Airway stability and heterogeneity in the constricted lung

Abstract

The effect of bronchoconstriction on airway resistance is known to be spatially heterogeneous and dependent on tidal volume. We present a model of a single terminal airway that explains these features. The model describes a feedback between flow and airway resistance mediated by parenchymal interdependence and the mechanics of activated smooth muscle. The pressure-tidal volume relationship for a constricted terminal airway is computed and shown to be sigmoidal. Constricted terminal airways are predicted to have two stable states: one effectively open and one nearly closed. We argue that the heterogeneity of whole lung constriction is a consequence of this behavior. Airways are partitioned between the two states to accommodate total flow, and changes in tidal volume and end-expiratory pressure affect the number of airways in each state. Quantitative predictions for whole lung resistance and elastance agree with data from previously published studies on lung impedance.

Relationship between airway narrowing, patchy ventilation and lung mechanics in asthmatics

“…This network model is predictive of the formation of the VDefs and change in airway diameter as a result of dynamic interactions among different airways of the tree unlike the 3-D airway tree model, which is not predictive of the formation of the VDefs, and requires airway diameters and the location of ventilation defects as inputs. More specifically, the network model incorporated the effects of tidal stretch on smooth muscle [21,22], the interdependence between airway wall and parenchymal forces [23,24] and the interdependent behaviour between airways within a branching tracheobronchial tree [25]. This model was assumed to be virtually symmetrical and with uniform structural and functional properties to demonstrate that heterogeneity in those properties was not a requirement to develop the heterogeneity in constriction observed in asthma.…”

Airway Bistability Is Modulated by Smooth Muscle Dynamics and Length-Tension Characteristics

“…There are arguably two key analyses of static airway bistability: those of Anafi and Wilson (2,3), and Affonce and Lutchen (1). Although the physiological motivations differ in important ways, in both cases the crux of the analysis is a balance between the constricting force of ASM, and the restoring forces of the airway wall (and parenchymal tethering).…”

“…There are several distinct, yet related, ideas: static bistability, either in an isolated airway (1) or in a terminal airway unit with coupled parenchymal tethering (2); dynamic coupling of the airway with airway smooth muscle (3)(4)(5); and mechanisms by which spatial organization of airway closure or near closure may lead to clustered ventilation defects (6,7). All are interrelated, but as of yet there is no integrated synthesis of all three mechanisms.…”

Mechanotransduction, asthma and airway smooth muscle

“…1. To arrive at a mathematical expression that relates the airway diameter to these forces, we follow the approach suggested by Lambert et al [19], Anafi and Wilson [20] and Latourelle et al [21], and construct a so-called free-body diagram of the airway. To do so, the airway is imagined to be cut lengthwise (see Fig.…”

“…During expiration, a positive feedback cycle leading to flow limitation and airway instability can arise in the following way: if the P lumen − P alv pressure difference becomes sufficiently negative, it can lead to a decrease in airway diameter, a subsequent increase in airway resistance and an even more negative P lumen − P alv pressure [20,22,23]. Anafi and Wilson modeled this interdependence between airway resistance, gas flow, and transmural gas pressure difference by a set of simple linear equations [20]. The most important finding of their work was to demonstrate that the transmural gas pressure difference and hence the mechanical load of an airway is not at all static but rather highly dynamic and history dependent.…”