In patients with
alpha 1-antitrypsin deficiency, the development of
emphysema is believed to be caused by the unchecked action of
proteases on lung tissue. We evaluated the feasibility, safety, and biochemical efficacy of intermittent infusions of
alpha 1-antitrypsin in the treatment of patients with
alpha 1-antitrypsin deficiency. Twenty-one patients were given 60 mg of active plasma-derived
alpha 1-antitrypsin per kilogram of
body weight, once a week for up to six months. After a steady state had been reached, the group had trough serum levels of
alpha 1-antitrypsin of 126 +/- 1 mg per deciliter as compared with 30 +/- 1 mg per deciliter before treatment, and serum anti-
neutrophil elastase capacities of 13.3 +/- 0.1 microM as compared with 5.4 +/- 0.1 microM. The
alpha 1-antitrypsin level in the epithelial-lining fluid of the lungs was 0.46 +/- 0.16 microM before treatment, and the anti-
neutrophil elastase capacity was 0.81 +/- 0.13 microM. Six days after infusion,
alpha 1-antitrypsin levels (1.89 +/- 0.17 microM) and anti-
neutrophil elastase capacities (1.65 +/- 0.13 microM) in the lining fluid were significantly increased (P less than 0.0001). Because of the chronicity of the disorder and the lack of sensitive measures of lung destruction, the clinical efficacy of this
therapy could not be studied rigorously. No changes in lung function were observed in our patients over six months of treatment. The only important adverse reactions to the 507 infusions were four episodes of self-limited
fever. This study demonstrates that infusions of
alpha 1-antitrypsin derived from plasma are safe and can reverse the biochemical abnormalities in serum and lung fluid that characterize this disorder. Together with lifetime avoidance of cigarette smoking, replacement
therapy with
alpha 1-antitrypsin may be a logical approach to long-term medical treatment.