Asthma is heterogeneous with respect to clinical presentation, underlying disease mechanisms and response to existing drugs making tailored therapy desirable. Pharmacogenetics, the study of the influence of genetic polymorphisms on drug efficacy and/or adverse effects, is relatively advanced in asthma with replicated genetic associations identified in the main drug classes. In the present issue of Clinical Science , Lipworth and co-workers report a proof-of-concept study and demonstrate that, in asthmatic children carrying the β 2 -adrenergic receptor gene Arg 16 polymorphism, a combination of corticosteroid plus leukotriene receptor antagonist provides superior asthma control (e.g. quality of life scores) compared with corticosteroid plus a long-acting β 2 -adrenergic receptor agonist as add-on therapy. The basis of these observations is well founded, as it has been demonstrated previously that the Arg 16 polymorphism may confer an increased risk of exacerbation following prolonged β 2 -adrenergic receptor agonist use. These results suggest Gly16Arg genotyping in Caucasian asthma patients may have a role in the clinical management of asthma by influencing the decision of which add-on therapy to prescribe; however, larger studies are required to provide definitive conclusions regarding the clinical utility of this approach.

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 Arg 16 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.