Rationale: Inhaled corticosteroids (ICS) are commonly prescribed with long-acting β2-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 μg twice daily (BID). The participants were then randomized to budesonide/formoterol (Bud + Form; 400/12 μg BID), fluticasone/salmeterol (Flu + Salm; 250/50 μg BID), or formoterol only (12 μg 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 α-diversity were significantly different across groups, especially between Flu + Salm and Form groups (Δrichness: P = 0.02; ΔShannon 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 α-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).

中文翻译：

---

吸入皮质类固醇/长效 β2-激动剂组合对慢性阻塞性肺疾病患者气道微生物组的影响：一项随机对照临床试验 (DISARM)。

原理：吸入性皮质类固醇 (ICS) 通常与长效 β2-激动剂 (LABA) 一起用于治疗慢性阻塞性肺疾病 (COPD)。迄今为止，ICS 疗法对 COPD 气道微生物群的影响尚不清楚。目的：确定 ICS/LABA 对 COPD 患者气道微生物组的影响。方法：临床稳定的 COPD 患者被纳入 4 周的磨合期，在此期间停止 ICS，所有参与者每天服用 12 μg 福莫特罗 (Form) 两次 (BID)。然后将参与者随机分配至布地奈德/福莫特罗（Bud + Form；400/12 μg BID）、氟替卡松/沙美特罗（Flu + Salm；250/50 μg BID）或仅福莫特罗（12 μg BID）组，持续 12 周。参与者在 12 周治疗期之前和之后接受了支气管镜检查。主要终点是 ICS/LABA 组和仅 LABA 组在试验期间气道微生物组变化的比较。测量和主要结果：63 名参与者接受了随机化：Bud + Form (n = 20)、Flu + Salm (n = 22) 和 Form (n = 21) 组；56 名受试者完成了所有访问。治疗期后，α-多样性的变化在各组之间显着不同，尤其是在 Flu + Salm 和 Form 组之间（Δrichness：P = 0.02；ΔShannon 指数：P = 0.03）。纵向差异丰度分析显示，氟替卡松（与仅布地奈德或福莫特罗相比）组的微生物从基线发生了更明显的变化。结论：基于氟替卡松的 ICS/LABA 治疗改变了 COPD 的气道微生物组，导致 α 多样性相对减少和更多的细菌分类群变化。这些数据可能对因 ICS 出现肺炎的患者产生影响。在 www.clinicaltrials.gov 注册的临床试验 (NCT02833480)。