Association between calcium channel blocker use and the risk of interstitial lung disease and idiopathic pulmonary fibrosis: A longitudinal cohort study

Introduction: Ca2+ signaling in fibroblasts would be one of the important mediators of lung fibrosis. This study investigated the relationship between calcium channel blocker usage and the risk of developing interstitial lung disease and idiopathic pulmonary fibrosis. Material and methods: This cohort study used data from the Korean National Health Screening Cohort spanned from January 1, 2004, to December 31, 2015. The study included 394,142 participants. CCB usage, as a time- dependent variable assessed every two years, was categorized by medication status (ever-users and never- users) and further divided into five groups based on cumulative defined daily dose: <182.5, 182.5-365.0, 365.0-547.5, and >= 547.5. Incidence rates of ILD and IPF among CCB users compared to never-users, analyzed using time-dependent Cox regression models. Results: The incidence rates were 27.7 per 100,000 person-years for ILD and 15.0 per 100,000 person-years for IPF among never-users, compared to 19.5 per 100,000 person-years for ILD and 13.9 per 100,000 person-years for IPF among ever-users. The adjusted hazard ratios (aHRs) were 0.68 [95 % confidence interval (CI), 0.55-0.83] for ILD and 0.69 (95 % CI, 0.54-0.88) for IPF. Increasing categories of CCB usage were significantly associated with a lower risk of ILD [aHRs: 1.23 (95 % CI, 0.97-1.56), 1.20 (0.85-1.71), 0.49 (0.30-0.81), and 0.27(0.19-0.39)] and IPF [aHRs: 1.21 (95 % confidence interval, 0.89-1.64), 1.45 (0.96-2.20), 0.83 (0.52-1.33), and 0.25 (0.16-0.38)], compared to never-users. Conclusions: This study found that individuals using CCBs had a significantly lower risk of interstitial lung disease and idiopathic pulmonary fibrosis compared to never-users in a dose-response manner.