A clustering approach to identify and characterize the asthma and chronic obstructive pulmonary disease overlap phenotype
A clustering approach to identify and characterize the asthma and chronic obstructive pulmonary disease overlap phenotype
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DOI：
10.1111/cea.12970
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发表时间：
2017-11-01
影响因子：
6.1
通讯作者：
Itoh, K.
中科院分区：
文献类型：
--
作者：
Hirai, K.;Shirai, T.;Itoh, K.
背景：哮喘和慢性阻塞性肺疾病（COPD）是异质性疾病。具有哮喘和COPD的临床特征的表型仍然不完全了解。目的：使用聚类方法阐明哮喘和COPD亚组的哮喘-COPD重叠表型的最佳鉴别器。方法：本研究评估了病理生理学参数，包括辅助细胞相关转录因子，即TBX 21（Th 1），GATA 3（Th 2），RORC（Th 17）和FOXP 3（Treg），在哮喘患者（n= 152）和COPD患者（n= 50）的外周血单核细胞。使用k-means聚类确定聚类。在1年的随访period.Results：聚类分析显示了四个生物学聚类：聚类1，主要是COPD患者;聚类2，哮喘-COPD重叠表型患者;聚类3，非特应性和迟发性哮喘患者;聚类4，早发性特应性哮喘患者。与其他聚类中的患者相比，聚类1中急性加重的风险比为2.5（95%置信区间[CI]，1.1-5.6），聚类2中急性加重的风险比为2.3（95% CI，1.0-5.0）。通过总血清IgE水平>= 310 IU/mL、血嗜酸性粒细胞计数>= 280个细胞/μ L、TBX 21/GATA 3的较高比率、FEV 1/FVC比率< 0.67 and smoking >= 10包-年且曲线下面积为0.94，将聚类2与其他聚类区分开（95%CI，0.90-0.98）。结论和临床相关性：哮喘-COPD重叠表型的特征是外周血嗜酸性粒细胞增多和较高水平的IgE，尽管Th 2-低内源型。
Background: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases. The phenotypes that have clinical features of both asthma and COPD are still incompletely understood.Objective: To clarify the best discriminators of the asthma-COPD overlap phenotype from asthma and COPD subgroups using a clustering approach.Methods: This study assessed pathophysiological parameters, including mRNA expression levels of Thelper cell-related transcription factors, namely TBX21 (Th1), GATA3 (Th2), RORC (Th17) and FOXP3 (Treg), in peripheral blood mononuclear cells in asthma patients (n= 152) and in COPD patients (n= 50). Clusters were determined using k-means clustering. Exacerbations of asthma and COPD were recorded during the 1-year follow-up period.Results: The cluster analysis revealed four biological clusters: cluster 1, predominantly patients with COPD; cluster 2, patients with an asthma-COPD overlap phenotype; cluster 3, patients with non-atopic and late-onset asthma; and cluster 4, patients with early-onset atopic asthma. Hazard ratios for exacerbation were 2.5 (95% confidence interval [CI], 1.1-5.6) in cluster 1 and 2.3 (95% CI, 1.0-5.0) in cluster 2 compared with patients in other clusters. Cluster 2 was discriminated from other clusters by total serum IgE level >= 310 IU/mL, blood eosinophil counts >= 280 cells/mu L, a higher ratio of TBX21/GATA3, FEV1/FVC ratio < 0.67 and smoking >= 10 pack-years with an area under the curve of 0.94 (95% CI, 0.90-0.98) in the receiver operating characteristic analysis.Conclusions and Clinical Relevance: The asthma-COPD overlap phenotype was characterized by peripheral blood eosinophilia and higher levels of IgE despite the Th2-low endotype.