Abstract
This review explores the conceptual and technological factors integral to the development of laboratory-based, automated real-time open-circuit mixing-chamber and breath-by-breath (B × B) gas-exchange systems, together with considerations of assumptions and limitations. Advances in sensor technology, signal analysis, and digital computation led to the emergence of these technologies in the mid-20th century, at a time when investigators were beginning to recognise the interpretational advantages of nonsteady-state physiological-system interrogation in understanding the aetiology of exercise (in)tolerance in health, sport, and disease. Key milestones include the ‘Auchincloss’ description of an off-line system to estimate alveolar O2 uptake B × B during exercise. This was followed by the first descriptions of real-time automated O2 uptake and CO2 output B × B measurement by Beaver and colleagues and by Linnarsson and Lindborg, and mixing-chamber measurement by Wilmore and colleagues. Challenges to both approaches soon emerged: e.g., the influence of mixing-chamber washout kinetics on mixed-expired gas concentration determination, and B × B alignment of gas-concentration signals with respired flow. The challenging algorithmic and technical refinements required for gas-exchange estimation at the alveolar level have also been extensively explored. In conclusion, while the technology (both hardware and software) underpinning real-time automated gas-exchange measurement has progressively advanced, there are still concerns regarding accuracy especially under the challenging conditions of changing metabolic rate.
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Notes
Conventionally, ventilation is measured as ‘expired’.
A nomenclature introduced by Whipp in 1978 which apportioned the nonsteady-state period following the onset of constant WR exercise into two distinct temporal domains, based on their underlying determinants of pulmonary gas exchange: phase 1, the initial short period in which pulmonary gas exchange is effectively isolated from the demands of increased muscle metabolic rate and is, therefore, dominated by increases in cardiac output or, more properly, pulmonary blood flow; and phase 2, having the additional challenge presented by the exercise-induced changes in mixed-venous blood composition. The eventual steady state is termed phase 3 (Whipp 1978).
A mixing chamber is a container within the expiratory line that operates as a temporary reservoir into which several consecutive expirates flow (the number depending on the chamber size). Their exit is delayed by having to travel past a series of baffles that both slow transit and promote turbulence, facilitating mixing of the dead space and alveolar components of each expirate. At the chamber outlet, a continuous aliquot of the resulting ‘mixed-expired’ gas is drawn into gas analysers for measurement.
Time required for a response to a step input to increase from 10 to 90% of its steady-state value.
As gas volumes are measured under ambient conditions, correction to STPD and BTPS conditions is required, as appropriate. For example, as \(\dot {V}{{\text{O}}_2}\) and \(\dot {V}{{\text{O}}_2}\) are referenced to STPD, \({\dot {V}_{\text{I}}}\) and \({\dot {V}_{\text{E}}}\) should be expressed as STPD for these particular calculations.
Time required for a response to attain 63% of its final value, with this being effectively attained within a time equal to ~ 4 time constants.
Time required for a response to attain 50% of its final value, with no assumptions being made about model order.
Deconvolution requires solution of the dynamic input–output relationship for the mixing chamber, by inversion of its transfer function (e.g., Finklestein and Carson 1985).
EDL, an XML application that provides a standard way of describing scientific experiments.
The decomposition of a function into its simple sinusoidal or harmonic components (e.g., Bendat and Piersol 1986).
The correlation of a signal with a lagged version of itself as a function of the lag time (e.g., Bendat and Piersol 1986).
\({({V_{\text{I}}} \cdot {F_{\text{I}}}{{\text{N}}_2} - {\text{ }}{V_{\text{E}}} \cdot {F_{\overline {{\text{E}}} }}{{\text{N}}_2})^i} - {\text{ }}V_{{\text{A}}}^{{i - 1}}({F_{\text{A}}}{\text{N}}_{2}^{i} - {\text{ }}{F_{\text{A}}}{\text{N}}_{2}^{{i - 1}}){\text{ }}+{\text{ }}{F_{\text{A}}}N_{2}^{i}(V_{A}^{i} - {\text{ }}V_{A}^{{i - 1}}){\text{ }}={\text{ }}0\) and \({F_{\text{A}}}{\text{N}}_{2}^{i}(V_{{\text{A}}}^{i} - {\text{ }}V_{{\text{A}}}^{{i - 1}}){\text{ }}={({V_{\text{I}}} \cdot {F_{\text{I}}}{{\text{N}}_2} - {\text{ }}{V_{\text{E}}} \cdot {F_{\overline {{\text{E}}} }}{{\text{N}}_2})^i} - {\text{ }}V_{{\text{A}}}^{{i - 1}}({F_{\text{A}}}{\text{N}}_{2}^{i} - {\text{ }}{F_{\text{A}}}{\text{N}}_{2}^{{i - 1}})\).
