Alveolar volume and sequential filling impact the estimation of D LCO and DLNO

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 (D_L) on alveolar volume (V_A). 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+bV_A) and an exponential (αV_A^β) dependence of D_L are used to describe the volume dependence of D_L 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) D_L depends on lung volume (strongly for NO, weakly for CO), and (2) the effect of sequential filling must be considered when estimating D_L