SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1713256
The Impact of Proton Pump Inhibitor Exposure on Pneumonia: An Updated Meta-Analysis Based on Randomized Controlled Trials
Provisionally accepted
- 1Ningbo Zhenhai Hospital of Traditional Chinese Medicine, Ningbo, China
- 2Zhejiang Chinese Medical University, Hangzhou, China
- 3Yinzhou No.2 Hospital, Ningbo, China
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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 (RCTs) in PubMed, Web of Science, EMBASE and Cochrane Library from January 2000 to March 2025. Relative ratio (RR) and 95% confidence interval (CI) were calculated to quantify the association between PPI 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.
Keywords: proton pump inhibitor, Pneumonia, Asia, pantoprazole, Hospital-acquired pneumonia, Meta-analysis
Received: 25 Sep 2025; Accepted: 17 Oct 2025.
Copyright: © 2025 Wu, Wu, Xiang, Qiu, Xuan and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shengying Zhang, huaian0612@163.com
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