A MULTICENTRE randomised controlled trial has investigated how different inhaled corticosteroids (ICS) affect the airway microbiome in patients with severe chronic obstructive pulmonary disease (COPD).
Inhaled Corticosteroid Withdrawal
The MUSIC trial enrolled patients with forced expiratory volume in 1 second (FEV₁) below 50% predicted and/or a history of two or more exacerbations per year. Participants underwent a 4-week ICS washout period, intended to remove residual effects of previous therapy. During this period, ICS withdrawal proved poorly tolerated: 61 of 122 patients withdrew before randomisation, and 45 experienced exacerbations, highlighting the clinical challenges of stopping ICS in severe COPD.
Following washout, 61 patients were randomised to receive 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. Over 3 months, participants underwent monthly induced sputum collection and oropharyngeal and nasopharyngeal swabs for bacterial load assessment and 16S rRNA sequencing. Inflammatory markers were also measured in sputum and blood to monitor host immune response. The study’s primary outcome was bacterial load in oropharyngeal swabs comparing BF400 versus FS500, with sputum bacterial load as a key secondary endpoint.
Effects of Inhaled Corticosteroids on Airway Microbiome
The primary comparison of BF400 versus FS500 revealed no significant difference in oropharyngeal bacterial load. However, by Month 3, FS500-treated patients exhibited a significant increase in sputum bacterial load compared to BF400, whereas FS250 did not show this effect. No notable changes in microbiome α-diversity were observed over time, and adverse events were similar across all groups. The study indicates that high-dose fluticasone selectively alters lower airway bacterial burden without affecting upper airway microbial communities.
These results emphasise the importance of considering microbiome effects when prescribing ICS, especially in patients with severe COPD, while highlighting the clinical challenge of ICS withdrawal, given the high rate of exacerbations during washout. Physicians should weigh the potential microbiome impact of high-dose fluticasone alongside its therapeutic benefits, particularly for patients at risk of bacterial colonisation or recurrent exacerbations.
Reference
Richardson H et al. The effect of different inhaled corticosteroid and long-acting bronchodilator combinations on the airway microbiome in patients with severe COPD: a randomised trial (MUSIC). Eur Respir J. 2025;66(4):2500287.
