Association of alpha 1-antitrypsin deficiency with lung and liver diseases.

alpha(1)-Protease inhibitor (alpha(1)-Pi) deficiency is associated with emphysema, neonatal hepatitis and cirrhosis. The deficiency associated with emphysema has multiple alleles. Cigarette smoke may influence the onset of emphysema in a twofold manner: by overwhelming the concentration of alpha(1)-Pi by increasing elastase release, and by inactivating the alpha(1)-Pi active site through oxidation. alpha(1)-Pi-associated hepatic disease occurs primarily in children with the allele PiZZ, most of whom are asymptomatic although in a small percentage severe obstructive jaundice and fatal junvenile cirrhosis develop. Pharmacologic intervention and alpha(1)-Pi replacement therapy are being tested against alpha(1)-Pi-associated emphysema.