title: A biomarker panel (Bioscore) incorporating monocytic surface and soluble TREM-1 has high discriminative value for ventilator-associated pneumonia: a prospective observational study.
abstract: BACKGROUND
  Ventilator-associated pneumonia (VAP) increases mortality in critical illness. However, clinical diagnostic uncertainty persists. We hypothesised that measuring cell-surface and soluble inflammatory markers, incorporating Triggering Receptor Expressed by Myeloid cells (TREM)-1, would improve diagnostic accuracy.
  
  
  METHODS
  A single centre prospective observational study, set in a University Hospital medical-surgical intensive Care unit, recruited 91 patients into 3 groups: 27 patients with VAP, 33 ventilated controls without evidence of pulmonary sepsis (non-VAP), and 31 non-ventilated controls (NVC), without clinical infection, attending for bronchoscopy. Paired samples of Bronchiolo-alveolar lavage fluid (BALF) and blood from each subject were analysed for putative biomarkers of infection: Cellular (TREM-1, CD11b and CD62L) and soluble (IL-1β, IL-6, IL-8, sTREM-1, Procalcitonin). Expression of cellular markers on monocytes and neutrophils were measured by flow cytometry. Soluble inflammatory markers were determined by ELISA. A biomarker panel ('Bioscore'), was constructed, tested and validated, using Fisher's discriminant function analysis, to assess its value in distinguishing VAP from non VAP.
  
  
  RESULTS
  The expression of TREM-1 on monocytes (mTREM-1) and neutrophils (nTREM-1) and concentrations of IL-1β, IL-8, and sTREM-1 in BALF were significantly higher in VAP compared with non-VAP and NVC (p<0.001). The BALF/blood mTREM-1 was significantly higher in VAP patients compared to non-VAP and NVC (0.8 v 0.4 v 0.3 p<0.001). A seven marker Bioscore (BALF/blood ratio mTREM-1 and mCD11b, BALF sTREM-1, IL-8 and IL-1β, and serum CRP and IL-6) correctly identified 88.9% of VAP cases and 100% of non-VAP cases.
  
  
  CONCLUSIONS
  A 7-marker bioscore, incorporating cellular and soluble TREM-1, accurately discriminates VAP from non-pulmonary infection.
authors.affiliation: Magill Department of Anaesthesia, Critical Care and Pain, Chelsea and Westminster Hospital National Health Service Foundation Trust, London, United Kingdom; Immunology Section, Department of Medicine, Imperial College, London, United Kingdom; Department of Surgery and Cancer, Imperial College, London, United Kingdom.
authors.forename: Vimal
authors.initials: V
authors.lastname: Grover
authors.affiliation: Immunology Section, Department of Medicine, Imperial College, London, United Kingdom; Department of Immunology, Imperial College Healthcare National Health Service Trust, London, United Kingdom.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Pantelidis
authors.affiliation: Magill Department of Anaesthesia, Critical Care and Pain, Chelsea and Westminster Hospital National Health Service Foundation Trust, London, United Kingdom; Department of Surgery and Cancer, Imperial College, London, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Soni
authors.affiliation: Department of Surgery and Cancer, Imperial College, London, United Kingdom.
authors.forename: Masao
authors.initials: M
authors.lastname: Takata
authors.affiliation: Department of Respiratory Medicine, Chelsea and Westminster Hospital National Health Service Foundation Trust, London, United Kingdom; Department of Respiratory Medicine, Royal Brompton & Harefield Hospitals National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Pallav L
authors.initials: PL
authors.lastname: Shah
authors.affiliation: Department of Respiratory Medicine, Royal Brompton & Harefield Hospitals National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Athol U
authors.initials: AU
authors.lastname: Wells
authors.affiliation: Immunology Section, Department of Medicine, Imperial College, London, United Kingdom; Department of Immunology, Imperial College Healthcare National Health Service Trust, London, United Kingdom.
authors.forename: Don C
authors.initials: DC
authors.lastname: Henderson
authors.affiliation: Immunology Section, Department of Medicine, Imperial College, London, United Kingdom; Department of Immunology, Imperial College Healthcare National Health Service Trust, London, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Kelleher
authors.affiliation: Magill Department of Anaesthesia, Critical Care and Pain, Chelsea and Westminster Hospital National Health Service Foundation Trust, London, United Kingdom; Department of Surgery and Cancer, Imperial College, London, United Kingdom; Department of Respiratory Medicine, Chelsea and Westminster Hospital National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Suveer
authors.initials: S
authors.lastname: Singh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D039481:CD11b Antigen / Q000378:metabolism; D002116:Calcitonin / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D007362:Intensive Care Units; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D053717:Pneumonia, Ventilator-Associated / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011498:Protein Precursors / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D039481:CD11b Antigen; C508600:IL6 protein, human; C509295:ITGAM protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D011498:Protein Precursors; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D019041:L-Selectin; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide