Effects of beta2-agonists on airway tone and bronchial responsiveness

In evaluating the clinical consequences of beta(2)-agonist therapy, it is important to consider the possibility of reduced asthma control and increased bronchial responsiveness with regular or long-term use. Some studies have noted reductions in protective effects but not complete loss of protection with short-acting beta(2)-agonist therapy. These reductions vary, depending on the use of nonspecific, indirect, or immunologic challenges, but it appears there is a greater loss of protective effect against indirect stimuli. Tachyphylaxis to the bronchodilatatory effects of long-acting beta(2)-agonists appears to be minimal. Individuals homozygous for arginine at locus 16 of the beta(2)-adrenergic receptor gene have a decline in pulmonary function during beta(2)-agonist use, and they are at greater risk of asthma exacerbations during beta(2)-agonist therapy than patients with other genotypes. Important questions for further research are whether small differences in tachyphylaxis and bronchoprotection have relevant clinical effects and to what extent tachyphylaxis and tolerance to bronchoprotection are caused by pharmacogenetic interactions.