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.
RCT Entities:
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.
Authors: Kelan G Tantisira; Amy Damask; Stanley J Szefler; Brooke Schuemann; Amy Markezich; Jessica Su; Barbara Klanderman; Jody Sylvia; Rongling Wu; Fernando Martinez; Homer A Boushey; Vernon M Chinchilli; Dave Mauger; Scott T Weiss; Elliot Israel Journal: Am J Respir Crit Care Med Date: 2012-04-26 Impact factor: 21.405
Authors: Niloufar Farzan; Susanne J Vijverberg; Anand K Andiappan; Lambang Arianto; Vojko Berce; Natalia Blanca-López; Hans Bisgaard; Klaus Bønnelykke; Esteban G Burchard; Paloma Campo; Glorisa Canino; Bruce Carleton; Juan C Celedón; Fook Tim Chew; Wen Chin Chiang; Michelle M Cloutier; Denis Daley; Herman T Den Dekker; F Nicole Dijk; Liesbeth Duijts; Carlos Flores; Erick Forno; Daniel B Hawcutt; Natalia Hernandez-Pacheco; Johan C de Jongste; Michael Kabesch; Gerard H Koppelman; Vangelis G Manolopoulos; Erik Melén; Somnath Mukhopadhyay; Sara Nilsson; Colin N Palmer; Maria Pino-Yanes; Munir Pirmohamed; Uros Potočnik; Jan A Raaijmakers; Katja Repnik; Maximilian Schieck; Yang Yie Sio; Rosalind L Smyth; Csaba Szalai; Kelan G Tantisira; Steve Turner; Marc P van der Schee; Katia M Verhamme; Anke H Maitland-van der Zee Journal: Pharmacogenomics Date: 2017-06-22 Impact factor: 2.533
Authors: Gary L Larsen; Wayne Morgan; Gregory P Heldt; David T Mauger; Susan J Boehmer; Vernon M Chinchilli; Robert F Lemanske; Fernando Martinez; Robert C Strunk; Stanley J Szefler; Robert S Zeiger; Lynn M Taussig; Leonard B Bacharier; Theresa W Guilbert; Shelley Radford; Christine A Sorkness Journal: J Allergy Clin Immunol Date: 2008-12-12 Impact factor: 10.793
Authors: Robert C Strunk; Leonard B Bacharier; Brenda R Phillips; Stanley J Szefler; Robert S Zeiger; Vernon M Chinchilli; Fernando D Martinez; Robert F Lemanske; Lynn M Taussig; David T Mauger; Wayne J Morgan; Christine A Sorkness; Ian M Paul; Theresa Guilbert; Marzena Krawiec; Ronina Covar; Gary Larsen Journal: J Allergy Clin Immunol Date: 2008-10-25 Impact factor: 10.793