Biological clustering supports both "Dutch" and "British" hypotheses of asthma and chronic obstructive pulmonary disease.
Biological clustering supports both "Dutch" and "British" hypotheses of asthma and chronic obstructive pulmonary disease.
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DOI：
10.1016/j.jaci.2014.06.035
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发表时间：
2015-01
影响因子：
14.2
通讯作者：
Brightling, Chris E.
中科院分区：
文献类型：
--
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.
哮喘和慢性阻塞性肺疾病（COPD）是异质性疾病。我们试图根据他们的痰细胞和介质谱来确定它们在多大程度上代表不同或重叠的疾病，支持“英国”或“荷兰”的气道疾病发病机制假设。我们比较了86例重度哮喘患者和75例中重度COPD患者的临床和生理特征以及痰液介质。对18种痰液细胞因子进行因子分析和聚类分析，确定生物学亚组。在独立的重度哮喘（n = 166）和COPD（n = 58）队列中对亚组进行了验证。使用两种技术将验证受试者分配到亚组：线性判别分析，或最佳识别的细胞因子（单一细胞因子）结合受试者疾病状态（哮喘或COPD）。判别分析区分严重哮喘从COPD完全使用临床和生物学变量的组合。痰液细胞因子谱的因子和聚类分析揭示了3个生物聚类：聚类1：哮喘为主，嗜酸性，高TH 2细胞因子;聚类2：哮喘和COPD重叠，嗜酸性;聚类3：COPD为主，混合嗜酸性和嗜酸性。使用判别分析或疾病状态与痰IL-1β表达的二元评估将验证受试者分为3个亚组。验证亚组的痰液细胞和细胞因子特征与试验研究亚组相似。痰液细胞因子谱可以确定不同的和重叠的哮喘和COPD受试者组，支持英国和荷兰的假设。这些发现可能有助于改善患者分类，以实现分层医学。
Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases. We sought to determine, in terms of their sputum cellular and mediator profiles, the extent to which they represent distinct or overlapping conditions supporting either the “British” or “Dutch” hypotheses of airway disease pathogenesis. We compared the clinical and physiological characteristics and sputum mediators between 86 subjects with severe asthma and 75 with moderate-to-severe COPD. Biological subgroups were determined using factor and cluster analyses on 18 sputum cytokines. The subgroups were validated on independent severe asthma (n = 166) and COPD (n = 58) cohorts. Two techniques were used to assign the validation subjects to subgroups: linear discriminant analysis, or the best identified discriminator (single cytokine) in combination with subject disease status (asthma or COPD). Discriminant analysis distinguished severe asthma from COPD completely using a combination of clinical and biological variables. Factor and cluster analyses of the sputum cytokine profiles revealed 3 biological clusters: cluster 1: asthma predominant, eosinophilic, high TH2 cytokines; cluster 2: asthma and COPD overlap, neutrophilic; cluster 3: COPD predominant, mixed eosinophilic and neutrophilic. Validation subjects were classified into 3 subgroups using discriminant analysis, or disease status with a binary assessment of sputum IL-1β expression. Sputum cellular and cytokine profiles of the validation subgroups were similar to the subgroups from the test study. Sputum cytokine profiling can determine distinct and overlapping groups of subjects with asthma and COPD, supporting both the British and Dutch hypotheses. These findings may contribute to improved patient classification to enable stratified medicine.
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影响因子：
168.9
作者：
Brightling, CE;Monteiro, W;Pavord, ID
通讯作者：
Pavord, ID
DOI：
10.1164/rccm.201108-1553oc
发表时间：
2012-07-01
影响因子：
24.7
作者：
Bafadhel, Mona;McKenna, Susan;Brightling, Christopher E.
通讯作者：
Brightling, Christopher E.
影响因子：
10
作者：
Brightling, CE;McKenna, S;Bradding, P
通讯作者：
Bradding, P
DOI：
10.1056/nejmoa0808991
发表时间：
2009-03-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Haldar P;Brightling CE;Hargadon B;Gupta S;Monteiro W;Sousa A;Marshall RP;Bradding P;Green RH;Wardlaw AJ;Pavord ID
通讯作者：
Pavord ID
DOI：
10.1016/j.jaci.2007.10.028
发表时间：
2008-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Brightling C;Berry M;Amrani Y
通讯作者：
Amrani Y