title: BreathDx - molecular analysis of exhaled breath as a diagnostic test for ventilator-associated pneumonia: protocol for a European multicentre observational study.
abstract: The diagnosis of ventilator-associated pneumonia (VAP) remains time-consuming and costly, the clinical tools lack specificity and a bedside test to exclude infection in suspected patients is unavailable. Breath contains hundreds to thousands of volatile organic compounds (VOCs) that result from host and microbial metabolism as well as the environment. The present study aims to use breath VOC analysis to develop a model that can discriminate between patients who have positive cultures and who have negative cultures with a high sensitivity.
  
  
  
  The Molecular Analysis of Exhaled Breath as Diagnostic Test for Ventilator-Associated Pneumonia (BreathDx) study is a multicentre observational study. Breath and bronchial lavage samples will be collected from 100 and 53 intubated and ventilated patients suspected of VAP. Breath will be analysed using Thermal Desorption - Gas Chromatography - Mass Spectrometry (TD-GC-MS). The primary endpoint is the accuracy of cross-validated prediction for positive respiratory cultures in patients that are suspected of VAP, with a sensitivity of at least 99% (high negative predictive value).
  
  
  
  To our knowledge, BreathDx is the first study powered to investigate whether molecular analysis of breath can be used to classify suspected VAP patients with and without positive microbiological cultures with 99% sensitivity.
  
  
  
  UKCRN ID number 19086, registered May 2015; as well as registration at www.trialregister.nl under the acronym 'BreathDx' with trial ID number NTR 6114 (retrospectively registered on 28 October 2016).
authors.affiliation: Institute of Inflammation and Repair, University of Manchester, Oxford Road, Manchester, M13 9PL, UK. pouline.vanoort@gmail.com.
authors.forename: Pouline M P
authors.initials: PM
authors.lastname: van Oort
authors.affiliation: Philips Research, Eindhoven, The Netherlands.
authors.forename: Tamara
authors.initials: T
authors.lastname: Nijsen
authors.affiliation: Philips Research, Eindhoven, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Weda
authors.affiliation: Philips Research, Eindhoven, The Netherlands.
authors.forename: Hugo
authors.initials: H
authors.lastname: Knobel
authors.affiliation: Salford Royal NHS Foundation Trust, Greater Manchester, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Dark
authors.affiliation: University Hospital of South Manchester NHS Foundation Trust, Manchester, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Felton
authors.affiliation: Manchester Institute of Biotechnology (MIB), School of Chemistry, University of Manchester, Manchester, UK.
authors.forename: Nicholas J W
authors.initials: NJ
authors.lastname: Rattray
authors.affiliation: Institute of Inflammation and Repair, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.
authors.forename: Oluwasola
authors.initials: O
authors.lastname: Lawal
authors.affiliation: Institute of Inflammation and Repair, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.
authors.forename: Waqar
authors.initials: W
authors.lastname: Ahmed
authors.affiliation: Manchester Institute of Biotechnology (MIB), School of Chemistry, University of Manchester, Manchester, UK.
authors.forename: Craig
authors.initials: C
authors.lastname: Portsmouth
authors.affiliation: Intensive Care, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
authors.affiliation: Intensive Care, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.affiliation: Intensive Care, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Zakharkina
authors.affiliation: Critical Care Department, CIBER Enfermedades Respiratorias, Corporacion Sanitaria Universitaria Parc Tauli, Sabadell, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Artigas
authors.affiliation: Hospital de São Fransisco Xavier, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Povoa
authors.affiliation: Department of Clinical Medicine, St James's Hospital, Multidisciplinary Intensive Care Research Organization (MICRO), Trinity Centre for Health Sciences, Dublin, Ireland.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Martin-Loeches
authors.affiliation: Institute of Inflammation and Repair, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Fowler
authors.affiliation: Intensive Care, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lieuwe D J
authors.initials: LD
authors.lastname: Bos
mesh_terms: D001944:Breath Tests / Q000379:methods*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D008401:Gas Chromatography-Mass Spectrometry; D006785:Hospitals, University; D006801:Humans; D007362:Intensive Care Units; D016015:Logistic Models; D055432:Metabolomics; D009426:Netherlands; D053717:Pneumonia, Ventilator-Associated / Q000175:diagnosis* / Q000382:microbiology*; D011446:Prospective Studies; D012107:Research Design; D012680:Sensitivity and Specificity; D055549:Volatile Organic Compounds / Q000032:analysis*
chemical_list: D055549:Volatile Organic Compounds
keywords: Breath analysis; Metabolomics; Sensitivity; Specificity; Ventilator-associated pneumonia; Volatile organic compounds