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Individualized therapy for persistent asthma in young children

Published:October 21, 2016DOI:https://doi.org/10.1016/j.jaci.2016.09.028

      Background

      Phenotypic presentations in young children with asthma are varied and might contribute to differential responses to asthma controller medications.

      Methods

      The Individualized Therapy for Asthma in Toddlers study was a multicenter, randomized, double-blind, double-dummy clinical trial in children aged 12 to 59 months (n = 300) with asthma necessitating treatment with daily controller (Step 2) therapy. Participants completed a 2- to 8-week run-in period followed by 3 crossover periods with daily inhaled corticosteroids (ICSs), daily leukotriene receptor antagonists, and as-needed ICS treatment coadministered with albuterol. The primary outcome was differential response to asthma medication based on a composite measure of asthma control. The primary analysis involved 2 stages: determination of differential response and assessment of whether 3 prespecified features (aeroallergen sensitization, previous exacerbations, and sex) predicted a differential response.

      Results

      Seventy-four percent (170/230) of children with analyzable data had a differential response to the 3 treatment strategies. Within differential responders, the probability of best response was highest for a 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 eosinophil counts of 300/μL or greater. In these children daily ICS use was associated with more asthma control days and fewer exacerbations compared with the other treatments.

      Conclusions

      In young children with asthma necessitating Step 2 treatment, phenotyping with aeroallergen sensitization and blood eosinophil counts is useful for guiding treatment selection and identifies children with a high exacerbation probability for whom treatment with a daily ICS is beneficial despite possible risks of growth suppression.

      Graphical abstract

      Key words

      Abbreviations used:

      ACD (Asthma control day), ECP (Eosinophil cationic protein), ICS (Inhaled corticosteroid), INFANT (Individualized Therapy for Asthma in Toddlers), LTE4 (Leukotriene E4), LTRA (Leukotriene receptor antagonist), mAPI (Modified Asthma Predictive Index), PEAK (Prevention of Early Asthma in Kids)
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      Linked Article

      • Nonatopic persistent asthma in children, a missed phenotype of asthma?
        Journal of Allergy and Clinical ImmunologyVol. 140Issue 4
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          We read with great interest the study by Fitzpatrick et al,1 showing how, in preschool children with persistent asthma, the type 2 inflammation biomarkers (ie, aeroallergen sensitization and/or increased blood eosinophilic counts) are strong predictors of a positive therapeutic response to daily inhaled corticosteroid treatment. To our knowledge, Fitzpatrick et al's study is the first to extrapolate and clearly identify a particular phenotype of persistent eosinophilic asthma, without pneumoallergen sensitization.
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