Modeling of Aerosol Transport in Alveolated Airways

描述(申请人提供)：这项研究的长期目标是更好地了解可吸入颗粒物(PM)在人类肺部的命运。无论PM暴露是由大气污染、生物战和职业因素还是吸入性药物治疗引起的，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非常令人担忧，因为它可以深入腺泡。到目前为止，最逼真的人腺泡模型由二维肺泡管(AD)的多分支结构组成。在本研究中，我们将建立具有高度解剖真实感的儿童和成人肺的三维腺泡模型。第一种类型的模型将由带有刚性墙的AD的单个分支组成。第二种类型的模型将研究呼吸过程中肺泡壁运动的影响，并将形成一个最多四个连续分叉的真实结构。这将是迄今开发的最全面的研讨模型。PM的传输和沉积(DE)将被模拟为颗粒直径(DP)范围为0.005-5(M)和流速从安静的呼吸到适度运动的范围。对于0.5&lt；dp&lt；5(m，De主要是由于重力沉积作用，主要受构造相对于重力矢量的方位影响。对于Dp&lt；0.5(m，De主要是由于布朗扩散，受可供PM沉积的肺泡表面的影响。速度分布、肺泡壁的节律性运动和PM的本征运动对整体对流混合的贡献将被确定。对流混合导致吸入的PM不可逆地转移到居民空气中。因此，一些PM在正常呼气结束时仍悬浮在远端呼吸道，并在下一次呼吸中深入肺内，最终沉积。也将模拟拉伸和折叠的过程，其中由于肺内流动的不可逆性，空气流线变回折叠本身，以确定它是否对腺泡中的额外混合负责，从而导致比先前预测的更高的DE。最后，将数值预测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联系，即使是看似温和的PM暴露也会导致或加剧肺部疾病的机制，也将有助于更好地设计吸入性药物的空间靶向。

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.