title: Childhood asthma clusters and response to therapy in clinical trials.
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.
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Chang
authors.affiliation: 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.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Lemanske
authors.affiliation: Department of Health Evaluation Sciences, Pennsylvania State University, Hershey, Pa.
authors.forename: David T
authors.initials: DT
authors.lastname: Mauger
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fitzpatrick
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Sorkness
authors.affiliation: Department of Pediatrics, National Jewish Health and University of Colorado School of Medicine, Denver, Colo.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Szefler
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gangnon
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
authors.forename: C David
authors.initials: CD
authors.lastname: Page
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wis. Electronic address: djj@medicine.wisc.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Jackson
mesh_terms: D000085:Acetates / Q000008:administration & dosage; D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives; D000730:Androstadienes / Q000008:administration & dosage; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage; D002648:Child; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D000068298:Fluticasone; D000068297:Fluticasone-Salmeterol Drug Combination; D005541:Forced Expiratory Volume; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage; D008297:Male; D011804:Quinolines / Q000008:administration & dosage; D013440:Sulfides
chemical_list: D000085:Acetates; D058666:Adrenergic beta-2 Receptor Agonists; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D003521:Cyclopropanes; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D000068298:Fluticasone; C093875:montelukast; D000420:Albuterol
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