The effect of different inhaled corticosteroid and long-acting bronchodilator combinations on the airway microbiome in patients with severe COPD: a randomised trial (MUSIC).

Inhaled corticosteroid (ICS) treatment has been reported to alter the microbiome through modulating host defence.

吸入性皮质类固醇（ICS）治疗已被报道通过调节宿主防御来改变微生物群。

How ICS alters the microbiome and whether effects are equal between different ICS preparations is debated.

ICS如何改变微生物群以及不同ICS制剂的效果是否相同，这一点存在争议。

The aim of the MUSIC trial was to investigate whether commonly used ICS therapies have different effects on the airway microbiome in COPD.

MUSIC试验的目的是调查常用的ICS疗法是否对COPD患者的气道微生物群有不同的影响。

Methods

This was a multicentre randomised controlled trial. After a 4-week washout period during which they withdrew from ICS, patients with COPD (forced expiratory volume in 1 s <50% predicted at baseline and/or a history of two or more exacerbations per year) were randomised to 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).

这是一项多中心随机对照试验。在为期4周的洗脱期后，患者停止使用ICS，患有COPD（基线时第一秒用力呼气容积<50%预测值和/或每年有两次或更多次加重病史）的患者被随机分配到四种治疗之一（布地奈德/福莫特罗400/12微克（BF400）、氟替卡松/沙美特罗500/50微克（FS500）、氟替卡松/沙美特罗250/50微克（FS250）或阿立哌唑/福莫特罗340/12微克，每日两次）。

Patients were followed-up for 3 months with monthly induced sputum, oropharyngeal and nasopharyngeal swabs for bacterial load and 16S rRNA sequencing to characterise the microbiome.

患者被随访3个月，每月进行诱导痰液、口咽和鼻咽拭子细菌负荷检测以及16S rRNA测序以表征微生物群。

Inflammatory markers were measured in sputum and blood.

在痰液和血液中测量了炎症标志物。

The primary outcome was bacterial load in oropharyngeal swabs comparing BF400 versus FS500, with sputum bacterial load the key secondary end-point.

主要结果是比较BF400与FS500在口咽拭子中的细菌负荷，其中痰液细菌负荷是关键的次要终点。

Results

122 participants started the washout period.

122名参与者开始了洗脱期。

ICS withdrawal was poorly tolerated; 61 participants withdrew before randomisation with 45 experiencing an exacerbation. 61 patients were randomised.

ICS停药耐受性差；61名参与者在随机分组前退出，其中45人经历了加重。61名患者被随机分组。

No statistically significant differences were observed for the primary comparison of BF400 versus FS500 in oropharyngeal bacterial load.

在口咽部细菌负荷的主要比较中，BF400与FS500之间未观察到统计学上的显著差异。

There was, however, a significant increase in sputum bacterial load with FS500 compared to BF400 by month 3.

然而，与BF400相比，FS500在第3个月时痰液细菌负荷显著增加。

This difference was not seen with FS250.

使用FS250时未观察到这种差异。

No significant differences in microbiome α-diversity were observed over time.

随时间观察到的微生物群落α多样性没有显著差异。

Adverse events were similar between the groups.

两组之间的不良事件相似。

Conclusions

FS500 increased sputum but not upper airway bacterial loads.

FS500增加了痰液量，但并未增加上呼吸道的细菌负荷。

ICS withdrawal was poorly tolerated in severe COPD.

在重度COPD患者中，吸入性糖皮质激素的停用耐受性较差。