Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12 to 18 months
Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12 to 18 months
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DOI：
10.1016/j.jaci.2020.04.018
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发表时间：
2021-01-05
影响因子：
14.2
通讯作者：
Maitland-van der Zee, Anke H.
中科院分区：
文献类型：
--
作者：
Abdel-Aziz, Mahmoud, I;Brinkman, Paul;Maitland-van der Zee, Anke H.
背景：哮喘是一种异质性疾病，其特征是不同的表型以及相关的微生物失调。目的：我们的目的是根据痰微生物组特征识别严重哮喘表型，并评估其 12 至 18 个月后的稳定性。进一步的目的是在纳入独立的轻度至中度哮喘患者队列后评估集群的稳健性。方法：在这项纵向多中心队列研究中，在基线和 12 至 18 个月的随访后，从预测呼吸系统疾病结果的无偏生物标志物成年患者队列的子集中收集痰样本进行微生物组分析。通过使用微生物谱的 Bray-Curtis b 多样性测量来进行无监督的层次聚类。对于内部验证，应用了围绕中心点的分区、共识集群分布、引导和拓扑数据分析。研究后续样本以评估严重哮喘患者的患者内聚类稳定性。通过使用轻度至中度哮喘患者的独立队列来评估聚类稳健性。结果：可获得 100 名重度哮喘受试者（中位年龄 55 岁；42% 男性）的数据。确定了两个微生物组驱动的簇；他们的特征是哮喘发作、吸烟状况、居住地点、血液和/或痰中性粒细胞和巨噬细胞的百分比、肺活量测定结果和并发哮喘药物的差异（所有 P 值）
Background: Asthma is a heterogeneous disease characterized by distinct phenotypes with associated microbial dysbiosis. Objectives: Our aim was to identify severe asthma phenotypes based on sputum microbiome profiles and assess their stability after 12 to 18 months. A further aim was to evaluate clusters' robustness after inclusion of an independent cohort of patients with mild-to-moderate asthma.Methods: In this longitudinal multicenter cohort study, sputum samples were collected for microbiome profiling from a subset of the Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes adult patient cohort at baseline and after 12 to 18 months of follow-up. Unsupervised hierarchical clustering was performed by using the Bray-Curtis b-diversity measure of microbial profiles. For internal validation, partitioning around medoids, consensus cluster distribution, bootstrapping, and topological data analysis were applied. Follow-up samples were studied to evaluate within-patient clustering stability in patients with severe asthma. Cluster robustness was evaluated by using an independent cohort of patients with mild-to-moderate asthma.Results: Data were available for 100 subjects with severe asthma (median age 55 years; 42% males). Two microbiome-driven clusters were identified; they were characterized by differences in asthma onset, smoking status, residential locations, percentage of blood and/or sputum neutrophils and macrophages, lung spirometry results, and concurrent asthma medications (all P values