Classification Of Moderate-severe Asthma Clinical Phenotypes And Difference Of Airway Remodeling And Airway Inflammation Between Phenotypes

Objectives: To identify asthma phenotypes using cluster analysis in order to improve our understanding of clinical heterogeneity in asthma.Methods: Clustering approaches were applied to 112 clinical,physiologic and inflammatory variables from 203 subjects,diagnosed as bronchial asthma in Xin Hua Hospital(Jan 2012 to Dec 2015).The initial 112 clinical variables included general information,questionnaire scores,blood test,lung function test and so on.After variables reduction,21 core variables were used to performed on 203 subjects.Meanwhile,120 participants' MSCT(Multi-slice spiral computer tomography)examations and 30 bronchoscope mucosal biopsies were used to describe the phenotypes from the point of pathology and pathophysiology.This study was approved by the institutional review board.Results: Four groups were identified.Subjects in Cluster 1(n=52)have early onset atopic asthma with normal lung function.Cluster 2(n=65)consists of subjects with small airway obstruction and atopic asthma,but less than cluster 1.Cluster 3(n=52)is a unique group of patients with late-onset non-atopic asthma,frequent exacerbations and poor response in ICS therapy.Subjects in Clusters 4(n=34)have severe airflow obstruction,frequent use of oral corticosteroids to manage exacerbations and obvious airway remodeling in MSCT.According to immunohistochemistry of IL-5 and IL-17,cluster 1 and cluster 2 might due to Th2 immune response,while cluster 3 and cluster 4 due to Th17 immune response.Conclusions: Four distinct clinical phenotypes of asthma have been identified using cluster analysis.The results of MSCT and pathological examination show the difference between those four phenotypes.It may suggest specific pathogenesises among the phenotypes.