Biological variation of resting measures of ventilation and gas exchange in a large healthy cohort

Eur J Appl Physiol. 2019 Sep;119(9):2033-2040. doi: 10.1007/s00421-019-04190-x. Epub 2019 Jul 18.


Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Coefficient of variation; Decision level; Index of heterogeneity; Index of individuality; Reference change value.

MeSH terms

  • Adult
  • Carbon Dioxide / metabolism
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Oxygen / metabolism
  • Pulmonary Gas Exchange / physiology*
  • Respiration
  • Respiratory Function Tests / methods
  • Rest / physiology*
  • Retrospective Studies
  • Tidal Volume / physiology
  • Ventilation / methods
  • Young Adult


  • Carbon Dioxide
  • Oxygen