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. 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. 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. 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.

中文翻译：

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纵向多中心COPD队列中的微生物负荷和病毒恶化。

慢性阻塞性肺疾病（COPD）是一种异质性疾病，其特征在于与疾病阶段无关的频繁加重表型。越来越多的证据表明，微生物群在疾病的进展和严重程度中起着作用，但是缺乏对病毒和细菌群落变异加剧的长期和国际多中心评估。来自欧洲和北美的200名重度COPD患者被纵向随访3年。我们对20种呼吸道病毒进行了核酸检测，并进行了16S核糖体RNA基因测序，以评估在稳定，急性加重和随访中收集的1179份痰标本中的细菌菌群。与保加利亚和捷克共和国相比，在美国患者中发现了相似的病毒和细菌类群，但它们的微生物组多样性差异显着（P <0.001），并且不影响病情加重。病毒感染与急性发作密切相关（P <5E-20）。人鼻病毒（13.1％），冠状病毒（5.1％）和流感病毒（3.6％）是引发急性发作的主要病毒病原体。急性发作期间，莫拉菌和嗜血杆菌是主要微生物群的5倍和1.6倍。诸如假单胞菌或葡萄球菌等变形杆菌的存在与病情加重相关（OR> 0.17; P <0.02），但与病情加重频率的相关性更强（OR> 0.39; P <4E-10），如通过细菌微生物群的纵向变化和生物分型所证实的，并暗示了微生物群在致敏肺中的作用。这项研究突出了细菌类群在肺致敏和COPD恶化中的病毒触发因素中的作用。它提供了药物开发的各种目标的全球概述，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。