Heterogeneity of Paucigranulocytic Asthma: A Prospective Cohort Study with Hierarchical Cluster Analysis

Ke Deng; Xin Zhang; Ying Liu; Li Zhang; Gang Wang; Min Feng; Brian G Oliver; Lei Wang; Philip M Hansbro; Lin Qin; Min Xie; Zhi Hong Chen; Jodie Simpson; Jie Zhang; Wei Min Li; Gang Wang; Peter Gerard Gibson

doi:10.1016/j.jaip.2021.01.004

Heterogeneity of Paucigranulocytic Asthma: A Prospective Cohort Study with Hierarchical Cluster Analysis

J Allergy Clin Immunol Pract. 2021 Jun;9(6):2344-2355. doi: 10.1016/j.jaip.2021.01.004. Epub 2021 Jan 20.

Authors

Ke Deng¹, Xin Zhang², Ying Liu³, Li Zhang³, Gang Wang⁴, Min Feng⁵, Brian G Oliver⁶, Lei Wang⁷, Philip M Hansbro⁸, Lin Qin⁹, Min Xie¹⁰, Zhi Hong Chen¹¹, Jodie Simpson¹², Jie Zhang¹³, Wei Min Li¹⁴, Gang Wang¹⁵, Peter Gerard Gibson¹⁶

Affiliations

¹ Department of Respiratory and Critical Care Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu, Sichuan, China.
² Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
³ Department of Respiratory and Critical Care Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu, Sichuan, China; Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
⁴ Department of Respiratory and Critical Care Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu, Sichuan, China; Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China; West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
⁵ Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu, Sichuan, China; Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China; West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
⁶ School of Life Sciences, University of Technology Sydney, Ultimo, NSW, Australia; Respiratory Cellular and Molecule Biology, Woolcock Institute of Medical Research, the University of Sydney, Sydney, NSW, Australia.
⁷ Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu, Sichuan, China; Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
⁸ Centre for Inflammation, Centenary Institute, Sydney, NSW, Australia; Faculty of Science, University of Technology Sydney, Ultimo, NSW, Australia; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, Australia.
⁹ Department of Pulmonary and Critical and Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
¹⁰ Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science & Technology, Wuhan, Hubei, China.
¹¹ Shanghai Institute of Respiratory Disease, Respiratory Division of Zhongshan Hospital, Fudan University, Shanghai, China.
¹² Priority Research Center for Healthy Lungs, Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW, Australia.
¹³ Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Jilin University, Changchun, Jilin, China.
¹⁴ Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
¹⁵ Department of Respiratory and Critical Care Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu, Sichuan, China. Electronic address: wcums-respiration@hotmail.com.
¹⁶ Priority Research Center for Healthy Lungs, Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW, Australia; Department of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.

PMID: 33482419
DOI: 10.1016/j.jaip.2021.01.004

Abstract

Background: Asthma, a heterogeneous disease, can be divided into 4 inflammatory phenotypes using induced sputum cell counts-eosinophilic asthma (EA), neutrophilic asthma (NA), mixed granulocytic asthma, and paucigranulocytic asthma (PGA). Although research has focused on EA and NA, there is little known about PGA.

Objective: To study the heterogeneity of PGA and identify possible PGA clusters to guide clinical treatment.

Methods: Patients with PGA were grouped by hierarchical cluster analysis and enrolled into a prospective cohort study to validate the clusters, relative to future risk of asthma exacerbations in a real-world setting. Clusters were validated by tree analysis in a separate population. Finally, we explored PGA stability.

Results: Cluster analysis of 145 patients with PGA identified 3 clusters: cluster 1 (n = 110, 75.9%) was "mild PGA," cluster 2 (n = 20, 13.8%) was "PGA with psychological dysfunction and rhinoconjunctivitis and other allergic diseases," and cluster 3 (n = 15, 10.3%) was "smoking-associated PGA." Cluster 3 had significantly increased risk of severe exacerbation (relative risk [RR] = 6.43, P = .01), emergency visit (RR = 8.61, P = .03), and hospitalization (RR = 12.94, P < .01). Results of the cluster analysis were successfully validated in an independent PGA population classified using decision tree analysis. Although PGA can transform into or develop from other phenotypes, 70% were stable over time.

Conclusions: Among 3 identified PGA clusters, cluster 3 had a higher risk of severe exacerbation. PGA heterogeneity indicates the requirement of novel targeted interventions.

Keywords: Asthma; Cluster analysis; Heterogeneity; Paucigranulocytic asthma; Phenotypes.

Publication types

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

MeSH terms

Asthma* / epidemiology
Cluster Analysis
Humans
Phenotype
Prospective Studies
Sputum