In-Vitro Studies of Airway Wall Properties: the Effects of Dynamic Stress
The dynamic stress imposed on airways during typical breathing has been shown to have important and distinct effects on healthy versus asthmatic lungs. The effects of this dynamic stress on lung function have been studied on many different scales, ranging from lung function tests on healthy and asthmatic patients to measurements on isolated airway smooth muscle (ASM) before and after bronchoconstriction. Indeed, studies from isolated ASM suggest that reduced dynamic ASM length oscillations, as might occur in situ in asthmatics (because of airway inflammation), can serve to amplify the ASM contractile force. However, the intrinsic physiological responses to dynamic stress of the ASM in concert with the isolated airway itself have primarily been left unstudied. Examining airways in-vitro allows for their complex structure to be studied independent of the interactions of the lung. To date, in-vitro studies of airway segments have mainly focused on static airway wall properties, without considering the dynamic nature of breathing. In this project, we aim to investigate the effects of in-vivo-like breathing patterns on airway segments, before and after bronchoconstriction. The main focus is to understand how dynamic stress from different breathing patterns regulates the airway’s response to bronchoconstriction. Our long term goal is to connect mechanisms applicable to isolated airway systems to those which occur in situ, and then integrate these mechanisms over the entire airway tree. We hypothesize that dynamic stress, depending on its amplitude, can attenuate or enhance airway constriction by altering both the ASM contractile phenotype and the after-loads of the passive layers of the airway wall. It is this intrinsic airway response that is responsible for the effects of different breathing patterns seen in-vivo.