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World J Transplant. Mar 18, 2023; 13(3): 58-85
Published online Mar 18, 2023. doi: 10.5500/wjt.v13.i3.58
Primary graft dysfunction following lung transplantation: From pathogenesis to future frontiers
Sanjeet Singh Avtaar Singh, Sudeep Das De, Ahmed Al-Adhami, Ramesh Singh, Peter MA Hopkins, Philip Alan Curry
Sanjeet Singh Avtaar Singh, Ahmed Al-Adhami, Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, United Kingdom
Sanjeet Singh Avtaar Singh, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom
Sudeep Das De, Heart and Lung Transplant Unit, Wythenshawe Hospital, Manchester M23 9NJ, United Kingdom
Ahmed Al-Adhami, Department of Heart and Lung Transplant, Royal Papworth Hospital, Cambridge CB2 0AY, United Kingdom
Ramesh Singh, Mechanical Circulatory Support, Inova Health System, Falls Church, VA 22042, United States
Peter MA Hopkins, Queensland Lung Transplant Service, Prince Charles Hospital, Brisbane, QLD 4032, Australia
Philip Alan Curry, Department of Cardiothoracic Surgery, Golden Jubilee National Hospital, Glasgow G81 4DY, United Kingdom
Author contributions: The idea behind the manuscript was by Avtaar Singh SS; Data collection and literature review was conducted by Avtaar Singh SS along with Das De S and Al-Adhami A; The subsequent manuscript was written by Avtaar Singh SS and Das De S with primary editing by Al-Adhami A; The sections were reviewed by Singh R, Hopkins PM and Curry PA; Further revisions were made by Avtaar Singh SS and Das De S; The final manuscript was submitted to all authors for final review and approval.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Sanjeet Singh Avtaar Singh, MBChB, MSc, PhD, Academic Fellow, Academic Research, Surgeon, Department of Cardiothoracic Surgery, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, United Kingdom.
Received: September 15, 2022
Peer-review started: September 15, 2022
First decision: October 27, 2022
Revised: November 11, 2022
Accepted: February 17, 2023
Article in press: February 17, 2023
Published online: March 18, 2023

Lung transplantation is the treatment of choice for patients with end-stage lung disease. Currently, just under 5000 lung transplants are performed worldwide annually. However, a major scourge leading to 90-d and 1-year mortality remains primary graft dysfunction. It is a spectrum of lung injury ranging from mild to severe depending on the level of hypoxaemia and lung injury post-transplant. This review aims to provide an in-depth analysis of the epidemiology, pathophysiology, risk factors, outcomes, and future frontiers involved in mitigating primary graft dysfunction. The current diagnostic criteria are examined alongside changes from the previous definition. We also highlight the issues surrounding chronic lung allograft dysfunction and identify the novel therapies available for ex-vivo lung perfusion. Although primary graft dysfunction remains a significant contributor to 90-d and 1-year mortality, ongoing research and development abreast with current technological advancements have shed some light on the issue in pursuit of future diagnostic and therapeutic tools.

Keywords: Primary graft dysfunction, Lung transplantation, Pathophysiology, Risk factors, Extracorporeal membranous oxygenation

Core Tip: Primary graft dysfunction is spectrum of lung injury ranging from mild to severe depending on the level of hypoxaemia and lung injury post-transplant. It has significant bearings on short and long term mortality and morbidity with chronic lung allograft dysfunction playing a major part. While the pathophysiology remains uncertain, it is felt to be a result of ischaemic reperfusion injury. The contributive factors, risks and treatment and management options are scrutinized in this manuscript to provide the readers with a clear insight into the enigma that is primary graft dysfunction.