Microbial burden and viral exacerbations in a longitudinal multicenter COPD cohort
Microbial burden and viral exacerbations in a longitudinal multicenter COPD cohort
复制标题
DOI：
10.1186/s12931-020-01340-0
复制
发表时间：
2020-03-30
影响因子：
5.8
通讯作者：
Jin, Hong
中科院分区：
文献类型：
--
作者：
Bouquet, Jerome;Tabor, David E.;Jin, Hong
背景慢性阻塞性肺疾病（COPD）是一种异质性疾病，其特征是频繁恶化表型，与疾病阶段无关。越来越多的证据表明，微生物群在疾病进展和严重程度中发挥着作用，但缺乏对病毒和细菌群落变化作为病情恶化驱动因素的长期和国际多中心评估。方法对来自欧洲和北美的200名严重COPD患者进行为期3年的纵向随访。我们对 20 种呼吸道病毒进行了核酸检测和 16S 核糖体 RNA 基因测序，以评估稳定期、急性加重期和随访期间收集的 1179 份痰样本中的细菌微生物群。结果与保加利亚和捷克共和国的患者相比，在美国患者中发现了类似的病毒和细菌分类群，但其微生物组多样性显着不同（P < 0.001），并且不影响病情恶化率。病毒感染与恶化事件密切相关（P < 5E-20）。人鼻病毒（13.1%）、冠状病毒（5.1%）和流感病毒（3.6%）构成引发病情加重的首要病毒病原体。在恶化事件期间，莫拉氏菌和嗜血杆菌成为主要微生物群的可能性分别是原来的 5 倍和 1.6 倍。变形菌如假单胞菌或葡萄球菌等的存在与恶化事件相关（OR > 0.17；P < 0.02），但与恶化频率的相关性更强（OR > 0.39；P < 4E-10），正如细菌微生物群的纵向变化和生物分型所证实的那样，并表明微生物群在致敏中的作用 肺。结论 本研究强调了肺部致敏中的细菌分类群和 COPD 恶化中的病毒触发因素。它提供了药物开发不同目标的全球概述，并探索新的微生物组分析方法来指导未来的患者管理应用。
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.