Exhaled breath condensate profiles of U.S. Navy divers following prolonged hyperbaric oxygen (HBO) and nitrogen-oxygen (Nitrox) chamber exposures - PubMed (original) (raw)

Randomized Controlled Trial

. 2023 Jun 12;17(3):10.1088/1752-7163/acd715.

doi: 10.1088/1752-7163/acd715.

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Randomized Controlled Trial

Exhaled breath condensate profiles of U.S. Navy divers following prolonged hyperbaric oxygen (HBO) and nitrogen-oxygen (Nitrox) chamber exposures

David M Fothergill et al. J Breath Res. 2023.

Abstract

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 h. One test gas consisted of 100% O2(HBO) and the other was a gas mixture containing 30.6% O2with the balance N2(Nitrox). The high O2stress dive (HBO) and low O2stress 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.

Keywords: breath analysis; metabolomics; oxygen toxicity; pulmonary hyperoxic stress.

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Figures

Figure 1.

Figure 1.

EBC collection device based upon the design described in Valenzuela & Encina 2009 (12). The condensers were immersed in a cooler containing ice to condense the exhaled breath. Picture taken by the author.

Figure 2.

Figure 2.

Boxplots from targeted data presenting pre vs. post differences from subjects exposed to hyperbaric oxygen at 2 ATA for 6.5 hours. a) Y predicted values from PLS-DA model defining pre samples classified as pre (Y = 0) and post samples classified as post (Y = 1). b) Boxplots of concentrations from individual compounds that are characteristic from the defined PLS-DA model (VIP>1 and p<0.05).

Figure 3.

Figure 3.

Untargeted data PLS-DA model for pre vs. post differences from subjects exposed to 2 ATA of HBO for 6.5 hours. a) Q residual and Hotelling T2 plot for the PLS-DA model using all subjects’ data, b) PLS-DA scores plot built deleting outlier sample (Subject 05); c) Y predicted values defining pre samples classified as pre (Y = 0) and post samples classified as post (Y = 1).

Figure 4.

Figure 4.

Untargeted PLS-DA model of the normalized EBC data for the HBO dive that differentiates those subjects who reported pulmonary oxygen toxicity symptoms following the dive from those without symptoms. A) PLS-DA scores plot, and B) Y predicted values defining HBO samples showing symptoms (Y=1) and showing no symptoms (Y=0) after the HBO dive.

Figure 5.

Figure 5.

Untargeted data PLS-DA model for “pre”, “post-N2O2”, and “post-O2” differences. A) PLS-DA scores plot presenting 3 groups of classes; b) Predicted ROC curve values; and c) Y predicted values defining individual classes classified as is (Y = 0) and rest of the classes (Y = 1).

Figure 6.

Figure 6.

Untargeted data PLS-DA model to differentiate Nitrox (N2O2) and HBO (O2) exposures after data normalization. A) PLS-DA scores plot; b) Y predicted values defining samples from “N2O2” class (Y = 1) and from “O2” class (Y = 0).

References

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