Statins Use and Pneumonia

CHEST Statins Use and Pneumonia To the Editor: We read with interest the recent article in CHEST (November 2009) by Chopra and Flanders,1 which proposes that statins, through pleiotropic antiinflammatory effects, might reduce mortality in pneumonia. We agree that a “healthy user” effect is unlikely to be the basis of this finding. In a recent review of statin use in COPD, we also challenge the proposition that a healthy-user effect may underlie the consistent benefits observed with statin use in patients with COPD.2 First, patients taking statins have a much higher prevalence of cardiovascular disease and, therefore, may be at greater risk of death than those not on statins.2 One would expect this to result in greater mortality in those with pneumoniaCOPD taking statins because of comorbid cardiovascular disease (ie, confounding by drug indication) in contrast to the lower mortality reported by the majority of studies.1,3 Second, in a clinic population of patients with COPD, we show lung function is no different between statin users and nonusers.2 This is highly relevant because FEV1 is a good marker of cardiovascular mortality, respiratory mortality, and all-cause mortality.2,3 We suggest FEV1 is a biomarker of an elevated inflammatory disposition driven primarily by smoking and a genetic predisposition.3 Third, when we reviewed the large observational studies comparing various outcomes in COPD, we could find no significant differences in statin users compared with nonusers with respect to age, smoking exposure, and socioeconomic status (consistent with the findings of Chopra and Flanders).2 Fourth, the proposed basis of the healthy-user effect in statin users is a greater uptake of “preventive therapies” (eg, vaccinations and screening) over nonusers. Given that this greater uptake is small in absolute terms and affects only a minority of statin users, it is hard to see how such preventive therapies account for the 30% to 50% mortality reductions observed.2 Evidence linking statins to improved outcomes in pneumonia and COPD comes from longitudinal studies showing that (1) elevated interleukin (IL)-6 predicts hospitalization for pneumonia,4 and (2)  50% of adult pneumonia cases have preexisting COPD.5 Statins, through antiinflammatory effects (eg, inhibition of IL-6, IL-8, tumor necrosis factor-a and IL-1b), inhibit neutrophil migration into inflamedinfected pulmonary tissues, reduce serum tissue cytokines, and reduce vascular leak.3 In agreement with Chopra and Flanders,1 we suggest statins also confer a mortality benefit in COPD and its comorbidities, specifically coronary artery disease, chest infection (pneumonia and infective exacerbations), and lung cancer,2,3 through antiinflammatory effects. Robert P. Young, MD, PhD Raewyn J. Hopkins, BN, PGDipPH Auckland, New Zealand Affiliations: From the Department of Medicine, Auckland Hospital, University of Auckland. www.chestpubs.org

Correspondence

Financialnonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Young is a shareholder and chief scientific officer of Synergenz BioScience Ltd and involved in genetic susceptibility testing for lung cancer. Ms Hopkins is an employee of Synergenz BioScience Ltd and involved in genetic susceptibility testing for lung cancer. Correspondence to: Robert Young, MD, PhD, Department of Medicine, Auckland Hospital, Private Bag 92019, Auckland, New Zealand; e-mail: [email protected] © 2010 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestpubs.org sitemiscreprints.xhtml). DOI: 10.1378/chest.09-2779

References 1. Chopra V, Flanders SA. Does statin use improve pneumonia outcomes? Chest. 2009;136(5):1381-1388. 2. Young RP, Hopkins RJ, Eaton TE. Potential benefits of statins on morbidity and mortality in chronic obstructive pulmonary disease: a review of the evidence. Postgrad Med J. 2009;85(1006):414-421. 3. Young RP, Hopkins R, Eaton TE. Pharmacological actions of statins: potential utility in COPD. Eur Respir Rev. 2009; 18(114):222-232. 4. Yende S, Tuomanen EI, Wunderink R, et al. Preinfection systemic inflammatory markers and risk of hospitalization due to pneumonia. Am J Respir Crit Care Med. 2005;172(11): 1440-1446. 5. Mannino DM, Davis KJ, Kiri VA. Chronic obstructive pulmonary disease and hospitalizations for pneumonia in a US cohort. Respir Med. 2009;103(2):224-229.

Response To the Editor: We thank Drs Young and Hopkins for their letter regarding our article in CHEST (November 2009)1 on the potential impact of statin use on pneumonia outcomes. We concur that the “healthyuser” effect may not be the only explanation for the positive association between statins and pneumonia. However (as discussed in our review), the precise manner by which statins modulate pneumonia outcomes remains unclear. Though plausible theories exist, no randomized controlled trial has yet addressed this issue. We note that since the release of our article, however, a populationbased, case-control study found that statin use was not associated with a decrease in pneumonia risk.2 At this controversial crossroad, we argue that the question we should be asking is how better to design studies to capture any effect (positive or negative) of statins on pneumonia. In their retrospective review, Thomsen et al3 found that mortality among statin users with pneumonia was lower than that of nonusers at 30- and 90-day intervals. In a prospective study, Chalmers et al4 reported that statins decreased 30-day mortality in their cohort of 1,007 patients (adjusted odds ratio, 0.46; 95% CI, 0.25-0.85; P , .01). In contrast, the recent study by Dublin et al2 reported CHEST / 137 / 5 / MAY, 2010

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