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