TY - JOUR

T1 - A randomized clinical trial of α1-antitrypsin augmentation therapy

AU - Dirksen, Asger

AU - Dijkman, Joop H.

AU - Madsen, Flemming

AU - Stoel, Berend

AU - Hutchison, Duncan C.S.

AU - Ulrik, Charlotte S.

AU - Skovgaard, Lene T.

AU - Kok-Jensen, Axel

AU - Rudolphus, Arjan

AU - Seersholm, Niels

AU - Vrooman, Henri A.

AU - Reiber, Johan H.C.

AU - Hansen, Niels C.

AU - Heckscher, Thomas

AU - Viskum, Kaj

AU - Stolk, Jan

PY - 1999

Y1 - 1999

N2 - We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, α1-antitrypsin, can prevent the progression of pulmonary emphysema in patients with α1-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with α1-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV1 between 30% and 80% of predicted) participated in a double-blind trial of α1-antitrypsin augmentation therapy. The patients were randomized to either α1-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 was 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 for placebo as compared with 1.5 ± 0.41 g/L/yr for α1- 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.

AB - We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, α1-antitrypsin, can prevent the progression of pulmonary emphysema in patients with α1-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with α1-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV1 between 30% and 80% of predicted) participated in a double-blind trial of α1-antitrypsin augmentation therapy. The patients were randomized to either α1-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 was 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 for placebo as compared with 1.5 ± 0.41 g/L/yr for α1- 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.

UR - http://www.scopus.com/inward/record.url?scp=0032724157&partnerID=8YFLogxK

U2 - 10.1164/ajrccm.160.5.9901055

DO - 10.1164/ajrccm.160.5.9901055

M3 - Journal article

C2 - 10556107

AN - SCOPUS:0032724157

VL - 160

SP - 1468

EP - 1472

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 5 I

ER -