An in silico study examining the role of airway smooth muscle dynamics and airway compliance on the rate of airway re-narrowing after deep inspiration.

Abstract

Deep inspirations are a widely studied topic due to their varied effectiveness as a bronchodilator in asthmatic and non-asthmatic patients. Specifically, they are known to be effective at reversing bronchoconstriction in non-asthmatic patients but may fail to prevent bronchoconstriction in asthmatic patients. Inspired by a recent study on the effect of deep inspirations on the rate of re-narrowing of an isolated airway, we investigate whether the latch-bridge dynamics of smooth muscle cross-bridge theory, coupled with non-linear compliance of the airway wall, can account for the reported results: namely that only the rate of renarrowing after DI is sensitive to the interval between deep inspirations, while other measures are unaffected. We develop and present length- and pressure-controlled protocols which mimic both the experiments performed in the study, as well as simulate in vivo conditions respectively. Both protocols are simulated and show qualitative agreement with the results reported by the experiments, suggesting that latch-bridge dynamics coupled with airway wall non-compliance may be sufficient to explain these results. Moreover pressure- and length-controlled protocols show important differences which should be considered when designing in vitro experiments to mimic in vivo conditions.