Tailored second-line therapy in asthmatic children with the Arg16 genotype

Brian J. Lipworth, Kaninika Basu, Helen P. Donald, Roger Tavendale, Donald F. MacGregor, Simon A. Ogston, Colin N. A. Palmer, Somnath Mukhopadhyay

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    67 Citations (Scopus)


    The Arg16 ß2 receptor genotype confers increased susceptibility to exacerbations in asthmatic children taking regular LABA (long-acting ß2 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 FEV1 (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 Arg16 genotype, a move towards a personalized medicine approach to management.


    The FDA has recently highlighted concerns about long-term safety of LABA exposure, especially in children.
    Our study evaluated second-line therapy in 15% of genetically susceptible asthmatic children possessing the Arg16 genotype.
    We show that patients with the Arg16 genotype may fare better by using montelukast than salmeterol as add-on therapy to inhaled corticosteroids. This in turn provides evidence for genotype directed personalized medicine.
    Original languageEnglish
    Pages (from-to)521-528
    Number of pages8
    JournalClinical Science
    Issue number8
    Publication statusPublished - Apr 2013


    • Asthma
    • beta(2) receptor
    • Children
    • montelukast
    • Salmeterol


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