New aspects of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability, but has only recently been extensively explored from a cellular and molecular perspective. In COPD there is a chronic inflammation that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterized by increased numbers of alveolar macrophages, neutrophils and cytotoxic T lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines and growth factors). A high level of oxidative stress may amplify this inflammation. There is also increased elastolysis and evidence of the involvement of several elastolytic enzymes, including serine proteases, cathepsins and matrix metalloproteinases. The inflammation and proteolysis observed in COPD are 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.