Non-targeted screening for Alpha-1 Antitrypsin Deficiency

This retrospective study was a non-targeted screening in patients referred to office bound pneumologists. It was hypothesized that Alpha-1 Antitrypsin deficiency (AATD) disease penetrance is incomplete, and health status as well as physiologic parameters can be preserved until higher ages. Measurement of serum levels of Alpha-1 Antitrypisn (AAT) was performed in subsequent patients referred for respiratory reasons (respiratory group), or for non-respiratory reasons (e.g. allergies, suspected sleep apnoea; non-respiratory group). The measurements were performed in routine blood test with standard techniques. This study was approved by the local Ethic Committees (reference code EK-BR-9/24-1). In 5,325 consecutive patients, serum AAT was measured. 2,790 (52.4 %) were respiratory, 2,535 (47.5 %) non-respiratory cases. Serum-levels ≤ 0,5 g/l were detected in 40 patients (0,75 %), age range 27 to 88 years, 60 % male. 24 tests were positive in respiratory, 16 in non-respiratory cases. PI*ZZ was the dominating defective genetic type. Liver function was normal, except in one patient. One patient developed symptoms before the age of 40 years. Above 40, 16/32 cases developed lung disease. Lung function deteriorated depending on age, with progressive lung hyperinflation and reduction in FEV1. Nine out of 16 non-respiratory cases had a smoking history (mean age 52.5), but only one experienced lung disease. Untargeted screening revealed an unexpected high frequency of severe AATD even in asymptomatic cases, demonstrating incomplete disease penetrance. More than half of the deficient patients had a smoking history, but many of them did not develop respiratory symptoms, even at higher ages.