Stability of Pullmonary Airways

肺气道的稳定性

• 批准号: 7293114
• 负责人: JAMES Bernard GROTBERG
• 金额: $ 36.38万
• 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/7293114
• 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; Closure; Complex; Condition; Congestive Heart Failure; Couples; Critical Illness; Cystic Fibrosis; Decongestants; Dependence; Development; Disease; Doctor of Philosophy; Effectiveness; Effectiveness of Interventions; 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; Numbers; Outcome; Patients; Personal Satisfaction; Pharmaceutical Preparations; Physiology; Population; Prevalence; Process; Property; Pulmonary Emphysema; Pulmonary function tests; Rate; 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; interfacial; lung pressure; lung volume; mathematical model; mortality; novel; 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)：这份修订后的提案旨在开发一个用于肺气道稳定性的数学模型，这是对健康、疾病及其治疗方法改变肺的呼吸道闭合机制的基本探讨。关闭的原因是表面张力不稳定，在适当的条件下，这种不稳定往往会将气道拉到较小的直径，同时可能会推动液体衬里形成塞子。塞子堵塞管腔，阻止气体交换和气雾剂药物的输送。例如，它可以是哮喘发作的晚期事件。从纯粹的流体力学角度来看，塞子的形成与否取决于液体的物理性质。疾病(哮喘、肺气肿、囊性纤维化)中显著的非牛顿流体特性包括粘弹性、剪切变稀粘度和屈服应力，所有这些都可以改变液体的运动。气液界面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。发生闭合时的肺体积就是闭合体积，这是一种常见的肺功能测试，通常很难解释，主要是因为模型不够充分。这种表面张力/流体系统与呼吸道和肺的弹性特性相结合。这一修订的新内容包括非线性气道弹性、气道平滑肌动力学和周围实质系留的影响。这种新颖的效应组合将允许开发一种理论，该理论可以结合哮喘和肺气肿等疾病提出的同时问题，其中支气管收缩、实质组织弹性变化和流体特性改变(非牛顿流体)共同作用呈现复杂的机械状况；所提出的模型将提供一个平台，用于预测这些相互作用对关闭体积的影响，以及预测治疗的有效性，其中可能包括针对表面活性物质、液体材料特性、或支气管收缩或实质的治疗。这一建议概述了一套数学模型，从最简单到最复杂地建立，检查液体衬里气道的稳定性，因为它取决于(1)牛顿流体和非牛顿流体，(2)具有实质和平滑肌张力的刚性管道和软管，(3)轴对称和非轴对称变形，(4)表面活性剂的影响，(5)强迫的、振荡的核心流动的影响。