Part IV: Genetic variations in beta2-adrenergic receptors: long-acting and short-acting beta2-agonists and therapeutic response.
Inhaled beta2-agonists are the most commonly used treatment for asthma. It has been hypothesized that patients who exhibit functional polymorphic variants of the beta2-adrenergic receptor may be more likely to experience adverse outcomes with the regular use of beta2-agonists, particularly the short-acting beta2-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 beta2-adrenergic receptor may experience worsening asthma outcomes after regular beta2-agonist use. Data regarding the impact of polymorphic variants of the beta2-adrenergic receptor on response to long-acting beta2-agonists are conflicting. However, recent data indicate that use of long-acting beta2-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 beta-agonists should only be used on an as-needed basis and to prevent exercise-induced asthma symptoms, and long-acting beta-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 beta2-agonist in addition to an inhaled corticosteroid should be carefully monitored for possible adverse asthma outcomes.
Peters
Stephen
S
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. sppeters@wfubmc.edu
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D019943:Amino Acid Substitution / Q000235:genetics; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2