Multiscale Study of the Respiratory Airway Mechanics for Cellular Inflammation

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Cellular inflammatory responses in respiratory airways during mechanical ventilation is a complex process dealings airway pressures/strains and cellular tissue compliance at multiple length scales. In order to gain understanding of this complex inflammation process and to aid in experiments, building computational simulations is necessary and may lead to a paradigm shift in mechanical ventilation for patients with respiratory failures. The overall goal of the proposed research is to develop a multi-scale model of cellular inflammation in compliant lung geometry during mechanical ventilation. The specific research objectives are: (i) Development of an organ level model based on continuum description for studying the behaviors of the respiratory airway; (ii) Development of a tissue level model based on continuum description for studying the stress/strain behaviors of the airway tissue; and (iii) Development of a cellular level model based on discrete system for studying the behaviors of the cellular inflammation. Results of these computational simulations at multiple levels will be used to develop correlations that will be capable of testing the outcomes of various mechanical ventilation strategies with respect to airway pressures and stress parameters to minimize the potential for damage to the lung.The intellectual merit of the proposed research come from integrating discrete cellular models of tissue inflammation with continuum description of tissue and organ level models to capture the complex pressures/stresses and cellular inflammation parameters in lung geometry due to mechanical ventilation. Besides developing models to understand the mechanical ventilation effects, the research results will provide new computational simulation models of the airway (fluid-solid interactions) and a rule based inflammation model at a cellular level which might help further to assess optimal characteristics for lung stresses and cellular inflammation parameters while minimizing the potential for damage to the lung tissue. The broad impact of this proposed research stems from the development of multi-scale computational models which will advance our knowledge on mechanical ventilation strategies to avoid lung related injuries in patients. The proposed research pioneers the beginning of a new approach to mechanical ventilation by combining advances in engineering simulation techniques with clinical applications. The benefits to society may include repairing lung injury in patients with respiratory failures resulting from multiple sources. If successful, this project will open a venue for patient specific computational simulations to avoid respiratory failures both in children and adults. The research results will be integrated into PI's educational activities and explore outreach activities with middle school and high school students through programs such as Richmond?s ?QUESTERS? program, and YMCA Metro Teens at VCU. Dissemination will be through journal and conference publications along with a website for carrying out virtual simulations of respiratory failures and strategies to avoid them.