Observational studies examining the association between proton pump inhibitor (PPI) use and risk of community-acquired pneumonia are conflicting. To assess systematically the association between risk of community-acquired pneumonia and PPI use in adults. We searched MEDLINE, EMBASE and CINAHL databases between 1988 and January 2010. Two reviewers independently selected studies based on eligibility criteria and extracted data. Included studies evaluated adults (> or =18 years) who took PPIs as an out-patient. The primary outcome was community-acquired pneumonia. Only observational studies with a comparison arm were included. Over 2600 citations were reviewed. Six studies were included. All were nested case-control studies. Meta-analysis found an increased risk of community-acquired pneumonia associated with PPI use [OR 1.36 (95% CI 1.12-1.65)]; significant heterogeneity remained (I(2) 92%, P < 0.001). In exploratory subgroup analysis, short duration of use was associated with an increased odds of community-acquired pneumonia [OR 1.92 (95% CI 1.40-2.63), I(2) 75%, P = 0.003], whereas chronic use was not [OR 1.11 (95% CI 0.90-1.38), I(2) 91%, P < 0.001], a significant interaction (P < 0.005). Heterogeneity precluded interpretation of the summary statistic. Exploratory analysis revealed that duration of PPI use may impact the risk of community-acquired pneumonia, a finding that should be explored in future studies.
