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J Allergy Clin Immunol. 2014 Feb;133(2):363-9. doi: 10.1016/j.jaci.2013.09.002. Epub 2013 Oct 15.

Childhood asthma clusters and response to therapy in clinical trials.

Author information

1
Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
2
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.
3
Department of Health Evaluation Sciences, Pennsylvania State University, Hershey, Pa.
4
Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga.
5
Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
6
Department of Pediatrics, National Jewish Health and University of Colorado School of Medicine, Denver, Colo.
7
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wis. Electronic address: djj@medicine.wisc.edu.

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.

KEYWORDS:

Asthma; BADGER; Best ADd-on Therapy Giving Effective Responses; CARE; CLIC; Characterizing Response to Leukotriene Receptor Antagonist and Inhaled Corticosteroid; Childhood Asthma Research and Education; LDA; Linear discriminant analysis; PACT; Pediatric Asthma Controller Trial; QDA; Quadratic discriminant analysis; SARP; Severe Asthma Research Program; clinical trials; clustering; pediatric; replication; therapy response

PMID:
24139497
PMCID:
PMC3960405
DOI:
10.1016/j.jaci.2013.09.002
[Indexed for MEDLINE]
Free PMC Article

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