Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion

• Published in: European journal of cardio-thoracic surgery Vol. 51; no. 3; pp. 577 - 586
• Main Authors: Andreasson, Anders S I, Karamanou, Danai M, Gillespie, Colin S, Özalp, Faruk, Butt, Tanveer, Hill, Paul, Jiwa, Kasim, Walden, Hannah R, Green, Nicola J, Borthwick, Lee A, Clark, Stephen C, Pauli, Henning, Gould, Kate F, Corris, Paul A, Ali, Simi, Dark, John H, Fisher, Andrew J
• Format: Journal Article
• Language: English
• Published: Germany Oxford University Press 01.03.2017
• Subjects: Adolescent; Adult; Biomarkers - metabolism; Bronchoalveolar Lavage Fluid - chemistry; Feasibility Studies; Female; Humans; Inflammation Mediators - metabolism; Lung Transplantation - methods; Male; Middle Aged; Organ Preservation - methods; Organ Preservation Solutions - chemistry; Perfusion - methods; Pilot Projects; Prognosis; Tissue and Organ Procurement - methods; Transplantation and Mechanical Circulatory Support; Treatment Outcome; Young Adult; Biomarkers; Inflammation; EVLP; Lung transplant; Lung injury
• ISSN: 1010-7940; 1873-734X
• DOI: 10.1093/ejcts/ezw358

Availability of donor lungs suitable for transplant falls short of current demand and contributes to waiting list mortality. Ex vivo lung perfusion (EVLP) offers the opportunity to objectively assess and recondition organs unsuitable for immediate transplant. Identifying robust biomarkers that can stratify donor lungs during EVLP to use or non-use or for specific interventions could further improve its clinical impact. In this pilot study, 16 consecutive donor lungs unsuitable for immediate transplant were assessed by EVLP. Key inflammatory mediators and tissue injury markers were measured in serial perfusate samples collected hourly and in bronchoalveolar lavage fluid (BALF) collected before and after EVLP. Levels were compared between donor lungs that met criteria for transplant and those that did not. Seven of the 16 donor lungs (44%) improved during EVLP and were transplanted with uniformly good outcomes. Tissue and vascular injury markers lactate dehydrogenase, HMGB-1 and Syndecan-1 were significantly lower in perfusate from transplanted lungs. A model combining IL-1β and IL-8 concentrations in perfusate could predict final EVLP outcome after 2 h assessment. In addition, perfusate IL-1β concentrations showed an inverse correlation to recipient oxygenation 24 h post-transplant. This study confirms the feasibility of using inflammation and tissue injury markers in perfusate and BALF to identify donor lungs most likely to improve for successful transplant during clinical EVLP. These results support examining this issue in a larger study.