Department of Pulmonary and Critical Care, Cleveland Clinic Florida, Weston, FL, USA.
Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, Charleston, SC, USA.
Int J Chron Obstruct Pulmon Dis. 2020 Dec 3;15:3193-3199. doi: 10.2147/COPD.S263725. eCollection 2020.
The extent of the survival benefit of augmentation therapy for alpha-1 antitrypsin deficiency (AATD) in individuals with advanced COPD is difficult to define. We performed a retrospective analysis using all available data from the observational registry of individuals with severe deficiency of alpha-1 antitrypsin (AAT) conducted by the NHLBI investigators.
Individuals (N=1129) with severe deficiency of AAT were evaluated for mortality using all data sources and stratified by 10% increments of baseline forced expiratory volume in 1 second (FEV1) percent predicted and by augmentation therapy status (ever receiving versus never receiving). Kaplan-Meier survival curves were constructed for each of the deciles comparing survival in treated vs non-treated groups. A multivariable model was performed to define the correlates of survival in individuals with FEV1 <30% predicted.
Amongst all subjects, augmentation was associated with improved survival (p<0.0001). Among the individuals ever receiving augmentation therapy, survival was better than for those not receiving augmentation at all 10% increments of FEV1% predicted from 10% to 60% (P values <0.05 in all deciles). In subgroups of participants with hyperinflation defined as residual volume (RV)>120% predicted and in subgroups of participants with reduced diffusing capacity for carbon monoxide (DLCO) <70% predicted, there was significantly better survival for those ever receiving augmentation therapy than for those who never received augmentation (p<0.001). A multivariable analysis showed that mortality benefit is influenced by age, DLCO % predicted, and augmentation therapy.
There is a survival benefit from augmentation therapy in AATD between FEV1 values in the 10-60% predicted range. Screening and treatment of AATD patients should therefore not be limited by the severity of illness as defined by FEV1.
对于晚期 COPD 患者，α-1 抗胰蛋白酶缺乏症（AATD）的增强治疗的生存获益程度难以确定。我们使用由 NHLBI 研究人员进行的严重缺乏α-1 抗胰蛋白酶（AAT）个体的观察性登记处的所有可用数据进行了回顾性分析。
使用所有数据源评估严重缺乏 AAT 的个体的死亡率，并按基线 1 秒用力呼气量（FEV1）预测值的 10%递增和增强治疗状态（是否接受治疗）进行分层（从未接受过治疗与从未接受过治疗）。为每个十位数构建治疗组与非治疗组之间的生存 Kaplan-Meier 生存曲线。进行多变量模型以定义 FEV1 <30%预测值个体的生存相关因素。
在所有受试者中，增强治疗与生存改善相关（p<0.0001）。在所有接受过增强治疗的个体中，与从未接受过增强治疗的个体相比，在 FEV1%预测值从 10%到 60%的每个 10%递增中，生存情况更好（所有十位数的 P 值均<0.05）。在定义为残气量（RV）>120%预测值的过度充气亚组和定义为一氧化碳弥散量（DLCO）<70%预测值的降低亚组的参与者中，与从未接受过增强治疗的个体相比，那些接受过增强治疗的个体的生存率明显更高（p<0.001）。多变量分析表明，死亡率的获益受到年龄、DLCO%预测值和增强治疗的影响。
在 FEV1 值为 10-60%预测值范围内，AATD 中增强治疗具有生存获益。因此，AATD 患者的筛查和治疗不应仅限于 FEV1 定义的疾病严重程度。
