Uptake distribution of ozone in human lungs: intersubject variability in physiologic response

The primary hypothesis of this study was that intersubject variation in uptake of inhaled ozone causes corresponding variation in the resulting physiologic response. The second hypothesis was that differences in breathing pattern and lung anatomy induce differences in ozone uptake. Sixty healthy nonsmokers participated in three exposure protocols during which their minute ventilation was 30 L/min, corresponding to moderate exercise. For the intermittent bolus exposure to ozone (BO3*), we measured the penetration volume at which 50% of the bolus was taken up (VP50%). Before and after continuous clean air exposure (Ca) and continuous ozone exposure (CO3: 0.25 ppm ozone), we measured forced expiratory volume in 1 second (FEV1), calculated as the percent change after exposure relative to start of exposure [%FEV1]). We also measured the cross-sectional area of the peripheral lung (Ap) for carbon dioxide (CO2) diffusion, calculated as the percent change after exposure relative to start of exposure (%Ap). After the CO3 session, we also measured ozone uptake (as ozone uptake rate) and fractional ozone uptake efficiency. Uptake efficiency ranged from 0.70 to 0.98 among all subjects. It was inversely correlated with breathing frequency (P = 0.000) but was not correlated with conducting airways volume (P = 0.333). VP50% ranged from 67 to 135 mL among all subjects and was directly correlated with conducting airways volume (P = 0.000). These results indicate that overall ozone uptake was related to breathing frequency but not to airway size, whereas internal distribution of ozone shifted distally as airway size increased. Values of %FEV1 (mean +/- SD: -13.71 +/- 12.99) and %Ap (-7.80 +/- 9.34) were both significantly more negative (P = 0.000) in the CO3 session than in the Ca (control) session (-0.055 +/- 4.57 and 0.40 +/- 11.03, respectively). Ozone uptake rate correlated with individual %Ap (P = 0.008) but not with individual %FEV1 (P = 0.575). Nor were individual %Ap or %FEV1 correlated with VP50%. Therefore, ozone uptake did not explain intersubject differences in forced expiratory responses in this study, but it did partially explain differences in the cross-sectional area available for gas diffusion in the peripheral lung.