Childhood asthma clusters and response to therapy in clinical trials.

Journal Article (Journal Article)

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 FEV1 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.

Full Text

Duke Authors

Cited Authors

  • Chang, TS; Lemanske, RF; Mauger, DT; Fitzpatrick, AM; Sorkness, CA; Szefler, SJ; Gangnon, RE; Page, CD; Jackson, DJ; Childhood Asthma Research and Education (CARE) Network Investigators,

Published Date

  • February 2014

Published In

Volume / Issue

  • 133 / 2

Start / End Page

  • 363 - 369

PubMed ID

  • 24139497

Pubmed Central ID

  • PMC3960405

Electronic International Standard Serial Number (EISSN)

  • 1097-6825

Digital Object Identifier (DOI)

  • 10.1016/j.jaci.2013.09.002


  • eng

Conference Location

  • United States