Effect of alveolar volume and sequential filling on the diffusing capacityof the lungs: I. Theory

The diffusing capacity, DL, is a critical physiological parameter of the lu ng 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 m ethod. In addition, all previous models have assumed a constant DL, which i s independent of alveolar volume, VA. in contrast, experimental data provid e evidence for a non-uniform alveolar region coupled with sequential fillin g of the lung. In addition, although the DL for carbon monoxide is a weak f unction of VA, the DL of nitric oxide depends strongly on VA. We have devel oped a new mathematical model of the single breath maneuver that considers both a variable degree of sequential filling and a variable DL. Our model p redicts that the Jones-Meade method overestimates DL when the exhaled gas s ample is collected late in the exhalation, but underestimates DL if the exh aled gas sample is collected early in the exhalation phase due to the effec t of sequential filling. Utilizing a prolonged constant exhalation method, or a three-equation method, will also produce erroneous predictions of Dr. We conclude that current methods may introduce significant error in the est imation of DL by ignoring the sequential filling of the lung, and the depen dence of DL on VA. (C) 2000 Elsevier Science B.V. All rights reserved.