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Fluid flow and particle dispersion in lung acini.

机译：肺痤疮中的流体流动和颗粒分散。

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The acinar region of the human lung comprises about 300 million alveoli which are the smallest units of the lung and are responsible for gas exchange between the lung and the blood. The ability of the alveoli to exchange gas is often compromised by the deposition of harmful inhaled particulate matter on the alveolar wall. At the same time, the alveoli can also be exploited as effective delivery sites for inhaled therapeutic aerosols for local and systemic ailments.;In healthy lungs, the expansion/contraction of the alveolar cavity during each breathing cycle is typically synchronized with the oscillating fluid flow in the bronchiole and is known as synchronous ventilation. Synchronous ventilation can be compromised by a variety of lung ailments such as chronic bronchitis or emphysema leading to a condition known as asynchronous ventilation. Although gas transport is governed primarily by diffusion due to the small length scales associated with the acinar region (∼500 mum), the transport and deposition of inhaled aerosol particles is influenced by convective airflow patterns. Therefore, understanding alveolar fluid flow and mixing is a necessary first step towards predicting aerosol transport and deposition in the human acinar region.;In the current work, acinar airflow patterns were measured using a simplified in-vitro alveolar model consisting of a single alveolus located on a bronchiole. The model comprised a transparent elastic 5/6th spherical cap (representing the alveolus) mounted over a circular hole on the side of a rigid circular tube (representing the bronchiole). Our model alveolus is capable of expanding and contracting in-phase and out-of-phase with the oscillatory flow through the tube thereby simulating synchronous and asynchronous ventilation, respectively. Realistic breathing conditions were achieved by exercising the model at physiologically relevant Reynolds and Womersley numbers. Particle image velocimetry was used to measure the resulting flow patterns. The particle maps were used to calculate the transport and deposition statistics of massless and finite-size particles under the influence of flow advection and/or gravity. Velocity measurements and particle transport calculations were divided into three categories.;First, we focused on synchronous ventilation wherein the experimental conditions were matched with tidal breathing in healthy humans. Our results show that the alveolar wall motion enhances mixing between the bronchiole and alveolar fluid and increases particle transport and deposition on the alveolar wall for all particle sizes. Furthermore, particles ≤ 0.25 mum follow the fluid streamlines quite closely whereas particles ≥ 1 mum cross streamlines and exhibit complex trajectories due to the cumulative effect of flow advection and gravity.;Next, we measured flow patterns and calculated particle trajectories for asynchronous ventilation which is typical of diseased lungs. A range of realistic phase lags between the bronchiole flow oscillation and the alveolar wall oscillation was considered. Particle trajectories were calculated over multiple breathing cycles for massless and finite-size particles of diameter = 1.5 mum. The asynchronous ventilation results show that fluid mixing and particle deposition display a non-monotonic behavior as the phase lag is increased from 0 to pi/2; fluid mixing and particle deposition are lowest for 11pi/90 and highest for pi/2.;Finally, we characterized flow patterns and particle trajectories for a range of physiologically relevant dimensionless parameters and particle size for the case of synchronous ventilation. Our study shows that particles smaller than 0.25 micron follow fluid streamlines without deviation, particles in the range 0.25 mum ≤ dp ≤ 3 mum are transported under the combined influence of convection and gravity, and particles larger than 3 micron sediment rapidly due to gravity. Our parametric study shows that the geometric parameters (beta and DeltaV/V) primarily affect the velocity magnitudes, and the dynamic parameters (Re and alpha) distort the flow symmetry in addition to altering the velocity magnitudes. The particle trajectories also display a greater influence of dynamic parameters compared to geometric parameters.;Overall, this work can benefit the research community engaged in the risk assessment of toxicological inhaled aerosols, as well as the pharmaceutical industry, by providing improved insight and understanding of flow patterns and particle transport in the acini. Specifically, the asynchronous ventilation results can contribute to the design of pharmaceutical aerosols with the optimal characteristics and the associated pulmonary drug delivery protocols.
机译：人肺的腺泡区域包含约3亿个肺泡，这些肺泡是肺的最小单位，负责肺与血液之间的气体交换。肺泡交换气体的能力通常因有害的吸入颗粒物在肺泡壁上的沉积而受到损害。同时，肺泡还可以作为局部和全身疾病的吸入性治疗性气雾剂的有效递送部位。；在健康的肺中，每个呼吸周期内肺泡腔的扩张/收缩通常与振荡液流同步在细支气管中被称为同步通气。各种慢性疾病如慢性支气管炎或肺气肿会导致同步通气受损，从而导致称为异步通气的疾病。尽管由于与腺泡区域相关的小尺度（约500微米），气体的传输主要受扩散控制，但​​吸入的气溶胶颗粒的传输和沉积受对流气流模式的影响。因此，了解肺泡液的流动和混合是预测人类腺泡区域内气溶胶运输和沉积的必要第一步。;在当前工作中，使用简化的体外肺泡模型测量了腺泡的气流模式，该模型由单个肺泡组成在细支气管上该模型包括一个透明的弹性5/6球形帽（代表肺泡），该帽安装在刚性圆形管（代表细支气管）一侧的圆孔上。我们的模型肺泡能够通过管内的振荡流同相和异相膨胀和收缩，从而分别模拟同步和异步通气。通过在生理上相关的雷诺数和沃默斯利数下锻炼模型，可以实现现实的呼吸条件。粒子图像测速仪用于测量所得的流型。粒子图用于计算在流动对流和/或重力作用下无质量和有限尺寸粒子的传输和沉积统计数据。速度测量和颗粒迁移计算分为三类：首先，我们关注同步通气，其中实验条件与健康人的潮气匹配。我们的结果表明，对于所有粒径的肺泡壁运动，都可增强细支气管和肺泡液之间的混合，并增加颗粒在肺泡壁上的运输和沉积。此外，≤0.25 mum的颗粒非常接近流体流线，而≥1 mm的颗粒则由于流动对流和重力的累积作用而呈现出复杂的轨迹。典型的患病肺。考虑了细支气管流动振荡和肺泡壁振荡之间的实际相位滞后范围。对于直径= 1.5微米的无质量和有限尺寸粒子，在多个呼吸循环中计算了粒子轨迹。异步通风结果表明，当相位滞后从0增大到pi / 2时，流体混合和颗粒沉积表现出非单调性。流体混合和颗粒沉积在11pi / 90时最低，在pi / 2时最高。最后，在同步通气的情况下，我们针对一系列生理相关的无量纲参数和粒径对流型和颗粒轨迹进行了表征。我们的研究表明，小于0.25微米的颗粒遵循流体流线而无偏差，在对流和重力的共同作用下，0.25 um≤dp≤3微米范围内的颗粒得以运输，并且大于3微米的颗粒由于重力而迅速沉积。我们的参数研究表明，几何参数（β和DeltaV / V）主要影响速度幅度，而动态参数（Re和alpha）除了改变速度幅度之外，还会使流动对称性变形。与几何参数相比，粒子轨迹还显示了更大的动态参数影响。总体而言，这项工作可以通过提供对以下方面的更好的了解和理解，使从事毒理学吸入气雾剂风险评估的研究团体以及制药行业受益。 acini中的流动模式和颗粒传输。具体而言，异步通气结果可有助于设计具有最佳特性的药物气雾剂和相关的肺部药物输送方案。

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