Aerosol mechanics in replicas of extrathoracic airways of infants and children

儿童吸入性气雾剂的沉积越来越引起人们的兴趣，部分原因是治疗疾病的气雾剂吸入疗法的进步，但也是因为越来越多的城市人口对暴露于环境气雾剂的健康影响的认识不断提高。为了预测吸入药物气雾剂的疗效或评估环境气雾剂的吸入剂量学，有必要首先预测胸外区域(包括鼻子、口腔和喉咙)的气雾剂沉降量。不幸的是，在儿童中很少有数据可以为此目的开发经过验证的数学模型，这主要是因为缺乏数据来作为此类模型的基础。为了解决这种缺乏知识的问题，在目前的应用中，我们建议建立儿科胸外呼吸道的物理复制品，然后测量这些台面复制品中单分散的气溶胶沉积。数值模拟(计算流体力学)将被用来补充实验工作。我们在成人身上做的类似的实验和计算工作使无因次相关性的发展能够很好地准确地预测个体受试者的胸外沉积。我们建议为儿童建立类似的特定科目的相关性。这项工作的结果将是代数无量纲方程，可以用来先验地预测个别儿童的胸外剂量。此外，我们还建议开发理想化的儿科呼吸道物理模型，用于药物气雾剂开发的台式测试。我们在成人身上所做的类似工作已经产生了一种理想化的口喉几何形状，该几何形状被公司广泛用于设备和配方开发。

Deposition of inhaled aerosols in children is of increasing interest, partly due to advances in aerosol inhalation therapy for treating disease, but also due to increased awareness of the health effects of exposure to environmental aerosols in an increasingly urban population. In order to predict the efficacy of an inhaled pharmaceutical aerosol or to assess inhalation dosimetry of an environmental aerosol, it is necessary to first predict the amount of aerosol depositing in the extrathoracic region (consisting of the nose, or mouth, and throat). Unfortunately, little data is available in children to develop validated mathematical models for this purpose, largely because of a lack of data on which to base such models. To address this lack of knowledge, in the present application we propose to build physical replicas of pediatric extrathoracic airways and then measure monodisperse aerosol deposition in these bench-top replicas. Numerical simulation (computational fluid dynamics) will be used to supplement the experimental work. Similar experimental and computational work done by us in adults allowed development of dimensionless correlations that predict extrathoracic deposition in individual subjects with good accuracy. We propose to develop similar subject-specific correlations for children. The result of this work will be algebraic dimensionless equations that can be used to predict, a priori, extrathoracic doses to individual children. In addition to the above, we propose to develop idealized physical models of pediatric airways that can be used in bench-top testing for the development of pharmaceutical aerosols. Similar work by us in adults has resulted in an idealized mouth-throat geometry that is widely used by companies in device and formulation development.