [0.05] mm. Baseline and post NTG diameters were significantly different (p ⬍ 0.01). The FMD and NMD were 1% [2%] and 11% [3%], respectively (p⬍ 0.001). Our study did not have enough power to detect any difference in FMD and NMD in elderly versus middle-aged adults. CONCLUSION: Endothelial dependent vascular function is impaired in subjects with moderate to severe OSA. Further studies will evaluate the effect of therapeutic intervention to determine if this is a reversible alteration in vascular function. CLINICAL IMPLICATIONS: Restoration of endothelial dependent vascular function may be useful in evaluation obstructive sleep apnea treatment. DISCLOSURE: Hossein Sharafkhaneh, None. THE NEW PERICARDIAL STRUCTURE IN VIBROACOUSTIC DISEASE Jose´ I. Fragata PhD* Emanuel Monteiro MD Mariana Alves-Pereira MS Nuno A. Castelo-Branco MD Pediatric Cardiac Surgical Unit, SantaMarta Hospital, Lisbon, Portugal PURPOSE: The anatomical study of the pericardium in vibroacoustic disease (VAD) patients was prompted by the echo-imaging results obtained initially in aircraft technicians. With informed consent of VAD patients, submitted to cardiac surgery for other reasons, pericardial fragments were removed for study in order to determine the nature of this abnormal thickening. METHODS: The parietal pericardium fragments were removed during surgery. None had a record of any kind of pericarditis, nor of any type of diastolic problems, and there was no previous history of diabetes or repeated streptococcal infections. Fragments were removed at the beginning of the surgery, during the opening of the pericardial sac. Each fragment was divided in two and pinned in dentist wax in a Petry dish with the serosal surface facing up. The specimens for light microscopy were formalin-fixed, paraffin-embedded, hematoxylin, eosin and fuschsin-rhesorcin stained. RESULTS: Normal pericardium has three layers: serosa, fibrosa and epipericardium. Five layers of tissue were identified, instead of the classical three: serosa, internal fibrosa, loose tissue layer, external fibrosa, and epipericardium. The external and internal fibrosa are composed of organized, wavy collagen bundles. Images of apoptotic (programmed) death were seen in the mesothelial layer, and non-apoptotic (mechanical) cell death was observed in all other layers. A large amount of cellular debris was present in all fields, however, not inflammatory process was present. Imaging frequently disclosed the presence of cell debris inside the small lymphatic vessels. CONCLUSION: Given the large amount of cellular debris, autoimmune situations are certain to arise. Drainage of cellular debris seems to be a major function of the surrounding lymphatic vessels. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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DISCLOSURE: Mohammad-Reza Movahed, None.

VASCULAR FUNCTION IS ABNORMAL IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA Hossein Sharafkhaneh MD* Max Hirshkowitz PhD Biykem Bozkurt MD Amir Sharafkhaneh MD Baylor College of Medicine, Houston, TX

Wednesday, November 2, 2005 Cardiology: Diagnosis of Cardiovascular Disease, continued CLINICAL IMPLICATIONS: Pericardial thickening with no adiastole, and no inflammatory process is a VAD diagnosis, and can certainly be the cause of auto-immune situations. DISCLOSURE: Jose´ Fragata, None. MECHANOTRANSDUCTION IN PERICARDIAL TISSUE OF VIBROACOUSTIC DISEASE PATIENTS Mariana Alves-Pereira MS* Jose´ I. Fragata PhD Emanuel Monteiro MD Nuno A. Castelo-Branco MD Environmental Sciences & Engineering, New Univ Lisbon, Caparica, Portugal PURPOSE: Mechanical signalling among cells and tissues has been shown to be an important, albeit lesser known, form of transducing pathological stimuli. Cytoskeletal (CSK) structures are organized in accordance with tensegrity architecture and, as such, can bear mechanical loads. Vibroacoustic disease (VAD) is a systemic pathology characterized by the abnormal proliferation of extra-cellular matrices (ECM) in the absence of an inflammatory process. The goal of this report is to qualitatively analyse the images obtained from vibroacoustic disease (VAD) pericardial fragments within the context of tensegrity structures. METHODS: Drawing upon the numerous scanning and transmission electron microscopy images of VAD patients’ parietal pericardium, which is abnormally thickened and discloses mechanical cell death in all layers. The abnormal thickening is due to the splitting of the fibrosa layer into two halves and, in between, the neo-formation of a loose tissue layer. The internal fibrosa layer follows the systolic and diastolic movements very closely while the external layer does not. The implications of these situations for CSK and ECM mechanotransduction are qualitatively analysed. RESULTS: The new pericardial structure, composed of five layers instead of three (due to fibrosa splitting and neo-formation of loose tissue layer) is reminiscent of a pneumatic structure. The wave length of the wavy collagen fibres found in the internal fibrosa seem to be more variable than that found in the external fibrosa. The loose tissue layer contains adipose tissue that, due to its viscoelastic properties, can attenuate external mechanical forces. In the meseothelial layer, there is a reinforcement of cell-cell connections, through an increased amount of desmosomes. No hemidesmosomes were identified, however the boundary between mesothelial layer and lower basal lamina exhibits unusual connection, reminiscent of anti-sesmic structures. CONCLUSION: Tensegrity architecture of cells and tissue can greatly contribute to the understanding of the biological response to LFNexposure. CLINICAL IMPLICATIONS: It is probable that pharmacological solutions for LFN-induced pathology targeting CSK and ECM tension would be most successful. DISCLOSURE: Mariana Alves-Pereira, None.

Cardiology: Echocardiography 12:30 PM - 2:00 PM SMALL PULMONARY ARTERIOVENOUS MALFORMATIONS IDENTIFIED BY SALINE CONTRAST ECHOCARDIOGRAPHY ARE ASSOCIATED WITH MIGRAINE HEADACHE Timothy D. Woods MD* Suresh Ramamurthy MD Medical College of Wisconsin, Milwaukee, WI PURPOSE: Patent foramen ovale (PFO) has been linked to migraine headache (MH), probably resulting from an unidentified vasoactive substance bypassing pulmonary metabolism. The prevalence of pulmonary arteriovenous malformations (PAVM) in a population without respiratory symptoms or hereditary hemorrhagic telangiectasia (HHT), a disease associated with PAVM, has not been described and may also be associated with MH. METHODS: Sixteen patients ages 20-55 undergoing a transthoracic echo for reasons other than pulmonary disease or symptoms were consented to also undergo a saline contrast echocardiogram (SCE) with and without Valsalva. If ⱖ 1 clear bubble(s) appeared in the left heart ⱕ 3 cardiac cycles of right heart opacification at rest or with Valsalva, it was classified a PFO. If ⱖ 1 bubble(s) were evident in the left heart at ⱖ 5

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cardiac cycles of right heart opacification at rest AND with Valsalva, it was labeled late left heart contrast (LLHC), compatible with presence of a PAVM. Patients then completed a questionnaire previously shown in studies to be accurate in diagnosis of MH. RESULTS: Three of the 16 patients (19%) had LLHC (5-20 bubbles), compatible with small PAVM. All 3 patients had questionnaires diagnostic of MH. CONCLUSION: Small amounts of LLHC during SCE is not uncommon in patients without respiratory symptoms or HHT, and is compatible with the presence of small PAVM. Small PAVM appear to be significantly associated with MH. The presence of right-to-left shunt appears associated with MH independent of the shunt mechanism. CLINICAL IMPLICATIONS: Small amounts of LLHC are compatible with small PAVM and are not uncommon in patients without respiratory disease. They should not be ignored when interpreting a SCE, as it appears they have clinical significance. The mechanism linking small PAVM and MH may involve a vasoactive substance escaping pulmonary endothelial metabolism, and requires further investigation. SCE Result Migraine Present Normal PFO PAVM TOTAL

9 4 3 16

1 2 3 6

p Compared to Normal

p⫽0.04 p⫽0.013

p⫽0.035

p Values computed using Two-Tailed Fisher’s Exact Test DISCLOSURE: Timothy Woods, None.

EVALUATION OF ASYMPTOMATIC PATIENTS WITH CRONIC CHAGAS DISEASE TRHOUGH THE ANALISYS OF DYNAMIC ELECTROCARDIOGRAM, ECHOCARDIOGRAM AND B-TYPE NATRIURETIC PEPTIDES Divina S. Oliveira-Marques PhD* Manoel F. Canesin PhD Claudio J. Fuganti MD Antonio C. Pereira-Barretto PhD Londrina State University, Londrina, Brazil PURPOSE: To evaluate asymptomatic patients with chronic Chagas‘ disease in relation to the prevalence of ventricular arrhythmia, left ventricular dysfunction, and B-type natriuretic peptide levels ( BNP). METHODS: Clinical evaluation, electrocardiogram (EKG). cardiothoracic index (CTI),dynamic electrocardiogram, echocardiogram and BNP dosing were used to evaluate 106 patients from the Chagas Disease Outpatient Clinic, distributed into three groups: GI (50- normal EKG). GIIA (31-EKG with alterations characteristic of Chagas disease, and GIIB ( 25- EKG with other types of alterations). RESULTS: The most prevalent electrocardiographic alterations were: GIIA group: right bundle branch block, anterior division of de left bundle branch block and inactive areas (18% each); GIIB group: alterations in the infero-lateral repolarization and left ventricular hypertrophy (26%). CTI mean values were similar (p⫽0,383). The prevalence of ventricular arrhythmia was greater in the GIIA (77%) and GIIB (75%) groups than in the GI group (46%) (p⫽0,002). Ventricular dysfunction was more frequent in the GIIA (52%) and GIIB (32%) groups than in the GI group (14%) (p⫽ 0,001). Systolic dysfunction was more prevalent in the GIIA group (29%) than in the GIIB (20%) and GI (2%) (p⬍ 0,001). Diastolic dysfunction was more frequent in the GII (42%) and GIIB (28%) groups than in the GI (12%) group (p⫽0,005). B-type natriuretic peptide levels were 30 ⫾ 88 pg/ml for the GI group, 66 ⫾ 194 for the GIIA group and 24 ⫾ 82 for the GIIB group (p⫽0,121), respectively. CONCLUSION: Arrhythmia and left ventricular dysfunction were more prevalent in the asymptomatic patients with chronic Chagas‘ disease and EKG alterations than in patients with normal EKGs. BNP levels were similar among the groups. CLINICAL IMPLICATIONS: Patients with asymptomatic chronic form of the Chagas‘disease and electrocardiographic alterations will have to be submitted to the inquiry in relation to the presence of arrhythmias and ventricular dysfunction. DISCLOSURE: Divina Oliveira-Marques, None. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Cardiology: Echocardiography, continued GENDER SPECIFIC ECHOCARDIOGRAPHIC PREVALENCE OF VALVULAR HEART DISEASE IN A DATABASE OF 24,265 PATIENTS Mohammad-Reza Movahed MD* Mastaneh Ahmadi-Kashani BS Babak Kasravi MD Ali Ghorbani MD University of California, Irvine Medical Center, Orange, CA

Type of Valvular Disease

Prevalence in Females (%)

Prevalence in Males (%)

Overall Prevalence (%)

MR, all MR, mild MR, moderate MR, severe MS, all** MVP* AR, all AR, mild** AR, moderate AR, severe** AS, all Bicuspid aortic valve** TR, all** TR, mild TR, moderate* TR, severe**

24.4 16.5 6.1 1.9 1.6 0.4 5.5 11.5 2.6 0.4 2.1 0.3 18.5 11.9 4.4 2.3

25.0 16.5 6.3 2.2 0.4 0.7 14.9 10.1 2.5 1.0 2.3 0.9 16.7 11.6 3.7 1.5

24.7 16.5 6.2 2.0 1.0 0.6 15.2 10.9 2.6 0.7 2.2 0.6 17.7 11.7 4.0 1.9

* p ⬍ 0.01 DISCLOSURE: Mohammad-Reza Movahed, None. DENTITION AND AORTIC ATHEROSCLEROSIS; A TRANSESOPAHAGEAL ECHOCARDIOGRAPHIC STUDY Ricardo Castillo MD Louis Salciccioli MD Jason M. Lazar MD* SUNY Downstate Medical Center, Brooklyn, NY PURPOSE: Prior studies have shown a relationship between periodontal disease, acute myocardial infarction, and atherosclerosis. Microbes indigenous to the oral cavity and DNA of periodontal pathogens have been found in atheromatous carotid plaques. Oral pathogens may promote inflammation and thrombosis leading to atherogenesis Periodontal disease has been found associated with coronary artery, carotid, and peripheral vascular disease. The objective of this study was to determine a possible association between dental loss and aortic atherosclerotic disease. Transesophageal echocardiography (TEE) is an excellent technique to assess aortic atherosclerotic plaque. METHODS: In 115 patients (age 59 ⫾15 years, 63% female) referred for TEE, clinical data were recorded. Periodontal disease was determined

PREVALENCE AND PROGNOSIS OF INTRAPULMONARY SHUNTS IN PATIENTS WITH HEPATIC CIRRHOSIS Manisha Das MD* Wilbert S. Aronow MD Michael Langiulli MD Pierre Salomon MD John A. McClung MD Leona Kim-Schluger MD David Wolf MD Robert N. Belkin MD New York Medical College, Valhalla, NY PURPOSE: The purpose of this study was to investigate the prevalence and prognosis of intrapulmonary shunts in patients with hepatic cirrhosis. METHODS: We investigated the prevalence and prognosis of intrapulmonary shunts in 82 patients (56 men and 26 women), mean age 54 years, with hepatic cirrhosis referred for contrast echocardiography as part of an evaluation for liver transplantation. Mean follow-up was 41 months in patients with intrapulmonary shunts and 42 months in patients without intrapulmonary shunts (p not significant). RESULTS: Intrapulmonary shunts were present in 49 of 82 patients (60%) with hepatic cirrhosis. Baseline characteristics including the MELD score were not significantly different between patients with and without intrapulmonary shunts. At 41-month mean follow-up, 8 of 49 patients (16%) with intrapulmonary shunts and 4 of 33 patients (12%) without intrapulmonary shunts had died (p not significant). CONCLUSION: Intrapulmonary shunts do not significantly increase mortality in patients with hepatic cirrhosis at long-term follow-up. CLINICAL IMPLICATIONS: Patients with hepatic cirrhosis with and without intrapulmonary shunts have a similar mortality at long-term follow-up. DISCLOSURE: Manisha Das, None. ECHO-IMAGING FEATURES IN CARDIOVASCULAR STRUCTURES IN VAD PATIENTS Amilcar Arau´jo MD* Joaquim Carranca MD E´lia Batista MD Nuno A. Castelo-Branco MD Cardiology Unit (UTIC), St. Maria University Hospital, Lisbon, Portugal PURPOSE: Previous studies show that low frequency noise (LFN, ⬍500 Hz, including infrasound) induces changes in the extra-cellular matrices (ECM). The pathology induced by excessive exposure to LFN is called vibroacoustic disease (VAD). The diagnostic method of choice has been echocardiography because proliferation of the ECM can be visualized in thickened cardiac structures, namely pericardium and valves. Recently echocardiograms revealed an anatomical feature that could be a consequence of Echo reveale anatomical feature echo revelased anatomical consequence of theis extra-thoracic pressure: visible hyperplasia of the eustaquian valve in the inferior vena cava. Is being observed in all patients in this currently ogoing project. METHODS: Study population: 30 selected male flight attendants, ave. age 48 (range 30-61), and 30 female flight attendants, ave. age 43 (range 27-57). Total exposure time of all individuals was ⬎ 8 yr. Echo-Doppler studies were recorded on coded videotapes. Using a 0 to 3 point scoring system, 3 morphological parameters were evaluated: thickening of the pericardium, mitral & aortic valves and vena cava’ eustachian valve. RESULTS: Echocardiograms of flight attendants (males and females) disclose pericardial thickening that may appear concurrently with cardiac valve thickening , but with no consequences for diastolic mechanics. Thickened eustachian valve of the inferior vena cava were clearly visible all the study population. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: : Prevalence of different valvular pathologies has not been reported in female and male patients in large population-based studies. The goal of this study was to report gender specific prevalence of various valvular pathologies. METHODS: We retrospectively analyzed 24,265 echocardiograms performed at our institution between 1984 and 1998. The prevalence of mitral valve prolapse (MVP), regurgitation (MR) and stenosis (MS), aortic valve regurgitation (AR) and stenosis (AS), bicuspid aortic valve and tricuspid regurgitation (TR) were calculated in female and male patients. RESULTS: Echocardiograms were performed in 12,926 (53%) female patients and 11,339 (47%) male patients. Gender specific echocardiographic prevalence of different valvular abnormalities is shown in Table 1. CONCLUSION: Conclusion: In this study, we compared echocardiographic prevalence of different valvular disease in female and male patients. MS and moderate to severe TR were more prevalent in female patients. MVP, bicuspid aortic valve and severe AR were more prevalent in male patients. The other valvular conditions studied had similar prevalence in both female and male patients. CLINICAL IMPLICATIONS: There are significant difference in the occurrence of Valvular abnormalities between men and women that needs further investigation.

as the number of missing teeth. Maximal aortic plaque thickness was measured by TEE. Analysis was performed to determine correlates of number of missing teeth and aortic plaque thicknes. RESULTS: Univariate correlates of tooth loss were age, hypertension, aortic plaque size, Ca-channel blocker use, and a trend toward B-blocker use. There was an inverse correlation with smoking. Univariate predictors of aortic plaque thickness were age(r⫽. 41, p⬍.001), dental loss (r⫽.27, p⫽.003), and Ca-channel blocker use(p⫽.006). There was an inverse association with smoking. Stepwise regression demonstrated age to be the strongest predictor of aortic atherosclerosis, with dental loss and Cachannel blocker use also found to be independent predictors. CONCLUSION: In conclusion, aortic atherosclerosis as determined by maximal plaque size is associated with periodontal disease. CLINICAL IMPLICATIONS: Poor dentition may be a simple clinical indicator of atherosclerosis. The association between poor dentition and aortic atherosclerosis may be related to common risk factors or to chronic inflammation. DISCLOSURE: Jason Lazar, None.

Wednesday, November 2, 2005 Cardiology: Echocardiography, continued CONCLUSION: At the cellular level, LFN-exposed humans and animals disclose transitory generalized fluid retention, which is maintained throughout the duration of LFN exposure (occupational or environmental). This is very discreet, decays with ceasing LFN exposure, and is not comparable to generalized common oedema, This can cause unsuspected interthoracic hypertension and can, in turn, lead to generalized extra-thoracic stasis. CLINICAL IMPLICATIONS: Echo observation of a thicken eustaquian valve can alert for a possible VAD diagnosis. DISCLOSURE: Amilcar Arau´jo, None.

IMPORTANCE OF EARLY FLUIDS RESUSCITATION IN MURINE SEPSIS: ECHOCARDIOGRAPHIC STUDY Massimiliano Guglielmi MD* Sergio Zanotti MD Walker Tracy MD Magali Zanotti BA Felicitas Ross BA Joseph E. Parrillo MD Steven M. Hollenberg MD Cooper University hospital/UMDNJ, Camden, NJ PURPOSE: Fluid resuscitation and antibiotic administration are critical components of the early treatment of sepsis. We evaluated the impact of three different early resuscitation regimens on cardiac performance in a murine model of sepsis. METHODS: 3 groups of 8 C57Bl/6 mice were made septic by cecal ligation and double perforation (CLP); 5 controls had sham ligation. After CLP animals received 1 of 3 fluid regimens: 35mL/kg normal saline bolus SQ after surgery only (None), 35mL/kg after surgery and then every 6hr, (Partial) and 100mL/kg after surgery and then every 6hr (Full). All 3 groups received ceftriaxone, 30mg/kg and clindamycin, 25mg/kg at 6 and 12hr. Animals were anesthetized briefly with isoflurane for echocardiography using a high-resolution ultrasound system (30Mhz scan-head). Stroke volume (SV, ␮L) was assessed by Doppler in the aortic outflow tract and fractional shortening (FS, %) by M-mode in the short axis view. Cardiac output (CO, mL/min) was calculated as SV*HR. RESULTS: From 3 to 9hr after CLP, CO was reduced from 25⫾2 to 13⫾2 (None), 24⫾4 to 15⫾5 (Partial) and 26⫾5 to 17⫾4mL/min (Full), largely due to a reduction in SV, from 56⫾6 to 23⫾2 (None), 51⫾6 to 28⫾7 (Partial), and 58⫾7 to 32⫾5␮L; (Full) (p⬍0.05 vs baseline and sham operated animals in all groups. Heart rate did not change significantly. Animals that received aggressive resuscitation (Full) reached a normodynamic state at 15hours, CO 23⫾7; SV 48⫾9; HR 475⫾74, p⫽NS vs baseline and sham operated animals. Unresuscitated and underresuscitated animals remained in a hypodynamic state, CO 14⫾6; SV 30⫾10; HR 470⫾50 (None) and CO 15⫾3; SV 40⫾9; 395⫾35 (Partial), p⬍0.05 vs baseline, sham operated and aggressively resuscitated animals (Full). CONCLUSION: Adequate fluid resuscitation is mandatory to restore a normodynamic state in sepsis. In this murine model, which replicates clinical sepsis, early underresuscitation can lead to a sustained hypodynamic state. Early and aggressive resuscitation is necessary to reestablish normal hemodynamics. CLINICAL IMPLICATIONS: Even seemingly minor degrees of underresuscitation early could potentially impair hemodynamics in later phases of sepsis in patients. DISCLOSURE: Massimiliano Guglielmi, University grant monies.

Cardiology: Epidemiology of Heart Failure 12:30 PM - 2:00 PM SURVIVAL BENEFIT ASSOCIATED WITH DISEASE MANAGEMENT IN RURAL INDIGENT SYSTOLIC HEART FAILURE PATIENTS Kathy Hebert MD Ron Horswell PhD Lee Arcement MD* Chabert Medical Center, Houma, LA PURPOSE: Heart failure (HF) produces significant morbidity and mortality. Although HF disease management (HFDM) programs have been shown to decrease this morbidity, there is a paucity of data of their effect on mortality, especially in indigent settings. The objective was to determine whether participation in a HFDM program would be associated with reduced mortality in an indigent population from rural Louisiana.

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METHODS: Proportional hazards modeling was used to determine whether patients participating in the HFDM program had improved survival compared with patients receiving traditional outpatient care at the same institution. Inclusion criteria consisted of an index hospitalization with discharge occurring between July 1, 1997 and May 30, 2002, hospital discharge diagnosis of HF, left ventricular systolic dysfunction ⬍ 40% documented during hospitalization, and at least 1 subsequent outpatient visit. Data from patients having participated in the HFDM program prior to their index hospitalization were excluded. Patients were allocated to the different management strategies in a nonrandomized non-blinded fashion at the discretion of the discharging physician. RESULTS: Compared with patients who were given traditional care (n ⫽ 100), HFDM patients (n ⫽ 156) were younger (56.7 vs 60 years; P ⫽ 0.031), more likely to be African American (48.7% vs 33.0%; P ⫽ .014), more likely to be uninsured (47.4% vs 27%; P ⫽ .001), and more likely to have an ejection fraction of 25% (73.1% vs 36%; P ⬍.001). Overall comorbidity did not differ significantly between the groups. After controlling for differences in demographics, ejection fraction, and comorbidities, participation in the HFDM program was associated with a significant reduction in mortality compared with traditional care (adjusted hazard ratio, 0.33; P ⬍.001). Median annual income for both groups was $ 11,300. CONCLUSION: In this indigent population, participation in a HFDM program was associated with decreased mortality compared with traditional follow-up care. CLINICAL IMPLICATIONS: Utilizing disease management in this deadly disease should be considered and ascertaining the impact of this exact disease management model in other heart failure populations should be undertaken. DISCLOSURE: Lee Arcement, None.

EXERCISE INDUCED DIASTOLIC DYSFUNCTION Vimesh K. Mithani MD Fayez Shamoon MD Sanjeev M. Patel MD* Dulce De Guzman Phillip John Emlata Tarnate Irvin Goldfarb MD St. Michael’s Medical Center, Seton Hall University School of Graduate Medical E, Newark, NJ PURPOSE: Diastolic function is not evaluated routinely during stress echocardiography. Little information exits regarding the incidence of diastolic dysfunction induced by exercise. The aim of this study was to assess change in diastolic function by exercise echocardiography. We hypothesized that patients with dyspnea may have higher incidence of exercise-induced diastolic dysfunction without evidence of ischemia. METHODS: We evaluated a cohort of 32 patients referred for exercise echocardiography for dyspnea. Transmitral inflow pattern and Tissue Doppler of mitral valve annulus were analyzed at rest and stress, along with evidence of ischemia. RESULTS: Echocardiographic evidence of diastolic dysfunction at baseline was found in 13 patients. Out of 19 patients who had normal diastolic function at rest, 9 patients (47%) developed exercise-induced diastolic dysfunction at stress without evidence of segmental wall motion abnormality suggestive of ischemia. These patients demonstrated evidence of a relaxation abnormality with transmitral inflow pattern and Tissue Doppler of mitral valve annulus. Exercise-induced diastolic dysfunction was more prevalent in female (67%), and hypertensive patients (78%), and it was associated with reduced exercise capacity (7 METs vs. 9 METs). It was not related to age, exercise-induced ischemia or higher left ventricular diastolic pressure evaluated by the ratio of early transmitral flow velocity with the early diastolic velocity of the mitral valve annulus (E/e´ ⬎ 10). CONCLUSION: Exercise-induced diastolic dysfunction in patients with dyspnea is common in female and hypertensive patients. It is not related with exercise-induced ischemia. CLINICAL IMPLICATIONS: Exercise-induced diastolic dysfunction is common in patients who undergo stress echocardiography for symptoms of dyspnea. It should be one of the parameter evaluated during the test for these patients. DISCLOSURE: Sanjeev Patel, None. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Cardiology: Epidemiology of Heart Failure, continued THE IMPACT OF RENAL DYSFUNCTION IN OUTPATIENTS WITH SYSTOLIC HEART FAILURE Jun R. Chiong MD* Binu Jacob MD Robert F. Percy MD Hector P. Sanchez MD Anabel C. Castro MD Alan B. Miller MD University of Florida, Jacksonville, FL

DISCLOSURE: Jun Chiong, None.

PURPOSE: Left ventricular (LV) dysfunction is known to be present in HIV infected subjects. The prevalences of other risk factors for cardiomyopathy including hypertension, diabetes, coronary disease, obesity, and alcohol use are also high in this patient population in the United States, but are quite low in HIV infected Africans. This study sought to determine the prevalence of LV systolic and diastolic function in HIV infected Rwandans. METHODS: In Rwanda, 41 unselected patients (age 36⫹/-9 years, 10% male) without known cardiac disease underwent echocardiography. No patient had been treated with anti-retroviral therapy. LV mass and ejection fractions (EF) were calculated according to the American Society of Echocardiography standards. Diastolic dysfunction was studied with pulsed Doppler echocardiography. For each echo variable, 3-5 cardiac cycles were averaged. Significant LV systolic function dysfunction was predefined as ⬍50%. Diastolic dysfunction was defined as E/A ratio⬍1.0 or ⬎1 with either a prolonged deceleration time (⬎250msecs) or a prolonged isovolumic relaxation time (⬎120msecs). Clinical data were recorded. RESULTS: There were low prevalences of cardiovascular risk factors including: hypertension 2.4%, diabetes 2.4%, smoking 0%. LV systolic dysfunction was present in 2.4% of patients and diastolic dysfunction was present in 14.6%. LV dysfunction was unrelated to age or duration of infection. CONCLUSION: In conclusion, LV dysfunction is common in HIV infected Rwandans, and is predominantly diastolic rather than systolic. LV dysfunction was less common than prior reports from the United States possibly because of a lower prevalence of cardiomyopathy risk factors. CLINICAL IMPLICATIONS: Further study of additional patients is warranted in order to substantiate these initial findings. There may be an interaction between HIV and other risk factors for LV dysfunction. DISCLOSURE: Jason Lazar, None.

CLINICAL CHARACTERISTICS OF OBESE AND NORMAL WEIGHT HEART FAILURE PATIENTS Jun R. Chiong MD* Robert F. Percy MD Binu Jacob MD Hector P. Sanchez MD Anabel C. Castro MD Alan B. Miller MD University of Florida, Jacksonville, FL PURPOSE: Excess weight is associated with a significantly increased risk of coronary artery disease, heart failure, and death in the general population. In patients with established heart failure, studies suggest that a higher body mass index (BMI) results in better outcomes compared to patients with a “healthy BMI”. It is unclear if these findings are applicable to the population of outpatients with stable heart failure, as these observations are not the primary design or endpoints of these trials. METHODS: Given the uncertain role of obesity in the clinical management of patients with heart failure, we examined the relationship of weight and outcomes among our outpatients with stable disease. RESULTS: We analyzed obese (BMI ⬎30 kg/m2) compared to normal weight patients (BMI 18.5 – 25 kg/m2) in our clinical information management for heart failure database (CIM-HF); there were 121 patients who fulfilled the criteria. Fifty-one patients had a normal BMI and seventy patients were classified as obese. There was no difference in age, gender or medical therapy for heart failure. More obese patients had a previous history of hypertension (90% vs. 71% p⫽0.008), diabetes (64% vs. 14% p⫽⬍0.0001), advanced New York Heart Association (NYHA) functional class III and IV (66% vs. 53%, p⫽0.046) compared to normal BMI patients. Hospitalizations were higher for obese patients (1.5 ⫹ 1.7 vs. 1.1 ⫹ 1), but this was not significant. CONCLUSION: Symptoms are worse and co-morbidities are more prevalent in obese patients with systolic dysfunction and stable heart failure, compared to normal weight patients. CLINICAL IMPLICATIONS: Obese patients with chronic stable heart failure and systolic dysfunction (ejection fraction ⬍40%) have worse outcomes than similar patients with normal body mass index. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: Renal function is an underappreciated prognostic factor in heart failure (HF), and renal insufficiency is commonly viewed as a relative contraindication for some proven efficacious therapies. It is unclear whether ACE inhibitors, aldosterone antagonists and beta-blockers exert similar benefits in patients with kidney disease as these patients are infrequently enrolled in HF trials. METHODS: We analyzed data from a prospective cohort of heart failure patients followed in a specialty clinic. Renal insufficiency was defined as creatinine clearance ⬍60 mL /min using the Cockcroft-Gault equation. Our hypothesis was that renal insufficiency was an independent predictor of outcome as measured by hospitalizations. RESULTS: In our database of 167 outpatients, 71 (42%) had creatinine clearances calculated at ⬎ 60 mL/min (Group 1; mean creatinine clearance of 81.6 mL/min); 96 (58%) had creatinine clearances calculated ⬍ 60 mL/min (Group 2; mean creatinine clearance of 39.7 mL/min). There was no difference in the presence of co-morbidities including hypertension, diabetes, and hyperlipidemia. Group 2 patients were older (71⫾17 versus 60⫾9 years) and had more atrial fibrillation (32% vs. 18%; p⫽0.043). The log of pro-brain natriuretic peptide (pro-BNP) level was higher in Group 2 (7.6 ⫹ 1.5 vs. 6.7 ⫹ 1.5; p⬍0.0001). The two Groups were similar regarding the etiology of heart failure (52% ischemic in Group 1; 57% in Group 2; p⫽NS), and advanced heart failure NYHA III/IV (61% in Group 1; 62% in Group 2; p⫽NS). Patients in both groups received identical therapy, except statin therapy (61% in Group 1; 41% in Group 2; p⫽0.011). All cause hospitalization rate for Group 2 was greater compared to Group 1 patients (1.6 vs. 1.2 admissions per patient; p⬍0.05). CONCLUSION: Despite similarities in therapies, co-morbidities, NYHA functional class and etiology of heart failure, patients with renal dysfunction with systolic heart failure had a greater all cause hospitalization rate than patients with preserved renal function. CLINICAL IMPLICATIONS: Abnormal renal function is prevalent in patients with systolic heart failure and is an independent prognostic factor for hospitalization.

LEFT VENTRICULAR SYSTOLIC AND DIASTOLIC FUNCTION IN HIV INFECTED RWANDANS: A PILOT STUDY Jason M. Lazar MD* Biana Trost MD Louis Salciccioli MD Kathryn Anastos MD SUNY Downstate Medical Center, Brooklyn, NY

Wednesday, November 2, 2005 Cardiology: Epidemiology of Heart Failure, continued CONCLUSION: Health-related quality of life is severely impaired in patients with pulmonary arterial hypertension and is associated with measures of functional status. CLINICAL IMPLICATIONS: Specific determinants of impaired quality of life suggest areas for targeted intervention. DISCLOSURE: Darren Taichman, Consultant fee, speaker bureau, advisory committee, etc. Advisory board or speaker bureau for Actelion, Pfizer and CoTherix. PREVALENCE AND IMPACT OF ANEMIA ON SURVIVAL IN INDIGENT SYSTOLIC HEART FAILURE PATIENTS RECEIVING STANDARD MEDICAL THERAPY Lee M. Arcement MD* Ron Horswell PhD Richy Lee PharmD Kathy Hebert MD Chabert Medical Center, Houma, LA

DISCLOSURE: Jun Chiong, None.

HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION Darren B. Taichman MD* Jennifer Shin MD Laryssa Hudd BA Christine Archer-Chicko RN Sandra Kaplan RN Robert Gallop MS Jason Christie MD John Hansen-Flaschen MD Harold Palevsky MD University of Pennsylvania, Philadelphia, PA PURPOSE: Improved outcomes with expanding treatment options for patients with pulmonary arterial hypertension present the opportunity to consider additional end-points in approaching therapy, including factors that influence health-related quality of life. However, comparatively little is known about quality of life and its determinants in patients with pulmonary arterial hypertension. The purpose of this study was to evaluate health-related quality of life in adults with pulmonary arterial hypertension, and identify factors associated with better or worse status. METHODS: Health-related quality of life was evaluated in 216 outpatients with pulmonary arterial hypertension using generic and respiratory-disease specific measurement tools. Most patients had either World Health Organization functional Class II or III symptoms. Demographic, hemodynamic and treatment variables were assessed for association with quality of life scores. RESULTS: Patients with pulmonary arterial hypertension suffered severe impairments in both physical and emotional domains of healthrelated quality of life. Patients with idiopathic (“primary”) pulmonary arterial hypertension had the best, and those with systemic sclerosis the worst health-related quality of life. Greater six-minute walk distance correlated with improved quality of life scores, as did functional Class II versus Class III symptoms. Hemodynamic measurements, however, did not correlate with quality of life scores. No differences in health-related quality of life were found between patients treated with calcium channel antagonists, bosentan or continuously infused epoprostenol.

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PURPOSE: Previous studies have shown an association between anemia and mortality in patients with heart failure. One question not addressed is the anemia-mortality relationship within a heart failure population enrolled in a disease management program receiving standard medical therapy including Ace inhibitors and beta blocker medications. Also, the independant effect of anemia on survival has not been well described in a rural indigent population. METHODS: The sample included 328 patients with EF ⱕ 40% who enrolled in a heart failure disease management program from 1999 to 2003 in rural South Louisiana. Our database was reviewed and a proportional hazards survival model was estimated. Anemia was defined as a hemoglobin of ⬍12g/dl in females and ⬍13 g/dl in males. Terms considered for inclusion into the model were gender, African-American race, age, ejection fraction (⬍ 25% vs. 25-40%), QRS duration, NYHA class (III/IV vs I/II), use of beta blockers, and use of ACE inhibitors. RESULTS: The prevalence of anemia in this group was 29%. The final model included age (HR⫽1.04, p⫽.023), ejection fraction ⬍ 25% (HR⫽2.71, p⫽.002), African-American race (HR ⫽ 1.21, p⫽.576), and anemia (HR⫽ 2.55, p⫽.002, 95% CI 1.40 - 4.67). The median annual income was $ 11,300 for both cohorts. CONCLUSION: Anemia is common in this cohort. Anemia is strongly associated with mortality in a younger rural indigent heart failure population, even when patients are enrolled in a disease management program receiving both Ace inhibitors and beta blockers. CLINICAL IMPLICATIONS: Identifying this high risk subgroup is important and treating anemia may be considered. Ascertaining the impact of treating anemia in this subgroup must be undertaken in future clinical trials. DISCLOSURE: Lee Arcement, None. DIABETES IS INDEPENDENTLY ASSOCIATED WITH DECREASE LEFT AND RIGHT VENTRICULAR FUNCTION Norah Milne MD June Herman MD Daniel Stobbe MD Kenneth P. Lyons MD Mohammad-Reza Movahed MD* University of California, Irvine Medical Center, Orange, CA PURPOSE: Diabetes mellitus(DM) has been found to be an impendent risk for decreasing congestive heart failure and decreasing left ventricular function. However, right ventricular dysfunction has not been studied in detail patients with DM. The goal of this study was to evaluate the occurrence of left and right ventricular dysfunction in diabetes patients. METHODS: Randomly selected case of 200 patients, who underwent left ventricular ejection fraction (LVEF) determination using blood pooled scintigraphy, underwent simultaneous measurement of right ventricular ejection fraction (RVEF). The presence of diabetes mellitus was studied in patients with depressed LVEF and RVEF using uni- and multi-variate analysis. RESULTS: A total of 152 patients had RVEF and 155 LVEF measurements. Four out of 26 DM patients had RVEF less than 30 % (15.4%) vs 4 of 126 control ( 3,2%), p⫽0.01. Eleven out of 27 (40.7%) patients with DM had LVEF less than 30% vs 9 out of 128 patients (7%) of control, p⬍0.0001 Using multivariate analysis adjusting for coronary artery disease, hypertension and chronic obstructive pulmonary disease, DM remained independently associated with LVEF or RVEF less than 30% (for RVEF ⬍ 30%: odds ratio: 5.7 CI: 1.3-25.4, p⫽ 0.02), for LVEF ,30%: odds ratio: 12.9 CI: 3.8-43.7). CONCLUSION: Diabetes mellitus is independently associated with left and right ventricular dysfunction. The involvement of both ventricles CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Cardiology: Epidemiology of Heart Failure, continued in DM patients, suggest that diabetic causes global toxic effect on myocardial cells. CLINICAL IMPLICATIONS: The deleterious effect of diabetes mellitus on global right and left ventricles, in part, may explain high mortality rate in this population. DISCLOSURE: Mohammad-Reza Movahed, None.

CLINICAL IMPLICATIONS: Obese persons with a decreased DLCO have an increased prevalence of moderate or severe LVDD, which predisposes them to develop diastolic heart failure. DISCLOSURE: Gautham Ravipati, None.

VALUE OF SERUM CREATININE LEVELS IN CARDIORENAL PATIENTS REFERRED FOR CARDIAC TRANSPLANTATION Shun Kohsaka MD* Kimberly Albright MD Reynolds M. Delgado, III MD Biswajit Kar MD Frank W. Smart MD Texas Heart Institute, Baylor College of Medicine, Houston, TX

Cough 12:30 PM - 2:00 PM

ASSOCIATION OF REDUCED CARBON MONOXIDE DIFFUSING CAPACITY WITH MODERATE OR SEVERE LEFT VENTRICULAR DIASTOLIC DYSFUNCTION IN OBESE PERSONS Gautham Ravipati MD* Wilbert S. Aronow MD Jasdeep Sidana MD George P. Maguire MD John A. McClung MD Robert N. Belkin MD Stuart G. Lehrman MD New York Medical College, Valhalla, NY PURPOSE: To determine the association of reduced carbon monoxide diffusing capacity (DLCO) with moderate or severe left ventricular diastolic dysfunction (LVDD) in obese persons. METHODS: We investigated in 105 obese persons, mean age 45 years, the association of DLCO with LVDD. An abnormal DLCO was ⬍80%. LVDD was investigated by Doppler and by tissue Doppler echocardiography. The Doppler echocardiographic data were analyzed blindly without knowledge of the clinical characteristics or whether the DLCO was normal or abnormal. RESULTS: An abnormal DLCO was present in 62 of 105 persons (59%). Moderate or severe LVDD was present in 35 of 105 persons 33%).Moderate or severe LVDD was present in 25 of 62 persons (40%) with an abnormal DLCO and in 10 of 43 persons (23%) with a normal DLCO (p⬍0.05). CONCLUSION: Obese persons with a decreased DLCO have an increased prevalence of moderate or severe LVDD.

PURPOSE: Patients with laryngeal dysfunction may present initially to a pulmonary practice with complaints of hoarseness, hypophonic pressive speech, aphonia, cough, or aspiration. The goals of this study were to identify a primary diagnosis, establish a program of goal directed therapy, and assess clinical response. METHODS: Patients were evaluated and treated by a pulmonologist and speech-language pathologist with outside consultations by ENT specialists. Treatments included: (1) Recruitment and habituation of the muscles of articulation, phonation and respiration resulting in improved clarity of articulation (Lee Silverman Voice Techniques); (2) Softening of glottal attack (resonance training, lingual hyperextension, open glottal exercises); (3) Vocal elicitation (gravity resistance exercises, vegetative and glottal sound production). RESULTS: Fourteen patients were evaluated and treated. Diagnoses were: neuromuscular disease (Parkinson’s disease, von-Recklinghausen’s disease, idiopathic vocal cord paralysis), vocal cord injury (radiation necrosis, atresia, intubation injury, carcinoma with scar tissue formation), hypertonic vocal cord strain, functional vocal cord weaknesss (presbyphonia, vocal cord misuse and overuse, phycogenic etiologies).Concurrent pulmonary diagnoses included COPD, severe kyphoscoliosis, sinusitis, allergies and asthma.Treatment outcomes of 50% to 100% improvement in intelligibility of spoken content occurred in 13 patients, but was unsuccessful in one patient (von-Recklinghausen’s disease). CONCLUSION: Goal directed therapy of the patient with laryngeal dysfunction, often in the setting of a concurrent pulmonary disorder, is successful in improving vocal function. CLINICAL IMPLICATIONS: Pulmonologists should be aware of the benefit of an interdisciplinary program for the patient with laryngeal dysfunction. DISCLOSURE: Clifford Risk, None. EPIDEMIOLOGY OF CHRONIC COUGH IN A SPECIALIST COUGH CLINIC Lee L. Phoa MBBS Wee Yang Pek MBBS* Tan Tock Seng Hospital, Singapore, Singapore PURPOSE: To study the epidemiology of chronic cough in patients who have failed earlier treatment in a primary healthcare setting. METHODS: A prospective study was conducted on patients with cough for 3 or more weeks referred to our specialist cough clinic over a 6 month period in year 2004. A total of 112 patients with normal Chest Xray were recruited. Patients’ cough severity was assessed using a cough symptom score (score of 1 to 8 based on severity of daytime and nocturnal cough) before and after treatment. All patients were subjected to a standardized protocol for history taking, examination, investigations and treatment. Investigations included rhinoscopy, spirometry or methacholine challenge test, skin prick test, thoracic and sinus imaging when appropriate. Patients were started on empiric gastroesophageal reflux (GERD) treatment when no other obvious causes of cough were found. A protocol for pH monitoring in the event of poor response to GERD treatment was in place. RESULTS: Median age of our patients was 48 years (range 14 to 86) and median cough duration was 12 weeks (range 3 to 416). The mean cough score at 1st consultation was 3.9 ⫾ 1.2 and 59 patients (49%) had a cough score of 4 at the 1st consult. At the end of the treatment period, 13.6% of the patients were diagnosed to have asthma, 46.6% had post-nasal drip and 47.7% had GERD. Eighty-six patients (90.5%) CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: pproximately one third to one half of patients with heart failure have renal insufficiency, which is one of the strongest predictors of mortality in these patients. However, there is little evidence with which to weigh the risks of cardiac transplantation in heart failure patients who have mild renal dysfunction. METHODS: We reviewed the clinical and laboratory data of 140 consecutive, stable heart failure patients who had mild renal insufficiency (serum creatinine, 1.1-2.5) referred to our institution for evaluation for cardiac transplantation from May 2004 to April 2005. We then assessed the association between renal dysfunction and 1-year outcomes (either death from any cause or admission for heart failure). The combined endpoint was compared with various levels of baseline serum creatinine values: mild (1.1-1.5), moderate (1.6-2.0), and severe (2.1-2.5). Of the 140 patients, 98 had follow-up visits where laboratory values were obtained. In this subgroup, logistic regression analysis was performed to the model hazard ratio (HR) to achieve the combined endpoint. RESULTS: The cohort was predominantly Caucasian (45%) and male (68%). After 1-year, the combined endpoint was met in 43%, 57%, and 42% of patients with mild, moderate, and severe elevations of serum creatinine, respectively. There was no statistical difference between the 3 groups (Kruskal-Wallis One-Way ANOVA p⫽0.36). However, in the 98 patients who had follow-up laboratory testing during the study period, a dynamic change in serum creatinine levels was strongly associated with a combined outcome (HR, 1.70; 95%CI, 1.22-24.6; P⫽0.02). This association remained significant even after adjustment for other clinical variables, including patient age and baseline serum creatinine levels (HR, 1.71; 95%CI, 1.18-26.1; P⫽0.02). CONCLUSION: A dynamic change in serum creatinine values during follow-up is a strong independent predictor of a worse prognosis for heart failure patients. CLINICAL IMPLICATIONS: These findings suggest that monitoring of serum creatinine values may offer a readily accessible tool to identify which heart failure patients would or would not benefit from cardiac transplantation. A prospective, randomized trial to test this hypothesis is warranted. DISCLOSURE: Shun Kohsaka, None.

EVALUATION AND TREATMENT OF PATIENTS WITH LARYNGEAL DYSFUNCTION IN A PULMONARY PRACTICE Clifford G. Risk MD* Nadine Y. Smith MS Clifford Risk, MD, Marlborough, MA

Wednesday, November 2, 2005 Cough, continued reported improvement to treatment. The median time taken for symptom improvement or resolution (final cough score 0 or 1) was 28 days (range 7 to 256). CONCLUSION: GERD and post-nasal drip were the 2 most common causes of chronic cough in patients treated in our specialist cough clinic. Though common, they were not identified and treated promptly in the primary healthcare setting. CLINICAL IMPLICATIONS: A greater awareness of GERD and post-nasal drip as conditions resulting in chronic cough should be promoted in the primary healthcare setting. Although diagnosis of these conditions were delayed, they responded well to appropriate treatment. DISCLOSURE: Wee Yang Pek, None. COUGH-INDUCED RIB FRACTURES: REVIEW OF 54 CASES Viktor Hanak MD* Thomas Hartman MD Jay Ryu MD Mayo Clinic Foundation, Rochester, MN PURPOSE: To define the demographic, clinical, and radiologic features of patients with cough-induced rib fractures. METHODS: Retrospective single-center study. Fifty-four patients with cough-induced rib fractures diagnosed over an 9-year period from 1996 to 2004. RESULTS: The mean (⫾ SD) age at presentation was 55 (⫾ 17) years, 42 patients were female (78%). Patients presented with chest wall pain following the onset of cough. Cough had been present for ⱖ 3 weeks at the time of the diagnosis in 85% of patients. Rib fractures were radiologically documented by chest radiography, rib film, computed tomography or bone scan. Chest radiography had been performed in 52 patients and revealed rib fracture in 30 patients (58%). There were 112 fractured ribs in 54 patients. One-half of the patients had more than one fractured rib. Right-sided rib fractures alone were present in 17 patients (26 fractured ribs), left-sided in 23 patients (35 fractured ribs), and bilateral in 14 patients (51 fractured ribs). The most commonly fractured rib on both sides was the 6th rib. The fractures were most common at the lateral aspect of the rib cage. Bone densitometry was done in 26 patients and revealed osteopenia or osteoporosis in 17 (65%). CONCLUSION: Cough-induced rib fractures occur mostly in women in whom reduced bone density is likely a risk factor. However, coughinduced rib fractures can occur in the presence of normal bone density. Chest radiography has a relatively low sensitivity for the diagnosis of cough-induced rib fractures. CLINICAL IMPLICATIONS: Cough-induced rib fractures are associated with chronic cough as opposed to acute cough, prevalence is much higher in females compared to males, and fractures may also occur in patients with normal bone density. DISCLOSURE: Viktor Hanak, None.

CLINICAL IMPLICATIONS: . In the absence of other explanations for chronic cough on initial evaluation, sinus CT should be considered. DISCLOSURE: Kaiser Lim, None.

A SURVEY OF PATIENT’S PERCEPTION OF DISEASE BURDEN IN CHRONIC COUGH Kaiser G. Lim MD* Ashok Patel MD Timothy I. Morgenthaler MD Mayo Clinic, Rochester, MN PURPOSE: We hypothesized that the burden of disease associated with chronic cough may include health care factors and concern over the “meaning” of the cough. We sought to understand how chronic cough affected patients socially, psychologically and physically. METHODS: All consenting adult patients presenting to our Pulmonary Division with chronic cough between November and February of 2003 were surveyed with a Cough-related Disease Burden Questionnaire (CRDBQ) prior to their evaluation and again 6 months afterward. RESULTS: 139 subjects were available for analysis. Sixty-five returned the second questionnaire. The top four complaints are shown in Table 1. Anxiety over underlying illness correlated with lifestyle interference, frequent doctor visits, medical expense, prescription expenses, frustration and spouse moving out of the bedroom. Sleep disturbances correlated with exhaustion (p ⬍0.001). A third of patients under 65 years old had a spouse or roommate move out of the bedroom. On followup 6 months later, 18% reported complete resolution of cough, 34% had more than 50% improvement, 20 % had less than 50% improvement, 28 % reported that cough was worse (1/56) or unchanged (26.7%). Improved cough outcome was associated with less anxiety about an underlying serious illness at baseline (p⬍0.001). CONCLUSION: Both psychological and physical sufferings or burden of disease appear to be chief reasons for seeking medical evaluation. Aside from Anxiety, two important major sources of suffering for the patients are a) frequent physician visits and testing, and b) sleep disturbances. CLINICAL IMPLICATIONS: Frequent doctor’s visit and testing for cough as a disease burden is an important consideration since many chronic cough algorithms employ empirical therapy and multiple return visits. Anxiety, physician visits, medications, and sleep disturbances weigh highly in patients concerns about chronic cough.

Table 1—Top 4 Complaints of Patients with Chronic Cough

Complaints

SINUS CT FINDINGS IN THE EVALUATION OF 702 CONSECUTIVE PATIENTS WITH CHRONIC COUGH Timothy I. Morgenthaler MD Ashok Patel MD Kaiser G. Lim MD* Mayo Clinic, Rochester, MN PURPOSE: Evaluation of chronic cough in pulmonary practice often requires either empiric trials of therapy or testing. The prevalence of chronic sinusitis and the role of CT sinus is debated, with some suggesting it has no role, and others suggesting that it may be a useful test late in an algorithmic approach. Previous recommendations have been based on relatively small series of patients. We wished to evaluate the role of CT sinus in our tertiary referral chronic cough practice. METHODS: Retrospective review of chronic cough registry data. RESULTS: CT sinus was obtained in 159 (22.6%) patients referred for chronic cough. Obtaining a CT was far more common among those with abnormal ENT physical exam findings (31% of 702, p⬍0.0001). When chronic rhinosinusitis was suspected clinically, the CT sinus was abnormal in 123 (77.4%). An abnormal CT findings was not significantly associated with abnormal ENT exam (p⫽0.5782). Fluid levels indicating acute sinusitis was present in 51 (32%), and again, an abnormal ENT exam was not predictive of acute sinusitis (p⫽0.0833). CONCLUSION: Nearly three-quarters of patients who underwent CT for a clinical suspicion of rhinosinusitis had and abnormal CT and nearly one third had acute sinusitis. Physical exam was not predictive of acute or chronic sinus findings. It follows that occult sinus disease likely plays a significant role in many patients with chronic cough referred to a tertiary cough clinic.

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Frustrated/Irritable/ Angry Frequent MD visit & testing for cough Sleep Disturbances Interferes w/ social gatherings

F (%)

M (%)

⬍65 yrs (%)

65 y/o (%)

Cough ⬍18 mos (%)

Cough 18 mos (%)

78

78

79

76

74

81

77

75

77

76

69

82

78 74

82 75

82 78

76 71

83 69

76 80

DISCLOSURE: Kaiser Lim, None. THE EFFECTS OF AGING ON THE HUMAN COUGH REFLEX D. A. Sams DO* Thomas Truncale DO Stuart M. Brooks MD University of South Florida, Tampa, FL PURPOSE: This study was designed to examine if there is a difference in the cough reflex between younger and older persons. A difference might explain the greater susceptibility of older persons to respiratory tract infections and pneumonia. METHODS: The study was the first granted approval by the Food and Drug Administration under an Investigational New Drug (IND) protocol for human capsaicin inhalation investigation. Two groups of normal subjects were recruited. All had normal spirometry, were current nonsmokers ⱖ 10 years, had no prior/current respiratory disease/complaints CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Cough, continued

Critical Care Management 12:30 PM - 2:00 PM UTILITY OF BRONCHOSCOPY IN MECHANICALLY VENTIALTED PATIENTS WHO DEVELOPED HEMOPTYSIS IN THE INTENSIVE CARE UNIT Maya Juarez BS* Petey Laohaburanakit MD Ken Y. Yoneda MD U.C. Davis School of Medicine, Sacramento, CA PURPOSE: The etiology of hemoptysis in mechanically ventilated ICU patients includes a wide spectrum of disorders. We evaluate the utility of fiberoptic bronchoscopy when used to identify and diagnose the bleeding source and potentially achieve hemostasis in such patients. METHODS: A retrospective review of medical records of ICU patients who developed hemoptysis while on mechanical ventilation at a tertiary-care, 700-bed teaching hospital. All bronchoscopies done from April 1998 to December 2003 were reviewed. RESULTS: Seventy-one bedside fiberoptic bronchoscopies were performed in 56 ICU patients on mechanical ventilation. Mean age was 55 years, 35 were male. The amount of hemoptysis ranged from persistent blood-streaked sputum to massive. The bleeding source was localized during 66.2% (n⫽47) of all bronchoscopies, although additional diagnostics (radiology, repeat bronchoscopy, etc) after bronchoscopy were required in 23% (n⫽16) of cases. Bronchoscopic findings were consistent with the final consensus etiology of hemoptysis in 77% of cases (n⫽55). Only in 42% (n⫽30) of cases was the clinical impression prior to bronchoscopy consistent with the final diagnosis of the cause for hemoptysis. Etiologies of hemoptysis included: pneumonia, coagulopathy, suction trauma, pulmonary edema, trauma, neoplasm, pulmonary embolism, and granulation tissue. Diagnostic samples taken during 23 bronchoscopies yielded positive results in 17 cases.Patients underwent at least one therapeutic intervention after 51% of bronchoscopies (anticoagulation discontinued, antibiotics changed, transfusion, etc). Bronchoscopic interventions were performed in 8 cases (11%), including deployment of fogarty balloon, application of neosynephrine, repositioning of endotracheal tube, and removal of blood clots. Minor complications were evident in 3 (4%) cases within 24 hours after bronchoscopy: transient desaturation once, transient hypotension twice. The transient hypotension resolved spontaneously, while the desaturation required slight endotracheal tube repositioning. CONCLUSION: Localization of the source of hemoptysis and determination or confirmation of the etiology of hemoptysis is frequently achieved bronchoscopically, although intraoperative treatment is seldom done.

CLINICAL IMPLICATIONS: Bedside fiberoptic bronchoscopy is a safe diagnostic tool with adequate diagnostic yield when used for the evaluation of hemoptysis in mechanically ventilated patients in the ICU. DISCLOSURE: Maya Juarez, None. EMPIRIC USE OF NOCTURNAL CONTINUOUS POSITIVE AIRWAY PRESSURE IN MORBIDLY OBESE PATIENTS POST EXTUBATION Ali A. El Solh MD* Alan T. Aquilina MD Lilibeth Pineda MD Eileen Berbary RN University at Buffalo, Buffalo, NY PURPOSE: To assess whether empiric nocturnal nasal continuous positive airway pressure (CPAP) in non surgical critically ill morbidly obese patients reduces pulmonary complications post extubation. METHODS: We conducted a nonconcurrent prospective study of normocapnic morbidly obese patients (BMIⱖ40 kg/m2) requiring mechanical ventilation for at least 48 hours. Analysis of pulmonary complications post extubation of critically ill morbidly patients assigned to either empiric nocturnal nasal CPAP or to standard medical therapy were performed. Data collected included sociodemographic variables, comorbidity index, presence of obstructive sleep apnea (OSA), APACHE II score, and hospital length of stay. RESULTS: Out of the 123 non surgical morbidly obese patients who met the inclusion criteria, 53 patients were assigned to nocturnal nasal CPAP and 70 to standard medical therapy. Forty six patients were known to have OSA on admission and 53 were diagnosed after hospital discharge. Twenty seven complications were reported during the course of the study. Sixteen needed rescue noninvasive positive pressure ventilation, 9 required reintubation, and 2 developed cardiopulmonary arrest. The rate of complications was comparable between those assigned to empiric CPAP and those to standard medical therapy (10 and 17 events respectively, p⫽0.7). The presence and severity of sleep apnea did not correlate with the development of cardiopulmonary complications. CONCLUSION: Although treatment of morbidly obese patients with the diagnosis of OSA should resume post extubation, the application of empiric nocturnal nasal CPAP in normocapnic morbidly obese patients may not reduce pulmonary complications post extubation. CLINICAL IMPLICATIONS: Pending a randomized controlled study, the empiric use of nocturnal CPAP in non surgical critically ill morbidly obese patients may not reduce cardiopulmonary complications post extubation. DISCLOSURE: Ali El Solh, None. PROSPECTIVE APPLICATION OF A CLINICAL GUIDELINE TO DIAGNOSE AND TREAT VENTILATOR ASSOCIATED PNEUMONIA IN TRAUMA PATIENTS IMPROVES OUTCOMES Scott Newbrough MD* Nikki Freeman PharmD Brian J. Daley MD Dana Taylor MD Ed Varnadoe PharmD UTMCK, Knoxville, TN PURPOSE: Determine if a clinical guideline increased the initial administration of appropriate empiric anti-microbial treatment to trauma patients with ventilator associated pneumonia (VAP). Secondary objectives evaluated duration of mechanical ventilation, ICU and hospital lengths of stay (LOS), drug cost of VAP treatment, and development of super-infection. METHODS: A VAP guideline for diagnosis and treatment was developed with the guidelines of the American College of Chest Physicians and the institution’s antibiogram. Once VAP was diagnosed, cultures were obtained and intravenous antibiotics were started within twelve hours vancomycin 15 mg/kg (renal ajusted dosing), ciprofloxacin 400 mg every eight hours, and piperacillin/tazobactam 4.5 grams every six hours. Once culture and susceptibilities were received, treatment was modified, and limited to seven days. Prospectively enrolled patients were compared to a retrospective cohort before the guideline. Super infection was defined as developing an infection with Serratia, Pseudomonas, Acinetobacter, Citrobacter, Enterobacter, or MRSA.T-test and Chi squared analysis had significance assigned at p⬍ 0.05. RESULTS: Forty-nine trauma patients comprise this study; 36 retrospective (12/2002 through 7/2003) and 13 prospective (12/2003 through 12/2004). Before the guideline only 1/36 (2.8%) received appropriate initial antibiotics; after implementation 4/13 patients (30.8%) received appropriate initial antibiotics at maximal doses, a significant improvement. Prospective patients had shoter duration of ventilation and ICU LOS just missing statitiscal validity and hospital lengths of stay were statistically CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

and no history of allergy or asthma. Measurements of exhaled breath nitric oxide (ENO), impulse oscillometry (IOS), and spirometry were recorded. Capsaicin inhalation challenge testing was performed according to the method of Dicpinigaitis et al (Chest 123:685-8, 2003). RESULTS: There were 27 participants with 17 younger (median age, 22; range, 18-27 yrs.) and 10 older persons (median age, 74; range, 67-77 yrs.) recruited. ENO was higher for older vs. younger subjects (37.8 and 22.2 ppb respectfully, p⬍0.006). There was a tendency for the capsaicin dose for cough initiation and C2 to be higher for older subjects, but there was no significant difference for C5. Mean values for log C2 and C5 were recorded, p values equaled 0.58 and 0.41 respectively. Serial IOS and FEV1 remained unchanged and showed good consistency. No adverse reactions were observed in any subject. CONCLUSION: Capsaicin challenge using pharmaceutical grade capsaicin is safe for normal subjects of all ages. Serial monitoring with repeated IOS and spirometry showed good reproducibility. Elevated NO levels in the older age group suggested possible baseline airway inflammation and confirms our earlier published data. While there is some tendency for capsaicin cough initiation and C2 to be higher in older persons, the values among the 2 groups were similar for C5. CLINICAL IMPLICATIONS: Cough reflex sensitivity and underlying inflammation may be important factors in determining why older people are more susceptible to respiratory tract infections and pneumonia. DISCLOSURE: D. Sams, None.

Wednesday, November 2, 2005 Critical Care Management, continued lower in the prospective study group. The mean cost of VAP antibiotic treatment per patient for the retrospective group was significantly higher than the prospective group. Super-infection developed in 29/36 patients (80.6%) in the retrospective group, 8/13 patients (61.5%) developed a super-infection in the prospective group, a decrease which just missed statistical significance. CONCLUSION: The guideline diagnosed VAP more carefully decreasing unnecessary antibiotics and ultimately cost of treatment. It also increased appropriate intial treatment and decreased length of hospital stay, time on mechanical ventilation and super infections. CLINICAL IMPLICATIONS: Precisely defining diagnosis, evidence based treatment plans and reduced therapeutic variation improved outcome in complex trauma ICU patients. DISCLOSURE: Scott Newbrough, None.

CURRENT PRACTICE OF CHEST RADIOGRAPHY IN CRITICALLY ILL PATIENTS IN THE NETHERLANDS: A POSTAL SURVEY Marleen E. Graat Peter E. Spronk PhD Marcus J. Schultz PhD* Academic Medical Center, Amsterdam, Netherlands PURPOSE: Although the consensus opinion of the American College of Radiology is that daily routine chest radiographs (routine CXRs) are indicated in all ventilated patients (http://www.acr.org), studies suggest that routine CXRs can be safely abandoned (Krivopal, Chest 2004; Price, CCM 2000). METHODS: To ascertain current practice of CXRs in Dutch ICUpatients, a questionnaire was sent to ICUs throughout the Netherlands. Questionnaires were sent to the lead clinicians of ICUs with ⬎ 5 beds. RESULTS: From the number of units responding (n ⫽ 28, 43.1%), the majority (n ⫽ 17, 60.7%) practiced a routine CXR-strategy, as opposed to a CXR on indication-approach. In most ICUs it was deemed necessary to have (routine) CXRs to ordeal on the presence or absence of ARDS, pneumonia or pneumothorax (n ⫽ 20; 71.4%, n ⫽ 19; 67.9% and n ⫽ 21; 75.0%, respectively), as well as the position of invasive devices (n ⫽ 21; 75.0%). In most hospitals a daily meeting with the radiologist was held to discuss CXRs (n ⫽ 19; 67.9%), but in more than half of hospitals the ICU-physician thought that radiologists were not experienced enough to adequately judge CXR of critically ill patients (n ⫽ 16; 57.1%). If a CXR was judged to be indicated, the reasons were in the majority of ICUs: introduction of invasive devices, such as endotracheal tubes, intravenous lines and thoracic drains (n ⫽ 22; 78.6%, n ⫽ 21; 75.0% and n ⫽ 27; 96.4%, respectively), and hemodynamic/ventilatory deterioration (n ⫽ 14; 50.0%); surprisingly, CXRs were also performed after resuscitation (n ⫽ 12; 42.9%) and (mini)-tracheotomy (n ⫽ 18; 64.3%). Finally, most ICU-physician thought that CXRs, either routine or on demand, influenced daily practice in not more than 20% of performed CXRs. CONCLUSION: In the Netherlands, the majority of ICUs still use routine CXRs, although this survey suggests that a large number of intensivists is doubting its value. CLINICAL IMPLICATIONS: There is important lack of concensus on usefulness of routine CXRs in the Netherlands. DISCLOSURE: Marcus Schultz, None.

A CLINICAL TRIAL TO COMPARE THROMBOPROPHYLAXIS OPTIONS IN THE MEDICAL ICU: CHALLENGES TO TREATMENT Tara Roque MD JulieAnne Thompson MD Tunay Kuru MD* Georgetown University, Washington, DC PURPOSE: To compare the efficacy of low-dose unfractionated heparin (LDUH) and enoxaparin for the prevention of deep venous thrombosis (DVT) in the medical ICU. METHODS: This was a prospective, randomized double-blinded trial to compare LDUH 5000 BID with enoxaparin. Patients were screened with a bedside Doppler ultrasound of the lower extremities at 48-72 hours of ICU admission and again at 7 days. All patients, older than 18 years of age, admitted to the MICU at Georgetown University Hospital were eligible. Exclusion criteria included pregnancy; contraindication to anticoagulation (e.g. uncontrolled hypertension,hemorrhagic stroke in the past 3 months, active gastrointestinal bleeding); ongoing anticoagulant therapy; intolerance to heparin; platelet count ⬍80,000/ml; international normalized ratio (INR) ⬎ 2.0. Written informed consent was obtained

296S

prior to randomization.The primary endpoint was the diagnosis of DVT by Dopplers or death. RESULTS: From March 2003 to March 2004, 308 patients were screened. Thirty(9.75%) were enrolled. Two patients (6.7%), one in each study arm, were diagnosed with DVT by 72 hours; and one(3.3%)in the enoxaparin arm by 7 days.Patients were excluded for the following reasons: Active gastrointestinal bleeding: 59 (19%), intracranial hemorrhage: 18 (6%), hemorrhage from other sites (e.g. retroperitoneal): 4 (1%), already anticoagulated: 53 (17%), thrombocytopenia: 15 (5%), other coagulopathy: 27 (9%), acute renal failure and denied entry by treating physician: 19 (6%), Expected ICU stay ⬍48 hours: 61 (20%), withdrawal of support within 48 hours of ICU admission: 4 (1%), patient or family declined enrollment: 14 (4.5%), miscellaneous (morbid obesity, aortic dissection, intolerance to heparin: 4 (1%). CONCLUSION: Despite medical prophylaxis, 10% of MICU patients developed DVT. Almost half the patients (49%, excluding those with MICU length of stay ⬍48 hours and those already on anticoagulation) had contraindications to medical thromboprophylaxis. CLINICAL IMPLICATIONS: Incidence of DVT in the MICU remains high, despite medical prophylaxis. Therefore, for MICU patients, combined medical and mechanical thromboprophylaxis should be considered. Furthermore, a significant proportion of MICU patients have contraindications to medical thromboprophylaxis. For this patient population, routine screening Dopplers may be warranted. DISCLOSURE: Tunay Kuru, None.

Critical Care Outcomes 12:30 PM - 2:00 PM LIVER TRANSPLANTATION IN PATIENTS OVER SEVENTY YEARS OF AGE Bangarulingam Sujay MD* Javier F. Aduen MD Rolland C. Dickson, MD Wolf H. Stapelfeldt MD Denise M. Harnois, DO Jeffery . L. Steers, MD David J. Kramer, MD Mayo Clinic, Jacksonville, FL PURPOSE: To investigate whether age at Liver Transplant (LT), older than 70 years compared with that of patients younger than 60 years is associated with patient survival, length of stay, readmissions, or complications. METHODS: We retrospectively identified all first LT recipients at Mayo Clinic in Jacksonville, Florida, from February 1998 to May 2004 aged ⬎70 years and case-matched with recipients ⬍60 years according to the etiology of end-stage liver disease, model for end-stage liver disease (MELD) score, and gender. The following data were collected: demographics, Operative Time (OT),Warm Ischemic Time(WIT),Cold Ischemic Time(CIT), intraoperative fluid requirement, length of ICU and hospital stay, complications, rate of readmissions, and survival. Numerical data was summarized with the sample median and range. A log-rank test was used to compare survival according to age group at LT. Wilcoxon’s rank sum test was used to compare length of hospital and ICU stay, and readmissions per month between groups. Fisher’s exact test was used to compare the occurrence of rejection and complications between groups. RESULTS: Forty patients older than 70 years underwent LT during the study period. Table 1 depicts the demographics and operative characteristics which are similar in both groups except for fluids required intraoperatively which was higher in patients ⬎70 years. Rejection appears to occur more often in patients ⬍60 years. Although it did not reach a statistically significant difference, there was a tendency for higher infectious complications and bile leak in patients older than 70.However, there was no difference in survival at 1 month or 1 year. Length of ICU and hospital stay and need for ICU and hospital readmissions were also similar between the two groups (Table 2). CONCLUSION: The outcome of liver transplantation in the elderly is similar to that of younger patients, when they are matched for acuity and etiology. Older patients have less rejection and similar rates of infection and biliary complications. CLINICAL IMPLICATIONS: Patients should not be denied Liver Transplantation based on age alone. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Critical Care Outcomes, continued

Table 1—Demographics and Operative Characteristics of the Liver Transplant Patients 70 yrs. BMI

Patients ⬍60 yrs

⬎70 yrs

P Value

Age yrs

MELD

Kg/m2

OT Hrs

WIT min

CIT hrs

Fluids ml

(S.D)

(S.D)

(S.D)

(S.D)

(S.D)

(S.D)

(S,D)

49.8

16.41

28.53

5.35

35.08

7.21

3784

(⫹/-1.18)

(⫹/-6.94)

(⫹/-5.37)

(⫹/-1.57)

(⫹/-2.45)

(⫹/-32)

(⫹/-1068)

71.5

16.88

26.77

4.77

33.88

6.68

5535

(⫹/-0.34)

(⫹/-6.82)

(⫹/-4.32)

(⫹/-1.36)

(⫹/-1.55)

(⫹/-29)

(⫹/-2716)

0.9

0.27

0.09

0.86

0.60

0.003*

DISCLOSURE: Bangarulingam Sujay, None.

PURPOSE: To describe the development and validation of APACHE IV benchmarks for ICU length of stay. METHODS: The equations used to generate ICU length of stay benchmarks were developed using ICU day 1 data for 116,209 admissions to 104 ICUs at 45 hospitals during 2002 and 2003. Of these admissions 69,692 were used for model development and 46,517 were used to validate the model. A linear regression procedure was used to estimate exact ICU stay in days and fractions of days. Predictor variables were similar to those used for APACHE III estimates, but new variables (mechanical ventilation, thrombolysis, the impact of sedation on Glasgow Coma Score (GCS), and a rescaled GCS and PaO2:FIO2) were added, and different statistical modeling (restricted cubic splines) was used. We assessed the accuracy of APACHE IV ICU stay predictions by examining the degree of correspondence between mean observed and mean predicted ICU stay (paired Student’s t-test), and by calculating a correlation coefficient (R2). RESULTS: Based on relative explanatory power, the most important predictor variables were the acute physiology score (50%), ICU admission diagnosis (14%), ventilator status (11%) and the inability to assess a GCS due to sedation (11%). As the acute physiology score rose there was a linear increase in ICU stay until the score exceeded 80, at which point ICU stay decreased. For the validation data set the aggregate mean observed ICU stay was 3.86 days and mean predicted was 3.78 days (p⬍0.001). Among 116 ICU admission diagnoses there were only two significant differences (p⬍0.01) between mean observed and mean predicted ICU stay. The model’s R2 was 0.215 indicating that the model accounted for 21.5% of the variation in ICU stay. CONCLUSION: APACHE IV predictions of ICU stay are well calibrated and should provide useful benchmarks for evaluating efficiency in U.S. ICUs. CLINICAL IMPLICATIONS: Clinicians can use these benchmarks to assess their unit’s throughput efficiency and monitor the impact of protocols aimed at reducing ICU stay for specific patient groups. DISCLOSURE: Jack Zimmerman, Consultant fee, speaker bureau, advisory committee, etc. Medical and Research Consultant. HIGH TROPONIN LEVELS IN CRITICALLY ILL PATIENTS WITH RENAL FAILURE AND NO ACUTE CORONARY SYNDROME: INCIDENCE AND IMPACT ON MORTALITY Vijo Poulose MBBS* Siau Chuin MBBS Alvin Ng MBBS Chong-Hiok Tan MB, ChB Changi General Hospital, Singapore, Singapore PURPOSE: High cardiac troponin levels are commonly seen in medical intensive care (MICU) patients with renal failure and no clinical evidence of acute coronary syndrome (ACS). We looked at the incidence

GASTRIC IMPEDANCE SPECTROSCOPY AND HEMODYNAMIC VARIABLES BEHAVIOR IN DIFFERENT OUTCOMES AFTER CARDIAC SURGERY Nohra E. Beltran Vargas MS* Gustavo Sanchez-Miranda MD Montserrat Godı´nez Ursina Dı´az Emilio Sacristan PhD Universidad Autonoma Metropolitana, Iztapalapa, Mexico City, Mexico PURPOSE: When blood flow is arrested during cardiopulmonary bypass (CPB), the tissue suffers progressive alterations. Gastric impedance spectroscopy, a novel tool used to monitor and detect tissue ischemia is compared with hemodynamic variables as CI, MAP, MPAP, CVP, PCWP; and regional perfusion variables as PCO2 gap and gastric intramucosal pH, to find differences according to outcome for patients undergoing elective cardiovascular surgery. METHODS: Impedance spectrometry probe and nasogastric tube (ISP/NGT), and a tonometer were placed in the stomach of 56 patients under coronary artery bypass (CABG) and/or valvular surgery with CPB and aortic cross-clamp. Hemodynamic monitoring was performed via pulmonary artery and radial artery catheters, inserted before the operation. Impedance spectra of the gastric wall and hemodynamic variables were recorded perioperatively and for up to 4 hours after surgery. Pre-surgical and post- surgical measurements comparison was made to assess which variable is better associated with mortality using ANOVA. RESULTS: Eighteen (34.61%) patients developed complications within a 72h period after surgery; seven (13.46%) died. Nine (17.3%) patients developed complications after ICU release. Table 1 shows that impedance spectroscopy variables (R316 and X316) and CI showed significant differences between survivors and non survivors. The other hemodynamic and regional perfusion variables did not differ between groups. Only CI, CO2 gap and pHi showed statistical differences before and after surgery. CONCLUSION: Our data suggest that gastric impedance spectra may be a good predictor of outcome after cardiac surgery. Further analysis is ongoing to extract and assess the diagnostic/prognostic value of these measurements. CLINICAL IMPLICATIONS: Gastric impedance spectroscopy may be a useful tool to assess splanchnic perfusion and tissue viability in critical care patients. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

ACUTE PHYSIOLOGY AND CHRONIC HEALTH EVALUATION (APACHE)IV ICU LENGTH OF STAY BENCHMARKS FOR TODAY’S CRITICALLY ILL PATIENTS Jack E. Zimmerman MD* Andrew A. Kramer PhD Douglas S. McNair MD Fern M. Malila MS George Washington University, Washington, DC

of elevated troponin levels in this group of patients and the impact on mortality. METHODS: We prospectively collected data on all MICU patients who met the following criteria:a) Renal failure - defined as serum creatinine ⬎ 140 ␮mol/L (upper limit of reference range) b) No evidence of ACS (anginal pain, acute ST or T changes on ECG). All patients who fell into the study group had a troponin T level done within the first 24 hours of ICU admission. Troponin T levels ⱖ 0.1 ng/mL were considered as high. Our primary outcome was the 28-day all cause mortality. We also looked at the correlation between the troponin levels and creatinine clearance as calculated from the Cockroft-Gault equation. RESULTS: Fifty one patients met the study criteria. Twenty two patients (43%)had elevated troponin T levels. Six of these 22 patients died (mortality rate 27%). The mortality rate in the 29 patients with normal troponin levels was 34%. The severity of illness was similar in both groups(using the Logistic Organ Dysfunction Score). The troponin levels poorly correlated with the levels of creatinine clearance(r2⫽0.005). CONCLUSION: In the absence of ACS, elevated troponin T levels in MICU patients with renal insufficiency do not appear to confer an increased mortality. CLINICAL IMPLICATIONS: High troponin T levels in this group of patients may not be an important risk factor for death. Larger studies are needed to validate this finding. DISCLOSURE: Vijo Poulose, None.

Wednesday, November 2, 2005 Critical Care Outcomes, continued Table 1 Table 1 Survivors

Non Survivors

Variable

Pre-surgery

Post-surgery

Pre-surgery

Post-surgery

R316 X316 CI CO2gap pHi MAP PCWP CVP MPAP

74.2⫾3.5 -16.6⫾1.5 2.4⫾0.1 7.0⫾1.2 7.34⫾0.01 75.0⫾1.3 17.2⫾0.9 10.4⫾0.6 27.3⫾1.2

75.2⫾3.5 -19.4⫾1.5 3.3⫾0.1 18.2⫾1.2 7.21⫾0.01 80.7⫾1.3 11.4⫾0.9 10.3⫾0.6 25.2⫾1.3

96.4⫾9.3 -26.9⫾3.9 2.3⫾0.3 8.6⫾3.3 7.30⫾0.04 73.8⫾3.3 12.6⫾2.4 9.2⫾1.6 26.5⫾3.5

79.3⫾9.3 -27.1⫾3.9 2.3⫾0.3 25.2⫾3.3 7.17⫾0.04 75.7⫾3.3 14.8⫾2.4 13.9⫾1.6 24.5⫾3.5

p

0.0024* 0.0003* 0.0270* 0.0841 0.2384 0.2181 0.7532 0.3031 0.7743

DISCLOSURE: Nohra Beltran Vargas, Grant monies (from industry related sources) This research was supported by a grant from Innovame´dica S.A. de C.V. with concurrent support from CONACYT.; Product/ procedure/technique that is considered research and is NOT yet approved for any purpose. Innovamedica is sole assignee of the patent related to the technology using in this work. The impedance spectrometer is not commercial yet.

PRE–INTENSIVE CARE UNIT LENGTH OF STAY AND OUTCOME IN CRITICALLY ILL PATIENTS Raquel Nahra MD* Christa Schorr RN David R. Gerber DO Cooper University Hospital, Camden, NJ PURPOSE: To evaluate the relationship between pre-intensive care length of stay and outcomes of patients transferred to the Intensive Care Unit (ICU). METHODS: Data was obtained from the Project Impact database. Patients without a previous ICU admission transferred to the MedicalSurgical ICU (MSICU) between October 2002 and November 2004 were reviewed. Medical patients came from general care and telemetry floors. Surgical patients came from these areas, the operating room (OR), and the post anesthesia care unit. Patients were classified as surgical if surgery was performed in the OR within 7 days prior to ICU admission. Patients were grouped by hospital length of stay (HLOS) prior to ICU admission: medical patients HLOS ⱕ5 days (Group M1) or HLOS ⱖ6 days (Group M2); surgical patients HLOS ⱕ5 but ⬎1 day (Group S1) or HLOS ⱖ6 days (Group S2). Variables analyzed included age, SAPS II survival probability, ICU and hospital LOS, and mortality. RESULTS: Groups were demographically similar. Group M2 was sicker than M1. Acuity was similar between S1 and S2. Mortality was higher among patients with pre-ICU LOS ⱖ6 days versus those with pre-ICU LOS ⱕ5 days. HLOS was longer in groups M2 vs. M1 and S2 vs. S1. ICU LOS did not differ based on pre-ICU LOS. Observed deaths exceeded predicted in group S2. CONCLUSION: ICU admission from a general care floor after ⱖ6 days is associated with poor outcome as compared to earlier admission. Previous studies have invoked suboptimal care prior to ICU admission as the reason for poorer outcomes. This idea is supported by the higher acuity of patients in Group M2. Poor organization, insufficient knowledge, failure to appreciate clinical urgency, inadequate supervision and failure to seek advice have been previousely suggested as factors in this suboptimal care. CLINICAL IMPLICATIONS: Improving outcomes in patients transferred to the ICU may require institutional changes. Prompt recognition of deteriorations in patient condition and earlier interventions, such as the institution of a rapid response team may result in securing better outcomes.

298S

Medical Patients

M1

M2

p Value

Number Mean ICU LOS (SD) Mean Hosp LOS (SD) Survival ProbabilitySAPS II (SD) Expected MortalitySAPS II Actual Mortality Surgical Patients

181 5.4 (7.1)

49 5.6 (6.3)

0.85

20.3 (24.5)

34.4 (23.6)

0.0004

0.70 (0.29)

0.57 (0.32)

0.0082

30.00%

43%

32% S1

53% S2

96 15.2 (8.9)

103 28.3 (23.6)

0.0001

0.87 (0.180)

0.84 (0.21)

0.28

13.00%

16%

8.30%

24%

Number Mean Hosp LOS (SD) Survival ProbabilitySAPS II (SD) Expected MortalitySAPS II Actual Mortality

0.0115 p Value

0.0037

Table 2—Differences Between Actual and Predicted Survival (%)

M1 M2 S1 S2

Predicted Survival

Actual survival

p

70 57 87 84

68 47 91.7 76

0.55 0.15 0.17 0.02

DISCLOSURE: Raquel Nahra, None.

STUDY OF BACTEREMIA IN ICU PATIENTS Avanti Vigg MBBS* Arul Vigg MBBS Ajit Vigg MD Royal Preston Hospital, Preston, United Kingdom PURPOSE: To evaluate the incidence, microbiological pattern & clinical outcomes of blood stream infection among ICU patients. METHODS: A Retrospective study from a medical ICU (12 beds) in a tertiary care urban teaching hospital.Data was collected retrospectively for all patients admitted to medical ICU from 1st January to 31st December 2004. Number of blood cultures collected were noted isolated organisms were recorded. RESULTS: A total of 3657 patients were admitted to MICU during the 12 month study period. 2091 blood cultures were sent during the period. There were a total of 370 episodes of bacteremia. Seven patients had more than two episodes of bacteremia.The organisms were as follows :-Klebseilla Pneumoniae ⫽ 10; Klebseilla species ⫽ 40; Klebseilla Ornitholytica⫽3; Pseudomonas aerogenosa ⫽12; Pseudomonas species ⫽ 67; Staph.aureus ⫽ 72; Strep.Pneumoniae⫽21; E.coli⫽26; Candida albicans ⫽ 45; Citrobacter diversus⫽2; Citrobacter freundii⫽3; Enterobacter species⫽9; Acinetobacter species⫽3; Salmonella typhi ⫽ 3; Coagulase negative Staphylococcus⫽23; Streptococcus group ‘b’⫽2 & group ‘d’ ⫽ 5. The mortality in patients with bacteremia was 177/370 (47.8%) while it was 103/1721 (5.9%). The mortality in those patients with 2 or more episodes of bacterima was 4/7 (57.1%). CONCLUSION: Bacteremia occurred in 10% of all ICU admissions. 1.9% had multiple episodes of bacteremia. Gram negative pathogens were the commonest organisms seen in our clinical practice. Pseudomonosa species were the commonest(n⫽79) followed by Staph.aureus (n⫽72) & CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Critical Care Outcomes, continued Klebseilla(n⫽53). Candida species were grown on blood cultures in 12.1% of our ICU population. CLINICAL IMPLICATIONS: Those with proven bacteremia had higher mortality than those without bacteremia.Hence it is prudent to recognize early these crtically ill patients with bacteremia and initiate prompt therapy to improve clinical outcomes. DISCLOSURE: Avanti Vigg, None. IMPACT OF A SEDATION PROTOCOL ON TRAUMA PATIENT’S CRITICAL CARE LENGTH OF STAY Diane K. Schuetze PharmD Rajesh R. Gandhi MD* Hillcrest Baptist Medical Center, Waco, TX

THROMBOCYTOPENIA IN A COMMUNITY HOSPITAL ICU IN LEBANON Ali H. Debek MD* Hani Lababidi MD Pierre K. Bou-Khalil MD Othman Itani MD Anas Mugharbil MD American University of Beirut-MC, Beirut, Lebanon PURPOSE: To determine the incidence, risk factors and outcome of patients with thrombocytopenia admitted to Makassed General Hospital ICU Community Hospital ICU in Lebanon. METHODS: A retrospective study of 103 medical and surgical patients admitted to a 6-bed ICU in a 200-bed community hospital from January 1 to June 30, 2000. RESULTS: Thrombocytopenia (platelet count ⬍ 100,000/mm3) occurred in 21 patients (20.4%). In multivariate analysis, female gender, sepsis, shock, transfusion requirements, duration of stay, and APACHE II score of ⬎ 20 were found to be independent risk factors for the development of thrombocytopenia. Thrombocytopenic patients had a significantly higher mortality rate when compared to nonthrombocytopenic patients (52.4% vs. 25.6%, p ⫽ 0.018). Highest mortality (80%) was observed when thrombocytopenia and DIC coexisted. Interestingly, none of the patients with corrected platelet count died. CONCLUSION: Thrombocytopenia in ICU patients is associated with higher mortality particularly in the setting of DIC. This probably reflects the severity of the overall clinical status and the underlying disease. Its correction seems to improve prognosis. CLINICAL IMPLICATIONS: Thrombocytopenia is an alarming sign for the intensivists to be aware of, because such patients have a high

THE EFFECT OF THE SEVERITY OF INHALATION SEVERITY ACCORDING TO BURN SIZE ON EARLY MORTALITY IN SEVERELY BURNED PATIENTS Cheol H. Kim MD* Jin K. Kim MD Heung J. Woo MD Young I. Park MD In G. Hyun MD Jung W. Shim MD Young M. Ahn MD Department of Internal Medicine, Hallym University College of Medicine, Seoul, South Korea PURPOSE: Inhalation injury is a major cause of morbidity and mortality in burned patients. We performed this study to know the severity of lower airway injury due to inhalation and the influence of these airway injury on early mortality in severely burned patients. METHODS: From Jan, 2004 to Jul, 2004, major burn patients with inhalation injury were enrolled prospectively. Bronchoscopic biopsy was done either at carina or at right (or left) 2nd carina. The pathologic grades of biopsy was classified as follows: 0 ⫽ normal or minimal epithelial injury; 1 ⫽ loss of cilia or moderate epithelial injury; 2 ⫽ severe epithelial injury or basement membrane alteration; 3 ⫽ extensive ulceration. We analyzed APACHE II scores, P/F ratio, 30-day ICU mortality and their correlation with pathologic grades. RESULTS: 68 patients (M⫽49, F⫽19) were enrolled. In survivors (40 cases) and non-survivors (28 cases), there were no statistically significant difference was seen among the patient’s age, sex, initial COHb, APACHE II scores and PaO2/FiO2 ratio. But the percent of total body surface area (%TBSA) burn and APACHE II scores were higher in non-survivors than in survivors (p⬍0.05, p⬍0.05). In total patients, there were no significant difference between the %TBSA and the pathologic grades of airway (p⫽0.056) but significant increased in trends of pathologic grade as increasing the %TBSA (p⫽0.008). There were not correlation between pathologic grade of airway and APACHE II scores, PaO2/FiO2 ratio in survivors and non-survivors. In survivors, significant negative correlation was seen between the %TBSA and the pathologic grade of airway (r⫽-0.442, p⫽0.004) but, not in non-survivors (r⫽-0.226, p⫽0.25). Also, there were no significant difference in 30-day ICU mortality according to each pathologic grade (p⫽0.708). CONCLUSION: Increasing burn size concomitant with inhalation showed increase in trends of severity of airway injury, but further study may be needed whether the extents of lower airway injury due to inhalation affect on early mortality in severely burned patients. CLINICAL IMPLICATIONS: The extents of initial airway injury due to inhalation may not be sustained. DISCLOSURE: Cheol Kim, None. MAGNESIUM LEVEL PATTERNS AMONG CRITICALLY ILL TRAUMATIC AND NON TRAUMATIC BRAIN INJURY PATIENTS Ousama Dabbagh MD* Hussam Jabri MBBS Haifa M. Malaika MBBS Sofia Junaid MBBS Yaseen Arabi MD Abdullah Al Shimemeri MD King Abdulaziz Medical City, Riyadh, Saudi Arabia PURPOSE: To study the pattern of magnesium levels among traumatic (TBI)and non traumatic brain injury (CVA) critically ill patients. METHODS: Patients admitted to ICU from january 2004 to january 2005 were included .Inclusion criteria were the presence of traumatic brain injury (TBI), thrombotic or hemorrhagic non traumatic strokes (CVA).Data was abstracted from a prospectively collected ICU database .Magnesium levels were collected retrospectively for the first seven days of admission .Patients were classified into three groups (Contusion , Hemmorhage and Thrombosis) based on their radiographic findings . RESULTS: 90 patients were included (46 TBI and 44 CVA). CVA patients were older (60.84⫾16.4 vs. 28.21⫾14.9 p⬍0.001) had higher APACHE scores (23.8⫾7.1 vs. 20.16 ⫾4.6 p⫽0.01)and higher Glascow coma scores GCS (8.9⫾4 vs. 5.5⫾2.6 p⫽0.006) .On the other hand TBI patients had lower magnesium on admission (0.75⫾0.13 vs. 0.89⫾0.2 p⫽0.019) and for the most part of the first week (see figure).There was no difference in ICU mortality between the two groups . 25% of patients in the TBI group had hypomagnesemia on admission versus 16% of the CVA group .27.2% of CVA patients had hemorrhage versus 56.5% among TBI group (P⬍0.001).Serum magnesium levels were compared among several groups of brain injury (hemorrhage versus thrombosis versus contusion ) CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

299S

POSTER PRESENTATIONS

PURPOSE: Sedation management is an integral part of managing ventilated patients. A standardized sedation practice to reduce intensive care unit (ICU) length of stay (LOS) through implementation of a protocol was the intention of the study. METHODS: Evidence-based sedation guidelines for ventilated trauma patients were developed with input from physicians, nursing and pharmacy. The staff was inserviced and the protocol implemented in September 2003. The protocol promoted propofol for short-term sedation (less than 48 hours) and midazolam for long-term sedation (greater than 48 hours). Medication titration to a Modified Ramsey Scale of 3, daily awakenings and dose reductions were included in the protocol. The results were retrospectively examined with a prospective application of the protocol. A historic control group was used from the months prior to implementation of the protocol. Two six-month retrospective reviews of mechanically ventilated patients, baseline (Jan-June 2003) and postprotocol (Jan-June 2004), were performed. RESULTS: A total of 39 patients were evaluated (baseline n ⫽ 14, post-protocol n ⫽ 25). The patients were predominately male (80% and 68%) and the average age (32.8 years vs. 37.4 years) and Injury Severity Scores (20.5 vs. 26.4) were not significantly different between groups. The amount of time on propofol was lower in the protocol group (24.1 vs. 35.3 hours). The mean ICU LOS in the protocol group was lower than the baseline group (5.2 days vs. 7.1 days). Overall LOS was lower in the protocol group than baseline (7.96 days vs. 11.14 days). Preliminary data is presented. CONCLUSION: Utilization of a sedation protocol that includes proper selection of pharmacologic agents, sedation goals, daily awakenings and daily dose reductions resulted in a trend toward decreased ICU LOS and overall LOS. More data is needed to show significance. CLINICAL IMPLICATIONS: Implementation of a sedation protocol may be an effective means to reduce the number of ventilator days and subsequent ICU LOS. DISCLOSURE: Rajesh Gandhi, None.

mortality. Aggressive attempts to correct thrombocytopenia may alter the patient’s outcome. DISCLOSURE: Ali Debek, None.

Wednesday, November 2, 2005 Critical Care Outcomes, continued based on the radiologic findings and were not statistically different.There was no correlation between admission serum magnesium and Glascow coma score GCS (R⫽0.03 ,P⫽0.8). CONCLUSION: Serum magnesium levels seems to be lower among traumatic brain injury than non traumatic brain injury patients .Radiographic findings such as hemorrhage or thrombosis do not appear to influence serum magnesium . CLINICAL IMPLICATIONS: Magnesium levels on admission and during ICU stay are not influenced by the radiographic findings of brain injury .TBI seems to be associated with lower magnesium levels than CVA. Whether this is specific to TBI or attached to other reasons is not known.Other factors such as comorbid conditions and possibly hormonal or metabolic disturbances may be potential reasons .Further larger studies are necessary to clarfiy these findings.

DISCLOSURE: Ousama Dabbagh, None.

INCIDENCE AND RISK FACTORS FOR HYPERCALCEMIA IN INTENSIVE CARE UNIT Nathalie Gagnon MD* Francois Lauzier MD Francois J. LeBlanc MD Laval University, Quebec, PQ, Canada PURPOSE: Immobilisation may be associated with excessive bone resorption leading to hypercalcemia and its complications such as delirium, renal failure and bowel dysfunction. Incidence, risk factors as well as clinical consequences of immobilisation-associated hypercalcemia are not known for patients with extended intensive care unit (ICU) stay. This retrospective cohort study was designed to evaluate the incidence as well as the risk factors of hypercalcemia for adult patients with extended (more than 28 days) ICU stay. METHODS: All medical records of adult patients with an ICU stay of more than 28 days from 2002 to 2005 were reviewed. For each patient, the highest ionized calcemia was noted as well as the following informations: age, gender, race, weight, admission diagnosis, date of highest ionized calcemia with its associated creatinine level, diagnosis of septic shock, diagnosis of acute respiratory distress syndrome (ARDS), continuous veno-venous hemofiltration (CVVH), mechanical ventilation, parenteral nutrition, and corticotherapy. RESULTS: Seventy-nine patients stayed in ICU for more than 28 days. Mean age was 53 ⫾ 18 year-old. Twelve patients (15%) died. 59 patients (75%) had mechanical ventilation, 13 (16%) had CVVH, 29 (37%) had ARDS. Sixteen patients (20%) had hypercalcemia with a mean ionized calcemia of 1,44 ⫾ 0,13 mmol/L (normal 1,15-1,29 mmol/L). Twelve of these patients were under CVVH. CONCLUSION: Hypercalcemia is frequent in patients with extended ICU stay. CVVH seems to be strongly associated with hypercalcemia. For those patients under CVVH, hypercalcemia may be explained by the high calcium concentration in our reinjection solutions (1,75 mmol/L). A prospective study is needed to determine the real incidence of immobilisation-associated hypercalcemia in patients without CVVH.

300S

CLINICAL IMPLICATIONS: Clinicians may considered looking at ionized calcemia in patients with extended ICU stay. DISCLOSURE: Nathalie Gagnon, None.

Critical Care Therapeutics 12:30 PM - 2:00 PM IS ULTRA-SLOW INTRAVENOUS VITAMIN K ADMINISTRATION SUPERIOR TO FRESH FROZEN PLASMA FOR ACUTE REVERSAL OF ELEVATED INR? Murtaza Y. Dawood MD* Zubair A. Hashmi MD Uday K. Dasika MD Forum Health - WRCS/NEOUCOM, Youngstown, OH PURPOSE: The purpose of this study is to demonstrate the safety and efficacy of Vitamin K when administered as an ultra-slow intravenous drip (IVPB) in comparison to standard acute INR reversal utilizing fresh frozen plasma (FFP). METHODS: A chart review of 44 patients was performed. Patients were treated with PO, SQ, IV Push (IVP), IVPB, and IM Vitamin K for reversal of elevated INR at the attending physician’s discretion. IVPB was administered at 1mg Vitamin K in 50-100cc of 0.9% NaCl solution over 2-4 hours. Acute INR reversal is defined as correction within 24 hours. Several patients were also treated with FFP after given Vitamin K. Initial INR, reversed INR, time to reversal, method of reversal, and complications were recorded. Our results were reviewed in conjunction with established clinical data utilizing IV vitamin K therapy. RESULTS: There were 22 (50%) males and 22 (50%) females in our study. Vitamin K was administered as an IVPB in 16 (36.4%) patients, IVP in 2 (4.5%), IM in 2 (4.5%), PO/SQ in 24 (54.5%). Eleven (25.0%) patients also received FFP. Of those, 1 had received an initial IVPB drip of Vitamin K, 10 had received either SQ, PO, or SQ/PO doses of Vitamin K. There were no complications from Vitamin K administration irrespective of the route. Preliminary findings show, IVPB administration reversed the INR within 14h43m (⫾12h22m), IVP 12h13m (⫾5h43m), IM 29h11m (⫾22h39m), PO/SQ 35h50m (⫾14h22m). Patients who received FFP had INR reversal within 16h03m (⫾13h06m). Additionally, average costs for INR reversal with IM, IVP, IVPB, SQ/PO, and FFP were $8.00, $4.10, $5.23, $6.72, and $251.85, respectively. CONCLUSION: IVPB Vitamin K administration is a safe, effective and economically sound method of acute INR reversal. IVPB is superior to the standard agent of FFP for acute reversal of elevated INR. CLINICAL IMPLICATIONS: Based upon our results, a further study should be developed to consider the initial treatment of choice for acute reversal of elevated INR. DISCLOSURE: Murtaza Dawood, None. CHEMOTHERAPY ADMINISTRATION IN THE ICU: A 5-YEAR RETROSPECTIVE ANALYSIS Nina D. Raoof MD* Mark Knott Stephen M. Pastores MD Louis P. Voigt MD Neil A. Halpern MD Memorial Sloan Kettering Cancer Center, New York, NY PURPOSE: To characterize patients who received chemotherapy during their intensive care unit (ICU) admission in a cancer hospital over a 5-year period. METHODS: All ICU admissions between October 1998 and September 2003 were identified from the institutional database and those who received chemotherapy while in the ICU were specifically targeted for further study. We compared demographic data between patients who received chemotherapy and those who did not. Variables assessed included age, gender, ICU length of stay (LOS), ICU mortality, post-ICU LOS to hospital discharge, and long-term mortality as of October 2004. We constructed a clinical model to distinguish four subsets of patients receiving chemotherapy: three classes of critically ill patients (illness due to their cancer, illness not due to their cancer, and illness due to other disease in a patient with no cancer) and one group of non-critically ill patients receiving high-risk chemotherapy. RESULTS: There were 2,756 ICU admissions during the study period. Of these, 111 (4%) received chemotherapy representing 4.2% of ICU admissions annually. Though they had similar gender distribution, paCHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Critical Care Therapeutics, continued tients receiving chemotherapy were younger, had longer ICU LOS, higher ICU mortality, longer post-ICU LOS to hospital discharge, and higher long-term mortality than ICU patients who did not receive chemotherapy. (Table 1) Of the patients receiving chemotherapy, the majority (78.4%) were critically ill from their cancer. Less than 10% had critical illness unrelated to their cancer or were critically ill without cancer and 11.7% were not critically ill, but required ICU admission for high-risk chemotherapy. (Table 2). CONCLUSION: ICU LOS and mortality, post-ICU LOS to hospital discharge and overall mortality were higher in cancer patients who received chemotherapy in the ICU than ICU patients who did not.. The majority of patients who received chemotherapy during their ICU admission were critically ill from their cancer. CLINICAL IMPLICATIONS: Further analyses may identify patients for whom chemotherapy administration in the ICU is beneficial. Until then, we recommend careful patient selection.

Table 1—Comparison of Chemotherapy and NonChemotherapy Receiving ICU Patients Non-Chemotherapy (n⫽2,756)

51.5⫾16.4 43:57 9.1⫾10.8

61.3⫾15.5 41:59 5.5⫾7.7

22.5 23.4⫾22.4

17.7 13.6⫾16.5

81.4

65.6

POSTER PRESENTATIONS

Age yr (M⫾SD) Gender (%F:%M) ICU LOS days (M⫾SD) ICU mortality (%) Post-ICU LOS days (M⫾SD) Mortality % (10/07/ 04)

Chemotherapy patients (n⫽111)

minute (700 mg total). DOS measurements and concurrent physiological measurements including arterial and venous blood gases, CO, and oxygen saturation, were obtained throughout the experiment. The non-invasive DOS methods were compared to traditional invasive methods. RESULTS: Broadband DOS measurements were able to monitor the progression of cyanide toxicity and subsequent treatment with OHCO noninvasively. By monitoring the tissue oxygen profile (OxyHb and DeOxyHb concentrations and STO2) and the concentration changes of cytochrome c oxidase redox states, we successfully monitored the severity of in vivo cyanide toxicity and therapeutic effects of OHCO. CONCLUSION: DOS enables non-invasive detection of CN toxicity and reversal using OHCO. DOS provides an opportunity for quantitative non-invasive monitoring for a range of clinical conditions where specific solute concentration measurements may be important. CLINICAL IMPLICATIONS: DOS can be a effective method for in vivo non-invasive monitoring of diseases associated with hemoglobin saturation, or cytochrome oxidase dysfunction such as cyanide toxicity, and could be also be used to monitor a wide range of chromophores that absorb in the near infrared region.

Table 1—Chemotherapy Models Chemo groups (4) Critically ill

Due to their cancer Not due to their cancer Non-cancer disease Non-critically ill; receiving high-risk chemotherapy for their cancer

n (111)

% of total n

87 7 4 13

78.4 6.3 3.6 11.7

DISCLOSURE: Nina Raoof, None. DIFFUSE OPTICAL SPECTROSCOPY MONITORING OF CYANIDE TOXICITY AND TREATMENT USING HYDROXOCOBALAMIN IN AN ANIMAL MODEL K. Kreuter BA* J. Lee PhD D. Mukai BS S. Mahon PhD T. Waddington MD J. Armstrong BA A. Cerussi PhD B. Tromberg PhD M. Brenner MD University of California Irvine, Irvine, CA PURPOSE: Currently, no reliable non-invasive methods of monitoring the severity of in vivo cyanide toxicity and resulting physiological responses. We developed a Broadband Diffuse Optical Spectroscopy (DOS) prototype system that combines multi-frequency domain photon migration with near infrared spectroscopy to measure bulk tissue absorption and scattering between 600 and 1000nm wavelengths. This system was used to optically monitor CN toxicity and treatment using Hydroxocobalamin (OHCO) by simultaneously quantifying oxy- and deoxy- hemoglobins, tissue saturation (StO2), and redox states of cytochrome C oxidase. METHODS: A cyanide toxicity and treatment model using New Zealand White (NZW) rabbits we developed was used. A DOS probe was placed on the shaved inner thigh over the muscle of the right hind leg. A sodium cyanide solution of 6mg in 60cc saline was infused over thirty minutes at a rate of 1.4cc per minute (4.2 mg total). Resultant CN toxicity was then reversed by infusing Hydroxocobalamin at a rate of 0.5cc per

DISCLOSURE: K Kreuter, Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Unapproved procedure-use of hydroxocobalamin for treatment of cyanide poisoning. IMPROVED OUTCOMES AMONG PATIENTS WITH HIGHEST LIKELIHOOD OF HAVING SEVERE SEPSIS WHO ARE TREATED EARLIER WITH DROTRECOGIN ALFA (ACTIVATED) Frank R. Ernst PharmD* Shankar Viswanathan Ganesh Vedarajan Jason Reynolds Bob Kohli Eli Lilly and Company, Indianapolis, IN PURPOSE: Drotrecogin alfa (activated) (DrotAA) is indicated for patients with severe sepsis (SS) at high risk of death. ICD-9-CM code 995.92 for SS became available in October 2002. We sought to characterize the likelihood of having SS and determine whether patients most likely to have SS experience different outcomes depending on timing of DrotAA treatment. METHODS: We conducted a retrospective analysis of 2002-2003 discharge data from ⬎400 hospitals in the Premier Perspective(TM) Comparative Database (PCD). The PCD is a large U.S. clinical and economic database developed for quality and utilization benchmarking. We modeled patients’ likelihood of having SS, based on having code 995.92. Our model included medication use, organ dysfunctions, patient demographics and comorbidities, disease state indicators, DRGs, and medical service use. We also stratified patients receiving DrotAA by timing of initiation (Same-day, Next-day, or Later) relative to the first date CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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Wednesday, November 2, 2005 Critical Care Therapeutics, continued of evident SS. Then we compared outcomes and resource use between the timing-based subgroups. RESULTS: Among patients receiving DrotAA who had the top 5% of propensity/likelihood scores, 1,265, 1,034, and 1,101 were Same-day, Nextday, and Later patients, respectively. Among these, Same-day and Next-day DrotAA recipients experienced similar hospital survival rates (53.5% and 52.9%), and higher rates than Later patients (41.8%; both p⬍.001). Average costs were lower for Same-day versus Next-day patients ($44,251 vs. $52,139; p⫽.0001), and both were lower than for Later patients ($87,227; both p⬍.0001). Average LOS was also shorter for Same-day versus Next-day patients (16 days vs. 19 days; p⫽.0002), and both of these were shorter than for Later patients (30 days; both p⬍.0001). CONCLUSION: Patients with the highest likelihood of having SS who receive DrotAA earlier experience improved survival, costs, and LOS. However, most patients with the highest likelihood of having SS never receive DrotAA. CLINICAL IMPLICATIONS: This may be the first study to examine variation in timing of DrotAA treatment among patients most likely to have SS, as determined by propensity scoring. For treated patients, earlier initiation of treatment for SS is associated with improved outcomes. DISCLOSURE: Frank Ernst, Employee Eli Lilly and Company

UTILITY OF INHALED NITRIC OXIDE IN ADULT POSTOPERATIVE CARDIAC PATIENTS WITH RIGHT VENTRICULAR FAILURE Rammohan Marla MD* Douglas Oberly RRT Kevin P. Keating MD Frederick Knauft MD Hartford Hospital, Hartford, CT PURPOSE: Inhaled nitric oxide (INO) acts as a pulmonary vasodilator and has been FDA approved for hypoxic respiratory failure of the term and near term neonate. By lowering pulmonary vascular resistance, INO would be of potential benefit in patients with severe right ventricular dysfunction. This report describes the largest series in the literature on the effects of INO in adult postoperative cardiac patients with right ventricular failure. METHODS: Patients were considered eligible for inhaled nitric oxide therapy if they were ⬎ 18 years of age, were post cardiac surgery, had moderate to severe right ventricular dysfunction by echocardiography, had a PAOP ⬎ 18 mmHg or RVEDV ⬎ 120 ml/m2, PVR ⬎ 200 dynes/sec and were unresponsive or intolerant to maximal pharmacotherapy. Nitric oxide was initiated at 5 ppm and increased until maximal benefit was observed (maximum dose 80 ppm). Outcomes measured included oxygenation and hemodynamic variables, dose and duration of therapy, and mortality. RESULTS: Between March 1998 and October 2004, 97 patients received INO therapy. 40 (41%) patients survived to discharge from hospital. 57 (59%) died before discharge from hospital. Mean INO dose was 48 ppm for the survivors and 53 ppm for non-survivors. Hemodynamic parameters in all groups are shown in the Table. CONCLUSION: Our experience has shown that INO does decrease PVR and improve both CI and REF in patients with severe right ventricular dysfunction who have proven refractory to maximal pharmacotherapy. Our experience shows improved right heart hemodynamics. Using Receiver Operating Characteristic Curve, a CI of 2.5 discriminates survivors and non-survivors, however with low sensitivity (62.5) and specificity (66.7). CLINICAL IMPLICATIONS: INO can be effectively used to improve right heart function in postoperative cardiac surgical patients who did not respond to maximal pharmacotherapy. It is a useful adjunctive therapy in lieu of right ventricular assist devices in such patients.

DISCLOSURE: Rammohan Marla, None.

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THREE YEAR EXPERIENCE WITH A DROTRECOGIN-ALPHA PROTOCOL FOR SEVERE SEPSIS: ANALYSIS OF USE, COST, AND MORBIDITY IN A UNIVERSITY HOSPITAL Sonja D. Bartolome MD* Steven Q. Simpson MD Steve Flaherty PharmD Amy R. O’Brien-Ladner MD Timothy Dwyer MD Timothy Williamson MD University of Kansas, Kansas City, KS PURPOSE: The PROWESS trial delineated a role for the use of drotrecogin-␣ in severe sepsis. However, this drug is associated with significant cost, which was projected to be $1.5 million annually in our university hospital setting, based on charts coded for septicemia. Therefore, a protocol to allow its appropriate use but discourage misappropriation was needed. A group of pharmacists, critical care physicians and nurses developed a protocol using data from the trial. METHODS: Physicians prescribing drotrecogin were required to complete a standardized order form which required that the infected patient display ⱖ2 signs of the systemic inflammatory response syndrome (SIRS), and a minimum of one organ dysfunction. Also, an intensivist was required to approve the use. Exclusion criteria were left at the discretion of the intensivist. These forms were collected over a 40 month period and demographics, associated costs, and adverse events were compiled. RESULTS: 122 patients were prescribed drotrecogin between 12/01 and 04/05. Of these patients, 53.3% were in the medical ICU, 30.3% were surgical, and 16.4% were in the burn ICU. The average age was 49.1 years (range 18 - 91. 55.1% were male, 44.9% female. Mean APACHE II at time of infusion in 82 patients was 25.6 (range 12 - 45). The most frequent adverse events in this population were death during infusion (14.9% or 18 patients) and bleeding (6% or 7 patients). Total hospital cost of the drug was $806,669, or an average of $7333 per patient. Overall 28 day all cause mortality was 33.6%. CONCLUSION: Drotrecogin in our institution was used in patients with a high severity of illness as assessed by APACHE II. Complications were comparable to previous studies. Drug costs were well below anticipated numbers. CLINICAL IMPLICATIONS: A prescribing protocol for the use of drotrecogin in severe sepsis which indicates inclusion criteria but not exclusion criteria, and is approved by a critical care specialist, can aid in guiding the use of this drug while promoting cost containment. DISCLOSURE: Sonja Bartolome, Consultant fee, speaker bureau, advisory committee, etc. Simpson is a member of the Lilly Lecture Bureau and has received consulting fees from Eli Lilly.

