COPD Patients Apoptosis of Circulating Neutrophils in

Apoptosis of Circulating Neutrophils in COPD Patients Mathias W. R. Pletz and Hartmut Lode Chest 2005;127;1464-1465 DOI 10.1378/chest.127.4.1464 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/127/4/1464.full.html

Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright2005by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692

Downloaded from chestjournal.chestpubs.org by guest on October 17, 2011 © 2005 American College of Chest Physicians

When an intermediate type I patient needs invasive ventilation, we maintain mechanical ventilation for 3 weeks. Then, after the tube is removed, the patient continues with nasal nocturnal ventilation and intermittent positive-pressure ventilation for 20 min three times a day. If, despite this management, the patient requires invasive ventilation more than three times during the same year or requires nasal ventilation not only during sleeping, but also while awake, a tracheostomy is performed. Treatment has changed over the years. We agree with Dr. Bach that patients with respiratory paralysis benefit from preventive noninvasive treatment with hyperinsufflation and noninvasive nocturnal ventilation, which is associated with help in coughing. At the present time, we also use percussion therapy with respiratory physiotherapy every day at home, and these treatments delay the acute respiratory worsening. In our experience, patients with tracheostomy tubes are no longer hospitalized until spine surgery and are less dependent on their environment. Severely affected children cannot attend a boarding school while using noninvasive ventilation. So, even now we perform a tracheostomy in ventilatory-dependent children who require daylong therapy. Dr. Bach said that “many of their patients needed to be intubated on 10 or more occasions before age 5” and that “patients . . . use high span BPPV [bilevel positive pressure ventilation] at least when sleeping and as many as 60 use it up to 24 hours a day.” In our opinion, for a patient who needs continuous nasal ventilation, or requires invasive ventilation more than three times during the same year, we prefer the use of tracheostomy, which allows a better quality of life. Mechanical ventilation with good thoracic expansion prevents pectus excavatum. Christine Ioos, MD Hoˆpital Raymond Poincare´ Garches, France

Surprisingly, they were not able to find a difference between the COPD patients and the control subjects. Their conclusion was that neutrophil apoptosis in COPD patients occurred at a rate similar to that found in healthy individuals and smokers with normal lung function. We agree with the methodology used; however, we believe that this conclusion is misleading. An increase in systemic cytokines (eg, interleukin-6), inhibiting the apoptosis of circulating neutrophils,2 is present in stable-state COPD patients but is not as pronounced as in those with acute exacerbations.3 In addition, the spontaneous apoptosis rates of circulating neutrophils show a high degree of interindividual variation.4 Therefore, a larger number of subjects than that investigated by Noguera et al might be needed to find a statistically significant difference between healthy volunteers and COPD patients in the stable state. According to the guidelines of the Global Initiative for Chronic Obstructive Lung Disease,5 exacerbations are the main factor in the progression of COPD. Therefore, we performed a very similar study but enrolled only hospitalized patients who had experienced an acute exacerbation of COPD.4 Neutrophil apoptosis was measured at hospital admission, after 3 to 5 days, and at hospital discharge. In addition, we assessed spontaneous apoptosis rates in healthy volunteers. We were able to show that neutrophil apoptosis is significantly suppressed at the beginning of an acute exacerbation (p ⬍ 0.0001 [paired t test, and the parametric distribution of the data was confirmed by the ShapiroWilks test]), and that it increases progressively after treatment and clinical remission, reaching the values of healthy subjects on the day of hospital discharge. Therefore, we believe that delayed neutrophil apoptosis is an important key feature of COPD pathogenesis and deserves further investigation to avoid missing any potential new treatment options for COPD, which is a disease with a high burden.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]). Correspondence to: Christine Ioos, MD, Hoˆpital Raymond Poincare´, 104 Blvd Raymond Poincare´, Garches, France 92380; e-mail: [email protected]

Reference 1 Ioos C, Leclair-Richard D, Mrad S, et al. Respiratory capacity course in patients with infantile spinal muscular atrophy. Chest 2004; 126:831– 837

Mathias W. R. Pletz, MD Hartmut Lode, MD Chest Hospital Heckeshorn Berlin, Germany Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]). Correspondence to: Mathias W. R. Pletz, MD, Department of International Health, Emory University, Atlanta, GA 30322; e-mail: [email protected]

