Rationale: The airway microbiome has the potential to shape chronic obstructive pulmonary disease (COPD) pathogenesis, but its relationship to outcomes in milder disease is unestablished. Objectives: To identify sputum microbiome characteristics associated with markers of COPD in participants of the Subpopulations and Intermediate Outcome Measures of COPD Study (SPIROMICS). Methods: Sputum DNA from 877 participants was analyzed using 16S ribosomal RNA gene sequencing. Relationships between baseline airway microbiota composition and clinical, radiographic, and mucoinflammatory markers, including longitudinal lung function trajectory, were examined. Measurements and Main Results: Participant data represented predominantly milder disease (Global Initiative for Chronic Obstructive Lung Disease stage 0-2 obstruction in 732 of 877 participants). Phylogenetic diversity (i.e., range of different species within a sample) correlated positively with baseline lung function, decreased with higher Global Initiative for Chronic Obstructive Lung Disease stage, and correlated negatively with symptom burden, radiographic markers of airway disease, and total mucin concentrations (P < 0.001). In covariate-adjusted regression models, organisms robustly associated with better lung function included Alloprevotella, Oribacterium, and Veillonella species. Conversely, lower lung function, greater symptoms, and radiographic measures of small airway disease were associated with enrichment in members of Streptococcus, Actinobacillus, Actinomyces, and other genera. Baseline sputum microbiota features were also associated with lung function trajectory during SPIROMICS follow-up (stable/improved, decline, or rapid decline groups). The stable/improved group (slope of FEV1 regression ⩾66th percentile) had greater bacterial diversity at baseline associated with enrichment in Prevotella, Leptotrichia, and Neisseria species. In contrast, the rapid decline group (FEV1 slope ⩽33rd percentile) had significantly lower baseline diversity associated with enrichment in Streptococcus species. Conclusions: In SPIROMICS, baseline airway microbiota features demonstrate divergent associations with better or worse COPD-related outcomes.

中文翻译：

---

气道系统发育多样性的丧失与慢性阻塞性肺疾病疾病发展的临床和病理生物学标志物相关。


理由：气道微生物组有可能影响慢性阻塞性肺病 (COPD) 的发病机制，但其与较轻疾病结果的关系尚未确定。目的：确定 COPD 亚群和中期结果测量研究 (SPIROMICS) 参与者中与 COPD 标志物相关的痰微生物组特征。方法：使用 16S 核糖体 RNA 基因测序分析 877 名参与者的痰液 DNA。研究人员检查了基线气道微生物群组成与临床、放射学和粘膜炎症标志物（包括纵向肺功能轨迹）之间的关系。测量和主要结果：参与者数据主要代表较轻的疾病（全球慢性阻塞性肺病倡议 877 名参与者中有 732 人患有 0-2 期阻塞）。系统发育多样性（即样本中不同物种的范围）与基线肺功能呈正相关，随着全球慢性阻塞性肺疾病倡议阶段的升高而降低，并与症状负担、气道疾病的放射学标记物和总粘蛋白浓度呈负相关。 P < 0.001）。在协变量调整回归模型中，与更好的肺功能密切相关的生物体包括异普雷沃菌属、奥里杆菌属和韦荣球菌属。相反，肺功能降低、症状加重和小气道疾病的放射学检查与链球菌属、放线杆菌属、放线菌属和其他属成员的富集有关。基线痰菌群特征也与 SPIROMICS 随访期间的肺功能轨迹相关（稳定/改善、下降或快速下降组）。 稳定/改善组（FEV1 回归斜率≥66%）在基线时具有更高的细菌多样性，与普雷沃菌属、细毛菌属和奈瑟菌属物种的富集相关。相比之下，快速下降组（FEV1 斜率≤第 33 个百分位数）与链球菌物种富集相关的基线多样性显着较低。结论：在 SPIROMICS 中，基线气道微生物群特征表明与 COPD 相关结局的好坏存在不同的关联。