Heterogeneity of therapeutic responses in asthma
Heterogeneity of therapeutic responses in asthma
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DOI：
10.1258/0007142001903535
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发表时间：
2000-01-01
影响因子：
6.7
通讯作者：
Lee, TH
中科院分区：
文献类型：
--
作者：
Drazen, JM;Silverman, EK;Lee, TH
哮喘是一种复杂的临床综合征，其表型表达受多种遗传和环境因素的影响。这种病因学的异质性增加了解决抗哮喘治疗反应差异时的复杂性。目前，有三种主要的治疗方法：(I)具有多种作用机制的吸入糖皮质激素；(Ii)PI激动剂，它是非常有效的支气管扩张剂，主要作用于呼吸道平滑肌；以及(Iii)半胱氨基-白三烯抑制剂。对治疗反应的重复性(R)的分析表明，r值在60-80%之间，表明治疗反应的大部分变异可能是遗传的。在可能导致观察到的治疗反应异质性的变异性来源中，潜在的炎症程度，如糖皮质激素耐药性，以及编码药物靶标的基因，如β(2)-肾上腺素能受体和5-脂氧合酶的多态。
Asthma is a complex clinical syndrome with multiple genetic and environmental factors contributing to its phenotypic expression. This aetiological heterogeneity adds to the complexity when addressing variation in the response to antiasthma treatment. Currently, there are three main lines of treatment available: (i) inhaled glucocorticoids which have multiple mechanisms of action; (ii) Pi agonists which are very effective bronchodilators and act predominantly on airway smooth muscle; and (iii) cysteinyl-leukotriene inhibitors. Analysis of the repeatability (r) of the treatment response, defined as the fraction of the total population variance which results from among-individual differences, shows values of r between 60-80% indicating that a substantial fraction of the variance of the treatment response could be genetic in nature. Among the sources of variability that could contribute to the observed heterogeneity in the response to treatment are the degree of underlying inflammation, such as in glucocorticoid resistance, and polymorphisms in the genes encoding the drug target, such as beta (2)-adrenoceptor and 5-lipoxygenase.