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 associated 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 not pneumonia or COVID-19-related outcomes. In conclusion, 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.

中文翻译：

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质子泵抑制剂与肺炎、流感和 COVID-19 易感性的关联：来自大规模人群队列研究的证据

质子泵抑制剂（PPI）的不良反应引起了广泛关注。PPI 与流感的关联尚未被探索，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 的使用是否会增加这些呼吸道感染的风险。目前的研究包括 160,923 名符合基线条件的参与者，他们完成了来自英国生物银行的药物使用调查问卷，其中包括 PPI 或组胺 2 受体拮抗剂 (H2RA)。Cox 比例风险回归和倾向评分匹配分析用于估计风险比 (HR) 和 95% 置信区间 (CI)。与 H2RA 用户进行了比较测试。PPI的使用与患流感（HR 1.32，95%CI 1.12-1.56）和肺炎（风险比[HR] 1.42，95%置信区间[CI] 1.26-1.59）的风险增加相关。相比之下，COVID-19 感染的风险与定期使用 PPI 无关（HR 1.08，95%CI 0.99-1.17），而重症 COVID-19 的风险（HR 1.19。95%CI 1.11-1.27）和死亡（HR 1.37。95%CI 1.29-1.46）增加。然而，与 H2RA 用户相比，PPI 用户与更高的流感风险相关（HR 1.74，95%CI 1.19-2.54），但与肺炎或 COVID-19 相关结果无关。总之，与非用户相比，PPI 用户与流感、肺炎以及 COVID-19 严重程度和死亡率的风险增加相关，而与非用户相比，使用 PPI 对肺炎或 COVID-19 相关结果的影响减弱H2RA 的使用。需要在综合评估的基础上合理使用 PPI。