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 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.