Journal Article

Breath‐by‐breath measurement of alveolar gas exchange must preserve mass balance and conform to a physiological definition of a breath

Capelli, Carlo, Ferguson, Carrie, Ward, Susan A., Girardi, Michele, Rossiter, Harry B.

2025

Overview

Tidal breathing in awake humans is variable. This variability causes changes in lung gas stores that affect gas exchange measurements. To overcome this, several algorithms provide solutions for breath‐by‐breath alveolar gas exchange measurement; however, there is no consensus on a physiologically robust method suitable for widespread application. A recent approach, the ‘independent‐breath’ (IND) algorithm, avoids the complexity of measuring breath‐by‐breath changes in lung volume by redefining what is meant by a ‘breath’. Specifically, it defines a single breathing cycle as the time between equal values of the FO2 ${F_{{{\\mathrm{O}}_2}}}$ /FN2 ${F_{{{\\mathrm{N}}_2}}}$(or FCO2 ${F_{{\\mathrm{C}}{{\\mathrm{O}}_2}}}$ /FN2 ${F_{{{\\mathrm{N}}_2}}}$ ) ratio, that is, the ratio of fractional concentrations of lung‐expired O2 (or CO2) and nitrogen (N2). These developments imply that the end of one breath is not, by necessity, aligned with the start of the next. Here we demonstrate how the use of the IND algorithm fails to conserve breath‐by‐breath mass balance of O2 and CO2 exchanged between the atmosphere and tissues (and vice versa). We propose a new term, within the IND algorithm, designed to overcome this limitation. We also present the far‐reaching implications of using algorithms based on alternative definitions of the breathing cycle, including challenges in measuring and interpreting the respiratory exchange ratio, pulmonary gas exchange efficiency, dead space fraction of the breath, control of breathing, and a broad spectrum of clinically relevant cardiopulmonary exercise testing variables. Therefore, we do not support the widespread adoption of currently available alternative definitions of the breathing cycle as a legitimate solution for breath‐by‐breath alveolar gas exchange measurement in research or clinical settings. What is the central question of this study? The IND algorithm for breath‐by‐breath alveolar gas exchange computation redefines ‘a breath’: what are the implications of this approach for the measurement of gas exchange at rest and during exercise? What is the main finding and its importance? The IND algorithm does not maintain continuity between consecutive breaths, violating the conservation of mass for breath‐by‐breath alveolar gas exchange measurements. A volume correction to the algorithm is provided to address this discrepancy and preserve mass balance. However, by redefining the conventional breathing cycle, the IND algorithm has additional implications for cardiopulmonary exercise testing interpretation because variables with demonstrated diagnostic and prognostic value cannot be accurately determined.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Algorithms / Alveoli / breathing cycle / Carbon dioxide / CPET / Gas exchange / Humans / kinetics / Lung - physiology / Methods and Techniques / Oxygen - metabolism / Pulmonary Alveoli - physiology / Pulmonary Gas Exchange - physiology / Respiration / Tidal Volume - physiology