Anti-inflammatory effects of tiotropium in COPD: a randomised double-blind trial

Lisa H van Smoorenburg, Tatiana Karp, Benedikt Ditz, Wouter H van Geffen, Victor Guryev, Ali Almusa, Loes Kistemaker, Reinoud Gosens, Maarten van den Berge, Huib A M Kerstjens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

BACKGROUND: COPD is a major global health issue characterised 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.

METHODS: We conducted the prospective, double-blind, randomised controlled ANTIOFLAM trial. Patients with COPD Global Initiative for Chronic Obstructive Lung Disease stage II or worse, aged ≥40 years and a smoking history of ≥10 pack-years were included. After a 4-week washout period of inhaled corticosteroids and anticholinergics, participants were randomised to 6 weeks of treatment with placebo or tiotropium (soft mist inhaler, 5 µg daily). Our primary end-point was a decrease of sputum interleukin (IL)-6 and IL-8 levels in the tiotropium group when compared to the placebo group.

RESULTS: We evaluated samples of 33 participants (n=17 placebo and n=16 tiotropium). Changes in sputum proteins IL-6 and IL-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 IL-6 and IL-8.

CONCLUSION: We 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.

Original languageEnglish
Article number00735-2024
Number of pages9
JournalERJ Open Research
Volume11
Issue number2
DOIs
Publication statusPublished - Mar-2025

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