Augmentation therapy for emphysema due to alpha-1-antitrypsin deficiency.

Alpha-1 antitrypsin deficiency (AAT) is a hereditary recessive autosomal disease caused by mutations in the AAT gene. This disease is characterized by abnormally low AAT concentrations in plasma, which, in its homozygote form, carries a high risk for the development of early pulmonary emphysema and liver damage. Since the end of the 1980s augmentation therapy with AAT from human plasma has been available for specific treatment of emphysema due to AAT deficiency. Intravenous augmentation therapy has been demonstrated to be safe and weekly infusions of AAT have resulted in plasma AAT concentrations above those considered protective for the lungs. However, life-long weekly infusions are not well accepted by patients, therefore pharmacokinetic studies have been performed to try to individualize the therapeutic regimen in order to obtain adequate trough serum AAT levels with prolonged intervals of administration. Therapeutic regimens administered every two weeks appear to be safe and result in adequate trough serum concentrations, but less-frequent administrations result in trough levels below the target. Alpha-1-antitrypsin deficiency is largely unrecognized and underdiagnosed. The foundation of national and international registries is a valid strategy to increase awareness about the disease and collect information about the natural history of this deficiency. Furthermore, the identification of a large number of patients will allow the development of new clinical trials aimed at finding better treatments for this infrequent condition.