Stability of Pullmonary Airways

肺气道的稳定性

• 批准号: 7644955
• 负责人: JAMES Bernard GROTBERG
• 金额: $ 37.08万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7644955
• 关键词: Adult; Adult Respiratory Distress Syndrome; Aerosols; Air; Alveolus; Antihistamines; Area; Asthma; Astronauts; Automobile Driving; Behavior; Breathing; Bronchoconstriction; Bronchodilation; Bronchodilator Agents; Caliber; Characteristics; Childhood; Childhood Asthma; Clinical; Closing Volume; Complex; Congestive Heart Failure; Couples; Critical Illness; Cystic Fibrosis; Decongestants; Dependence; Development; Disease; Doctor of Philosophy; Effectiveness; Elasticity; Elements; Event; Expectorants; Film; Gases; Health; Intervention; Laws; Lead; Life; Liquid substance; Lubrication; Lung; Mechanics; Microgravity; Modeling; Modification; Movement; Mucous body substance; Muscle Tonus; Neonatal; Outcome; Patients; Pharmaceutical Preparations; Physiology; Prevalence; Process; Property; Pulmonary Emphysema; Pulmonary function tests; Research Personnel; Respiratory physiology; Risk; Rupture; Scheme; Shapes; Smooth Muscle; Staging; Steam; Stress; Surface Tension; System; Testing; Thick; Tissues; Trees; Tube; Ventilator; Viscosity; Work; clinically relevant; flexibility; interfacial; intervention effect; lung pressure; lung volume; mathematical model; mortality; novel; patient population; physical property; planetary Atmosphere; pressure; respiratory smooth muscle; surfactant; surfactant deficiency; theories; viscoelasticity

DESCRIPTION (provided by applicant): This revised proposal to develop a mathematical model for the stability of pulmonary airways is a basic inquiry into the mechanisms that lead to airway closure of the lung in health, disease, and its modifications by therapies. Closure results from a surface tension instability that tends to pull the airway to a smaller diameter while potentially driving the liquid lining into the formation of a plug, given the right conditions. A plug blocks the lumen, stopping gas exchange and delivery of aerosol medications. It can be the terminal event in an asthmatic attack, for example. From purely the fluid mechanical perspective, the plug may or may not form depending on the liquid physical properties. Significant non-Newtonian fluid properties in disease (asthma, emphysema, cystic fibrosis) include viscoelasticity, shear-thinning viscosity, and a yield stress, all of which can alter the fluid movement. Surfactants at the air-liquid interface also influence the instability by reducing surface tension and creating surface tension gradients. The lung volume at which closure occurs is the closing volume, and it is a common pulmonary function test that is often difficult to interpret, due largely to inadequate models. This surface-tension/fluid system couples to the airway and lung elastic properties. New to this revision is the inclusion of non-linear airway elasticity, airway smooth muscle dynamics, and effects of a surrounding parenchymal tethering. This novel combination of effects will allow the development of a theory which can incorporate the simultaneous issues presented by diseases such as asthma and emphysema where bronchoconstriction, parenchymal tissue elasticity changes, and fluid property modifications (non-Newtonian fluids) acting together present a complex mechanical situation; The proposed model will provide a platform for predicting the impact of these interactions on closing volumes, as well as predict the effectiveness of therapies which may include those aimed at surfactants, or liquid material properties, or bronchoconstriction or the parenchyma. This proposal outlines a set of mathematical models, building from the simplest to the more complex, that examine the stability of a liquid-lined airway tube as it depends on (1) Newtonian vs non-Newtonian fluids, (2) rigid vs flexible tubes with parenchyma and smooth muscle tone, (3) axisymmetric vs non-axisymmetric deformations, (4) effects of surfactants, (5) effects of a forced, oscillatory core flow.

描述（由申请人提供）：本修订提案旨在开发肺气道稳定性的数学模型，是对导致健康、疾病状态下肺气道闭合的机制及其治疗改变的基本探究。封闭是由表面张力不稳定引起的，在适当的条件下，表面张力不稳定往往会将气道拉到较小的直径，同时可能会促使液体衬里形成堵塞。一个塞子阻塞了管腔，停止了气体交换和气雾剂药物的输送。例如，它可能是哮喘发作的终末事件。从纯粹的流体力学观点来看，取决于液体的物理性质，可以形成或不形成栓塞。疾病（哮喘、肺气肿、囊性纤维化）中重要的非牛顿流体性质包括粘弹性、剪切稀化粘度和屈服应力，所有这些都可以改变流体运动。空气-液体界面处的表面活性剂也通过降低表面张力和产生表面张力梯度来影响不稳定性。发生闭合的肺体积是闭合体积，并且它是通常难以解释的常见肺功能测试，这主要是由于模型不足。该表面张力/流体系统耦合到气道和肺弹性特性。新的修订是纳入非线性气道弹性，气道平滑肌动力学，和周围的实质栓系的影响。这种新的效应组合将允许一种理论的发展，该理论可以结合由诸如哮喘和肺气肿等疾病同时提出的问题，其中支气管收缩、实质组织弹性改变和流体性质改变（非牛顿流体）共同作用呈现复杂的力学情形;所提出的模型将提供一个平台，用于预测这些相互作用对闭合体积的影响，以及预测治疗的有效性，其中可能包括针对表面活性剂的治疗，或液体物质性质，或支气管收缩或实质。该提案概述了一组数学模型，从最简单到更复杂地构建，其检查液体衬里的气道导管的稳定性，因为其取决于（1）牛顿流体与非牛顿流体，（2）具有实质和平滑肌张力的刚性管与柔性管，（3）轴对称变形与非轴对称变形，（4）表面活性剂的影响，（5）强制的影响，振荡核心流