Part IV: Genetic variations in β₂-adrenergic receptors: long-acting and short-acting β₂-agonists and therapeutic response

ABSTRACT

Inhaled β₂-agonists are the most commonly used treatment for asthma. It has been hypothesized that patients who exhibit functional polymorphic variants of the β₂-adrenergic receptor may be more likely to experience adverse outcomes with the regular use of β₂-agonists, particularly the short-acting β₂-agonist albuterol. This hypothesis has been confirmed in retrospective studies and in a prospective clinical trial. Results from these studies demonstrate that patients with the Arg/Arg phenotype at the 16th amino acid position of the β₂-adrenergic receptor may experience worsening asthma outcomes after regular β₂-agonist use. Data regarding the impact of polymorphic variants of the β₂-adrenergic receptor on response to long-acting β₂-agonists are conflicting. However, recent data indicate that use of long-acting β₂-agonists may be associated with an increased risk of life-threatening asthma or asthma-related deaths, which might be increased among African-Americans and patients who do not use inhaled corticosteroids. Until more data are available, short-acting β-agonists should only be used on an as-needed basis and to prevent exercise-induced asthma symptoms, and long-acting β-agonists should only be used as an adjunct to controller therapy with inhaled corticosteroids. Any patient with asthma who requires adjunctive use of a long-acting β₂-agonist in addition to an inhaled corticosteroid should be carefully monitored for possible adverse asthma outcomes.

Key words::

• β2-Adrenergic receptors
• Arg/Arg genotype
• Genetic polymorphism
• Long‐acting β2‐agonists
• Short‐acting β2‐agonists
• Therapeutic response