Simultaneous Monitoring of Ozone Dose and Response in the Human Respiratory Tract

Brenza, Timothy

Simultaneous Monitoring of Ozone Dose and Response in the Human Respiratory Tract

Open Access

Author:: Brenza, Timothy
Graduate Program:: Chemical Engineering
Degree:: Doctor of Philosophy
Document Type:: Dissertation
Date of Defense:: July 11, 2008
Committee Members:: James S Ultman, Committee Chair/Co-Chair
Ali Borhan, Committee Chair/Co-Chair
Abdellaziz Ben Jebria, Committee Member
Darrell Velegol, Committee Member
Rebecca Bascom, Committee Member
Keywords:: Ozone
Pulmonary Response
Real-Time Dose Response Measurements
Simulated Ozone Uptake
Abstract:: The goal of this research was to establish a relationship between the retained dose of O3 and pulmonary response. Dose and response were measured through controlled exposure experiments on sixty test subjects. Test subjects were recruited based on their smoking status to evaluate the impact of smoking on O3 sensitivity (30 smoking subjects, and 30 non-smoking subjects).In the exposure session, the subjects exercised on a cycle ergometer at a workload that was adjusted to maintain their breathing at a constant ventilation rate for a one-hour period. During this exposure session the subject inhaled air that contained 0.3 ppm O3. Simultaneous measurements were made of flow, O3 concentration and CO2 concentration for the full session. From these measurements, the inhaled dose (DI) and the retained dose (DT) during complete respiratory cycles were computed.Pulmonary response was measured by both static and dynamic methods. The static pulmonary response measurements were taken prior to and just after the O3 exposure session at a fixed breathing condition, whereas the dynamic pulmonary response was measured simultaneous to the exposure. The statically measured parameters consisted of the forced expired volume (FEV1), the CO2 dead space volume (VD), and the normalized slope of the CO2 alveolar plateau (SN). The dynamically measured parameters included the tidal volume (VT), respiratory rate (RR), VD, and SN. An additional goal was to elucidate the course of response in these parameters during the exposure session. Regional dose of O3 was estimated by simulating the longitudinal distribution of O3 within the respiratory tract during the breathing cycle. The liquid-phase reaction rate constant (kr) was used as an adjustable parameter in the model the fit the simulation to the experimentally measured uptake O3 uptake efficiency (UE). The median values of kr were: 2.9 x 106 s-1 for non-smoking subjects, 2.1 x 106 s-1 for smoking subjects, 1.8 x 106 s-1 for female subjects, and 2.4 x 106 s-1 for male subjects. DT was partitioned into the regional dose (DR) within specific segments of the respiratory tract. DI, DT, and DR were compared to the response variables to determine the existence of correlations.The dynamic values of ΔVT (difference between an air control and O3 exposure session at the same time point) and ΔVD were correlated with the retained dose (DT). Regression analysis determined a rate of change in ΔVT of -0.11 ± 0.03 mL/µg (mean ± SD) and a rate of change in ΔVD of -0.014 ± 0.005 mL/µg. The smoking subjects exhibited the same dose-response relationships as the non-smoking subjects for these parameters.The population average regional dose (DR) was: 142 ± 114 µg (mean ± SD) in the upper airways (UA), 549 ± 115 µg in the conducting airways (CA), and 97 ± 113 µg in the respiratory airspaces (RA). No significant differences were observed between smoking and non-smoking subjects with respect to DR. Significant differences were observed in DR within the CA between female (487 ± 88 µg) and male (589 ± 114 µg) subjects, but not within the UA or RA. No correlations were determined between DR and the statically evaluated percent change in FEV1, VD, and SN.

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