This article summarises the pros and cons of different algorithms developed for estimating breath-by-breath (B-by-B) alveolar O2 transfer (VO2A) in humans. VO2A is the difference between O2 uptake at the mouth and changes in alveolar O2 stores (VO2s), which for any given breath, are equal to the alveolar volume change at constant the O2 alveolar fraction change at constant volume, where V Ai-1 is the alveolar volume at the beginning of a breath. Therefore, VO2A can be determined B-by-B provided that V Ai-1 is: (a) set equal to the subject`s functional residual capacity (algorithm of Auchincloss, A) or to zero; (b) measured (optoelectronic plethysmography, OEP); (c) selected according to a procedure that minimises B-by-B variability (algorithm of Busso and Robbins, BR). Alternatively, the respiratory cycle can be redefined as the time between equal FO2 in two subsequent breaths (algorithm of Grønlund, G), making any assumption of V Ai-1 unnecessary. All the above methods allow an unbiased estimate of VO2 at steady state, albeit with different precision. Yet the algorithms "per se" affect the parameters describing the B-by-B kinetics during exercise transitions. Among these approaches, BR and G, by increasing the signal-to-noise ratio of the measurements, reduce the number of exercise repetitions necessary to study VO2 kinetics, compared to A approach. OEP and G (though technically challenging and conceptually still debated), thanks to their ability to track VO 2s changes during the early phase of exercise transitions, appear rather promising for investigating B-by-B gas exchange.
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