A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy

We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, alpha(1)-antitrypsin, can prevent the progressi on of pulmonary emphysema in patients with alpha(1)-antitrypsin deficiency. Twenty-six Danish and SO Dutch ex-smokers with alpha(1)-antitrypsin defici ency of PI*ZZ phenotype and moderate emphysema (FEV1 between 30% and 80% of predicted) participated in a double-blind trial of alpha(1)-antitrypsin au gmentation therapy. The patients were randomized to either alpha(1)-antitry psin (250 mg/kg) or albumin (625 mg/kg) infusions at 4-wk intervals for at least 3 yr. Self-administered spirometry performed every morning and evenin g at home showed no significant difference in decline of FEV1 between treat ment and placebo. Each year, the degree of emphysema was quantified by the 15th percentile point of the lung density histogram derived from computed t omography (CT). The loss of lung tissue measured by CT (mean +/- SEM) was 2 .6 +/- 0.41 g/L/yr for placebo as compared with 1.5 +/- 0.41 g/L/yr for alp ha(1)-antitrypsin infusion (p = 0.07). Power analysis showed that this prot ective effect would be significant in a similar trial with 130 patients. Th is is in contrast to calculations based on annual decline of FEV1 showing t hat 550 patients would be needed to show a 50% reduction of annual decline. We conclude that lung density measurements by CT may facilitate future ran domized clinical trials of investigational drugs for a disease in which lit tle progress in therapy has been made in the past 30 yr.