Animal models of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is the fifth leading cause of death in the UK,1 causing 26 000 deaths and 240 000 hospital admissions and costing the NHS £486 million per annum. It is also a global problem, reaching almost epidemic proportions in the developing world. Despite this, it receives relatively little attention compared with diseases with a similar impact such as coronary heart disease and cancer. The research into new treatments to prevent the development and progression of this condition presents a major challenge. It is thus important to develop tools that can both direct development of new drugs and provide insights into assessment of their efficacy before extensive human trials are undertaken. Animal models act as a bridge between in vitro studies in the laboratory and studies in humans. As such, they have had a major impact on the investigation of many medical conditions. In COPD, in particular, animal models would enable basic research to investigate the mechanisms of inflammatory cell recruitment and abnormal matrix repair (the proteinase/antiproteinase hypothesis2) and alternative hypotheses of the pathogenesis of emphysema such as those implicating lung cell apoptosis as a primary event.3 They would also facilitate the testing of new treatments such as gene therapy (in cystic fibrosis and α1-antitrypsin deficiency (A1AT)) and “designer drugs” targeting specific cytokines or biochemical pathways. By leading to a clearer understanding of the key events in the pathophysiology of COPD and enabling short term studies to develop appropriate strategies, animal models can provide a framework for the rational and safe design of expensive and long term clinical studies. The mouse provides the best choice for an animal model4 because the mouse genome has been extensively studied and sequenced and close similarities exist with the human genome. In addition, complementary antibodies and probes …