Exhaled breath condensate profiles of US Navy divers following prolonged hyperbaric oxygen (HBO) and nitrogen-oxygen (Nitrox) chamber exposures.
David Mark FothergillEva BorrasMitchell M McCartneyEdward SchelegleCristina E DavisPublished in: Journal of breath research (2023)
Prolonged exposure to hyperbaric hyperoxia can lead to pulmonary oxygen toxicity (PO2tox). PO2tox is a mission limiting factor for special operations forces divers using closed-circuit rebreathing apparatus and a potential side effect for patients undergoing hyperbaric oxygen (HBO) treatment. In this study, we aim to determine if there is a specific breath profile of compounds in exhaled breath condensate (EBC) that is indicative of the early stages of pulmonary hyperoxic stress/PO2tox. 
Using a double-blind, randomized "sham" controlled, cross-over design 14 U.S. Navy trained diver volunteers breathed two different gas mixtures at an ambient pressure of 2 ATA (33 fsw, 10 msw) for 6.5 hours. One test gas consisted of 100% O2 (HBO) and the other was a gas mixture containing 30.6% O2 with the balance N2 (Nitrox). The high O2 stress dive (HBO) and low O2 stress dive (nitrox) were separated by at least seven days and were conducted dry and at rest inside a hyperbaric chamber. EBC samples were taken immediately before and after each dive and subsequently underwent a targeted and untargeted metabolomics analysis using liquid chromatography coupled to mass spectrometry (LC-MS). 
Following the HBO dive, 10 out of 14 subjects reported symptoms of the early stages of PO2tox and one subject terminated the dive early due to severe symptoms of PO2tox. No symptoms of PO2tox were reported following the nitrox dive. A Partial Least-Squares Discriminant Analysis of the normalized (relative to pre-dive) untargeted data gave good classification abilities between the HBO and nitrox EBC with an AUC of 0.99 (± 2%) and sensitivity and specificity of 0.93 (± 10%) and 0.94 (± 10%), respectively. The resulting classifications identified specific biomarkers that included human metabolites and lipids and their derivatives from different metabolic pathways that may explain metabolomic changes resulting from prolonged HBO exposure.

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Keyphrases
- mass spectrometry
- liquid chromatography
- visible light
- high resolution mass spectrometry
- patients undergoing
- air pollution
- pulmonary hypertension
- high performance liquid chromatography
- double blind
- randomized controlled trial
- high resolution
- room temperature
- machine learning
- deep learning
- open label
- gas chromatography
- endothelial cells
- carbon dioxide
- capillary electrophoresis
- depressive symptoms
- oxidative stress
- electronic health record
- solid phase extraction
- sleep quality
- risk assessment
- stress induced
- cancer therapy
- clinical trial
- climate change
- particulate matter
- artificial intelligence
- human health