RESIDENTS’ KNOWLEDGE AND LEARNING OF CRITICAL CARE PHARMACOTHERAPY: EVALUATION OF A FORMALIZED WEB-BASED EDUCATIONAL MODEL Nicole Weimert PharmD Brian R. Zeno MD* Joseph Mazur PharmD Alice Boylan MD Medical University of South Carolina, Charleston, SC PURPOSE: Little data have been published that define the knowledge base of US housestaff regarding critical care pharmacotherapy or whether this knowledge base can be effectively improved through a web-based self-study program. We therefore sought to determine housestaff knowledge of key critical care concepts, and to reassess this knowledge following completion of a series of educational modules. METHODS: This was a single center pilot study using housestaff (PGY1 through PGY3). Housestaff were given pretests consisting of 40 questions in ABIM format from several different aspects of critical care pharmacotherapy. This was followed by didactic powerpoint modules on each of the subjects designed by subspecialists in critical care. Following completion of each of the modules, a posttest consisting of the same questions was provided to evaluate objective improvement. The following subjects were included: antibiotics, antifungals, vasopressors and inotropes, status epilepticus, hypertensive emergencies, toxicology, sedation, neuromuscular blockade and nutrition. RESULTS: Fifteen housestaff completed the pretest, modules, and posttest. The pretest showed a deficit in knowledge across all subjects with an average of 29% of the questions being answered correctly. Although the posttest showed a modest 5% relative improvement following the modules, this did not reach statistical significance (p⫽.18). CONCLUSION: Our housestaff come from a multitude of medical schools across the country and have USMLE scores well above the national average. Despite this, there was a uniform lack of education and/or retention in this area despite formalized pharmacology education during medical school. It appears that this an area that needs either CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Critical Care Therapeutics, continued increased emphasis or periodic reeducation and exists as a significant vulnerability to patient safety in its current state. CLINICAL IMPLICATIONS: Housestaff need to be able to properly manage critically ill patients. Didactic lectures may serve to improve knowledge of key concepts and facilitate appropriate patient management. Given the limited time and resources of busy academic critical care clinicicans and work hour restrictions of housestaff, this model allows residents an opportunity for structured didactic education without affecting patient care or lengthening rounds. DISCLOSURE: Brian Zeno, None.

CONCLUSION: nNO levels had little day-to-day variation in healthy non-smokers. Additionally, nNO levels were not different when tracheotomized patients were breathing either on or off MV. There was no significant relationship between nNO and aNO either in healthy nonsmokers or tracheotomized patients, whether on or off MV. CLINICAL IMPLICATIONS: Measurement of exhaled NO has been proposed as a non-invasive marker of airway inflammations. Further study is necessary to determine influence of an artificial airway and aNO levels on nNO.

nNO and ANO levels in Healthy Non-smokers and Tracheotomized Patients

DEATH: A ONE-COMPARTMENT DRUG MODEL EQUATION Terry Fagan MD* VA Medical Center, Wilkes-Barre, PA

DAILY MEASUREMENT OF NASAL NITRIC OXIDE (NO) IN HEALTHY NON-SMOKERS AND TRACHEOTOMIZED MECHANICALLY VENTILATED PATIENTS JiYeon Choi MSN* Leslie A. Hoffman PhD Jigme M. Sethi MD University of Pittsburgh School of Nursing, Pittsburgh, PA PURPOSE: To describe the day-to-day variation in nasal NO (nNO) and ambient NO (aNO) and examine the relationship between nNO and aNO in healthy non-smokers and tracheotomized patients. METHODS: Two groups were recruited: 1) ten healthy non-smokers (50% male), aged 33.9 ⫾ 7.8 years with a body mass index ⬍ 30, no cold or flu-like symptoms in 30 days, known allergies, prescribed medications in 7 days, or diagnosis of acute or chronic illness, and 2) three tracheotomized patients (33% male), aged 77.0 ⫾ 5.2 years, on mechanical ventilation (MV) for 43.67 ⫾ 31.90 days and undergoing daily weaning trial. Tracheotomy placement was 8.33 ⫾ 4.51 days after initiation of MV. nNO and aNO levels were measured using a chemiluminescence analyzer (Model LR2000; Logan Research, Rochester, UK) with a sampling flow rate of 250 ml/minute. RESULTS: In normals (n⫽10), nNO was measured for 3 consecutive days (30 measures). There was no significant day-to-day difference in nNO (p⫽NS). In tracheotomized subjects (n⫽3), nNO was measured for two, 3 consecutive day periods with an intervening 10 days (18 measures). Twelve measures occurred while on MV and 6 measures occurred after weaning from MV (mean ⫾ SD ⫽ 723.66 ⫾ 391.75 ppb, and 1083.31 ⫾ 302.90 ppb respectively). aNO levels varied each day in both normal and tracheotomized patients (range 0.65 – 104.50 ppb, and 1.00 – 112.20 ppb, respectively). In both groups, there were no significant correlations between nNO and aNO (p⫽NS).

Measures nNO A

NO

On MV

Off MV

30 1020.28 ⫾266.68 36.17⫾20.68

12 723.66 ⫾391.75 8.93⫾10.25

6 1083.31 ⫾302.90 50.4⫾46.23

DISCLOSURE: JiYeon Choi, Product/procedure/technique that is considered research and is NOT yet approved for any purpose. The chemiluminescence analyzer (Model LR2000; Logan Research, Rochester, UK) is only available for research purposes at this time.

Critical Care Treatment 12:30 PM - 2:00 PM USE OF AN INCLINOMETER-DATA LOGGER TOOL FOR CONTINUOUS RECORDING OF HEAD OF BED POSITION IN PATIENTS UNDERGOING MECHANICAL VENTILATION Boaz A. Markewitz MD* Jeanmarie Mayer MD Dwayne Westenskow PhD Stephanie Richardson PhD University of Utah, Salt Lake City, UT PURPOSE: Ventilator-associated pneumonia remains a common problem with attributable morbidity and mortality. Several preventive strategies are recommended including semi-recumbent positioning (head of bed angle at 30 degrees or above) in the absence of contraindications. Most studies that describe this practice, however, assess head of bed (HOB) position infrequently (i.e., often just once per day). As such, the data provided may not be reflective of what is occurring over longer time intervals. We sought to determine the angle of the HOB once per minute in patients receiving mechanical ventilation. METHODS: The HOB angle was measured using an inclinometer (Rieker, Inc.; Folcroft, PA) and the information was stored in a data logger (Onset Computers; Bourne, MA) until it was downloaded. The inclinometer-logger system was housed in a box which attached to the undersurface of the head of the bed. Calibration curves for each of six inclinometer-logger boxes was obtained between 0 to 60 degrees at 5 degree intervals. Each morning during the week a box was placed under the head of the bed of an intubated patient if the clinical team expected the patient to remain intubated at least for that day. Data was collected until the patient was extubated. RESULTS: 30 intubated patients were evaluated over a two month period. The median time of intubation was 47 hours (range 2-340 hours). The mean HOB angle for each of the 30 patients ranged from 0-27 degrees (median 21 degrees). The median percentage of time spent at or above a 30 degree angle was 3% (range 0-62%). The median percentage of time spent at or above a 45 degree angle was 0% (range 0-2%). CONCLUSION: This study indicates that semi-recubancy is rarely achieved in patients receiving mechanical ventilation. We have developed a tool which allows for continuous measurement of HOB angle. This method of monitoring shows promise as an assessment tool to improve patient care and provide feedback to the healthcare team. CLINICAL IMPLICATIONS: There is much room for improvement in pneumonia prevention. DISCLOSURE: Boaz Markewitz, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: To find an easier way to estimate and use serum levels of vancomycin and aminoglycosides. METHODS: The one compartment model with volume of distribution (Vd) in liters, and drug clearance (CLd) in liters/day was examined with drug clearance approximated by creatinine clearance (CCR). This model generally gives a reasonable approximation for vancomycin and the aminoglycosides. The equation for serum level half-life (T1/2) ⫽ 0.693 * VD / CLd was used, along with peak serum level (P) and trough serum level (T), to give a useful one-compartment equation called DEATH. RESULTS: Define D as mg of drug given per day. Define H as number of drug half-lives between doses of the drug. Define E as drug excretion ⫽ CCR. Define the amplitude A as P-T. Define T ⫽ 2. Manipulation gives D ⫽ E*A*T/H. Example1: CCR ⫽ 40. You desire vancomycin P ⫽ 32 and T ⫽ 8. Then E ⫽ 40, A ⫽ 24, and the number of half-lives from 32 down to 8 is 2 . D ⫽ 40*24*2/2 ⫽ 960. If vancomycin Vd ⫽ 40 L, each dose would be 40*(32-8) ⫽ 960. Hence your dosing would be 960 mg QD. Example2 CCR ⫽ 20 , tobramycin 200 mg QD, estimated tobramycin VD ⫽ 20 L. Then E ⫽ 20, A ⫽ 10 and D ⫽ 200. Then 200 ⫽ 20*10*2/H. Hence H ⫽ 2 half-lives. Thus the trough T must be 1/4 of the peak P, and since P-T ⫽ 10, then P ⫽ 13.3 and T ⫽ 3.3. Example3: Amikacin 500mg Q 12h gives trough ⫽ 10. Amikacin Vd ⫽ 25 L. D ⫽ 1000, A ⫽ 20. The peak ⫽ T⫹20 ⫽ 30. Peak of 30 to trough 10 requires 1.5 half-lives. Using the DEATH equation: 1000 ⫽ E*20*2/1.5 gives E ⫽ CCR ⫽ 38 ml/min. CONCLUSION: The DEATH equation D⫽E*A*T/H can be used to estimate dose, serum levels, and CCR. CLINICAL IMPLICATIONS: The DEATH equation is useful for vancomycin and aminoglycosides. DISCLOSURE: Terry Fagan, None.

Tracheostomy

Healthy non-smokers

Wednesday, November 2, 2005 Critical Care Treatment, continued ROLE OF KINETIC BEDS IN THE PREVENTION OF ATELECTASIS IN MECHANICALLY VENTILATED PATIENTS Rachna Sahityani MD* Lawrence DeLorenzo MD Safdar Khan MD Wilbert Aronow MD Dipak Chandy MD New York Medical College, Valhalla, NY

EFFECT OF THE PERIOPERATIVE METHYLPREDNISOLONE ADMINISTRATION IN THE PAO2/FIO2 RELATION AFTER ESOPHAGEAL RESECTION FOR ESOPHAGUS CARCINOMA Antonio M. Raimondi MD* Jose L. Amaral MD Universidade Federal de Sa˜o Paulo/ Escola Paulista de Medicina, Sao Paulo, Brazil

PURPOSE: Kinetic beds are designed to prevent pulmonary complications, including atelectasis. The objective of this study was to determine the effect of kinetic beds on the incidence of atelectasis in mechanically ventilated patients. METHODS: 50 kinetic beds, 20 Rotation modules and 20 Percussion modules were introduced to the Westchester Medical Center on July 26, 2001. A retrospective chart review of all mechanically ventilated patients at this tertiary-care medical center who underwent bronchoscopy for atelectasis was conducted for 2 separate periods. The first was for the period immediately preceding the arrival of these beds i.e. July 2000 to June 2001. The second period was from July 2002 to June 2003 which allowed a year to pass after the introduction of these beds in order for healthcare personnel to become aware of their presence and potential benefits. RESULTS: Of the 3399 ICU admissions between July 2000 and July 2001, 71 patients developed atelectasis while being mechanically ventilated. Of the 3065 ICU admissions between July 2002 and June 2003, 83 patients developed atelectasis. There was no significant difference in the hospital and ICU length of stay, ventilator utilization by the hospital and the Case-mix Index between these 2 periods. CONCLUSION: There was no decrease in the incidence of atelectasis in mechanically ventilated patients at our institution after the introduction of these kinetic beds despite their widespread availability. CLINICAL IMPLICATIONS: Most studies have shown kinetic beds to be potentially beneficial. However, all these studies were performed under a strict protocol to ensure appropriate usage. Our institution did have a protocol but did not require a physician’s order, thereby ensuring that usage was almost entirely dependent on nursing personnel. The fact that our study showed no reduction in the incidence of atelectasis after the introduction of these beds is probably related to their underutilization and not to their lack of efficacy. To obtain a benefit from such an expensive investment, institutions should consider physician orders as a means of ensuring appropriate utilization of these beds. DISCLOSURE: Rachna Sahityani, None.

PURPOSE: Preoperative glucocorticoid administration has been proposed to reducing postoperative morbidity. It isn⬘t widely used before esophageal resection due incomplete knowledge of its effectiveness.Objective:To assess the effects of preoperative glucocorticoid administration in adults underwent esophageal resection for esophageal carcinoma. METHODS: SEARCH STRATEGY: Studies were identified by searching the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CancerLit, SCIELO, Cochrane Library and handsearching from relevant articles. The date of the last search for clinical trials for this systematic review was December 2004. SELECTION CRITERIA: This review included randomized of patients with potentially resectable carcinomas of the esophagus that compare glucocorticoid with placebo before surgeries. DATA COLLECTION & ANALYSIS: Data were extracted by the same reviewers, and the trial quality was assessed using the Jadad scoring. Relative risk and weight mean difference with 95% confidence limits were used to assess the significance of the difference between the treatment arms. RESULTS: There were four randomized trials involving 146 patients. There weren’t differences in postoperative mortality, sepsis, anastomotic leakage, hepatic and renal failure between glucocorticoid and placebo groups. There was a decrease in postoperative respiratory complications (p ⫽ 0.005), multiple postoperative complications (p ⫽ 0.004) and postoperative plasma levels of interleukin-6 (p ⫽ 0.00001) with preoperative glucocorticoid administration. There was a increase in postoperative PaO2/FiO2 ratio (p ⫽ 0.0001) with preoperative glucocorticoid administration. CONCLUSION: Prophylactic administration of glucocorticoids is associated with a amelioration in postoperative PaO2/FiO2 relation. CLINICAL IMPLICATIONS: Perioperative methylprednisolone administration represented a potentially important biologic modifier of postoperative inflammatory responses and organ dysfunction.

ACCURACY OF CLINICAL EVALUATION OF HEAD OF BED ELEVATION Nasir Awan MD* Chanaka Seneviratne MD Zenia Ceniza RN Taek S. Yoon MD Yizhak Kupfer MD Sidney Tessler MD Maimonides Medical Center, Brooklyn, NY PURPOSE: Maintaining head of bed elevation (HOBE) greater than 30° has been shown to decrease the incidence of ventilator associated pneumonia. We prospectively studied the accuracy of clinical estimation of HOBE. METHODS: HOBE was set at two levels 30° and 45° with the use of a protractor. Nurses and physicians were asked to determine the HOBE angle. The position of the observer, whether the estimation was performed at the foot or the side of the bed, was evaluated. RESULTS: One hundred and fifty nurses and fifty physicians participated in the study. Overall, when HOBE was 30°, the average clinical estimation was 50° (P⬍0.001). When the HOBE was 45°, the average clinical estimation was 70° (P⬍0.001). When the observer was at the foot of the bed, only 32 (16%) correctly estimated the position versus 90 (45%) of the observers correctly estimated bed position from the side of the bed (P⫽0.001). There was no difference between physicians and nurses in the accuracy of the clinical estimation of HOBE. CONCLUSION: Clinical evaluation of the angle of HOBE tends to overestimate the angle of elevation. Measurement of the HOBE from the side rather than the foot of the bed is more accurate. CLINICAL IMPLICATIONS: Use of protractors rather than clinical estimation should be encouraged to maintain HOBE greater than 30°. DISCLOSURE: Nasir Awan, None.

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DISCLOSURE: Antonio Raimondi, None. CURRENT PRACTICE OF TRACHEOTOMY IN EUROPE: A POSTAL SURVEY IN THE NETHERLANDS Denise P. Veelo MD Marleen E. Graat Peter E. Spronk PhD Marcus J. Schultz PhD* Academic Medical Center, Amsterdam, Netherlands PURPOSE: Tracheotomy is increasingly performed in critically ill patients requiring prolonged respiratory support, weaning and frequent broncho-pulmonary toilet. METHODS: To ascertain current practice of tracheotomy in critically ill patients a simple questionnaire was sent to intensive care units (ICUs) throughout the Netherlands. Questionnaires were sent to the lead clinicians of ICUs with ⬎ 5 beds. RESULTS: From the number of units responding (n ⫽ 28, 43.1%), the majority (n ⫽ 17, 60.7%) practiced percutaneous tracheotomy as opposed to open surgical tracheotomy. In the majority of hospitals tracheotomy was performed by the intensivist (n ⫽ 19, 67.9%), followed by the surgeon (n ⫽ 15; 53.6%), and the ENT-physician (n ⫽ 9, 32.1%). Tracheotomies were mainly performed in the ICU (n ⫽ 20; 71.4%), than in the operation room, and more tracheotomies were performed by a team (i.e., for each tracheotomy procedure more than one physician was present, n ⫽ 22, 78.6%) than by a single physician (n ⫽ 2, 7.1%). In the majority of ICUs no antimicrobial prophylaxis was given before tracheotomy (n ⫽ 23; 82.1%). Reasons for tracheotomy were polyneuropathy (n ⫽ 13; 46.4%), prolonged mechanical ventilation (⬎ 14 days) (n ⫽ 22; 78.6%), and low GCS (n ⫽ 18; 64.3%). Although it was the policy to perform the CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Critical Care Treatment, continued procedure as soon as possible after it was clear that the patient fulfilled criteria for tracheotomy, in more than half of the cases tracheotomy was performed not earlier than after one week. Reasons varied from no operating room available (n ⫽ 5; 17.9%) to uncertainty about indication (n ⫽ 8; 28.6%). CONCLUSION: In the Netherlands, the majority of tracheotomies are performed by the intensivist in the ICU, by using the percutaneous technique, and without antimicrobial prophylaxis. CLINICAL IMPLICATIONS: Our data suggest that guidelines must be developed for this frequently performed procedure. DISCLOSURE: Marcus Schultz, None. PERCUTANEOUS TRACHEOSTOMY EXPERIENCE AT A SINGLE INSTITUTION Francis J. Podbielski MD* Peter H. Bagley MD Ann E. Connolly MSN Patrick H. Bagley UMass Memorial Healthcare, Worcester, MA

IS PERCUTANEOUS TRACHEOSTOMY MORE LIKELY TO CAUSE TRACHEAL STRICTURE THAN OPEN TRACHEOSTOMY? John R. Roberts MD* Gary K. Lovelady MD The Surgical Clinic, Nashville, TN PURPOSE: Tracheostomies are often done to facilitate weaning from the ventilator, or to prevent tracheal strictures from prolonged intubation. After the technique of open tracheostomy was developed, reports of strictures were found in the literature, and techniques to avoid those strictures were developed. Percutaneous tracheostomy allows bedside tracheostomy in the ICU, and thus avoid transporting a sick patient. After finding tracheal strictures in several patients who had undergone percutaneous tracheostomy we evaluated our experience in tracheal resections after tracheostomy. METHODS: All patients who had undergone tracheal resection were anlyzed. Their age, sex, race, length of stay, ICU stay, reason for tracheostomy, reason for intubation and pulmonary function tests were evaluated. Data were analyzed with means and standard deviations. Student’s t test was used to compare means– 0.05 was accepted as significant.

IMPLEMENTATION OF AN INTENSIVE INSULIN THERAPY PROTOCOL IN MECHANICALLY VENTILATED TRAUMA PATIENTS John P. Kepros MD* Jim Chalk MD Emmett McGuire MD Lisbeth Harris MS David Bar Or MD Michael Craun MD Kate Wilmes RN Michigan State University Department of Surgery, Lansing, MI PURPOSE: Intensive insulin therapy has been shown to reduce mortality in adult patients receiving mechanical ventilation admitted to the intensive care unit. The use of exogenous insulin to maintain the blood glucose level at no higher than 110 mg/dL was found to reduce morbidity and mortality regardless of whether the patients had diabetes. We studied the safety and feasibility of widespread implementation of a standardized intensive insulin therpay protocol targeted to this range as part of a mechanical ventilation bundle on a trauma service. METHODS: 50 patients admitted to the ICU on the trauma service and requiring mechanical ventilation were treated with insulin infusions per a standardized protocol to keep the blood glucose between 80 and 110 mg/dL. Compliance with the protocol, mortality, frequency of hypoglycemia, rate of infusion and duration of insulin required, and cause of mortality were measured and recorded. RESULTS: Physician compliance in ordering the protocol was 90%. Only 5 did not receive the protocol. Of the other 45 patients who had intensive insulin therapy ordered, 42 actually required insulin administration (93.3%). Three patients died (6.0%) during the ICU stay. Hypoglycemia (glucose 40 mg/dL or less) only occured in 2 patients (4.0%)without adverse sequelae. The mean duration of intensive insulin therapy was 6.5 days. The range of insulin required was from 0 to 15 units/h. The causes of death were MODS from sepsis, a fatal cervical spine injury, and severe traumatic brain injury. CONCLUSION: Intensive insulin therapy with a continuous infusion of insulin according to a standardized protocol can easily be performed in critically ill trauma patients requiring mechanical ventilation. A determined approach to glucose control can be taken with minimal fear of hypoglycemia. CLINICAL IMPLICATIONS: Intensive insulin therapy has been recommended for implementation as standard therapy as part of a mechanical ventilation bundle. Unfamiliarity, lack of real world data, and fear of hypoglycemia have been barriers to implementation. This study shows that intensive insulin therapy with tight glucose contol is feasible in a critically ill population. DISCLOSURE: John Kepros, None. THE EFFECTIVENESS OF THE MISTY-OX HIGH FRACTION OF INSPIRED OXYGEN (FIO2)-HIGH FLOW NEBULIZER AND THE THERA MIST AIR ENTRAINMENT NEBULIZER IN DELIVERING HIGH OXYGEN CONCENTRATIONS Donna D. Gardner RRT* David L. Vines RRT Richard B. Wettstein RRT Juan Garcia MD Jay I. Peters MD University of Texas Health Science Center at San Antonio, San Antonio, TX PURPOSE: Misty-Ox (MO)® nebulizer was developed to overcome shortcomings of conventional air-entrainment devices. The MISTY OX ® is designed to deliver FIO2s from 0.60 to 0.96 with total gas flows from 42 to 80 L/min. The THERA MIST® nebulizer is designed to deliver FIO2s CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

PURPOSE: To review a single institution’s experience in the treatment of patients requiring long-term airway access. METHODS: Medical and surgical patients requiring tracheostomy were evaluated by a single surgeon. A decision for bedside percutaneous versus open tracheostomy was based on hemodynamic stability, patient anatomy, and coagulation profile. RESULTS: A total of 131 patients underwent a planned percutaneous tracheostomy between 11/05/2001 and 04/12/2005. There were 74 men and 57 women, with an average age of 66.1 ⫾ 16.5 yrs (median ⫽ 71). The duration of mechanical ventilation prior to tracheostomy was 16.1 ⫾ 8.7 d (median ⫽ 15). The majority of patients received a size #8 tube (n ⫽ 117), and the remainder a size #7 tube. There was one death in post-operative period (i.e., within 30 d of the procedure) secondary to bleeding into the airway after the tracheostomy was downsized. One procedure required conversion to an open procedure due to excessive bleeding. Complications included three bedside explorations for bleeding (tracheostomy completed successfully), one case of bleeding on POD #2 with a respiratory arrest who was resuscitated successfully and had no further intervention, one semi-open procedure at the bedside secondary to morbid obesity, and four cases done percutaneously in the OR for patient issues. Of the 130 procedures performed successfully, 50 were done in a post-operative setting and the remainder (n ⫽ 80) done for medical conditions. CONCLUSION: Percutaneous tracheostomy is a widely employed technique used by surgeons, pulmonologists, and critical care physicians to provide long-term airway access for patients requiring protracted weaning from mechanical ventilation. It generally does not require use of operating room facilities, and in skilled hands is safe and reliable. Our series demonstrates common complications encountered during this procedure and should be kept in mind by those physicians who are learning this procedure. CLINICAL IMPLICATIONS: Physicians performing percutaneous tracheostomy should be prepared to manage issues of bleeding and emergent airway access in the event of complications when performing this procedure. DISCLOSURE: Francis Podbielski, None.

RESULTS: Twelve patients underwent resection for tracheal stricture due to tracheostomy. Their average age was 51.6 years (range 28-76) and 33% (4 patients) were women. Ten of twelve had preoperative pulmonary function testing–average FEV1% was 36%. No patient was reintubated, but three patients spent additional time in the ICU (average 0.38 days; standard deviation 0.81 days). No patients died, nor suffered signficant complications. Three patients had strictures from open tracheostomy (25%) and nine from percutaneous tracheostomy (75%). CONCLUSION: We can not compare the incidence of stricture between the procedures because the denominators are unknown. However, these patients were drawn from a large geographic region where open tracheostomy is still more common than percutaneous tracheostomy. These data suggest that patients with percutaneous tracheostomy are at signficant risk of tracheal stricture, perhaps more than those undergoing open tracheostomy. CLINICAL IMPLICATIONS: Patients undergoing percutaneous tracheostomy are at risk for tracheal stricture. DISCLOSURE: John Roberts, None.

Wednesday, November 2, 2005 Critical Care Treatment, continued from 0.36-0.96 with total gas flows from 47 to 74 L/min. We sought to determine the actual delivered FIO2 when using the MISTY OX® and the THERA MIST® via aerosol mask in normal subjects. METHODS: Following informed consent, 12 healthy volunteers, had a size 8 french nasal catheter (NC) inserted through one of the nares with the tip positioned at the level of the uvula. Subjects were placed on the THERA MIST® connected to large bore tubing and an aerosol mask. Oxygen therapy was then initiated at a set FIO2 of 0.60 at 15 L/min, then 0.80 and 0.95 at flush for a period of five minutes. The subjects were also placed on the Misty-Ox ® connected to large bore tubing and an aerosol mask. Oxygen therapy was then initiated at a set FIO2 of 0.65, 0.85 and 0.96 at 40 L/min flow using a high-flow flowmeter for a period of five minutes. With the subject breathing normally the gas was analyzed at three sites: the nebulizers’ outlet, the subjects’ lip and from the subjects’ pharynx. A previously calibrated oxygen analyzer measured the FIO2 of these samples. Three samples were obtained from each site, at each FIO2 setting and the mean and standard deviations were calculated. RESULTS: Means, standard deviations and ranges for the analyzed oxygen concentrations are included in the Table. CONCLUSION: Delivered FIO2 using the Thera Mist and the Misty Ox nebulizers can vary significantly from the set value. The delivered O2 can be 10 - 20 percent below the set value. CLINICAL IMPLICATIONS: Care should be taken when interpreting patients’ clinical response to oxygen therapy when using these devices. Patient may be receiving a FIO2 much less than anticipated based on the nebulizer setting. DISCLOSURE: Donna Gardner, None.

RESULTS: 103 patients treated with intensive insulin therapy were analyzed. Patients were treated for a mean of 8.8 ⫾ 6.7 days (range 1-33 days) and a total of 914 treatment days. The mean inclusion blood sugar was 10.7 ⫾ 4.5 (range 6.1-27). The target blood glucose was reached in a mean of 6.7⫾3.3 hours. Average daily blood glucose levels are shown in the figure. There were a total of 7480 readings above the target averaging 8 /100 treatment days. There were a total of 138 hypoglycemic episodes averaging 15/100 treatment days. CONCLUSION: Intensive insulin therapy protocol was effective in achieving the target level of 4.1-6.1 mmol/l in a relatively short time (6.7 hours) and for most of the treatment duration. This therapy was associated with the occurrence of hypoglycemia at a rate of 15/100 treatment days. CLINICAL IMPLICATIONS: Physicians using intensive insulin therapy need to be aware of the frequency of complications; the impact of which can be minimized by at least hourly monitoring of blood glucose.

Analyzed FIO2 (SD) for High Oxygen Concentration Devices* Device Set FIO2

Thera Mist .060

0.80

Misty Ox 0.95

0.65

0.85

0.96

DISCLOSURE: Ousama Dabbagh, None. Location of Analysis Nebulizer Outlet Subject’s Lip Oropharynx

.53(.03) .74(.05) .86(.05) .64(.03) .80(.03) .86(.04) .56(.04) .72(.06) .84(.05) .63(.03) .79(.04) .84(.04) .47(.03) .65(.05) .75(.06) .56(.04) .70(.06) .73(.06)

* Mean (SD) of all subjects

Critical Care: Intensive Glucose 12:30 PM - 2:00 PM EFFICACY OF INTENSIVE INSULIN PROTOCOL AMONG CRITICALLY ILL MEDICAL AND SURGICAL PATIENTS Ousama Dabbagh MD* Yaseen Arabi MD Ziad Memish MD Samir Haddad MD Salim Baharoon MD Sofia Junaid MBBS Hema Giridhar MBBS Craig Grant RN Riette Brits RN Monica Pillay RN Salim Kahoul RN Abdullah Al Shimemeri MD King Abdulaziz Medical City, Riyadh, Saudi Arabia PURPOSE: to evaluate the efficacy of intensive insulin protocol to control blood sugar in target of 4.4-6.1 mmol/l. METHODS: Data was abstracted from an ongoing randomized controlled trial in a 21– bedded medical surgical ICU at a tertiary center in Saudi Arabia. Patients were included if admission blood glucose was 6.1 mmol/l or higher.Patients were randomized to receive intensive insulin therapy (target blood glucose 4.4-6.1 mmol/l) or standard insulin therapy (target 10-11.1 mmol/l) using prewritten protocols. This study examines the efficacy of intensive insulin protocol in controlling blood glucose. We examined the time to achieve the target defined as the time (hours) needed to reach the upper limit of the target (6.1 mmol/l) for at least one reading. The number of blood sugar episodes above the target were also recorded (excluding the day of enrollment) and adjusted to the number of treatment days. We also recorded the number of hypoglycemic episodes (blood glucose below 2.2 mmol/l) and adjusted to the number of treatment days.

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INTENSIVIST DIRECTED PROTOCOL REDUCES ICU ADMISSIONS FOR PATIENTS IN DIABETIC KETOACIDOSIS Jay M. Nfonoyim MD* Joseph Ng MD Igor Berengolts MD Fasika Weldearegay MD Saint Vincents Catholic Medical Center, Staten Island, NY PURPOSE: Over 90,000 U.S. hospital admissions have DKA as a primary diagnosis. Despite published management guidelines, there are significant differences in treatment plan, rate of ICU admissions and length of stay. The use of an early intensivist directed protocol reduces the duration of acidemia and ICU admissions. METHODS: Patients admitted into the ED, with a primary diagnosis of DKA during a two month period in 2005 (Intervention) were treated with early intensivist driven protocol utilizing crystalloids and a constant infusion of insulin with IV boluses. Patients were treated with the standard 0.1 units/kg IV bolus and 0.1 unit/kg/hour IV infusion of insulin titrated to the blood glucose. However, in this study, the treatment was complimented with IV boluses of insulin based on blood glucose measurements. Outcomes measured were duration of acidemia, admission to ICU, and length of hospital stay. Controls were retrospectively obtained by reviewing an equal number of randomly selected charts of patients admitted for DKA during the same period in 2004. RESULTS: Both groups were matched according to their APACHE II scores. The duration of acidemia in the intervention group ranged from 2-13 hours, (mean 5.9) compared to the control group which ranged from 7-19.5 hours (mean 11) p⬍0.001. Of the intervention group, 10 percent were admitted to the ICU, compared to 30 percent of the control group. The mean length of stay for the intervention group was 4.0 days, compared to 4.5 days for the control group. CONCLUSION: In the management of DKA, early intervention by an intensivist directed protocol of crystalloids and insulin with intravenous boluses during and in addition to a constant infusion of insulin, reduces the duration of acidemia, subsequent admissions to the ICU and a trend towards a shorter length of stay. CLINICAL IMPLICATIONS: Involving a critical care team in the management of DKA patients early in their admission to the ER reduces the rate of admissions to the ICU thereby decreasing the total cost of the hospitalization. DISCLOSURE: Jay Nfonoyim, None. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Critical Care: Intensive Glucose, continued VALIDATION OF AN INSULIN INFUSION PROTOCOL IN DIABETIC PATIENTS UNDERGOING CARDIAC SURGERY Vinay K. Sharma MBBS* Salim Harianawala MBBS Olukunle Ajagbe MBBS Sohail Khan MBBS Alan D. Haber MD Graduate Hospital, Philadelphia, PA

COMPUTERIZED PROTOCOLS FOR INTENSIVE INSULIN THERAPY: VARIATIONS IN RECOMMENDATIONS BASED ON DIFFERENT METHODS OF GLUCOSE MEASUREMENT Srinivas B. Chakravarthy MBBS* James F. Orme MD Boaz A. Markewitz MD Chris Lehman MD University of Utah, Salt Lake City, UT PURPOSE: Insulin protocols are increasingly used in ICUs to achieve desired glucose ranges while minimizing practice variation and potentially, harm to patients. Glucose levels may vary, however, with different testing methods, and these differences may be clinically significant. Point of care testing with glucometers is now widely performed, however, the adequacy of this method in critically ill patients is largely unknown. The purpose of this study is to evaluate the variations in recommendations given by a computerized insulin protocol to glucose levels obtained by different testing methods. METHODS: Patients admitted to the ICU with shock (SBP ⬍ 90 mm Hg despite adequate volume resuscitation or requiring vasopressor therapy) were evaluated. When indicated, an arterial blood sample was obtained and glucose was measured using a glucometer (ACCU-CHEK Comfort Curve, Roche), as well as in the clinical laboratory (“gold standard”) using the colorimetric plasma glucose analyzer (VITRIOS). A simulation was subsequently run using this patient abstracted data on our computerized insulin protocol. The computerized protocol has been implemented in our ICU since January of 2003 and targets a glucose level of 80 to 110 mg/dl. The protocol uses the current blood glucose level as well as the rate of decline in glucose to determine the insulin infusion rate. RESULTS: Simulations were run on glucose results from 21 patients (61 total samples). The protocol treatment recommendation obtained for each glucose level determined by the glucometer was compared to the recommendation obtained for the corresponding glucose level determined by the clinical lab. See table for the results. Two out of the 21 patients in our simulation had a difference of greater than 1 unit/hour of insulin infusion rate, between the recommendations.

Table—Results Protocol recommendation Glucometer- Clinical based lab-based Total insulin (units)

Mean

SD Range Insulin rate Mean (units/ hour) SD Range

15.16

12.69

Difference

P

2.47

0.0025

12.84 0 to 42.18 2.09

11.76 3.19 0 to 41.22 -0.8 to 13.41 1.74 0.31 0.0017

1.52 0 to 4.82

1.43 0.44 0 to 4.71 -0.12 to 1.55

DISCLOSURE: Srinivas Chakravarthy, Grant monies (from sources other than industry) This study was supported by an award from The CHEST Foundation of the American College of Chest Physicians and Ortho Biotech Products, LP.; Grant monies (from industry related sources) The glucometer, chemistry strips and reagents were provided by Roche. NON-SUCCESSFUL INTENSIVE INSULIN THERAPY IN ICU PATIENTS IS NOT ASSOCIATED WITH CHANGES IN QUALITY OF LIFE Jose´ Hofhuis RN Jan Bakker PhD Marcus J. Schultz MD Johannes H. Rommes MD Peter E. Spronk MD* Gelre Hospitals (Lukas site), Apeldoorn, Netherlands PURPOSE: Recent data showed that intensive insulin therapy (IIT) improved the mortality and morbidity in post-operative intensive care patients. IIT, bears the risk of hypoglycaemia, which might be associated with a decreased health related quality of life (HRQOL). We hypothesized that changes in HRQOL may be related to IIT. METHODS: All measured blood glucose values (BGs) in all patients admitted ⬎48 hours to a 10-bed mixed IC from 2001 – 2003 were retrospectively collected. Severe hypoglycemia (BG ⬍ 2.2 mmol/) and hypoglycemia (BG ⬍ 4.4 mmol/l) were defined. Patient data were divided in two groups: successful IIT group: patients with ⬎75% of BGs in normal range, and no (severe) hypoglycemia at any time during IIT; unsuccessful IIT group: patients that did not fulfil the former criteria. HRQOL was assessed using the Short-Form (SF)-36. Patients or proxies completed this questionnaire in the first 48 hours of admission and 6 months thereafter. RESULTS: Mean BG was 6,9 ⫾ 1,5 mmol/l in the succesful group (N⫽45) and 8,7 ⫾ 3,2 mmol/l in the unsuccesful group (N⫽286). In the succesful group, the percentage of patients with severe hypoglycemia and hypoglycemia was 3,3% and 31%, respectively. In the first group, scores in the physical functioning and general health domains decreased in the 6 month evaluation period (P ⫽ 0,003 and P⬍0,001, respectively). No changes were found in the role physical, vitality, pain, social functioning, role emotional; and mental health domains. In the unsuccessful IIT group, scores in the physical functioning, role physical and general health domains decreased in the same period (all P⬍0,001). No changes were observed in the vitality, pain, social functioning, role emotional, and mental health domains. No differences between the groups could be demonstrated with respect to scores in the HRQOL domains 6 months after ICU discharge. CONCLUSION: HRQOL decreases after IC-treatment, particularly with respect to physical functioning and general health. This decrease was independent of successfulness of IIT. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

PURPOSE: An increasing body of literature suggests that poor glycemic control is associated with worse outcome in critically ill patients and that achieving good glycemic control with aggressive insulin therapy reduces morbidity and mortality. In our institution, a fairly simple insulin infusion protocol has been in place for patients undergoing cardiac surgery. The hourly insulin drip rate is calculated as: (patient glucose in gm/dl – 60) x factor. The initial factor is usually 0.03 and is adjusted subsequently. However, the source and validity of this protocol were not elucidated despite a literature search. This retrospective study aims to ascertain the validity of the protocol. METHODS: Charts of patients undergoing coronary artery bypass graft (CABG) surgery were reviewed and 20 diabetic patients identified; 10 who received the insulin protocol and 10 that did not. Data abstracted included patient demographics, parameters needed to determine the APACHE III score on the day of surgery, and all fingerstick glucose readings on 3 consecutive days starting from the day of surgery. RESULTS: Nineteen of the 20 patients were males. The mean age (65 ⫾ 15 vs. 65 ⫾ 10) and mean APACHE III scores (14.4 ⫾ 8 vs. 14.6 ⫾ 12) were similar between the control and insulin protocol groups, respectively. The mean glucose levels on each of the three days were 162, 151 and 179 mg/dl in the control group and 157, 148 and 141 in the protocol group. Glucose level was £145mg/dl in 41% (76/184) of readings in the control group and 65% (228/353) of readings in the protocol group (p⬍0.0001; Chi-square). Glucose levels ⬍60mg/dl occurred in 2.7% (5/184) of control and 0.6% (2/353) of protocol group readings (p⬍0.05; Fisher Exact Test). CONCLUSION: In our cohort, this insulin protocol resulted not only in significantly better glycemic control, but also a significant reduction in the incidence of hypoglycemia. CLINICAL IMPLICATIONS: This relatively simple insulin protocol appears to optimise glycemic control in CABG patients and may also have utility in non-CABG, critically ill patents. DISCLOSURE: Vinay Sharma, None.

CONCLUSION: Blood glucose determinations made with a glucometer can result in patients receiving higher doses of insulin, per our simulation. CLINICAL IMPLICATIONS: While our study shows statistical significance in variations in insulin dosage, if a glucometer is used, the clinical significance is uncertain.

Wednesday, November 2, 2005 Critical Care: Intensive Glucose, continued CLINICAL IMPLICATIONS: The impact of ICU treatment on HRQOL is not influenced by IIT. DISCLOSURE: Peter Spronk, None.

General Thoracic Surgery 12:30 PM - 2:00 PM SUPERIOR MANAGEMENT OF ESOPHAGEAL PERFORATIONS: AN EMPHASIS ON DIVERSION AND DRAINAGE Thomas A. Brown MD* Geoffrey M. Graeber MD Michael F. Szwerc MD Gordon F. Murray MD West Virginia University, Morgantown, WV PURPOSE: Uncontained esophageal perforation is a devastating injury with a mortality rate approaching 20%. Early surgical repair supported by esophageal exclusion, early nutrional support, gastric drainage, and thorough pleural drainage should yield superior results. METHODS: The records of all patients treated esophageal perforations at one university medical center from 1988-2003 were collected and analyzed. Optimal treatment consisted of surgical repair, proximal esophageal and gastric decompression, thorough pleural drainage, initiation of nutritional support within 2 days, and IV antibiotics. RESULTS: Forty patients were identified (37 adult and 3 pediatric). The age range was 0-87 years (mean 59.1). The male: female ratio was 1:1. Overall mortality rate primarily, had nasogastric suction, pleural and/or mediastinal drainage, and nutritional support. All had successful repairs with 0% mortality.Thirty-four patients had esophageal perforations in the distal two-thirds. Seven received conservative therapy of drainage, IV antibiotics, nutritional support, but no primary repair. Two died of continuing sepsis and five survived. Twenty-six patients were treated early with 11.5% mortality and 7 patients were treated late with 14.3% mortality. Twelve patients received suboptimal therapy with one or more of the major components of treatment being omitted. Four of these patients died (mortality rate 33.3%). Fifteen received optimal treatment with all of the major components with 0% mortality. Number of pleural and mediastinal drains placed was proportional to survival, with 4-6 drains yielding 0% mortality. CONCLUSION: Prompt surgical repair supported by proximal esophageal exclusion without defunctionalization, gastric decompression, thorough pleural drainage, nutritional support within 2 days, and IV antibiotics yields excellent results in patients suffering from uncontained perforations of the distal two-thirds esophagus. CLINICAL IMPLICATIONS: Early drainage and appropriate nutritional support yield excellent results in complex esophageal perforations. DISCLOSURE: Thomas Brown, None. THE EFFECT OF IMMUNOSTAINING WITH ANTI-OCT4 ANTIBODIES ON THE EXPRESSION OF OCT4 IN MEDIASTINAL GERM CELL TUMORS Pao-Hsien Chu MD* Shih-Ming Jung MD Chang Gung Memorial Hospital and Chang Gung University, Taipei, Taiwan ROC PURPOSE: The Primary germ cell tumor (GCT) is a relatively rare tumor usually located in the anterior mediastinum. A previous study has postulated that OCT4 is a nuclear transcription factor that is expressed in pluripotent embryonic germ cells. This study attempted to identify and characterize OCT4 expression in the GCTs originating in the mediastinum. METHODS: A retrospective study conducted between 1983 and 2005 included 46 consecutive patients with GCTs in the mediastinum whose tumors had been surgically excised. We examined histological sections from 46 primary GCTs in the mediastinum, including teratoma (n⫽27; 58.7%), seminoma (n⫽10; 21.7%), yolk sac tumor (n⫽6; 13%), embryonal carcinoma (n⫽1; 2.1%), and mixed GCTs (n⫽2; 4%; one consisted of teratoma and yolk sac tumor, and the other teratoma, yolk sac tumor and seminoma). Each tumor was examined with hematoxylin and eosin staining and with anti-OCT4 antibodies. An overexpression of OCT4 was studied using immunohistochemistry. RESULTS: The patient population was comprised of 16 (34.8%) women and 30 (65.2%) men. The mean age of patient participants was 25.1 years, with an age range of 9 to 56 years. The presentations included:

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asymptomatic tumor (28.5%), dyspnea (17.1%), coughing (22.8%), superior vena syndrome (5.7%), chest pain (20%), and fever (5.7%). The therapies administered were surgical excision (75%), followed by chemotherapy (48.6%) and/or radiotherapy (31.4%). Serum tumor markers were measured for twenty (47%) of the 46 patients whose, including 68% elevated alpha-fetoprotein, 30% elevated beta subunits of human chorionic gonadotropin, and 17% elevated carcinoembryonic antigen. There was greater than 90% nuclear staining of the embryonal carcinoma and seminoma tumor cells with little to no background staining. The other GCT components (yolk sac tumor and teratoma) showed no staining. CONCLUSION: We conclude that immunostaining with anti-OCT4 antibodies is a useful diagnostic tool in the identification of primary embryonal carcinomas and seminomas in the GCT originating in the mediastinum. CLINICAL IMPLICATIONS: anti-OCT4 antibodies is a useful diagnostic tool in the identification of mediastinal primary embryonal carcinomas and seminomas. DISCLOSURE: Pao-Hsien Chu, None. UTILITY OF OPEN LUNG BIOPSY IN CRITICALLY ILL PATIENTS Kalpaj R. Parekh MD* Timothy L. Van Natta MD Joan Ricks-McGillin RN Kelley McLaughlin RN Mark D. Iannettoni MD University of Iowa Hospitals and Clinics, Iowa City, IA PURPOSE: The role of open lung biopsy in critically ill adult patients remains controversial. The aim of this study was to determine the diagnostic ability, mortality and therapeutic impact of open lung biopsy critical versus non-critically ill patients. METHODS: We conducted a retrospective review of all open lung biopsies performed at our institution for diagnostic indications in the last 5 years. RESULTS: From January 2000-December 2004, 68 patients were identified who underwent open lung biopsy. Of these, 18 were critically ill (defined as requiring mechanical ventilation patients or requiring FiO2 ⫽1.0 by face mask). Fifty patients were non-critically ill (defined as in-patient/out-patient referrals with FiO2 requirements ⬍1.0). Therapeutic change, defined as addition of a new agent was made in 9/18 (50%) for critically ill patients, and in 25/50 (50%) non-critical patients. The operative mortality was 8/18 (44%) for the critical patients while it was 0/50 (0%) in the non-critical patients. Of the critical patients for whom a therapeutic change was initiated, 6/9 (67%) survived and were discharged. CONCLUSION: Our results indicate that open lung biopsy in critically ill patients remains a high risk procedure with a high operative mortality. It does however have a diagnostic yield similar to that in non-critically ill patients. CLINICAL IMPLICATIONS: Open lung biopsies continue to be a challenging problem in this difficult subset of patients. However, despite the significant inherent risks it may still be considered to direct a therapeutic change when other non-invasive modalities have been exhausted. DISCLOSURE: Kalpaj Parekh, None. VIDEO-ASSISTED THORACOSCOPIC LUNG BIOPSY FOR THE DIAGNOSIS OF DIFFUSE INTERSTITIAL LUNG DISEASE Noriyasu Usami MD* Kohei Yokoi MD Division of General Thoracic Surgery, Nagoya University School of Medicine, Nagoya, Japan PURPOSE: Video-assisted thoracoscopic lung biopsy (VTLB) is getting a position of the diagnostic methods for diffuse interstitial lung disease (DILD). In this study, we review our experience with this technique in terms of postoperative complications and diagnostic accuracy. METHODS: From January 1995 to December 2004, 50 consecutive patients were intended to undergo surgical lung biopsy for the diagnosis of DILD. Actually 46 patients (88%) underwent VTLB and 4 (12%) were needed to conversion to open lung biopsy (OLB) due to the adhesion or pulmonary injury. We retrospectively analyzed those patients. RESULTS: The patients consisted of 25 men and 25 women with mean age of 58.2 years (20-77 years). The preoperative respiratory functions were %VC: 76.6 ⫾ 21.2% (38.5-131%), %FEV1.0: 83.8 ⫾ 22.6% (37.8139.3%), %DLco: 65.2 ⫾ 19.3% (30.6-101.7%), and the blood gas analyses were PaCO2: 41.4 ⫾ 3.8 torr (33.3-52.1 torr) and PaO2: 74.9 ⫾ 9.3 torr (53.0-97.4 torr). Mean operative time was 55 minutes for VTLB and 83 minutes for OLB. The overall mean duration of chest tube CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 General Thoracic Surgery, continued drainage was 1.3 days. There was no operative mortality. Postoperative complications were seen in 4 cases (8%). Two patients had pneumothorax, and the other two experienced the exacerbation of DILD, which were successfully treated with steroid pulse therapy. Although only one biopsy was considered inconclusive (2%), the remaining 49 patients established a final diagnosis. Histological diagnosis revealed non-specific interstitial pneumonia in 26 patients, usual interstitial pneumonia in 11, and other type of idiopathic interstitial pneumonias in the remainder. CONCLUSION: VTLB for the diagnosis of DILD is a safe method even in patients with impaired pulmonary function, although some patients needed to conversion to OLB due to the pleural adhesion or lung injury. This study also supports the notion that patients with idiopathic interstitial pneumonias may be at risk of exacerbation of their underlying disease following VTLB. CLINICAL IMPLICATIONS: VTLB will contribute to the safe and effective pathologic diagnosis of DILD in most cases, even if the pulmonary function is considerably impaired. DISCLOSURE: Noriyasu Usami, None.

PURPOSE: The reported accuracy of surgical biopsy for interstitial lung disease (ILD) is highly variable. We have audited our results to determine whether operative techniques do alter outcomes. METHODS: 123 patients [68 men and 55 women with a median age of 57 (range from 18 to 84) years] underwent lung biopsy for diffuse interstitial lung disease in our unit from 1992 to 2004. Video assisted thoracoscopy (VATS) was used on 66 cases (54%) and the rest underwent traditional open biopsy. Outcomes of the study were: rate of definitive specific diagnosis, change of diagnosis and change of therapy, complications, and to assess the weight of surgical variables (surgical procedure, side, number and size of samples) as predictors of outcomes. RESULTS: There was one postoperative death (0.8%) and 13 patients (10%) had any complication. A definitive specific diagnosis was obtained in 91 cases (74%). A different diagnosis from presumed pre-operative one was encountered on 59 (48%) cases, and a definite change of therapy was confirmed on 27 (22%) of cases. The type of procedure (either VATS or open), or number and size of specimens did not significantly affect the chance of a definitive diagnosis, complications, change of diagnosis, or change in therapy. (Table 1, p⫽ non significant in all cases). CONCLUSION: Lung biopsy can be done safely with high rates of specific diagnosis and low incidence of complications. We have not proven that surgical variables alter the outcomes in terms of definitive or change of diagnosis, complications or change of therapy. CLINICAL IMPLICATIONS: Different approaches and techniques do not contribute to increase usefulness of surgical biopsy for ILD.

PURPOSE: Development of 3D-image guiding system for the thoracoscopic surgery. METHODS: Pneumothorax with radiologically-detectable bulla was selected as objective disease for this study. This is partly because the target lesions are located on the surface of the lungs, and partly because images of the virtual thoracoscopy derived from half-collapsed lungs most mimic the real thoracoscopic images.MPR images and virtual thoracoscopic images were reconstructed by 3-Dworkstation. The workstation monitor was set next to the thoracoscopic monitor to facilitate the comparison of these two images. Real-time virtual thoracoscopy guiding was performed by an assistant surgeon who reconstructs, moves, and rotates the 3D images of the lung synchronizedly with the real thoracoscopic images. Marks were given to each bulla in the virtual images so as the surgeons easily detect on the real thoracoscopy. RESULTS: Virtual images gave good simulation to the real thoracoscopic images. Even small bulla was detected under assistance of marking on the virtual image. CONCLUSION: We report real-time 3D-image guiding system for the thoracoscopic surgery. This system gives reliable detection of bulla and reduction of operation time. Furthermore, operator could reduce the risk of misidentification of anatomical structure through comparison of real and virtual images. CLINICAL IMPLICATIONS: Endoscopic surgery is accompanied with limited view and lack of perspective. On site real-time computerguided endoscopic surgery system may be the key to this problem, but introduction of such technology to thoracic surgery has been outstripped in comparison with craniomaxillofacial surgery, cerebral nerve surgery, and orthopedic surgery.

Specific Change of Change of diagnosis diagnosis therapy Technique VATS (n⫽66) Open (n⫽57) Side Right (n⫽ 64) Left (n⫽ 59) Number 1 sample (n⫽105) 1 sample (n⫽18) Size ⬍4cm (n⫽ 69) ⬎4cm (n⫽54)

50 (76%) 41 (72%) 47 (73%) 44 (75%) 76 (72%) 15 (83%) 50 (72%) 39 (72%)

28 (42%) 31 (54%) 33 (51%) 26 (44%) 51 (49%) 8 (44%) 30 (43%) 27 (50%)

DISCLOSURE: Bhanumathi Lakshminarayanan, None.

14 (21%) 13 (23%) 13 (20%) 14 (24%) 22 (21%) 5 (28%) 12 (17%) 15 (28%) DISCLOSURE: Toshihiko Sato, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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DOES VARIATION ON SURGICAL TECHNIQUES ALTER OUTCOME OF LUNG BIOPSY FOR INTERSTITIAL LUNG DISEASE? Bhanumathi Lakshminarayanan MD* Antonio E. Martin-Ucar MD Michael F. Maguire MD Lynda Beggs David Beggs MD John P. Duffy MD Ellis Morgan MD Thoracic Surgery, Nottingham City Hospital, Nottingham, United Kingdom

THREE DIMENSIONAL IMAGE GUIDING SYSTEM FOR THE THORACOSCOPIC SURGERY Toshihiko Sato MD* Seiki Hasegawa PhD Teruhisa Takuwa MD Yoshitomo Okumura MD Hyogo College of Medecine, Nishinomiya, Japan

Wednesday, November 2, 2005 General Thoracic Surgery, continued FUNCTIONAL ASSESSMENT OF A NEW STAPLE LINE REINFORCEMENT IN LUNG RESECTION Douglas M. Downey MD* Michael Michel MD Joseph G. Harre DVM Jerry W. Pratt MD Keesler Medical Center, Biloxi, MS PURPOSE: Staple line reinforcement is routinely performed during nonanatomic lung resection utilizing bovine pericardium (peri-strips) and expanded polytetrafluorethylene (ePTFE). Both materials have been previously shown to increase staple line durability and reduce the overall incidence of prolonged air leak, however neither material has been shown to be truly absorbable in in vivo studies. Porcine small intestinal submucosa (SIS) has had many applications as a bioabsorbable tissue reinforcement, but has not previously been studied in either a human or animal model as a reinforcement for nonanatomic pulmonary resection. Its healing properties are well documented in human and animal studies. Our study strictly assessed immediate staple line strength in healthy pig lung tissue at different intrabronchial pressures to demonstrate SIS as an effective pulmonary staple line reinforcement. METHODS: Eight pigs were subjected to bilateral apical lung resections with a GIA stapling device; one side was reinforced with SIS, while the other was not reinforced. The lung reinforced was chosen at random so that each animal may serve as its own control. The lungs were then inflated to sequentially increased intrabronchial pressures (5 – 75 cm H2O) for 60-second intervals while the chest was filled with saline under direct visualization monitoring for air leak. RESULTS: Staple lines reinforced with porcine small intestinal submucosa had significantly better durability as determined by Kaplan-Meier survival calculations with respect to leak rate as a function of pressure. CONCLUSION: Reinforcement of staple lines with small intestinal submucosa (SIS) allows pulmonary staple lines to tolerate significantly higher intrabronchial pressures without demonstrating air leak at the staple line. CLINICAL IMPLICATIONS: Staple line reinforcement with SIS is effective in terms of improving the leak threshold of the GIA staple lines. Potentially, SIS may prove to be a more suitable material for pulmonary staple line reinforcement in individuals requiring nonanatomic lung resection, due to its healing properties. Long-term in vivo studies are underway to characterize the SIS tissue reaction in the chest, its tendency toward generation of pleural adhesions, resorption and tissue encapsulation. DISCLOSURE: Douglas Downey, Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Cook, Inc. for providing the (10) staple line reinforcements (at the time of the project not yet available for human use)for our project at no cost to our institution. Each valued at $150.

MINIMALLY INVASIVE CLOSURE TECHNIQUES FOR RECALCITRANT BRONCHOPLEURAL FISTULAS Lindsey Clemson BS* James Lynch RRT Eric Walser MD Joseph Zwischenberger MD Thomas Black MD University of Texas Medical Branch, Galveston, TX PURPOSE: The treatment most often recommended for persistent symptomatic central bronchopleural fistulas (BPF) involves thoracotomy with suture closure and transposition of a vascularized muscle flap or omentum to the bronchial leak site unfortunately, this can be ineffective or medically contraindicated. We used minimally invasive closure techniques including bioadhesives (glues), stainless steel coils and prolene mesh in combination with different imaging techniques to treat recalcitrant central BPF to achieve successful closure in 3 of 5 patients. METHODS: We initially (n⫽2) utilized cyanoacrylate glue injected transthoracically under fluoroscopic guidance into the BPF lumen forming a plug. Next, two patients failed muscle flap transposition and CT guided transthoracic injection of a single coil plus Albumin/Glutaraldehyde glue into the fistula. We then used a transtracheal guidewire positioned under fluoroscopy to identify the fistula and thoracoscopic placement of a prolene mesh patch over the defect secured by fibrin sealant to prevent glue dislodgement. Most recently, stainless steel coils and cyanoacrylate glue were transthoracically injected into and adjacent to a postpneumonectomy bronchial stump under thoracoscopic visualization. RESULTS: Glue injection under fluoroscopic guidance was successful once while in another, the glue plug was dislodged by coughing. Placing a prolene mesh patch over the BPF secured with fibrin sealant was successful in 1/2 patients. Our most recent effort was to traverse the fistula

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with coils and inject glue transthoracically. The coils served as a scaffold to stabilize the glue within the tissue and successfully occluded the BPF. CONCLUSION: Utilizing these minimally invasive alternative closure techniques, we present the evolution of successful management of recalcitrant central BPFs in 3 of 5 patients. Due to a high intrathoracic to bronchial pressure gradient, one must stabilize the fistula plug. The use of prolene mesh to cover the stump or the injection of coils perpendicularly to the fistula provides a site for inflammation and fibrosis to occlude the fistula. CLINICAL IMPLICATIONS: These image-guided transthoracic techniques provide alternative management for recalcitrant central BPFs in medically compromised patients. DISCLOSURE: Lindsey Clemson, None. THE CHEST WINDOW IN THE TREATMENT OF COMPLEX INTRA-THORACIC INFECTIONS Robin Varghese MD* Richard I. Inculet MD Dalilah Fortin MD Richard A. Malthaner MD London Health Sciences Center, London, ON, Canada PURPOSE: Patients with an primary empyema,lung abcess,or postpneumonectomy empyema, who are critically ill , may only tolerate surgical drainage of the infection. A study was undertaken to examine the outcome of patients who had a complex intra-thoracic infection managed by rib resection and the creation of an open chest window. METHODS: A retrospective review was undertaken of all patients presenting to a single institution with a complex intra-thoracic infection and who were treated with a rib resection and creation of a chest window. RESULTS: Between 1998 and 2005, a total of 35 patients (8 females, 27 males, average age 59 years) were treated in this fashion. There was insufficient data available for 3 patients. Twelve patients (34%) presented with a primary intra-thoracic infection (PII). Twenty patients (57%), developed an intra-thoracic infection secondary to an obstructing lung cancer or following a recent thoracotomy and pulmonary resection(SII). Average post-operative length of stay was 13 days (median 7.5 days). There were 5 postoperative deaths (14.3%); 4(SII)patients(2 died from sepsis,1 from hemorrhage,1 from other cause) and 1 (PII) patient died from sepsis. Eight (SII) patients (23%) died after discharge from hospital from non- septic causes. Primary closure of the window was successfully performed in 2 (SII) patients (average time to closure-15.5 months) and 5 (PII) patients (13.2 months). Closure of the window by secondary healing occurred in 5 (SII) and 3 (PII) patients. Windows presently remain open or were open until death in 9 (SII) patients and 3 (PII) patients. CONCLUSION: The open chest window technique successfully managed the intra-thoracic infection in 84% of the patients. It is associated with acceptable post operative mortality and length of hospital stay. Closure of the window, either by surgery or by secondary healing, can be accomplished in large percentage of patients. CLINICAL IMPLICATIONS: The use of the open chest window to manage the desparately ill patient, with a complex intra-thoracic infection, remains an effective treatment strategy. DISCLOSURE: Robin Varghese, None. ENDOSCOPIC AND THORACOSCOPIC TRAINING ON THIEL HUMAN CADAVERS: A MODEL TO TEACH ADVANCED PROCEDURES Philippe Morand MD* Isabelle Fresard MD Christian Chanson MD Gunter Rager MD Lukas Kra¨henbu¨hl MD Hopital Cantonal Fribourg, Fribourg, Switzerland PURPOSE: The endoscopic procedures became more and more complex over the past years. These procedures require a special training which can be effectively and safely performed outside the operating theatre. Several training programs have been developed for teaching basic surgical skills to young residents but very few methods are available for advanced endoscopy and surgery. The Thiel method has several advantages over other training systems. Training on cadavers, compared to animal models offers an anatomy identical to that found in patients without needing anesthesia. Moreover, a same cadaver can be used for several different procedures belongings to surgery and pneumology. METHODS: The conservation of human cadavers is realized by the Thiel method (Ann Anat 1992, 174: 185-195). The technique allows a floppy preservation of human tissue similar to that found in living counterparts. Our center organizes courses for endoscopy, thoracic surgery, bariatric, antireflux, abdominal wall, colon and rectum surgery. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 General Thoracic Surgery, continued Five video monitors with camera system are available with the possibility of computerized image recording. RESULTS: Different courses were performed and evaluated by the participants (6 was the best and one the lowest voting). Course evaluation was performed on an anonymous questionnaire for the course organisation, theoretical and practical aspects and the tutors. The results were for thoracic surgery 5.73 ⫾ 0.05, endoscopy 5.82 ⫾0.07. CONCLUSION: Training on cadaver specimens gives the opportunity to perform major operations in endoscopy and thoracic surgery respecting the human ethics. Difficult endoscopical and surgical procedures can be teached step by step under real anatomic situations in small groups. Therefore, it is probably the best method for advanced surgeons to improve their performance. A good preservation of the tissue depends on a special know-how necessitating a tight collaboration with an anatomical department. From this point of view this method is reserved to a small quantity of recognized national or international centers. CLINICAL IMPLICATIONS: Reduced learning curve of complex surgical procedures and higher quality control. DISCLOSURE: Philippe Morand, None.

PURPOSE: We hypothesized that dyspnea in patients with emphysema was related with hyperinflation by highly destructed part with excessive trapped air and poor perfusion which could be expressed as “air-oma”. Accordingly we selected patients for LVRS with functional imaging modalities (HRCT, perfusion scan, dynamic MRI etc.)as well as functional examinations. We report early and long-term results of LVRS for consecutive 31 patients. METHODS: Between October 1995 and June 2003 we selected 31 patients who felt severe dyspnea during walk. Their characteristics and mean values in function testing were as follows; a mean age of 68 yr (range 52 - 80), BMI of 18 Kg/m2 (15-23), %FEV1 of 27% (11- 46), %RV of 263 % (178-385), and 6 MWD of 287m (75 – 450). We decided airoma in the upper lobes of 12 patients, in the lower lobes of 12 patients, in both lobes of 6 patients, and in the middle lobe of 1 patient, and resected these by bilateral procedure in 17 patients, and by unilateral procedure in others. All patients were followed ranging from 1.8 to 9.5 years (median 6.5 yrs). RESULTS: There was no in-hospital mortality. Two patients underwent reexploration for air leak, and two patients needed mechanical ventilation for a few months one month after LVRS. All patients except one reported decrease in dyspnea, and were satisfied with surgery. Eleven patients out of 22 patients who underwent LVRS by Dec 1999 survived more than 5 years. The Kaplan-Meier survival after LVRS were 96.8%, 93.6%, 90.1%, 72.1%, 49.3% at 1,2,3,4,and 5 years, respectively. There were no difference between survival of patients with upper lobe airoma and those with lower lobe airoma. CONCLUSION: Lung volume reduction surgery for patient with emphysema selected by functional imaging modalities produces symptomatic improvement in early-term, and better survival at least 3 years. CLINICAL IMPLICATIONS: Lung volume reduction surgery is a good and promising palliative treatment for patients with advanced emphysema wherever the target area , or airoma, is located. DISCLOSURE: Koji Chihara, None. EMERGENCY LUNG RESECTIONS FOR LIFE-THREATENING MASSIVE HEMOPTYSIS Alexandru M. Botianu MD* Petre A. Botianu RN University of Medicine and Pharmacy From Targu-Mures, Romania, Targu-Mures, Romania PURPOSE: This study analyses the outcome of patients with massive hemoptysis without response to conservative treatment and requiring emergency thoracotomy for hemostasis. METHODS: Between 1990 and 2005 we performed emergency thoracotomy with lung resection in 4 patients with life-threatening hemoptysis with no response to conservative treatment. Etiology was tuberculosis in all patients, one being with an anaerobic overinfection and one with atypical mycobacteria. The procedures performed were: lobec-

General Thoracic Surgery Interventions 12:30 PM - 2:00 PM USE OF RECOMBINANT FACTOR VII ACTIVATED IN SURGERY FOR PLEURAL EMPYEMA Petre V. Botianu RN* Alexandru A. Botianu MD University of Medicine and Pharmacy from Targu-Mures, Romania, Targu Mures, Romania PURPOSE: The aim of our study is to evaluate the advantages of using recombinant factor VII activated to improve hemostasis during surgery for empyema and to establish the optimal dose and moment of administration. METHODS: During 36 months (march 2002 - march 2005) we used recombinant factor VII activated in 34 patients who underwent major surgery for empyema: 26 patients with pleuro-pulmonary decortication (4 for overinfected posttraumatic hemothorax, 16 non-specific empyemas and 6 tuberculous empyemas) and 8 thoracopleuroplasties. A number of 10 decortications were performed in cirrhotic patients. Intraoperative findings and clinical criteria were used to evaluate the quality of hemostasis. RESULTS: In all cases we achieved good hemostasis. We had no re-operation for hemostasis. There was a significant reduction of perioperative blood losses and of transfused blood. Most patients required only small doses (1,2 - 2,4 mg/60 - 120 IU) administered at the beginning of the procedure. We encountered no side effects and only one postoperative death through sepsis in a patient with pulmonary gangrene. CONCLUSION: Recombinant factor VII activated appears as an excellent hemostatic agent for diffuse bleeding during surgery for pleural empyema; it also improves closure of small aerian leaks and facilitates re-expansion of the lung. CLINICAL IMPLICATIONS: Use of recombinant factor VII activated may improve the outcome of patients undergoing major surgery for pleural empyema. For a complete and correct evaluation, further prospective randomised studies are required. DISCLOSURE: Petre Botianu, None.

TISSUE SEALANTS: THE ROLE OF ALBUMIN/GLUTARALDEHYDE IN THORACIC SURGERY Thomas Black BS* James E. Lynch RRT Joseph Zwischenberger MD University of Texas Medical Branch–Galveston, Galveston, TX PURPOSE: Sealants have been developed to achieve hemostasis or tissue adhesion during surgery. We examined the use of an Albumin/ Glutaraldehyde sealant in 16 thoracic surgery patients as an adjunct to controlling air leaks on the lung parenchyma following resection. Air leak CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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EARLY AND LONG-TERM RESULTS OF LUNG VOLUME REDUCTION IN PATIENTS WITH EMPHYSEMA Koji Chihara MD* Daisuke Nakajima MD Akihiko Yamashina MD Masanao Nakai MD Hisashi Sahara MD Toru Tsuda MD Tomoya Kono MD Akihiro Osumi MD Akihiro Aoyama MD Fenshi Chen MD Noritaka Isowa MD Shotaro Iwakiri MD Shizuoka City Shizuoka Hospital, Shizuoka, Japan

tomy - 2 cases (one with simultaneous artery-bronchus stapling in a patient with 2 intraoperative cardiac arrests), pneumonectomy - 1 case and one non-anatomic resection with lateral suture of a pulmonary artery branch. RESULTS: In all cases we achieved good hemostasis with no postoperative bleeding. We encountered a high rate of peri-operative complications: one patient with 2 intraoperative cardiac arrests, 3 patients with postoperatve pneumonia and one postoperative death in a patient with pneumonectomy performed after 2 cardiac arrests resuscitated in another unit. Only one patient had an uneventful postoperative course. CONCLUSION: Emergency thoracotomy and resection for massive hemoptysis has a high morbidity and mortality, especially when other complications occur (such as tracheo-bronchial innundation, acute anemia or cardio-respiratory arrest). It should be reserved as a life-saving procedure when other conservative treatments are ineffective or unavailable. CLINICAL IMPLICATIONS: Treatment of massive hemoptysis should be early and aggressive. If conservative treatment (hemostatic drugs, bronchoscopic hemostasis, embolisation) fail, the thoracic surgeon should be called immediately. Surgery gives good results if resection is performed in patients with stable hemodinamic and respiratory status, before development of other severe complications. DISCLOSURE: Alexandru Botianu, None.

Wednesday, November 2, 2005 General Thoracic Surgery Interventions, continued following pulmonary resection has been associated with an increase in morbidity as well as increased length of stay. METHODS: Since April of 2002 we have used an Albumin/Glutaraldehyde sealant selectively at this institution for the intraoperative treatment of recalcitrant air leaks following pulmonary resections. All patients had pulmonary resection with persistent air leaks intraoperatively at the parenchymal staple line or at the fissure dissection site at 20 cmH2O pressure lung inflation. After obtaining local IRB approval, we retrospectively compared 16 patients in which an Albumin/Glutaraldehyde sealant was used with a “plug and cap” technique to seal air leaks on the surface of the lung to 16 case matched controls in which no air leaks were noted intraoperatively. We examined these patient’s records for differences in length of operation, ICU time, number of days with chest tube, number of days with air leak, chest tube output, and total hospital length of stay. RESULTS: We found no difference in length of operation, ICU time, days with chest tube, days with air leak, chest tube output, or length of stay. Patients treated with an Albumin/Glutaraldehyde sealant exhibited no adverse reactions or need for reoperation for closure of persistent air leak. CONCLUSION: Despite attempts to match with historical controls, we had a selection bias towards more severe airleaks in the sealant group. In this unblinded, retrospective, matched controlled outcomes study Albumin/Glutaraldehyde sealant normalized patients with recalcitrant intraoperative parenchymal airleaks following resection to those without intraoperative airleaks. CLINICAL IMPLICATIONS: Albumin/Glutaraldehyde sealants represent a valuble tool in the management of intraoperative closure of recalcitrant airleaks following resection. DISCLOSURE: Thomas Black, Grant monies (from industry related sources) This study was funded in part by Cryolife the manufacturer of BioGlue® an Albumin/Glutaraldehyde sealant. PROOF-OF-PRINCIPLE CLINICAL TRIAL OF BEXAROTENE FOR THE TREATMENT OF NON-SMALL CELL LUNG CANCER W J. Petty MD* Konstantin H. Dragnev MD Vincent A. Memoli MD James R. Rigas MD David Johnstone MD Ethan Dmitrovsky MD Dartmouth Medical School, Hanover, NH PURPOSE: Certain non-classical retinoids including the rexinoid compound, bexarotene, bypass clinical resistance to classical retinoids. Bexarotene-treatment is associated with an improvement in survival in a subset of patients. We sought to determine mechanisms of reponse or resistance to bexarotene. METHODS: Bexarotene-treatment was studied using a derived, RAresistant human bronchial epithelial cell line and several non-small cell lung cancer cell lines. We then performed a proof-of-principle clinical trial in patients with resectable NSCLC. Patients underwent a pretreatment biopsy followed by eight days of oral bexarotene and surgical resection. Pharmacokinetics and biomarker changes were assessed. RESULTS: Bexarotene-treatment repressed expression of cyclin D1, cyclin D3, EGFR, and phospho-EGFR in vitro. In the proof-of-principle clinical trial, ten patients were evaluable for pharmacokinetic and lipid measurements and four patients were evaluable for changes in biomarkers. A strong correlation existed between hyperlipidemia and tumor tissue drug levels. The cases with the highest tissue concentrations of the drug demonstrated repression of cyclin D1, cyclin D3, or EGFR while cases with lower tissue concentrations did not. CONCLUSION: Bexarotene treatment represses cyclin D1 and cyclin D3 both in vitro and in clinical lung cancers. A tumor tissue pharmacokinetic and pharmacodynamic relationship exists for this drug. CLINICAL IMPLICATIONS: A correlation between tumor tissue bexarotene concentrations and bexarotene-induced hyperlipidemia may help to explain why this drug would prolong survival in patients who develop hyperlipidemia. DISCLOSURE: W. Petty, None. ADJUVANT CHEMOTHERAPY AFTER SURGICAL RESECTION FOR SMALL-CELL CARCINOMA OF LUNG Euntaik Jeong MD* Hakryul Kim MD Wonkwang Univ. Hospital, Iksan Jeonbuk, South Korea PURPOSE: Small-cell carcinoma of lung has a tendency of rapid growth and early wide metastasis. In spite of high response rate of combination chemotherapy alone or with radiotherapy, overall long term

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survival rate is very disappointed. According to autopsy findings, the common cause of failure is local recurrence in primary cancer site. So, surgical resection with combined chemotherapy has been recently attempted for very early stage of small-cell carcinoma of lung. METHODS: We treated 10 patients (TNM I: 5 cases, II: 5 cases) undergoing surgical resection for small-cell carcinoma of lung with adjuvant chemotherapy in an attempt to prolong survival. Of these, 9 patients received chemotherapy, and retrospective study was undertaken for survival (Kaplan-Meier analysis). RESULTS: Median survival time was 26 months, 2-, 5-year survival rate was 68.6%, 46.7%. If 1 patient without chemotherapy was excluded, 2-, 5-year survival rate was 76.2%, 50.8%. No survival difference was seen between patients with TNM I, II stages. CONCLUSION: Adjuvant chemotherapy after surgical resection results in prolonged survival for patients with TNM stage I, II small-cell carcinoma of lung. CLINICAL IMPLICATIONS: We can apply this adjuvant chemotherapy after surgical resection for the improvemnet of survival of patients with early stage small-cell carcinoma of lung. DISCLOSURE: Euntaik Jeong, None. RADIOTHERAPY FOR NON-SMALL CELL LUNG CANCER IN PATIENTS WITH COMPROMISED HEARTS Federico L. Ampil MD* Shawn Milligan MD Glenn M. Mills MD Gloria Caldito PhD Louisiana State University Health Sciences Center, Shreveport, LA PURPOSE: Objective: Therapeutic options for patients with non-small cell lung cancer (NSCLC) and compromised hearts are limited. Such individuals are not often included in randomized trials. Therefore, optimal therapy in this particular group of people is unclear. We present our experience using radiotherapy for NSCLC in eight patients with cardiac compromise because few reports of patient outcomes exist. METHODS: Methods: Between 1993 and 2003, eight individuals with compromised hearts (necessitating pacemaker assistance, coronary artery bypass surgery, or cardiac valve replacement) were treated by radiation alone (7 patients) or with chemotherapy (1 patient) for lung cancer. The mean follow-up period was 12.5 months. RESULTS: Results: At diagnosis, the average patient age was 62 years. In most patients, tumor histology was non-small cell cancer, the disease stage was advanced (stage III, 5 patients or IV, 3 patients), and a long history of smoking was documented. The survival rates at 6 months, 1 year, and 2 years were 50%, 25%, and 25% respectively. The median survival was longer in patients with stage III compared to that of persons with stage IV disease (11 months and 3 months respectively, p⫽0.04). There were no adverse cardiac events during and after irradiation. CONCLUSION: Conclusion: The presence of cardiac compromise in lung cancer patients should not be viewed as a general contraindication for radiotherapy. Management of these neoplasms by radiation deserves consideration because this treatment could favorably influence survival in select patients with advanced, non-disseminated malignancy. CLINICAL IMPLICATIONS: Although most patients with advanced lung cancer and coexisting, significant cardiac disorders may not live long enough to develop delayed cardiovascular sequelae, radiotherapy should be administered with great caution to these individuals. DISCLOSURE: Federico Ampil, None. PROGNOSTIC FACTORS AND SURVIVAL IN PRE- AND PEROPERATIVE DETECTED AND RESECTED N2 NON-SMALL CELL LUNG CANCER Edwin Van Velzen MD* Meander Medical Centre, Amersfoort, Netherlands PURPOSE: Patients with stadium III (pN2) non-small cell lung cancer form a heterogeneous group with broad differences in survival. Some selected patients seem to benefit from surgery, but in most patients other therapies are preffered. The present study was performed to select groups of patients who will and will not benefit from surgery. METHODS: A total of 242 patients with stadium III (pN2) who all underwent mediastinoscopy and tumor resection between 1977 and 1995 were retrospectively reviewed. Mean age was 64.2 years. Mediastinoscopy showed malignancy in 56 patients (23.1%). Resection was complete in 198 patients. Most patients (n⫽150) had one mediastinal lymph node station involved and T2 was the most frequently found T-status. Hundred and CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 General Thoracic Surgery Interventions, continued sixty-six patients received adjuvant therapy, mainly radiotherapy.Statistical analyses were performed, using the Kaplan-Meier method, the log rank test and Cox’s proportional hazards model. RESULTS: The cumulative post-operative survival at 5 years was 20.3%. The number of mediastinal stations involved (ⱕ 2; p⫽0.03)(Fig.1.) and age (ⱕ 60 years; p⫽0.035) significantly influenced survival whereas T-status (T1/T2 versus T3/T4; p⫽0.056) approached significance. No differences in survival between patients with a positive versus negative mediastinoscopy, or between patients with a complete versus incomplete resection were found. However, all patients with a positive mediastinoscopy and incomplete resection died within 3 years. Multivariate analysis showed the number of mediastinal lymph node stations involved (RR of 0.33, 95% CI of 0.163 to 0.663; p⫽0.002) and age (RR of 1.013, 95% CI of 1.0 to 1.027; p⫽0.048) to be prognostic for survival. CONCLUSION: Stadium III (pN2) patients with ⱕ 2 mediastinal stations involved (even detected at mediastinoscopy) and those aged ⱕ 60 years can benefit from surgery. Patients with ’bulky’or fixed multistation disease and those with a T3 or T4 tumor should not be operated upon. CLINICAL IMPLICATIONS: Accurate staging of pN2 patients may prevent them from an advanced (incomplete) resection with high morbidity and even mortality, but on the other hand, can sort out the patients who will benefit from surgery.

SLEEVE-PNEUMONECTOMY FOR LUNG CANCER: FOR WHICH PATIENTS? Dragan R. Subotic PhD* Dragan V. Mandarich PhD Nikola D. Atanasiadis MD Ljiljana V. Andrich MD Institute for Lung Diseases, Belgrade, Serbia

DISCLOSURE: Edwin Van Velzen, None. PHARMACOKINETIC ANALYSIS OF ISOLATED LUNG PERFUSION WITH MELPHALAN IN PATIENTS WITH RESECTABLE PULMONARY METASTASES Marco J. Grootenboers MD* Jeroen M. Hendriks PhD Wim J. van Boven MD Catherijne A. Knibbe PharmD Paul E. Van Schil PhD Franz M. Schramel PhD St. Antonius Hospital, Nieuwegein, Utrecht, Netherlands PURPOSE: Prognosis of patients with pulmonary metastases remains poor with a 5-year survival of approximately 20-40% after complete surigical resection. Isolated lung perfusion (ILuP) is a promising surgical technique to deliver high-dose chemotherapy with minimal systemic toxicity, however exact pharmacokinetics of melphalan (MN) during ILuP remain unclear. An extension trial of a previous reported phase-I clinical trial of IluP with MN combined with pulmonary metastasectomy for resectable lung metastases was conducted to perform pharmacokinetic analysis.

PURPOSE: To analyse operative mortality, morbidity and factors influencing long term survival in patients who underwent sleeve pneumonectomy for primary NSCLC. METHODS: Retrospective study including 42 patients who underwent sleeve pneumonectomy for primary NSCLC in the period 1995-2004. Survival, operative mortality and morbidity were analysed and compared with control group of extended resections in the same period. Particular analysis of the influence of the N-factor to survival was done. Statistics: X-square test, survival analysis using the Kaplan-meier method. RESULTS: In the analysed group, 39 pts. underwent right and 3 one-stage left sleeve pneumonectomy (M:F ratio 6:1). Compared to the period 1995-2002 with 36 pts, after inclusion of additional 6 pts. till 2004, operative mortality decreased from 19.44% to 16.66%. Operative morbidity was 26.19%. Before inclusion of the last 6 pts, 3 and 5-year survival was 27.7% and 11.1% respectively. Two of the new 6 pts. are still alive two years after the operation, whilst two of them died 7 and 7.5 months after the operation from cancer dissemination. Additional two survived more than one year and are still alive. There were no long term survivors with N2 disease. CONCLUSION: Sleeve pneumonectomy can be done with acceptable mortality that should be well below 15%. Nevertheless, we support the attitude that such an operation is justified only if associated with 5-year survival of at least 20%. CLINICAL IMPLICATIONS: detailed preoperative assessment in order to assess N-component is mandatory to achieve optimal patient selection for this type of lung resection. DISCLOSURE: Dragan Subotic, None. PREDICTIVE VALUE OF POSITIVE CYTOLOGY IN VIDEOASSISTED THORACIC SURGERY (VATS) PERICARDIAL WINDOW Siyamek Neragi-Miandoab MD* Luis M. Argote-Greene MD William G. Richards PhD Lambros Zellos MD Raphael Bueno MD David J. Sugarbaker MD Michael T. Jaklitsch MD Boston Medical Center, Boston University School of Medicine, Boston, MA PURPOSE: Pericardial effusions represent a terminal stage in patients with malignant disease. A VATS pericardial window (PW) can palliate symptoms. Longevity of the procedure may depend on pericardial fluid cytology. METHODS: Retrospective review of 66 VATS PW for malignant pericardial effusion (MPE); males/female ratio 36/30, mean age 54.8 ⫾ CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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METHODS: From May 2001 to December 2004, 23 patients underwent ILuP with MN in increasing doses of 15, 30, 45 and 60 mg melphalan at 37°C and 42°C consecutively, followed by surgical resection of lung metastases. The pharmacokinetics of MN during ILuP were investigated using concentrations in tumour, lung tissue, perfusate and plasma with different perfusate drug concentrations and perfusion temperatures. RESULTS: In total, 29 procedures of ILuP with complete metastasectomy were performed. High concentrations of MN were recorded in the perfusate in comparison to low systemic concentrations. Although there was a trend to correlation between the averaged MN concentrations in the perfusate after initiation of the procedure and the dose of MN at the start of the procedure, no significant correlation between perfusate and lung tissue or tumour MN concentrations could be recorded due to large variability in MN concentrations and the small number of patients per dose level. CONCLUSION: ILuP with melphalan resulted in high-dose local chemotherapy with minimal systemic concentrations. In this study, no significant correlation between perfusate MN concentrations and tumour or lung tissue MN concentrations could be observed. CLINICAL IMPLICATIONS: The absence of correlation between the perfusate and tumour or lung tisssue concentrations justifies further investigation of the pharmacokinetics of drugs during IluP in order to be able to account for observed variability. DISCLOSURE: Marco Grootenboers, None.

Wednesday, November 2, 2005 General Thoracic Surgery Interventions, continued 14.3 (ranging from 19 to 79). Kaplan-Meyer survival curve and Log-Rank List were used to analyze the data. RESULTS: Mean hospital stay was 8.7 ⫾ 5.5 days. Overall median survival was 5.4 months: 43% at 1 yr, 17.6% at 3 yrs, 10% 5 yrs. There was no difference in survival between patients younger than 65 compared to older patients. There was no difference in survival between genders. Mean survival in cytology negative patients (n⫽32) was 12 ⫾ 0.9 months, compared to 4.7 ⫾ 0.09 months in cytology positive patients (n⫽34, Log-Rank, p⫽0.0416). The 5-year survival in cytology negative patients was 19%. Positive cytology predicted death within 36 months. There was no correlation between length of hospital stay and survival. The one year survival in lung and esophageal cancer patients was 32.7% and for all other cancers 44.8%, and the 2 year survival was 19.8% and 28.9% respectively(p ⫽ NS).Seven patients (8.2%) required repeat PW . Recurrence occurred in 4 cases after anterior PW only, in 2 cases after posterior PW only, and in 1 case after combined anterior and posterior PW. CONCLUSION: Pericardiotomy is an effective palliative intervention that avoids repeated invasive procedures in 90% of cases. Positive cytology of the pericardial effusion is predictive of short survival. Survival in this series is better than literature benchmarks. CLINICAL IMPLICATIONS: Both an anterior and posterior PW should be placed to avoid recurrence. Fluid cytology should be obtained during PW for prognostic purposes.

Pathology of Malignant Pericardial Effusion

n⫽

NSCLC&SCLC Breast Cancer Esophageal Neoplasm Non-Hodgkin-Lymphoma Leukemia Other Tumors and Metastatic Disease*

32 8 5 5 3 13

*(Thymoma 1, malig melanoma 1, chodrosarcoma 1, angiosarcoma 1, osteosarcoma 1, spindle cell neoplasm 1, rhabdomyosarcoma 1, nerve sheath tumor 1, mesothelioma 1, colon ca 1, ovarien ca 1, testicular ca 1, UKO)

DISCLOSURE: Siyamek Neragi-Miandoab, None. COMPUTER ASSISTED STAPLE RESECTION: UTILIZATION OF A NEW TECHNIQUE FOR MAJOR PULMONARY RESECTION DURING MINIMAL ACCESS THORACIC SURGERY Wickii T. Vigneswaran MBBS* Loyola University Medical Center, Maywood, IL PURPOSE: Computer assisted stapling of tissues (CAST) is a new technology in evolution. It provides the surgeon with more ability to carry out procedures when minimal access is used for major surgical procedures. Preservation of the chest wall mechanics is a major factor in patient recovery following pulmonary resection (PR). The posterolateral muscle dividing thoracotomy, the ‘standard ‘approach for major PR is associated with decreased pulmonary function and late muscle atrophy. The alter-

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nate approach of VATS for PR has major limitation including it is restricted to small tumors, inadequate mediastinal lymphadenectomy and tumor implantation at port sites. A totally muscle sparing lateral thoracotomy (MATS) is another approach that does not have the above limitations. The purpose of this report is to give our experience with CAST to divide lung parenchyma and to secure the vascular and bronchial structures during PR employing MATS. METHODS: One hundred consecutive patients undergoing major PR using the CAST, forms the basis of this report. All patients underwent MATS, sparing both latissimus dorsi and serratus anterior muscles. The data were collected prospectively for analysis. RESULTS: The procedures included 77 lobectomies, 5 pnuemonectomies and 18 major wedge or segmental resections. The median numbers of staples used were 5(range 1-13). Major malfunctions were encountered in 4 instances. Dislodgement of the cartridge from the cable occurred after successful deployment of the staples in two instances and in one instance an incomplete staple formation on a vessel requiring additional suture placement and one bronchial stapling failed requiring suture closure. CONCLUSION: We conclude that CAST for PR is feasible. The resection of lung is made simpler, particularly of the bronchial and vascular structures. The use of this new technology is advantageous when MATS is performed for lung resections. CLINICAL IMPLICATIONS: The technology is a significant advancement in currently available techniques for pulmonary resection. This will allow wider use of complete muscle sparing thoracotomy as a standard of practice for lung resection in the future. DISCLOSURE: Wickii Vigneswaran, Consultant fee, speaker bureau, advisory committee, etc. Advisory committee, Power Medical Interventions. EXTENDED THYMECTOMY BENEFITS PATIENTS WITH MYASTHENIA GRAVIS Jennifer Knight MD* Laurie Gutmann MD Michael Szwerc MD Geoffrey M. Graeber MD West Virginia University, Morgantown, WV PURPOSE: Treatment of Myasthenia Gravis includes medical therapies; anticholinesterase agents, immunosuppressive drugs, plasmaphoresis and gammagloubulin, also surgical therapy of a thymectomy. Medical therapies produce a remission rate low as 15%, surgical therapies high as 80%. We will show that early thymectomy relative to the onset of symptoms results in remission or improvement of symtoms of Myasthenia Gravis. METHODS: A 10-year retrospective review (1993-2002) of all thymectomies in myasthenic patients performed at one institution was undertaken. RESULTS: 28 patients reviewed (13 male/15 female), ages ranged from 5 to 74 (mean age of 39). Follow-up was 3 months to 6 years (3 patients lost to follow-up). 11 patients had their thymus removed within 5 months of the onset of symptoms, 10 of 11 (91%) had complete remission or improvement of symptoms. Those whose thymus was removed within 1 year of the onset of symptoms 15 of 19 (79%) had remission or improvement. Those whole thymus was removed within 6 years, 19 of 25 had remission or improvement. The mortality rate was 0 and the complication rate was 35% with complications that included respiratory and cardiac problems, infections, and DVTs. While all patients underwent a median sternotomy, 2 patients had their thymectomies with a CABG and one patient was a redo. 5 of the 28 (18%) had thymomas.Patient Status Time 0-5 months 12 months 6 yearsNo symptoms 8 4 (12) 4 (16)Improvement 2 1 (3) 0 (3)Same 1 1 (2) 1 (3)Worse 0 2 (2) 1 (3)Total 11 7 (19) 6 (25). CONCLUSION: Promptness of surgery relative to the onset of symptoms clearly shows a favorable outcome of thymectomy in myasthenia gravis. 91% of patients had improvement or complete resolution of symptoms if their thymus was removed within 5 months of the onset of symptoms. The benefit of a thymectomy is seen even for longstanding myasthenics. Performing a thymectomy early as possible will greatly increase the chances for complete remission of this disease. CLINICAL IMPLICATIONS: Complete thymectomy means better improvement in symptoms. DISCLOSURE: Jennifer Knight, None. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Interstitial Lung Disease 12:30 PM - 2:00 PM INFLUENCE OF INHALED DEXAMETHASONE ON THE BLEOMYCIN-INDUCED LUNG FIBROSIS IN RATS Li Xia MD* Shanghai pulmonary hospital, Shanghai, Peoples Rep of China

PURPOSE: Follicular bronchiolitis is a bronchiolar lesion characterized by the presence of hyperplastic lymphoid follicles with reactive germinal centers distributed along bronchovascular bundles. This disorder can be idiopathic or occur in association with systemic disorders such as connective tissue diseases or immunodeficiency syndromes. Relatively little is known regarding prognostic implications and treatment of this disorder. METHODS: We conducted a computer-assisted search of the Mayo Clinic database to identify cases of follicular bronchiolitis seen in adults (21 years of age or older) at our institution over a 9-year period, January 1, 1996 through December 31, 2004. Twelve patients were identified; relevant medical records and imaging studies were reviewed. RESULTS: The median range of these 12 patients was 54.5 years (range, 33-81 years) and included 4 men. Four patients had a smoking history and included 3 current smokers. Most patients presented with cough and/or exertional dyspnea. Six patients (50%) manifested crackles but no digital clubbing was observed. The histopathologic diagnosis of follicular bronchiolitis had been obtained by surgical lung biopsy in 11 patients (92%) and by bronchoscopic biopsy in one. Associated histopathologic findings included granulomas (2 cases), nonspecific interstitial pneumonia (1 case), usual interstitial pneumonia (1 case), patchy desquamative interstitial pneumonia (1 case), and carcinoid tumorlets (1 case). CT findings were variable and included nodules, ground-glass opacities, consolidation, and linear opacities. Pulmonary function findings were similarly variable. Underlying disorders included Sjo¨gren’s syndrome (1 patient), common variable immunodeficiency syndrome (1 patient), and bronchiectasis (1 patient). Six other patients had an elevated antinuclear antibody titer or rheumatoid factor. Most patients were treated with prednisone ⫾ azathioprine with generally favorable response. CONCLUSION: Follicular bronchiolitis is an uncommon form of bronchiolar lesions that can be idiopathic or occur in association with connective-tissue disorders, immunodeficiency syndromes, or ill-defined hypersensitivity reactions. This disorder is associated with variable findings on pulmonary function testing and CT scan. CLINICAL IMPLICATIONS: Corticosteroid therapy appears to be beneficial in the management of follicular bronchiolitis for most patients. DISCLOSURE: Michelle Aerni, None.

PURPOSE: To compare the effect and mechanism of inhaled with systemic dexamethasone on the bleomycin-induced lung fibrosis in rats. METHODS: 60 Sprague-Dawley rats were divided randomly into three groups including bleomycin-induced lung fibrosis group (Group A,n⫽20), inhaled dexamethasone group (Group B, n⫽20) and dexamethasone group (Group B, n⫽20). Each group was again divided into four subgroups, which were sacrificed on 1, 7 ,14 or 28 day. Bronchoalveolar lavage fluid (BALF)was got and the cells counting aswell as differentiation were figured out, HE stain was performed on the lung tissue sections to observe the extent of alveolitis and fibrosis, the semi-quantity of apoptosis cells in lung tissue was assay by in situ TUNEL(terminal deoxynucleotidy transferase-mediateddUTP nick endlabeling). RESULTS: (1)Compared group B and C with group A got lower percentage of neutrophils (P⬍0.05). (2)More severe fibrotic lesion was shown in the histological examination of the lung tissue sections of group A Compared with group B and C. (3)the apoptosis index (AI) of inflammatory cells in each subgroups of group B and C was higher than in group A, and there were no significance compared group B with C. CONCLUSION: Inhaled dexamethasone can induce apoptosis of pulmonary inflammatory cells and ameliorate the formation of bleomycininduced pulmonary fibrosis as well as systemic dexamethasone. CLINICAL IMPLICATIONS: Inhaled steroid drugs maybe improve interstial lung disease. DISCLOSURE: Li Xia, None.

LUNG FUNCTION IMPROVEMENTS WITH TIOTROPIUM BROMIDE IN CONSTRICTIVE BRONCHIOLITIS Ronaldo A. Kairalla MD* Marcelo J. Rocha MD Carlos R. Carvalho MD Pulmonary Division-Heart Institution (InCor), University of Sa˜o Paulo, Medical, Sa˜o Paulo, Brazil PURPOSE: Constrictive bronchiolitis is characterized by a fibrosing inflammatory process that surrounds rather than fills airways lumen, resulting in hyperinsufflation. HRCT demonstrates mosaic areas of decreased attenuation and vascularity and evidence of air-trapping. The disease is poorly responsive to steroids and adrenergics bronchodilators. Tiotropium bromide is a synthetic quaternary anticholinergic agent that is functionally selective for specific muscarinic receptors that mediate airway smooth-muscle contraction, and has an extremely long duration of action. METHODS: Six patients, 3 female, mean age 54.8y (⫾8.7)nonsmonkers, with clinical, HRCT and functional diagnosis of constrictive bronchiolitis, with lung biopsy in 4, were submitted to a trial of once-daily inhalation of tiotropium (18 mcg). RESULTS: Spirometry was performed before and 21 days after the medicationThe initial spirometry showed a an obstructive pattern (mean⫾SD): FVC⫽1.3⫾0.3L and FEV1⫽0.74⫾0.3L. After 21 days of tiotropium, in all patients the FVC improve more than 10%. Mean FVC also significatively improve (1.65⫾0.4, p⫽0.004), but not the FEV1 (0.91⫾0.4). CONCLUSION: In spite of fibrosing predominance in constrictive bronchiolitis, we observed a significant improvement of pulmonary function after 21 days of tiotropium. CLINICAL IMPLICATIONS: The influence of this finding on the evolution of the disease needs further investigation. DISCLOSURE: Ronaldo Kairalla, None.

SACOIDOSIS IN CHINA: A REVIEW OF HOSPITAL BASED COHORT Haiqing Chu MD* Tao Gui Shengxiang Ren BA Jingpo Zhang Huiping Li MD Guojun He MD Shanghai Pulmonary Hospital, Shanghai, Peoples Rep of China PURPOSE: To study how to avoid delaying the diagnosis and misdiagnosis through the substantive cases analyzed retrospectively. METHODS: Selected the sarcoidosis cases involved from 1980 to now from the archive of our hospital, analyzed their clinical manifestations, radiographic presentations, lab examinations such as PPD test, SACE, pulmonary function test, urine calcium and sera-calcium, 67Ga lung scan, and the way to confirm diagnosis. RESULTS: 1,There were 125 female patients (63.1%) and 73 male patients(36.9%) with the average age of 35.1 years old. The average duration of the disease was 6.1 months and stage evaluation showed that there were 3, 86, 91 and 18 cases from stage 0 to 3 respectively. 2,35.4% of the cases were found by the physical examination, while other 64.6% by complaint of various symptoms such as cough, breathless, fever, chest pain. The main extrapulmonary manifestation was superficial lymph node enlargement, eyesight faintness, and skin lesions. 3,The usual presentation of the chest X-ray and CT was hilar and/or mediastinal lymph node enlargement accompanied with bilateral diffusion lesion or not. It was prone to make a wrong diagnosis and the rate of misdiagnosis is as high as 39.9%. 4,Among the various biopsy means, mediastinoscopy lymph node biopsy is the most valuable, and the superficial lymph nodes, skin nodus, bronchial mucous and transbronchial lung biopsy are worth recommending. CONCLUSION: We should pay higher attention to sarcoidosis when the followings happen: middle-aged patients or young femalepatients; long duration of disease; mild respiratory tract symptoms accompanied with superficial lymph node enlargement or skin;eye involved; bilateral lung diffusion lesion in radiographic presentation accompanied with or without hilar, mediastinal lymphadenopathy. To avoid failing to diagnose or mistaking diagnosis ,we should go all out to confirm the diagnosis through the tissue pathological examination . CLINICAL IMPLICATIONS: The multifarious forms and presentations of Sarcoidosis and the low morbidity can make the diagnosis challenging, and it is prone to misdiagnosis in China.Through analyzing the cases respectively,we can learn more about this disease and enhance the diagnosis accurate rate. DISCLOSURE: Haiqing Chu, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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FOLLICULAR BRONCHIOLITIS: ANALYSIS OF 12 CASES Michelle R. Aerni DO* Robert Vassallo MD Jay H. Ryu MD Mayo Clinic, Rochester, MN

Wednesday, November 2, 2005 Interstitial Lung Disease, continued THE SIGNIFICANCE OF PARTICULATE MATTER DETECTED IN SARCOID GRANULOMAS USING POLARIZING LIGHT MICROSCOPY Navasuma Havaligi MD* Adarsh Bhimraj MD Robert T. Ownbey MD Han C. Ryoo PhD Frank Patrick Herbert Patrick MD Drexel University College of Medicine, Philadelphia, PA PURPOSE: We previously noted particulate matter (PM) under polarizing light microscopy within the granulomas of patients diagnosed with sarcoidosis (Chest 2002;122:148S-149S). However, our preliminary research lacked a control group. Therefore, we designed this study to examine tissue samples for the presence of PM from patients without granulomas. METHODS: Tissues samples from patients diagnosed with sarcoidosis were retreived using slides routinely prepared and stored in Pathology Departments. Normal tissues were selected from among autopsy specimens at our University hospital. A single pathologist reviewed each tissue sample using: 1) light microscopy for the presence of granulomas, and 2) polarizing light microscopy for the presence of PM within the multinucleated giant cells of the granuloma. Results were expressed as a two-by-two table. This research project was approved by our University’s Institutional Review Board as an exempt protocol. RESULTS: Eighty tissue samples from patients diagnosed with sarcoidosis and eighty normal tissue samples were studied by light microscopy and polarizing light microsccopy. Age and gender differences between the groups were not significant. The two-by-two Table below displays the Results. The majority of tissues in both groups had PM detected. The differences between the groups was not significant. CONCLUSION: PM was noted in the majority of tissues from both patients diagnosed with sarcoidosis and from normals. CLINICAL IMPLICATIONS: The ubiquitous nature of PM in tissues may result in granulomatous inflammation in patients diagnosed with sarcoidosis by PM contact, PM inhalation and/or PM ingestion. Granuloma formation appears to require the presence of host susceptibility causing a reaction to the PM. Future investigations of the etiology of sarcoidosis should include polarizing light examination of tissue for PM, identification of the chemical composition and structural heterogeneity of the PM, and new tests designed to identify host susceptibility to the PM.

Granulomatous Inflammation ⫹, n ⫽ 80 Granulomatous Inflammation -, n ⫽ 80

Polarizable material ⫹

Polarizable material -

62%

38%

80%

20%

DISCLOSURE: Navasuma Havaligi, None. RESPONDER ANALYSES IN PATIENTS RECEIVING INFLIXIMAB FOR CHRONIC SARCOIDOSIS WITH PULMONARY INVOLVEMENT M. Drent MD* M. A. Judson MD U. Costabel MD R. M. duBois MD M. Kavuru MD K. H. Lo MD C. Andresen MD R. Schlenker-Herceg MD E. S. Barnathan MD R. P. Baughman MD University Hospital of Maastricht, Maastricht, Netherlands PURPOSE: Response to drug therapy may not be uniform across a heterogeneous population. Responder analyses, which dichotomize the response at a specific level of interest, can be helpful in gauging the utility of an intervention. The objective of this study was to evaluate the response to infliximab therapy in a randomized trial of 138 patients with chronic pulmonary sarcoidosis using clinically meaningful dichotomous endpoints for pulmonary function, symptoms, and physical function. METHODS: Primary and major secondary endpoint data at 24 weeks from a placebo-controlled study of infliximab were explored. The analyses are presented as the number (%) of responders using varying definitions for improvements in forced vital capacity (FVC), St. George’s Respiratory Questionnaire (SGRQ) score, Borg’s CR10 dyspnea score post 6 minute walk (6MW), and 6 MW distance (6MWD). RESULTS: At week 24, there was a trend for more subjects having improved pulmonary function as measured by FVC with infliximab

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treatment using all definitions.All three groups responded similarly in SGRQ. For the combined infliximab group, there were more responders using Borg’s CR score post 6MW (p⫽0.028) or 6MWD (p⫽0.011). For 6MWD, the difference would translate into a number needed to treat (NNT) of 6. CONCLUSION: Responder analyses can be helpful in identifying clinically meaningful treatment effects, and can be useful to help gauge the NNT to achieve the level of benefit of interest. CLINICAL IMPLICATIONS: Infliximab appears to be associated with larger improvements in some endpoints in a subset of subjects, despite aggressive medical therapy. A larger trial of infliximab in such a population appears warranted.

DISCLOSURE: M Drent, Grant monies (from industry related sources) Research grants; Consultant fee, speaker bureau, advisory committee, etc.; Employee.

TREATMENT OF IDIOPATHIC PULMONARY FIBROSIS SOLELY WITH ANTI-ACID GASTRO-ESOPHAGEAL REFLUX THERAPY: A CASE SERIES OF FOUR PATIENTS WITH LONGTERM FOLLOW-UP Ganesh Raghu MD Steve T. Yang MBBS* Carolyn Spada RN Jennifer Hayes RN Carlos Pelligrini MD Singapore General Hospital, Singapore, Singapore PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a relentless, progressive and fatal disease with no known effective treatment. Increased acid gastro-esophageal reflux (GER) has been associated with IPF. We speculate that acid gastroesophageal reflux (GER) is an important factor for the development and/or progression of IPF. METHODS: Patients with new onset IPF and presenting with symptoms and documented gastro-esophageal reflux disease (GERD) or abnormal acid GER by 24-hour esophageal pH probe testing, who refused conventional therapy (prednisone and azathioprine) or other concurrent medical treatments implicated for IPF and chose to be treated solely with anti-acid GER therapy. RESULTS: Adequate suppression of acid GER was ascertained by 24-hour esophageal pH monitoring. Patients were followed regularly with pulmonary function tests (PFT) over 2-6 years. The PFTs (Forced vital capacity [FVC] and diffusion capacity for carbon monoxide [DLCO]) in all 4 patients stabilised or improved while being maintained on adequate daily treatment for acid GER, and were alive at last follow-up. None of the patients manifested acute exacerbation of IPF nor needed additional treatment for respiratory problems or antibiotics during this period. After maintaining 4 years of improved status in PFTs and exercise testing while adhering to treatment for acid GER, one patient’s deterioration correlated with poor compliance to daily treatment during the 5th year, although the PFTs at last follow-up 6 years since diagnosis showed stabilisation compared to baseline. Another patient stabilised upon adhering to anti-acid GER treatment after an initial period of deterioration that was associated with non-adherence. CONCLUSION: This case series suggests that acid GER might be an important risk factor for IPF progression and that adequate treatment for abnormal acid GER may in part improve the outcome of patients with IPF. We also hypothesize that pulmonary fibrosis occurs in individuals who are genetically susceptible to develop fibrosis from recurrent chronic acid GER. CLINICAL IMPLICATIONS: Future clinical studies are indicated to determine the efficacy of treatment for acid GER in IPF either in combination with other agents or as a sole agent. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Interstitial Lung Disease, continued CYCLOSPORIN A TREATMENT FOR ACUTE EXACERBATION OF IDIOPATHIC PULMONARY FIBROSIS Susumu Sakamoto PhD* Sakae Homma PhD Hisashi Takaya PhD Atsushi Miyamoto PhD Masateru Kawabata PhD Kazuma Kishi PhD Eiyasu Tsuboi PhD Kunihiko Yoshimura PhD Toranomon Hospital, Tokyo, Japan

AEROSOLIZED INTERFERON GAMMA: A NOVEL APPROACH TO THERAPY IN IDIOPATHIC PULMONARY FIBROSIS? Hooman Mobassery MD* Rany Condos MD Gerald C. Smaldone MD SUNY at Stony Brook University Hospital, Stony Brook, NY PURPOSE: In controlled studies, subcutaneous injection of interferon gamma (IFN-␥) has been shown to be ineffective in the treatment of idiopathic pulmonary fibrosis (IPF). One explanation for the lack of efficacy may be inadequate drug levels in the lung interstitium using subcutaneous dosing strategies. We have developed an aerosol of IFN-␥ designed to target the airways directly. We present the dose to the lung, local cytokine response, and clinical course in a 38 year old woman with biopsy proven usual interstitial pneumonia, treated with aerosolized IFN-␥. METHODS: The patient received 400 ␮g of aerosol IFN-␥ (two 200 ␮g doses) three times per week. Pulmonary function test (PFT), exercise testing, and the University of California, San Diego shortness of breath questionnaire (SOBQ) were performed and completed prior to starting IFN-␥ therapy and at the end of three months. Subsequent PFTs were performed at the discretion of the patient’s private pulmonologist. Bronchoalveolar lavage was assayed for transforming growth factor-beta (TGF-␤) prior to the start and at the end of three months. The pattern of deposition and dose to the lung parenchyma were measured by gamma camera. RESULTS: Clinical responses included decreased dyspnea with improvement in her SOBQ measurement, stabilization of pulmonary function tests (improvement in DLCO/VA from 51% to 68% and stabilization of FEV1 and TLC) and improvement in objective parameters during exercise testing (increased maximal oxygen consumption). The dose to the lung parenchyma, as measured by gamma camera, was 54.4 ␮g per treatment with a peripheral deposition pattern. With this regimen, bronchoalveolar lavage TGF-␤, a key molecular mediator of matrix deposition, levels decreased. CONCLUSION: This is the first report of aerosol treatment with IFN-␥ and measurement of lung deposition in a patient with IPF. This study illustrates the potential use of aerosolized IFN-␥ for the treatment of IPF by means of targeted therapy directly at the site of disease. CLINICAL IMPLICATIONS: This is a novel approach in the treatment of IPF. DISCLOSURE: Hooman Mobassery, Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Interferone gamma is FDA approved but the delivery of this drug by aerosol is considered experimental.

ACUTE EXACERBATION AS PRESENTING OR COMPLICATING FEATURE OF IDIOPATHIC PULMONARY FIBROSIS Joseph G. Parambil MD* Jeffrey L. Myers MD Jay H. Ryu MD Mayo Clinic, Rochester, MN PURPOSE: To define the clinicopathologic features and outcome of acute exacerbations that occur in patients with idiopathic pulmonary fibrosis (IPF), a disorder that is generally characterized by slowly progressive course. METHODS: Retrospective single-center study. RESULTS: The median age of these seven patients was 70 years (range, 59 years to 74 years); two were women. Four patients had a smoking history and included two current smokers. All patients were experiencing an exacerbation of dyspnea for a median duration of 14 days (range, 7 days to 28 days) prior to presentation. In three of these patients, the acute deterioration was the presenting feature of IPF while in the remaining four patients the diagnosis of IPF had previously been established. Chest radiography demonstrated bilateral mixed alveolar-interstitial infiltrates in all of them. Computed tomography revealed ground-glass opacities and consolidation bilaterally in all patients with associated peripheral honeycombing in six of them. Echocardiography was performed in six patients and demonstrated pulmonary hypertension in all. Bronchoalveolar lavage fluid was obtained in five patients and revealed neutrophilia in all. Surgical lung biopsy showed diffuse alveolar damage (DAD) in five patients with associated collagen fibrosis and honeycomb changes typical of usual interstitial pneumonia (UIP). One biopsy showed a combination of UIP and organizing pneumonia while one biopsy showed only DAD. Despite treatment with lung-protective ventilation strategies and high-dose systemic corticosteroids, six patients (86%) died during their hospitalization. CONCLUSION: Although IPF is typically associated with an insidious, slowly progressive clinical course, acute exacerbations occur and may be the presenting manifestation in some patients. In either situation, current management strategies including high-dose corticosteroid therapy appear to be relatively ineffective and the mortality rate is high. CLINICAL IMPLICATIONS: Acute exacerbations of IPF occur and may be the presenting or complicating manifestation in patients with IPF. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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DISCLOSURE: Steve Yang, None.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a devastating prognosis. Acute excerebation (AE) is considered to be the worst condition during the clinical course of IPF, as it is unresponsive to most of the conventional therapies such as corticosteroid (CS) and eventually leads to death. New therapeutic approaches need to be explored. METHODS: We conducted a retorospective study on autopsied IPF cases developing AE who were then treated with CS combined with Cyclosporin A (CsA) during the period from 1994 to 2004 to evaluate the efficacy of CsA for AE of IPF. The subjects comprised of 11 male individuals with a mean age of 69.9 years. The clinical features of the CsA-treated group were compared to those of the control non-CsAtreated group of 11 patients (11 males with a mean age of 67.0 years). RESULTS: For AE, CS pulse therapy followed by CS maintenance treatment (0.5-1.0 mg/kg) were conducted in all cases. The patients in the CsA-treated group also received a low dose of CsA (100-150 mg/day). Although 7 out of 11 patients (63.6%) in the CsA-treated group died of AE, 4 (36.4%) recovered from AE. Only two patients died of the first AE, and other nine responded to the initial treatments and survived. However, they experienced repetitive AE and 5 cases eventually died of AE afterwards. In comparison, 7 out of 11 patients (63.4%) in the non-CsAtreated group did at the initial AE, and died other 4 at the following second AE. The mean survival period after the first onset of AE was 285 days in the CsA-treated group and 60 days the in non-CsA-treated group, respectively. CONCLUSION: The prognosis in the CsA-treated group was significantly better than that in the group without CsA treatment in AE of IPF. CLINICAL IMPLICATIONS: Administration of CsA combined with CS may be an efficacious approach for AE of IPF. DISCLOSURE: Susumu Sakamoto, None.

