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      We thank Young and Hopkins
      • Young R.P.
      • Hopkins R.J.
      Statin use in pneumonia.
      for their thoughtful letter. As a principal aim of our study was to inform the design of a randomized-controlled trial, we are pleased our analysis is being used for this purpose.
      • Chopra V.
      • Rogers M.A.
      • Buist M.
      • et al.
      Is statin use associated with reduced mortality after pneumonia? A systematic review and meta-analysis.
      Because of the association between smoking, chronic obstructive pulmonary disease (COPD), and inflammation, Young and Hopkins
      • Young R.P.
      • Hopkins R.J.
      Statin use in pneumonia.
      suggest that a COPD cohort may be ideal for a statin-pneumonia randomized-controlled trial. Recent studies support the statin-COPD-inflammation hypothesis. In a nested case-control analysis, statin treatment decreased the risk of mortality in patients with COPD by 39%. Importantly, reduced mortality was observed only when baseline levels of C-reactive protein were >3 mg/L.
      • Lahousse L.
      • Loth D.W.
      • Joos G.F.
      • et al.
      Statins, systemic inflammation and risk of death in COPD: the Rotterdam study.
      In an animal model, simvastatin treatment reversed smoke-induced pulmonary hypertension and prevented emphysema.
      • Wright J.L.
      • Zhou S.
      • Preobrazhenska O.
      • et al.
      Statin reverses smoke-induced pulmonary hypertension and prevents emphysema but not airway remodeling.
      Finally, a prospective study of patients hospitalized with acute exacerbations of COPD found lower risk of subsequent exacerbations and improved quality of life among statin users.
      • Bartziokas K.
      • Papaioannou A.I.
      • Minas M.
      • et al.
      Statins and outcome after hospitalization for COPD exacerbation: a prospective study.
      These findings highlight the importance of a systemic anti-inflammatory strategy in COPD.
      As with any research proposal, we must be mindful of perils that threaten the validity of this schema. First, smoking was reported variably among studies included in our analysis: our findings thus reflect only a selection of the available literature. Second, we estimated effect sizes based on inclusion of smoking in multivariable models: thus, the pooled effect reported (odds ratio 0.63; 95% confidence interval, 0.48-0.83) cannot be solely attributed to this covariate, but to adjusted effects when smoking was included as one among many covariates in fully adjusted models. Third, because smoking is a primary risk factor for both COPD and coronary artery disease, many of these patients are already taking statins. Recruiting statin-naïve patients with spirometrically confirmed COPD may thus prove challenging.
      As no study has, to date, specifically examined the effects of statins in patients with COPD and pneumonia, pilot feasibility studies may offer a prudent first step to test Young and Hopkins’ proposal. One setting for such research is the US Veterans Affairs (VA) Medical Centers, where the trifecta of coronary artery disease, COPD, and smoking are highly prevalent. VA investigators have contributed substantially to this area of research, and trials involving statins, COPD, and pneumonia will benefit from their involvement.

      References

        • Young R.P.
        • Hopkins R.J.
        Statin use in pneumonia.
        Am J Med. 2013; 126: e11-e12
        • Chopra V.
        • Rogers M.A.
        • Buist M.
        • et al.
        Is statin use associated with reduced mortality after pneumonia? A systematic review and meta-analysis.
        Am J Med. 2012; 125: 1111-1123
        • Lahousse L.
        • Loth D.W.
        • Joos G.F.
        • et al.
        Statins, systemic inflammation and risk of death in COPD: the Rotterdam study.
        Pulm Pharmacol Ther. 2013; 26 (Available at:) (Accessed December 20, 2012): 212-217
        • Wright J.L.
        • Zhou S.
        • Preobrazhenska O.
        • et al.
        Statin reverses smoke-induced pulmonary hypertension and prevents emphysema but not airway remodeling.
        Am J Respir Crit Care Med. 2011; 183: 50-58
        • Bartziokas K.
        • Papaioannou A.I.
        • Minas M.
        • et al.
        Statins and outcome after hospitalization for COPD exacerbation: a prospective study.
        Pulm Pharmacol Ther. 2011; 24: 625-631

      Linked Article

      • Statin Use in Pneumonia
        The American Journal of MedicineVol. 126Issue 7
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          In the recent systematic review by Chopra et al,1 they conclude that although prior statin use appears to lower mortality following pneumonia, the effect is substantially diminished following subgroup stratification and adjustment for confounding covariates. We note that an important exception to this conclusion is observed in smokers (current and former), where mortality reduction from statin use was 37% (and unaffected by adjustment).1 We describe below why this observation is important.
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