OZONE EFFECT ON RESPIRATORY TRACT MUCUS AND PERMEABILITY

理由：臭氧是光化学烟雾的主要成分， 微粒对呼吸道有高度刺激性。拟议 研究旨在表征人体气道对 臭氧和研究之间的联系粘液纤毛清除，上皮 完整性、区域通风、颗粒沉积和 脂质膜过氧化存在于肺气体中。 假设：气道上皮的粘膜生理学是一种 肺对刺激性刺激反应的主要决定因素。 具体目标：本提案的目的是为了更好地了解 臭氧如何可能伤害肺通过调查之间的联系， 粘膜纤毛功能、上皮完整性、局部通气，以及 脂质膜过氧化的标志物。我们还将研究几个 这些因素可能会降低肺的反应（适应）， 是经常性的。其他降低对臭氧敏感性的因素，吸烟 和老化，也将进行研究，以揭示反应所必需的变量。 由于气溶胶经常被发现在高氧化剂分布期间共存， 我们还将确定是否预先暴露于臭氧放大， 肺中总颗粒和局部颗粒沉积的可能性， 超微米和1亚微米大小的实验室气溶胶，反映了 城市空气中存在的总悬浮颗粒物。 方法：健康个体和对以下物质敏感性改变的受试者 将对臭氧进行研究，以揭示对应对至关重要的变量。 还将启动再暴露研究，以评估适应机制 复发性氧化剂损伤。臭氧效应将被测量 在室暴露于臭氧期间和之后， 可渗透的放射性标记颗粒，其已经沉积在 呼吸道放射性标记气体的区域通风， 将使用伽马照相机评价颗粒的转移/清除 显像臭氧毒性的修改将尝试使用 在臭氧暴露之前和期间补充抗坏血酸。存在 挥发性碳氢化合物的浓度将在收集的 通过气相色谱法采集肺部气体样本，并评价为潜在的 氧化剂暴露的预测因子和对大气道和小气道的耐受性 损伤

Rationale: Ozone, the major component of photochemical smog, and suspended particulate are highly irritating to the respiratory tract. The proposed research is intended to characterize the response of the human airway to ozone and investigate linkage between mucociliary clearance, epithelial integrity, regional ventilation, particulate deposition, and markers of lipid membrane peroxidation present in lung gas. Hypothesis: Mucus membrane physiology of the airway epithelium is a primary determinant of the lung response to irritant stimuli. Specific Aims: The aim of the proposal is to obtain a better understanding of how ozone may injure the lung by investigating the linkage between mucociliary function, epithelial integrity, regional ventilation, and markers of lipid membrane peroxidation. We will also study how several of these factors may decrease the lung response (adaptation) when exposures are recurrent. Other factors which reduce sensitivity to ozone, smoking and aging, will also be studied to unmask variables essential to response. Since aerosols are often found to co-exist during high oxidant profiles, we will also determine whether pre-exposure to ozone amplifies the potential for total and regional particle deposition in the lung using 2 supra- and 1 submicronic sized laboratory aerosols, reflective of the total suspended particulate present in urban air. Methods:. Healthy individuals and subjects with altered sensitivity to ozone will be studied to unmask variables essential for response. Reexposure studies will also be initiated to evaluate adaptive mechanisms of the lung to recurrent oxidant injury. Ozone effects will be measured during and following chamber exposures to ozone using insoluble and permeable radiolabelled particles which have been deposited onto the respiratory tract. Regional ventilation of radiolabelled gases and transfer/clearance of the particles will be evaluated using gamma camera imaging. Modification of ozone toxicity will be attempted using supplemental ascorbate prior to, and during ozone exposures. The presence and concentration of volatile hydrocarbons will be assayed in collected samples of lung gas by gas chromatography and evaluated as potential predictors of oxidant exposure and correlatable to large and small airway injury.