Inhaled corticosteroids and mortality on copd


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Commentary on the use of inhaled corticosteroids in COPD

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Inhaled corticosteroids and mortality on copd

  1. 1. Inhaled Corticosteroids and Mortality in COPD Chest 2007;131;939-940 DOI 10.1378/chest.06-2473 The online version of this article, along with updated information and services can be found online on the World Wide Web at: Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright2007by 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. ( ISSN:0012-3692Downloaded from by guest on May 13, 2011 © 2007 American College of Chest Physicians
  2. 2. The authors have reported to the ACCP that no significant 2 Hak E, Verheij TJ, Grobbee DE, et al. Counfounding byconflicts of interest exist with any companies/organizations whose indication in non-experimental evaluation of vaccine effec-products or services may be discussed in this article. tiveness: the example of prevention of vaccine complications.Reproduction of this article is prohibited without written permission J Epidemiol Community Health 2002; 56:951–955from the American College of Chest Physicians ( ResponseCorrespondence to: Ruzena Tkacova, MD, PhD, Louis PasteurTeaching Hospital, Medical Faculty of PJ Safarik University,Department of Respiratory Medicine, Rastislavova 43, Kosice 041 To the Editor:90, Slovakia; e-mail: rtkacova@central.medic.upjs.skDOI: 10.1378/chest.06-2660 I read with interest the recent article by Macie and colleagues (September 2006).1 I congratulate them on an exhaustive analysis References of a well-designed observational study. I disagree, however, with 1 Joppa P, Petrasova D, Stancak B, et al. Systemic inflammation the conclusion on several points. First, it is stated in the abstract in patients with COPD and pulmonary hypertension. Chest that therapy “with ICSs [inhaled corticosteroids] reduced mor- 2006; 130:326 –333 tality in COPD patients.” Causality cannot be inferred from a 2 Andreas S, Anker SD, Scanlon PD, et al. Neurohumoral case-control observational study no matter how well statistically activation as a link to systemic manifestation of chronic lung modeled. Further, could undetected bias explain the association disease. Chest 2005; 128:3618 –3624 between ICS use and reduced mortality? The effect of ICSs on 3 Andreas S, Herrmann-Lingen C, Raupach T, et al. Angioten- mortality may have been overestimated because of healthy user sin II blockers in obstructive pulmonary disease: a random- and provider selection bias.2,3 Could ICS users be a more robust ised controlled trial. Eur Respir J 2006; 27:972–979 4 Morrell NW, Higham MA, Phillips PG, et al. Pilot study of group in terms of cardiovascular risk factors, or behavioral or losartan for pulmonary hypertension in chronic obstructive lifestyle modifications? Further, providers might be more in- pulmonary disease. Respir Res 2005; 6:88 clined to prescribe ICSs to less ill, more motivated COPD 5 Farber HW, Loscalzo J. Pulmonary arterial hypertension. patients. The article supports this notion on several occasions. In N Engl J Med 2004; 351:1655–1665 Table 1, ICS users were more likely to receive other medications, visit physicians more frequently, and in older patients had less comorbidity. “In subjects who were 65 years of age . . . who died had more comorbidities . . . received more prescriptions . . .Inhaled Corticosteroids and Mortality other than ICSs than did control subjects.” It would have beenin COPD instructive if the authors could have stratified the data on the basis of the percentage of patients in each group who received aTo the Editor: prescription of ICSs but was later not dispensed. This would have provided insight into healthy user and provider selection bias. I appreciate the thoughtful discussion in a recent issue of Examples of confounders not adjusted for in analyses includeCHEST (September 2006)1 by Macie et al of the limitations of tobacco usage, body mass index, statin use, severity of COPD,database analyses, as well as of the adjustments made in their social class, and physical activity. Model adjustments for complexstudy for the confounding factors of comorbid illness and other social and behavioral factors are difficult and are outside therespiratory medications. However, their analysis may have over- scope of observational studies in general.4 The patient out-of-looked potential confounding by indication, which may be highly pocket costs of medical therapy in COPD are considerable. It issignificant in this population. The prescribing of inhaled cortico- incumbent on pulmonologists to parcel out the data carefully leststeroids may be reflective of the prescribers’ implementation of an ineffective therapy for reducing COPD-related mortalityevidence-based medicine, and of the fact that patients to whom becomes the standard of care.inhaled corticosteroids were prescribed for treatment of theirCOPD may have been more likely to have been prescribed Edward Omron, MD, MPH, FCCPaspirin, -blockers, and angiotensin-converting enzyme inhibi- Novi, MItors for treatment of their cardiovascular disease. Including theseprescriptions in the multivariable model would account for this The author has no conflicts of interest to disclose.effect.2 Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Giora Netzer, MD, MSCE Correspondence to: Edward Omron, MD, MPH, FCCP, 39650 University of Maryland School of Medicine Orchard Hill Place, Suite 100, Novi, MI 48375-5331; e-mail: Baltimore, MD DOI: 10.1378/chest.06-2620The author has reported to the ACCP that no significant conflictsof interest exist with any companies/organizations whose products Referencesor services may be discussed in this article. 1 Macie C, Wooldrage K, Mandreda J, et al. Inhaled cortico-Reproduction of this article is prohibited without written permission steroids and mortality in COPD. Chest 2006; 130:640 – 646from the American College of Chest Physicians (www.chestjournal. 2 Garbe E, Suissa S. Hormone replacement therapy and acuteorg/misc/reprints.shtml).Correspondence to: Giora Netzer, MD, MSCE, University of coronary outcomes: methodological issues between random-Maryland School of Medicine, MSTF Room 800, 685 W Baltimore ized and observational studies. Hum Reprod 2004; 19:8 –13St, Baltimore, MD 21201-1192; e-mail: gnetzer@medicine. 3 Rosenberg A, Hofer T, Strachan C, et al. Accepting ill transfer patients: adverse effect on referral center’s out-DOI: 10.1378/chest.06-2473 come and benchmark measures. Ann Intern Med 2003; 138:882– 890 4 Lawlor D, Smith G, Bruchdorfer K, et al. Those confounded References vitamins: what can we learn from the differences between 1 Macie C, Wooldrage K, Manfreda J, et al. Inhaled cortico- observational versus randomized trial evidence? Lancet 2004; steroids and mortality in COPD. Chest 2006; 130:640 – 646 363:1724 – CHEST / 131 / 3 / MARCH, 2007 939 Downloaded from by guest on May 13, 2011 © 2007 American College of Chest Physicians
  3. 3. Response IPF.5 Presence of anti-topoisomerase antibodies (that produce a nucleolar pattern on immunofluorescence testing) among pa-To the Editor: tients with IPF has also been reported.6 The authors of the current study1 had, in fact, recently demonstrated by means of a We thank Drs. Netzer and Omron for their interest in our retrospective analysis that ANA positivity (with a nucleolararticle. We agree that observational data such as we used are staining pattern) occurred in 25 patients with IPF (8.8%), moretricky and cannot consider all potential confounders. Confound- than half of whom also had presence of anti-Th/To antibodies.7ing by indication is always the weakness of this kind of work. The small number of patients with ANA positivity, absence ofHowever, we tried to avoid this, and could not identify plausible cutaneous features of SSc in all the patients, and lack ofcauses for this kind of confounding. Dr. Netzer points out that we differences (in clinical features, pulmonary physiologic-cum-gasdid not look at markers of cardiovascular disease, such as cardiac exchange parameters and survival) between patients with ANAdrugs, and she is right. However, in another study we have looked positivity and those without, as well as between patients withat cardiovascular morbidity as a function of respiratory drugs and anti-Th/To antibody positivity and those without makes it difficultfound that inhaled steroids tended to be protective, but this to substantiate the authors’ conclusions of attributing the pulmo-effect was independent of interaction with cardiac drugs. Dr. nary fibrosis as being related to SSc. The fact is that pulmonaryOmron is not convinced that users of inhaled steroids were as sick fibrosis (occurring in the setting of both IPF and SSc) isas people who did not receive these drugs. We would argue that commonly associated with the presence of GER as well asthe evidence favors them being at least as sick; we regard autoimmunity, and differentiating idiopathic from nonidiopathicfrequent physician visits and multiple drugs as evidence of entities often remains a challenging issue for treating clinicians.perceived severity, not the reverse. Further, we studied dis- Navneet Singh, MDpensed drugs only; we had no data regarding drugs that were Postgraduate Institute of Medical Education and Researchprescribed but not dispensed. The fact that the steroid effect was Chandigarh, Indiamost notable soon after