Journal Article

Cluster Analysis and Clinical Asthma Phenotypes

Shaw, Dominic E, Thomas, Michael, Haldar, Pranab, Pavord, Ian D, Berry, Michael A, Green, Ruth H, Wardlaw, Andrew J, Brightling, Christopher E

2008

Overview

Heterogeneity in asthma expression is multidimensional, including variability in clinical, physiologic, and pathologic parameters. Classification requires consideration of these disparate domains in a unified model. To explore the application of a multivariate mathematical technique, k-means cluster analysis, for identifying distinct phenotypic groups. We performed k-means cluster analysis in three independent asthma populations. Clusters of a population managed in primary care (n = 184) with predominantly mild to moderate disease, were compared with a refractory asthma population managed in secondary care (n = 187). We then compared differences in asthma outcomes (exacerbation frequency and change in corticosteroid dose at 12 mo) between clusters in a third population of 68 subjects with predominantly refractory asthma, clustered at entry into a randomized trial comparing a strategy of minimizing eosinophilic inflammation (inflammation-guided strategy) with standard care. Two clusters (early-onset atopic and obese, noneosinophilic) were common to both asthma populations. Two clusters characterized by marked discordance between symptom expression and eosinophilic airway inflammation (early-onset symptom predominant and late-onset inflammation predominant) were specific to refractory asthma. Inflammation-guided management was superior for both discordant subgroups leading to a reduction in exacerbation frequency in the inflammation-predominant cluster (3.53 [SD, 1.18] vs. 0.38 [SD, 0.13] exacerbation/patient/yr, P = 0.002) and a dose reduction of inhaled corticosteroid in the symptom-predominant cluster (mean difference, 1,829 mug beclomethasone equivalent/d [95% confidence interval, 307-3,349 mug]; P = 0.02). Cluster analysis offers a novel multidimensional approach for identifying asthma phenotypes that exhibit differences in clinical response to treatment algorithms.

• Publisher: Am Thoracic Soc,American Lung Association,Oxford University Press
• Subject: Adrenal Cortex Hormones - therapeutic use / Adult / Aged / Algorithms / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Asthma / Asthma - classification / Asthma - drug therapy / Asthma - physiopathology / Biological and medical sciences / Chronic obstructive pulmonary disease, asthma / Classification / Cluster Analysis / Datasets / Family physicians / Female / Humans / Inflammation / Inflammation - physiopathology / Intensive care medicine / Male / Medical sciences / Middle Aged / Phenotype / Pneumology / Primary care / Prospective Studies / Steroids / Taxonomy