Childhood asthma clusters and response to therapy in clinical trials

• Type of Material: Article
• Authors: Timothy S. Chang, University of Wisconsin; Robert F. Lemanske, University of Wisconsin; David Mauger, Pennsylvania State University; Anne Fitzpatrick, Emory University; Christine A. Sorkness, University of Wisconsin; Stanley J. Szefler, University of Colorado; Ronald E. Gangnon, University of Wisconsin; C. David Page, University of Wisconsin; Daniel J. Jackson, University of Wisconsin
• Language: English
• Date: 2014-02-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 American Academy of Allergy, Asthma & Immunology.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jaci.2013.09.002
• Title of Journal or Parent Work: Journal of Allergy and Clinical Immunology
• ISSN: 0091-6749
• Volume: 133
• Issue: 2
• Start Page: 363
• End Page: +
• Grant/Funding Information: Supported also by grants (5U10HL064287, 5U10HL064288, 5U10HL064295, 5U10HL064307, 5U10HL064305, and 5U10HL064313) from the NHLBI; a grant (5UL1RR02499204) from the Washington University School of Medicine CTSA Infrastructure for Pediatric Research; a grant (1UL1RR025011) from the Madison CTSA; a grant (UL1RR025780) to the Colorado CTSA from the National Center for Research Resources; and grants to the General Clinical Research Centers at Washington University School of Medicine (M01 RR00036), National Jewish Health (M01 RR00051), and the University of New Mexico (5M01 RR00997).; Supported by the Clinical and Translational Science Award (CTSA) program through the National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS) UL1TR000427 and National Heart Lung and Blood Institute (NHLBI) Fellowship F30HL112491.
• Keywords: Science & Technology; Asthma; EQUATIONS; clustering; pediatric; Immunology; IMPUTATION; therapy response; PHENOTYPES; Allergy; IDENTIFICATION; replication; Life Sciences & Biomedicine; clinical trials; CHILDREN
• Research Categories: Health Sciences, Rehabilitation and Therapy; Biology, Biostatistics

Abstract

Background Childhood asthma clusters, or subclasses, have been developed by computational methods without evaluation of clinical utility. Objective To replicate and determine whether childhood asthma clusters previously identified computationally in the Severe Asthma Research Program (SARP) are associated with treatment responses in Childhood Asthma Research and Education (CARE) Network clinical trials. Methods A cluster assignment model was determined by using SARP participant data. A total of 611 participants 6 to 18 years old from 3 CARE trials were assigned to SARP pediatric clusters. Primary and secondary outcomes were analyzed by cluster in each trial. Results CARE participants were assigned to SARP clusters with high accuracy. Baseline characteristics were similar between SARP and CARE children of the same cluster. Treatment response in CARE trials was generally similar across clusters. However, with the caveat of a smaller sample size, children in the early-onset/severe-lung function cluster had best response with fluticasone/salmeterol (64% vs 23% 2.5× fluticasone and 13% fluticasone/montelukast in the Best ADd-on Therapy Giving Effective Responses trial; P =.011) and children in the early-onset/comorbidity cluster had the least clinical efficacy to treatments (eg, -0.076% change in FEV 1 in the Characterizing Response to Leukotriene Receptor Antagonist and Inhaled Corticosteroid trial). Conclusions In this study, we replicated SARP pediatric asthma clusters by using a separate, large clinical trials network. Early-onset/severe-lung function and early-onset/comorbidity clusters were associated with differential and limited response to therapy, respectively. Further prospective study of therapeutic response by cluster could provide new insights into childhood asthma treatment.