Nathan Rabinovitch1, David T Mauger2, Nichole Reisdorph3, Ronina Covar3, Jonathan Malka3, Robert F Lemanske4, Wayne J Morgan5, Theresa W Guilbert4, Robert S Zeiger6, Leonard B Bacharier7, Stanley J Szefler3. 1. Department of Pediatrics, National Jewish Health and University of Colorado Denver School of Medicine, Denver, Colo. Electronic address: rabinovitchn@njhealth.org. 2. Department of Health Evaluation Sciences, Pennsylvania State University, Hershey, Pa. 3. Department of Pediatrics, National Jewish Health and University of Colorado Denver School of Medicine, Denver, Colo. 4. University of Wisconsin School of Medicine and Public Health, Madison, Wis. 5. Arizona Respiratory Center, University of Arizona, Tucson, Ariz. 6. Department of Allergy, Kaiser Permanente, and the Department of Pediatrics, University of California-San Diego, San Diego, Calif. 7. Department of Pediatrics, Washington University, St Louis, Mo.
Abstract
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.
RCT Entities:
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.
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