1. Alpha-1 Antitrypsin Augmentation Therapy Improves Survival in Severely Deficient Patients with Predicted FEV1 Between 10% and 60%: A Retrospective Analysis of the NHLBI Alpha-1 Antitrypsin Deficiency Registry.
- Author
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Rahaghi FF, Monk R, Ramakrishnan V, Beiko T, and Strange C
- Subjects
- Forced Expiratory Volume, Humans, National Heart, Lung, and Blood Institute (U.S.), Registries, Retrospective Studies, United States, alpha 1-Antitrypsin, Pulmonary Disease, Chronic Obstructive diagnosis, Pulmonary Disease, Chronic Obstructive drug therapy, alpha 1-Antitrypsin Deficiency diagnosis, alpha 1-Antitrypsin Deficiency drug therapy
- Abstract
Purpose: 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., Patients and Methods: 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., Results: 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., Conclusion: 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., Competing Interests: TB reports grants with Grifols, outside the submitted work. CS is employed in part by AlphaNet, a disease management company for Alpha-1 antitrypsin deficiency. He reports grants from Adverum, Arrowhead, CSL Behring, Grifols, MatRx, Takeda, and Vertex. He has received personal fees from CSL Behring, Dicerna, and Vertex, all outside the submitted work. FR reports grants and personal fees, from Grifols, and Takeda outside the submitted work. The authors report no other conflicts of interest in this work., (© 2020 Rahaghi et al.)
- Published
- 2020
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