There are 2 million individuals in the U.S.A. with emphysema. Two percent develop the disease because of inheritance of a deficiency of alpha 1-antitrypsin (alpha 1AT), an antiprotease that protects the lower respiratory tract from destruction mediated by elastase released by neutrophils. The neutrophil elastase cDNA and genomic DNA have been cloned and sequenced and the site expression of this gene has been localized to promyelocytes in bone marrow. Cloning, sequencing and oligonucleotides have been used to detect specific mutations in the alpha 1AT gene causing the deficiency states. The """"""""null"""""""" alpha 1AT state is associated with an intact gene, but contains various different mutations causing stop codons in the alpha 1AT mRNA. Therapy of alpha 1AT deficiency with alpha 1AT purified from pooled plasma has demonstrated that the anti- neutrophil-elastase defenses of the lung can be re-established with intermittent intravenous administration of alpha 1AT weekly or monthly as well as with intermittent aerosol administration daily.
