ABSTRACT
ObjectiveConcerns have been raised about the widespread use of proton pump inhibitors (PPIs), and current findings linking the regular use of PPIs to respiratory infections remain inconsistent. Our study aims to evaluate whether PPI use increases the risk of pneumonia, influenza, and COVID-19. MethodThe presented study included 160,923 eligible participants from the UK Biobank (mean age 56.5 years, 53% women). Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Effect modifications by stratifications, including indications and CYP2C19 phenotypes were tested. ResultsThe regular use of PPIs was associated with increased risks of developing pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26-1.59) and influenza (HR 1.31, 95% CI 1.11-1.55). However, the risk of COVID-19 infection among regular PPI users was not significantly increased (HR 1.05, 95% CI 0.95-1.16). The burden was more notably observed in patients without indications of PPI use (HR 1.52, 95% CI 1.33-1.73 for pneumonia; HR 1.36, 95% CI 1.12-1.64 for influenza). The risk for pneumonia was higher among the CYP2C19 rapid and ultrarapid metabolizers (HR 1.45, 95% CI 1.22-1.73, P for interaction < 0.001). The propensity score-matching analyses yielded similar trends. ConclusionsThe regular use of PPIs is associated with increased susceptibility to pneumonia and influenza, but not COVID-19 infection. The risks are even higher among recipients without main indications. Our study highlights the appropriate use and de-prescribing of PPIs according to indications and CYP2C19 phenotypes for patients and clinical practitioners. What is already known on this topicO_LIProton pump inhibitors (PPIs) have been extensively used in clinical practice, while emerging studies suggest the adverse effects associated with their long-term use. C_LIO_LIThe linkage between PPIs and respiratory infections has been indicated, whereas controversy remains. C_LI What this study addsO_LIIn the large cohort involving 160,923 individuals, regular use of PPIs was associated with 42% and 31% increased risks of pneumonia and influenza, respectively, but not COVID-19 infection. C_LIO_LIThe burdens were more evident among PPI users without main indications, and CYP2C19 rapid and ultrarapid metabolizers. C_LI How this study might affect research, practice or policyO_LIConsidering the potential risk of respiratory infections, appropriate use following indications and metabolic phenotypes, as well as de-prescribing of PPIs are highlighted. C_LI
