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.