Differences in molecular diffusivity do not explain discrepancy in Lung Clearance Index measured by nitrogen and SF6 washout

Background: Lung Clearance Index (LCI) seems to be significantly affected by the tracer gas used, with several recent studies showing a higher LCI with nitrogen (N2) washout when compared to SF6 washout from the same subjects. It has been suggested that this may be partly accounted for by differences in diffusivity, since the heavier gas SF6 has a steeper, more distal diffusion front than the lighter N2.

Method: We have developed a computational model of coupled ventilation and gas transport, representative of lung physiology. The upper airways connecting the lobes were explicitly simulated, while each lobe was represented by a ‘trumpet’ model of the bronchioles and acinar airways. MBW was simulated for a healthy adult male (FRC 3.0L, 1.0L tidal volume, 170ml deadspace), as well as a model with the same parameters but with constrictions of the smaller bronchioles, randomly assigned to the lobes. The latter case represents a simplified model of early CF pathophysiology. 50 washouts were simulated for each value of constriction severity considered.

Results: In all cases we observed that SF6 washout showed small but consistent increase in measured LCI relative to N2. In the healthy lung model, we observed an increase from 5.21 to 5.35 (3%). Increased ventilation heterogeneity enlarged the measured LCI (up to 9.57±1.63) but there was a similar relative increase in LCI from N2 to SF6 washout, ranging from 3% to 4%.

Conclusion: The lower diffusivity of SF6 relative to N2 should generically increase measured LCI values. We have demonstrated this with simulations representing healthy and reduced lung function. Experimental differences in measured between N2 and SF6 are in the opposite direction, suggesting they are likely due to other factors. Contributions from N2 absorbed into the blood may account for observed differences in clinical measurements.