Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Laboratory of Clinical Pharmacogenomics, Shizuoka General Hospital, Shizuoka, Japan.
Clin Exp Allergy. 2017 Nov;47(11):1374-1382. doi: 10.1111/cea.12970. Epub 2017 Aug 1.
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.
To clarify the best discriminators of the asthma-COPD overlap phenotype from asthma and COPD subgroups using a clustering approach.
This study assessed pathophysiological parameters, including mRNA expression levels of T helper 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.
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/μL, a higher ratio of TBX21/GATA3, FEV /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.
The asthma-COPD overlap phenotype was characterized by peripheral blood eosinophilia and higher levels of IgE despite the Th2-low endotype.
哮喘和慢性阻塞性肺疾病（COPD）是异质性疾病。具有哮喘和 COPD 临床特征的表型仍不完全清楚。
使用聚类方法阐明哮喘-COPD 重叠表型与哮喘和 COPD 亚组的最佳鉴别特征。
本研究评估了生理病理参数，包括外周血单个核细胞中转录因子相关的 T 辅助细胞的 mRNA 表达水平，即 TBX21（Th1）、GATA3（Th2）、RORC（Th17）和 FOXP3（Treg），在哮喘患者（n=152）和 COPD 患者（n=50）中。使用 k-均值聚类法确定聚类。在 1 年的随访期间记录哮喘和 COPD 的加重情况。
聚类分析显示存在四个生物学聚类：聚类 1，主要为 COPD 患者；聚类 2，哮喘-COPD 重叠表型患者；聚类 3，非特应性和晚发性哮喘患者；聚类 4，早发性特应性哮喘患者。与其他聚类的患者相比，聚类 1 和聚类 2 的哮喘加重风险比分别为 2.5（95%置信区间[CI]，1.1-5.6）和 2.3（95% CI，1.0-5.0）。与其他聚类相比，聚类 2 可通过总血清 IgE 水平≥310 IU/mL、血嗜酸性粒细胞计数≥280 个/μL、TBX21/GATA3 比值较高、FEV/FVC 比值<0.67 和吸烟≥10 包年来区分，曲线下面积为 0.94（95% CI，0.90-0.98），ROC 分析。
尽管 Th2 低表型，哮喘-COPD 重叠表型的特征为外周血嗜酸性粒细胞增多和 IgE 水平升高。
