Identification of cough-variant asthma phenotypes based on clinical and pathophysiologic data - 08/09/23

Doi : 10.1016/j.jaci.2023.04.017

Wenzhi Zhan, MD, PhD ^a, Feng Wu, MD ^b, Yunhui Zhang, MD ^c, Lin Lin, MD ^d, Wen Li, MD, PhD ^e, Wei Luo, MD ^a, Fang Yi, MD, PhD ^a, Yuanrong Dai, MD ^f, Suyun Li, MD, PhD ^g, Jiangtao Lin, MD ^h, Yadong Yuan, MD, PhD ⁱ, Chen Qiu, MD, PhD ^j, Yong Jiang, MD ^k, Limin Zhao, MD, PhD ^l, Meihua Chen, MD ^m, Zhongmin Qiu, MD, PhD ⁿ, Ruchong Chen, MD, PhD ^a, Jiaxing Xie, MD, PhD ^a, Chunxing Guo, MD ^a, Mei Jiang, MD, PhD ^a, Xiaohong Yang, MD ^o, Guochao Shi, MD, PhD ^p, Dejun Sun, MD, PhD ^q, Rongchang Chen, MD ^a,^j, Nanshan Zhong, MD ^a, Huahao Shen, MD, PhD ^e, Kefang Lai, MD, PhD ^a,^⁎
^a 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
^b Department of Pulmonary and Critical Care Medicine, Huizhou the Third People’s Hospital, Guangzhou Medical University, Huizhou, China
^c Department of Pulmonary and Critical Care Medicine, the First People’s Hospital of Yunnan Province, Kunming, China
^d 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
^e 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
^f Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
^g Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
^h Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China
ⁱ Department of Pulmonary and Critical Care Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, China
^j 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
^k Department of Respiratory and Critical Care Medicine, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China
^l Department of Respiratory and Critical Care Medicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, China
^m Department of Pulmonary and Critical Care Medicine, Songshan Lake Central Hospital of Dongguan City, the Third People’s Hospital of Dongguan City, Dongguan, China
ⁿ Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
^o 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
^p Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
^q Department of Pulmonary and Critical Care Medicine, the Inner Mongolia Autonomous Region People’s Hospital, Hohhot, China

^∗Corresponding author: Kefang Lai, MD, PhD, 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, 151 Yanjiang Rd, Guangzhou, 510120, China.National Center for Respiratory Medicine151 Yanjiang Rd, GuangzhouParis510120China

Graphical abstract

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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.

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Key words : Cough-variant asthma, cough, cluster, transcriptome, treatment response, airway inflammation

Abbreviations used : ACT, APAC, BMI, CDF, CVA, Feno, FEV₁ (% predicted), GO, HC, IQR, KEGG, LCQ, MMEF (% predicted), VAS, WGCNA

Plan

Methods

APAC CVA cohort study design and patients

Measurement and assessment

Clinical variables for cluster analysis

Data preprocessing and cluster analysis

Conditional inference tree learning

Bulk RNA sequencing and data analysis

Statistical analysis

Results

Patients and cluster identification

Clinical features of clusters at baseline

Sputum transcriptional profiling of clusters at baseline

Response to antiasthmatic treatment, spirometry, and airway inflammation of clusters

Conditional inference tree classification

Discussion

Disclosure statement

All sequencing data have been deposited in the public, open access repository of the National Institutes of Health’s Sequence Read Archive (BioProjects PRJNA890702 and PRJNA878650).

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Vol 152 - N° 3

P. 622-632 - septembre 2023 Retour au numéro

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Identification of cough-variant asthma phenotypes based on clinical and pathophysiologic data - 08/09/23

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Abstract

Background

Objective

Methods

Results

Conclusion

Plan

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