Biological variation of resting measures of ventilation and gas exchange in a large healthy cohort
Resting measures of ventilation and gas exchange are impacted by a variety of physiological stressors, such as those resulting from a research intervention or an extreme environment. However, the biological variation of these parameters, an important statistical consideration for identifying a meaningful physiological change, has not been quantified.
We performed a retrospective analysis of 21 studies completed by the U.S. Army Research Institute of Environmental Medicine (USARIEM) from 1985 to present, totaling 411 healthy volunteers. First, we determined the intraindividual, interindividual, and analytic coefficients of variation (CVI, CVG, and CVA, respectively) and subsequently the index of individuality and heterogeneity (II and IH, respectively). Second, when deemed appropriate via these outcomes, we defined the accompanying static and dynamic thresholds, beyond which a significant deviation from normal is indicated.
End-tidal partial pressure of oxygen (PETO2) and the respiratory exchange ratio (RER) approached the II threshold required to be considered useful in the static assessment of physiological deviations from normal. PETO2 and peripheral oxygen saturation (SpO2) approached the IH threshold required to be considered useful in the dynamic assessment of physiological deviations from normal.
This analysis identifies RER and PETO2 as parameters that might be most useful when aiming to identify a meaningful ventilatory change following a research intervention or stressor. Alternatively, other parameters of ventilation and gas exchange, such as PETCO2 and VE, may be less useful for observing an anticipated physiological change.
KeywordsCoefficient of variation Reference change value Decision level Index of individuality Index of heterogeneity
Acute mountain sickness
Body mass index
Body surface area
Analytic coefficient of variation
Interindividual coefficient of variation
Intraindividual coefficient of variation
Index of heterogeneity
Index of individuality
End-tidal partial pressure of carbon dioxide
End-tidal partial pressure of oxygen
Reference change value
Respiratory exchange ratio
Peripheral oxygen saturation
Carbon dioxide production
The authors wish to thank Upendra Bhattarai for his assistance with data compilation and Chuck Fulco for his editorial support. This work was funded by the US Army Medical Research Materiel Command’s Military Operational Medicine Research Program. This research was also supported in part by an appointment to the Student Research Participation Program at the U.S. Army Medical Research Institute of Environmental Medicine administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and USAMRMC.
KEC, SNC, RMS, and RWK conceived and designed the research. KEC analyzed the data and wrote the manuscript. All authors read, edited, and approved the manuscript.
Compliance with ethical standards
Conflict of interest
The opinions or assertions contained herein are the private views of the author(s) and are not to be construed as official or reflecting the views of the Army or the Department of Defense. Any citations of commercial organizations and trade names in this report do not constitute an official Department of the Army endorsement of approval of the products or services of these organizations. No authors have any conflicts of interest to disclose. Approved for public release; distribution is unlimited.
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