Short-term supplementation therapy does not affect elastin degradation in severe alpha(1)-antitrypsin deficiency. The American-Italian AATD Study Group.
Short-term supplementation therapy does not affect elastin degradation in severe alpha(1)-antitrypsin deficiency. The American-Italian AATD Study Group.
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短期补充疗法不会影响严重 α(1)-抗胰蛋白酶缺乏症的弹性蛋白降解。
DOI：
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发表时间：
2000
影响因子：
24.7
通讯作者：
G. Snider
中科院分区：
文献类型：
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作者：
D. Gottlieb;M. Luisetti;P. Stone;L. Allegra;J. CANTEY;C. Grassi;G. Snider
我们评估了静脉补充α 1-抗胰蛋白酶（AAT）治疗8名男性和4名女性因严重的先天性AAT缺乏（范围17-69 mg/dl）而导致肺气肿的患者，以降低锁链素（DES）（弹性蛋白降解的特异性标志物）的尿排泄率的能力。9人以前吸烟，2人目前吸烟，1人从未吸烟;他们的平均年龄为54岁（SD 12），平均FEV（1）为预测值的41（18%）。采用同位素稀释法和高效液相色谱法测定尿DES。在开始补充AAT之前，平均DES排泄量为13.0（5.0）微克/克肌酐，比健康的非吸烟者高73%。在8周的补充治疗期间，平均尿DES排泄量为13.0（5.9）μ g/g肌酐，与基线期相比无变化（重复测量ANOVA，p = 0.85）。我们的结论是，基线水平的弹性蛋白降解严重AAT缺乏的肺气肿患者异常高，8周的AAT补充治疗并没有明显降低弹性蛋白降解率。这些发现提高了肺中AAT保护水平不足或这些受试者肺中弹性蛋白降解此时不依赖于中性粒细胞弹性蛋白酶的可能性。
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 women with emphysema due to severe, congenital deficiency of AAT (range 17-69 mg/dl). Nine were former cigarette smokers, two were current smokers, and one reported never smoking; their mean age was 54 (SD 12) yr and their mean FEV(1) was 41 (18%) of predicted. Urinary DES was measured by isotope dilution and HPLC. Prior to the start of AAT supplementation, mean DES excretion was 13.0 (5.0) microg/g creatinine, 73% higher than in healthy nonsmokers. During 8 wk of supplementation therapy, mean urinary DES excretion was 13.0 (5.9) microg/g creatinine, unchanged from the baseline period (p = 0.85 by repeated measures ANOVA). We conclude that baseline levels of elastin degradation in emphysematous patients with severe AAT deficiency were abnormally high and that 8 wk of AAT supplementation therapy did not appreciably reduce the rate of elastin degradation. These findings raise the possibilities that protective levels of AAT in the lungs are insufficient or that elastin degradation in the lungs of these subjects is not dependent upon neutrophil elastase at this time.