Lung transplant outcomes for recipients with alpha-1 antitrypsin deficiency, by use of alpha-1 antitrypsin augmentation therapy
Atharv V. Oak, MEng,
Jessica M. Ruck, MD, PhD,
Alfred J. Casillan, MD, PhD,
Armaan F. Akbar, BS,
Ramon A. Riojas, MD, PhD,
Pali D. Shah, MD,
Jinny S. Ha, MD, MHS,
Sara Strout, PharmD,
Allan B. Massie, PhD,
Dorry L. Segev, MD, PhD,
Christian A. Merlo, MD, MPH,
Errol L. Bush, MD
Affiliations
Atharv V. Oak, MEng
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
Jessica M. Ruck, MD, PhD
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
Alfred J. Casillan, MD, PhD
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
Armaan F. Akbar, BS
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
Ramon A. Riojas, MD, PhD
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
Pali D. Shah, MD
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
Jinny S. Ha, MD, MHS
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
Sara Strout, PharmD
Department of Pharmacy, Johns Hopkins University School of Medicine, Baltimore, Maryland
Allan B. Massie, PhD
Department of Surgery, New York University Grossman School of Medicine and Langone Health, New York, New York; Department of Population Health, New York University Grossman School of Medicine and Langone Health, New York, New York
Dorry L. Segev, MD, PhD
Department of Surgery, New York University Grossman School of Medicine and Langone Health, New York, New York; Department of Population Health, New York University Grossman School of Medicine and Langone Health, New York, New York; Scientific Registry of Transplant Recipients, Minneapolis, Minnesota
Christian A. Merlo, MD, MPH
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
Errol L. Bush, MD
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland; Corresponding author: Errol L. Bush, MD, Advanced Lung Disease and Lung Transplant Program, Department of Surgery, Johns Hopkins Medical Institutions, Blalock 240, 600 North Wolfe Street, Baltimore, MD 21287.
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.
