痰微生物组分鉴定出12-18个月时相对稳定的重症哮喘表型
2020/05/14
摘要
背景：哮喘是一种异质性疾病，具有不同的微生物失调相关的表型。
目的：根据痰菌群鉴定重症哮喘表型并评估其在12-18个月后的稳定性。此外，纳入一个独立的轻中度哮喘患者群体，评估群体的稳健性。
方法：在这项纵向多中心队列研究中，从成人患者队列的一个子集中收集患者基线和随访12-18个月后的痰样本进行微生物组学分析。利用微生物Bray-Curtis β多样性检测进行无监督分层聚类。内部验证采用了中心点算法、一致性聚类分布、自助法和拓扑数据分析等方法。评估随访样本重症哮喘患者群体疾病的稳定性。使用一个独立的轻中度哮喘队列来评估群体的稳健性。
结果：100例重症哮喘患者（中位年龄55岁，42%为男性）数据可用。确定了两个微生物群驱动的群体，其在哮喘发作、吸烟状态、居住地点、血和/或痰中性粒细胞和巨噬细胞百分比、肺活量测定和同时使用哮喘药物等方面的存在差异（均p＜0.05）。第2组患者与第1组相比，具有一个共生缺陷的细菌谱，这与哮喘预后更差有关。重度哮喘患者12-18个月后随访中，群体纵向分析显示出较高的相对稳定性。进一步纳入的24个独立轻中度哮喘患者的聚类分配一致。
结论：无偏倚微生物群驱动的聚类显示了两种不同的重症哮喘表型，表现出相对长时间的稳定性。这表明痰菌群可以作为更好地表征哮喘表型的生物标志物。
Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12-18 months.
Abdel-Aziz MI, Brinkman P, Vijverberg SJH, Neerincx AH, Riley JH, Bates S, Hashimoto S, Kermani NZ, Chung KF, Djukanovic R, Dahlén SE, Adcock IM, Howarth PH, Sterk PJ, Kraneveld AD, Maitland-van der Zee AH; U-BIOPRED Study Group.
Abstract
BACKGROUND:Asthma is a heterogeneous disease characterized by distinct phenotypes with associated microbial dysbiosis.
OBJECTIVE:To identify severe asthma phenotypes based on sputum microbiome profiles and assess their stability after 12-18 months. Furthermore, to evaluate clusters' robustness after inclusion of an independent mild-to-moderate asthmatics.
METHODS:In this longitudinal multicenter cohort study, sputum samples were collected for microbiome profiling from a subset of the U-BIOPRED adult patient cohort at baseline and after 12-18 months of follow-up. Unsupervised hierarchical clustering was performed using the Bray-Curtis β-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 severe asthmatics. Cluster robustness was evaluated by an independent mild-moderate asthma cohort.
RESULTS:Data were available for 100 severe asthma subjects (median age: 55 yrs, 42% males). Two microbiome-driven clusters were identified, characterized by differences in asthma onset, smoking status, residential locations, percentage of blood and/or sputum neutrophils and macrophages, lung spirometry, and concurrent asthma medications (all p-values <.05). Cluster 2 patients displayed a commensal-deficient bacterial profile which was associated with worse asthma outcomes compared to cluster 1. Longitudinal clusters revealed high relative stability after 12-18 months in the severe asthmatics. Further inclusion of 24 independent mild-to-moderate asthmatics was consistent with the clustering assignments.
CONCLUSIONS:Unbiased microbiome-driven clustering revealed two distinct robust severe asthma phenotypes, which exhibited relative overtime stability. This suggests that the sputum microbiome may serve as a biomarker for better characterizing asthma phenotypes.
背景：哮喘是一种异质性疾病，具有不同的微生物失调相关的表型。
目的：根据痰菌群鉴定重症哮喘表型并评估其在12-18个月后的稳定性。此外，纳入一个独立的轻中度哮喘患者群体，评估群体的稳健性。
方法：在这项纵向多中心队列研究中，从成人患者队列的一个子集中收集患者基线和随访12-18个月后的痰样本进行微生物组学分析。利用微生物Bray-Curtis β多样性检测进行无监督分层聚类。内部验证采用了中心点算法、一致性聚类分布、自助法和拓扑数据分析等方法。评估随访样本重症哮喘患者群体疾病的稳定性。使用一个独立的轻中度哮喘队列来评估群体的稳健性。
结果：100例重症哮喘患者（中位年龄55岁，42%为男性）数据可用。确定了两个微生物群驱动的群体，其在哮喘发作、吸烟状态、居住地点、血和/或痰中性粒细胞和巨噬细胞百分比、肺活量测定和同时使用哮喘药物等方面的存在差异（均p＜0.05）。第2组患者与第1组相比，具有一个共生缺陷的细菌谱，这与哮喘预后更差有关。重度哮喘患者12-18个月后随访中，群体纵向分析显示出较高的相对稳定性。进一步纳入的24个独立轻中度哮喘患者的聚类分配一致。
结论：无偏倚微生物群驱动的聚类显示了两种不同的重症哮喘表型，表现出相对长时间的稳定性。这表明痰菌群可以作为更好地表征哮喘表型的生物标志物。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2020 Apr 27. pii: S0091-6749(20)30565-0. doi: 10.1016/j.jaci.2020.04.018.)
(J Allergy Clin Immunol. 2020 Apr 27. pii: S0091-6749(20)30565-0. doi: 10.1016/j.jaci.2020.04.018.)
Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12-18 months.
Abdel-Aziz MI, Brinkman P, Vijverberg SJH, Neerincx AH, Riley JH, Bates S, Hashimoto S, Kermani NZ, Chung KF, Djukanovic R, Dahlén SE, Adcock IM, Howarth PH, Sterk PJ, Kraneveld AD, Maitland-van der Zee AH; U-BIOPRED Study Group.
Abstract
BACKGROUND:Asthma is a heterogeneous disease characterized by distinct phenotypes with associated microbial dysbiosis.
OBJECTIVE:To identify severe asthma phenotypes based on sputum microbiome profiles and assess their stability after 12-18 months. Furthermore, to evaluate clusters' robustness after inclusion of an independent mild-to-moderate asthmatics.
METHODS:In this longitudinal multicenter cohort study, sputum samples were collected for microbiome profiling from a subset of the U-BIOPRED adult patient cohort at baseline and after 12-18 months of follow-up. Unsupervised hierarchical clustering was performed using the Bray-Curtis β-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 severe asthmatics. Cluster robustness was evaluated by an independent mild-moderate asthma cohort.
RESULTS:Data were available for 100 severe asthma subjects (median age: 55 yrs, 42% males). Two microbiome-driven clusters were identified, characterized by differences in asthma onset, smoking status, residential locations, percentage of blood and/or sputum neutrophils and macrophages, lung spirometry, and concurrent asthma medications (all p-values <.05). Cluster 2 patients displayed a commensal-deficient bacterial profile which was associated with worse asthma outcomes compared to cluster 1. Longitudinal clusters revealed high relative stability after 12-18 months in the severe asthmatics. Further inclusion of 24 independent mild-to-moderate asthmatics was consistent with the clustering assignments.
CONCLUSIONS:Unbiased microbiome-driven clustering revealed two distinct robust severe asthma phenotypes, which exhibited relative overtime stability. This suggests that the sputum microbiome may serve as a biomarker for better characterizing asthma phenotypes.
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重症嗜酸粒细胞性哮喘患者血嗜酸粒细胞计数变化及动力学研究
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