Abboud R T, Ford G T, Chapman K R
University of British Columbia, Vancouver, Canada.
Can Respir J. 2001 Mar-Apr;8(2):81-8. doi: 10.1155/2001/824273.
To prepare new guidelines for the Canadian Thoracic Society (CTS) regarding severe alpha1-antitrypsin (AAT) deficiency and AAT replacement therapy.
Previously published guidelines and the medical literature about AAT deficiency and AAT replacement were reviewed. The prepared statement was reviewed and approved by the CTS Standards and Executive Committees.
Three studies evaluated AAT replacement. The National Heart, Lung and Blood Institute's AAT Registry was a nonrandomized comparison of patients receiving and not receiving AAT replacement, and evaluated the decline in forced expiratory volume in 1 s (FEV1) in 927 subjects. The rate of FEV1 decline was significantly less in those receiving AAT treatment (66 +/- SE 5 mL/year versus 93 +/- SE 11 mL/year; P=0.03) only in the subgroup with FEV1 35% to 49% predicted. In another study comparing 198 German patients receiving weekly AAT infusions and 97 untreated Danish patients, the mean annual decline in FEV1 was significantly less in treated patients only in the subgroup with FEV1 31% to 65% predicted (62 mL versus 83 mL, P=0.04). Neither of these studies was a randomized, controlled study and, thus, cannot be taken as proof of efficacy. A randomized, double-blind, placebo controlled trial of monthly replacement therapy over three years in 56 exsmokers with severe AAT deficiency and moderate emphysema showed a trend (P=0.07) favouring slower progression of emphysema by computed tomography scan in the group receiving AAT replacement.
AAT replacement therapy has not been proven definitively to be clinically effective in reducing the progression of disease in AAT-deficient patients, but there is a possible benefit to selected patients. A placebo controlled, randomized clinical trial of AAT replacement therapy is required. The authors recommend reserving AAT replacement therapy for AAT-deficient patients with impaired FEV1 of 35% to 50% predicted who have quit smoking and are on optimal medical therapy but continue to show a rapid decline in FEV1, and participation of all AAT-deficient subjects in the Canadian AAT Registry.
为加拿大胸科学会（CTS）制定关于严重α1-抗胰蛋白酶（AAT）缺乏症及AAT替代疗法的新指南。
回顾先前发表的关于AAT缺乏症及AAT替代疗法的指南和医学文献。编写的声明经CTS标准委员会和执行委员会审核并批准。
三项研究评估了AAT替代疗法。美国国立心肺血液研究所的AAT注册研究对接受和未接受AAT替代疗法的患者进行了非随机比较，并评估了927名受试者1秒用力呼气量（FEV1）的下降情况。仅在FEV1为预测值35%至49%的亚组中，接受AAT治疗的患者FEV1下降率显著更低（66±标准误5毫升/年对93±标准误11毫升/年；P=0.03）。在另一项研究中，比较了198名接受每周一次AAT输注的德国患者和97名未治疗的丹麦患者，仅在FEV1为预测值31%至65%的亚组中，治疗组患者的FEV1平均年下降率显著更低（62毫升对83毫升，P=0.04）。这两项研究均非随机对照研究，因此不能作为疗效的证据。一项针对56名患有严重AAT缺乏症和中度肺气肿的戒烟者进行的为期三年的每月替代疗法随机、双盲、安慰剂对照试验显示，接受AAT替代疗法的组通过计算机断层扫描显示肺气肿进展较慢有一定趋势（P=0.07）。
AAT替代疗法尚未被明确证明在临床上能有效减缓AAT缺乏症患者的疾病进展，但对部分患者可能有益。需要进行一项AAT替代疗法的安慰剂对照随机临床试验。作者建议，对于FEV1为预测值35%至50%且已戒烟、接受最佳药物治疗但FEV1仍快速下降的AAT缺乏症患者，保留AAT替代疗法，并建议所有AAT缺乏症患者参与加拿大AAT注册研究。
