Biochemical links between cigarette smoking and pulmonary emphysema.

A large body of circumstantial evidence has accumulated in the last 20 yr, suggesting that alveolar effacement in pulmonary emphysema is due to unrestrained proteolytic (elastolytic) activity in lung connective tissue. Even though this hypothesis still requires rigorous proof, newer information is rapidly developing that links the protease-pathogenesis model to the primary environmental risk factor associated with the disease, namely cigarette smoking. A triad of chemical and cellular effects produced by cigarette smoke have been suggested as factors contributing to altered elastin metabolism and eventual development of emphysema in smokers. The present article reviews some of these observations, seeks to place them within the overall framework of the protease model, and attempts to raise questions for future study.