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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL031429-02
Application #
3342540
Study Section
Toxicology Study Section (TOX)
Project Start
1984-03-01
Project End
1987-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Foster, W M; Stetkiewicz, P T; Freed, A N (1997) Retention of soluble 99mTc-DTPA in the human lung: 24-h postdeposition. J Appl Physiol 82:1378-82
Groeben, H; Foster, W M; Brown, R H (1996) Intravenous lidocaine and oral mexiletine block reflex bronchoconstriction in asthmatic subjects. Am J Respir Crit Care Med 154:885-8
Foster, W M; Jiang, L; Stetkiewicz, P T et al. (1996) Breath isoprene: temporal changes in respiratory output after exposure to ozone. J Appl Physiol 80:706-10
Foster, W M; Stetkiewicz, P T (1996) Regional clearance of solute from the respiratory epithelia: 18-20 h postexposure to ozone. J Appl Physiol 81:1143-9
Foster, W M; Wills-Karp, M; Tankersley, C G et al. (1996) Bloodborne markers in humans during multiday exposure to ozone. J Appl Physiol 81:794-800
Wagner, E M; Foster, W M (1996) Importance of airway blood flow on particle clearance from the lung. J Appl Physiol 81:1878-83
Weinmann, G G; Weidenbach-Gerbase, M; Foster, W M et al. (1995) Evidence for ozone-induced small-airway dysfunction: lack of menstrual-cycle and gender effects. Am J Respir Crit Care Med 152:988-96
Smaldone, G C; Foster, W M; O'Riordan, T G et al. (1993) Regional impairment of mucociliary clearance in chronic obstructive pulmonary disease. Chest 103:1390-6
Foster, W M; Silver, J A; Groth, M L (1993) Exposure to ozone alters regional function and particle dosimetry in the human lung. J Appl Physiol 75:1938-45
Emmons, K M; Weidner, G; Foster, W M et al. (1992) Improvement in pulmonary function following smoking cessation. Addict Behav 17:301-6

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