Aerosol mechanics in replicas of extrathoracic airways of infants and children

儿童吸入气溶胶的沉积越来越引起人们的兴趣，部分原因是用于治疗疾病的气溶胶吸入疗法取得了进展，但也由于越来越多的城市人口日益认识到接触环境气溶胶对健康的影响。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，有必要首先预测在胸外区域（包括鼻子、嘴和喉咙）沉积的气雾剂的量。不幸的是，很少有儿童数据可用于为此目的开发经过验证的数学模型，主要是因为缺乏作为这些模型基础的数据。为了解决这一问题，在目前的应用中，我们建议建立儿童胸外气道的物理复制品，然后在这些台式复制品中测量单分散气溶胶沉积。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发展无量纲相关性，可以很准确地预测个体受试者的胸外沉积。我们建议为儿童开发类似的特定学科相关性。这项工作的结果将是代数无量纲方程，可用于预测，先验，胸部外剂量的个别儿童。除此之外，我们建议开发理想的儿童气道物理模型，可用于开发药用气雾剂的台式测试。我们在成人中进行的类似工作已经产生了理想的口喉几何形状，广泛用于设备和配方开发的公司。

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.