Lung Transplant Outcomes for Recipients with Alpha-1 Antitrypsin Deficiency, by use of Alpha-1 Antitrypsin Augmentation Therapy

For patients with alpha-1 antitrypsin (AAT) deficiency, AAT augmentation therapy can be an important part of care. However, for those who require a lung transplant (LT), there is currently only limited information to guide use of AAT augmentation therapy post-LT. We identified all LT recipients from 2011-2021 in the Scientific Registry of Transplant Recipients with an AAT deficiency diagnosis. We categorized recipients by use of AAT augmentation therapy post-LT and compared their baseline characteristics using Fisher’s Exact test and Wilcoxon rank-sum tests. We used Kaplan-Meier analyses and estimated the average treatment effect (ATE) of post-LT AAT augmentation therapy on mortality and all-cause graft failure (ACGF). The ATE measures the observed effect we would see if everyone in the population received the intervention as opposed to just a subset. Among the 447 recipients with AAT deficiency, 109 used AAT augmentation therapy pre-LT, of which 32 (29.4%) continued post-LT. Recipients who used augmentation therapy post-LT were younger (56.5 [53-59.75] vs 57 [53.75-63], P=0.04) and had shorter ischemia time (mean 311 vs 363 minutes, P=0.03) than those who did not. The age-adjusted ATE estimate of post-LT augmentation therapy use on time to death and ACGF, was +1.69 years and +1.48 years respectively. Post-LT augmentation therapy use was associated with a mortality reduction in the top quartile bilirubin subgroup (P=0.02, log-rank test). In our study, use of augmentation therapy post-LT was associated with improved survival. Confirmatory prospective studies should be considered to inform post-LT AAT therapy guidelines.