Stability of Pullmonary Airways

描述（由申请人提供）：本修订提案旨在建立一个肺气道稳定性的数学模型，是对健康、疾病和治疗中导致肺气道关闭的机制的基本探讨。在适当的条件下，由于表面张力不稳定，气道会被拉到更小的直径，同时可能导致液体衬里形成堵塞物。一个塞堵塞了腔，阻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。从纯粹的流体力学角度来看，堵塞可能形成也可能不形成，这取决于液体的物理性质。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、剪切变薄粘度和屈服应力，所有这些都可以改变流体运动。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。肺闭合时的肺体积是闭合体积，这是一种常见的肺功能测试，通常难以解释，主要是由于模型不完善。这种表面张力/流体系统与气道和肺的弹性特性耦合。本次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栓系的影响。这种新的效应组合将允许发展一种理论，该理论可以结合哮喘和肺气肿等疾病同时提出的问题，其中支气管收缩，实质组织弹性变化和流体性质改变（非牛顿流体）共同作用，呈现复杂的机械情况；所提出的模型将为预测这些相互作用对闭合体积的影响提供一个平台，以及预测治疗的有效性，这些治疗可能包括针对表面活性剂、液体材料特性、支气管收缩或实质的治疗。本建议概述了一组数学模型，从最简单的到更复杂的，这些模型检查了液体衬里气道管的稳定性，因为它取决于(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)轴对称与非轴对称变形，(4)表面活性剂的影响，(5)强制振荡核心流的影响。

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.