Clinical features and molecular characteristics of alpha 1-antitrypsin deficiency

Abstract

Alpha-1-antitrypsin deficiency is a common, underrecognized disorder manifested by emphysema in adults and liver disease in children. Early diagnosis and subsequent prevention of lung inflammation due to cigarette smoking, infection, and airborne irritants form the most rational approach to slow the progression of the lung destruction associated with alpha 1AT deficiency. Currently, liver transplantation is the only therapy available to patients with severe liver disease due to alpha 1AT deficiency. Less commonly, many inflammatory and/or immune-mediated diseases have been described in association with alpha 1AT deficiency. These observations are probably related to the role that alpha 1AT plays in the immune response both as a target for modulation by cytokines and as a modulator of the immune response. At present, therapy for the emphysema associated with alpha 1AT is limited to weekly augmentation therapy with recombinant alpha 1AT. Future therapeutic modalities include aerosol alpha 1AT, secretory leukocyte proteinase inhibitor, low molecular weight inhibitors of neutrophil elastase, and gene transfer via viral vector.