References

Apoptosis of Circulating Neutrophils in COPD Patients To the Editor: We read with great interest the study by Noguera et al (May 2004)1 on the apoptosis of circulating neutrophils in COPD patients. Neutrophils exhibit a short half-life and are primarily removed by apoptosis. In contrast to apoptosis, neutrophil necrosis results in the release of aggressive enzymes, leading to tissue destruction and increased inflammation. Noguera et al compared ex vivo the spontaneous apoptosis rates of circulating neutrophils from COPD patients in stable condition with those from smokers with normal lung function and healthy nonsmokers. Since it is known that spontaneous neutrophil apoptosis is decreased in various inflammatory conditions and that neutrophils are considered to play a crucial role in COPD pathogenesis, they expected to find a decreased or delayed apoptosis. They incubated the cells and measured spontaneous apoptosis rates after 2, 8, and 24 h by flow cytometry. 1464

1 Noguera A, Sala E, Pons AR, et al. Expression of adhesion molecules during apoptosis of circulating neutrophils in COPD. Chest 2004; 125:1837–1842 2 Biffl WL, Moore EE, Moore FA, et al. Interleukin-6 delays neutrophil apoptosis. Arch Surg 1996; 131:24 –29 3 Wedzicha JA, Seemungal TA, MacCallum PK, et al. Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels. Thromb Haemost 2000; 84:210 –215 4 Pletz MW, Ioanas M, de Roux A, et al. Reduced spontaneous apoptosis in peripheral blood neutrophils during exacerbation of COPD. Eur Respir J 2004; 23:532–537 5 Pauwels RA, Buist AS, Calverley PM, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary. Am J Respir Crit Care Med 2001; 163:1256 –1276 To the Editor: We thank Drs. Pletz and Lode for their interest in our work (May 2004).1 We agree with their comments and suggestions. Of Communications to the Editor


course, in vivo conditions may differ very substantially from in vitro ones. Thus, the comments made by Drs. Pletz and Lode with respect to our work are well taken. We would like, however, to highlight another potential source of confusion. In the article by Pletz et al,2 patients were studied during exacerbations. As such, they were receiving intense steroid therapy, among other types of therapy. As is known by the authors, steroids can interfere both with systemic inflammation3 and neutrophil apoptosis.4 We therefore fully agree with Drs. Pletz and Lode that the role of neutrophil apoptosis in COPD deserves further study. Aina Noguera, MD Ernest Sala, MD Hospital Universitari Son Dureta Palma de Mallorca, Spain Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: [email protected]). Correspondence to: Aina Noguera, MD, Servei Ana´lisi Cliniques, Hospital Universitari Son Dureta, Andrea Doria 55, Palma de Mallorca, Spain 07014; e-mail: [email protected]

References 1 Noguera A, Sala E, Pons AR, et al. Expression of adhesion molecules during apoptosis of circulating neutrophils in chronic obstructive pulmonary disease. Chest 2004; 125: 1837–1842 2 Pletz MW, Ioanas M, De Roux A, et al. Reduced spontaneous apoptosis in peripheral blood neutrophils during exacerbation of COPD. Eur Respir J 2004; 23:532–537 3 Sin DD, Lacy P, York E, et al. Effects of fluticasone on systemic markers of inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004; 170: 760 –765 4 Zhang X, Moilanen E, Kankaanranta H. Beclomethasone, budesonide and fluticasone propionate inhibit human neutrophil apoptosis. Eur J Pharmacol 2001; 431:365–371

SNAP Technology and Sleep Apnea To the Editor: As a Fellow of the American College of Chest Physicians, a medical adviser to SNAP Laboratories, and a SNAP Laboratories test user of many years, I read with surprise the study by Liesching et al (March 2004),1 as well as the accompanying editorial by Collop.2 Using data derived from a poorly designed study, Liesching et al unjustifiably concluded that the agreement between the apnea-hypopnea index determined by SNAP testing and polysomnography can only be characterized as “fair.” The authors then offered the opinion that SNAP studies may not accurately assess the severity of obstructive sleep apnea. In an additional reply to this article, Collop2 correctly pointed out that “the study is not without faults.” As noted, the study by Liesching et al1 was a retrospective comparison of nonsimultaneous studies performed in the laboratory with those performed at home. In actuality, the mean time frame between tests that were compared was 5 months. The decision to compare data collected from different and nonsequential nights is a major flaw. Despite the rebuttal of one study by Liesching et al, there is a substantial body of research3–5 that documents the first-night and night-to-night variability of sleep apnea. This variability is compounded by the week-to-week or month-to-month variability inherent in their study. Therefore, their data were clearly impacted by variables such as changes in www.chestjournal.org

