Dimethyl ether uptake dynamics in human airways

Uptake of soluble dimethyl ether (DME) gas in the airways has previously been used to estimate airway mucosal interstitial volume and bloodflow. Animal studies indicate that following inhalation of 100% DME, a dynamic equilibrium is rapidly reached and the time-dependent reduction in airway DME is nearly linear and a function of mucosal bloodflow. For human use, DME must be given in lower concentrations, and helium (He) gas is used to correct exhaled DME for axial gas phase dispersion. We tested the assumption that a steady-state uptake of dilute DME is rapidly achieved in human airways by having four adult subjects inhale 500ml boluses of 10% DME and 5% He in oxygen near TLC, followed by breathholds of 2,4,6,8,10, 12, 16. and 20 seconds. Breathhold times were repeated three times at random. The He-corrected DME concentrations measured from 200-250 ml of exhaled volume, averaged for the four subjects, are shown in the figure. The rate of DME uptake was not constant, as indicated by the significantly larger slope of changing DME concentration from 6s to 10s of breathhold (A) vs. 16s to 20s of breathhold (B) (paired t-test on slopes normalized for mean differences between subjects; p < .005). Further studies indicate that short breathhold DME uptake is DME concentration dependent. (Figure Presented) We conclude that DME uptake during short breathhold times is due to airway bloodflow and equilibration in the tissue and blood, whereas with longer breathholds uptake is primarily airway bloodflow dependent.