Short-term supplementation therapy does not affect elastin degradation in severe alpha(1)-antitrypsin deficiency

We evaluated the ability of intravenous supplementation therapy with alpha (1)-antitrypsin (AAT) to reduce the rate of urinary excretion of desmosine (DES), a specific marker of elastin degradation, in eight men and four wome n with emphysema due to severe, congenital deficiency of AAT (range 17-69 m g/dl). Nine were former cigarette smokers, two were current smokers, and on e reported never smoking; their mean age was 54 (SD 12) yr and their mean F EV, was 41 (18%) of predicted. Urinary DES was measured by isotope dilution and HPLC. Prior to the start of AAT supplementation, mean DES excretion wa s 13.0 (5.0) mug/g creatinine, 73% higher than in healthy nonsmokers. Durin g 8 wk of supplementation therapy, mean urinary DES excretion was 13.0 (1.9 ) mug/g creatinine, unchanged from the baseline period (p = 0.85 by repeate d measures ANOVA). We conclude that baseline levels of elastin degradation in emphysematous patients with severe AAT deficiency were abnormally high a nd that 8 wk of AAT supplementation therapy did not appreciably reduce the rate of elastin degradation. These findings raise the possibilities that pr otective levels of AAT in the lungs are insufficient or that elastin degrad ation in the lungs of these subjects is not dependent upon neutrophil elast ase at this time.