This application proposes a scientific meeting on pulmonary emphysema and proteolysis. Since the association of alpha 1 protease inhibitor deficiency and emphysema in 1963, both clinical and basic studies of emphysema were greatly advanced. The protease antiprotease theory of emphysema evolved which suggested that the lungs of patients were not protected from destruction by white cell proteases by the antiprotease screen. The majority of patients develop emphysema, however, in the presence of normal blood levels of protease inhibitors. An additional mechanism was proposed which demonstrated that alpha 1 protease inhibitor could be inactivated by oxidants present in cigarette smoke and in white cells, thus potentially creating a temporary deficiency of alpha 1 protease inhibitor in the lung. This still could not fully explain why only 20% of smokers proceed to develop significant airways obstruction. Recently, the potential involvement of abnormal antioxidants in the disease process has been suggested. The symposium proposed aims to define our current status of knowledge on a) the protease antiprotease theory of emphysema and b) oxidant antioxidant interactions with proteases and antiproteases. It will explore a) genetic polymorphisms and deficits in these molecules, b) other theories of lung injury and their relation to proteases and oxidants and c) provide future direction to biochemical and epidemiological studies including possible therapeutic approaches.