Wednesday, November 2, 2005 Interstitial Lung Disease, continued In either situation, current management strategies including high-dose corticosteroid therapy appear to be relatively ineffective and the mortality rate is high. DISCLOSURE: Joseph Parambil, None. NONSPECIFIC INTERSTITIAL PNEUMONIA: COMPARISON OF THE CLINICOPATHOLOGIC FEATURES AND PROGNOSIS WITH USUAL INTERSTITIAL PNEUMONIA Li Xia MD* Shanghai Pulmonary Hospital, Shanghai, Peoples Rep of China PURPOSE: Although nonspecific interstitial Pneumonia(NSIP) has recently been proposed as a histologic subtype of idiopathic interstitial pneumonia(IIP), a broad spectrum of clinicopathologic findings and a variable prognosis are less well characterized. In particular, it is less clear how NSIP relates to usual interstitial pneumonia (UIP). the aim of this study was to investigate the clinicopathologic features and prognosis of NSIP, and its differential diagnosis from UIP. METHODS: We analyzed the clinical, pathological findings and follow-up information of 21 NSIP patients and 18 UIP patients with biopsy-proven by open or video-assisted thoracoscopic lung biopsy. RESULTS: NSIP was more often appeared in female and the clinical manifestations were nonspecific. High-resolution computed tomography (HRCT) demonstrated ground-glass, net and patchy attenuation in lung. Semiquantitative HRCT showed that the median fibrosis score in NSIP was found to be 3 (rang ,0 to 7) compared with 5 (rang ,2 to 7) in UIP (p⬍0.01). Pathological characteristic showed a heterogeneous appearance. According to pathological characteristic, NSIP was separated into cellar and fibrosing patterns. The cellar NSIP ,fibrosing NSIP and UIP had a mean age of 41,50 and 59, respectively. The frequencies of Fibroblast foci, muscle sclerosis, honeycombing change and pulmonary architectural destruction of NSIP and UIP were 26.2% and 100% (P⬍ 0.001), 35.6% and 81.2% (P⬍ 0.05), 28.4% and 85.8% (P⬍ 0.001), 42.9% and 100% (P⬍0.05), respectively. A response to glucocorticoid and a prognosis was significantly better in NSIP than in UIP. CONCLUSION: NSIP was not easily differential from UIP in the general clinical manifestations. HRCT was helpful for the differential diagnosis of cellar NSIP and UIP. The definite diagnosis of idiopathic interstitial pneumonia was depended on open lung biopsy. CLINICAL IMPLICATIONS: Open lung biopsy was very important in diagnosis of interstitial lung disease. DISCLOSURE: Li Xia, None.

Intervention and Therapy for Pleural Effusions 12:30 PM - 2:00 PM TISSUE PLASMINOGEN ACTIVATOR INCREASES THE VOLUME OF PLEURAL FLUID BY INFLAMMATORY RESPONSES IN RABBITS WITH EMPYEMA Moon Jun Na MD* Huai Liao MD Charalampos Moschos MD Oner Dikensoy MD Wonder Drake MD Kirk B. Lane PhD Richard W. Light MD Pulmonary Department of Saint Thomas Hospital, Vanderbilt University, Nashville, TN PURPOSE: Recently, alteplase, a recombinant tPA, has been used for loculated parapneumonic effusions in humans. In rabbits with empyema, the administration of alteplase leads to the production of large amounts of pleural fluid with no effects on the empyema. To analyze the characteristics of the increased volumes of pleural fluid seen after tPA is administered to rabbits. METHODS: A chest tube was inserted into the right pleural cavity and empyema was induced by administering Pasteurella multocida intrapleurally in 2 subgroups of rabbits, with each subgroup receiving 6 doses of tPA 1mg (n⫽2) or 4mg (n⫽4) for 3 days. The pleural fluid volume, pH, glucose, protein, LDH, WBC count of pleural fluid were measured. After 10days, the rabbits were sacrificed and an empyema score and a pleural thickening score were recorded. RESULTS: The total amount of pleural fluid drained was significantly greater in tPA 4mg group than tPA 1mg group (204.5 ml vs 104.3 ml

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p⬍0.05). The protein, glucose, pH, LDH, and WBC counts did not differ significantly between tPA 1mg and 4mg group (p⬎0.05). But in both groups, the WBC counts were markedly increased to approximately 100,000/mm3, the pH was consistently below 7.10 and the LDH levels were markedly increased to 20x the upper normal limit for serum. The Gram stains were positive only for 1day after induction of empyema. CONCLUSION: The intrapleural administration of tPA in rabbits with empyema markedly increases the volume of pleural fluid. The pleural fluid is highly inflammatory as evidenced by very high WBC and LDH and reduced pH. CLINICAL IMPLICATIONS: The results of this study suggest that the increased drainage seen with fibrinolytics may be the result of augmentation of the pleural inflammatory response rather than facilitated drainage. DISCLOSURE: Moon Jun Na, Grant monies (from sources other than industry) supported by Saint Thomas Foundation. EXPERIMENTAL PLEURODESIS: INTRAPLEURAL INJECTION OF AZYTHROMYCIN, CLARITHROMYCIN OR LEVOFLOXACIN Renam U. Bumlai Francisco S. Vargas MD Milena M. Acencio BS Leila Antonangelo MD Gabriela G. Carnevale PharmD Evaldo Marchi MD Lisete R. Teixeira MD* Pulmonary Division, Heart Institute (InCor), Sao Paulo Medical School, Sao Paulo, Brazil PURPOSE: Pleurodesis is commonly used to treat recurrent pleural effusion or pneumothorax. The ideal agent for pleurodesis is still being sought. Previous studies demonstrated that intrapleural instillation of erythromycin, a macrolide antibiotic, could be a potential pleural sclerosing agent. There is no studies demonstrating the effect of quinolones as pleural sclerosing. The aim of this study was to evaluate the intrapleural injection of azythromycin, clarithromycin or levofloxacin as pleural sclerosing agents. METHODS: Thirty rabbits, divided in 3 groups received, through a chest tube, intrapleural administration of azythromycin (15mg/kg), clarithromycin (15 mg/kg) or levofloxacin (10 mg/kg) in a total volume of 2ml. After 28 days the animals were sacrificed and the degree of pleural adhesions were evaluated in a score from 0 (no adhesions ) to 4 (complete obliteration of pleural space). Pleurodesis are considered when score ⬎3. We also evaluated the microscopic changes for inflammation and fibrosis in scores from 0 to 4 according to the intensity of process. Statistical analysis: Descriptive Analysis (mean ⫹ standard deviation) and Kruskall Wallis ANOVA . RESULTS: After the intrapleural administration of azythromycin, clarithromycin or levofloxacin we observed a few macroscopic adhesions. The scores were 1.2 ⫾ 0.5, 1.2 ⫾ 1.0 and 1.0 ⫾ 0.5 respectively, and no statistical difference were observed among the groups. The microscopic analysis of pleura and parenchyma showed discrete changes for all drugs, with a greater scores of pleural fibrosis in the clarithromycin group. CONCLUSION: The intrapleural injection of azythromycin, clarithromycin or levofloxacin was ineffective in creating pleurodesis in our experimental model. CLINICAL IMPLICATIONS: Macrolides or quinolones should not be recommended as a pleural sclerosing agent, when a pleurodesis is attempt. DISCLOSURE: Lisete Teixeira, None. INTRAPLEURAL HEPARIN OR HEPARIN COMBINED WITH HUMAN RECOMBINANT DNAASE IS NOT EFFECTIVE IN THE TREATMENT OF EMPYEMA IN A RABBIT MODEL Oner Dikensoy MD Moon J. Na MD* Zhiwen Zhu MD Wonder Drake MD Edwin O. Donnelly MD Richard W. Light MD St. Thomas Hospital and Vanderbilt University, Nashville, TN PURPOSE: To investigate the effectiveness of intrapleural heparin or heparin combined with human recombinant DNAase in the treatment of empyema. METHODS: Empyema was induced in rabbits using 109 Pasteurella multocida organisms in infusion agar injected via a surgically placed chest tube. Once empyema was verified, a blinded investigator administered drugs via the chest tube. Randomly selected 6 rabbits in each treatment group received either 1000 IU Heparin or 1000 IU heparin plus 1mg human recombinant DNAase via chest tube. Control group (n⫽6) received 3 ml saline only. The rabbits received treatment every 12 hours CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Intervention and Therapy for Pleural Effusions, continued for a total of 6 treatments. The animals were sacrificed at day 10 and the amount of empyema and pleural thickening was scored macroscopically on a scale of 0 to 6. All the animals received intramuscular 100,000 U procaine penicilline every 24 hours until sacrifice. RESULTS: The volume of gross pleural effusion was markedly higher in the heparin group (25.8⫾ 10.7 mL) compared to either saline (8⫾8.9) or heparin plus human recombinant DNAase (6.8⫾6.1) groups (p⫽0.003). Comparison of the mean empyema and pleural thickening scores did not show any significant difference between the groups (p⫽0.8, p⫽0.5, respectively). A week correlation found between total volume of aspirated pleural fluid and pleural parameters of white blood cell counts and lactate dehydrogenase levels (r⫽0.546 and p⫽0.02, r⫽0.631 and p⫽0.02, respectively). One rabbit in saline group died of right heart failure and two rabbits in heparin group died of diarrhea. CONCLUSION: The intrapleural administration of either heparin or combination of heparin with human recombinant DNAase is not more effective than saline in the treatment of empyema in rabbits. Intrapleural heparin significantly increased the drainage of pleural fluid compared to combination and saline group. CLINICAL IMPLICATIONS: The intrapleural administration of heparin alone or in combination with human recombinant DNAase is not effective in the treatment of empyema in rabbits. DISCLOSURE: Moon Na, None.

PURPOSE: The experimental model of pleurodesis in rabbits has been useful in understanding the pathophysiology of the pleural inflammatory injury induced by several sclerosing agents. However, restrictions for the use of rabbits in laboratory investigation are making this model less accessible. The aim of this study is to present a new experimental model of pleurodesis in mice using talc or silver nitrate. METHODS: Two groups of ten C57BL/6 mice received 0.5mL intrapleurally of talc 4mg/gr or 0.05% silver nitrate. After 28 days the animals were sacrificed and the pleural cavity was opened and evaluated for evidence of macroscopic pleural adhesions and hemothorax (scores 0 to 4), atelectasis (scores 0-2) and microscopic pleural and alveolar inflammation and fibrosis (scores 0 to 4). Statistics: student t-test. RESULTS: Although both agents produced an efficient pleurodesis, silver nitrate was more effective than talc, with significant higher scores for pleural adhesions, microscopic pleural inflammation and fibrosis. Hemothorax, atelectasis and microscopic alveolar inflammation and fibrosis were negligible in both groups. CONCLUSION: Either talc 4mg/gr or 0.05% silver nitrate produced an efficient pleurodesis in our experimental model in mice. CLINICAL IMPLICATIONS: We describe a new model of pleurodesis that may overcome the restrictions to the use of large and medium-sized animals in laboratory investigation.

DISCLOSURE: Evaldo Marchi, None.

PURPOSE: establish the effectiveness of pleurodesis according to treatment option (tetracycline, talc slurry or thoracoscopic talc poudrage) correlating analytical parameters of pleural fluid. METHODS: retrospective analysis over a five year period from January 2000 to December 2004 which included 71 procedures carried out in a Pulmonology department.Fifteen cases were excluded from the study for not fulfilling the required criteria. RESULTS: Fifty-six pleurodesis were performed on 54 patients; 34 procedures the sclerosant agent used was tetracycline and in 22 talc. 47 cases the underlying cause was malignant pleural effusion, four pleural effusions of unknown aetiology, one pleural effusion due to Waldenstrom macroglobulinemia with lung involvement, one recurrent pneumothorax and 1 hydropneumothorax.Failure was indicated by evidence of recurrent pleural fluid. Pleurodesis with talc was successful in 29 of 34 (85%) and with tetracycline in 17 of 22 (77%).Analytical parameters of pleural fluid were thoroughly evaluated showing mean pH measurement of 7.56,total protein 4.24 mg/dl. glucose 95 mg/dl, LDH 922 U/L, ADA 16.2 mg/dl in successful pleurodesis with talc;mean pH measurement of 7.34,total protein 4.39 mg/dl. glucose 88.8mg/dl, LDH 734.7 U/L, ADA 15.8 mg/dl in successful pleurodesis with tatracycline; mean pH measurement of 7.73,total protein 4.39 mg/dl, glucose 88.8 mg/dl, LDH 734.7 U/L, ADA 15.8 mg/dl in successful pleurodesis with talc; mean ph 7.34, total protein 4.04 mg/dl,glucose 54.5 mg/dl, LDH 3078 U/L, ADA 9.87 mg/dl in unsuccessful pleurodesis with tetracycline; mean pH measurement of 7.52, total protein 4.9mg/dl, glucose 45.5, LDH 3078 U/L, ADA 9.87 mg/dl in unsuccessful pleurodesis with talc.Total cell count of pleural fluid, blood measurement of reactive C protein and LDH were also considered in this study. CONCLUSION: pleurodesis with talc was more successful than with tetracycline. The comparative study of successful and unsuccessful cases with both the pleural sclerosants shows there are significant variations of pleural glucose, LDH and ADA in talc pleurodesis and pH, glucose and LDH in tetracycline pleurodesis. CLINICAL IMPLICATIONS: Talc is the agent of choice when utilizing pleurodesis and pleural analytival parameters may be useful prognostic tools. DISCLOSURE: Sara Freitas, None. EFFICACY OF TALC PLEURODESIS DEPENDING ON THE AMOUNT OF PLEURAL FLUID DRAINAGE AND CHEST XRAY FINDINGS PRIOR TO THERAPY George Thommi MD* Michelle Christensen Patrick Meyers MD Chris Shehan MD Mathew McLeay MD Creighton University/Methodist Hospital, Omaha, NE PURPOSE: To document the success or failure of talc pleurodesis depending on CXR findings and the amount of pleural fluid drainage in twenty four hours prior to pleurodesis. METHODS: A retrospective analysis was performed over a period of five years on patients treated with talc pleurodesis through chest tubes or by surgery (VATS or thoracotomy). The amount of pleural fluid drained within 24-hours and chest x-ray findings were evaluated prior to pleurodesis. Success was documented if no recurrences of these effusions were noted for at least period of three months and no further intervention was necessary. RESULTS: 94 patients fit our criteria. 16 patients were discarded as no CXR was performed after pleurodesis. With CXRs showing minimal residual pleural effusions, talc pleurodesis was successful in 100% of patients if the pleural fluid drainage was less than 100mls in 24 hours (30/30 patients); 60% successful if pleural fluid drainage was between 100mls and 200mls in 24 hours (9/15 patients); 38% successful if the pleural fluid drainage was between 200mls and 300mls in 24 hours (5/13 patients); and 20% successful if pleural fluid drainage was over 300mls in 24 hours (4/20 patients). Only one out of eleven patients with pleural fluid drainage over 300mls in twenty hours had talc pleurodesis via VATS that was successful (9%). CONCLUSION: Talc pleurodesis is very successful when the pleural fluid drainage is less than 100mls in 24 hours regardless of the method of administration. Patients with pleural fluid drainage less than 250mls in 24 CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

A NEW, RELIABLE MODEL OF EXPERIMENTAL PLEURODESIS IN MICE Evaldo Marchi MD* Francisco S. Vargas MD Milena M. Acencio BS Gabriela G. Carnevale BS Leila Antonangelo MD Eduardo H. Genofre MD Lisete R. Teixeira MD Pulmonary Division, InCor and University of Sao Paulo Medical School, Sao Paulo, Brazil

PLEURODESIS WITH TETRACYCLINE OR WITH TALC-VARIABLES MEASURED IN TERMS OF EFFECTIVENESS Sara Freitas MD* Jessica Cemlyn-Jones MD Carlos R. Cordeiro PhD Luis C. Oliveira PhD Manuel F. Baganha PhD Departamento de Cieˆncias Pneumolo´gicas e Alergolo´gicas dos HUC, Coimbra, Portugal

Wednesday, November 2, 2005 Intervention and Therapy for Pleural Effusions, continued hours may also be successful if the chest x-ray shows minimal residual effusions. Talc pleurodesis should not be performed if the pleural fluid drainage is over 300mls or if CXR shows moderate and loculated pleural effusions. CLINICAL IMPLICATIONS: The success of talc pleurodesis depends on the amount of pleural fluid drained in 24 hours as well as the amount of pleural fluid noted on chest x-rays prior to therapy, regardless if performed via chest tubes or by VATS. DISCLOSURE: George Thommi, None. THORACOSCOPIC TALC POUDRAGE INDUCES FEVER AND SYSTEMIC INFLAMMATION Marios E. Froudarakis MD* Maria Klimathianaki MD Mihalis Pougounias MD Medical School of Crete, Heraklion, Greece PURPOSE: Recent studies have reported fever as a side effect of talc poudrage during thoracoscopic pleurodesis. However, thoracoscopy itself is likely to induce systemic inflammatory reaction, as it is an interventional procedure. The aim of the study was to investigate whether systemic inflammatory response is due to talc poudrage or to thoracoscopy. METHODS: We prospectively studied two groups of patients: the first group, of 18 patients, underwent thoracoscopic talc poudrage and the second, of 17 patients, underwent only diagnostic thoracoscopy. We measured body temperature, as well as white blood cells (WBC) count and CRP before (baseline), at 24h and 48h after the procedure. No anti-inflammatory medication was permitted before, during or after the procedure. All patients have a 3-month follow-up. RESULTS: Baseline patients’ characteristics were similar in both groups. Temperature increased significantly in the thoracoscopic talc poudrage group (overall p⫽0.005) especially at 9, 12 and 24 hour after the procedure. Overall WBC count (p⫽0.004), neutrophils (p⫽0.03) and CRP (p⬍0.0001) were significantly increased in the group of patients who underwent thoracoscopic talc poudrage. In the contrary, lymphocytes were significantly decreased (overall p⫽0.01) in the thoracoscopic talcage group during the same period. Mild side effects were noted such as pain during and after thoracoscopy and subcutaneous emphysema. No severe complication, such as infection or acute respiratory failure, was noted in both groups during the hospitalization or during the follow-up period. CONCLUSION: According to our results, fever and systemic inflammatory reaction is due to talc poudrage and not to thoracoscopy. CLINICAL IMPLICATIONS: Fever, especially in patients with talc poudrage, is only due to a short term inflammatory reaction. This observation should decrease significantly the overall cost of thoracoscopy. DISCLOSURE: Marios Froudarakis, None. THORACOSCOPY TALC POUDRAGE INDUCES T-LYMPHOPENIA IN THE PERIPHERAL BLOOD Marios E. Froudarakis MD* Maria Klimathianaki MD Mihalis Pougounias MD Helen A. Papadaki MD Department of Pneumonology, Medical School of Crete, Heraklion, Greece PURPOSE: We have demonstrated that thoracoscopic talc poudrage (TTP) induces peripheral blood granulocytosis and lymphopenia. The aim of this study is to investigate whether lymphopenia concerns T-, or B-lymphocytes. METHODS: We measured lymphocytes of the peripheral blood in patients who underwent TTP, before (baseline), at 24h and 48h after the procedure. Absolute lymphocyte numbers were analysed by flow cytometry for the evaluation of the CD3⫹, CD4⫹, CD8⫹ cells (total Tlymphocyte, helper T-lymphocytes, cytotoxic T-lymphocytes respectively), the CD19⫹ cells (B-lymphocytes), and the CD16⫹, CD56⫹ and CD57⫹ cells (NK-cells). No anti-inflammatory medication was permitted before, during or after the procedure. To this day 11 patients have been analysed. We used ANOVA repeated measurements for statistical analysis. RESULTS: The mean age of our patients was 65.5⫾15.8 years. Male patients were 6 (54.5%). All patients but one had carcinomatous pleural effusion (91%). The overall lymphocytes count was significantly decreased from baseline in peripheral blood (p⫽0.007). Also, the CD3⫹, CD4⫹ and CD8⫹ count were significantly decreased from baseline in the peripheral blood (p⫽0.005, 0.02 and 0.03 respectively). No significant difference was found in the absolute number of CD19⫹, CD16⫹, CD56⫹, and CD57⫹ cells. CONCLUSION: Patients undergoing TTP display peripheral blood T-lymphopenia following the procedure, probably due to enhanced

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extravasation in the pleura. The duration of the lymphopenia and the possible effect on the inflammatory process of pleurodesis is under investigation. CLINICAL IMPLICATIONS: To understand the systemic effects of thoracoscopic talc pleurodesis.This study is in part supported by a grant from Pierre Fabre Farmaka. DISCLOSURE: Marios Froudarakis, None. INTRAPLEURAL ALTEPLASE FOR THE COMPLICATED PARAPNEUMONIC EFFUSION Beth Y. Besecker MD* Lindsay Pell PharmD Maria Lucarelli MD Mary Beth Shirk PharmD The Ohio State University, Columbus, OH PURPOSE: To review the outcomes of patients who received intrapleural alteplase for complicated parapneumonic effusion (PPE) at our institution. METHODS: We conducted a retrospective review of all patients who received alteplase for complicated PPE from January 2002 through October 2003 at our 1,000 bed university hospital. Complicated PPE was determined by presence of pneumonia (diagnosed by chest xray or presence of organisms by bronchoalveolar lavage) and presence of pleural fluid with loculations or evidence of infection (pH⬍7.2; glucose ⬍ 60 mg/dl; or organisms present). Efficacy was defined as radiographic resolution of complicated PPE without requiring surgery. Safety was defined as lack of blood transfusion within 72 hours after alteplase. RESULTS: Nine patients were reviewed. Pleural fluid pH ranged from 6.0-8.0 and glucose 4-63mg/dL. Four drained frank pus consistent with empyema. Pleural fluid cultures were positive in 5 patients. Duration of symptoms prior to chest tube placement ranged from hours to 4 weeks (median 7 days). Seven patients showed radiographic evidence of loculations. All patients received alteplase 16mg in 100ml 0.9%NaCl instilled and retained in the chest tube for 2-4 hours daily until adequate response. Number of alteplase doses per patient ranged from 1-7. Seven patients showed complete or almost complete radiographic resolution of the PPE; one expired due to ARDS and one required surgical decortication. One patient received a blood transfusion 2 days after the last alteplase dose; no causality was established. CONCLUSION: Alteplase had acceptable efficacy and safety when used according to the described regimen. Alteplase led to radiographic improvement more often than expected considering the prolonged symptom-to-treatment time in our patients. CLINICAL IMPLICATIONS: Literature supports early surgical intervention for patients with complicated PPE. When surgery is not an option, intrapleural fibrinolytics may be used. Studies have evaluated urokinase and streptokinase for management of complicated PPE, but alteplase data in adults is limited to case series. With the intermittent availability of urokinase and streptokinase and concern about streptokinase use in patients with streptococcal infections, alteplase is a viable alternative. DISCLOSURE: Beth Besecker, None. MEDICAL THORACOSCOPY USING A FLEXIRIGID THORACOSCOPE IN THE DIAGNOSIS OF PLEURAL EFFUSION OF UNKNOWN CAUSE Atsuko Ishida MD* Teruomi Miyazawa MD Yuka Miyazu MD Yasuo Iwamoto MD Koji Kanoh MD Mika Zaima MD Takeo Inoue MD St. Marianna Univ. School of Medicine, Kawasaki, Japan PURPOSE: To evaluate the efficacy of the flexirigid thoracoscope as a tool for the diagnosis in pleural effusions of unknown etiology. METHODS: Between May 2002 and October 2004, 19 patients with pleural effusion who had remained undiagnosed even after thoracentesis were performed medical thoracoscopy under local anesthesia using a flexirigid thoracoscope, a rigid thoracoscope with a bidirectional flexible tip. Patients were examined using supplemental oxygen, either in the endoscopy suite, or at the bedside in a general ward after premedicated with an intramuscular injection of hydroxyzine and pentazocine. RESULTS: The mean age was 69 years, with a male/female ratio of 5:1. A definitive diagnosis was made in 17 of the 19 patients (89%), 6 malignant pleural mesothelioma, 5 metastatic pleural carcinoma, 4 tuberculous pleurisy, 1 empyema, and 1 uremic pleurisy. The mean examination time was 22 minutes. Complications observed were; 1 case of CO2 narcosis, 1 case of pneumothorax, and 5 cases of subcutaneous emphysema. There were no fatalities. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Intervention and Therapy for Pleural Effusions, continued CONCLUSION: The flexirigid thoracoscopy under local anesthesia can be considered to be a rapid, easy, less invasive, and moreover an accurate diagnostic procedure. CLINICAL IMPLICATIONS: It is expected to become a routine examination for pleural effusion of unknown etiology. DISCLOSURE: Atsuko Ishida, None.

A MODIFIED SIMPLE TECHNIQUE FOR CHRONIC INTRAPLEURAL CATHETER PLACEMENT IN THE MANAGEMENT OF MALIGNANT PLEURAL EFFUSIONS Maria Cirino MD* Jennifer Greenheck Kevin L. Kovitz MD Tulane University Health Sciences Center, New Orleans, LA

SINGLE CENTER EXPERIENCE WITH 250 TUNNELLED PLEURAL CATHETER INSERTIONS FOR MALIGNANT PLEURAL EFFUSION Alain Tremblay MD Gaetane C. Michaud MD* University of Calgary, Calgary, AB, Canada PURPOSE: To describe the use of tunneled pleural catheter in the management of malignant pleural effusion in a large group of patients in a clinical setting. METHODS: Retrospective analysis of 250 sequential tunneled pleural catheter insertions in patients with malignant pleural effusion in a single tertiary care center. RESULTS: 250 tunneled pleural catheter procedures for malignant pleural effusion were performed in 223 patients (19 contralateral procedures and 8 repeat ipsilateral procedures) during a 3 year period. Symptom control was complete following 97 (38.8%) procedures, partial in 125 (50%), absent in 8 (3.2%) in addition to 11 (4.4%) failed insertions and 9 (3.6%) without assessment of symptoms at the 2 week follow-up visit. Spontaneous pleurodesis occurred following 103 (42.9%) of the 240 successful tunneled pleural catheter procedures and was more frequent when 20% or less of the hemithorax had fluid at 2 week follow-up (57.2% vs. 25.3%, p⬍0.001). Catheters stayed in place for a median of 56 days. Following successful catheter placement, no further ipsilateral pleural procedures were required in 90.1% of cases. Overall median survival

ROLE OF INDWELLING TUNNELED PLEURAL CATHETER IN TREATMENT OF HEPATIC HYDROTHORAX Shaheen U. Islam MD* Carla Lamb MD Fredric Gordon MD John Beamis MD Richard Palladino MD Lahey Clinic Medical Center, Burlington, MA PURPOSE: Hepatic hydrothorax (HH) occurs in 5% of cirrhotic patients. Current treatment includes repeated thoracentesis, trans-jugular intrahepatic porto-systemic shunt (TIPS), pleurodesis, pleuroperitoneal or peritoneovenous shunt. Use of indwelling tunneled pleural catheter (ITPC) in symptomatic HH has not been reported. We present our experience on the effectiveness and utility of ITPC in patients with HH and poor functional status, either as palliation or as a bridge to transplant. METHODS: This is a retrospective case series. Patients had symptomatic HH from hepatic failure and were not candidates for immediate liver transplantation. Over a period of 9 months we placed ITPC (PleurX; Denver Biomedical) in 4 patients. Follow-up data was collected by clinical assessment and chart review. RESULTS: The baseline characteristics are presented in table 1. ITPC remained in place from 4 to 155 days. ITPC placed in one patient for palliation to avoid repeated thoracentesis for respiratory distress died after 11 days from hepatic failure. The second patient died at 4 days from sepsis unrelated to ITPC placement. A third patient with failed TIPS is continuing to drain his symptomatic HH at home. The ITPC was removed after one month in a fourth patient as her HH improved.There were no bleeding complications. ITPC was placed in two patients while receiving mechanical ventilation. Pleural fluid cultures after two months with ITPC were negative in one patient. Another patient developed a subcutaneous swelling at the catheter site from leakage of pleural fluid. The cuff of ITPC migrated outside the skin in one patient after one month.

Table 1: Baseline Characteristics at the Time of ITPC Placement Median (range) Age (years) Platelet count (k/dL) Hematocrit (percent) Serum creatinine (mg/dL) International normalized ratio (INR) Total serum bilirubin (mg/dL) Model of End-stage Liver Disease (MELD) score Etiology of hepatic failure

59 (49-78) 98 (58-194) 29.9 (29-38.5) 0.9 (0.8-1.7) 1.4 (1.2-2.0) 3.6 (1.0-6.5) 16 (8-23)

Alcoholic cirrhosis & hepatitis C (n⫽3) Cryptogenic cirrhosis (n⫽1)

CONCLUSION: ITPC can relieve symptomatic HH, improve quality of life and reduce the number of repeated thoracentesis without an increased risk for encepahlopathy. No serious immediate or long-term complications were experienced. A randomized controlled trial would identify benefits of ITPC in HH. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: Bronchogenic carcinoma contributes to approximately one third of malignant pleural effusions, followed by breast cancer and lymphoma. Chronic tunneled intrapleural catheters are effective in the management of recurrent malignant effusions, significantly reducing symptoms with minimal patient discomfort and decreased length of hospital stay. The Pleurx® catheter is usually placed into the pleural space using the Seldinger technique by inserting a dilator with a peel-away sheath over a wire. This step is the most difficult. The catheter is fed through the sheath and the sheath is peeled away. We report a simpler option. METHODS: We describe our experience using a modified technique for placement of the 16 catheters in 13 patients (eight as a primary procedure, eight as part of a thoracoscopy, 3 repeats). All but 2 had trapped lung. All patients had symptomatic malignant pleural effusions and the catheter was placed for palliation. Technique: Entry site is identified; sterile preparation and local lidocaine are used. 2 cm skin incisions are made 5cm apart. The catheter is inserted directly into the pleural space using forceps after tunneling between incisions without the need for a guide wire or dilator sheath. Suction of pleural contents confirms position. Anchoring and postoperative care are not changed. RESULTS: All patients had immediate relief of symptoms and catheters were placed where desired. There were no early or late complications. Catheters were removed when drainage ceased (1 removed by an ER practitioner unfamiliar with its function). Repeat catheters were placed for later occurring symptomatic effusions or in alternate large loculated spaces. CONCLUSION: This modified technique is simple, safe and we believe more efficient when performed by physicians trained for chest tubes and minimally invasive procedures. It is easy to learn, eliminates the introducer step, allows targeting of smaller, narrower, or oddly shaped spaces and does not increase the rate of complications. CLINICAL IMPLICATIONS: This modified technique may improve efficiency and widen the range of practitioners who safely and comfortably perform this important palliative procedure. DISCLOSURE: Maria Cirino, None.

following catheter insertion was 144 days. Complication rates were low and compared favourably with those seen with other treatment options. CONCLUSION: Tunneled pleural catheter placement is an effective method of palliation for malignant pleural effusion which allows outpatient management and low complication rates. Tunneled pleural catheters should be considered as a first line treatment option in the management of malignant pleural effusion. CLINICAL IMPLICATIONS: The use of tunneled pleural catheters for malignant pleural effusion is safe, simple and effective and should be considered in the palliation of this patient group. DISCLOSURE: Gaetane Michaud, Consultant fee, speaker bureau, advisory committee, etc. Dr. Michaud received an honorarium from Denver Biomedical for speaking at the Societe des pneumonlogues de la langue francaise about the use of the Pleurx catheter for malignant pleural effusions.

Wednesday, November 2, 2005 Intervention and Therapy for Pleural Effusions, continued CLINICAL IMPLICATIONS: ITPC may be a safe, reversible and less invasive alternative treatment of HH, with a palliative intent in terminal patients or as a transition in patients awaiting transplantation. DISCLOSURE: Shaheen Islam, None.

A SENSITIVITY ANALYSIS OF TUBE THORACOSTOMY FAILURE IN PLEURAL EFFUSION APPLICATIONS Kelvin K. Shiu DO* Mark J. Rosen MD Paul Mayo MD Beth Israel Medical Center, New York, NY PURPOSE: Tube thoracostomy is commonly used for the treatment of complicated pleural effusions. A fibrinolytic agent is often administered through the tube as an adjunctive treatment when drainage is deemed “inadequate”, but this decision is neither standardized nor consistent. We examined the variations in the definition of inadequate drainage and the potential failure modalities associated with the procedure. METHODS: This study applied probabilistic risk assessment (PRA) to perform a quantitative evaluation of different failure modalities. An event tree analysis was performed to model the temporal event sequence of identification of effusion location, assessment of loculation, and thoracostomy tube insertion and maintenance. Fault tree analysis was performed for each of these events taking into account multiple tube insertions, tube clogging and dislocations. Numerical values used for the quantification of tube thoracostomy failure were obtained from reviews of recently published trials and studies. A sensitivity analysis was also performed to prioritize the different failure contributors. RESULTS: The analyses showed that the presence of multiple loculations contributes significantly to the overall rate of tube thoracostomy failure in about 50% of cases. There are other failure modalities that lead to inadequate tube drainage, many of which are operator dependent, and others procedural and protocol dependent. Sensitivity analysis reveals that improvements in tube placement and in tube maintenance procedures could result in up to fifty percent reduction in tube thoracostomy failure. They may include pleural ultrasonography, and operator training. CONCLUSION: Many factors contribute to failure of adequate tube thoracostomy drainage, the most important being loculations of the effusion. Failure rates may be reduced with improvements in procedures and protocols related to tube placement and maintenance. CLINICAL IMPLICATIONS: This study reveals the potential difficulties of comparing different tube thoracostomy studies when the study populations comprise different loculated effusion percentages. Differences in tube insertion protocols and tube maintenance could also significantly affect the success of tube drainage. Our study further suggests that improvement in operator training in tube insertion and placement may reduce tube thoracostomy failure. DISCLOSURE: Kelvin Shiu, None.

RESULTS OF A SIMPLE METHOD IN PREDICTING THE THERAPEUTIC DECISION FOR THE MANAGEMENT OF PARAPNEUMONIC PLEURAL EFFUSIONS Evaldo Marchi MD* Andre L. Casarim MS Arianne C. Pereira MS Thoracic Surgery - Medical College of Jundiai, Jundiai, Sao Paulo, Brazil PURPOSE: Parapneumonic pleural effusions (PPE) are a common complication of pneumonias. Although several studies have suggested parameters to guide the management of PPE, this subject remain controversial. In this study we describe the outcome of patients with PPE treated based on a simple model of evaluation that guides the optimal therapeutic decision. METHODS: Seventy-five patients with PPE and negative bacteriological findings were evaluated according to their image (chest radiograms, ultrasound or CT scans) and pleural fluid (WBC counts, neutrophil percent and LDH levels) parameters. Based on the results of each parameter, models were created to test the sensitivity, specificity and predictive positive and negative values of the clinical or surgical (thoracostomy) therapeutic decision in predicting the outcome of the treated groups. RESULTS: PPE patients with bacteriological negative findings and with small effusions, WBC ⬍ 1,000cels/mm3, %N ⬍ 75% and LDH ⬍ 1,000IU/L were clinically treated with a successful outcome (SE ⫽ 92%; SP ⫽ 90%). PPE patients with moderate or large effusions, or WBC ⬎ 1,000cels/mm3, %N ⬎ 75% or LDH ⬎ 1,000IU/L were treated with early chest tube drainage and successful outcome (SE ⫽ 95% and SP ⫽ 92%).

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CONCLUSION: Simple models including the image evaluation of the pleural effusions and the levels of pleural fluid WBC, neutrophil percent and LDH were able to predict the optimal therapeutic decisions to treat patients with PPE with higher sensibility and specificity. CLINICAL IMPLICATIONS: Simple models including few parameters can be applied in the clinical practice to predict the optimal treatment for patients with PPE. DISCLOSURE: Evaldo Marchi, None.

Interventional Pulmonology and Airway Malignancies 12:30 PM - 2:00 PM SYNCHRONOUS LESIONS IN THE AIRWAYS OF AFRICAN AMERICAN MEN DIAGNOSED WITH LUNG CANCER Eric L. Flenaugh MD* Sadia Habib MD Nneka Okafor MD Nitin Puri MD Morehouse School of Medicine, Atlanta, GA PURPOSE: To determine the percentage of African American(AA) men with synchronous lesions present at the time lung cancer is diagnosed. METHODS: AA men with newly diagnosed lung cancer underwent autofluorescencebronchoscopy (AF) with the D-Light system (Storz, Tuttlingen, Germany). Synchronous lesions were detected, locations recorded, and biopsied. Findings were classified as metaplasia, dysplasia, carcinoma-in-situ(CIS), and carcinoma by independent pathologists. RESULTS: Twenty-three AA men with newly diagnosed lung cancer were enrolled.Thirty-five lesions were biopsied. Squamouscell carinoma was the histopathology of the primary lesion in 57% of patients, adenocarcinoma and small cell carcinoma in 26% and 17%,respectively. Of the synchronous lesions, 51% were metaplasia, 13% were dysplasia, 13% were CIS, 10% were synchronous carcinoma, and 13% were metastatic carcinoma. Significant changes in pre-procedure staging occurred in 13% of the patients following AF. CONCLUSION: 1. Cancerization was present in 87% of AA men at the time of the initial diagnosis with primary lung cancer.2. AF helped identify patients with lesions that carry a high risk of developing into second primary lung cancers. 3. AF improved the accuracy of staging and identified synchronous lesions in 13% of the patients studied. This resulted in a change of the tumor staging and treatment options. CLINICAL IMPLICATIONS: In select patient populations, AF could prove to be an essential tool for improving healthcare disparities. DISCLOSURE: Eric Flenaugh, Grant monies (from sources other than industry) The Georgia Cancer Center of Excellence: NIH #5 P60 MD 47-1. INCIDENCE OF ENDOBRONCHIAL MESTASTASES IN A NATIONAL REFERRAL ONCOLOGY THORACIC SERVICE Javier Kelly-Garcı´a MD* Favio Martinez-Flores MD Marco Antonio Fernandez-Corzo MD Silvia Colmenero-Zubiate MD Eric Marco GarciaBazan MD David Zamora-Lemus MD Hospital de Oncologia, Mexico City, Mexico PURPOSE: To determine the incidence of endobronquial metastases in a National Referral Thoracic Oncology Service. METHODS: We reviewed 5 years of bronchoscopic procedures. We only included patients where endobronchial metastases were suspected. Information was registered with respect to the primary tumor, symptoms, X ray studies, and location of endobronquial lesion, technique for obtaining samples, diagnosis and decision for surgical intervention. RESULTS: From May 1999 to December 2004, 1735 bronchoscopic studies were practiced, of these 127 were done to determine lung metastases from extrathoracic tumors. In 41 patients bronchoscopic findings consisted of tumor in 21 cases, mucosal infiltration 16 cases and extrinsic compression 4 cases. The most frequent symptom was cough and the radiologic abnormality was presence of a mass. The primary tumor according to frecuency was breast, kidney and larynx. The majority of lesions were in the right bronchial tree. Endobronchial biopsy was positive in 37.5%, cytology brushing 25% and bronchial washing in 10%. Combination of the three techniques was diagnostic in 34.1%, increasing to 60% CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Interventional Pulmonology and Airway Malignancies, continued when other methods were utilized. Five patients underwent resection of the lesion. CONCLUSION: Endobronquial metastases are associated with advanced metastatic disease and bronchoscopy is useful in establishing the diagnosis and determining treatment in selected cases. CLINICAL IMPLICATIONS: Provide better quality of life in patients with endobronquial metastatic disease by improving treatment options. DISCLOSURE: Javier Kelly-Garcı´a, None. THE CORRELATION BETWEEN BRONCHOSCOPIC AND RADIOGRAPHICAL CHANGES OF ENDOBRONCHIAL LESIONS TREATED BY ELECTROCAUTERY Emad H. Ibrahim MD* Ahmed Mehalal MD Alexandria Faculty of Medicine, Alexandria, Egypt

ARGON PLASMA COAGULATION FOR THE MANAGEMENT OF ENDOBRONCHIAL LESIONS VIA FLEXIBLE BRONCHOSCOPY Su-Ying Low MB, BCh* Philip Eng MBBS Singapore General Hospital, Singapore, Singapore PURPOSE: To evaluate the effectiveness and safety of argon plasma coagulation (APC) via flexible bronchoscopy (FFB) for the management of both benign and malignant airway lesions. METHODS: Retrospective review of consecutive case records of all patients treated at the Singapore General Hospital with APC via FFB from May 2002 to December 2004. RESULTS: A total of 35 patients underwent 41 procedures, all of which were performed via flexible bronchoscopy under conscious sedation. Mean age was 62.4⫾16.4years, of whom 25/35 (71.4%) were male. Of the 41 procedures, 25/41 (61%) were performed on an outpatient basis. 2/41 (4.9%) of patients were in the intensive care unit requiring mechanical ventilation for respiratory failure. Majority of patients 27/35 (77.1%)

A COMPARISON OF ENDOBRONCHIAL ULTRASOUND GUIDED BIOPSY AND POSITRON EMISSION TOMOGRAPHY WITH INTEGRATEDCOMPUTED TOMOGRAPHY IN LUNG CANCER STAGING Mark Krasnik MD* Felix Herth MD Peter Vilmann MD Birgit G. Skov MD Søren S. Larsen MD Gentofte University Hospital, Copenhagen, Denmark PURPOSE: Exact staging of patients with non-small-cell lung cancer (NSCLC) is important to improve selection of resectable and curable patients for surgery. Positron emission tomography with integrated computed tomography (PET/CT) and endoscopic ultrasound guided fine needle aspiration biopsy (EBUS-TBNA) are new and promising methods, but indications in lung cancer staging are controversial. No studies have compared the 2 methods. The aim of this study was to assess and compare the diagnostic values of PET/CT and EBUS-TBNA for diagnosing advanced lung cancer in patients, who had both procedures performed. METHODS: 25 patients considered to be potential candidates for resection of verified or suspected NSCLC underwent PET/CT and EBUS-TBNA. The PET/CT and EBUS-TBNA diagnoses were confirmed either by open thoracotomy/scopy, mediastinoscopy or clinical follow-up. Mediastinal involment of lung cancer was defined as tumour-stage ⱖ IIIA(N2), corresponding to N2-N3. Diagnostic values of PET/CT and EBUS-TBNA, with regard to the diagnosis of mediastinal involment of lung cancer, were assessed and compared. RESULTS: 10 patients had a pos PETCT for mediastinal involment while mediastinal involment were found in 5 patients with EBUS TBNA.The sensitivity of PET/CT and EBUS-TBNA were respectively 67%% versus 100% for N2-N3 disease . PET/CT had a specificity of 68%, positive predictive value (PPV) of 40% and a negative predictive value (NPV) of 87%. EBUS-TBNA had a specificity of 100%, PPV of 100%, NPV of 100% for mediastinal involment. CONCLUSION: EBUS-TBNA had a sensitivity , NPV and PPV for diagnosing advanced lung cancer, superior to PET/CT. DISCLOSURE: Mark Krasnik, None. WHICH AREA IN A METASTATIC LYMPH NODE OF LUNG CANCER SHOULD WE PUNCTURE BY ENDOBRONCHIAL ULTRASONOGRAPHY GUIDED TRANSBRONCHIAL NEEDLE ASPIRATION? Noriaki Kurimoto MD* Hiroaki Osada MD Teruomi Miyazawa MD Yuka Miyazu MD Atsuko Ishida MD St. Marianna University, Kawasaki, Japan PURPOSE: To assess the location of cancer cells in a metastatic lymph node from lung cancer for endobronchial ultrasonography guided transbronchial needle aspiration (EBUS-TBNA). METHODS: We checked 124 metastatic lymph nodes (LNs), which were resected at the operation, histopathologically. We classified 124 metastatic LNs into 3 major stages and 3 sub-stages. Stage I: early stage: stage Ia (marginal stage: metastasis located in the marginal area, the width CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: To determine the correlation between the changes of bronchoscopic narrowing of the endobroncial lesions and radiographical changes and lung functions following therapy by fiberoptic application of electrocautery. METHODS: Consecutive 22 patients with endobronchial lesions. Electrocautery was applied and data were measured before and after one week of treatment. The radiographic signs were collected before and after electrocautery from plain x-ray and computed tomograpgy including the presence of masses, atelectases, metasis, and pleural effusion. Any reduction in the size of the tumour or atelectasis were considered radiographic improvement. The circumference area of the patent area of the bronchus affected measured using the recorded video tape before and after one week of electrocautery. Correlation between the improvement of bronchoscopic view and radiographic data were measured. Also, pulmonary functions were compared before and after one week of electrocautery. RESULTS: Twenty two consecutive patients with endobrnochial lesions were included in the study. Age 54⫾12.39 and males were 77.3% of patients. Malignant lesions were found in 90.9% of patients; of those patients 40.9% had squamous cell carcinoma, 13.6% had small cell carcinoma. The majority (54.5%) had radiological evidence of lung masses, followed by atelectasis in 31.8% of patients. There was evidence of bronchoscopic improvement in 86.4% of patients and radiographic improvement in 54.5% of patients. There was a positive correlation between bronchoscopic and radiographic improvement (p ⫽ 0.001). Also, we found a significant improvement in lung functions and oxgen tension after electrocautery.Oxygen tension before and after (65.2⫾11.3 & 79.1⫾10.4)(P⬍0.001). FEV1/FVC was 76.4⫾10.5 and 83.6⫾8.1 respectively(p⫽ 0.001) FEF25-75 was 1.7⫾0.7 and 2.5⫾1.2 respectively (p⫽0.004). Six minute walking was 214.1⫾50.2 and 277.9⫾48.1 respectively (p⬍0.001). There was an increase in the patent affected bronchus narrowed by the lesions (1.1⫾0.2 cm)and (1.9⫾1.3cm)respectively (P⬍0.001). CONCLUSION: Endobronchial lesions treated by electrocautery are associated with improvement in lung fuctions, radiographic features and bronchoscopic narrowing caused by the lesions. CLINICAL IMPLICATIONS: Electrocautery is a cheap effective method to treat endobroncial lesions. DISCLOSURE: Emad Ibrahim, None.

had malignant endobronchial lesions. The remaining 8/35 (22.9%) patients had benign airway lesions due to granulation tissue or benign strictures causing airway obstruction. The mean APC procedure time was 32.7⫾20minutes. There was no procedure-related morbidity or mortality. All patients experienced immediate symptomatic improvement in their dyspnoea. The 2 patients who required mechanical ventilation could be weaned off the ventilator immediately post procedure and eventually discharged home. Repeat APC procedures were required in 4 patients (2 patients needed 2 procedures, 2 patients needed 3 procedures) to maintain airway patency. The median time between each procedure was 63days (range 23-288days). Five patients proceeded on to have rigid bronchoscopy (with or without NdYAG laser application and stent deployment) for further management of their airway obstruction. CONCLUSION: APC can be used to help restore airway patency for both the palliation of airway obstruction in malignant diseases and treatment of benign lesions. It is a safe, simple, and economic alternative to the current available array of therapeutic bronchoscopic modalities. However, repeated procedures may be required to maintain airway patency. CLINICAL IMPLICATIONS: APC is a useful adjunct for the management of both benign and malignant airway problems which can be safely and effectively performed via FFB under conscious sedation. DISCLOSURE: Su-Ying Low, None.

Wednesday, November 2, 2005 Interventional Pulmonology and Airway Malignancies, continued of the metastasis is less than 1/4 of the width of the LN), stage Ib (marginal invasive stage: metastasis located in the marginal area, the width of the metastasis is less than 1/2 of the width of the LN), stage Ic (central stage: metastasis located in the central area, the width of the metastasis is less than 1/2 of the width of the LN), Stage II: invasive stage (metastasis advanced beyond the center of the LN, the width of the metastasis is greater than 1/2 and less than 9/10 of the width of the LN), Stage III: advanced stage (the width of the metastasis is greater than 9/10 of the width of the LN). RESULTS: In 124 LNs, Stage I had 37 LNs (29%), Stage II had 16 LNs (13%), and Stage III had 75 LNs (58%). In 79 LNs which width was greater than 5 mm, Stage I had 16 LNs (20%). There was no LN of Stage Ic in 124 LNs. In 72 LNs of adenocarcinoma, Stage I, II, III had 32%, 6%, and 62%, respectively. In 44 LNs of squamous cell carcinoma, Stage I, II, III had 27%, 27%, and 46%, respectively. In 12 LNs of small cell carcinoma, Stage I, II, III had 25%, 50%, and 25%, respectively. CONCLUSION: Metastasis existed in marginal area, not beyond the center of the LN, in 20-29% (Stage Ia⫹Ib) LNs of total LNs. We should puncture the marginal area of metastatic LNs by EBUS-TBNA. CLINICAL IMPLICATIONS: It is necessary to study the yield of TBNA with the puncture in the ceter area vs.marginal area. DISCLOSURE: Noriaki Kurimoto, None. ASSESSMENT OF POSITRON EMISSION TOMOGRAPHY POSITIVE LYMPH NODES: ULTRASOUND-GUIDED TRANSBRONCHIAL NEEDLE ASPIRATION OR MEDIASTINOSCOPY? Philippe E. Pierard MD* Gavin Plat MD Jean Faber MD Thierry Prigogine MD Vincent Ninane PhD CHU Charleroi, Charleroi, Belgium PURPOSE: Positron emission tomography with 18-fluorodeoxyglucose (FDG-PET) is more accurate than CT scan for staging of mediastinal and hilar lymph nodes. Nevertheless, histological sampling of positive lymph nodes is required to exclude false positives. The diagnostic/staging yield of endobronchial ultrasound (EBUS) guided transbronchial needle aspiration (TBNA) was assessed in this particular clinical setting. The number of avoided surgical procedures was evaluated. METHODS: All consecutive patients referred for staging and/or diagnosis of mediastinal FDG-PET positive lesions were included. Data were prospectively collected. TBNA sampling of lymph nodes was performed after EBUS. In case of negative results, further surgical sampling or follow-up allowed to reach the diagnosis. RESULTS: From January 2003 to June 2004, 33 patients were included. The average number of TBNA samples per patient was 4.2 ⫾ 1.5. Sensitivity of EBUS-TBNA for sampling of positive FDG-PET lymph nodes was 93%, negative predictive value 71% and accuracy was 94%. CONCLUSION: The present study shows that TBNA combined with EBUS is a very safe and effective method to assess patients with FDG-PET positive lymph nodes. In 25 (76%) of the 33 patients, surgical staging procedures were suppressed. CLINICAL IMPLICATIONS: EBUS-TBNA should be considered as a primary method of evaluation of FDG-PET positive lymph nodes and may replace the majority of surgical mediastinal staging/diagnostic procedures. DISCLOSURE: Philippe Pierard, None. STAGING PATIENTS FOR CARCINOMA OF ESOPHAGUS WITH FLEXIBLE BRONCHOSCOPY Rogerio G. Xavier MD* Marcelo Gazzana MD Pierangelo Baglio MD Roger Rodrigues MD Fa´bio Svartman MD Sabrina Garcia MD Ronaldo Costa MD Hugo Oliveira MD Hospital de Clı´nicas de Porto alegre, Porto Alegre, Brazil PURPOSE: Cancer of esophagus is one of the more prevalent neoplasms from the aerodigestive tract. Although capable to be cured by its early recognition, patients have poor prognosis due to advanced stages seen at time of diagnosis. Because invasion of adjacent structures are mainly to the lower airways in cases of cancer located in the upper 2/3 of esophagus, bronchoscopic evaluation of such patients is recommended. METHODS: Study design of historic cohort in a series of 87 patients with carcinoma of esophagus submitted to flexible bronchoscopy (FB) from January 2003 to April 2005. They were predominant male (83.9%), 67.5 y.o. mean age (SD ⫾ 8.4). Related symptoms were cough (41.4%), weight loss (39.1%), anorexia (13.8%), dyspnea (11.5%), weakness (11.5%). Smoking (94.3%) and alcohol (63.2%) consumption were high. After careful description of the bronchoscopy findings, a statistical analysis was made by chi-square and Fischer exact tests (p⬍0.05).

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RESULTS: Patients were examined by FB after nasal insertion (73.6%), intravenous sedation using propofol (90.8%) and fentanil (79.3%). The main findings were extrinsic compression (33.3%), secretion (14.9%), blunt carina (10.3%), vocal cord paralysis or larynx lesion (8.4%), mucosal infiltration (9.2%), endobronchial tumor (8.0%) and normal (31.0%). Diagnostic samples were taken with bronchial biopsy (13.8%), bronchoalveolar lavage (6.9%), transbronchial punction (4.6%) and bronchial brushing (3.4%). Complications registered persistent hypoxemia (2.3%), bleeding (2.3%) and bronchospasm (1.1%). Association was confirmed between respiratory symptoms and abnormal findings at FB (p⬍0.05). CONCLUSION: FB demonstrates significant alterations closely related to neoplasm in the airways of patients with carcinoma of esophagus (69%), without major complications. CLINICAL IMPLICATIONS: Bronchoscopic evaluation is an easy and safe method for staging patients with carcinoma of esophagus. DISCLOSURE: Rogerio Xavier, None.

FIBER BUNDLE OPTICAL COHERENCE TOMOGRAPHY SYSTEM FOR ENDOSCOPIC AIRWAY IMAGING Sari B. Mahon PhD* David S. Mukai BS Tuqiang Xie PhD Zhongping Chen PhD Matthew Brenner MD University of California, Irvine, Irvine, CA PURPOSE: Optical coherence tomography (OCT) is a novel, noninvasive technology which can provide high and ultrahigh resolution structural and functional endoscopic/bronchoscopic imaging information in biological tissues, in-vivo, in real time, at resolutions as fine as 1um. Movable components such as MEMS micro motors, mirrors and lenses, etc., needed to provide scanning for image generation in 2 or 3 dimensions have limited the utility of OCT endoscopy. We describe a novel approach to development of 3-D OCT probes using fiber-bundles for airway and pleural endoscopy that overcomes the requirement for internal moving parts within the probe. METHODS: Using high resolution coherent optical conduits, a fiber bundle comprised of ⬎50,000 individual fiber cores was fabricated. Various lengths were tested, and performance was optimized with GRIN lenses at the proximal and distal ends, angled end polishing to prevent back reflections, and index matching between optical components. The coherence of the bundle preserves spatial identity from proximal to distal ends. This approach enables all moving parts to be located externally, proximal to the probe. Planar images are then scanned and constructed with our OCT system. RESULTS: This novel system was used to image samples of excised rabbit trachea (Figure 1). The OCT image can delineate the micro morphology of the normal rabbit trachea including mucosa, sub mucosa, glands and cartilage rings. When compared to the OCT image from our bench top OCT system, the current fiber bundle image fidelity, including signal to noise ratio, image depth, and contrast, is good, but slightly degraded. CONCLUSION: We describe a novel OCT endoscopic imaging probe approach based on a coherent fiber-optic bundle and demonstrate its feasibility in imaging tracheal tissue at transverse and axial resolution of approximately 12 and 10 um, respectively. CLINICAL IMPLICATIONS: Optimization of this fiber bundle method will enable the production of compact and solid 3-D capable imaging probes without any moving parts, that may be used for high and ultra-high resolution endoscopic diagnostics including airway and pleural applications.

DISCLOSURE: Sari Mahon, Grant monies (from sources other than industry) Department of Defense; Grant monies (from industry related CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Interventional Pulmonology and Airway Malignancies, continued sources) Independent peer reviewed research grant to develop lung cancer diangnositics from Philip Morris (3 year research grant). A THIN 4MM VIDEOBRONCHOSCOPE WITH A 2MM OPERATING CHANNEL IS USEFUL IN BYPASSING CENTRAL AIRWAYS OBSTRUCTION AND IN PROVIDING DIAGNOSTIC ACCESS TO PERIPHERAL PULMONARY LESIONS Rex C. Yung MD* Jack Hill BSc Loretta Colvin RN Michael Drummond MD Eric Schmidt MD Johns Hopkins University, Baltimore, MD

AWAKE TRACHEOBRONCHIAL DILATATION WITHOUT THE USE OF RIGID BRONCHOSCOPY Andrew C. Chang MD* Allan Pickens MD Mark B. Orringer MD University of Michigan Medical Center, Ann Arbor, MI PURPOSE: Benign tracheal strictures have historically been treated by repeated dilatations using rigid bronchoscopy and general anesthesia. An alternative approach utilizing conscious sedation, fluoroscopy, flexible bronchoscopy and Savary-Gilliard esophageal dilators is reported. METHODS: A retrospective review of our patients undergoing awake tracheobronchial dilatation was performed, after approval for IRB exemption was obtained. The procedure, performed with the patient receiving intravenous conscious sedation, is accomplished with flexible bronchoscopy through the oropharynx, passage of a guidewire into the airway, and sequential Savary-Gilliard bougie dilatation using fluoroscopic confirmation of guidewire and dilator position. RESULTS: Since 2002, of 14 consecutive patients requiring bronchoscopy and tracheobronchial dilatation without other associated procedures, 8 patients have undergone awake dilatation (AD) without rigid bronchoscopy (RB). Primary diagnoses included Wegener’s granulomatosis, idiopathic tracheal stenosis, and anastomotic stricture or tracheomalacia. The

Interventional Pulmonology: General Interventional Pulmonology 12:30 PM - 2:00 PM CT-SCAN DETERMINATION OF ADVANCED, HETEROGENEOUS UPPER LOBE EMPHYSEMA AT SITES PARTICIPATING IN A MULTICENTER TRIAL OF THE INTRABRONCHIAL VALVE DO NOT REQUIRE A CENTRAL CORE LAB FOR CONFIRMATION David Ost MD* Justin P. Smith MD Xavier Gonzalez MD Steven C. Springmeyer MD Robert McKenna MD Northshore, Long Island Jewish, Manhasset, NY PURPOSE: Results of the National Emphysema Treatment Trial (NETT) demonstrated that patients with advanced, predominant upper lobe emphysema benefit the most from lung volume reduction surgery. Subjective upper lobe predominance and classification of emphysema as heterogeneous or homogeneous was based on scoring done by the designated radiologist at each NETT site. A central core lab was used by NETT for quality control. The purpose of this study was to evaluate if centers participating in a multicenter trial to evaluate the Spiration intrabronchial valve (IBV™) system could correctly select patients with advanced heterogeneous, predominant upper lobe emphysema without the need of a central core lab. NETT radiological criteria and grading was recommended to the sites. METHODS: CT-scans corresponding to patients enrolled in the study were evaluated by an independent, Board Certified Radiologist. The radiologist was blinded to patient and clinical site identification. The radiologist provided an independent determination of emphysema severity, predominance and heterogeneity based on a grading scale 0 (no emphysema)to 4 (severe emphysema) using NETT guidelines. RESULTS: CT-scans corresponding to 27 patients enrolled and treated with IBV valves between January and July 2004 at 5 clinical sites were reviewed and evaluated. Average grading values of 3.11⫾0.75 and 3.07⫾0.78 were assigned to the right and left upper zones by the independent radiologist. Values of 1.33⫾0.55 and 1.33⫾0.48 were assigned the right and left lower zones. CONCLUSION: Radiologist and/or investigators at each clinical site participating in the IBV multicenter trial, correctly selected and enrolled patients with advanced, heterogeneous and upper lobe emphysema. Guidelines established by the NETT study allowed for adequate selection without the need of using a central core lab. CLINICAL IMPLICATIONS: CT-scan based selection of patients with advanced heterogeneous emphysema can be effectively done using appropriate radiological training and guidelines at new clinical sites participating in the IBV trial. DISCLOSURE: David Ost, Grant monies (from industry related sources) Spiration Inc. is sponsoring clinical trial at my institution; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Intrabronchial Valve IBV being evaluated for the treatment of advanced emphysema. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: Flexible fiberoptic and video bronchoscopes (FOB and VB) are used for central airways examination and though the working channels clinical samples are retrieved by a variety of methods and using a number of FOB/VB instruments. Ultrathin bronchoscopes have been built to negotiate past central airways narrowing and to direct sampling of peripheral parenchymal lesions. However the 2.2mm to 3.5mm instruments either have no working channels or a small calibered channel that often preclude retrieval of diagnostic specimen. This report details utility of a new thin videobronchoscope with improved manueverability, good imaging and a 2mm working channel through which diagnostic specimens are retrievable. METHODS: Diagnostic bronchoscopy is performed sequentially with Olympus series 160 VB and when necessary with a prototype 4mm Olympus thin VB (XBF-4B140Y1)to bypass central airways (up to 3rd generation segmentations)obstruction or to direct sampling of peripheral lesions. Number of airway generations reached by the respective “normal” caliber bronchoscope (5.2 - 5.8mm) are recorded by segment, corresponding number of airway segments reached by the thin instrument is subsequently recorded. Time spent on exam and diagnostic yield are noted. RESULTS: 18 cases involving 10 males, 8 females ranging from ages 38 to 83 were performed. 16 cancers (11 NSCLC and 5 metastases), 1 aspergilloma and 1 tracheobronchomalacia cases included. 3 have had airway stents placed, 2 had central airways obstruction and 4 had narrowing of segmentalk airways leading to lesions. On average,the thin VB reaches 5.95 generations of airways per airway segment, versus 4.42 with standard bronchoscope. The number of segments reached is greater in the lower lobe segments (6.8 on right and 7.0 on left) than the upper and middel lobe segments (5.0 and 5.5). No thin-bronchoscope related complications noted. CONCLUSION: A new 4mm videobronchoscope with a full sized working channel is a useful addition to the current range of diagnostic flexible bronchoscopes. CLINICAL IMPLICATIONS: Availability and training in the use of thin bronchoscopes may enable greater diagnostic accuracy in sampling of more frequently detected peripheral lesions. DISCLOSURE: Rex Yung, Consultant fee, speaker bureau, advisory committee, etc. I am a consultant to Boston Scientific Corporation, which manufactures some of the bronchoscopy equipment used in my diagnostic procedures and that may be mentioned in the course of my presentation.; Other Olympus USA, manufacturer of the thin bronchoscope described in this abstract, has provided a prototype for our testing and use.

maximal dilator size achieved was significantly greater for patients undergoing AD rather than RB (median size, 33F v. 30F, p⬍0.001, Student’s t-test). All patients undergoing AD had lesions that were due to inflammatory disease or that were not amenable to tracheal resection. No pneumothorax, tracheal laceration, procedural death or complications occurred. Patients were typically discharged several hours after the procedure. Improvement in symptoms of airway obstruction was achieved in 7 patients. With a median follow-up of 9 months (range, 2 weeks to 34 months), 3 patients have required repeat dilatation. CONCLUSION: Tracheobronchial stenoses can be dilated effectively and safely using the Savary-Gilliard guidewire dilatation system under fluoroscopic guidance. CLINICAL IMPLICATIONS: Awake flexible bronchoscopy and Savary-Gilliard wire-guided tracheobronchial dilatation appears to be less traumatic than rigid bronchoscopy and can be accomplished on an outpatient basis without the use of either rigid bronchoscopy or general anesthesia. DISCLOSURE: Andrew Chang, None.

Wednesday, November 2, 2005 Interventional Pulmonology: General Interventional Pulmonology, continued USE OF ENDOBRONCHIAL VALVE FOR THE TREATMENT OF POSTPNEUMONECTOMY BRONCHOPLEURAL FISTULA COMPLICATED BY EMPYEMA Rabih I. Bechara MD* Armin Ernst MD Simon Ashiku MD Robert Garland RRT David Feller-Kopman MD Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA PURPOSE: A novel, multidisciplinary, approach to the management of refractory bronchopleural fistula using a one-way endobronchial valve. METHODS: Emergent approval was obtained from our Internal Review Board for the use of an endobronchial valve to obstruct the segmental bronchus leading to the site of a bronchopleural fistula. The patient had a persistent air leak and empyema despite aggressive therapy with antibiotics, thoracotomy with a muscle flap and tisseal closure. In the operating theater, rigid bronchoscopy was performed under general anesthesia, and the exact location of the bronchopleural fistula was identified. A guidewire was placed under vision, and a small size endobronchial valve (Emphasys Medical Inc., Redwood City, CA) was loaded, inserted and deployed into the involved airway with excellent fit. The segmental bronchus was then identified by thoracic surgery and a latissimus dorsi muscle flap was again used to buttress the fistula and fill the pleural cavity. RESULTS: Our new approach resulted in complete healing of the bronchopleural fistula, resolution of the empyema, and complete success of the surgical repair. CONCLUSION: We conclude that the placement of an endobronchial valve can prevent persistent air leak in the setting of refractory bronchopleural fistula. CLINICAL IMPLICATIONS: A multi-disciplinary approach to the treatment of refractory bronchopleural fistula is necessary. Further studies are required to define the role of segmental bronchial occlusion for patients with this disease. DISCLOSURE: Rabih Bechara, Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Endobronchial valves (Emphasys Medical Inc., Redwood City California) are currently approved for endoscopic lung volume reduction in Europe, and are currently being investigated in the United States. This abstract presents a novel use, which was approved.

HEMODYNAMIC IMPACTS OF EXPIRATORY DYNAMIC COLLAPSE OF THE TRACHEA Faisal Khan MD* Elamin M. Elamin MD Mansura Ghani MD Southern Illinois University, Springfield, IL PURPOSE: Expiratory Dynamic Collapse of Trachea (DCT) was recently recognized as a possible mechanism for congestive heart failure (CHF). We studied the short and long term hemodynamic impact of tracheal stenting on DCT-CHF. METHODS: A 68 year-old male was evaluated for repeated episodes of CHF after prolonged coughing spells in spite of different treatments. Extensive cardiac and pulmonary diagnostic evaluation for CHF was unrevealing. At bronchoscopy, there was ⬎90% expiratory collapse of the lower 6 cm of the posterior tracheal wall, without cartilaginous involvement. The hemodynamic impact of DTC was assisted by impedance cardiography with stroke volume index (SVI) measured at rest, during coughing, then two and four minutes after cessation of cough (Figure 1). Similar hemodynamic measurements (HM) were obtained six and twelve months after placement of an uncovered ultraflex tracheal stent (Microvasive, Natick, MA) to support the collapsible portion of the trachea. RESULTS: At six and twelve months post-stenting the patient had no recurrence of CHF with HM demonstrated a statistically significant stabilization of the SVI (p⬍0.01) (Figure 1). CONCLUSION: This was the first documented report of DCT-CHF with cough induced intrinsic-positive end expiratory pressure leading to decrease in SVI. The later was reversed by tracheal stenting with the benefits persisted at six and twelve months follow up. A prospective study is currently under way for further evaluation of that process. CLINICAL IMPLICATIONS: Expiratory Dynamic Collapse of Trachea should be considered in the work up of congestive heart failure.

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DISCLOSURE: Faisal Khan, None. SILICONE AIRWAY STENTS IN THE TREATMENT OF PATIENTS WITH DIFFUSE TRACHEOBRONCHOMALACIA Adnan Majid MD* Rabih Bechara MD Yoshihiro Nakamura MD David Feller-Kopman MD Simon Ashiku MD Malcom DeCamp MD Armin Ernst MD Tufts-New England Medical Center, Boston, MA PURPOSE: To evaluate the effectiveness of airway stents in the treatment of diffuse tracheobronchomalcia (TBM) and their complications. METHODS: Single center retrospective analysis of medical records from patients with diffuse TBM referred to a major academic center from January 2002 to June 2004 who underwent central airway stenting (tracheal, main bronchus or both). Patient charts were reviewed for improvement of symptoms and complications. RESULTS: Number of patients stented: 29; number of patients with improvement of symptoms: 23(80%), without improvement of symptoms 6(20%); how did symptoms improve: off mechanical ventilation 4 (17%), less cough 12(52%), less shortness of breath 17(74%), less medications 4(17%); number of complications:24 (83%),time of complications: ⬍3 months 20 (83%), ⬎3months 4(17%), median 26 days (3-865 days); procedure related: 3(13%), stent related:21(87%) (infection 6(29%), migration 6(29%), obstruction 12(57%), breakage 1(5%),hemoptysis 1(5%),respiratory failure 2(10%), cough 2(10%)). CONCLUSION: Silicone stents improve symptoms in carefully selected patients with moderate to severe TBM. Unfortunately, treatment with these stents is associated with a significant number of short and long-term complications that limits their use. CLINICAL IMPLICATIONS: Airway stents currently have a role in identifying patients with diffuse TBM who will benefit from central airway stabilization. DISCLOSURE: Adnan Majid, None. USE OF SILICONE STENTS IN THE MANAGEMENT OF TRACHEOBRONCHIAL STENOSIS DUE TO TUBERCULOSIS Yonju Ryu MD* Eun Hae Kang MD Won-Jung Koh MD Gee Young Suh MD Man Pyo Chung MD O. Jung Kwon MD Hojoong Kim MD Division of Pulmonary and Critical Care Medicine, Samsung Medical Center, Seoul, South Korea PURPOSE: To assess the usefulness and safety of silicone stents placement and to compare those between widely used Dumon stents and newly designed Natural silicone stents in the management of tracheobronchial stenosis due to tuberculosis. METHODS: The medical records of 69 patients (31 Dumon and 38 Natural) requiring the placement of 75 silicone stents (35 Dumon and 40 Natural) for airway stenosis due to tracheobronchial tuberculosis were reviewed and analyzed. RESULTS: Ballooning was the leading method of dilation before stenting (90%). Immediate and lasting relief of dyspnea or improvement of FEV1 was no difference between the Dumon and the Natural group. In both treatment groups, an equal proportion of patients (58% of the Dumon group and 61% of the Natural group) had successful stent removal with median 18 months vs 13 months of stent in situ, orderly. During follow-up, the occurrence of stent-related complications such as migration (39% vs 63%), granuloma formation (42% vs 58%), mucostasis (19% vs 18%) and restenosis (48% vs 37%) were not significant different CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Interventional Pulmonology: General Interventional Pulmonology, continued between the Dumon and the Natural group, respectively. Natural stents and Dumon stents were equally easily inserted and removed. During follow up for median 32months, clinical outcome was stationary in all patients.Conclusion: The silicone stents replacement should be considered in treating tracheobronchial stenosis due to tuberculosis. Both of Dumon and Natural silicone stents seemed to be appropriate, since the efficacy and safety of Natural stent proved to be similar to those of Dumon stent in the management of airway stenosis due to tracheobronchial tuberculosis. CONCLUSION: Both of Dumon and Natural silicone stents seemed to be appropriate, since the efficacy and safety of Natural stent proved to be similar to those of Dumon stent in the management of airway stenosis due to tracheobronchial tuberculosis. CLINICAL IMPLICATIONS: The silicone stents replacement should be considered in treating tracheobronchial stenosis due to tuberculosis. DISCLOSURE: Yonju Ryu, None.

PURPOSE: This study was performed to understand the structure of both central and peripheral airways including bronchiloles and the alveolar space by the virtual bronchoscopy method. Image data for virtual navigation were obtained from three-dimensional data of multi-detector CT (MDCT) and of micro-focused cone-beam CT (MCT). METHODS: Three-dimensional data of the chest were obtained from clinical MDCT scans. Data of peripheral lung structure were obtained from MCT scanning of a resected lung specimen which was chemically fixed and inflated by Heitzman’s method. Virtual navigation of the bronchial space on personal computers was performed by the custommade program that was created by one of the author K.M. RESULTS: Observation of the internal structures of the lung was possible on any three dimensional sectional planes by volume rendering display mode. High speed navigation from the trachea to subsegmental bronchi was performed on clinical chest MDCT data. Navigation to the bronchioles, respiratory bronchioles, alveolar ducts, and alveoli were made successfully on MCT data. Precise structures of alveoli were clearly observed on MCT data. CONCLUSION: Virtual navigation from trachea to alveoli was performed. This method was useful for non-destructive three dimensional understanding of the airways. Repeated non-limited navigation was possible. CLINICAL IMPLICATIONS: This system was useful for understanding of the airways in education, training, and pre-bronchoscopic informed consent for the patient with bronchial lesions or peripheral lung diseases that require trans-bronchial lung biopsy. DISCLOSURE: Hiroshi Natori, None. NAVIGATED BRONCHOSCOPY AND ENDOBRONCHIAL ULTRASOUND FOR BRACHYTHERAPY OF INOPERABLE PERIPHERAL LUNG CANCER: A FEASIBILITY STUDY Heinrich D. Becker MD* Wolfgang Harms MD Thoraxklinik, Heidelberg, Germany PURPOSE: To prove the feasibility and the safety of endobronchial high dose radiation of inoperable peripheral tumors of the lung by catheter placement based on electromagnetic navigation and endobronchial ultrasound. METHODS: After localization of the lesion by electromagnetic navigation, confirmation of the position by endobronchial ultrasound and assessment of histology a brachytherapy catheter is placed via an extended working channnel, fixed at the nose and left in place for one week. The patient is transferred to the radiotherapy department. A total dose of 15Gy is applied by introducing an Ir192 source three times a week based on geometrical optimization to the target volume. Follow-up includes ultrasound guided biopsies and chest CT. RESULTS: Six patients have been treated so far. The treatment has been tolerated without major side effects or complications. The longest observation period is more than one year with only minor cytological

EBUS TBNA IN DIAGNOSING HILLAR AND MEDIASTINAL LESIONS Mark Krasnik MD* Peter Vilmann MD Birgit G. Skov MD Felix Herth MD Gentofte University Hospital, Copenhagen, Denmark PURPOSE: The aim of the present study was to test the use of EBUS-TBNA in the evaluation of mediastinal and hillar lesions in patients with an undiagnosed solid lesion of unknown origin in the mediastinum and hillar regions or enlarged lymph nodes in the mediastinum outlined by CT. METHODS: EBUS TBNA was prospective performed in 110 patients. 7 patients with a tumour in the mediastinum and 103 patients with enlarged lymph nodes in the mediastinum or the hillar regions. Bronchoscopy and TBNA have been performed in all patients without obtaining a diagnosis. RESULTS: A total of 7 tumours and 230 lymph nodes were biosied. EBUS TBNA was positive for cancer in 144 lymph nodes and 6 tumours. In 7 lesions the specimen was without conclusive material.In 85 patients a malignant diagnose was obtained. In 18 patients a specific non malignant diagnose was obtained (sarcoidosis, thymus, ectopic thyroid, granolomateous infection and fungal infection).. All the diagnosis was confirmed either by EUS, mediastinoscopy or Thoracotomy/scopy. The diagnostic yield was 98% In 8 patients the malignant diagnose was obtained by puncture of N1 lymph nodes. CONCLUSION: EBUS TBNA is an effective and non invasive method to obtain a diagnose in patients with lesions of unknown origin in the mediastinum and hillar regions. DISCLOSURE: Mark Krasnik, None. REAL-TIME VIRTUAL ASSISTANCE FOR TRANSBRONCHIAL NEEDLE ASPIRATION: FEASIBILITY STUDY Jae J. Choi PhD* Eric D. Anderson MD Kevin Cleary PhD Seong K. Mun PhD Georgetown University, Washington, DC PURPOSE: Transbronchial needle aspiration(TBNA) is a common procedure for diagnosis of mediastinal and hilar lymphadenopathy. Currently, pulmonologists prepare for this procedure by examining CT image slices; then, they estimate the location of the lymph node or tumor during the bronchoscopy. The success rate for this approach is near 70%. Our study aims to increase this success rate. By utilizing electromagnetic tracking and a registration technique, corresponding virtual images that show the lymph node or mass behind the airway may be displayed simultaneously alongside the real bronchoscope images. This technique may increase the accuracy of TBNA. METHODS: A custom phantom was CT-scanned with fiducials on the surface. We also developed image guidance software that includes manual segmentation, point-based registration, tracking, 3D visualization, and virtual bronchoscopy components. Using this software, we manually segmented the mass and generated a centerline to the biopsy target. Before inserting the bronchoscope, we registered the CT space and the patient space by providing corresponding points in two spaces based on the fiducials. For bronochoscope tracking, we used the Aurora electromagnetic tracking device. Using a flexible bronchoscope, we inserted an electromagnetically tracked catheter into the phantom. Using the framegrabber card, we could capture the video sequence from the bronchoscope. RESULTS: The average root-mean-square (RMS) registration error was 2.5 mm. The phantom model showed good correlation between the virtual and video bronchoscopic images. The software displayed lymph nodes, great vessels, and adjacent structures by making the airways transparent. By providing real-time virtual display during the actual bronchoscopy, we expect to improve the accuracy of TBNA. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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VIRTUAL NAVIGATION OF CENTRAL AND PERIPHERAL AIRWAYS Hiroshi Natori MD* Hirotsugu Takabatake MD Masaki Mori MD Hiroyuki Koba MD Kensaku Mori PhD Takayuki Kitasaka PhD Yasuhito Suenaga PhD Sapporo Medical University School of Medicine, Sapporo, Japan

residuals. The ultrasonic image of the tumor changed significantly corresponding to the histological response. CONCLUSION: Brachytherapy of inoperable peripheral lung tumors is feasible and is a safe procedure. CLINICAL IMPLICATIONS: Brachytherapy could become a promising approach for potentially even curative treatment of inoperable peripheral tumors of the lung sparing major damage to radiosentitive surrounding tissue. DISCLOSURE: Heinrich Becker, Grant monies (from industry related sources); Technical support by SuperDimension Co., Herzliya, Israel.

Wednesday, November 2, 2005 Interventional Pulmonology: General Interventional Pulmonology, continued CONCLUSION: This study is the first step towards our final goal of providing real-time assistance for TBNA with virtual images. Next, we will develop a real-time registration algorithm to align virtual and video bronchoscope images. We will narrow the search space by using the electromagnetic tracking device, and estimate the virtual location that best matches the virtual and video images. CLINICAL IMPLICATIONS: Virtual bronchoscopy with electromagnetic tracking may lead to an improved yield of TBNA. DISCLOSURE: Jae Choi, None.

CT-GUIDED TRANSTHORACIC NEEDLE BIOPSY OF SARCOIDOSIS Alisa Johnson BA* Jeffrey S. Klein MD Santiago Miro MD University of Vermont College of Medicine, Burlington, VT PURPOSE: To determine the utility, sensitivity and complication rate of CT-guided transthoracic needle aspiration and core biopsy for sampling enlarged hilar and mediastinal lymph nodes in patients with presumptive sarcoidosis. METHODS: A retrospective review of all transthoracic needle biopsies performed at one institution from 1995-present for diagnosis of enlarged hilar or mediastinal lymph nodes thought to reflect sarcoidosis and either 1) symptoms requiring definitive diagnosis for treatment or 2) a history of malignancy where metastatic disease was a differential diagnostic consideration. RESULTS: 28 patients, age range 34-74, males ⫽ 13, females ⫽ 15, underwent CT-guided aspiration (n⫽28) and core (n⫽19) biopsy using an extrapleural approach when possible. 9 patients had a history of prior or concurrent malignancy. Using a combination or cytologic and histologic material, a diagnosis of sarcoidosis and exclusion of malignancy was possible in all patients (sensitivity ⫽ 100%). 8/28 patients (28%) developed a postbiopsy pneumothorax, with 2 (7%) requiring small bore catheter drainage and one patient with self-limited hemoptysis. CONCLUSION: CT-guided transthoracic needle biopsy, using a combination of aspiration and core biopsy techniques, has a high yield and acceptable complication rate for the diagnosis of sarcoidosis presenting with enlarged mediastinal and hilar lymph nodes. CLINICAL IMPLICATIONS: This minimally-invasive technique can provide definitive pathologic diagnosis of sarcoidosis in patients with enlarged mediastinal and hilar lymph nodes, confidently excluding malignancy and obviating the need for further invasive diagnostic procedures. DISCLOSURE: Alisa Johnson, None.

THE EFFECTS OF THE AGE DURING FLEXIBLE BRONCHOSCOPY: PREDICTORS OF COMPLICATIONS Mario Polverino MD* ASL Salerno 1, Cava De Tirreni, Italy PURPOSE: Elderly patients generally show a good tolerance of flexible bronchoscopy (FBS). Patients’ age has not emerged as a specific risk factor for bronchoscopy complications; FBS is well tolerated in the elderly, so that major modifications of the procedure because of patients’ age alone are generally unnecessary. (Clin Chest Med 2001;22.2:301). In contrast, Davies et al. reported that 21% of patients over 60 yrs developed potentially serious, albeit transient, cardiac ischaemic events/rhythm disturbances (ERJ 1997;10:695). The aim of our study was to evaluate predictors of complications in FBS related to the patients’ age. METHODS: We retrospectively analyzed clinical and functional characteristics, as well as bronchoscopic procedures referring to 88 patients, divided into two groups: group A): 43 patients £ 65-yrs old and group B: 45 patients 3 66-yrs old. Collapse or consolidation were the most common indications for FBS in elderly patients (56%), whereas indications in group A were more heterogeneous. RESULTS: 2 out of 43 patients of group A (4.65%) and 9 out of 45 patients of group B (20%) showed minor complications during or after FBS. The greater prevalence of complications in the elderly was related to the greater number of diagnostic procedures in these patients (48 vs. 30) and to the comorbidities which were present in 9 out of 45 patients of group B: it is worth mentioning that no elderly patient suffered from complications in absence of comorbidity. CONCLUSION: Elderly age is not a risk factor for complications in flexible bronchoscopy. If any, they are due to the comorbidities and to the greater number of diagnostic procedures, related to the different pattern of clinical indications.

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CLINICAL IMPLICATIONS: Our paper analyze the predictors of complications during flexible bronchoscopy and the relationship with patient age. DISCLOSURE: Mario Polverino, None. RISK OF CANDIDEMIA IN PATIENTS WITH CANDIDA IN THE BRONCHIOALVEOLAR LAVAGE Theophilus T. Ogungbamigbe MB, ChB* Kennedy Eneh MD Marie F. Schmidt MD Sharon Ngan MD Sekar Natarajan MD Danilo Enriquez MD Joseph Quist MD Interfaith Medical Center, Brooklyn, NY PURPOSE: Candida is a common flora found in the mouth, throat and gastrointestinal tract of healthy individuals; although the presence of candida in patients who are acutely or chronically ill may have different clinical implications. This study was performed to define the relationship between the presence of candida in the bronchioalveolar lavage (BAL) and the subsequent development of candida in the blood. METHODS: We reviewed the records of 62 patients with BAL positive for candida. All patients with oral thrush and those on antifungal agents were excluded from the study. None of the patients had candidemia prior to the isolation of candida in the BAL. Out of those 62 patients, 37 were male and 25 were female. The mean age was 58.2 (21 to 93). In terms of comorbidity 21 patients out of 62 (33%) were HIV/AIDS, 14 (23%) had lung cancer, 18 (29%) were on mechanical ventilator for more than 7 days. RESULTS: 5 out of 62 patients (8%) developed candidemia, 3 out of those 5 also had candida in the urine leaving only 2 out of 62 patients (3%) with candida both in BAL and blood. These 2 patients developed candidemia within 1 to 6 weeks after confirming candida in the BAL. None of those 5 patients with candidemia had transbronchial biopsy positive for candida. All 5 patients expired. CONCLUSION: Since only 2 out of 62 had candida in both BAL and blood, it could be inferred that the isolation of candida in the BAL does not appear to increase the risk of disseminated candida infection. Once candidemia develops the mortality becomes very high. However it is not clear whether death resulted from candidemia; or rather from the associated comorbid conditions. CLINICAL IMPLICATIONS: The isolation of Candida in the BAL does not appear to be of great clinical significance. It does not seem to increase the risk of candidemia. The small sample size might be a limitation in our study. A larger study is required to confirm this result. DISCLOSURE: Theophilus Ogungbamigbe, None. DO OXYGEN SUPPLEMENTATION REQUIRED DURING FIBEROPTIC BRONCHOSCOPY Mayank Vats MD* Rakesh C. Gupta MD Deepa V. Khandelwal MBBS Neeraj Gupta MD Maheep Saluja MD Mukesh Tailor MBBS J.L.N. Medical College, Ajmer, Rajasthan, India PURPOSE: Most common indication of flexible bronchoscopy (FOB) in our setting is bronchogenic carcinoma, usually associated with ChronicObstructive-Pulmonary-Disease, concomitant infection, and hence hypoxia. The aim of study was to establish the value of O2 -supplementation during FOB to avoid catastrophic consequences of hypoxemia. METHODS: Forty patients of C.O.P.D. and 10 controls were studied for oxygen saturation (SpO2) by pulse-oximetry during FOB and classified into: -Group-1 (n⫽10):Age-&-sex matched healthy controls. Group-2A (n⫽10):FOB without O2-supplementationGroup-2B (n⫽15):FOB with O2-supplementation {nasal-catheter (rate-3 liters/min)}.Group-2B (n⫽15):FOB with O2-supplementation {pharyngeal-catheter (rate-3 liters/min)}. RESULTS: In control-group mean % fall from baseline-values in PFT after premedication and local anaesthesia (L.A.) and in studygroup after premedication it was insignificant (p⬎0.05). In studygroup mean % fall from baseline after L.A. was 16.4⫾4% in FVC, 11.2⫾2.6% in FEV1 and 12.1⫾5.5% in PEFR in group-2A, 14.8⫾3.5% in FVC, 15.5⫾3.9% in FEV1 and 16⫾6% in PEFR in group-2B and 15.9⫾5.4% in FVC, 16.3⫾5.5% in FEV1 and 13⫾1.1% in PEFR in group-2C patients (p⬍0.01, Highly Significant). In control-group mean-SaO2 at baseline was 97.7⫾2%.( Mean decline was-1.1%) (p⬎0.05). In 2A-group mean-fall in SpO2 after L.A. was insignificant but highly significant fall of 7.9% in the mean SpO2 during FOB (p⬍0.001) and significant rise of 3.5% just after BronchoAlveolar Lavage( BAL) (p⬍0.001) were observed. In group-2B patients signifCHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Interventional Pulmonology: General Interventional Pulmonology, continued icant rise in SpO2 was observed during FOB (p⬍0.01) and after BAL (p⬍0.001) and mean SpO2 were higher than the baseline. In group2C, significant rise in mean SpO2 were observed during, after BAL and 20-min after FOB. Transient hypoxemia (SpO2 ⬍85%) was observed in group-2A-40% cases , 2B-6.6% and 2C-1.2% cases. Minimum SpO2 observed during FOB were group-2A-87⫾4% , group-2B-92⫾3% and group-2C- 94⫾4%. CONCLUSION: During FOB, SaO2 levels were significantly better in patients with O2 –supplementation and were almost similar with nasal and pharyngeal-catheters. CLINICAL IMPLICATIONS: The need for pulse-oximetry and significance of O2-supplementation in patients with hypoxia is emphasized. DISCLOSURE: Mayank Vats, None. FLEXIBLE BRONCHOSCOPY PROCEDURES AT HIGH ALTITUDE AND INDICATION FOR ADDITIONAL OXYGEN SUPPORT: THE MORELIA MULTICENTER EXPERIENCE E. A. Maldonado-Ortiz MD* Hector Herrera MD Julia Ramirez Pulmonary and Respiratory Care Uniit, Hospital de la Mujer, Morelia, Michoacan, Mexico

Lung Cancer Biologic Markers 12:30 PM - 2:00 PM EXPRESSION OF AQP1, AQP3 AND AQP5 IN THE HUMAN LUNG CANCER TISSUE Makoto Sugita MD* Sumiko Maeda MD Motoyasu Sagawa MD Miyako Shimasaki MS Yoshimichi Ueda MD Tsutomu Sakuma MD Kanazawa Medical University, Ishikawa, Japan PURPOSE: The movement of water across cell membrane is essential to life. Recent investigations have demonstrated that aquaporins (AQPs), a family of water channels, are essential for maintaining the transmembrane water transport. Among at least 11 AQPs identified in mammalian tissues, AQP1, AQP3, AQP4, and AQP5 have been recognized in the lung, however, their expression and functions in the normal and diseased human lungs are poorly understood. In this study, we aimed to investigate the expression of AQPs in the human lung cancer tissue. We examined

PROMOTER -202 A/C POLYMORPHISM OF INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-3 GENE AND NONSMALL CELL LUNG CANCER RISK Jin Wook Moon MD* Yoon Soo Chang MD Young Sam Kim MD Chang Hoon Han MD Shin Myung Kang MD Moo Suk Park MD Sung Kyu Kim MD Joon Chang MD Se Kyu Kim MD Chul Min Ahn MD Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea PURPOSE: Insulin-like growth factor binding protein-3 (IGFBP-3) inhibits the mitogenic and anti-apoptotic activity of insulin-like growth factor (IGF) by blocking the binding of IGF to its receptor. However, under certain circumstances, IGFBP-3 can enhance the activity of IGF by protecting IGF from degradation. More than half of the inter-individual variations in IGFBP-3 levels are known to be genetically determined by the polymorphism at -202 locus of IGFBP-3 gene. Therefore, we attempted to ascertain whether the A-202C polymorphic variation of IGFBP-3 gene constitutes a risk factor for non-small cell lung cancer (NSCLC). METHODS: Our study included 209 NSCLC patients and 209 age-, gender-, and smoking status-matched control subjects. After extracting the genomic DNA, we amplified the 168-base-pair (bp) fragment encompassing the A-202C polymorphic site in IGFBP-3 gene. Each PCR product was digested with FspI enzyme and electrophoresed. The allele was designated either C or A depending on whether the FspI restriction site was present or not. RESULTS: The frequencies of each polymorphic variation in the control population were as followes: AA ⫽ 95 (45.5%), AC ⫽ 91 (43.5%), and CC ⫽ 23 (11.0%). In the NSCLC subjects, the genotypic frequencies were as follows: AA ⫽ 131 (62.7%), AC ⫽ 73 (34.9%), and CC ⫽ 5 (2.4%). We detected statistically significant differences in the genotypic distribution between the NSCLC and the control subjects (p ⬍0.05, Pearson’s ␹2 –test). The NSCLC risk correlated significantly with AA genotype. Using CC genotype as a reference, the odds ratio (OR) for the subjects with AC genotype was 2.45 (95% CI: 1.17 - 5.40) and the OR for the ones with AA genotype was 4.58 (95% CI: 2.17 - 10.30). CONCLUSION: Our results indicate that there are differences in the genotypic distribution at the A-202C polymorphic site of IGFBP-3 gene between NSCLC and general populations. CLINICAL IMPLICATIONS: The dysregulation of IGF axis should now be considered as another important risk factor for NSCLC, a potential target for novel antineoplastic therapies, and preventative strategies in high-risk groups. DISCLOSURE: Jin Wook Moon, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: Clinical desaturation could be present during diagnosis/ therapeutical procedures using flexible fiberbronchoscopy FBC. The use of additional oxygen is subjet to great variations both withing and between countries. The role of geographical altitude during FBC and the indication of additional oxygen support has not been well defined.To evaluate at 1951 meters above sea level the incidence of additional oxygen support and the main indication during FBC at 5 differents community hospitals. METHODS: Consecutive patients who underwent FB were prospectively evaluated. Epidemiological data, indications and oxygen saturation was monitored before, during and after procedure and recorded at 5 different intervals: a) in supine position,b) through nasal/oral route until epiglotis, c) during tracheal evaluation, d) diagnostic/therapeutical procedure, e) at any moment when desaturation was detected. RESULTS: 83 patients were enrolled but 3 excluded because domiciliary oxygen support. FBC was performed transnasally (97%), 100% of p presented an episode of desaturation ⬍90% for a period ⬍30 seg. 35/80p, received additional oxygen support during FBC: nasal catheter (5/14.3%), face mask (22/62.8%), ventury mask (2/5.7%) and non invasive mechanical ventilation (6/17.1%). CONCLUSION: Despite high altitude, in The Morelia multicentric experience, the use of additional oxygen support to all population is not mandatory during FBC. CLINICAL IMPLICATIONS: The rational use of additional oxygen support could be elegible to those population who really need it, with potential economical impact. DISCLOSURE: E Maldonado-Ortiz, None.

expression of AQP1, AQP3, and AQP5 by immunohistochemical staining and real-time PCR. METHODS: A total 48 fresh frozen lung tissue samples including 45 lung cancer samples (27 adenocarcinomas, 10 squamous cell carcinomas, 4 large cell carcinomas, and 4 small cell carcinomas) and 3 normal lung tissue samples were studied. Expression of AQP1, AQP3, and AQP5 were examined by immunohistochemical staining with polyclonal antibodies against AQP1, AQP3, and AQP5. Their mRNA was extracted following laser-captured microdissection, and real-time PCR was used for quantitative analyses of mRNA expression of AQP1, AQP3, and AQP5. RESULTS: AQP3 was well expressed in non-mucinous bronchioloalveolar carcinoma (BAC) and well-differentiated adenocarcinoma, however, AQP3 was poorly expressed in mucionus BAC. In contrast, AQP5 was poorly expressed in non-mucinous BACs, however, AQP5 was well expressed in mucious BAC. In mucinous BAC and well-differentiated adenocarcinoma, AQP1 was well expressed in 50% of the cases. The real-time PCR study confirmed the results of immunohistochemical staining. CONCLUSION: Our results indicate that AQP1, AQP3, and AQP5 are differentially expressed in the human lung cancer tissue. The results were confirmed by both immunohitochemical staining and real-time PCR. Furthermore, the expression patterns of AQPs are found to be associated with pathohistological characteristics. CLINICAL IMPLICATIONS: We speculate that the distinct expression patterns of AQPs are associated with cancer-related genes. Therefore, expression patterns of AQPs may be used not only for markers of the lung cancer, but also for the therapeutic targets. DISCLOSURE: Makoto Sugita, None.

Wednesday, November 2, 2005 Lung Cancer Biologic Markers, continued CIGARETTE SMOKE EXTRACT INHIBITS ALVEOLAR MACROPHAGE CYTOTOXICITY AGAINST TUMORAL CELLS Lea-Isabelle Proulx MS* Annie Spahr BSc Elyse Y. Bissonnette PhD Centre de Recherche, Hoˆpital Laval, Institut Universitaire de Cardiologie et de, Que´bec, PQ, Canada

LIPID PEROXIDATION AND PROSTAGLANDINS IN HUMAN LUNG CARCINOMA George G. Chen PhD* Tak W. Lee MD Hu Xu PhD Johnson H. Yip MPH Anthony P. Yim MD Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong, Shatin NT, Hong Kong PRC

PURPOSE: Cigarette smoke is composed of more than 4000 compounds including 20 pulmonary carcinogens. It is well known that cigarette smoke contributes to the development of lung cancer, but there is limited information about its role in the formation and the proliferation of tumoral cells. Alveolar macrophages (AM) play a major role in pulmonary homeostasis via mediator production and cytotoxicity against tumoral cells. Therefore, we hypothesized that cigarette smoke extract (CSE) inhibits AM functions contributing to the development and the proliferation of tumoral cells. METHODS: NR8383, a rat AM cell line, was exposed or not to CSE 3% for 20 h in presence of LPS (10 ng/ml) and tumor necrosis factor (TNF) production was assessed in cell-free supernatants. AM cytotoxicity against WEHI-164, a TNF-sensitive fibrosarcoma cell line, was also measured using a chromium51 release assay. RESULTS: CSE significantly inhibited both AM TNF production (41.53 ⫾ 3.8 %) and TNF-dependent cytotoxicity (42.81 ⫾ 1.08 % for control cells compared to 36.41 ⫾ 1.40 % for exposed cells). CONCLUSION: The inhibition of AM TNF production by CSE may contribute to the inhibition of AM cytotoxicity against TNF-sensitive cells. CLINICAL IMPLICATIONS: A reduce cytotoxic activity of AM against tumoral cells may explain the persistence and the proliferation of these cells in people exposed to cigarette smoke. DISCLOSURE: Lea-Isabelle Proulx, None.

PURPOSE: Lung cancer formation is a multifactorial process. Lipid peroxidation is one of oxidative conversion of polyunsaturated fatty acids to products known as malondialdehyde (MDA) or lipid peroxides. However, there is limited information available for a systemic examination of lipid peroxidation, prostaglandin production and Bcl-2 in human lung cancer. METHODS: The present study was to measure the lipid peroxidation in human lung cancer and to analyze how lipid peroxidation was associated the prostaglandin production and Bcl-2 expression. Fifty-two non-small cell lung carcinoma (NSCLC) tissue samples and their corresponding non-cancer tissue samples were used in this study. RESULTS: The level of MDA was significantly increased in the lung cancer tissues, compared with non-cancer lung tissues. Of two prostaglandins measured, thromboxane B2 (TXB2) was much higher in the cancer tissues than non-cancer tissues. Though prostaglandin E2 (PGE2) showed no significant difference. The changes in both TXB2 and PGE2 were not related to cigarette smoking in cases we studied. The expression of Bcl-2, which is also functioned as an antioxidant agent, was significantly elevated in the tumor tissues, compared to the non-tumor tissues. There was a positive correlation between MDA and TXB2 in both cancer and non-cancer lung tissues. MDA level was correlated with Bcl-2 in lung cancer tissues of Stages I and II but was not with those of Stage III. The cancer at the advanced stage appeared to have a higher level of TXB2. CONCLUSION: An increase in the lipid peroxidation may be regarded as an oxidant insult and also a marker for high-turn over of TXB2. In conclusion, our study demonstrated that the production of TXB2 was increased in lung caner tissue and that such an increase can result in lipid peroxidation which may be met by an elevation in Bcl-2 expression. CLINICAL IMPLICATIONS: Our study suggests that the level of lipid peroxidation, thromboxane and Bcl-2 may serve as a marker for assessing the stage of the tumor and also monitoring the potential metastasis. DISCLOSURE: George Chen, None.

CD1 GENOTYPES IN LUNG CANCER PATIENTS Mehrnoosh Doroudchi PhD* Hossein Golmoghaddam MS Seid Mohammad A. Ghayoomi MD Abbas A. Ghaderi PhD Shiraz University of Medical Sciences, Shiraz, Iran PURPOSE: It has been suggested that CD1a and CD1d molecules induce tumor-specific immune responses by presentation of tumor cell glycolipids to specific T cells and NKT cells. A decrease in the CD1a expressing dendritic cells in lung cancer as a mechanism of tumor escape from immune system has been reported. Therefore, this study was conducted to compare the genotypic frequencies of CD1a and CD1d genes in lung cancer patients and healthy controls. METHODS: Polymorphisms in exon 2 of CD1A (C622T) and CD1D (A354T) genes, were studied in 64 Iranian lung cancer patients compared to 95 age/sex/ethnicity matched and 311 non-matched healthy blood donors by a Polymerase Chain Reaction Sequence Specific Primer method. RESULTS: The frequencies of CC, CT and TT genotypes of CD1A gene among patients were 75%, 18.8% and 6.2% compared to 78.9%, 28.1% and 0% in the matched control group and 79.7%, 18.7%, and 1.6% in the non-matched control group, respectively. There was a significant difference in the genotype frequencies of CD1A between lung cancer patients and matched controls (P ⫽ 0.047). However, the difference became less significant by comparing CD1A genotypes between patients and 311 non-matched blood donors (P ⫽ 0.085). No deviations from Hardy-Weinberg equilibrium in control groups were observed. The only observed genotype of CD1D among patients and controls was AA hompzygote genotype. CONCLUSION: Our results suggest that there is a correlation between CD1A genotypes and lung cancer. Although the exact effect of this polymorphism on the protein expression or function is not understood, the resulted substitution of Threonine with Isoleucine in the antigen binding groove of the CD1a protein might affect antigen presentation potential of the molecule. CLINICAL IMPLICATIONS: This study will help us in better understanding of genetic susceptibility to lung cancer and might provide opportunities for developing screening methods and/or lipid vaccines for cancer therapy in future. DISCLOSURE: Mehrnoosh Doroudchi, None.

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SOLUBLE HER-2/NEU OVEREXPRESSION IN PATIENTS WITH LUNG CANCER Mohammad A. Ghayumi MD* Mehrnoosh Doroodchi MD Kambiz Aghasadeghi MD Shiraz University of Medical Sciences, Shiraz, Iran PURPOSE: The Her-2/neu oncogene encode a growth factor receptor, P185. Overexpression of this protein is thought to confer a growth advantage to tumors and has been associated with an adverse outcome in Non Small Cell Lung Cancer. METHODS: This study is a case-control, cross sectional study to evaluate the clinical usefulness of soluble Her-2/neu as a marker in the diagnosis of lung cancer. Level of soluble Her-2/neu in 43 lung cancer patients and 42 age/sex matched controls, measured by an enzyme immunoassay method. RESULTS: More than 93% of patients aged more than 55 years and 83% of lung cancer patients were smoker. Mean serum level of soluble Her-2/neu in cancer patients was 6.07⫾10.37 ngr/ml which was significantly higher than that of control (P ⬍ 0.05). Cigarette smoking has no effect on the level of soluble Her-2/neu. A cut off level of 6.1 ngr/ml revealed a high specificity (95%) for diagnosis of lung cancer, with very low sensitivity (14%). Conclusion: The results of this study show the higher level of soluble Her-2/neu in the sera of lung cancer patients with high specificity and low sensitivity for a cut off level of 6.1 ngr/ml. CONCLUSION: The results of this study show the higher level of soluble Her-2/neu in the sera of lung cancer patients with high specificity and low sensitivity for a cut off level of 6.1 ngr/ml. DISCLOSURE: Mohammad Ghayumi, None. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Lung Cancer Biologic Markers, continued HOXB4-INDUCED APOPTOSIS IN REH CELLS IS NOT MEDIATED VIA THE INTRINSIC CASPASE-9 PATHWAY Kamal K. Mubarak MD* Robert J. Pauley PhD Yanni Zhuang Larry Tait PhD Amro Aboukameel Ramzi M. Mohammad PhD Wayne State University, Detroit, MI

P53 CODON 72 POLYMORPHISM IN IRANIAN LUNG CANCER PATIENTS Mehrnoosh Doroudchi PhD* Seid Mohammad A. Ghayoomi MD Abdulmohammad Pezeshki MS Mohammad J. Fattahi MS Abbas A. Ghaderi PhD Shiraz University of Medical Sciences, Shiraz, Iran PURPOSE: To investigate G/C (Arg/Pro) polymorphism in exon 4 of the p53 tumor suppressor gene in Iranian lung cancer patients. METHODS: In this study, the frequency of the respective p53 alleles was investigated in 64 Iranian lung cancer patients and 205 ethnicitymatched healthy blood donors by an Allele-Specific Polymerase Chain Reaction method. RESULTS: The frequency of Arg allele was 59% in control group compared to 49% in the lung cancer patients. The frequencies of Pro allele in control and patient groups were 41% and 51%, respectively. Accordingly, there was no significant difference in the allele and genotype frequencies between the patients and controls, as a whole. However, a highly significant increase in the Pro allele was observed in patients with small cell lung cancer compared to controls (71% vs. 41%, P ⫽ 0.009). In addition, a trend of increase in the Pro allele was observed in small cell lung cancer compared to non-small cell carcinoma of lung (71% vs. 46%, P ⫽ 0.05). No significant difference was observed in the frequencies of p53 alleles between smoker and non-smoker patients (P ⫽ 0.4). CONCLUSION: Our data indicate that, as a whole, there is no association between p53 codon 72 polymorphism and lung cancer, however, there is an accumulation of Pro allele in the small cell lung cancer in our patients. CLINICAL IMPLICATIONS: The presence of Pro allele of the p53 tumor suppressor gene in Iranian small cell lung cancer increases

Lung Cancer Evaluation and Diagnosis 12:30 PM - 2:00 PM USEFULNESS OF DETECTION OF P16 PROMOTER METHYLATION OF TUMOR SUPPRESSOR GENES IN SERUM DNA FROM NON-SMALL CELL LUNG CANCER PATIENTS USING REAL-TIME PCR Yasuhiro Suga MD* Kuniharu Miyajima PhD Hidetoshi Honda MD Jitsuo Usuda PhD Tatsuo Ohira PhD Masahiro Tsuboi PhD Norihiko Ikeda PhD Takashi Hirano PhD Harubumi Kato PhD Tokyo Medical University, Tokyo, Japan PURPOSE: The application of molecular markers specific for lung cancer offers new possibilities for early detection. Recent evidence suggests that tumor cells may release DNA into the circulation, which is enriched in the serum and plasma. p16 tumor suppressor gene can be inactivated by promoter lesion methylation in many tumor types including lung cancer, We examined whether aberrant p16 methylation might also be found in the serum of patients with non-small cell lung cancer using real-time PCR. METHODS: Serum samples were obtained from 95 patients with non-small cell lung cancer, 66 adenocarcinomas, 23 squamous cell carcinomas, 6 large cell carcinomas and 32 normal controls. All patient were diagnosed at our hospital. We tested 127 samples to determine the quantity of p16 promoter methylation using real-time PCR. RESULTS: Aberrant p16 promoter methylation of the tumor suppressor gene was detected in 25 of 95 NSCLC patients (mean: 18.613⫾5.090), but only 2 of 32 normal control (mean: 1.258⫾0.871). There was a statistical difference between non small cell lung cancer patients and normal control (t-test: p⬍0.003). We drew the cutoff line at 3.0. Sensitivity was 26.3%, specificity was 93.8%, accuracy was 43.3%, positive predictive value was 92.6%. However there were no significant differences between p16 promoter methylation in serum and gender, smoking history, histological type and stage. Interestingly, we found a statistical difference about aging between less than 62 years old and over 63 years old in relation to p16 promoter methylation in serum of patient with non small cell lung cancer patients and normal control.(p⫽0.0088; Fisher’s exact test) Some cases were initially positive for methylated p16 DNA in serum before surgery, and all tuned negative after curative surgery. CONCLUSION: There was a significant difference between non small cell lung cancer patients and normal control about the p16 methylation level. CLINICAL IMPLICATIONS: Detection of aberrant p16 promoter rmethylation in serum using real time PCR appears useful for lung cancer diagnosis, early detection and clinical follow up. DISCLOSURE: Yasuhiro Suga, None. TISSUE LEVELS OF PLATELET-DERIVED ENDOTHELIAL CELL GROWTH FACTOR/ THYMIDINE PHOSPHORYLASE, VASCULAR ENDOTHELIAL GROWTH FACTOR AND CATHEPSIN-D IN LUNG CANCER PATIENTS Aliae A. Mohamed MD* Nagla T. Elmelegy MD Assiut University Hospital, Assiut, Egypt PURPOSE: The present study aimed to acquire more information about the role of platelet derived-endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), vascular endothelial growth factor (VEGF) and cathepsin-D (Cath-D) as angiogenic factors in the pathogenesis and progression of lung cancer. METHODS: Patients: The study included histopathologically confirmed lung biopsies of 37 patients with bronchogenic carcinoma, 12 patients with benign chest diseases and 12 non -inflammatory non malignant biopsies as control. Bronchogenic carcinoma cases were classified into squamous cell carcinoma (14), adenocarcinoma (10), large cell carcinoma (6) and small cell lung carcinoma (7). CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

PURPOSE: Pathogenesis of primary pulmonary mucosa-associated lymphoid tumors (MALT) and lymphomas remains unknown, but is thought to involve antigen stimulation leading to immortalization, and then subsequent transformation into a more aggressive phenotype. HOXB4 is a homeobox transcription factor that is known to clonally expand hematopoietic stem cells. We have previously shown that HOXB4 is also an apoptotic agent in the pre-B acute lymphoblastic leukemia cell line REH via the extrinsic pathway that activates caspase-8 and caspase-3 leading to DNA disintegration. We now demonstrate that despite the fact that HOXB4 is homologous to the Drosophila gene Deformed, HOXB4induced apoptosis in REH cells is not mediated via the intrinsic pathway cascade that involves the second mitochondria-derived activator of caspase (SMAC) and caspase-9. METHODS: The HOXB4 cDNA was ligated into the mammalian expression vector pLNCX2 and REH cells were transfected with the plasmid construct using lipofection. Constitutive expression was confirmed by immunocytochemistry. RESULTS: The REH cells transfected with control plasmid began to grow exponentially 4 weeks after transfection. Cells transfected with pLNCX2-HoxB4 declined in number and died. Immunocytochemical staining with anti-SMAC antibody was negative at 2, 3, and 4 weeks after transfection. Similarly, no caspase-9 activity was detected at 2, 3, or 4 weeks. Parallel experiments re-demonstrated that FLASH (FLICE-associated huge protein) expression was expressed faintly at 2 weeks, and more strongly at subsequent time points. Caspase-8 and caspase-3 were faintly expressed at 3 weeks and more strongly thereafter. CONCLUSION: Despite the sequence homology between the human protein HOXB4 and the Drosophila protein Deformed, the pathway of apoptosis induced by these proteins is different. Deformed activates Reaper, but HOXB4 does not activate SMAC (a homolog of Reaper). Apoptotic pathways have diverged during the course of evolution. CLINICAL IMPLICATIONS: Our results provide further mechanistic insight into the apoptosis induced by HOXB4 in cell lines derived from hematological malignancies. Since HOXB4 causes clonal proliferation of hematopoietic stem cells and apoptosis of hematological malignant cell lines, targeting this pathway may be of therapeutic benefit. DISCLOSURE: Kamal Mubarak, None.

heritable susceptibility to the disease and might provide clues for lung cancer screening in our population. DISCLOSURE: Mehrnoosh Doroudchi, None.

