Self-organized ventilation defects in asthma: insights and open-source implementation of the Venegas–Winkler model

Abstract The Venegas–Winkler model is a seminal model in asthma pathophysiology, providing both a conceptual and quantitative framework for extending a posited bistability between open and closed states at the level of the individual, terminal airway to the lung as a whole. In doing so, it offers an explanation for the characteristic ventilation heterogeneity (or clustered ventilation defects) seen in asthma. The terminal airway bistability is based on the Anafi–Wilson model, and this is embedded and extended into a symmetric bifurcating airway tree, in which an enforced tidal volume target and an imposed degree of airway smooth-muscle activation interact to generate spatially structured ventilation patterns. Here, we provide the first open-source implementation of the Venegas–Winkler bronchoconstriction cascade model and use it to identify several previously undescribed properties: both the tree depth and wall thickness assumptions affect the bifurcation onset, tidal volume and acinar elastance assumptions require careful interpretation for a model at sub-lung scale and airway geometry assumptions strongly affect driving pressures and bifurcation cascade characteristics.