REGIONAL DEPOSITION OF INHALED PARTICLES

本研究的长期目标是：1）确定 人体呼吸道内的吸入颗粒; 2）表征 作为呼吸流量的函数的吸入颗粒的运输， 气道和空域大小; 3）在诊断协议中应用气溶胶， 吸入污染物对肺的早期影响 上皮细胞和/或鉴定可能对以下特别敏感的个体： 吸入化学物质 这里提出的研究将扩展我们过去和现在的工作， 在人体内的局部沉积分为：1）其在体内的应用 测量由单个和多个不同类型的飞机造成的 家兔每日重复暴露于吸入刺激物;和2） 比较气溶胶行为、沉积和对 吸入的香烟烟雾和其他刺激物在人类的肺部和 实验动物兔子 具体目标包括：1）确定气道分支的影响 和流型对单通道气道内颗粒分布的影响 2）扩展和改进气溶胶探针 用于有效检测和表征的早期变化的技术 人和实验室动物的气道形态; 3）确定 冷空气、SO2和 香烟烟雾对人和兔子气溶胶分散的影响;以及4） 确定肺气道早期形态学变化的影响 低水平慢性污染物暴露对气溶胶扩散的影响， 人类和动物的呼吸功能，以及它们的呼吸反应 关系。 气溶胶诊断测试将为以下方面提供强大的新工具：1） 在实验室动物中，检查参与 慢性肺部疾病的发病机制和进展;以及2）环境 流行病学，通过将吸入暴露与肺功能丧失联系起来 容量和/或气流分布的变化。 比较 人和动物的气溶胶沉积和刺激反应的研究 将加强动物模型的价值，研究机制， 污染物对肺上皮细胞的损伤，并作为一种有效的测试系统， 表征污染物、环境和宪法的影响 因素的反应。

The long-term objectives of this research are: 1) to define the fate of inhaled particles within the human respiratory tract; 2) to characterize the transport of inhaled particles as a function of respiratory flow and airway and airspace sizes; 3) to apply aerosols in diagnostic protocols for the identification of the early effects of inhaled pollutants on lung epithelia and/or to identify individuals who may be especially sensitive to inhaled chemicals. The research proposed here will extend our past and current work on regional deposition in humans into: 1) its application for the in vivo measurement of airway and airspace size changes resulting from single and repetitive daily exposures to inhaled irritants in the rabbit; and 2) studies of comparative aerosol behavior, deposition and responses to inhaled cigarette smoke and other irritants in the lungs of humans and an experimental animal, the rabbit. Specific aims include: 1) To determine the influence of airway branching and flow patterns on distributions of particles using single pathway airway casts of humans and rabbits; 2) To extend and refine aerosol probe techniques for efficient detection and characterization of early changes in airway morphology in humans and laboratory animals; 3) To determine the effects of transient bronchoconstriction induced by cold air, SO2, and cigarette smoke on aerosol dispersion in humans and rabbits; and 4) To determine the influence of early morphological changes in lung airways caused by low-level chronic pollutant exposures on aerosol dispersion and respiratory function in humans and animals, and their exposure-response relationships. The diagnostic tests with aerosols will provide powerful new tools for: 1) examination, in laboratory animals, of the factors involved in the pathogenesis and progression of chronic lung disease; and 2) environmental epidemiology, by relating inhalation exposures to loss of lung functional capacity and/or changes in the distribution of airflow. The comparative studies of aerosol deposition and irritant responses in humans and animals will strengthen the value of the animal model for studying mechanisms of pollutant damage to lung epithelia, and as an efficient test system for characterizing the influence of pollutant, environmental and constitutional factors on responses.