Numerical Simulation of the Effect of Smooth Muscle Layer Thickening on Stress Distribution in the Airway Wall

Abstract

Many chronic respiratory diseases are associated with airway remodeling such as hyperplasia and/or hypertrophy of the smooth muscle cells. It is well known that the hyperplasia and hypertrophy of the smooth muscle cells directly affects the mechanical properties of the smooth muscle layer. Consequently, it may cause uneven distribution of stress and thus local stress stimulation of the cells and tissues in the airway wall, possibly leading to pathogenesis of airway dysfunction such as airway hyperresponsiveness. However, it is difficult to experimentally study the effect of smooth muscle layer on stress distribution in the airway wall. Therefore, in the present work, we built a finite element model which simplified the anatomical structure of the airway wall as a three-layer structure that included an inner wall layer, a smooth muscle layer and an adventitia layer. Based on this model, we varied the smooth muscle layer thickness either uniformly or locally and then computed the stress distribution in the modeled airway wall. The results revealed that the minimum stress occurred in the adventitia layer, and the maximum stress occurred in the smooth muscle layer. More importantly, the smooth muscle layer thickening, occurred either uniformly or locally, led to elevated stress level and enhanced stress concentration in the smooth muscle layer. And the enhancement of stress level and concentration was variable depending on the pattern of smooth muscle layer thickening. For a given extent of smooth muscle layer thickening, the stress level and concentration appeared to be determined by the number of locations and the separation distance between the locations at which the smooth muscle layer thickening occurred. In other words, the maximum stress level in the smooth muscle layer increased from 2.712kPa to 2.842KPa depending on whether the local thickening occurred at one location, 3 or 5 equally separated locations, 2 connected and 1 distanced location, or 3 all connected locations. These simulation results provide important insight for better understanding the mechanism through which the airway smooth muscle is involved in the alteration of airway dysfunction in health and disease, which may be helpful in developing novel diagnosis/therapy via targeting smooth muscle hyperplasia and/or hypertrophy for the prevention/treatment of asthma.