The airway smooth muscle response to strain and the relationship with airway hyper-responsiveness

[Truncated abstract] Airway hyper-responsiveness (AHR, i.e. excessive bronchoconstriction to an inhaled bronchial challenge) is believed to be a major contributor to airflow limitation, a primary characteristic of asthma. The cause(s) of AHR remain unclear but likely involve abnormalities in airway smooth muscle (ASM) and/or airway wall structure/function. More recently, the dynamic mechanical environment of the lung has been identified as an important regulator of airway responsiveness and may be susceptible to inflammatory disease processes, contributing to AHR. In normal healthy individuals, deep inspiration (DI) produces a transient reversal of bronchoconstriction (i.e. bronchodilation). The underlying mechanism by which DI produces bronchodilation is thought to involve stretch-induced relaxation of ASM, due to perturbed cross-bridge binding and/or de-polymerisation of the contractile apparatus. However, the bronchodilatory response to DI is attenuated or abolished in patients with asthma and this may contribute to the development of AHR.
The general aim of this thesis is to better understand the ASM response to strain during breathing manoeuvres and the relationship with AHR.