Wednesday, November 2, 2005 Lung Cancer Evaluation and Diagnosis, continued RESULTS: The present study showed a significant increase in the tissue levels of studied bioindices in patients with lung cancer in comparison to other groups, with significant higher levels in patients with inoperable cancer, advanced stages, bulky tumors and with lymph node metastasis. Also, Significant higher tissue levels of VEGF and Cath-D were also demonstrated in lung adenocarcinoma cases. CONCLUSION: The present study indicates the importance of the studied bioindices as angiogenic factors in pathogenesis and progression of lung cancer. CLINICAL IMPLICATIONS: Therefore the development of new therapeutic agents with an anti- angiogenic action may be of great importance in the management of patients with lung cancer.

Table 1: Clinical Characteristics of the Studied Patients and Controls. Patients with

Variable

benign chest

Lung cancer

Controls

disease

patients

(n⫽12)

(n⫽12)

(n⫽37)

Number

12

12

37

Gender (m/f)

8/4

5/7

27/10

45.6⫾11.6

45.0⫾12.7

61.2⫾7.52

22-70

20-62

42-72

8 (80%)

7 (58.3%)

8 (21.6%)

2 (20%)

2 (16.7%)

11(29.7%)

0 (0%)

3 (25%)

18 (48.7%)

12 (100%) ----

-5 (41.8%)

-----

Age (mean⫾ SD) Range Smoking Non smokers Ex-smokers Smokers Final diagnosis Free COPD IPF Bronchiectasis Old pulmonary TB

3 (25.0%) 2 (16.6%) 2 (16.6%)

DISCLOSURE: Aliae Mohamed, None.

CORRELATION BETWEEN SURVIVIN EXPRESSION AND PROGNOSIS IN NON-SMALL CELL LUNG CANCER ¨ nsal MD Funda Demirag MD Deniz Ko¨ksal Su¨kran Atikcan MD* Ebru U MD Aydin Yilmaz MD Atatu¨rk Chest Diseases and Chest Surgery Education Hospital, Ankara, Turkey PURPOSE: Survivin is a recently identified protein as an inhibitor of apoptosis, which supresses programmed cell death and regulates cell division. In this study, we investigated the prognostic significance of both nuclear and cytoplasmic survivin expression in non small cell lung cancer (NSCLC) and examined the association with clinicopathological parameters. METHODS: The study comprised 58 male patients diagnosed NSCLC with a mean age of 57.29⫾8.82 years; range 40-76 years. Patients underwent lobectomy (36%) or pneumonectomy (64%) with hilar and mediastinal lymph node sampling. Paraffin embedded tumor sections were retrieved for evaluation of nuclear and cytoplasmic staining of survivin. Clinicopathological data, stage and survival of patients were all determined. RESULTS: Cytoplasmic staining was found significantly increased in squamous cell carcinoma (p⫽0.003), whereas there was no association between nuclear staining and histopathological type (p⫽0.837). Also, both nuclear and cytoplasmic staining did not show any association with tumor stage (p⬎0.05). In univariate analysis there was significant correlation between nuclear survivin and short survival (p⫽0.0002). In multivariate survival analysis using Cox regression, only nuclear staining of survivin was determined as an independent prognostic factor (p⫽0.001). CONCLUSION: Localisation of survivin expression might have an important regulatory mechanism in carcinogenesis and tumor progression. Nuclear survivin expression in tumor tissues might predict the prognosis in NSCLC, whereas cytoplasmic survivin has no prognostic significance.

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CLINICAL IMPLICATIONS: Survivin expression in tumor tissues can be used as a prognostic factor in lung cancer and can be helpful in the evaluation of disease. DISCLOSURE: Su¨kran Atikcan, None.

MANAGEMENT OF PATIENTS AT RISK OF LUNG CANCER USING CYTOMETRIC ASSAYS Bojana Turic MD* Roger A. Kemp PhD Perceptronix Medical Inc., Vancouver, BC, Canada PURPOSE: We believe that Automated Cytometry of Quantitatively (AQC) stained cells from sputum and buccal mucosa provide information that can be used to guide the management of patients at risk for lung cancer. We have studied whether it is possible to construct a management regime for patients at risk of developing lung cancer based on sequential application of simple assays. METHODS: Induced sputum specimens and buccal scrapings were collected from 120 patients with confirmed lung cancer and 810 high risk negative patients. The specimens were prepared to slide and stained using the Feulgen-thionin process, which highlights DNA distribution in cell nuclei. They were scanned using a fully automated image cytometer which produces a single score for each specimen, indicating the likelihood of presence of malignancy. The buccal and sputum cytometry scores were compared to see if the assay results provide essentially the same information or if they complement each other. The answer to this question suggests how the two tests can be used for patient management. RESULTS: The correlation of the tests’ outcomes was significant (correlation⫽0.37) and suggests the assays could be used in a sequential approach for managing patients. The buccal assay eliminated 262 negatives (32%) at the cost of 9 false negatives (7.5%). See the figure below. After the addition of the sputum assay results, 87 lung cancer cases were deemed “suspicious” (72.5%) at the cost of 125 (15.4%) false positives. CONCLUSION: A simple buccal test can eliminate one third of patients from more comprehensive testing. The further application of the sputum assay provides high sensitivity and specificity for detecting lung cancer. The AQC testing approach has undergone a validation trial involving 1183 patients from clinical sites in six countries. Patients were accrued from March 2003 until October 2004. Results of the trial will be unblinded in June 2005 and presented at the conference. CLINICAL IMPLICATIONS: Cytometry based assays may prove to be an important tool for management of high risk patients.

DISCLOSURE: Bojana Turic, Employee Perceptronix Medical Inc. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Lung Cancer Evaluation and Diagnosis, continued LUNG ADENOCARCINOMAS WITH MIXED SUBTYPES: A DISTINCT BIOLOGIC ENTITY? Joon H. Yim MD* Lee C. Zhu MD Andre Moreira MD New York University Medical Center, New York, NY

DISCLOSURE: Joon Yim, None.

PURPOSE: Whether asbestos exposure per se can increase the risk of lung cancer or if asbestosis is a necessary prerequisite for this disease has been and is still hotly debated in the literature (1-2). Pleural plaques is a fairly common radiological finding among men in the general population and (provided that the plaques are properly defined radiologically) is a good indicator of former usually occupational exposure. In 1997, it was shown that in a material of more than 1500 persons with pleural plaques but without radiological or functional signs of asbestosis, mortality in lung cancer was significantly increased (3). This cohort has now been followed further to see whether the lung cancer risk remains high. METHODS: The identity of all patients with lung cancer from 1992 to 2003 from the Swedish Cancer Registry was matched with the plaque cohort. The study was approved by the Ethical Committe. RESULTS: Between 1970 and 1985, 1596 men were include in the material, the vast majority from findings of a health survey. They were born between 1887 and 1948. At the end of 1991, 1126 were still alive. From 1992 to 2003, 10 lung cancers occurred in this small cohort. This is more than expected. CONCLUSION: The risk of lung cancer in the Plaque cohort is moderately increased, strengthening the hypothesis that asbestos and not asbestosis is a contributing cause of lung cancer. CLINICAL IMPLICATIONS: Pleural plaques should alert the clinician that the person in question has been exposed to asbestos and therefore has a moderately increased risk for bronchial carcinoma.References: 1 Hillerdal G, Henderson DW. Scand J Work Environ Health 1997;23:93-103.2. Weiss W. Chest 1999;115:536-49.3. Hillerdal G. Chest 1994; 105:144-50. DISCLOSURE: Gunnar Hillerdal, None. ENDOSCOPIC ULTRASOUND WITH FINE NEEDLE ASPIRATION FOR THE DIAGNOSIS AND STAGING OF ADVANCED LUNG CANCER Rosemary F. Kelly MD* Vita V. Sullivan MD Robert A. Kratzke MD Amy M. Holmstrom RN Frank A. Lederle MSN Douglas B. Nelson MD Mandeep S. Sawhney MBBS VA Medical Center, Minneapolis, MN PURPOSE: More than 70% of patients with lung cancer are not candidates for a curative resection. Though many of these patients are symptomatic and may benefit from palliative therapy, available modalities fail to obtain a tissue diagnosis in up to 30% of patients. Endoscopic ultrasound (EUS) guided biopsy is a technique, not routinely used in lung cancer, that would allow sampling of lung masses and metastasis involving the mediastinum, liver and adrenals. The accuracy and feasibility of EUS was reviewed to define its role in lung cancer diagnosis and staging. METHODS: From March 2003 to January 2005, all patients at the Minneapolis Veterans Affairs Medical Center with suspected lung cancer and not candidates for curative surgery, were identified. Computed tomography (CT) and positron emission tomography scans were reviewed. Patients with lesions approachable by EUS were enrolled in the study. Outcomes were analyzed by final tissue diagnosis or serial imaging. RESULTS: 68 patients met inclusion criteria. Three patients refused further studies. The remaining 65 patients constituted the study population. EUS made a correct diagnosis in 57/65 patients (45 with malignant and 12 with benign pathology). 29% of these patients had undergone a failed prior attempt at tissue diagnosis. Over all, the sensitivity of EUS was 85%, specificity 100% and accuracy 88%. In the 8/65 patients were EUS failed to obtain a tissue diagnosis, EUS was technically infeasible in 3. Malignancy was confirmed in these 8 patients using video-assisted thoracoscopy (n⫽1), mediastinoscopy (n⫽3), CT guided biopsy (n⫽2) and bronchoscopy (n⫽1). Two complications of chest pain and hemoptysis were self-limited and resolved without intervention. CONCLUSION: EUS provides an alternative method of tissue diagnosis for advanvced lung cancer that is highly safe and accurate. CLINICAL IMPLICATIONS: EUS complements bronchoscopy and CT by reaching central areas that are traditionally difficult to access. If available, it should be consider along with bronchoscopy and transthoracic needle aspiration as a “first line” diagnostic procedure. DISCLOSURE: Rosemary Kelly, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

PURPOSE: To present a new category of lung carcinoma termed “minimally invasive” adenocarcinoma, give criteria for its definition, and to present data validating such a designation. METHODS: 164 cases of primary lung adenocarcinomas resected between 1992-2004 were reviewed and divided into 4 groups. Group I: BAC only (49); Group II: Mixed subtype with ⬍⬍26⬎5 mm invasive component (16); Group III: Mixed subtype with ⬎5 mm invasive component (63); Group IV: Invasive carcinoma only (36). Tumor size and lymph nodes metastasis were compared. P53 and Ki-67 staining were analyzed in 72 cases (14 from Group I; 9 from Group II; 13 from Group III; 36 from Group IV). The Ki-67 labeling index (LI) was determined by counting 500-1000 tumor cells in three high-power fields (400X) of the most highly labeled areas. P53 overexpression was defined as the presence of nuclear staining in ⬎20% of tumor cells. RESULTS: Progressively greater lymph node involvement was seen from Group I to Group IV (0%, 0%, 14.8%, 75%). The mean Ki-67 LI (6.2%, 7.5%, 22%, 44.6%) and frequency of p53 overexpression (8%, 11%, 33.1%, 56.3%) also showed an increasing tendency from group I to IV. CONCLUSION: Data shows that adenocarcinomas with mixed subtypes (groups II, III) have characteristics between BAC (group I) and purely invasive carcinoma (group IV), supporting the idea that this entity is an intermediate lesion between BAC and invasive cancer. A subgroup of this entity (group II) has characteristics and behavior more similar to BAC, suggesting that this subgroup could be defined as a form of early invasive cancer, and may be clinically managed as such. CLINICAL IMPLICATIONS: An increasing number of lung adenocarcinomas resected fall into this category of mixed subtype adenocarcinoma. Many of them are being treated similarly to purely invasive adenocarcinoma. This data suggests that such treatment is not necessary; more conservative therapy may be mandated.

PLEURAL PLAQUES AND RISK OF LUNG CANCER: A PROSPECTIVE FOLLOW-UP STUDY Gunnar N. Hillerdal MD* Karolinska Hospital, Stockholm, Sweden

Wednesday, November 2, 2005 Lung Cancer Evaluation and Diagnosis, continued EARLY RESULTS FROM LUNG CANCER SCREENING USING SPIRAL CT OF HIGH-RISK INDIVIDUALS Lynn Huffman MD* Prakash Pandalai MD Michael F. Reed MD Jeffery Neu MSN Elsira Pina DO Kevin Redmond MD Abdul-Rahman Jazieh MD Christopher Meyer MD Ralph Shipley MD John Howington MD University of Cincinnati College of Medicine, Cincinnati, OH PURPOSE: Lung cancer is the number one cancer killer. Chest computed tomography (CT) for early lung cancer detection is an approach that relies on a presymptomatic phase for identification and intervention. Our objective was to determine if screening with chest CT can identify early-stage lung cancer in high-risk individuals in the Ohio River Valley. METHODS: Study subjects were recruited by local advertisement, letters to community and university physicians, and information provided on multiple university web sites. Inclusion criteria were: volunteers able to understand informed consent; age over 50 years; and a minimum of a twenty pack-year smoking history. Exclusion criteria were: symptomatic lung cancer at the time of screening; or a history of cancer in the past five years. Subjects completed a questionnaire conducted by research personnel and then underwent a screening thoracic spiral CT. Management of nodules was based on a defined algorithm including the following criteria: annual follow-up CT for ⬍5mm or no nodules; 6-month follow-up CT for 5-7mm; review by committee for 8-12mm; and biopsy for ⬎12mm. RESULTS: From August 2001 through April 2005 131 subjects were evaluated. Sex distribution was nearly equal. The average age was 64. The average subject started smoking at 17. The average age of those who quit was 56. The average pack-per-day smoked was 1.6. The average pack-year smoking history was 62. Fifty-six percent had at least one non-calcified nodule. Five subjects had nodules greater than 12mm and four underwent biopsy. Three patients had stage IA non-small cell lung cancer (NSCLC) and one had stage IIIA NSCLC. All patients diagnosed with lung cancer underwent complete resections: two VATS lobectomies, one open lobectomy, and one open bilobectomy. There was no operative mortality. To date no volunteer has undergone biopsy for a benign nodule. CONCLUSION: Screening chest CT can identify early-stage lung cancer in high-risk individuals. CLINICAL IMPLICATIONS: Early diagnosis allows surgical resection that is often curative. A larger study will identify the specific parameters that define high-risk patients among whom screening will increase survival. DISCLOSURE: Lynn Huffman, None.

EFFECT OF SMOKING CESSATION AFTER DIAGNOSIS OF LUNG CANCER ON PERFORMANCE STATUS AND SURVIVAL Sevin Baser MD* Georgie A. Eapen MD Carlos A. Jimenez MD Amir Onn MD Vickie R. Shannon MD Leendert Keus Rodolfo C. Morice MD E. Lin The University of Texas MD Anderson Cancer Center, Houston, TX PURPOSE: To evaluate the impact of smoking history and smoking cessation after diagnosis on performance status and survival in patients with lung cancer. METHODS: Retrospective analysis of patients with NSCLC seen at our pulmonary function laboratuary between Jan’01 and Nov‘01. Clinical characteristics, smoking history, comorbidities, survival, performance status, and pulmonary function tests were reviewed. We estimated the association between smoking status after diagnosis and survival and performance change from baseline to 6 months and 12 months. RESULTS: We studied 206 patients: 93 (45%) were smokers, 15 (7%) were nonsmokers, and 98 (48%) were former smokers (⬎1year). There was no significant association between smoking history at diagnosis and change in performance status (ZUBROD) and survival. Of the 93 smokers, 46 quit and 47 continued smoking after diagnosis. Stage, age, gender, and comorbidities were similar between these two groups. There was no significant association between smoking status after diagnosis and patients’ survival. However, those who quit smoking maintained a better performance status at 6 and 12 months (p⫽0.006 and p⫽0.008) than those who continued smoking. CONCLUSION: Smoking history before and after diagnosis of lung cancer did not affect survival, but patients who quit smoking maintained a better performance status than those who continued smoking. CLINICAL IMPLICATIONS: Smoking cessation after diagnosis of lung cancer has a beneficial effect on performance status but not on survival.

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DISCLOSURE: Sevin Baser, None. CORRELATION BETWEEN LUNG MASS SIZE IN NON-SMALL CELL LUNG CANCER (NSCLC) AND BRAIN METASTASES H. Aziz MD A. Blamoun MD M. Shubair MD M.M. Ismail MD* M.A. Khan MD St. Joseph’s Regional Medical Center, Paterson, NJ PURPOSE: The aim of our study was to determine whether the size of a primary NSCLC predicts the presence of brain metastases. METHODS: We retrospectively reviewed the size of lung mass by CT scan of the chest in 35 patients (16 males, 19 females, age range 41-95 yrs; mean age 67.4yrs) who were diagnosed with NSCLC during the past two years whose CT scans of the brain were negative for brain metastases. We then compared it with the size of the lung mass in CT scan of the chest in 35 patients (16 males, 19 females, age range 41-91 yrs; mean age 65.7 Yrs) who were also diagnosed with NSCLC but had CT scans of the brain that showed brain metastases. RESULTS: The size of lung mass in patients without brain metastases was smaller (mean 3.311⫾1.668cm; 95%CI⫽ 2.738-3.884) than in those with brain metastases (mean 4.866⫾2.612cm; 95%CI⫽3.969-5.763). At a cut-off of 3.9cm (determined by ROC curve analysis), the odds ratio of brain metastases was 13.96 (P⬍0.0001). CONCLUSION: There is direct correlation between the size of the lung mass and brain metastases in NSCLC. CLINICAL IMPLICATIONS: Lung mass size ⱖ 3.9cm in NSCLC predicts the presence of brain metastases.

Lung Mass Size (cm) ⱖ3.9 ⬍3.9

Metastases

No Metastases

26 9

6 29

DISCLOSURE: M.M. Ismail, None. IMPACT OF PULMONARY DYSFUNCTION AS A CAUSE OF INOPERABILITY FOR PATIENTS WITH NON-SMALL CELL LUNG CANCER Sevin Baser MD* Vickie R. Shannon MD Georgie A. Eapen MD Carlos A. Jimenez MD Amir Onn MD Leendert Keus Rodolfo C. Morice MD E Lin University of Texas, MD Anderson Cancer Center, Houston, TX PURPOSE: To determine the role of pulmonary dysfunction as a reason for inoperability for patients with NSCLC who were considered for surgical treatment at the time of diagnosis. METHODS: We studied all patients with NSCLC referred for preoperative evaluation to our pulmonary function laboratory between January 2001 and November 2001. Clinical characteristics, staging, smoking history, comorbidities, and clinical notes were reviewed. Pulmonary function testing consisted of spirometry, lung volumes, DLCO, 133Xenon quantitative V/Q studies, and exercise testing when indicated. RESULTS: We evaluated 206 patients (M⫽120;F⫽86) with NSCLC. Mean age was 64.7⫾10.1 yrs. Average predicted FEV1⫽70.3%⫾19.6% (range 25%-123%). One hundred and thirty- two (64%) patients had at CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Lung Cancer Evaluation and Diagnosis, continued least one comorbidity: DM 15 (7%), HTN 66 (32%), CAD 47(23%), COPD 18(9%), and asthma 5(2%). In addition, 59(29%) had history of other malignancies. One hundred and ninety-one (93%) were smokers or former smokers. After completion of their evaluation, tumor staging was: IA:28 (14%), IB:27(13%), IIA:8(4%), IIB:31(15%), IIIA:48(23%), IIIB: 39(19%) and IV:25(13%). The histologic types were: adenocarcinoma 87(42%), squamous 72(35%), large cell 43(21%), and BAC 4(2%). One hundred had surgery. The remaining 106 did not have surgery because of the following reasons:. CONCLUSION: Pulmonary dysfunction alone is the cause for inoperability for nearly one-fifth of patients initially considered for surgical treatment for NSCLC. CLINICAL IMPLICATIONS: Clear understanding of the frequency of pulmonary dysfunction amongst lung cancer patients is cornerstone for development of treatment strategies alternative to surgery ( ie conformal XRT) or methods of improving lung function preoperatively (ie lung volume reduction or pulmonary rehabilitation).

Reason for Inoperability

38 34 22 2 2 2 1 5

(19%) (17%) (11%) (1%) (1%) (1%) (0.5%) (2%)

DISCLOSURE: Sevin Baser, None.

THE PULMONARY FUNCTION LOSS TO SMOKING PACKYEAR IS AN INDEPENDENT PROGNOSTIC FACTOR IN NONSMALL CELL LUNG CANCER PATIENTS HAVING SMOKING HISTORY Jeong-Seon Ryu MD* Hun-Jae Lee MD Jae-Hwa Cho MD Seung-Min Kwak MD Hong-Lyeol Lee MD Tai-Hoon Moon MD Jae-Kap Lee MD Inha University Hospital, Incheon, South Korea PURPOSE: Smoking is a major risk factor causing lung cancer and chronic obstructive pulmonary disease. Smoking status has been known to be an independent prognostic factor of lung cancer patients. We conducted this study to know if individual susceptibility to smoking is related to the survival in locally advanced or advanced non-small cell lung cancer (NSCLC) patients. METHODS: From our prospective cohort of the lung cancer, after excluding non-smokers, we included locally advanced or advanced NSCLC patients who were completed with treatment(n⫽186) or treated only conservatively(n⫽151) in this study. All patients were performed pulmonary function testing at the time of diagnosis. We estimated individual susceptibility to smoking using a formula of (100-%predicted FEV1)/pack-year and categorized it by quartile based on the distribution among study subjectsThe statistical analysis of the survival data was performed using SAS program (version 8.1). The duration of median survival were defined as the time from diagnosis to death attributed to lung cancer and that were estimated by Kaplan-Meier method. The difference of survival curve among subgroups were evaluated by log-rank test. To evaluate the effect of susceptibility to smoking on survival was prognosis, Cox proportional hazard regression analysis was performed. RESULTS: Clinical stage of the patients was IIIA in 65(19.3%), IIIB in 120(35.6%) and IV in 152(45.1%). The median survival time was 13.2months(95% CI: 11.9-15.0 months) for treatment group and 4.9months(95% CI: 3.8-6.5 months) for conservative care group (P⬍0.001). In log-rank test survival time were significantly different according to age, sex, body weight loss (⬎5%), %predicted FEV1, clinical stage and individual susceptibility to smoking(P⬍0.005, 0.036, ⬍0.001, 0.006, ⬍0.001 and ⬍0.001, respectively). The hazard ratio adjusting covariates among patients of highest quartile of susceptibility to smoking was 1.90(95% CI: 1.49-2.38). CONCLUSION: Therefore we suggest that individual susceptibility to smoking is an independent prognostic factor of stage III and IV NSCLC patients.

EFFECT OF PULMONARY DYSFUNCTION ON SURVIVAL AND PERFORMANCE IN PATIENTS WITH NON-SMALL CELL LUNG CANCER Sevin Baser MD* Amir Onn MD Carlos A. Jimenez MD Georgie A. Eapen MD Vickie R. Shannon MD Leendert Keus Rodolfo C. Morice MD E Lin University of Texas, MD Anderson Cancer Center, Houston, TX PURPOSE: To evaluate the effect of FEV1 (% of predicted) at the time of diagnosis on survival and performance status for patients with NSCLC. METHODS: Retrospective analysis of patients with NSCLC referred to our pulmonary function test laboratory between January 2001 and November 2001. Clinical characteristics, smoking history, comorbidities, survival, pulmonary function tests, and performance status (ZUBROD) at baseline, 6 months and 1 year were reviewed. RESULTS: We studied 206 patients (M⫽120;F⫽86) with NSCLC. Mean age was 64.7⫾10.1 yrs. Fourty-five percent were smokers, 48% were former smokers, and 7% were nonsmokers. Average predicted percent FEV1⫽70.3%⫾19.6% (range 25%-123%). Smokers and former smokers averaged 52.4⫾30 pack-yr. Sixty-three percent of patients had at least one type of comorbidity; DM 15 (7%), HTN 66 (32%), CAD 47(23%). Also 59 (29%) patients had other type of malignancies. The histologic types were; Adenocarcinoma 87(42%), squamous 72(35%), large cell 43(21%), and BAC 4(2%). The stages of patients were IA:28 (14%), IB:27(13%), IIA:8(4%), IIB:31(15%), IIIA:48(23%), IIIB:39(19%) and IV:25(13%). When corrected for tumor stage, comorbidities, and age there was no significant association between initial FEV1% and patients’ survival and change of their performance status. CONCLUSION: Pulmonary dysfunction measured by FEV1 % of predicted at the time of diagnosis did not independently affect survival or change in performance status for patients with NSCLC. CLINICAL IMPLICATIONS: Degree of pulmonary dysfunction measured by FEV1 is important for selection and outcome of surgically treated patients, but is not a determinant factor of performance and survival for patients with NSCLC overall. DISCLOSURE: Sevin Baser, None.

IMPACT OF PRE-TREATMENT SYMPTOM BURDEN, RESPONSE TO TREATMENT, AND LABORATORY PARAMETERS ON SURVIVAL IN SMALL CELL LUNG CANCER Anant Mohan MD* Abha Goyal Preet P. Singh Siddharth Singh R. M. Pandey MD Ashutosh K. Pathak PhD Manisha Bhutani MD Randeep Guleria MD All India Institute of Medical Sciences, New Delhi, India PURPOSE: Predictors of survival and response to treatment in patients with small cell lung cancer (SCLC) are ill-defined and unclear. In an attempt to assess the impact of simple characteristics like presenting symptoms and laboratory values on survival, we undertook this retrospective review of patients with SCLC. METHODS: All newly diagnosed SCLC cases from December 2001 through December 2004 were identified and clinical data on presenting symptoms and laboratory findings from their hospital records noted. The influence of various pretreatment factors on survival was investigated using Kaplan-Meier plots and Cox multivariate regression model. RESULTS: 76 subjects were included (84% males, 91% smokers). 57% patients had five or more symptoms at presentation. The median survival duration in patients with limited and extensive disease was 15.3 and 9.8 months respectively. Overall survival was significantly associated with cumulative symptom burden (p⫽0.02), and strongly with symptomatic response to treatment (p⬍0.001). Survival was also significantly associated with Karnofsky Performance Status (KPS)(p⫽0.04) and disease extent (p⫽0.03). Patients with higher hemoglobin, serum sodium and serum globulin had significantly better survival (p⫽0.02, 0.04, and 0.02 respectively). By multivariate regression analysis, hemoglobin, KPS and brain metastases were found to be significant predictors of survival (p⫽0.01, p⫽0.02, and p⬍0.01 respectively). Multimodal therapy with both chemotherapy (CT) and radiotherapy (RT) resulted in significantly greater CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

Pulmonary dysfunction Unresectable local-regional disease Distant metastasis Cardiac dysfunction Cardiac risk⫹pulmonary dysfunction Recurrence of disease Patient refusal Lost F/U

N⫽206 (%)

CLINICAL IMPLICATIONS: This study may be first of showing individual susceptibility to smoking is an independent prognostic factor of locally advanced or advanced NSCLC patients. DISCLOSURE: Jeong-Seon Ryu, None.

Wednesday, November 2, 2005 Lung Cancer Evaluation and Diagnosis, continued survival benefit than unimodal (either CT or RT), or no therapy (p ⬍ 0.001 and p ⬍ 0.001 respectively). CONCLUSION: Cumulative symptom burden, KPS, disease extent, and symptomatic improvement after treatment are useful predictors of survival in SCLC. CLINICAL IMPLICATIONS: Assessment of symptomatology and other clinical variables may be used as simple tools for risk-stratifying patients into those most likely to achieve survival benefit after therapy. This may also prove more cost-beneficial in developing countries for evaluating response to treatment compared to costly imaging procedures. DISCLOSURE: Anant Mohan, None. UTILITY OF SYMPTOMS AND RESPIRATORY STATUS IN THE ASSESSMENT OF QUALITY OF LIFE IN PATIENTS WITH LUNG CANCER Anant Mohan MD* Preet P. Singh MBBS Siddharth Singh MBBS Abha Goyal MBBS Manisha Bhutani MD Ashutosh K. Pathak PhD Randeep Guleria MD All India Institute of Medical Sciences, New Delhi, India PURPOSE: A significant proportion of lung cancer patients depend on palliative care, hence it is imperative to evaluate and maintain a satisfactory quality of life (QoL) in them. However, data with regard to India patients is sparce. Quality of life was assessed in newly diagnosed patients with lung cancer and its relationship with pre-treatment clinical parameters and respiratory status was studied. METHODS: A 30-item, self-administered European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3) questionnaire in Hindi was used. Clinical symptoms, Karnofsky performance status (KPS), and measures of respiratory status (including spirometry) were recorded. RESULTS: The study included 93 patients (76 males, 80% smokers) with a mean (SD) age of 57.2 (11.0) years. 90% had non- small cell lung cancer. Median KPS was 70 (range, 50-90). Median number of symptoms was 4 (range, 1-7). Lowest scores were seen in the global health status and physical function scales (Table). Fatigue, appetite loss and pain scored highest among symptom scales. Higher KPS significantly correlated with better global health status (p⬍0.001) and healthy level of functioning (p⬍0.001). The number of symptoms was significantly associated with global QoL (p⫽0.04) and physical, role, emotional and cognitive function scales (p⬍0.05); however individual respiratory symptoms showed no correlation with QoL. Forced vital capacity, forced expiratory volume in 1 second and peak expiratory flow rate showed positive correlation with all functional scales (p⬍0.05) except social scale. Age, gender, smoking status, pack years, histological type and symptom duration had no influence on QoL. CONCLUSION: Patients with lung cancer have unsatisfactory quality of life, with the global health status and physical functions being most affected. Number of symptoms, performance status, and pulmonary functions has a significant bearing on quality of life. CLINICAL IMPLICATIONS: Appropriate attempts to improve symptoms and augment respiratory capacity may improve quality of life in lung cancer.

Table 1. Mean (SD) EORTC- QLQ C30 Scores Domain Global Health Status Physical Function Role Function Emotional Function Cognitive Function Social Function

Mean Score (SD) 39.0(20.9) 48.7(27.2) 56.5(33.5) 57.3(28.6) 69.8(28.7) 66.1(30.8)

DISCLOSURE: Anant Mohan, None. PATTERN AND DETERMINANTS OF SURVIVAL AMONG LUNG CANCER PATIENTS IN WESTERN PART OF INDIA Ramakant Dixit MD Sidharth Sharma MBBS* J.L.N. Medical College, Ajmer, India PURPOSE: As a global problem, India is also witnessing the increasing trends of lung cancer in both sexes. Despite many sporadic reports on the

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clinical, radiological and pathological features of lung cancer from different part of country, Indian literature is scanty on the survival aspect of lung cancer patients. The present study is first one on pattern and determinants of survival among various histological types of lung cancer patients from Western India. METHODS: cases of histologically proven lung cancer patients were evaluated in the light of clinical, radiological & pathological features. According to the histological diagnosis stage of the disease and performance status, patients received various treatment modalities. Those coming in follow up constituted the study population. RESULTS: Lifespan could be assessed in 122 patients (110 males and 12 females). 75.3% patients died within 6 moths of diagnosis and only 6.5% survived more than a year. About 50% patients having performance India 3 or 4 died within 3 months of their diagnosis. 42.8% cases of squamous cell carcinoma, 45.4% of adenocarcinoma and 50% of small cell carcinoma survived no longer than 6 months. Average life span in SCLC was 4.9% months and 4.1 months in NSCLC 55% of SCLC patients with ED died within 3 months of diagnosis while similar proportion of stage III b and 83% of stage IV NSCLC patients died within 6 months In both SCLC and NSCLC, Survival was better in those with performance index zero or one and those receiving the chemotherapy. Generalized debility due to relapse, progression of disease or treatment related advance effects was the commonest terminal event (67.2%) followed by pulmonary embolism (31.1%), renal failure (14.7%) & others. CONCLUSION: In our study the survival of patients with advanced disease was poor and survival decreased further with poor performance status. CLINICAL IMPLICATIONS: : Survival in lung cancer patients is poor in this vary part of India and is significantly influenced by stage of the disease, histological type, performance index and treatment modalities etc. DISCLOSURE: Dr.Sidharth Sharma, None. IMPLEMENTATION OF GUIDELINES: PREOPERATIVE ASSESSMENT OF PATIENTS UNDERGOING LUNG RESECTION SURGERY FOR LUNG CARCINOMA; A CASE STUDY Naim Y. Aoun MD* Eduardo Velez MD Katherine P. Hendra MD St. Elizabeth Medical Center, Boston, MA PURPOSE: The pre-operative evaluation of patients with lung carcinoma being considered for resection has been outlined in a number of published guidelines, including those from the American College of Chest Physicians (ACCP) (Chest Supplement 2003). The current investigation was designed to assess the utilization of these recommendations by thoracic surgeons. METHODS: A web-based survey of 13 questions utilizing the ACCP step-wise physiologic approach to these patients was e-mailed to all US members of the “Society of Thoracic Surgeons”. RESULTS: The response rate was 10% (n⫽243). The geographical location and practice type were evenly distributed. The majority of surgeons (99%) routinely requested pre-operative pulmonary function testing (PFT). Most (82.6%) proceed with resection if the PFT is normal (FEV1 ⬎60%), while 17.4% required more investigations. If the FEV1⬍60%, five physicians (2.1%)declined surgery, while the remainder proceed with further secondary evaluation including split function V/Q scan (60.3%), stair climbing (18%), cardio-pulmonary exercise testing (CPET) (14.2%) or walk test (5.4%). Abnormal results prompted further testing in 85.2% of respondents, while 14.8% declined surgery. When responses were stratified based on the surgeons’ primary hospital affiliation, community (n⫽94) vs. teaching community and university (n⫽146), those without an academic affiliation withhold surgical resection based on abnormal secondary testing (29.5% v/s 15.1%, p⬍0.05). Similar results were found in practitioners performing fewer than 50 resections a year (n⫽157) as compared to those performing ⬎ 50 (n⫽86)(27.7% v/s 8.5%; p⬍0.05). CONCLUSION: The results of this survey demonstrate that the majority of thoracic surgeons are following the ACCP guidelines for pre-operative evaluation of patients with lung carcinoma. However, surgeons in the community, and those performing fewer resections more frequently decline surgery before completing the recommended physiologic assessment. CLINICAL IMPLICATIONS: For some patients with lung carcinoma surgical resection remains the best option for cure. Given this factor, a complete pre-operative physiologic evaluation should be completed before patients are declined for resection. Broader implementation CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Lung Cancer Evaluation and Diagnosis, continued of guidelines outlining this assessment, especially at the community level, may allow more patients to proceed with surgical therapy.

significantly underestimate postoperative lung function after pneumonectomy, but are acceptable for lobectomy. CLINICAL IMPLICATIONS: Exercise tests may be better indicators of functional capacity after lung resection than measurements of FEV1 and FVC or DLCO at rest. DISCLOSURE: Jeng-Shing Wang, None.

IMPORTANCE OF EXERCISE TESTING IN DETERMINING EARLY RETURN TO WORK AFTER THE LUNG RESECTION Yoshinori Nagamatsu MD* National Hospital Organization Omuta National Hospital, Omuta Fukuoka, Japan

Lung Cancer Surgery 12:30 PM - 2:00 PM EFFECT OF LUNG RESECTION ON EXERCISE CAPACITY AND ON CO DIFFUSING CAPACITY DURING EXERCISE Jeng-Shing Wang MD* E-Da Hospital & I-Shou University, Kaohsiung, Taiwan ROC PURPOSE: To evaluate the effect of lung resection on lung function and exercise capacity values including DLCO during exercise, and to determine whether postoperative lung function including exercise capacity and DLCO during exercise could be predicted from the preoperative lung function and the number of functional segments resected. METHODS: Design: Prospective study.Setting: Clinical pulmonary function laboratory in a university teaching hospital.Patients: Twentyeight patients undergoing lung resection at Vancouver General Hospital from October 1998 to May 1999, were studied preoperatively and one year postoperatively. Interventions: We determined FEV1 and FVC, and maximal oxygen uptake (VO2max/kg) and maximal workload (Wmax) achieved during incremental exercise testing. We used the 3-equation modification of the single breath DLCO technique, method, to determine DLCO at rest and during steady state exercise at 70% of Wmax, and the increase in DLCO from rest to exercise (70%-R)DLCO. We calculated the predicted postoperative (ppo) values for all the above parameters using the preoperative test data and the extent of functioning bronchopulmonary segments resected, and compared results with the actual one year postoperative results. RESULTS: Following lung resection, there was a significant reduction in FEV1, FVC, and DLCO with decreases of 12%, 13%, and 22% of predicted respectively. There were also significant decreases in VO2max/kg of 2.1 ml/min/kg ( 8% of predicted VO2max) and in Wmax of 12watts (7% of predicted Wmax). However, (70%-R)DLCO, did not significantly decrease after lobectomy but decreased after pneumonectomy. The calculated ppo values significantly underestimated postoperative values in pneumonectomy, but were acceptable for lobectomy. CONCLUSION: Predicted postoperative results calculated by estimating the functional contribution of the resected segments, are comparable with those obtained using ventilation perfusion lung scanning, and

DOES PREOPERATIVE INTERVENTION PROGRAM IMPROVE POSTOPERATIVE OUTCOME IN HIGH-RISK PATIENTS UNDERGOING THORACIC SURGERY? Wai Ming M. Yung MBBS* Y.W. T. Mok MBBS S.O. Ling MBBS Y.N. Poon MBBS K.C. Wong MBBS C.W. Yim MBBS Kowloon Hospital, Hong Kong, Hong Kong PRC PURPOSE: To assess the effectiveness of preoperative intervention program in reducing the incidence of postoperative pulmonary complications (PPCs) and 30-day mortality rate after thoracic surgery in high-risk patients. METHODS: A 3-week preoperative intervention program, consisting of chest physiotherapy, exercise training, smoking cessation and psychological counseling, was offered to high-risk patients with preoperative FEV1⬍80% predicted or current smokers in a tertiary respiratory medical centre before undergoing thoracic surgery. The 30-day mortality rate and incidence of PPCs, which are defined as pneumonia, atelectasis, PaCO2 greater than 50mmHg lasting for more than 48 hours after surgery, and respiratory failure requiring mechanical ventilation, was compared to those of a group of patients who did not participate in the program (control group). RESULTS: Between April 1, 2000 and March 31, 2002, 42 patients in the intervention group and 27 controls were studied. The baseline characteristics between the 2 groups were comparable except age and the percentage of malignancy. 62% of patients in the intervention group completed the 3-week training. In the intervention group, the mean 6-minute walk distance improved by 38.6 metre (p⬍0.05) after training. There was no difference in the rates of PPCs and postoperative ICU admission & the hospital stay between the intervention and control CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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DISCLOSURE: Naim Aoun, None.

PURPOSE: Issue of earlier return to work after the lung resection is very important for patients. Yet, there must be a determination of patient’s physical ability to go back to work. Therefore, the institute has conducted this study after lung resection. METHODS: Between 1998 and 2005, the institute operated total of 97 cases. 88 cases were lobectomy and 7 cases were bilobectomy, and 2 cases pneumonectomy. 55 out of 97 patients were male and 42 patients were female. The average age is 68 years old. The exercise testing and spirometric lung function testing were done before and after the surgery. The exercise testing measured the maximum oxygen uptake per minute per the body surface area (VO2max/m2) to determine patient’s physical ability, and spirometric lung function testing used two measurements such as the vital capacity per the body surface area (VC/ m2) and forced expiratory volume in 1.0 sec per the body surface area (FEV1.0/ m2). The institute decided 100 as its baseline before the surgery. RESULTS: The average results of two weeks after the surgery were the following: VO2max/m2 was 82%, VC/m2 was 68.7%, and FEV1.0/m2 was 72.4% compared to results from before the surgery. 4 weeks later: VO2max/m2 result was up to 88.1%, VC/m2 increased to 74.8%, and FEV1.0/m2 went up to 77.7%. In this study, predetermined physical ability level was 80% as acceptable level to return to work. 60 cases out of 96(62.5%) exceeded this level two weeks after the surgery; 71 cases out of 94 cases (75.5%) met this level 4 weeks after. CONCLUSION: The research shows the patient’s physical ability recoveries are quick after the lung resection; 62.5% patients have enough physical ability to return to work after two weeks, and 75.5% patients can go back to work 4 weeks after the surgery. CLINICAL IMPLICATIONS: It is possible to use these exercise tests to determine when a patient is able to go back to work and to encourage them to do so after the lung resection. DISCLOSURE: Yoshinori Nagamatsu, None.

Wednesday, November 2, 2005 Lung Cancer Surgery, continued groups. The 30-day mortality rate, however, was lower in the intervention group and the difference approached statistical significance. CONCLUSION: Preoperative intervention program improves the mean 6-minute walk distance with statistical significance. It also reduces the 30-day mortality rate. Randomized controlled trial is warranted for better assessment of its efficacy. CLINICAL IMPLICATIONS: Pulmonary complications are common contributors to mortality and morbidity after thoracic surgery. The risk is increased in smokers and those with preexisting lung diseases. Preoperative intervention program may help to improve the postoperative outcome in this group of patients. DISCLOSURE: Wai Ming Yung, None.

ANEMIA AFFECTS OUTCOME AFTER SURGICAL RESECTION FOR EARLY STAGE LUNG CANCER Cliff P. Connery MD* Louis Harrision MD Karen McGinnis MD Maureen Reyes Andy Nabong BS Robert C. Ashton MD St. Luke’s Roosevelt Hospital, New York, NY PURPOSE: Anemia has been implicated as a significant factor in the failure of response for solid tumors in patients undergoing radiation therapy and chemotherapy. The purpose of our study was to analyze the correlation of preoperative hemoglobin levels and survival after surgical resection for early stage lung cancer. METHODS: All patients undergoing resection for Stage I and II non-small lung cancer from January 2002 through December 2003 comprised the cohort. Patients were followed up to December 2004 or death. Demographics and risk factors, including age, prior thoracic surgery, coronary artery disease, congestive heart failure, hypertension, diabetes, renal failure, peripheral vascular disease, steroid use, ASA classification, Zubrod score, and neoadjuvent therapy, were analyzed along with preoperative hemoglobin levels. Data was collected prospectively, based on Society of Thoracic Surgeons database model. RESULTS: Preoperative hemoglobin was found to be an independent predictor of intermediate survival for patients undergoing surgical resection for early stage lung cancer. Hemoglobin levels greater than 14 resulted in 100 percent survival as compared to levels less than 12 which resulted in a 73.7 percent survival during the follow-up period. Using the Pearson Correlation, hemoglobin was a significant factor in survival (p ⫽ 0.007). The mean time to death was shortest in Group I, 5.41 (0.1-13.8). One death occurred in perioperative period in the cohort, Group I. There was one transfusion in the cohort, group III. CONCLUSION: For patients with non-small cell lung cancer undergoing surgical resection, hemoglobin was found to be a predictor of survival. The exact mechanism or cause/effect relationship is theoretical at this time. The effects of tissue hypoxemia and free radical generation need to be studied to assess the effects they have on tumor cell survival. CLINICAL IMPLICATIONS: Further investigation is warranted to determine if hemoglobin is a marker of overall risk or if it is a determinant of survival. Additionally, the question of optimization of preoperative hemoglobin prior to surgical therapy and its effect on survival should also be investigated.

EFFICACY OF CYBERKNIFER STEREOTACTIC RADIOSURGERY WITH SYNCHRONYTM MOTION TRACKING MODULE FOR TREATMENT OF MALIGNANCIES IN THE THORAX Amit V. Patel MD* Brian Collins MD Shakun Malik MD Carlos Jamis-Dow MD David Earl-Graef MD Gregory Gagnon MD Eric D. Anderson MD Georgetown University Medical Center, Washington, DC PURPOSE: To discern the effectiveness of CyberKnifeR stereotactic radiosurgery with SynchronyTM motion tracking on both central and peripheral thoracic tumors measured by both CT and PET imaging at three-month and six-month intervals. METHODS: All patients who underwent CyberKnife with Synchrony for treatment of thoracic malignancies were enrolled. Patients were divided into two groups according to the location of their tumors within the thorax. Peripheral nodules received a total of 45– 60 Gy applied in 3 fractions over a 7-10 day period while those with central tumors received doses of 18-30 Gy over 3-5 treatments. CT of the chest and PET scans were obtained at three-month and six-month intervals post treatment. RESULTS: A total of 24 patients were enrolled since July 2004. Etiology of the ten peripheral malignancies consisted of primary NSCLC (7) and metastatic diseases including esophageal (1), muscle (1), and skin (1). Etiology of the 14 central lesions consisted of primary NSCLC (11), and metastatic diseases including colon (1), breast (1) and kidney (1). Tumor size ranged from 7mm to 8cm. The major side effect consisted of fatigue. At three months, partial response was noted in first 7 patients treated for peripheral nodules. A complete response was noted at 6 months in the first patient with a peripheral nodule. Two patients with central tumors showed stable disease at three months. One central tumor patient showed initial improvement, followed by progression of disease at three months. CONCLUSION: All patients tolerated the treatment well. Patients with peripheral lung nodules who received Cyberknife with Synchrony had a significant response to treatment. CLINICAL IMPLICATIONS: Cyberknife stereotactic radiosurgery with Synchrony motion tracking is a safe and effective modality for treating tumors in the thorax. This treatment may be suitable for non-surgical candidates and patients who refuse surgery. Cyberknife may also be an option in patients who have received prior irradiation.

Hemoglobin (G/DL) Range

Mean

Frequency

Percent

I

9.7-12.0

11.1

II

12.1-13.0

12.5

III

13.1-13.9

13.48

IV

14.0-16.1

14.85

Alive 14 Dead 6 Alive 18 Dead 3 Alive 16 Dead 2 Alive 20 Dead 0

70 30 86 14 89 11 100 0

Groups

DISCLOSURE: Cliff Connery, None.

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DISCLOSURE: Amit Patel, None. WEDGE VERSUS LOBECTOMY: COMPARING SURVIVAL IN STAGE I NON-SMALL CELL LUNG CANCER Dennis J. Rassias MD* Alexander Kraev BA John Vetto MD Mikhail Torosoff MD Adebambo Kadri MD Pasala Ravichandran MD Christina Clement BS Riivo Ilves MD Albany Medical Center, Albany, NY PURPOSE: The selection of lobectomy or wedge resection in stage I lung cancer remains controversial. We investigated the impact of each procedure on long term survival in a multi-center analysis. METHODS: The records of 293 patients were reviewed for age, sex, type of resection, tumor size, number of lymph nodes dissected, and pathology. Data was obtained through the Federal Social Security Death Index and Cancer Registries. Kaplan-Meier, Wilcox, Logistic Regression, CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Lung Cancer Surgery, continued and t-test analyses were used to examine survival, predictors of mortality, and correlations. RESULTS: 217 patients underwent lobectomy and 76 had wedge resection for Stage I lung cancer. The groups were similar with respect to age, tumor size and other co-morbidities. Overall, there was a trend towards improved survival in patients who had lobectomy (mean survival 5.8⫾0.3 vs. 4.1⫾0.3 years, respectively; p⫽0.112, see Graph 1). This trend gained statistical significance in smaller cancers, where lobectomies for tumors less than 30mm had better survival when compared to patients that had wedge resection (p⫽0.029, see Graph 2). CONCLUSION: Although the overall difference in survival between lobectomy and wedge resection is insignificant, patients with tumors smaller than 30mm showed a statistically significant survival benefit after lobectomy. CLINICAL IMPLICATIONS: Tumor size, therefore, is an important factor to be considered in pre-operative planning. Randomized trials are necessary to confirm these findings.

PRIMARY LUNG CANCERS DISCOVERED AS SOLITARY PULMONARY NODULE: REVIEW OF 209 CASES Pier Luigi Filosso MD* Davide Turello MD Giovanni Donati MD Fausto Pernazza MD Ottavio Rena MD Caterina Casadio MD Enrico Ruffini MD Alberto Oliaro MD University of Torino, Department of Thoracic Surgery, Torino, Italy

DISCLOSURE: Dennis Rassias, None.

PROGNOSIS AND SURVIVAL FOLLOWING SURGICAL RESECTION FOR LUNG CANCER WITH N2 INVOLVEMENT OF THE MEDIASTINUM Adebambo M. Kadri MD* Dennis Rassias MD Riivo Ilves MD Albany Medical College, Albany, NY PURPOSE: Surgical resection remains the primary modality for the potentially curative treatment of anatomically resectable non small cell lung cancer. The presence of mediastinal lymph node metastasis (N2 disease) is known for its association with a poor prognosis. The value and desirability of surgical resection for N2 disease remains controversial. The purpose of the study is to estimate the actuarial survival following surgical resection for N2 disease and determine the prognostic factors which influence survival.

PURPOSE: to assess the prognostic factors and outcome of primary lung cancers (PLCs) discovered as solitary pulmonary nodules (SPNs). METHODS: between 1999 and 2003 314 patients (223 male-71%-, mean age 64 years-range 21-81 years-) underwent surgical resection of a SPN. Of these 209 (66%) were PLCs, 56 (17%) lung metastases and 49 benign lesions. RESULTS: One hundred and ten (75%) out of 209 PLCs were adenocarcinomas, 58 (18.7%) squamous cell carcinomas, 12 bronchioloalveolar carcinomas, 8 large cell carcinomas and 12 bronchial carcinoids. Nine patients had mixed tumors. Twenty-six (12.6%) were less than 1 cm. in size; 100 (47.5%) between 1.1 and 2 cm, and 83 (39.9%) between 2.1 and 3 cm. One hundred thirty-seven (65.7%) were N0; 25(11.9%) were N1 and N2, respectively; in 22 (10.5%) lymphadenectomy was not performed. Three and five year overall survival rates were 70% and 52%, respectively. The following prognostic variables resulted statistically significant at multivariate analysis: the tumor histology (p⫽0.0005), the tumor size (p⫽0.007), the presence of lymphnodal metastases (p⫽0.00001), the visceral pleura invasion (p⫽0.0002) and the extent of resection (anatomic vs. limited resection) (p⫽0.004). CONCLUSION: this is a surgical series with a high PLCs percentage (66%), the majority of which were at early stage. An early diagnosis and surgical treatment represent the treatment of choice, especially in high risk patients, providing a good survival. CLINICAL IMPLICATIONS: in high risk patients PLC should be considered in occasionally discovered SPN. Early diagnosis and possible surgical treatment are mandatory. DISCLOSURE: Pier Luigi Filosso, None. DEATH HAZARDS FOLLOWING SURGICAL RESECTION FOR NON SMALL CELL PRIMARY BRONCHIAL CANCER: A STUDY ON THE POSSIBLE CURABILITY OF THE DISEASE Adebambo M. Kadri MD* Riivo Ilves MD Albany Medical Center, Albany, NY PURPOSE: The favourable survival benefits of surgical resection for early stage non small cell primary bronchial cancer is well recognized. The value of lung resection for advanced lung cancer with locoregional spread CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

METHODS: Between 1994 and 2003, 51 patients underwent lung resection for pathologically proven N2 disease. The records of these patients were retrieved from the Cancer Registry Database of the Albany Medical College and retrospectively analysed. Survival analysis was performed using the Kaplan-Meir method. The influence of several prognostic factors on survival was evaluated using the logrank test. RESULTS: There were 51 patients, (30 men), mean age 64 years (range 37 to 85 years). Operative mortality was 2.2 years. The distribution of age, sex, and cell type was similar between the patients with N2 diseas and 241 other patients without N2 involvement, who underwent lung resection in the same time period. Advanced overall stage and advanced T stage were significantly more common in the presence of N2 diseease (P⬍0.001), and pneumonectomy was more commonly employed in the presence of N2 disease (P⬍0.001). Overall 5 year survival was 20.3%. Survival was not influenced by stage, T stage, cell type, type of lung resection or the application of multimodality treatment. CONCLUSION: The study confirms the poor prognosis associated with lung cancer with N2 involvement of the mediastinum. The lack of prognostic importance of cell type, disease stage and type of lung resection suggests that in advanced lung cancer the important factor in prognosis is the presence of extrapulmonary disease. CLINICAL IMPLICATIONS: The low operative mortality and the 20.3% 5 year survival justifies surgical resection for those patients who are found at intraoperative pathological staging to have N2 disease. DISCLOSURE: Adebambo Kadri, None.

Wednesday, November 2, 2005 Lung Cancer Surgery, continued or extrapulmonary disease is less clear. The aim of the study is to determine the influence of disease stage on survival after resection for lung cancer, compare the annual death hazards for different stages of the disease and determine if the prognostic significance of disease stage changes with time. METHODS: The study cosisted of a retrospective interrogation of the prospectively collected information in the Albany Medical College Cancer Registry Database on 292 patients who underwent pulmonary resection for lung cancer over a 10 year period. Survival analysis was performed using the Kaplan-Meir method. Hazard Function calculations were performed to determine the annual risk of dying in the different stage groups. RESULTS: Operative mortality was 2.4%. Overall survival was 42.8%. Survival was significantly different for the different stages of the disease (P⫽0.001). Estimation of the instantaneous risk of dying revealed annual death hazards to be highest during the 5 year period for stage 3 disease. Death hazards subsequently declined for all stages. By the 5th year of followup, the difference in death hazards between the stages had nearly dissapeared. CONCLUSION: The study suggests that the prognostic significance of disease stage on early survival is diminished in later follow up. CLINICAL IMPLICATIONS: The chance of potential cure increases with longer follow up for patients with lung cancer with no evidence of systemic spread, who have undergone locoregional control by surgical resection. DISCLOSURE: Adebambo Kadri, None.

Lung Transplantation 12:30 PM - 2:00 PM ASSESSING REGIONAL LUNG FUNCTION IN SINGLE LUNG TRANSPLANT (SLT) RECIPIENTS USING A NEW VIBRATION RESPONSE IMAGING (VRI*) TECHNOLOGY Mordechai R. Kramer MD* Yael Raviv MD Ruth Hardoff MD Merav Gat MA Igal Kushnir MD Rabin Medical Center, Petach Tikva, Israel PURPOSE: Background: In a well functioning graft following SLT most of the ventilation (V) and perfusion (Q) shifts to the transplanted (Tx) side. A routing V/Q scan is performed periodically to asses the graft function. Chest auscultation usually discloses a difference between the Tx and non-Tx lungs, however no quantitative nor regional assessment can be done by the physical examination.VRI is a new system that records the vibrations produced by airflow and converts the signals to a dynamic image of the lung. The vibration energy throughout the breathing cycle can be quantified for any lung region, by integrating the energy over 40 acoustic sensors .Objective: To evaluate the correlation between regional vibration (VRI) energy and regional lung function as assessed by radionuclide V/Q scan. METHODS: We examined 28 stable patients (12 F/16 M; age 58.6⫹9.8 yrs: FEV1 58.3⫹15%) who underwent SLT (18 Left lung, 10 Right lung). Patients underwent V/Q scans and VRI testing. For each mode, the chest was divided into 6 areas, 3 at each side, and the corresponding regional signals (fraction of the total radioactivity vs. fraction of the VRI energy units) were integrated and compared. RESULTS: The regional VRI evaluations were found to be highly correlated with the V/Q results (R⫽0.92, p⬍0.001) (see figure). The images of all subjects shared similar features with hyperdynamic vibration of the transplanted lung as compared to the native side with excellent correlation to the V/Q. CONCLUSION: VRI has excellent corellation to lung V/Q scan in stable patients following SLT. CLINICAL IMPLICATIONS: These preliminary findings suggest that VRI may provide a simple, radiation-free novel tool to assess qualitatively and quantitatively lung function in lung transplanted patients and to monitor the patient during the post-operative period for acute or chronic rejection.* www.deepbreeze.com.

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DISCLOSURE: Mordechai Kramer, None. ROLE OF LUNG TRANSPLANTATION IN THE MANAGEMENT OF PATIENTS WITH LAM: BASELINE DATA FROM THE NIH LAM REGISTRY Janet R. Maurer MD* Jar-Chi Lee MS Gerald Beck PhD Kevin K. Brown MD Joel Moss MD Jay H. Ryu MD CIGNA HealthCare, Avon, CT PURPOSE: Data on candidate selection and post-transplant follow-up in LAM patients is limited. An NIH-funded a Registry collected data on LAM patients including outcomes of patients undergoing or anticipating lung transplantation. Baseline pulmonary function (PFT) and quality of life data from that population is summarized. METHODS: Patients enrolled between 8/98 and 10/01. Six centers registered 243 patients. Initially, patients completed questionnaires detailing medical history, symptoms, laboratory values, treatment, and quality of life. PFTs were done. Follow-ups were at six months and/or yearly. RESULTS: Of the 243, 13 (5.3%) were transplanted before enrollment (Group A); 21 (8.6%) were transplanted during the Registry period (Group B); 48 (19.8%) were waitlisted or evaluated for transplant during the Registry period (Group C); 161 (66.3%) were not listed or considered for transplant (Group D). Baseline PFTs of Group D and Group A patients were not significantly different; however, baseline PFTs of Group B patients were significantly worse than PFTs of Group A or Group D patients (p⫽0.015 and ⬍0.001, resp.). Group A patients scored better than Group B patients in the SF-36 physical domain (p⫽0.003) and in the overall St. George Questionnaire (p⫽0.006) and it’s activity domain (p⬍0.001). Group D and Group A scores were similar. CONCLUSION: More than one-third of LAM Registry enrollees either had undergone transplant or were considered for transplant. CLINICAL IMPLICATIONS: Pulmonary transplantation appears to be associated with both better pulmonary function and quality of life compared to patients with physiologically advanced disease prior to transplant (Group B). Funded by NIH (NHLBI) Grant No 1 U01 HL58440.

.

N Group Group Group Group

A B C D

N*

% Pred. FEV1

Mean (S.D.)

13 21 48 161

2 20 47 151

70.5(27.6) 46.0(20.0) 56.7(19.0) 77.7(22.2)

N* ⫽ number of patients with FEV1 values DISCLOSURE: Janet Maurer, None. READMISSION TO AN INTENSIVE CARE UNIT AFTER LUNG TRANSPLANTATION: EXPERIENCE OF A SINGLE CENTER Deborah J. Levine MD* Luis Angel MD Sako Edward MD Stephanie Levine MD University of Texas Health Science Center San Antonio, San Antonio, TX PURPOSE: Short-term survival after lung transplantation has improved such that over 90% of recipients are discharged post-operatively. Long term survival, however, can be complicated by the need for readmission to an ICU in many patients. Respiratory failure is the most common cause for re-admission, however,we found that a significant number of admissions are required for non-pulmonary issues. The purpose of this study is to evaluate the nature and frequency of icu readmissions post transplant. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Lung Transplantation, continued

Table 1: Primary Diagnoses for Lung Transplant Recipients Readmitted to the ICU Cause Pulmonary Cardiac Hematologic/Oncologic Neurologic Infectious Disease (not including pneumonia) Renal Endocrine

Percent 59% (pneumonia, rejection, pleural effusion, pulmonary embolus) 10% 8% 8% 6% 6% 2%

DISCLOSURE: Deborah Levine, None. BRONCHODILATOR RESPONSE AS A PREDICTOR OF BRONCHIOLITIS OBLITERANS SYNDROME IN SINGLE AND DOUBLE LUNG TRANSPLANTS Forest H. Mealey DO* Kevin McCarthy RRT Jeffrey Chapman MD Cleveland Clinic Foundation, Cleveland, OH PURPOSE: Brochodilator (BD) response is frequently requested in lung transplant patients. In earlier studies, bronchial hyperreactivity, as determined by BD response and methacholine challenge, has been shown to correlate with the development of Bronchiolitis Obliterans (BO) and BO Syndrome (BOS), however, these studies were limited by small sample size, small numbers of single lung transplants (SLT) and the evolution of transplant medicine since completion. We reviewed data to determine if BD response predicts BOS in single and double lung transplants. METHODS: Data from 432 patients, transplanted from 1991-2005, were reviewed. Exclusion criteria included expiration within one year of transplant, follow up less than one year and anastomotic stenosis. All patients had serial spirometry per protocol pre and post albuterol MDI. BD response was determined by current ATS guidelines. BOS was determined by decline in FEV1 as per current ISHLT criteria. Data were analyzed using the chi-squared test. RESULTS: 221 patients met criteria. SLT was performed in 141 (63.8%) patients. 31/221(14%) patients had a significant BD response. 12/31 (38.7%) patients in the BD responder group developed BOS vs. 45/145 (31%) of non-responders. The difference was not significant (p⫽0.484). In SLT, 8/24 (33%) with BD response developed BOS vs. 29/119 (24.4%) non-responders (p⫽0.84). There were no significant

associations between BD response and single vs. double lung transplantation (p⫽0.394). COPD was the pre-transplant diagnosis in 12/24 SLT patients with BD response vs. 21/90 SLT patients without BD response (p⫽0.084). CONCLUSION: In this study BD response was not associated with the development of BOS in DLT or SLT transplant patients. COPD was more commonly associated with BD response in SLT patients, though this difference was not significant. CLINICAL IMPLICATIONS: BD response appears to have limited clinical utility in predicting BOS. DISCLOSURE: Forest Mealey, None.

MYCOBACTERIA ABSCESSUS IN LUNG ALLOGRAFT RECIPIENTS Leonardo Seoane MD* Denise Fuchs RN Gisele A. Lombard RN Stephanie G. Laplace RN David E. Taylor MD Vincent G. Valentine MD Ochsner Clinic Foundation, New Orleans, LA PURPOSE: Most rapidly growing nontuberculous mycobacterial infections are due to Mycobacterium abscessus. Isolated reports of M. abscessus infection after lung transplantation (LT) suggest this species poses a significant threat to lung allograft recipients(LARs). We report our experiences and clinical outcomes of M. abscessus infection following LT. METHODS: We performed a retrospective chart review of 197 LARs performed at our institution between 1991 and 2005. Infection was defined as symptoms in the prescence of chest radiograph changes and positive cultures from a bronchoalveolar lavage (BAL). RESULTS: Eight (4%) LARs were diagnosed with M. abscessus pulmonary infection. The transplant diagnosis included cystic fibrosis (3), emphysema (3), idiopathic pulmonary fibrosis (IPF)(1), and sarcoid (1). One LAR had M. abscessus prior to transplant and died because of disseminated infection peri-operatively. All underwent bilateral lung transplants except the LAR with IPF. The most common symptoms were dyspnea, cough, and fever. Two deaths may be directly attributable to M. abscessus, since both patients died of respiratory failure with granulomatous pnuemonia on autopsy. Five patients responded to therapy as demonstrated by improved symptoms and culture negativity on repeat BAL. CONCLUSION: The prevalence of M. abscessus is relatively low post LT. Although it may be a potentially fatal pathogen in LARs, the majority of infected LARs respond to therapy. A multi-institutional study may further our understanding of M. abscessus infections among LARs. CLINICAL IMPLICATIONS: M. absessus poses a significant threat to LARs. However, successful treatment of M. abscessus is possible post LT. DISCLOSURE: Leonardo Seoane, None.

LONG-TERM OUTCOME FOLLOWING LUNG TRANSPLANTATION FOR PATIENTS WITH SARCOIDOSIS Amit Gaggar MD* Keith Wille MD Kevin Leon MD Katherine Hart BS Susan Kerkhof RN David McGiffin MD K. R. Young MD University of Alabama at Birmingham, Birmingham, AL PURPOSE: End-stage sarcoidosis is characterized by severe pulmonary fibrosis and often poorly responsive to medical therapy. Lung transplantation, therefore, may be the only treatment option. Currently, there are few studies evaluating long-term outcomes following transplantation for these patients. The aim of this investigation is to evaluate the post-transplant morbidity and mortality of patients with sarcoid, compared to recipients transplanted for idiopathic pulmonary fibrosis (IPF). METHODS: This study is a retrospective review of all lung transplant recipients at a tertiary care center over a 10-year time period (1994-2004). Data collected include patient demographics, bronchoscopy results, spirometry, development of bronchiolitis obliterans syndrome (BOS), and median survival post-transplantation. RESULTS: Over the study period, 300 patients underwent lung transplantation. Fourteen (4.7%) had sarcoidosis and 48 (16.0%) had IPF. Recipients in the sarcoid group were younger (mean age 41.3 versus 55.8 years*) and predominantly female (93% versus 38%*), compared to recipients in the IPF group at the time of transplant (* p ⬍ 0.01, Mann-Whitney). Five of 14 (36%) sarcoid patients developed BOS versus 15 of 48 (31%) IPF patients (p⫽ns). There was no significant difference in the time to BOS onset. Median survival was 1,365 days for the sarcoid CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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METHODS: We performed a single center review of 83 consecutive lung transplant recipients who were successfully discharged post transplant between 1/1999 and 4/2004. Evaluation included patient demographics, pretransplant diagnoses, and time and diagnoses of admission to University Hospital’s ICU up until 7/2004. Patient charts and ICD-9 codes were used to document distribution of the primary diagnoses. Demographics were compared to patients who did not require readmission during the study period. RESULTS: A total of 83 single (21%)and bilateral (79%)lung transplants were performed at our institution from 1/99 to 5/2004. 28 patients(34%) required re-admission to University Hospital’s ICU 49 times until 7/2004. Demographics including age, type of transplant, sex, and pre-transplant diagnosis were not significantly different from those not requiring re-admission. Distribution of primary readmission diagnoses are outlined in Table 1. Pulmonary dysfunction was the major complication leading to ICU admission (59%). 41% of admissions were distributed between non-pulmonary complications. Time to readmission ranged from 27 days to 540 days with a mean of 200 days. CONCLUSION: Respiratory failure was the most common reason for readmission to our ICU post lung transplantation. However, there was a distinct subset of characteristic non-pulmonary issues that occurred with enough frequency (41%), that they warrant further evaluation. CLINICAL IMPLICATIONS: Further study is needed to identify which clinical factors (pre-transplant co-morbidities,immunosuppression,etc), either pre- or post transplantation, may predict a return to the ICU after initial discharge following transplantation.

Wednesday, November 2, 2005 Lung Transplantation, continued group and 1,593 days for the IPF group (Hazard Ratio 1.28 by KaplanMeier analysis; [95% CI] 0.55-3.14; p ⫽ 0.54). CONCLUSION: We observe similar long term outcomes for sarcoid and IPF recipients following lung transplantation. CLINICAL IMPLICATIONS: Lung transplantation remains an option for the treatment of end-stage sarcoidosis, as BOS and mortality rates post-transplant are comparable to IPF. DISCLOSURE: Amit Gaggar, None. EFFECT OF OBESITY IN THE OUTCOMES OF LUNG TRANSPLANT RECIPIENTS Cesar A. Keller MD Debra Boswell RN* Javier Aduen MD Heidy David-Robinson RN Jefreey Shalev BS Francisco Alvarez MD Mayo Clinic, Jacksonville, FL PURPOSE: Previous studies have reported increased mortality among obese lung transplant (LT) recipients. This retrospective study evaluated the short and long term outcomes of obese (Body Mass Index or BMI equal or ⬎30) lung transplant recipients, compared to non-obese (BMI⬍30) patients. METHODS: Retrospective collection of data from the Mayo Clinic Lung Transplant Database among 63 patients receiving lung transplants from June 2001 to June 2004 at the Mayo Clinic. Demographic data, height and weight at time of transplant, BMI, clinical outcomes and survival rates were collected and compared among the 2 groups. RESULTS: Out of 63 LT recipients, 48 (76%) were Non-Obese (weight⫽ 67 ⫹-15 kg and BMI⫽ 24⫹-4), and 15 (14%) were Obese (weight⫽ 92.4⫹-9 and BMI 31.4⫹-1). Clinical outcomes during lung transplant were as follows: For Non-Obese recipients, the ICU stay was 9⫹-11 days. The Lenght of stay (LOS) was 24⫹-19 days. Obese patients required an ICU stay of 8⫹-9 days. The LOS was 24⫹-18 days (Not statistically significant) The survival at 1 month, 6 months and 12 months were as follows. Non-Obese: 98%, 84% and 76% (mean survival 20⫹-12 months). Obese recipients: 100%, 100% and 100% (mean survival 24⫹-10 months up to the current date). CONCLUSION: In our experience, 15 patients who were obese at the time of transplant (BMI ranging from 30 to 35.6) had as good or better immediate post-op course after lung transplantation compared to NonObese patients (BMI ranging from 18 to 29.7). Survival rates for obese lung transplant recipients up to one year after transplant were as good or better than non-obese patients. CLINICAL IMPLICATIONS: The assumption that a BMI ⬎ 30 represents likelihood of increased morbidity or mortality among lung transplant recipients may not be necessarily true. Larger studies with longer follow up may find expanded criteria for potential lung transplant recipients with BMI as high as 35 if these preliminary results are confirmed by larger clinical trials. DISCLOSURE: Debra Boswell, None. VORICONAZOLE VERSUS ITRACONAZOLE FOR FUNGAL PROPHYLAXIS AFTER LUNG TRANSPLANTATION John H. Sherner MD* Scott Barnett PhD Shahzad Ahmad MD Nelson Burton MD Mary Schmidt MD Steven Nathan MD Walter Reed Army Medical Center, Washington, DC PURPOSE: Aspergillus and other fungal infections are common causes of morbidity and mortality in lung transplant recipients. Most patients receive prophylaxis against fungal infections, but the optimal regimen has not been defined. The purpose of this study was to assess the efficacy of voriconazole as fungal prophylaxis. METHODS: We retrospectively reviewed data from 56 lung transplant recipients. Group A (n ⫽ 23) consisted of patients who underwent transplantation after the introduction of voriconazole prophylaxis. Group B (n⫽23) consisted of patients transplanted immediately prior to the introduction of voriconazole, in whom itraconazole was used as prophylaxis. Both groups received inhaled amphotericin B during their initial hospitalization adn continued oral antifungal prophylaxis until one year post-transplantation. The primary endpoint was positive BAL fungal cultures during the first year. We also assessed clnical events related to aspergillus and overall mortality. RESULTS: The incidence of patients with positive bronchial cultures for aspergillus at 1 year was 5/28 (18%) in the group A and 10/28 (36%) in group B (p ⫽ 0.134, ns). At the time of recovery of aspergillus, 4/5 (80%) patients in group A were actually receiving voriconazole, versus

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90% (9/10) in group B receiving itraconazole. The incidence of patients with positive bronchial cultures for candida was 0 in group A versus 50% (14/28) in group B (p ⫽ ⬍ 0.0001). At one year, there was one clinical aspergillus event in each group, non-fatal in group A and fatal in group B. There was an additional fatal aspergillus event in group B at month 25, as well as an episode of scedosporium sepsis at month 13. CONCLUSION: In our lung transplant population, the use of voriconazole results in decreased airway colonization with aspergillus and candida. CLINICAL IMPLICATIONS: These findings suggest that voriconazole is effective antifungal prophylaxis for lung transplant recipients. The overall low rate of clinically significant fungal events do not allow any further conclusions to be drawn. DISCLOSURE: John Sherner, None. DIFFERENCES IN QUALITY OF LIFE AMONG PATIENTS LISTED FOR LUNG TRANSPLANTATION Leonardo Seoane MD* Valerie Schacter Connie E. Thonpson RN LaPlace G. Stephanie RN David E. Taylor MD Vincent G. Valentine MD Ochsner Clinic Foundation, New Orleans, LA PURPOSE: There have been few studies on the quality of life among patients awaiting lung transplantation (LT). Patients with end stage lung disease can be divided into those with either airflow obstruction (emphysema and cystic fibrosis) or restrictive physiology (idiopathic pulmonary fibrosis). We assessed the quality of life of LT candidates with respect to obstuctive physiology (O) versus restrictive physiology (R). METHODS: Of 108 patients listed for LT between January of 2000 and August of 2004, 64 consented and completed the Medical Outcomes Study Short Form 36 (SF-36). Demographics and other clinical characteristics obtained during evaluation for LT were analyzed and compared with the results of SF-36. RESULTS: There were 18 patients in group R and 46 in Group O. Group O included an equal number of cystic fibrosis and emphysema patients. Group O was significantly younger. Younger patients reported less dyspnea with exercise and longer six minute walk distances. Comparisons of the two groups are shown in table 1. There was a trend towards lower scores among group O in the social function (p⫽0.09) and bodily pain (p⫽0.06) domains. The O group also had a trend towards increase physical function (p⫽0.07) However, there was a significantly worse general health score in the O group (p⫽0.003). CONCLUSION: Group O patients reported significantly worse general health than group R, despite being younger and having a trend towards more physical function and less bodily pain. CLINICAL IMPLICATIONS: The physiologic basis for impairment O vs R and age should be taken into consideration when interpreting SF-36 quality of life in patients listed for LT.

TABLE 1 Obstructive Restrictive Age (years) 42 ⫾ 18 BMI (kg/m2) 21.4 ⫾ 4.3 Borg scale dyspnea with exercise 5.2⫾ 2.3 Exercise O2 sat 87 ⫾ 8 6-min walk distance (ft) 1143 ⫾ 421

56 ⫾ 10 26.8⫾ 2.5 5.8 ⫾ 2.5 79 ⫾ 10 1196 ⫾ 284

p Value ⬍0.01 ⬍0.01 0.93 ⬍0.01 0.11

DISCLOSURE: Leonardo Seoane, None. INCIDENCE OF UNDETECTED LUNG NEOPLASMS IN EXPLANTS OF LUNG TRANSPLANT RECIPIENTS: EXPERIENCE OF A SINGLE CENTER Deborah J. Levine MD* Luis Angel MD Andres Pelaez MD Scott Johnson MD John Calhoon MD Stephanie Levine MD University of Texas Health Science Center San Antonio, San Antonio, TX PURPOSE: Many pre-lung transplant recipients with end-stage lung disease are at high risk for lung cancer. Evidence of lung cancer has been considered a contraindication to lung transplantation mainly because of CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Lung Transplantation, continued

Table 1: Data of Five Lung Transplant Recipients With Undetected Lung Carcinoma Pre-Transplant CXR CT Scan Indication Age/

for

Smoking

Case Sex Transplantation History 1

60 M

Emphysema

Yes

Type of Neoplasm Adenocarcinoma

Grade of

6 months

Survival

Prior to

Post

Neoplasm Transplantation Transplantation Stage 1

Negative

Dead -14 months

(poorly differentiated) 2

43 F

Emphysema

Yes

Adenocarcinoma

Stage 1

Negative

Dead-36 months

3

53 F

Emphysema

Yes

Bronchoalveolar

Stage 1

Negative

Dead-4 months

Dead-1 day

Carcinoma 4

59 F

UIP

Yes

Small Cell Carcinoma

Stage 1

Negative

5

45 F

␣-one

Yes

Adenocarcinoma

Stage 1

Negative

anti-trypsin

(Invasive)

Alive 32 months

DISCLOSURE: Deborah Levine, None.

SURVIVAL AFTER WEST NILE VIRUS MENINGOENCEPHALITIS IN A LUNG TRANSPLANT RECIPIENT Dale C. Lien MD* Justin G. Weinkauf MD Kathleen B. Jackson RN Pam Brown RN Andrea Taskinen RN Neil Skjodt MD University of Alberta, Edmonton, AB, Canada PURPOSE: Although the majority of West Nile Virus (WNV) infections are asymptomatic, severe neurologic injury and death may occur. Immunosuppressed lung transplant recipients are potentially at higher risk. However, the probability of developing severe disease after exposure, the clinical presentations, and the outcomes for lung transplant recipients contracting WNV are not well known. METHODS: We report one case of community acquired WNV infection in a lung transplant recipient who survived severe meningoencephalitis but with permanent neuromuscular impairment. The patient was a 48 year old male 2.5 years post bilateral transplant for idiopathic pulmonary fibrosis on immunosuppression with tacrolimus, mycophenalate, and alternate day prednisone. He was a farmer in rural western Canada in a highly endemic area of WNV in the summer of 2003.

RESULTS: He initially presented with fever, malaise and headache, and over the course of 5 days went on to develop confusion, decreased level of consciousness, and coma. Investigations included a series of 4 computerized tomographic head scans over 23 days which were normal. MRI was not done because of loose sternal wires. Lumbar puncture showed a lymphocytic pleocytosis with mildly elevated protein and negative WNV IgM. Initial WNV IgM in blood 5 days afer onset of symptoms was negative but became positive 14 days after symptoms began. The patient remained comatose on life support for nearly 3 months before neurologic recovery began. He received no specific treatment except initial empiric therapy with intravenous acyclovir in case of Herpes simplex encephalitis, and withholding of immunosuppression for 1 week followed by reinstitution at lower dosages. One year after presentation he has normal mentation but continues to have severe muscle weakness and dyscoordination limiting mobiity. Lung function remains unchanged from baseline levels. CONCLUSION: This case illustrates that lung transplant recipients even though immunocompromised, may recover from severe WNV meningoencephalitis. CLINICAL IMPLICATIONS: This case also emphasizes that prolonged life support may be required and that recovery may be incomplete. DISCLOSURE: Dale Lien, None.

Medical Education 12:30 PM - 2:00 PM COMPETENCY IN CHEST RADIOGRAPHY: A COMPARISON OF MEDICAL STUDENTS, RESIDENTS AND FELLOWS Lewis A. Eisen MD* Abhijith Hegde MD Jeffrey S. Berger MD Mangala Narasimhan DO Roslyn F. Schneider MD Beth Israel Medical Center, New York, NY PURPOSE: Accurate interpretation of chest radiographs (CXR) is essential since house officers are required to make clinical decisions based on their readings. We sought to evaluate CXR interpretation competency at different levels of training and to determine if specific factors are associated with successful interpretation. METHODS: Participants (n⫽145) from a single teaching hospital were third year medical students (MS) (n⫽25), internal medicine (IM) interns (n⫽44), residents (n⫽60) from the departments of IM and radiology, and fellows (n⫽16) from the divisions of cardiology and pulmonary/critical care. Participants reported their confidence in interpreting CXR on a scale of 0-10. They also reported their interest in a pulmonary career and perceived adequacy of CXR training. Ten conventional CXR were selected from the teaching file of the IM Department. The CXR included one normal radiograph and three examples of emergencies (pneumothorax, misplaced central line and pneumoperitoneum). Participants were asked to record the most important diagnosis. Two investigators independently scored each CXR on a scale of 0-2. RESULTS: The median interpretative score was 11 out of 20. An increased level of training was associated with an increased score (MS 8, intern 10, resident 15, fellow 15, p⬍0.001). Self-reported confidence (0-10) in interpreting CXR also increased (MS 4.0, intern 4.5, resident 6.0, fellow 6.0 p⬍0.001). Certainty was significantly correlated with interpretative score (r⫽0.606, p⬍0.001). IM interns and residents interested in a pulmonary career scored 14 while those not interested scored 11 (p⫽0.037). Radiology residents were more confident (7.0 vs. 5.0, p⫽0.021) and scored higher (18 vs. 11, p⬍0.001) than IM residents. Pneumothorax, misplaced central line and pneumoperitoneum were diagnosed correctly 9%, 26% and 46% of the time, respectively. Only 20 of 131 (15%) participants felt that their CXR training was sufficient. CONCLUSION: We identified several factors associated with successful CXR interpretation - level of training, field of training and confidence. Although interpretation improved with training, important diagnoses were often missed. CLINICAL IMPLICATIONS: More training in CXR interpretation is required with an emphasis on emergencies. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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the risk of dissemination secondary to immunosuppression post transplant. Experience is therefore limited on how patients with carcinoma progress post transplantation. The purpose of this study was to assess the frequency and spectrum of lung cancer found incidently at time of pneumonectomy for transplantation at our center. METHODS: We reviewed the charts of all lung transplant recipients at the University of Texas Health Science Center, San Antonio. Patient demographics including age, sex, indication for transplant, and smoking history were collected. Explant pathologic reports and pre-transplant radiographic studies were evaluated. RESULTS: There was 232 lung transplants performed on 229 patients from 11/1987 to 4/2005 (37 bilateral and 196 single). There were 120 males and 109 females. Mean age at time of transplant was 50 years. Five recipients (2.2%) were found to have carcinoma in the explanted lung. A significant increase in the proportion of smokers and women in the recipients with carcinoma was found. There was no radiographic evidence of possible neoplasm on CT Scan within 6 months prior to transplant or on chest radiograph on the day of transplantation. See Table 1. CONCLUSION: Discovering previously undetected neoplasms in the explanted lung of transplant recipients is an uncommon phenomenon. Although many recipients listed for transplantation are at high risk for lung cancer (diagnoses of emphysema and usual interstitial pneumonitis), those at highest risk are those who also have a significant smoking history. CLINICAL IMPLICATIONS: Patients listed for lung transplantation often wait for greater then two years for a graft. The evaluation including chest radiographs and CT scans are often performed prior to or at the time of listing. In patients who are at highest risk for developing primary lung carcinomas, repeat CT scan screening should be considered shortly before transplantation.

Wednesday, November 2, 2005 Medical Education, continued TABLE. Publication No

Sponsor

Yes

% Success

Pharmaceutical Company Local Health Authority Federal Granting Agency Charity Other

60

72

46

11

34

24*

11

1

91*

3 0

0 3

100 0

*p⬍0.05 vs Pharmaceutical Company DISCLOSURE: Richard Hall, None.

DISCLOSURE: Lewis Eisen, None.

PUBLICATION OF RESEARCH UNDERTAKEN IN A CANADIAN TEACHING CENTRE: A REVIEW BY A RESEARCH ETHICS BOARD Richard I. Hall MD* Cecilia DeAntueno Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada PURPOSE: Reporting of results from clinical investigations is an important component of the ethical conduct of research. We conducted a review of the publication record of all protocols submitted to our Research Ethics Board (REB) for the periods 1995-1996. METHODS: Protocols for studies closed by the principal investigator (PI) were identified from the REB database. We identified the local PI, the sponsor, and the phase of clinical investigation. For each publication, we identified publication authors, publication title, journal, and whether a randomised clinical trial or not. For data analysis Systat V10 was utilised. p⬍0.05 was taken as statistically significant. RESULTS: We identified 110 unpublished studies and 85 publications (44%). The median time to publication was 32.5 mos (975 days)(mean 33.1⫾17.8 mos) and the median number of subjects enrolled per study was 329. For unpublished studies, subject recruitment was reported for 45 studies. In these studies there was a median of 2 subjects recruited by local investigators per study. Physicians authored 79/85 publications (93%) and were the principal investigators in 89% (173/195) of studies. Publication by sponsor is given in the Table. Of the 85 published studies, results could be described as positive findings in 72 (85%). Of 13 negative published trials, 11 were sponsored by the pharmaceutical industry, one by the health authority, and one by a federal granting agency. CONCLUSION: Publication of research results was unacceptable, less likely to occur if sponsored by the pharmaceutical industry, and more likely to occur if reporting positive findings. Calls for public registration of clinical trials appear warranted. CLINICAL IMPLICATIONS: Publication of research results is an ethical obligation of researchers and failure to publish results is considered by some to represent scientific misconduct. In addition failure to publish scientific results violates the social contract research subjects undertake when they participate in research and misinforms public policy through failure to provide adequate information upon which to base guidelines and perform meta-analysis. Our results suggest much further education around these issues is required.

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SURVEY OF CURRENT PRACTICES IN PULMONARY AND CRITICAL CARE FELLOWSHIP ORIENTATION PROCEDURES Maria R. Lucarelli MD* Catherine Lucey MD John Mastronarde MD The Ohio State University, Columbus, OH PURPOSE: The purpose of this survey was to identify current practices in fellow orientation procedures. METHODS: A 10 question survey was sent via email to current pulmonary and critical care medicine program directors identified in the American Thoracic Society (ATS) web registry. The survey sought to identify common characteristics of fellow orientation programs including duration, content and educational methods. RESULTS: Of the 141 deliverable email addresses, 87 responded (61.7%). Of the programs who responded, 86% had a formal fellows’ orientation. The mean time frame spent in fellow orientation was 5-10 hours in didactic sessions and 0-5 hours in wet labs. Only twenty-four programs (28%) spent more than 15 hours in didactic sessions while no programs spent more than 15 hours in wet labs. The most common didactic topics were bronchoscopy in 69 programs (80.2%), pulmonary function testing in 63 programs (73.3%) and orientation to hospital services in 63 programs (73.3%). The least commonly covered topics were moderate/deep sedation in 38 programs (44.2%) and intubation in 39 programs (45.3%). The most common use of wet labs was for bronchoscopy training in 60 programs (81.1%) and ventilator management in 45 programs (60.8%). Thirty-seven responding programs (43%) used simulators in fellow orientation. The most frequently used simulator was a bronchoscopy simulator in 31 programs (36%). The majority of program directors did not offer formal wet lab or simulator training, relying instead on on-the-job training experiences during their fellowship. CONCLUSION: This survey demonstrates that early fellowship training experiences differ across programs in terms of duration, content and methodology. Given the variability in skill level exhibited by entering fellows and understanding the importance of procedural competence to patient safety, an early standardized approach to clinical and procedural training can assure that entering fellows possess the requisite cognitive and psychomotor skills to safely embark on training in the critical care arena. CLINICAL IMPLICATIONS: Establishing competency earlier in fellow training, has the potential to decrease medical errors and procedure related complications. DISCLOSURE: Maria Lucarelli, None.

QUALITY OF EDUCATION IN THE INTENSIVE CARE UNIT: A SUBSET ANALYSIS Jason M. Golbin DO* Robert Bruno DO Gerald Bahr MD Bushra Mina MD Lenox Hill Hospital, New York, NY PURPOSE: The ICU rotation at our hospital is often described as the most valuable educational experience in the internal medicine residency. Previously presented data demonstrated that this educational enhancement cannot be measured. We performed a subset analysis of this data to evaluate disparity among individual ICU topics. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Medical Education, continued

Selected ABIM Topic Pulmonary Artery Catheterization Acid-Base / Electrolyte Disorders COPD/Asthma Nutrition in the Critical Care Patient DKA / Hyperosmolar Coma Sepsis APACHE Medical Ethics in the ICU GI Bleed Weaning

Pre-Test Percentage Correct (%)

n

Post-Test Percentage Correct (%)

n

Percent Change (⫹/-%)

12.5

8

15.3

11

⫹2.8

50.0

12

72.7

11

⫹22.7

72.7 33.3

11 6

80.0 32.5

10 8

⫹7.3 -0.8

50.0

10

77.7

9

⫹27.7

23.0 14.2 85.7

13 7 7

70.0 11.1 88.8

10 9 9

⫹57.0 -3.1 ⫹3.1

60.0 22.2

5 9

88.8 53.8

9 13

⫹28.8 ⫹31.6

determine the length of service in the mines in relation to the disease states. METHODS: Between 28th May 1997 and 27th May 1999, 2080 former mineworkers were examined at the “Benefit Examination Clinic” in the Pulmonology unit of Umtata General Hospital (UGH). The mining history of each attendee was recorded and an identification form completed. The form was either signed or fingerprinted by the miner. After physical examination, a chest radiograph was taken. The radiographs were sent to an independent radiologist, experienced in Occupational Lung Diseases, for assessment. These were rated according to International Labor organization (ILO) guidelines. RESULTS: The age of those studied ranged from 35 to 70 years (mean 51.6 years) and their length of service in the mines ranged from 1 to 48 years. On radiological examination 5.5% showed only silicosis and 28.4% had silicosis with pulmonary tuberculosis (Relative risk⫽5.08, ␹2 ⫽ 27.3, p⬍0.01). Among subjects up to 35 years 9.1% had mild, 10.6% marked, and 1.5% severe silicosis. A probable diagnosis was made on 9.1% of the cases. The least number of afflicted was seen in the 36 to 45 year age group (21.2%). Surprisingly, most number of cases were in those 35 years or less (30.3%). About half (48.4%) the silicotic subjects had worked in the mines between 11 to 20 years. CONCLUSION: Pulmonary TB is 5- times higher in silicotic than in non-silicotic subjects. CLINICAL IMPLICATIONS: These findings will help clinicians, epidemiologists, compensation authorities and policy makers in understanding of the silicosis problem in this region of South Africa. DISCLOSURE: Banwari Lal Meel, None. PREVALENCE OF ASBESTOS EXPOSURE OF THE MINEWORKFORCE FROM TRANSKEI, SOUTH AFRICA Banwari L. Meel MD* Ruchika Meel MB, ChB University of Transkei, Umtata, South Africa PURPOSE: To determine the prevalence of asbestos exposure among the mine workforce from Transkei. METHODS: Between May 1997 and May 2000, 2,027 ex-mineworkers were examined at the Benefit Examination Clinic, a clinic located in the chest section of Umtata General Hospital (UGH), the teaching hospital of the University of Transkei, Eastern Cape, South Africa. A structured questionnaire with 17 questions were prepared and posted to 644 randomly selected ex-mineworkers. Four hundred and six (63%) duly completed questionnaires were received, which were later, compiled and analyzed with the help of Epi Info6 computer programme. RESULTS: Of the 644 questionnaires posted, 406 were returned. Of them 81(20 %) has had exposure to asbestos. Half the number 41(50%) of those exposed was between 40-59 years old. Among those who had been exposed, 8(10%) were smokers, 63(78%) asthmatics, and 56(69%) had a history of tuberculosis. Seventy- three (90%) complained of deterioration of health. CONCLUSION: One fifth of the mine workforce has had exposure to asbestos. CLINICAL IMPLICATIONS: These findings will help compensation authorities, policy makers, and clinicians in understanding of the asbestos problem in this region of South Africa. DISCLOSURE: Banwari Meel, None.

DISCLOSURE: Jason Golbin, None.

Occupational and Environmental 12:30 PM - 2:00 PM THE DEGREE OF CO-MORBIDITY OF SILICOSIS AND PULMONARY TUBERCULOSIS AMONG EX-MINEWORKERS OF THE FORMER HOMELAND OF TRANSKEI, SOUTH AFRICA. AN X-RAY BASED STUDY Banwari Lal Meel MD* Ruchika MEEL MB, BCh University of Transkei, Umtata, South Africa PURPOSE: This study was done to determine the degree of comorbidity of silicosis and pulmonary tuberculosis in ex-mineworkers, measure distribution of the conditions in different age groups and to

EXHALED BREATH CONDENSATE IN ASBESTOS EXPOSURE Daniela Pelclova MD* Zdenka Fenclova MD Petr Kacer PhD Marek Kuzma PhD Jindriska Lebedova MD Pavlina Klusackova MD Marie Balikova PhD Tomas Navratil PhD Dept. Occupational Medicine, Charles University, Prague, Czech Republic PURPOSE: To analyse exhaled breath condensate in subjects exposed to asbestos in the past, as experimental studies in animals have shown increased lipid peroxidation. Isoprostanes, leukotrien B4 and cysteinyl leukotriens have not yet been studied in humans exposed to asbestos. METHODS: Thirteen persons were examined, mean age 71.4 years, previous exposure to asbestos 25.5 years on average. Five subjects were diagnosed asbestosis as occupational disease, 8 had pleural hyalinoses. Control group was represented by 10 subjects, mean age 66.3 years, without occupational history of fibrogenic dusts exposure.Lung functions were measured, isoprostaglandin F2alpha; (8-isoprostane) was analyzed by HPLC/MS; leukotrien B4 by SPE, and leukotriens C4, D4, and E4 using LC/MS. Cotinine in urine was detected to confirm the smoking CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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METHODS: A question bank of over 100 multiple-choice questions was created based on the ABIM Critical Care topics. All questions were reviewed independently by two board-certified intensivists. Interns and residents rotating through the ICU completed a randomized 25 question pre-test within the first 2 days of the month, and a randomized 25 question post-test within the last 2 days of the month (allowing for different call schedules). No changes were made in the standard ICU curriculum, which allows for a daily teaching conference, and twice-daily attending-led bedside rounds. RESULTS: See Table 1. CONCLUSION: The above results demonstrate a wide variance in the testable medical knowledge gained during the ICU rotation. While these results did not achieve statistical significance, likely secondary to small sample size, there was a trend towards significance in many categories. We believe that this illustrates a number of points: (a)In topics commonly encountered in our ICU (sepsis, DKA, and weaning), residents had a measurable increase in testable knowledge. (b)In topics not emphasized in our ICU (APACHE and PA catheters), residents did not demonstrate an increase in testable knowledge. (c)In topics emphasized throughout the internal medicine residency curriculum (Ethics and Acid-Base/Electrolytes), residents maintained an excellent fund of knowledge. CLINICAL IMPLICATIONS: We believe that this information can be used to identify weaknesses and strengths in our ICU curriculum, and will allow us to modify that curriculum to further enhance residents’ testable knowledge.

Wednesday, November 2, 2005 Occupational and Environmental, continued status. Student t-test and correlation coefficient were used for statistical comparison of the groups. RESULTS: Mean level of 8-isoprostane in persons exposed previously to asbestos and controls was 60⫾20 and 37 ⫾15 pg/mL, respectively. Different values in exposed and control groups were detected (p⫽0.91). Mean levels of leukotriens B4, C4, D4, and E4 in exposed and controls were 42⫾23; 96⫾40; 11⫾5; 17⫾7 and 38⫾15; 98⫾47; 20⫾11; 23⫾11 pg/mL, respectively. In asbestos-exposed persons the concentration of 8-isoprostane correlated with TLCO/Hb (p⫽0.96) and leukotriens B4 (p⫽0.99), D4 (p⫽0.99), and E4 (p⫽0.99). CONCLUSION: In preliminary results, 8-isoprostane seems to be important parameter in asbestos-exposed persons. Leukotriens levels did not differ in exposed and control groups, however in subjects with asbestos exposure leukotriens B4, D4, and E4 were positively correlated with 8-isoprostane. CLINICAL IMPLICATIONS: The level of 8-isoprostane in the exhaled breath condensate might be a useful marker of oxidation stress also in asbestos-exposed subjects; besides that leukotriens B4, D4, and E4 seem to play a role. Acknowledgement: IGA NR/8107-3. DISCLOSURE: Daniela Pelclova, None.

MARKERS IN BREATH CONDENSATE IN PATIENTS WITH OCCUPATIONAL ASTHMA AND RHINITIS Jindriska Lebedova MD Pavlina Klusackova MD Petr Kacer PhD Marek Kuzma Daniela Pelclova MD* Tomas Navratil PhD Zdenka Fenclova MD Department of Occupational Medicine, 1st Medical Faculty Charles University, Prague, Czech Republic PURPOSE: Specific provocation tests are used to confirm diagnosis of occupational asthma or rhinitis. Decreases of FEV1 or nasal flow are considered to be main markers of positivity. Analysis of breath condensate brings more information for monitoring processes in airways during these tests. METHODS: Six patients (average age 38.7 years) with suspicion on occupational asthma (OA) and rhinitis (OR) and four controls (average age 53.8 years) were examined. Total immunoglobuline E (IgE), blood eosinophils, spirometry, rhinomanometry, non-specific bronchoprovocation test, specific bronchoprovocation tests with occupational allergens were performed. Leukotrienes C4, D4, E4 from breath condensate were analyzed by HPLC/MS, leukotriene B4 on solid phase extraction. Student t-test and correlation coefficient were used for statistical analysis. RESULTS: Occupational asthma was finally diagnosed in three patients, occupational rhinitis in three patients. In patients with OA, OR and controls IgE levels were 828.3 vs. 564.0 vs. 34.8 mg/l; FEV1 80.3 vs. 95.6 vs. 109.0 % predicted values; leukotrienes on admission B4 43.3 vs. 2.6 vs. 46.3 pg/mL; C4 114.0 vs. 54.7 vs. 85.0 pg/mL; D4 17.0 vs. 10.7 vs. 35.5 pg/mL; E4 20.0 vs. 13.7 vs. 28.3 pg/mL. Significant changes in FEV1 (p⬍0.05) were found between asthmatics and controls.Breath condensate leukotrienes were analysed also before specific test and at the time of maximal decrease of FEV1 or nasal flow during the test: OA patients - B4 (53.7 vs. 56.7 pg/mL), C4 (121.7 vs. 198.0 pg/mL), D4 (17.0 vs. 17.0 pg/mL), E4 (21.3 vs. 21.0 pg/mL), OR patients - B4 (13.0 vs. 17.3 pg/mL), C4 (266.3 vs. 257.3 pg/mL), D4 (19.3 vs. 17.0 pg/mL), E4 (17.3 vs. 15.6 pg/mL). No significant correlations were found. CONCLUSION: Maximum decrease of FEV1 during specific tests with occupational allergens in our small group of patients does not to seem to correspond with elevation of markers of obstruction in breath condensate. CLINICAL IMPLICATIONS: Changes in obstruction markers in breath condensate probably precede or follow decrease of FEV1. These possibilities will be tested in further provocation tests measurements. Acknowledgement: IGAMZCR NR8109-3/2004. DISCLOSURE: Daniela Pelclova, None.

XENON DIFFUSING CAPACITY DETECTS ABNORMAL GAS EXCHANGE IN A RAT MODEL OF PNEUMONITIS CAUSED BY STACHYBOTRYS CHARTARUM SPORE INHALATION Nishard Abdeen MD* Greg Cron PhD Albert Cross PhD Thomas Rand PhD Steven White MS Giles Santyr PhD Carleton University, Ottawa, ON, Canada PURPOSE: Xenon diffusing capacity, a novel noninvasive technique of measuring gas exchange analogous to carbon monoxide diffusion capacity,

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was evaluated in a rat model of pnemonitis caused by intratracheal instillation of Stachybotrys chartarum spores. METHODS: The xenon diffusing capacity was defined analogously to the carbon monoxide diffusing capacity as the product of a gas transfer time or time constant of uptake into lung parenchyma (determined by hyperpolarized 129 Xenon dynamic spectroscopy) and alveolar volume(determined by hyperpolarized 129 Xenon magnetic resonance imaging). The xenon diffusing capacity was compared in a group of normal and diseased rats with histologically proven pneumonitis caused by intratracheal instillation of Stachybotrys chartarum spores. RESULTS: The xenon diffusing capacity for lung parenchyma was significantly reduced in a group of 6 rats with pneumonitis caused by intratracheal instillation of Stachybotrys chartarum spores relative to a group of 6 normal rats(29⫹/-11 mL/min/mmHg and 66⫹/-10 mL/min/ mmHg, p⬍0.05). Gas transfer times and lung volumes were significantly reduced for the diseased rats (22⫹/-3 ms and 11⫹/-2mL respectively)relative to normal rats (35⫹/-8 ms and 16 ⫹/-2 mL respectively). CONCLUSION: Xenon diffusing capacity is an effective at detecting gas exchange abnormalities on a millisecond time scale in a rat model of pneumonitits.These results support further evaluation of xenon diffusing capacity in characterization of experimental lung disease. CLINICAL IMPLICATIONS: Xenon diffusing capacity quantifies gas exchange abnormalities on a much shorter (millisecond) time scale than the carbon monoxide diffusing capacity. The method may prove to be a useful adjunct to the carbon monoxide diffusing capacity in lung diseases charcaterized by a gas diffusion abnormalitities. DISCLOSURE: Nishard Abdeen, Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Hyperpolarized 129 xenon spectroscopy and MR imaging.

LONG-TERM RESPIRATORY DISORDERS IN CLAIMERS WITH EXPOSURE TO CHEMICAL WARFARE AGENTS (CWA): REVIEW OF METHACHOLINE CHALLENGE TEST (MCT) RESULTS Abbas Nemati MD* Mahdi Rahmati MD Ali Moghimi MD Artesh University of Medical Sciences, Tehran, Iran PURPOSE: It is well documented that inhalation of sulfur mustard causes injury of the respiratory system. While all of the reports and surveys thoroughly document long-term pulmonary effects after significant exposure to mustard, there is no direct evidence that addresses the issue of long-term respiratory effects in individuals who were exposed to very low level of mustard and suffered no acute respiratory tract injury. The aim of this study is to evaluate the MCT findings in the veteran claiming exposure to CWA during Iran-Iraq war. METHODS: We studied 395 subjects which were selected among all those who were in chemically contaminated areas with chemical warfare agents (CWA) and had been registered for an annual checkup. Background data were collected. All subjects underwent diagnostic bronchoscopy and biopsy which was performed by one specialist. In all patients MCT, according to ATS guidelines, performed. RESULTS: Subjects were 395 men with the mean age of 41.46 (SD, 5.43) years which exposed to CWA averagely 18.7 (SD, 1.74) years ago. 132 patients (33.3%) had positive MCT. Results of MCT did not relate to the cigarette smoking (p⫽0.82), length time after exposure (p⫽0.88), age (p⫽0.36), bronchospic findings (p⫽0.36) and the presence of interstitial fibrosis (p⫽0.71). Kappa coefficient of the results of bronchoscopy and MCT in determining patients with airway disorders was not significant (p⫽0.36). CONCLUSION: This study shows that a major proportion (33%) of patients exposed CWA show airway hypersensitivity in their MCT which does not relate to any underlying factor, though it is not a diagnostic finding. In addition the results of bronchoscopy and MCT are not in concordance with each other. CLINICAL IMPLICATIONS: About one third of patients exposed CWA show airway sensitivity. DISCLOSURE: Abbas Nemati, None. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Occupational and Environmental, continued RADIOLOGIC PATTERN OF PULMONARY DISEASE ASSOCIATED WITH MYCOBACTERIUM INTRACELLULARE-AVIUM IN HOT TUB USERS (HOT TUB LUNG) Viktor Hanak MD* Jay Ryu MD Thomas Hartman MD Mayo Clinic Foundation, Rochester, MN

PURPOSE: To determine whether the M40 protective chemical gas mask (M40 mask) increases bronchial airway hyperreactivity in military active duty soldiers with exercise induced bronchospasm (EIB). The point of prevalence of EIB in the US Army is 7% and many of these soldiers are capable of performing their exertional military duties. However, it is unclear how soldiers with EIB will perform when they are required to use the M40 mask for prolonged periods. Furthermore, there are anecdotal concerns of increased EIB exacerbations when these individuals wear the M40 mask. METHODS: Active duty soldiers were screened in the Pulmonary clinic for EIB. Diagnostic criteria for EIB included a history of exertional dyspnea, normal baseline spirometry and a positive methacholine challenge test ⱕ 4mg/ml. Subjects who participated in the study completed exercise spirometry breathing room air. A repeat exercise spirometry was performed two days later with the subject wearing a full face M40 mask. A matched number of participants with no history of EIB or other pulmonary disorders were included in the control group. The FEV1 post exercise challenge testing (ECT) with and without the M40 mask was compared in both subject and control groups. RESULTS: Nine subjects with EIB and 3 controls were evaluated. Both the subjects and controls underwent baseline (ECT) with and without the M40 mask. The FEV1 post ECT was compared and there was no statistical difference in both groups with or without the M40 mask. One of the nine subjects with EIB had a positive ECT while wearing the M40 mask. CONCLUSION: Our pilot study revealed that soldiers with EIB who exercised wearing the M40 mask infrequently had bronchospasm exacerbations. CLINICAL IMPLICATIONS: Our results support the US Army retention standards of soldiers with EIB. Because one subject did have a positive ECT while wearing the M40 mask we recommend screening ECT while the protective mask is worn in soldiers with EIB retained on active duty. DISCLOSURE: Pedro Lucero, None.

PURPOSE: The purpose of this study was to evaluate the radiologic features of Hot Tub Lung disease. METHODS: The CT scans of 15 patients (13 high resolution and 2 conventional CT scans) were evaluated for the distribution and extent of nodules, irregular lines and ground glass attenuation. RESULTS: Nodules were present in 11/15 cases. They were bilateral and symmetric in 9 and bilateral and asymmetric in 2. In 9 cases there was a diffuse distribution of the nodules in the cephalocaudal plane with a centrilobular distribution in the transaxial plane. In the other 2 cases, the nodules had an upper lung distribution in the cephalocaudal plane and a random distribution in the transaxial plane. In 5 cases the nodules were well-defined and in 6 cases poorly defined. Ground glass attenuation was seen in 11/15 cases, and was bilateral and symmetric when present. The ground glass attenuation was diffuse in the cephalocaudal plane with a random distribution in the transaxial plane in 10/11 cases. In the other 1 case the areas of ground glass attenuation had lower lung predominance with a random distribution in the transaxial plane. In 6 cases the areas of ground glass attenuation involved ⬎40% of the lungs and in 5 involved ⬍ 40% of the lungs. Both the nodules and ground glass attenuation were present in 7 cases (nodules only were present in 3 patients; ground glass only present in 3 patients). One patient had nodules, areas of ground glass attenuation and irregular linear opacities. Irregular linear opacities were present in only 1 case. They were bilateral and asymmetric with a subpleural and lower lung predominance and involved ⬍10% of the lungs. In 7 cases expiratory images were obtained and all showed evidence of air trapping. CONCLUSION: The patterns of centrilobular nodules, ground glass attenuation and air trapping are very similar to findings of subacute hypersensitivity pneumonitis. CLINICAL IMPLICATIONS: In cases where the CT findings suggest hypersensitivity pneumonitis, hot tub lung should also be a diagnostic consideration. DISCLOSURE: Viktor Hanak, None.

AIR POLLUTION IN A SMALL MICHIGAN COMMUNITY Rachna B. Reddy* Elizabeth Busdicker Sridhar P. Reddy MD Port Huron Northern High School, Port Huron, MI PURPOSE: The objective of this study was to assess the effects of air pollution on emergency room (ER) visits for respiratory problems and school absences over a period of 90 days. METHODS: Air Quality Index (AQI) is a simple aggregate measure of air quality used by the Michigan Department of Environmental Quality (DEQ) to document the quality of air. It measures Particulate Matter, Ozone, Sulfur Dioxide, Nitrogen Dioxide, and Carbon Monoxide. AQI levels range from 0-500, with 500 being the worst possible air quality. AQI levels, ER visits for respiratory problems, and school absences were recorded daily from October 2004 to January 2005. RESULTS: Data was charted with no lag, with a one-day lag, two-day lag, and a three-day lag. A Pearson Coefficient of Correlation was performed and was best with a two-day lag for ER visits. The data from the two-day lag was separated into quartiles by AQI values. The AQI levels in the highest quartile ranged from 66-80, and in the lowest from 20-35. The average number of ER visits in the highest AQI quartile (poor air quality) was greater than in the lowest quartile(20.5 visits vs. 12.8 visits per day; p value of 0.09. School absences did not show a significant difference. CONCLUSION: In conclusion there was a trend for the number of respiratory-related ER visits to be greater when the air quality was poor. CLINICAL IMPLICATIONS: These results have implications for a small community in allocating resources for health care utilization based on real time simple air pollution measures. The results suggest a need for increased health care personnel in the emergency room two days subsequent to poor air quality. DISCLOSURE: Rachna Reddy, None.

ANTI-GLOMERULAR BASEMENT MEMBRANE ANTIBODYNEGATIVE, GOODPASTURE-LIKE ALVEOLAR HEMORRHAGE SYNDROME IN YOUNG WOMEN WITH METHAMPHETAMINE USE AND MANUFACTURE Carl A. Kaplan MD* Michael S. Plisco MD Ashok Palagiri MD Saint Louis University School of Medicine, Saint Louis, MO PURPOSE: Illicit substances, such as cocaine, are associated with alveolar hemorrhage. Anti-Glomerular Basement Membrane (GBM) Disease and Goodpasture Syndrome with alveolar hemorrhage are rare immunologic diseases that are associated with a number of risk factors, and without treatment have significant mortality rates. Methamphetamine use is a growing public health concern, and its manufacture is common in regions of the United States. Methamphetamine has not previously been associated with alveolar hemorrhage. This study addresses the association with alveolar hemorrhage and methamphetamine. METHODS: A single institution retrospective case study from an urban university tertiary care hospital and referral center. A systematic review of pathology reports and database of cases with alveolar hemorrhage. RESULTS: A total of two cases (n ⫽ 2), both 22 year-old females, were admitted with frank hemoptysis and acute respiratory failure. The medical history was significant for substance abuse, tobacco abuse and both were associated with the use and manufacturing of methamphetamine. Bronchoalvelar lavage demonstated alveolar hemorrhage in both, with increasingly bloody lavage fluid. Urinalysis was bland with normal creatinines. The open lung biopsy demonstrated, in both, primarily alveolar hemorrhage, with one associated with capillaritis with areas of organization. Immunofluorescence revealed prominant linear staining of the alveolar basement membranes for immunoglobulin IgG and complement C3, as did the glomerular basement membranes on the renal biopsies. Both were serum anti-GBM antibody negative. Plasmapheresis was performed in addition to the administration of parenteral corticosteroids, with resolution of the acute respiratory failure. There were no recurrences. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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DOES PROTECTIVE MASK (M40) INCREASE REACTIVE AIRWAY DISEASE IN MILITARY ACTIVE DUTY WITH EXERCISE INDUCED BRONCHOSPASM Pedro F. Lucero MD* Patrick Perkins MD Michael J. Morris MD Brooke Army Medical Center, San Antonio, TX

Wednesday, November 2, 2005 Occupational and Environmental, continued CONCLUSION: This study demonstrates the association of an AntiGBM negative, Goodpasture-like Alveolar Hemorrhage Syndrome with Methamphetamine, its manufacture, or related to a component of manufacturing. Further studies are necessary to elucidate this new association. CLINICAL IMPLICATIONS: This study raises a new serious public health concern with the increase appearance of the manufacturing and use of methamphetamine in the Midwest region of the United States. This is a new association based on a Medline Search from 1966 – 2005 for alveolar hemorrhage, anti-GBM disease, Goodpasture syndrome, and methamphetamine.

