Carson JL, Terrin ML, Duff A, Kelley MA. Pulmonary embolism ... NúËnez B, Jaume Sauleda J, Antó JM, Julia` MR, Orozco M, Monsó E,. Noguera A, Gómez FP, ...
Correspondence
acquired pneumonia (CAP). We agree with the authors that the database on the ability of PCT to discriminate between bacterial and viral CAP is incomplete. The authors quote several pediatric papers in addition to those we referenced that demonstrate PCT levels significantly differ between groups of patients with documented viral and documented bacterial pneumonia. However, these studies do not address the ability of PCT to withhold antibiotics in an individual patient, the critical decision for use of PCT. In particular, patients with CAP with atypical pathogens, such as Mycoplasma pneumoniae and Chlamydophila pneumoniae, may have low PCT levels (1). While many of these patients have a self-limited pneumonia and may recover without antibiotics, the recovery time and risk of adverse consequences may be decreased with appropriate antibiotic therapy. The authors mention aspiration and anaerobic pathogens, but a recent study did not demonstrate that PCT could reliably discriminate between those with chemical pneumonitis alone and those with bacterial infection (2). Recent studies have also demonstrated that even patients bacteremic from various sources can have PCT levels less than 0.5 ng/ml (3). Conversely, in the recent novel 2009 H1N1 influenza A pandemic, a higher PCT threshold was required to discriminate between bacterial and viral pneumonia, suggesting that severe viral pneumonia alone may elevate PCT (4, 5). Even in the landmark study of Christ-Crain and colleagues, 22/23 of patients with CAP with positive serology (only 3 of which may have had M. pneumoniae [the rest were viral]) were given antibiotics per their PCT algorithm (6). Based on the articles quoted by the authors and much of the large published database on PCT, we maintain that our statement that “the clinical discriminating value of PCT remains unclear” is an accurate reflection of the current state of knowledge (7). Hopefully, larger studies with routine use of molecular techniques to enhance both bacterial and viral diagnosis, such as the CDC-sponsored Epidemiology of Pneumonia in Hospitalized Persons (CDC-EPIC) study, will add clarity. Author Disclosure: R.G.W.’s institution has received grants from BioMerieux; he has received consultancy fees from BioMerieux and Siemens. G.W.W. has received consultancy and lecture fees from GlaxoSmithKline and AstraZeneca. J.R. has received board membership fees from Astellas, and consultancy fees from Pfizer.
Richard G. Wunderink, M.D. Northwestern University Feinberg School of Medicine Chicago, Illinois Grant W. Waterer, M.D., Ph.D. University of Western Australia Perth, Western Australia, Australia and Northwestern University Feinberg School of Medicine Chicago, Illinois Jordi Rello, M.D., Ph.D. Vall d’Hebron University Hospital Barcelona, Spain References 1. Masia M, Gutierrez F, Padilla S, Soldan B, Mirete C, Shum C, Hernandez I, Royo G, Martin-Hildago A. Clinical characterisation of pneumonia caused by atypical pathogens combining classic and novel predictors. Clin Microbiol Infect 2007;13:153–161. 2. El-Solh AA, Vora H, Knight PR III, Porhomayon J. Diagnostic use of serum procalcitonin levels in pulmonary aspiration syndromes. Crit Care Med 2011;39:1251–1256. 3. Koeze J, Hendrix MR, van den Bergh FA, Brouwer RM, Zijlstra JG. In critically ill patients the procalcitonin level can be misleading. Crit Care 2011;15:422.
1211 4. Hammond NE, Corley A, Fraser JF. The utility of procalcitonin in diagnosis of H1N1 influenza in intensive care patients. Anaesth Intensive Care 2011;39:238–241. 5. Cuquemelle E, Soulis F, Villers D, Roche-Campo F, Ara Somohano C, Fartoukh M, Kouatchet A, Mourvillier B, Dellamonica J, Picard W, et al. Can procalcitonin help identify associated bacterial infection in patients with severe influenza pneumonia? A multicentre study. Intensive Care Med 2011;37:796–800. 6. Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M, Mulle B. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet 2004;363:600–607. 7. Waterer GW, Rello J, Wunderink RG. Management of community-acquired pneumonia in adults. Am J Respir Crit Care Med 2011;183:157–164.
