Abstract
INTRODUCTION: If Multiple Breath Washout (MBW) derived acinar ventilation heterogeneity (Sacin) really represents peripheral units, the N2 phase-III of the first MBW exhalation should be curvilinear. This is due to the superposed effect of gas diffusion and convection resulting in an equilibration of N2 concentrations between neighbouring lung units throughout exhalation. We investigated this in smokers with CT-proven functional small airway disease. METHODS: Instantaneous N2slopes were computed over 40ms intervals throughout phase-III and normalized by mean phase-III N2 concentration. N2phase-III (concave) curvilinearity was quantified as the rate at which the instantaneous N2 slope decreases past the phase-II peak over a 1s interval; for a linear N2phase-III unaffected by diffusion, this rate would amount to 0L-1/s. N2phase-III curvilinearity was obtained on the experimental curves and on existing model simulations of N2curves from a normal peripheral lung model and one with missing terminal bronchioles (either 50% or 30% TB left). RESULTS: In forty-six smokers (66 (+8) years; 49 (+26) packyears) with CT-evidence of peripheral lung destruction, instantaneous N2 slope decrease was compared between those with (fSAD+fEmphys)>20% (-0.26+0.14(SD) L-1/s;n=24) and those with (fSAD+fEmphys)<20% (-0.16+0.12(SD)L-1/s;n=22) (P=0.014). Experimental values fell in the range predicted by a realistic peripheral lung model with progressive reduction of terminal bronchioles: values of instantaneous N2-slope decrease obtained from model simulations were -0.09L-1/s (normal lung;100%TB left), -0.17L-1/s (normal lung 50%TB left) and -0.29L-1/s (30%TB left). DISCUSSION : In smokers with CT-based evidence of functional small airways alterations, it is possible to demonstrate that Sacin really does represent the most peripheral airspaces.
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