@article{dd4214b0afcc4bf797f113898e752242,
title = "Validation of volatile metabolites of pulmonary oxidative injury: a bench to bedside study",
abstract = "Background Changes in exhaled volatile organic compounds (VOCs) can be used to discriminate between respiratory diseases, and increased concentrations of hydrocarbons are commonly linked to oxidative stress. However, the VOCs identified are inconsistent between studies, and translational studies are lacking. Methods In this bench to bedside study, we captured VOCs in the headspace of A549 epithelial cells after exposure to hydrogen peroxide (H2O2), to induce oxidative stress, using high-capacity polydimethylsiloxane sorbent fibres. Exposed and unexposed cells were compared using targeted and untargeted analysis. Breath samples of invasively ventilated intensive care unit patients (n=489) were collected on sorbent tubes and associated with the inspiratory oxygen fraction (FIO2) to reflect pulmonary oxidative stress. Headspace samples and breath samples were analysed using gas chromatography and mass spectrometry. Results In the cell, headspace octane concentration was decreased after oxidative stress ( p=0.0013), while the other VOCs were not affected. 2-ethyl-1-hexanol showed an increased concentration in the headspace of cells undergoing oxidative stress in untargeted analysis ( p=0.00014). None of the VOCs that were linked to oxidative stress showed a significant correlation with FIO 2 (Rs range: -0.015 to -0.065) or discriminated between patients with FIO 2.0.6 or below (area under the curve range: 0.48 to 0.55). Conclusion Despite a comprehensive translational approach, validation of known and novel volatile biomarkers of oxidative stress was not possible in patients at risk of pulmonary oxidative injury. The inconsistencies observed highlight the difficulties faced in VOC biomarker validation, and that caution is warranted in the interpretation of the pathophysiological origin of discovered exhaled breath biomarkers.",
keywords = "HYDROCARBON BREATH TEST, ORGANIC-COMPOUNDS, LUNG-CANCER, CELL-LINE, STRESS, BIOMARKERS, INDEX",
author = "D. Fenn and T.A. Lilien and L.A. Hagens and M.R. Smit and N.F.L. Heijnen and {Tuip-de Boer}, A.M. and A.H. Neerincx and K. Golebski and D.C.J.J. Bergmans and R.M. Schnabel and M.J. Schultz and {Maitland-Van Der Zee}, A.H. and P. Brinkman and L.D.J. Bos and {DARTS Consortium}",
note = "Funding Information: Support statement: L.D.J. Bos was supported by the Young Investigator Award and Dirkje Postma Award from the Dutch Lung Foundation (Longfonds) for sample analysis performed in this study, and by the Health Holland and the Amsterdam UMC fellowship, outside of submitted work. Funding information for this article has been deposited with the Crossref Funder Registry. Funding Information: Conflict of interest: D. Fenn has nothing to disclose. T.A. Lilien has nothing to disclose. L.A. Hagens has nothing to disclose. M.R. Smit has nothing to disclose. N.F.L. Heijnen has nothing to disclose. A.M. Tuip-de Boer has nothing to disclose. A.H. Neerincx has nothing to disclose. K. Golebski has nothing to disclose. D.C.J.J. Bergmans has nothing to disclose. R.M. Schnabel has nothing to disclose. M.J. Schultz has nothing to disclose. A.H. Maitland-van der Zee has received research grants outside the submitted work from GSK, Boehringer Ingelheim and Vertex; she is the principal investigator of a P4O2 (Precision Medicine for more Oxygen) public–private partnership sponsored by Health Holland involving many private partners that contribute in cash and/or in kind (Boehringer Ingelheim, Breathomix, Fluidda, Ortec Logiqcare, Philips, Quantib-U, Roche, Smartfish, SODAQ, Thirona, TopMD and Novartis); and she has served in advisory boards for AstraZeneca, GSK and Boehringer Ingelheim, with money paid to her institution. P. Brinkman has nothing to disclose. L.D.J. Bos reports grants from the Dutch Lung Foundation (Young investigator grant), grants from the Dutch Lung Foundation and Health Holland (Public–Private Partnership grant), grants from the Dutch Lung Foundation (Dirkje Postma Award), grants from IMI COVID19 initiative, and grants from Amsterdam UMC fellowship, outside the submitted work; he has also served in advisory capacity for Santhera and Janssen with money paid to his institution. Publisher Copyright: {\textcopyright} The authors 2023.",
year = "2023",
month = mar,
day = "1",
doi = "10.1183/23120541.00427-2022",
language = "English",
volume = "9",
journal = "ERJ Open Research",
issn = "2312-0541",
publisher = "European Respiratory Society",
number = "2",
}