Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2025 Oct 7;66(4):2500287.
doi: 10.1183/13993003.00287-2025. Print 2025 Oct.

The effect of different inhaled corticosteroid and long-acting bronchodilator combinations on the airway microbiome in patients with severe COPD: a randomised trial (MUSIC)

Hollian Richardson  1 , Daniela Alferes De Lima Headley  1 , Clare Clarke  1 , Abirami Veluchamy  2 , Petra Rauchhaus  3 , Jennifer Pollock  1 , Thomas Pembridge  1 , Diane Cassidy  1 , Holly R Keir  1 , Simon Finch  1 , Furrah Hussain  3 , Margaret Band  3 , Andrew Smith  4 , Manish Patel  4 , Mohammad Paracha  5 , Gourab Choudhury  6 , Devesh Dhasmana  7   8 , Rekha Chaudhuri  9 , Philip M Short  10 , James D Chalmers  11
Affiliations
Randomized Controlled Trial

The effect of different inhaled corticosteroid and long-acting bronchodilator combinations on the airway microbiome in patients with severe COPD: a randomised trial (MUSIC)

Hollian Richardson et al. Eur Respir J. .

Abstract

Background: The microbiome is associated with exacerbation risk, quality of life and mortality in COPD. Inhaled corticosteroid (ICS) treatment has been reported to alter the microbiome through modulating host defence. How ICS alters the microbiome and whether effects are equal between different ICS preparations is debated. The aim of the MUSIC trial was to investigate whether commonly used ICS therapies have different effects on the airway microbiome in COPD.

Methods: This was a multicentre randomised controlled trial. After a 4-week washout period during which they withdrew from ICS, patients with COPD (forced expiratory volume in 1 s <50% predicted at baseline and/or a history of two or more exacerbations per year) were randomised to one of four treatments (budesonide/formoterol 400/12 µg (BF400), fluticasone/salmeterol 500/50 µg (FS500), fluticasone/salmeterol 250/50 µg (FS250) or aclidinium/formoterol 340/12 µg, twice daily). Patients were followed-up for 3 months with monthly induced sputum, oropharyngeal and nasopharyngeal swabs for bacterial load and 16S rRNA sequencing to characterise the microbiome. Inflammatory markers were measured in sputum and blood. The primary outcome was bacterial load in oropharyngeal swabs comparing BF400 versus FS500, with sputum bacterial load the key secondary end-point.

Results: 122 participants started the washout period. ICS withdrawal was poorly tolerated; 61 participants withdrew before randomisation with 45 experiencing an exacerbation. 61 patients were randomised. No statistically significant differences were observed for the primary comparison of BF400 versus FS500 in oropharyngeal bacterial load. There was, however, a significant increase in sputum bacterial load with FS500 compared to BF400 by month 3. This difference was not seen with FS250. No significant differences in microbiome α-diversity were observed over time. Adverse events were similar between the groups.

Conclusion: FS500 increased sputum but not upper airway bacterial loads. ICS withdrawal was poorly tolerated in severe COPD.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: H.R. Keir reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Insmed Incorporated. A. Smith reports grants from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Oncimmune and Roche, and consultancy fees from AstraZeneca, GSK and Chiesi. M. Patel reports support for attending meetings from Chiesi. M. Paracha reports consultancy fees from AstraZeneca and GSK, and participation on a data safety monitoring board or advisory board with AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Oncimmune and Roche. G. Choudhury reports grants from AstraZeneca and GSK, payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK, AstraZeneca and Chiesi, and participation on a data safety monitoring board or advisory board with AstraZeneca. R. Chaudhuri reports grants from AstraZeneca, payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK, AstraZeneca, Teva, Chiesi and Sanofi, participation on a data safety monitoring board or advisory board with GSK, AstraZeneca and Celltrion, and support for attending meetings from Sanofi and GSK. P.M. Short reports payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, and support for attending meetings from Chiesi. J.D. Chalmers is Chief Editor of the European Respiratory Journal, and reports grants from AstraZeneca, Genentech, Gilead Sciences, GSK, Insmed, Grifols, Novartis and Boehringer Ingelheim, and consultancy fees from AstraZeneca, Chiesi, GSK, Insmed, Grifols, Novartis, Boehringer Ingelheim, Pfizer, Janssen, Antabio and Zambon. The remaining authors have no potential conflicts of interest to disclose.

Comment in

Publication types

MeSH terms

LinkOut - more resources