Identification of cough-variant asthma phenotypes based on clinical and pathophysiologic data

Wenzhi Zhan; Feng Wu; Yunhui Zhang; Lin Lin; Wen Li; Wei Luo; Fang Yi; Yuanrong Dai; Suyun Li; Jiangtao Lin; Yadong Yuan; Chen Qiu; Yong Jiang; Limin Zhao; Meihua Chen; Zhongmin Qiu; Ruchong Chen; Jiaxing Xie; Chunxing Guo; Mei Jiang; Xiaohong Yang; Guochao Shi; Dejun Sun; Rongchang Chen; Nanshan Zhong; Huahao Shen; Kefang Lai

doi:10.1016/j.jaci.2023.04.017

Identification of cough-variant asthma phenotypes based on clinical and pathophysiologic data

J Allergy Clin Immunol. 2023 Sep;152(3):622-632. doi: 10.1016/j.jaci.2023.04.017. Epub 2023 May 11.

Authors

Wenzhi Zhan¹, Feng Wu², Yunhui Zhang³, Lin Lin⁴, Wen Li⁵, Wei Luo¹, Fang Yi¹, Yuanrong Dai⁶, Suyun Li⁷, Jiangtao Lin⁸, Yadong Yuan⁹, Chen Qiu¹⁰, Yong Jiang¹¹, Limin Zhao¹², Meihua Chen¹³, Zhongmin Qiu¹⁴, Ruchong Chen¹, Jiaxing Xie¹, Chunxing Guo¹, Mei Jiang¹, Xiaohong Yang¹⁵, Guochao Shi¹⁶, Dejun Sun¹⁷, Rongchang Chen¹⁸, Nanshan Zhong¹, Huahao Shen⁵, Kefang Lai¹⁹

Affiliations

¹ Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
² Department of Pulmonary and Critical Care Medicine, Huizhou the Third People's Hospital, Guangzhou Medical University, Huizhou, China.
³ Department of Pulmonary and Critical Care Medicine, the First People's Hospital of Yunnan Province, Kunming, China.
⁴ Department of Pulmonary and Critical Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, the Second Clinical School of Guangzhou University of Chinese Medicine, Guangzhou, China.
⁵ Department of Pulmonary and Critical Care Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
⁶ Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁷ Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
⁸ Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China.
⁹ Department of Pulmonary and Critical Care Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, China.
¹⁰ Department of Respiratory and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital, the First Affiliated Hospital of Southern University of Science and Technology, the Second Clinical Medical College of Jinan University, Shenzhen, China.
¹¹ Department of Respiratory and Critical Care Medicine, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China.
¹² Department of Respiratory and Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, China.
¹³ Department of Pulmonary and Critical Care Medicine, Songshan Lake Central Hospital of Dongguan City, the Third People's Hospital of Dongguan City, Dongguan, China.
¹⁴ Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
¹⁵ Department of Respiratory and Critical Care Medicine, Xinjiang Interstitial Lung Disease Clinical Medicine Research Center, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
¹⁶ Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
¹⁷ Department of Pulmonary and Critical Care Medicine, the Inner Mongolia Autonomous Region People's Hospital, Hohhot, China.
¹⁸ Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Department of Respiratory and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, Shenzhen People's Hospital, the First Affiliated Hospital of Southern University of Science and Technology, the Second Clinical Medical College of Jinan University, Shenzhen, China.
¹⁹ Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address: klai@163.com.

PMID: 37178731
DOI: 10.1016/j.jaci.2023.04.017

Abstract

Background: Cough-variant asthma (CVA) may respond differently to antiasthmatic treatment. There are limited data on the heterogeneity of CVA.

Objective: We aimed to classify patients with CVA using cluster analysis based on clinicophysiologic parameters and to unveil the underlying molecular pathways of these phenotypes with transcriptomic data of sputum cells.

Methods: We applied k-mean clustering to 342 newly physician-diagnosed patients with CVA from a prospective multicenter observational cohort using 10 prespecified baseline clinical and pathophysiologic variables. The clusters were compared according to clinical features, treatment response, and sputum transcriptomic data.

Results: Three stable CVA clusters were identified. Cluster 1 (n = 176) was characterized by female predominance, late onset, normal lung function, and a low proportion of complete resolution of cough (60.8%) after antiasthmatic treatment. Patients in cluster 2 (n = 105) presented with young, nocturnal cough, atopy, high type 2 inflammation, and a high proportion of complete resolution of cough (73.3%) with a highly upregulated coexpression gene network that related to type 2 immunity. Patients in cluster 3 (n = 61) had high body mass index, long disease duration, family history of asthma, low lung function, and low proportion of complete resolution of cough (54.1%). T_H17 immunity and type 2 immunity coexpression gene networks were both upregulated in clusters 1 and 3.

Conclusion: Three clusters of CVA were identified with different clinical, pathophysiologic, and transcriptomic features and responses to antiasthmatics treatment, which may improve our understanding of pathogenesis and help clinicians develop individualized cough treatment in asthma.

Keywords: Cough-variant asthma; airway inflammation; cluster; cough; transcriptome; treatment response.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Anti-Asthmatic Agents* / therapeutic use
Asthma*
Cough
Female
Humans
Male
Phenotype
Prospective Studies

Substances

Anti-Asthmatic Agents