Investigating the mechanism of inhaled corticosteroids associated pneumonia by longitudinal characterisation of the airway microbiome in patients with severe COPD.

The microbiome affects exacerbation risk, quality of life and mortality in COPD. ICS may affect the microbiome through modulating host defence. How ICS affect the microbiome and whether effects are equal between different ICS preparations is unknown. The aim of this study was to investigate whether commonly used ICS therapies have different effects on the airway microbiome in COPD. After a four-week washout period, patients with COPD (FEV1 less than 50 percent predicted at baseline or a history of 2 or more exacerbations per year) were randomized to one of 4 treatments (budesonide 400 and formoterol 12, fluticasone 500 and salmeterol, fluticasone 250 and salmeterol, or aclidinium and formoterol). Patients were followed-up for 3 months with monthly induced sputum, oropharyngeal and nasopharyngeal swabs for bacterial load and 16S sequencing. Inflammatory markers were measured in sputum and blood. The primary outcome was bacterial load in oropharyngeal swabs, with sputum bacterial load the key secondary endpoint.

微生物组（microbiome）可影响慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease, COPD）患者的急性加重风险、生活质量及死亡率。吸入性糖皮质激素（Inhaled Corticosteroids, ICS）可通过调节宿主防御机制影响微生物组，但目前尚不明确ICS如何作用于微生物组，且不同ICS制剂的作用是否存在差异。本研究旨在探讨临床常用的ICS治疗方案对COPD患者气道微生物组的影响是否存在差异。经过4周洗脱期后，符合入组标准的COPD患者[基线时一秒用力呼气容积（Forced Expiratory Volume in 1 second, FEV1）占预计值百分比＜50%，或每年急性加重病史≥2次]被随机分配至4种治疗方案之一：布地奈德（budesonide）400+福莫特罗（formoterol）12、氟替卡松（fluticasone）500+沙美特罗（salmeterol）、氟替卡松250+沙美特罗，或阿地溴铵（aclidinium）+福莫特罗。随后对患者进行为期3个月的随访，每月采集诱导痰、口咽拭子及鼻咽拭子样本，用于检测细菌载量并开展16S测序（16S sequencing）；同时检测患者痰液与血液中的炎症标志物水平。本研究的主要结局指标为口咽拭子的细菌载量，痰液细菌载量为关键次要结局指标。