Chaotic Mixing of Aerosol in Rhythmically Expanding Lung

性状（由申请方提供）：吸入颗粒物在诱发或加重呼吸道疾病方面起主要作用。腺泡区域具有极大的表面积和非常薄且脆弱的血液/气体屏障，特别容易受到沉积颗粒的破坏性影响。了解肺腺泡中毒性颗粒暴露相关过程以及通过气雾吸入进行靶向给药的重要步骤是表征沉积并阐明相关机制。在此之前，我们已经奠定了一个新的概念框架的基础，腺泡沉积的研究，通过建立理论和实验，与普遍持有的观点，腺泡气流可以是运动学上不可逆的，并通过显示，混乱的混合，表现为拉伸和折叠模式，可以是一个主要的贡献者气溶胶沉积。本项目建立在这些成果的基础上，旨在研究拉伸和折叠运动学的具体机制。我们的主要假设是，潮汐空气前锋演变成一个巨大的拉伸层吸入后，覆盖内表面的腺泡气道，从而使空气中的气溶胶非常接近肺泡隔表面，并促进其沉积。在呼气过程中，先前拉伸的层的折叠导致气溶胶的横向运输，也显著有助于沉积过程。这一新的假设将在三个特定的目标进行严格的测试：目标1解决了计算详细的机制，在腺泡结构的覆盖和折叠。目的2解析研究多分支结构中异步流引起的混沌混合、叠加和折叠。目的3实验性地解决了吸入的气溶胶团的行为与各种不同的解释性操作，以及可视化和量化的披盖和折叠的程度。这些实验将在正常大鼠和肺气肿大鼠模型中进行。我们的总体目标是确定，通过这些理论和实验研究相结合，由气流运动学在肺外周的独特结构的气溶胶沉积的重要机制，从而提高我们的了解暴露于雾化污染物的风险和有针对性的治疗药物输送的积极潜力。

DESCRIPTION (provided by applicant): Inhaled particles play a major role in inducing or exacerbating respiratory diseases. The acinar region, with its enormously large surface area and very thin and delicate blood/gas barrier, is particularly vulnerable to the damaging effects of depositing particles. An essential step in understanding toxic particle exposure associated processes in the pulmonary acinus, as well as targeted drug delivery by aerosol inhalation, is to characterize deposition and to elucidate the mechanisms involved. Previously we have laid the foundation of a new conceptual framework for acinar deposition studies by establishing theoretically and experimentally that, contrary to a commonly held view, acinar gas flow can be kinematically irreversible, and by showing that chaotic mixing, manifested by stretching and folding patterns, can be a major contributor to aerosol deposition. This proposed project builds on these achievements and aims to study the specific mechanisms of the stretch and fold kinematics. Our main hypothesis is that tidal air front evolves into an enormously stretched layer upon inhalation which drapes the inner surface of the acinar airways, thus bringing airborne aerosols very close to the alveolar septal surface and promoting their deposition. During exhalation, folding of the previously stretched layer leads to lateral transport of aerosols, also significantly contributing to the deposition process. This novel hypothesis will be rigorously tested in three specific aims: Aim 1 addresses computationally detailed mechanisms of draping and folding in the acinar structure. Aim 2 investigates analytically the chaotic mixing, draping and folding induced by asynchronous flows in multiply branching structures. Aim 3 addresses experimentally the behavior of an inhaled bolus of aerosol with various ventilatory maneuvers, as well as visualizing and quantifying the extent of draping and folding. These experiments will be performed in normal rats and in a rat model of emphysema. Our overall goal is to identify, through the combination of these theoretical and experimental studies, the important mechanisms of aerosol deposition governed by airflow kinematics in the unique structure of the lung periphery and thereby to advance our understanding of the risks of exposure to aerosolized pollutants and the positive potential of targeted therapeutic drug delivery.