Stoller James K
Education Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States.
Chronic Obstr Pulm Dis. 2022 Jan 27;9(1):95-102. doi: 10.15326/jcopdf.2021.0261.
Alpha-1 antitrypsin deficiency (AATD) predisposes to emphysema, liver disease, and panniculitis. This emphysema risk naturally invites a comparison between "regular" chronic obstructive pulmonary disease (COPD) (i.e., unrelated to AATD) and AATD-associated emphysema. Several features characterize both conditions. Both can be life-limiting and highly debilitating. Both are highly under-recognized. An important corollary of this comparison between "regular" COPD and AATD-associated COPD is whether both should be treated similarly and whether clinical trials to assess new therapies can be conducted similarly in both. Here, the distinctions between "regular" COPD and AATD-associated COPD are quite pronounced. Therapeutically, sparse available data suggest that lung volume reduction surgery confers less improvement in forced expiratory volume in 1 second (FEV1) in AATD and that such benefits are shorter-lived. Perhaps the most striking contrast between the 2 conditions is that clinical trial designs and conduct are necessarily very different. The relative scarcity of diagnosed individuals with AATD hampers recruitment to trials. Furthermore, primary outcome measures in trials of "regular" COPD must differ markedly from those of AATD-associated emphysema. Specifically, power calculations show that FEV1 and exacerbation frequency, which are amply represented as endpoints in large COPD trials, are infeasible in studies of AATD-associated emphysema. Rather, in the 3 available randomized controlled trials of intravenous augmentation therapy, the rate of emphysema progression based on serial computed tomography densitometry measurements has been the only feasible primary outcome measure. These considerations underscore the distinctive challenges and needs of conducting treatment trials in AATD-associated emphysema and emphasize that, with regard to clinical study design, the 2 conditions are "more unalike than alike."
α-1抗胰蛋白酶缺乏症（AATD）易引发肺气肿、肝脏疾病和脂膜炎。这种肺气肿风险自然引发了对“普通”慢性阻塞性肺疾病（COPD）（即与AATD无关）和AATD相关肺气肿的比较。这两种病症有几个共同特征。两者都可能危及生命且使人极度虚弱。两者都未得到充分认识。“普通”COPD与AATD相关COPD之间比较的一个重要推论是，两者是否应采用相似的治疗方法，以及评估新疗法的临床试验在两者中是否可以相似地进行。在此，“普通”COPD与AATD相关COPD之间的区别相当明显。在治疗方面，现有稀少的数据表明，肺减容手术在AATD患者中对1秒用力呼气量（FEV1）的改善较小，且这种益处持续时间较短。这两种病症之间最显著的差异或许在于临床试验设计和实施必然非常不同。AATD确诊个体相对稀少，这妨碍了试验招募。此外，“普通”COPD试验中的主要结局指标必须与AATD相关肺气肿的指标有显著差异。具体而言，功效计算表明，在大型COPD试验中作为充分代表的终点指标FEV1和急性加重频率，在AATD相关肺气肿研究中并不可行。相反，在3项现有的静脉补充治疗随机对照试验中，基于系列计算机断层扫描密度测量的肺气肿进展速率一直是唯一可行的主要结局指标。这些考虑凸显了在AATD相关肺气肿中开展治疗试验的独特挑战和需求，并强调在临床研究设计方面，这两种病症“差异大于相似”。
