A single dose of crystalline, porcine pancreatic elastase injected intratracheally into hamsters induces widespread alveolar enlargement with subpleural bullae. A uniformly severe lesion is consistently induced by 0-2 mg elastase per 100 g body weight and with negligible mortality. Compared with controls, which showed no lesion, elastase-damaged lungs show a highly significant (P less than or equal to 0-001) increase in alveolar size and a decrease in internal surface area. Taken with the associated physiological abnormalities, these findings closely simulate human emphysema of the panlobular (panacinar) type. Histologically it appears that elastase converts the fine elastic fibres in alveolar walls and pleura into thickened, nodular fibres which may also be broken along their length. With higher doses of elastase, i.e., 0-5 mg/100 g body weight, many pulmonary arteries showed segmental loss of inner and outer elastic laminae, usually with thrombosis on the overlying endothelium. The mechanism of this thrombosis is unclear. These experiments suggest that damage to elastic fibres may be an important element in the development of human panacinar emphysema, and that the damage could be one pathogenetic mechanism which produces damage of elastic fibres.

A B S T R A C T A single intratraclheal instillation of pancreatic elastase in hamsters indtuces a lesion resembling human panacinar emphysema. This paper reports the occurrence of irreversible goblet cell metaplasia in the bronchiial epithelitum of hamsters similarly exposed to elastase. The goblet cell change was dose related; a dose of 0.1 mg/100 g body wt or less at 16 days, prodtuced slight or moderate goblet cell metaplasia in fewer than half the animals, whereas 84% of animals treated with a dose between 0.2 and 0.5 mg/100 g body wt developed goblet cell metaplastic lesions, more than half of which were considered to be severe. The percentage of goblet cells in the epithelium of elastase-treated hamsters (32.5) was significantly higher (P < 0.005) than that of tunexposed (12.2) and saline-exposed controls (18.7). All hamsters examined 6 and 12 mo after elastase treatment showed the lesion. The pathogenesis of the changes is unclear btut the possibility is raised that the bronchial changes may be dtue to disturbance of an endogenous protease-antiprotease system. The findings suggest the hypothesis that, uinder appropriate circu-mstances, a single puilmonary insult in man could lead to a permanent luing injtury demonstrating the anatomic lesions of both chronic bronchitis and panacinar emphysema.

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