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

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 (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 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.