The role of proteolytic enzymes in the pathogenesis of emphysema.

Alphai-antitrypsin (aiAT) deficiency states, which predispose one to the development of pulmonary emphysema, have been described with increasing frequency. While the precise physiologic role of this protein is not known, it appears certain that it protects the lung from proteolytic digestion by a number of enzymes. Data are now available which mimic this situation in the experi­ mental animal and demonstrate the protective effect of aiAT. Mechanisms of this genetic model for autodigestion and a number of pathological and bio­ chemical considerations are offered in this paper. Laurell originally observed that the ab­ sence of the alpha1 band on routine pro­ tein electrophoresis strips was associated with pulmonary disease. 29 Subsequent studies by Eriksson, 5 elucidating the clin­ ical nature of pulmonary emphysema asso­ ciated with deficiency of alpha-l-antitrypsin have led to increasing interest in the role of this acute phase protein, or lack of it, in the pathogenesis of chronic obstruc­ tive pulmonary disease. Furthermore, what appears to be a genetic model for “auto­ digestion of the lung” has led to studies focusing on this disease from various view­ points. The alpha-l-antitrypsin deficiency state represents less than five percent of the total emphysema population. 2 1 It differs from classical emphysema only in that it occurs * Recipient of the Pulmonary Academic Award NHLIHT-116-72. at a younger age and is evenly distributed between male and female. 6 Afflicted indi­ viduals appear to have less of a bronchitic component than the emphysema popula­ tion at large but, by all parameters of phys­ iological testing no distinct abnormality of lung function separates aiAT deficient pa­ tients from other emphysema patients. Alpha-l-antitrypsin deficient patients char­ acteristically have radiological evidence of lower zone emphysema, 1 loss of elastic re­ coil, and abnormal ventilation/perfusion ratios in the lower lobes in addition to evidence of obstructive lung disease by spirometry. 7 Studies of frequency depen­ dent compliance and other sophisticated procedures have been reported and have only confirmed the similarity between aiAT deficient patients and the general population of emphysema patients. 8 Emphysematous destruction of the lower lobes with dilatation of the air spaces and