Current definitions of the breathing cycle in alveolar breath-by-breath gas exchange analysis

Identification of the breathing cycle forms the basis of any breath-by-breath gas exchange analysis. Classically, the breathing cycle is defined as the time interval between the beginning of two consecutive inspiration phases. Based on this definition, several research groups have developed algorithms designed to estimate the volume and rate of gas transferred across the alveolar membrane ("alveolar gas exchange"); however, most algorithms require measurement of lung volume at the beginning of the i^th breath (V₁; i.e., the end-expiratory lung volume of the preceding i^th breath). The main limitation of these algorithms is that direct measurement of V₁ is challenging and often unavailable. Two solutions avoid the requirement to measure V₁ by redefining the breathing cycle. One method defines the breathing cycle as the time between two equal fractional concentrations of lung expired oxygen (Fo) (or carbon dioxide; Fco), typically in the alveolar phase, whereas the other uses the time between equal values of the Fo/Fn (or Fco/Fn) ratios [i.e., the ratio of fractional concentrations of lung expired O₂ (or CO₂) and nitrogen (N₂)]. Thus, these methods identify the breathing cycle by analyzing the gas fraction traces rather than the gas flow signal. In this review, we define the traditional approach and two alternative definitions of the human breathing cycle and present the rationale for redefining this term. We also explore the strengths and limitations of the available approaches and provide implications for future studies.