Predictors of asthma control and lung function responsiveness to step 3 therapy in children with uncontrolled asthma

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 beta(2)-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 E-4 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 E-4 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.