title: Biomarker kinetics in the prediction of VAP diagnosis: results from the BioVAP study.
abstract: BACKGROUND
  Prediction of diagnosis of ventilator-associated pneumonia (VAP) remains difficult. Our aim was to assess the value of biomarker kinetics in VAP prediction.
  
  
  METHODS
  We performed a prospective, multicenter, observational study to evaluate predictive accuracy of biomarker kinetics, namely C-reactive protein (CRP), procalcitonin (PCT), mid-region fragment of pro-adrenomedullin (MR-proADM), for VAP management in 211 patients receiving mechanical ventilation for >72 h. For the present analysis, we assessed all (N = 138) mechanically ventilated patients without an infection at admission. The kinetics of each variable, from day 1 to day 6 of mechanical ventilation, was assessed with each variable's slopes (rate of biomarker change per day), highest level and maximum amplitude of variation (Δ (max)).
  
  
  RESULTS
  A total of 35 patients (25.4 %) developed a VAP and were compared with 70 non-infected controls (50.7 %). We excluded 33 patients (23.9 %) who developed a non-VAP nosocomial infection. Among the studied biomarkers, CRP and CRP ratio showed the best performance in VAP prediction. The slope of CRP change over time (adjusted odds ratio [aOR] 1.624, confidence interval [CI]95% [1.206, 2.189], p = 0.001), the highest CRP ratio concentration (aOR 1.202, CI95% [1.061, 1.363], p = 0.004) and Δ (max) CRP (aOR 1.139, CI95% [1.039, 1.248], p = 0.006), during the first 6 days of mechanical ventilation, were all significantly associated with VAP development. Both PCT and MR-proADM showed a poor predictive performance as well as temperature and white cell count.
  
  
  CONCLUSIONS
  Our results suggest that in patients under mechanical ventilation, daily CRP monitoring was useful in VAP prediction. Trial registration NCT02078999.
authors.affiliation: Polyvalent Intensive Care Unit, Centro Hospitalar de Lisboa Ocidental, São Francisco Xavier Hospital, Estrada do Forte do Alto do Duque, 1449-005, Lisbon, Portugal. pedrorpovoa@gmail.com.|NOVA Medical School, CEDOC, New University of Lisbon, Lisbon, Portugal. pedrorpovoa@gmail.com.
authors.forename: Pedro
authors.initials: P
authors.lastname: Póvoa
authors.affiliation: Critical Care Center, Sabadell Hospital, Corporación Sanitaria Universitaria Parc Taulí, Universitat Autonoma de Barcelona, Sabadell, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Martin-Loeches
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Intensive Care Unit, University Hospital La Fe, Valencia, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Ramirez
authors.affiliation: Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lieuwe D
authors.initials: LD
authors.lastname: Bos
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Respiratory Disease Department, Hospital Clínic i Provincial de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Esperatti
authors.affiliation: Polyvalent Intensive Care Unit, Centro Hospitalar de Lisboa Ocidental, São Francisco Xavier Hospital, Estrada do Forte do Alto do Duque, 1449-005, Lisbon, Portugal.|NOVA Medical School, CEDOC, New University of Lisbon, Lisbon, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Silvestre
authors.affiliation: Critical Care Center, Sabadell Hospital, Corporación Sanitaria Universitaria Parc Taulí, Universitat Autonoma de Barcelona, Sabadell, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Gisela
authors.initials: G
authors.lastname: Gili
authors.affiliation: Critical Care Center, Sabadell Hospital, Corporación Sanitaria Universitaria Parc Taulí, Universitat Autonoma de Barcelona, Sabadell, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Goma
authors.affiliation: Laboratory Department, UDIAT, Corporación Sanitaria Universitaria Parc Taulí, Sabadell, Spain.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Berlanga
authors.affiliation: Laboratory Department, UDIAT, Corporación Sanitaria Universitaria Parc Taulí, Sabadell, Spain.
authors.forename: Mateu
authors.initials: M
authors.lastname: Espasa
authors.affiliation: NOVA Medical School, CEDOC, New University of Lisbon, Lisbon, Portugal.|Microbiology Department, Centro Hospitalar de Lisboa Ocidental, Egas Moniz Hospital, Lisbon, Portugal.
authors.forename: Elsa
authors.initials: E
authors.lastname: Gonçalves
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Respiratory Disease Department, Hospital Clínic i Provincial de Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Torres
authors.affiliation: Critical Care Center, Sabadell Hospital, Corporación Sanitaria Universitaria Parc Taulí, Universitat Autonoma de Barcelona, Sabadell, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Artigas
keywords: Biomarkers; C-reactive protein; Clinical Pulmonary Infection Score; Diagnosis; Mid-region fragment of pro-adrenomedullin; Prediction; Procalcitonin; Ventilator-associated pneumonia