TY - JOUR
T1 - Childhood asthma clusters and response to therapy in clinical trials
AU - Chang, Timothy S.
AU - Lemanske, Robert F.
AU - Mauger, David
AU - Fitzpatrick, Anne M.
AU - Sorkness, Christine A.
AU - Szefler, Stanley J.
AU - Gangnon, Ronald E.
AU - Page, C. David
AU - Jackson, Daniel J.
N1 - Funding Information:
Disclosure of potential conflict of interest: T. S. Chang has received research support from the National Institutes of Health (NIH)/National Center for Research Resources, NIH/National Heart, Lung, and Blood Institute (NHLBI), and NIH/Medical Scientist Training Program . R. F. Lemanske, Jr has received research support, travel support, and fees for participation in review activities from the NIH; has received consultancy fees from Merck, Sepracor, SA Boney and Associates Ltd, GlaxoSmithKline (GSK), American Institute of Research, Genentech, Inc, Double Helix Development, Inc, and Boehringer Ingelheim; is employed by the University of Wisconsin School of Medicine and Public Health; has received research support from the NHLBI and Pharmaxis ; has received lecture fees from Michigan Public Health Institute, Allegheny General Hospital, the American Academy of Pediatrics, West Allegheny Health Systems, California Chapter 4 AAP, the Colorado Allergy Society, Pennsylvania Allergy and Asthma Association, Harvard Pilgrim Health, California Society of Allergy, the NYC Allergy Society, the World Allergy Organization, the American College of Chest Physicians, Asia Pacific Association of Pediatric Allergy, Respirology and Immunology, and the Western Society of Allergy, Asthma, and Immunology; has received payment for manuscript preparation from the American Academy of Allergy, Asthma & Immunology (AAAAI); and receives royalties from Elsevier and UpToDate. D. T. Mauger has received research support from the NIH/NHLBI ; has received provision of a study drug from GSK and Merck; and has received consultancy fees from GSK, Merck, Boehringer Ingelheim, and Biocryst. A. M. Fitzpatrick has received consultancy fees from MedImmune, Inc, Consulting, Merck Scientific Advisory Board, GSK Scientific Advisory Board, and Genentech Consulting. C. A. Sorkness has received research support from the NHLBI Care Network. S. J. Szefler has received research support, travel support, fees for participation in review activities, and payment for writing/reviewing the manuscript from the NHLBI; has received consultancy fees from Merck, Genentech, Boehringer Ingelheim, and GSK; has received research support from GSK; has received lecture fees from Merck; has received payment for manuscript preparation from Genentech; and has a previously submitted patent with the NHLBI. C. D. Page has received research support from the NIH and has received consultancy fees from MedSeek. D. J. Jackson has received research support from the NIH and Pharmaxis and has received consultancy fees from Gilead and GSK. R. E. Gangnon declares that he has no relevant conflicts of interest.
Funding Information:
This study was supported by the Clinical and Translational Science Award (CTSA) program through the National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS) UL1TR000427 and National Heart, Lung, and Blood Institute (NHLBI) Fellowship F30HL112491 . The study was also supported by grants ( 5U10HL064287, 5U10HL064288, 5U10HL064295, 5U10HL064307, 5U10HL064305, and 5U10HL064313 ) from the NHLBI ; a grant ( 5UL1RR02499204 ) from the Washington University School of Medicine CTSA Infrastructure for Pediatric Research ; a grant ( 1UL1RR025011 ) from the Madison CTSA ; a grant ( UL1RR025780 ) to the Colorado CTSA from the National Center for Research Resources ; and grants to the General Clinical Research Centers at Washington University School of Medicine ( M01 RR00036 ), National Jewish Health ( M01 RR00051 ), and the University of New Mexico ( 5M01 RR00997 ).
PY - 2014/2
Y1 - 2014/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jaci.2013.09.002
DO - 10.1016/j.jaci.2013.09.002
M3 - Article
C2 - 24139497
AN - SCOPUS:84895058912
VL - 133
SP - 363-369.e3
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 2
ER -