Copyright ª2011 by the American Thoracic Society
Trends in Cause-Specific Mortality in Oxygen-dependent COPD: What about Pulmonary Embolism? To the Editor: We read with great interest the study by Ekstro¨m and coworkers recently published in the Journal (1). This study represents a huge work, describing the trends in cause-specific mortality in 7,628 Swedish patients with oxygen-dependent chronic obstructive pulmonary disease (COPD), between January 1, 1987 and December 31, 2004. In the “At a Glance” comment, the authors stated that “In oxygen-dependent COPD, mortality has decreased for respiratory disease and increased for nonrespiratory causes, such as cardiovascular disease. This supports the importance of treating comorbidity to improve survival in severe COPD.” This finding is of major interest, because of its therapeutic implications. But, in this view, we are surprised to read no words about a frequent cause of death in COPD, but also preventable and nonfatal in the majority of treated cases: pulmonary embolism (PE). COPD is a moderate risk factor of a global disease called venous thromboembolism (VTE) (2), which integrates PE and deep venous thrombosis (DVT). PE is a major cause of hospital-acquired death, and past autopsic studies found PE to be the cause of death in almost one third of hospitalized patients with COPD (3). But diagnosing PE in patients with COPD, particularly in those with the most advanced form (such as patients with indication of longterm oxygen therapy), may be challenging. Hence, COPD have been associated with an increased risk of dying from an unsuspected fatal PE (4). Do the authors have specific data on this cause of death? If yes, were these patients classified as respiratory or cardiovascular death? Of note, authors found an increase in the proportion of women and in the mean age of patients starting long-term oxygen therapy, during the study period. Increasing age is one of the most important VTE risk factors (2), and PE was found more frequently in older patients with COPD (5). Moreover, female sex is more often associated with PE rather than DVT presentation (6). Therefore, part of the increased rate of death for nonrespiratory causes may be due to PE (diagnosed or undiagnosed), despite the fact that PE was not clearly mentioned in the manuscript. PE is a preventable and—most of the time—treatable disease. An increased awareness of this diagnosis may allow hope for a better prognosis in COPD patients. Author Disclosure: L.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. P.M. has received fees for board membership activities from Boehringer Ingelheim (BI), Bayer, and SanofiAuthor Contributions: L.B., P.M., and H.D. analyzed data and drafted the manuscript.
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Aventis; he has received payment for development of educational presentations from BI, Bayer, and Sanofi-Aventis; his institution has received travel expenses from BI, Bayer, and Sanofi-Aventis. H.D. has received fees for board activities from Bayer, Daiichi-Sankyo, and Sanofi-Aventis; his institution has received grants from Bayer, BI, and Pfizer/BMS, and travel expenses from Bayer, and Daiichi-Sankyo.
Laurent Bertoletti, M.D., Ph.D. Patrick Mismetti, M.D., Ph.D. Herve Decousus, M.D., Ph.D. Universite´ Jean-Monnet St-Etienne, France INSERM, CIC-CIE3 St-Etienne, France and Centre Hospitalier Universitaire St-Etienne, France References 1. Ekstro¨m MP, Wagner P, Stro¨m KE. Trends in cause-specific mortality in oxygen-dependent COPD. Am J Respir Crit Care Med 2011;183:1032. 2. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie` N, Pruszczyk P, Bengel F, Brady AJB, Ferreira D, Janssens U, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008;29:2276–2315. 3. Neuhaus A, Bentz RR, Weg JG. Pulmonary embolism in respiratory failure. Chest 1978;73:460–465. 4. Pineda LA, Hathwar VS, Grant BJ. Clinical suspicion of fatal pulmonary embolism. Chest 2001;120:791–795. 5. Carson JL, Terrin ML, Duff A, Kelley MA. Pulmonary embolism and mortality in patients with COPD. Chest 1996;110:1212. 6. Monreal M, Barba R, Tolosa C, Tiberio G, Todolı´ J, Samperiz AL. Deep vein thrombosis and pulmonary embolism: the same disease? Pathophysiol Haemost Thromb 2006;35:133–135.
