Impact of Respiratory and Cardiovascular Drug Exposure on Lung Function Trajectories

Abstract

Rationale: Research suggests that respiratory and cardiovascular drugs can ameliorate the rate of lung function decline. Objectives: To investigate the impact of respiratory and cardiovascular pharmacotherapy on lung function trajectories in the general population. Methods: Repeated spirometry was performed in the Rotterdam Study, a population-based cohort of adults aged >45 years. Exposure to long-acting b2-agonists (LABAs), long-acting muscarinic antagonists, inhaled corticosteroids (ICS), cardioselective b-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and statins was quantified from pharmacy records to account for therapy adherence. Propensity score matching and multinomial logistic regression were performed to model medication effects on lung function trajectories, which were previously identified on the basis of forced expiratory volume in 1 second and forced vital capacity patterns. Models were also stratified by genetic variation in each drug target. Results: Among 3,783 individuals, 2,974 (78.6%) were classified as normal lung function decliners, 432 (11.4%) as rapid decliners, and 377 (10.0%) as improvers. Exposure to LABA (odds ratio [OR], 1.09 [95% confidence interval (CI), 1.03–1.16] per 10% increase in exposure), ICS (OR, 1.08 [95% CI, 1.02–1.14]), and statins (OR, 1.04 [95% CI, 1.02–1.06]) significantly increased the odds of being an improver compared with a normal decliner. b1-Blocker use was associated with higher odds of being a rapid decliner (OR, 1.04 [95% CI, 1.00–1.09]), which was driven by incident users. Pharmacogenetic analysis suggests that the effects of LABA, ICS, and b1-blockers are dependent on genetic variation in their drug targets. Conclusions: Our study suggests that LABA, ICS, and statins may favorably modulate lung function trajectories in adults, whereas initiation of b1-blockers was associated with rapid lung function decline.