[Long-term substitution in homozygous alpha 1-antitrypsin deficiency. Effect of the proteinase-antiproteinase equilibrium in plasma and sputum].
Long-term replacement with human alpha 1-antitrypsin (60 mg/kg once a week intravenously) was carried out in seven patients with homozygous alpha 1-antitrypsin deficiency (7 males, mean age 50.8 [40-59] years) and progressive pulmonary emphysema for an average of 16 (13-20) weeks. After at least 12 weeks' therapy the concentrations of alpha 1-antitrypsin, elastase-alpha 1-antitrypsin complex, alpha 2-macroglobulin, lactoferrin and elastase inhibition capacity in plasma and sputum were assayed, these assays being performed before starting the alpha 1-antitrypsin infusion and at various times during the following week. After the infusion the plasma concentration of alpha 1-antitrypsin rose from a depressed initial level (median 1.22 g/l) to a level approximately five times higher (median after 1 hour: 5.96 g/l, P less than 0.001), and then declined exponentially, though it never fell below the threshold of 35% of normal which is regarded as the protective level. Elastase inhibition capacity displayed similar changes (r = 0.85). The sputum concentration of alpha 1-antitrypsin rose more slowly than the plasma concentration; from the initial level (median 8 mg/l) it reached a maximum about four times higher after 24 hours (median 36 mg/l; P less than 0.02). Elastase inhibition capacity rose from 151 mIU/ml (median) before the alpha 1-antitrypsin infusion to 450 mIU/ml at 24 hours. These findings suggest that alpha 1-antitrypsin replacement will have beneficial effects on proteinase-antiproteinase equilibrium. Determination of elastase inhibition capacity in the sputum is suitable for monitoring dosage during replacement therapy.
Braun
J
J
Klinik für Innere Medizin, Medizinische Universität Lübeck.
Welle
S
S
van Wees
J
J
Winterhoff
R
R
Wood
W G
WG
Dalhoff
K
K
Wiessmann
K J
KJ
D000328:Adult; D010450:Endopeptidases / Q000097:blood / Q000378:metabolism*; D005260:Female; D006720:Homozygote; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000097:blood / Q000378:metabolism*; D011656:Pulmonary Emphysema / Q000150:complications*; D013183:Sputum / Q000201:enzymology*; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000032:analysis; D019896:alpha 1-Antitrypsin Deficiency
D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; D010450:Endopeptidases; D010196:Pancreatic Elastase
Dauersubstitution bei homozygotem alpha 1-Antitrypsin-Mangel. Einfluss auf das Proteinasen-Antiproteinasen-Gleichgewicht in Plasma und Sputum.