Severe and moderate alpha-1-antitrypsin deficiency at the age of 30

Abstract: Alpha-1-antitrypsin (AAT) is a glycoprotein synthesised in the liver. Its main role is to protect lung tissue from destruction by neutrophil elastase. In severe (PiZZ) AAT deficiency, there is an increased risk of emphysema, especially in smokers. The deficiency is caused by the retention and aggregation by polymerization of the AAT molecules in the liver, which increases the risk of neonatal cholestasis in infancy, and cirrhosis and hepatocellular carcinoma in adulthood. To investigate the prevalence of severe and moderate (PiSZ) AAT deficiency and follow its natural course, all 200,000 Swedish new-born children were screened in 1972-74. Among these, 128 individuals with severe and 55 with moderate AAT deficiency were identified. They and a group of controls were invited to a follow-up at the age of 30. The participants answered a questionnaire including questions about occupation, smoking habits and respiratory symptoms. Pulmonary function tests and CT densitometry were performed. Blood samples were obtained to analyse liver enzymes and serum proteins. The AAT-deficient individuals smoked less than the controls but the PiZZ individuals who had smoked had more respiratory symptoms than the other subgroups. The PiZZ current smokers had a lower FEV1/VC ratio and diffusion capacity for carbon monoxide compared to the other subgroups. As a group, the AAT-deficient individuals did not differ in respiratory symptoms, lung function or CT densitometry from the controls. The AAT-deficient individuals had normal levels of liver enzymes but mean ASAT and ALAT were significantly higher than in the control subjects. At the age of 30, individuals with severe (PiZZ) and moderate (PiSZ) AAT deficiency are healthy. However, smokers have more respiratory symptoms and alterations in lung function, which may be early signs of COPD. Compared to healthy controls, the AAT-deficient individuals had higher levels of liver transaminases.