Modeling of Aerosol Transport in Alveolated Airways

肺泡气道中气溶胶传输的建模

• 批准号: 7385997
• 负责人: CHANTAL DARQUENNE
• 金额: $ 23.59万
• 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/7385997
• 关键词: Acinus organ component; Address; Adult; Adverse reactions; Aerosols; Affect; Age; Agreement; Air; Air Pollution; Airborne Particulate Matter; Alveolar; Alveolar Duct; Alveolar wall; Alveolus; Area; Back; Behavior; Biological Warfare; Breathing; Caliber; Characteristics; Child; Complex; Computer Simulation; Condition; Data; Deposition; Depth; Diffusion; Dimensions; Distal; Duct (organ) structure; Exposure to; Force of Gravity; Frequencies; Funding; Gases; Generations; Grant; Health; Heterogeneity; Hot Spot; Human; Lead; Left; Life; Link; Liquid substance; Location; Lung; Lung diseases; Measurement; Measures; Medical; Modeling; Moderate Exercise; Morbidity - disease rate; Motion; Occupational; Particle Size; Particulate Matter; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Physiological; Play; Pollution; Positioning Attribute; Principal Investigator; Process; Property; Pulmonary Heart Disease; Radial; Range; Rate; Relative (related person); Research; Role; Sedimentation process; Simulate; Space Perception; Spatial Design; Stretching; Structure; Study models; Surface; Suspension substance; Suspensions; Techniques; Testing; Thinking; Time; Validation; age effect; drug inhalation; expiration; human subject; mathematical model; mortality; particle; physical model; pollutant; programs; research study; scale up; three-dimensional modeling; two-dimensional; vector

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）在人体肺部的命运。无论PM暴露是由于大气污染、生物战、职业因素还是吸入药物治疗，这一点都很重要。越来越多的证据表明，空气中细小颗粒物的存在与心肺疾病有关。这种PM非常令人担忧，因为它可以深入到腺泡中。迄今为止，最真实的人类腺泡模型由二维肺泡管（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感的儿童和成人肺腺泡三维模型。第一种类型的模型将由带有刚性壁的单一AD分岔组成。第二种类型的模型将解决呼吸过程中肺泡壁运动的影响，并将形成一个多达四个连续分叉的现实结构。这将是迄今为止开发的最全面的腺泡模型。将模拟颗粒直径（dp）范围为0.005-5 (m)，流速范围为安静呼吸到适度运动的PM运输和沉积（DE）。对于0.5<dp<5 (m)， DE主要由重力沉降引起，且主要受相对于重力矢量的构造方位影响。当dp < 0.5 (m)时，DE主要由布朗扩散引起，并受PM可沉积的肺泡表面的影响。速度分布、肺泡壁的有节奏运动和PM固有运动对整体对流混合的贡献将被确定。对流混合使吸入的PM不可逆地转移到常驻空气中。因此，在正常呼气结束时，一些PM仍悬浮在远端气道中，并在下一次呼吸时深入肺部并最终沉积。拉伸和折叠的过程，由于肺内流动的不可逆性，空气流线被折叠起来，也将被模拟，以确定它是否负责在腺泡中额外的混合，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。这项研究的结果将为看似适度的PM暴露可能导致或加剧肺部疾病的机制提供联系，也将有助于更好地设计吸入药物的空间靶向。