Phenotypic predictors of long-term response to inhaled corticosteroid and leukotriene modifier therapies in pediatric asthma

Background: In children with mild-to-moderate persistent asthma, identification of phenotypic predictors to guide selection of a controller regimen is essential. Objective: We sought to identify phenotypic characteristics having predictive value for the difference in treatment responses between twice-daily fluticasone and once-daily montelukast. Methods: Data from the Pediatric Asthma Controller Trial were assessed with multivariate analysis. Outcomes included the change in asthma control days (ACDs), FEV₁, peak expiratory flow, and time to first asthma exacerbation measured over a 1-year treatment period. Results: The mean age was 9.6 ± 2.1 years, 60% were male, 50% had a parental history of asthma, and 78% had positive aeroallergen skin prick test responses. The mean percent predicted prebronchodilator FEV₁ was 97.8% ± 12.9%, the median PC₂₀ value was 0.93 mg/mL, and the median exhaled nitric oxide (eNO) level was 25.2 ppb. A history of parental asthma best predicted the expected treatment benefit with fluticasone compared with montelukast in terms of gain in ACDs (adjusted P = .02) and time to first exacerbation (adjusted P = .05). Increased baseline eNO levels predicted the differential treatment response for fluticasone regarding the gain in ACDs (adjusted P = .01). Prior inhaled corticosteroid (ICS) use (adjusted P = .01) and low PC₂₀ values (adjusted P = .03) each predicted the expected treatment benefit with fluticasone over montelukast regarding time to first exacerbation. No phenotypic characteristics predicted treatment benefits for montelukast over fluticasone for either outcome. Conclusions: Physicians treating children with a parental history of asthma, increased eNO levels, low PC₂₀ values, or a history of ICS use can expect the best long-term outcomes with ICS therapy compared with treatment with leukotriene receptor antagonists.