Heterogeneity of therapeutic responses in asthma

Asthma is a complex clinical syndrome with multiple genetic and environment al factors contributing to its phenotypic expression. This aetiological het erogeneity adds to the complexity when addressing variation in the response to antiasthma treatment. Currently, there are three main lines of treatmen t available: (i) inhaled glucocorticoids which have multiple mechanisms of action; (ii) Pi agonists which are very effective bronchodilators and act p redominantly on airway smooth muscle; and (iii) cysteinyl-leukotriene inhib itors. 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 gen etic in nature. Among the sources of variability that could contribute to t he observed heterogeneity in the response to treatment are the degree of un derlying inflammation, such as in glucocorticoid resistance, and polymorphi sms in the genes encoding the drug target, such as beta (2)-adrenoceptor an d 5-lipoxygenase.