Lung transplant outcomes for recipients with alpha-1 antitrypsin deficiency, by use of alpha-1 antitrypsin augmentation therapy

Background 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 the use of AAT augmentation therapy post-LT. Methods 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. Results 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 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). Conclusions In our study, the use of augmentation therapy post-LT was associated with improved survival. Confirmatory prospective studies should be considered to inform post-LT AAT therapy guidelines.