OZONE EFFECT ON RESPIRATORY TRACT MUCUS AND PERMEABILITY

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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.