Adrenergic ß2-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol

Background On-demand inhaled albuterol is commonly prescribed worldwide. We have shown that the Arg16 allele of the adrenergic ß2-receptor agonist gene (ADRB2) predisposes to exacerbations in young asthmatic patients taking regular salmeterol. Objective We have now extended our previous population by 636 patients and explored the role of the Arg16 allele on asthma exacerbations in the context of the use of on-demand albuterol and regular salmeterol. Methods Arg/Gly status at position 16 of ADRB2 was assessed in 1182 young asthmatic patients (age, 3-22 years) from Scotland. Asthma exacerbations, use of ß-agonists and other medications over the previous 6 months, and lung function were also studied. Results An increased risk of exacerbations per copy of he Arg16 allele was observed in asthmatic patients, regardless of treatment regimen (odds ratio [OR], 1.30; 95% CI, 1.09-1.55; P = .003). This appears to be largely due to exposure to ß2-agonists because the risk of exacerbations observed in patients with the Arg16 allele was only observed in those receiving daily inhaled long- or short-acting ß2-agonist treatment (OR, 1.64; 95% CI, 1.22-2.20; P = .001). In contrast, there was no genotypic risk for exacerbations in patients using inhaled ß2-agonists less than once a day (OR, 1.08; 95% CI, 0.85-1.36; P = .525). The Arg16 genotype–associated risk for exacerbations was significantly different in those exposed to ß2-agonists daily versus those that were not (test for interaction, P = .022). Conclusion The Arg16 genotype of ADRB2 is associated with exacerbations in asthmatic children and young adults exposed daily to ß2-agonists, regardless of whether the exposure is to albuterol or long-acting agonists, such as salmeterol.