Sputum Microbiome Is Associated with 1-Year Mortality after Chronic Obstructive Pulmonary Disease Hospitalizations
Sputum Microbiome Is Associated with 1-Year Mortality after Chronic Obstructive Pulmonary Disease Hospitalizations
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DOI：
10.1164/rccm.201806-1135oc
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发表时间：
2019-05-15
影响因子：
24.7
通讯作者：
Sin, Don D.
中科院分区：
文献类型：
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作者：
Leitao Filho, Fernando Sergio;Alotaibi, Nawaf M.;Sin, Don D.
基本原理：肺生态失调促进气道炎症和局部免疫力下降，可能在慢性阻塞性肺疾病（AECOPD）急性加重的发病机制中发挥作用。Objectives：我们试图确定AECOPD住院时痰液微生物组与COPD队列1年死亡率之间的关系。所有受试者出院后随访1年。通过16 S rRNA基因测序评估微生物组谱。根据1年死亡率状态进行微生物组分析。为了研究α多样性指标和分类特征对死亡时间的影响，我们应用了考克斯比例风险回归模型，并获得了与这些变量相关的风险比（HR）。我们观察到显著较低的a多样性值，非幸存者（n = 19，18.6%）的物种多样性（丰富度，Shannon指数，均匀度和Faith的系统发育多样性）高于幸存者（n = 83，81.4%）。β-多样性分析也证明了两组之间的显著差异（校正的置换多变量ANOVA，P = 0.010）。幸存者有较高的相对丰度韦荣氏球菌，相反，非幸存者有较高的丰度葡萄球菌。1年死亡率的校正HR随着α多样性的降低而显著增加。我们还观察到痰液样本中韦荣氏球菌阴性的患者生存率较低（HR，13.5; 95%置信区间，4.2-43.9; P < 0.001）或葡萄球菌阳性（HR，7.3; 95%置信区间，1.6-33.2; P = 0.01）。AECOPD患者痰液的微生物组特征与1年死亡率相关，可用于识别住院时预后不良的受试者。
Rationale: Lung dysbiosis promotes airway inflammation and decreased local immunity, potentially playing a role in the pathogenesis of acute exacerbations of chronic obstructive pulmonary disease (AECOPD).Objectives: We sought to determine the relationship between sputum microbiome at the time of AECOPD hospitalization and 1-year mortality in a COPD cohort.Methods: We used sputum samples from 102 patients hospitalized because of AECOPD. All subjects were followed for 1 year after discharge. The microbiome profile was assessed through sequencing of 16S rRNA gene. Microbiome analyses were performed according to 1-year mortality status. To investigate the effect of a-diversity measures and taxon features on time to death, we applied Cox proportional hazards regression models and obtained hazard ratios (HRs) associated with these variables.Measurements and Main Results: We observed significantly lower values of a-diversity (richness, Shannon index, evenness, and Faith's Phylogenetic Diversity) among nonsurvivors (n = 19, 18.6%) than survivors (n = 83, 81.4%). beta-Diversity analysis also demonstrated significant differences between both groups (adjusted permutational multivariate ANOVA, P = 0.010). The survivors had a higher relative abundance of Veillonella; in contrast, nonsurvivors had a higher abundance of Staphylococcus. The adjusted HRs for 1-year mortality increased significantly with decreasing a-diversity. We also observed lower survival among patients in whom sputum samples were negative for Veillonella (HR, 13.5; 95% confidence interval, 4.2-43.9; P < 0.001) or positive for Staphylococcus (HR, 7.3; 95% confidence interval, 1.6-33.2; P = 0.01).Conclusions: The microbiome profile of sputum in AECOPD is associated with 1-year mortality and may be used to identify subjects with a poor prognosis at the time of hospitalization.