OZONE EFFECT ON RESPIRATORY TRACT MUCUS AND PERMEABILITY

在健康受试者中，呼吸道膜将被放射性标记 用不溶性氧化铁颗粒或可溶性DTPN颗粒， 分别测量粘液清除率或膜渗透性， 使用伽马照相机成像的非侵入性技术。 急性的影响 连续暴露于0.2或0.4 ppm臭氧水平的时间将 评估。 目前，肺机械通气的阈值浓度 变化和主观不适在0.3和0.4 ppm之间。 这些 这些研究将在以下三个层面上提供有关臭氧影响的新信息： 呼吸道已被确定为损伤的焦点， 动物模型：1）气管和大支气管; 2）小支气管和 细支气管;以及3）远端细支气管和近端肺泡管，以及 肺泡 该技术对中心气道的改变敏感 外周肺粘液转运速度和粘液纤毛功能 气道，以及基底、中肺和 肺尖区。 急性和再暴露期的结果， 臭氧将支持或挑战气管支气管 粘液和/或呼吸道渗透性是 暴露在臭氧中的人引起的直接机械变化， 随后发生的这些变化，同时发生的拘留， 再次暴露于臭氧。 粘膜功能的测量可能超过 机械功能标准指标在鉴定中的灵敏度 低水平臭氧暴露（小于0.2 ppm）时的组织损伤，因此 需要重新评估人类臭氧阈值水平。目前， 研究仅限于健康受试者（非吸烟者）， 在臭氧暴露期间进行轻度运动的间隔，但未来的研究将 包括肺病群体。 一旦粘膜效应被 确定，与作用机制和改善 可以引发臭氧效应。

In healthy subjects the respiratory tract membranes will be radio-labeled with either insoluble iron oxide particles or soluble DTPN particles to measure mucus clearance or membrane permeability, respectively, by non-invasive techniques using gamma camera imaging. The influence of acute and consecutive exposure periods to ozone at 0.2 or 0.4 ppm levels will be assessed. Presently, the threshold concentration for lung mechanical changes and subjective discomfort is between 0.3 and 0.4 ppm. These studies will provide new information on ozone effects at three levels of the respiratory tract which have been identified as foci of injury in animal models: 1) Trachea and large bronchi; 2) Small bronchi and bronchioles; and 3) Distal Bronchioles and proximal alveolar ducts and alveoli. The techniques are sensitive to alterations in central airway velocities of mucus transport and mucociliary function of peripheral lung airways, and to changes in solute absorption within basal, mid-lung and apical lung regions. The results of acute and re-exposure periods with ozone will either support or challenge the hypotheses that tracheobronchial mucus and/or respiratory tract permeability are contributing factors for the immediate mechanical changes induced in man exposed to ozone, and the subsequent detention of these changes that occurs co-incident with re-exposure to ozone. Measurements of mucus membrane function may surpass the sensitivity of standard indices of mechanical function in identifying tissue damage at low levels of ozone exposure (less than 0.2 ppm), and thus require re-evaluation of the ozone threshold level in man. The present investigation is confined to healthy subjects (non-smokers) who will have intervals of light exercise during ozone exposures, but future studies will include pulmonary disease groups. Once mucus membrane effects have been determined, studies related to mechanisms of action and amelioration of ozone effects can be initiated.