Particles in Developing Lung: Bioengineering Approach

描述：(由申请人提供)：这个生物工程跨学科合作项目计划利用工程专业知识开发一系列工具，包括计算流体力学、颗粒技术的发展和动物模型中的生理学方法，用于对发育中的肺中颗粒沉积、滞留和清除途径的综合研究。在我们的社会中，没有比保护儿童健康更重要的当务之急了，然而，在评估与环境暴露气雾剂颗粒有关的健康风险时，新生儿、儿童和成人肺结构的具体差异尚未得到解决。儿童的肺部在出生后经历了显著的结构变化，例如肺泡的急剧增加，以及大小的增加。我们最近的研究清楚地表明，腺泡气道的结构对细颗粒的沉积有深刻的影响。因此，婴儿和幼儿的颗粒沉积、滞留和清除途径很可能与成人的显著不同。特别是，我们的初步数据表明，健康风险可能在出生后迅速上升，并在2至5年内达到顶峰。然而，人们对发育中肺部颗粒沉积的定性和定量方面知之甚少，主要是因为出于伦理和技术原因，临床研究或实验无法了解这些问题。我们建议：(1)建立计算流体力学方法并研究肺发育过程中结构变化对沉积的影响；(2)利用工程示踪颗粒开发最先进的高精度肺功能/吸入检测方法；以及(3)应用这一新方法来研究颗粒在出生后发育的大鼠动物模型中是如何沉积和保留的。这些拟议的研究将使我们第一次能够全面了解与肺发育相关的颗粒沉积-滞留的变化。这一知识对估计颗粒性空气污染造成的健康危害和确定气雾剂提供的治疗药物的适龄剂量具有重要意义。

DESCRIPTION: (provided by applicant): This bioengineering interdisciplinary partnership project plans to use engineering expertise to develop a combination of tools, including computational fluid mechanics, the development of particle technology, and physiological approaches in animal models, to be utilized in a comprehensive study on particle deposition, retention, and clearance pathways in the developing lung. There is no more important imperative in our society than to protect the health of children, yet the specific differences in pulmonary structure between newborn, children, and adult lungs have not been addressed in assessing health risks associated with environmental exposure to aerosol particulates. Children's lungs postnatally undergo remarkable structural changes, such as a dramatic increase in alveolation, in addition to an increase in size. Our recent studies clearly indicate that the structure of the acinar airways has a profound influence on fine particle deposition. It is, therefore, very likely that particle deposition, retention, and clearance pathways in infants and young children are significantly different from those in adults. In particular, our preliminary data suggest that health risks may rise rapidly postnatally and peak between 2 and 5 years. However, little is known about the qualitative and quantitative aspects of particle deposition in developing lungs, mostly because these questions are not accessible to clinical studies or experimentation for ethical and technical reasons. We propose: (1) to establish computational fluid mechanics methods and investigate the effects of structural changes during lung development on deposition; (2) to develop a state-of-the-art high precision lung function/inhalation detection methodology utilizing engineered tracer particles; and (3) to apply this new methodology to investigate how particles are deposited and retained in the postnatally developing rat animal model. These proposed studies will allow us, for the first time, to get a comprehensive picture of changes in particle deposition-retention associated with lung development. This knowledge has important implications for the estimation of health hazards posed by particulate air pollution and for the establishment of age-appropriate doses of therapeutic drugs delivered by aerosols.