Characterization of within-subject responses to fluticasone and montelukast in childhood asthma.
BACKGROUND
Responses to inhaled corticosteroids (ICSs) and leukotriene receptor antagonists (LTRAs) vary among asthmatic patients.


OBJECTIVE
We sought to determine whether responses to ICSs and LTRAs are concordant for individuals or whether asthmatic patients who do not respond to one medication respond to the other.


METHODS
Children 6 to 17 years of age with mild-to-moderate persistent asthma were randomized to one of 2 crossover sequences, including 8 weeks of an ICS, fluticasone propionate (100 microg twice daily), and 8 weeks of an LTRA, montelukast (5-10 mg nightly depending on age), in a multicenter, double-masked, 18-week trial. Response was assessed on the basis of improvement in FEV 1 and assessed for relationships to baseline asthma phenotype-associated biomarkers.


RESULTS
Defining response as improvement in FEV 1 of 7.5% or greater, 17% of 126 participants responded to both medications, 23% responded to fluticasone alone, 5% responded to montelukast alone, and 55% responded to neither medication. Compared with those who responded to neither medication, favorable response to fluticasone alone was associated with higher levels of exhaled nitric oxide, total eosinophil counts, levels of serum IgE, and levels of serum eosinophil cationic protein and lower levels of methacholine PC(20) and pulmonary function; favorable response to montelukast alone was associated with younger age and shorter disease duration. Greater differential response to fluticasone over montelukast was associated with higher bronchodilator use, bronchodilator response, exhaled nitric oxide levels, and eosinophil cationic protein levels and lower methacholine PC(20) and pulmonary function values.


CONCLUSIONS
Response to fluticasone and montelukast vary considerably. Children with low pulmonary function or high levels of markers associated with allergic inflammation should receive ICS therapy. Other children could receive either ICSs or LTRAs.
Szefler
Stanley J
SJ
Department of Pediatrics, National Jewish Medical and Research Medical Center and University of Colorado Health Sciences Center, Denver, CO 80206, USA. szeflers@njc.org
Phillips
Brenda R
BR
Martinez
Fernando D
FD
Chinchilli
Vernon M
VM
Lemanske
Robert F
RF
Strunk
Robert C
RC
Zeiger
Robert S
RS
Larsen
Gary
G
Spahn
Joseph D
JD
Bacharier
Leonard B
LB
Bloomberg
Gordon R
GR
Guilbert
Theresa W
TW
Heldt
Gregory
G
Morgan
Wayne J
WJ
Moss
Mark H
MH
Sorkness
Christine A
CA
Taussig
Lynn M
LM
D000085:Acetates / Q000008:administration & dosage / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000293:Adolescent; D000730:Androstadienes / Q000008:administration & dosage / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D018592:Cross-Over Studies; D003521:Cyclopropanes; D004311:Double-Blind Method; D047150:Eosinophil Cationic Protein / Q000097:blood; D004804:Eosinophils / Q000473:pathology; D045853:Exhalation; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D009569:Nitric Oxide; D011237:Predictive Value of Tests; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D013440:Sulfides; D014797:Vital Capacity
D000085:Acetates; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D003521:Cyclopropanes; D011804:Quinolines; D013440:Sulfides; D009569:Nitric Oxide; D007073:Immunoglobulin E; D000068298:Fluticasone; D047150:Eosinophil Cationic Protein; C093875:montelukast