Multiscale Modeling of Airway Inflammation Induced by Mechanical Ventilation

Abstract

MULTISCALE MODELING OF AIRWAY INFLAMMATION INDUCED BY MECHANICAL VENTILATION By Kittisak Koombua, M.S.M.E. A Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Engineering at Virginia Commonwealth University. Virginia Commonwealth University, 2009 Major Director: Ramana M. Pidaparti, Ph.D. Professor, Department of Mechanical Engineering Mechanical ventilation (MV) is a system that partially or fully assists patients whose respiratory system fails to achieve a gas exchange function. However, MV can cause a ventilator-associated lung injury (VALI) or even contribute to a multiple organ dysfunction syndrome (MODS) in acute respiratory distress syndrome (ARDS) patients. Despite advances in today technologies, mortality rates for ARDS patient are still high. A better understanding of the interactions between airflow from mechanical ventilator and xxi the airway could provide useful information used to develop a better strategy to ventilate patients. The mechanisms, which mechanical ventilation induces airway inflammation, are complex processes and cover a wide range of spatial scales. The multiscale model of the airway have been developed combining the computational models at organ, tissue, and cellular levels. A model at the organ level was used to study behaviors of the airway during mechanical ventilation. Strain distributions in each layer of the airway were investigated using a model at the tissue level. The cellular inflammatory responses during mechanical ventilation were investigated through the cellular automata (CA) model incorporating all biophysical processes during inflammatory responses. The multiscale modeling framework started by obtaining airway displacements from the organ-level model. They were then transferred to the tissue-level model for determining the strain distributions in each airway layer. The strain levels in each layer were then transferred to the cellular-level model for inflammatory responses due to strain levels. The ratio of the number of damage cells to healthy cells was obtained through the cellular-level model. This ratio, in turn, modulated changes in the Young’s modulus of elasticity at the tissue and organ levels. The simulation results showed that high tidal volume (1400 cc) during mechanical ventilation can cause tissue injury due to high concentration of activated immune cells and low tidal volume during mechanical ventilation (700 cc) can prevent tissue injury during mechanical ventilation and can mitigate tissue injury from the high tidal volume ventilation. The multiscale model developed in this research could provide useful xxii information about how mechanical ventilation contributes to airway inflammation so that a better strategy to ventilate patients can be developed.