Clinical Subtypes of Neutrophilic Asthma: A Cluster Analysis From Australasian Severe Asthma Network

Li Xiu He; Ke Deng; Ji Wang; Xin Zhang; Lei Wang; Hong Ping Zhang; Min Xie; Zhi Hong Chen; Jie Zhang; Alan Chen-Yu Hsu; Li Zhang; Brian G Oliver; Peter A B Wark; Ling Qin; Peng Gao; Hua Jing Wan; Dan Liu; Feng Ming Luo; Wei Min Li; Gang Wang; Peter Gerard Gibson

doi:10.1016/j.jaip.2023.09.023

Clinical Subtypes of Neutrophilic Asthma: A Cluster Analysis From Australasian Severe Asthma Network

J Allergy Clin Immunol Pract. 2024 Mar;12(3):686-698.e8. doi: 10.1016/j.jaip.2023.09.023. Epub 2023 Sep 29.

Authors

Li Xiu He¹, Ke Deng², Ji Wang², Xin Zhang³, Lei Wang³, Hong Ping Zhang³, Min Xie⁴, Zhi Hong Chen⁵, Jie Zhang⁶, Alan Chen-Yu Hsu⁷, Li Zhang⁸, Brian G Oliver⁹, Peter A B Wark¹⁰, Ling Qin¹¹, Peng Gao⁶, Hua Jing Wan¹², Dan Liu¹³, Feng Ming Luo², Wei Min Li¹⁴, Gang Wang¹⁵, Peter Gerard Gibson¹⁶

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, China; State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, China; Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China; Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, Sichuan University, Chengdu, China.
² Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, China; State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, Sichuan University, Chengdu, China.
³ Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, Sichuan University, Chengdu, China; Division of Internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.
⁴ Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
⁵ Shanghai Institute of Respiratory Disease, Respiratory Division of Zhongshan Hospital, Fudan University, Shanghai, China.
⁶ Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Jilin University, Changchun, Jilin, China.
⁷ Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore.
⁸ Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, China; State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, Sichuan University, Chengdu, China; Division of Internal Medicine, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.
⁹ School of Life Sciences, University of Technology Sydney, Ultimo, New South Wales, Australia; Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
¹⁰ Priority Research Center for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia; Department of Respiratory and Sleep Medicine, John Hunter Hospital, University of Newcastle, Newcastle, New South Wales, Australia.
¹¹ Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, China.
¹² Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, Sichuan University, Chengdu, China.
¹³ Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, China; State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, China; Respiratory Microbiome Laboratory, Frontiers Science Center for Disease-Related Molecular Network, Sichuan University, Chengdu, Sichuan, China.
¹⁴ Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, China; State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, China; Respiratory Microbiome Laboratory, Frontiers Science Center for Disease-Related Molecular Network, Sichuan University, Chengdu, Sichuan, China. Electronic address: weimi003@scu.edu.cn.
¹⁵ Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, China; State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, China; Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-Related Molecular Network, Sichuan University, Chengdu, China. Electronic address: wcums-respiration@hotmail.com.
¹⁶ Priority Research Center for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia; Department of Respiratory and Sleep Medicine, John Hunter Hospital, University of Newcastle, Newcastle, New South Wales, Australia; National Health and Medical Research Council Center for Excellence in Severe Asthma, Newcastle, New South Wales, Australia.

PMID: 37778630
DOI: 10.1016/j.jaip.2023.09.023

Abstract

Background: Clinical heterogeneity may exist within asthma subtypes defined by inflammatory markers. However, the heterogeneity of neutrophilic asthma (NA) remains largely unexplored.

Objective: To explore potential clusters and the stability of NA.

Methods: Participants with NA from the Australasian Severe Asthma Network underwent a multidimensional assessment. They were then asked to participate in a 12-month longitudinal cohort study. We explored potential clusters using a hierarchical cluster analysis and validated the differential future risk of asthma exacerbations in the identified clusters. A decision tree analysis was developed to predict cluster assignments. Finally, the stability of prespecified clusters was examined within 1 month.

Results: Three clusters were identified in 149 patients with NA. Cluster 1 (n = 99; 66.4%) was characterized by female-predominant nonsmokers with well-controlled NA, cluster 2 (n = 16; 10.7%) by individuals with comorbid anxiety/depressive symptoms with poorly controlled NA, and cluster 3 by older male smokers with late-onset NA. Cluster 2 had a greater proportion of participants with severe exacerbations (P = .005), hospitalization (P = .010), and unscheduled visits (P = .013) and a higher number of emergency room visits (P = .039) than that of the other two clusters. The decision tree assigned 92.6% of participants correctly. Most participants (87.5%; n = 7) in cluster 2 had a stable NA phenotype, whereas participants of clusters 1 and 3 had variable phenotypes.

Conclusions: We identified three clinical clusters of NA, in which cluster 2 represents an uncontrolled and stable NA subtype with an elevated risk of exacerbations. These findings have clinical implications for the management of NA.

Keywords: Asthma; Cluster analysis; Heterogeneity; Neutrophilic asthma; Phenotype variability; Phenotypes.

MeSH terms

Asthma* / diagnosis
Cluster Analysis
Comorbidity
Humans
Longitudinal Studies
Phenotype