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

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.

Keywords: AACD; ACD; AX; Annualized asthma control day; Asthma; Asthma control day; BADGER; Best Add-On Giving Effective Response; FP; FVC; Feno; Fluticasone propionate; Forced vital capacity; Fraction of exhaled nitric oxide; ICS; IOS; Impulse oscillometry; Inhaled corticosteroids; Kilopascal per liter per second; LABA; LTRA; Leukotriene receptor antagonist; Long-acting β(2)-agonist; R5; Reactance area; Resistance at 5 Hz; Urinary leukotriene E(4); children; fraction of exhaled nitric oxide; impulse oscillometry; inhaled corticosteroids; kPa/L/s; leukotriene E(4); leukotriene receptor antagonist; long-acting β(2)-agonist; uLTE(4).