Childhood asthma clusters and response to therapy in clinical trials

Timothy S. Chang, Robert F. Lemanske, David Mauger, Anne M. Fitzpatrick, Christine A. Sorkness, Stanley J. Szefler, Ronald E. Gangnon, C. David Page, Daniel J. Jackson

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)363-369.e3
JournalJournal of Allergy and Clinical Immunology
Volume133
Issue number2
DOIs
StatePublished - Feb 2014

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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