Lung Injury Assessment: EVLP inflammation markers as prognostic outcome indicators

Inflammation score, interleukin-1β and pro-IL-1β can effectively predict successful transport outcomes.

The need to objectively assess donor lungs during ex-vivo lung perfusion (EVLP) to determine which lungs can be successfully transplanted, or reconditioned during EVLP, has driven the search for reliable predictive biomarkers. A couple of new publications from both sides of the Atlantic have recently reported important progress on this front.

From Toronto(15), Sage A et al have developed a protein-based assay to more precisely assess lung injury during EVLP. Perfusate samples were collected from over 230 clinical EVLP cases to derive and validate an inflammation score based on IL-6 and IL-8 protein levels in the perfusate. The accuracy of the inflammation score to predict the decision to transplant was then validated against lung transplant outcomes, including lungs more likely to develop primary graft dysfunction at 72-hours post-transplant. A model comprised of the inflammation score and Delta PO2 was able to determine EVLP transplants that were likely to have excellent recipient outcomes, with an accuracy of 87%.

Another predictive pro-inflammatory cytokine (IL-1β, or more recently its precursor Pro-IL 1β) has been the subject of similar work in UK(16). The study found the most effective markers to differentiate between in-hospital survival and non-survival post-transplant were perfusate interleukin (IL)-1β (p = 0.002) and tumor necrosis factor-α (p = 0.006) after 30 minutes of EVLP. Interestingly, both these biomarkers can nowadays be rapidly detected by a new rapid cytokine assay(17), using microfluidics which yields point of care results 30 to 45 mins into EVLP. (These assays previously took 24 -48 hours!)

More recently, the same group(18) have further refined their work on IL-1β by investigating the role of its precursor, Pro-IL-1β and its processing enzyme, caspase-1, in the EVLP perfusate of human lungs that had either been rejected or were successfully transplanted.

Significant increases in pro-IL-1β and caspase-1 were observed in the perfusate from human lungs that did not recondition during EVLP compared with those that successfully reconditioned and were used for transplantation. The authors suggest that pro-IL-1β is passively released following cellular necrosis of the donor lung.

XVIVO Insights PB-2021-04-20


15. Sage A T, et al: Prediction of donor related lung injury in clinical lung transplantation using a validated ex vivo lung perfusion inflammation score. J Heart Lung Transplant . 2021 Mar 5;S1053-2498(21)02219-1. doi: 10.1016/j.healun.2021.03.002. (link to Abstract)
16. Andreasson A S, et al: The role of interleukin-1β as a predictive biomarker and potential therapeutic target during clinical ex vivo lung perfusion.  J Heart Lung Transplant. 2017 Sep;36(9):985-995 (link to Abstract)
17. A.S. Andreasson A S, et al: A Near Point of Care Test for Interleukin 1B During Human Ex-Vivo Lung Perfusion. The Journal of Heart and Lung Transplantation, Vol 37, No 4S, p S56 April 2018 (link to Abstract)
18. Major T, et al , Pro-IL-1β Is an Early Prognostic Indicator of Severe Donor Lung Injury During Ex Vivo Lung Perfusion. Transplantation . 2021 Apr 1;105(4):768-774. doi: 10.1097/TP.0000000000003463 (link to Abstract)