title: Tailored second-line therapy in asthmatic children with the Arg(16) genotype.
abstract: The Arg(16) β(2) receptor genotype confers increased susceptibility to exacerbations in asthmatic children taking regular LABA (long-acting β(2) agonists). We therefore evaluated using montelukast as an alternative to salmeterol as tailored second-line asthma controller therapy in children expressing this susceptible genotype. A total of 62 persistent asthmatic children with the homozygous Arg16 genotype were randomized to receive salmeterol (50 μg, b.i.d.) or montelukast (5 or 10 mg, once daily) as an add-on to inhaled fluticasone for 1 year. School absences (the primary outcome) were reduced with montelukast compared with salmeterol {difference in score=-0.40 [95% CI (confidence interval), -0.22 to -0.58]; P=0.005}. Salbutamol use was also reduced with montelukast compared with salmeterol [difference in score=-0.47 (95% CI, -0.16 to -0.79); P<0.0001]. Greater improvements occurred in both symptom and quality of life scores with montelukast against salmeterol, whereas there was no difference in FEV(1) (forced expiratory volume in 1 s). In conclusion, montelukast may be suitable as tailored second-line controller therapy instead of salmeterol in asthmatic children expressing the susceptible Arg(16) genotype, a move towards a personalized medicine approach to management.
authors.affiliation: Asthma and Allergy Research Group, Division of Medicine and Therapeutics, University of Dundee, Dundee DD2 4BF, Scotland, UK. b.j.lipworth@dundee.ac.uk
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lipworth
authors.forename: Kaninika
authors.initials: K
authors.lastname: Basu
authors.forename: Helen P
authors.initials: HP
authors.lastname: Donald
authors.forename: Roger
authors.initials: R
authors.lastname: Tavendale
authors.forename: Donald F
authors.initials: DF
authors.lastname: Macgregor
authors.forename: Simon A
authors.initials: SA
authors.lastname: Ogston
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
authors.forename: Somnath
authors.initials: S
authors.lastname: Mukhopadhyay
mesh_terms: D000085:Acetates / Q000627:therapeutic use; D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use; D000420:Albuterol / Q000031:analogs & derivatives / Q000627:therapeutic use; D020816:Amino Acid Motifs; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011804:Quinolines / Q000627:therapeutic use; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000068299:Salmeterol Xinafoate; D013440:Sulfides
chemical_list: D000085:Acetates; D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D011804:Quinolines; D018343:Receptors, Adrenergic, beta-2; D013440:Sulfides; D000068299:Salmeterol Xinafoate; D001120:Arginine; C093875:montelukast; D000420:Albuterol