Multiscale Study of the Respiratory Airway Mechanics for Cellular Inflammation

细胞炎症呼吸气道力学的多尺度研究

• 批准号: 1430379
• 负责人: Ramana Pidaparti
• 金额: $ 25.74万
• 依托单位: University of Georgia Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-03 至 2016-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1430379&HistoricalAwards=false
• 关键词: Multiscale; Study; Respiratory; Airway; Mechanics

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 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 research comes 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 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 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.

在机械通气期间呼吸道中的细胞炎症反应是在多个长度尺度上处理气道压力/应变和细胞组织顺应性的复杂过程。为了了解这种复杂的炎症过程并帮助实验，建立计算模拟是必要的，并可能导致呼吸衰竭患者机械通气的范式转变。本研究的总体目标是建立一个多尺度的机械通气过程中顺应性肺几何结构中细胞炎症的模型。具体的研究目标是：（i）开发基于连续描述的器官水平模型，用于研究呼吸道的行为;（ii）开发基于连续描述的组织水平模型，用于研究气道组织的应力/应变行为;以及（iii）开发基于离散系统的细胞水平模型，用于研究细胞炎症的行为。这些多层次的计算模拟结果将用于开发相关性，这些相关性将能够测试各种机械通气策略与气道压力和应力参数的结果，以最大限度地减少对肺部的潜在损伤。该研究的智力价值来自于将组织炎症的离散细胞模型与组织和器官水平模型的连续描述相结合，以捕获机械通气导致的肺几何结构中的复杂压力/应力和细胞炎症参数。除了开发模型来了解机械通气的影响，研究结果还将提供新的气道计算模拟模型（流体-固体相互作用）和基于规则的细胞水平炎症模型，这可能有助于进一步评估肺应力和细胞炎症参数的最佳特征，同时最大限度地减少对肺组织的损伤。这项研究的广泛影响源于多尺度计算模型的发展，这将促进我们对机械通气策略的了解，以避免患者的肺相关损伤。该研究通过将工程模拟技术的进步与临床应用相结合，开创了机械通气的新方法。对社会的益处可能包括修复由多种来源引起的呼吸衰竭患者的肺损伤。如果成功，该项目将为患者特定的计算模拟打开一个场所，以避免儿童和成人的呼吸衰竭。研究成果将被整合到PI的教育活动中，并通过里士满？的“探索者”计划，和基督教青年会地铁青少年在VCU。将通过期刊和会议出版物以及一个网站进行传播，该网站沿着，用于进行呼吸衰竭的虚拟模拟以及避免呼吸衰竭的策略。