Meta-analysis: Proton Pump Inhibitor Use and the Risk of Community-acquired Pneumonia

Background: Observational studies examining the association between proton pump inhibitor (PPI) use and risk of community-acquired pneumonia are conflicting.

Aim: To assess systematically the association between risk of community-acquired pneumonia and PPI use in adults.

Methods: 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.

Results: 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).

Conclusions: 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.