Personalised prescribing for asthma - is pharmacogenetics the answer?

Abstract

An individual's response to anti-asthma medication is likely to arise from a complex interaction between social, environmental and inherited factors. Studies indicate that genetic factors may account for 60-80% of the heterogeneity in treatment responsiveness in asthmatics. Identifying the genetic variants responsible may potentially lead to the development of novel treatments, improved effectiveness in the use of existing treatments and better prediction of efficacy in phase II and III trials. This article will briefly outline the current methods of identifying relevant treatmentresponsive genes and their genetic variants. The pharmacogenetics of the main asthma treatment groups will then be reviewed in detail. Finally, the impact of pharmacogenetics on the pharmaceutical industry, and clinical practice in the future will be discussed.

Asthma, Genes, and Air Pollution

“…Indeed, a thorough understanding of mechanisms may lead to not only isolation of genetic determinants, but also more effective pharmacologic treatment. 31 Although much needs to be learned about the pathophysiology of asthma, the major mechanism is reversible obstruction of the small airways, with airway inflammation being a predominant finding. 32,33 The inflammatory response of asthma involves numerous mediators, including eosinophils, mast cells, and CD 4ϩ lymphocytes.…”

Beta-agonists modulate T-cell functions via direct actions on type 1 and type 2 cells

“…[7][8][9][10][11] Moreover, the ␤ 2 AR has received extensive attention as a candidate gene (ADRB) for asthma. [12][13][14] The endogenous circulating ␤-agonist epinephrine has been reported to influence T-cell responses in heart failure patients, who typically have elevated levels of serum epinephrine. Yndestad et al reported that peripheral T cells, but not monocytes, from heart failure patients exhibit increased expression of chemokines, IFN-␥, interleukin-18 (IL-18), and tumor necrosis factor (TNF) superfamily genes.…”

Comparison of Glucocorticoid (Budesonide) and Antileukotriene (Montelukast) Effect in Patients with Bronchial Asthma Determined with Body Plethysmography

“…This forecast on response generally reflects our limited knowledge on the physiopathology of asthma. Moreover, some components of these changes are possible to explain by many pharmacogenetics factors ( 17 ).…”