Long-term Use of Inhaled Corticosteroids and the Risk of Pneumonia in Chronic Obstructive Pulmonary Disease

BACKGROUND: Recent studies have suggested a possible association between pneumonia and the use of inhaled corticosteroids. We aimed to ascertain the risk of pneumonia with long-term inhaled corticosteroid use among patients with chronic obstructive pulmonary disease (COPD). METHODS: We performed systematic searches with no date restrictions through June 30, 2008, of MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, regulatory documents, and trial registries. We included randomized controlled trials of any inhaled corticosteroid vs a control treatment for COPD, with at least 24 weeks of follow-up and reporting of pneumonia as an adverse event. Outcomes evaluated included any pneumonia, serious pneumonia, pneumonia-related mortality, and overall mortality. RESULTS: Eighteen randomized controlled trials (n = 16 996) with 24 to 156 weeks of follow-up were included after a detailed screening of 97 articles. Inhaled corticosteroids were associated with a significantly increased risk of any pneumonia (relative risk RR, 1.60; 95% confidence interval CI, 1.33-1.92 P < .001; I(2) = 16%) and serious pneumonia (1.71; 1.46-1.99 P < .001; I(2) = 0%) but without a significantly increased risk of pneumonia-related mortality (1.27; 0.80-2.03 P = .31; I(2) = 0%) or overall mortality (0.96; 0.86-1.08 P = .51; I(2) = 0%). Inhaled corticosteroids were associated with a significantly increased risk of serious pneumonia when compared with placebo (RR, 1.81; 95% CI, 1.44-2.29 P < .001) or when the combination of inhaled corticosteroids and long-acting beta-agonists was compared with long-acting beta-agonists (1.68; 1.20-2.34 P = .002). CONCLUSION: Among patients with COPD, inhaled corticosteroid use for at least 24 weeks is associated with a significantly increased risk of serious pneumonia, without a significantly increased risk of death.