INTRODUCTION: If Multiple Breath Washout (MBW) derived acinar ventilation heterogeneity (Sacin) really represents peripheral units, the N₂ phase-III slope of the first MBW exhalation should be curvilinear, due to the ability of gas diffusion to continuously equilibrate N₂ concentrations between neighbouring lung units, and thus reduce the slope as exhalation continues. We investigated this in smokers with CT-proven functional small airway disease.

METHODS: Instantaneous N₂ slopes were computed over 40ms intervals throughout phase-III and normalized by mean phase-III N₂ concentration.  N₂ phase-III curvilinearity was the rate at which the instantaneous N₂-slope decreases past the phase-II peak over a 1s interval; for a linear phase-III slope unaffected by diffusion, this rate would amount to 0 L^-1/s.

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 (f^SAD+f^Emphys)>20% (-0.26 +0.14(SD)L^-1/s; n=24) and those with (f^SAD+f^Emphys)<20% (-0.16+0.12(SD)L^-1/s; n=22) (P=0.014); experimental values fell in the range predicted by a realistic for progressive reduction of terminal bronchioles (-0.09 to -0.56 L^-1/s).

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.