title: Contribution of damage-associated molecular patterns to transfusion-related acute lung injury in cardiac surgery.
abstract: BACKGROUND
  The incidence of transfusion-related acute lung injury (TRALI) in cardiac surgery patients is high and this condition contributes to an adverse outcome. Damage-associated molecular pattern (DAMP) molecules, HMGB1 and S100A12, are thought to mediate inflammatory changes in acute respiratory distress syndrome. We aimed to determine whether DAMP are involved in the pathogenesis of TRALI in cardiac surgery patients.
  
  
  METHODS
  This was a secondary analysis of a prospective observational trial in cardiac surgery patients admitted to the Intensive Care Unit of a university hospital in the Netherlands. Fourteen TRALI cases were randomly matched with 32 transfused and non-transfused controls. Pulmonary levels of HMGB1, S100A12 and inflammatory cytokines (interleukins-1β, -6, and -8 and tumour necrosis factor-α) were determined when TRALI evolved. In addition, systemic and pulmonary levels of soluble receptor for advanced glycation end products (sRAGE) were determined.
  
  
  RESULTS
  HMGB1 expression and levels of sRAGE in TRALI patients did not differ from those in controls. There was a trend towards higher S100A12 levels in TRALI patients compared to the controls. Furthermore, S100A12 levels were associated with increased levels of markers of pulmonary inflammation, prolonged cardiopulmonary bypass, hypoxemia and duration of mechanical ventilation.
  
  
  CONCLUSIONS
  No evidence was found that HMGB1 and sRAGE contribute to the development of TRALI. S100A12 is associated with duration of cardiopulmonary bypass, pulmonary inflammation, hypoxia and prolonged mechanical ventilation and may contribute to acute lung injury in cardiac surgery patients.
authors.affiliation: Department of Intensive Care Medicine, Academic Medical Centre at the University of Amsterdam, The Netherlands Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Academic Medical Centre at the University of Amsterdam, The Netherlands.
authors.forename: Marcella C A
authors.initials: MC
authors.lastname: Müller
authors.affiliation: Department of Intensive Care Medicine, Academic Medical Centre at the University of Amsterdam, The Netherlands Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Academic Medical Centre at the University of Amsterdam, The Netherlands.
authors.forename: Pieter R
authors.initials: PR
authors.lastname: Tuinman
authors.affiliation: Department of Intensive Care Medicine, Academic Medical Centre at the University of Amsterdam, The Netherlands Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Academic Medical Centre at the University of Amsterdam, The Netherlands.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Vlaar
authors.affiliation: Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Academic Medical Centre at the University of Amsterdam, The Netherlands.
authors.forename: Anita M
authors.initials: AM
authors.lastname: Tuip
authors.affiliation: Centre for Experimental and Molecular Medicine (CEMM), Academic Medical Centre at the University of Amsterdam, The Netherlands.
authors.forename: Kelly
authors.initials: K
authors.lastname: Maijoor
authors.affiliation: Centre for Experimental and Molecular Medicine (CEMM), Academic Medical Centre at the University of Amsterdam, The Netherlands.
authors.forename: Achmed
authors.initials: A
authors.lastname: Achouiti
authors.affiliation: Centre for Experimental and Molecular Medicine (CEMM), Academic Medical Centre at the University of Amsterdam, The Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Van t Veer
authors.affiliation: Department of Intensive Care Medicine, Academic Medical Centre at the University of Amsterdam, The Netherlands Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Academic Medical Centre at the University of Amsterdam, The Netherlands.
authors.forename: Margreeth B
authors.initials: MB
authors.lastname: Vroom
authors.affiliation: Department of Intensive Care Medicine, Academic Medical Centre at the University of Amsterdam, The Netherlands Laboratory of Experimental Intensive Care and Anaesthesiology (L.E.I.C.A.), Academic Medical Centre at the University of Amsterdam, The Netherlands.
authors.forename: Nicole P
authors.initials: NP
authors.lastname: Juffermans
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055371:Acute Lung Injury / Q000097:blood / Q000209:etiology; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D016207:Cytokines / Q000097:blood; D024243:HMGB1 Protein / Q000097:blood; D053717:Pneumonia, Ventilator-Associated / Q000097:blood; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000209:etiology; D009418:S100 Proteins / Q000097:blood; D000067616:S100A12 Protein; D065227:Transfusion Reaction; D016032:Randomized Controlled Trials as Topic
chemical_list: D016207:Cytokines; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human