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 E(4) (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 LTE(4)/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
LTE(4)/FE(NO) ratios were associated with a greater response to montelukast than FP therapy for FEV(1) 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 ACD responsiveness to MT than FP therapy (0.6 ACD increase, P=.03) [corrected]. In a combined study analysis, LTE(4): FE(NO) ratios were associated with greater response to MT than FP therapy for FEV(1) (1.8% increase, P =.0005) and ACDs (0.4 increase, P =.001)[corrected].Children with LTE(4)/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.


CONCLUSIONS
LTE(4)/FE(NO) ratios predict a better response to montelukast than FP therapy in children with mild-to-moderate asthma.
Rabinovitch
Nathan
N
Department of Pediatrics, National Jewish Health and the University of Colorado Denver School of Medicine, Denver, Colo 80206, USA.
Graber
Nora J
NJ
Chinchilli
Vernon M
VM
Sorkness
Christine A
CA
Zeiger
Robert S
RS
Strunk
Robert C
RC
Bacharier
Leonard B
LB
Martinez
Fernando D
FD
Szefler
Stanley J
SJ
D000085:Acetates / Q000627:therapeutic use*; D000293:Adolescent; D017668:Age of Onset; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002648:Child; D003521:Cyclopropanes; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis*; D011237:Predictive Value of Tests; D011804:Quinolines / Q000627:therapeutic use*; D013440:Sulfides; D016896:Treatment Outcome
D000085:Acetates; D015415:Biomarkers; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D009569:Nitric Oxide; D007073:Immunoglobulin E; D017999:Leukotriene E4; C093875:montelukast
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