Exhaled breath metabolomics reveals a pathogen-specific response in a rat pneumonia model for two human pathogenic bacteriaCitation formats

  • External authors:
  • Pouline M P van Oort
  • Paul Brinkman
  • Gitte Slingers
  • Gudrun Koppen
  • Adrie Maas
  • Joris J T H Roelofs
  • Ronny Schnabel
  • Dennis C Bergmans
  • Marc Raes
  • Marcus J Schultz
  • Lieuwe D Bos
  • BreathDx Consortium

Standard

Exhaled breath metabolomics reveals a pathogen-specific response in a rat pneumonia model for two human pathogenic bacteria : a proof-of-concept study. / van Oort, Pouline M P; Brinkman, Paul; Slingers, Gitte; Koppen, Gudrun; Maas, Adrie; Roelofs, Joris J T H; Schnabel, Ronny; Bergmans, Dennis C; Raes, Marc; Goodacre, Royston; Fowler, Stephen J; Schultz, Marcus J; Bos, Lieuwe D; BreathDx Consortium.

In: American journal of physiology. Lung cellular and molecular physiology, 2019.

Research output: Contribution to journalArticle

Harvard

van Oort, PMP, Brinkman, P, Slingers, G, Koppen, G, Maas, A, Roelofs, JJTH, Schnabel, R, Bergmans, DC, Raes, M, Goodacre, R, Fowler, SJ, Schultz, MJ, Bos, LD & BreathDx Consortium 2019, 'Exhaled breath metabolomics reveals a pathogen-specific response in a rat pneumonia model for two human pathogenic bacteria: a proof-of-concept study' American journal of physiology. Lung cellular and molecular physiology. https://doi.org/10.1152/ajplung.00449.2018

APA

van Oort, P. M. P., Brinkman, P., Slingers, G., Koppen, G., Maas, A., Roelofs, J. J. T. H., ... BreathDx Consortium (2019). Exhaled breath metabolomics reveals a pathogen-specific response in a rat pneumonia model for two human pathogenic bacteria: a proof-of-concept study. American journal of physiology. Lung cellular and molecular physiology. https://doi.org/10.1152/ajplung.00449.2018

Vancouver

van Oort PMP, Brinkman P, Slingers G, Koppen G, Maas A, Roelofs JJTH et al. Exhaled breath metabolomics reveals a pathogen-specific response in a rat pneumonia model for two human pathogenic bacteria: a proof-of-concept study. American journal of physiology. Lung cellular and molecular physiology. 2019. https://doi.org/10.1152/ajplung.00449.2018

Author

van Oort, Pouline M P ; Brinkman, Paul ; Slingers, Gitte ; Koppen, Gudrun ; Maas, Adrie ; Roelofs, Joris J T H ; Schnabel, Ronny ; Bergmans, Dennis C ; Raes, Marc ; Goodacre, Royston ; Fowler, Stephen J ; Schultz, Marcus J ; Bos, Lieuwe D ; BreathDx Consortium. / Exhaled breath metabolomics reveals a pathogen-specific response in a rat pneumonia model for two human pathogenic bacteria : a proof-of-concept study. In: American journal of physiology. Lung cellular and molecular physiology. 2019.

Bibtex

@article{d7545ac973344b9db2937251edb07157,
title = "Exhaled breath metabolomics reveals a pathogen-specific response in a rat pneumonia model for two human pathogenic bacteria: a proof-of-concept study",
abstract = "INTRODUCTION: Volatile organic compounds (VOCs) in breath can reflect host and pathogen metabolism and might be used to diagnose pneumonia. We hypothesized that rats with Streptococcus pneumoniae ( SP) or Pseudomonas aeruginosa ( PA) pneumonia can be discriminated from uninfected controls by thermal desorption - gas chromatography - mass-spectrometry (TD-GC-MS) and selected ion flow tube - mass spectrometry (SIFT-MS) of exhaled breath.METHODS: Male adult rats ( n=50) received an intra-tracheal inoculation of 1) 200 µL saline, 2) 1x107 colony forming units (CFU) of SP or 3) 1x107 CFU of PA. 24 hours later the rats were anaesthetized, tracheotomized and mechanically ventilated. Exhaled breath was analyzed via TD-GC-MS and SIFT-MS. Area under the receiver operating characteristic curves (AUROCCs) and correct classification rate (CCRs) were calculated after leave-one-out cross-validation of sparse partial least squares-discriminant analysis (sPLS-DA).RESULTS: Analysis of GC-MS data showed an AUROCC (95{\%} CI) of 0.85 (0.73 - 0.96) and CCR of 94.6{\%} for infected vs. non-infected animals, AUROCC 0.98 (0.94 - 1) and CCR of 99.9{\%} for SP vs. PA, 0.92 (0.83 - 1.00) and CCR of 98.1{\%} for SP vs. controls and 0.97 (0.92 - 1.00) and CCR of 99.9{\%} for PA vs. controls. For these comparisons the SIFT-MS data showed AUROCCs of 0.54, 0.89, 0.63 and 0.79, respectively.DISCUSSION: Exhaled breath analysis discriminated between respiratory infection and no infection, but with even better accuracy between specific pathogens. Future clinical studies should not only focus on the presence of respiratory infection, but also on the discrimination between specific pathogens.",
author = "{van Oort}, {Pouline M P} and Paul Brinkman and Gitte Slingers and Gudrun Koppen and Adrie Maas and Roelofs, {Joris J T H} and Ronny Schnabel and Bergmans, {Dennis C} and Marc Raes and Royston Goodacre and Fowler, {Stephen J} and Schultz, {Marcus J} and Bos, {Lieuwe D} and {BreathDx Consortium}",
year = "2019",
doi = "10.1152/ajplung.00449.2018",
language = "English",
journal = "AJP: Lung Cellular and Molecular Physiology",
issn = "1522-1504",
publisher = "American Physiological Society",

