Chapman Kenneth R, Chorostowska-Wynimko Joanna, Koczulla A Rembert, Ferrarotti Ilaria, McElvaney Noel G
Department of Medicine, University of Toronto, Toronto, ON, Canada.
Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland.
Int J Chron Obstruct Pulmon Dis. 2018 Jan 31;13:419-432. doi: 10.2147/COPD.S149429. eCollection 2018.
Alpha 1 antitrypsin deficiency is a hereditary condition characterized by low alpha 1 proteinase inhibitor (also known as alpha 1 antitrypsin [AAT]) serum levels. Reduced levels of AAT allow abnormal degradation of lung tissue, which may ultimately lead to the development of early-onset emphysema. Intravenous infusion of AAT is the only therapeutic option that can be used to maintain levels above the protective threshold. Based on its biochemical efficacy, AAT replacement therapy was approved by the US Food and Drug administration in 1987. However, there remained considerable interest in selecting appropriate outcome measures that could confirm clinical efficacy in a randomized controlled trial setting. Using computed tomography as the primary measure of decline in lung density, the capacity for intravenously administered AAT replacement therapy to slow and modify the course of disease progression was demonstrated for the first time in the Randomized, Placebo-controlled Trial of Augmentation Therapy in Alpha-1 Proteinase Inhibitor Deficiency (RAPID) trial. Following these results, an expert review forum was held at the European Respiratory Society to discuss the findings of the RAPID trial program and how they may change the landscape of alpha 1 antitrypsin emphysema treatment. This review summarizes the results of the RAPID program and the implications for clinical considerations with respect to diagnosis, treatment and management of emphysema due to alpha 1 antitrypsin deficiency.
α1抗胰蛋白酶缺乏症是一种遗传性疾病，其特征是血清中α1蛋白酶抑制剂（也称为α1抗胰蛋白酶[AAT]）水平较低。AAT水平降低会导致肺组织异常降解，最终可能导致早发性肺气肿的发生。静脉输注AAT是唯一可用于将水平维持在保护阈值以上的治疗选择。基于其生化疗效，AAT替代疗法于1987年获得美国食品药品监督管理局批准。然而，对于选择合适的结局指标以在随机对照试验环境中确认临床疗效仍有相当大的兴趣。在α1蛋白酶抑制剂缺乏症强化治疗随机、安慰剂对照试验（RAPID）中，首次证明了静脉注射AAT替代疗法减缓并改变疾病进展过程的能力，该试验将计算机断层扫描作为肺密度下降的主要测量指标。基于这些结果，欧洲呼吸学会召开了一次专家评审论坛，讨论RAPID试验项目的结果以及这些结果可能如何改变α1抗胰蛋白酶肺气肿治疗的格局。本综述总结了RAPID项目的结果以及对α1抗胰蛋白酶缺乏症所致肺气肿的诊断、治疗和管理的临床考量的影响。
