REGIONAL DEPOSITION OF INHALED PARTICLES

这项研究的长期目标是：1)定义 人体呼吸道内的吸入颗粒物；2)表征 吸入颗粒物的传输作为呼吸流量和 气道和空域大小；3)在诊断方案中应用气雾剂 吸入性污染物对肺部早期影响的识别 上皮细胞和/或识别可能对 吸入的化学物质。 这里提出的研究将扩展我们过去和现在的工作 在人体内的区域沉积：1)其在体内的应用 测量由单个和多个空域引起的气道和空域大小变化 兔每天重复暴露于吸入刺激物；以及2) 气溶胶行为、沉积和响应的比较研究 吸入香烟烟雾和其他刺激物对人类和 实验动物，兔子。 具体目标包括：1)确定气道分支的影响 以及单通道通道中颗粒分布的流型 人和兔子的铸模；2)扩展和改进气溶胶探头 用于有效检测和表征早期变化的技术 人和实验动物的呼吸道形态；3)确定 冷空气、二氧化硫和空气诱导的一过性支气管收缩的影响 香烟烟雾对人和兔体内气溶胶扩散的影响；以及4) 确定早期肺气道形态改变对肺功能的影响 由低水平的慢性污染物暴露对气溶胶扩散和 人和动物的呼吸功能及其暴露反应 两性关系。 气溶胶诊断试验将为以下方面提供强大的新工具：1) 在实验动物身上，检查涉及的因素 慢性肺部疾病的发病机制和进展；2)环境 通过将吸入暴露与肺功能丧失联系起来的流行病学 气流分布的容量和/或变化。可比性 人体和动物气溶胶沉积和刺激性反应的研究 将加强动物模型对研究其发病机制的价值。 污染物对肺上皮细胞的损害，并作为一种有效的测试系统 描述污染物、环境和宪法的影响 影响反应的因素。

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.