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Title: | Exhaled breath metabolomics reveals a pathogen-specific response in a rat pneumonia model for two human pathogenic bacteria: a proof-of-concept study | Authors: | van Oort, Poulin M. Brinkman, Paul SLINGERS, Gitte Koppen, Gudrun Maas, Adrie Roelofs, Joris J. Schnabel, Ronny Bergmann, Dennis C. RAES, Marc Goodacre, Royston Fowler, Stephen J. Schultz, Marcus J. Bos, Lieuwe D. |
Issue Date: | 2019 | Publisher: | AMER PHYSIOLOGICAL SOC | Source: | AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 316(5), p. L751-L756 | Abstract: | Volatile organic compounds 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 tubemass spectrometry (SIFT-MS) of exhaled breath. Male adult rats (n = 50) received an intratracheal inoculation of 1) 200 mu l saline, or 2) 1 x 10(7) colony-forming units of SP or 3) 1 x 10(7) CFU of PA. Twenty-four hours later the rats were anaesthetized, tracheotomized, and mechanically ventilated. Exhaled breath was analyzed via TDGC- 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. Analysis of GC-MS data showed an AUROCC (95% confidence interval) of 0.85 (0.73-0.96) and CCR of 94.6% for infected versus noninfected animals, AUROCC of 0.98 (0.94-1) and CCR of 99.9% for SP versus PA, 0.92 (0.83-1.00), CCR of 98.1% for SP versus controls and 0.97 (0.92-1.00), and CCR of 99.9% for PA versus controls. For these comparisons the SIFT-MS data showed AUROCCs of 0.54, 0.89, 0.63, and 0.79, respectively. 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. | Notes: | [van Oort, Poulin M.; Brinkman, Paul; Maas, Adrie; Roelofs, Joris J.; Schultz, Marcus J.; Bos, Lieuwe D.] Univ Amsterdam, Med Ctr, Acad Med Ctr, Dept Intens Care, Amsterdam, Netherlands. [Slingers, Gitte; Raes, M.] Hasselt Univ, Hasselt, Belgium. [Koppen, Gudrun] Flemish Inst Technol Res, Mol, Belgium. [Schnabel, Ronny; Bergmann, Dennis C.] Maastricht Univ, Med Ctr, Maastricht, Netherlands. [Goodacre, Royston] Manchester Inst Biotechnol, Manchester, Lancs, England. [Fowler, Stephen J.] Univ Manchester, Manchester, Lancs, England. | Keywords: | biomarkers; exhaled breath analysis; infection; pneumonia;exhaled breath analysis; pneumonia; infection; biomarkers | Document URI: | http://hdl.handle.net/1942/30042 | ISSN: | 1040-0605 | e-ISSN: | 1522-1504 | DOI: | 10.1152/ajplung.00449.2018 | ISI #: | 000465073800008 | Rights: | 2019 the American Physiological Society | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2020 |
Appears in Collections: | Research publications |
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