body mass index, medications, and site of testing. In addition, of the original 39 subjects, only 31 had complete data for analysis. Considering the limitations of the study, it is remarkable that it was considered to be an empirical foundation for any conclusions. A more appropriate conclusion, if any were to be drawn, would be that SNAP home testing variability is no greater than that documented between nights in a sleep center. In addition to pointing out this study’s shortcomings, Collop has noted previously6 that “given the outdated sleep staging rules, inconsistent equipment between labs, variable scoring parameters . . . it is a wonder that there can be any consistent scoring of PSGs [between trained sleep professionals].” In another publication7 Collop concluded that “clinicians should be aware that there is tremendous variability among polysomnography technologists regarding the scoring of polysomnography.” Given the disagreement levels reported by Collop in this study (eg, the record of the same patient yielded apnea-hypopnea index scores of 5 and 74 by two differently trained technicians), the SNAP results criticized by Liesching et al1 are in fact impressive. Thus, even if the SNAP test had been in perfect agreement with the scoring done by the Brown Sleep Laboratory physician used in this study, scoring by personnel at another laboratory would in all likelihood differ. This would lead Liesching et al1 to the same conclusions that they reached in their study. SNAP testing is being held to a different standard from that the sleep industry sets for itself. The sleep medicine community has been aware for years of the high level of disagreement between two trained professionals scoring the same record on the same night. Why then should they be surprised when SNAP results vary between a review by one technician and that of another technician performed months later in an entirely different environment? Perhaps one should question why we should subject patients to laboratory-based polysomnography at significantly greater expense and inconvenience when same-test scoring agreement is no more accurate than that reported by a SNAP home test. The SNAP test is not a “black box,” as suggested in the editorial by Collop,2 but instead requires a full night of continuous recording of at least four data channels. These raw data are analyzed by a trained technician who analyzes the full night of digitally recorded raw data, just as is done in the sleep laboratory. All data with marked events are available to the referring physician on request. The SNAP test technology and scoring procedure have been validated on five separate occasions by accredited sleep centers. All of these studies used a protocol of recording SNAP data and conventional polysomnography data on the same night in sleep laboratories, with quite impressive results. Previous attempts to publish these side-by-side blind studies have been met with strong resistance by journals with review committees dominated by sleep specialists. In other cases, after the data were collected and analyzed, the sleep laboratory involved in the study simply refused to submit the results for publication. Despite these obstacles, a recent study performed at the University of Chicago was published8 that simultaneously compared SNAP to PSG, as was suggested by Liesching et al. The authors concluded that “the results of this validation study demonstrate that there is good correlation between SNAP and PSG in quantifying RDI with reliable sensitivity, specificity, positive and negative predictive values in a laboratory setting.” Thus “SNAP is an excellent tool for the diagnosis of OSAS.” As a medical adviser I have been assured by SNAP Laboratories of their willingness to participate in any well-designed, objective study that will yield a fair and accurate assessment of SNAP sleep testing. Thomas J. Kehoe, MD, FCCP Evanston Northwestern Healthcare Evanston, IL CHEST / 127 / 4 / APRIL, 2005


1465

Apoptosis of Circulating Neutrophils in COPD Patients Mathias W. R. Pletz and Hartmut Lode Chest 2005;127; 1464-1465 DOI 10.1378/chest.127.4.1464 This information is current as of October 17, 2011 Updated Information & Services Updated Information and services can be found at: http://chestjournal.chestpubs.org/content/127/4/1464.full.html References This article cites 8 articles, 6 of which can be accessed free at: http://chestjournal.chestpubs.org/content/127/4/1464.full.html#ref-list-1 Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.chestpubs.org/site/misc/reprints.xhtml Reprints Information about ordering reprints can be found online: http://www.chestpubs.org/site/misc/reprints.xhtml Citation Alerts Receive free e-mail alerts when new articles cite this article. To sign up, select the "Services" link to the right of the online article. Images in PowerPoint format Figures that appear in CHEST articles can be downloaded for teaching purposes in PowerPoint slide format. See any online figure for directions.
