British Medical Bulletin 56:1054-1070 (2000)
© 2000 The British Council
research-article |
Heterogeneity of therapeutic responses in asthma
1Department of Medicine, Brigham and Women's Hospital and Harvard Medical School Boston USA
2Department of Respiratory Medicine and Allergy, Guy's, King's and Thomas School of Medicine, Guy's Hospital London, UK
Correspondence to:Prof. TH Lee, Department of Respiratory Medicine and Allergy, 5th floor Thomas Guy House, Guy's Hospital, London SEl 9RT, UK.
Abstract
Asthma is a complex clinical syndrome with multiple genetic and enviromental 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)ß2-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 respone 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 durg target, such as ß2-adrenoceptor and 5-lipoxygenase.
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