INTERSUBJECT VARIABILITY IN OZONE UPTAKE BY THE HUMAN LUNG
Open Access
- Author:
- Reeser, Wade Howard
- Graduate Program:
- Bioengineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- October 12, 2007
- Committee Members:
- James S Ultman, Committee Chair/Co-Chair
Roger Paul Gaumond, Committee Member
Rana Arnold, Committee Member
Richard Laurence Tutwiler, Committee Member - Keywords:
- ozone
uptake
respiratory
dosimetry - Abstract:
- Ozone O3 is a major component of the air pollution commonly referred to as ‘smog’, and inhalation of O3 causes a decrease in lung function and can initiate inflammatory responses within the lung. Ozone is a very powerful oxidizing agent. As such, it readily reacts with biological molecules found within the mucous layer of the respiratory system including glycoproteins, lipids and antioxidants. The reaction of O3 with the molecules in the mucous layer is so rapid that O3 itself might not contact the underlying endothelial tissue of the lung. Instead, the reaction products are frequently toxic and could diffuse through the mucous layer and produce the physiological responses that are responsible for observed decrements in lung function. Numerous studies have established that while decrements in pulmonary function are reproducible within subjects, there exists a large variability between subjects for a given inhaled O3 concentration, ventilation rate, body surface area and age of the subject. It is hypothesized that this unexplained variability in response between subjects is due to differences in local dose to target tissues which, in turn, may depend upon variations in the anatomy and biochemistry of their respiratory system. An understanding of the local dose and uptake of O3 within the human lung is important for predicting the detrimental health effects for individuals exposed to O3. To this end, mathematical models that predict the uptake of O3 within the lung may be used to determine important model parameters and infer the uptake of O3 for exposure conditions that would be unsafe for human subjects. In this work, the specific objectives were: 1) to measure the uptake efficiency of O3 for a large group of men and women for a given exposure condition, 2)to use a mathematical model to predict uptake efficiency of O3 for a given subject and exposure condition and 3) to identify model parameters that can be adjusted for each subject to match the predicted uptake efficiency of the model to that individual’s uptake data. Sixty subjects were exposed to continuous O3 concentrations of 0.25 parts per million for a 1-hour exposure at a target ventilation of 30 liters per minute. An apparatus monitored both the respired flow and O3 concentration at the airway opening from which the overall O3 uptake, tidal volume, breathing frequency and uptake efficiency were calculated for each minute of the exposure. Physiological measurements were also made to determine the total lung volume and respiratory dead space for each subject. A single-path model of the respiratory system was used to calculate the internal O3 distribution and uptake efficiency for a given inhaled O3 concentration, tidal volume, minute volume, lung volume and respiratory dead space. Physical parameters were identified in the single-path model as likely candidates to explain the between-subject variation, including mucous layer thickness, hydraulic diameter, longitudinal dispersion constant and reaction rate constant. Parameters that would likely explain the differences in uptake efficiency between the model and the data were identified by sensitivity analysis using physiologically relevant variation of the parameters. It is demonstrated that reaction rate constants of substrates within the mucous layer can be adjusted on a subject by subject basis in the simulation to generate estimates of uptake efficiency that match individual subject data. For the 60 experimental subjects the numerical values of the adjusted reaction rate constants were in the range reported in the literature.