dispensation we take as evidence favoringdrug use. The author has no conflicts of interest to disclose. Reproduction of this article is prohibited without written permission Nicholas R. Anthonisen, MD from the American College of Chest Physicians (www.chestjournal. University of Manitoba org/misc/reprints.shtml). Winnipeg, MB, Canada Correspondence to: Navneet Singh, MD, Department of Pulmo- nary Medicine, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012, India; e-mail:The author has no conflict of interest to disclose. navneetchd@yahoo.comReproduction of this article is prohibited without written permission DOI: 10.1378/chest.06-2511from the American College of Chest Physicians ( ReferencesCorrespondence to: Nicholas R. Anthonisen, MD, University of 1 Fischer A, Meehan R, Feghali-Bostwick C, et al. UniqueManitoba, RS 319 Health Sciences Centre, 810 Sherbrook St, characteristics of systemic sclerosis sine scleroderma-associ-Winnipeg, MB, Canada R3A 1R8; e-mail: nanthonisen@exchange. ated interstitial lung disease. Chest 2006; 130:976 –981hsc.mb.caDOI: 10.1378/chest.06-2984 2 Raghu G, Freudenberger TD, Yang S, et al. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Respir J 2006; 27:136 –142 3 Raghu G, Yang ST, Spada C, et al. Sole treatment of acidReflux and Autoimmunity gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series. Chest 2006; 129:794 – 800 4 Jindal SK, Agarwal R. Autoimmunity and interstitial lungCommon Links Among Patients With disease. Curr Opin Pulm Med 2005; 11:438 – 446Pulmonary Fibrosis? 5 Raghu G, Brown KK. Interstitial lung disease: clinical evalu- ation and keys to an accurate diagnosis. Clin Chest Med 2004;To the Editor: 25:409 – 419 6 Meliconi R, Negri C, Borzi RM, et al. Antibodies to topo- I read with interest the article by Fischer and colleagues isomerase II in idiopathic pulmonary fibrosis. Clin Rheumatol 1993; 12:311–315(October 2006),1 wherein they describe the characteristics of 7 Fischer A, Pfalzgraf FJ, Feghali-Bostwick CA, et al. Anti-th/systemic sclerosis (SSc)-associated interstitial lung disease in to-positivity in a cohort of patients with idiopathic pulmonarypatients who presented with an initial diagnosis of idiopathic fibrosis. J Rheumatol 2006; 33:1600 –1605interstitial pneumonia. Symptomatic gastroesophageal reflux(GER) was one of the clinical features that was identified by the Responseauthors1 as being indicative of the presence of SSc-associatedinterstitial lung disease. However, GER is very common among To the Editor:patients with idiopathic pulmonary fibrosis (IPF), the mostcommonly encountered idiopathic interstitial pneumonia. Raghu We appreciate Dr. Singh’s interest in our article.1 We agreeand colleagues2 recently demonstrated with the use of 24-h pH that it can sometimes be challenging to differentiate nonidio-monitoring and esophageal manometry that GER was present in pathic forms of interstitial lung disease (ILD) from idiopathicmajority (87%) of patients with IPF, almost half of whom were forms. It was in this light that we identified the unique featuressymptomatic. Furthermore, the same group3 reported stabiliza- of systemic sclerosis sine scleroderma (ssSSc)-ILD in patientstion and even improvement in pulmonary function test results who otherwise would have been categorized as having idiopathicover a period of 2 to 6 years in a small series of patients with IPF pulmonary fibrosis (IPF).who were treated with anti-GER medications alone. Similarly, As stated in our article, the diagnosis of ssSSc was made only ifthe presence of autoimmunity in IPF is well known and was the patient had at least three or more manifestations that werehighlighted in a review.4 Anti-nuclear antibodies (ANAs) are typical of systemic sclerosis (SSc). We chose these manifestationsdemonstrable in serum in as many as 10 to 20% of patients with based on the proposed diagnostic criteria for ssSSc.2940 Correspondence Downloaded from by guest on May 13, 2011 © 2007 American College of Chest Physicians
  4. 4. Inhaled Corticosteroids and Mortality in COPD Chest 2007;131; 939-940 DOI 10.1378/chest.06-2473 This information is current as of May 13, 2011Updated Information & ServicesUpdated Information and services can be found at: article cites 6 articles, 5 of which can be accessed free at: & LicensingInformation about reproducing this article in parts (figures, tables) or in its entirety can befound online at: about ordering reprints can be found online: AlertsReceive 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 formatFigures that appear in CHEST articles can be downloaded for teaching purposes inPowerPoint slide format. See any online figure for directions. Downloaded from by guest on May 13, 2011 © 2007 American College of Chest Physicians