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.