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.