title: Protein expression profiling predicts graft performance in clinical ex vivo lung perfusion.
abstract: OBJECTIVE
  To study the impact of ex vivo lung perfusion (EVLP) on cytokines, chemokines, and growth factors and their correlation with graft performance either during perfusion or after transplantation.
  
  
  BACKGROUND
  EVLP is a modern technique that preserves lungs on normothermia in a metabolically active state. The identification of biomarkers during clinical EVLP can contribute to the safe expansion of the donor pool.
  
  
  METHODS
  High-risk brain death donors and donors after cardiac death underwent 4 to 6 hours EVLP. Using a multiplex magnetic bead array assay, we evaluated analytes in perfusate samples collected at 1 hour and 4 hours of EVLP. Donor lungs were divided into 3 groups: (I) Control: bilateral transplantation with good early outcome [absence of primary graft dysfunction- (PGD) grade 3]; (II) PGD3: bilateral transplantation with PGD grade 3 anytime within 72 hours; (III) Declined: lungs unsuitable for transplantation after EVLP.
  
  
  RESULTS
  Of 50 cases included in this study, 27 were in Control group, 7 in PGD3, and 16 in Declined. From a total of 51 analytes, 34 were measurable in perfusates. The best marker to differentiate declined lungs from control lungs was stem cell growth factor -β [P < 0.001, AUC (area under the curve) = 0.86] at 1 hour. The best markers to differentiate PGD3 cases from controls were interleukin-8 (P < 0.001, AUC = 0.93) and growth-regulated oncogene-α (P = 0.001, AUC = 0.89) at 4 hours of EVLP.
  
  
  CONCLUSIONS
  Perfusate protein expression during EVLP can differentiate lungs with good outcome from lungs PGD3 after transplantation. These perfusate biomarkers can be potentially used for more precise donor lung selection improving the outcomes of transplantation.
authors.affiliation: *Toronto Lung Transplant Program, University Health Network; and †Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Tiago N
authors.initials: TN
authors.lastname: Machuca
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cypel
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Yeung
authors.forename: Riccardo
authors.initials: R
authors.lastname: Bonato
authors.forename: Ricardo
authors.initials: R
authors.lastname: Zamel
authors.forename: Manyin
authors.initials: M
authors.lastname: Chen
authors.forename: Sassan
authors.initials: S
authors.lastname: Azad
authors.forename: Michael K
authors.initials: MK
authors.lastname: Hsin
authors.forename: Tomohito
authors.initials: T
authors.lastname: Saito
authors.forename: Zehong
authors.initials: Z
authors.lastname: Guan
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001926:Brain Death; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D006331:Heart Diseases / Q000401:mortality; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008168:Lung / Q000098:blood supply*; D016040:Lung Transplantation; D009864:Ontario; D010477:Perfusion / Q000379:methods*; D011237:Predictive Value of Tests; D014019:Tissue Donors; D009927:Tissue and Organ Procurement / Q000379:methods
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins