Antitrypsin and emphysema. Perspective and prospects.

Abstract

AN ARRAY of serine proteinase inhibitors (serpins) modulate important proteolytic cascades in blood and tissue. A high concentration of the major serpin, α 1 -antitrypsin, in plasma reflects the prevalence and potential threat of its primary target enzyme, neutrophil elastase. The observation that the inherited deficiency of antitrypsin was often associated with premature airflow limitation due to panacinar emphysema led to the concept that normal lung structure depends on a balance between the destructive effects of neutrophil elastase and the protective effects of the serpins, especially α 1 -antitrypsin. Wide variability exists in the tendency for emphysema to develop among subjects with the deficiency, but those who smoke cigarettes become disabled 15 to 20 years earlier than those who do not. Definitive therapy was not available until recently; the protein has been purified on a commercial scale. Early results indicate that weekly injections of antitrypsin safely sustain normal levels in