Characterization of within-subject responses to fluticasone and montelukast in childhood asthma - 18/08/11
, Brenda R. Phillips, MS g, Fernando D. Martinez, MD a, Vernon M. Chinchilli, PhD g, Robert F. Lemanske, MD b, Robert C. Strunk, MD f, Robert S. Zeiger, MD, PhD d, e, Gary Larsen, MD c, Joseph D. Spahn, MD c, Leonard B. Bacharier, MD f, Gordon R. Bloomberg, MD f, Theresa W. Guilbert, MD a, Gregory Heldt, MD d, Wayne J. Morgan, MD a, Mark H. Moss, MD b, Christine A. Sorkness, PharmD b, Lynn M. Taussig, MD cfor the Childhood Asthma Research and Education Network of the National Heart, Lung, and Blood Institute
Reprint requests: Stanley J. Szefler, MD, National Jewish Medical and Research Center, Department of Pediatrics, Room J313, 1400 Jackson St, Denver, CO 80206.Tucson, Ariz, Madison, Wis, Denver, Colo, San Diego, Calif, St Louis, Mo, and Hershey, Pa
Abstract |
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 μg 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 FEV1 and assessed for relationships to baseline asthma phenotype-associated biomarkers.
Results |
Defining response as improvement in FEV1 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 PC20 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 PC20 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.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, biomarkers, exhaled nitric oxide, fluticasone propionate, inhaled corticosteroids, montelukast, pulmonary response
Abbreviations used : ECP, eDEM, eNO, FVC, ICS, LTRA, TEC, uLTE4
Plan
| Writing Committee: S. Szefler (Chair), B. Phillips, F. Martinez, V. Chinchilli, R. Lemanske, R. Strunk, R. Zeiger, G. Larsen, and J. Spahn. Supported by grants 5U10HL064287, 5U10HL064288, 5U10HL064295, 5U10HL064307, 5U10HL064305, and 5U10HL064313 from the National Heart, Lung, and Blood Institute. This study was carried out in part in the General Clinical Research Centers at Washington University School of Medicine (M01 RR00036) and National Jewish Medical and Research Center (M01 RR00051). Potential conflicts of interest: Stanley J. Szefler has consultant arrangements with AstraZeneca, GlaxoSmithKline, Aventis, and Merck, and has received grants/research support from National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) Childhood Asthma Management Program, NIH/NHLBI Inflammation, Airway Reactivity and Asthma, NIH/National Institute of Child Health and Development (NICHD) Pediatric Pharmacology Research Unit Network, NHLBI Childhood Asthma Research and Education Network, NIH/NHLBI Asthma Clinical Research Network, NIH/National Institute of Allergy and Infectious Diseases (NIAID) Inner City Asthma Consortium, Ross Pharmaceuticals, and AstraZeneca; Fernando D. Martinez serves on the Merck Advisory Board and has received lecture fees from GlaxoSmithKline and Merck; Vernon M. Chinchilli has consultant arrangements with Wyeth Pharmaceutical, Bristol-Myers Squibb Pharmaceutical, and Procter & Gamble Pharmaceutical, has a provisional patent application for “Genetic predictor of efficacy of anti-asthmatic agent for improving pulmonary function,” and is the principal investigator for a Childhood Asthma Research and Education Network Data Coordinating Center, funded by the NHLBI; Robert Lemanske, Jr, has consultant arrangements with Aventis and AstraZeneca, has a patent pending on β receptor haplotypes and their relationship to responses to asthma medications, and is on the Speakers' Bureau of Aventis, AstraZeneca, Merck, GlaxoSmithKline, Schering, and Novartis; Robert S. Zeiger has consultant arrangements with GlaxoSmithKline, Merck, Astra, and Novartis/Genentech; Gary L. Larsen is an Advair Pediatric Specialist for GlaxoSmithKline and has received grants/research support from NIH; Joseph D. Spahn has consultant arrangements with, has received grants/research support from, and is on the Speakers' Bureau of GlaxoSmithKline and AstraZeneca, as well as receiving grants/research support from Merck; Leonard B. Bacharier has received grants/research support from NIH/NHLBI and is on the Speakers' Bureau of GlaxoSmithKline, Merck, and Genentech/Novartis; Theresa Guilbert has consultant arrangements with, has received grants/research support from, and is on the Speakers' Bureau of GlaxoSmithKline and is also on the Speakers' Bureau of AstraZeneca; Wayne J. Morgan has consultant arrangements with Genentech; Christine A. Sorkness has consultant arrangements with and has received grants/research support from GlaxoSmithKline, as well as being on the Speakers' Bureau for GlaxoSmithKline, AstraZeneca, and Genentech/Novartis; and Lynn M. Taussig has consultant arrangements with Glaxo. |
Vol 115 - N° 2
P. 233-242 - février 2005 Retour au numéro
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