OZONE EFFECT ON RESPIRATORY TRACT MUCUS AND PERMEABILITY

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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.