Advancing precision medicine for asthma in young children

Published Online: October 21, 2016

Although asthma treatment guidelines have resulted in standardization of care and improved outcomes for children, phenotypic heterogeneity is abundant. Young children are particularly diverse with variable presentations in early life that correspond to different disease trajectories, yet they are incompletely studied and significant treatment gaps remain. For example, many young children with asthma have prolonged asymptomatic periods, raising the question whether daily treatment with inhaled corticosteroids (ICS) is truly necessary.  urthermore, even among young children with persistent symptoms, the response to ICS is inconsistent.

In a recent report published in The Journal of Allergy and Clinical Immunology (JACI), Fitzpatrick and colleagues present the results of the NIH/NHLBI AsthmaNet’s Individualized Therapy for Asthma in Toddlers (INFANT) trial, which characterized phenotypic heterogeneity in young children with emerging asthma eligible for receiving treatment with daily asthma controller medications and examined the relationship between phenotypic features and biomarkers to asthma medication response profiles. Children 12-59 months of age at 18 sites in the United States completed a run-in period of 2-8 weeks followed by a randomized cross-over of three 16-week treatment periods with daily ICS, daily leukotriene receptor antagonist (LTRA), and as-needed albuterol co-administered with ICS. Biomarkers were quantified at the randomization visit and included peripheral blood eosinophil counts, serum eosinophil cationic protein (ECP) concentrations, total serum immunoglobulin E (IgE) and specific IgE concentrations, urinary leukotriene E4 (LTE4) concentrations.  

The primary outcome was the differential response to the three asthma therapies based on two asthma control measures, which encompassed the domains of risk and impairment. Children were defined as differential responders if, first, the time to an asthma exacerbation was at least four weeks longer, or second, if the number of annualized asthma control days was at least 31 days more for one treatment than another, in that order. If neither threshold was met, the participant was considered a “non-differential responder.” The primary analysis involved two stages: first determining whether one group responded better to one treatment than the others, and second to determine whether a number of pre-specified phenotypic characteristics affected outcomes.

Seventy-four percent (170 of 230) of children had a differential response to the three treatment strategies. Within differential responders, the probability of best response was highest for daily ICS for just over half of the children. Within differential responders, aeroallergen sensitization was associated with a differential response favoring daily ICS. 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. No predictor identified a group in which LTRA or as-needed ICS were more likely than daily ICS to yield best response

The INFANT study demonstrates, for the first time, differential responses to asthma medications in young children that can be predicted with clinical biomarkers. In young children with asthma necessitating long-term controller 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. The results support personalization of asthma therapy in this age group. The next step will be to characterize the population likely to respond best to alternative management strategies.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

Close-up of pine tree branches in Winter Close-up of pine tree branches in Winter