Chronic obstructive pulmonary disease: towards pharmacogenetics

Abstract

Chronic obstructive pulmonary disease (COPD) is a common problem worldwide, and it is recognized that the term encompasses overlapping sub-phenotypes of disease. The development of a sub-phenotype may be determined in part by an individual's genetics, which in turn may determine response to treatment. A growing understanding of the genetic factors that predispose to COPD and its sub-phenotypes and the pathophysiology of the condition is now leading to the suggestion of individualized therapy based on the patients' clinical phenotype and genotype. Pharmacogenetics is the study of variations in treatment response according to genotype and is perhaps the next direction for genetic research in COPD. Here, we consider how knowledge of the pathophysiology and genetic risk factors for COPD may inform future management strategies for affected individuals.

Figure 1

A possible COPD treatment algorithm based on pharmacogenetics. The chart shows a hypothetical system of using pharmacogenetics in COPD. After receiving a diagnosis of COPD, patients would undergo further tests to identify specific clinical features known to be influenced by genetics. Genotyping for the important polymorphisms would then be carried out to identify pathophysiologically important pathways, and therapy would be directed at those most active in the individual. Specific monitoring of response using target protein levels or clinical phenotype would then be carried out. This treatment algorithm might be used alongside established treatments, such as bronchodilators, or be used to aid rational use of expensive treatments.