Acinar and conductive ventilation heterogeneity in severe CF lung disease: Back to the model

•In severe CF lung disease, interpretation of multibreath washout (MBW) is difficult.•Conceptual models of ventilation mechanisms can help MBW interpretation.•Acinar and conductive MBW indices can be linked to specific ventilation mechanisms.•The acinar MBW index likely reflects the best ventilated peripheral units.

Severe convective ventilation heterogeneity occurring in CF lung disease requires a modified method to determine acinar and conductive components of ventilation heterogeneity from normalized phase III slope (Sn) curves. Modified Sacin* and Scond* (as opposed to standard Sacin and Scond) are proposed and interpreted on the basis of 2 conceptual mechanisms: (a) flow asynchrony between two convection-dependent units with a different specific ventilation, but with an identical acinus inside each unit (generating an identical diffusion-convection-dependent portion of Sn); (b) different specific ventilation (without any flow asynchrony) between two convection-dependent units with the worst ventilated unit containing an abnormal acinus generating the greatest diffusion-convection-dependent portion of Sn. In CF patients with an abnormal lung clearance index (LCI), Scond* (but not Scond) and Sacin* were significant contributors to LCI (β(Scond*) = 0.70; β(Sacin*) = 0.49; P < 0.001 for both). Mechanism (a) can entirely account for experimental Scond* values, while mechanism (b) implies that experimental Sacin* values are likely dominated by peripheral ventilation heterogeneity in the best ventilated portions of the lung.