Structure-function in smokers: when a small airways test really reflects the small airways.

Abstract

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 essentially due to the superposed effect of gas diffusion and convection resulting in an equilibration of N2 concentrations between neighboring lung units throughout exhalation. We investigated this in smokers with computed tomography (CT)-proven functional small airway disease. Instantaneous N2-slopes were computed over 40-ms intervals throughout phase-III and normalized by mean phase-III N2 concentration. N2 phase-III (concave) curvilinearity was quantified as the rate at which the instantaneous N2-slope decreases past the phase-II peak over a 1-s interval; for a linear N2 phase-III unaffected by diffusion, this rate would amount to 0 L-1/s. N2 phase-III curvilinearity was obtained on the experimental curves and on existing model simulations of N2 curves from a normal peripheral lung model and one with missing terminal bronchioles (either 50% or 30% TB left). In 46 smokers [66 (±8) yr; 49 (±26) pack·yr] with CT-based 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 -0.09 L-1/s (normal lung; 100% TB left), -0.17 L-1/s (normal lung 50% TB left), and -0.29 L-1/s (30% TB left). In smokers with CT-based evidence of functional small airway alterations, it is possible to demonstrate that Sacin really does represent the most peripheral airspaces.NEW & NOTEWORTHY In smokers with computed tomography-based evidence of functional small airway alterations by parametric response mapping, it is possible to demonstrate that the multiple-breath washout-derived Sacin, an index of acinar ventilation heterogeneity, actually does represent the most peripheral airspaces. This is done by verifying on experimental N2 washout curves of the first breath, N2 phase-III concavity predicted by the diffusion-convection interdependence model.