Department of Gastroenterology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Elife. 2024 Jul 16;13:RP94973. doi: 10.7554/eLife.94973.
Adverse effects of proton pump inhibitors (PPIs) have raised wide concerns. The association of PPIs with influenza is unexplored, while that with pneumonia or COVID-19 remains controversial. Our study aims to evaluate whether PPI use increases the risks of these respiratory infections.
The current study included 160,923 eligible participants at baseline who completed questionnaires on medication use, which included PPI or histamine-2 receptor antagonist (H2RA), from the UK Biobank. Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).
Comparisons with H2RA users were tested. PPI use was associated with increased risks of developing influenza (HR 1.32, 95% CI 1.12-1.56) and pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26-1.59). In contrast, the risk of COVID-19 infection was not significant with regular PPI use (HR 1.08, 95% CI 0.99-1.17), while the risks of severe COVID-19 (HR 1.19. 95% CI 1.11-1.27) and mortality (HR 1.37. 95% CI 1.29-1.46) were increased. However, when compared with H2RA users, PPI users were associated with a higher risk of influenza (HR 1.74, 95% CI 1.19-2.54), but the risks with pneumonia or COVID-19-related outcomes were not evident.
PPI users are associated with increased risks of influenza, pneumonia, as well as COVID-19 severity and mortality compared to non-users, while the effects on pneumonia or COVID-19-related outcomes under PPI use were attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive evaluation is required.
This work is supported by the National Natural Science Foundation of China (82171698, 82170561, 81300279, 81741067, 82100238), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), the Guangdong Basic and Applied Basic Research Foundation (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Program of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital (DFJH201923, DFJH201803, KJ012019099, KJ012021143, KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL).
质子泵抑制剂 (PPI) 的不良反应引起了广泛关注。PPIs 与流感的关联尚未得到探索，而与肺炎或 COVID-19 的关联仍存在争议。我们的研究旨在评估 PPI 使用是否会增加这些呼吸道感染的风险。
本研究共纳入了 160923 名基线时完成了药物使用调查问卷的合格参与者，该问卷包括来自英国生物库的 PPI 或组胺 2 受体拮抗剂 (H2RA)。使用 Cox 比例风险回归和倾向评分匹配分析来估计风险比 (HR) 和 95%置信区间 (CI)。
与 H2RA 使用者进行了比较。PPI 使用与流感（HR 1.32，95%CI 1.12-1.56）和肺炎（危险比 [HR] 1.42，95%置信区间 [CI] 1.26-1.59）的发病风险增加相关。相比之下，定期使用 PPI 与 COVID-19 感染风险无显著关联（HR 1.08，95%CI 0.99-1.17），但 COVID-19 重症（HR 1.19，95%CI 1.11-1.27）和死亡率（HR 1.37，95%CI 1.29-1.46）的风险增加。然而，与 H2RA 使用者相比，PPI 使用者患流感的风险更高（HR 1.74，95%CI 1.19-2.54），但肺炎或 COVID-19 相关结局的风险并不明显。
与非使用者相比，PPI 使用者与流感、肺炎以及 COVID-19 严重程度和死亡率的风险增加相关，而与 H2RA 相比，PPI 使用者在肺炎或 COVID-19 相关结局方面的风险减弱。需要根据综合评估来合理使用 PPI。
本工作得到了国家自然科学基金（82171698、82170561、81300279、81741067、82100238）、中国高端外国专家引进计划（G2022030047L）、广东省杰出青年自然科学基金（2021B1515020003）、广东省基础与应用基础研究基金（2022A1515012081）、广东省科技厅外国杰出人才计划（KD0120220129）、广东省人民医院引进人才攀登项目和高水平医院建设项目（DFJH201923、DFJH201803、KJ012019099、KJ012021143、KY012021183）和 VA 临床功绩和 ASGE 临床研究基金的部分支持。