RESULTS: Observed hospital mortality was 13.8%. The MPM0-III model includes MPM0-II variables and several interaction terms. Lead time and pre-ICU location did not influence outcome. Addition of a “zero-factor” term for patients with no risk factors other than age improved calibration. Coefficients are in the table, and improved calibration can be seen in the figure. Validation set HL-GOF⫽10.94, p⫽0.36 and ROC AUC⫽0.823.

CONCLUSION: MPM0-III is well calibrated to current clinical data and requires collecting only one additional term (code status). CLINICAL IMPLICATIONS: Use of MPM0-III will allow more accurate comparisons of actual versus expected outcomes based on patient condition at the time of ICU admission.

DISCLOSURE: Carl Kaplan, None.

Outcomes Assessment 12:30 PM - 2:00 PM UPDATED MORTALITY PROBABILITY MODEL (MPM-III) Thomas L. Higgins MD* Daniel Teres MD Wayne Copes PhD Brian Nathanson PhD Maureen Stark MS Andrew Kramer PhD Baystate Medical Center/Tufts University School of Medicine, Springfield, MA PURPOSE: The Mortality Probability Model on ICU admission (MPM0-II), developed on an international sample of 12,610 patients treated in 1989-90, is used by Project IMPACT as a benchmarking tool, but no longer calibrates. We updated the model based on 2001-2004 patient data. METHODS: Project IMPACT data on 124,855 patients age⬎18 and eligible for MPM scoring were randomly split into development (60%) and validation (40%) samples and analyzed using logistic regression. Independent variables considered were MPM-II variables, patient location and lead time prior to ICU admission and code status at the time of ICU admission. Discrimination was assessed by area under the ROC curve (AUC) and calibration by graphic display and Hosmer-Lemeshow Goodness of Fit (HL-GOF) C-statistics.

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Variable

Coefficient

Constant Coma-stupor HR ⬎150 bpm SBP ⬍ 90 mmHg Chronic Renal Chronic GI Metastatic Neoplasm Acute Renal Dysrhythmia Cerebrovascular Incident GI Bleed Intracranial Mass Age (in years) CPR w/i 24hr Mech. Ventilation Medical/Unscheduled Surgical Admission Zero Factors Full Code SBP x MV Admit Age x Coma Age x SBP⬍90 Age x ChronicGI Age x Mets Age x CardDys Age x ICM Age x CPR

-5.397338 2.032949 0.4286778 1.578148 0.4041341 2.078154 3.187064 0.7026929 0.8247331 0.4103774 -0.1593359 1.838082 0.0387999 1.499682 0.891268 0.916912 -0.4025265 -0.8016462 -0.1620224 -0.0074014 -0.0092765 -0.0225957 -0.0328078 -0.0100795 -0.0168818 -0.0112155

DISCLOSURE: Thomas Higgins, Consultant fee, speaker bureau, advisory committee, etc. Dr. Higgins serves on the Cerner Critical Care Transformation Council (advisory committee). CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Outcomes Assessment, continued MORTALITY PROBABILITY MODELS (MPM0-III) FOR SPECIALIZED PATIENT POPULATIONS Brian Nathanson PhD Wayne Copes PhD Maureen Stark MS Andrew Kramer PhD Daniel Teres MD Thomas L. Higgins MD* Baystate Medical Center/Tufts University School of Medicine, Springfield, MA

Variable

Score

Presence of decubitus ulcer Hyperleukocytosis or inflammatory syndrome (WBC ⬎ 17,000/mm3 or CRP ⬎ 20 mg/dL) Maximal sequential organ failure assessment (SOFA) score ⬎ to 9 Paroxysmal atrial fibrillation or need for anti-arrhythmic medication Chronic obstructive pulmonary disease (COPD) or asthma requiring chronic treatment Morbid obesity or parenteral nutrition or decompensated diabetes Hypoalbuminemia (serum albumin ⬍3.5 g/dL) Alteration of mental status, polytrauma or notable physical dependence

12 6 6 4 4 4 3 2

DISCLOSURE: Michae¨l De Cubber, None.

Other Subgroup

Complex

Model

Cardiovascular

Trauma

Sample Size

Elective

Neuro-

Emergency

Surgery

Medical

surgical

Surgery

3434

4248

9812

26633

2298

3605

H-L statistic

10.38

9.17

16.44

12.20

6.01

11.63

p Value

0.41

0.52

0.09

0.07

0.81

0.31

ROC AUC

0.87

0.90

0.79

0.79

0.85

0.79

DISCLOSURE: Thomas Higgins, Consultant fee, speaker bureau, advisory committee, etc. Dr. Higgins serves on the Cerner Critical Care Transformation Council; Grant monies (from industry related sources); Dr. Nathanson received grant funding from Cerner.

THE ICU DISCHARGE SCORE TO EVALUATE THE RISK OF READMISSION Michae¨l De Cubber MD* Marta Trabbach MD Francesca Garcia Lizana MD Christian Me´lot MD Jean-Louis Vincent MD Erasem Hospital, Brussels, Belgium PURPOSE: To determine the clinical and laboratory features of patients who are readmitted to the ICU after discharge, and to use these to develop a score to predict risk of readmission. METHODS: In this observational cohort study in a mixed, 31-bed, medico-surgical intensive care unit, 226 consecutive adult ICU admissions were included during a 13-week period (excluding patients admitted for uncomplicated postoperative surveillance).Variables related to epidemiology, past history, clinical and lab data were recorded. Data were analyzed by univariate regression analysis. Continuous variables were transformed in categorical variables using the threshold obtained by a Lowess smoothing function. The categorical variables were entered into a multiple logistic regression model. The coefficients of the regression were used to compute the score for each significant item. A p ⬍ 0.05 was considered significant.

DATA MINING THE ELECTRONIC MEDICAL RECORD TO EXAMINE OUTCOMES IN THE EMERGENCY DEPARTMENT Patricia B. Cerrito PhD* Dave Pecoraro University of Louisville, Louisville, KY PURPOSE: To use data mining techniques on the electronic medical record (EMR) in the Emergency Department (ED) with the intent of improving care while reducing costs. METHODS: All patient records for a 6-month period were examined. All records with an initial complaint related to shortness of air or related were extracted for a total of 1329 patient records. There were 53,000⫹ charges ordered for these patients in the ED. The data mining techniques of text analysis, transactional time series, and association rules were used to examine the data. RESULTS: A total of 187 patients were discharged to ICU after the ED, with 25 of the 187 originally triaged as non-urgent. In contrast, only 2 out of 626 discharged home were triaged as emergent. Although there is no standardization in the language of initial patient complaints, there is a general grouping of ten different complaints as listed in the table. Bronchitis and asthma require a similar amount of time in ED treatment; COPD requires an extra 100 minutes of treatment time on average compared to the other two conditions. Patients complaining of shortness of air were tracked into a heart protocol, receiving tests of Troponin and CBC; or were tracked into a respiratory protocol, receiving oxygen and mini-nebulizer treatment. There was 87% confidence that glucose testing was associated with EKG and CBC, a 70% confidence that it was associated with Troponin test, but almost no association with SOA treatments. CONCLUSION: Data mining the EMR can provide useful information that can be used to improve care while reducing costs. There is sufficient variability in treatment for patients with similar complaints that the variability can be examined and reduced while developing optimal treatment patterns. CLINICAL IMPLICATIONS: Once the variability in treatment is documented, it can be examined to develop standardized protocols for patient complaints. Optimal paths of care can be developed. Specific protocols can also reduce the time needed to treat patients in the ED. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

PURPOSE: The Mortality Probability Model on ICU admission (MPM0) is used by Project IMPACT as a benchmarking tool. A recent update (MPM0-III) has been validated and shown to perform well on a large dataset. New MPM models based on specific patient subsets have been constructed to improve assessment with specialized ICU populations. METHODS: Project IMPACT data from 2001-2004 for 124,855 patients eligible for MPM scoring treated in 135 ICUs were randomly split into design (60%) and validation (40%) samples. Logistic regression models were developed to predict hospital mortality from MPM0-III variables for patients in each of the following subgroups: Complex Cardiovascular, Trauma, Elective Surgery, Medical, Neurosurgery and Other Emergency Surgery. Discrimination was assessed by area under the Receiver Operator Characteristic (ROC) curve and calibration by Hosmer Lemeshow Goodness of Fit (HL-GOF) C-statistics. We compared ICUspecific Standardized Mortality Ratios (SMRs) and associated confidence intervals (CIs) from MPM0-III to those based on the Subgroup models, using the validation sample. RESULTS: The six Subgroup models had good calibration and discrimination on the validation sample (Table 1-performance on validation dataset). MPM0-III and Subgroup model SMRs and CIs were in substantial agreement (overall agreement 94.8%, Kappa Statistic 0.88; p-value⬍0.001). Important SMR differences were observed for some units with an atypical case mix or when a unit’s CI bordered on significance. CONCLUSION: The MPM0-III Subgroup models calibrate well on specialized populations and complement the general MPM0-III model for benchmarking. CLINICAL IMPLICATIONS: MPM0-III Subgroup models are useful when ICU case mix is atypical or SMR performance is near the significance boundary. Subgroup models will also be valuable in studies of specific patient subsets.

RESULTS: Of 226 admissions during the study period, 34 (17.4%) patients died in the ICU. The mean length of ICU stay was 6.4 days. A total of 42 patients (22%) were readmitted. The score developed from the statistical analysis of the 272 variables includes 8 simple variables with a maximum score of 41 (Table). The area under the receiving operating characteristic (ROC) curve was 0.74. CONCLUSION: This simple score, based on routinely collected variables, can help to evaluate the risk of readmission to the ICU after discharge. CLINICAL IMPLICATIONS: ICU readmission is associated with worse outcomes. Identifying patients at risk of readmission may prevent premature ICU discharge, may promote the use of increased surveillance such as intermediate care unit or telemetry on the floor, and may help prepare the patient, the relatives, and the heath care professionals for the possibility of readmission.

Wednesday, November 2, 2005 Outcomes Assessment, continued DISCLOSURE: Patricia Cerrito, Grant monies (from sources other than industry) NIH grant #1UC1HS014897-01, ED Information SystemsKentucky & Indiana Hospitals, Dave Pecoraro, PI, Patricia Cerrito, co-PI.

ASSESSMENT OF ACUTE PHYSIOLOGIC AND CHRONIC HEALTH EVALUATION AND THE SIMPLIDIED PHYSIOLOGIC SCORES IN A POST-TRAUMATIC SURGICAL INTENSIVE CARE UNIT Meurant Francois MPH* Hoˆpital Kirchberg, Luxembourg, Luxembourg PURPOSE: The Acute Physiologic and Chronic Health Evaluation (APACHEII ) has been extensively used in Intensive Care Unit (ICU) setting over the past 10 years ,as has been the Injury Severity Score (ISS) using an anatomical descriptive scoring . The Simplified Acute Physiology Score( IGSII ) belongs to a new generation of scoring systems : its main innovation is that the different parameters and their weighting are derived from statistical analysis. However the accuracy of APACHE II and IGSII scoring systems have to date not been specifically studied in general trauma surgical patients(TSP).To assess whether the APACHE II and IGS II scores and their derived predictors of risk of death(ROD)are applicable to TSP?. METHODS: During a16 month period TSP admitted to our ICU had APACHE II and IGSII scores with their derived ROD calculated. Receiver Operating Characteristic (ROC) curves and Goodness-of-Fit test were used to assess the accuracy of the scores. RESULTS: 62 TSP were included over 93 total trauma patients (median ISS score was 16.0, range 11 to 43), there were 10 in-hospital deaths from haemorrhage. The median APACHE II score was 12.0( range 0 to 40) with a mean ROD of 17.0 ⫾ 19.6%. The median IGSII was 22.0 ( range 0 to 60) and its derived mean ROD was 15.0 ⫾ 19.2%. The area under the ROC curves was 0.850 for the APACHE II and 0.858 for the IGS II demonstrate a good discrimination. The goodness-of-fit test indicated that both scores were well calibrated (P ⬎0.1 for APACHE II and P ⬎0.25 for IGSII). Standardised mortality ratio was 0.65 from APACHE II and 0.86 from IGSII. CONCLUSION: The APACHEII and IGSII scores are both reliable and accurate in post-traumatic patients. Bleeding appeared as a poor prognostic factor. CLINICAL IMPLICATIONS: The IGSII scoring, using actually in european ICU, could be applied in all of critical intensive care patients, including traumatics patients, improving quality of job. DISCLOSURE: Meurant Francois, None.

Pediatric Chest I 12:30 PM - 2:00 PM

reduced need for mechanical ventilation and lower incidence of reactive airway disease. CLINICAL IMPLICATIONS: The use of thickened feeds during RSV bronchiolitis is a simple intervention to prevent the subsequent short and long-term morbidity. DISCLOSURE: Dean Edell, None.

EPIDEMIOLOGY OF WHEEZING INFANTS REFERRED TO A TERTIARY MEDICAL CENTER Heather Huxol MD Kimberly Kim MD Ron Morton MD Nemr S. Eid MD* University of Louisville, Louisville, KY PURPOSE: Persistent or recurrent wheezing is a common cause for referral to pediatric pulmonology. These patients require a detailed work-up to elicit the etiology of wheezing as they often represent a diagnostic dilemma. Objective: To examine the components of the diagnostic course typically taken in these infants and the primary diagnoses given. To compare the epidemiology of patients referred for wheezing with the two most common diagnoses, gastroesophageal reflux (GER) and asthma. METHODS: A retrospective review was performed on 56 infants, mean age 10 months; range 2- 31 months, referred for recurrent or persistent wheezing. All of these patients had infant pulmonary function tests. The majority of patients had chest x-rays, pH probe studies, and upper GI series. A few others had modified barium swallow studies, allergy testing, and sweat chloride tests depending on the clinical presentation. RESULTS: The most common diagnoses were GER and asthma. Asthma, both as a primary diagnosis or with secondary diagnoses, was found in 40/56 or 71% of patients. GER, alone or with other diagnoses, was found in 27/56 or 48% of patients. There was no difference between these two groups regarding a parental history of asthma, prematurity, or NICU stay. There was no difference in family size. There was no difference in reported cases of bronchiolitis or pneumonia between the two groups. Environmental smoke exposure was slightly more common in the GER group. More patients with asthma had pets versus those with GER. A history of breastfeeding was less common in the asthma group. More patients with asthma had attended daycare versus those with GER. A clinical history of reflux was much more common in the GER group. CONCLUSION: Although wheezy infants constitute a heterogeneous group of patients, the most common diagnosis in this cohort is asthma and gastroesophageal reflux. CLINICAL IMPLICATIONS: The aspects of epidemiology most helpful in distinguishing the asthma patients versus the GER patients included clinical history of reflux, history of breastfeeding, history of daycare attendance, and history of eczema. DISCLOSURE: Nemr Eid, None.

EFFECTS OF PREVENTION OF ASPIRATION DURING RSV BRONCHIOLITIS Dean Edell MD* Douglas Savino MD Vikram Khoshoo MD West Jefferson Medical Center, Marrero, LA

THE 24-HOUR TUBERCULIN TEST: A COMPARISON WITH THE 48-HOUR AND 72-HOUR READINGS AND ITS PREDICTIVE VALUE Alfredo A. Yap MD* Olivia C. Go MD University of Santo Tomas Hospital, Manila, Philippines

PURPOSE: To evaluate the effects of prevention of aspiration, with the use of thickened feeds, during RSV bronchiolitis in previously healthy infants. METHODS: Previously healthy infants with RSV bronchiolitis, who were hospitalized, were divided into two categories: those given regular feeds (Control group, n⫽30) and those who received feeds thickened with rice cereal as a proven strategy for prevention of aspiration(Study group, n⫽44). All received similar conservative management with oxygen, IV fluids and bronchodilators. Control and Study groups were matched for age, sex, duration of illness, acidosis, oxygen saturation and respiratory rate. All infants underwent followup every two weeks after discharge from the hospital. RESULTS: The duration of hospital stay was longer (p⬍0.05)in the Control group(4.9 days) as compared to the Study group(3.2 days). The percentage of infants requiring mechanical ventilation was higher (p⬍0.05) in Control(13%) versus Study group(2%). At one year followup 27% of Study and 43% of Control patints were being treated for recurrent wheezing (p⬍0.05). CONCLUSION: Use of thickened feeds during RSV bronchiolitis, with a view to prevent aspiration, is associated with shorter hospital stay,

PURPOSE: This study was done to determine the value of the 24-hour tuberculin test (TT), its comparison with the currently recommended 48and 72-hour readings, and the factors which may affect it. METHODS: A 0.1 ml 5 TU PPD was administered using the Mantoux Method. Induration was measured at 24, 48 and 72 hours. An induration ⱖ8mm at 72 hours defined a positive test. The subjects were 230 children, 6-15 years old, from Bukidnon, Southern Philippines, who were not previously diagnosed or treated for tuberculosis (TB), never had a TT and had no condition/s that may cause anergy. RESULTS: Among 230 subjects,117(50.8%)had positive tests at 72 hours. The mean (SD)induration size (mm) was significantly larger at 72 hours [9.48 (5.65)] than at 48- [8.17 (5.23)] and 24 hours [5.81 (3.7)], respectively. A positive correlation existed between the induration sizes at the three periods. At 24 hours, the presence of any induration had a sensitivity of 96.58%, specificity of 51.33% and positive predictive value (PPV) of 67.26%; an induration ⱖ4mm (half the cut-off),had PPV of 81.15%; an induration ⱖ8 mm had a sensitivity of 34.18% , but 100% specificity and PPV;an induration ⬍8mm had a NPV of 59.74%; any induration associated with chest x-ray (CXR) suggestive of tuberculosis,

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CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Pediatric Chest I, continued among other factors, had a PPV of 98.18%.The absence of an induration at 24 hours had a negative predictive value (NPV) of 93.55%. CONCLUSION: Any induration at 24 hours may increase with time. At 24 hours, any induration has a low specificity, high sensitivity, and low PPV; induration ⱖ4mm(half the cut-off point) has high PPV; induration ⱖ8mm has high specificity, low sensitivity, and high PPV; ⬍8mm has low NPV; any induration associated with CXR suggestive of tuberculosis has high PPV;the absence of any induration has high NPV. CLINICAL IMPLICATIONS: This study suggests that the tuberculin test be read at 72 hours whenever possible. However, when pressed for time, the 24-hour TT may be utilized with caution. DISCLOSURE: Alfredo Yap, None. LUNG DEPOSITION OF QVAR (HFA134A-BDP) IN NEWBORN INFANTS WITH BRONCHOPULMONARY DYSPLASIA (BPD) Myrna B. Dolovich* David Millar MB, BCh Lori Sterling RN Rod Rhem BSc Andrew P. Bosco BSc Haresh Kirpalani MB, BCh McMaster University, Hamilton, ON, Canada

SERIAL EVALUATION OF PULMONARY FUNCTION LONGTERM AFTER LUNG CONTUSION Jan Sulc MD* Jan Bruthans MD Karel Dlask MD Karel Cvachovec MD Michal Andrlik PhD Jiri Kofranek MD Kardiocentrum, University Hospital Motol, Prague, Czech Republic PURPOSE: Lung contusions (LC) in children are frequent findings after road accidents. Possible residual lesions may potentially influence long-term lung development. Study on serial evaluation of pulmonary function in identical subjects has not published yet. METHODS: Forty four chidren injured at the age of 10.0⫾4.0 (ranged 2.3-17.5) yrs were diagnosed and treated for LC. These subjects were studied serially 2.0⫾1.8 (ranged 0.1-6.6) yrs and later again 8.4⫾3.3 (ranged 0.8-12.6) yrs after injury (when only 21 subject were accessible). The same protocol was used in both studies: static lung volumes by body plethysmography, lung elasticity using esophageal balloon technique and airway patency (by body plethysmography and flow-volume curves). 29/44 were ventilated by conventional CMV 13.9⫾14.0 (ranged 2-70) days,

LUNG FUNCTION TEST OF TOLUENE ABUSERS AMONG URBAN STREET CHILDREN AGES 7 TO 18 YEARS OLD Fatima B. Pogoy MD* Teresita S. de Guia MD Philippine Heart Center, Quezon City, Philippines PURPOSE: Toluene, an industrial solvent in adhesive compound is the most commonly abused inhalant among street children in Metro Manila. This study aims to determine the physiologic effects of inhaling toluene on the respiratory function of the study population. METHODS: General health status was assessed by history, physical examination and a questionnaire with emphasis on the respiratory symptoms. Spirometry using a Microloop (Micro Medical Limited) was performed using the standards of the American Thoracic Society. RESULTS: Thirty one (31) street children, 26 (84%)males, 5 (61%) females, with a mean age of 14⫹/-2 years were included. The mean duration of drug use is 2.6 ⫹/- 2.5 years with a frequency of 23 ⫹/- 20 hr per week. The most common respiratory symptoms in this series include dyspnea (38.7%, cough (35.5%), rhinorrhea (29%)and choking (12.9%). Results of spirometric studies showed 13 (41.9%)subjects with low FVC values ⬍ 80% of predicted indicative of restrictive ventilatory pattern in patients who tested positive for toluene in the blood. FEV1 values were all normal (mean FEV1 89⫹/- 14.9%). There was a statistically significant correlation between the duration/frequency of inhalant abuse with toluene levels in the blood (p⫽0.04) and urine (p⫽0.006). CONCLUSION: This study has shown a positive correlation between toluene abuse by inhalation and the development of restrictive ventilatory pattern which is directly related to the frequency and duration of toluene inhalation. CLINICAL IMPLICATIONS: Solvent abuse is popular among children and young adults. Sniffing the fumes causes the hunger, pain and loneliness to be numbed for a moment providing escape from realities of life. It is now well recognized that solvent abuse not only can result in sudden death but also cause pathological changes in the lungs. It is therefore, the aim of this study to investigate the effects of Toluene exposure on the pulmonary function of these children. DISCLOSURE: Fatima Pogoy, Other Philippine Foundation for Lung Health Research and Development, Inc.research and Development, Inc.

CHRONIC INHALED CORTICOSTEROIDS DO NOT AFFECT SEVERE ACUTE ASTHMA EXACERBATIONS IN CHILDREN Christopher L. Carroll MD* Anita Bhandari MD Aaron R. Zucker MD Craig M. Schramm MD Connecticut Children’s Medical Center, Hartford, CT PURPOSE: Chronic therapy with inhaled corticosteroids (ICS) is known to reverse and suppress airway inflammation and can also increase airway responsiveness to beta-adrenergic agonists. We theorized that the chronic use of ICS would be associated with shorter duration of hospitalization in severely ill children with status asthmaticus. METHODS: An eight-year retrospective chart review (April 1997 to May 2005) was conducted of all children greater than two years old admitted to the ICU with a primary diagnosis of status asthmaticus. Baseline demographics and outcome measures were compared between children receiving and not receiving ICS prior to admission. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

PURPOSE: Aerosol delivery to ventilated newborns is known to be poor. CFC beclomethasone dipropionate (BDP) pMDI has been reformulated as an HFA134a solution (QVAR, 3M Pharmaceuticals, London, ON) with a demonstrably lower mass median aerodynamic diameter (MMAD) of 1.1 ␮m and geometric standard deviation (GSD) 2.5 than the CFC aerosol. We hypothesised that an aerosol with these properties would result in increased delivery to the peripheral lung with a greater total pulmonary deposition. Aim: To investigate the total pulmonary deposition following inhalation of radiolabelled HFA 134a BDP in ventilated neonates. METHODS: Data expressed as mean(sd). Eight ventilated neonates with BPD, 40.3 (10.9) days old at time of study, with a mean corrected age of 32.2 (1.65) weeks post-gestation) were enrolled. Babies weighed 823.5 (222.7)g at birth and 1182.9 (188.3)g at time of study. Vital signs were monitored throughout the study. One dose of radiolabelled BDP (186 (57)␮Ci in 47 (14)␮g BDP) was given via a Neonatal Ventilator Aerosol Delivery System (NVADS, Trudell Medical Inc, London, ON), a tube spacer with low dead-space connectors to interface to the ventilator circuit. Posterior images of the lungs and lateral head were obtained over 10 min using a GE Starcam gamma camera. Tissue attenuation factors for each baby were obtained using a phantom. RESULTS: O2 saturation was unchanged during delivery of the aerosol (predose: 90.8 (5.2)%; dosing: 89.5 (5.1)%; post-dose: 91.6 (4.2)%). Most of the radiolabelled drug was captured in the NVADS (80.0 (13.1)%) and circuit tubing and connectors. Lung deposition was 1.27 (0.95)% of the recovered emitted dose ex-actuator or 8.63 ⫾ 7.39% of the dose ex-spacer. These percentages translated into an average deposited lung dose of 0.6␮g BDP. CONCLUSION: These values are similar to prior work with CFC formulations of salbutamol and appear to show no advantage in the total dose of HFA134a BDP delivered to these ventilated neonates. CLINICAL IMPLICATIONS: Clinical trials would need to be undertaken to determine if even this low deposition efficiency could provide a beneficial clinical outcome. DISCLOSURE: Myrna Dolovich, Grant monies (from industry related sources); Study funded by 3M Pharmaceuticals Canada.

FiO2 0.50⫾0.2 (ranged 0.3-0.4). The following findings were detected: pneumo- or hemothorax (n⫽6), sepsis (n⫽18), ARDS (n⫽6) and/or ribs/clavicle fractures (n⫽14). No previous history of chronic lung disease was ascertained. RESULTS: Normal lung size (both in 1st and 2nd study, respectively), i.e., TLC 97⫾12 and 102⫾12% predicted, N.S.) was found. Normal airway patency (PEF 99⫾21% vs 105⫾23% predicted, resp., P⬍0.04 as well as MEF25/TLC 92⫾32% vs 87⫾22% predicted, resp., N.S.) was also found over the years. No signs of hyperinflation were also found in both studies. Initial finding of stiffer lung normalized in the 2nd study: lung recoil at 100% TLC decreased from 123⫾30% to 119⫾31% predicted, resp., N.S.). CONCLUSION: In conclusion, despite serious lung injury during childhood the next favourable lung development till early adolescence was confirmed. CLINICAL IMPLICATIONS: Children who recovered after a lung contusion will not suffer from significant late pulmonary dysfunction. DISCLOSURE: Jan Sulc, None.

Wednesday, November 2, 2005 Pediatric Chest I, continued RESULTS: During the study period, 241 children were admitted to the ICU for status asthmaticus, and 107 (44%) were receiving chronic ICS at the time of admission. Chronic ICS use was associated with asthma severity (NIH asthma classification), previous hospitalization for asthma (79% vs. 45%, p⬍0.01) and public insurance status (67% vs. 53%, p⫽0.03). However, ICS use had no effect on hospital or ICU length of stay, type and duration of treatments received, or the rate of recovery. When examining subsets of patients, including children with persistent asthma and those who received intravenous terbutaline, there was also no improvement in outcomes with the use of chronic ICS. However, children with persistent asthma were less likely to receive supplemental therapy with non-invasive positive pressure ventilation (5% vs. 15%, p⫽0.03) if they were receiving chronic ICS. CONCLUSION: The chronic use of inhaled corticosteroids does not appear to reduce ICU length of stay or improve response to beta agonists in severely ill children with status asthmaticus. CLINICAL IMPLICATIONS: Although useful preventively, the chronic use of ICS does not appear to affect the course of acute exacerbations in pediatric patients. DISCLOSURE: Christopher Carroll, None. CLASSIFICATION OF ASTHMA SEVERITY AMONG STEROIDNAı¨VE PEDIATRIC SUBJECTS PREVIOUSLY RECEIVING SHORT-ACTING BETA2-AGONISTS: DO THE GUIDELINES NEED REVISITING? Bradley Chipps MD Joseph Spahn MD Christine Sorkness PharmD Amanda Emmett MS Laura Sutton PharmD Paul M. Dorinsky MD* GlaxoSmithKline, Research Triangle Park, NC PURPOSE: According to national/international asthma guidelines, subjects with asthma can be classified into one of 4 categories (intermittent, or mild, moderate, or severe persistent) based upon lung function, symptoms, and albuterol use. Guideline criteria for mild asthma based on symptomatology or rescue use is broad, suggesting that they may not define a distinct group of patients. METHODS: This analysis evaluated 276 subjects previously receiving short-acting beta2-agonists alone from 5 completed 12-week trials in which subjects received placebo. Subjects were initially stratified by baseline PEF ⱖ80% or ⬍80% predicted and further stratified by symptoms and/or albuterol use on ⱕ2 days/wk, 3-6 days/wk or 7 days/wk. RESULTS: For subjects with PEF ⱖ80% and symptoms/albuterol use 1-2 days/wk, the majority of weeks were spent in intermittent (76%) or mild (11%) categories, based on overall assessment of asthma severity. By contrast, for subjects with PEF ⱖ80% and symptoms/albuterol use 7 days/wk, approximately 51% of weeks were spent in the moderate category. When subjects with PEF ⱖ80% and symptoms/albuterol use 3-6 days/wk were considered, subjects who would be classified with mild persistent asthma using current guidelines, approximately 34% of weeks were spent in moderate or severe categories. Furthermore, subjects with PEF ⬍80% and symptoms/albuterol use on 3-6 days/wk, spent only 36% of weeks in intermittent or mild categories and those with PEF ⬍80% and daily symptoms/albuterol spent only 20% of weeks in intermittent or mild categories. CONCLUSION: This analysis clearly demonstrates that asthma severity cannot be determined in many pediatric subjects by discrete, pointin-time assessments of lung function, albuterol use or symptoms. More importantly, these observations suggest that the current classification system for persistent asthma needs to be re-evaluated as many pediatric subjects who meet current guideline criteria for mild persistent asthma would appear to be more appropriately classified as having moderate or severe persistent asthma. CLINICAL IMPLICATIONS: These data highlight the importance of ensuring that pediatric patients are carefully monitored and receive appropriate maintenance therapy for asthma control. DISCLOSURE: Paul Dorinsky, Shareholder I am a GSK shareholder; Employee I am a GSK employee. ROUTINE TRACHEAL ASPIRATES: ROLE IN THE MANAGEMENT OF RESPIRATORY TRACT INFECTIONS Jeff McQuade RRT Andrew Braude MD Lily Yang RRT* Bloorview MacMillan Children’s Centre, Toronto, ON, Canada PURPOSE: The lower respiratory tract is considered to be sterile to bacteria in healthy humans. The insertion of a tracheostomy tube results

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in the lower respiratory tract becoming colonized with bacteria. Mechanical ventilation enhances the severity of these risk factors. The ability to predict the likely organism and initiate earlier appropriate empiric antibiotic therapy should improve the client’s outcome. To date there is no considered standard approach to attempting to predict specific organisms or to predicting a specific antibiotic choice for lower respiratory tract infections in patients with a tracheostomy who may or may not be mechanically ventilated.Our hypothesis is that regular tracheal swabs will detect the likely causative organism in lower respiratory tract infections in predisposed tracheotomized patients. This knowledge will improve antibiotic choice and reduce morbidity and mortality. METHODS: For this study, 17 patients with chronic tracheotomies, 9 of whom were mechanically ventilated were selected. Periodic tracheal aspirates were obtained for bacterial culture and resistance profile to standard antibiotics. Clinically, when a determination of a lower respiratory tract infection was made, an antibiotic was chosen based on physician preference. At the same time a tracheal aspirate was obtained prior to the initiation of antibiotics. RESULTS: If Pseudomonas Aeruginosa was present as a colonizing orgainsm in the tracheal aspirate done when well, it was always present in heavy growth when the patient was ill. Thus making the choice of antibiotic one which would be effective against this organism.With respect to other gram negative and positive isolates, no apparent correlation could be found necessitating empiric coverage for these organisms at times of clinical infection. CONCLUSION: Knowlege of colonizing tracheal organisms in patients compromised with a tracheostomy tube and/or mechanically ventilated is valuable in that Pseudomonas Aeruginosa, if present, should be empirically covered for when clinical infection occurs. Thereafter no other prediction of infecting organisms could be drawn. CLINICAL IMPLICATIONS: At times of clinically documented infection, the prior knowledge of tracheal aspirate microbiology was of limited application for appropriate antibiotic choice. DISCLOSURE: Lily Yang, None.

THE EFFECT OF APNEA ON SLEEP ARCHITECTURE IN INFANTS WITH GENETIC OR METABOLIC DISEASE Wish Banhiran MD* Chulaluck Techakittiroj MD Teeradej Kuptanon MD Narong Simakajornboon MD Tulane University School of Medicine, New Orleans, LA PURPOSE: Several studies have shown that infants with genetic or metabolic disease have increased incidence of both central and obstructive apnea. However, those studies have not assessed the effect of sleep apnea on sleep architecture. Since apnea and associated hypoxemia and hypoventilation can lead to sleep fragmentation due to respiratory arousals, we evaluated the effect of apnea on sleep architecture in this population. METHODS: A retrospective review of polysomnographic recordings was performed in infants with genetic or metabolic disease and normal control infants who were referred to our sleep laboratory from 1999-2004. All infants underwent an overnight polysomographic studies. Any infants with significant lung diseases or infants who were on respiratory stimulants, or supplemental oxygen were excluded from the study. RESULTS: Thirty three infants met the criteria for entry into the analysis; 17 infants with metabolic or genetic disease [S] and 15 age-matched controls [C]. The average apnea index of infants with genetic or metabolic disease was 23.9⫾6.8/hr; 58.8 % (10/17) had predominately central apnea and 41.2 % (7/17) had predominately obstructive apnea. Infants with genetic or metabolic disease had significant lower average SpO2 (95.6⫾3.4 %[S] vs. 99.1⫾0.9[C]; P⬍0.05) and higher average EtpCO2 (44.6⫾5.7 mmHg[S] vs. 38.7⫾4.9[C]; P⬍0.05) during sleep. However, there was no significant difference in the sleep efficiency (73.1⫾12.8%[S] vs. 78.6⫾5.5[C]; P⫽NS), percentage of REM sleep (54.3⫾16.2%[S] vs. 53.0⫾8.0[C]; P⫽NS) and NREM sleep (42.2⫾14.3%[S] vs. 43.5⫾8.2[C]; P⫽NS) between infants with genetic or metabolic disease and control. Analysis of the respiratory arousals revealed that only 11.6 % of apnea in infants with genetic or metabolic disease was followed by arousals. CONCLUSION: It is concluded that apnea in infants with genetic or metabolic disease is not associated with significant changes in sleep CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Pediatric Chest I, continued architecture. It is speculated that the intact sleep architecture despite the presence of central and obstructive apnea may be due to blunted arousal response in these infants. CLINICAL IMPLICATIONS: Infants with genetic or metabolic disease may be at risk of developing significant adverse events from sleep apnea. DISCLOSURE: Wish Banhiran, None. THE USE OF SPIROMETRY AND IMPULSE OSCILLOMETRY IN THE DIAGNOSIS OF VOCAL CORD DYSFUNCTION IN THE PEDIATRIC PATIENT Shannon Boudreaux MD* Khalilah Lewis-Brown MD Glenn Hildreth RRT Kevin D. Maupin MD University of Florida Department of Pediatrics/ Sacred Heart Children’s Hospital, Pensacola, FL

PHYSIOLOGICAL RESPONSES COMPARATION AND REPRODUCTIBILITY OF SIX MINUTE WALKING TEST IN CYSTIC FIBROSIS AND NORMAL CHILDREN Cristiane C. Coelho MA* Dorcas C. Almeida BA Gisele C. Oliveira BA Roberta C. Pinto BA Ivana M. Oliveira MA Evanirso S. Aquino BS Uni-BH, PUC MInas-Betim, Belo Horizonte, Brazil PURPOSE: The aim of this study was to investigate pulmonary and cardiovascular responses during the six minute walking test (6MWT) in cystic fibrosis and normal children and to assess the test-retest of 6MWT in the studied population. METHODS: The subjects recruited were distributed in two groups: cystic fibrosis (CF) and normal group (NG). The study consisted the test-retest of 6MWT by comparing performance on two consecutive 6MWT in both groups. The children had a rest of 30 minutes between the tests. The responsiveness of the 6MWT was determined by assessing the ability of the test to detect changes in exercise capacity. The variables analyzed were distance walked during the test, heart rate overload (% of HR), oxygen saturation (SpO2) and Borg score. RESULTS: A total of 28 children were recruited in this study, 18 boys and 10 girls. The mean age was 11.53 ⫾2,60 and 10,72⫾2,88 years for CF and NG respectively. The mean values for lung volumes were (FEV1⫽ 86.34⫾27.11; FRC⫽94.85⫾25.19) for CF and (FEV1⫽100.99⫾8.92; FRC⫽112.26⫾15.56) for NG. The comparison between the groups showed that the distance walked (CF⫽577.57⫾60.22 NG⫽673⫾55.32; p⫽0.0004) and Borg score(CF⫽9.92⫾2.32 CN⫽12.42⫾2.4; p⫽0.01) were statistically different. However, there were no differences in %HR (CF⫽72.46⫾9.15 NG⫽72.54⫾12.19; p⫽0,85) and SpO2 (CF⫽94.07⫾5.16 CN⫽96.28⫾2.12; p⫽0.13) between the groups. The test-retest in cystic fibrosis group showed a significant increase in the walk distance in the second test (p⫽0.012), the others variables analyzed did not change. In the normal children group just the Borg Score had a significant increase in the second test (p⫽0,019).

Pediatric Chest II 12:30 PM - 2:00 PM ELECTRICAL ACTIVITY OF THE LARYNGEAL CONSTRICTOR AND DILATOR MUSCLES DURING CENTRAL APNEAS IN THE NEWBORN LAMB Nathalie Samson MS* Franc¸ois Moreau-Bussie`re MS Joelle RouillardLafond MD Jean-Paul Praud MD Universite´ de Sherbrooke, Sherbrooke, PQ, Canada PURPOSE: A complete active glottal closure in inspiratory position is present throughout 90% of central apneas in the preterm newborn lamb, partly preventing the post-apneic desaturation. However, results of the literature (Hutchison A, 2002) suggest that some induced neonatal apneas are characterized by an active laryngeal opening by contraction of the dilator muscles of the larynx. Thus, the goal of this study is to test the hypothesis that the larynx is actively open during some induced and spontaneous central apneas in newborn lambs. METHODS: Ten full-term lambs were chronically instrumented for recording electroencephalogram, eye movements, electrocardiogram, SaO2, nasal flow, subglottal pressure. In addition, the electrical activity (EMG) of the diaphragm, a laryngeal constrictor (thyroarytenoid muscle, TA, n ⫽ 4) and two laryngeal dilators (cricothyroid muscle, CT, n ⫽ 7 and posterior cricoarytenoid muscle, PCA, n ⫽ 7) was recorded. Polysomnographic recordings were performed in non-sedated lambs, using our custom-made radiotelemetry system to study both induced and spontaneous apneas on two different occasions. RESULTS: The results show a continuous TA EMG throughout 73% of all induced central apneas, and during the first two thirds of 89% of all spontaneous central apneas (mostly after a sigh). TA EMG was interrupted by CT EMG alone or with PCA EMG in 13% of all spontaneous and induced central apneas. The presence of the CT and/or PCA EMG during induced central apneas was consistently associated with both a fall of the subglottal pressure to atmospheric pressure and a decrease in lung volume below the preceding end-expiratory lung volume. CONCLUSION: In conclusion, a few central apneas in newborn lambs are characterized by both an active closure and opening of the larynx, occurring sequentially. CLINICAL IMPLICATIONS: Active opening of the glottis is associated with a fall of the subglottal pressure, which consequently leads to a decreased in lung volume during central apnea. DISCLOSURE: Nathalie Samson, None. COMPARISON OF DIFFERENT PROTOCOLS OF INSPIRATORY MUSCLES INCREMENTAL TEST IN NORMAL CHILDREN Cristiane Cenachi-Coelho MA* Lı´dia M. Barreto BA Maria Fernanda F. Correa BA Rose A. Miranda Figueira BA Evanirso S. Aquino BSc Uni-BH, PUC Minas-Betim, Belo Horizonte - MG, Brazil PURPOSE: To evaluate the applicability and acceptability of three different protocols of inspiratory muscles incremental test in normal children. METHODS: The children recruited were aleatory submitted to three inspiratory muscles incremental tests (IMT). JOHNSON et al (IMTI), JONG et al (IMTII) e NICKERSON E KEENS (IMTIII). Each protocol was performed with 24 hours between them. The inspiratory muscles endurance was performed 30 minutes after the IMT conforming, and was defined, as the time the subject was able to sustain breathing against an inspiratory pressure load equivalent to 80% of the maximal tolerated load in the IMT. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: The diagnosis of paradoxical vocal cord dysfunction is suggested by the patient’s clinical history. It is definitively made by observing the vocal cords via flexible laryngoscopy/bronchoscopy. Paradoxical vocl cord dysfunction can also be suggested by a flat inspiratory limb of the spirometry flow-volume loop. An increase in airway resistance via impulse oscillometry may also suggest paradoxical vocal cord dysfunction. The purpose of this study was to evaluate the usefulness of spirometry and impulse oscillometry in the diagnosis of pardoxical vocal cord dysfunction. METHODS: We retrospectively reviewed patient charts with a diagnosis of paradoxical vocal cord dysfuntcion that were seen in our Pediatric Pulmonary Clinic over a 6-month period. We reviewed fourteen charts for the following parameters; sex, inspiratory limb of the flow-volume loop, and airway resistance via impulse oscillometry. The diagnosis had been made by flexible fiberoptic bronchoscopy performed on all the patients. RESULTS: Five(35.7%) of the patients were male and nine(64.3%) of the patients were female. All of the patients had a normal inspiratory limb of the flow-volume loop. All of the patients had a normal RAW. CONCLUSION: In this study, the inspiratory limb of the flow-volume loop and the airway resistance via impulse oscillometry were both normal. CLINICAL IMPLICATIONS: The inspiratory limb of the flowvolume loop and the airway resistance via impulse oscillometry are not useful in the disgnosis of paradoxical vocal cord dysfunction. The diagnosis should only be made by fiberoptic laryngoscopy/bronchoscopy. DISCLOSURE: Shannon Boudreaux, None.

CONCLUSION: There was no difference in heart rate overload in the 6MWT in cystic fibrosis and normal children. However, the cystic fibrosis children had a lower perception of exercise intensity and walked concerning underwear distances when compared with normal children. CLINICAL IMPLICATIONS: The 6MWT can be applied in cystic fibrosis children as in normal children, however, the cystic fibrosis children has to be previously familiarized with the test. DISCLOSURE: Cristiane Coelho, None.

Wednesday, November 2, 2005 Pediatric Chest II, continued RESULTS: A total of 24 children completed the study, 13 boys and 11 girls. The mean age was 10,4⫾2,1 years. The mean values for lung volumes were withing normal limits. There were no statistically significant between initial and final heart rate, breathing frequency, oxygen saturation and dyspnea score; the time of the test; inspiratory muscles endurance comparing the three tests studied. However, the children were unable to sustain the maximal load in the (IMTIII) so they did not do the inspiratory muscles endurance. About the Borg score and the sustained load the results showed IMTI ⫽ IMT II⬍ IMTIII (p⬍ 0,001) and IMT II ⫽ IMTIII ⬎ IMTI (p⬍ 0,001) respectively. IMTIII was the only protocol witch the children did not achieve the maximal load during the test. CONCLUSION: The results suggest that the IMT II protocol demonstrated better applicability and acceptability in normal children as compared with IMTI and IMTIII. CLINICAL IMPLICATIONS: The best inspiratory muscles test to evaluate the inspiratory muscles endurance in normal children was IMTII because it does not underestimate the maximal load sustained. DISCLOSURE: Cristiane Cenachi-Coelho, None.

NIL NOCERE: ACQUIRED RESTRICTIVE THORACIC DYSTROPHY Francis Robicsek MD Alexander A. Fokin MD* Peter N. Kane MD Chad R. Swan MD Heineman Medical Research Laboratories, Carolinas Medical Center, Charlotte, NC PURPOSE: In 1995, Haller reported on a peculiar group of adolescents suffering from a condition coined “acquired Jeune’s syndrome,” later also known as “Acquired restrictive thoracic dystrophy” (ARTD). All these patients underwent pectus excavatum repair at an early age, after which their chest failed to grow adequately and became rigid with severely restricted respiratory function. METHODS: To shed light on the cause of this heretofore unknown disease, we have studied clinically five patients with ARTD and coordinated our findings with the scarce literary data available on the subject. RESULTS: All the patients whose data were available presented with severe respiratory impairment. Evidently, in the course of their pectus repair their costal cartilages from the second rib down were radically extirpated, including their medial and lateral centers of growth. Some of the operative reports and all of our imaging studies also indicated that the perichondrial strips were sewn together behind the sternum to maintain its corrected position (Fig. 1). As a result, the patient developed a rib cage that remained infantile in size, odd in appearance and failed to rise in inspiration or fall when the patient exhales.

CLINICAL IMPLICATIONS: The sparing of the growth plates and synovial joints of the ribs during cartilage resection preserves growth potential of the thoracic cage, prevents the development of acquired restrictive thoracic dystrophy after pectus excavatum repair and allows surgical correction of chest wall deformities to be done at early age. DISCLOSURE: Alexander Fokin, None. HIGH FREQUENCY CHEST WALL OSCILLATION IMPROVES OUTCOMES IN CHILDREN WITH CEREBRAL PALSY Penny M. Overgaard RN Peggy J. Radford MD* Phoenix Children’s Hospital, Phoenix, AZ PURPOSE: Children with cerebral palsy (CP) have an increased risk of recurrent pneumonia from impaired airway clearance. Ineffective cough, poor oral secretion control, reduced mucociliary function from recurrent infections and chest wall abnormalities contribute to poor airway clearance. Improving airway clearance may reduce the number of pneumonias. There is very little information regarding the value of high frequency chest wall oscillation (HFCWO) in this population. METHODS: We performed a retrospective quality assurance review on 13 children with CP, follow0ed in our pediatric pulmonary clinic, who use HFCWO to enhance airway clearance. RESULTS: Of the 13 children with CP, 5 are females, 8 males. Three children have tracheostomies, 7 have gastrostomy buttons. Hospital and clinic charts were reviewed to determine the number of emergency room (ER) visits and hospitalizations for respiratory problems including pneumonia and asthma. Calls were made to families to assess HFCWO usage and parental satisfaction. Parent recall and patient records documented 8 hospitalizations and 5 ER visits 1 year before HFCWO. Parents reported frequent illnesses requiring multiple antibiotics, 1 child missed 50 days of school, and another required increased oxygen use. After using HFCWO, 5 hospitalizations and 1 ER visit were documented. Parents reported less respiratory illnesses, less antibiotic use, and 1 child had a 58% reduction in missed school days. Six of the children have used HFCWO for more than 1 year; seven for at least 6 months. The average minutes of HFCWO use per day calculated from the hour meter was 41.3 minutes for 11 patients; information was not available on 2. Parental satisfaction with HFCWO was high with 9 parents expressing improvement in their child’s health and quality of life. CONCLUSION: This retrospective analysis would suggest that there is benefit from HFCWO use in children with CP by declines in respiratory illnesses, antibiotic use, missed school days, hospitalizations and ER visits. CLINICAL IMPLICATIONS: A controlled, prospectively designed study would be able to provide more scientific support for the use of the vest in this population. DISCLOSURE: Peggy Radford, None. THE MEASUREMENT OF RESPIRATORY MUSCLE FUNCTION IN ADOLESCENT IDIOPATHIC SCOLIOSIS Rupali Bansal MD* Narong Simakajornboon MD Salvador Cangiamella RRT Robert C. Beckerman MD Michael Kiernan MD Tulane University, Department of Pediatrics, New Orleans, LA

CONCLUSION: Performing repair of pectus excavatum the way described above is a grave mistake and should be avoided. We also disagree with those who suggest that the best way to avoid ARTD is to delay pectus repair to the age when the chest is already fully developed. As our experience of 300 patients operated at a very early childhood shows, the operation may be safely performed at any age, given appropriate operative plan and technique.

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PURPOSE: Restrictive lung disease is the most commonly reported pulmonary abnormality in adolescents with idiopathic scoliosis(IS). There is limited data on respiratory muscle function in IS. Since spinal deformity and decrease in lung volumes may lead to reduction in respiratory muscle strength, we studied these relationships. METHODS: Between 1999-2004, we retrospectively studied preoperative IS. All performed spirometry, lung volumes and respiratory muscle assessments. Degree of scoliosis was measured radiographically by the Cobb Angle(CA). The following parameters were analyzed: CA,FEV1,FVC,FEV1/FVC,FEF 25-75,MVV,PImax,PEmax,and static lung volumes. Neuromuscular disease,lung disease patients and incomplete records were excluded. RESULTS: Seventy four IS met the criteria for the study. The average age was 13.8⫾ 2.1 years. Cobb Angles(CA) ranged between 23° and 84°, mean 50.7⫾ 13.6°. Patients were divided into two groups, CA ⱕ 45° (M), and CA ⬎ 45° (S).]. There were significant differences in FVC (97.9⫾14.9(M) vs 84.5⫾14.6%(S), P⬍0.05) and PEmax (85.4⫾22.5(M) vs 64.9⫾28.3%(S), P⬍0.05. between M and S groups. However, there were no significant differences in PImax, MVV or ERV between the two groups. Using linear regression analysis, there was a strong negative correlation between CA and FVC (r⫽ -0.36; p ⫽ 0.002). There was a CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Pediatric Chest II, continued RESULTS: In children the incidence of BI is very rare due to the elasticity of the tissues. Most injuries occur in the proximity of the carina. It was the initial delay in the diagnosis, as well as the clinical stability of the patient, that led us to the consideration of using low dose steroids in an attempt to limit the inflammation and stenosis of the involved bronchus. Whether or not the use of low dose steroids contributed to less scarring and a successful repair cannot be stated from a single case and should be further investigated. CONCLUSION: We conclude that in selected cases of BI, a short course of low dose steroids can reduce the inflammation related to trauma, allow some healing, and possibly reduce the amount of scarring. CLINICAL IMPLICATIONS: The option of using a short course of low dose steroids when presented with a late diagnosis of tracheobronchial injury should be considered. DISCLOSURE: Alden Kirk, None.

RELATIONSHIPS BETWEEN RESPIRATORY FUNCTION AND SPINAL CHARACTERISTICS IN PATIENTS WITH SEVERE MOTOR AND INTELLECTUAL DISABILITIES SYNDROME Naoki Mori MS* Hajime Kurosawa MD Azuma Hiramoto MD Kayomi Matumoto MS Yuko Sano MS Emiko Fukuda PhD Hiromi Fujii PhD Masahiro Kohzuki MD Dep. of Int. Med. and Reha. Tohoku Univ. Graduate School of Medicine, Sendai, Miyagi, Japan

CONTINUUM OF CARE: THE ROLE OF TEACHING PROGRAMS IN THE PROVISION OF CARE TO VENTILATORASSISTED INDIVIDUALS IN URBAN AND RURAL REGIONS OF QUEBEC Rita Troini MA* McGill University Health Centre, Montreal, PQ, Canada

PURPOSE: Severe motor and intellectual disabilities syndrome (SMIDS) is a term used to describe a heterogeneous group of disorders with severe physical disabilities and profound mental retardation. Patients with SMIDS have spinal deformity in high incidence, and showed to multiple scoliosis curve pattern. The purpose of this study is to examine the correlation between spinal characteristics (including scoliosis curve pattern and respiratory function. METHODS: Thirty patients with SMIDS (M:F 18:12, Age, 33.5 ⫾ 12.1, means ⫾ SD)who were studied. All subjects were severe cerebral palsy, and were unable to sit independently. Spinal deformity were measured by Cobb Method (Cobb angles :CA) and Nash & Moe technique (vertebrae rotation grade :VRG). Scoliosis curve pattern were divided into three groups(thoracic, thoracolumbar and lumbar ) according to the different apical vertebrae by X-ray image. We measured tidal volume&, respiratory frequency observed during tidal breathing at static supine posture. RESULTS: CA and VRG, both were inversely correlated with tidal volume (CA:r⫽-0.71, p⬍0.01,VRG:rs⫽-0.59, p⬍0.01). CA and VRG, both were correlated with respiratory frequency(CA: r⫽0.67, p⬍0.01, VRG:rs⫽0.56, p⬍0.01). However, We did not find significant differences of respiratory function among curve patterns in patient with SMIDS. CONCLUSION: These results suggest that the spinal deformity restrictively affect respiratory patterns in patients with SMIDS. Scoliosis curve pattern did not affect respiratory function. CLINICAL IMPLICATIONS: To care to prevent spinal deformities especially in CA and VRG is very important in terms of maintaining respiratoy function. DISCLOSURE: Naoki Mori, None.

DELAYED SLEEVE RESECTION OF DISTAL LEFT MAIN BRONCHUS CRUSHING INJURY IN A CHILD AFTER SHORT COURSE OF STEROIDAL TREATMENT: CASE REPORT Alden H. Kirk MD* Giorgio M. Aru MD Fermin Romero MD University of Mississippi - Division of Cardiothoracic Surgery, Jackson, MS PURPOSE: We report for the first time on the delayed repair of a distal bronchial injury (BI) in a child, treated with steroids prior to definitive surgical repair. METHODS: An 8 year old child, run over by a truck, developed a left sided tension pneumothorax treated with a chest tube. Ten days later she was transferred to us for atelectasis of the left lung. The initial air leak had resolved and a flexible bronchoscopy showed bronchial disruption of the very distal left main stem bronchus. We planned a delayed repair considering that the injury in the distal left main bronchus carried a high risk of pneumonectomy during an early surgical repair for possible friability of the bronchial biforcation. She was discharged on low dose steroids and after 2 weeks a limited sleeve resection of the distal left main stem bronchus was performed through the left 4th intercostal space . Four years later, she is doing well and has a normal CXR.

PURPOSE: To present how the use of teaching programs can contribute to standardizing the care of ventilator-assisted individuals (VAI’s) across hospitals, rehabilitation centers and regions to which VAI’s return once discharged home. The National Program for Home Ventilatory Assistance (NPHVA) is a university-based program responsible for providing respiratory equipment and related homecare services to an adult and pediatric population requiring long-term mechanical ventilation. Diagnoses include neuromuscular diseases, Ondine’s syndrome, amyotrophic lateral sclerosis and high spinal cord injury. The NPHVA provides services to all regions of Quebec over a vast demographic area. In an effort to provide VAI’s with the same care across all regions, the NPHVA developed teaching programs covering topics related to each VAI’s illness, treatments and equipment. These programs are used in the training of patients, families, health care partners and frontline community health workers involved in the care of the patient at home. Binders personalized to each VAI’s needs are provided. METHODS: We analyzed patient/family satisfaction surveys and other quality indicators to identify key elements contributing to the success of the NPHVA in providing homecare services to VAI’s in urban and rural regions of Quebec. RESULTS: Three key elements were identified: 1) Teaching/training provided to the patient/family and frontline community health workers; 2) Regular home visits; 3) Timely exchange of information between the program’s clinical specialists and frontline community health workers providing care to the patient in their region. CONCLUSION: The use of teaching programs contributes to an open exchange between all health care partners involved in the care of VAI’s and can contribute to improving the continuity of care and the quality of life of this patient population. CLINICAL IMPLICATIONS: The training and dissemination of information to frontline health care workers in conjunction with continuous exchange of clinical and technical information between universitybased centers of expertise and community workers may prevent needless hospitalizations of VAI’s due to lack of knowledge and training in home ventilator management and associated therapies. DISCLOSURE: Rita Troini, None. THE EVOLUTION AND CURRENT STATUS OF RESPIRATORY TECHNOLOGY DEPENDENT CHILDREN IN MANITOBA Raquel J. Consunji-Araneta MD* Karen Wachnian RN Diane Lauder RRT University of Manitoba, Winnipeg, MB, Canada PURPOSE: To describe the demographic and clinical characteristics of and type of respiratory technology utilized by respiratory technology dependent children (RTDC) in Manitoba (1982-2005). METHODS: Demographic and clinical data (age, sex, underlying condition) were collected retrospectively together with specific information regarding respiratory technology utilized (oxygen, tracheostomy, CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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correlation approaching significant between CA and PImax (r⫽ -0.23; p ⫽ 0.05). But there were no significant correlations between the CA and PEmax, MVV, or ERV. CONCLUSION: FVC is the most sensitive marker of abnormal lung function in adolescents with idiopathic scoliosis. Respiratory muscle function, such as PEmax is significantly decreased in moderate to severe IS. But there is also a trend toward significant correlation between PImax and the degree of spinal curvature. CLINICAL IMPLICATIONS: We speculate that the rib cage deformity and secondary respiratory muscle dysfunction in these patients impairs the ability to generate normal inspiratory and expiratory pressures. Assessment of respiratory muscle function may be a useful additional tool in adolescents with IS who are evaluated preoperatively for spinal stabilization procedures. DISCLOSURE: Rupali Bansal, None.

Wednesday, November 2, 2005 Pediatric Chest II, continued non-invasive or invasive ventilation – continuous or nocturnal) and current location/situation. RESULTS: In 1982 the first ventilated child was sent home on an LP3 ventilator. The establishment of the Pediatric Sleep Program in 1989 contributed to more children requiring ventilator support. Majority of the 115 children dependent on respiratory technology since 1982 have been managed at home. Ventilatory support was discontinued in twenty-nine patients and thirteen were successfully decannulated. Seventeen children have been transitioned to the Adult Program. Mortality rate is 16.5% (19/115). The current population of RTDC in Manitoba consists of 11 children ventilated by tracheostomy and 20 who receive support non-invasively at home; another 15 children have tracheostomy tubes only and 17 receive oxygen supplementation. Only two tracheostomized/ventilated and 2 tracheostomized children remain in hospital. One patient on BiPap support remains admitted (requiring other therapies). Patients’ underlying conditions were classified as neuromuscular diseases, central nervous system disorders, spinal injuries, craniofacial syndromes, chronic respiratory diseases (BPD, BOOP) and others (tracheomalacia, trauma, etc). Tracheostomized/ventilated children require on average 1-2 hospitalizations/year while children with tracheostomy tubes or O2 only are admitted 0-1 times/year. All patients managed at home are assessed at least 2-4 times/year at the Technology Dependent Children’s Clinic. CONCLUSION: Majority of RTDC children in Manitoba have been and are successfully cared for at home. CLINICAL IMPLICATIONS: Advanced medical technology and developments in critical care have increased the number of children with chronic medical conditions that are dependent on respiratory technology. Together with a well-structured Home Care Program, dedicated efforts of Respiratory Therapists, Pediatric nurses and Specialists, majority of these patients can be managed effectively in the home setting.

LUNG PROTECTIVE STRATEGY DURING MECHANICAL VENTILATION OF PEDIATRIC PATIETNS WITH ARDS IS ASSOCIATED WITH REDUCED INCIDENCE OF CHEST TUBES INSERTION FOR PNEUMOTHORACES BUT WITH INCREASED INCIDENCE OF CHEST TUBES INSERTION FOR PLEURAL EFFUSIONS Michael P. Miller MD* Mayer Sagy MD Schneider Children’s Hospital, New Hyde Park, NY PURPOSE: To test the hypothesis that the overall incidence of chest tubes insertion for pneumothoraces in pediatric ARDS patients has decreased with protective lung strategy (PLS) during mechanical ventilation (MV) while the incidence of chest tubes insertion for pleural effusions has increased. METHODS: We retrospectively reviewed charts of pediatric ARDS patients who required a minimum PEEP level of 8 cm of water. Data of patients treated in our PICU during years 1992 – 1993 (pre-PLS) were compared with those of years 2000-2003 (post-PLS). Pre-PLS was defined as a period during which unlimited peak airway pressures (PIP) were allowed during MV and the tidal volumes used were ranging between 10 ml/kg and 20 ml/kg. Post-PLS was characterized by MV with smaller tidal volumes (6-10 ml/kg) and by PIP values not exceeding 40 cm of water. RESULTS: Twenty seven patients were studied in the pre-PLS period and 59 patients in the post-PLS period. The incidences of chest tubes insertion was 55% (15 out of 27) and 19% (11 out of 59), respectively (p⬍0.05). In the pre-PLS period, 14 out of the 15 chest tubes (93%) were inserted for pnemothoraces evacuation and 1 (7%) for evacuation of pleural effusion. In the post-PLS period 5 of the chest tubes (45%) were for pnumothoraces and 6 (55%) for pleural effusion (p⬍0.05). CONCLUSION: The overall incidences of tube thoracostomy for pneumothoraces and for pleural effusions with PLS implementation has significantly decreased and increased, respectively. CLINICAL IMPLICATIONS: Our study supports the clinical theory that the ‘Starling resistor’ principles for pressure relationship within lung units could explain why the high pre-PLS airway pressures could prevent pulmonary exudates (effusions) but not pneumothoraces and vice versa. DISCLOSURE: Michael Miller, None.

SIGNIFICANT IMPROVEMENT IN SPIROMETRY AFTER STEM CELL TRANSPLANTATION IN ONE DUCHENNE MUSCULAR DYSTROPHY PATIENT Zhiping Li RRT Yubiao Guo MD* Xiaoli Yao MD Cheng Zhang MD Canmao Xie MD Department of Pulmonary & Critical Care Medicine, the First Affiliated Hospital, Guangzhou, Peoples Rep of China

DISCLOSURE: Raquel Consunji-Araneta, None.

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PURPOSE: To describe the pattern of lung function abnormality and to investigate the changes in spirometry before and after autologus hematopoietic stem cell transplantation in one duchenne muscular dystrophy (DMD) patient. METHODS: Lung function was measured by maximum expiratory flow-volume loops and whole body plethysmography in one 14-yr old DMD patient before and three months after stem cell transplantation. RESULTS: Lung function test was characterized by restrictive pattern manifested by lung volume reduction and increased FEV1/FVC due to muscular weakness. Before stem cell transplantation, the FVC, FEV1 and MVV were 1.4L, 1.4L and 59.5L respectively. 3 months after stem cell transplantation, the patient’s FVC, FEV1 and MVV were significantly increased to 2.12L, 2.12L and 118.0L respectively. CONCLUSION: Although genetically modified myoblast transplantation remains controversial for DMD, a significant change in spirometry was found in this DMD patient after stem cell transplantation. CLINICAL IMPLICATIONS: Spirometric measurement provides a simple and useful means of assessing disease progression in DMD patients and should be considered when stem cell transplantation is planning.Furthermore, since DMD characterized by gradually developing muscular weakness, pulmonary physical rehabilitation should focus on the training of respiratory accessory muscles. DISCLOSURE: Yubiao Guo, None. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Pediatric Chest II, continued

Pleural Disease 12:30 PM - 2:00 PM

THE BENEFIT OF ROUTINE CHEST RADIOGRAPHY IN THE PEDIATRIC PATIENT AFTER FLEXIBLE FIBEROPTIC BRONCHOSCOPY Susie N. FitzHarris MD* Khalilah Lewis-Brown MD Kevin D. Maupin MD University of Florida Department of Pediatrics/Sacred Heart Children’s Hospital, Pensacola, FL

A CHRONIC PNEUMOTHORAX AND FITNESS TO FLY Graeme P. Currie MD* Annie Kennedy MB, ChB Ed Paterson MB, BCh Stephen Watt MB, ChB Aberdeen Royal Infirmary, Aberdeen, United Kingdom

C-FIBER BLOCKADE INFLUENCE NON-NUTRITIVE SWALLOWING IN NEWBORN LAMBS Charles Duvareille PhD* Philippe Reix MD Carole Langlois Julie Arsenault MS Patrick Le´tourneau MS The´ophile Niyonsenga PhD Nathalie Samson MS Jean-Paul Praud MD Centre Hospitalo-Universitaire de Sherbrooke, Fleurimont, PQ, Canada PURPOSE: Non-nutritive swallowing (NNS) is especially important in the neonatal period for clearing secretions and gastro-pharyngeal reflux, and has been associated with neonatal apneas. One previous study has reported that systemic C-fiber blockade (CFB) inhibits induced swallowing in adult guinea pigs (Jin, Y et al, Am J Respir Crit Care Med. 1994). The aim of our present study was to investigate the effects of CFB on apnea and NNS frequency, and on the coordination between NNS and phases of the respiratory cycle in newborn lambs. METHODS: Eight CBF and 7 control lambs were chronically instrumented for recording electroencephalogram, eye movements, diaphragm and thyroarytenoid muscle activity, nasal airflow and electrocardiogram. CFB was induced by subcutaneous injection of capsaı¨cin (30mg/kg). All experiments were conducted in non-sedated lambs at 4 days of age, using a custom-made radiotelemetry system. RESULTS: CFB lambs spent more time in active sleep than controls (15 ⫾ 4% vs. 9 ⫾ 3%, p ⫽ 0,03). Apnea frequency was not significantly different between CFB and control lambs, whatever the state of alertness (p between 0.2 and 0.8). NNS frequency was higher in CBF than control lambs (32 ⫾ 8/h vs. 20 ⫾ 10/h, p ⫽ 0.01) in QS. Finally, systemic C-fiber blockade had no effect on the coordination between NNS and phases of the respiratory cycle, whatever the state of alertness. CONCLUSION: Our results suggest that C fibers inhibit NNS, but have no effect on the coordination between NNS and phases of the respiratory cycle in the neonatal period. Moreover, C fiber blockade has no effect on apnea frequency. CLINICAL IMPLICATIONS: such studies may prove to be important in the use of capsaicin agonists or antagonists in the treatment of various conditions, including swallowing difficulties. DISCLOSURE: Charles Duvareille, None.

PREVALENCE OF EMPHYSEMA-LIKE CHANGES OF THE LUNGS AMONG YOUNG HEALTHY ADULTS, AND AMONG THOSE WITH SIMILAR PHYSIOGNOMY TO PATIENTS WITH PRIMARY SPONTANEOUS PNEUMOTHORAX: A THORACOSCOPIC EVALUATION Kayvan Amjadi MD* Eef Vanderhelst MD Brigitte Velkeniers MD Marc Noppen MD Queen’s University, Kingston, ON, Canada PURPOSE: To thoracoscopically determine the prevalence of emphysema like changes (ELCs) among young healthy adults, and among healthy individuals who are age, gender, height, weight and smoking habit-matched to patients with diagnosis of primary spontaneous pneumothorax (PSP). METHODS: We performed bilateral thoracoscopic evaluation of the lungs in healthy individuals who were referred to us for thoracoscopic thoracic sympathectomy. Presence of ELCs, age, gender, height, weight, smoking habits, and pulmonary function tests were documented. Comparisons of these parameters were made between ELC-positive and ELC-negative individuals. Participants were enrolled into a registry, allowing long-term follow-up (6 years). Individuals were then matched to a group of 12 PSP patients (all male, mean age 29.9, range 17 – 43, mean height ⫾ standard deviation (SD); 1.79 ⫾ 0.07 meters, mean weight ⫾ SD; 68.7 ⫾ 9.9 kilogram, mean body mass index (BMI) ⫾ SD; 21.3 ⫾ 2.7, smoker/non-smoker 0.6). Prevalence of ELCs among healthy individuals with matched characteristics was evaluated. RESULTS: Analysis was performed on 250 consecutive cases (male/ female 0.4, mean age ⫾ SD; 29 ⫾ 10 years). ELCs were observed in 15/250 (6%) individuals (male/female 6/9, mean age 25.3, range 15 – 51). Compared to ELC-negative group, ELC-positive individuals had a significantly lower body mass index (BMI) (20.7 ⫾ 2.4 vs. 22.7 ⫾ 3.4; P ⫽ 0.027), whereas all other parameters were similar. ELCs tended to be more prevalent among smokers; however, statistical significance was not achieved (P ⫽ 0.76). Similarly, in the matched group, ELCs were observed in 6/101 (6%) individuals. During 6 years of follow-up, none of the ELC-positive individuals has developed pneumothorax. CONCLUSION: Thoracoscopically, ELCs were present in 6% of young healthy adults with no underlying lung disease. Low BMI (⬍ 22) appears to play an important role in the development of ELCs. CLINICAL IMPLICATIONS: Given that far less than 6% of the population develops PSP, we hypothesize that ELC’s in PSP population is at least in part due to their physiognomic features and not the obligatory cause of pnemothorax. DISCLOSURE: Kayvan Amjadi, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: Flexible fiberoptic bronchoscopy in pediatric patients is considered to be a low risk procedure with minimal complications. The purpose of this study was to evaluate the usefulness of routinely performing chest radiography after flexible fiberoptic bronchoscopy with bronchoalveolar lavage in the pediatric patient. METHODS: We retrospectively reviewed the charts of 51 pediatric patients that had undergone flexible fiberoptic bronchoscopy with bronchoalveolar lavage. We reviewed the charts for the following parameters: age, diagnosis for which the procedure was performed, chest radiography findings and for any complications that occurred during the procedure that necessitated stopping the procedure. RESULTS: Patients’ ages ranged from 1 month old to 19 years old. The diagnosis were chronic cough(11), cystic fibrosis(4), foreign body evaluation(2), hoarseness(2), persistent atelectasis(3), recurrent pneumonia(2), stridor(20), tracheomalacia(1), tracheostomy evaluation(1), tuberculosis(2), upper airway obstruction(1), and vocal cord dysfunction(2). 50 of the patients had chest radiographs and 1 patient had a chest CAT scan. The chest radiographs and the CAT scan revealed no complications or acute changes from flexible fiberoptic bronchoscopy with bronchoalveolar lavage. There were no complications that necessitated stopping of the procedure and all procedures were completed. CONCLUSION: This study has shown that chest radiography in pediatric patients undergoing flexible fiberoptic bronchoscopy with bronchoalveolar lavage, 4with no intraoperative complications that necessitated the procedure to be stopped, had no clinical usefulness or benefit for the patient. CLINICAL IMPLICATIONS: Chest radiography should not be routinely performed after uncomplicated flexible fiberoptic bronchoscopy with bronchoalveolar lavage. It is not cost effective, adds no benefit to patient management, and exposes the pediatric patient to unecessary radiation. DISCLOSURE: Susie FitzHarris, None.

PURPOSE: Without definitive intervention, individuals with an untreated pneumothorax should not participate in commercial flying. Whether this advice applies to patients with a long-standing pneumothorax is uncertain. We report two adults with persistent pneumothoraces who underwent further investigation to determine the safety of doing so. METHODS: Following clinical assessment, both subjects had chest computerised tomographic (CT) imaging and underwent a hypoxic challenge test (breathing 15% oxygen). The individuals then proceeded to cabin altitude simulation in a hypobaric chamber. RESULTS: Case 1 - Chest CT showed a small left pneumothorax (estimated volume 110 millilitres). During a hypoxic challenge test, the oxygen saturation fell to 90%. During cabin altitude simulation, the patient remained asymptomatic and oxygen saturation fell to 90%. He was considered fit to fly and has completed over a dozen transatlantic flights without difficulty.Case 2 - Chest CT showed a loculated right sided pneumothorax (estimated volume 250 millilitres) and during a hypoxic challenge test, the oxygen saturation fell to 93%. An altitude chamber test was tolerated without symptoms and the oxygen saturation fell to a minimum of 92%. She was therefore considered fit to fly in commercial aircraft. CONCLUSION: Some patients with a closed chronic pneumothorax can fly without adverse consequences. CLINICAL IMPLICATIONS: This risk should be determined after thorough assessment incorporating chest CT, a hypoxic challenge test and simulation of flying at altitude in a decompression chamber with close monitoring of symptoms and oxygen saturation. DISCLOSURE: Graeme Currie, None.

Wednesday, November 2, 2005 Pleural Disease, continued DIAGNOSTIC VALUE OF TUMOR MARKERS CEA, CA 125, CA 15-3 AND NSE LEVEL DETERMINATION IN THE SERA AND PLEURAL FLUIDS IN PATIENTS WITH MALIGNANT PLEURAL EFFUSIONS Samrad Mehrabi MD* Mohammad Ali Ghayyumi MD Abbas Ghaderi PhD Mehrnoush Doroudchi PhD Kurdisatn University of Medical Sciences, Sanandaj, Iran PURPOSE: The aim of this study was to evaluate the individual and combined

RESULTS: Using the cutoff values of 29.7 U/ml for CA 15-3, 10.36 ␮g/L for NSE, 2.95 ␮g/L for CEA and 50.65 U/ml for CA 125 in serum and cutoff values of 21.11 U/ml, 5.21 ␮g/L, 3.60 ␮g/L and 1196.67 U/ml for pleural fluid CA 15-3, NSE, CEA and Ca 125 respectively, the sensitivity (%) and specificity (%) of these tumor markers for differentiating malignant from benign effusions were as follows: in serum CA 15-3 59.5/63.5, NSE 38.9/63.6, CEA 47.2/81.8 and CA 125 50/48.5; and in pleural fluid CA 15-3 70/83.3, NSE 68.4/75, CEA 47.4/85 and CA 125 48.6/70.6. The highest specificity in the diagnosis of pleural malignancy was obtained with combination of CA 15-3 in serum, and CA 15-3 and NSE in pleural fluid and also with combination of CA 15-3 in serum, and CA 15-3, NSE and CEA in pleural fluid and was 100%.The best combination of tumor markers which revealed 100% specificity and 100% PPV with 76.5% sensitivity could be obtained by measurement of CA 15-3 in serum and pleural fluid plus NSE in pleural fluid. CONCLUSION: The findings of this study suggest that a combination assay of tumor markers in addition with pleural fluid cytology can use as a diagnostic test in diagnosis of malignant pleural effusion. CLINICAL IMPLICATIONS: The use of combination of CA15-3/ NSE/CEA determination in pleural effusion coulld reduce the need for invasive measures in undiagnosed exudative pleural effusions. DISCLOSURE: Samrad Mehrabi, None. ANALYSIS OF 112 CONSECUTIVE CASES OF THORACIC EMPYEMA OVER A 19-YEAR PERIOD Basil Varkey MD Manish Joshi MBBS* Veterans Affairs Medical Center and Medical College of Wisconsin, Milwaukee, WI

Operating Characteristics of Each Tumor Marker and Combinations of Tumor Markers in Patients With Pleural Effusion % Tumor Marker

Cutoff

%

%

%

Sensitivity Specificity PPV NPV

% Accuracy

Serum CA 15-3

29.07

59.5

63.6

64.7 58.3

61

NSE

10.36

38.9

63.6

51.1 46.2

49

CEA

2.95

47.2

81.8

42.6 26.1

37

50

48.5

53

50

CA 125

50.65

47.2

Pleural Fluid CA 15 -3 NSE CEA

21.11 5.21

70

83.3

82.4 71.4

76

68.4

75

74.3 69.2

72

3.60

47.4

85.3

78.3 59.2

65

1196.67

48.6

70.6

42

34.5

39

CA 15-3⫹NSE

57.5

91.9

88.5 66.7

74

CA 15-3 in serum ⫹

71.4

86.4

87

70.4

78

76.2

77.3

76.3 77.3

77

80

88.9

88.9 80

84

CA 125

CA 15-3 in pleural fluid CA 15-3 in serum ⫹ NSE in pleural fluid CA 15-3 in serum ⫹ CA 15-3 and CEA in pleural fluid CA 15-3 in serum ⫹ CA 15-3

76.5

100

100

77.8

87

80

100

100

81.3

89

and NSE in pleural fluid CA 15-3 in serum ⫹ CA 15-3, NSE and CEA in pleural fluid

diagnostic utility of four tumor markers in patients with pleural effusion. METHODS: Pleural and serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA 15-3), neuron specific enolase (NSE) and cancer antigen 125 (CA 125) were assayed prospectively in 77 patients with pleural effusion (40 malignant and 37 benign).

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PURPOSE: To analyze pathogenesis, bacteriology, drainage methods and outcomes of thoracic empyema in one institution over a nineteen year period. (1986-2004). METHODS: Retrospective review of medical and microbiology records of thoracic empyema (culture positive pleural fluid and /or pus) and analysis of patient demographics, pathogenesis, bacteriology, drainage methods and outcome. RESULTS: One hundred and twelve cases (culture ⫹ ⫽ 107, pus ⫽ 5) of empyema were identified. The patients were predominantly men over 45 yrs of age (45-65 yrs⫽52%, ⬎65yrs ⫽42%). Most common pathogenetic factors were post pneumonic in 66(60%) and post thoracotomy in 18(16%). Sixty percent of the empyemas were community-acquired and the remaining were hospital- acquired. The 107 culture positive cases yielded 154 bacterial isolates. Pleural fluid isolates showed only aerobes in 80 cases (74.8%) anaerobes alone or with aerobes in 27 cases (25.2%). The most common aerobes were staphylococci (38.6% of aerobic isolates) and streptococci (31.0%) followed by gram negative bacilli (17%) and Streptococcus pneumoniae (6.7%).The most common anaerobes isolated were Bacteroides (28.5% of anaerobic isolates), Fusobacterium (17%), peptostreptococcus (14.2%), diptheroids 4(11.4%) and micro-aerophilic streptococci (8.5%). In all cases appropriate antibiotics were given. The initial drainage procedure employed was closed chest tube in 91 patients (20 required subsequent surgical procedures) and thoracotomy in 13 patients. Eight patients were drained by thoracentesis alone. Eighty one (72.3%) patients were cured, 9 patients (8%) died of empyema and 22 patients (19.6 %) with co-morbid conditions died while empyema was active. CONCLUSION: Most empyemas are postpneumonic and in a quarter of cases anaerobes are the causative microbes. Closed chest tube drainage is effective in most cases but additional surgical procedures may be needed in 20%. Mortality due to empyema was 8%; however a larger number of patients with co-morbid conditions died. CLINICAL IMPLICATIONS: Information on patient demographics, pathogenetic mechanisms, bacteriology, treatment and outcome of empyema from this large series may be useful in devising better treatment and improving outcome. DISCLOSURE: Manish Joshi, None. A RETROSPECTIVE ANALYSIS OF THE MANAGEMENT OF PARAPNEUMONIC EMPYEMAS IN A COUNTY TEACHING FACILITY FROM 1992-2004 Glena Cheng MD* Janine R. Vintch MD Harbor-UCLA Medical Center, Torrance, CA PURPOSE: To characterize how patients with empyemas are managed initially at our facility and to determine how “less aggressive” treatments (no drainage, repeat thoracentesis, tube thoracostomy) affect short term CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Pleural Disease, continued

PROTEIC PROFILE OF PLEURAL EFFUSIONS SECONDARY TO TUBERCULOSIS AND MALIGNANCY Leila Antonangelo MD Francisco S. Vargas MD Eduardo H. Genofre MD Lisete R. Teixeira MD Milena M. Acencio BS Ma´rcia Seiscento MD Evaldo Marchi MD Roberta K. Sales MD* Pulmonary Division, Heart Institute (InCor), University of Sa˜o Paulo Medical Sc, Sa˜o Paulo, Brazil PURPOSE: To evaluate the proteic profile of tuberculous and neoplastic pleural effusions. METHODS: Pleural fluid and pleural-serum ratio (PSR) of total protein and eletrophoretic (EF) albumin, alpha, beta and gamma globulin were analysed from 403 patients having tuberculosis (200) or malignant pleural effusions(203). Univariate analysis was applied to compare the results between the groups. Significant difference was considered for a p⬍0.05. RESULTS: The results are expressed in median with p value.

Protein (mg/dl) PSR-Protein Albumin-EF PSR-Albumin ␣1 globulin-EF PSR-␣1 globulin ␣2 globulin-EF PSR-␣2 globulin ␤ globulin-EF PSR-␤ globulin ␦ globulin-EF PSR ␦ globulin

Tuberculosis

Malignancy

5.4 (4.9 – 5.7) 0.69 (0.65 – 0.73) 2.63 (2.35 – 2.9) 0.77 (0.71 – 0.83) 0.23 (0.2 – 0.3) 0.62 (0.54 – 0.7) 0.47 (0.4 – 0.6) 0.52 (0.46 – 0.6) 0.8 (0.62 – 0.9) 0.69 (0.6 – 0.77) 1.14 (0.9 – 1.4) 0.64 (0.57 – 0.7)

4.3 (3.7 – 4.9) * 0.61 (0.54 – 0.65) * 2.5 (2.1 – 2.8) * 0.77 (0.64 – 0.77) * 0.2 (0.14 - 0.23) * 0.53 (0.41 – 0.62) * 0.3 (0.2 – 0.4) * 0.36 (0.28 – 0.43) * 0.6 (0.46 – 0.71) * 0.52 (0.41 – 0.63) * 0.7 (0.52 – 0.9) * 0.55 (0.46 – 0.65) *

* p⬍0.05 CONCLUSION: Total proteins and their subsets were significantly higher in the pleural effusion due to tuberculosis as compared to the malignant, suggesting a more intense inflammatory response in the tuberculous group. CLINICAL IMPLICATIONS: These data may colaborate in the differentiation between the tuberculous and malignant pleural effusions. DISCLOSURE: Roberta Sales, None.

CORRELATION OF WHITE BLOOD CELLS (WBC) WITH PLEURAL FLUID PH VALUES COLLECTED IN HEPARINIZED AND NON-HEPARINIZED SYRINGES Ali H. Debek MD* Mohammad Khatib PhD Ghassan Jamaleddine MD Ahmad Husari MD Pierre Bou-Khalil MD American University of Beirut - MC, Beirut, Lebanon PURPOSE: In a previous study done at our institution, we reported a statistically significant decrease in pleural fluid pH when samples were delayed up to two hours after collection. The aim of this study is to investigate the effect of WBC on pleural fluid pH values measured at various time intervals. METHODS: This is a prospective study at an academic tertiary medical center. From 40 consecutive (n⫽40) thoracentesis, 1ml of pleural fluid was collected anaerobically in each of six 3 ml syringes. Three syringes were coated with heparin. Samples in each syringe type (heparinized (H) and non-heparinized (NH)) were processed for pleural fluid pH measurements at time 0 (T0), one hour (T1) and two hours (T2) post collection. All specimens were preserved at room temperature until the measurements were carried out in duplicates by a calibrated blood gas analyzer. In addition, WBC count was determined at T0 by an automated WBC counter. RESULTS: With the heparinized syringes, there was a statistically significant negative correlation between pleural fluid pH and WBC at T1 and T2. With the non-heparinized syringes, there was a statistically significant negative correlation between pleural fluid pH and WBC only at T2.(table 1). CONCLUSION: Our data showed an effect of WBC on pleural fluid pH measurement. For pleural fluid samples collected in non-heparinized syringes, there is up to two hours time before the WBC will have its effect on pH measurements. While for pleural fluid samples collected in heparinized syringes, the effect of WBC on pH measurements starts at one hour after collection of pleural fluid sample. CLINICAL IMPLICATIONS: It is advisable to process pleural fluid for pH measurements no later than one hour of collection when using heparinized syringes, and up to two hours when using non heparinized syringes.

Table 1

Type of syringe & time H - T0 H - T1 H - T2 NH - T0 NH - T1 NH - T2

r

p

0.16 0.34 0.45 0.13 0.26 0.264

0.32 0.03 0.003 0.42 0.10 0.001

DISCLOSURE: Ali Debek, None. COMPARISON BETWEEN PLEURAL FLUID PH MEASUREMENTS OF SPECIMENS COLLECTED IN HEPARINIZED VERSUS NON-HEPARINIZED SYRINGES Ali H. Debek MD* Pierre Bou-Khalil MD Ghassan Jamaleddine MD Nadim Kanj MD Mohammad Khatib PhD American University of Beirut -MC, Beirut, Lebanon PURPOSE: Pleural fluid pH measurement is an important tool for characterizing the type of pleural fluid, establishing a diagnosis, and guiding clinical management. The current standard and widely accepted practice is to collect pleural fluid samples for pH measurement in heparinized syringes and to instantaneously process these samples at room temperature. We conducted a prospective study to investigate the changes in pleural fluid pH measurements collected in heparinized versus non heparinized syringes and processed at various time intervals while the samples are preserved at room temperatur. METHODS: This is a prospective study in an academic tertiary medical center. From 50 consecutive (n⫽50) thoracentesis, 1ml of pleural fluid was collected anaerobically in each of six 3 ml syringes. Three syringes were coated with heparin. Samples in each syringe type (heparinized (H) and non-heparinized (NH)) were processed for pleural fluid pH measurements at time 0 (T0), one hour (T1) and two hours (T2) post collection. All specimens were preserved at room temperature until the CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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outcomes (inpatient mortality and need for a second intervention) compared to “more aggressive” treatments (intrapleural fibrinolytics, videoassisted thoracoscopic surgery, or other surgery). We will also assess if fewer patient co-morbidities, earlier diagnosis, earlier antibiotic treatment, and consulting appropriate services improve mortality. METHODS: A retrospective chart analysis was performed in a county teaching hospital in Los Angeles, California on seventy-two adult inpatients with parapneumonic empyemas. Mortality and need for second intervention rates were calculated and compared with data published in the 2000 American College of Chest Physicians Consensus Statement on the management of parapneumonic effusions using Fisher’s exact tests. Comparisons were made between empyema survivors and non-survivors using t-tests and chi-squared tests. RESULTS: All 72 patients were managed with “less aggressive” initial treatments. There were no difference in mortality when our patients were compared to the literature’s “less aggressive” group (6% vs. 9%, P⫽0.40, RR 0.6, 95% CI: 0.23-1.62) or “more aggressive” group (6% vs. 3%, P⫽0.29, RR 1.8, 95% CI: 0.64-5.23). There was no difference between the second intervention rate of our patients and the “less aggressive” group (47% vs. 43%, P⫽0.47 RR 1.1, 95% CI: 0.86-1.42) although there was a difference when compared to the “more aggressive” group (47% vs. 11%, P⬍.0001, RR 4.5, 95% CI: 3.20-6.31). There were no differences in number of patient co-morbidities, time of diagnosis, timing of antibiotic treatment, or number of services consulted when survivors and non-survivors were compared. CONCLUSION: Patients with empyemas at our hospital are treated with “less aggressive” initial treatments and have a higher second intervention rate when compared to patients described in the literature who were initially managed with “more aggressive” treatments. CLINICAL IMPLICATIONS: Given these findings, it would be worthwhile to evaluate the impact of treating empyemas with “more aggressive” initial interventions at our institution. DISCLOSURE: Glena Cheng, None.

Wednesday, November 2, 2005 Pleural Disease, continued measurements were carried out in duplicates by a calibrated blood gas analyzer. RESULTS: Pleural fluid pH values were significantly (p⬍0.05) lower when collected in heparinized versus non-heparinized syringes at all time intervals (T0: pH(H)⫽7.37⫾0.10 vs. pH(NH)⫽7.39⫾0.10, T1: pH(H)⫽7.37⫾0.11 vs. pH(NH)⫽ 7.39⫾0.11, T2: pH(H)⫽7.37⫾0.12 vs. pH(NH)⫽7.38⫾0.11). With heparinized syringes, there was a significant (p⬍0.05) decrease in pleural pH values only at T2 versus T1. There were no significant changes in pleural pH values over time with the nonheparinized syringes. CONCLUSION: There were statistical differences in the values of pleural pH when using heparinized versus non-heparinized syringes.In heparinized syringes, the pleural pH values decreased at two hours but not at one hour post collection, therefore it is advisable to process pleural fluid for pH measurements no later than one hour of collection when using heparinized syringes. CLINICAL IMPLICATIONS: for serial pleural pH measurements the same type of syringes (either heparinized or non-heparinized) should be consistently used and samples collected in heparinized syringes can be processed up till one hour of collection. DISCLOSURE: Ali Debek, None. DOES STORAGE TIME AND TEMPERATURE INTERFERE IN THE ADENOSINE DEAMINASE MEASUREMENT IN PLEURAL EFFUSIONS? Leila Antonangelo MD* Francisco S. Vargas MD Luciana P. Almeida PharmD Milena M. Acencio BS Fabrı´cio D. Gomes BS Roberta K. Sales MD Ma´rcia Seiscento MD Lisete R. Teixeira MD Pulmonary Division, Heart Institute (InCor) and Department of Pathology of Univer, Sao Paulo, Brazil PURPOSE: To evaluate the interference of pre-analytic factors as storage time and temperature in pleural fluid adenosine deaminase (ADA) measurement in pleural effusions. METHODS: 27 pleural effusions obtained from patients with neoplasm (20) or tuberculosis (07) were analyzed. The pleural effusions were collected into tubes containing EDTA. The ADA determination was realized 1, 3, 7, 10 and 28 days after the toracocentesis and the samples were stored at 4°C (refrigerator) or -20°C (freezer). The ADA determined immediately after the pleural collection (T1) was used as gold standart to the comparison with the results obtained from the other times. The ADA activity was determined by the modified Giusti method. Statistical analysis: The Wilcoxon test was used to compare T1 with the resuts obtained at 1, 3, 7, 10 and 28 days, for both temperatures. We used the Pearson coefficient to evaluate the correlation between T1 and the other times evaluated. RESULTS: Pleural ADA from T1 was 36.45 U/L (23.2 ⫾ 55.1). We do not observe differences statistically significant between this measurement with those obtained from 1, 3, 7, 10 and 28 days, for both temperatures (4°C or -20°C). The correlations between T1 and the other times were superior to 0.90 until the tenth day for both temperatures, with a tendency of decreasing around the 28th for the temperature of 4°C (r⫽ 0.86) or -20°C(r⫽0.83). CONCLUSION: ADA levels are stable for at least 28 days in samples of pleural fluids if they were maintained refrigerated (4°C) or freezed (20°C). CLINICAL IMPLICATIONS: Considering that samples of pleural effusion can be sended to ADA determination many hours after the toracocentesis or that frequently we have to confirm ADA results, we consider safe to quantify this enzyme until at least 28 days after the collection, if the samples were maintained at refrigerator or freezer. DISCLOSURE: Leila Antonangelo, None. RELATIONSHIP BETWEEN METALLOPROTEINASE AND EXUDATIVE PLEURAL EFFUSIONS An Chang Hyeok MD* Kim Yu Jin MD Kyung Sun Young MD Lee Sang Pyo MD Park Jeong Woong MD Jeong Seong Hwan MD Gachon Medical School Gil Medical Center, Incheon, South Korea PURPOSE: Residual pleural thickening is common complication of tuberculous pleurisy and sometimes in parapneumonic effusion. The aim of this study was assess the expression of MMP-1 and –9 and TGF-␤, and then compared with amount of pleural fluid at the first time of detection and the end of follow-up.

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METHODS: Patients with newly diagnosis of pleural fluid was enrolled from June 2004 to January 2005. MMP-1, MMP-9 and TGF-␤ were determined by ELISA in plasma and pleural fluid. The amount of pleural fluid and pleural thickening were measured on the simple chest PA films. RESULTS: The study included 39 patients with pleural effusion. Twenty-three was tuberculous, 7 parapneumonic effusion, 7 malignant effusion, and 2 transudates. The patients with malignant effusion(mean age 62⫾15 years) was more older than of tuberculos(40⫾18)(p⫽0.028). MMP-1 concentrations of parapneumonic effusion(9.6⫾8.5 pg/mL) was significantly higher than other pleural fluid(tuberculous 3.9⫾2.3, p⫽0.012; malignant 2.7⫾1.7, p⫽0.016, transudate 1.8⫾0.2, p⫽0.094). MMP-9 of parapneumonic effusion(383.6⫾410.0 ng/mL) was also significantly higher than other pleural fluid(tuberculous 74.0⫾68.7, p⫽0.002; malignant 62.1⫾61.0, p⫽0.007, transudate 40.0⫾42.4, p⫽0.058). In tuberculous effusion, the absortion of pleural fluid or thickening was significantly increased in accordance with lower concentration of MMP1(p⫽0.011).In parapneumonic effusion, higher concentration of MMP-1, the amount of pleural fluid at the fist detection was significantly larger(p⫽0.014), but there was no correlation with absortion of pleural fluid or thickening. There was no correlation between TGF-␤ and pleural fluid or thickening. CONCLUSION: Inconclusion, elevated MMP-1 and –9 expression was found in parapneumonic pleural effusion. The concentration of MMP-1 was correlated with amount or absortion in several exudative pleural effusion. CLINICAL IMPLICATIONS: MMP-1 could be implicated in the resolution of pleural fluid or residual pleural thickening in tuberculous pleurisy and in the production of pleural fluid in parapneumonic effusion. DISCLOSURE: An Chang Hyeok, None.

VIBRATION RESPONSE IMAGING (VRI): A NEW MODALITY FOR EVALUATION AND FOLLOW-UP OF PLEURAL EFFUSION (PE) Ram Mor MD* Tatiana Boikaner MD Avi Man MD Zipi Yemini Igal Kushnir MD Joel Greif MD Pulmonary Institute, Tel Aviv Med Center, Tel-Aviv, Israel PURPOSE: Imaging is essential for confirmation of PE, especially prior to taping. Chest X-ray (CXR) cannot be done effectively at bedside and involves radiation. Ultrasound requires expensive equipment and special skills. Follow-up of patients after drainage usually involves repeated radiation for weeks or months.The VRI system constructs a dynamic lung image from vibrations produced by airflow. The vibrations, hence the image, are altered by the airway and parenchymal abnormalities. The vibration energy from 40 sensors, attached to the back, is processed during breathing cycles and creates a dynamic image. The presence of fluid as well as compression and displacement of the lungs by PE are easily detected by this method. Changes in the amount of pleural fluid can be seen in successive VRI recordings. To evaluate this novel technology in the monitoring of PE compared to conventional CXR. METHODS: We analyzed the VRI of 10 patients (6 males) with avg. 69.7 yrs with PE. The presence of PE was confirmed by a standard CXR; one case of large PE (⬎ 2 Lit.), 6 with moderate PE (1–2 Lit.) and 2 with small PE (⬍ 1 Lit.). Repeated CXR and VRI were obtained following drainage in all cases. RESULTS: The characteristic VRI image of PE showed a meniscus shape in the lower lobe(s) and absence of vibration response (VR) in the area of the pleural fluid. Absence of VR was correlated to the region of PE as determined by the CXR in 9/10 (90%) patients. Following treatment, VRI images showed increased vibration response in the drained area in all 10 cases, which corresponded with CXR clearing. The decrease in fluid level after drainage was evident in all the VRI recordings. CONCLUSION: The VRI provides a simple, bedside, radiation-free approach to follow the course of pleural effusion; thereby, improving the cost effectiveness of bedside evaluation and follow up. CLINICAL IMPLICATIONS: The VRI provides a simple, radiationfree approach to follow the course of pleural effusion; thereby, improving the cost effectiveness of bedside follow up. DISCLOSURE: Ram Mor, None. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Pleural Disease, continued CAN PLEURAL FLUID DENSITY MEASURED BY HOUNSFIELD UNITS(HU) ON CHEST CT BE USED TO DIFFERENTIATE BETWEEN TRANSUDATE AND EXUDATE? Vijay A. Rupanagudi MD* Ashwini Sahni MD Karthikeyan Kanagarajan MD Hima Kona MD Daniel Contractor MD Padmanabhan Krishnan MD Coney Island Hospital, Brooklyn, NY

DISCLOSURE: Vijay Rupanagudi, None.

PURPOSE: Evaluate the changes over pulmonary mechanics and pleural effusion in the first six days after CABG.

POSTER PRESENTATIONS

PURPOSE: Density of lesions as measured by hounsfield units on chest CT is used to characterize the nature of thoracic lesions as solid versus cystic versus calcific. The aim of the study was to see if density of pleural effusion as measured by HU on chest CT could be used to differentiate transudative versus exudative pleural effusion; a non-invasive technique not being used for this purpose at this time. METHODS: 38 patients with pleural effusion who had thoracentesis done and had chest CT were identified and evaluated retrospectively. Pleural fluid was classified as transudate or exudate using light’s criteria.Pleural fluid density using hounsfield units was calculated on CT chest as a mean of fluid density taken at four rectangular areas as shown in the figure. RESULTS: 17 patients had transudative effusion with mean(⫾SD) HU of 7.8(5.6). 21 had exudative effusion with mean(⫾SD) HU of 17.5(7.4). Based on the results 15 HU was used as cut off to differentiate between transudative and exudative effusion. CONCLUSION: HU on CT of more than 15 can be used to characterize a pleural effusion as an exudate. Transudative effusions for the most part have HU less than 15. However HU ⬍15 can be seen in exudative pleural effusions. Therefore this technique cannot be used to differentiate transudative from exudative pleural effusion when HU is ⬍15. CLINICAL IMPLICATIONS: In patients with HU ⬎15 further work up is indicated and will include thoracentesis and possibly pleural biopsy. In patients with HU ⬍15 thoracentesis is indicated only when the clinical picture indicates that the pleural effusion cannot be explained by disorders that cause transudative effusion.

ACUTE PLEURAL-PULMONARY ALTERATIONS AFTER CABG (CORONARY ARTERY BYPASS GRAFT) Marcelo A. Vaz MD* Daniela B. Mont’alverne Maria I. Feltrim Lisete R. Teixeira MD Francisco S. Vargas MD Heart Intitute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil

METHODS: We analyze FVC, Maximum Inspiratory Pressure (PImax), Maximum Expiratory Pressure (PEmax) daily until the 6th day after CABG, and Atelectasis and pleural effusion (X-ray and CT) on the 6th day after CABG. It was studied 60 patients consecutively after CABG. Lower lobe atelectasis at X-ray was scored (0 ⫽ no atelectasis; 1 ⫽ plate-like atelectasis; 2 ⫽ atelectasis of a single segment; 3 ⫽ atelectasis of more than one segment; 4 ⫽ lobar atelectasis). Pleural effusion on X-ray was scored (0 ⫽ no pleural effusion; 1 ⫽ blurring of the costo-phrenic angle; 2 ⫽ effusion occupying one to two intercostal spaces; 3 ⫽ effusion occupying more than two intercostal spaces). Pleural effusion volume on computerized tomography was estimated through the formula d 2 x l 2, CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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Wednesday, November 2, 2005 Pleural Disease, continued where d ⫽ greatest depth of the effusion on a single CT image and l ⫽ greatest length of the effusion. Were considered significant p⬍0.05. RESULTS: Were observed a decline in PImax, PE max and FVC in the 1st day after CABG, with a slow recovery over the first six days after the CABG (Graphic1). On X-Ray there were a high frequence of atelectasis (70% of the patients)and pleural effusion (83% of the patients), and CT scan revealed a greater amount of atelectasis(92%), when compared with X-ray. The estimated volume of pleural effusion on the 6th day after CABG was 73.72 ⫹/- 188.31 ml (rigth side) and 258.72 ⫹/- 400.62 ml (left side). CONCLUSION: CABG induces a deep decline of strength and volumes (bigger than 50% of decline)acutelly after the surgery. This procedure will leave an amount of pleural effusion and atelectasis on the 6th day after the surgery. CLINICAL IMPLICATIONS: Despite we do not observe major complications after CABG, these procedure may be harmful for patients with pulmonary impairment, or lung disease before the surgery.

DISCLOSURE: Marcelo Vaz, None.

Pulmonary Function Testing: Exercise Testing 12:30 PM - 2:00 PM EXERCISE CAPACITY IN CLINICALLY STABLE HIV PATIENTS AS A FUNCTION OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY William W. Stringer MD* Mallory D. Witt MD Michelle Cao MD Rose Sandoval Kathy E. Sietsema MD Los Angeles Biomedical Institute at Harbor-UCLA Medical Center, Torrance, CA PURPOSE: Exercise capacity is reported to be reduced in HIV infection, but the cause (s) remains unclear. Highly Active Antiretroviral therapy (HAART) has markedly improved longevity and health status for HIV infected patients, however, these drugs are associated with diverse side-effects which could independently decrease exercise function, including nucleoside reverse transcriptase inhibitor (NRTI) -related mitochondrial toxicity. We hypothesized that patients on HAART with elevated resting blood lactate levels (La, ⬎2.2, EL) would have lower exercise capacity on cardiopulmonary exercise testing, as compared to ART treated patients with normal resting lactate levels (NL), or HIV infected non-ART treated controls (NoH). METHODS: Therefore, we compared exercise capacity (as measured by peak oxygen uptake, VO2) in these three groups during cycle ergometry. We studied 29 clinically stable HIV⫹ infected subjects (27M/2F) without co-morbid conditions which would affect exercise function. RESULTS: Mean CD4 count for the group was 477 (134, Mean(SD)) cells/mm3 [EL 418 (94), NL 583 (237), NoH 478 (159]. Lean mass was measured by DEXA. Demographics, resting La concentration and Peak VO2 are shown in the table. CONCLUSION: Among all three groups peak VO2 and peak VO2/kg were low relative to expected for normal subjects, however, they did not differ significantly with respect to HAART status or resting lactate level. CLINICAL IMPLICATIONS: It appears that reduced exercise capacity is characteristic of HIV infection, regardless of HAART status or resting La values, and could reflect deconditioning or other factors.This study was supported by NIH # R21DK063644 and M01 RR00425.

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La N

Peak

Peak

Peak

Age

(Rest)

BMI

VO2

VO2/kg

VO2/kg

(y)

(mmol)

kg/m2

(l/min)

(ml/min/kg)

(ml/min/lean kg) 29.6 (6.3)

EL

10

45 (6)

2.58 (.49)*

25.3 (3.9)

1.73 (0.48)

22.8 (5.9)

NL

9

46 (3)

1.17 (.30)

24.8 (2.8)

1.69 (0.48)

23.5 (7.0)

31.4 (7.5)

10

41 (7)

1.51 (.68)

24.0 (4.0)

1.73 (0.41)

25.4 (6.0)

32.5 (6.4)

NoH

*⫽P⬍0.01 for differences between groups DISCLOSURE: William Stringer, None. THE VALUE OF CARDIO-PULMONARY EXERCISE TESTING (CPET) IN THE DETECTION OF CARDIAC DISEASE IN RESPIRATORY IMPAIRED (RI) PATIENTS Bohdan M. Pichurko, FCCP MD* J. Trosell RRT D. Luneack RRT C. Rubner RRT A. Pichurko Providence Hospital and Medical Centers, Southfield and Novi, MI PURPOSE: Cardiovascular disease (CVD) in respiratory impaired patients is a likely co-morbidity since key risk factors (e.g. tobacco use, age) are shared. As symptoms of dyspnea and chest tightness are non-specific, underlying CVD may too long remain undiagnosed; to the patient’s detriment. To determine the diagnostic value of CPET alone and as an addition to conventional cardiac exercise testing in detecting CVD in RI pts, we performed the following experiment. METHODS: 92 subjects, (50M, 42F) were evaluated for persistent dyspnea by CPET utilizing a stationary bicycle and watt-ramp protocol. Each had a known respiratory disorder (COPD, asthma, sarcoid, RADS) under treatment. 68 of these were also cardiac stress tested over the same interval; with 56 patients considered “low-risk for ischemia”. CPET analysis was performed without knowledge of cardiac test results. RESULTS: 81 subjects exhibited a reduced work capacity (⬍85% of the VO2max pred.) with 65 (80%) exhibiting a pattern of respiratory limitation (Breathing reserve ⬍15%; O2sat ⬍89%; FEV1 ⬎15% decline) at peak exercise. 16 (20%) manifest a CV limitation (VO2 AT ⬍40% of VO2max; reduced O2/pulse). Of the latter CV-limited group, 10 (63%) tested “low-risk for ischemia”. All 16 patients underwent re-evaluation including medication changes and/or catheterization. CONCLUSION: Respiratory impaired patients appear to be at risk for undetected concurrent cardiovascular disease. Even when utilized, conventional cardiac testing (combining exercise with ultrasound or scintiographic imaging) may overlook non-ischemic CVD. CPET, a metabolically based assessment of global cardiovascular function/oxygen delivery, is sensitive to non-ischemic cardiac dysfunction that may evade conventional cardiac stress testing. CLINICAL IMPLICATIONS: Respiratory impaired patients pose particular challenges to clinical suspicion and diagnosis of concurrent cardiovascular disease by conventional cardiac testing modalities. CVD due to hypertension, valvular dysfunction, and primary myocardial disorders may evade cardiac stress testing that principally targets ischemia. A high index of suspicion for concurrent CVD coupled with selective use of CPET may help detect significant cardiovascular impairment and may lead to improved treatment. DISCLOSURE: Bohdan Pichurko, FCCP, None. GAS EXCHANGE ASSESSMENT AT REST AND DURING EXERCISE IN PATIENTS WITH EISENMENGER SYNDROME Edgar G. Bautista MD* Ma. Luisa M. Guerra MD Toma´s Pulido MD ˜ amendys MD Jose´ L. Sandoval MD Gerardo Efre´n Santos MD Silvio A. N Rojas MD David Mendoza MD Julio Sandoval MD Instituto Nacional de Cardiologı´a “Ignacio Cha´vez”, Mexico City, Mexico PURPOSE: To assess gas exchange and distribution of ventilation in Eisenmenger syndrome patients at rest and while performing submaximal exercise at an altitude of 2240 mts above sea level. METHODS: 93 patients with Eisenmenger syndrome due to ASD 49p, VSD 27p, PDA 20p; 74 females, 19 males. Age 36⫾14(20-73)yo, height 1.53⫾0.1 m, weight 59⫾17 Kg. PAP 98⫾27 mmHg, PaO2 50⫾8 mmHg, V-A shunt QsQt% 14.9⫾5, Hb gr/dl 17.7⫾4.2. Gas exchange (GE) was assessed in 70 p at room air(ra),FiO2 1 (100%) and at the end of exercise (e). Independent student t test; p⬍0.05 * was considered as significative when compared to ra values also regression analysis with SPSS 10 was applied to data. RESULTS: Spirometry; FEV1 mls. 1877⫾646; FEV1% 70⫾18, FEVI/ FVC% 78⫾14, FEF% 56⫾30. GE is presented in table 1. A trend to CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Pulmonary Function Testing: Exercise Testing, continued decrease in PaO2 and pH was observed at the end of exercise although not statistically significant. Distribution of ventilation and gas exchange between rest r and submaximal exercise e (mets 1.60⫾0.5 to 3.45⫾1 )as follows :VE; Minute ventilation 10.2L⫾3.3 to 22L⫾7.2 *, AV Alveolar Ventilation 5.5L⫾1.9 to 12.8⫾4.4 *, VO2 mls/min; Oxygen consumption 230⫾64 to 514⫾130 *, VCO2mls/min; CO2 production 218⫾65 to 528⫾146 *. CONCLUSION: Despite severe Pulmonary Arterial Hypertension and a significant right to left shunt, the change in paO2 during exercise is remarkable low even with a significant change in VO2. As it is also remarkable the preservation of pH and paCO2 with such an increase in VE and VA. We consider that the ventilatory pump may contribute significantly to the ability of these patients to perform exercise even in disadvantage conditions, as it is high altitude. CLINICAL IMPLICATIONS: No limitation to perform regular activities and even light exertion could be recomended in this group of patients. More data is needed about the impact of long term exercise on the disease. DISCLOSURE: Edgar Bautista, None.

populations, ME of the lower limb was comparable to that of the upper limb. In COPD patients within homogenous and sever air flow limitation, during upper-limb exercise, as observed in previous study, we noted that exercise capacity was relatively more preserved than during leg exercise. CONCLUSION: To explain this situation, we hypothesized that a part of the upper limb mass muscle is relatively less deconditioned compared to lower limb and could explain why maximal workload values are relatively well preserved during arm exercise. Furthermore, it’s seems to be possible that a level of exercise was reached beyond which the VO2 could not be increased. CLINICAL IMPLICATIONS: improvements in upper-limb strength or endurance resulting from training could lead to improved overall functional capacity and ability to perform activities of daily living.

Table 1. Data at Peak Exercise. Arm Crank

EXERCISE PERFORMANCE AND VENTILATION IN CO2– RICH ATMOSPHERE IN COAL MINE Matjaz Flezar MD* Mitja Kosnik MD Marjan Bilban MD University Hospital Golnik, Golnik, Slovenia

ARM EXERCISE AND LOWER LIMB EXERCISE CAPACITIES ARE SIMILAR IN PATIENT WITH SEVERE COPD Castagna Olivier MD* IMNSSA, Toulon, France PURPOSE: In patients with COPD, upper limb solicitation was important in daily activity. However, very few studies concerning upper limb physiological adaptation during exercise was available. The purpose of this study was to assess and compare the upper limb and lower limb capacities in severe COPD patients during incremental and constant load exercises. METHODS: Ten COPD patients with homogenous age and severe air flow limitation (age 65 ⫾ 6.1 [SD]yr; FEV1: 35% ⫾ 5% predicted) and ten healthy control (age 63 ⫾ 5.3 [SD]yr; FEV1: 102 ⫾ 4% predicted) subjects were studied. RESULTS: at peak exercise, maximal values of load, VO2, RER, VE, and HR were significantly lower in patient with COPD, compared with healthy controls for both conditions(p⬍0.001). On the opposite, no significant difference was observed between arm and leg for these parameters in COPD patients. For both conditions (arm vs. leg), mechanical efficiency (ME) was significantly lower in patients with COPD than in control subjects (20.97 % ⫾ 2.33 % and 25.90 % ⫾ 3.30 % for arm ; 20.91 % ⫾ 2.92 % and 27.38 % ⫾ 3.03 % for leg, p⬍ 0.001). In both

COPD

Controls

COPD

PMA, watts

94⫾12.65†

54⫾8.54*

162⫾21.50

58⫾10.33*

V;⶿S⶿UP6(.O2 , ml.min-1.

