Pulmonary diffusing capacity in the presence of ventilation inhomogeneity

A model has been developed to quantify the effectiveness of alveolar-capillary transport in the presence of ventilation inhomogeneity. The exhalation dynamics of carbon monoxide (CO), argon (Ar), and lung volume from a single-breath experiment are analyzed simultaneously. A membrane transport coefficient (MTCO) that does not vary with lung volume is evaluated by a two-stage optimization procedure and related to diffusing capacity. Also, the model allows for a decrease in membrane transport rate associated with reduced lung volume. The model is tested by simulation studies and experiments with human subjects having normal or diseased (mainly obstructed) lungs. The MTCO provides a clear distinction between normal and obstructed lungs with respect to alveolar-capillary transport, whereas the semilog slope of the Ar alveolar plateau characterizes the ventilation inhomogeneity. Only when the diffusing capacity is corrected by the Ar slope, DLCO(Ar), do the breathing maneuvers performed from different preinflation volumes (residual volume or functional residual capacity) yield the same results for lungs with ventilation inhomogeneity. The uncorrected DLCO overestimates the effectiveness of alveolar-capillary transport in the presence of ventilation inhomogeneity.