European Journal of Applied Physiology

, Volume 118, Issue 6, pp 1119–1130 | Cite as

Assessing breath-by-breath alveolar gas exchange: is the contiguity in time of breaths mandatory?

  • Valentina Cettolo
  • Maria Pia FrancescatoEmail author
Original Article



A new algorithm is illustrated for the determination of breath-by-breath alveolar gas exchange that neglects the contiguity in time of breaths, i.e. it allows the breaths to be partially superimposed or disjoined in time.


Traces of oxygen, carbon dioxide fractions, and ventilatory flow were recorded continuously over 20 min in 15 healthy subjects in resting conditions; at 5-min intervals, subjects voluntarily hyperventilated for ~ 30 s to induce abrupt changes in lung gas stores. Gas exchange data were calculated applying the new algorithm and were compared to those yielded by a reference algorithm, also providing values at the alveolar level.


Average O2 uptakes (V′O2) obtained with the two algorithms were similar during quiet breathing (0.28 ± 0.06 vs. 0.29 ± 0.06 L/min; two-sided paired t test, n = 45, p = NS); during hyperventilation, average V′O2 was significantly lower applying the new algorithm compared to the reference algorithm (0.57 ± 0.15 vs. 0.65 ± 0.17 L/min; difference − 0.077 ± 0.048 L/min; two-sided paired t test, n = 45, p < 0.001). The first breath of each hyperventilation manoeuvre showed the greatest difference in V′O2 (− 0.25 ± 0.23 L/min, z test against zero, n = 45, p < 0.001). The volumes of O2 considered twice (or neglected) because of the lack of contiguity of breaths were overall small (maximum of 3 mL) and, if accounted for, had only a slight softening effect on the fluctuations of the O2 uptake.


The new algorithm, which assumes each breath as the leading subject, was able to effectively account for changes in lung gas stores without requiring any predetermined value or off-line optimisation procedure.


Oxygen uptake Respiratory cycle Hyperventilation 





Breath frequency


Body temperature pressure saturated


End-expiratory lung volume that matched breath-by-breath changes in end-expiratory measurements so as to minimize the breath-by-breath variation, according to the approach proposed by Swanson and Sherrill (1983) and defined by the authors as “nominal effective lung volume”

FCO2, FN2, FO2

Instantaneous carbon dioxide, non-exchangeable gas at alveolar level (essentially nitrogen) and oxygen fractions


“Independent breath” approach, i.e. the breath-by-breath alveolar gas exchange algorithm under investigation


Repeated measures multivariate analysis of variance


Standard temperature pressure dry


“Swanson’s” approach, i.e. the breath-by-breath alveolar gas exchange algorithm taken as reference



ti, te

Starting times of inspiration and expiration, respectively; defined on the flow trace where flow changes direction


Time of the end-expiratory exchanged gas fraction, defined on the FO2 (or FCO2) trace

t1, t2

Start and end times of the j-th breath for the “independent breath” approach; defined on the FO2/FN2 (or FCO2/FN2) trace

\(\dot {V}\)

Respiratory flow at the mouth

\(\dot {V}E\)

Ventilation, in STPD conditions


End-expiratory lung volume

\(\dot {V}{\text{O}}_{2}^{{{\text{IND}}}}\)

Oxygen uptake calculated applying the “independent breath” approach, in STPD conditions

\(\dot {V}{\text{O}}_{2}^{{{\text{SW}}}}\)

Oxygen uptake calculated applying the “Swanson's” approach, in STPD conditions


Tidal volume, in STPD conditions



We thank the Cortex GmbH (Liepzig, Germany) company for having provided us with the metabolic unit. Cortex GmbH, however, was not involved in the study design, data collection, analysis or interpretation. We thank Dr. Petra Golja (University of Ljubljana) for helpful discussion and revision of the manuscript.

Author contributions

Experimentation was carried out at the Human Exercise Physiology laboratory of the Department of Medicine, University of Udine (Italy). CV and FMP equally contributed in conception and design of the work; both performed the experiments, analysed the data and interpreted them; FMP drafted the paper. Both authors read and approved the final version of the manuscript. CV and FMP agree to be accountable for all aspects of the work. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed.


This work was supported by funding of the Department of Medicine of the University of Udine to Dr. M.P. Francescato.

Compliance with ethical standards

Conflict of interest

Valentina Cettolo and Maria Pia Francescato had no competing interests.


  1. Auchincloss JHJ, Gilbert R, Baule GH (1966) Effect of ventilation on oxygen transfer during early exercise. J Appl Physiol 21:810–818CrossRefGoogle Scholar
  2. Beaver WL, Wasserman K, Whipp BJ (1973) On-line computer analysis and breath-by-breath graphical display of exercise function tests. J Appl Physiol 34:128–132CrossRefGoogle Scholar
  3. Beaver WL, Lamarra N, Wasserman K (1981) Breath-by-breath measurement of true alveolar gas exchange. J Appl Physiol 51:1662–1675CrossRefGoogle Scholar
  4. Busso T, Robbins PA (1997) Evaluation of estimates of alveolar gas exchange by using a tidally ventilated nonhomogenous lung model. J Appl Physiol 82:1963–1971CrossRefGoogle Scholar
  5. Capelli C, Cautero M, di Prampero PE (2001) New perspectives in breath-by-breath determination of alveolar gas exchange in humans. Pflugers Arch 441:566–577CrossRefGoogle Scholar
  6. Capelli C, Cautero M, Pogliaghi S (2011) Algorithms, modelling and VO2 kinetics. Eur J Appl Physiol 111:331–342. CrossRefPubMedGoogle Scholar
  7. Cautero M, Beltrami AP, di Prampero PE, Capelli C (2002) Breath-by-breath alveolar oxygen transfer at the onset of step exercise in humans: methodological implications. Eur J Appl Physiol 88:203–213. CrossRefPubMedGoogle Scholar
  8. Cettolo V, Francescato MP (2015) Assessment of breath-by-breath alveolar gas exchange: an alternative view of the respiratory cycle. Eur J Appl Physiol 115:1897–1904. CrossRefPubMedGoogle Scholar
  9. Cettolo V, Francescato MP (2017) Effects of abrupt changes in lung gas stores on the assessment of breath-by-breath gas exchange. Clin Physiol Funct Imaging. CrossRefPubMedGoogle Scholar
  10. di Prampero PE, Lafortuna CL (1989) Breath-by-breath estimate of alveolar gas transfer variability in man at rest and during exercise. J Physiol 415:459–475CrossRefGoogle Scholar
  11. Grønlund J (1984) A new method for breath-to-breath determination of oxygen flux across the alveolar membrane. Eur J Appl Physiol 52:167–172CrossRefGoogle Scholar
  12. Swanson G (1980). Breath-to breath considerations for gas exchange kinetics. In: P Cerretelli, BJ Whipp (eds) Exercise bioenergetics and gas exchange. Elsevier/North Holland, Amsterdam, pp 211–222Google Scholar
  13. Swanson G, Sherrill D (1983) A model evaluation of estimates of breath-to-breath alveolar gas exchange. J Appl Physiol Respir Environ Exerc Physiol 55:1936–1941PubMedGoogle Scholar
  14. Wessel H, Stout R, Bastanier C, Paul M (1979) Breath-by-breath variation of FRC: effect on VO2 and VCO2 measured at the mouth. J Appl Physiol Respir Environ Exerc Physiol 46:1122–1126PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of MedicineUniversity of UdineUdineItaly

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