Copyright ª2011 by the American Thoracic Society
From the Authors: We thank Dr. Bertoletti and colleagues for their interesting comments. Venous thromboembolism (VTE) was the underlying cause of death in 32 patients (0.6% of total deaths), 13 women and 20 men, in our study. Unfortunately, there were too few deaths to estimate the trends in mortality from VTE. The entity was therefore not reported separately, but was included in the entities circulatory disease and nonrespiratory disease (1). We agree that pulmonary embolism is likely to be underdiagnosed, both as a comorbidity and cause of death in severe chronic obstructive pulmonary disease (COPD), which is likely reflected in the low number of deaths from VTE in our patient population. In addition to the studies cited by Bertoletti and colleagues, the association between VTE and COPD was supported by a previous study by our group, which found an increased excess mortality from VTE in oxygen-dependent COPD compared with the general population. Bertoletti and colleagues propose that the increasing nonrespiratory mortality over time in oxygen-dependent COPD might be partly due to an increase in undiagnosed VTE. However, this interesting hypothesis needs to be tested through studies involving standardized diagnostic algorithms. Author Disclosure: M.P.E.’s institution has received grants from the Swedish Heart and Lung Foundation, Research Council of Blekinge, and the Swedish National Board of Health and Welfare. P.W. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. K.E.S.’s institution has received grants from the Swedish Association of Local Authorites and Regions, and the Swedish Heart and Lung Association; she has received fees for board activities from the Swedish Heart and Lung Association, lecture fees
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from Boehringer Ingelheim, travel support from Nycomed and UCB, and grants from the Blekinge County Council.
Magnus P. Ekström Kerstin E. Ström Blekinge Hospital Karlskrona, University of Lund Lund, Sweden Philippe Wagner Ska˚ne University Hospital Lund, Sweden Reference 1. Ekstro¨m PM, Wagner P, Stro¨m KE. Trends in cause-specific mortality in oxygen-dependent chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2011;183:1032–1036.
Copyright ª2011 by the American Thoracic Society
Is Autoimmunity Really Related to the Pathogenesis of COPD? To the Editor: ~ez and colleagues We read with interest the recent article by N un (1). They suggested that an autoimmune component might play a significant role in the pathogenic mechanism of chronic obstructive pulmonary disease (COPD). A similar hypothesis has also been proposed by others (2). However, if autoimmunity was really related to the pathogenesis of COPD, then systemic corticosteroid therapy would be expected to be effective for COPD. Moreover, COPD more often should be associated with connective tissue diseases. However, no study has shown a significant benefit of systemic corticosteroid treatment in stable COPD (3). In addition, we could not find any study that demonstrated a high incidence of connective tissue diseases in COPD, although systemic inflammation associated with COPD could result in several systemic manifestations, such as cardiovascular diseases and metabolic abnormalities (4). From these observations, we think that a high prevalence of auto-antibodies in COPD might be an incidental finding resulting from lung parenchymal tissue destruction, and autoimmunity itself does not play a significant role in the pathogenic mechanisms of COPD. Our hypothesis also can explain the relation between anti-tissue antibodies and lung function in COPD. To clarify this notion, further investigations will be needed. Author Disclosure: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
Mikio Toyoshima, M.D., Ph.D. Hamamatsu Rosai Hospital Hamamatsu, Japan and Hamamatsu University School of Medicine Hamamatsu, Japan Kingo Chida, M.D., Ph.D. Takafumi Suda, M.D., Ph.D. Hamamatsu University School of Medicine Hamamatsu, Japan Masaki Sato, M.D., Ph.D. Hamamatsu Rosai Hospital Hamamatsu, Japan References ~ez B, Jaume Sauleda J, Ant 1. N un o JM, Julia` MR, Orozco M, Mons o E, Noguera A, G omez FP, Garcia-Aymerich J, Agustı´ A. Anti-tissue
