Exacerbation Risk by Chronic Proton Pump Inhibitor Use in Obstructive Lung Diseases.

Abstract

Previous studies have shown inconsistent results regarding the use of proton pump inhibitors (PPIs) and the risk on exacerbations in patients with chronic obstructive airway diseases (COADs). Is long-term PPI use associated with exacerbation risk? Using Belgian nationwide claims-based data of adult patients receiving long-term medication for COADs between 2017 and 2022, we investigated the association between PPI use and exacerbation risk using multivariable Cox models. Based on defined daily doses (DDDs) dispensed during the prior year, dose-dependent associations were assessed by inverse probability of treatment weighted Cox regression models. Among 932,135 included patients with COADs, 416,087 patients (44.6%) were PPI users, of whom 57,540 patients (13.8%) received 1-28 DDDs of PPIs, 128,017 patients (30.8%) received 29-180 DDDs, 127,981 patients (30.8%) received 181-365 DDDs, and 102,549 patients (24.6%) received > 365 DDDs in the previous year. Beyond age, sex, smoking, socioeconomic status, exacerbation history, short-acting bronchodilator use, frailty, and comorbidities, PPI use was associated with an increased risk of exacerbations (adjusted hazard ratio [HR], 1.18 [95% CI, 1.17-1.19]). Moreover, compared with patients who did not use PPIs, the risk of exacerbations increased with cumulative DDDs (≤ 28 DDDs: HR, 1.09 [95% CI, 1.07-1.10]; ≤ 180 DDDs: HR, 1.15 [95% CI, 1.14-1.16]; ≤ 365 DDDs: HR, 1.19 [95% CI, 1.18-1.20]; and > 365 DDDs: HR, 1.25 [95% CI, 1.23-1.26]). Sensitivity analyses indicated that the association with exacerbation risk was most pronounced in patients younger than 50 years, who were not frail, and with theoretically increased PPI plasma concentrations, and was not significant when used short-term in patients with gastroesophageal reflux disease. Cumulative PPI use in patients with obstructive lung diseases was associated with an increase in exacerbation risk. This highlights the need to consider PPI use carefully in clinical respiratory practice.