New approaches to the management of COPD.
Airflow limitation in COPD is a result partially of bronchospasm, but it is also caused by a reduction in airway caliber, the number of small airways, airway collapse because of loss of connective tissue support, excess mucus in the airways, and edema of the airway wall. Structural changes also occur because of long-term destruction of interstitial connective tissue, including elastin. Therefore, in addition to the traditional aim of reversing bronchospasm with bronchodilators, disease-modifying approaches are being investigated. The enzyme neutrophil elastase is implicated in the induction of bronchial disease causing structural changes in lungs, impairment of mucociliary clearance, and impairment of host defenses. The precise mechanism pathway of neutrophil elastase is uncertain, but the effects of influencing the pathway in order to slow disease progression are being investigated. Oxidants may also have a role in the development of COPD, with increased levels activating airway cells and cytokine production.
Stockley
R A
RA
Department of Medicine, Queen Elizabeth Hospital, Birmingham, UK.
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000502:physiology; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000209:etiology; D020556:Neutrophil Infiltration / Q000187:drug effects; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000378:metabolism
D000975:Antioxidants; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D019272:Leukocyte Elastase