A clustering approach to identify and characterize the asthma and chronic obstructive pulmonary disease overlap phenotype

• Published in: Clinical and experimental allergy Vol. 47; no. 11; pp. 1374 - 1382
• Main Authors: Hirai, K., Shirai, T., Suzuki, M., Akamatsu, T., Suzuki, T., Hayashi, I., Yamamoto, A., Akita, T., Morita, S., Asada, K., Tsuji, D., Inoue, K., Itoh, K.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.11.2017
• Subjects: Age; Aged; Asthma; Asthma - diagnosis; Asthma - etiology; Asthma - metabolism; asthma‐COPD overlap syndrome; Atopy; Biomarkers; Chronic obstructive pulmonary disease; Cluster Analysis; Comorbidity; Diagnosis, Differential; Disease Progression; Eosinophilia; eosinophils; exacerbation; Female; Foxp3 protein; GATA-3 protein; Gene expression; Gene Expression Regulation; Genotype & phenotype; Helper cells; Humans; IgE; Immunoglobulin E; Leukocytes (mononuclear); Lung diseases; Lymphocytes T; Male; Middle Aged; Obstructive lung disease; Peripheral blood mononuclear cells; Phenotype; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - etiology; Pulmonary Disease, Chronic Obstructive - metabolism; Quality of Life; Respiratory Function Tests; Risk Factors; ROC Curve; Smoking; Symptom Assessment; Transcription factors; T‐cell transcription factors; eosinophils; quality-of-life; asthma-COPD overlap syndrome; IgE; T-cell transcription factors; exacerbation
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/cea.12970

Summary 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 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. 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/μL, 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.