纵向多中心 COPD 队列中的微生物负担和病毒加重。
Microbial burden and viral exacerbations in a longitudinal multicenter COPD cohort.
机构信息
Clinical Pharmacology & Safety Sciences, Biopharmaceuticals R&D, AstraZeneca, South San Francisco, USA.
Respiratory Inflammation and Autoimmunity, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, USA.
出版信息
Respir Res. 2020 Mar 30;21(1):77. doi: 10.1186/s12931-020-01340-0.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by frequent exacerbation phenotypes independent of disease stage. Increasing evidence shows that the microbiota plays a role in disease progression and severity, but long-term and international multicenter assessment of the variations in viral and bacterial communities as drivers of exacerbations are lacking.
METHODS
Two-hundred severe COPD patients from Europe and North America were followed longitudinally for 3 years. We performed nucleic acid detection for 20 respiratory viruses and 16S ribosomal RNA gene sequencing to evaluate the bacterial microbiota in 1179 sputum samples collected at stable, acute exacerbation and follow-up visits.
RESULTS
Similar viral and bacterial taxa were found in patients from the USA compared to Bulgaria and Czech Republic but their microbiome diversity was significantly different (P < 0.001) and did not impact exacerbation rates. Virus infection was strongly associated with exacerbation events (P < 5E-20). Human rhinovirus (13.1%), coronavirus (5.1%) and influenza virus (3.6%) constitute the top viral pathogens in triggering exacerbation. Moraxella and Haemophilus were 5-fold and 1.6-fold more likely to be the dominating microbiota during an exacerbation event. Presence of Proteobacteria such as Pseudomonas or Staphylococcus amongst others, were associated with exacerbation events (OR > 0.17; P < 0.02) but more strongly associated with exacerbation frequency (OR > 0.39; P < 4E-10), as confirmed by longitudinal variations and biotyping of the bacterial microbiota, and suggesting a role of the microbiota in sensitizing the lung.
CONCLUSIONS
This study highlights bacterial taxa in lung sensitization and viral triggers in COPD exacerbations. It provides a global overview of the diverse targets for drug development and explores new microbiome analysis methods to guide future patient management applications.
背景
慢性阻塞性肺疾病（COPD）是一种异质性疾病，其特征是频繁发生与疾病阶段无关的加重表型。越来越多的证据表明，微生物组在疾病进展和严重程度中发挥作用，但缺乏对病毒和细菌群落作为加重驱动因素的长期和国际多中心评估。
方法
200 名来自欧洲和北美的严重 COPD 患者进行了为期 3 年的纵向随访。我们对 1179 份稳定期、急性加重期和随访期采集的痰液样本进行了 20 种呼吸道病毒的核酸检测和 16S 核糖体 RNA 基因测序，以评估细菌微生物群。
结果
与保加利亚和捷克共和国的患者相比，来自美国的患者具有相似的病毒和细菌分类群，但它们的微生物多样性有显著差异（P<0.001），且不影响加重率。病毒感染与加重事件密切相关（P<5E-20）。人鼻病毒（13.1%）、冠状病毒（5.1%）和流感病毒（3.6%）是引发加重的主要病毒病原体。在加重期间，莫拉菌和嗜血杆菌分别有 5 倍和 1.6 倍的可能性成为主要的微生物群。在其他细菌中，变形菌门如铜绿假单胞菌或金黄色葡萄球菌等的存在与加重事件相关（OR>0.17；P<0.02），但与加重频率的相关性更强（OR>0.39；P<4E-10），这通过细菌微生物群的纵向变化和生物型分析得到证实，并提示微生物群在使肺部致敏方面发挥作用。
结论
本研究强调了细菌群在 COPD 加重中的致敏作用和病毒触发因素。它提供了一个全球范围内对药物开发多样化目标的概述，并探索了新的微生物组分析方法，以指导未来的患者管理应用。
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