LONG-TERM TREATMENT OF ALPHA(1)-ANTITRYPSIN DEFICIENCY-RELATED PULMONARY-EMPHYSEMA WITH HUMAN ALPHA(1)-ANTITRYPSIN

alpha(1)-antitrypsin (alpha(1)-AT) deficiency is a genetic disorder ch aracterized by low serum levels of alpha(1)-AT and a high risk of pulm onary emphysema at a young age. The resulting surplus of proteases, ma inly of neutrophil elastase, can be balanced by i.v. augmentation with alpha(1)-AT. However, it is not clear if affected patients benefit fr om long-term augmentation therapy and no long-term safety data are ava ilable. We examined 443 patients with severe alpha(1)-AT deficiency an d pulmonary emphysema receiving weekly i.v. infusions of 60 mg.kg body weight(-1) alpha(1)-AT in addition to their regular medication, The p rogression of the disease was assessed by repeated lung function measu rements, particularly the decline in forced expiratory volume in one s econd (Delta FEV1), Four hundred and forty three patients with alpha(1 )-AT deficiency tolerated augmentation therapy well with fen adverse r eactions, The Delta FEV1 in 287 patients with available follow-up data was 57.1+/-31.1 mL.yr(-1). Stratified for baseline FEV1, the decline was 35.6+/-21.3 mt in the 108 patients with an initial FEV1 <30% and 6 4.0+/-26.4 mt in the 164 with FEV1 30-65% of predicted normal (p=0.000 8). The remaining 15 patients had an initial FEV1 >65% pred. Long-term treatment with i.v. alpha(1)-antitrypsin in patients with severe alph a(1)-antitrypsin deficiency is feasible and safe, The decline in force d expiratory volume in one second is related to the initial forced exp iratory volume in one second as in alpha(1)-antitrypsin deficient pati ents not receiving augmentation therapy.