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

Abstract

Background In children with mild-moderate persistent asthma, identification of phenotypic predictors to guide selection of a controller regimen is essential. Objective Identify phenotypic characteristics retaining predictive value for the difference in treatment responses between twice daily fluticasone and once-daily montelukast. Methods Data from the Pediatric Asthma Controller Trial (PACT) 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 one-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 tests. The mean %-predicted pre-bronchodilator FEV1 was 97.8 +/-12.9, median PC20 was 0.93 mg/ml and median exhaled nitric oxide (eNO) was 25.2 ppb. A history of parental asthma best predicted the expected treatment benefit with fluticasone compared to montelukast in terms of gain in ACDs (adjusted p=0.02) and time to first exacerbation (adjusted p=0.05). Elevated baseline eNO predicted the differential treatment response for fluticasone regarding the gain in ACDs (adjusted p=0.01). Prior inhaled corticosteroid (ICS) use (adjusted p=0.01) and low PC20 (adjusted p=0.03) 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 parental history of asthma, elevated eNO, low PC20, or history of ICS use can expect the best long-term outcomes with ICS therapy, as compared to treatment with leukotriene receptor antagonists.

Individualized Therapy for Persistent Asthma in Young Children

“…14 Our primary predictor analysis was based on these prior observations 14 as well as findings from older children. 24,37,48,49 The fact that sex and previous exacerbations did not differentiate best response in the present study was surprising but may be due to differences in the baseline severity of the populations studied. However, a recent analysis of a birth cohort similarly found no association between sex and phenotype in young children at high risk for asthma development.…”

Advances in pediatric asthma in 2009: Gaining control of childhood asthma

“…Bacharier et al 45 reported that more favorable responses to an ICS than to placebo in high-risk preschool children over a 2-year period were more likely in those with an emergency department visit or hospitalization for asthma within the past year, children with aeroallergen sensitization, boys, and white participants. Knuffman et al 46 noted that in older children those with a parental history of asthma, increased fraction of exhaled nitric oxide (FeNO) levels, low methacholine PC 20 values, or a history of ICS use can expect the best long-term outcomes with ICS therapy compared with leukotriene receptor antagonists (LTRAs).…”

Fractional Exhaled Nitric Oxide: Indications and Interpretation

“…High FE NO (median 17.4 ppb) is associated with a good FEV 1 response (>15 % increase) while lower FE NO (median 11.1 ppb) is associated with a poor response (<5 % increase) [107]. FE NO is predictive of steroid responsiveness more consistently than spirometry, bronchodilator response, peak flow variation, or airway hyperreactivity to methacholine [107,[110][111][112], even when no sputum eosinophilia is demonstrated [113]. The reduction response of FE NO to corticosteroid treatment is both rapid (within 1 week, potentially as early as 48 h) and dose dependent [112,114,115].…”