Effect of alveolar volume and sequential filling on the diffusing capacity of the lungs: I. theory

The diffusing capacity, DL, is a critical physiological parameter of the lung used to assess gas exchange clinically. Most models developed to analyze experimental data from a single breath maneuver have assumed a well-mixed or uniform alveolar region, including the clinically accepted Jones-Meade method. In addition, all previous models have assumed a constant DL, which is independent of alveolar volume, VA. In contrast, experimental data provide evidence for a non-uniform alveolar region coupled with sequential filling of the lung. In addition, although the DL for carbon monoxide is a weak function of VA, the DL of nitric oxide depends strongly on VA. We have developed a new mathematical model of the single breath maneuver that considers both a variable degree of sequential filling and a variable DL. Our model predicts that the Jones-Meade method overestimates DL when the exhaled gas sample is collected late in the exhalation, but underestimates DL if the exhaled gas sample is collected early in the exhalation phase due to the effect of sequential filling. Utilizing a prolonged constant exhalation method, or a three-equation method, will also produce erroneous predictions of DL. We conclude that current methods may introduce significant error in the estimation of DL by ignoring the sequential filling of the lung, and the dependence of DL on VA.