Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program.

TitleIdentification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program.
Publication TypeJournal Article
Year of Publication2010
AuthorsMoore WC, Meyers DA, Wenzel SE, Teague GW, Li H, Li X, D'Agostino R, Castro M, Curran-Everett D, Fitzpatrick AM, Gaston B, Jarjour NN, Sorkness R, Calhoun WJ, Chung K F, Comhair SAA, Dweik RA, Israel E, Peters SP, Busse WW, Erzurum SC, Bleecker ER
Corporate AuthorsNational Heart, Lung, and Blood Institute's Severe Asthma Research Program
JournalAm J Respir Crit Care Med
Volume181
Issue4
Pagination315-23
Date Published2010 Feb 15
ISSN1535-4970
KeywordsAdolescent, Adrenal Cortex Hormones, Adult, Age Factors, Age of Onset, Aged, Aged, 80 and over, Anti-Asthmatic Agents, Asthma, Biological Markers, Bronchodilator Agents, Child, Cluster Analysis, Cohort Studies, Discriminant Analysis, Female, Humans, Male, Middle Aged, Phenotype, Respiratory Function Tests, Sex Factors, Young Adult
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 FEV(1), 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.

DOI10.1164/rccm.200906-0896OC
Alternate JournalAm. J. Respir. Crit. Care Med.
PubMed ID19892860
PubMed Central IDPMC2822971
Grant ListHL087665 / HL / NHLBI NIH HHS / United States
HL69116 / HL / NHLBI NIH HHS / United States
HL69130 / HL / NHLBI NIH HHS / United States
HL69149 / HL / NHLBI NIH HHS / United States
HL69155 / HL / NHLBI NIH HHS / United States
HL69167 / HL / NHLBI NIH HHS / United States
HL69170 / HL / NHLBI NIH HHS / United States
HL69174 / HL / NHLBI NIH HHS / United States
HL69349 / HL / NHLBI NIH HHS / United States
M01 RR018390 / RR / NCRR NIH HHS / United States
M01 RR03186 / RR / NCRR NIH HHS / United States
M01RR07122 / RR / NCRR NIH HHS / United States
UL1 RR024992-04 / RR / NCRR NIH HHS / United States

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