Childhood asthma clusters and response to therapy in clinical trials.

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

Journal: The Journal of allergy and clinical immunology 2014;133(2):363-9

PMID: 24139497

Free Full Text on PubMed Central View on PubMed

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 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.

Address: Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wis.; Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wis; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.; Department of Health Evaluation Sciences, Pennsylvania State University, Hershey, Pa.; Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga.; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.; Department of Pediatrics, National Jewish Health and University of Colorado School of Medicine, Denver, Colo.; Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wis. Electronic address: [email protected].

DOI: 10.1016/j.jaci.2013.09.002

Link outs

Free resources

Full Text Sources:

Medical:

Other Literature Sources:

https://scite.ai/reports/24139497

Miscellaneous:

https://assays.cancer.gov/CPTAC-994

Subscription / membership required

Full Text Sources:

MeSH Terms: Acetates, Adolescent, Adrenergic beta-2 Receptor Agonists, Albuterol, Androstadienes, Anti-Asthmatic Agents, Asthma, Bronchodilator Agents, Child, Cross-Over Studies, Cyclopropanes, Double-Blind Method, Drug Combinations, Female, Fluticasone, Fluticasone-Salmeterol Drug Combination, Forced Expiratory Volume, Humans, Leukotriene Antagonists, Male, Quinolines, Sulfides