Anti-inflammatory effects of tiotropium in copd: a randomized double-blind trial

Abstract

IntroductionChronic Obstructive Pulmonary Disease (COPD) is a major global health issue characterized by respiratory symptoms and exacerbations, significantly impacting mortality and quality of life. Muscarinic antagonists are known to prevent exacerbations, possibly by mitigating airway inflammation. This study evaluated the anti-inflammatory effects of tiotropium in patients with COPD by examining inflammatory protein profiles in sputum and blood, and genome-wide expression in sputum.MethodsWe conducted the prospective, double-blind, randomized-controlled ANTIOFLAM trial. Patients with COPD GOLD II and worse, aged≥40 years and with≥10 smoking pack years were included. After a 4-week wash-out period of inhaled corticosteroids (ICS) and anticholinergics, participants were randomized to 6 weeks of treatment with placebo or tiotropium (soft mist inhaler, 5 µg daily). Our primary endpoint was a decrease of sputum interleukin-6 and interleukin-8 levels in the tiotropium group when compared to the placebo group.ResultsWe evaluated samples of 33 participants (n=17 placebo and n=16 tiotropium). Changes in sputum proteins interleukin-6 and interleukin-8 were significantly higher after treatment with tiotropium when compared to placebo (p<0.05). Differential expression analysis did not reveal gene expression differences including interleukin-6 and −8.ConclusionWe did not find tiotropium to have anti-inflammatory effects in sputum or blood of patients with COPD. In contrast, we found 6 weeks of treatment with tiotropium to increase the concentration of almost all tested sputum inflammatory proteins when compared to placebo, while RNA expression levels did not change.