Predictors of asthma control and lung function responsiveness to step 3 therapy in children with uncontrolled asthma - 30/01/14
, David T. Mauger, PhD b, Nichole Reisdorph, PhD a, Ronina Covar, MD a, Jonathan Malka, MD a, Robert F. Lemanske, MD c, Wayne J. Morgan, MD d, Theresa W. Guilbert, MD c, Robert S. Zeiger, MD, PhD e, Leonard B. Bacharier, MD f, Stanley J. Szefler, MD aAbstract |
Background |
Predictors of improvement in asthma control and lung function to step 3 therapy in children with persistent asthma have not been identified despite reported heterogeneity in responsiveness.
Objective |
We sought to evaluate potential predictors of asthma control and lung function responsiveness to step 3 therapy.
Methods |
A post hoc analysis from the Best Add-On Giving Effective Response (BADGER) study tested the association between baseline biological, asthma control, pulmonary function, and demographic markers and responsiveness to step-up to a higher dose of inhaled corticosteroid (ICS step-up therapy) or addition of leukotriene receptor antagonist (LTRA step-up therapy) or long-acting β2-agonist (LABA step-up therapy).
Results |
In multivariate analyses higher impulse oscillometry reactance area was associated (P = .048) with a differential FEV1 response favoring LABA over ICS step-up therapy, whereas higher urinary leukotriene E4 levels were marginally (P = .053) related to a differential FEV1 response favoring LTRA over LABA step-up therapy. Predictors of differential responses comparing ICS with LTRA step-up therapy were not apparent, probably because of suppression of allergic markers with low-dose ICS treatment. Minimal overlap was seen across FEV1 and asthma control day predictors, suggesting distinct mechanisms related to lung function and asthma control day responses.
Conclusion |
Levels of impulse oscillometry reactance area indicating peripheral airway obstruction and urinary leukotriene E4 levels indicating cysteinyl leukotriene inflammation can differentiate LABA step-up responses from responses to LTRA or ICS step-up therapy. Further studies with physiologic, genetic, and biological markers related to these phenotypes will be needed to predict individual responses to LABA step-up therapy.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, Best Add-On Giving Effective Response, children, fraction of exhaled nitric oxide, inhaled corticosteroids, impulse oscillometry, long-acting β2-agonist, leukotriene E4, leukotriene receptor antagonist
Abbreviations used : AACD, ACD, AX, BADGER, Feno, FP, FVC, ICS, IOS, kPa/L/s, LABA, LTRA, R5, uLTE4
Plan
| Supported by grants from the National Heart, Lung, and Blood Institute (HL064307, HL064288, HL064295, HL064287, HL064305, and HL064313); the National Institute of Allergy and Infectious Diseases (T32AI007635); and the Clinical Translational Science Award program of the National Center for Research Resources (UL1-RR025011 [Wisconsin] and UL1-RR024992 [St Louis]). This study was performed in part by the General Clinical Research Centers at Washington University School of Medicine (M01-RR00036) and the University of Wisconsin (M01-RR03186). This study was also supported by Colorado CTSA Grant UL1 RR025780 from NCRR/NIH and UL1 TR000154 from NIH/NCATS. |
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| Disclosure of potential conflict of interest: N. Rabinovitch has received a grant from the National Institutes of Health (NIH) and has a patent through the NIH for measurement and analysis of leukotrienes. D. T. Mauger has received a grant from the National Heart, Lung, and Blood Institute (NHLBI); has received donated study drug and matching placebo from GlaxoSmithKline (GSK) and Merck; and has consultant arrangements with GSK and Merck. R. Covar has received grants from the NHLBI, GSK, and Boehringer Ingelheim and has consultant arrangements with GSK. R. F. Lemanske has received a grant, travel support, and fees for participation in review activities from the NIH; has consultant arrangements with Merck, Sepracor, SA Boney and Associates, LTD, GSK, the American Institute of Research, Genentech, Double Helix Development, and Boerhinger Ingelheim; is employed by the University of Wisconsin School of Medicine and Public Health; has received grants from the NHLBI and Pharmaxis; has received payment for lectures from Michigan Public Health Institute, Allegheny General Hospital, the American Academy of Pediatrics, West Allegheny Health Systems, California Chapter 4 of the American Academy of Pediatrics, the Colorado Allergy Society, the Pennsylvania Allergy and Asthma Association, Harvard Pilgrim Health, the California Society of Allergy, the NYC Allergy Society, the World Allergy Organization, the American College of Chest Physicians, APAPARI, the Western Society of Allergy, Asthma, and Immunology, and the Aspen Allergy Conference; has received payment for manuscript preparation from the American Academy of Allergy, Asthma & Immunology; and has received royalties from Elsevier and UpToDate. W. J. Morgan has received a grant and travel support from the NIH/NHLBI; is a board member for the American Lung Association of Arizona; has consultant arrangements with the Cystic Fibrosis Data Safety Monitoring Board and Genentech; is employed by the University of Arizona; has received grants from the Cystic Fibrosis Foundation, the National Institute of Allergy and Infectious Disease, and the NHLBI; has received payment for lectures from the American Academy of Allergy, Asthma & Immunology, Indiana University/Riley Children's Hospital, University of Tennessee/LeBonheur Children's Hospital, and the American Thoracic Society; and has received royalties from Elsevier. T. W. Guilbert has received a grant from the University of Wisconsin–Madison; is a board member for the American Board of Pediatrics Pediatric Pulmonary Subboard; has consultant arrangements with Teva, MAP Pharmaceuticals, GSK, and Merck; has received grants from the Centers for Disease Control and Prevention, the Department of Health and Human Services, Altus Pharmaceuticals, Inspire Pharmaceuticals, the NIH, the University of Wisconsin Medical and Education Research Committee, Array Biopharma, Teva, Mylan, the Forest Research Institute, F. Hoffman-LaRoche, GSK & Development Limited, MedImmune, KaloBios Pharmaceuticals, Vertex Pharmaceuticals, Roxane Laboratories and the CompleWare Corporation, Cystic Fibrosis Foundation Therapeutics, and Roche/Genentech; has received payment for lectures from Merck/Schering-Plough; has received royalties from UpToDate; and has received payment for development of educational presentations from Teva. R. S. Zeiger has received a grant and travel support from the NHLBI; is on the Research Advisory Board for DBV Technologies; has consultant arrangements with GSK, Genentech, Novartis, the NHLBI/Penn State, Aerocrine, Sunovion, and AstraZeneca; has received grants from Genentech, GSK, Aerocrine, Merck, MedImmune, and ThermoFischer; and has stock/stock options in DBV Technologies. L. B. Bacharier has consultant arrangements with Aerocrine, GSK, Genentech/Novartis, Merck, Schering, and Cephalon; has received a grant from the NIH/NHLBI; and has received payment for lectures from Aerocrine, AstraZeneca, Genentech, GSK, Merck, and Schering. S. J. Szefler has received a grant, travel support, fees for participation in review activities, and payment for writing or reviewing this manuscript from the NHLBI; has consultant arrangements with Merck, Genentech, Boehringer Ingelheim, and GSK; has received a grant from GSK; has received payment for lectures from Merck; has received payment for manuscript preparation from Genentech; and has submitted a patent for β-adrenergic receptor polymorphism through the NHLBI Childhood Asthma Research and Education Network. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 133 - N° 2
P. 350-356 - février 2014 Retour au numéro
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