Clinical course and prognosis of individuals with severe alpha 1-antitrypsin deficiency (PiZZ)

University dissertation from Clinical Sciences, Lund University

Abstract: Severe alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with increases risk of developing of chronic obstructive lung disease and liver disease. The Swedish National Registry for individuals with severe AATD was started 1991.Up to October 2008, a total of 1349 individuals were included in the registry. The aims of the studies in this thesis which bases on AATD registry are to analyse the mortality of PiZZ individuals with respect to smoking habits and mode of identification, to analyse the predictors of mortality and to analyse the most common causes of death, by including a large number of never-smoking individuals. Further aims were to assess whether there is a survival benefit of lung transplantation in PiZZ individuals with severe emphysema. In study I and II, the PiZZ individuals had a significantly increased mortality risk compared with general Swedish population. We found that the smokers had a significantly higher mortality rate than the never-smokers and than the general population. The never-smoking individuals identified by screening did not have an increased mortality risk compared with the general population. Emphysema is still the main underlying cause of death in smoker-and never-smokers. Liver cirrhosis-related mortality seems to be increased in elderly never-smoking individuals, cirrhosis and its complications were the cause of death in 26 of 93 never-smokers. Increasing age, decreasing FEV1 % of predicted value and presence of respiratory symptoms were associated with increased mortality risk in PiZZ individuals. Study III shows a significant survival benefit for lung transplantation in PiZZ individuals with severe emphysema, with an estimated median survival time of 11 years compared to 7 years in the non-transplant patients. Furthermore, in Sweden, patients seem to be referred to the lung transplantation centers late in the disease which may result in an unnecessarily increased mortality for this group of patients. In study IV we did not find any significant differences in age, gender or smoking habits between the index and non-index siblings. Neither was there any significant difference in lung function at inclusion. Our study population was young in both groups with a mean age of 40 years or younger and the majority of both them were identified by screening.

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