Adrenergic beta2-receptor genotype is associated with inhaled salbutamol response in young children with recurrent wheeze: randomised controlled trial

Inhaled salbutamol is commonly used for recurrent wheeze. Some children respond poorly to salbutamol. Studies suggest increased risk of asthma exacerbations in children with one or both Arg16 alleles (Arg/Arg or Arg/Gly) on the gene encoding the beta2 adrenoceptor (ADRB2), if they are receiving regular salbutamol or salmeterol, compared with Gly/Gly variant status. We tested the hypothesis that presence of Arg variants in ADRB2 is associated with differences in response to salbutamol, measured by change in airway resistance using the interrupter technique (Rint), in 2-7 year olds with recurrent wheeze. We also studied variation in the dose of salbutamol required to produce a significant response and whether this was influenced by ADRB2 Arg 16 variant status. Children (n=77), 74/77 had GINA based asthma control data – 18 uncontrolled, 35 partially controlled, 21 well controlled, with no correlation to genotype (n=77) - Gly/Gly 25, Arg/Gly 36, Arg/Arg 16. They were randomized to receive two successive doses of salbutamol, 30 minutes apart: (100, 300), (100, 500), (200, 600), and (200, 200) (µg). Rint was measured at baseline and 30 minutes after each dose. The relationship between the Rint and salbutamol dose was analysed using a non-linear mixed modelling approach. Children with a) Arg/Arg b) Arg/Gly c) history of hospitalisation in previous 12 months, required a higher salbutamol dose to reach 50% of maximal bronchodilator response compared to Gly/Gly children and those not hospitalised (a-p=0.003; b-p=0.012; c-p=0.004). Tailoring short acting beta2 agonists as per Arg/Gly genotype might improve their efficacy in young children.