The potential role of elastase inhibitors in emphysema treatment

Several lines of evidence, albeit most of them circumstant ia l, support the protease-antiprotease imbalance concept in the pathogenesis of emphysema. Neutrophil elastase (NE) has become the key enzyme for several reasons. NE is insufficiently inhibited by a( antitrypsin (AAT) (a 1 -proteinase inhibitor) in inherited deficiency states when the extracellular level of the predominant antiprotease AAT is low as in AATdeficiency, PiZ, and other rare genetic variants. NE .is the target enzyme of AA T, the rate of association between them being extremely rapid (1]. AAT is the archetype of the so called serpin (serine proteinase inhibitors) super family of highly homologous proteins, including the protease inhibitors a 1 -