Heterogeneity of Severe Asthma in Childhood: Confirmation by Cluster Analysis of Children in the NIH/NHLBI Severe Asthma Research Program (SARP)

• Type of Material: Article
• Authors: Anne M Fitzpatrick, Emory University; W. Gerald Teague, University of Virginia; Deborah A. Meyers, Wake Forest University; Stephen P. Peters, Wake Forest University; Xingnan Li, Wake Forest University; Huashi Li, Wake Forest University; Sally E. Wenzel, University of Pittsburgh; Shean Aujla, University of Pittsburgh; Mario Castro, Washington University; Leonard B. Bacharier, Washington University; Benjamin M. Gaston, University of Virginia; Eugene R. Bleecker, Wake Forest University; Wendy C. Moore, Wake Forest University
• Language: English
• Date: 2011-02
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 American Academy of Allergy, Asthma and Immunology. Published by Mosby, Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jaci.2010.11.015
• Title of Journal or Parent Work: Journal of Allergy and Clinical Immunology: In Practice
• ISSN: 2213-2201
• Volume: 127
• Issue: 2
• Start Page: 382
• End Page: 389.e1-13
• Grant/Funding Information: The Severe Asthma Research Program is a multicenter asthma research group funded by the National Heart Lung Blood Institute (NHLBI); This work was supported by National Institute of Health grants RO1 HL069170, RO1 HL069167, RO1 HL069174, RO1 HL69149, RO1 HL091762 and was supported in part by the Center for Developmental Lung Biology, Children’s Healthcare of Atlanta, and PHS grants UL1 RR025008, KL2 RR025009, TL1 RR025010, and UL1 RR024992 from the Clinical and Translational Science Award Program, National Institutes of Health, National Center for Research Resources
• Keywords: Children; Lung function; Phenotype; Asthma guidelines; Asthma; Severe asthma; Allergic sensitization; Cluster analysis
• Research Categories: Health Sciences, Immunology

Abstract

Background Asthma in children is a heterogeneous disorder with many phenotypes. Although unsupervised cluster analysis is a useful tool for identifying phenotypes, it has not been applied to school-age children with persistent asthma across a wide range of severities. Objectives This study determined how children with severe asthma are distributed across a cluster analysis and how well these clusters conform to current definitions of asthma severity. Methods Cluster analysis was applied to 12 continuous and composite variables from 161 children at 5 centers enrolled in the Severe Asthma Research Program (SARP). Results Four clusters of asthma were identified. Children in Cluster 1 (n = 48) had relatively normal lung function and less atopy, while children in Cluster 2 (n = 52) had slightly lower lung function, more atopy, and increased symptoms and medication usage. Cluster 3 (n = 32) had greater co-morbidity, increased bronchial responsiveness and lower lung function. Cluster 4 (n = 29) had the lowest lung function and the greatest symptoms and medication usage. Predictors of cluster assignment were asthma duration, the number of asthma controller medications, and baseline lung function. Children with severe asthma were present in all clusters, and no cluster corresponded to definitions of asthma severity provided in asthma treatment guidelines. Conclusions Severe asthma in children is highly heterogeneous. Unique phenotypic clusters previously identified in adults can also be identified in children, but with important differences. Larger validation and longitudinal studies are needed to determine the baseline and predictive validity of these phenotypic clusters in the larger clinical setting.