Identification of Asthma Phenotypes Using Cluster Analysis in the Severe Asthma Research Program

TLDR

The Severe Asthma Research Program cohort comprises persistent asthma patients with detailed phenotypic data, and prior studies have compared mild, moderate, and severe asthma features using univariate methods. The study seeks to identify novel asthma phenotypes using unsupervised hierarchical cluster analysis. After reducing 628 variables to 34 core variables by eliminating redundancy and converting categorical data to ranked ordinal composites, the authors performed unsupervised hierarchical cluster analysis on 726 subjects. Cluster analysis revealed five distinct phenotypes: Cluster 1—early‑onset atopic asthma with normal lung function and minimal medication use; Cluster 2—early‑onset atopic asthma with preserved lung function but higher medication and utilization; Cluster 3—older obese women with late‑onset nonatopic asthma, moderate FEV1 reduction, and frequent oral steroid use; Clusters 4 and 5—severe airflow obstruction with bronchodilator responsiveness but differing in normal lung function attainment, age of onset, atopy, and steroid use; all clusters meet ATS severe asthma criteria, underscoring clinical heterogeneity and the need for new severity classification approaches.

Abstract

Rationale: The Severe Asthma Research Program cohort includes subjects with persistent asthma who have undergone detailed phenotypic characterization. Previous univariate methods compared features of mild, moderate, and severe asthma.Objectives: To identify novel asthma phenotypes using an unsupervised hierarchical cluster analysis.Methods: Reduction of the initial 628 variables to 34 core variables was achieved by elimination of redundant data and transformation of categorical variables into ranked ordinal composite variables. Cluster analysis was performed on 726 subjects.Measurements and Main Results: Five groups were identified. Subjects in Cluster 1 (n = 110) have early onset atopic asthma with normal lung function treated with two or fewer controller medications (82%) and minimal health care utilization. Cluster 2 (n = 321) consists of subjects with early-onset atopic asthma and preserved lung function but increased medication requirements (29% on three or more medications) and health care utilization. Cluster 3 (n = 59) is a unique group of mostly older obese women with late-onset nonatopic asthma, moderate reductions in FEV1, and frequent oral corticosteroid use to manage exacerbations. Subjects in Clusters 4 (n = 120) and 5 (n = 116) have severe airflow obstruction with bronchodilator responsiveness but differ in to their ability to attain normal lung function, age of asthma onset, atopic status, and use of oral corticosteroids.Conclusions: Five distinct clinical phenotypes of asthma have been identified using unsupervised hierarchical cluster analysis. All clusters contain subjects who meet the American Thoracic Society definition of severe asthma, which supports clinical heterogeneity in asthma and the need for new approaches for the classification of disease severity in asthma.