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 (V_D), and the normalized slope of the CO₂ alveolar plateau (SN). The dynamically measured parameters included the tidal volume (V_T), respiratory rate (RR), V_D, and S_N. 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 (k_r) 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 10 ⁶ s^-1 for female subjects, and 2.4 x 10⁶ s^-1 for male subjects. D_T was partitioned into the regional dose (D_R) within specific segments of the respiratory tract. D_I, D_T, and D_R were compared to the response variables to determine the existence of correlations.

The dynamic values of ΔV_T (difference between an air control and O₃ exposure session at the same time point) and ΔV _D were correlated with the retained dose (DT). Regression analysis determined a rate of change in ΔV_T of -0.11 ± 0.03 mL/ìg (mean ± SD) and a rate of change in ΔV_D of -0.014 ± 0.005 mL/ìg. 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 ìg 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 D_R and the statically evaluated percent change in FEV ₁, V_D, and S_N.