Larj Michael J, Bleecker Eugene R
Division of Pulmonary and Critical Care Medicine, Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
J Allergy Clin Immunol. 2002 Dec;110(6 Suppl):S304-12. doi: 10.1067/mai.2002.130045.
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.
在评估β₂受体激动剂治疗的临床后果时，重要的是要考虑到长期或常规使用可能导致哮喘控制降低和支气管反应性增加。一些研究指出，短效β₂受体激动剂治疗会使保护作用降低，但并非完全丧失保护作用。这些降低程度各不相同，取决于非特异性、间接或免疫性刺激的使用情况，但似乎对间接刺激的保护作用丧失更大。长效β₂受体激动剂的支气管扩张作用出现快速减敏的情况似乎很少。β₂肾上腺素能受体基因第16位点为精氨酸纯合子的个体在使用β₂受体激动剂期间肺功能会下降，与其他基因型患者相比，他们在接受β₂受体激动剂治疗时哮喘加重的风险更高。进一步研究的重要问题是，快速减敏和支气管保护方面的微小差异是否具有相关临床效应，以及快速减敏和对支气管保护的耐受性在多大程度上是由药物遗传学相互作用引起的。
