title: Increased Extravascular Lung Water and Plasma Biomarkers of Acute Lung Injury Precede Oxygenation Impairment in Primary Graft Dysfunction After Lung Transplantation.
abstract: After lung transplantation (LT), early prediction of grade 3 pulmonary graft dysfunction (PGD) remains a research gap for clinicians. We hypothesized that it could be improved using extravascular lung water (EVLWi) and plasma biomarkers of acute lung injury.
  
  
  
  After institutional review board approval and informed consent, consecutive LT recipients were included. Transpulmonary thermodilution-based EVLWi, plasma concentrations of epithelial (soluble receptor for advanced glycation endproducts [sRAGE]) and endothelial biomarkers (soluble intercellular adhesion molecule-1 and endocan [full-length and cleaved p14 fragment]) were obtained before and after LT (0 [H0], 6, 12, 24, 48 and 72 hours after pulmonary artery unclamping). Grade 3 PGD was defined according to the International Society for Lung and Heart Transplantation definition, combining arterial oxygen partial pressure (PaO2)/inspired fraction of oxygen (FiO2) ratio and chest X-rays. Association of clinical risk factors, EVLWi and biomarkers with grade 3 PGD was analyzed under the Bayesian paradigm, using logistic model and areas under the receiver operating characteristic curves (AUCs).
  
  
  
  In 47 LT recipients, 10 developed grade 3 PGD, which was obvious at H6 in 8 cases. Clinical risk factors, soluble intercellular adhesion molecule-1 and endocan (both forms) were not associated with grade 3 PGD. Significant predictors of grade 3 PGD included (1) EVLWi (optimal cutoff, 13.7 mL/kg; AUC, 0.74; 95% confidence interval [CI], 0.48-0.99), (2) PaO2/FiO2 ratio (optimal cutoff, 236; AUC, 0.68; 95% CI, 0.52-0.84), and (3) sRAGE (optimal cutoff, 11 760 pg/mL; AUC, 0.66; 95% CI, 0.41-0.91) measured at H0.
  
  
  
  Immediate postreperfusion increases in EVLWi and sRAGE along with impaired PaO2/FiO2 ratios were early predictors of grade 3 PGD at or beyond 6 hours and may trigger early therapeutic interventions.
authors: 1 Hôpitaux Universitaires de Strasbourg, Pôle d'Anesthésie-Réanimation SAMU-SMUR, Service d'Anesthésie-Réanimaton Chirurgicale, Hôpital de Hautepierre, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut de Physiologie, Strasbourg, France. 2 Hôpitaux Universitaires de Strasbourg, Pôle d'Anesthésie-Réanimation SAMU-SMUR, Service d'Anesthésie-Réanimations Chirurgicales, Nouvel Hôpital Civil, Strasbourg, France. 3 Hôpitaux Universitaires de Strasbourg, Pôle de Pathologie Thoracique, Service de Pneumologie, Nouvel Hôpital Civil, Strasbourg, France. 4 Hôpitaux Universitaires de Strasbourg, Pôle de Pathologie Thoracique, Service de Chirurgie Thoracique, Nouvel Hôpital Civil, Strasbourg, France. 5 Hôpitaux Universitaires de Strasbourg, Pôle de Biologie, Laboratoire Central d'Immunologie, Nouvel Hôpital Civil, Strasbourg, France. 6 Laboratoire d'ImmunoRhumatologie Moléculaire, LabEx Transplantex, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, France. 7 Hôpitaux Universitaires de Strasbourg, Service de Santé Publique, Groupe Méthode en Recherche Clinique, Strasbourg, France. 8 Université de Strasbourg, Faculté de Médecine, Laboratoire de Biostatistique et Informatique Médicale, EA3430 Progression Tumorale et Microenvironnement. Approches translationnelles et Epidemiologie', LabEx IRMIA, Strasbourg, France. 9 Hôpitaux Universitaires de Strasbourg, Pôle de Pathologie Thoracique, Service de Physiologie et d'Explorations Fonctionnelles, Nouvel Hôpital Civil, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut de Physiologie, Strasbourg, France. 10 Institut National de la Santé et de la Recherche Médicale, U1019, Pulmonary Immunity team and Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
authors: Julien
authors: J
authors: Pottecher
authors: Anne-Claude
authors: AC
authors: Roche
authors: Tristan
authors: T
authors: Dégot
authors: Olivier
authors: O
authors: Helms
authors: Jean-Gustave
authors: JG
authors: Hentz
authors: Jean-Paul
authors: JP
authors: Schmitt
authors: Pierre-Emmanuel
authors: PE
authors: Falcoz
authors: Nicola
authors: N
authors: Santelmo
authors: François
authors: F
authors: Levy
authors: Olivier
authors: O
authors: Collange
authors: Béatrice
authors: B
authors: Uring-Lambert
authors: Siamak
authors: S
authors: Bahram
authors: Mickaël
authors: M
authors: Schaeffer
authors: Nicolas
authors: N
authors: Meyer
authors: Bernard
authors: B
authors: Geny
authors: Philippe
authors: P
authors: Lassalle
authors: Pierre
authors: P
authors: Diemunsch
authors: Gilbert
authors: G
authors: Massard
authors: Romain
authors: R
authors: Kessler
authors: Annick
authors: A
authors: Steib
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D000328:Adult; D019540:Area Under Curve; D001499:Bayes Theorem; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D042241:Early Diagnosis; D015633:Extravascular Lung Water / Q000378:metabolism*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood; D010100:Oxygen / Q000097:blood*; D010313:Partial Pressure; D011237:Predictive Value of Tests; D055031:Primary Graft Dysfunction / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D011509:Proteoglycans / Q000097:blood; D011654:Pulmonary Edema / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D012372:ROC Curve; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood; D012720:Severity of Illness Index; D013815:Thermodilution; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C000593871:AGER protein, human; D015415:Biomarkers; C101134:ESM1 protein, human; C573420:ICAM1 protein, human; D009363:Neoplasm Proteins; D011509:Proteoglycans; D000067759:Receptor for Advanced Glycation End Products; D018799:Intercellular Adhesion Molecule-1; D010100:Oxygen