Estimating hypoxia-induced brain dysfunction and cognitive decline through exhaled breath monitoring

Abstract Background Hypoxia remains a concern for aircrew operating high performance aircraft. Sensing and mitigating hypoxia is a line of active research within the US Air Force and US Navy. It is hypothesized that changes in exhaled breath volatile organic compound content could indicate, not only...

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Main Authors: Sean W. Harshman, Kiersten J. Weatherbie, Alena R. Veigl, Anne E. Jung, Madison A. Stoner-Dixon, Aubrianne I. Dash, Christopher J. Land, Dylan T. Slizewski, Eli F. Kelley, Jennifer Schwanekamp-Kerr, Timothy Halverson, Christina N. Davidson, Christopher W. Myers, Kara J. Blacker, Jennifer A. Martin, Rhonda L. Pitsch
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Respiratory Research
Online Access:https://doi.org/10.1186/s12931-025-03296-5
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author Sean W. Harshman
Kiersten J. Weatherbie
Alena R. Veigl
Anne E. Jung
Madison A. Stoner-Dixon
Aubrianne I. Dash
Christopher J. Land
Dylan T. Slizewski
Eli F. Kelley
Jennifer Schwanekamp-Kerr
Timothy Halverson
Christina N. Davidson
Christopher W. Myers
Kara J. Blacker
Jennifer A. Martin
Rhonda L. Pitsch
author_facet Sean W. Harshman
Kiersten J. Weatherbie
Alena R. Veigl
Anne E. Jung
Madison A. Stoner-Dixon
Aubrianne I. Dash
Christopher J. Land
Dylan T. Slizewski
Eli F. Kelley
Jennifer Schwanekamp-Kerr
Timothy Halverson
Christina N. Davidson
Christopher W. Myers
Kara J. Blacker
Jennifer A. Martin
Rhonda L. Pitsch
author_sort Sean W. Harshman
collection DOAJ
description Abstract Background Hypoxia remains a concern for aircrew operating high performance aircraft. Sensing and mitigating hypoxia is a line of active research within the US Air Force and US Navy. It is hypothesized that changes in exhaled breath volatile organic compound content could indicate, not only changes in oxygen saturation (SpO2), but also brain activity and cognitive function. Methods On-line exhaled breath monitoring via proton transfer reaction mass spectrometry was used to observe changes in volatile organic compound concentrations during mask-free hypoxic exposures. Additionally, electroencephalography measurements in response to an odd-ball paradigm and cognitive tasks were collected throughout the exposures. Results The data show hypoxic exposures induced a physiological response including a significant reduction in SpO2, a decrease in the electroencephalography waveform peak-to-peak amplitude (p < 0.05), a significant increase in psychomotor vigilance test response time, and an increase in perceived symptomatology. Exhaled breath results indicate 19 volatile organic compound features are significantly different between hypoxia and normoxia (p < 0.05) with 13 showing an increase in exhaled breath compared to background measurements (p < 0.05). Linear mixed modeling with stepwise reduction demonstrates 7 of the features are significantly indicative of changes in SpO2 with 3 and 4 features indicative of changes in brain wave functions and psychomotor vigilance test response times, respectively. Conclusions The data establish, for the first time, differences in exhaled breath volatile concentrations that indicate changes in cognition derived from hypoxic insult.
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spelling doaj-art-a822ce69832444a788b79dbcb69bf3fd2025-08-20T03:45:32ZengBMCRespiratory Research1465-993X2025-06-0126111410.1186/s12931-025-03296-5Estimating hypoxia-induced brain dysfunction and cognitive decline through exhaled breath monitoringSean W. Harshman0Kiersten J. Weatherbie1Alena R. Veigl2Anne E. Jung3Madison A. Stoner-Dixon4Aubrianne I. Dash5Christopher J. Land6Dylan T. Slizewski7Eli F. Kelley8Jennifer Schwanekamp-Kerr9Timothy Halverson10Christina N. Davidson11Christopher W. Myers12Kara J. Blacker13Jennifer A. Martin14Rhonda L. Pitsch15711th Human Performance Wing, Air Force Research LabNaval Medical Research Unit DaytonUES Inc., 711th Human Performance Wing, Air Force Research LabUES Inc., 711th Human Performance Wing, Air Force Research Lab711th Human Performance Wing, Air Force Research Lab711th Human Performance Wing, Air Force Research Lab711th Human Performance Wing, Air Force Research Lab711th Human Performance Wing, Air Force Research Lab711th Human Performance Wing, Air Force Research LabUES Inc., 711th Human Performance Wing, Air Force Research LabAptima, Inc711th Human Performance Wing, Air Force Research Lab711th Human Performance Wing, Air Force Research LabNaval Medical Research Unit Dayton711th Human Performance Wing, Air Force Research Lab711th Human Performance Wing, Air Force Research LabAbstract Background Hypoxia remains a concern for aircrew operating high performance aircraft. Sensing and mitigating hypoxia is a line of active research within the US Air Force and US Navy. It is hypothesized that changes in exhaled breath volatile organic compound content could indicate, not only changes in oxygen saturation (SpO2), but also brain activity and cognitive function. Methods On-line exhaled breath monitoring via proton transfer reaction mass spectrometry was used to observe changes in volatile organic compound concentrations during mask-free hypoxic exposures. Additionally, electroencephalography measurements in response to an odd-ball paradigm and cognitive tasks were collected throughout the exposures. Results The data show hypoxic exposures induced a physiological response including a significant reduction in SpO2, a decrease in the electroencephalography waveform peak-to-peak amplitude (p < 0.05), a significant increase in psychomotor vigilance test response time, and an increase in perceived symptomatology. Exhaled breath results indicate 19 volatile organic compound features are significantly different between hypoxia and normoxia (p < 0.05) with 13 showing an increase in exhaled breath compared to background measurements (p < 0.05). Linear mixed modeling with stepwise reduction demonstrates 7 of the features are significantly indicative of changes in SpO2 with 3 and 4 features indicative of changes in brain wave functions and psychomotor vigilance test response times, respectively. Conclusions The data establish, for the first time, differences in exhaled breath volatile concentrations that indicate changes in cognition derived from hypoxic insult.https://doi.org/10.1186/s12931-025-03296-5
spellingShingle Sean W. Harshman
Kiersten J. Weatherbie
Alena R. Veigl
Anne E. Jung
Madison A. Stoner-Dixon
Aubrianne I. Dash
Christopher J. Land
Dylan T. Slizewski
Eli F. Kelley
Jennifer Schwanekamp-Kerr
Timothy Halverson
Christina N. Davidson
Christopher W. Myers
Kara J. Blacker
Jennifer A. Martin
Rhonda L. Pitsch
Estimating hypoxia-induced brain dysfunction and cognitive decline through exhaled breath monitoring
Respiratory Research
title Estimating hypoxia-induced brain dysfunction and cognitive decline through exhaled breath monitoring
title_full Estimating hypoxia-induced brain dysfunction and cognitive decline through exhaled breath monitoring
title_fullStr Estimating hypoxia-induced brain dysfunction and cognitive decline through exhaled breath monitoring
title_full_unstemmed Estimating hypoxia-induced brain dysfunction and cognitive decline through exhaled breath monitoring
title_short Estimating hypoxia-induced brain dysfunction and cognitive decline through exhaled breath monitoring
title_sort estimating hypoxia induced brain dysfunction and cognitive decline through exhaled breath monitoring
url https://doi.org/10.1186/s12931-025-03296-5
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