Prediction of donor related lung injury in clinical lung transplantation using a validated ex vivo lung perfusion inflammation score

Andrew T Sage Melissa Richard-Greenblatt Kathleen Zhong Xiao Hui Bai Matthew B Snow Monica BabitsAadil Ali Cristina Baciu Jonathan C Yeung Mingyao Liu Marcelo Cypel Kevin C Kain Shaf Keshavjee J Heart Lung Transplant . 2021 Mar 5;S1053-2498(21)02219-1. doi: 10.1016/j.healun.2021.03.002. Online ahead of print. PMID: 33781664 DOI:

Background:
Ex vivo lung perfusion (EVLP) is an isolated organ assessment technique that has revolutionized the field of lung transplantation and enabled a safe increase in the number of organs transplanted. The objective of this study was to develop a protein-based assay that would provide a precision medicine approach to lung injury assessment during EVLP.

Methods:
Perfusate samples collected from clinical EVLP cases performed from 2009 to 2019 were separated into development (n = 281) and validation (n = 57) sets to derive and validate an inflammation score based on IL-6 and IL-8 protein levels in perfusate. The ability of improve accuracy of EVLP decision-making. Inflammation scores were compared to conventional clinical EVLP assessment parameters and associated with outcomes, including primary graft dysfunction and patient care in the ICU.

Results:
An inflammation score accurately predicted the decision to transplant (AUROC 68% [95% CI 62-74]) at the end of EVLP and those transplants associated with short ventilator times (AUROC 73% [95% CI 66-80]). The score identified lungs more likely to develop primary graft dysfunction at 72-hours post-transplant (OR 4.0, p = 0.03). A model comprised of the inflammation score and ∆PO2 was able to determine EVLP transplants that were likely to have excellent recipient outcomes, with an accuracy of 87% [95% CI 83-92].

Conclusions:
The adoption of an inflammation score will improve accuracy of EVLP decision-making and increase confidence of surgical teams to determine lungs that are suitable for transplantation, thereby improving organ utilization rates and patient outcomes.

Keywords:
cytokines; ex vivo lung perfusion; personalized medicine; post-transplant outcomes; predictive biomarkers.

Copyright © 2021. Published by Elsevier Inc.