The impact of proton pump inhibitor exposure on pneumonia: an updated meta-analysis based on randomized controlled trials

Abstract

Background: The association between proton pump inhibitor (PPI) use and pneumonia risk remains inconclusive. This meta-analysis explores the impact of PPI use on the risk of pneumonia. Methods: We systematically searched for relevant randomized controlled trials in PubMed, Web of Science, EMBASE and Cochrane Library from January 2000 to March 2025. Relative ratio and 95% confidence interval were calculated to quantify the association between proton pump inhibitor use and pneumonia incidence. Results: The analysis included 20 RCTs involving 29,100 participants. Compared to the non-PPI group, the PPI-exposed group showed a higher incidence of pneumonia in the general population (RR = 1.10, 95% CI: 0.99-1.21, p = 0.07) and for hospital-acquired pneumonia (HAP) (RR = 1.12, 95% CI: 1.00-1.26, p = 0.06), although the differences were not statistically significant. A higher incidence of pneumonia was observed in the intervention group among the Asian population (RR = 1.30, p = 0.02), particularly in Iran (RR = 2.73, p < 0.001) and among Asian users of pantoprazole (RR = 1.94, p = 0.05). No significant differences in pneumonia incidence were found between groups among participants from Europe (RR = 1.04, p = 0.67) or America (RR = 1.02, p = 0.95), for ventilator-associated pneumonia (VAP) (RR = 1.17, p = 0.11), or among participants in intensive care units (ICUs) (RR = 1.05, p = 0.29) or out of ICUs (RR = 1.28, p = 0.14). Conclusion: The use of PPI might increase the risk of pneumonia in general population, especially among Asians (in Iran and in the Asian users of pantoprazole), HAP. Systematic Review Registration: Identifier, CRD420251021884.