Biological exacerbation clusters demonstrate asthma and chronic obstructive pulmonary disease overlap with distinct mediator and microbiome profiles.
Biological exacerbation clusters demonstrate asthma and chronic obstructive pulmonary disease overlap with distinct mediator and microbiome profiles.
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DOI：
10.1016/j.jaci.2018.04.013
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Brightling CE
中科院分区：
文献类型：
--
作者：
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
哮喘和慢性阻塞性肺疾病（COPD）的恶化是异质的。我们试图研究哮喘和慢性阻塞性肺病恶化的痰细胞、介质和微生物组特征。患有严重哮喘或中度至重度慢性阻塞性肺病的患者被前瞻性地招募到一个中心。在 32 名哮喘患者和 73 名 COPD 恶化时评估的患者中存在痰介质。通过对一组痰介质进行因子和聚类分析来确定生物聚类。对已确定的集群的临床参数、痰介质和微生物群落的模式进行了评估。哮喘患者和慢性阻塞性肺病患者具有不同的临床特征和炎症特征，但微生物生态相似。确定了三个恶化生物簇。第 1 组以 COPD 为主，其中 27 名 COPD 患者和 7 名哮喘患者表现出血液和痰中性粒细胞计数、促炎介质（IL-1β、IL-6、IL-6 受体、TNF-α、TNF 受体 1 和 2 以及血管内皮生长因子）以及细菌门变形菌比例增加。第 2 组有 10 名哮喘患者和 17 名 COPD 患者，其血液和痰中嗜酸性粒细胞计数、2 型介质（IL-5、IL-13、CCL13、CCL17 和 CCL26）以及拟杆菌门比例均增加。第 3 组有 15 名哮喘患者和 29 名 COPD 患者，其 1 型介质（CXCL10、CXCL11 和 IFN-γ）以及放线菌门和厚壁菌门的比例增加。生物聚类方法揭示了哮喘和慢性阻塞性肺病恶化的 3 个亚组，每个亚组中患有重叠哮喘和慢性阻塞性肺病的患者比例不同。各簇之间的痰介质和微生物组特征不同。
Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous. We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations. Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center. Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation. Biologic clusters were determined by 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. The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology. Three exacerbation biologic clusters were identified. Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria. Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes. Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes. A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD. The sputum mediator and microbiome profiles were distinct between clusters.
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影响因子：
14.2
作者：
Ghebre, Michael A.;Bafadhel, Mona;Desai, Dhananjay;Cohen, Suzanne E.;Newbold, Paul;Rapley, Laura;Woods, Jo;Rugman, Paul;Pavord, Ian D.;Newby, Chris;Burton, Paul R.;May, Richard D.;Brightling, Chris E.
通讯作者：
Brightling, Chris E.
通过PCR分层确定的痰液中的微生物组平衡会使COPD恶化，并显示出选择性使用抗生素的潜力。
影响因子：
3.7
作者：
Haldar K;Bafadhel M;Lau K;Berg A;Kwambana B;Kebadze T;Ramsheh MY;Barker B;Haldar P;Johnston S;Ketley JM;Brightling CE;Barer MR
通讯作者：
Barer MR
影响因子：
168.9
作者：
Brightling, CE;Monteiro, W;Pavord, ID
通讯作者：
Pavord, ID
影响因子：
76.2
作者：
Brightling, Christopher E.;Bleecker, Eugene R.;van der Merwe, Rene
通讯作者：
van der Merwe, Rene
影响因子：
168.9
作者：
Gibson, Peter G.;Yang, Ian A.;Simpson, Jodie L.
通讯作者：
Simpson, Jodie L.