Abbreviations
- B × B:
-
Breath-by-breath
- BTPS:
-
Body temperature and pressure, saturated
- CO2 :
-
Carbon dioxide
- CPET:
-
Cardiopulmonary exercise testing
- EELV:
-
End-expiratory lung volume
- f B :
-
Breathing frequency
- \({F_{\overline {{\text{E}}} }}{{\text{CO}}_2}\) :
-
Mixed-expired CO2 fraction
- \({F_{\overline {{\text{E}}} }}{{\text{N}}_2}\) :
-
Mixed-expired N2 fraction
- \({F_{\overline {{\text{E}}} }}{{\text{O}}_2}\) :
-
Mixed-expired O2 fraction
- F ETCO2 :
-
End-tidal CO2 fraction
- F ETO2 :
-
End-tidal O2 fraction
- F ICO2 :
-
Inspired CO2 fraction
- F IN2 :
-
Inspired N2 fraction
- F IO2 :
-
Inspired O2 fraction
- FRC:
-
Functional residual capacity
- N2 :
-
Nitrogen
- O2 :
-
Oxygen
- PCO2 :
-
Partial pressure of CO2
- P ACO2 :
-
Alveolar partial pressure of CO2
- pdf:
-
Probability-density function
- PH2O:
-
Water-vapour pressure
- PO2 :
-
Partial pressure of O2
- P AO2 :
-
Alveolar partial pressure of O2
- RER:
-
Respiratory exchange ratio
- SD:
-
Standard deviation
- STPD:
-
Standard temperature and pressure, dry
- τ:
-
Time constant
- t :
-
Time
- t 1/2 :
-
Half-time
- t 90 :
-
10–90% response time
- T D :
-
Transport delay
- V :
-
Volume
- V A :
-
Alveolar volume
- V BV :
-
Breathing valve volume
- VCO2, st:
-
Volume of lung CO2 stores
- VN2, st:
-
Volume of lung N2 stores
- VO2, st:
-
Volume of lung O2 stores
- V T :
-
Tidal volume
- \(\dot {v}\) :
-
Instantaneous flow
- \({\dot {V}_{\text{A}}}\) :
-
Alveolar ventilation
- \({\dot {V}_{\text{E}}}\) :
-
Expired ventilation
- \({\dot {V}_{\text{I}}}\) :
-
Inspired ventilation
- \({\dot {V}_{\text{E}}}/\dot {V}{\text{C}}{{\text{O}}_2}\) :
-
Ventilatory equivalent for CO2
- \({\dot {V}_{\text{E}}}/\dot {V}{{\text{O}}_2}\) :
-
Ventilatory equivalent for O2
- \(\dot {V}{\text{C}}{{\text{O}}_2}\) :
-
Carbon dioxide output
- \(\dot {V}{\text{C}}{{\text{O}}_{2A}}\) :
-
Alveolar carbon dioxide output
- \(\dot {V}{{\text{O}}_2}\) :
-
Oxygen uptake
- \(\dot {V}{{\text{O}}_{2A}}\) :
-
Alveolar oxygen uptake
- WR:
-
Work rate
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Acknowledgements
I dedicate this article to the late Brian James Whipp PhD, DSc, to whom I remain indebted for his mentorship and collaboration in our journeys through kinetic analysis in exercise.
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Communicated by Michael Lindinger.
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Ward, S.A. Open-circuit respirometry: real-time, laboratory-based systems. Eur J Appl Physiol 118, 875–898 (2018). https://doi.org/10.1007/s00421-018-3860-9
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DOI: https://doi.org/10.1007/s00421-018-3860-9