Analysis of exhaled breath to identify critically ill patients with ventilator‐associated pneumonia

Author:

Felton T. W.12ORCID,Ahmed W.1,White I. R.3,van Oort P.4,Rattray N. J. W.5,Docherty C.6,Bannard‐Smith J.2,Morton B.78,Welters I.79,McMullan R.1011,Roberts S. A.12,Goodacre R.13,Dark P. M.114,Fowler S. J.115

Affiliation:

1. Faculty of Biology, Medicine and Health, School of Biological Sciences University of Manchester UK

2. Department of Critical Care Medicine Manchester University Hospitals NHS Foundation Trust Manchester UK

3. Laboratory for Environmental and Life Sciences University of Nova Gorica Slovenia

4. Department of Anaesthesiology Academic Medical Centre Amsterdam the Netherlands

5. Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde Glasgow UK

6. Department of Medicine Liverpool University Hospitals NHS Foundation Trust Liverpool UK

7. Liverpool University Hospitals NHS Foundation Trust Liverpool UK

8. Liverpool School of Tropical Medicine Liverpool UK

9. Department of Cardiovascular and Metabolic Medicine Institute of Life Course and Clinical Sciences, University of Liverpool UK

10. Department of Microbiology Belfast Health and Social Care Trust Belfast UK

11. Wellcome‐Wolfson Institute for Experimental Medicine, Queen's University Belfast UK

12. Faculty of Biology, Medicine and Health, Centre for Biostatistics, School of Health Sciences University of Manchester UK

13. Department of Biochemistry and Systems Biology Institute of Systems, Molecular and Integrative Biology, University of Liverpool UK

14. Northern Care Alliance NHS Group, Greater Manchester UK

15. Department of Respiratory Medicine Manchester University Hospitals NHS Foundation Trust Manchester UK

Abstract

SummaryVentilator‐associated pneumonia commonly occurs in critically ill patients. Clinical suspicion results in overuse of antibiotics, which in turn promotes antimicrobial resistance. Detection of volatile organic compounds in the exhaled breath of critically ill patients might allow earlier detection of pneumonia and avoid unnecessary antibiotic prescription. We report a proof of concept study for non‐invasive diagnosis of ventilator‐associated pneumonia in intensive care (the BRAVo study). Mechanically ventilated critically ill patients commenced on antibiotics for clinical suspicion of ventilator‐associated pneumonia were recruited within the first 24 h of treatment. Paired exhaled breath and respiratory tract samples were collected. Exhaled breath was captured on sorbent tubes and then analysed using thermal desorption gas chromatography–mass spectrometry to detect volatile organic compounds. Microbiological culture of a pathogenic bacteria in respiratory tract samples provided confirmation of ventilator‐associated pneumonia. Univariable and multivariable analyses of volatile organic compounds were performed to identify potential biomarkers for a ‘rule‐out’ test. Ninety‐six participants were enrolled in the trial, with exhaled breath available from 92. Of all compounds tested, the four highest performing candidate biomarkers were benzene, cyclohexanone, pentanol and undecanal with area under the receiver operating characteristic curve ranging from 0.67 to 0.77 and negative predictive values from 85% to 88%. Identified volatile organic compounds in the exhaled breath of mechanically ventilated critically ill patients show promise as a useful non‐invasive ‘rule‐out’ test for ventilator‐associated pneumonia.

Funder

Invention for Innovation Programme

Manchester Biomedical Research Centre

Publisher

Wiley

Subject

Anesthesiology and Pain Medicine

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