A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy.
A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy.
复制标题
α(1)-抗胰蛋白酶增强疗法的随机临床试验。
DOI：
--
复制
发表时间：
1999
影响因子：
24.7
通讯作者：
J. Stolk
中科院分区：
文献类型：
--
作者：
A. Dirksen;J. Dijkman;F. Madsen;B. Stoel;D. C. Hutchison;C. S. Ulrik;L. T. Skovgaard;A. Kok;A. Rudolphus;N. Seersholm;H. A. Vrooman;J. H. Reiber;N. C. Hansen;T. Heckscher;K. Viskum;J. Stolk
我们研究了中性粒细胞弹性蛋白酶及其抑制剂α 1-抗胰蛋白酶之间的平衡是否可以阻止α 1-抗胰蛋白酶缺乏症患者肺气肿的进展。26名丹麦和30名荷兰前吸烟者，患有PI * ZZ表型的α（1）-抗胰蛋白酶缺乏症和中度肺气肿（FEV（1）在预测值的30%和80%之间），参加了α（1）-抗胰蛋白酶增强治疗的双盲试验。患者被随机分为α（1）-抗胰蛋白酶（250 mg/kg）或白蛋白（625 mg/kg）输注组，每4周输注一次，至少持续3年。每天早晨和晚上在家中进行的自我肺功能测定显示，治疗组和安慰剂组的FEV（1）下降无显著差异。每年，肺气肿的程度通过计算机断层扫描（CT）得出的肺密度直方图的第15个百分位点来量化。通过CT测量的肺组织损失（平均值+/-SEM）为安慰剂组2.6 +/-0.41 g/L/年，而α（1）-抗胰蛋白酶输注组为1.5 +/-0.41 g/L/年（p = 0.07）。功效分析表明，在130例患者的类似试验中，这种保护作用将是显著的。这与基于FEV（1）年下降的计算结果相反，该计算结果显示需要550名患者才能显示年下降减少50%。我们的结论是，肺密度测量的CT可能会促进未来的随机临床试验的研究药物的疾病，在过去的30年中，在治疗方面取得了很大的进展。
We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, alpha(1)-antitrypsin, can prevent the progression of pulmonary emphysema in patients with alpha(1)-antitrypsin deficiency. Twenty-six Danish and 30 Dutch ex-smokers with alpha(1)-antitrypsin deficiency of PI*ZZ phenotype and moderate emphysema (FEV(1) between 30% and 80% of predicted) participated in a double-blind trial of alpha(1)-antitrypsin augmentation therapy. The patients were randomized to either alpha(1)-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 FEV(1) 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 alpha(1)-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 FEV(1) 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.