}

RIS

TY - JOUR

T1 - Exhaled breath metabolomics reveals a pathogen-specific response in a rat pneumonia model for two human pathogenic bacteria

T2 - a proof-of-concept study

AU - van Oort, Pouline M P

AU - Brinkman, Paul

AU - Slingers, Gitte

AU - Koppen, Gudrun

AU - Maas, Adrie

AU - Roelofs, Joris J T H

AU - Schnabel, Ronny

AU - Bergmans, Dennis C

AU - Raes, Marc

AU - Goodacre, Royston

AU - Fowler, Stephen J

AU - Schultz, Marcus J

AU - Bos, Lieuwe D

AU - BreathDx Consortium, null

PY - 2019

Y1 - 2019

N2 - INTRODUCTION: Volatile organic compounds (VOCs) in breath can reflect host and pathogen metabolism and might be used to diagnose pneumonia. We hypothesized that rats with Streptococcus pneumoniae ( SP) or Pseudomonas aeruginosa ( PA) pneumonia can be discriminated from uninfected controls by thermal desorption - gas chromatography - mass-spectrometry (TD-GC-MS) and selected ion flow tube - mass spectrometry (SIFT-MS) of exhaled breath.METHODS: Male adult rats ( n=50) received an intra-tracheal inoculation of 1) 200 µL saline, 2) 1x107 colony forming units (CFU) of SP or 3) 1x107 CFU of PA. 24 hours later the rats were anaesthetized, tracheotomized and mechanically ventilated. Exhaled breath was analyzed via TD-GC-MS and SIFT-MS. Area under the receiver operating characteristic curves (AUROCCs) and correct classification rate (CCRs) were calculated after leave-one-out cross-validation of sparse partial least squares-discriminant analysis (sPLS-DA).RESULTS: Analysis of GC-MS data showed an AUROCC (95% CI) of 0.85 (0.73 - 0.96) and CCR of 94.6% for infected vs. non-infected animals, AUROCC 0.98 (0.94 - 1) and CCR of 99.9% for SP vs. PA, 0.92 (0.83 - 1.00) and CCR of 98.1% for SP vs. controls and 0.97 (0.92 - 1.00) and CCR of 99.9% for PA vs. controls. For these comparisons the SIFT-MS data showed AUROCCs of 0.54, 0.89, 0.63 and 0.79, respectively.DISCUSSION: Exhaled breath analysis discriminated between respiratory infection and no infection, but with even better accuracy between specific pathogens. Future clinical studies should not only focus on the presence of respiratory infection, but also on the discrimination between specific pathogens.

AB - INTRODUCTION: Volatile organic compounds (VOCs) in breath can reflect host and pathogen metabolism and might be used to diagnose pneumonia. We hypothesized that rats with Streptococcus pneumoniae ( SP) or Pseudomonas aeruginosa ( PA) pneumonia can be discriminated from uninfected controls by thermal desorption - gas chromatography - mass-spectrometry (TD-GC-MS) and selected ion flow tube - mass spectrometry (SIFT-MS) of exhaled breath.METHODS: Male adult rats ( n=50) received an intra-tracheal inoculation of 1) 200 µL saline, 2) 1x107 colony forming units (CFU) of SP or 3) 1x107 CFU of PA. 24 hours later the rats were anaesthetized, tracheotomized and mechanically ventilated. Exhaled breath was analyzed via TD-GC-MS and SIFT-MS. Area under the receiver operating characteristic curves (AUROCCs) and correct classification rate (CCRs) were calculated after leave-one-out cross-validation of sparse partial least squares-discriminant analysis (sPLS-DA).RESULTS: Analysis of GC-MS data showed an AUROCC (95% CI) of 0.85 (0.73 - 0.96) and CCR of 94.6% for infected vs. non-infected animals, AUROCC 0.98 (0.94 - 1) and CCR of 99.9% for SP vs. PA, 0.92 (0.83 - 1.00) and CCR of 98.1% for SP vs. controls and 0.97 (0.92 - 1.00) and CCR of 99.9% for PA vs. controls. For these comparisons the SIFT-MS data showed AUROCCs of 0.54, 0.89, 0.63 and 0.79, respectively.DISCUSSION: Exhaled breath analysis discriminated between respiratory infection and no infection, but with even better accuracy between specific pathogens. Future clinical studies should not only focus on the presence of respiratory infection, but also on the discrimination between specific pathogens.

U2 - 10.1152/ajplung.00449.2018

DO - 10.1152/ajplung.00449.2018

M3 - Article

JO - AJP: Lung Cellular and Molecular Physiology

JF - AJP: Lung Cellular and Molecular Physiology

SN - 1522-1504

ER -