Effects of inhaled corticosteroid/long-acting β2-agonist combination on the airway microbiome of patients with chronic obstructive pulmonary disease: A randomized controlled clinical trial (DISARM)

초록

Rationale: Inhaled corticosteroids (ICS) are commonly prescribed with long-acting b2-agonists (LABA) in chronic obstructive pulmonary disease (COPD). To date, the effects of ICS therapy on the airway microbiome in COPD are unknown. Objectives: To determine the effects of ICS/LABA on the airway microbiome of patients with COPD. Methods: Clinically stable patients with COPD were enrolled into a 4-week run-in period during which ICS was discontinued and all participants were placed on formoterol (Form) 12 mg twice daily (BID). The participants were then randomized to budesonide/ formoterol (Bud 1 Form; 400/12 mg BID), fluticasone/salmeterol (Flu 1 Salm; 250/50 mg BID), or formoterol only (12 mg BID) for 12 weeks. Participants underwent bronchoscopy before and after the 12-week treatment period. The primary endpoint was the comparison of changes in the airway microbiome over the trial period between the ICS/LABA and LABA-only groups. Measurements and Main Results: Sixty-three participants underwent randomization: Bud 1 Form (n = 20), Flu 1 Salm (n = 22), and Form (n = 21) groups; 56 subjects completed all visits. After the treatment period, changes in a-diversity were significantly different across groups, especially between Flu 1 Salm and Form groups (Drichness: P = 0.02; DShannon index: P = 0.03). Longitudinal differential abundance analyses revealed more pronounced microbial shifts from baseline in the fluticasone (vs. budesonide or formoterol only) group. Conclusions: Fluticasone-based ICS/LABA therapy modifies the airway microbiome in COPD, leading to a relative reduction in a-diversity and a greater number of bacterial taxa changes. These data may have implications in patients who develop pneumonia on ICS. Clinical trial registered with www.clinicaltrials.gov (NCT02833480).

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