Morphometric studies in ozone-exposed animals indicate that ozone (O3) toxicity is focal in nature, causing an inflammatory response and epithelial cell injury which are more pronounced in the proximal alveolar region than in other airways. Mathematical stimulations indicate that the same airways are the site of maximum O3 dose to tissue. These findings suggest that the internal distribution of O3 dose is an important determinant in the lung response to O3 exposure. Using a newly-developed bolus-response method, one can noninvasively measure the fraction of inhaled O3 that is absorbed into intact human lungs during a single breath (f). Moreover, f can be determined as a function of longitudinal penetration from the airway opening (Vp). The long range-objectives of this research are: 1) to measure the O3 dose distribution, f(Vp), in different categories of human subjects under a variety of relevant breathing and pollutant exposure conditions; and (2) use these data as a foundation for building a computer model which gives fundamental insights into the diffusion and chemical reaction processes governing the uptake of O3 into lung tissue. During the four years of this research, bolus-response measurements will be performed on a group of healthy men and women in order to achieve the following specific aims: 1. Compare the distribution of O3 dose during nasal breathing and during oral breathing. The hypothesis being tested is that the nose is more effective in protecting the lower airways from O3 than is the mouth. 2. Carry out bolus-response tests at different combinations of inspiratory and expiratory flows. The hypothesis being tested is that the O3 dose distribution is more sensitive to inspiratory than the expiratory flow conditions. 3. Study changes in the O3 dose distribution during exposure to 0.12 ppm O3 or to low concentrations of two copollutants, nitrogen dioxide (NO2) and sulfur dioxide (SO2). The underlying hypotheses are that exposure to O3 and to NO2 cause a distal shift in O3 dose toward the small airways while SO2 exposure causes a proximal shift toward the large airways. 4) Develop a computer simulation of the O3 bolus-response method. Initially, this simulation will be based on a symmetric branching lung geometry with a uniform flow distribution. Modifications to the simulation, such as asymmetric branching, may later become necessary to provide an adequate fit to experimental measurements. 5) Use the simulation to estimate the values of fundamental physico- chemical parameters. Values of the mass transfer and dispersion coefficients in various lung regions will be evaluated as a function of inspiratory and expiratory flow and of pre-exposure conditions by simulating the data collected in aims 1 to 3.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES006075-02
Application #
3254383
Study Section
Toxicology Subcommittee 2 (TOX)
Project Start
1992-08-01
Project End
1996-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Schools of Engineering
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802
Rutkowski, Joseph M; Santiago, Lizzie Y; Ben-Jebria, Abdellaziz et al. (2003) Development of an assay for ozone-specific antioxidant capacity. Inhal Toxicol 15:1369-85
Bush, M L; Zhang, W; Ben-Jebria, A et al. (2001) Longitudinal distribution of ozone and chlorine in the human respiratory tract: simulation of nasal and oral breathing with the single-path diffusion model. Toxicol Appl Pharmacol 173:137-45
Rigas, M L; Catlin, S N; Ben-Jebria, A et al. (2000) Ozone uptake in the intact human respiratory tract: relationship between inhaled dose and actual dose. J Appl Physiol 88:2015-22
Nodelman, V; Ultman, J S (1999) Longitudinal distribution of chlorine absorption in human airways: a comparison to ozone absorption. J Appl Physiol 87:2073-80
MacDougal, C S; Rigas, M L; Ben-Jebria, A et al. (1998) A respiratory ozone analyzer optimized for high resolution and swift dynamic response during exercise conditions. Arch Environ Health 53:161-74
Rigas, M L; Ben-Jebria, A; Ultman, J S (1997) Longitudinal distribution of ozone absorption in the lung: effects of nitrogen dioxide, sulfur dioxide, and ozone exposures. Arch Environ Health 52:173-8
Bush, M L; Raybold, T; Abeles, S et al. (1996) Longitudinal distribution of ozone absorption in the lung: simulation with a single-path model. Toxicol Appl Pharmacol 140:219-26
Asplund, P T; Ben-Jebria, A; Ultman, J S (1996) A portable inhalation system for personal exposure to ozone. Arch Environ Health 51:138-45
Asplund, P T; Ben-Jebria, A; Rigas, M L et al. (1996) Longitudinal distribution of ozone absorption in the lung: effect of continuous inhalation exposure. Arch Environ Health 51:431-8
Bush, M L; Asplund, P T; Miles, K A et al. (1996) Longitudinal distribution of O3 absorption in the lung: gender differences and intersubject variability. J Appl Physiol 81:1651-7

Showing the most recent 10 out of 12 publications