Effects of Inhaled Corticosteroid/Long-Acting beta(2)-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 beta(2)-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 mu g twice daily (BID). The participants were then randomized to budesonide/formoterol (Bud+Form; 400/12 mu g BID), fluticasone/salmeterol (Flu+Salm; 250/50 mu g 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 + Form (n = 20), Flu + Salm (n = 22), and Form (n = 21) groups; 56 subjects completed all visits. After the treatment period, changes in alpha-diversity were significantly different across groups, especially between Flu + Salm and Form groups (Delta richness: P = 0.02; Delta Shannon 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 alpha-diversity and a greater number of bacterial taxa changes. These data may have implications in patients who develop pneumonia on ICS.

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