Chronic obstructive pulmonary disease is a leading cause of death and disability, but has only recently been extensively explored from a cellular and molecular perspective.There is a chronic inflammation that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterised by increased numbers of alveolar macrophages, neutrophils and cytotoxic T-lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). A high level of oxidative stress may amplify this inflammation. There is also increased elastolysis and evidence for involvement of several elastolytic enzymes, including serine proteases, cathepsins and matrix metalloproteinases.The inflammation and proteolysis in chronic obstructive pulmonary disease is an amplification of the normal inflammatory response to cigarette smoke. This inflammation, in marked contrast to asthma, appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease. Eur Respir J 2003; 22: 672-688.

Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide, and we have little specific therapy to offer these patients. One potential strategy to limit loss of lung function in COPD would be to inhibit matrix-degrading proteinases. Several serine proteinases and matrix metalloproteinases are expressed in association with COPD in humans. Application of gene-targeted macrophage elastase and neutrophil elastase to a mouse model of cigarette-smoke-induced emphysema has uncovered roles for these proteinases in airspace enlargement, and has identified many interactions between these proteolytic systems.

Animal models play an important role in the understanding of the pathogenesis of chronic obstructive pulmonary disease (COPD). The applicability of findings to human COPD depends upon several factors, including the disease model, and similarities in mouse structure and function between species.There are many examples in the literature of transgenic mice that have contributed to the understanding of COPD. Several studies demonstrate the complexity of inflammatory networks and how unexpected findings in animal models have led to the search for new potential mediators in human disease.Gene-targeting studies into a 1 -antitrypsin (a 1 -AT) and emphysema in mice have demonstrated that the genetic locus for a 1 -AT in mice is very complex and that the loss of one gene is lethal in embryo lung development. This underlines the differences between mice and humans that limit the ability to translate between systems in some instances. Gene targeting has also highlighted complex roles for transforming growth factor-b in COPD and has been used to determine important molecules and pathways in COPD.Both transgenic and gene-targeted models suffer limitations and their applicability to human chronic obstructive pulmonary disease may be dependant on several factors, some of which are still being learnt. The more that is known about similarities and differences, the better the knowledge will be that is gained to develop for chronic obstructive pulmonary disease.