Individualized Therapy for Persistent Asthma in Young Children

Abstract Background Phenotypic presentations in young children with asthma are varied and may contribute to differential responses to asthma controller medications. Methods The Individualized Therapy for Asthma in Toddlers (INFANT) study was a multicenter, randomized, double-blind, double-dummy, clinical trial in children age 12-59 months (n=300) with asthma necessitating treatment with daily controller (Step 2) therapy. Participants completed a 2-8 week run-in period followed by three crossover periods with daily inhaled corticosteroid (ICS) , daily leukotriene receptor antagonist (LTRA) , and as-needed ICS treatment co-administered with albuterol. The primary outcome was differential response to asthma medication based on a composite measure of asthma control. The primary analysis involved two stages: determination of differential response, and assessment of whether three pre-specified features (aeroallergen sensitization, previous exacerbations, sex) predicted differential response. Results 74% (170 of 230) of children with analyzable data had a differential response to the three treatment strategies. Within differential responders, the probability of best response was highest for daily ICS and was predicted by aeroallergen sensitization, but not exacerbation history or sex. The probability of best response to daily ICS was further increased in children with both aeroallergen sensitization and blood eosinophils ≥300/μL. In these children, daily ICS was associated with more asthma control days and fewer exacerbations compared to the other treatments. Conclusions In young children with asthma necessitating Step 2 treatment, phenotyping with aeroallergen sensitization and blood eosinophils is useful for guiding treatment selection and identifies children with a high exacerbation probability for whom treatment with daily ICS is beneficial despite possible risks of growth suppression.