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

Zhu-Jun Wu, Yixuan Wu, Zhiyi Xiang, Yi Qiu, Wangyi Xuan, Shengying Zhang

Frontiers in Pharmacology, 2025

29,100 participants · 6 citations

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…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 29,100 participants or records.

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