吸入性皮质类固醇选择性改变慢性阻塞性肺疾病患者小气道中的微生物群和宿主转录组。
Inhaled Corticosteroids Selectively Alter the Microbiome and Host Transcriptome in the Small Airways of Patients with Chronic Obstructive Pulmonary Disease.
作者信息
Yip William, Li Xuan, Koelwyn Graeme J, Milne Stephen, Leitao Filho Fernando Sergio, Yang Chen Xi, Hernández Cordero Ana I, Yang Julia, Yang Cheng Wei Tony, Shaipanich Tawimas, van Eeden Stephan F, Leung Janice M, Lam Stephen, McNagny Kelly M, Sin Don D
机构信息
Centre for Heart Lung Innovation, The University of British Columbia, St. Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada.
School of Biomedical Engineering, Faculties of Medicine and Applied Sciences, The University of British Columbia, St. Paul's Hospital, Vancouver, BC V6T 1Z3, Canada.
出版信息
Biomedicines. 2022 May 11;10(5):1110. doi: 10.3390/biomedicines10051110.
BACKGROUND
Patients with chronic obstructive pulmonary disease (COPD) are commonly treated with inhaled corticosteroid/long-acting ß2-agonist combination therapy. While previous studies have investigated the host-microbiome interactions in COPD, the effects of specific steroid formulations on this complex cross-talk remain obscure.
METHODS
We collected and evaluated data from the Study to Investigate the Differential Effects of Inhaled Symbicort and Advair on Lung Microbiota (DISARM), a randomized controlled trial. Bronchoscopy was performed on COPD patients before and after treatment with salmeterol/fluticasone, formoterol/budesonide or formoterol-only. Bronchial brush samples were processed for microbial 16S rRNA gene sequencing and host mRNA sequencing. Longitudinal changes in the microbiome at a community, phylum and genus level were correlated with changes in host gene expression using a Spearman's rank correlation test.
FINDINGS
In COPD patients treated with salmeterol/fluticasone, the expression levels of 676 host genes were significantly correlated to changes in the alpha diversity of the small airways. At a genus level, the expression levels of 122 host genes were significantly related to changes in the relative abundance of . Gene enrichment analyses revealed the enrichment of pathways and biological processes related to innate and adaptive immunity and inflammation. None of these changes were evident in patients treated with formoterol/budesonide or formoterol alone.
INTERPRETATION
Changes in the microbiome following salmeterol/fluticasone treatment are related to alterations in the host transcriptome in the small airways of patients with COPD. These data may provide insights into why some COPD patients treated with inhaled corticosteroids may be at an increased risk for airway infection, including pneumonia.
FUNDING
The Canadian Institute of Health Research, the British Columbia Lung Association, and an investigator-initiated grant from AstraZeneca.
背景
慢性阻塞性肺疾病（COPD）患者通常接受吸入性糖皮质激素/长效β2受体激动剂联合治疗。虽然先前的研究已经调查了COPD中宿主-微生物群的相互作用，但特定类固醇制剂对这种复杂相互作用的影响仍不清楚。
方法
我们收集并评估了一项随机对照试验——吸入性信必可都保和舒利迭对肺部微生物群差异影响的研究（DISARM）的数据。对COPD患者在使用沙美特罗/氟替卡松、福莫特罗/布地奈德或仅使用福莫特罗治疗前后进行支气管镜检查。对支气管刷检样本进行微生物16S rRNA基因测序和宿主mRNA测序。使用Spearman秩相关检验将微生物群在群落、门和属水平的纵向变化与宿主基因表达的变化进行关联。
结果
在接受沙美特罗/氟替卡松治疗的COPD患者中，676个宿主基因的表达水平与小气道α多样性的变化显著相关。在属水平上，122个宿主基因的表达水平与某一属相对丰度的变化显著相关。基因富集分析显示与先天和适应性免疫及炎症相关的通路和生物学过程富集。在接受福莫特罗/布地奈德或仅接受福莫特罗治疗的患者中，这些变化均不明显。
解读
沙美特罗/氟替卡松治疗后微生物群的变化与COPD患者小气道中宿主转录组的改变有关。这些数据可能有助于解释为什么一些接受吸入性糖皮质激素治疗的COPD患者气道感染（包括肺炎）风险增加。
资助
加拿大卫生研究院、不列颠哥伦比亚省肺脏协会以及阿斯利康发起的一项研究者资助项目。
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