This paper presents the development, testing, and application to experimental data of a new model to: 1) estimate the degree of sequential filling during inhalation, and 2) the dependence of the diffusing capacity (DL) on alveolar volume (VA). The model assesses sequential filling through a single parameter, k, where k = 0 represents complete alveolar mixing, and k = 1 represents no alveolar mixing (sequential filling). A linear (a+bVA) and an exponential (αVAβ) dependence of DL are used to describe the volume dependence of DL for carbon monoxide (CO) and nitric oxide (NO), respectively. Application of the model to experimental data from 7 normal humans predicts k = 0.51 (0.35), b = 0.69 (0.79), and β = 0.65 (0.19) (mean (SD)). We conclude: 1) DL depends on lung volume (strongly for NO, weakly for CO), and 2) the effect of sequential filling must be considered when estimating DL.
