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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.

Adult

Pulmonary diffusing capacity in adult cystic fibrosis: reduced positional changes are partially reversed by hyperoxia.

In seated adult cystic fibrosis (CF) patients, vascular recruitment of the relatively normal regions of the pulmonary circulation could occur in response to vascular destruction or hypoxia elsewhere in the pulmonary vasculature, thus limiting overall reductions in the single breath CO diffusing capacity (DLcoSB) with advancing disease. The purpose of this study was to determine the extent to which pulmonary capillary recruitment limits reductions in DLcoSB in seated adult cystic fibrosis patients, to define the role of hypoxia, and to develop strategies to improve detection of diffusion abnormalities in this disease. In normal subjects and adult CF patients breathing room air, and in a subgroup, after breathing both 40% and 100% O2 for 20 min, we measured changes (compared to sitting) in the three equation DLcoSB by changing transvascular pressure either with 15 degrees head down position (15 degrees HD), or with high negative inspiratory pressure (HNIP). In CF patients breathing room air, the changes in DLcoSB with both 15 degrees HD and HNIP were significantly smaller (p less than 0.01) than in controls and the positional changes correlated with the degree of airway obstruction. Although CF patients had no significant positional changes in diffusional resistance (1/DLcoSB) breathing room air, the positional changes in 1/DLcoSB after breathing 100% O2 for 20 min were similar in magnitude to the positional changes in normal subjects. We conclude that compensatory pulmonary capillary recruitment occurs in the relatively normal regions of the pulmonary vasculature breathing room air in the resting seated position in CF patients, thus minimizing reductions in DLcoSB in the seated position. This accounts for reduced responses of DLcoSB to both position and HNIP. The improved positional changes in 1/DLcoSB breathing hyperoxic gas mixtures in CF patients suggests that the vascular recruitment breathing room air is partly due to hypoxic vasoconstriction rather than due solely to fixed pathological changes in the pulmonary vasculature.

Adolescent