Aerosol mechanics in replicas of extrathoracic airways of infants and children

儿童吸入气溶胶的沉积越来越受到关注，部分原因是用于治疗疾病的气溶胶吸入疗法的进步，但也是由于越来越多的城市人口对暴露于环境气溶胶的健康影响的认识提高。为了预测吸入药物气雾剂的功效或评估环境气雾剂的吸入剂量学，必须首先预测沉积在胸外区域（包括鼻或口和喉）中的气雾剂的量。不幸的是，很少有数据可用于儿童开发验证数学模型，主要是因为缺乏数据的基础上，这样的模型。为了解决这种知识的缺乏，在本申请中，我们提出建立小儿胸外气道的物理复制品，然后测量这些台式复制品中的单分散气溶胶沉积。数值模拟（计算流体动力学）将用于补充实验工作。我们在成人中进行的类似实验和计算工作允许开发无量纲相关性，预测个体受试者的胸外沉积具有良好的准确性。我们建议为儿童开发类似的特定主题的相关性。这项工作的结果将是代数无量纲方程，可用于预测，先验，个别儿童的胸外剂量。除上述内容外，我们建议开发儿科气道的理想化物理模型，可用于开发药物气雾剂的实验室测试。我们在成人中进行的类似工作产生了理想化的口腔-咽喉几何形状，该几何形状被公司广泛用于器械和制剂开发。

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.