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

Nathan Rabinovitch, Nora J. Graber, Vernon M. Chinchilli, Christine A. Sorkness, Robert S. Zeiger, Robert C. Strunk, Leonard B. Bacharier, Fernando D. Martinez, Stanley J. Szefler

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58 Scopus citations


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 (FENO) 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/FENO 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/FENO 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/FENO 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/FENO 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/FENO ratios predict a better response to montelukast than FP therapy in children with mild-to-moderate asthma.

Original languageEnglish
Pages (from-to)545-551.e1-e4
JournalJournal of Allergy and Clinical Immunology
Issue number3
StatePublished - Sep 2010


  • Asthma
  • biomarkers
  • fluticasone propionate
  • inhaled corticosteroids
  • leukotriene E
  • montelukast


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