title: Profiling inflammation and tissue injury markers in perfusate and bronchoalveolar lavage fluid during human ex vivo lung perfusion.
abstract: 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.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.|Cardiopulmonary Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Anders S I
authors.initials: AS
authors.lastname: Andreasson
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Danai M
authors.initials: DM
authors.lastname: Karamanou
authors.affiliation: School of Mathematics & Statistics, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Colin S
authors.initials: CS
authors.lastname: Gillespie
authors.affiliation: Cardiopulmonary Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Faruk
authors.initials: F
authors.lastname: Özalp
authors.affiliation: Cardiopulmonary Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Tanveer
authors.initials: T
authors.lastname: Butt
authors.affiliation: Cardiopulmonary Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Hill
authors.affiliation: Cardiopulmonary Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Kasim
authors.initials: K
authors.lastname: Jiwa
authors.affiliation: Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Walden
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.|Cardiopulmonary Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Green
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Borthwick
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.|Cardiopulmonary Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Clark
authors.affiliation: Cardiopulmonary Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Henning
authors.initials: H
authors.lastname: Pauli
authors.affiliation: Cardiopulmonary Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Kate F
authors.initials: KF
authors.lastname: Gould
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.|Cardiopulmonary Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Corris
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Simi
authors.initials: S
authors.lastname: Ali
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.|Cardiopulmonary Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: John H
authors.initials: JH
authors.lastname: Dark
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.|Cardiopulmonary Transplantation, Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fisher
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000737:chemistry; D010477:Perfusion / Q000379:methods; D010865:Pilot Projects; D011379:Prognosis; D009927:Tissue and Organ Procurement / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D019188:Organ Preservation Solutions
keywords: Biomarkers; EVLP; Inflammation; Lung injury; Lung transplant 