Clinical course and prognosis of never-smokers with severe alpha-1-antitrypsin deficiency (PiZZ)

Abstract

Background: Previous studies of non-smoking individuals with severe alpha-1-antitrypsin deficiency (PiZZ) have been sparse and included only a limited number of individuals, mostly identified by respiratory symptoms. The aim of this study was to estimate the prognosis of non-smoking PiZZ individuals and to analyze the most common causes of death by including a large number of individuals who had been identified due to reasons other than respiratory symptoms.

Methods: The study included 568 non-smoking PiZZ subjects who were selected from the Swedish National AAT Deficiency Registry and followed-up from 1991 to September 2007. Of these, 156 (27%) were identified by respiratory symptoms (respiratory cases) and 412 were identified by extra pulmonary symptoms or screening (non-respiratory cases).

Results: Ninety-three subjects (16%) died during the follow-up time. The specific Standardized Mortality Rate (SMR) for the whole study population was 2.32 (95% confidence interval (CI) 1.87-2.83) with no significant difference between men and women. The SMR was 2.55 (95% CI 1.91-2.83) for the respiratory cases and 2.07 (95% CI 1.49-2.81) for the non-respiratory cases. Further calculation of SMR for subgroups in the non-respiratory cases showed that the SMR was 0.70 (95% CI 0.14-2.04) for individuals identified by family/population screening. Emphysema and liver cirrhosis were the most common causes of death (45% and 28%, respectively). Malignant transformation was found in 38% of the cirrhotic cases.

Conclusion: Non-smoking PiZZ individuals identified by screening do not have an increased mortality risk compared with the Swedish general population