Particles in Developing Lung: Bioengineering Approach

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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.