Heterogeneity of therapeutic responses in asthma

被引:240
作者
Drazen, JM
Silverman, EK
Lee, TH
机构
[1] Guys Hosp, Guys Kings & St Thomas Sch Med, Dept Resp Med & Allergy, London SE1 9RT, England
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Dept Med, Boston, MA USA
关键词
D O I
10.1258/0007142001903535
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1054 / 1070
页数:17
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