In patients with alpha1-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 alpha1-antitrypsin in the treatment of patients with alpha1-antitrypsin deficiency. Twenty-one patients were given 60 mg of active plasma-derived alpha1-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 alpha1-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 μM as compared with 5.4±0.1 μM. The alpha1-antitrypsin level in the epithelial-lining fluid of the lungs was 0.46±0.16 μM before treatment, and the anti-neutrophil elastase capacity was 0.81 ±0.13 μM. Six days after infusion, alpha1-antitrypsin levels (1.89±0.17 μM) and anti-neutrophil elastase capacities (1.65±0.13 μM) in the lining fluid were significantly increased (P<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 alpha1-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_rantitrypsin may be a logical approach to long-term medical treatment. (N Engl J Med 1987; 316:1055–62.)