Heterogeneity of therapeutic responses in asthma.
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 anti-asthma treatment. Currently, there are three main lines of treatment available: (i) inhaled glucocorticoids which have multiple mechanisms of action; (ii) beta 2-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.
Drazen
J M
JM
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
Silverman
E K
EK
Lee
T H
TH
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000276:immunology; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D008565:Membrane Proteins / Q000378:metabolism; D011110:Polymorphism, Genetic; D011943:Receptors, Adrenergic, beta / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics; D016896:Treatment Outcome
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D016207:Cytokines; D005938:Glucocorticoids; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D011943:Receptors, Adrenergic, beta; D011965:Receptors, Glucocorticoid