Clinical features and prognosis of life time non-smokers withsevere α1-antitrypsin deficiency

BACKGROUND—The hereditary disorderα₁-antitrypsin deficiency is characterised by developmentof severe emphysema at an early age with smoking being the mostsignificant additional risk factor. The purpose of the present paperwas to analyse potential risk factors other than smoking for emphysemaand to estimate the prognosis of life time non-smokers.
METHODS—Patients were identified through the filesof the Danish α₁-antitrypsin deficiency register whichcontains information on more than 700 persons with the condition. Manyof the patients, the non-index cases, were identified from family studies.
RESULTS—There were 75 life time non-smokers withPiZ (27 index cases and 48 non-index cases) aged 20 years or more atentry. Twenty one subjects died during the follow up period. TheStandardised Mortality Ratio (SMR) was 3.0 (95% confidence intervals(CI) 1.9to 4.6). There was no significant difference in SMR betweenmales 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 onfive deaths. The overall mean % predicted forced expiratory volume inone 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 forcedvital capacity (FVC) was also highly significant with values of 0.57and 0.79 for index and non-index cases, respectively (p<0.001). In thenon-index group only three had an FEV₁% predicted of less than 70%.
CONCLUSIONS—Occupational exposure to airwayirritants did not have any significant influence on the development ofemphysema. Only a few life time non-smokers develop severe emphysema;most never develop pulmonary symptoms and thus remain undetected unlessfamily members of index cases are screened.