Proton-Pump Inhibitor Use and the Risk for Community-Acquired Pneumonia

Background: Recent studies suggest that proton-pump inhibitors (PPIs) may increase the risk for community-acquired pneumonia (CAP). Objective: To examine the association between PPI use and CAP in adults followed in general practices in the United Kingdom. Design: Nested case–control study. Setting: The General Practice Research Database (1987 to 2002) in the United Kingdom. Participants: Patients age 18 years or older with at least 6 months of initial pneumonia-free follow-up in the database. Case patients (n = 80 066) were defined as those who received an incident diagnosis of CAP. Control participants (n = 799 881) were selected by using incidence density sampling, matching on practice site, calendar period, and follow-up duration. Measurements: Use of PPIs within 30 days before the index date. Adjusted odds ratios (ORs) were estimated by using conditional logistic regression, adjusting for potential confounders. Results: Overall, current PPI use was not associated with an increased risk for CAP (adjusted OR, 1.02 [95% CI, 0.97 to 1.08]) or risk for CAP that required hospitalization (adjusted OR, 1.01 [CI, 0.91 to 1.12]). There was a strong increase in risk for CAP associated with current use of PPI therapy that was started within the previous 2 days (adjusted OR, 6.53 [CI, 3.95 to 10.80]), 7 days (adjusted OR, 3.79 [CI, 2.66 to 5.42]), and 14 days (adjusted OR, 3.21 [CI, 2.46 to 4.18]), but there was no statistically significant association for longer-term current PPI therapy. A separate matched case–control analysis, which included the 3 strongest confounders as additional matching factors, yielded similar results as the primary analysis (adjusted OR, 0.96 [CI, 0.91 to 1.02]). Limitations: Adherence to PPI prescription was assumed to be 100%. No radiographic evidence was available to corroborate a diagnosis of CAP. Conclusion: Proton-pump inhibitor therapy started within the past 30 days was associated with an increased risk for CAP, whereas longer-term current use was not.