Multidimensional Assessment of Asthma Identifies Clinically Relevant Phenotype Overlap: A Cross-Sectional Study

Yu Yu Han; Xin Zhang; Ji Wang; Gang Wang; Brian G Oliver; Hong Ping Zhang; De Ying Kang; Lei Wang; Zhi Xin Qiu; Wei Min Li; Gang Wang

doi:10.1016/j.jaip.2020.07.048

Multidimensional Assessment of Asthma Identifies Clinically Relevant Phenotype Overlap: A Cross-Sectional Study

J Allergy Clin Immunol Pract. 2021 Jan;9(1):349-362.e18. doi: 10.1016/j.jaip.2020.07.048. Epub 2020 Aug 11.

Authors

Yu Yu Han¹, Xin Zhang¹, Ji Wang¹, Gang Wang², Brian G Oliver³, Hong Ping Zhang⁴, De Ying Kang⁵, Lei Wang⁴, Zhi Xin Qiu⁶, Wei Min Li⁶, Gang Wang⁷

Affiliations

¹ Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, 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, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, 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; West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.
³ School of Life Sciences, University of Technology Sydney, Ultimo, Sydney, NSW, Australia; Respiratory Cellular and Molecule Biology, Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia.
⁴ Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, 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.
⁵ Department of Evidence-based Medicine and Clinical Epidemiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
⁶ Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
⁷ 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.

PMID: 32791248
DOI: 10.1016/j.jaip.2020.07.048

Abstract

Background: Asthma is a heterogeneous disease with multiple phenotypes; however, the relevance of phenotype overlap remains largely unexplored.

Objective: To examine the relationship between phenotype overlap and clinical and inflammatory profiles of asthma.

Methods: In this cross-sectional study, adult participants with stable asthma (n = 522) underwent multidimensional assessments. The 10 most common phenotypes of asthma were defined and then classified into those commonly associated with Type (T) 2 or non-T2 inflammation. Furthermore, phenotype overlap scores (POS), representing the cumulative concomitant phenotypes, were used to analyze its association with clinical and inflammatory asthmatic profiles.

Results: Among the 522 participants, 73.4% (n = 383) had phenotype overlap, and mixed T2 and non-T2 inflammation coexisted in 47.5% (n = 248). T2 POS was positively associated with eosinophils, IgE, and fractional exhaled nitric oxide (FeNO), and negatively with Asthma Quality of Life Questionnaire (AQLQ), sputum neutrophils, IL-17A, IL-8, and TNF-α. Non-T2 POS was positively associated with Asthma Control Questionnaire, neutrophils and sputum IL-8, and negatively with AQLQ, forced expiratory volume in 1 s, blood eosinophils, IgE, and FeNO (all P < .05). Patients with phenotypes that are associated with mixed T2 and non-T2 inflammation had elevated T2 inflammation biomarkers but worse asthma control. Both T2 (adjusted β = -0.191, P = .035) and non-T2 (adjusted β = 0.310, P < .001) POS were significantly associated with severe exacerbations.

Conclusions: Phenotype overlap is extremely common in asthmatic patients and significantly associated with clinical and inflammatory profiles. Patients with phenotypes associated with mixed T2 and non-T2 inflammation might be unresponsive to medications owing to increased non-T2 inflammation. Multidimensional asthma assessment identifies clinically relevant phenotype overlap.

Keywords: Asthma; Exacerbation; Overlap; Phenotype.

Publication types

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

MeSH terms

Adult
Asthma* / diagnosis
Asthma* / epidemiology
Biomarkers
Cross-Sectional Studies
Eosinophils
Humans
Nitric Oxide
Phenotype
Quality of Life*
Sputum

Substances

Biomarkers
Nitric Oxide