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

Autor:	Kazuyuki Inoue, Takefumi Akita, Akito Yamamoto, Toshihiro Shirai, Takahito Suzuki, Satoru Morita, Keita Hirai, Kazuhiro Asada, Taisuke Akamatsu, Ichiro Hayashi, Kunihiko Itoh, Masayuki Suzuki, Daiki Tsuji
Rok vydání:	2017
Předmět:	Male medicine.medical_specialty Endotype Exacerbation Immunology Comorbidity Immunoglobulin E Gastroenterology Diagnosis Differential Pulmonary Disease Chronic Obstructive 03 medical and health sciences FEV1/FVC ratio 0302 clinical medicine Risk Factors Internal medicine medicine Cluster Analysis Humans Immunology and Allergy 030212 general & internal medicine Aged Asthma COPD biology business.industry Hazard ratio Area under the curve Middle Aged medicine.disease Respiratory Function Tests respiratory tract diseases Phenotype Gene Expression Regulation ROC Curve 030228 respiratory system Disease Progression Quality of Life biology.protein Female Symptom Assessment business Biomarkers
Zdroj:	Clinical & Experimental Allergy. 47:1374-1382
ISSN:	0954-7894
DOI:	10.1111/cea.12970
Popis:	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 & Clinical Relevance The asthma-COPD overlap phenotype was characterized by peripheral blood eosinophilia and higher levels of IgE despite the Th2-low endotype. This article is protected by copyright. All rights reserved.
Databáze:	OpenAIRE
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