Adrenergic β₂-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 β₂-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 β-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 β₂-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 β₂-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 β₂-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 β₂-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 β₂-agonists, regardless of whether the exposure is to albuterol or long-acting agonists, such as salmeterol.

Key words: Asthma, child, polymorphism, asthma exacerbations, albuterol, salmeterol, β₂-adrenoceptor, adrenergic β₂-receptor agonist gene

Abbreviations used: ADRB2, Adrenergic β₂-receptor agonist gene, BTS, British Thoracic Society, OR, Odds ratio