Exhaled breath metabolomics reveals a pathogen-specific response in a rat pneumonia model for two human pathogenic bacteria: a proof-of-concept study

• Published in: American journal of physiology. Lung cellular and molecular physiology 2019-05, Vol.316 (5), p.L751-L756
• Main Authors: van Oort, Pouline M, Brinkman, Paul, Slingers, Gitte, Koppen, Gudrun, Maas, Adrie, Roelofs, Joris J, Schnabel, Ronny, Bergmans, Dennis C, Raes, M, Goodacre, Royston, Fowler, Stephen J, Schultz, Marcus J, Bos, Lieuwe D
• Format: Article
• Language: English
• Subjects: Animals; Breath Tests; Confidence intervals; Discriminant analysis; Disease Models, Animal; Gas chromatography; Gas Chromatography-Mass Spectrometry; Humans; Inoculation; Male; Mass spectrometry; Mass spectroscopy; Metabolism; Metabolome; Metabolomics; Organic compounds; Pathogens; Pneumonia; Pneumonia, Pneumococcal - metabolism; Pseudomonas aeruginosa; Pseudomonas Infections - metabolism; Rats; Rats, Sprague-Dawley; Scientific imaging; Spectroscopy; Streptococcus infections; Streptococcus pneumoniae; Trachea; VOCs; Volatile organic compounds
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00449.2018

Volatile organic compounds in breath can reflect host and pathogen metabolism and might be used to diagnose pneumonia. We hypothesized that rats with ( ) or ( ) 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. Male adult rats ( = 50) received an intratracheal inoculation of ) 200 µl saline, or ) 1 × 10 colony-forming units of or 3) 1 × 10 CFU of . Twenty-four 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. 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 versus , 0.92 (0.83-1.00), CCR of 98.1% for versus controls and 0.97 (0.92-1.00), and CCR of 99.9% for 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.