Mechanisms of smoking-induced lung injury

A considerable body of evidence has been and continues to be accumulated that supports involvement of proteolytic enzymes and oxidants in the pathogenesis of smoking-induced lung injury. Still at issue are the host factors that modulate the effects of smoking in the individual subject. It remains unclear why a large proportion of smokers are protected from the deleterious effect of tobacco exposure. A potential problem with the protease-antiprotease hypothesis is that its focus may be too narrow. Whereas it appears that the balance between proteolytic enzymes and their inhibitors is important in determining the integrity of pulmonary structure and function, the role of other inflammatory pathways in the pathogenesis of smoking-induced lung injury remains to be elucidated. Furthermore, lung injury contingent on the effects of proteolytic enzymes or oxidants may be significantly influenced by either genetic or environmental factors. As recently reviewed, clarification of important protective mechanisms that modulate the effects of cigarette smoking may await the application of biochemical and molecular methodology to traditional epidemiologic analyses of smoking-related disease. Current information derived from clinical and experimental studies provides a reasonable explanation for the apparent link between smoking and chronic obstructive pulmonary disease. However, elucidation of the truly important effectors of lung injury present in cigarette smoke and the defenses against these agents remains the major challenge for future investigation.