1597⫾168.†

1054⫾67*

2190⫾271

1109⫾116*

RER

1.15⫾0.04

1.09⫾0.03*

1.14⫾0.05

1.08⫾0.03*

V;⶿S⶿UP6(.E , l.min-1.

61.8⫾6.2†

28.9⫾3.21*

77.2⫾9.53

31.6⫾4.06*

V;⶿S⶿UP6(.E / MVV, %

60.2⫾4.8†

88.6⫾1.6*

74.9⫾5.8

95⫾2.1*

VT, l.

1.64⫾0.13†

0.92⫾0.18*

1.95⫾0.23

0.98⫾0.17*

fb, breaths min-1.

37.8⫾2.9†

31.5⫾3.4*

39.8⫾3.34

32.5⫾3.3*

HR, beats min-1.

156⫾5.7

117⫾6*

157⫾5.1

125⫾8.8*

Table 2:Values are means ⫾ SE; V;⶿S⶿UP6(.O2, O2 consumption; V;⶿S⶿UP6(.CO2, CO2 excretion; RER, respiratory exchange ratio; V;⶿S⶿UP6(.E, minute ventilation; MVV, maximal voluntary ventilation; VT, tidal volume; fb, frequency of breathing; HR, heart rate; † p⬍0.05 arm vs leg; * p⬍0.05 COPD patients vs control. DISCLOSURE: Castagna Olivier, None.

PARAMETERS OF RESPIRATORY FUNCTION AS INDICATORS OF AEROBIC CAPACITY ATHLETE’S Nenad Ponorac MD Amela Matavulj MD* Nikola Grujic MD Zvezdana Rajkovaca MD Pedja Kovacevic MD Medical School, Department for Physiology, Banjaluka, Bosnia-Herzegovina PURPOSE: The term aerobic capacity represents the sum of aerobic metabolic processes in human organism. It is the bases of the physical working capacity. Parameters of respiratory function are very informative and appropriate for aerobic capacity researching. The purpose of this study was to check possibilities of using respiratory parameters as the indicators of aerobic capacity in athletes and to check differences in regard to non- athletes [1, 2]. The goals were: 1.Analyses of respiratory function parameters in various sports athletes 2.Comparison with values obtained in non-athletes. METHODS: This study included 67 athletes (rowers, soccer’s, and judo) and 28 non-athletes. Respiratory parameters (maximal voluntary ventilation / Ve, respiratory volume / RV and breathing frequency / Fr) were measured during determination VO2max, direct method. RESULTS: Results obtained show statistically higher Ve values in rowers (142 L/min) in regard to soccer’s (123 L/min) and judo (111 L/min). Successfully rowing requires high anaerobic capacity and so effective maximal voluntary ventilation. CONCLUSION: These results express the grater values of Ve and other parameters too, in athletes in regard to non-athletes. Reason for these results is just process of training. Other parameters of respiratory function were not useful for determination the aerobic capacity. CLINICAL IMPLICATIONS: These parameters are limitation factors for physical activities only in patients with obstructive and restrictive diseases. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

PURPOSE: Long-term exposure to high CO2 in coal mine environment could lead to diminished exercise performance, acid-base changes and other health effects. CPET testing and blood gas analysis during the work at the head of coal mine excavation would provide an accurate estimate of true workplacerelated impact on physical performance and health status. METHODS: We performed lung function testing (spirometry and single breath DlCO), blood gasses and modified Masters step test in 76 coal miners, that worked at least 10 years in a row as a head-excavation miners. CPET parameters were measured using portable metabolic analyzer. Tests were performed in duplicates: every subject underwent the same procedure out and in a coal mine – approximately 430 m under the ground level. CO2 in a coal mine was continuously monitored and mean value of was 1.21%. Paired tests were used for presentation of results. RESULTS: There was no chronic acid-base disorder. pO2 of arterial blood, spirometry values and DlCO after exercise in and out of the coal mine were not significantly different. Ventilation in the coal mine was elevated with an average increase of 11%. Increase in ventilation was mainly due to increase in tidal volume. Increase in heart rate was lower during exercise and oxygen consumption was 11% less in the mine (same level of exercise). Anaerobic threshold did not differ. CONCLUSION: No lung function of blood gas deficit was noted in tested coal miners. Exercise performance in coal mine atmosphere was not affected by increase in ventilation. Lower oxygen consumption during the same level of exercise in a coal mine could be due to more efficient skeletal muscle recruitment or unknown influence of other atmosphere conditions on sceletal muscle performance. CLINICAL IMPLICATIONS: Physical work in a coal mine with increased CO2 levels of average 1.21% is not associated with chronic or acute respiratory and muscular changes. DISCLOSURE: Matjaz Flezar, None.

Controls

Leg Cycle

Wednesday, November 2, 2005 Pulmonary Function Testing: Exercise Testing, continued FUNCTIONAL CHANGES OF RESPIRATORY MUSCLES IN PULMONARY HYPERTENSIVE RATS Frances De Man BSc* Brechje van Beek-Harmsen BSc Anton VonkNoordegraaf PhD Willem van der Laarse PhD VU University Medical Centre, Amsterdam, Netherlands

DISCLOSURE: Amela Matavulj, None.

Pulmonary Hypertension 12:30 PM - 2:00 PM ENVIRONMENTAL TOBACCO SMOKE AND HEALTH STATUS IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION Hubert Chen MD* Mark D. Eisner MD Carla M. Teehankee BA Paul D. Blanc MD Teresa De Marco MD UCSF, San Francisco, CA PURPOSE: We sought to quantify environmental tobacco smoke (ETS) exposure among patients treated for pulmonary arterial hypertension (PAH), and to determine whether ETS exposure is related to health status in these patients. METHODS: We enrolled consecutive patients referred to a tertiary care center for PAH. Criteria for inclusion were elevated mean pulmonary artery pressure (MPAP) ⬎25 mmHg by right heart catheterization and medical stability on PAH therapy for ⱖ3 months. ETS exposure was assessed using a validated passive smoke exposure questionnaire, as well as by urine cotinine. Exercise capacity was assessed by six-minute walk (6MW) distance. Disease-specific qualityof-life was assessed using both the 20-item Airways Questionnaire (AQ20) and Minnesota Living with Heart Failure Questionnaire (MLHFQ). RESULTS: We analyzed 91 patients with the following characteristics: mean age 49⫾13 yrs; 70% female; mean MPAP 50⫾14 mmHg; WHO class I-II (42%), III (51%), and IV (7%). Forty (44%) patients reported exposure to ETS. Urine cotinine was positive in 45 (57%) of 79 tested. Self-reported ETS exposure correlated significantly with urine cotinine level (r⫽0.42, p⫽0.0003). There was no significant correlation between self-reported ETS exposure and either 6MW distance (p⫽0.26) or quality-of-life (AQ20: p⫽0.80; MLHFQ: p⫽0.83). Similarly, there was no significant association between urine cotinine positivity and either 6MW distance (p⫽0.14) or quality-of-life (AQ20: p⫽0.77; MLHFQ: p⫽0.90). CONCLUSION: ETS exposure is common among patients treated for PAH, however, its relationship with exercise capacity and quality-of-life remain uncertain. CLINICAL IMPLICATIONS: Patients on PAH therapy should be encouraged to avoid ETS exposure until stronger evidence regarding its effects are available. DISCLOSURE: Hubert Chen, None.

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PURPOSE: Patients with pulmonary hypertension have impaired respiratory muscle function. We investigated whether functional changes of inspiratory and expiratory muscles (diaphragm, external and internal intercostal muscles) are similar. METHODS: Six male Wistar rats (body weight 180g) were injected subcutaneously with 40 mg monocrotaline (MCT) per kilogram body weight. Another six rats were age-matched controls. The animals were sacrificed after 2 or 4 weeks. During anesthesia the intercostal muscles and diaphragm were dissected. Calibrated histochemical methods were used to determine muscle fiber cross-sectional area (CSA), maximum rate of oxygen consumption (VO2max), myoglobine (Mb) concentration and the number of capillaries per fiber. Statistical analyses were performed with the use of 2 way Analysis of Variance. RESULTS: The diaphragm shows a significant decrease in VO2max x CSA ((P⬍0.0001) and a decrease in Mb x CSA (P⬍0.01) after 2 weeks. The number of capillaries per fiber was constant. The external intercostal muscle shows a significant decrease of VO2max x CSA (P⬍0.0001) and a decrease in Mb x CSA (P⬍0.0001) after 4 weeks. The number of capillaries per fiber was constant. The internal intercostal muscle shows, however, a significant increase of VO2max x CSA (P⬍0.0001), a decrease of Mb x CSA (P⬍0.01) and a decrease in number of capillaries per fiber (P⬍0.05). CONCLUSION: The internal intercostal muscles show a training effect after 4 weeks of MCT, whereas there is reduced maximum power output in the diaphragm and external intercostal muscles. The results suggest that a reduction of lung compliance causes shortening of the fibers in the diaphragm and the external intercostal muscle and stretch of the internal intercostal muscles, which are known regulators of muscle atrophy and hypertrophy, respectively. CLINICAL IMPLICATIONS: Functional changes of respiratory muscles in pulmonary hypertensive patients may be muscle-dependent. DISCLOSURE: Frances De Man, None. PULMONARY VENO-OCCLUSIVE DISEASE IN ASSOCIATION WITH CREST SYNDROME (LIMITED SCLERODERMA): CLINICAL, RADIOLOGIC, HEMODYNAMIC AND PATHOLOGIC CHARACTERIZATION William T. Mansfield MD* Linda Allred RN Thomas E. Van der Kloot MD Joel A. Wirth MD Maine Medical Center, Portland, ME PURPOSE: Pulmonary Arterial Hypertension (PAH) is a rare disease sometimes associated with collagen vascular diseases, usually Limited Scleroderma (CREST Syndrome). Pulmonary Veno-occlusive Disease (PVOD) is an uncommon subtype of PAH with a particularly poor prognosis. PVOD is usually idiopathic, however it has also been associated with chemotherapy exposure and rheumatic diseases. PVOD has rarely been associated with CREST Syndrome, however few clinical data exist concerning this connection. We present clinical, radiographic, hemodynamic and pathologic data on two patients with PVOD and associated CREST Syndrome. METHODS: Two patients managed at our institution for PVOD with concomitant CREST Syndrome were studied via retrospective chart analysis. All available clinical, radiographic, hemodynamic, and pathologic data were reviewed. RESULTS: Two female patients (aged 63 and 71 years) were diagnosed with CREST Syndrome (8 and 20 years) prior to onset of pulmonary hypertension symptoms or diagnosis. Both were treated with nifedipine, prednisone, and cyclophosphamide for scleroderma, and warfarin, oxygen and epoprostenol for PAH. One received sitaxsentan prior to epoprostenol initiation. Both presented with dyspnea, (WHO Class III), accentuated P2 heart sound, RV heave, and II/VI tricuspid regurgitation murmurs. Both were seropositive for anticentromere antinuclear antibodies (titres: 1:1280 and 1:2048). Thoracic CTs demonstrated very mild interstitial Lung Disease (ILD). PFTs showed mild reductions in TLC with marked reductions in DLCO. Right heart catheterization showed: mean PAP 53 and 63 mmHg, PCWP 14 and 7 mmHg, CO 3.1 and 2.2 L/min, MVO2 44 and 37%, RAP 14 and 9 mmHg, respectively. Clinical courses were notable for rapid clinical deterioration (death within several weeks) characterized by progressive right heart failure, pleural effusions and CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Pulmonary Hypertension, continued pulmonary edema when given epoprostenol. Autopsies demonstrated PVOD without significant ILD in both cases. CONCLUSION: PVOD and CREST Syndrome are two relatively rare conditions which may co-exist. The association carries a particularly poor prognosis in these cases, marked by clinical deterioration upon initiation of epoprostenol. CLINICAL IMPLICATIONS: Clincians should consider PVOD in patients with scleroderma and pulmonary hypertension, particularly if thoracic CT scanning suggests ILD. DISCLOSURE: William Mansfield, Grant monies (from industry related sources) Encysive, LP Myogen Biopharmaceutical; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. sitaxsentan.

SECONDARY PULMONARY HYPERTENSION IN GERIATRIC POPULATION Sotir Polena MD Eirene Mamakos MD* Anwar Hague MD Christos Iakovou MD Rick Conetta MD Rajen Maniar MD Flushing Hospital Medical Center, Flushing, NY

ESTABLISHING A MINIMALLY IMPORTANT DIFFERENCE IN 6-MINUTE WALK DISTANCE AND SF-36 AMONG PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION Claire Gilbert* Martin C. Brown Joseph C. Cappelleri PhD Tamiza Parpia PhD Stephen P. McKenna PhD Pfizer Ltd, Sandwich, United Kingdom PURPOSE: There are currently no guidelines or standards to help physicians determine whether or not the treatment provided to patients with pulmonary arterial hypertension (PAH) results in a clinically important benefit. This study was undertaken to define the level of change in exercise capacity, as measured by the 6-minute walk distance (6MWD), and functioning and well-being, as measured by the SF-36, that is clinically meaningful in patients with PAH: a minimally important difference (MID). METHODS: Data from a 12-week sildenafil study were used to evaluate an MID for 6MWD and the physical functioning, role-physical, social functioning, and vitality domains of the SF-36 in patients with PAH, using the following distribution-based approaches: Effect Size (ES), Standard Error of Measurement (SEM), and Standard Error of the

Minimally Important Differences for Pre-specified SF36 Domains and 6MWD Outcome

MID

Range of estimates

SF-36 physical functioning SF-36 role physical SF-36 social functioning SF-36 vitality 6MWD (m)

11 21 16 13 39

3.8-20.9 8-40.5 5.2-33.1 4.3-25 12.7-77.9

DISCLOSURE: Claire Gilbert, Shareholder Pfizer Ltd; Employee Pfizer Ltd. OUTCOMES OF INVESTIGATING PULMONARY ARTERY HYPERTENSION Vinay K. Sharma MBBS* Karim Djekidel MD Graduate Hospital, Philadelphia, PA PURPOSE: With increasing use of echocardiography, an increasing number of patients are being identified as having pulmonary artery hypertension (PAH). In patients with normal systolic left ventricular (LV) function, extensive work up is often performed, even in patients in whom a comprehensive history, physical examination and chest radiograph does not suggest an underlying diagnosis. This descriptive study investigates the characteristics of these patients and the outcomes of diagnostic testing. METHODS: Pulmonary consult sheets over a period of 4 years were reviewed, and patients with newly diagnosed PAH, by echocardiography, identified. Patients with a likely etiology for PAH on history or examination were excluded from the study. Medical records were then reviewed and the following data abstracted: patient demographics, co-morbid conditions, medications taken, and results of echocardiography, chest CT scan, PFT, polysomnogram, serologies for connective tissue disorders, and tests for pulmonary embolism (PE) (ventilation-perfusion scan or PE protocol chest CT). RESULTS: Twenty-six patients were included in the study. Twenty (77%) were women. Mean age was 66 (⫾11) years and 19 (73%) were hypertensive. The mean pulmonary artery systolic pressure was 60 (⫾12) mmHg and LVH was present in 19 (73%). An average of 3.5 diagnostic studies were done. Three of 22 chest CT scans were abnormal: 2 with interstitial lung disease and one with severe emphysema. One of 18 PE studies was abnormal. Nine of 12 polysomnograms revealed obstructive sleep apnea. Two of 12 serologies were abnormal. 23 patients had PFTs: 16 had minor abnormalities, 4 had severe restriction and one severe obstruction. Five (19%) had relatively normal studies except for elevated PAP on echocardiography. Seven (27%) patients had LVH and no other abnormality that adequately explained PAH. Six (23%) patients had LVH and OSA. CONCLUSION: The prevalence of hypertension and LVH was unexpectedly high in our cohort of PAH. Except for polysomnograms, the other studies had poor diagnostic yields. CLINICAL IMPLICATIONS: LVH with diastolic dysfunction may be the underlying etiology in a significant proportion of patients with PAH. DISCLOSURE: Vinay Sharma, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

365S

POSTER PRESENTATIONS

PURPOSE: Pulmonary hypertension (PH) is a disease with a very poor prognosis. Although primary PH remains a rare pathology, PH related to other diseases is being diagnosed quite often. Chronic respiratory disorders, hypoxia, thromboembolic events, valvular disorders, systolic and diastolic dysfunction etc have all been listed as potential pathologies that can lead to the development of the secondary PH. One of the reasons for the increased prevalence of the secondary PH is attributed to the aging population. The aim of our study is to identify the etiological factors (comorbidities) that contribute to the development of the secondary PH in geriartric population. METHODS: We conducted a retrospective analysis of 153 elderly patient charts after an echocardiografic study, which identified moderate pulmonary hypertension (⬎50mm Hg). The medical charts were reviewed in detail, data from the echo-lab and findings from the computerized tomography (CT) of the chest were analyzed. RESULTS: The study population consisted of elderly patients (mean age 76.8) 66% male and 44 females. Systemic hypertension was found to be present on 72 % of the patients (110). Two (1.3%) patients were found to have severe mitral valve dysfunction. Left atrium and left ventricule diameter was enlarged in 75% (115) of the patients. Moderate to severe systolic dysfunction (EF⬍30%) was recorded in 28% (43) of the patients and dyastolic dysfunction in 17% (26). CT findings were categorized in normal findings, airway disease, interstitial/ inflammatory changes, and pulmonary embolisms (PE), respectively 12%, 20%, 68%, 11%. In a few CT’s combined interstitial changes with pulmonary embolism were found. CONCLUSION: The etiology of secondary pulmonary in geriartric population is mainly attributed to systemic hypertension, interstitial/ inflammatory pulmonary disorders, systolic and diastolic dysfunction. History of airway disease, PE, and valvular dysfunction are also important. CLINICAL IMPLICATIONS: Aggressive treatment of cardiopulmonary disorders in geriartric population can delay or even stop the development of the secondary PH. DISCLOSURE: Eirene Mamakos, None.

Difference (Sdiff). The total population enrolled in the study, including the placebo- and the sildenafil-treated groups, was used for these analyses. RESULTS: An MID was established for each of the end points based on the average of the distribution-based estimates (Table). These estimates are a point change in score for the SF-36 and a change in distance walked in meters for the 6MWD. CONCLUSION: A wide range of estimates were obtained for each end point using three distribution-based methods to explore a minimally important change. The average of these was then taken as an MID value for each end point. This is the first clinical investigation to establish an MID for key SF-36 domains and 6MWD in patients with PAH. Further work incorporating the patient and clinical perspective of change using anchor-based methods would complement and supplement the findings reported here. CLINICAL IMPLICATIONS: The analyses and results presented here may be useful in establishing clinical guidelines to determine the effectiveness of PAH therapies objectively.

Wednesday, November 2, 2005 Pulmonary Hypertension, continued BOSENTAN THERAPY IN PATIENTS WITH PULMONARY HYPERTENSION SECONDARY TO CONGENITAL HEART DISEASE (EISENMENGER PHYSIOLOGY) Michele D’Alto PhD* Berardo Sarubbi PhD Carmine D. Vizza PhD Emanuele Romeo MD Giuseppe Santoro MD Paola Argiento MD Maria G. Russo MD Raffaele Calabro` MD Chair of Cardiology, Second University, V. Monaldi Hospital, Naples, Italy

CONCLUSION: Pulmonary rehabilitation improves 6MW distance and CRDQ Score(Dyspnea, Fatigue, Mastery Domains)in Class III-IV pulmonary hypertension patients. The high severity of illness in the PAH group lead to low program completion. Earlier referral to PR may be beneficial. CLINICAL IMPLICATIONS: Pulmonary rehabilitation improves physical conditioning and overall “well being”. It is an effective and safe treatment for patients with PH.

PURPOSE: To evaluate safety, tolerability, clinical and haemodynamic impact of bosentan, an orally administered endothelin-1 antagonist, in patients with pulmonary hypertension due to congenital heart disease (Eisenmenger syndrome). METHODS: Twelve patients with ES (5M, 7F, mean age 33.6⫾8.7) were treated with oral bosentan (62.5 mg x 2/die for the first month and then 125 mg x 2/die). Patient clinical status, liver enzymes, WHO functional class, resting oxygen saturations, 6 min walk test and transthoracic echocardiography were assessed at baseline and at 1, 3 and 6 month. Haemodynamic evaluation with cardiac catheterization was performed at baseline and at 6 month follow-up. RESULTS: At baseline 10 patients were in III and 2 in IV WHO functional class. Six had ventricular septal defect, 3 single ventricle, 2 atrio-ventricular canal, 1 truncus arteriosus. All 12 patients well tolerated bosentan, but in 2 patients we reduced the maintenance dose from 125 mg x 2/die to 62.5 mg x 2/die for a transient elevation of liver enzyme (1 patient) and transient leg oedema (1 patient). After six month therapy, oxygen saturation at rest (78.3⫾9.3% vs 85.8⫾5.6%; p⬍0.05) and after 6-min walk test (64.4⫾8.8% vs 73.5⫾12%; p⬍0.05), the distance travelled in the 6-min walk test (321⫾101 vs 445⫾45 m; p⬍0.05) and Borg’s index (5,9⫾1.4 vs 3⫾2.3; p⬍0.05) significantly improved. A significant change of total pulmonary indexed resistances (19.1⫾9.5 vs 9.3⫾5.3 WU, p⬍0.05), arterial pulmonary indexed resistances (15.2⫾7.2 vs 7.62⫾4.7 WU, p⬍0.05) and systemic-topulmonary blood flow ratio (0.74⫾0.34 vs 1.36⫾1.14, P⬍0.05) was observed suggesting an improvement of pulmonary haemodynamics. At six month follow-up 5 patients were in II, 6 in III and 1 in IV WHO functional class. CONCLUSION: Bosentan treatment was safe and well tolerated in adults with ES after a mid-term follow-up (6 months of oral therapy). Oxygenation, functional status and pulmonary haemodynamics of patients improved with minimal side effects. CLINICAL IMPLICATIONS: Bosentan is useful in the management of the Eisenmenger syndrome in adults but larger clinical investigation are necessary. DISCLOSURE: Michele D’Alto, None.

Hemodynamics

EFFICACY AND SAFETY OF PULMONARY REHABILITATION IN PATIENTS WITH PULMONARY HYPERTENSION: PRELIMINARY RESULTS Maria Carrillo MD* Cheryl A. Szymanski RN Sandy K. Truesdell MSN Lisa D. Stagner DO Kevin M. Chan MD Henry Ford Hospital, Detroit, MI PURPOSE: Pulmonary rehabilitation(PR) is recommended for patients with pulmonary hypertension (PH) but little is known about its efficacy and safety. We evaluated the outcomes of our PR patients with pulmonary arterial hypertension(PAH)and pulmonary hypertension associated with lung disease(PHLD). METHODS: Patients enrolled in our single center PR program diagnosed with these conditions were reviewed. Demographics, outcomes and Chronic Respiratory Disease Questionaire(CRDQ)data were analyzed and compared. RESULTS: 8 patients with PAH(2 IPAH, 4 CTEPH, 1 PSS, 1 Drug induced) and 12 with PHLD(7 COPD, 2 IPF, 1 Sarcoidosis, 2 OSA)were identified. The PAH group was all female and slightly younger(63⫾13) than the PHLD(68⫾12)group(8F, 4M). The number of exercise sessions(24⫾13 vs 25⫾8), days to complete therapy(72⫾14 vs 65⫾17), pre-6MW distance(260m⫾79 vs 264m⫾100), supplemental O2(3L⫾2.14 vs 2.8⫾1.9), and WHO Symptom Class(3.5⫾0.76 vs 3.4⫾0.55) were similar. 4/8 PAH patients completed PR; 2 expired while enrolled, 1 developed knee pain, 1 had symptomatic PVCs during exercise. 8/12 PHLD patients completed PR; 1 expired, 1 received a lung transplant, 2 were lost to follow up. 6 MW distance improved post PR in the combined group of PH patients from 268m⫾105 to 351⫾47(p⫽0.006). CDRQ data revealed improvement in Dyspnea(17.6⫾2.7 to 22.1⫾4), Fatigue(14.6⫾5 to 19.2⫾4), and Mastery(21⫾2.3 to 24⫾3).

366S

Echo PASP(mmHg) RV diameter(cm) mPAP(mmHg) PVR(WU)

PAH

PHLD

79⫾19 3.06⫾0.7 52⫾16 12.7⫾7

60⫾17 2.11⫾0.5 32⫾4

p⫽0.04 p⫽0.009 p⫽0.04

DISCLOSURE: Maria Carrillo, None.

WARFARIN MANAGEMENT IN PULMONARY ARTERIAL HYPERTENSION IS SIMILAR BETWEEN BOSENTAN, PLACEBO, AND SITAXSENTAN Terrance Coyne MD* Richard Dixon PhD Encysive Pharmaceuticals, Houston, TX PURPOSE: Warfarin, commonly used in pulmonary arterial hypertension (PAH) is a difficult therapy to use, requiring frequent and ongoing monitoring to achieve safe and effective anticoagulation, with dosing influenced by changes in diet as well as drugs. As an inducer of CYP2C9, bosentan (BOS), a twice daily, nonselective ETRA, interacts with the metabolism of warfarin. As an inhibitor of CYP2C9, sitaxsentan (SITAX), a once daily, highly ETA selective ETRA, also interacts with the metabolism of warfarin. Here, we report on the management of warfarin from a multi-center, placebo (PBO)-controlled study, STRIDE-2. METHODS: STRIDE 2 included SITAX 100mg once daily, 50mg once daily, PBO, and an open-label, efficacy rater blinded, arm of BOS BID. BOS was dosed according to label. The protocol recommended that patients (pts) on warfarin randomized to SITAX or PBO were, at study entry, to have a single reduction in warfarin dose of 80%, followed by usual management. Pts on warfarin at study entry and randomized to BOS did not have warfarin dose adjusted. Warfarin doses at endpoint and the total number of dosing changes in the 18 week trial were assessed. RESULTS: 47% of pts were on warfarin at study entry. Results for wk 18 mean warfarin dose and mean number of dose changes per pt are shown in Table 1. CONCLUSION: Warfarin dose was higher in BOS pts and lower in SITAX pts than PBO, consistent with expectations. Nonetheless, warfarin dosing changes were equally frequent for pts treated with BOS, SITAX, or PBO, indicating no meaningful difference in management complexity. CLINICAL IMPLICATIONS: Warfarin is a difficult therapy to use and requires frequent and continuous monitoring. The management of warfarin in patients with PAH is similar between no ETRA therapy and the use of either bosentan or sitaxsentan.

Treatment Groups (n) PBO (33)

SITAX 50mg (26)

SITAX 100mg (27)

Bosentan BID (29)

Warfarin dose at wk 18 3.7 ⫾ 2.7 2.8 ⫾ 1.2 2.1 ⫾ 1.0 5.1 ⫾ 2.9 (mg/d; mean ⫾ sd) Mean # of changes in 1.6 1.8 1.8 1.7 warfarin dosing per pt DISCLOSURE: Terrance Coyne, Employee Encysive Pharmaceuticals; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Sitaxsentan. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Pulmonary Hypertension, continued RESPONSE OF PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION THAT DO NOT QUALIFY FOR TREATMENT WITH BOSENTAN TO TREATMENT WITH BOSENTAN Zoheir Bshouty MD* University of Manitoba, Winnipeg, MB, Canada

Duration of sildenafil therapy Dose of sildenafil

Patient 2

Patient 3

9 months

7 months

15 months

50mg QID

50 mg TID

50 mg TID

Pre

Post

Pre

Post

Pre

Post

PASP (mm)

96

85

94

57

90

85

PADP (mm)

40

28

52

24

40

33

mPAP (mm)

60

50

66

38

60

51

mRAP (mm)

20

3

29

0

23

5

CO (L/min)

2.0

7.7

2.7

4.5

3.5

4.0

CI (L/min)

1.1

3.9

1.3

2.2

1.8

2.2

PCWP (mm)

16

7

N/A*

3

N/A*

7

1760

447

N/C

622

N/C

880

PVR (dynes/sec/cm5) PaO2 sat%

34

67

47

73

58

68

6MWD (ft)

375

875

ND#

1350

250

1500

NYHA Class

4

3

4

1

4

1

Hemoglobin (g/dL)

11

10.4

16.1

17

12.5

14.6

Platelets (103 /mcl)

24

49

72

95

39

48

PASP ⫽ pulmonary arterial systolic pressure, PADP ⫽ pulmonary arterial diastolic pressure, mPAP ⫽ mean pulmonary arterial pressure, mRAP ⫽ mean right atrial pressure, CO ⫽ cardiac output, CI ⫽ cardiac index, PCWP ⫽ pulmonary capillary wedge pressure, 6MWD ⫽ six minute walk distance, NYHA ⫽ New York Heart Association, Patient 1

Patient 2

Patient 3

Age

56

59

53

Gender

F

M

M

cryptogenic

alcohol

Hepatitis C,

B

B

B

EV,GV,

EV, thrombocytopenia

Encephalopathy,

Etiology of cirrhosis

alcohol Child-Pugh class Complications

DISCLOSURE: Zoheir Bshouty, None.

portal vein thrombosis,

thrombocytopenia

thrombocytopenia

TREATMENT OF PORTOPULMONARY HYPERTENSION WITH ORAL SILDENAFIL Shiraz A. Daud MD* Murali M. Chakinala MD Washington University in Saint Louis, St Louis, MO PURPOSE: Pulmonary arterial hypertension (PAH) in the setting of portal hypertension, or Porto-pulmonary Hypertension (PPHTN), has an estimated prevalence of 3.5% to 12.5% in patients referred for liver transplantation. Complications of cirrhosis such as encephalopathy, high cardiac output state, and thrombocytopenia have made treatment with prostanoids challenging. Furthermore, Bosentan is contraindicated in chronic liver disease and severe pulmonary hypertension is a contraindication to liver transplantation. We report our experience with oral Sildenafil monotherapy in PPHTN. METHODS: This is a case series of three patients with PPHTN treated with off-label Sildenafil. Secondary causes of pulmonary hypertension were excluded. Laboratory and hemodynamic data, New York Heart Association functional class, and six-minute walk distance (6MWD) were obtained at baseline and after treatment for an extended period with Sildenafil. RESULTS: All three patients had improvements in their hemodynamics and 6MWD. Functional improvement was evident in all three patients. During the 31 patient-months of follow-up, there were no directly attributable side effects or complications of Sildenafil. CONCLUSION: Sildenafil is a safe and effective pulmonary vasodilator for patients with PPHTN. CLINICAL IMPLICATIONS: Because conventional PAH therapies are potentially problematic in the setting of cirrhosis, sildenafil should be considered as a chronic therapeutic choice in PPHTN and may serve as a “bridge” to liver transplantation.

Symptoms at presentation

Progressive breathlessness, lower

Progressive

Exertional

extremity edema, syncope

breathlessness, syncope

breathlessness, syncope

EV ⫽ esophageal varices, GV ⫽ gastric varices DISCLOSURE: Shiraz Daud, None. TREATMENT OF SECONDARY PULMONARY ARTERIAL HYPERTENSION WITH ENDOTHELIN RECEPTOR BLOCKADE Satyendra Sharma MBBS* Roger Philipp MD Tarik Kashour MD University of Manitoba, Winnipeg, MB, Canada PURPOSE: Secondary pulmonary arterial hypertension (SPAH) is an adverse outcome of a variety of systemic disorders. These include collagen vascular diseases, chronic thromboembolism, human immunodeficiency virus (HIV), portal pulmonary hypertension and other diseases. Progression of SPAH may persist despite stabilization of the causative disease and contributes to the poor quality of life and unfavorable survival in these patients. Treatment of the underlying cause and oxygen supplementation may alleviate symptoms, but no specific therapy to treat SPAH currently exists. Endothelin receptor blockade with bosentan has been shown to be beneficial therapy in the treatment of primary pulmonary hypertension but efficacy of this therapy in SPAH has not been established. METHODS: Retrospective review of patients followed through our clinic. RESULTS: We describe a case series of six patients with disparate causes of SPAH, who benefited from endothelin receptor blockade CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

367S

POSTER PRESENTATIONS

PURPOSE: To asses the response of patients with underlying pulmonary arterial hypertension who do not qualify for treatment with bosentan to treatment with bosentan. METHODS: Fifteen patients (8 females and 7 males) with underlying pulmonary arterial hypertension who did not qualify for treatment with bosentan [3 with chronic thromboembolic disease (CTED), 2 with congenital and valvular disease (CVD), 3 with interstitial lung disease and severe fibrosis (ILD), and 7 with connective tissue disease and severe fibrosis (CTD⫹FIB)] where treated with bosentan. Bosentan was started at 62.5 mg PO BID and increased to 125 mg PO BID after 4 weeks. One patient with CTED was started on dual therapy with bosentan and sildenafil. Primary end points where 6-minute walk distance and NYHA functional class. Patients were assessed at baseline, 3 and 6 months. RESULTS: The overall 6-minute walk distance at baseline, 3 and 6 months (Mean⫾SE, meters) were 262.2⫾36.76, 357.4⫾38.60, and 366.3⫾44.92 respectively. Individual as well as group data (CTED, CVD, ILD, CTD⫹FIB) are shown in Figure 1. Overall NYHA class dropped from an average of 3 to 2.2 both at 3 and 6 months. All patients tolerated the treatment well. Two patients required a reduction in dose down to 62.5 mg PO BID. CONCLUSION: Patients with underlying pulmonary arterial hypertension that do not qualify for treatment with endothelin receptor antagonists may still benefit from treatment. CLINICAL IMPLICATIONS: More RCT are needed to assess the response to treatment in wider groups of patients with underlying pulmonary arterial hypertension.

Patient 1

Wednesday, November 2, 2005 Pulmonary Hypertension, continued therapy. The causes of SPAH in this series included collagen vascular disease (scleroderma 1, systemic lupus erythematosis 2), chronic thromboembolic disease (2) and granulomatous vasculitis from sarcoidosis (1). Therapy with bosentan led to symptomatic improvement, shift in New York Heart Association functional class and walking distance in all patients. 6 minute walk test demonstrated an increase from a mean of 151.67⫾69.30 meters at baseline to 314.83⫾89.09 meters following average 14 months of bosentan treatment. Pulmonary arterial pressure decreased in most but not in all six patients on follow up echocardiogram. CONCLUSION: The patients in this series very likely improved secondary to the antiproliferative effects of bosentan on pulmonary vasculature.These patients were treated with multiple therapies including calcium channel blocker and anticoagulation. Although, calcium channel blockers and anticoagulation may have contributed to the therapeutic effect in these patients, they have not been shown to improve exercise capacity or functional class in advanced pulmonary hypertension. CLINICAL IMPLICATIONS: This case series makes a compelling argument for a systematic, controlled study of endothelin receptor antagonists in patients with SPAH. DISCLOSURE: Satyendra Sharma, None.

Respiratory Failure Outcomes 12:30 PM - 2:00 PM FACTORS ASSOCIATED WITH FAVORABLE LTACH DISCHARGE OUTCOMES Linda L. Wolfenden MD* Grant T. Anderson BA Nancy E. Clardy MSN Nancy V. Murrah RN Emir Veledar PhD Emory University, Atlanta, GA PURPOSE: Long term acute care hospitals (LTACHs) can continue the care for high risk patients who are deemed medically stable to leave an ICU. Little is known about the type and frequency of discharge destinations from LTACHs. Factors such as age, prior debility and number of comorbidities are significantly associated with survival to discharge from LTACHs. We sought to understand the factors associated with a favorable discharge outcome, beyond survival. METHODS: A prospective, observational medical record review and survey. Inclusion criteria: ICU patients with principal diagnosis of respiratory insufficiency or failure, referred to the Emory LTACH pulmonary service for ventilator and tracheostomy weaning. Exclusion criteria: prior admission to LTACH. A favorable outcome was defined as any discharge destination other than re-admission to an acute care hospital, hospice or death. RESULTS: 62 patients enrolled. Mean age: 60.5 ⫹/- 16.3 years; 51.6% female; 53.2% non-white race; 27.4% active smokers. ICU indications were as follows: 29.0% CNS disease; 19.3% post-operative; 16.1% acute lung injury; 12.9% MSOF; 9.7% cardiac disease; 6.5% chronic lung disease; 6.5% other. The distribution of discharge destinations was as follows: 27.4% acute rehabilitation facility; 25.8% readmission to acute care hospital ICU; 22.6% subacute rehabilitation facility; 14.5% home; 6.5% died; 3.2% nursing home. See table. CONCLUSION: Most (68%) patients in our study experienced a favorable discharge outcome. Younger age, more education, history of prior independence and absence of renal disease were all statistically significant factors associated with a favorable discharge outcome. Lower initial ICU albumin; lower initial LTACH albumin and lower initial LTACH hemoglobin; and higher initial LTACH creatinine were all significantly associated with unfavorable discharge outcomes. A significant minority of patients (26%) required re-admission to the acute care hospital ICU. CLINICAL IMPLICATIONS: Most patients experienced a favorable LTACH discharge outcome. Factors associated with favorable ICU outcomes (age, history of renal disease, albumin, creatinine, hemoglobin) are also associated with favorable LTACH outcomes in our study. More research is needed to determine what factors within the LTACH course can improve patient outcomes.

368S

Factor Demographics mean age –years High school graduate Female gender White race Never smoker Past Medical History Prior independence History of renal disease ICU day one albumin (g/dL) – mean creatinine (mg/dL) – median hemoglobin (g/dL) – median ICU LOS (days) – median LTACH day one albumin (g/dL) – mean creatinine (mg/dL) – median hemoglobin (g/dL) – median LTACH LOS (days) – median

Favorable (N ⫽ 42)

Unfavorable (N ⫽ 20)

p Value

56.3⫾ 15.4 36 (86%)

69.3⫾ 14.8 11 (55%)

0.0023 0.0411

22 (52%) 22 (52%) 18 (43%)

10 (50%) 7 (35%) 5 (25%)

0.8608 0.1998 0.1736

31 (74%)

9 (45%)

0.0441

7 (17%)

8 (40%)

0.0449

2.80⫾ 0.85

2.31⫾ 0.58

0.0296

0.95

1.3

0.0502

12.1

11.75

0.2802

30

27

0.133

2.37 ⫹/- 0.5

2.03 ⫹/- 0.5

0.0125

0.75

1.0

0.0320

10.75

9.9

0.0157

24

13

0.010

DISCLOSURE: Linda Wolfenden, None.

OUTCOME OF CHRONIC VENTILATED PATIENTS TRANSFERRD TO A STEP-DOWN RESPIRATORY CARE CENTER IN TAIWAN Fung J. Lin MD* Chang-Yi Lin MD Pei-Jan Chen MD Hsu-Tah Kuo MD MacKay Memorial Hospital, Taipei, Taiwan ROC PURPOSE: The aim of the study was to investigate the outcome of prolonged ventilated patients after their transferal from intensive care units (ICU) to the step-down respiratory care center (RCC) in Taiwan. METHODS: This was a retrospective observational study in a stepdown RCC. Adult patients who was admitted to RCC from October 2000 to September 2001 were eligible for the study. Admission criteria of RCC included age ⬎17 years old, MV for ⬎14 days, arterial oxygenation ⬎60mmHg with the fraction of inspired oxygen (FiO2)⬍0.55, and positive end-expiratory pressure of ⬍10 cmH2O. The primary outcome was the survival in the RCC and after discharge from the RCC. RESULTS: Total 224 cases were eligible for the survey, and 108(48.2%) patients were successfully liberated in the RCC. Those who failed weaning had a longer stay in the ICU and RCC (25.1 vs. 20.9 days, and 31.4 vs. 18.6 days with p⬍0.05). After discharge from the RCC, another 4.9% of the failed patients were weaned within the one year. Patients who failed weaning in RCC had a shorter survival time (5.2 vs. 10.4 months, p⬍0.05) and a lower one-year survival (23.6% vs. 44.6%, p⬍0.05). CONCLUSION: Patients who were transferred to RCC were still in critical condition, and 25% of these patients died during their stay in the RCC. However, a step-down RCC cound offer a continual care of these pronlonged ventilated (PMV) patients who could not be weaned when in CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Respiratory Failure Outcomes, continued ICU with a reduced cost and resource. Establishing a functional position of step-down RCC in selected PMV patients can be cost-effective. CLINICAL IMPLICATIONS: Early transfer of stable PMV patients to RCC can be cost-effective. DISCLOSURE: Fung Lin, None.

FACTORS AFFECTING WEANING AND SURVIVAL OUTCOMES IN PATIENTS ON PROLONGED MECHANICAL VENTILATION Debapriya Datta MD* Paul Scalise MD Manchester Hospital, Manchester, CT

TABLE 1—Studied Parameters in Patients Liberated and Failed-To-Wean Parameters

Liberated

Failed

Age (years) Dvs (days) BMI (kg/sqm) % IBW Protein (gm/dL) Albumen (gm/dL) Prealbumen (mg/dL) BUN (mg/dL) Cr (mg/dL) CrCl (ml/min) Hb (gm/dL) WBC TLC (cells/cumm) TSH (mU/L)

66⫾7 51⫾32 27⫾8 121⫾36 5.9⫹0.8 2.6⫹0.5 20⫾7 29⫾21 0.8⫾0.9 69⫾34 10⫾1.4 10⫾5 1672⫾1060 4.2⫾9

68⫾15 61⫾66 26⫾8 119⫾36 5.5⫾0.8 2.5⫾0.5 20⫾8 32⫾17 0.8⫾0.8 61⫾32 10⫾1.3 10⫾3 1597⫾995 3.9⫾11

DISCLOSURE: Debapriya Datta, None.

PURPOSE: To examine predictors of ability to wean from mechanical ventilation (MV), functional ability and health-related quality of life (HRQoL) in patients who required prolonged mechanical ventilation (PMV) (ⱖ 7 days) six months after Medical Intensive Care Unit (MICU) discharge. METHODS: Consenting patients (n⫽145) completed questionnaires rating their functional ability (Health Assessment Questionnaire [HAQ]) one week before MICU admission (baseline), MICU discharge, 1 and 6 months post discharge and HRQoL (SF-36) at baseline, 1 and 6 months. Proxy responses of family members were used when patients could not respond. RESULTS: At 6 months, 60.7% patients were living. Survivors were 55.7% female, 59.8⫾ 16.7 yrs of age and on MV for 23.4⫾ 22.5 days at MICU discharge. Complete sets of questionnaires were obtained from 52% patients for SF-36 and 72% for HAQ. At baseline, no differences were seen in SF-36 or HAQ scores. Patients on MV exhibited a statistically significant interaction between MV and Time (p⫽.034) with higher HAQ scores (worse functional ability) at 1, but not 6 months. SF-36 physical component scores were lower (worse ratings) at 1 (p⫽.003), but not 6 months. No significant changes were seen in SF-36 mental component scores. Using logistic regression, cormobidity was identified as a significant predictor of ability to wean from MV following MICU discharge (71.4% cases correctly predicted). Age, gender, APACHE III, baseline HAQ and SF-36 scores were not identified as significant predictors. CONCLUSION: PMV survivors rate HRQoL similarly 6 months after MICU discharge, regardless of ability to wean from MV. Those not weaned from MV were more compromised in functional ability at 1, but not 6-months. Cormorbidity was the best predictor of ability to wean following MICU discharge. CLINICAL IMPLICATIONS: Inability to wean from PMV does not appear to influence ratings of HRQoL 6 months after MICU discharge. Potential reasons include changes in reference point (expectations) or lack of instrument sensitivity. Cormorbidity significantly influences ability to wean following MICU discharge. DISCLOSURE: Leslie Hoffman, None. TIME TO WEAN AFTER TRACHEOTOMY IN CRITICALLY ILL PATIENTS Denise P. Veelo MD Dave A. Dongelmans MD Johanna C. Korevaar PhD Marcus J. Schultz PhD* Academic Medical Center, Amsterdam, Netherlands PURPOSE: To estimate time to wean from mechanical ventilation after tracheotomy in critically ill patients. METHODS: Prospective observational study in translaryngeally intubated mechanically ventilated patients that received a tracheostomy during their stay in an academic ICU. RESULTS: Approximately 7% of all ICU-patients required a tracheostomy. Significant more tracheotomies were performed in neurosurgical/ neurology patients and patients who were acutely admitted to the ICU (14% and 12%, respectively). Patients after cardiac arrest as the reason for the present ICU-admittance were tracheotomized in 15%. Tracheotomy was performed at a median time of 8 days (interquartile range, 4-13) after ICU-admittance. Within one week after tracheotomy, the probability of having breathed spontaneously without assist of the mechanical ventilator ⬎ 4 hours/day was 89%, 78% for ⬎ 8, 72% for ⬎ 12, and 60% for ⬎ 24 hours/day. By day 28, the probability of having breathed spontaneously ⬎ 4 hours/day was 98%, 97% for ⬎ 8, 94% for ⬎12 and 93% for ⬎ 24 hours/day. Mean time to wean after tracheotomy was 5 days (2-11) for all patients. At day 7, 77% of the neurosurgery/neurology patients, 66% of cardiopulmonary surgery patients and 63% of the cardiology patients, but only 41% of surgical patients and 34% of medical patients were weaned completely from the mechanical ventilator. CONCLUSION: Time to wean completely from mechanical ventilation after tracheotomy differs among the separate ICU-patient groups. CLINICAL IMPLICATIONS: After tracheotomy, the majority of patients are quickly able to breathe spontaneously without assist of the mechanical ventilator for several hours/day. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: Literature is limited on weaning and survival outcomes in patients on prolonged mechanical ventilation (PMV), which is defined as ventilatory support ⬎21 days . The objective of this study was to determine factors affecting weaning and survival outcomes in patients on PMV. METHODS: We retrospectively studied patients on PMV admitted for weaning to a regional weaning center over a 3-year period. The following data was abstracted from records: patients’ age, sex, precipitating cause of respiratory failure, duration of ventilatory support (Dvs), percent ideal bodyweight (%IBW), body mass index (BMI), serum albumin, prealbumen, BUN, serum creatinine (Cr), creatinine clearance (CrCl), hemoglobin (Hb), WBC count, total lymphocyte count (TLC) and serum TSH levels. Outcomes noted were liberation from PMV, defined as being off ventilatory support for ⬎ 7 days and survival (alive at discharge or not). Multivariate analysis was used to determine relation between studied parameters and outcome. Chi square test was used to test statistical significance, with p ⬍ 0.05 being deemed statistically significant. RESULTS: Of 202 patients studied, 48% were males. Mean age was 66.3⫾16 years. Cause of respiratory failure was cardiovascular surgery in 27%; other surgery in 14.5%; COPD in 21%; pneumonia in 9%; ARDS in 6%; neurological disease in 18.5% and CHF in 4%. Mean Dvs was 60.8 days (range 21-680 days). Sixty-seven percent were liberated from PMV; 33% failed to wean. Seventy-one percent survived to discharge. Dvs ⬍ 12 weeks was associated with better weaning outcome. Table 1 depicts studied parameters in liberated patients and patients that failed to wean. On multivariate analysis, factors associated with adverse impact on liberation were: COPD as cause of respiratory failure, longer Dvs, lower CrCl. Factors associated with adverse survival outcome were CHF and COPD as causes of respiratory failure, higher Cr and lower TLC. CONCLUSION: Multiple factors affect weaning and survival outcomes in patients on PMV. CLINICAL IMPLICATIONS: More studies are needed to develop screening criteria for selection of appropriate patients on PMV for admission to weaning facilities.

PREDICTORS OF ABILITY TO WEAN FROM PROLONGED MECHANICAL VENTILATION SIX MONTHS AFTER DISCHARGE FROM A MEDICAL INTENSIVE CARE UNIT Leslie A. Hoffman PhD* JiYeon Choi MSN Thomas H. Miller PhD Keiko Kobayashi MSN Thomas G. Zullo PhD Michael P. Donahoe MD University of Pittsburgh School of Nursing, Pittsburgh, PA

Wednesday, November 2, 2005 Respiratory Failure Outcomes, continued DISCLOSURE: Marcus Schultz, None. MEASUREMENT OF BRAIN NATRIURETIC PEPTIDE LEVELS IN PATIENTS WITH RESPIRATORY FAILURE DUE TO CHRONIC OBSTRUCTIVE PULMONARY DISEASE Christopher R. Powers MD* Daniel R. Ouellette MD Brooke Army Medical Center, Fort Sam Houston, TX PURPOSE: The measurement of serum BNP levels is advocated in the acute evaluation of patients with dyspnea as an aid leading to the diagnosis of congestive heart failure. The presence of elevated serum BNP levels in other groups of patients with acute respiratory disease would limit the usefulness of serum BNP measurement. Additionally, elevated serum BNP levels in patients with respiratory failure due to COPD might suggest a role for right heart failure in these patients. METHODS: Enrolled patients had a new or existing diagnosis of COPD and were admitted to the intensive care unit (MICU at the enrolling institutions ) with acute respiratory failure and no evidence of acute left or right heart failure or myocardial ischemia. Enrolling institutions included Brooke Army Medical Center (BAMC) and Wilford Hall Medical Center (WHMC). The control population consisted of clinically stable patients with COPD enrolled in the outpatient setting. Measurements included brain natriuretic peptide (BNP), transthoracic echocardiogram, and pulmonary function testing when medically stable. ICU patients had competing diagnoses such as pneumonia, ischemia, congestive heart failure, or thromboembolic disease ruled out by appropriate clinical testing within the standard of care. RESULTS: Seven inpatients were enrolled with an average BNP level of 320.4 were enrolled during this initial phase of the study. These seven patients were compared to seven stable COPD outpatients with moderate to severe COPD whose average BNP level was 21.4. Statistical analysis was performed using the Student t-Test for independent samples and a one tailed test of hypothesis was significant at the 0.05 level with a P value of 0.033. CONCLUSION: BNP levels are significantly elevated in patient’s with moderate to severe COPD who are hospitalized in the intensive care unit with respiratory failure during an acute COPD exacerbation. CLINICAL IMPLICATIONS: Elevated serum BNP levels in patients with respiratory failure due to COPD suggest a role for right heart failure in these patients. Further research is needed to determine possible treatments for ongoing right ventricular strain due to severe COPD. DISCLOSURE: Christopher Powers, None.

Respiratory Infections: Bronchitis and Pneumonia 12:30 PM - 2:00 PM COMPARATIVE EVALUATION OF THE EFFICACY, SAFETY AND TOLERABILITY OF EXTENDED-RELEASE (ER) CEFUROXIME AXETIL TABLETS 500 MG (ONCE DAILY) AND CEFIXIME TABLETS 200 MG (TWICE DAILY) IN PATIENTS WITH ACUTE TONSILLOPHARYNGITIS: A PILOT STUDY Anish A. Desai MD* U Venkatesan MD G S. Kadam MD Ashish S. Gawde MD Vidyagauri P. Baliga PhD Glenmark Pharmaceuticals Ltd, Mumbai, India PURPOSE: A new Extended –Release(ER) formulation of Cefuroxime axetil 500 mg tablets has been recently developed. This pilot study was undertaken to compare the efficacy, safety and tolerability of this new formulation and Cefixime tablets in patients with acute tonsillopharyngitis. METHODS: Adult patients(n⫽100) with a clinical diagnosis of acute pharyngotonsillitis, fulfilling the selection criteria were enrolled in this prospective, multicentric, randomized, assessor-blind, comparative pilot study after obtaining their informed consent. Patients were randomized to receive either 500 mg ER- Cefuroxime axetil tablets once– daily or cefixime 200 mg tablets twice daily for 10 days. Efficacy outcomes included monitoring of clinical and bacteriological response at end of therapy. Safety and tolerability were assessed by monitoring adverse events and laboratory parameters.

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RESULTS: A total of 96 patients completed the study with 4 drop-outs (2 from each group) being lost to follow-up. There was a significant decline in mean scores of sore throat, dysphagia, tonsillar erythema, pharyngeal or tonsillar exudate and tender anterior cervical nodes from baseline at end of treatment in both groups. However, difference between groups was not statistically significant. Cure was observed in 91.7% patients in ER-Cefuroxime axetil group and 93.7% patients in cefixime group at end of study (p⬎0.05). Bacteriological response was observed in similar number of patients in both groups(ER-Cefuroxime axetil(95.8%); Cefixime (97.9%)) at end of therapy. Similar incidences of mild to moderate adverse events mostly gastrointestinal in nature were reported in both groups(ER-Cefuroxime axetil 6% & cefixime - 8%). No abnormalities were detected in the laboratory parameters. CONCLUSION: ER-Cefuroxime axetil tablets once daily were comparable in efficacy, safety and tolerability to Cefixime tablets twice daily in patients with acute tonsillopharyngitis. CLINICAL IMPLICATIONS: Once-daily ER-Cefuroxime axetil is a better therapeutic option than twice daily cefixime tablets in patients with acute tonsillopharyngitis on account of its dosage convenience. DISCLOSURE: Anish Desai, None.

ASSESSMENT OF THE EFFICACY AND SAFETY OF SINGLEDOSE EXTENDED-RELEASE (ER) CEFUROXIME AXETIL IN ADULT INDIAN PATIENTS WITH ACUTE EXACERBATIONS OF CHRONIC BRONCHITIS (AECB) Anish A. Desai MD* A B. Mishra MD G Bhatia MD R S. Murlidaharn MD G S. Kadam MD Ashish S. Gawde MD Vidyagauri P. Baliga PhD Glenmark Pharmaceuticals Ltd, Mumbai, India PURPOSE: Cefuroxime axetil possesses activity against Streptococcus pneumoniae Moraxella catarrhalis and Hemophilus influenzae and has beta-lactamase stability. It is therefore useful in the treatment of acute exacerbations of chronic bronchitis. An extended-release (ER)preparation of cefuroxime axetil has been recently formulated. The present study evaluated the efficacy, tolerability and safety of this new ER- formulation of Cefuroxime in adult Indian patients with AECB. METHODS: Adults patients(n⫽125) with clinically and radiologically confirmed AECB were enrolled in this prospective, multicentric , open label, non-comparative Phase III study after obtaining informed consent. The study was approved by the respective Institutional Review Boards. Patients fulfilling the selection criteria received 1g. ER-Cefuroxime axetil once-daily for 10 days. Efficacy outcomes included clinical and bacteriological response at the end of therapy. Safety was assessed by monitoring. RESULTS: Following therapy with ER –Cefuroxime, there was a significant reduction in body temperature, chills, dyspnea, chest pain by Day 3 which further improved on Day 10. There was a significant improvement in the quantity, consistency, nature and odour of sputum, intensity of cough and ausculatory findings by Day 3 which was sustained till the end of study. The effects of therapy on primary outcome measures are depicted in Table 1. Adverse events were reported by only 12% of the study population. CONCLUSION: ER-Cefuroxime axetil 1g. once daily was effective and safe in the treatment of AECB. CLINICAL IMPLICATIONS: ER-Cefuroxime axetil 1g. once daily is a useful therapeutic option in the treatment of Acute exacerbations of Chronic bronchitis.

Table 1—Effect of Therapy With ER-Cefuroxime Axetil in Patients With AECB Clinical response

% of patients

Bacteriological response

% of patients

Cure Improvement Failure Not-evaluable

71.8% 25.8% 2.4% -

Clearance Partial clearance Failure Colonization/Not evaluable

64.5% 28.3% 3.2% 4%

DISCLOSURE: Anish Desai, None. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Respiratory Infections: Bronchitis and Pneumonia, continued THE EFFECT OF DISEASE SEVERITY ON CLINICAL OUTCOME WITH ACUTE EXACERBATION OF CHRONIC BRONCHITIS PATIENTS TREATED WITH GEMIFLOXACIN I. Morrissey MD* T.M. File Jr. MD L.A. Mandell MD G.S. Tillotson MS G.R. Micro Ltd., London, United Kingdom PURPOSE: Gemifloxacin is approved to treat acute bacterial exacerbations of chronic bronchitis (AECB). Patients with AECB associated with COPD and a history of recurrent acute episodes can be difficult to treat. Data from 10 AECB clinical trials were analysed for number of exacerbations in last year (NELY), disease duration, history of asthma or chronic bronchitis. METHODS: Clinical response (success/failure) at end of therapy (EOT), follow-up Clinical response at end of therapy (EOT), follow-up and long follow-up (LFU, ⫹2/52) was evaluated. Comparators were clarithromycin, levofloxacin , trovafloxacin , amoxycillin-clavulanate , ceftriaxone/cefuroxime and ofloxacin. RESULTS: See Table. CONCLUSION: These data support the utility of gemifloxacin in AECB. Improved success at FU and LFU suggests that use of gemifloxacin may reduce time before next exacerbation with COPD patients. CLINICAL IMPLICATIONS: Combined COPD/Respiratory medical histories show higher clinical success with gemifloxacin at FU and LFU.

THE EFFECT OF COMPUTERIZED ORDER SETS ON QUALITY INDICATORS FOR HOSPITALIZED PATIENTS WITH COMMUNITY ACQUIRED PNEUMONIA Kathryn Wood MPH Allyson Mirabella MD* Jonathan Gottlieb MD Thomas Jefferson University, Philadelphia, PA PURPOSE: Evaluate the impact of a computerized order set on the adherence to core measures in patients with Community Acquired Pneumonia (CAP). METHODS: Study was conducted as a retrospective chart review at a tertiary care academic medical center with mandatory computerized physician order entry (CPOE). Study population was defined as all adult patients admitted between December 2003 and October 2004 whose physicians used a standardized CAP order set. Controls were matched on age and gender over the same time period from patients without use of a CAP order set but within DRG 89 or 90. The groups were compared on five core measures: oxygenation assessment, pneumoccocal vaccination, smoking cessation counseling, and time to blood culture and antibiotics. Length of stay, appropriateness of antibiotic, and admitting services were also compared. RESULTS: The records of 20 order set and 20 controls were abstracted. Combining all CAP indicators, use of the order set was associated with a significantly greater proportion of quality indicators than controls (60% vs. 40%, p⫽0.0017). Use of order sets was associated with greater proportion of every quality indicator, although differences were not

COMPARATIVE EFFICACY OF ORAL AND SEQUENTIAL INTRAVENOUS/ORAL MOXIFLOXACIN IN THE TREATMENT OF COMMUNITY ACQUIRED PNEUMONIA (CAP) IN THE VERY ELDERLY (AGE >ⴝ75 YEARS) Antonio Anzueto MD* Daniel Haverstock MS Frank Kruesmann PhD Shurjeel Choudhri MD Univ. of Texas Health Sci. Ctr., San Antonio, TX PURPOSE: To evaluate the efficacy and safety of sequential IV/PO and PO moxifloxacin (MXF) versus that of comparator (COMP) antibiotics in very elderly (ⱖ75 years old) patients with CAP. METHODS: Data were pooled from all global, randomized, controlled trials of IV/PO (5 trials) and PO (5 trials) of MXF in the treatment of CAP. The pooled data were used to determine the clinical success rates and adverse event rates in the very elderly for both MXF and COMP-treated patients. The comparators were clarithromycin and amoxicillin in the PO studies and trovafloxacin, levofloxacin, ceftriaxone ⫾ azithromycin and amoxicillin/clavulanate ⫾ clarithromycin in the sequential IV/PO studies. RESULTS: Of the 908 very elderly patients identified in the pooled analysis, 215 (114 MXF, 101 COMP) received PO and 693 (349 MXF, 344 COMP) received sequential IV/PO therapy. Of these, 158 PO-treated (84 MXF, 74 COMP) and 497 IV/PO-treated (248 MXF, 249 COMP) patients were valid for the primary efficacy analysis. Clinical success rates in IV/PO studies were 90% (222/248) for MXF vs. 83% (206/249) for COMP (95% CI 0.3%, 12%). For PO studies clinical success rates were 95% (80/84) for MXF vs. 86% (64/74) for COMP (95% CI 0.7%, 18.6%). Adverse and serious adverse event rates were similar in MXF- and COMP-treated patients. CONCLUSION: Both IV and PO moxifloxacin were highly efficacious and safe in treating community acquired pneumonia in the very elderly and overall cure rates were significantly better in moxifloxacin treatedpatients than those achieved with the comparator regimens. CLINICAL IMPLICATIONS: Moxifloxacin appears to have excellent efficacy when used as empiric monotherapy for the treatment of CAP in very elderly patients. DISCLOSURE: Antonio Anzueto, Employee Dan Haverstock, Frank Kruesmann, Shurjeel Choudhri; Consultant fee, speaker bureau, advisory committee, etc.

RESISTANCE PHENOTYPES OF STREPTOCOCCUS PNEUMONIAE AND CLINICAL OUTCOME OF RESPIRATORY TRACT INFECTIONS TREATED WITH GEMIFLOXACIN Ian Morrissey PhD Thomas File MD* Lionel Mandell MD Glenn S. Tillotson MS SUMMA Healthcare, Akron, OH PURPOSE: Gemifloxacin (GEM) is a potent fluoroquinolone with excellent activity against respiratory tract infection (RTI) pathogens, including S. pneumoniae (SP). Pooled data from 17 phase III clinical trials for GEM with community-acquired pneumonia, acute bacterial sinusitis & acute exacerbation of chronic bronchitis patients (pts. METHODS: 530 Pts where SP was the sole pathogen & SP susceptibility known, were evaluated.Clinical success at end of therapy (EOT) & at follow-up (FU, approx. 1-3 weeks after treatment) was studied. Main comparators (CMP) were cefuroxime (61 pts), amoxicillin-clavulanate (37 pts), trovafloxacin (34 pts), cefuroxime & clarithromycin (28 pts), levofloxacin or clarithromycin (11 pts). Percentage success based on susceptibility to penicillin G (Pen) and/or macrolides (Mac) is shown (Table, S ⫽ susceptible, NS ⫽ non-susceptible, R ⫽ resistant, N ⫽ pts/group). RESULTS: See Table. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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DISCLOSURE: I Morrissey, Grant monies (from industry related sources) Oscient; Shareholder Oscient; Employee Oscient; Consultant fee, speaker bureau, advisory committee, etc. Oscient.

significant for individual indicators. Proportion of patients receiving appropriate antibiotics (85% vs.75%) and length of stay were not significantly different between the two groups. CONCLUSION: Patients whose physicians used the CAP order set were more likely to receive appropriate care. CLINICAL IMPLICATIONS: Use of order sets combined with CPOE may help improve standardization of care and compliance with guidelines established by regulatory agencies. Due to the small size of the study population, the insignificant differences in individual core measures may not accurately predict larger populations. These findings should encourage the support of order set utilization within existing CPOE systems. DISCLOSURE: Allyson Mirabella, None.

Wednesday, November 2, 2005 Respiratory Infections: Bronchitis and Pneumonia, continued CONCLUSION: GEM showed good clinical success against all resistance phenotypes. These data support the use of GEM in the treatment of RTI, especially where MacR SP prevails. CLINICAL IMPLICATIONS: The emergence of antibacterial resistance may effect empirical therapy, gemifloxacin has been shown to be effective against resistant phenotypes of th emost common bacterial respiratory pathogen.

% Success (N) Phenotype All SP PenS PenNS MacS MacR PenR & MacR

Treatment

EOT

FU

GEM CMP GEM CMP GEM CMP GEM CMP GEM CMP GEM CMP

92.5% (321) 90.4% (209) 93.3% (252) 91.0% (166) 89.7% (68) 88.4% (43) 93.0% (256) 92.0% (175) 90.3% (62) 81.3% (32) 85.7% (28) 82.4% (17)

88.8% (321) 86.0% (207) 88.9% (252) 86.0% (164) 88.2% (68) 86.0% (43) 88.3% (256) 86.2% (174) 90.3% (62) 83.9% (31) 85.7% (28) 82.4% (17)

DISCLOSURE: Thomas File, Consultant fee, speaker bureau, advisory committee, etc. TF & LM are consultants to Oscient. DOES TELITHROMYCIN EXHIBIT IMMUNOMODULATORY PROPERTIES IN CHRONIC AIRWAY INFLAMMATION? Maysah S. El-Deen MD Abdalla A. Abu Hussein MS* Gamal A. El-Kholy MD Amany Abouzeid MD Tanta Int’l Cardiothoracic Vascular Center, Tanta, Egypt PURPOSE: The role of telithromycin in the treatment of respiratory tract infections is well established. However, telithromycin seems to have immunomodulatory properties in chronic airway inflammation, including the inflammatory allergic condition bronchial asthma. The aim of this trial was to establish whether our clinical observation of an extended 1-2 months treatment with telithromycin in patients with chronic inflammatory airway disorder is beneficial. METHODS: Open comparative clinical trial with male and female patients aged 18-65 years with persistent cough, chronic obstructive bronchitis (with and without acute exacerbations), COPD or bronchial asthma. We compared post-treatment symptomatic relief and peak flow meter results with baseline recordings, while monitoring for adverse events, including abnormal laboratory values. RESULTS: 84 patients (46 males, 38 females, age 37.3 ⫾ 8.4 years) were enrolled. After 60 days of treatment (47.3 ⫾ 3.2 days), symptomatic relief and improved spirometry were significantly better (p⬍0.05) than baseline recordings. The main adverse events were diarrhea and dizziness. CONCLUSION: Telithromycin may have a role in the treatment of chronic airway inflammatory conditions including bronchial asthma. This may be explained by its high tissue penetration characteristic, and the increasing evidence that atypical respiratory pathogens (Mycoplasma pneumonia, Moraxella catarrhalis, and Legionella pneumophila), against which telithromycin is reportedly active, play a major role in the pathogenesis and prognosis of chronic inflammatory airway disorders. CLINICAL IMPLICATIONS: Extended treatment with telithromycin may provide further benefits to patients with chronic airway inflammation, especially where atypical respiratory pathogens are suspected. DISCLOSURE: Abdalla Abu Hussein, None. PATIENT RISK FACTORS IN COMMUNITY-ACQUIRED PNEUMONIA INFECTIONS OUTCOME FOLLOWING TREATMENT WITH GEMIFLOXACIN I Morrissey MD T.M. File Jr. MD L.A. Mandell MD* G.S. Tillotson MS McMaster University, Hamilton, ON, Canada PURPOSE: Respiratory fluoroquinolones are important agents in the management of patients with community-acquired pneumonia (CAP).

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Gemifloxacin is a new potent fluoroquinolone with excellent activity against CAP pathogens. METHODS: Pooled data from 5 phase III CAP gemifloxacin clinical trials were evaluated. Patients were grouped based on risk factors indicated in the IDSA guidelines [Mandell et al.2003 CID 37:1405]. Clinical response (success or failure) at end of therapy (EOT) & at follow-up (FU, approx. 1-3 weeks after treatment) was studied. Main comparators for CAP patients were cefuroxime & clarithromycin (322 patients), trovafloxacin (282 patients) & amoxicillin-clavulanate (156 patients). RESULTS: Percent success is shown in table (AB, antibiotics, COPD, chronic bronchitis and obstructive lung disease, HD, heart disease, *includes patients that did not score a response at FU and were counted as clinical failure). CONCLUSION: These data support the use of gemifloxacin in the treatment of CAP, especially where the patient has recognised IDSA risk factors. CLINICAL IMPLICATIONS: Although gemifloxacin showed lower % success than comparator against CAP patients with no defined risk factor, gemifloxacin was considerably more successful than comparator against patients associated with risk factors. This advantage was even more prominent at FU than at EOT. Patients with other comorbidities such as renal failure or malignancy were not recruited in sufficient number for analysis.

Risk Factor CAP All Prior AB Diabetes COPD HD

% Success (number of patients) Treatment

EOT

FU

Gemifloxacin Comparator Gemifloxacin Comparator Gemifloxacin Comparator Gemifloxacin Comparator Gemifloxacin Comparator

86.9% (1166) 87.2% (933) 86.9% (291) 86.6% (262) 87.6% (129) 86.6% (82) 85.6% (181) 83.7% (190) 88.8% (356) 86.0% (299)

80.9% (1164) 81.6% (928) 82.1% (291) 79.0% (262) 82.2% (129) 77.8% (81) 77.3% (181) 73.7% (190)* 82.9% (356) 79.9% (298)

DISCLOSURE: LA Mandell, Grant monies (from industry related sources) Oscient; Shareholder Oscient; Employee Oscient.

CARDIO-PULMONARY MEDICAL HISTORY AND THE EFFECT ON CLINICAL OUTCOME OF COMMUNITY-ACQUIRED PNEUMONIA INFECTIONS TREATED WITH GEMIFLOXACIN I. Morrisey MD T.M. File Jr. MD L.A. Mandell MD G.S. Tillotson MS* Oscient, Waltham, MA PURPOSE: Gemifloxacin is a potent new fluoroquinolone with excellent activity against community-acquired pneumonia (CAP) pathogens. METHODS: Pooled data from 5 phase III CAP gemifloxacin clinical trials were evaluated. Patients were grouped based on cardio-pulmonary disease and medical history (CPD). Clinical response (success or failure) at end of therapy (EOT) & at follow-up (FU, approx. 1-3 weeks after treatment) was studied. Main comparators for CPD patients were cefuroxime & clarithromycin (97 patients), trovafloxacin (66 patients) & amoxicillin-clavulanate (55 patients). RESULTS: Percent success is shown in the table (* includes all 3 CPD groups in table plus patients with a medical history of angina, pulmonary heart disease, cardiomyopathy, cardiac murmurs, tachycardia or myocardial infarction). CONCLUSION: Although in general ,gemifloxacin showed slightly lower success than pooled comparators against CAP patients , gemifloxacin showed higher success rates than comparator against CPD patients.This difference was greater at FU than at EOT. CLINICAL IMPLICATIONS: These data support the use of gemifloxacin in the treatment of CAP, especially where the patient has a history of CPD. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Respiratory Infections: Bronchitis and Pneumonia, continued % Success (Number of patients) CPD group CAP All ALL CPD*

Treatment

EOT

FU

Gemifloxacin Comparator Gemifloxacin

86.9% (1166) 87.2% (933) 88.8% (356)

80.9% (1164) 81.6% (928) 82.9% (356)

DISCLOSURE: GS Tillotson, Grant monies (from industry related sources) Oscient; Shareholder Oscient; Employee Oscient; Consultant fee, speaker bureau, advisory committee, etc. Oscient.

(Shimadzu LC-9A pump, SPD-6A detector, CR-4A data processor, Simmetry Shield RP8 water column). RESULTS: The blood levels after 10 to 16 hours from the end of infusion (n° 6) ranged from 3.4 to 2.1 mg/l-gr, while the tissue levels ranged from 0.9 to 1.59 mg/l-gr; 18 to 22 hours after blood infusion (n° 6) levels ranged from 1.8 to 0.9 mg/l-gr; 23 to 25 hours after infusion (n° 6) blood and the tissue levels ranged from 1.8 to 0.98 mg/l-gr and 1.48 to 2.38 mg/l-gr. CONCLUSION: These data support the consistent lung tissue diffusion of L-AmB in patients with lung cancers. The L-AmB plasma concentration was gradually decreasing in all the cases. CLINICAL IMPLICATIONS: The relationship between these data can effort the best choice of drug in possible fungal infections as for a prophylactic employment for lower dosage and for lower collateral side effects. DISCLOSURE: Cosimo Lequaglie, None. RESPONSE TO ITRACONAZOLE IN PATIENTS WITH MEDIASTINAL GRANULOMA Talaat A. Al Shuqairat MD* University of Missouri-Columbia, Columbia, MO

PURPOSE: To value the effect of quinolone therapy in lung cancer resected patients with nosocomial pulmonary infection. METHODS: A multicentric study is reported on 38 complicated patients and submitted to pulmonary resection for cancer after prophylaxis with cephalosporin. The patients developed a microbiological tested pulmonary infection after resection procedure. A history of chronic bronchopulmonary disease was present in 26 cases, bronchial asthma in 4. The isolated pathogens on bronchoalveolar lavage were Haemophilus influenzae (n° 15), Streptococcus pneumoniae (n° 11), Moraxella catarrhalis (n° 3), Mycoplasma pneumoniae (n° 7), Chlamydia pneumoniae (n° 1) and Legionella pneumophila (n° 1). A quinolone, the Levofloxacin, was employed to the dosing of 500 mg IV twice day for 10 days.The patients have been observed for 10 days by the basal find of nosocomial infection after pulmonary resection. The basal sputum results positive in 8 cases as also to the first control at 4th day of therapy, without presence of pathogens at the 2nd test. The basal bronchoalveolar lavage results positive in the remainders 30 cases as also in 4th day, and it has been positive at the 2nd test in alone 2 cases, but with reduction of the bacterial count. All the isolated pathogens were sensitive in vitro to Levofloxacin. RESULTS: There was a clinical improvement with resolution of the symptoms in 36/38. Eradication was in 34 cases about the pathogen in cause and a presumed eradication in 2 ones: in the remainders 2, the partial eradication in 1, while in the last one there was a colonization. Five patients had diarrhea for about 5 days, 3 headache for 2 days of which 1 with nausea and 1 asthenia for 6 days. CONCLUSION: On the escort of the microbiological finds the effected therapy has allowed to not only reach the microbiological eradication but also a clean improvement of the symptoms with reduction of the postoperative hospitalization. CLINICAL IMPLICATIONS: The clean improvement of the symptoms with reduction of the postoperative hospitalization increased reduces the costs of admission. DISCLOSURE: Cosimo Lequaglie, None.

PURPOSE: Mediastinal Granuloma is an uncommon cause of a mediastinal mass. It is thought to be due to Histoplasma infection. Surgical resection is advocated to prevent the possible progression of mediastinal granuloma to fibrosing mediastinitis. Antifungals are also thought to be helpful. We evaluated the role of itraconazole in treatment of patients with mediastinal granuloma. METHODS: We evaluated five patients with mediastinal granuloma who were seen in the pulmonary clinic at the University of MissouriColumbia Hospital over the last three years. The patients were 30.6 ⫾ 9.9 years of age, and 3 of them were females. The diagnosis of mediastinal granuloma was confirmed by biopsy in all patients. Three patients were treated with Itraconazole (200 mg once a day). One patient had surgical resection only, and another patient had resection followed by treatment with Itraconazole. Patients were followed up for at least four months. Fungal stains and cultures were negative for all patients. Two patients had positive Histoplasma antibodies. RESULTS: Four months after starting therapy, patients receiving itraconazole alone were asymptomatic and they had almost total resolution of the mediastinal mass. The patient who had surgical resection did not have any recurrence on follow up. The patient who had resection followed by Itraconazole treatment had partial improvement. None of the patients treated with Itraconazole had liver function derangements. The most common side effect was diarrhea. CONCLUSION: Despite lack of evidence for active Histoplasma infection, patients with mediastinal granuloma responded well to treatment with Itraconazole. The medication was effective, safe and welltolerated. Itraconazole should be considered as the first line of treatment for mediastinal granuloma. CLINICAL IMPLICATIONS: Patients hwo have Mediastinal Gransuloma, whether diagnosed by biopsy or clinically, may have no evidence of a previous Histoplasma infection. Such patients would still respond to Itraconazole treatment, without the need for surgical resection of the mass. DISCLOSURE: Talaat Al Shuqairat, None.

PENETRATION OF AMPHOTERICIN B IN HUMAN LUNG TISSUE AFTER SINGLE LIPOSOMAL AMPHOTERICIN B INFUSION Cosimo Lequaglie MD* Franco Fraschini PhD Germana Demartini PhD Franco Scaglione PhD Centro di Riferimento Oncologico Basilicata, Rionero in Vulture, Italy PURPOSE: To investigate the tissue levels and distribution of amphotericin B in lung after i.v. administration of liposomal amphotericin B (L-AmB) in patients with lung cancer resected. METHODS: We enrolled 18 adult (⬎18 ys) patients with primary or secondary lung cancers. All patients were informed about the prospective study. There were 12 males and 6 females, both sexes ranging in weight from 53 to 86 kg, and in age from 28 to 65 years. L-AmB was administered by 1 hour single infusion at fixed doses of 1,5 mg/kg, and it was administered from 10 to 25 hours before the surgery. The starting and the end points of infusion were noted, the same for arterial and vein ligatures, and the end point of pulmonary tissue sample collection. Moreover, 10 ml of blood sample at the artery closure were collected. L-AmB was assayed in blood and lung tissue by an HPLC validated method of Bekersky et all

Respiratory Infections: Challenges 12:30 PM - 2:00 PM MICROORGANISMS RESPONSIBLE FOR FAILURE OF MACROLIDE TREATMENT OF ACUTE EXACERBATION OF CHRONIC BRONCHITIS: RESULTS OF BRONCHOSCOPIC CULTURES Robert P. Baughman MD* University of Cincinnati, Cincinnati, OH PURPOSE: Macrolide therapy is associated with clinical failure in some cases of acute exacerbation of chronic bronchitis (AECB). While the most likely reason for failure is resistant pathogens, there is little reliable microbiologic information in these patients. We have previously demonstrated that protected brush sample (PBS) provides the most reliable culture information in AECB (Baughman, R. P. et al. J Bronchology 2000;7:221-5). We used this technique to evaluate patients who failed azythromycin treatment for AECB. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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FLUOROQUINOLONE AS 2ND CHOICE THERAPY IN NOSOCOMIAL PULMONARY COMPLICATIONS AFTER RESECTION FOR LUNG CANCER Cosimo Lequaglie MD* Gabriella Giudice MD Centro di Riferimento Oncologico Basilicata, Rionero in Vulture, Italy

Wednesday, November 2, 2005 Respiratory Infections: Challenges, continued METHODS: Patients with a history of COPD and a clinical course consistent with AECB who had been treated with azythromycin and had persistent symptoms were evaluated. All patients underwent bronchoscopy with a PBS taken from the lower respiratory tract. The specimen was sent for semi-quantitative cultures. Patients were then treated with five days of moxifloxacin and repeat bronchoscopy was performed. No patient had been hospitalized in the prior six months. RESULTS: Thirteen patients have been studied. Eleven patients had one or more bacteria identified in the initial PBS specimen. Seven patients had at least one bacteria growing at ⬎1000 colony forming units (cfu)/ml from the initial PBS specimen. S. aureus was isolated in five (38%) of the initial PBS cultures. The S. aureus was sensitive to oxacillin in 4/5 case, ciprofloxacin 4/5 cases, and trimethoprim/sulfamethoxazole in 5/5 cases. Only one S. aureus was sensitive to erythromycin. After five days of moxifloxacin, no respiratory pathogens were identified in the repeat PBS specimen. CONCLUSION: Significant bacterial infection was identified in patients with persistent symptoms despite azythromycin therapy for their AECB. Among the pathogens was S. aureus. Treatment with a moxifloxacin was associated with clearance of the micro organism. CLINICAL IMPLICATIONS: Patients with repeated AECB infections and previously treated with macrolide therapy are at risk for multi drug resistant bacteria, including S. aureus. DISCLOSURE: Robert Baughman, Grant monies (from industry related sources) Bayer/Schering Plough; Consultant fee, speaker bureau, advisory committee, etc. Bayer/Schering Plough. NOSOCOMIAL PNEUMONIA AND ANTIBIOTIC RESISTANCE Prashant S. Borade MD* Daniel K. Lee MD Department of Respiratory Medicine, Ipswich Hospital, Ipswich, Suffolk, England, United Kingdom PURPOSE: The emergence of antibiotic resistant pathogens poses a significant threat to patients with nosocomial pneumonia. It is therefore important to evaluate the relationship between hospital-acquired pathogens and antibiotic resistance. METHODS: A prospective study was conducted in 100 consecutive patients with hospital-acquired infections admitted to the intensive care unit of which 46% had clinical, laboratory, and radiological evidence of nosocomial pneumonia. RESULTS: Isolated pathogens consisted of Klebsiella spp. (29%), Pseudomonas spp. (16%), Acinetobacter spp. (13%), Staphylococcus aureus (11%), Escherichia coli (10%), Enterobacter spp. (9%), methicillin-resistant S. aureus (2%), and Candida spp. (9%). Details of antibiotic resistance are shown in Table 1. Mortality was 33% in patients with nosocomial pneumonia.

CLINICAL IMPLICATIONS: Patients with nosocomial pneumonia remain at risk from antibiotic resistant pathogens.

Table 1⫺Antibiotic Resistance in Hospital-acquired Pathogens.

Amikacin Cefazolin Cefoperazone Cefotaxime Ceftazidime Ceftriaxone Ciprofloxacin Cloxacillin Co-amoxiclav Piperacillin

Klebsiella spp.

Pseudomonas spp.

Acinetobacter spp.

40%

39%

32%

S. aureus

55% 71% 60% 46% 48% 68%

46% 79% 79%

76%

36% 45% 73%

70% 60% 15%

25%

DISCLOSURE: Prashant Borade, None. DETECTION OF HISTOPLASMA CAPSULATUM ANTIGEN IN BRONCHIAL ALVEOLAR LAVAGE SPECIMENS BY IMPROVED ANTIGEN DETECTION ENZYME-LINKED IMMUNOASSAY Lawrence J. Wheat MD Ann M. Le Monte BS Chadi Hage MD* Kenneth S. Knox MD Debra Blue-Hnidy MD Thomas E. Davis MD Indiana University School of Medicine, Indianapolis, IN PURPOSE: Detection of H. capsulatum antigen by Enzyme-linked Immunoassay (EIA) is well documented, and an improved 2nd generation assay exhibits increased sensitivity and specificity for urine and serum specimens as compared to the original EIA. The purpose of this study is to compare sensitivity for detection of antigen in bronchial alveolar lavage (BAL) specimens in the 2nd generation vs. original H. capsulatum antigen assay. METHODS: BAL specimens previously submitted for H. capsulatum antigen detection were evaluated concurrently in the new 2nd generation vs. original immunoassays. RESULTS: Of the 39 BALs tested, 14 were positive in the 2nd generation assay vs. 10 in the original assay. For the positive specimens, the median antigen level was 4.15 EIA units in the 2nd generation vs. 1.36 EIA units in the original assay. CONCLUSION: Testing of BAL samples for H. capsulatum antigen may aid in rapid diagnosis. Sensitivity of antigen detection in BALs was greater in the 2nd generation assay. CLINICAL IMPLICATIONS: Bronchoscopy with BAL for Histoplasma antigen determination offers an adjunctive method for rapid diagnosis of pulmonary histoplasmosis. Improvements in the antigen immunoassay increase its sensitivity for diagnosis. DISCLOSURE: Chadi Hage, None. ENDOBRONCHIAL ASPERGILLOMA: A RETROSPECTIVE CASE REVIEW Doyun Kim MD* Yoonsu Chang MD Hyungjung Kim MD Chulmin Ahn MD Department of Internal Medicine Yonsei University College of Medicine, Seoul, South Korea

CONCLUSION: Antibiotic resistance in hospital-acquired pathogens is significant.

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PURPOSE: As compared to aspergilloma which is usually developed after complication of tuberculosis in Korea, endobronchial aspergilloma is a rare disease entity and clinical findings and natural course is not well known. We retrospectively analyze the clinical, radiological, and bronchoscopic finding and treatment options in patients confirmed as endobronchial aspergilloma. METHODS: From 1993 to 2005, eight patients were identified with endobronchial aspergilloma in Yongdong Severance hospital. We reviewed medical records for analysis of clinical, radiological, and bronchoscopic finding, and treatment options and result. All cases are confirmed as endobronchial aspergillosis by bronchoscopic biopsy and pathological finding. The patients ranged in age from 46 to 67 (mean 55.3). There are 3 males and 5 females. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Respiratory Infections: Challenges, continued

CYTOPATHIC CHANGES OF HERPES SIMPLEX VIRUS IN MECHANICALLY VENTILATED PATIENTS: WHAT DOES IT MEAN? Howard S. Weiss DO* Peter Spiegler MD Maritza L. Groth MD Winthrop University Hospital, Mineola, NY PURPOSE: Herpes Simplex Virus(HSV) causes tracheobronchitis and pneumonitis in critically ill patients. The characteristic endobronchial appearance is mucosal ulceration and membrane formation. We describe a series of critically ill patients with a normal endobronchial exam and cytopathic changes of HSV. METHODS: We reviewed all bronchoscopies performed in mechanically venilated patients in the medical ICU between October 2003 and March 2005 for evidence of mucosal lesions and cytopathic changes of HSV. Data including age, cause of respiratory failure, duration of mechanical ventilation and hospitalization prior to diagnosis, and level of HSV-1 IgG and IgM antibody(Ab)titers were recorded. RESULTS: Of 52 bronchoscopies performed, 7 subjects with cytopathic changes of HSV were identified (13.5%) and one with bronchoscopic features of HSV. This patient was immunosupressed and was excluded. The average age was 64.9 yrs (49-84 yrs). The duration of ventilation prior to diagnosis was 9.4d (0-14) and of hospitalization was 15.1d (8-47). HSV-1 Ab titers were obtained in 4 of 7 subjects. The HSV-1 IgG Ab was elevated in 4 of 4 subjects(100%)with an average level of 31.0(normal⬍0.90). The HSV-1 IgM Ab titer was elevated in 2 of 4 subjects with an average level of 1.3 of those with elevated levels (normal⬍0.91). Respiratory failure (RF) was due to pneumonia or atelectasis in all but one patient, who had microscopic polyangiitis. Five patients received therapy with acyclovir. No specific clinical features were seen in the subjects with HSV cytopathic changes compared to the rest of the sample. CONCLUSION: Cytopathic changes of HSV without obvious airway or parenchymal involvement are common in critically ill ventilated patients. To our knowledge, this has not been previously described in RF due to pneumonia or atelectasis. All cases occurred in fall and winter months (October to February). CLINICAL IMPLICATIONS: The significance of HSV cytopathic changes in critically ill ventilated adults and whether antiviral treatment is beneficial remains unknown. This may represent true herpes infection or that of another etiologic agent. Further studies are indicated to define whether treatment is necessary. DISCLOSURE: Howard Weiss, None.

DEVELOPMENT OF SURFACE OF PROTEIN CHIP FOR CHLAMYDIA PNEUMONIAE Woo J. Kim MD* Jong Seol Yuk PhD Se-Hui Jung Ji Hyun Sung Sung Joon Lee MD Seung-Joon Lee MD Kwon-Soo Ha PhD Kangwon National University, Chunchon, Kangwon-do, South Korea PURPOSE: Chlamydia pneumoniae is an important pathogen which is etiologic agent of acute and chronic infection. The diagnosis of chlamydial infection is based on serology. Current gold standard of diagnosis is MIF(microimmunoflurescence), but it is subjective and time-consuming. Recently, protein microarray using SPR(surface plasmon resonance) sensor is suggested to be a method for detection of infection. For development of protein chip for diagnosis of chlamydial infection, we investigated the morphology of surface with AFM(atomic force microscopy) on gold chip and detected interaction between antibody for Chlamydia pneumoniae and EB(elementary body) immobilized on surface by wavelength shift using SPR sensor. METHODS: For surface antigen, EBs of Chlamydia pneumoniae LKK1 were purified after they were grown in Hep-2 cells. For chip surface, gold arrays on glass slides were prepared and cleaned with NH4OH/H2O2/H2O at 80°C for 10 min. Charged arrays were prepared by PDDA(polydiallyldimethylammonium chloride) which has a positive charge and PSS(poly(sodium 4-styrenesulfonate) which has negative charge. After immobilization of chlamydial EB on PDDA surface and PSS surface, we investigated the surface using atomic force microscopy. After immobilization of EB of Chlamydia pneumoniae on surface, antibody for Chlamydia was applied on chip. We monitored the SPR wavelength-shift to detect antigen-antibody interaction using self-assembled SPR sensor. RESULTS: The chlamydial EBs on positively charged PDDA were visible on surface by atomic force microscopy but EBs on PSS surface were not detected. SPR wavelength increased after interaction of antibody for Chlamydia pneumoniae with EBs immobilized on charged gold surface. The wavelength-shift was correlated with concentration of antigens. CONCLUSION: We identified surface immobilization of EBs on gold surface with charged arrays and antigen-antibody interaction on gold chip. More researches are needed to apply to clinical implication. CLINICAL IMPLICATIONS: It may possible that protein chip would be used to diagnosis the atypical pneumonia using SPR sensor. DISCLOSURE: Woo Kim, None.

BACTERIAL DIFFERENTIATION BY ION MOBILITY SPECTROMETRY: FIRST RESULTS OF A PILOT STUDY Pattrick Litterst Michael Westhoff MD* Lutz Freitag MD Vera Ruzsanyi PhD Jo¨rg I. Baumbach PhD Lungenklinik Hemer, Hemer, Germany PURPOSE: Early diagnosis and specification of bacterial airway infection is of importance, especially in patients who are at high risk for respiratory failure, invasive or non-invasive ventilation and a prolonged hospital stay. METHODS: Ion mobility spectrometer (IMS) coupled to a multicapillary-column (MCC) identifies and quantifies volatile metabolites down to the ng/L- and pg/L-range of analytes within less than 500 s and without any pre-concentration. The IMS investigations are based on different drift times of swarms of ions of metabolites formed directly in air at ambient pressure. Head space over selected microbiological cultures was directly sampled for IMS-chromatograms. RESULTS: In this in-vitro study IMS-chromatograms of different bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus agalactiae, Haemophilus influenzae, Klebsiella pneumoniae, Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, Enterobacter cloacae) and Candida albicans were obtained. The selected bacteria and Candida albicans could be defined and distincted by different metabolites. CONCLUSION: Ion mobility spectometry seems to provide a tool for precise bacterial analysis. The results of this pilot study have to be proved by an in-vivo study, especially in patients with airway infections as COPD-exacerbation and pneumonia. CLINICAL IMPLICATIONS: A future aspect might be the implementation of an “IMS – beside-test” for the rapid diagnosis of airway infection including bacterial differentiation. DISCLOSURE: Michael Westhoff, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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RESULTS: All patients were symptomatic when hospitalization. Most common symptome is hemoptysis (100%), cough (63%), sputum (25%), chest discomfort (25%), and general weakness (13%). Most common underlying diseases were pulmonary tuberculosis (75%), bronchiectasis (25%), and small cell lung cancer (13%). Bronchoscopic finding is typical and more diagnostic than radiological findings. Seven out of eight cases had endobronchial aspergilloma in upper lobe bronchus. The location of endobronchial aspergilloma were right upper lobe bronchus (50%), left upper lobe bronchus (25%), left upper lobe lingular bronchus (13%), and lower lobe bronchus (13%). Endobronchial aspergilloma was developed right upper lobectomy stump site in a lung transplanted patient. Recurrent and moderate to large amount of hemoptysis was common, serious and unique symptoms. Five patients were surgically managed and the prognosis was good. A patient who refused surgery showed intermittent hemoptysis. Endobrochial aspergilloma in transplanated case and a case with acute pneumonia, DM and end stage renal disease was aggravated to invasive aspergillosis and patients were expired. CONCLUSION: Endobronchial aspergilloma is unique form of aspergillosis followed by pulmonary tuberculosis and most common symptom is recurrent hemoptysis. Surgery is choice of treatment in immunecompetent patient. CLINICAL IMPLICATIONS: Aspergillus organism in patient who had previous pulmonary tuberculosis occasionally forms endobronchial aspergilloma. DISCLOSURE: Doyun Kim, None.

Wednesday, November 2, 2005 Respiratory Infections: Challenges, continued CURRENT KNOWLEDGE AND PRACTICE TO DIAGNOSE PATIENTS WITH SEVERE COMMUNITY-ACQUIRED PNEUMONIA ADMITTED TO THE ICU Marcos I. Restrepo MD* Antonio Anzueto MD Eric M. Mortensen MD Jacqueline A. Pugh MD Mark L. Metersky MD Patricio Escalante MD Richard G. Wunderink MD Bonita T. Mangura MD on behalf Chest Infections Network VERDICT/STVHCS/UTHSCSA, San Antonio, TX PURPOSE: Community acquired pneumonia (CAP) is a common problem in clinical practice. Different recommendations regarding type and degree of diagnostic testing in patients admitted to the intensive care unit (ICU) are found in CAP guidelines from various professional societies. Our aim was to document the diagnostic procedures that clinicians use to assess patients with CAP admitted to the ICU. METHODS: Self-administered survey to assess physician preferences about CAP diagnostic approach in patients admitted to the ICU. Survey was generated based on literature review and committee consensus regarding diagnostic tests for CAP patients admitted to the ICU. Subgroup analysis was performed comparing academic practitioners vs. non-academic practitioners, and whether they work in an open ICU vs. closed ICU. The survey was e-mailed to ACCP members (in Chest infections and Critical Care network) in 2004. RESULTS: A total of 393 questionnaires (19% of submitted) were returned. The most common diagnostic methods used by clinicians were blood cultures (97%), sputum gram stain (83%), sputum culture (85%), Legionella urinary antigen (77%) and endotracheal aspirate (76%). Academic practitioners (n⫽182) ordered more endotracheal aspirates (79% vs. 68%; p⫽0.03), Legionella cultures (37% vs. 27%; p⫽0.05), but less serologic tests for atypical pathogens (34% vs. 46%; p⫽0.03) than non-academic practitioners (n⫽203). Practitioners working in a closed ICU (n⫽159) ordered more blood cultures (99% vs. 93%; p⫽0.01), and Legionella sputum cultures (39% vs. 26%; p⫽0.01) than those working in an open ICU (n⫽224). No other statistical significant differences were observed between groups for other diagnostic methods. CONCLUSION: Important differences were found in academic versus non-academic practitioners, and open ICU versus closed ICU situations regarding the diagnostic methods use in clinical practice for patients in the ICU with CAP. Current clinical practice guidelines for CAP diagnosis are applied differently according to type of practitioners and the setting where they work. CLINICAL IMPLICATIONS: Differences in clinician practice preferences in regard to diagnosis of CAP patients in the ICU should be taken into account for future, clinical, educational and research studies. DISCLOSURE: Marcos Restrepo, None. PULMONARY MANIFESTATIONS IN MALARIA Umashankar Mishra MD* Gandharva Ray MD M.K.C.G. Medical College, Berhampur, India PURPOSE: Malaria is still the major killer in developing countries like India. In recent years respiratory system is being recognized as one of the major manifestations of falciparum malaria. It is very important to recognize that the pulmonary involvement is due to malaria to institute treatment to reduce morbidity and mortality. Our study was to detect the incidence of pulmonary involvement in malaria and its impact on outcome. METHODS: Our study included 150 cases of slide positive malaria. Out of these 72(48%) Plasmodium vivax, 54(36%) Plasmodium falciparum and 24(16%) were mixed infections. The patients were thoroughly investigated for involvement of respiratory system. Besides routine hematological and biochemical investigations E.C.G. and chest x-ray were done in all patients. Patients having ARDS and acute pulmonary edema were subjected to echocardiography, haemodynamic monitoring by SwamGanz catheter and oxymetry. These patients were treated in ICU with mechanical ventilatory support with high concentration of inspired oxygen and use of Positive End Expiratory Pressure. RESULTS: Out of 150 cases of malaria 45 patients presented with respiratory symptoms in the form of cough (80%), dyspnoea (40%), expectoration (32%), chest pain (18%) and haemoptysis (4%). The clinical presentations were in the form of bronchitis (23 cases), pneumonia (8cases), acute pulmonary edema (2 cases), ARDS (7 cases), pulmonary tuberculosis (3 cases) and respiratory muscle fatigue (2 cases). Out of the 45 cases with respiratory symptoms 42 (93.4%) had falciparum malaria. Four out of 7 patients of ARDS and both the 2 patients with acute pulmonary edema died. CONCLUSION: Malarial atypical respiratory presentations are higher than reported in the literature. P. falciparum malaria is responsible for

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most of the respiratory manifestations. Acute pulmonary edema and ARDS have high-grade mortality in spite of intensive care. CLINICAL IMPLICATIONS: Patients of high fever with respiratory symptoms should have always blood slide examination for malarial parasites in endemic areas and prompt antimalarial therapy should be started to save life. DISCLOSURE: Umashankar Mishra, None.

Sepsis and Shock: Treatment 12:30 PM - 2:00 PM EFFECTS OF AUTOTRANSFUSION ON MICROVASCULAR PERFUSION USING PASSIVE LEG-RAISING IN PATIENTS WITH SEPTIC SHOCK Peter E. Spronk PhD* Danie¨l F. Faber MD Johannes H. Rommes PhD Gelre Hospitals (Lukas site), Apeldoorn, Netherlands PURPOSE: Passive leg raising (PLR) can be used effectively to treat hypotension associated with hypovolemia. Shock is associated with impairment of microvascular flow. We investigated the microvascular response to PLR in patients with shock. METHODS: Patients who were admitted to the ICU with septic shock (defined by MAP⬍60 mm Hg and sepsis according to standard criteria) were assessed for sublingual microvascular perfusion by orthogonal polarization spectral (OPS) imaging before and 1 minute after PLR (45 degrees upward). Perfusion was estimated using a semi-quantitative microvascular flow index (MFI) in small (diameter 10-25 ␮m), medium (25-50 ␮m), and large-sized (50-100 ␮m) capillaries (0⫽no flow; 1⫽sludging (0 – 0,5 mm/s), 2⫽moderate flow (0,5 – 1,0 mm/s), 3⫽high flow (1,0 – 3,0 mm/s)). RESULTS: Ten patients (2 female, 8 male; mean age 67 years) participated in this study. Mean APACHE-II score was 23 (range 13-33). Mean lactate levels were 3.5 mmol/l. MAP and CVP inceased after PLR (table). Microvascular flow increased in parallel in most patients, i.e. flow increased predominantly in small microvessels, while flow in the larger microvessels remained relatively preserved. In 4 patients, microvascular flow hardly improved after PLR. Also, after infusion of fluids until CVP was above 10, in 3 of those 4 patients flow had still not normalized. After giving 0,5 mg nitroglycerin iv as described before, flow normalized in all cases. CONCLUSION: Changes in sublingual microvascular perfusion after PLR reflect the recruitment of blood from the venous leg pool in shock patients. Microvascular flow improves by volume infusion in most cases. Some patients may require additional infusion of nitroglycerin to actively open the microvascular system. CLINICAL IMPLICATIONS: OPS imaging may be a valuable bed-side tool for assessing optimal fluid resuscitation.

MAP CVP MFI MFI MFI (mean, (mean; small medium large mm Hg) mm Hg) microvessels microvessels microvessels Before PLR After PLR

50 57 P⬍0,05

4 8 P⬍0,01

0,8 1,7 P⬍0,01

1,9 2,6 P⬍0,05

2,8 3,0 P⬍0,05

DISCLOSURE: Peter Spronk, None. USE OF VASOPRESSIN FOR SEPTIC SHOCK IN A NONMONITORED SETTING Manoj L. Karwa MBBS Kaye Hale MD* Montefiore, Bronx, NY PURPOSE: To review cases of septic shock treated outside the intensive care unit (ICU) setting with a fixed non-titratable continous infusion of vasopressin, determining its effects on survival, hemodynamics, and any adverse effects. METHODS: With permission from our IRB, we conducted a retrospective review of all patients that received vasopressin infusion for septic shock, between the dates of January 1, 2003 and December 31, 2003. In CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Sepsis and Shock: Treatment, continued a tertiary care academic medical center. Values were expressed as percentages and means (standard deviation). RESULTS: Of 193 patients that received vasopressin infusion, 29 patients with septic shock were identified as having been treated outside the ICU. They had the following characteristics Age of 74.7 years (16.1), 45% male, 45% were intubated, APACHE II score 20.1 (7.2), and 52% of the cases had do not resuscitate orders in place. 19 (65%) of these patients had survived the hospitalization. All received a non-titrating infusion of 0.04 units/minute of vasopressin the average duration of which was 64.8 (54.8) hours. Systolic blood pressure had increased by 25.7% from 82.7 mmHg at onset to 101-mmHg post 48 hours infusion. Mean arterial pressure had increased by 21% from 60.9 to 78 mmHg. Serum Lactate decreased from 1.7 at onset to 0.84 at end of the infusion period, BUN from 43.9(33) to 27.8(21), and serum creatinine from 1.7 (1.6) to 1.3 (1.5). 10.3% patients died during the infusion. Bradyarrythmias and tissue necrosis were not observed in any of the cases. CONCLUSION: For patients with septic shock who do not meet admission criteria to the ICU, therapy for with a non-titrating dose of vasopressin may be an additional therapy utilized on the regular hospital ward. CLINICAL IMPLICATIONS: Vasopressin at a fixed dose of 0.04 units for use in patients with septic shock who do not otherwise meet criteria for admission into the ICU may have significant implications on the utilization of resources such as cardiac and hemodynamic monitoring, as well as nursing resources. DISCLOSURE: Kaye Hale, None.

PURPOSE: Hypoxia induces an inflammatory cascade that results in injury to the microvasculature. Specifically, leukocyte adhesion to the endothelium begins, and leukocyte emigration and vascular leak follow. The mechanism of hypoxia related injury is incompletely understood, but involves oxidant stress. Infusion of antioxidants has been shown to prevent hypoxia induced microvascular injury. Activated protein C is reported to have anticoagulant and anti-inflammatory properties. Its protective role is best described during sepsis. However, it has been utilized, with some success, in experimental models of ischemic injury. Our experiments are designed to characterize the effects of activated protein C on the microvasculature during systemic hypoxia and compare them to those of a potent antioxidant, alpha-lipoic acid. METHODS: Experiments utilize intravital microscopy of the intact rat venular bed. Five groups were utilized: saline control, activated protein C infusion alone (100mcg/kg bolus), hypoxia alone (10% O2), simultaneous hypoxia ⫹ activated protein C infusion, and hypoxia ⫹ alpha lipoic acid. Measurements of leukocyte adherence (# per 100um venule), leukocyte emigration (# per 4000 um2), and venular leak by fluorescein isothiacyanate-labeled albumin (Fi/Fo) are reported below. RESULTS: ⫾ SEM. CONCLUSION: Activated protein C infusion and antioxidant infusion prevent hypoxia-related microvascular injury as evidenced by measurements of leukocyte adherence, leukocyte emigration and vascular leak. CLINICAL IMPLICATIONS: This similarity may reflect a common mechanism of action. This work is important because the understanding of the hypoxia-induced inflammatory cascade is essential to a plethora of disease states, such as myocardial infarction, sepsis, ARDS and trauma. Further characterization of the effects of activated protein C in hypoxic injury could lead to new therapeutic use.

Normoxia Hypoxia Activated protein C Activated protein C ⫹ hypoxia Alpha-lipoic acid ⫹ hypoxia

Leukocyte Adherence

Leukocyte Emigration

Vascular Leak

1.6 ⫾ .5 14.5 ⫾ 1.2 2.0 ⫾ .8 4.4 ⫾ 1.5

2.6 ⫾ .19 12.3 ⫾ 2.2 3.1 ⫾ .4 3.5 ⫾ .3

.14 .82 .19 .25

0.6 ⫾⳪⳪0.4

2.3 ⫾ .3

DISCLOSURE: Sonja Bartolome, None.

⫾ ⫾ ⫾ ⫾

.04 .14 .05 .14

.10 ⫾ .04

PURPOSE: PROGRESS is an international, prospective, observational registry on severe sepsis patients in Intensive Care Units. METHODS: Patients diagnosed with severe sepsis (suspected on proven infection ⫹ ⬎1 acute sepsis induced organ dysfunction[s]) were included; there were no exclusion criteria. Data were entered from participating institutions via secured website. An independent advisory committee governs PROGRESS. Software development and website maintenance are funded by Eli Lilly. RESULTS: Results As of 3/11/05 there were 11,925 patients in the registry with 8,456 from the top 10 enrolling countries. (Table #1). CONCLUSION: Management of severe sepsis varies across geographic regions and mortality rates are high. The similarity of ROC curves provides support for the validity of the database and are independent predictors of death despite these variations. CLINICAL IMPLICATIONS: More research is necessary to explore the reasons for differing patient management and outcomes.

Germany Argentina Brazil Canada India Malaysia Australia US Mex Philippines

ICU Mortality APACHE II

n

n

n

n

n

n

n

1436

1326

921

889

841

684

679

671 516

n

n

493

38%

46%

56%

32%

37%

56%

22%

33% 39%

41%

27

23

23

24

20

24

21

26

n

22

24

(mean) ⬎2 OD

90%

75%

93%

90%

93%

91%

87% 93%

94%

Vent use

89%

79%

92%

90%

64%

99%

89%

76% 95%

76%

Vasopres.

93%

69%

75%

64%

59%

89%

88%

76% 90%

79%

Fluid resuscitation 95%

86%

94%

na

63%

93%

86%

84% 97%

67%

9%

10%

na

37%

29%

53%

19% 32%

14%

46%

30%

59%

38%

29%

11%

30%

29% 30%

25%

Renal replacement 33%

Albumin Low dose

4.5%

na

steroids 12%

21%

14%

15%

22%

26%

18% 13%

17%

5%

2%

7%

8%

4%

2%

8%

27% 11%

2%

Unfx heparin*

63%

59%

55%

73%

8%

34%

61%

30% 10%

8%

Low mole. Wt.

48%

14%

45%

14%

21%

16%

16%

32% 58%

17%

DroAA

Heparin*

*Sum may exceed 100% due to possibility of sequential treatment DISCLOSURE: Konrad Reinhart, Consultant fee, speaker bureau, advisory committee, etc. Speaker is a member of the PROGRESS advisory committee. EVALUATION OF THE MANAGEMENT OF SEPSIS IN THE EMERGENCY DEPARTMENT Maria I. Rudis PharmD* Kathy L. Rowland PharmD Jill M. Hara PharmD Philip Bretsky PhD Mark Hollinger RN Kathryn Challoner MD Ed Newton MD USC School of Pharmacy, Los Angeles, CA PURPOSE: The 2004 Surviving Sepsis Campaign Guidelines (SSCG)emphasize the importance of early aggressive sepsis treatment to reduce mortality. We sought to determine compliance with the SSCG in patients(pts) with sepsis in the ED, specifically the timeliness and extent offluid administration and antimicrobial therapy, the use of earlygoaldirected therapy (EGDT), and the nature of vasopressor use. METHODS: Retrospective cohort of consecutive pts with an ED diagnosis of’sepsis’ in ourlarge, urban, county, level I trauma center from 12/03-5/04. Pts wereexcluded if age⬍18yrs,had arequirement for immediate surgery, DNR status or were incarcerated. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

ACTIVATED PROTEIN C INFUSION MIMICS ANTIOXIDANT EFFECTS ON HYPOXIA-INDUCED MICROVASCULAR INJURY Sonja D. Bartolome MD* Alan J. Casillan John G. Wood PhD Steven Q. Simpson MD Amy R. O’Brien-Ladner MD University of Kansas School of Medicine, Kansas City, KS

DATA FROM THE TOP TEN ENROLLING COUNTRIES CONTAINED IN THE PROGRESS (PROMOTING GLOBAL RESEARCH EXCELLENCE IN SEVERE SEPSIS) REGISTRY DEMONSTRATES VARIATIONS IN TREATMENT AND HIGH MORTALITY RATES Konrad Reinhart* Jean-Louis Vincent Graham Ramsay Claudio Martin Eliezer Silva Richard Beale Frank M. Brunkhorst Mitchell Levy Gregory Martin Mary Ann Turlo Samiha Sarwat Jonathan Janes Universitasklinikum Jena, Jena, Germany

Wednesday, November 2, 2005 Sepsis and Shock: Treatment, continued RESULTS: After excluding 23 pts who did not meet inclusion criteria fromall ptswith sepsis (n⫽107), our cohort consisted of 84 pts with a mean age of 50.2⫾ 19.6 yrs and 49% males. The ethnicity reflects that ofourgeneral ED population (62% latino, 18% caucasian, 11% Asian and9%African American). Mean volume of IV fluid administered in the first 6h in the ED was 1951 ⫾ 1644 ml, with the majority of pts(60.7%) receiving 1-3.5 L. Mean time to antibiotic administration fromtime ofpresentation (4.7 ⫾ 4.3 h) or from physician evaluation (2.3 ⫾ 2.9 h) exceeds the recommended 1 h by the SSCG. Vasopressorswere given to 26 (30.9%) pts, with the majority receiving dopamine(25.0%) and norepinephine (6%) as first line agents. No pt was managed using EGDT. Mean LOS in the ED,ICU and hospital were 21.6 ⫾18.6h, 8.9 ⫾ 13.8d, and 13.6 ⫾ 18.3 d, respectively. CONCLUSION: ED management of pts with sepsis does not currently meet the parameters as set by SSCG. Assessment of 28-day mortality may determine impact of ED treatment of septic pts. CLINICAL IMPLICATIONS: Interventions to optimize compliance with SSCG are needed in the ED. DISCLOSURE: Maria Rudis, None.

INDEPTH DATABASE OF SEVERE SEPSIS PATIENTS SHOWS FEWER CARDIAC EVENTS IN DROTRECOGIN ALFA (ACTIVATED) PATIENTS VS PLACEBO PATIENTS Darell Heiselman DO* Stephen Lowry MD Jean-Francois Dhainaut MD Pierre-Francois Laterre MD Roland Schein MD Michael Seneff MD Jean-Pierre Sollet MD Antonio Artigas MD Jonathan Janes Frank Booth MD Andreas Sashegyi PhD Michael Cobas Meyer MD Akron General Medical Center, Akron, OH PURPOSE: This study was done to better understand treatment risks and benefits of drotrecogin alfa (activated) (DrotAA). METHODS: A blinded, independent clinical evaluation committee evaluated all serious adverse events (SAEs) within INDEPTH, a 4459 patient integrated database of five clinical trials of patients with severe sepsis. Trials were conducted by a single sponsor (Eli Lilly and Company). We report the incidence of cardiac serious adverse events in placebo treated patients (n⫽1231) and in those treated with DrotAA (n⫽3228). RESULTS: SAEs were characterized as occurring either during the study drug infusion period or during the 28-day survival observation period. Sepsis-related clinical outcomes and sepsis-related deaths were not considered SAEs unless attributable to study drug. Despite higher survival in DrotAA, overall SAEs rates were similar in both groups. Observed rates for MI and arrhythmia were significantly lower during infusion period and at 28 days.

