Clinical features and prognosis of life time non-smokers with severe alpha 1-antitrypsin deficiency

Abstract

Background: The hereditary disorder alpha 1-antitrypsin deficiency is characterised by development of severe emphysema at an early age with smoking being the most significant additional risk factor. The purpose of the present paper was to analyse potential risk factors other than smoking for emphysema and to estimate the prognosis of life time non-smokers.

Methods: Patients were identified through the files of the Danish alpha 1-antitrypsin deficiency register which contains information on more than 700 persons with the condition. Many of the patients, the non-index cases, were identified from family studies.

Results: There were 75 life time non-smokers with PiZ (27 index cases and 48 non-index cases) aged 20 years or more at entry. Twenty one subjects died during the follow up period. The Standardised Mortality Ratio (SMR) was 3.0 (95% confidence intervals (CI) 1.9 to 4.6). There was no significant difference in SMR between males and females. The SMR was 8.8 (95% CI 5.0 to 14) for the index cases and 0.96 (95% CI 0.3 to 2.3) for the non-index cases based on five deaths. The overall mean % predicted forced expiratory volume in one second (FEV1) at entry was 83% with a significant difference between index cases (54%) and non-index cases (100%) (p < 0.001). The difference in the ratio of FEV1 to forced vital capacity (FVC) was also highly significant with values of 0.57 and 0.79 for index and non-index cases, respectively (p < 0.001). In the non-index group only three had an FEV1% predicted of less than 70%.

Conclusions: Occupational exposure to airway irritants did not have any significant influence on the development of emphysema. Only a few life time non-smokers develop severe emphysema; most never develop pulmonary symptoms and thus remain undetected unless family members of index cases are screened.