title: Tumor necrosis factor receptor 1 (TNFRI) for ventilator-associated pneumonia diagnosis by cytokine multiplex analysis.
abstract: BACKGROUND
  The diagnosis of ventilator-associated pneumonia (VAP) is challenging. An important aspect to improve outcome is early recognition of VAP and the initiation of the appropriate empirical treatment. We hypothesized that biological markers in plasma can rule out VAP at the moment of clinical suspicion and could rule in VAP before the diagnosis can be made clinically.
  
  
  METHODS
  In this prospective study, patients with VAP (n = 24, microbiology confirmed) were compared to controls (n = 19) with a similar duration of mechanical ventilation. Blood samples from the day of VAP diagnosis and 1 and 3 days before were analyzed with a multiplex array for markers of inflammation, coagulation, and apoptosis. The best biomarker combination was selected and the diagnostic accuracy was given by the area under the receiver operating characteristic curve (ROC-AUC).
  
  
  RESULTS
  TNF-receptor 1 (TNFRI) and granulocyte colony-stimulating factor (GCSF) were selected as optimal biomarkers at the day of VAP diagnosis, which resulted in a ROC-AUC of 0.96, with excellent sensitivity. Three days before the diagnosis TNFRI and plasminogen activator inhibitor-1 (PAI-1) levels in plasma predicted VAP with a ROC-AUC of 0.79. The slope of IL-10 and PAI-1 resulted in a ROC-AUC of 0.77. These biomarkers improved the classification of the clinical pulmonary infection score when combined.
  
  
  CONCLUSIONS
  Concentration of TNFRI and PAI-1 and the slope of PAI-1 and IL-10 may be used to predict the development of VAP as early as 3 days before the diagnosis made clinically. TNFRI and GCSF may be used to exclude VAP at the moment of clinical suspicion. Especially TNFRI seems to be a promising marker for the prediction and diagnosis of VAP.
authors.affiliation: Multidisciplinary Intensive Care Research Organization (MICRO), Department of Clinical Medicine, Trinity Centre for Health Sciences, St James's University Hospital, James's Street, Dublin 8, Ireland. drmartinloeches@gmail.com.|CIBER enfermedades respiratorias (CIBERES), Critical Care Center, Sabadell Hospital, Corporación Sanitaria Universitaria Parc Taulí, Universitat Autonoma de Barcelona, Sabadell, Spain. drmartinloeches@gmail.com.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Martin-Loeches
authors.affiliation: Department of Intensive Care and Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lieuwe D
authors.initials: LD
authors.lastname: Bos
authors.affiliation: Polyvalent Intensive Care Unit, São Francisco Xavier Hospital, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal.|Nova Medical School, CEDOC, New University of Lisbon, Lisbon, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Povoa
authors.affiliation: CIBER enfermedades respiratorias (CIBERES), Respiratory Disease Department, Hospital Clínic i Provincial de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Ramirez
authors.affiliation: Department of Intensive Care and Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.affiliation: Intensive Care Unit, University Hospital La Fe, Valencia, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Torres
authors.affiliation: CIBER enfermedades respiratorias (CIBERES), Critical Care Center, Sabadell Hospital, Corporación Sanitaria Universitaria Parc Taulí, Universitat Autonoma de Barcelona, Sabadell, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Artigas