Infusion Period: All SAE: N (%) All bleeding Arrhythmia w/o MI All non bleedingMyocardial Infarction Death at 28 Days following any Infusion Period SAE MI/ Thrombotic All stroke/ other arterial thrombotic events28 Day Observation Period: All SAE: N (%) Arrhythmia w/o MI Arrhythmia without MIMyocardial Infarction 0ther ? Death at 28 days YesDeath at 28 Days following any SAE

DrotAA N⫽3228

Placebo N⫽1231

p Value*

199 (6.2%) 37 (1.15%) 11 (0.34%)

78 (6.3%) 30 (2.44%) 10 (0.81%)

NS 0.0015 0.04

87/199 (43.7%)†

47/78 (60.3%)†

0.013

425 (13.2%)

170 (13.8%)

NS

54 (1.67%) 17 (0.53%)

43 (3.49%) 15 (1.22%)

⬍0.001 0.014

137/425 (32.2%)†

72/170 (42.4.3%)†

0.02

†In these rows only, the denominator for the calculation of percentage mortality is the number of patients at that time point with an SAE. 378S

AUTONOMIC NERVOUS SYSTEM-BASED EARLY GOAL DIRECTED THERAPY IN THE TREATMENT OF SEVERE SEPSIS AND SEPTIC SHOCK: PRELIMINARY EVIDENCE William C. Shoemaker MD Adam Colombo DO Joseph Colombo PhD* Department of Science and Technology, Bucks County Community College, Newtown, PA PURPOSE: To investigate the clinical efficacy of early goal-directed therapy based on autonomic nervous system (ANS) monitoring (noninvasive, simultaneous, independent measures of sympathetic (SNS) and parasympathetic nervous system (PSNS) activity) in patients with severe sepsis and septic shock. METHODS: 208 severe sepsis and septic shock patients were studied in an urban, level 1 university-run trauma service.: ANS monitoring measured the sequential patterns of SNS and PSNS activity immediately after admission to the emergency department (ED). Also measured noninvasive hemodynamic patterns, including: cardiac index (CI) by bioimpedance, as well as HR, and mean arterial pressure (MAP) to evaluate cardiac function, pulse oximetry to reflect changes in respiratory function, and transcutaneous oxygen (PtcO2) to reflect tissue perfusion/ oxygenation. RESULTS: In all patients autonomic balance (the ratio of SNS to PSNS activity) was markedly abnormal. These patients also had low MAP, CI, and PtcO2/FiO2 values associated with increased HRV that reflect increased autonomic activity. Patients with improved or restored ANS early in their ED stay, all survived; while the latter admission to ED had mixed results. ANS balance was not well-correlated with HR, BP, and CI. CONCLUSION: In nonsurvivors, severe sepsis and septic shock were associated with pronounced ANS imbalance. Survivors had relatively normal ANS balance. Patients that first presented poor ANS balance had balance improved due to therapy, also survived. CLINICAL IMPLICATIONS: Shows a correlation between the condition of severe sepsis and septic shock patients and their autonomic balance. DISCLOSURE: Joseph Colombo, Shareholder Joe Colombo, PhD is a share holder and part owner of Ansar, Inc.; Employee Joe Colombo is the Executive VP and Medical Director of Ansar, Inc.

Sepsis: The Faces of Sepsis 12:30 PM - 2:00 PM

Table 1 Variable

CONCLUSION: These data show a possible association between DrotAA administration and a reduced rate of cardiac events in patients with severe sepsis. CLINICAL IMPLICATIONS: Further investigation may be justified. DISCLOSURE: Darell Heiselman, Consultant fee, speaker bureau, advisory committee, etc. Advisory panel fee.

PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE ARE AT HIGHER RISK OF SEPSIS David A. Hasselbacher MD* David M. Mannino MD Rolando Berger MD University of Kentucky, Lexington, KY PURPOSE: Although studies have been completed examining the cause of death and rates of sepsis in patients with chronic obstructive pulmonary disease (COPD) no study has been completed examining COPD as a risk factor for sepsis. The goal of our study was to prospectively examine COPD as a risk factor for sepsis. METHODS: Data from the Atherosclerosis Risk in Communities (ARIC) study (a prospective study of 15,792 U.S. adults age 45-65 years old) were used in this analysis, with up to 11 years of follow-up data available. A diagnosis of COPD was made using modified GOLD criteria (we added a “restrictive” category consisting of people with an FEV1/ FVC ⬎ 70% and an FVC ⬍ 80% predicted). Episodes of sepsis or pneumonia were obtained using diagnostic codes (ICD-9 codes 038 and 480-487, respectively) from hospital discharge. Out of 15,586 patients analyzed there were 136 documented cases of sepsis. A logistic regression, controlling for age, sex, cigarette smoking, body mass index, education CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Sepsis: The Faces of Sepsis, continued level, family income was completed using the SUDAAN software package. A second regression model added hospitalization for pneumonia to the above noted variables. RESULTS: The table depicts the classification of lung disease with incidence of sepsis, pneumonia, odds ratio for sepsis with 95% confidence intervals (controlling for the factors noted in the methods) and odds ratio for sepsis when controlled for pneumonia. Pneumonia was a very strong predictor of sepsis (odds ratio 22.7, 95% CI 14.5, 35.4). CONCLUSION: Patients with GOLD stage 2 or higher COPD and those with restrictive disease had an increased risk for sepsis in this cohort. After controlling for pneumonia, the risk was attenuated, and only significant in patients with restrictive disease. CLINICAL IMPLICATIONS: These findings suggest that most, but not all, of the increased risk of sepsis among patients with COPD is related to their increased risk of developing pneumonia.

Lung Disease

3 & 4 281 2 1491 1 1688 0 2192 1325 8609

% % Sepsis Pneumonia 3. 6 1.7 0.6 0.9 2.2 0.5

12.8 4.3 2.1 4.2 1.7 0.9

OR for Sepsis

OR controlled for Pneumonia

4.2(2.0-9.1) 2.3(1.3-3.8) 0.9(0.5-1.9) 1.5(0.9-2.6) 3.3(2.0-5.5) 1.0

1.9(0.8-4.4) 1.7(0.9-2.9) 0.8(0.4-1.7) 1.5(0.8-2.5) 2.4(1.4-4.2) 1.0

DISCLOSURE: David Hasselbacher, None.

SEVERE SEPSIS IS ASSOCIATED WITH AN APOPTOSIS-MEDIATED DECREASE IN HEPATIC BACTERIAL CLEARANCE Alix Ashare MD* Timur Yarovinsky PhD Martha Monick MS Gary Hunninghake MD University of Iowa, Iowa City, IA PURPOSE: The development of liver disease during the course of sepsis is associated with increased mortality. We hypothesized that worsening liver function would result in decreased bacterial clearance and be associated with increased dysfunction of other organs and increased mortality. METHODS: Mild and severe sepsis were generated in C57BL/6 mice via intratracheal inoculation with 103 or 104 organisms of Pseudomonas aeruginosa, respectively. To evaluate bacterial clearance by the liver, portal vein and right ventricle bacterial concentrations were measured using quantitative real-time PCR with primers specific for P. aeruginosa. Liver and cardiac injury was assessed by ALT and CK levels. Organ apoptosis was evaluated with a caspase-3 activity assay. Levels of IL-1 beta and TNF-alpha were measured by ELISA. To inhibit apoptosis, a subset of mice was pre-treated with the caspase inhibitor z-VAD-fmk. RESULTS: Mild and severe sepsis resulted in 20% and 60% mortality at 36 hours, respectively. Mild sepsis triggered a short but significant hepatic inflammatory response and some liver injury that returned to baseline by 24 hours. Effective bacterial clearance was not lost in this model. Severe sepsis caused a prolonged hepatic inflammatory response and liver injury that continued to worsen over time. Effective bacterial clearance was eventually lost in this model and was associated with increased injury to other organs, as well as increased mortality. Pretreatment with z-VAD-fmk resulted in preservation of hepatic bacterial clearance and increased survival 24 hours after infection with the severe sepsis model. CONCLUSION: We conclude that liver injury in sepsis is associated with decreased bacterial clearance, increased end-organ damage, and mortality. Inhibition of apoptosis preserves hepatic bacterial clearance and improves survival.

AUTONOMIC AND HEMODYNAMIC ACTIVITY IN SEPSIS William C. Shoemaker MD Charles C. Wo BS Payman Fathizadeh MD Joseph Colombo PhD* Department of Science and Technology, Bucks County Community College, Newtown, PA PURPOSE: The aim is to evaluate early hemodynamic patterns of patients with severe sepsis and septic shock and compare/contrast the effects of sepsis as a primary etiologic event versus sepsis as a secondary complication after trauma, surgery etc. with simultaneously monitored sympathetic (SNS) and parasympathetic nervous system (PSNS) activities measured by the variability of the heart rate (HR) and respiratory rate (RR). METHODS: Level 1 university-run trauma service in a public hospital.Non-invasively monitored the early hemodynamic patterns in 208 severely septic patients beginning shortly after admission to the emergency department (ED). Simultaneously, monitored and compared the spectrum of HR and RR variability patterns, as markers of autonomic activity, with temporal hemodynamic patterns in 73 of these septic patients. The HR variability was measured to evaluate the low frequency area (LFa), which reflects SNS. The high frequency area (RFa) is indicative of PSNS activity. The LFa/RFa, reflects the relationship of SNS to PSNS. Concurrent noninvasive hemodynamic monitoring consisting of: a) cardiac output by bioimpedance, HR, and mean arterial pressure (MAP) to reflect cardiac function, b) pulse oximetry (SapO2) to reflect changes in pulmonary function, and c) transcutaneous oxygen (PtcO2) indexed to the FiO2 as a marker of tissue perfusion/oxygenation. RESULTS: Non-survivors had higher LFa and RFa values than the survivors did. The increased RFa preceded the increases in LFa in non-survivors and a higher percentage of sympathetic activity. These changes were more marked when measured before sedation and pain medication. In survivors, these patterns were associated with increased cardiac index (CI), and HR, normal MAP, SapO2, and normal tissue perfusion indicated by PtcO2/FiO2 ratios. Nonsurvivors had relatively normal CI, hypotension, tachycardia, poor tissue perfusion, borderline SapO2, and reduced oxygen delivery. CONCLUSION: In the period immediately after ED admission of patients with sepsis increased ANS activity was observed more pronounced in non-survivors. This activity was associated with increased HR, MAP, and CI, and a tendency toward reduced tissue perfusion/oxygenation. CLINICAL IMPLICATIONS: Established relation between hemodynamic variables and the ANS balance of Sepsis patients. DISCLOSURE: Joseph Colombo, Shareholder Joe Colombo, PhD is a shareholder and part owner of Ansar, Inc.; Employee Joe Colombo is the Executive VP and Medical Director of Ansar, Inc.

RISK FACTORS FOR CANDIDEMIA: COMPARISON BETWEEN MEDICAL AND SURGICAL INTENSIVE CARE UNIT PATIENTS Stephen B. Heitner MD* Glenn Eiger MD Robert Fischer MD Emma C. Scott MD Aba Somers MD Albert Einstein Medical Center, Philadelphia, PA PURPOSE: Candidemia is a potentially lethal and common infection in the intensive care unit (ICU). A number of risk factors for invasive candidiasis have been identified in previous studies. Our objective is to determine if there is a difference in the risk factor profile of medical ICU (MICU) and surgical ICU (SICU) patients. METHODS: A retrospective analysis was conducted at a large community-based teaching hospital. Subjects had positive blood cultures for Candida species and were admitted to the MICU and SICU over a two-year time period. Patients with known malignancies or other immunocompromising states were excluded. Demographic variables, Simplified Acute Physiological Score (SAPS), and known risk factors for candidemia were compared between MICU and SICU patients. Chi-square analysis and independent-sample t-tests were applied. RESULTS: Forty-three patients were included for analysis. MICU patients had significantly higher SAPS scores (57.8 vs. 41.1, p⫽ 0.005.). CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

Gold Stage Gold Stage Gold Stage Gold Stage Restrictive Normal

N

CLINICAL IMPLICATIONS: This study suggests that bacterial clearance by the liver may be an important determinant of the outcome of sepsis. DISCLOSURE: Alix Ashare, None.

Wednesday, November 2, 2005 Sepsis: The Faces of Sepsis, continued SICU patients had a greater number of antibiotic days (42 vs. 18.38, p⬍0.001) and received a larger number of antibiotics (4.68 vs. 3.04, p⫽0.002). SICU patients were on mechanical ventilation longer (19.37 vs. 8.5 days, p⫽ 0.02) and had longer hospital stays (56.7 versus 35.3 days, p⫽0.03). SICU patients tended to have greater frequencies of other risk factors including parenteral nutrition and central venous catheters. There was no difference in mortality rate between the two populations. CONCLUSION: Significant differences exist between MICU and SICU patients who develop candidemia. The observed trend in our study is that SICU patients had higher frequencies of traditional risk factors, while MICU patients had worse physiological indices. CLINICAL IMPLICATIONS: Traditional risk factors for the development of candidemia need further analysis to determine whether they are equally applicable to both MICU and SICU patients. DISCLOSURE: Stephen Heitner, None.

MYCOBACTERIUM TUBERCULOSIS AN UNUSUAL YET HIGHLY FATAL CAUSE OF SEPTIC SHOCK Raquel Nahra MD* Sergio L. Zanotti-Cavazzoni MD Anand Kumar MD Cooper University Hospital, Camden, NJ PURPOSE: To describe a group of patients with septic shock caused by M. Tuberculosis and compare their outcomes to those of patients with septic shock caused by other microorganisms. METHODS: Data was extracted from a multicenter database with information from the records of 2731 patients with septic shock. Patients with septic shock caused by M. Tuberculosis were identified by positive blood or multi-site cultures. RESULTS: A total of 2731 patients with septic shock were studied. Eleven patients (0.4%) had septic shock caused by M.Tuberculosis (MTB group). In the MTB group, the mean age was 44.2 (⫾19.5) years, mean APACHE II score was 26 (⫾8), 36% were males and 64% were females. Comorbid conditions included; alcohol use 54%, non-HIV immunosupresive diseases 36.4%, and diabetes mellitus 18.2%. None of these patients had documented HIV. Overall mortality in the MTB group was 81.8 %, and mean length of stay in the ICU was 12.7(⫾ 17.1) days. Inapropriate initial antimicrobial coverage based on culture results was given to five patients (45.5%) in the MTB group. When compared to patients with septic shock caused by other microorganism (OTH group), patients in MTB group were younger (44.27(⫾19.5) years vs 62.66 (⫾16.4)) years p ⫽ 0.0002), and more likely to have alcohol use as a comorbidity (54.4% vs 13.8 %, p⫽ 0.0013). Patients in the MTB group were more likely to receive inappropriate initial antimicrobial therapy than patients in the OTH group (45.5% vs 18.6%, p⫽0.0039). Patients in the MTB group had a higher mean ICU LOS (12.21 days vs 8.1 days ), had a higher overall mortality (81.8% vs 56.2% , p ⫽ 0.12 ), and were more likely to develop hepatic failure (p 0.0039). CONCLUSION: M. Tuberculosis is an uncommon cause of septic shock. However, when it occurs it is associated with increased morbidity and mortality and a significant delay in institution of appropriate antituberculous treatment. CLINICAL IMPLICATIONS: Mycobacterium Tuberculosis should be thought of as a possible cause for septic shock in apropriate clinical situations. DISCLOSURE: Raquel Nahra, None.

Sleep Disorders: Other Than Sleep Apnea 12:30 PM - 2:00 PM QUANTIFYING MICROSLEEP TO ASSESS SLEEPINESS Allen J. Blaivas DO* Rajeshri Patel MD Kenneth Antigua David Hom Hormoz Ashtyani MD UMDNJ-New Jersey Medical School, Newark, NJ PURPOSE: The qualitative presence of microsleep during the Multiple Sleep Latency Test (MSLT) has been shown to correlate with an increased incidence of subjective complaints of sleepiness, tiredness, accidents/near accidents, and gap driving. However, there is no data as to how to quantify microsleep and effectively incorporate it as a diagnostic tool in the measurement of sleepiness. The purpose of this study is to

380S

integrate microsleep to the MSLT score and determine if it improves the correlation between the MSLT and symptomatic sleepiness. METHODS: The charts of 54 patients who had an MSLT score of greater than 5 minutes and the presence of microsleep on at least one nap were reviewed. If microsleep was present in a given nap it was used as a surrogate for sleep onset. This MSLT plus microsleep score (MSLT⫹) was then averaged into the total sleep latency and compared with the MSLT score to determine if it improves correlation with the ESS. RESULTS: Using the Spearman correlation the MSLT⫹ improved the association between ESS when compared to MSLT (r⫽0.106 versus r⫽0.063), but the results were not statistically significant. Of note, both the MSLT and MSLT⫹ were only weakly correlated to the ESS. CONCLUSION: The addition of microsleep onset to the MSLT score as a quantitative assessment tool failed to significantly enhance the correlation between subjective and objective accounts of sleepiness, beyond the improvement seen in the MSLT value by the simple presence of microsleep alone. CLINICAL IMPLICATIONS: The use of microsleep as a marker of excessive daytime sleepiness has been previously demonstrated, as has its qualitative presence as an enhancement to the MSLT score. Its clinical significance in daily life also can not be overstated, as it has been labeled as contributory in multiple large accidents and catastrophes. This study attempted to determine its exact implication on the way sleepiness is quantified; however the “holy grail” of accurately correlating objective sleep propensity to symptomatic excessive daytime sleepiness continues to elude us.

DISCLOSURE: Allen Blaivas, None.

THE CLINICAL SIGNIFICANCE OF SPONTANEOUS AROUSALS INDEX (SAI) DURING POLYSOMNOGRAPHY Joe G. Zein MD* Maroun M. Tawk MD Tarek Dernaika MD Gary T. Kinasewitz MD William C. Orr PhD The University of Oklahoma, Health Sciences Center, Oklahoma City, OK PURPOSE: Sleep arousals are important for reestablishing a patent airway subsequent to an obstructive event and to protect against prolonged hypoxemia. Spontaneous arousals (SA) are also considered among the clinical indicators of upper airway resistance syndrome (UARS). We examined the frequency and clinical significance of SA in patients referred for evaluation of obstructive sleep apnea (OSA). METHODS: This was a retrospective study of 118 consecutive adult patients presenting for polysomnography from October 2002 till March 2003. A multivariate logistic regression was constructed with the rate of SA as the dependent variable. Apnea Hypopnea Index (AHI), Sleep efficiency (SE), mean SaO2, and stage 1 were independent variables. Arousals were defined according to the American Academy of Sleep Medicine established criteria. Data are presented as mean ⫾ SEM. RESULTS: The mean total recording time was 396⫾6 with a total sleep time of 308⫾10 min. An increased SAI (⬎10/hr) was present in 20 CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Sleep Disorders: Other Than Sleep Apnea, continued patients (19%). Age, gender, Epworth Sleepiness Scale, sleep onset latency, periodic limb movement index were similar in patients with high and normal SAI. A higher SAI was associated with a higher AHI (57.8⫾6 vs.32.5⫾3; p⫽0.0002)(r⫽0.4; p⬍0.05), a lower SE (57⫾3 vs. 77⫾2%; p⫽0.002), a higher stage 1 sleep (11.5⫾1.2 vs. 6.5⫾0.6 %; p⫽0.0003) and a lower mean SaO2 (90.4⫾0.8 vs.92.1⫾0.4; p⫽0.04). There was a trend towards a higher respiratory arousal index (35⫾5 vs. 25⫾3; p⫽0.1) and hypoxemia (time SaO2⬍90%) (72⫾15 vs. 43⫾8; p⫽0.09) with a higher SAI. In the multivariate analysis, a higher SAI was associated with increased AHI (OR⫽7.6; 95 CI:2.7-34.7). In the high SAI group, while on CPAP , SAI improved from 17⫾2 to 3.2⫾1.2 events /hour (p⬍0.001), and correlated significantly with the improvement in AHI (r⫽0.6; p⬍0.05). CONCLUSION: High SAI is a marker of severe sleep apnea and correlates with the AHI. CLINICAL IMPLICATIONS: The SAI variable does not add appreciably to the available clinical information except when the SAI is high with substantially lower AHI, which would increase the index of suspicion for the presence of UARS. DISCLOSURE: Joe Zein, None.

PURPOSE: It is well known that arousals are often associated with tachycardia. Because polysomnography is costly as a screening test, we studied the correlation between the pulse rate obtained from overnight oximetry with polysomnographic parameters of sleep efficiency and fragmentation. METHODS: Polysomnography and pulse oximetry (Healthdyne Technologies, model 920M) were recorded simultaneously in 31 patients, 13 women and 18 men, referred for sleep studies. Highest, lowest and mean pulse rate, standard deviation and frequency distribution of pulse rate were correlated with parameters related to sleep efficiency and fragmentation using ANOVA. For frequency distribution 25 beats intervals (⬍50; 50-74; 74-99; 100-124; 125-149; 150-174; 175-199; ⬎200) were used. RESULTS: Age of the patients ranged from 14 to 77 years (mean 47,52 ⫹- SD 15,91). Body mass index was 27,42 ⫾ 4,44 (range of 17,78 – 39,96 kg/m2). The statistical analysis indicated that highest pulse rate and rate⬎ 100/min as a percentage of total recording time are good predictors of a low sleep efficiency (F⫽ 4,841; p⬍0,008). On the other hand, none of the variables tested can predict arousals, microarousals, reduced REM or reduced delta sleep. CONCLUSION: Our data show that tachycardia diagnosed by pulse oximetry can predict low sleep efficiency but not sleep arousals. Nevertheless, further studies can disclose other variables, which can be used in the construction of a model for screening of disturbed sleep. CLINICAL IMPLICATIONS: Low sleep efficiency is associated with tachycardia during sleep. This observation increases the usefullness of pulse oximetry as a screening tool for disturbed sleep. DISCLOSURE: Laercio Valenca, None. DOES SLEEP SPINDLE FREQUENCY AND DENSITY DISCRIMINATE BETWEEN THE VARIOUS TYPES OF EPILEPSY? Juliana C. Rajter MD* Sigmund G. Jenssen MD Han C. Ryoo PhD Siva K. Ramachandran MD Drexel University College of Medicine, Philadelphia, PA PURPOSE: During stage 2 sleep the thalamic reticular neurons release GABA, allowing sleep spindles to emerge at an oscillatory frequency of 12-14 Hz.There is evidence from from thalamic kindling in cats that spindle oscillations develop into seizures in corticothalamic systems. From computer modeling it is hypothesized that that there is cortical transformation of one of every 2 or more spindle waves to a spike component of spike and wave discharges and the other replaced by a slow wave1. This model predicts the evolvement of spindle waves to seizures.We pondered on the predictive relationship between spindle characteristics among different types of epilepsy and compared them to subjects without epilepsy. METHODS: 7 patients, each, with temporal lobe epilepsy, frontal lobe epilepsy, primary generalized epilepsy and 5 subjects without epilepsy were studied after IRB approval. At the time of EEG recordings 4 out of

Normal

Generalized

Temporal lobe

Frontal lobe

p

Mean spindle 0.69⫾0.24 0.72⫾0.21 1.47⫾1.12 0.63⫾0.21 0.37 duration in seconds (⫾SD) Spindle time /epoch in 0.03⫾0.02 0.02⫾0.03 0.05⫾0.08 0.02⫾0.01 0.84 stage 2 sleep Spindle number 3.4⫾3.3 2.8⫾2.8 2.6⫾2.2 3.4⫾1.8 0.37 per epoch

DISCLOSURE: Juliana Rajter, None. ADVANCED AUTOMATED ANALYSIS OF HUMAN ELECTROENCEPHALOGRAPHY (EEG) USING MULTIDIMENSIONAL MATHEMATICAL ANALYSES OF FREQUENCY CHANGES COMPARED TO TRADITIONAL RECHTSCHAFFEN AND KALES (R&K) SCORING OF A KNOWN BIOLOGICAL SLEEP SIGNAL Richard K. Bogan MD* Jo Anne Turner MSN Alex Novodvorets MS Koby Todros BS Baruch Levy BS SleepMed, Columbia, SC PURPOSE: To assess the use of an automated system (Morpheus) in the analysis of human EEG frequency changes in pre and post severe obstructive sleep apnea using a split night protocol. To correlate adaptive segmentation and fuzzy logic frequency changes using Markov models to traditional R&K. METHODS: A total of 23 adults were studied with a diagnosis of severe obstructive sleep apnea. Each subject underwent polysomnography (PSG) and received early intervention CPAP therapy during initial study. Only individuals with oxygen saturations greater than 85% and respiratory disturbance index (RDI) less than 10 episodes per hour during the ideal CPAP titration period were included. Fundamental frequency segments were measured using Morpheus algorhythms. Sleep states were analyzed using traditional R&K rules. RESULTS: Means and standard deviations are reported for 23 adults. RDI pre CPAP was 73.5 (26) with low oxygen saturation of 81%(7). Pre and post CPAP periods for the sleep states that reached statistical significance by automated analysis during study time were: high frequency(HF)⫽pre 30%(15), post 23%(11); low frequency(LF)⫽ pre 3%(4), post 8%(5); mixed frequency-1(MF1)⫽pre 15%(8), post 25%(7); delta⫽ pre 2%(4), post 4%(5); beta⫽ pre 5%(5),post 2%(2); under 4 Hz⫽ pre 5.2%(7), post 12.6%(5). Significant R&K sleep state results are as follows as a % of time in bed: sleep efficiency pre⫽ 76%(16), post 84%(9); Stage II pre⫽ 58%(16), post 35%(12); Stages III&IV pre⫽ 4%(8), post 15(9); REM pre⫽4%(9), post 26(11). Signals analyzed but not found to be statistically significant were: Morpheus mixed frequency 2, theta, alpha, and sigma segments; R&K Stage I. CONCLUSION: The automated analysis demonstrates a different methodogy for analyzing a known biological sleep signal. In this study CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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OVERNIGHT PULSE RATE RECORDING AS A SCREENING TEST FOR SLEEP DISTURBANCES Heloisa Glass PhD Maria Margarete d. Zembrsuski MS Ana Paula G. Garay Maria Alice M. Neves Laercio M. Valenca MD* Hospital das Forcas Armadas/Universidade Catolica de Brasilia, Brasilia, Brazil

5 normals were on benzodiazepines while the rest were on antiepileptic medications. From the whole night EEG recordings, segments of 300 seconds were extracted to assess spindle duration, number of spindles and fraction of spindle time per Epoch of stage 2 sleep by 2 independent scorers blinded to the clinical information. A 2 way ANOVA was used to test the differences between the various frequency categories. RESULTS: See attached table. CONCLUSION: 1.More spindles were seen in normal subjects. This represents medication effect on sleep.2. Although mean spindle duration and fraction of spindle time per epoch of stage 2 sleep occurred more in temporal lobe epilepsy, this was not statistically significant. 3.Overall spindle characteristics are not discriminative between the various types of epilepsy. CLINICAL IMPLICATIONS: In studying patients with epilepsy in the sleep laboratory, the morphology of spindles is unlikely to offer clues to assess either the origin or activity of spike and wave discharges.1. Traub RD, Contreras D et al. Single- column thalmocortical network model exhibiting gamma oscillations, sleep spindles and epileptogenic bursts. J Neurophysiol. 2005; 93:2194-232.

Wednesday, November 2, 2005 Sleep Disorders: Other Than Sleep Apnea, continued group with severe sleep apnea there was an improvement in sleep measures that reflect EEG synchrony comparable to that as measured by R&K. CLINICAL IMPLICATIONS: A completely automated analysis may expand knowledge of sleep states and processes from a high resolution multidimensional mathematical perspective thus allowing improved understanding of disease state mechanisms, medical risk, treatment outcomes, and quality of life measures.

invasive positive pressure ventilation pressures were adjusted with the aim of normalizing PcCO2 or reducing it by 10 to 15 mm Hg. Sensor drift for PcCO2 measurement was calculated to reduce the discrepancy between PcCO2 and awake arterial carbon dioxide tension. Epworth sleepiness score and patient satisfaction with home ventilation was charted on a 10 centimeter visual analogue scale before and after the study. RESULTS: Mean baseline PcCO2 was 45.4 ⫾ 6.5 mm Hg and drift corrected awake PcCO2 was 45.1 ⫾ 8.3 mm Hg. IPAP pressures were changed in nine patients and EPAP in eight patients. Epworth sleepiness score before and after the study showed no change in five patients, mild improvement in six patients and mild deterioration in one patient. Seven patients had a mild increase and five patients a mild decrease in their visual analogue scale score at follow up. CONCLUSION: Combined continuous PcCO2 and oximetry monitoring is feasible and permits the optimization of non-invasive positive pressure ventilation settings in patients with chronic hypercapnic respiratory failure due to hypoventilation. Continuous PcCO2 monitoring might serve as an important additional tool to complement diurnal arterial carbon dioxide tension values. CLINICAL IMPLICATIONS: A titration study with continuous PcCO2 measurement in patients receiving non-invasive positive pressure ventilation can be helpful to optimize the ventilator settings. DISCLOSURE: Prashant Chhajed, None. SLEEP-RELATED DESATURATION IN PATIENTS WITH UNILATERAL DIAPHRAGMATIC DYSFUNCTION Norman Wolkove MD* Osama Elkhouli MD Marc Baltzan MD Richard Dabrusin MD Mark Palayew MD Mount Sinai Hospital Center, Montreal, PQ, Canada

DISCLOSURE: Richard Bogan, Shareholder SleepMed Inc. OPTIMIZATION OF NON-INVASIVE VENTILATION PRESSURES USING COMBINED OXIMETRY AND CUTANEOUS CARBON DIOXIDE TENSION MONITORING Prashant N. Chhajed MD* Simone Gehrer Trupti P. Chhajed Ingrid Strobel Martin Brutsche MD Michael Tamm MD Werner Strobel MD Pulmonary Medicine, University Hospital Basel, Basel, Switzerland PURPOSE: To examine the safety, feasibility and utility of combined cutaneous carbon dioxide tension (PcCO2) and oximetry monitoring to re-titrate the non-invasive positive pressure ventilation settings in patients with chronic hypercapnic respiratory failure due to hypoventilation. METHODS: 12 patients with chronic hypercapnic respiratory failure underwent complete polysomnography and combined oximetry and PcCO2 measurement (Sentec AG, Switzerland) on the ear lobe. non-

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PURPOSE: Benign unilateral diaphragmatic dysfunction or paralysis (BUDDP) is not associated with known malignancy and may be idiopathic or due to previous trauma. BUDDP is generally thought to be of little clinical significance. Previous studies have been of limited scope, and have not included sleep studies. We assessed the physiologic and polysomnographic findings in 6 patients with BUDDP. METHODS: Six patients with suspected BUDDP and an elevated hemi-diaphragm on chest X-ray were identified and studied with chest fluoroscopy and sniff maneuver to quantify diaphragmatic movement (grade1⫽decreased movement, grade 2 ⫽ no movement, grade 3 ⫽ paradoxical movement). Additional studies included pulmonary function testing (PFTs), PI max, PE max and overnight polysomnography. RESULTS: Mean age of our patients was 63 years (range 39-73 years). Four patients were male, 3 patients had previous chest surgery. 3 patients were assessed as grade 1, 2 grade 2 and 1 grade 3. PFTs revealed mild restriction with mean TLC 78% predicted (70-96%) and 4 patients had superimposed obstruction (FV1/FVC ⬍ 75%). PI max and PE max were within normal limits (86% and 116% predicted). Mean obstructive apnea index was 7(0-30), mean RDI was 30 (2-97). Mean RDI during NREM and REM-sleep were 27(1-91) vs. 45 (5-76) (p⫽0.18). All patients demonstrated nocturnal desaturation. Mean lowest saturation during sleep was 80 %( 66-87%). Mean lowest saturation was 84 %( 70-94%) during NREM sleep and 69 %( 51-81%) during REM sleep. (p⫽0.0017). Severity of BUDDP was significantly correlated with FEV1, PI max and desaturation during REM sleep. CONCLUSION: During the wake state patients with BUDDP may be able to compensate for the unilateral loss of diaphragmatic function. However, during REM sleep, when the accessory respiratory muscles are inhibited, resultant hypoxemia can occur. CLINICAL IMPLICATIONS: Patients with BUDDP have mild restrictive lung disease and REM associated desaturation which correlates with the degree of diaphragmatic dysfunction. The resultant desaturation may be severe enough to require oxygen supplementation. DISCLOSURE: Norman Wolkove, None. PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION (PAH) HAVE POOR SLEEP QUALITY Chirag M. Pandya MD* Omar A. Minai MD J. A. Golish MD K. McCarthy MD Cleveland Clinic Foundation, Cleveland, OH PURPOSE: Sleep disturbances (SD) and severe nocturnal hypoxia of unclear etiology have been previously reported in patients with PAH. We performed sleep studies in PAH patients to evaluate their sleep characteristics and to look for possible factors associated with SD or NH. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Sleep Disorders: Other Than Sleep Apnea, continued

PNEUMATIC COMPRESSION DEVICES FOR TREATMENT OF RESTLESS LEGS SYNDROME Arn H. Eliasson MD* Walter Reed Army Medical Center, Washington, DC PURPOSE: Restless legs syndrome (RLS) is a troublesome condition manifested by sensory and motor symptoms that disrupt sleep onset or sleep maintenance. RLS is common, occuring with a estimated population prevalence of 10%. There are no consistently reliable treatment alternatives and pharmacological treatments are often associated with unacceptable side effects. An effective nonpharmacological treatment would be a highly attractive option. METHODS: A convenience sample of patients reliably diagnosed with RLS was asked to wear pneumatic compression devices for at least one hour each evening for at least 30 days. Symptoms of RLS severity and related quality of life measures were evaluated before and after treatment. RLS severity was measured using a validated 10-item questionnaire. Quality of life indices were scored using the RLS Foundaton Quality of Life Instrument. Daytime sleepiness was gauged using the Epworth Sleepiness Scale (ESS). Patients were asked to track compliance using logs. RESULTS: Of eight patients enrolled (mean age 55 years, range 37 to 81, 6 women), one man withdrew due to inability to comply. Of the other seven patients, all improved regarding RLS severity with three patients (43%) experiencing complete resolution. Mean severity decreased from 24/40 to 7/40 (p⫽0.003). Social functioning improved from 87% to 98% (p⫽0.05), daily functioning improved from 76% to 94% (p⫽0.06), sleep quality improved from 30% to 54% (p⫽0.01), and emotional well-being improved from 61% to 88% (p⫽0.05). ESS did not change significantly, decreasing from 9.9 to 8.6 (p⫽0.14). Compliance averaged 87% of nights (range 58% to 100%). One patient was able to discontinue previously prescribed gabapentin and pramipexole while experiencing improvement in RLS symptoms. CONCLUSION: Pneumatic compression devices worn for one hour per day over days to weeks improve RLS symptom severity and quality of life measures. A proportion of patients experience complete resolution of RLS symptoms. CLINICAL IMPLICATIONS: Pneumatic compression devices are an effective treatment alternative for patients with RLS. This nonpharmacological therapy may preclude resorting to medications which may be ineffective or have unacceptable side effects. DISCLOSURE: Arn Eliasson, Other Aircast Industries of New Providence NJ supplied six pneumatic compression devices for use in this study. No other financial incentive or support was received.

RESTLESS LEGS SYNDROME IN PATIENTS WITH CHRONIC RENAL FAILURE IS NOT RELATED TO SERUM FERRITIN OR SERUM IRON LEVELS Khalil Ansarin MD* Jafar Shabanpour MD Hasan Argani MD Hormoz Airomlou MD Tuberculosis and Lung Research Center, Tabriz University of Medical Sciences, Tabriz, Iran PURPOSE: Restless legs syndrome (RLS) is a sleep disorder thought to be related to iron stores and dopamine receptors of basal ganglia of brain. It occurs more commonly in patients with chronic renal failure (CRF), iron deficiency, and some other conditions. Its incidence in a few reports of patients with CRF from Asia varies from 1% to 60%. We studied this syndrome in patients with CRF and analyzed the effect of various parameters possibly involved in the etiology of RLS. METHODS: We investigated 194 patients (116 males and 78 females) with CRF diagnosed in Tabriz University Hospital using a structured questionnaire evaluating details of sleep, RLS, sleep apnea and other sleep disorders, and drug history. Daytime sleepiness was investigated with a modified Epworth Sleepiness Scale. Also a detailed laboratory investigation including serum, iron, ferritin, and PTH levels were performed. RESULTS: 56 (28.9 %) patients, 27(23.1 %) men and 29 (37.2%) women had symptoms compatible with RLS. (p⫽ 0.04). There was no significant difference on the mean levels of hemoglobin (9.7 ⫾ 0.18 versus 10.1 ⫾ .31; p⫽ 0.71) serum iron (72.2 ⫾ 3.63versus 74.3⫾ 6.66; p⫽ 0.87), and serum ferritin (684 ⫾ 97.4 versus 519 ⫾ 138; p⫽ 0.65) in patients with CRF who had RLS and those did not. There was a statistically significant difference daytime sleepiness in patient with CRF who did and did not have RLS ( 5.92⫾0.76 versus 2.95⫾0.34; p⫽0.0001). CONCLUSION: RLS syndrome is a common disorder in patients with CRF in Asian population of Azarbaydjan province of Iran.. Unlike general population in patients with CRF presence of RLS has no relationship with serum ferritin, serum iron level, or degree of anemia. These patients had poor quality of sleep that is at least partly related to the presence of RLS. CLINICAL IMPLICATIONS: RLS in patient with CRF is not related to serum ferritin or iron levels or degree of anemia and treatment on this direction is not expected to be as efficacious as patients without CRF. DISCLOSURE: Khalil Ansarin, University grant monies Supported by a gran from Tuberculosis and Lung Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

RESTLESS LEGS SYNDROME IN LUNG TRANSPLANT RECIPIENTS Jose C. Yataco MD* Joseph Golish MD Marie Budev DO Omar Minai MD Cleveland Clinic Foundation, Beachwood, OH PURPOSE: Restless legs syndrome (RLS) is a neurologic disorder with a prevalence between 2.5 and 15% in the general population. Among solid organ transplant recipients, RLS was found in 45% of patients after heart transplantation in a cross-sectional study. In a prospective study, RLS cases disappeared after kidney transplantation in a group of patients on hemodialysis. The goal of this study is to determine the prevalence, severity and risk factors of RLS in a population of lung transplant recipients. METHODS: This is a cross-sectional, observational study that recruited consecutive patients in the transplant clinic. For the diagnosis and severity assesment of RLS, we used previously validated questionnaires published by the international RLS study group (IRLSSG). Demographic data and possible risk factors were obtained from medical records. RESULTS: RLS had a prevalence of 47.6% in 42 lung transplant recipients recruited. Among the RLS patients, 80% had a moderate to severe disorder based on the IRLSSG. The mean age in RLS patients (46.4 years ⫾ 15.5) was similar to the mean age in patients without RLS (46.8 years ⫾ 15.6) but there were more women in the RLS group (75%) compared to the non-RLS group (40.9%). Diabetes mellitus had a prevalence of 45.2% in the overall group but the frequency of diabetes did not reach statistical difference between the two groups (p⬎0.05). Chronic renal failure (defined as creatinine clearance ⬍ 50cc/hr), was found in 42.8% in the overall group but had similar distribution in the RLS and non-RLS groups (p⬎0.05). CONCLUSION: RLS has a high prevalence in lung transplant recipients. Diabetes mellitus and chronic renal failure were frequent in lung transplant recipients but had similar distribution in the patients with or without RLS. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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METHODS: Patients followed at our PAH center who underwent sleep studies were included in the study. Variables analyzed included: apnea-hypopnea index (AHI), arousal index (AI), sleep stages, limb movements, oximetry, and EKG changes. Patients who spent more than 10% of the total sleep time (TST) with an oxygen saturation (SpO2) ⬍90% were considered nocturnal desaturators (ND) and patients with an arousal index (AI) ⬎10 or sleep efficiency ⬍70% were considered to have SD. RESULTS: Patients slept an average of 304⫾66 (mean⫾SD) min and spent 14⫾9% (mean⫾SD) of TST in REM, 9⫾8 %(mean⫾SD) in stage 1, 66⫾18%(mean⫾SD) in stage 2, and 5⫾6 % (mean⫾SD) in SWS. Out of the 20 patients, 12 (60%) were nocturnal desaturators. On average patients spent 22⫾27% (mean⫾SD) of their TST ⬍90% SpO2. Five patients spent ⬎ 30% of TST ⬍90% SpO2. Of the desaturators 3 patients were found to have OSA. Eight patients received supplemental oxygen during polysomnography. The overall arousal index was 19.5⫾12.8 (mean⫾SD), 11 of 15 (73%) had and arousal index ⬎10, the average sleep efficiency was 76⫾14% (mean⫾SD). Five patients had premature ventricular contractions. Periodic limb movement index (PLMI) was 24⫾31.5 (mean⫾SD) and four patients had a PLM arousal index ⬎10. None had OSA severe enough to be considered a potential cause of their PAH. CONCLUSION: Patients with PAH may have poor quality or nonrestorative sleep due to a variety of factors including PLMs, and nocturnal desaturation even in the absence of sleep disordered breathing. CLINICAL IMPLICATIONS: Patients with PAH may have poor sleep quality or non-restorative sleep and nocturnal hypoxia even in the absence of sleep-disordered breathing. DISCLOSURE: Chirag Pandya, None.

Wednesday, November 2, 2005 Sleep Disorders: Other Than Sleep Apnea, continued CLINICAL IMPLICATIONS: RLS is common and may have profound negative effects in the quality of life of transplant recipients causing insomnia, fatigue, reduced concentration, decreased motivation, depression and anxiety. Careful selection of therapy is necessary due to the potential interactions with the numerous medications taken by lung transplant recipients. DISCLOSURE: Jose Yataco, None. THE IMPACT OF SLEEP DISORDERS ON THE ATTENTION DEFICIT DISORDER IN THE ADULTPART II: THE NON-OSA PATIENT Clifford G. Risk MD* Nadine Y. Smith MS Clifford Risk, MD, Marlborough, MA PURPOSE: Patients with sleep disorders report excessive daytime fatigue, sleepiness, and attention impairment. This study will assess the impact of sleep disorders (other than sleep apnea) on the attention deficit disorder in patients who present with a wide spectrum of comorbid neuromuscular disorders, psychological disorders, auditory or reading impairments, learning impairments, executive function impairments, and organicity. METHODS: This study included 64 adult patients who presented to a nationally accredited sleep center for the evaluation of a slepe disorder other than obstructive sleep apnea. Scores were obtained for the degree of attention deficit, insomnia, excessive daytime sleepiness, anxiety, depression, fatigue, and pain, using standard scales of measuring severity. Neuropsyhcological testing of memory and learning was perfomred on a subset of these patients. RESULTS: Presenting comorbid diagnoses were as follows: Neuromuscular disease (16), anxiety and mood disorders (22), auditory or reading deficits (5), impaired executive function or memory impairment (15), organic brain injury (6).Sleep diagnoses were as follows: Insomnia (50), hypersomnia (2), periodic limb movements of sleep (2), REM behavior disorder (1), sleep terrors (1), fatigue/non-restorative sleep (8).Attention deficit was presented in 57 patients (90%), and strongly correlated with the severity of insomnia, anxiety and depression; auditory or reading deficits; memory or learning impairments; and organicity.Neuropsychological testing demonstrated significant impairments in auditory and visual learning and memory. Goal directed therapy undertaken in 15 patients, successfully decreased their attention deficit to the normal range. CONCLUSION: Sleep disorders other than obstructive sleep apnea have a strong impact on the presence of the attention deficit disorder in the adult. The slepe disorder and the comorbid contributing disorder must both be evaluated and treated to improve the daytime attention deficit disorder. CLINICAL IMPLICATIONS: Sleep specialists should be aware that evaluation and treatment of insomnia and of other slepe disorders requires concurrent assessment of comorbid diagnoses that contribute to the attention deficit presentation. This is best achieved by a multidisciplinary medical model. DISCLOSURE: Clifford Risk, None. RELATIONSHIP BETWEEN BODY FAT CONTENT AND ARTERIAL OXYGEN TENSION IN MILD-MODERATE OBESITY Khalil Ansarin MD* Mariam Nobari Tabrizi Jamal Ghaemmagami BS AliReza Ostadrahimi PhD Mehrnoush Toufan MD Tuberculosis and Lung Research Center, Tabriz University of Medical Sciences, Tabriz, Iran PURPOSE: Hypoxemia in obesity is attributed to gas exchange abnormality secondary to physical effect of obesity on the FRC and other lung volumes. However it seems that factors other than the physical effects of obesity are contributing to hypoxemia in obesity. We studied the relationship between fat content of mild-moderately obese subjects with their lung function changes and arterial oxygen pressure and saturation. METHODS: We selected 22 ( 2 men and 20 women) otherwise healthy obese subjects (BMI ⫽ 35.68 ⫾ 3.2 and ages 17 to 60 years) from Obesity Clinic of the Tabriz University of Medical Sciences. All subjects completed a structured questionnaire indicating full medical and sleep disorder history and underwent complete physical examination. All subjects had spirometry and lung volume studies (using Jaeger Bodyplethysmograph, Germany), arterial blood gases(using AVL 995, Austria), pulse oxymetry, capnography, body mass composition analysis (using Tanita TBF215 Analyzer, Japan), and echocardiography with estimation of

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pulmonary artery pressure. Matrix Pearson correlation was performed to obtain correlation between parameters. RESULTS: None of the subjects had CO2 retention. We found a significant negative correlation between both arterial oxygen pressure(PaO2) and saturation (O2Sat)and body fat mass, BMI and body fat % (r⫽ -0.56; p⫽0.007, r⫽ -0.57; p⫽ 0.008, r ⫽ -0.533; p⫽ 0.013 respectively) while there was no relationship between PaO2 and PaCO2, FRC%predicted, TLC%predicted, FVC%predicted or BMI. There was no meaningful relationship between lung function parameters and body fat mass or fat % which may be related to a less than severe degree of obesity in subjects studied. CONCLUSION: PaO2 and SaO2 in obese subjects are negatively but significantly related to fat mass and fat percent of the body which it seems to be at least partly independent of the effect of the obesity on the physical changes of respiratory system and lung function. CLINICAL IMPLICATIONS: Arterial oxygen tension in obesity may be related to factors other than physical effect of the obesity on the respiratory system and may be addressed accordingly for therapeutic purposes. DISCLOSURE: Khalil Ansarin, University grant monies From Tabriz University of Medical Sciences

THE IMPACT OF THE ATTENTION DEFICIT, MOOD, LEARNING AND PRAGMATIC DISORDERS ON THE PRESENTATION OF AN INSOMNIA DISORDER IN THE ADOLESCENT Clifford G. Risk MD* Nadine Y. Smith MS Clifford Risk, MD, Marlborough, MA PURPOSE: Adolescents presenting to a sleep center with a chief complaint of insomnia may suffer from an underlying attention deficit, mood, learning or pragmatic disorder. This study evaluated the presence of these dual diagnoses, and the effectiveness of patient-based therapeutic programs to improve the insomnia and comorbid diagnoses. METHODS: This study included 13 adolescents aged 10-17 who presented to a nationally accredited sleep center for evaluation of an insomnia condition. Diagnoses of attention deficit disorder, Asperger’s syndrome, non-verbal learning disorder, anxiety, and depression were established by prior neuropsychological and psychiatric assessments. A patient centered learning program was structured to address specific attention and learning deficits and build compensatory strategies for long term acquisition and memory and learning skills development. Treatment of insomnia included non-pharmacological interventions (sleep hygiene, sleep restriction, relaxation therapies) and pharmacological interventions (hypnotics, benzodiazapines). Treatment for morning sleepiness and attention deficit included, when indicated, a wake-promoting agent, and interventions by a speech language pathologist and professional doctoral level education specialist with appropriate modifications of the academic environment. RESULTS: Attention deficit disorder was found in 7 adolescents; Asperger’s syndrome and non-verbal learning disorder in 3; obsessive compulsive disorder, Tourette’s syndrome or an anxiety disordre in 3 patients; depression in 3 patients; and leraning disorder in 1 patient. (Some adolescents carried dual diagnoses.) Treatment interventions were effective in 6 patients treated by us with respect to an improvement in sleep structure and efficiency, and in improved alertness and attentiveness, and knowledge acquisition. CONCLUSION: Adolescents presenting with insomnia may suffer from significant disordres of attention deficit, pragmatic and specific learning impairments, or anxiety and mood disorders. Diagnoses and design of a therapeutic intervention may improve the sleep disorder and their daytime attention and wakefulness impairments, and academic performance. CLINICAL IMPLICATIONS: Physicians and parents should be attentive to sleep disorder evaluations in the treatment of the adolescent with a primary diagnosis of an attention, learning or mood disorder, and a comorbid diagnosis of either insomnia or delayed phase sleep disorder. DISCLOSURE: Clifford Risk, None. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Sleep Disorders: Other Than Sleep Apnea, continued ARE OROFACIAL PAIN PATIENTS PRONE TO OROPHARYNX RELATIONSHIP MODIFICATIONS, ALTERED RESPIRATORY PATTERNS OR SLEEP DISORDERS? Florence M. Sekito MS* Lucas N. Lemes MD State University of Rio de Janeiro, Rio de Janeiro, Brazil

City Age Gender Smokers Alcohol intake (gday) Heart disorders Lung disorders Pills Hours of sleep Hours of job

Odds Ratio

Std Err

zP⬎z

95% Conf Interval

0.855 0,98 1,2 0.88 1,25 1,14 1,92 0,96 0,88 1,05

0,94 0,007 0,25 0,21 0,24 0,27 0,50 0,26 0,05 0,04

-1,40 - 0,159 -1,57– 0,116 1,26- 0,205 -0,49 - 0,619 -1,15 - 0,24 -0,57 - 0,56 2,504 - 0,012 -0,13 - 0,89 -1,81- 0,07 -1,10 - 0,26

1,06 1,00 1,87 1,42 1,85 1,84 3,22 1,63 1,00 1,14

only statistical variables associated to somnolence. The prevalence of snores (33 %) and apnea suggestive episodes (4 %) were similar to numbers reported else were. CLINICAL IMPLICATIONS: Lungs Diseases seem to be more related to somnolence that any other condition. DISCLOSURE: Gur Levy, None.

Frequency Variable Mallampatti

0,25

Respiratory Pattern

0,99

Upper airways obstruction

Cases (n⫽75)

p value

0.40

1 2 3 1 2 3 1 2

13.33% 28,00% 58,67% 62.67% 5,33% 32,00% 56,76% 43,24%

Controls (n⫽75) 1 2 3 1 2 3 1 2

12.00% 17.33% 70.67% 62.67% 6.77% 30.67% 63.51% 36.49%

Mallampatti level: 1-normal; 2-parcial obstruction; 3- total obstruction DISCLOSURE: Florence Sekito, None.

SLEEP HABITS IN VENEZUELA AND ITS CORRELATION WITH HEART AND LUNG DISEASE Gur Y. Levy MD* Julio Castro MD Juan A. Cardenas MD Benito Rodriguez MD Dolores Moreno MD Ismenia Chaustre MD Arnoldo Soto MD Guillermo Isturiz MD Jose M. Lopez MD Universidad Central de Venezuela, Caracas, Venezuela PURPOSE: Evaluate sleep habits and disorders among individuals from three cities in Venezuela and its correlations with lung and heart diseases. METHODS: A self-reported questionnaire sponsored by the Venezuelan Association of Sleep Medicine, was designed in order to know socio-demographic profile, heart and lung diseases, alcohol intake, cigarette-smoking habits and sleep medication. Athens insomnia scale and Epworths sleepiness scale were also included. Epworth score was used as a main outcome logistic regression (Forward stepwise), two separates models were performed to rule out overfiting; model A include only the questions related to somnolence and model B include comorbid conditions and baseline characteristics. Significance level was considered as 0.05.

Smoking Cessation 12:30 PM - 2:00 PM INITIATING AN INPATIENT SMOKING CESSATION PROGRAM Jeanne McCabe RN Peter R. Smith MD Kathy A. Garrett-Szymanski RRT* Rosemarie Samuels RN Latoya Fyffe Michael Bergman MD Long Island College Hospital, Brooklyn, NY PURPOSE: Smoking remains a chief avoidable cause of morbidity and mortality in the US. Healthcare organizations should be in the vanguard of efforts to develop smoking cessation programs. Inpatient smoking cessation programs (ISCPs) are often more effective than those in the ambulatory setting. One year abstinence rates as high as 70% have been reported for cardiac patients enrolled in ISCPs. We report our experience with initiation of an ISCP at our institution. METHODS: Our 450 bed, university-affiliated hospital is in northwest Brooklyn. The goal was to provide cessation advice to all hospitalized smokers (smoked within the past twelve months) without new hires. Three staffers, all with other primary responsibilities (Asthma Center coordinator, Adult CF Nurse Coordinator, bronchoscopy RN) were trained as counselors using the 1996 US DHHS guideline. The 5Rs (Relevance, Risks, Rewards, Roadblocks, Repetition) and 5As (Ask, Advise, Assess, Assist, Arrange) were the key concepts learned and the focus for patient counseling. Understanding nicotine replacement therapy (NRT) and the use of buproprion were emphasized. A roster of newly admitted smokers is created by the hospital’s case managers each AM and faxed to the Smoking Cessation Center (SCC). Counselors see patients that day. Patients accepting, receive 5-10 minutes of counseling and written materials. Those declining, receive materials. Charts are stamped, documenting smoking cessation counseling. Physicians are encouraged to prescribe NRT and/or bupropion. Nursing staff are informed of the intervention. Monthly contacts via phone or email are attempted for patients agreeing to follow-up. RESULTS: The ISCP began 7/04. Outcomes through 3/05 are shown in the table. The project has been publicized widely and has enjoyed broad support from clinical leadership, providers and administration. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: Determine if in orofacial pain patients there are differences of the Mallampatti classification indexes, respiratory upper airways preference and intensity flow or sleep problems in relationship to healthy controls. METHODS: The study design was transversal, analyzing 145 consecutive healthy patients enrolled at UERJ Faculty of Dentistry, without any previous history of smoking or respiratory disease. The Mallampatti index was calculated in layed position according to the traditional description. They were classified by clinical examination in 3 groups according their mode of breathing: nasal-breathing, oral-breathing, mixed-breathing (turns nasal or oral mode). All patients were submitted to the Epworth sleepiness questionnaire. Their respiratory airflow were measured by the Forced Oscillation Technique (FOT), Oscilab-version 2.0, from nose and from mouth at a frequency of 5 Hz, to determine the obstruction in naso and oropharynx. RESULTS: The Qui-square and Fisher exact tests were used. No statistical differences were found in relation to Mallampatti index, respiratory patterns and upper airways obstruction between orofacial pain patients and controls. Pain patients had clinical sleepiness determined by Epworth index. CONCLUSION: Orofacial pain has no effect on tongue position at oropharynx and does not alter patients breathing mode. Orofacial pain patients have sleepiness when compared to controls. CLINICAL IMPLICATIONS: There was not any reference at the literature about orofacial pain patients and breathing patterns, respiratory flow evaluations, sleep disorders or tongue position in relationship to oropharynx. As far as we know this is the first description that neuromuscular orofacial pain doesn’t cause any influence on these subjects.

RESULTS: 946 questionnaires were analyzed. Age: 10 to 81 (mean 36.5) with 59 % of females. 15 % had heart disease, 12 % lung disorders, 33 % known as snores, 39 % with ethylic habits, 16 % used sleeping pills and Epworths scale of 6.7 ⫾ 4.4. Sleeping hours of 6.9 ⫾ 2.6 and working hours of 8.2 hours ⫾ 2.09. According to the Athens scale, 62 % had enough sleep time, 76 % had an overall satisfactory quality of sleep, 79 % had no awakening and 89 % had no somnolence. CONCLUSION: Lung disorders and overall quality of sleep were the

Wednesday, November 2, 2005 Smoking Cessation, continued CONCLUSION: Our experience suggests that ISCPs can be implemented without additional hires. Success requires broad institutional support, staff commitment based on an understanding of, and passion for, the task, and creative scheduling. CLINICAL IMPLICATIONS: Wide-scale development of ISCPs could reduce tobacco use in the US especially benefiting those with smoking-related illnesses resulting in hospital admission.

ISCP 9 Month Outcomes Total patients seen Committed to quit Agreed to follow-up Contacted ⱖ1 times Abstinent @ 1-9 mos

635 458 270 139 75

(72.1%) (42.5%) (51.5%) (54.0%)

DISCLOSURE: Kathy Garrett-Szymanski, None. A COMPARATIVE STUDY OF THE ROLE OF PHYSICIAN ADVICE AND NICOTINE REPLACEMENT THERAPY IN SMOKING CESSATION Ashrafjit S. Chahal MD* Jai Kishan MD Anmol Dhillon MBBS Mata Kaushalya Hospital, Patiala, India PURPOSE: Cigarette smoking is the most prevalent modifiable risk factor for increased morbidity and mortality in the world. The WHO estimates that worldwide 1.1 billion people smoke, representing one third of the global population aged 16 years and above. If the present trend continues there will be 1 billion deaths due to tobacco during the 21st century compared to 100 million deaths during the 20th century. A study was conducted to evaluate the comparative role of physician advice and nicotine replacement therapy on smoking cessation. METHODS: A total of 150 smokers were enrolled in the study. They were divided into 3 groups of 50 each. One group received physician advice, the other nicotine replacement therapy and the third was given placebo. Fagerstorm score was used to quantify smoking dependence. The patients were followed for 6 months. RESULTS: Advice alone is as effective as nicotine replacement therapy in smokers who have a Fagerstorm score of 4 to 7. Smokers with a Fagerstorm score of 8 or more require more than advice alone. CONCLUSION: Most of the time, physician advice alone goes a long way in making people quit smoking. In patients with high dependence, nicotine replacement therapy should be used alongwith. The progress a patients makes after intervention is directly related to what stage it was in prior to intervention. CLINICAL IMPLICATIONS: Considering the enormous hazards of smoking, every patient coming in contact of the physician should be asked and advised about smoking. DISCLOSURE: Ashrafjit Chahal, None. DOES INTENSIVE SPORT AT SCHOOL HAVE AN IMPACT ON SMOKING IN ADOLESCENTS? Dominique Lauwers MD* Jacques LeComte MD Jean-Pol Quarre MD Anne Hoyez MD Philippe E. Pierard MD CHU Charleroi, Charleroi, Belgium PURPOSE: It has been suggested that regular sporting practice might have a positive impact on smoking habits in young people. We tried to assess this impact in a group of adolescents. METHODS: Students at the same school, aged 14 to 20 years, were studied with a questionnaire relative to smoking habits, knowledge of tobacco risks, impact of media and school messages about smoking. Two groups were distinguished : a sporting department (more than 8 hours sporting per week), and a traditional section (less than 3 hours). RESULTS: 212 students were examined with a detailed questionnaire and 208 of them were fully completed and relevant : 122 in the sporting section, 86 in the other group. 70 % of boys and 66 % of girls are non smokers in the sporting section, versus respectively 64 and 57 % in the other group. In both groups, 90 % of smokers intend to stop definitely in the near future. Teaching messages at school are poorly received, but information carried by the media is well perceived and tobacco risks are generally known but addiction is massively misjudged. When they are smokers, there is no significant difference of consumption habits between

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the 2 groups. The use of drugs or alcoholic consumption is quite exclusively related with the group of smokers. CONCLUSION: Intensive sporting practice at school reduces significantly, but moderately, the risk to become a regular smoker. CLINICAL IMPLICATIONS: Intensive sporting practice at school seems to be a useful weapon for tobacco prevention in young people. But it is also clear that an improved policy and a better information on smoking is needed at school, with particular attention on the risks of addiction. DISCLOSURE: Dominique Lauwers, None. SMOKING CESSATION: WHO DESERVES BEHAVIORAL AND PHARMACOLOGICAL ASSISTANCE? Daiana Stolz MD* Anja Meyer Martin Brutsche MD Jo¨rg Leuppi MD Karl Fagerstro¨m MD Michael Tamm MD University Hospital Basel, Pneumology, Basel, Switzerland PURPOSE: To evaluate the appropriateness of the primary health care system to support smoking cessation as well as individual patterns for successful quitting. METHODS: University hospital employees (n⫽5218) were addressed through a two page, 17 questions questionnaire inquiring about past and current smoking behavior. Questions included daily cigarette consumption, pack-years, previous quitting attempts, smoking free period, and utilization of pharmacological therapies and counseling. RESULTS: 2574 (49.3%) questionnaires were returned. 791 subjects declared to have successfully quit smoking. A complete data set was available in 763 cases (mean age 44.4, range 17-68, 227 (29.8% male). Patients remained smoke free for a mean period of 11.8⫾ 9.7 years. Smoking cessation method in these subjects was: cold turkey in 89%; counseling 1.7%; nicotine replacement therapy in 4.5%; bupropion in 1.2%; and alternative approaches in 15.4%. On average, 2.4 ⫾ 3.02 attempts leaded to successful smoking cessation. Smoking cessation was achieved with one attempt in 53% of the cases, two in 19%, three in 13%, and more than three attempts in 14%, respectively. After two or more unsuccessful attempts, odds ratio for unsuccessful smoking cessation was 2.58 (95% CI 1.94 to 3.45). CONCLUSION: The majority of the ex-smokers quitted smoking without any behavioral or pharmacological support. The chance to successfully quit smoking without any help in a first or second attempt is considerable high. Accordingly, more than 50% of smokers have succeeded to quit on the first attempt. The risk for smoking recurrence after two ineffective quit attempts is markedly increased (OR 2.58). CLINICAL IMPLICATIONS: Behavioral and pharmacological therapies for smoking cessation are deemed effective and are supposed to be recommended to all patients who are attempting to quit smoking. However, in reality, the majority of smokers quit smoke without any help. According to our data, assistance should be offered particularly to subjects which already performed two unsuccessful attempts to quit. DISCLOSURE: Daiana Stolz, None. HABIT AND STIMULATION: ARE THESE IMPORTANT FACTORS OF SMOKING DEPENDENCY IN YOUNG PEOPLE? Marija M. Mitic Milikic PhD* Miodrag D. Vukcevic MD Snezana Stojanovic-Ristic MD Milan M. Grujic MD Institute for Pulmonary Diseases and TB, Belgrade, Serbia PURPOSE: In our previous study we showed that 39360 or 33.3% out of 118 342 students of University of Belgrade are smokers. The aim of this study was to examine the importance of two factors of smoking dependency in young people - habit and stimulation by Ohio State University “Why Do You Smoke” questionnaire (WDYSQ). METHODS: The study included 546 students of University of Belgrade: 499 (mean age 20.9 ⫾ 2.7) at the begging of the study (group A) and 47 (mean age 22 ⫾ 1.7) on the forth years of the study (group B). All of them fulfilled WDYSQ and six factors of smoking dependency were calculated. Two factors, stimulation and habit were evaluated. The difference between the groups A and B was evaluated by student’s t-test. RESULTS: The means values of stimulation and habit for whole group of students were 4.55 ⫾1.59 and 4.71 ⫾ 1.99 retrospectively. High level of smoking dependency (score ⱖ 11) were found in 24 (4%) students for stimulation and in 36 (7%) for habit There were not established statistically significant differences in the level of habit between groups A (4.7 ⫾ 2.02 ) and B (4.89 ⫾ 2.0), as well as in stimulation between groups A ( 4.49 ⫾ 1.53) and B ( 5.19 ⫾ 1.11). CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Smoking Cessation, continued CONCLUSION: Stimulation and habit are neither frequent factors of smoking dependency nor the factors with the high level of smoking addiction in young people. CLINICAL IMPLICATIONS: The subject study was performed on the young people having not been smoking for many years. These results may help them to give up smoking as well as to find the best way to do it. DISCLOSURE: Marija Mitic Milikic, None. EFFICACY OF A COUNTY GOVERNMENT EMPLOYEE BENEFITS SMOKING CESSATION PROGRAM UTILIZING AN ANTICHOLINERGIC INTRAMUSCULAR INJECTION COMBINED WITH COUNSELING Kirk G. Voelker MD* Lung Associates of Sarasota, Sarasota, FL

THE KANO TEST FOR SOCIAL NICOTINE DEPENDENCE (KTSND) IN SAMPLES FROM A PHARMACEUTICAL COMPANY Chiharu Yoshii MD* Masato Kano MD Yukiko Kawanami MD Masamitsu Kido MD Division of Respiratory Disease, University of Occupational and Environmental He, Kitakyushu, Japan PURPOSE: A smoking habit is maintained by psychological and physical dependence. We developed a new concept, in regard to social nicotine dependence, which is a part of psychological dependence, and made a new questionnaire, namely, “The Kano Test for Social Nicotine Dependence (KTSND)”. The KTSND has ten questions with a total score of 30. In order to investigate the validity of the KTSND, we applied it to pharmaceutical company employees. METHODS: We delivered the KTSND to a pharmaceutical company and received answers from 214 respondents. They consisted of 53 current smokers, 49 ex-smokers, and 112 non-smokers. RESULTS: Total scores of the KTSND were 18.62 ⫾ 5.60, 15.00 ⫾ 6.01, and 12.25 ⫾ 5.73 in current smokers, ex-smokers, and non-smokers respectively. In regard to the subject matter of the questions, that is, “Tobacco is one of life’s pleasures”, “Smokers’ lifestyles may be respected”, “Smoking sometimes enriches people’s life”, “Tobacco has positive physical or mental effects”, “Tobacco has effects to release stress”,

Testing Respiratory Function and Mechanics 12:30 PM - 2:00 PM INSPIRATORY RESISTIVE LOAD-INDUCED MODIFICATION OF TROPONIN T IN RAT DIAPHRAGM Jeremy A. Simpson PhD* Steve Iscoe PhD Queen’s University, Kingston, ON, Canada PURPOSE: Although the development of respiratory muscle fatigue has been well documented, its molecular basis is poorly understood. We wished to characterize the development of fatigue in rats subjected to severe inspiratory resistive loading (IRL) and identify IRL-induced changes to the diaphragmatic myofilament proteome. We hypothesized that inspiratory resistive loading (IRL) would elicit diaphragmatic fatigue (a decrease in the ratio of transdiaphragmatic pressure to integrated phrenic; Pdi/兰Phr) due, in part, to modifications to myofilament proteins. METHODS: We subjected 14 spontaneously breathing anesthetized rats to IRL until pump failure (decreased pressure generation) at which point we terminated the load and harvested diaphragmatic tissue for proteomic analysis. RESULTS: IRL elicited a rapid (⬃ 2 min) decrease in Pdi/兰Phr which plateaued until a later decrease at ⬃ 42 min; this was followed by central failure (decreased minute phrenic activity) and pump failure at ⬃ 44 min. One-dimensional western blot analysis of myofilament proteins indicated changes only to the fast isoforms of troponin T (TnT), particularly a loss of the dominant isoforms of type IIB fibers. In western blots of serum taken before and during IRL, we detected the presence of only the fast, not slow, isoform of troponin I, confirming damage to fast-twitch fibers. In addition, differential antibody immunoreactivity revealed an altered affinity to the other fast TnT isoforms, indicating the presence of a posttranslational modification. CONCLUSION: These results demonstrate for the first time that type IIB fibers are preferentially injured during inspiratory resistive loading and that TnT, a key contractile protein, is modified in the diaphragms of rats subjected to IRL. The exact nature of this modification remains to be determined but likely plays an important role in the development of fatigue. CLINICAL IMPLICATIONS: Our results suggest that fatigue and injury to fast fatiguable fibers alone is sufficient to cause respiratory pump failure. DISCLOSURE: Jeremy Simpson, University grant monies Wm. M. Spear Foundation (funds bequested to Queen’s University for respiratoryrelated research); Block Term Grant (funds awarded to Queen’s University from the Ontario Thoracic Society for respiratory-related research); Grant monies (from sources other than industry) Canadian Institutes for Health Research and Ontario Thoracic Society. THE CARDIOPULMONARY EFFECTS OF A CANNABINOID 1 RECEPTOR (CB1) AGONIST IS MEDIATED BY THE TRANSIENT RECEPTOR POTENTIAL VANILLOID 1 (TRPV1) CHANNEL Steven G. Smith BSc* Sandra G. Vincent Valerie F. Barrette John T. Fisher PhD Queen’s University, Kingston, ON, Canada PURPOSE: Anandamide (AEA), a cannabinoid 1 receptor (CB1) agonist, has been suggested to be involved in the pathogenesis of CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: To evaluate the efficacy of a county government employee benefits smoking cessation program utilizing counseling and an anticholinergic intramuscular injection. METHODS: Between January 1 and April 1, 2005 forty-five Sarasota county government employees enrolled in a smoking cessation program utilizing an anticholinergic intramuscular injection comprised of scopolamine and hydroxyzine in conjunction with a dedicated counseling program. Patients were supplied with a educational video and booklet at least one week prior to their office visit. They were also assigned a series of “homework” projects to be accomplished prior to their office visit. On the day of the office visit, they participated in group counseling lead by a physician followed by individual counseling and an intramuscular injection of scopolamine and hydroxyzine followed by 10 days of scopolamine based oral medication. The patients also received telephone counseling by the physician and trained counselors including a psychologist for as long as deemed necessary. RESULTS: One month success rates were compiled from patient follow up telephone calls and confirmed by independent postcard evaluations returned to the Sarasota county wellness development advisor. At the end of one month, 34 of 45 patients(76%)were still smoke free. This is in concordance with our previously reported data of an 80% success rate using this method. It is also consistent with our unpublished data of over 500 patients which has yielded a 75% 1 month quit rate. CONCLUSION: A smoking cessation program utilizing an intramuscular injection of scopolamine and hydroxyzine in combination with counseling and close follow up can be extremely effective when added to a governmental employee benefits program. CLINICAL IMPLICATIONS: By October 2005 we will be able to present independently verified 1 month smoking cessation data on over 100 Sarasota county employees as well as six month data on these 45 employees. We will also be able to present safety and efficacy data on over 1000 patients and six month follow up data on over 500 patients treated at our clinic. DISCLOSURE: Kirk Voelker, Shareholder American Medical Innovations Stop Smoking Clinics; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Scopolamine and Hydroxazine are not FDA approved for smoking cessation.

“Tobacco enhances the function of smokers’ brains”, “Doctors exaggerate the ill effects of smoking”, and “People can smoke at the place where ashtrays are available”, current smokers tended to answer positively (p⬍0.05). To the question regarding “Smoking itself is a disease”, current smokers answered negatively (p⬍0.05). There was no significant difference among the three groups to the question concerning “Tobacco is a part of culture”. CONCLUSION: From the results of the KTSND, we found there was a significant difference between current smokers and ex/non-smokers on social recognition and attitude to smoking. CLINICAL IMPLICATIONS: The KTSND has good possibilities to play a complementary role vis-a`-vis the FTND. DISCLOSURE: Chiharu Yoshii, None.

Wednesday, November 2, 2005 Testing Respiratory Function and Mechanics, continued hypertension (Lake et al, 1997) and cardiogenic shock (Wagner et al, 2001). AEA also binds to transient receptor potential vanilloid 1 (TRPV1) channels (Zygmunt et al, 1999), which are expressed on pulmonary C-fibers (Michael & Priestley, 1999). The latter are believed to be involved in the sensation of inflammation during lung disease (Lee & Widdicombe, 2001), and dyspnea during exercise (Paintal, 1973). In rats, intravenous injection of AEA elicits the pulmonary chemoreflex (apnea, bradycardia and hypotension; Lin & Lee, 2002), which is a C-fiber mediated reflex (Coleridge & Coleridge, 1984). However, the role of the transient receptor potential vanilloid 1 (TRPV1) receptor in this cardiopulmonary response remains unknown. METHODS: We measured the responses to AEA in anesthetized spontaneously breathing TRPV1⫹/⫹ (wildtype - WT) and TRPV1-/(knockout - KO) mice. We also measured the response to aerosolized AEA in conscious, chronically instrumented WT and KO mice. Respiratory frequency (f) and heart rate (HR) were measured using a whole body plethysmograph and telemetry respectively. Vehicle, and AEA (9mM) were aerosolized at 350ml/min. RESULTS: In anesthetized animals, the reflex pulmonary response to AEA was abolished in TRPV1 KO mice. In conscious mice, a significant bradycardia was observed during nebulization of AEA in the WT mice that was abolished in the TRPV1 KOs. CONCLUSION: We conclude that TRPV1 plays a critical role in the cardiopulmonary reflex response to AEA. CLINICAL IMPLICATIONS: We speculate that the TRPV1 protein is a primary molecular mechanism mediating C-fiber reflexes and may represent a therapeutic target for respiratory sensations involving bronchopulmonary C-fiber afferents. DISCLOSURE: Steven Smith, None. RESPIRATORY SYSTEM IMPEDANCE AND NASOPHARYNGEAL CLOSURE DURING PURSED-LIP BREATHING Yuko Sano MS* Hajime Kurosawa MD Yukio Katori MD Toshimitsu Kobayashi MD Kayomi Matsumoto MS Naoki Mori MS Masahiro Kohzuki MD Department of Internal Medicine and Rehabilitation Science, Tohoku University Sc, Sendai, Japan PURPOSE: To elucidate the mechanics of pursed-lip breathing (PLB), which is a traditional skill to alleviate dyspnea, especially in patients with severe airflow limitation such as chronic obstructive pulmonary disease (COPD). METHODS: Twenty healthy volunteers were studied. Of these, in 10 subjects (7 women and 3 men), aged 26 to 48 years (39.2 ⫾ 7.3 years; mean ⫾ SD), total respiratory system impedance (Zrs) was measured, and the other 10, aged 29 to 77 years (55.0 ⫾ 14.9 years), were examined for nasopharyngeal phenomena endoscopically. Informed consent was obtained from all the volunteers. Zrs during PLB with or without a noseclip was measured using the forced oscillation technique at 3 Hz. Zrs was measured through a mouthpiece during quiet normal breathing or through a facemask during PLB. To confirm the nasopharyngeal function during PLB, endoscopic observation was performed. RESULTS: Under the condition of wearing a noseclip, PLB significantly increased the Zrs from 0.37 ⫾ 0.15 to 0.87 ⫾ 0.34 (kPa/L/min; mean ⫾ SD). PLB also increased Zrs without a noseclip, showing similar results as those with a noseclip. The nasopharynx was widely opened during normal breathing. However, immediately after the start of PLB, the pharyngeal cavity was completely and strongly closed. This nasopharyngeal movement could consistently be observed in all the subjects. CONCLUSION: These results demonstrated 1) the extent of the oral resistance, and 2) the nasopharyngeal closure, during PLB. CLINICAL IMPLICATIONS: A noseclip is not necessary during PLB. Estimation of respiratory impedance during PLB would be helpful to estimate the dilating force on the small airways. DISCLOSURE: Yuko Sano, None. COMPUTED TOMOGRAPHY TO ASSESS RESPIRATORY MECHANICS IN TETRAPLEGIC PATIENTS Gabi Mueller MS* Claudio Perret PhD Pius Hofer BSc Markus Berger MD Franz Michel MD Swiss Paraplegic Research, Nottwil, Switzerland PURPOSE: The aim of this study was to evaluate the reproducibility of computed tomography (CT) to assess respiratory mechanics in tetraplegic subjects. Due to the lack of most expiratory muscles, tetraplegic subjects show big differences in respiratory mechanics compared to able-bodied

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subjects. To specify these differences, the reproducibility of chest-CTscans at maximal in- and expiration in tetraplegic subjects was assessed. METHODS: Eight chronic tetraplegic subjects with motor complete lesions between C5 and C8 were tested. All CT-scans were performed twice in supine position, with a repositioning of the patient in-between. At maximal in- and expiration, a topogram of the whole chest and 2 slices at the bottom plate of vertebral body Th4 and the cover plate of vertebral body Th9 were recorded. The raw values for diaphragm levitation, lung areas as well as frontal and sagital expansions of the chest were calculated by visual selection of the areas and distances using ’Osiris’ medical imaging software. Coefficients of variation (CV) were calculated for the variation between the first and second measurement of the patients and for the intra-tester reproducibility of 3 independent testers, analyzing everything twice. RESULTS: Mean CV of the 3 intra-tester calculations were 0.2⫾0.1% for lung areas, 0.6⫾0.2% for sagital and 0.3⫾0.1% for frontal distances and 2.9⫾1.0% for diaphragm levitation. Mean CV of the patients’ maximal in- and expiration were 3.8⫾2.6% for lung areas, 2.9⫾2.0% for sagital and 1.3⫾0.6% for frontal distances and 11.3⫾2.4% for diaphragm levitation. CONCLUSION: Our results showed a high intra-tester reproducibility of the calculated values with CV below 1%. CV of maximal in- and expiration of the patients were below 4%, indicating the measurement error which is relevant for the practical use of this method. Concerning diaphragm levitation, the rather weak reproducibility has to be taken into account. CLINICAL IMPLICATIONS: Computed tomography provides interesting possibilities to assess changes in respiratory mechanics due to training or degeneration in tetraplegic subjects. DISCLOSURE: Gabi Mueller, None.

POSTOPERATIVE PULMONARY COMPLICATIONS AFTER ABDOMINAL SURGERY Fayez Bader MD* Peter R. Smith MD Muhammed Baig MD Jason Akulian MD Veronica Brito MD Siddarth Shah MD Michael Bergman MD Antonio Alfonso MD Long Island College Hospital, Brooklyn, NY PURPOSE: The frequency of, and risks for postoperative pulmonary complications (PPCs) after abdominal surgery (AS) are incompletely understood. Definitions of PPCs have been variable and the range of PPCs reported in the literature is wide (2-19%). In the present study we have used a definition of PPCs that is clinically relevant in terms of affecting key outcomes including morbidity, mortality, and length of stay (LOS). METHODS: Data for 200 consecutive Pts in 2004 were collected using CPT codes to identify AS performed at our hospital. PPCs were defined as 2 or more of the following for at least 2 consecutive days, occurring within 7 days of surgery: 1) new cough /sputum production, 2) physical exam c/w segmental or greater atelectasis or pneumonia 3) radiographic findings c/w segmental or greater atelectasis or pneumonia 4) temp⬎38 C. Additionally, exacerbation of preexisting lung disease, respiratory failure, and pulmonary embolism defined PPCs. Incentive spirometry is used routinely at our hospital after AS. A stepwise multiple logistic regression model was used for statistical analysis. RESULTS: PPCs occured in 9 of 200 (4.5%) cases (Table I). There were no PPCs after laparoscopy. There were no deaths. Risk factors for PPCs identified in univariate analyses are shown in Table II. Nasogastric tubes and a history of cardiac disease independently predicted risk in multivariate analysis. LOS was statistically greater in patients with PPCs (OR⫽1.17, 95% CI 1.08-1.27, p⫽.001). CONCLUSION: These data suggest a low incidence of PPCs after AS. The reasons for a lower frequency of PPCs reflected by these data compared to many prior studies are multi-factorial including a more clinically relevant definition of PPCs, improved technology, and use of less invasive techniques (laparoscopy). CLINICAL IMPLICATIONS: Morbidity and potential mortality from PPCs can be reduced by preoperative risk assessment and appropriate perioperative management. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Testing Respiratory Function and Mechanics, continued Table I PPC Description

n

Atelectasis Pneumonia / Atelect. Resp. Failure Pulm. Emboli COPD exacerb.

3 1 2 2 1

Table II—Risk Factors for Post Operative Pulmonary Complications OR

95% CI

p Value

Age Smoking (ever) COPD Cardiac disease ASA Anesthesia time Upper abdo incision NG tube Non-pulm complic

1.04 4.0 9.11 5.37 4.99 7.13 8.88 39.97 4.36

1.002-1.088 1.10-14.53 .82-100.97 1.40-20.57 1.50-16.62 1.23-41.41 1.06-74.26 4.90-326.15 1.03-18.43

.039 .035 .072 .014 .009 .029 .044 .001 .045

DISCLOSURE: Fayez Bader, None. CORRELATION ANALYSIS BETWEEN SIX MINUTES WALK DISTANCE AND RESPIRATORY MUSCLES STRENGH AND RESPIRATORY MUSCLES INCREMENTAL TEST IN COPD PATIENTS Evanirso S. Aquino BSc* Fernanda M. e Castro BA Isabel B. Lopes BA Thaı´s M. Peres BA Cristiane Cenachi-Coelho MA Ina´cio T. Cunha Filho MD Uni-BH PUC Minas - Betim, Belo Horizonte, Brazil PURPOSE: The objective of this study was to correlate the respiratory muscles strengh(RMS) and respiratory muscles incremental test (RMIT)with six minutes walk distance (6MWD)in COPD patients. METHODS: COPD patients in clinically stable condition between 59 and 80 years of age were selected if they met following criteria: mild to severe airflow obstruction according to Global Initiative for Chronic Obstructive Lung Disease. All patients were submited to lung function test, respiratory muscles strength, assessed by maximal inspiratory mouth pressure and maximal expiratory mouth pressure (PImax and PEmax), respiratory muscles incremental test (RMIT) and 6MWT. RESULTS: 21 patients were studied (3 women and 18 mens). The mean age was 71,66⫾ 14,78 years. The results showed the positive correlation between Inspiratory endurance time assessed by RMIT and 6MWD (r ⫽ ⫹0,607 P⫽ 0,004), maximal inspiratory and expiratory load evaluated through RMIT with 6MWD (r ⫽ ⫹0,0598 P ⫽ 0,004) and (r ⫽ ⫹0,442 P ⫽ 0,004)respectively. PImax and PEmax were not statistically significant. CONCLUSION: The results of the present study demonstrate a moderate and positive correlation between respiratory muscles incremental test and six minutes walk distance. CLINICAL IMPLICATIONS: The respiratory muscles endurance training might contribute to exercise performance evaluated by six minutes walk distance in patients with chronic airflow limitation. DISCLOSURE: Evanirso Aquino, None. CORRELATION BETWEEN INDIRECT METHODS OF THE CORPORAL COMPOSITION ASSESSMENT AND RESPIRATORY MUSCLES STRENGTH AND ENDURANCE IN COPD PATIENTS Evanirso S. Aquino BS* Fernanda de M. Resgalla e Castro BA Isabel B. Vasconcellos Lopes BA Thaı´s M. Peres BA Ina´cio T. Cunha Filho MD UNI-BH PUC Minas-Betim, Belo Horizonte - MG, Brazil PURPOSE: To do a prospective analysis between indirect methods of the corporal composition assessment and respiratory muscle strength and endurance in chronic Obstructive Pulmonary Disease (COPD) patients.

THE OXYGEN CONCENTRATIONS DELIVERED BY DIFFERENT OXYGEN THERAPY SYSTEMS Juan A. Garcia MD* Donna Gardner RRT David Vines RRT David Shelledy PhD Richard Wettstein PhD Jay Peters MD University of Texas Health Science Center at San Antonio, San Antonio, TX PURPOSE: To test the oxygen concentrations delivered by some of the available oxygen therapy systems in normal subjects. METHODS: Two different groups of ten healthy volunteers participated in two parts of this study. Nasal cannula (NC) O2 delivery was tested in the first group Simple masks (SM) and non-rebreathing (NRB) masks were tested in the second group. Each subject had a # 8 French nasal catheter inserted through a nare with the tip positioned immediately behind the uvula. The nasal catheter’s proximal end was connected to a syringe stopcock “T” piece system with the oxygen analyzer in line. Oxygen was administrated via the high flow NC (model ref 1600, Salter Labs, Alvin, Ca) at flows 6-15 L/min. For the SM (Hudson RCI, Temecula, Ca), oxygen was administer at 6-12 L/m, and for the NRB mask (Hudson RCI, Temecula, Ca), the flow was 6-15 L/min. At each different oxygen flow the subject breathed normally for five minutes. Using the oxygen sampling system, three gas samples (60 mL each) were withdrawn from the pharynx during inspiration and directed to the oxygen analyzer. The average FiO2 delivered was recorded for each one of the oxygen flows administered with the different systems. RESULTS: Table 1 shows the means ⫾ SD for each device. Figure 1 shows the comparison between the different devices. CONCLUSION: The HFNC was able to provide higher mean FiO2 than the SM at flows of 6-10 L/min; at 12 L/min the delivered FiO2 was equal. HFNC compared to NRB mask delivered equal mean FiO2 at flows 8-15 L/min, and was superior at 6 L/min. Both masks will deliver less variable FiO2 than HFNC. CLINICAL IMPLICATIONS: If needed, HFNC can deliver similar FiO2 than NRB mask. Medical personnel should be aware of the high FiO2 variability this system may deliver.When switching from HFNC to SM, a higher O2 flow should be selected to achieve similar delivered FiO2. The simple rule for estimating delivered FiO2 with different oxygen systems is not accurate. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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Risk Factor

METHODS: COPD patients in clinically stable condition were recruited, and for the control group normal subjects around the same age and biotype. All the subjects and patients were submitted to pulmonary function test (spirometry), maximal respiratory pressures (PImax and Pemax), respiratory muscles incremental endurance test, six-minute walk test (6MWT), skinfold and body mass index (BMI) measurements. RESULTS: A total of 30 subjects completed the study, 6 women and 24 men. They were divided between three different groups: Group A; moderate to severe COPD (n⫽11); Group B, mild COPD (n⫽10) and Group C, control group (n⫽9). The mean age was ( 69,54 ⫾ 10,51years), ( 71,1 ⫾ 8,13 years), ( 70,11 ⫾ 5,86 years) and the mean values for the BMI was ( 24,00 ⫾ 3,66 Kg/m2), ( 24,41 ⫾ 0,58 Kg/m2) and (27,44 ⫾ 1,33 Kg/m2) respectively . The results showed that the correlations were not statistically significant between the anthropometric variables measured and the strength and endurance of the respiratory muscles. CONCLUSION: It is a literature consensus that diminish nutritional state evidenced through the weight loss causes an impairment of the peripheral and the respiratory muscles. Our study did not showed correlations statistically significant between the nutritional variables and the strength and endurance of the respiratory muscles. Other studies are necessary with a bigger sample and with subjects with different degrees of nutritional impairment to have a better analysis of the correlation between the nutritional state and the respiratory muscles of the COPD patients. CLINICAL IMPLICATIONS: There is no correlation between indirect methods of the corporal composition assessment and muscle respiratory strength and endurance in copd patients with body mass index lower than 20 Kg/m2. DISCLOSURE: Evanirso Aquino, None.

Wednesday, November 2, 2005 Testing Respiratory Function and Mechanics, continued Table 1

THE OXYGEN ADHERENCE MODEL: IMPROVING HOME OXYGEN USAGE Deborah L. Cullen* Indiana University, Indianapolis, IN

Nasal

Simple

Non-

cannula

Mask

rebreather

O2

FiO2 %

FiO2 %

FiO2 %

flow

(mean ⫾

Range

(mean ⫾

Range

(mean ⫾

Range

Predicted

(L/min)

SD)

FiO2 %

SD)

FiO2 %

SD)

FiO2 %

FiO2 %

6

54 ⫾ 13

35-89

43 ⫾ 2.6

38-47

45 ⫾ 2.9

40-49

45

8

58 ⫾ 14

33-87

41 ⫾ 2.6

37-47

57 ⫾ 4.6

51-65

53

10

66 ⫾ 13

40-88

57 ⫾ 3

52-63

68 ⫾ 2.3

64-71

61

12

69⫾ 13

37-93

69 ⫾ 3.3

64-74

68 ⫾ 2.7

64-73

69

15

75 ⫾ 13

39-98

Not tested

74 ⫾ 2.4

68-77

77

DISCLOSURE: Juan Garcia, None.

TRANSCUTANEOUS CARBON DIOXIDE TENSION AND OXYGEN SATURATION MONITORING VERSUS ARTERIAL BLOOD GAS MEASUREMENT Elisa Canturri MD Christian Domingo MD* Manel Luja´n MD Miguel Gallego MD Amalia Moreno MD Humildad Espuelas RN Merce` Gime´nez MD Albert Marı´n MD Corporacio´ Parc Taulı´, Sabadell, Spain PURPOSE: To evaluate the precision of a non-invasive digital ear-clip sensor providing continuous transcutaneous (Tc) monitoring of carbon dioxide tension (PaCO2) and oxygen saturation (SaO2%) using arterial blood gases (ABG) as the gold-standard technique. METHODS: Population: patients referred to the Pulmonary Function Testing Laboratory of our Institution. Instrumentation: Spirometry was performed on the admission day. The ear-clip V-signTM (SenTec) was placed and after stabilization, the lecture was performed. While the patient wore the ear-clip, ABG were performed, the blood was analyzed in two different blood gas analyzers and the mean value was taken as the gold-standard measurement. Statistical evaluation: Student’s t test for paired data was used to compare the mean values obtained from the Tc and the ABG measurement. A Pearson correlation coefficient (r) was obtained. Bland-Altman plot was used to detect bias in the readings. This evaluation was performed for the whole group and for sub-groups stratified according to lung obstruction severity and PaCO2 value (normalⱕ 45 mmHg; elevated PaCO2 (⬎45 mmHg). RESULTS: 130 patients were included (10 were excluded for calibration problems of the sensor in two consecutive days). Data are given as mean⫾SD.The subgroup analysis did not show relevant differences. The Bland Altman plot did not show marked dispersion at any values of PaC02. CONCLUSION: 1) The differences found in the measurements of PaCO2 and SaO2 with both methods, although statistically significant, were not clinically relevant. 2) Appropriate calibration and stabilization period of the Tc sensor is needed before a measurement is considered reliable. CLINICAL IMPLICATIONS: Tc measurement is a reliable method to determine carbon dioxide tension and oxygen saturation. In many cases, this technique can substitute ABG analysis.

ABG

Tc *

CO2 42.16⫾7.2 40.93⫾8.4 mmHg SaO2% 93.46⫾4.4 94.35⫾4.4

Mean Difference IC

r*

1.22⫾4.1

-1.9; -0.50,875

0.88⫾3.1

0.3; 1.40,747

* p⬍0.05 DISCLOSURE: Christian Domingo, None.

390S

(95%)

PURPOSE: A handful of studies have pointed to explanations related to a patient’s reluctance to wear a cannula or breathe oxygen for 15 hours a day. Fewer studies have determined strategies aimed at improving LTOT (Long Term Oxygen Therapy) use. Adherence is not generalizable and may differ with treatment or by condition. Adherence is a dimensional construct and no current explanatory theory or model specific to LTOT exists. LTOT adherence varies between 45-70% therefore an explanatory model is needed which addresses patient and treatment factors. METHODS: An Oxygen Adherence Model was developed which defined the variables, processes and barriers present when LTOT and a respiratory disability interact. This hierarchical and tiered model is related to established drug adherence constructs, respiratory health behavior theory, and physiologic variables inherent with chronic respiratory disease. RESULTS: Adherence will advance as the variables and domains in each tier are addressed. Tier 1, Chronic Respiratory Disability is defined by symptoms and physiologic deteriorization which is assisted via LTOT. Tier 2, Information Enhancement, is educational as the clinician assists the patient and family with understanding LTOT. Interventions and treatments related to Tier 3, Emotional and Psychological Limitations, should be focused to improving self-efficacy. Tier 4, Reduction of Treatment Barriers should be approached with the goal of therapeutic effectiveness. CONCLUSION: Health behavioral and psychological models explain general adherence behavior and have been effective in guiding interventional strategies for many conditions and health promotion. The Oxygen Adherence Model can be tested to determine approaches appropriate to limiting symptoms, improving physical limitations, educating the patient, addressing psychological and emotional variables as well as reducing barriers to more effective oxygen therapy. CLINICAL IMPLICATIONS: Chronic disease management includes adherence plans. Most patients find LTOT a complex treatment. New strategies and research related to LTOT adherence may assist with improved LTOT utilization by patients.

Tier 1

Chronic Respiratory Disability Symptoms: Dyspnea,

Tier 2

Tier 3

Tier 4

Information

Emotional and

Enhancement

Psychological Limitations

Treatment Barriers

Prescription

Denial Hopelessness

Poor provider support

Fatigue, Anxiety,

Knowledge

Apathy Misery Isolation

Limited clinician

Depressed Mood

Treatment

Burden Stigma Fear of

communication Not

Physiologic

rationale

addiction Fear of

practically portable

Deteriorization: Arterial

Technical ability

dependence Depressed

Expensive

Oxygen Desaturation

Motivational

mood Anger Health

Inconvenient

Exercise capacity Body

enhancement

belief conflicts

Duration of treatment

Mass Index Cognitive

Complexity Life style

status Functional status

interference

DISCLOSURE: Deborah Cullen, None. STANDARDIZATION AND ENHANCED SAFETY OF EXTERNAL BATTERY SYSTEMS USED TO OPERATE PORTABLE VENTILATORS IN THE HOME CARE SETTING OF THE PROVINCE OF QUEBEC Brigitte Fillion RRT* Mc Gill University Health Center, Montre´al, PQ, Canada PURPOSE: The aim of this project was to standardize and enhance the safety of the clients of the National Program for Home Ventilatory Assistance (NPHVA) using external battery systems to operate their portable ventilators in the home setting. METHODS: A partnership was formed between the McGill University Health Centre’s Biomedical department and the National Program for CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Testing Respiratory Function and Mechanics, continued

RELATIVE SENSITIVITY AND LOWER LIMITS OF NORMAL FOR SPIROGRAPHIC MARKERS OF AIRWAY OBSTRUCTION James E. Hansen MD* Xing Guo Sun MD Karlman Wasserman MD Harbor-UCLA Medical Center, Torrance, CA PURPOSE: 1) Develop mean and 95% confidence lower limit of normal (LLN) formulae for FEV3/FVC for Black, Latin, and White men and women to supplement the findings of Hankinson et al. 2) Ascertain comparative variability of FEV1/FVC, FEV3/FVC and FEF25-75 in never-smoking adults and evaluate their utility in measuring the effects of smoking on airway obstruction. 3) Develop and use the concept of 1-FEV3/FVC to identify airway obstruction. METHODS: We identified 5938 never-smokers and 3570 current smokers with spirometric data meeting American Thoracic Society standards from the NHANES-III nationwide database. In these groups we developed regression formulae for the FEV3/FVC, quantified variability and LLN of the FEV1/FVC, FEV3/FVC and FEF25-75 to identify abnormalities in current-smokers, and evaluated 1–FEV3/FVC as a marker of airflow obstruction. RESULTS: With normal aging, there were concurrent linear decreases in FEV1/FVC and FEV3/FVC and increases in 1-FEV3/FVC, the latter attributable to slower emptying of acini with longer time constants. By middle age these spirometric measurements worsened, on average, about 20 years earlier in current-smokers. Two-thirds of current-smokers who manifested airway obstruction had both FEV1/FVC and FEV3/FVC abnormal, while 1/6 had only FEV1/FVC abnormal and 1/6 had only FEV3/FVC abnormal. The normal variability of FEF25-75 is greatest and that of the FEV3/FVC is least. If ⬍80% of mean predicted FEF25-75 values were used to identify abnormality, ⬎25% of all never-smokers would have been falsely identified as abnormal. Using 95% confidence limits for FEF25-75, only 1% of never-smokers had isolated abnormal FEF25-75 while 42% of 683 smokers without restriction but with reduced FEV1/FVC and/or FEV3/FVC had normal FEF25-75 values (false negatives). CONCLUSION: FEV1/FVC, FEV3/FVC and 1-FEV3/FVC all characterize expiratory obstruction well. In contrast, FEF25-75 has an unacceptably large proportion of false negatives and false positives. CLINICAL IMPLICATIONS: Using ⬍80% of mean predicted to define abnormality is statistically invalid. For valid spirographic assessment of airways obstruction, we recommend requiring statistically correct LLN and replacement of the FEF25-75 with the FEV1/FVC and FEV3/FVC. DISCLOSURE: James Hansen, None.

DETERMINING THE LOWER LIMITS OF NORMAL OF SPIROMETRIC REFERENCE VALUES FOR ADULT CHINESE IN HONG KONG Johnny W. Chan MBBS* Sai-On Ling MBBS Daniel Fong PhD Agnes Lai MS Fanny W. Ko MB, ChB Kam-Sing Tang MBBS Arthur C. Lau MBBS Kahlin Choo MBBS Wai-Cho Yu MBBS Moira M. Chan-Yeung MBBS Mary S. Ip MD Queen Elizabeth Hospital, Hong Kong, Hong Kong PRC PURPOSE: Delineation of lower limits of normal (LLN) is important in the clinical utilization of reference values. In a cross-sectional multicenter study to derive the reference spirometric values of adult Chinese, we compared two methods of its determination in lung function parameters. METHODS: The study was carried out between January 2001 and March 2003. Healthy non-smoking Chinese subjects were recruited from the community by random digit dialing to undergo spirometry in lung function laboratories of eight hospitals of Hong Kong. Prediction equations for lung function parameters were developed using multiple regression analysis. LLN were determined by: (1) traditional method assuming constant difference between the mean and fifth percentile throughout the age range (mean-1.645 residual standard deviation); or (2) distributionfree estimation of age-related centiles described by Healy & Rabash (Annals of Human Biology 1988). RESULTS: Evaluable data of 1089 (494 males and 595 females) subjects aged 18 to 80 years were analysed. In deriving LLN, distributionfree estimation, when compared with the traditional equation, yielded better approximation to the fifth percentiles. To illustrate, 4.88% vs 4.05%, 4.66% vs 3.64% and 4.86% vs 3.85% of men were considered to have subnormal values of FEV1, FVC and FEV1/FVC ratio respectively. Equations from distribution-free estimation also yielded more stable age-related profiles of LLN. To illustrate, for FEV1, the proportions of subjects in four age stratifications who were classified as having subnormal values ranged from 3.33% to 6.58%, compared with 0.67% to 7.55% obtained with the traditional method. CONCLUSION: In determining LLN for spirometric values, the distribution-free estimation of age-related centiles, compared with another traditional method, yielded better proximity to fifth percentiles and more stable profiles in various age groups. CLINICAL IMPLICATIONS: Application of distribution-free estimation of age-related centiles was more appropriate in this study cohort. DISCLOSURE: Johnny Chan, Grant monies (from sources other than industry) This study was supported by a grant from Hong Kong Pneumoconiosis Fund Board; Other The study was conducted under the auspices of Hong Kong Thoracic Society and American College of Chest Physicians (HK and Macau Chapter). NORMAL REFERENCE VALUES FOR CARDIOPULMONARY EXERCISE TESTING AMONG FILIPINOS Lenora C. Fernandez MD* Camilo C. Roa MD Norman Maghuyop MD University of the Philippines, Manila, Philippines PURPOSE: Performance on cardiopulmonary exercise test (CPET) is influenced by genetic, racial and environmental factors. Normal reference values derived from Caucasian populations are not deemed appropriate if CPET is done among non-Caucasian subjects. It is important to establish a set of reference values for the Filipino population. The objectives of this study were to (1) establish the Maximum Working Capacity, Peak oxygen intake (VO2), Peak carbon dioxide output (VCO2), Tidal Volume (TV) for normal Filipinos during exercise, (2) determine the median perceived rate of exertion using the Borg Scale, and (3) derive prediction equation models for Maximum Working Capacity, Peak VO2 , Peak VCO2 and maximum attained TV. METHODS: The maximal cardiopulmonary responses were analyzed for one hundred eighteen healthy sedentary adult Filipino subjects who underwent CPET using a symptom limited incremental progressive cycle ergometer driven protocol. A Vista Mini-CPX Model 17670 was used. Models for predicting VO2 max, VCO2 peak, VT peak, and Work max were derived with height, weight, age and sex being screened for significance as predictors of the said parameters. Linear and non-linear regression was done. RESULTS: The maximum working capacity for males was 154.21⫾26.6 watts and 93.02⫾15.57 watts for females while the peak VO2 for males was 4.90⫾3.11 and 4.56⫾2.41 liters/minute for females. The predictive formulae derived from our study for maximum work capacity, peak VO2, VCO2 and tidal volume had acceptable correlation coefficients CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

391S

POSTER PRESENTATIONS

Home Ventilatory Assistance to identify Canadian Standard Association (CSA) recommendations regarding external battery systems for portable ventilators. Together we evaluated if the battery systems employed by our patient population met CSA standards and if these were safe for home usage. A cost analysis of available battery systems was also undertaken. RESULTS: The findings demonstrated that there was no standard for complete battery systems but only for individual components. Furthermore, the analysis of existing battery systems demonstrated that even the individual components used did not always meet CSA standards making the battery systems employed potentially hazardous for clients in the home setting. The costs analysis of the systems used by the patient population showed that the cost was inordinate compared to the cost of a custom-made external battery system composted with CSA approved components. CONCLUSION: This process allowed us to develop a custom-made external battery system that was composed completely of CSA approved components. In addition a preventive program for lead-acid batteries was also developed. CLINICAL IMPLICATIONS: The use of the custom-made external battery systems with CSA approved components has eliminated the incidents associated with the initial systems used by the population. Since one year of implementation there has been less reported service calls regarding battery systems. DISCLOSURE: Brigitte Fillion, None.

Wednesday, November 2, 2005 Testing Respiratory Function and Mechanics, continued and performed as well as other published predictive equations based on Caucasian and Asian populations. CONCLUSION: Cardiopulmonary exercise testing was performed on a community based, healthy, sedentary Filipino population using a standard maximal incremental cycle ergometry protocol. Predictive equation models were derived for Maximum Working Capacity(r2 ⫽0.728), peak VO2 (r2⫽0.123), peak VCO2(r2⫽0.648) and TV (r2 ⫽0.579). The derived predictive formulae performed as well as other published predictive equations. CLINICAL IMPLICATIONS: Differences in response to cardiopulmonary exercise testing among racial populations do exist and normal reference values for different populations should be obtained and utilized for proper interpretation of these tests. DISCLOSURE: Lenora Fernandez, Grant monies (from industry related sources) Boehringer-Ingelheim (Philippines) Research Medical Foundation, Incorporated.

RELIABILITY OF THE ERROR CODE FROM THE BEST TRIAL AS AN INDICATOR OF SPIROMETRIC TEST QUALITY USING AMERICAN THORACIC SOCIETY (ATS) CRITERIA Mayuko Fukunaga MD* Shobharani C. Sundaram MD Eugene J. Kim MD James Sullivan BA Steve H. Salzman MD Beth Israel Medical Center, New York, NY PURPOSE: Assessment of spirometric test quality is important in the interpretation of an individual patient’s study, in determining the overall quality of tests being performed by technologists, and when using the data in research. The 1994 ATS criteria for spirometry require three acceptable trials, two of which are reproducible. Computerized testing equipment often provide a five or six digit error code which summarizes whether these criteria have been met. The system in use at our institution provides an error code that identifies whether the reproducibility criteria have been met, yet reports acceptability only for the designated single best trial. The purpose of this study is to determine how frequently an error code from the best trial that is both acceptable and reproducible accurately indicates that all ATS criteria are met when all trial data are manually reviewed. METHODS: All spirometric tests performed on black, white or Hispanic patients in 2003 and 2004 at Beth Israel Medical Center were reviewed. Tests were performed in a SensorMedics Vmax 6200 Autobox (SenorMedics-Viasys, Yorba Linda, CA). The individual trials were manually reviewed for all spirometric studies that had an error code suggesting that ATS criteria for acceptability and reproducibility were met. RESULTS: There were 2416 tests which had an error code indicating that the best trial was acceptable and that reproducibility criteria were met. Among these 2416 tests, 1926 (79.7%) actually had three or more acceptable trials, 380 (16.0%) had two acceptable trials and 110 (4.6%) had only one acceptable trial. CONCLUSION: A final report error code which summarizes whether ATS criteria for reproducibility and acceptability were met can be misleading, unless it also reports how many individual trials meet ATS criteria for acceptability. CLINICAL IMPLICATIONS: Graphical and numerical data, including error codes, should be reviewed from all spirometric trials to best assess test quality prior to the use of the best trial data for interpretation or research. DISCLOSURE: Mayuko Fukunaga, None. SAFETY AND ACCURACY OF INHALATION OF CAPSAICIN AEROSOLS IN A NORMAL ADULT POPULATION D A. Sams DO* Thomas Truncale DO Stuart M. Brooks MD University of South Florida, Tampa, FL PURPOSE: A subject’s death at Johns Hopkins, after inhalation of hexamethonium, led to the FDA discouraging further human research involving inhalation of non-approved medications/drugs. This report describes the safety of inhalation studies using pharmaceutical grade capsaicin and looks at the results of high pressure liquid chromatography (HPLC) analyses of administered doses compared to their calculated concentrations.

392S

METHODS: 35 normal male subjects underwent capsaicin inhalation challenges under an Investigational New Drug (IND) protocol approved by the FDA. Study protocol included the use of pharmaceutical grade capsaicin (Formosa Laboratories, Taiwan), subject safety procedures, and preparation of capsaicin doses by a registered pharmacist. Serial measurements of spirometry and impulse oscillemetry were recorded as well as HPLC measurements of administered capsaicin doses. Continuous electrocardiography, blood pressure, and oxygen saturation were monitored. RESULTS: There were no adverse reactions at any dose tested, including the highest capsaicin concentration of 1000 micromoles. Spirometry and oscillemetry did not change. HPLC measurements of the administered capsaicin concentrations were significantly lower than the calculated doses. The solutions averaged 14.7% lower than the calculated values (2.2% lower at the highest dose of 1000 micromoles and 28.1% lower at the lowest dose of 0.48 micromoles). Coefficient of variation for the doses ranged between 1.7% (125 umol) and 5.4% (0.49 umol). There was stability of prepared capsaicin doses up to 4 months. CONCLUSION: Performance of capsaicin challenges can be considered safe for normal individuals when using pharmaceutical grade capsaicin and following strict safety procedures. HPLC documents accurate capsaicin concentrations for inhalation studies. The actual administered doses are lower than calculated, and HPLC analysis improves accuracy and reproducibility and insures the safety of subject volunteers. CLINICAL IMPLICATIONS: Performance of capsaicin challenges can be considered safe, but there is a discrepancy between calculated and actual dosages administered. This brings in to question the accuracy and reproducibility of previously reported data. DISCLOSURE: D Sams, None.

