Urinary leukotriene E₄/exhaled nitric oxide ratio and montelukast response in childhood asthma

Background: A subset of children with asthma respond better to leukotriene receptor antagonists than to inhaled corticosteroids. Information is needed to identify children with these preferential responses. Objective: We sought to determine whether the ratio of urinary leukotriene E₄ (LTE ₄) to fractional exhaled nitric oxide (FE_NO) delineates children with preferential responsiveness to montelukast compared with fluticasone propionate (FP) therapy. Methods: Data from 318 children with mild-to-moderate asthma enrolled in 2 National Heart, Lung, and Blood Institute Childhood Asthma Research and Education Network studies (Characterizing the Response to a Leukotriene Receptor Antagonist and an Inhaled Corticosteroid [CLIC] and the Pediatric Asthma Controller Trial [PACT]) were analyzed. The association between LTE₄/FE_NO ratios at baseline and improved lung function or asthma control days (ACDs) with montelukast and FP therapy was determined, and phenotypic characteristics related to high ratios were assessed. Results: LTE₄/FE_NO ratios were associated with a greater response to montelukast than FP therapy for FEV₁ measurements (2.1% increase per doubling of ratio, P = .001) and for ACDs per week (0.3-ACD increase, P = .009) in the CLIC study. In PACT the ratio was associated with greater FEV₁ responsiveness to montelukast than FP therapy (0.6% increase, P = .03). In a combined study analysis, LTE ₄/FE_NO ratios were associated with greater response to montelukast than FP therapy for FEV₁ (0.8% increase, P = .0005) and ACDs (0.3-ACD increase, P = .008). Children with LTE₄/FE_NO ratios at or above the 75th percentile were likely (P < .05) to be younger and female and exhibit lower levels of atopic markers and methacholine reactivity. Conclusion: LTE₄/FE_NO ratios predict a better response to montelukast than FP therapy in children with mild-to-moderate asthma.