Modeling of Aerosol Transport in Alveolated Airways

肺泡气道中气溶胶传输的建模

• 批准号: 6914718
• 负责人: CHANTAL DARQUENNE
• 金额: $ 25.69万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6914718
• 关键词: acinar cell; aerosols; air pollution; disease /disorder model; environmental exposure; lung; model design /development; particle; pulmonary respiration; sedimentation velocity; suspensions

DESCRIPTION (provided by applicant): The long-term objective of this study is to better understand the fate of inhaled particulate matter (PM) in the human lung. This is important whether PM exposure results from atmospheric pollution, biological warfare, and occupational factors or inhaled drug therapy. More and more evidence links the presence of fine PM in the air with cardiopulmonary diseases. This PM is of great concern because it can penetrate deep into the acinus. To date, the most realistic model of the human acinus consists of a multi-bifurcation structure of two-dimensional alveolated ducts (AD). In the present study we will develop three-dimensional acinar models of children and adult lung with a high degree of anatomical realism. A first type of model will consist of a single bifurcation of AD with rigid walls. A second type of model will address the effects of alveolar wall motions during breathing and will form a realistic structure of up to four successive bifurcations. This will be the most comprehensive acinar models yet developed. PM transport and deposition (DE) will be simulated for particle diameters (dp) ranging 0.005-5 (m and for flow rates ranging from quiet breathing to moderate exercise. For 0.5<dp<5 (m, DE is mainly due to gravitational sedimentation and is mainly affected by the structure orientation with respect to the gravity vector. For dp < 0.5 (m, DE is mainly due to Brownian diffusion and is affected by the alveolar surface available to PM to deposit. The contribution of velocity profiles, rhythmical motions of the alveolar walls and PM intrinsic motions to overall convective mixing will be determined. Convective mixing causes inhaled PM to be irreversibly transferred to the resident air. As a result, some PM remains in suspension in the distal airways at the end of a normal expiration and penetrates deeper in the lung during the next breath where it eventually deposits. The process of stretch and fold where, because of non-reversibility of flow in the lung, air streamlines become folded back on themselves, will also be simulated to determine whether it is responsible for additional mixing in the acinus, and consequently for higher DE than that previously predicted. Finally the numerical predictions will be compared to experimental data obtained in human subjects and in simple physical models. The results of this study will provide a link to the mechanisms by which even seemingly modest PM exposure can cause or exacerbate lung disease and will also help to better design spatial targeting of inhaled drugs.

描述（由申请人提供）：本研究的长期目标是更好地了解吸入颗粒物（PM）在人肺中的归宿。无论 PM 暴露是由大气污染、生物战、职业因素还是吸入药物治疗引起，这一点都很重要。越来越多的证据表明空气中细颗粒物的存在与心肺疾病有关。这种 PM 非常值得关注，因为它可以深入腺泡。迄今为止，最真实的人类腺泡模型由二维腺泡管（AD）的多分叉结构组成。在本研究中，我们将开发具有高度解剖真实性的儿童和成人肺部三维腺泡模型。第一种类型的模型将由具有刚性墙的 AD 的单个分叉组成。第二种类型的模型将解决呼吸过程中肺泡壁运动的影响，并将形成最多四个连续分叉的真实结构。这将是迄今为止开发的最全面的腺泡模型。 PM 输送和沉积 (DE) 将模拟粒径 (dp) 范围为 0.005-5 (m) 以及从安静呼吸到适度运动的流速。对于 0.5<dp<5 (m)，DE 主要是由于重力沉降主要受相对于重力矢量的结构方向的影响，对于 dp < 0.5 (m)，DE 主要是由于布朗扩散，并受到可用于 PM 沉积的肺泡表面的影响。将确定速度分布、肺泡壁的节律运动和 PM 固有运动对整体对流混合的贡献。对流混合导致吸入的 PM 不可逆地转移到驻留空气中，因此，一些 PM 仍悬浮在远端气道中。在正常呼气结束时，在下一次呼吸时深入肺部，最终沉积在拉伸和折叠的过程中，由于肺部流动的不可逆性，空气流线会折叠回去。它们本身也将被模拟，以确定它是否负责腺泡中的额外混合，从而导致比先前预测的更高的 DE。最后，数值预测将与在人类受试者和简单物理模型中获得的实验数据进行比较。这项研究的结果将提供一个机制的联系，即使是看似适度的PM暴露也会导致或加剧肺部疾病，并且还将有助于更好地设计吸入药物的空间靶向。