U.S. BORN ASIAN INDIANS HAVE HIGHER PULMONARY FUNCTION VALUES COMPARED TO IMMIGRANT ASIAN INDIANS Ahmet S. Copur MD Ashok Fulambarker MD* Mark E. Cohen PhD Monali Patel Sanjay Gill George Chacko RRT Joseph K. Rosman MD Frank Maldonado MD Rosalind Franklin University of Medicine and Science/The Chicago Medical School, North Chicago, IL PURPOSE: To evaluate differences in pulmonary function between US born Asian Indians and immigrant Asian Indians that might be attributable to environmental and socioeconomic factors. METHODS: We constructed regression equations to predict forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and mid-expiratory flow rate (FEF25-75) in 90 male and 90 female healthy, non-smoking US born Asian Indians and 160 male and 90 female healthy, non-smoking immigrant Asian Indians, using Age and Height as predictors, as well as these predictors in combination with the binary country of origin variable. Age range in both groups was 18-35. Values were obtained by using a Spirolab spirometer, following strict ATS guidelines. RESULTS: The regression equations for each sex from each country of origin are shown in Table 1. When data for countries were combined and Country was considered as an independent variable in the regression, P-values for Country approached significance for Males (0.0655, 0.0958, 0.3739) and were significant for females (⬍0.0001, ⬍0.0001, 0.0925) for FVC, FEV1, and FEF25-75, respectively. As shown in Table 2, US born subjects had higher values for all measurements. CONCLUSION: US Born, Asian Indian men and women had greater pulmonary function values compared to immigrant Asian Indians. These differences approached statistical significance for men and were significant for women. CLINICAL IMPLICATIONS: The differences in pulmonary function between these groups could be attributed to differences in environmental and socioeconomic factors. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Testing Respiratory Function and Mechanics, continued Table 1—Prediction Equations for US Born and Immigrant Asian Indian Men and Women US Born Asian Indian Men FVC ⫽ -3.378 ⫹ (0.0426)*HT ⫹ (0.0111)*Age R2⫽0.183 FEV1⫽ -1.562 ⫹ (0.0317)*HT ⫹ (-0.0100)*Age R2⫽0.1513 FEF25-75⫽ -2.909 ⫹ (0.0151)*HT ⫹ (-0.0504)*Age R2⫽0.026 Immigrant Asian Indian Men FVC⫽ -4.382 ⫹ (0.0498)*HT ⫹ (-0.0080)*Age R2⫽0.2860 FEV1⫽-2.339 ⫹ (0.0374)*HT ⫹ (-0.0249)*Age R2⫽0.3224 FEF25-75⫽1.979 ⫹ (0.0208)*HT ⫹ (-0.0597)*Age R2⫽0.094 US Born Asian Indian Women FVC⫽ -2.575 ⫹ (0.0329)*HT ⫹ (0.0173)*Age R2⫽0.2875 FEV1⫽ -1.272⫹ (0.0243)*HT ⫹ (0.0072)*Age R2⫽0.2081 FEF25-75⫽ -30.94 ⫹ (0.1716)*HT ⫹ (0.3634)*Age R2⫽0.0257

Table 2—Typical Pulmonary Function Values Derived for a 25 Year Old Man With a Height of 1.75 Meters and a 25 Years Old Woman With a Height of 1.65 Meters. Immigrant TEST

US Born

US Born Asian

Asian

Asian

Immigrant Asian

Indian Men

Indian Men

Indian Women

Indian Women 2.95

FVC⫽

4.35

4.13

3.29

FEV1⫽

3.74

3.59

2.92

2.60

FEF25-75⫽

4.29

4.13

6.46

3.04

DISCLOSURE: Ashok Fulambarker, None. EVALUATION OF THE CORRELATION BETWEEN IMPULSE OSCILLOMETERY (IOS) AND CONVENTIONAL SPIROMETERY PARAMETERS IN PATIENTS WITH POSITIVE METHACHOLIN CHALLENGE TEST (MCT) Ali Moghimi MD* Abbas Nemati MD Mahdi Rahmati MD Iran University of Medical Sciences and Health Care Services, Tehran, Iran PURPOSE: IOS is a new method for the evaluation of the bronchial airway narrowing. In comparison with conventional spirometery IOS is more convenient and needs less patient’s cooperation. The aim of this study is to evaluate the correlation between the IOS and spirometery parameters in patients with positive MCT. METHODS: 42 patients with respiratory symptoms suggesting asthma and positive MCT were studied. All of them had performed an IOS test with MS Jeager device which measures both IOS and spirometery parameters. After administration of different concentrations of methacholin IOS and spirometery parameters were measured. After at least 20% fall in the serial FEV1s, the case considered positive for MCT. The crude and percent changes for X5, Z5, R5, R20, R central and R peripheral of IOS and FEV1, PEFR, MMEF, FEF25%, FEF50% and FEF75% were measured and compared with each other. RESULTS: Percent changes of predicted MMEF and FVC were not correlated significantly with any IOS parameter mentioned above. Significant correlations between the percent changes FEF25%, FEF50%, FEF75% and PEFR and some IOS parameters was not clinically significant (r ⬍ 0.5). Changes in the percent of predicted FEV1 were correlated with percent changes of the predicted and crude values of R5 and R20, all with r ⬍ 0.5. CONCLUSION: This study shows although there are some correlations between IOS and spirometery parameters, these are not clinically

GREATER THAN 12% IMPROVEMENT IN FEV1 OR 25% IMPROVEMENT IN FEF25-75 AS PREDICTORS OF A POSITIVE METHACHOLINE CHALLENGE Zoheir Bshouty MD* Garth Rodgers RRT University of Manitoba, Winnipeg, MB, Canada PURPOSE: To assess the sensitivity, specificity, positive and negative predictive values of greater than 12% improvement in FEV1, or greater than 25% improvement in FEF25-75 as predictors of a positive methacholine challenge in patients with a suspected diagnosis of asthma. METHODS: 378 patients, 158 females and 220 males, with a suspected diagnosis of asthma underwent pulmonary function testing pre and post bronchodilator administration and a methacholine challenge. Sensitivity, specificity, positive and negative predictive values for FEV1, FEF25-75, and either parameter were calculated. Youden Index was also calculated to assess the overall best test. RESULTS: For FEV1, the sensitivity and specificity in predicting a positive methacholine challenge where 42.2% and 79.9% respectively [positive (PPV) and negative predictive values (NPV), 39.6% and 18.4% respectively]. For FEF25-75, the sensitivity and specificity in predicting a positive methacholine challenge where 26.8% and 89.2% respectively (PPV and NPV, 43.7% and 20.4% respectively). When using either FEV1 or FEF25-75, the sensitivity and specificity in predicting a positive methacholine challenge where 47.8% and 78.8% respectively (PPV and NPV, 41.4% and 17%, respectively). The Youden Index for FEV1 was 22%, for FEF25-75 was 15.9%, and for either FEV1 or FEF25-75 was 26.7%. CONCLUSION: FEV1 is a more sensitive test in predicting a positive methacholine test whereas FEF25-75 is a more specific test. The use of either criterion improved sensitivity at a small cost in specificity. Based on the Youden Index either criterion is the best over all test. CLINICAL IMPLICATIONS: Neither FEV1 nor FEF25-75 are good predictors of a positive methacholine challenge. The application of either test does not improve this predictibility. In patients with suspected asthma and negative bronchodilator response methacholine challenge should still be performed to assess the presence of underlying hyperreactive airways disease.

Table 1

Total Number of Patients

378

Males (%) / Females (%) Age [Mean (Range)] FEV1 ⬎ 12% [Number (%)] FEF25-75 ⬎ 25% [Number (%)] Positive Methacholine [Number (%)]

220 (58.2%) / 158 (41.8%) 44.5 (16-71) 96 (25.4%) 55 (14.6%) 90 (23.8%)

DISCLOSURE: Zoheir Bshouty, None. THE IMPACT OF CHRONIC LUNG DISEASES ON THE QUALITY OF LIFE OF PATIENTS MEASURED BOTH BY DISEASE SPECIFIC AND GENERIC INSTRUMENTS Siu Pui Lam MBBS* Pui Shan Lam MBBS Wai Woon Ho MBBS Ho Pui So MBBS Wong Tai Sin Hospital, Hong Kong, Hong Kong PRC PURPOSE: Chronic lung diseases affected the quality of life of patients. We aimed to (1) evaluate the health related quality of life (HRQOL) in patients with chronic lung diseases (2) examine the correlation among the HRQOL measures. METHODS: Patients who joined the Pulmonary Rehabilitation Program between August and December 2004 were included. Pulmonary function, blood gases and 6-min walking test were assessed. HRQOL instruments included: SF-36 (Hong Kong), St George’s Respiratory Questionnaire (SGRQ) and the Functional Impairment Checklist (FIC). RESULTS: The group consisted of 28 male (60.9.%) and 18 female (39.1%) with a mean age of 74.1 (SD ⫹ 9.5, range 39 – 87). The mean CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

Immigrant Asian Indian Women FVC⫽-0.700 ⫹ (0.0223)*HT ⫹ (-0.0011)*Age R2⫽0.1664 FEV1⫽ -0.403 ⫹ (0.0197)*HT ⫹ (-0.0099)*Age R2⫽0.2074 FEF25-75⫽ 1.452⫹ (0.0145)*HT ⫹ (-0.0320)*Age R2⫽0.0813

significant. It might be because of technical considerations to do a correct IOS test and standardization of that. CLINICAL IMPLICATIONS: Results of IOS test in determining airway narrowing have a low correlation with conventional spirometery. DISCLOSURE: Ali Moghimi, None.

Wednesday, November 2, 2005 Testing Respiratory Function and Mechanics, continued FEV1 was 0.76 (SD 0.46), FVC 1.4 (SD ⫹ 0.58) with the FEV1 % predicted 51.2% (SD 24.9). The pulmonary diagnosis included Chronic Obstructive Pulmonary Diseases (COPD 72%), chronic asthma (14%) and pulmonary tuberculosis (10%). The SF-36 domain scores were significantly impaired as compared with the population norms, particularly in physical functioning (mean: 37.4 vs. 91.8), role physical (mean: 35.9 vs. 82.4), general health (mean 37.1 vs. 55.98), vitality (mean 46.7 vs. 60.3) and role emotion (mean: 52.2 vs. 71.7). The norm-based physical component summary (PCS) was 25.7 (mean ⫹ SD 11.1) and mental component summary (MCS) was 52.8 (mean ⫹ SD 12.6). There was significant correlation between SF-36 PCS and FIC scales (FIC-symptom: -0.33, p ⫽ 0.027; FIC-disability: -0.62, p ⬍ 0.001). The SF-36 MCS correlated moderately with FIC-disability (-0.39, p ⫽0.008) but not with FICsymptom and with SGRQ domains. The SGRQ activity domain correlated moderately with SF-36 PCS (-0.44, p ⫽ 0.15) and FIC domains (FICsymptom: 0.37, p ⫽0.44; FIC-disability: 0.5, p ⫽ 0.005). However, the correlation between the other SGRQ domains and SF-36 / FIC was not significant. CONCLUSION: (1)The HRQOL of patients with chronic lung diseases was significantly impaired.(2)Moderate correlations existed among the different HRQOL instruments. CLINICAL IMPLICATIONS: Both generic and disease specific HRQOL instruments should be used as in the comprehensive assessment of patients suffering from chronic lung diseases. DISCLOSURE: Siu Pui Lam, None. THE VALUE OF A GOOD QUALITY FORCED EXPIRED FLOW BETWEEN 25% AND 75% OF THE VOLUME (FEF25-75) IN DETECTING AIRFLOW OBSTRUCTION Jason L. Williams MD* Marcy F. Petrini PhD University of Mississippi Medical Center, Jackson, MS PURPOSE: To determine whether an FEF25-75 from a good flowvolume loop contour provides any additional information. METHODS: The total number of tests performed in 2004 by a University Hospital Pulmonary Function Laboratory were retrospectively analyzed. We discarded tests that did not meet ATS standards, duplicate tests, tests from races other than Caucasian or African-American, or age ⬎ 80 years. The remaining 871 tests were categorized according to obstruction or non-obstruction and the FEF25-75 defined as normal or low according to the NHANES III predictive equations (age ⱕ 80 years). RESULTS: The Table shows the results. Of the 303 tests defined as obstructed by ratio of FEV1 to FVC, SVC (if available) or FEV6, 31% had a normal FEF25-75. Of the 568 non-obstructed tests, 7% had an abnormal FEF25-75. However, only 15 of these tests, or approximately 3%, had flow-volume loop contours that provided a reliable FEF25-75. CONCLUSION: Only 3% of the FEF25-75 provided potentially new information. However, this is the expected value for false positives. The FEF25-75 was normal in 31% of the obstructed tests where it would be expected to be abnormal. CLINICAL IMPLICATIONS: Obstruction is generally detected by using the FEV1/FVC, FEV1/SVC, or the newer FEV1/FEV6 ratio. Analyzing the FEF25-75 does not provide any additional useful information.

Numbers (%)

Obstructed

Non-Obstructed

FEF Normal FEF Low

93 (31%) 210 (69%)

531 (93%) 37 (7%)

DISCLOSURE: Jason Williams, None. DO WE REALLY NEED TO CORRECT FOR LUNG VOLUME WHEN INTERPRETING THE DIFFUSING CAPACITY? Todd Whitman MD David A. Kaminsky MD* University of Vermont College of Medicine, Burlington, VT PURPOSE: The diffusing capacity of the lung for carbon monoxide (DLCO) is commonly used as a measure of gas exchange. The DLCO is usually reported as both an absolute number (DLCO) and corrected for alveolar volume (DLCO/VA). However, it remains unclear which one to use in interpretation. To resolve this dilemma we determined whether abnormal DLCO or DLCO/VA was more closely associated with abnormal gas exchange as measured by exercise oximetry.

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METHODS: With Institutional Review Board approval, we retrospectively reviewed the charts of all patients who had both DLCO and 6-minute walk/oximetry testing at our University Pulmonary Clinic over a 2-year period. We analyzed the association between abnormal DLCO or DLCO/VA (defined as ⬍75% predicted) and abnormal gas exchange (defined as oxygen desaturation ⬎/⫽ 4%) using Chi-square or Fisher’s exact tests, and calculated sensitivity, specificity, positive and negative predictive values (PPV, NPV) and likelihood ratios (LR). We also measured the association between DLCO, DLCO/VA and oxygen desaturation using Spearman rank correlations. RESULTS: A total of 93 patients had valid and complete data. Their average age was 66 years, 54% were women and 60% had interstitial lung disease. The prevalence of oxygen desaturation was 44%. The % predicted values of DLCO and DLCO/VA were highly correlated (rho⫽0.91, p⬍0.0001), but both correlated only weakly with oxygen desaturation (rho ⫽ -0.37, p⫽0.0003; rho⫽ -0.42, p ⬍0.0001, respectively). Low DLCO predicted desaturation with a sensitivity of 0.95, specificity of 0.29, PPV of 0.51, NPV of 0.88 and LR of 1.34 (p⫽0.003). Low DLCO/VA predicted desaturation with a sensitivity of 0.90, specificity of 0.38, PPV of 0.54, NPV of 0.83 and LR⫽1.45 (p⫽0.002). The highest LR (1.91) was seen for DLCO/VA of patients with restriction (p⫽0.04). CONCLUSION: There were no differences in the ability of DLCO or DLCO/VA to predict abnormal gas exchange, but patients with abnormal gas exchange were slightly more likely to have an abnormal DLCO/VA than DLCO. CLINICAL IMPLICATIONS: Either the DLCO or DLCO/VA may be used to assess gas exchange. DISCLOSURE: David Kaminsky, None. A SIMPLE MODEL OF PARADOXICAL VENTILATION AND DIFFUSION-LIMITED GAS EXCHANGE Michael E. Perry MD* Antonio Vila BS Denver Lung, Centennial, CO PURPOSE: We observed a consistent paradoxical reduction of arterial pCO2 in patients with Adult Respiratory Distress Syndrome (ARDS) whenever we minimized minute ventilation with respiratory rates as low as 5/min using 4:1 inverse inspiratory/expiratory (I:E) mode ventilation. This effect was counter-intuitive and its magnitude was a qualitative departure from behavior anticipated by deadspace timing effects or other ventilation/perfusion (V/Q) mechanisms. We wondered whether incomplete CO2 equilibration between the end-capillary and gas-containing compartments could account for our observation. METHODS: We developed a rudimentary two compartment steadystate model of diffusion-limited gas exchange. The model determines the mixed-venous pCO2 value required in the pulmonary capillary to produce a diffusion flux across the boundary into the gas compartment equal to the metabolic production of CO2. The arterial pCO2 is in turn determined by stable metabolic production and cardiac output to be some constant amount less than this mixed-venous value. As opposed to V/Q-based analysis, there is no restriction that CO2 equilibration be complete between pulmonary end-capillary (arterial) blood and ‘alveolar’ gas. Our model maintains diffusion across the alveolar boundary proportional to the partial pressure difference between the mixed-venous blood compartment and the gas compartment. The gas compartment oscillates in an instantaneous fashion, partially emptying between end-inspiratory and endexpiratory positions analogous to the ventilatory cycle of the lung. The model addresses effects of airway dimension by allowing diffusion only during the maximal volume portion of each oscillation. A reconfiguration time corrects for the non-square-wave character of physiologic ventilation. RESULTS: Using a low diffusion co-efficient, inputs of I:E, respiratory rate and tidal volume yield output patterns which demonstrate the efficacy of inverse I:E ventilation and reproduce the phenomenon of paradoxical ventilation. CONCLUSION: Paradoxical ventilation may be a consequence of a diffusion-limited gas exchange regimen. CLINICAL IMPLICATIONS: By directing ventilator strategy in ARDS to maximize diffusion transfer, under certain circumstances much lower ventilator frequencies can be theoretically justified. Lower frequencies might limit ventilator-induced lung injury by minimizing lung movement. DISCLOSURE: Michael Perry, None. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Testing Respiratory Function and Mechanics, continued THE ROLE OF FEF50/0.5 FVC RATIO IN THE DIFFERENTIAL DIAGNOSIS OF VENTILATORY DISORDERS Marcelo T. Rodrigues PhD* Sergio S. Menna Barreto PhD Jussara Fiterman PhD Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil

AIRWAY RESISTANCE IN PATIENTS WITH AIRFLOW LIMITATION ESTIMATED BY THE INTERRUPTER TECHNIQUE Hajime Kurosawa MD* Katsuhiro Maruta PhD Wataru Hida MD Yuko Sano MS Kayomi Matsumoto MS Maki Yamakawa MD Junko Niisato MD Masahiro Kohzuki MD Dep Int Med & Reha Sci, Tohoku Univ Sch Med, Sendai, Japan PURPOSE: Measurement of airway resistance (Raw) requires body plethysmography, which makes difficult to monitor in disabled patients. On the other hand, measurement of airway resistance using the ineterrupter technique (Rint) does not require the big and expencive apparatus, and has been reported in animal models, healthy subjects, pre-school children, and geriatric patients. However, little is known about Rint in patients with high airway resistance. In this study, measurements of Rint was compared those of conventional Raw using body plethysmography in patients with airflow limitation such as COPD. METHODS: We studied 7 patients including 5 with COPD (M:F 5:2, age 59 ⫾ 6.4 years). Rint was measured using a commercialized system (HI-801, Chest M.I., Tokyo). The algorism of Rint measurement in this system is based on a report by Chowienczyk et al. (Eur Respir J 4: 623, 1991). Raw were measured using body plethysmography. RESULTS: The mean FEV1, Rint, and Raw were 1.20 ⫾ 0.64L ranged from 0.57 to 2.13L (51 28%pred, 24-92%), 0.59 ⫾ 0.30 kPa/l/sec (0.28-1.12), and 0.30 ⫾ 0.14 kPa/l/sec (0.05-0.46), respectively. Although Rint was significantly correlated with Raw (r⫽0.86, p⬍0.05), the differences tended to be bigger in patients with high Raw. Since airway pressure curve after interruption was not linear, the oral pressure determination at the time point (t15) immediately after the valve interruption, computed by back extrapolating a line drawn through two points (t30 and t70), was difficult to interprete. CONCLUSION: These results suggest that Rint may be useful to estimate airway resistance even in patients with severe airflow limitation in this system, although the value of the mesurements were higher than the conventionally measured Raw. The determination of the oral pressure at the interruption established by Chowienczyk is needed to be physiologically reexamined.

ASSOCIATION BETWEEN FEATURES OF VIBRATION RESPONSE IMAGING (VRI) OF THE LUNGS AND THE RESULTS OF METHACHOLINE INHALATION CHALLENGE TESTING Payam Aghassi MD* J. Mark Madison MD Issahar Ben-Dov MD University of Massachusetts Medical School, Worcester, MA PURPOSE: Vibration Response Imaging (VRI) is a novel non-invasive technology that creates images of the lungs by recording vibrations from the chest wall during the respiratory cycle. It was hypothesized that some features of VRI images at baseline might predict results of a subsequently performed methacholine inhalation challenge (MIC) test. METHODS: 14 patients underwent baseline VRI imaging immediately prior to a MIC test performed for evaluation of respiratory symptoms. Two readers that were blind to the MIC results independently scored these baseline VRI images, on a scale of 0-3, at different points of the respiratory cycle for shape and intensity, right-left symmetry, and maximum vibration energy detected. Regression analysis was used to test the association between the 16 subcomponent scores describing the VRI image and MIC test results. RESULTS: VRI images were satisfactory for analysis in 13 patients and MIC test results were positive in 6. There was a correlation between the total VRI scores by the two readers (r⫽0.62, p⫽0.03). Average of the total scores by the two readers had a poor association with MIC results (odds ratio⫽0.90, p⫽0.21). However, 3 subcomponent scores for specific image features (early inspiratory expansion, the direction of expansion during inspiration, and maximum vibration energy) showed, in aggregate, a predictive trend (odds ratio⫽3.0, p⫽0.07). The 3 patients with the lowest subcomponent scores had a positive MIC and the 2 patients with the highest scores had a negative MIC. CONCLUSION: Features of VRI images can be scored with interobserver correlation. Early inspiratory expansion, direction of image expansion during inspiration, and maximum vibration energy showed a trend for predicting MIC test results. A larger, prospective clinical evaluation of a scoring system based on these image features needs to be performed. CLINICAL IMPLICATIONS: A semi-quantitative scoring system based on specific features of the baseline VRI image may be useful for the diagnosis of asthma. If such a scoring system can be validated prospectively, VRI would be a new and potentially sensitive method for evaluating asthma. DISCLOSURE: Payam Aghassi, Grant monies (from industry related sources) Supported by Deep Breeze, Ltd.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. PULMONARY FUNCTION IN CHRONIC RENAL FAILURE: EFFECTS OF PERITONEAL DIALYSIS AND HAEMODIALYSIS Amela E. Matavulj MD* Pedja Kovacevic MD Slavimir Veljkovic MD Zvezdana Rajkovaca MD Mirjana Djekic-Cadjo MD Nenad Ponorac MD Medical school, Department of Physiology, Banjaluka, Bosnia-Herzegovina PURPOSE: In patients with chronic renal failure (CRF) there are increased systemic complications induced by the kidney disorders. Every system in the body can be affected, including the lung. Pulmonary oedema and pleural effusions are relatively common. Rarer complications include pulmonary fibrosis and calcification, pulmonary hypertension, haemosiderosis, pleuritis and pleural fibrosis. Renal replacement therapy my also result in complications. Haemodialysis causes recurrent episodes of hypoxaemia due to partial blockage of the pulmonary capillary bed by white cells or silicone microemboli. We estimate effect of different forms of renal replacement therapy (peritoneal dialysis and haemodialysis) on ventilator function improvement in patients with CRF [1, 2]. METHODS: We studied 43 patients (males, females) with CRF who were clinically and radiologically free from known chronic lung and chest wall disease. Twenty one patients (group 1) were receiving continuous ambulatory peritoneal dialysis (CAPD); we studied these patients with the abdomen containing dialysate. Twenty two patients (group 2) were being treated with regular haemodialysis. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow of vital CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: a) to evaluate the contribution of a new coefficient – FEF50/0.5 FVC ratio – from the maximal expiratory flow-volume (MEFV) curve in the differential diagnosis of ventilatory disorders; b) to evaluate the FEF50 / 0.5 FVC ratio in the separation of groups (Normal, Obstructive and Restrictive) of patients; c) to determine cut-off points for each functional diagnosis and the probability of a diagnosis from an individual value and to test the correlation between the FEV1 / FVC ratio and FEF50 / 0.5 FVC ratio. METHODS: After evaluating the MEFV curves of the groups (Normal, Obstructive and Restrictive), we calculated the FEF50 / 0.5 FVC ratio and its differences. The whole sample was then divided in two groups: obstructive and non-obstructive and the analysis of the likelihood ratio (LR) of the FEF50 / 0.5 FVC ratio between them was done. RESULTS: There were 621 forced expiratory maneuvers performed by adults with a broad range of pulmonary abnormalities and normal subjects. The FEF50 / 0.5 FVC ratio was different between the groups Normal (2.10⫾0.82), Restrictive (2.55⫾1.47) and Obstructive (0.56⫾0.29) (p⬍0,001). It also showed a positive correlation with FEV1 / FVC ratio in the obstructive group (r⫽0.83). The analysis of the likelihood ratios for the FEF50 / 0.5 FVC showed that values below 0.79 are strong indications of obstructive disorders and above 1.33 almost exclude this diagnosis. CONCLUSION: The FEF50 / 0.5 FVC ratio is a useful parameter in the differential diagnosis of ventilatory disorders and has positive correlation with the FEV1 / FVC ratio. CLINICAL IMPLICATIONS: Spirometry can provide information in order to make the diagnosis of a ventilatory disorder. Sometimes, however, the conventional approach cannot be used, and more sophisticated resources are necessary, not always available. The FEF50 / 0.5 FVC ratio can help in the differential diagnosis of ventilatory disorders. DISCLOSURE: Marcelo Rodrigues, None.

CLINICAL IMPLICATIONS: This technique would provide the rough value of the airway resistance. It will be useful to study at the bedside where the body plethysmography can not work. DISCLOSURE: Hajime Kurosawa, Employee One of the auther, K Maruta, is an employee of CHEST MI.

Wednesday, November 2, 2005 Testing Respiratory Function and Mechanics, continued capacity (FEF25, 50, 75) were recorded. The results were analyzed using Student t-test, and presented as mean ⫾ SD. All p values ⬍ 0,05 were considered significant. RESULTS: The values of ventilatory function (FEF25) were significantly lower in patients having continuous ambulatory peritoneal dialysis (table 1). CONCLUSION: The values of ventilatory function (FEF25) were significantly lower in patients having continuous ambulatory peritoneal dialysis. CLINICAL IMPLICATIONS: Preliminary observations suggest reversibility of airway obstruction with salbutamol.

Table 1 Replacement therapy predicted (⫾ SD) Function parameters FVC FEV1 FEF75⬍Tc⬎78 (24) FEF50 FEF25 *

Peritoneal dialysis (CAPD) 92(21) 94(23) 89(23) 64(31) 57(20)

Haemodialysis 100(17) 98(20) 75(35) 77(34)*

p ⬍ 0,05

CLINICAL IMPLICATIONS: By the mentioned model %FEV1 can be predicted by %PEFR. DISCLOSURE: Ali Moghimi, None.

DEEP BREATH MANEUVER ASSESSMENT ON GAS EXCHANGE IN EISENMENGER SYNDROME PATIENTS WITH OBESITY Maria-Luisa Martı´nez-Guerra MD Luis-Efren Santos-Martinez MD* Edgar Bautista MD Tomas Pulido MD Gerardo Rojas MD David ˜ amendys MD Alicia Mendoza MD Sandoval Jose-Luis MD Silvio N Castan˜on RN Julio Sandoval MD Instituto Nacional de Cardiologı´a Ignacio Cha´vez, Mexico City, Mexico PURPOSE: Hypoxemia in Eisenmenger syndrome (ES) is a common feature of the disease. Improvement in PaO2 of severely obese patients with hypoxemia through a deep breath maneuver (DBM) and improvement on the V/Q match has been described previously.Objetive: To assess the impact of DBM on gas exchange (GE) on patients with both, ES and obesity. METHODS: 30 patients with ES with obesity and obesity without ES, both with a body mass index (BMI) major than 35 were included. GE was evaluated with ABG sampling at room air and 100% oxygen fraction. They went through routine evaluation including echocardiography and pulmonary function test. Values were expressed as mean ⫾ SD. Independent student t test were used to compare groups. p⬍0.05 was considered as statistically significative. RESULTS: 30 patients were included in two groups: 1) ES ⫹ obesity and 2) Obesity; Demographics variables as age, weight and height were: 55 ⫾ 617; 11 years old, 87 ⫾ 17 kgs, and 153.1 ⫾ 9.5 respectively. The gas exchange values in the groups were:. CONCLUSION: No changes were observed on GE with DBM in ES with obesity patients. CLINICAL IMPLICATIONS: DBM in severely obese patients is useful to evaluate GE, but en ES with obesity patients, the DBM has important limitations.

DISCLOSURE: Amela Matavulj, None.

REGRESSION MODEL FOR THE ESTIMATION OF PREDICTED VALUES OF FORCED EXPIRATORY VOLUMES IN FIRST SECOND (FEV1) BY PREDICTED VALUES OF PEAK EXPIRATORY FLOW RATE (PEFR) IN YOUNG MEN Ali Moghimi MD* Abbas Nemati MD Mahdi Rahmati MD Iran University of Medical Sciences and Health Care Services, Tehran, Iran PURPOSE: FEV1 is accepted as gold standard of the assessing airway caliber which needs spirometer. Despite of FEV1, PEFR could be evaluated by simple peak flow meter instruments, so it will be very helpful to be able to estimate the amount of FEV1 in a patient by his or her PEFR. The aim of this study is to evaluate the correlation between the predicted values of FEV1 and PEFR in patients underwent methacholin challenge test (MCT) and design regression model of their correlation. METHODS: This is a prospective cross-sectional study on 142 young men with respiratory symptoms suggesting asthma which were candidates for MCT. All the patients underwent MCT and spirometery according to American Thorax Society guidelines. The measures of %FEV1 and %PEFR of patients were compared with each other. The normality of distributions was checked by Kolmogorov-Smirnov test. Pearson correlation coefficient was calculated and linear regression used for the statistical analysis. RESULTS: Mean age of patients was 20.83 (SD, 1.92) years and all were male. Although distribution of %FEV1 was not normal, that’s square was distributed normally. %PEFR and square of %FEV1 were significantly correlated (r⫽0.758;p⫽.000) and its regression model was (%FEV1 2 ⫽ 99.74 %PEFR – 381.05) with R⫽0.75. The model was not dependent on the %PEFR and the high and low measures did not affect model. CONCLUSION: It is believed that assessment of airway caliber through PEFR monitoring may not be valid in some asthmatic subjects; yet, study of FEV1 and PEFR correlation looks like a different subject. In addition, it is first report of assessing correlation of PEFR with square of FEV1 which seems to result in a fit model. Like any regression models lack of plausibility is a major problem though further studies have to be considered.

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DISCLOSURE: Luis-Efren Santos-Martinez, None.

Tuberculosis: Diagnostic Evaluation 12:30 PM - 2:00 PM USEFULNESS OF QUANTIFERON-TB AS A DIAGNOSTIC TOOL TO DETECT PLEURAL TUBERCULOSIS Youjeong Sohn MD Dookyung Yang MD* Junghun Huh MD Sookeol Lee MD Choonhee Son MD Minki Lee MD Yunsung Kim MD Eunju Song Chulhun Chang MD Dong-A University Hospital, Busan, Korea PURPOSE: Among several biological markers measured in pleural effusions, interferon (IFN)-gamma is the most sensitive and specific to diagnose pleural tuberculosis (TB). However the measurement of the IFN-gamma level in pleural fluid is not always available. The Quantiferon-TB test (QFT) is a whole-blood IFN-gamma assay for the recognition of cell-mediated immune response to Mycobacterium tuberculosis CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Tuberculosis: Diagnostic Evaluation, continued infection. We investigated whether QFT in whole-blood and pleural effusion is helpful to diagnose pleural TB. METHODS: QFT was performed with the pleural fluid and whole blood of patients with pleural effusion. We also measured pleural fluid adenosine deaminase (ADA) level and did pleural biopsy. Pleural TB was diagnosed if biopsy result shows chronic granulomatous inflammation. RESULTS: Of the 28 patients with pleural effusion, 20 patients were due to TB. The QFT of whole blood was positive in 12 out of 20 pleural TB patients, and sensitivity was 60.0%. The QFT of pleural fluid was positive in 8 out of 18 pleural TB patients. When we set cutoff value for ADA level 40 IU/L, the sensitivity was 85% to detect pleural TB. CONCLUSION: The sensitivity of the QFT in whole blood and pleural effusion was lower than the measurement of the pleural fluid ADA level. CLINICAL IMPLICATIONS: Our result demonstrates that the QFT in whole blood and pleural fluid is not helpful to diagnose pleural TB in the region where TB prevalence is high. DISCLOSURE: Dookyung Yang, None.

PURPOSE: The Quantiferon-TB test (QFT) is a whole-blood interferon (IFN)-gamma assay for the recognition of cell-mediated immune response to Mycobacterium tuberculosis infection. It is already known as a useful diagnostic tool for the latent tuberculosis, but there is no study whether it can be also used to detect active tuberculosis (TB). So we investigated usefulness of the QFT for the diagnosis of active TB. METHODS: We prospectively studied in two tertiary care hospitals from Aug. 2004 to Feb. 2005. 54 patients clinically suspected as active TB were enrolled; 39 patients were AFB culture positive or histologically confirmed and 15 patients were not. We measured IFN-gamma response to PPD in whole blood assay. RESULTS: The QFT of whole blood was positive in 25 out of 39 active TB patients and negative in 7 out of 15 non-TB patients. So the sensitivity, specificity, positive predictive value and negative predictive value of the QFT were 64.1%, 46.6%, 75.7% and 33.3%, respectively. CONCLUSION: Our result demonstrates that the QFT in whole blood is not useful for the diagnosis of active TB in the region where TB incidence is high. CLINICAL IMPLICATIONS: QFT in whole blood is not useful for the diagnosis of active TB in the region where TB incidence is high. DISCLOSURE: Dookyung Yang, None.

OXIDANTS STRESS AND ANTIOXIDANTS IN PULMONARY TUBERCULOSIS Kiranjit Kaur MD Jai Kishan MD* Gurdeep K. Bedi MD Rajinderjit S. Ahi MBBS TB & Chest Dept/Hospital Govt. Medical College, Patiala, India PURPOSE: Recent literature implicate free radicals in physiologic/ pathophysiologic processes and in wide spectrum of diseases.Tuberculosis is an ancient disease but has stayed in modern times. Mycobacteria are intracellular pathogens who grow and replicate in the host macrophages. In an attempt to kill mycobacteria, host cells namely-macrophages, neutrophills and monocytes generate huge amounts of reactive oxygen species, which also contribute to inflammatory injury to host tissues. Many studies are not avialable where oxidative stress and antioxidants have been studied in pulmonary tuberculosis (PTB). So present study was undertaken. METHODS: In 50 patients of PTB and 30 normal controls,malonyldialdehyde(MDA)as marker of oxidative stressand glutathione(GSM),Vit.C,superoxide dismutase(SOD)fot antioxidants status were studied.MDA,GSH,Vit. C and SOD were estimated by methods of Stocks and Dormandy(1971),Beutler et al (1963),varley (2004) and Marklund and Marklund (1974) respectively.Patients of PTB were classified according to radiological extant,sputum grading and cavity status. RESULTS: Levels of MDA,GSM,Vit.C &SOD and there statistical significance is as given in table below there was significant correlation between radiological extent,sputum grading and cavity status of PTB and the levels of MDA, GSM,Vit. C and SOD. CONCLUSION: There is oxidative stress and decreased antioxidants activity in patients of PTB which correlate with radiological extent,Sputum grading and cavity status. CLINICAL IMPLICATIONS: Antioxidants can have role in patients of PTB for prevention and treatment of infammatory damage.

Investigation MDA GSH Vit. C SOD

Study Group Mean ⫾ SD 706.24 31.59 0.68 18.83

⫾ ⫾ ⫾ ⫾

158.68 5.82 0.11 5.10

Control Group Mean ⫾ SD

Stat. Signi.

⫾ ⫾ ⫾ ⫾

HS HS HS HS

538.32 36.16 1.14 24.04

147.72 6.55 0.22 6.87

DISCLOSURE: Jai Kishan, None. THE PREVALENCE OF LATENT PULMONARY TUBERCULOSIS (LTB) IN A NORMAL AND A HIGH RISK POPULATION GROUP S. Ali MBBS* N. Chew MBBS P. Manning PhD N. Noonan MD J. Keane MD C. Bergin MD St. James’s Hospital, Dublin, Ireland PURPOSE: To assess the efficacy of screening and compare the incidence of Latent Tuberculosis (LTB) and clinical Tuberculosis in two different population groups. METHODS: We evaluated the screening data of two different groups in the country’s biggest Hospital. The normal population comprised the employees joining the Hospital, while the high risk group comprised of patients suffering from HIV. The cases with positive Mantoux had been offered CXR and once found clear of TB were labelled as LTB. RESULTS: The mean age of healthy group was 38 and HIV 51 years. 1948 were men in the healthy and 207 in HIV group. The number of native Irish in these groups was 2001 and 99, while that of Non Irish was 409 and 232. The number of Non Irish patients in HIV was 232(65.9%) from Sub Sahara, 33(9.3%) from Europe, 4(1.1%) from USA and 1(0.28%) from Asia. The number of individual having LTB (positive Montoux test and normal CXR) was 765(31.7%) in normal and 39(11.07) in HIV group. CONCLUSION: The data in our study indicates that a significant proportion of normal healthy population and HIV group had Latent Tuberculosis (LTB). While the incidence of LTB was higher in the normal healthy population, the incidence of clinical TB was higher in HIV group.

CHANGE OF IL-12 AND TNF-ALPHA PRODUCTIONS MEASURED BY WHOLE BLOOD CULTURE IN TUBERCULOSIS PATIENTS AFTER TREATMENT Young S. Kim MD* Jin W. Moon MD Chang H. Han MD Shin M. Kang MD Moo S. Park MD Se K. Kim MD Joon Chang MD Sung K. Kim MD Yonsei Univ College of Medicine, Seoul, South Korea PURPOSE: Tuberculosis is one of the leading infectious diseases in adults, causing around 3 million deaths annually. Research on understanding the host defense and immunopathogenesis of tuberculosis is necessary because there is an urgent need for a new vaccine and adjunctive immunotherapy, particularly in patients with drug resistant Mycobacterium tuberculosis infection. Recently, many aspects of cytokine dynamics in patients with active pulmonary tuberculosis have been investigated through ex-vivo studies with specific or crude mycobacterial antigens, or M. tuberculosis. METHODS: We used whole blood culture method in order to evaluate IL-12 and TNF-alpha productions in active TB patients, tuberculin skin test positive and negative healthy controls. We investigated the productions of IL-12, TNF-alpha in response to nonspecific mitogens and M. tuberculosis specific antigens. We used many tuberculous antigens for stimulation. The tuberculous antigens are culture filtrate proteins (CFP), purified protein derivatives (PPD), antigen 85A M. tuberculosis proteins (Ag85A), early secretory antigen target-6 (ESAT-6), 38k Dalton antigen CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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USEFULNESS OF QUANTIFERON-TB AS A DIAGNOSTIC TOOL FOR ACTIVE TUBERCULOSIS Youjeong Sohn MD Dookyung Yang MD* Junghun Huh MD Sookeol Lee MD Choonhee Son MD Minki Lee MD Yunsung Kim MD Eunju Son Chulhun Chang MD Dong-A University Hospital, Busan, Korea

CLINICAL IMPLICATIONS: This study strongly highlights the significance and need of screening for Tuberculosis. DISCLOSURE: S. Ali, None.

Wednesday, November 2, 2005 Tuberculosis: Diagnostic Evaluation, continued (38kDa), RNA polymerase ␤ subunit B1 (rpoB1), RNA polymerase ␤ subunits B2 (rpoB1), arabinofuranasyl lipoarabinomannan(araLAM), manosyl-capped lipoarabinomannan(manLAM), and non-specific mitogens are concanavalinA(ConA), lipopolysaccaride(LPS), phytohaemagglutinin(PHA). In addition, we monitored the changes of each cytokine production in TB patients during the course of therapeutic treatment. RESULTS: In our study, production of IL-12, TNF-alpha to nonmannose-capped lipoarabinomannan(araLAM) increased significantly in active tuberculosis patients compared to healthy controls, After 2 month, production of IL-12, TNF-alpha to araLAM decreased significantly throughout the therapeutic periods. CONCLUSION: Our study suggest that productions of IL-12, TNFalpha plays a important role in the pathogenesis and treatment of tuberculosis. CLINICAL IMPLICATIONS: Whole blood culture method to IL-12, TNF-alpha may be used in the diagnosis of active pulmonary tuberculosis. DISCLOSURE: Young Kim, None.

lymphadenitis was proven by lymph node biopsy based on the histology and/or growth of MTB on culture. RESULTS: The following results obtained. CONCLUSION: Foreign born particularly immigrants from Indian subcontinent constituted the predominant patient subgroups with TB lymphadenitis. Cervical lymphadenopathy constituted predominant lymph node group involved. PPD was positive in only 60%, while only 8% had sputum growing MTB. 72% of patients had positive lymph node culture for MTB and in others pathology showing caseating granulomas was needed to establish diagnosis. 6 months of treatment was adequate in most of the patients. Major reasons for prolonged duration were adverse reactions and non compliance. 8% of paradoxical reaction seen was similar to that described with TB involving other systems. CLINICAL IMPLICATIONS: In patients with subacute to chronic lymphadenitis especially from Indian subcontinent, TB should be strongly considered even if PPD is negative and sputum is negative for MTB. Lymph node pathology showing caseating granuloma establishes the diagnosis even if culture is negative.

TUBERCULOUS LYMPHADENITIS: CLINICAL CHARACTERISTICS AND OUTCOME IN A COMMUNITY HOSPITAL Tapan K. Gayen MD* Ravindra Hanumaiah MD Vijay Rupanagudi MD Karthikeyan Kanagarajan MD Santi Dhar MD Coney Island Hospital, Brooklyn, NY PURPOSE: Tuberculosis (TB) affecting the lymph nodes remain the most common extra pulmonary involvement by Mycobacterium Tuberculosis (MTB). In United States, over the last 35 years, the proportion of Tuberculous lymphatic disease has risen substantially, whereas reductions have been most pronounced in other forms of extra pulmonary TB. The aim of our study is to identify characteristics associated with its presentation, diagnosis and treatment. METHODS: Retrospective review of 50 cases of TB lymphadenitis seen between 1992 to 2005 in a community hospital. Diagnosis of TB

Variable

Value (%)

Median age Male: Female Demography Indian subcontinent US born Others PPD positive HIV positive Sputum culture ⫹ for MTB Lymph node Culture & Sensitivity Culture ⫹ for MTB Pansensitive Multi drug resistant TB Duration of treatment 6 months 9 months 12 months 18 months 24 months* Adverse reactions Abnormal Liver function tests Skin rash Paradoxical reaction Reasons for prolonged treatment Adverse reactions Non compliance Relapse Drug resistance

39 years 1:1 32 (64%) 8 (16%) 10 (20%) 30 (60%) 7 (14%) 4 (8%) 36 (72%) 35 (70%) 1 (2%) 35 (70%) 6 (12%) 4 (8%) 3 (6%) 2 (4%) 11 (22%) 4 (4%) 4 (8%) 6 (12%) 6 (12%) 2 (4%) 1 (2%)

*One patient with multi drug resistance and another patient with relapse received 24 months of treatment 398S

DISCLOSURE: Tapan Gayen, None. PULMONARY AND PLEURAL TUBERCULOSIS IN EXTREME ELDERLY Eun A Eum MD* Yangjin Jegal MD Moo Cheol Shin MD Kwang Won Seo MD Woon-Jung Kwon MD Jong-Joon Ahn MD Department of Pulmonology and Critical Care Medicine, Ulsan University Hospital, Ulsan, Korea PURPOSE: Several publications about tuberculosis in elderly patients have suggested that their clinical presentation and clinical course might be atypical from those in elderly. This tendency may be more strengthened with advancing years in age. The aim of this study was to compare clinical features of pulmonary and pleural tuberculosis in extreme elderly (ⱖ80 years old) with those in elderly (between 60 and 79). METHODS: Thirty-seven extreme elderly with pulmonary and pleural tuberculosis from Ulsan University hospital between January 2000 and December 2004 were compared with randomly selected fifty-six elderly patients. RESULTS: General weakness was the only symptom that was observed more frequently in extreme elderly than in elderly (p⫽0.016). Other symptoms such as cough, sputum, fever, weight loss, anorexia and chest pain were not different between two groups. Dyspnea tends to be more frequent, and hemoptysis tends to be less common in extreme elderly although they were not statistically significant (p⫽0.056, 0.053 respectively). Evolution time before diagnosis and laboratory findings at presentation were not different between two groups. The incidence of comorbid conditions such as chronic obstructive pulmonary disease, diabetes, gastrectomy and malignancies were not different between two groups. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Tuberculosis: Diagnostic Evaluation, continued Anorexia was more frequently observed in extreme elderly than elderly after initiation of antituberculous drugs. The incidences of hepatotoxicity, skin rash, optic neuritis and peripheral neuropathy were not different. Moreover, the mortality from tuberculosis was not different between two groups. Three cases died from tuberculosis in extreme elderly. The cause of death for those three cases was mainly discontinuation of antituberculous drug. CONCLUSION: The clinical features and prognosis of pulmonary and pleural tuberculosis in extreme elderly were not significantly different from those in elderly. CLINICAL IMPLICATIONS: Tuberculosis even in extreme elderly should be treated with standard regimens because adverse effects of antituberculous drugs and prognosis were not different from elderly patients. DISCLOSURE: Eun A Eum, None.

positive. Radiologically bilateral lesions were seen in 60.9% cases and unilateral in 39% of which most were left sided. Disease was far advanced in 46.8%, moderately advanced in 43.7% and minimal in 9.3% cases. Patchy infiltration and nodular pattern was most common (75%) followed by cavitary (15.6%), Pleural effusion (7.8) and miliary pattern (1.5%). Lesions were almost equally distributed in upper, mid and tower zones. 26.5% patients were having associated extrapulmonary tuberculosis. CONCLUSION: In alcoholics due to decreased immunity due to various factors tubecrculosis is extensive and may take serious form. CLINICAL IMPLICATIONS: In alcoholics, tuberculosis involvement is extensive and presents bilateral radiological shadows in majority of cases. Non cavitary exudative lesions are more common along with extrapulmonary involvement in significant proportion of cases. DISCLOSURE: Dr Sidharth Sharma, Product/procedure/technique that is considered research and is NOT yet approved for any purpose.

THORACIC COMPLICATIONS IN TUBERCULOSIS AND DIABETES PATIENTS Ma Cecilia Garcia-Sancho MS* Enrique L. Segundo MD Rafael V. Vazquez MS Alfredo Torres MD Manuel Castillejos MS Miguel Angel Salazar Lezama MD National Institute of Respiratory Diseases, Mexico, Mexico

PULMONARY COMPLICATIONS IN PATIENTS WITH TUBERCULOSIS Enrique Lopez Segundo MD* Rafael Valdez MS Ma. Cecilia Garcia Sancho MS Manuel Castillejos MS Alfredo Torres MD Miguel Angel Salazar MD National Institute of Respiratory Diseases, Mexico, Mexico

CLINICO-RADIOLOGICAL PROFILE OF PLUMONARY TUBERCULOSIS IN ALCOHOLICS Ramakant Dixit MD Sidharth Sharma MBBS* J.L.N. Medical College, Ajmer, India PURPOSE: Risk of tuberculosis is said to be higher in alcoholics due to defect in host defence, whether this is associated with altered clinicoradiological presentation, we conducted this prospective study over last 2 years. METHODS: 64 consequtive patients having history of almost regular alcohol intake of more than 5 years, in whom pulmonary tuberculosis was diagnosed were included in this study. Their HIV seropositivity was ruled out by Elisa. RESULTS: Most of the patients (70.3%) were above forty years of age. All were male and smoker. Cough (90.6%) and fever (65.6%) were chief symptoms followed by chest pain (45.3%) breathlessness (32.8%) and haemoptysis (10.9%). On initial sputum examination, 42.1% were smear

PURPOSE: To determine the prevalence of thoracic complications in tuberculosis patients. METHODS: This study was a cross-sectional survey based on the retrospective analysis of data of tuberculosis patients and was conducted at National Institute of Respiratory Diseases (INER), Mexico. RESULTS: One hundred and twenty four tuberculosis patients were included from July to December of 2003. Of124 patients, 58 (46.8%) were males, with a ratio male:female of 0.88. Median age was 48 (range 16-80 years). Of 124 patients (99/124) 80%% had 0-5 years since diagnosis. Complications were: bronchiectasis (107/124) 86.3%; pneumonia (7/124) 5.7%; pneumonia due to Mycobacterium tuberculosis (5/124) 4.0%; empiema (4/124) 3.2%; fistula (3/124) 2.4%; aspergilloma (2/124) 1.6%; tracheal obstruction (1/124) 0.8%; fibrothorax (15/124) 12.1% and hemoptysis (38/124) 30.2%. In multivariate analysis death was associated to pleural effusion (OR⫽ 15.07 [CI95% 1.12-201] p ⫽.04) controlling by crowding, pneumonia, empiema, hemoptysis, diabetes, time of diagnosis and age. CONCLUSION: The increased risk of bonchiectasis, pneumonia and hemoptysis observed is due to delay in tuberculosis diagnosis and treatment. CLINICAL IMPLICATIONS: Delay in tuberculosis diagnosis could be determinant in the quality of life and survival of these patients. DISCLOSURE: Enrique Lopez Segundo, None. DIAGNOSTIC ROLES OF BRONCHOSCOPY IN PULMONARY TUBERCULOSIS Sang-Ha Kim MD* Won-Yeon Lee MD Tae-Won Hong MD Nak-Won Lee MD Hoon Choi MD Suk-Joong Yong MD Kye-Chul Shin MD Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea PURPOSE: The fiberoptic bronchoscopy has been used widely in diagnosing pulmonary diseases. It is a useful procedure for evaluating suspected cases of pulmonary tuberculosis. The aim of the study was to classify bronchoscopic findings of pulmonary tuberculosis and to evaluate the diagnostic yield by bronchoscopic procedure. METHODS: We have analyzed the clinical characteristics of 93 patients who had visited our hospital and been performed bronchoscopic procedure for the diagnosis of pulmonary tuberculosis from March 1, 2003 to December 31, 2003, retrospectively. Pulmonary tuberculosis was confirmed by direct smear, culture, tissue biopsy and TB-PCR in all studied subjects. Bronchoscopic findings of pulmonary tuberculosis was classified into three types (endobronchial tuberculosis, bronchial anthracosis and normal bronchus) and endobronchial tuberculosis classified into seven subtypes as stenotic type with fibrosis, stenotic type without fibrosis, actively caseating type, tumorous type, ulcerative type, and granular type. RESULTS: Only 24.7% (30/93 patients) had the positive results of sputum smear and culture for AFB. For the bronchoscopic procedures, pulmonary tuberculosis was confirmed by direct smear and culture in 59.1% (55/93), bronchoscopic biopsy in 66.7% (26/39), TB-PCR in 86.3% (63/73). The patient with normal bronchial finding was 31.2% (29/93 patients) of the studied subjects. We observed that the prevalence of CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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PURPOSE: To determine the prevalence of thoracic complications among pulmonary tuberculosis and diabetes patients in comparison with patients with tuberculosis alone. METHODS: This study was a cross-sectional survey based on the retrospective analysis of data of tuberculosis subjects in diabetic and not diabetic patients. The study was conducted at Clinic of Tuberculosis of National Institute of Respiratory Diseases (INER), Mexico. RESULTS: One hundred and sixteen tuberculosis patients were included from July to December of 2003. Fifty-two cases of diabetes mellitus were identified among 116 tuberculosis patients, prevalence: 44.8%. Of116 patients, 56 (48.3%) were males, with a ratio male:female of 0.93. Of 116 patients 91.4% have bacteriological confirmation. Of 116 patients (92/116) 79.3% have from 0 to 5 years from diagnosis of tuberculosis. The tuberculosis and diabetes patients were older than tuberculosis patients (mean ⫾SD 52.38⫾11.35 versus 40.70⫾16.55 p ⬍.0001). Complications among diabetics or no diabetics patients were: bronchiectasis (96.2% versus 80.9%, p ⫽.01); pneumonia (9.6% versus 1.6%, p⫽.05); pneumonia by Mycobacterium tuberculosis (7.7% versus 1.6%, p ⫽.1) and hemoptysis (34.6% versus 29.7% p ⫽.6). In multivariate analysis diabetes mellitus was associated to older age (OR⫽ 1.06 years [CI95% 1.02-1.10] p ⬍.0001) and to the presence of bronchiectasis (OR⫽ 13.95 [CI95% 1.84-105] p ⫽.01), controlling by crowding, pneumonia, empiema, hemoptysis and time since tuberculosis diagnosis. CONCLUSION: The increased risk of bonchiectasies and pneumonia among patients with diabetes and tuberculosis suggest the difficulty of the host in the infection control. One of two tuberculosis patients was diabetics at INER. CLINICAL IMPLICATIONS: It is necessary to do bacteriological and clinical surveillance for pulmonary tuberculosis among diabetic patients and clinical and metabolic surveillance for diabetes among tuberculosis patients with the purpose to prevent sequels and deaths due to tuberculosis. DISCLOSURE: Ma Cecilia Garcia-Sancho, None.

Wednesday, November 2, 2005 Tuberculosis: Diagnostic Evaluation, continued bronchial anthracosis was 18.3% (17/93) and endobronchial tuberculosis was 50.5% (47/93). Out of the patients with endobronchial tuberculosis, actively caseating type and stenotic type without fibrosis were observed in 34.0% (14/47), 25.5% (12/47), respectively. And we observed that the nonspecific bronchitic type, stenotic with fibrosis, tumorous type, ulcerative type and granular type were 19.1% (9/47), 6.4% (3/47), 6.4% (3/47), 6.4% (3/47) and 2.1% (1/47), respectively. CONCLUSION: The endobronchial tuberculosis was the most frequent finding of pulmonary tuberculosis except normal bronchial finding. It is important to find out the cases with endobronchial tuberculosis early because it frequently combined with severe complications such as bronchial stenosis. CLINICAL IMPLICATIONS: We suggest that the bronchoscopy should be considered when we evaluate the possibility of pulmonary tuberculosis in the countries with high prevalence of it. DISCLOSURE: Sang-Ha Kim, None. DIAGNOSIS OF PULMONARY TUBERCULOSIS IN PATIENTS WITH CLINICAL OR RADIOLOGICAL EVIDENCE OF DISEASE AND NEGATIVE SPUTUM Viviane R. Figueiredo MD Francisco S. Vargas MD Ma´rcia Seiscento MD Jorge Kawakama MD Milena M. Acencio BS Ce´sar L. Moreira BS Evaldo Marchi MD Leila Antonangelo MD* Pulmonary Division-Heart Institute (InCor) and Department of Pathology, Sa˜o Paul, Sa˜o Paulo, Brazil PURPOSE: To evaluate the performance of laboratorial tests in diagnosing tuberculosis in patients with clinical or radiological evidence of disease but with negative sputum. METHODS: Thirty-four patients with clinical (cough, fever, weigh loss) or radiological (micronodules, consolidation, cavitation, nodules) suspicion of pulmonary tuberculosis but having negative sputum were submmited to fiberoptic broncoscopy to obtain bronchoalveolar lavage (BAL). Sensitivity, Specificity, PPV and NPV of BAL smear, culture, PCR and ADA (cut-off 2.5 U/L); bronchial biopsy;smear and culture from induced sputum (collected after the BAL)and PPD were evaluated. RESULTS: From the 34 patients with tuberculosis suspicion, only 22 (64.7%) had been confirmed the diagnosis. The performance of the tests is showed in the table bellow. CONCLUSION: PPD and cultures (BAL and sputum) were the most sensitive methods for the diagnosis of pulmonary tuberculosis. However, due to the low specificity of the PPD, this test may be judged with criteria in places where there is high prevalence of tuberculosis. CLINICAL IMPLICATIONS: The diagnosis of tuberculosis in patients with negative sputum is a clinical problem all over the world. The association of multiple laboaratory tests can improve the diagnosis field. BAL BAL BAL BAL Bronchial Pos BAL Pos BAL smear culture PCR ADA biopsy smear culture PPD Sensituvity (%) Specificity (%) PPV(%) NPV(%)

13.6 66.7 35 100 100 100 100 100 100 38.7 57.1 48.0

35.7 60 54.5 30.0

31.8 100 100 44.4

21.1 100 100 55.5

53.3 100 100 53.3

90 14.3 60.0 50

DISCLOSURE: Leila Antonangelo, None.

one way analysis of variance was used to compare the data between the groups. Significant statistical differences were considered for p⬍ 0.05. RESULTS: The results are expressed in median (CI 25-75%) and are demonstrated in the table below. CONCLUSION: We do not observe significant differences for IL-1␤, TNF␣ and TGF␤ among tuberculosis patients, patients with others pulmonary diseases and control group. CLINICAL IMPLICATIONS: This profile of cytokines do not contribute to differentiate tuberculosis from others pulmonary diseases and must not be used for diagnosis in patients with clinical or radiological suspicion of tuberculosis and negative smear.

Control IL-1␤ TNF-␣ TGF-␤1

Tuberculosis Non-Tuberculosis

p

7.8 (7.8-7.8) 7.8 (7.8-31.8) 7.8 (7.8-140.2) 0.515 15.6 (15.6-15.6) 24.5 (15.6-41.8) 15.6 (15.6-52.7) 0.213 31.2 (31.2-31.2) 31.2 (31.2-31.2) 31.2 (31.2-65.2) 0.503

DISCLOSURE: Leila Antonangelo, None. INDUCED SPUTUM VERSUS FIBEROPTIC BRONCHOSCOPY IN DIAGNOSIS OF PULMONARY TUBERCULOSIS Amr A. Darwish MD* Ahmed A. Abd el Rahman MD Wafaa A. Zahraan MD Nourane Y. Azab MD Mohammed A. Agha MD Menouffyia University, Menouffyia, Egypt PURPOSE: Tuberculosis (TB) remains one of the deadliest diseases in the world.Cases can’t expectorate sputum constitute a major problem especially in developing countries. Therefore, the aim of this study was to compare between sputum induction (SI) using nebulized hypertonic saline and fiberoptic bronchoscopy (FOB) in the diagnosis of pulmonary TB in clinically and radiologically suspected cases. METHODS: This study included 30 patients(17 males and 13 females)with clinical and radiological suspicion of pulmonary TB. They had either dry cough or negative repeated sputum examinations for AFB. Three successive SI using nebulized hypertonic saline and FOB were done for all patients. Ziehl-Neelson stain (Z.N.) and Lowenstein-Jensen media(L.J.) were be used for the diagnosis of tuberculosis. RESULTS: The sensitivity, specificity and accuracy of SI compared with bronchial washing using Z.N. were 80%,100% and 90% respectively.While,using L.J. media the sensitivity, specificity and accuracy of SI compared with bronchial washing were 88%, 100% and 90% respectively.The positive results of SI and post-bronchoscopic sputum were similar 22 cases (66.7%). There was no significant difference (P⬎0.05) between SI, 20 cases (66.7)and bronchial brushing,23 case (76.7) in diagnising pulmonary TB. The third SI sample is the most significant sample in detecting AFB (19 cases). CONCLUSION: Sputum induction is an easy, effective, cheap and non-invasive procedure for the diagnosis of pulmonary TB compared to FOB. Also, SI is very suitable diagnositic technique where FOB isnot available. CLINICAL IMPLICATIONS: Sputum induction must be done to every patient with clinical and radiological suspecion of pulmonary TB who can’t expectorate sputum or their sputum were negative for AFB. Fiberoptic bronchoscopy should be postponed until three induced sputum samples proved to be negative for AFB. DISCLOSURE: Amr Darwish, None.

CITOKYNES IN BRONCHOALVEOLAR LAVAGE FROM PATIENTS WITH PULMONARY TUBERCULOSIS AND NEGATIVE SPUTUM Leila Antonangelo MD* Milena M. Acencio BS Francisco S. Vargas MD Lisete R. Teixeira MD Ma´rcia Seiscento MD Wilson L. Pedreira Junior MD Gabriela G. Carnevale PharmD Viviane R. Figueiredo MD Pulmonary Division-Heart Institute (InCor) and Department of Pathology, Universi, Sao Paulo, Brazil

EVALUATING THE DIAGNOSIS OF TUBERCULOSIS IN INDUCED SPUTUM COLLECTION AND BRONCHOALVEOLAR LAVAGE SPECIMENS Rogerio G. Xavier MD* Fabricio L. Savegnago Fernanda Damian Nata´lia Fernandes Moˆnica Rodrigues Patrı´cia Passos Paulo Franciscatto Pedro Piccinini Luce´lia Henn MD Bronchology Unit, Hospital de Clı´nicas de Porto Alegre, Porto Alegre, Brazil

PURPOSE: To evaluate the IL-1␤, TNF-␣ and TGF␤1 profile in samples of brochoalveolar lavage obtained from patients with pulmonary tuberculosis and negative smear and culture sputum. METHODS: Samples of bronchoalveolar lavage obtained from 19 patients with pulmonary tuberculosis, 8 patients with others pulmonary diseases and 4 patients without pulmonary disease (control) were evaluated for IL-1␤, TNF␣ and TGF␤ by an ELISA assay. The Kruskal -Wallis

PURPOSE: Validation of induced sputum (IS) with aerosol hypertonic saline solution followed by bronchoalveolar lavage (BAL) through flexible bronchoscopy (FB) in patients without spontaneous sputum for the diagnosis of pulmonary tuberculosis (TB). METHODS: Sputum was induced after 3 or more unsatisfactory spontaneous collection for acid fast bacilli (AFB). FB was recommended to collect BAL in a series of 99 patients with clinical suspicion of TB that

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CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Tuberculosis: Diagnostic Evaluation, continued side of incidence (right or left) , size (⬎ or ⬍ 75% of the compromised hemithorax) and macroscopic appearance (hemorragic or not) were also analysed. Statistical analysis: Firstly, we used univariate tests to detect the variables that significantly differentiated the groups (Tb and Mal). After, we submit these selected variables to logistic regression. With the ␤ coefficients associated to the variables that composed the best models we purposed algorithms capable to do these diagnosis with the best efficiencies and lower costs. After, we tested the classificatory power of the models in 64 pleural exsudates whose diagnosis were unknown. RESULTS: For pleural tuberculosis, the best model included: ADA, globulin and negative oncotic cytology given a 99.4% sensitivity;96.1% specifity;95.7% PPV and 99.5% of NPV. For neoplastic pleurisy, the best model was composed by age, hemmorrhagic aspect, macrophage percentual and positive or suspicious cytology that given a 96.3% sensitivity; 91.4% specifity;91.1% PPV and 96.6 of NPV. When these models were applied to the 64 exsudates, the sensitivity, specificity, PPV and NPV were respectively: For tuberculosis diagnosis: 100%, 91.1%, 99.9% and 100%.For malignancy: 82.1%, 100%, 100% and 87.8%. CONCLUSION: These simplified models presented good efficiency in diagnosing pleural tuberculosis and malignancy and do this at the expense of routine and low-cost variables. CLINICAL IMPLICATIONS: The possibility of using these models in the clinical practice without to be necessary doing pleural biopsies.

ACCURACY OF THE RADIOMETRIC BACTEC IN THE DIAGNOSIS OF TUBERCULOUS PLEURAL EFFUSION COMPARED TO PLEURAL BIOPSY AND CLINICAL COURSE Bernardo D. Briones MD* Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines

Scoring system to predict tuberculosis and malignancy

PURPOSE: To determine the accuracy of the Bactec system in the diagnosis of Tuberculous Pleural Effusion compared to histopathology and clinical course. METHODS: All patients in the Chest Clinic Registry with Pleural Effusion confirmed by x-ray and or ultrasound between January, 1995 to December, 2003 were studied. All subjects had clinical evaluation, Mantoux test, thoracentecis/pleural biopsy, effusion Kinyoun AFB smear, pleural tissue Bactec culture and histopathology. Laboratory and pathologist had no prior knowledge of actual diagnosis. Patients were assessed independently based on a modified ATS Classification for TB Disease status and followed-up by same attending pulmonologist. RESULTS: Data of 175 of 185 registered patients were available for analysis. At 49.2% TB prevalence, Histopathology has 77.5% sensitivity, 98.9% specificity, 69.8% positive predictive value, 81.7% negative predictive value, 9.8 Likelihood ratio (⫹), 0.23 likelihood ratio (-) and 88.2% overall accuracy while Bactec has 30.9% sensitivity, 93.6% specificity, 83.3% positive predictive value, 55.6% negative predictive value, 4.8 likelihood ratio (⫹), 0.74 likelihood ratio (-) and 61.6% overall accuracy. CONCLUSION: Using a single pleural biopsy specimen, histopathology appears more accurate and faster than Bactec culture in the diagnosis of TBPE. There is no significant morbidity with the Cope Needle pleural biopsy. CLINICAL IMPLICATIONS: The etiology of Pleural Effusion is always a clinical dilema. Pleural biopsy with culture for M.TB often facilitates the diagnosis and treatment in a high prevalece setting. DISCLOSURE: Bernardo Briones, Grant monies (from sources other than industry) INCLEN Thesis grant on the original study of the serodiagnosis of PTB.

ADA (⬎46.5) Negative Oncotic Cytology Globulin (⬎2.05 mg/dl)

A COST-MINIMIZING DIAGNOSIS MODELS FOR DISCRIMINATION BETWEEN NEOPLASTIC AND TUBERCULOUS PLEURAL EFFUSIONS UTILIZING ROUTINE CLINICAL AND LABORATORY VARIABLES Roberta K. Sales MD* Ma´rcia Seiscento MD Francisco S. Vargas MD Lisete R. Teixeira MD Vera L. Capelozzi MD Milena M. Acencio BS Marcelo A. Vaz MD Leila Antonangelo MD Pulmonary Division - Heart Institute (InCor), University of Sa˜o Paulo Medical Sc, Sa˜o Paulo, Brazil PURPOSE: To identify clinical and laboratory parameters capable to differentiate between tuberculous and malignant pleural effusions with high efficiency and low-costs. METHODS: Laboratory tests (glucose, protein, albumin, globulin, lactate dehydrogenase, cholesterol, apolipoprotein A, apolipoprotein B, adenosine deaminase (ADA), quantitative and oncotic cytology) were analysed from 403 cases of confirmed tuberculous (Tb⫽200) or malignant (Mal⫽203) pleural effusions. Clinical variables like age, pleural effusions

Tuberculosis - Score ⬎ 8.5 points Characteristics Coefficient 6.288 6.456 1.897

Score 4.0 4.5 1.5

Malignancy - Score ⬎ 8.5 points Characteristics Age (⬎45.5 years) Hemorrhagic Aspect Macrophages Percentual Positive or Suspicious Oncotic Cytology

Coeficient 2.511 1.048 1.482 5.589

Score 6.0 2.5 1.5 5.0

DISCLOSURE: Roberta Sales, None.

A COMPARISON BETWEEN THE INCIDENCE OF TUBERCULOSIS (TBC) IN GREEK POPULATION AND THE POPULATION OF ECONOMICAL EMIGRANTS IN THE COUNTY OF EVIA GREECE Georgios S. Vlachogeorgos MD* Helen Nicolopoulou MD Stylianos Podaras MD General Hospital of Chalkis, Chalkida, Greece PURPOSE: To compare the incidence of TBC between the Greek population and the population of the economical emigrants in the county of Evia Greece. METHODS: All the new cases of TBC in the decade 1994-2003 in the county of Evia Greece were studied yearly. Greek population was studied in contrast with the population of the economical emigrants. The numbers of the populations were considered after the National Statistic Service of Greece. RESULTS: There is a statistical significant difference between the mean incidence in Greeks (3.57) and the economical emigrants (25.75) p⫽0.002. CONCLUSION: a)For the last 3 studied years the incidence of the TBC in the Greek population has risen in parallel with the rising of the incidence of the disease in the population of economical emigrants b)The economical emigrants may be one of the reasons of the reapperance of the TBC in the developed countries. CLINICAL IMPLICATIONS: The economical emigrants must have free admission to the public health services independent the legal status that they live in the respective country for the general benefit. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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remained negative after AFB in IS specimens. It comprised 41 female and 58 male individuals, 55 were HIV negative and 44 HIV positive. Microbiology results were analysed from cultures in Middlebrook and Loewenstein-Jensen media from IS and BAL specimens. RESULTS: Diagnosis of TB was confirmed in 38 patients, 28 with pulmonary and 10 with extrapulmonary involvement; 48 patients had other diagnosis confirmed but 13 other remained undiagnosed; 3 cases of MOTT were identified in HIV negative individuals without TB. In the 28 patients with pulmonary TB, 11 had a BAL procedure: AFB was positive in 8/28 at IS and 1/11 at BAL. M. tuberculosis was identified at cultures in IS specimens (22/28), BAL specimens (8/11) and both IS and BAL (7/28). Other diagnosis made at BAL in 5 HIV positive cases were pneumocystosis (n⫽2), cryptococcosis (n⫽2) and histoplasmosis (n⫽1). CONCLUSION: Direct microbiology diagnosis of TB in IS and BAL specimens have not been well accomplished. Improvements for faster results are needed. CLINICAL IMPLICATIONS: TB suspected patients without a positive AFB result in either spontaneous or induced sputum and BAL specimens still must be treated empirically for TB until the culture results are obtained. DISCLOSURE: Rogerio Xavier, None.

Wednesday, November 2, 2005 Tuberculosis: Diagnostic Evaluation, continued Table 1:

Year 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Incidence in Greeks (Cases)

Incidence in Emigrants (Cases)

2.26 ( 5) 5.37 (12) 3.90 ( 9) 8.22 (19) 4.75 (11) 0.86 ( 2) 1.72 ( 4) 0.93 ( 2) 3.25 ( 7) 4.46 (10)

12.74 ( 1) 11.82 ( 1) - ( 0) - ( 0) 9.52 ( 1) 18.24 ( 2) 8.81 ( 1) 25.77 ( 3) 33.49 ( 4) 87.84 (11)

DISCLOSURE: Georgios Vlachogeorgos, None.

POTT’S DISEASE “THE DILEMMA OF LOW BACK PAIN” HIGH RESOLUTION RADIODIAGNOSIS BY COMPUTERISRD SCAN (CT) & MAGNETIC RESONANCE (MRI) MADE POSSIBLE THE DIAGNOSISTIC ACUURACY IN INCONCLUSIVE CASES Mohammad M. Ishaq Khan MD* Imran Khan MD Sameera M. I MD Al-Junaid Hospital, Nowshera, Pakistan PURPOSE: Tuberculous spondylitis, i.e. Pott’s disease with relentless progress, shares the common clinical presentation with low back ache, seems to be of trivial nature may end in catastrophic complication i.e, “paraplegia”. METHODS: A total of 45 patients(n⫽45),age 15-60 years both sex with proven tuberculosis. The clinical and imaging details assessed in all 45 cases. RESULTS: Distribution of tuberculosis lesion in the order of frequency was cervical & cervicodorsal region(n⫽3,7%)dorsal/dorsolumber region(n⫽17,37.8%),Lumber(n⫽19,42%),Lunbosacral & sacral region(n⫽6,13%). The lamina were most commonly involved (24 patients, 53.3%; 8 bilateral, 16 unilateral) followed by pedicles 10 patients, 22.2%s%; 6 bilateral, 4 unilateral), articular processes (6 patients,13.3%; 3 bilateral, 3 unilateral), spinous process (3Patients,6.7%), and transverse processes (2 cases,4.4%;1 bilateral, 1 unilateral). Bone destruction and marrow changes were seen in all patients. Involvement of the entire posterior arch was seen in six patients. A total of 14 patients revealed extraspinal soft tissue collections.,Intraspinal extradural granulation tissue/ abscess was seen in 11 patients. Spinal cord was either displaced or compressed in 6 patients, and abnormal high signal intensity intrinsic cord changes were seen in eight patients. Gait may be limping with variable degree of muscle wasting. Off & on low grade fever was associated. Laboratory investigations had elevated ESR, relative lymphocytosis low hemoglobin & few with tuberculin reaction conversion detected. Plain x-rays had irregular erosion of the end plate of adjacent vertebral bodies & narrowing of the intervening disk spaces. CT & MRI had revealed the nature of the lesion .With anti tubercular drugs on empirical ground, added diagnostic yield . with following outcome.1.Individuals diagnosed on empirical (ATD), 10-15%2.Diagnosis established on clinical manifestations only (Patients with poor economy could not afford expenses of investigations), 5 - 10 % 3.Financially stable patients, diagnosis established on CT/MRI. 75 -85 %. CONCLUSION: A large tubercular abscess compressing on spinal cord is a medical emergency, may result in irreversible paraphrases. CLINICAL IMPLICATIONS: Patients with Pott’s disease has characteristic early insomnia from spasm of para spinal muscles, and late insomnia resulting from urinary bladder distension. DISCLOSURE: Mohammad Ishaq Khan, None.

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THE RISK OF TB INFECTION IN MEDICAL STUDENTS OF CHARLES UNIVERSITY Jiri Homolka MD* Frantisek Krejbich MD Pavel Simecek MD 1st Lung Department, Charles University, Prague, Czech Republic PURPOSE: The aim of our study was to determine the risk of tb infection in students of medical and non-medical faculties of Charles University during their studies. METHODS: Students of Charles University were repeatedly tested with tuberculin skin test (TST) at the beginning of their studies, in the 3rd year and in the 5th or 6th year depending on the length of studies. The increase of TST for 10 mm or more was considered as the conversion of TST. The annual risk of infection (ARI) was calculated according to Styblo method. RESULTS: 3116 students were tested with TST during the years 1993-2003. 1224 were medical students, 1892 were students of other faculties. At the beginning of their studies no significant differencies were observed concerning the results of TST between these two groups. 35% were TST negative, 62% had TST between 6-15 mm and 3% had TST 16 mm and more. Median of TST was 7 mm. In the 3rd year of studies the medical students showed a significant increase in TST results (14% TST negative, 74% TST 6-15 mm, 12% TST 16 mm and more, median TST 12 mm). There was no significant change in TST results in students of other faculties. The conversion of TST in the 3rd year of medical studies was detected in 22% of medical students and in 6.5% of students of other faculties (pⱕ 0.01).The annual risk of infection (ARI) was higher in medical students during the first three years of their studies (ARI 0.081)compared to the second three years (ARI 0.042). The ARI in students of other faculties was 0.011. CONCLUSION: Medical students are at significantly higher risk for tb infection compared to the students of other faculties of Charles University. The risk seems to be most prominent during the first three years of medical studies. CLINICAL IMPLICATIONS: Study of medicine carries a significat risk for acquiring tuberculosis even in countries with low prevalence of tuberculosis and functional system of tb control. DISCLOSURE: Jiri Homolka, None.

Tuberculosis: Treatment 12:30 PM - 2:00 PM PULMONARY RESECTION FOR MULTI DRUG RESISTANT TUBERCULOSIS Abulfazal Shirin Zadeh MD* Khalil Ansaarin MD Vahid Montazery MD Samad Mosaddeghi MD Mahmoodreza Miri MD Ashraf Fakhr Joo MD Mohsen Sokooti MD Thoracic Department, Imam Hospital, Tabriz, Iran PURPOSE: Tuberculosis was a scourge of early humans, as shown by its discovery in the lungs of Egyptian mummies. Nowadays mycobacterium tuberculosis(MTB) continues to be a major cause of morbidity and mortality throughout the world.The world health organization(WHO) declare MTB a global emergency.During MTB Therapy has been emergence of multi-drug resistant MTB(MDR-TB). MDR-TB is a strain of mycobacterium tuberculosis that is resistant to current anti-tuberculosis agent.Multi-drug resistant MTB often requires surgical intervention. METHODS: During 10 years period 50 patients (26 men and 24 women)Had surgical intervention that underwent pulmonary resections. All patients had a minimum of 4 month of medical therapy before operation.All patients had multi-drug resistant mycobacterium tuberculosis that were hospitalized at the thoracic surgery ward and underwent surgical operation. RESULTS: 50 patients underwent surgical operation. 19 patients (6 women,13 men) had positive sputum at the time of surgery. Left pulmonary involvement were 31 cases(62%) and right lung 19 cases(38%). 37 patients (74%) had been taken 4 drug regimen and 13 patients(26%) 2 drug regimen in the past. Emergence of MTB strains resistant to the primary antibiotics has largely been due to physicians and patient complacency (irregular taking of drugs and early discontinuing).Hemoptysis, total pulmonary destruction, hydropneumothorax, bronchopleural fistula and positive sputum were the main causes of surgery. 30 patients underwent lobectomy, 12 patients segmentectomy and 8 patients pneuCHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Tuberculosis: Treatment, continued monectomy. Operative mortality was 4% (2 patients) ,significant morbidity was 14% (7 patients).After the operation, the sputum remained positive in 3 patients(6%). Mean length of follow-up was 3.5 years (4 to 80 months). CONCLUSION: Surgery remains as an important adjunct to medical therapy for patients with multi-drug resistant mycobacterium tuberculosis (MDR-MTB). In the setting of localized diseases, persistent cavitary disease, lung or lobar destructions or patient intolerance to medical therapy, surgical resection of the lung should be undertaken. The surgical complications and post surgical mortality and morbidity are acceptable. Postponing the surgical operation will worsen the results. CLINICAL IMPLICATIONS: Timing of the operation and malnutrition are major problems to be considered. DISCLOSURE: Abulfazal Shirin Zadeh, None.

CYTOKINE CHANGES IN SEVERE PULMONARY TUBERCULOSIS AFTER INITIATION OF TREATMENT: A PILOT STUDY Mariko S. Koh MBBS* E-Shyong Tai MBBS Constance Lo MBBS Kenneth P. Chan MBBS Philip Eng MBBS Singapore General Hospital, Singapore, Singapore

DISCLOSURE: Mariko Koh, None.

PURPOSE: Directly observed therapy (DOT) is frequently seen as the answer to rising levels of tuberculosis. However, well conducted trials comparing DOT with self treatment have showed that the effects of DOT on cure or treatment completion are similar to those of self-administered treatment. The objective of this study was to determine the effect of DOT on the outcome of antituberculosis treatment. METHODS: Retrospective analysis covering the period 01/2000-09/ 2004; the information was retrieved from the files of the Tuberculosis Control Program, ISESALUD, Ensenada, Mexico. RESULTS: 524 patients were included in the analysis. 462 patients (88.16%) had never been treated before, 57 (10.8%) were relapses, and 5 (0.95%) were failures from a previous regimen. DOT was administered to 73.7% of the patients; in the rest (26.3%), treatment was self administered. Males defaulted treatment more frequently (25.5%) than females (16%; p⫽0.010). HIV/AIDS patients defaulted treatment more frequently (38.5%) than those not co-infected (20.3%), however due to the low number of coinfected patients (13), this difference was not statistically significant (p⫽0.11). Patients addicted to illegal drugs and/or alcohol also defaulted treatment more frequently (31.6% vs. 19.3%, p⫽0.014). In logistic regression analysis only male gender (odds of abandoning treatment: 1.70, CI95% 1.03, 2.81; p⫽0.03) and the absence of addictions (OR 0.55, CI95% 0.32, 0.97; p⫽0.04) were predictive of treatment completion. DOT was not predictive (1.33, CI95% 0.77, 2.30; p⫽0.30). CONCLUSION: DOT did not improve in this group of patients treatment completion, treatment failure and cure rates when compared with self-administered treatment. CLINICAL IMPLICATIONS: Universal DOT is an expensive strategy; TB programs from developing countries might benefit from selecting for DOT, patients with high risk for deafult.

Variable

DOT

Self-administered

p

Addictions HIV/AIDS Cured Defaulted Failed

16.6% 2.7% 77.7% 22.3% 2.3%

13.2% 1.7% 79.8% 20.2% 1.6%

0.37 0.53 0.70 0.70 0.92

DISCLOSURE: Rafael Laniado-Laborin, None. TREATMENT OUTCOME OF TUBERCULOSIS UNDER DIRECTLY OBSERVED TREATMENT SHORT COURSE ( DOTS ) IN PATIENTS PRESENTING AT CHEST & TB HOSPITAL, AMRITSAR Vishal Verma MBBS Jorawar Singh MBBS Nirmal Chand MS* J. S. Khalsa MBBS Dept. of Tuberculosis & Respiratory Diseases, Amritsar, India PURPOSE: The present study was undertaken to determine the treatment outcome of DOTS as prescribed under RNTCP. Side effects and radiological improvement was also noted. METHODS: A total of 150 cases of tuberculosis on the basis of history, sputum & radiological examination were selected. They were divided into three categories under RNTCP. All the patients were administered standard regimens of antitubercular drugs as prescribed under DOTS. Sputum of all patients was examined before the start of treatment and then at the end of intensive phase, 4or5or6 months and then at the end of treatment. X-ray was taken before and at the end of treatment. Treatment outcome was determined. RESULTS: 150 patients comprised of 91 males and 59 females. Cough was the major complaint in 70% . Sputum conversion rate was 81% & 85.71% for category I & II. Cure rate was 91% & 71.40% for category I & II. Treatment completion rate was 100% for category III. Overall default rate was 5.33%. Failure rate was 0.67%. Radiological improvement was seen in 73.33%. 60.67% gained weight in the range of 6-10 Kg. Fatigue was major side effect under DOTS in 24% cases. CONCLUSION: DOTS is an effective and economical treatment with successful treatment outcome, sputum conversion and minimal side effects for tuberculosis. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

PURPOSE: Sudden death occurs in a significant number of patients with pulmonary tuberculosis after the initiation of anti-tuberculous therapy. We postulate that a Jarisch-Herxheimer (JH) –type response which is characterized by surge in Interleukin – 6 (IL-6), Interleukin- 8 (IL-8) and Tumour necrosis factor alpha (TNF alpha) could be responsible for this phenomenon. METHODS: Five patients admitted to hospital for pulmonary tuberculosis were enrolled in this pilot study. These patients had multi-lobar involvement, were sputum smear positive for acid-fast bacilli and had low haemoglobin and albumin, signifying severe disease. Vital signs, temperature and clinical responses were monitored. Venepuncture was carried out 2, 4, 8, 12, 24, 48 and 72 hours after the first dose of anti-tuberculous therapy. These samples were analyzed to determine the concentrations of IL-6, IL-8 and TNF alpha at the various time points. RESULTS: Several patterns of cytokine changes were noted. In two patients, there was an increase in serum levels of IL-6 between 4 and 8 hours and these returned to baseline levels within 24 hours. Neither of these patients experienced an adverse clinical event. Two patients had relatively high IL-8 levels to start with compared to the other patients and had documented hypotensive episodes between 4 and 8 hours. Radiologically, these patients had more severe disease. CONCLUSION: An increase in IL-6 was observed in 2 patients which may be consistent with Jarisch-Herxheimer reaction. However, this was not accompanied by any clinical sequelae to support the occurrence of such a reaction. In contrast, patients with high IL-8 at baseline did exhibit clinically significant deterioration consistent with previous studies which have found that increased concentration of IL-8 were found in patients who died from tuberculosis compared to those who survived. Further studies should be carried out to clearly document the prognostic significance of serum levels of cytokine at baseline and within the first 24 hours following commencement of anti-tuberculous therapy for pulmonary tuberculosis. CLINICAL IMPLICATIONS: IL-6 and IL-8 levels may have prognostic significance in patients with pulmonary tuberculosis.

DOES UNIVERSAL DOT REALLY MAKES A DIFFERENCE IN TUBERCULOSIS TREATMENT? Patricia Radilla MD Rafael Laniado-Laborin MPH* Universidad Autonoma de Baja California, Tijuana, Mexico

Wednesday, November 2, 2005 Tuberculosis: Treatment, continued CLINICAL IMPLICATIONS: DOTS in an effective therapy in developing countries like india whose almost 40% of the population in infected with tuberculosis. DISCLOSURE: Nirmal Chand, None. RELAPSE AT 5 YEARS IN INDIAN REVISED NATIONAL TUBERCULOSIS CONTROL PROGRAMME CAT I DOTS REGIMEN Mukesh K. Tailor MBBS* J.L.N. Medical College, Ajmer, India PURPOSE: To see the relapse rate and point of relapse in cat-I DOTS treated patients after 5 years of chemotherapy under Indian Revised National Control Programme. METHODS: 128 patients of Pulmonary-tuberculosis registered under cat-I DOTS, between Oct-1999 and March-2000. Out of 128 cases, 22 defaulted, 14 died, 5 failure and 2 transferred-out during treatment were excluded from analysis. Of remaining 85 cured cases, only 53 were analyzed because 32 could not be traced due to various reasons. Out of these 53, only 41 were alive at the time of assessment and 12 were found dead. Of the 53 patients, 12 were irregular during treatment. 7 alive-cases and 5 dead-cases were re-registered in DOTS cat-II (documented relapses). Verbal autopsy was carried out in all dead-cases and was conclusive that they all died because of symptomatic PTB. RESULTS: 19 (35.85%) patients relapsed during 5 years post treatment period. Of these 6 (31.6%) relapsed within 6 months of completion of DOTS, 4(21%) between 6 to 18 months, 3(15.8%) between 19 to 36 months, 3 (15.8%) between 37 to 48 months and rest 3 during last 1 year of follow-up. CONCLUSION: Relapse rate following 5 years of cat-I treatment was very high (35.85%) and needs further studies to confirm these findings at large, because this has a significant bearing on eventual success of RNTCP in India. CLINICAL IMPLICATIONS: Relapse rate following 5 years of cat-I treatment was very high (35.85%) and needs further studies to confirm these findings at large, because this has a significant bearing on eventual success of RNTCP in India. We hypothesize high initial drug resistance prevalent in community, teething problem of 1st year of implementation and occasional defaults during DOTS possibly responsible for this high relapse rate. DISCLOSURE: Mukesh Tailor, Product/procedure/technique that is considered research and is not yet approved for any purpose. EVALUATION OF RISK FACTORS AND PREVALENCE OF DRUG RESISTANT TUBERCULOSIS IN NORTH INDIA J.N. Pande MD U.B. Singh MD Sanjeev Sinha MD* R.C. Agarwal MBBS SPN Singh PhD Department of Medicine, All India Institute of Medical Sciences, New Delhi, Ind, New Delhi, India PURPOSE: The prevalence of multi-drug resistant tuberculosis (MDR-TB) in different clinical settings [Primary health center (PHC), District tuberculosis center (DTC) and tertiary care center (Medical college )] had not been systematically worked out. There is a need to estimate the magnitude of problem and to define the factors responsible for its emergence. METHODS: A prospective study of risk factors of MDR-TB among patients seen at three sites during period of two years, 2000-2002. Patients included from PHC, Ballabhgarh, DTC, Faridabad and tertiary care center, All India Institute of Medical Sciences, (AIIMS), New Delhi. Total 1467 patients with pulmonary TB recruited from three sites and on whom the drug susceptibility results were available after adequate quality control. Of these 678 patients were enrolled at AIIMS, 346 at PHC and 443 at the DTC. RESULTS: Overall, 123 (18.9, 95%CI: 11.9-25.8%) patients had MDR-TB. Of the 329 patients without history of anti tuberculosis treatment (ATT) in the past, 28 (8.5,95%CI: 5.4-11.5%) patients had MDR organisms. The corresponding proportion amongst those with past history of ATT was 95 (29.7, 95%CI: 24.6-34.7%) out of 319. There was considerable variation in the proportion of patients with MDR organisms (without past history of ATT) at three sites (6.9-11.8%). The prevalence of MDR-TB in patients with past history of ATT at AIIMS hospital was 44.7, 95%CI: 35.5-53.8%, PHC 23.1, 95%CI: 14.6-31.5% and DTC was 20.0, 95%CI: 12.5-27.4%. Of the risk factors studied for MDR-TB, bacillary load and previous treatment of TB were found significant (p⬍0.05).34 had pauci-bacillary disease (smear negative but culture positive). The preva-

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lence of HIV amongst these patients was 2.77%. HIV status, tobacco smoking, excessive alcohol intake, age, sex, education and socio-economic status had no relation to infection with MDR organism. CONCLUSION: This study highlights important differences in the prevalence of MDR-TB at three different clinical settings. CLINICAL IMPLICATIONS: The findings of this study have major implications for the TB program in India. DISCLOSURE: Sanjeev Sinha, None. FREQUENCY OF VENOUS THROMBOEMBOLISM AMONG PATIENTS WITH TUBERCULOSIS DURING SHORT-COURSE CHEMOTHERAPY Marco Ambrosetti MD* Maurizio Ferrarese MD Luigi R. Codecasa MD Giorgio Besozzi MD Antonio Sarassi MD Piero Viggiani MD Giovanni B. Migliori MD Division of Cardiology, IRCCS Fondazione S. Maugeri, Tradate, Italy PURPOSE: The unexpected resurgence of tuberculosis (TB) in developed countries, as far as the possibility of an hypercoagulable state given by the infection “per se” and the use of anti-TB chemotherapy, provided the rationale for evaluating venous thromboembolism (VTE) as a possible complication of TB. Aim of the present study is to evaluate the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in a large national registry of actively treated TB patients in a low incidence country. METHODS: The AIPO/SMIRA study is a prospective national monitoring activity on TB treatment results based on a network of 46 TB units nationwide, under the leadership of the Italian Association of Hospital Pneumologists, the World Health Organization, and the Istituto Superiore di Sanita` (technical branch of the Italian Ministry of Health). To date, the registry enrolled 6,027 TB patients. An active survey for the appearance of clinically evident DVT and PE was conducted on a subset of 1,237 patients in the period 1998-2002. RESULTS: Five (0.4%) patients developed proximal DVT within one month after initiation of anti-TB chemotherapy, complicated in 2 (0.2%) cases by PE. Two (0.2%) additional cases of PE without DVT occurred in the first week of treatment. Overall, the prevalence rate of any VTE event was 0.6%, and all cases occurred among new pulmonary TB cases with rifampicin as part of the initial treatment. CONCLUSION: TB, as other infectious conditions, is likely to increase the risk of VTE. CLINICAL IMPLICATIONS: This evidence may support the use of appropriate venous thromboprophylaxis in selected cases. DISCLOSURE: Marco Ambrosetti, None. SURGICAL TREATMENT FOR CHRONIC TUBERCULOUS EMPYEMA Masanori Kaneda MD* Fumiaki Watanabe MD Tomohito Tarukawa MD Toshiya Tokui MD Takashi Sakai MD NHO Mie Chuo Medical Center, Hisai City, Japan PURPOSE: Despite advances in surgical techniques and supportive therapy, chronic empyema is still associated with considerable morbidity and mortality. The purpose of this study was to evaluate the efficacy of surgical procedures. METHODS: Thirty-seven patients with chronic tuberculous empyema were studied. Twenty cases had bronchopleural fistula. All patients were studied for more than three years. Mortality rates and recurrence rates were evaluated. RESULTS: Among 17 cases without bronchopleural fistula, 10 were treated with decortication. Lung resection was necessary in two cases. Extrapleural pneumonectomy was performed in two cases, and thoracoplasty in three cases. Other procedures included one muscle flap closure, and two open drainages. The mortality rate was 0% and the recurrence rate was 5.9%.Among the 20 cases with bronchopleural fistula, nine were initially treated with open drainage. In the second stage operation, one case was treated with extrapleural pneumonectomy, but died from cardio-respiratory failure. Extrapleural pneumonectomy combined with thoracoplasty (EPTP) was successfully performed in two cases, and thoracoplasty in four cases (two with omentopexy). One case was treated with a muscle flap closure. There was no recurrence, but the mortality rate was 11.1%. The other 11 cases with fistula were treated with a single-stage operation. Extrapleural pneumonectomy was performed in four cases, thoracoplasty in 5 cases, and a muscle flap closure with omentopexy was performed in one case. The result was two deaths and two recurrences. CHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Tuberculosis: Treatment, continued Recently, EPTP by anterior approach was successfully performed in one case with a severely damaged lung in spite of a poor general condition. The mortality rate of the single-stage operation was 18.2% and the recurrence rate was 18.2%. All the cases with recurrence were successfully treated with additional surgical operations. Overall efficacy of the surgical treatment was 86.5% (32/35). CONCLUSION: Surgical treatment was a effective method for the treatment of tuberculous empyema. CLINICAL IMPLICATIONS: Chronic tuberculous empyema is a difficult disease to cure. The result of the surgical treatment was much effectibe than that of medical treatment. DISCLOSURE: Masanori Kaneda, None.

Venous Thromboembolism 12:30 PM - 2:00 PM

PURPOSE: Venous thromboembolism (VTE) is a well-established cause of morbidity and mortality in the trauma patient. Soldiers injured in Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) are often aeromedically evacuated shortly posttrauma, subjecting them to lengthy transport and potential hypobaric hypoxia during the period of peak thrombogenesis. We sought to determine the observed incidence of VTE in soldiers injured in OEF and OIF who were admitted to the intensive care unit (ICU) of our military tertiary care facility. METHODS: We retrospectively identified all patients injured in OEF and OIF admitted directly to the ICU at our institution for the 16-month period between 28 March 2003 and 28 July 2004. Relevant variables determined from chart review included mechanism of injury, location of primary and secondary injuries, Revised Trauma Score, type of VTE prophylaxis, and radiographic studies performed. All cases of VTE and death were recorded. RESULTS: During the study period 231 trauma patients from OEF and OIF were admitted to the ICU. Forty patients (17.3%) developed VTE during hospitalization at our facility. Overall mortality was 2.2%. One of these five deaths was from pulmonary embolism. The most commonly used form of prophylaxis was enoxaparin (30 mg SQ BID). Inferior vena cava filters were placed infrequently. There was no observed difference in development of VTE between patients who received pharmacologic prophylaxis and those who did not (22/130, 16.9% vs. 18/101, 17.8%; p⫽0.863). CONCLUSION: VTE is common in the critically ill OEF/OIF population and incidence appears similar to that of civilian trauma populations. The VTE-related mortality appears to be low. CLINICAL IMPLICATIONS: Despite the high severity of injury, the rate of VTE in this population is no higher than that reported in other settings. VTE infrequently results in mortality. Ideal means of prophylaxis in this trauma population should be reassessed. DISCLOSURE: William Jackson, Jr., None.

DIABETES MELLITUS IS SIGNIFICANTLY ASSOCIATED WITH PULMONARY EMBOLISM AND PULMONARY HYPERTENSION Mohammad-Reza Movahed MD* Mehrtash Hashemzadeh MA M. Mazen Jamal MD University of California, Irvine Medical Center, Orange, CA PURPOSE: Patients with diabetes mellitus (DM) suffer from hypercoagulable state which may increase their risk for thromboembolism. However, the data about this association is contradictory in the literature. The goal of this study was to evaluate the occurrence of pulmonary embolism and pulmonary hypertension (HTN) in patients with DM after

CHARACTERISTICS AND PROGNOSTIC FACTORS OF PULMONARY SADDLE EMBOLUS Linda M. Lam DO* George Matuschak MD Stephen Trottier MD Saint Louis University, Saint Louis, MO PURPOSE: Pulmonary saddle embolism is a radiographic description of massive embolization implicitly assumed to confer increased mortality. However, supportive data are scant. This is a review of 19 patients with a pulmonary saddle embolus over a 5 year period at a university medical center, hypothesizing that: 1) such patients exhibit increased mortality; and 2) discrete prognostic factors stratify these and other adverse outcomes. METHODS: The medical records of patients between June 1999 and June 2004 were retrieved to identify those with pulmonary saddle embolus on helical CT chest . Data collection included demographic data, APACHE II score, shock defined as requiring vasopressors and/or MAP ⬍ 60 mmHg, need for mechanical ventilation, PaO2/FIO2 ratio, presence of deep venous thrombosis, echocardiographic findings, and hospital morbidity and mortality. Data was summarized by median calculation, means ⫾ standard error and evaluated by X2 analysis, and bivariate correlation (SPSS v. 13 .0). RESULTS: Saddle embolism was diagnosed in 6 females and 13 males (total n ⫽ 19), representing an incidence of 1.2%. Mean age was 58.2 years old ⫹/- SD 16.34 and median Apache II score of 9 (range 4-26). Five patients presented with hemodynamic instability, of which 2 patients demonstrated right ventricular systolic dysfunction. RV dilation found in 7/10 patients. Co-existing deep vein thrombosis found in 10 patients and superficial thrombophebitis in 4 patients. Median Pa02/FIO2 ratio found to be 233 (range 53-395). Four patients (22 %) required mechanical ventilation. No patients received thrombolytics. Seventeen (94 %) patients were anticoagulated with heparin infusion. No significant correlation existed among shock, occurrence or type of echocardiographic abnormalities, and degree of hypoxemia. All patients survived. CONCLUSION: Saddle pulmonary embolism is not consistently associated with shock, echocardiographic abnormalities, or hypoxemia in patients surviving the initial embolic event who were treated by standard anticoagulation regimens and/or caval interruption. CLINICAL IMPLICATIONS: Saddle pulmonary embolism is not associated with increase mortality based on shock, hypoxemia, or echcardiographic abnormalities. DISCLOSURE: Linda Lam, None. CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

OBSERVED INCIDENCE OF VENOUS THROMBOEMBOLISM IN SOLDIERS FROM OPERATION IRAQI FREEDOM AND OPERATION ENDURING FREEDOM ADMITTED TO A STATESIDE INTENSIVE CARE UNIT William L. Jackson, Jr. MD* Melanie Guerrero MD Kevin K. Chung MD Bryan A. Fisk MD Andrew F. Shorr MD Walter Reed Army Medical Center, Washington, DC

adjusting for coronary artery disease (CAD), congestive heart failure (CHF), hypertension and smoking using a large database. METHODS: We used patient treatment files (PTF) to document inpatients’ admissions containing discharge diagnoses (ICD-9 codes) from all Veterans Health Administration Hospitals. The patients were divided in two groups: ICD-9 code for DM (293,124) and a control group with ICD-code for hypertension (HTN) but no DM (552,623). ICD-9 codes for pulmonary embolism (415.19) and ICD-9 code for pulmonary hypertension (416.0) were used to study prevalence of these diseases in DM patients vs the control. We performed uni- and multi-variant analysis adjusting for CAD, CHF and smoking. Continuous variables and binary variables were analyzed using X2 and Fisher’s Exact tests. RESULTS: Pulmonary embolism was present in 2011 (0.7%) vs 2759 (0.5% ) in the control group. Pulmonary hypertension was present in 3356 (1.1%) vs 3357 (0.6%) in the control group. Using multivariate analysis, DM remained independently associated with pulmonary embolism (OR: 1.27; CI: 1.19 to 1.35; p⬍0.000) and with pulmonary hypertension (OR: 1.53; CI: 1.45 to 1.60; p⬍0.000). CONCLUSION: Patients with DM have significantly higher prevalence of pulmonary embolism and pulmonary hypertension independent of CAD, HTN, CHF or smoking. CLINICAL IMPLICATIONS: This finding could partially explain the higher risk of sudden death in diabetes patients in addition to other cardiovascular abnormalities. We suggest that the clinician should be more aware of this risk that could be potentially treated and life saving. DISCLOSURE: Mohammad-Reza Movahed, None.

Wednesday, November 2, 2005 Venous Thromboembolism, continued COMPARISON BETWEEN PERFUSION LUNG SCAN AND VENTILATION-PERFUSION LUNG SCAN IN PATIENTS WITH PULMONARY EMBOLISM G. Gandev MD* H. Rao MD S. Rashid BA K. Kanagarajan MD K. Gupta MD Coney Island Hospital, Brooklyn, NY PURPOSE: Use of ventilation-perfusion (V/Q) scan to diagnose PE is a well established practice. However performing the ventilation part of the scan is technicaly demanding and associated with significant degree of radiation exposure for both the technician and the patient. We conducted a retrospective study to compare the diagnostic abilities of perfusion lung scan and ventilation-perfusion (V/Q) scan for detecting pulmonary emboli. METHODS: We reviewed the charts of all 283 patients who underwent nuclear lung imaging studies in 2004. Of these 283 patients, 46 had both nuclear lung imaging and pulmonary CT angiogram within 48 hours of each other. Of these 46 patients, 16 had both ventilation and perfusion nuclear scan done and the remaining 30 had only perfusion scan done. We compared the sensitivity and specificity of nuclear lung imaging for both groups. We used pulmonary CT angiogram as a reference test for diagnosis of pulmonary embolism. RESULTS: There were 20 males and 26 females with age range: 18-88 years, and mean age 53.6 years. For the group of patients who had ventilation-perfusion (V/Q) scan done the sensitivity was 100% and the specificity 92%. For the group of patients who had only perfusion scan done the sensitivity was 100%, and the specificity was 80%. CONCLUSION: Compared to perfusion scan alone ventilation-perfusion (V/Q) scan has similar sensitivity, but higher specificity for detecting PE. CLINICAL IMPLICATIONS: Even though technically challenging and associated with higher degree of exposure to radiation performing ventilation scan along with perfusion scan will increase the diagnostic accuracy of nuclear lung imaging in the diagnosis of PE. DISCLOSURE: G. Gandev, None. CARDIOPULMONARY FINDINGS ON CT PULMONARY ANGIOGRAPHY IN PATIENTS WITH SUSPECTED PULMONARY EMBOLISM Shalin Amin MD* Tan-Lucien H. Mohammed MD Ruchi Yadav MBBS The Cleveland Clinic Foundation, Cleveland, OH PURPOSE: Multidetector CT pulmonary angiography (CTPA) has become the standard technique utilized to diagnose pulmonary embolus (PE). Current literature has demonstrated that CTPA is excellent for the assessment of various cardiopulmonary pathologies as well. Our study was performed to identify, catalogue and determine the frequency of common cardiopulmonary findings in a determined patient population. METHODS: CTPA and corresponding medical records of nearly 750 consecutive patients who underwent CTPA for PE at our institution between January 2005 and September 2005 were retropectively reviewed. All studies were re-evaluated by a team of one thoracic radiologist and two radiology residents. Correlative data, treatment outcome and short-term follow-up were used to confirm these findings and diagnoses. RESULTS: Cardiopulmonary pathologies were readily present in our patient population. Of these findings, pneumonia and emphysema were the most common. Other common findings included congestive heart failure, pulmonary fibrosis and coronary artery disease. Furthermore, cardiopulmonary findings which offered alternative and/or different diagnoses to explain the patients’ symptoms were present in nearly one third of cases. CONCLUSION: Nearly all patients with suspected PE frequently present with chest pain and/or dyspnea. However, these symptoms are nonspecific and can often signal cardiopulmonary pathology. CTPA, a technique which has wide-gained acceptance in the evaluation of PE, offers the additional benefit of allowing excellent assesment of cardiopulmonary structures in this population. Abnormalities such as pneumonia, congestive heart failure and exacerbated emphysema are readily apparent on CTPA studies. CLINICAL IMPLICATIONS: It is crucial for radiologists to include a systematic evaluation of the cardiopulmonary structures in their CTPA seach patterns. DISCLOSURE: Shalin Amin, None.

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SERUM ANGIOTENSIN CONVERTING ENZYME (ACE) IN PATIENTS WITH ACUTE PULMONARY THROMBOEMBOLISM Zothanmawii Khiangte MD* Martin H. Bluth MD Rose Hardin MD Emad Kamel MD Cathy M. Mueller BS Sanjay Chawla MD Tamar S. Norowitz PhD Michael Zenilman MD Matthew Pincus MD SUNY Downstate Medical Center, Brooklyn, NY PURPOSE: Angiotensin-converting enzyme (ACE) is produced by endothelial cells and is found in particularly high concentrations in the pulmonary vasculature. Circulating ACE levels are thought to represent either sloughing off of, or secretion from, endothelial cells. Pulmonary endothelial injury likely occurs during pulmonary insult, such as an acute thromboembolism, and measurement of serum ACE levels may provide a clinically useful marker of pulmonary injury. We therefore investigated the utility of serum ACE levels in the evaluation of patients with pulmonary embolism (PE). METHODS: Patients were evaluated for suspected PE either by cat scan angiography (CTA) or ventilation perfusion (V/Q) scans, results of which were interpreted by an independent radiologist. Serum samples were prospectively collected either at the time of admission or during a radiological procedure. ACE levels were measured by enzyme linked immunosorbant assay (ELISA) in a blinded manner. Patients receiving ACE inhibitors were excluded from the study and serum from healthy volunteers served as controls. ACE levels are expressed as ng/mL (mean ⫹SE) with significance between groups set at p ⬍ 0.05 (student’s t-test). RESULTS: Of the 45 patients evaluated, 19 were diagnosed with acute PE (15 CTA, 2 V/Q scan, 2 by both). Patients with PE tended to be older. At diagnosis, serum ACE levels for patients with pulmonary symptoms were as follows – PE: 312⫾30 ng/ml; non-PE: 299⫾24 ng/ml (p⫽NS). In contrast, ACE levels differed significantly in pulmonary pathology groups vs. normal controls (control ACE levels: 433⫹32 ng/ml; PE vs control, p⫽0.03; non-PE vs. control, p⫽0.006). CONCLUSION: Although ACE levels did not significantly differ between PE and non-PE patients, ACE levels were significantly decreased in patients presenting with pulmonary symptoms when compared with controls. CLINICAL IMPLICATIONS: Serum ACE levels can be useful in differentiating patients with pulmonary symptoms from those with nonpulmonary causes. Furthermore, additional studies are needed to determine if ACE can serve as a useful diagnostic marker in patients presenting in early vs. late stage PE and as a monitor of clinical course. DISCLOSURE: Zothanmawii Khiangte, None.

Venous Thromboembolism: Treatment 12:30 PM - 2:00 PM OPTIMAL DOSING OF UNFRACTIONATED HEPARIN IN OBESE PATIENTS WITH VENOUS THROMBOEMBOLISM Samar U. Khan DO* Maritza L. Groth MD Adam N. Hurewitz MD Winthrop University Hospital, Mineola, NY PURPOSE: Failure to achieve therapeutic anticoagulation in the first 24 hr after pulmonary embolism (PE) is associated with increased rate of recurrence in subsequent months. A weight-based nomogram is recommended for unfractionated heparin (UFH) to achieve the target PTT. However, for obese patients, the nomograms may not be accurate and would necessitate very high doses if followed. Clinicians hesitate to use UFH nomograms in obese patients for fear of bleeding complications. METHODS: We retrospectively reviewed the records of all obese patients (BMI ⬎ 29) diagnosed with PE at our institution over a six month interval who were treated with UFH. Patient data obtained included weight, age, height, and method of diagnosis of PE. We recorded the initial bolus and infusion rate of UFH as well as the infusion rate that ultimately achieved a therapeutic PTT (60-90 sec). RESULTS: Eight patients met all inclusion criteria. Their mean age was 58 yr (range 25-80 y). Six were females. BMI (mean) was 36 kg/m2 (range 29.3 - 44). Despite hospital guidelines, actual body weight (ABW) based nomogram was not used for either the bolus or the infusion rate. The average bolus was 55 units/kg (range 34-76). The average initial infusion rate was 14 units/kg (range 11-16). With these initial doses, 50% were over-anticoagulated and 25% were under-anticoagulated. The averCHEST 2005—Poster Presentations

Wednesday, November 2, 2005 Venous Thromboembolism: Treatment, continued age infusion rate to maintain therapeutic PTT was 12.8 units/kg (range 8.4-15.8). CONCLUSION: Weight based nomograms overestimate the dose of UFH required to achieve therapeutic aPTT. By contrast, calculations based on ideal body weight (IBW) result in inadequate anticoagulation. In the majority of patients the dose that produced a therapeutic PTT was 40% of the difference between the dose calculated based on IBW and ABW. CLINICAL IMPLICATIONS: The optimal dose of UFH to achieve a therapeutic PTT in obese patients should not be based on either ABW or IBW but rather an estimated value around 40% above the IBW. However, our data are based on a small population and should be confirmed with a larger sample. DISCLOSURE: Samar Khan, None. PLACEMENT OF FILTERS IN THE SUPERIOR VENA CAVA AND AZYGOS SYSTEM. PRELIMINARY EXPERIENCE Jaime Tisnado MD* Malcolm K. Sydnor MD Uma R. Prasad MD MCV Hospitals/VCU Medical Center, Richmond, VA

MASSIVE PULMONARY EMBOLISM: TRANSCATHETER LYSIS WITH RETEPLASE Jaime Tisnado MD* Muhammad S. Chaudhri MD Ferdinand K. Hui MD MCV Hospitals/VCU Medical Center, Richmond, VA PURPOSE: Massive pulmonary embolism (PE) is a serious and relatively common problem, sometimes very difficult to manage. The conventional treatment (systemic anticoagulation and/or thrombolysis) is associated with significant hemorrhagic and other complications. A new method of therapy is the selective, local, transcatheter infusion of Retavase (Reteplase, recombinant) into the pulmonary arteries. METHODS: Twelve patients (24-70 y.o.) with massive bilateral PE, hemodynamically unstable with severe respiratory compromise, were treated with transcatheter directed thrombolysis with Reteplase infusion at 0.5-1 U/hr. Two catheters were simultaneously inserted into one or both common femoral veins and placed in each one of the two pulmonary arteries. The infusion time lasted from 20 to 48 hours. RESULTS: All patients recovered well. All patients showed significant drops in pulmonary artery systolic pressures ranging from 13-34 mm of Hg. Improvements in pulmonary perfusion with resolution of clot occurred at 24 hours (n ⫽ 6) and 48 hours (n ⫽ 6) of infusion. No significant complications occurred despite the severity of the clinical condition of most patients. Concomitant heparin (400-500 U/hr) was given to some patients. CONCLUSION: Bilateral selective pulmonary artery infusion of Retavase is safe, effective and well tolerated for the management of patients with massive PE, especially those who are not candidates for the conventional means of therapy, and those patients being considered for a more aggressive management such as pulmonary embolectomy. CLINICAL IMPLICATIONS: A very serious and potentially lethal condition (massive PE) can be successfully managed with IR methods. Some of these patients would have needed, perhaps, open pulmonary embolectomy, associated with high morbidity and mortality. DISCLOSURE: Jaime Tisnado, None.

CHEST / 128 / 4 / OCTOBER, 2005 SUPPLEMENT

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POSTER PRESENTATIONS

PURPOSE: Filter placement in the IVC is an established procedure to prevent PE from DVT of lower extremities and pelvis. The incidence of PE from DVT of the upper extremities is increasing in this era of aggressive medical therapy and widespread use of central catheters. Some patients with IVC occlusion may develop large collaterals draining into the azygos veins. Therefore, in some of these patients the placement of a filter in the SVC and/or azygos is necessary to prevent PE from the SVC and upper extremities DVT. We understand that this topic is controversial and has not received adequate attention in the literature. We, therefore, present our experience with 20 patients. METHODS: We have placed filters in these very unusual locations in 20 patients. Filters were placed in the SVC in 17 patients and in the azygos vein in 3 patients. Some of these patients also required placement of filters in the IVC. Filters used were the “old” stainless steel Greenfield, the Titanium Greenfield, the “new” stainless steel Greenfield, the Simon Nitinol, the Gu¨nther tulip, and the Trap ease filters. RESULTS: All procedures were successful. No complications related to the procedures were recorded. No SVC or azygos occlusions were found. No migration or misplacement occurred. CONCLUSION: Placement of filters in the SVC and/or azygos system is a safe, easy, effective, albeit controversial, method to prevent PE in certain patients under specific circumstances.

CLINICAL IMPLICATIONS: Some patients with SVC and/or upper extremity DVT can benefit from placement of a filter in the SVC and/or azygos vein. It is safe to insert a filter in the SVC. DISCLOSURE: Jaime Tisnado, None.