生物加重群表明不同介质和微生物组的哮喘和COPD的重叠
2018/05/08
摘要
背景：哮喘和慢性阻塞性肺疾病（COPD）的急性加重是不一样的。
目的：本研究旨在调查哮喘和COPD加重时的痰细胞，介质和微生物组特征。
方法：招募重症哮喘或中重度COPD患者到一个中心。32例哮喘和73例COPD在急性加重期用痰液介质评估。使用痰液介质中的因子和聚类分析来确定生物群集。临床参数，痰液介质和微生物群体模式在所确定的群集中进行评估。
结果：哮喘和COPD患者具有不同的临床特点和炎症特征，但有类似的微生物生态学。确定了三个加重生物群。第1组以COPD为主，其中27例COPD和7例哮喘患者表现出血液和痰中性粒细胞，促炎症介质（IL-1β，IL-6，IL-6R，TNFα，TNF-R1，TNF-R2和VEGF），和变形杆菌的比例升高。第2组10例哮喘患者和17例COPD患者表现出血液和痰嗜酸性粒细胞，Th2型介质（IL-5，IL-13，CCL13，CCL17和CCL26）以及拟杆菌门菌比例升高。 第3组15例哮喘患者和29例COPD患者表现出Th1型介质（CXCL10，CXCL11和IFN-γ）及放线菌和厚壁菌的比例升高。
结论：生物群集方法揭示了哮喘和COPD加重的三个亚组，每个亚组哮喘和COPD患者重叠百分比不同。亚组间痰液介质和微生物组是不同的。痰液介质和微生物组分析可以确定哮喘和COPD生物加重组的不同和重叠，突出了加重时的异质性。
Biological exacerbation clusters demonstrate asthma and COPD overlap with distinct mediator and microbiome profiles.
Ghebre MA, Pang PH, Diver S, Desai D, Bafadhel M, Haldar K, Kebadze T, Cohen S, Newbold P, Rapley L, Woods J, Rugman P, Pavord ID, Johnston SL, Barer M, May RD, Brightling CE.
Abstract
BACKGROUND:Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous.
OBJECTIVE:We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations.
METHODS:Patients with severe asthma or moderate-to-severe COPD were prospectively recruited to a single centre. Sputum mediators were available in 32 asthma and 73 COPD patients assessed at exacerbation. Biologic clusters were determined using factor and cluster analyses on a panel of sputum mediators. Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters.
RESULTS:The asthma and COPD patients had different clinical characteristics and inflammatory profiles, but similar microbial ecology. Three exacerbation biologic clusters were identified. Cluster 1 was COPD predominant, with 27 COPD and 7 asthma patients exhibiting elevated blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6R, TNFα, TNF-R1, TNF-R2, and VEGF), and proportion of the bacterial phylum Proteobacteria. Cluster 2 had 10 asthma and 17 COPD patients with elevated blood and sputum eosinophil counts, Type 2 (T2) mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportion of the bacterial phylum Bacteroidetes. Cluster 3 had 15 asthma and 29 COPD subjects with elevated Type 1 (T1) mediators (CXCL10, CXCL11, and IFN-ϒ) and proportions of phyla Actinobacteria and Firmicutes.
CONCLUSIONS:A biologic clustering approach revealed three subgroups of asthma and COPD exacerbations each with different percentages of overlapping asthma and COPD patients. The sputum mediator and microbiome profiles were distinct between clusters. Sputum mediator and microbiome profiling can determine the distinct and overlapping asthma and COPD biologic exacerbation clusters, highlighting the heterogeneity of these exacerbations.
背景：哮喘和慢性阻塞性肺疾病（COPD）的急性加重是不一样的。
目的：本研究旨在调查哮喘和COPD加重时的痰细胞，介质和微生物组特征。
方法：招募重症哮喘或中重度COPD患者到一个中心。32例哮喘和73例COPD在急性加重期用痰液介质评估。使用痰液介质中的因子和聚类分析来确定生物群集。临床参数，痰液介质和微生物群体模式在所确定的群集中进行评估。
结果：哮喘和COPD患者具有不同的临床特点和炎症特征，但有类似的微生物生态学。确定了三个加重生物群。第1组以COPD为主，其中27例COPD和7例哮喘患者表现出血液和痰中性粒细胞，促炎症介质（IL-1β，IL-6，IL-6R，TNFα，TNF-R1，TNF-R2和VEGF），和变形杆菌的比例升高。第2组10例哮喘患者和17例COPD患者表现出血液和痰嗜酸性粒细胞，Th2型介质（IL-5，IL-13，CCL13，CCL17和CCL26）以及拟杆菌门菌比例升高。 第3组15例哮喘患者和29例COPD患者表现出Th1型介质（CXCL10，CXCL11和IFN-γ）及放线菌和厚壁菌的比例升高。
结论：生物群集方法揭示了哮喘和COPD加重的三个亚组，每个亚组哮喘和COPD患者重叠百分比不同。亚组间痰液介质和微生物组是不同的。痰液介质和微生物组分析可以确定哮喘和COPD生物加重组的不同和重叠，突出了加重时的异质性。
(中日友好医院呼吸与危重症医学科 王瑞茵 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2018 Apr 27. pii: S0091-6749(18)30625-0. doi: 10.1016/j.jaci.2018.04.013. [Epub ahead of print])
(J Allergy Clin Immunol. 2018 Apr 27. pii: S0091-6749(18)30625-0. doi: 10.1016/j.jaci.2018.04.013. [Epub ahead of print])
Biological exacerbation clusters demonstrate asthma and COPD overlap with distinct mediator and microbiome profiles.
Ghebre MA, Pang PH, Diver S, Desai D, Bafadhel M, Haldar K, Kebadze T, Cohen S, Newbold P, Rapley L, Woods J, Rugman P, Pavord ID, Johnston SL, Barer M, May RD, Brightling CE.
Abstract
BACKGROUND:Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous.
OBJECTIVE:We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations.
METHODS:Patients with severe asthma or moderate-to-severe COPD were prospectively recruited to a single centre. Sputum mediators were available in 32 asthma and 73 COPD patients assessed at exacerbation. Biologic clusters were determined using factor and cluster analyses on a panel of sputum mediators. Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters.
RESULTS:The asthma and COPD patients had different clinical characteristics and inflammatory profiles, but similar microbial ecology. Three exacerbation biologic clusters were identified. Cluster 1 was COPD predominant, with 27 COPD and 7 asthma patients exhibiting elevated blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6R, TNFα, TNF-R1, TNF-R2, and VEGF), and proportion of the bacterial phylum Proteobacteria. Cluster 2 had 10 asthma and 17 COPD patients with elevated blood and sputum eosinophil counts, Type 2 (T2) mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportion of the bacterial phylum Bacteroidetes. Cluster 3 had 15 asthma and 29 COPD subjects with elevated Type 1 (T1) mediators (CXCL10, CXCL11, and IFN-ϒ) and proportions of phyla Actinobacteria and Firmicutes.
CONCLUSIONS:A biologic clustering approach revealed three subgroups of asthma and COPD exacerbations each with different percentages of overlapping asthma and COPD patients. The sputum mediator and microbiome profiles were distinct between clusters. Sputum mediator and microbiome profiling can determine the distinct and overlapping asthma and COPD biologic exacerbation clusters, highlighting the heterogeneity of these exacerbations.
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年轻哮喘患者中血清IgE抗体的缺乏提示非2型超敏反应性疾病
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室内过敏原减少在哮喘管理中的有效性：一项系统评价
