Abstract

We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor,a1-antitrypsin, can prevent the progression of pulmonary emphysema in patients with a1-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with a1-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV1 between 30% and 80% of predicted) participated in a double-blind trial of a1-antitrypsin augmentation therapy. The patients were randomized to either a1-antitrypsin (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 evening at home showed no significant difference in decline of FEV1 between treatment and placebo. Each year, the degree of emphysema as quantified by the 15th percentile point of the lung density histogram derived from computed
tomography (CT). The loss of lung tissue measured by CT (mean +/- SEM) was 2.6 +/- 0.41 g/L/yr a1-antitrypsin infusion (p=0.07).Power analysis showed that this protective effect would be significant in a similar trial with 130 patients. This is in contrast to calculations based on annual decline of FEV1 showing that 550 patients would be needed to show a 50% reduction of annual decline. We conclude that lung density measurements by CT may
facilitate future randomized clinical trials of investigational drugs for a disease in which little progress in therapy has been made in the past 30 yr.

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