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© 2005 The American Thoracic Society
Pathogenesis of Chronic Obstructive Pulmonary Disease
Edinburgh Lung and the Environment Group Initiative/Colt Research Laboratories, Medical School, University of Edinburgh, Edinburgh, Scotland, United Kingdom
Correspondence and requests for reprints should be addressed to W. MacNee, M.D., Respiratory Medicine, ELEGI/Colt Research Laboratories, Wilkie Building, Medical School, Teviot Place, Edinburgh EH8 9AG, UK. E-mail: w.macnee{at}ed.ac.uk
The current paradigm for the pathogenesis of chronic obstructive pulmonary disease is that chronic airflow limitation results from an abnormal inflammatory response to inhaled particles and gases in the lung. Airspace inflammation appears to be different in susceptible smokers and involves a predominance of CD8+ T lymphocytes, neutrophils, and macrophages. Studies have characterized inflammation in the peripheral airspaces in different stages of disease severity. Two other processes have received considerable research attention. The first is a protease–antiprotease imbalance, which has been linked to the pathogenesis of emphysema. However, the hypothesis of an increased protease burden associated with functional inhibition of antiproteases has been difficult to prove and is now considered an oversimplification. The second process, oxidative stress, has a role in many of the pathogenic processes of chronic obstructive pulmonary disease and may be one mechanism that enhances the inflammatory response. In addition, it has been proposed that the development of emphysema may involve alveolar cell loss through apoptosis. This mechanism may involve the vascular endothelial growth factor pathway and oxidative stress.
Key Words: apoptosis • emphysema • inflammation • oxidative stress • protease–antiprotease imbalance
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