Because the National Ambient Air Quality Standard for ozone (O-3) is intended to protect the most sensitive individuals in the general population, it is necessary to identify sources of intersubject variation in the exposure-dose-response cascade. We hypothesize that differences in lung anatomy can modulate exposure-dose relationships between individuals, and this results in differences between their responsiveness to O-3 at a fixed exposure condition. During quiet breathing, the conducting airways remove the majority of inhaled O-3, so the volume of this region should have an important impact on O-3 dose distribution. Employing the bolus inhalation method, we measured the distribution of O-3 absorption with respect to penetration volume (V-P), and using the Fowler single-breath N-2 washout method, we determined the dead space volume (VD) in the lungs of 10 men and 10 women at a fixed respiratory flow of 250 ml/s. On average, the women absorbed O-3 at smaller V-P than the men, and the women had smaller VD than the men. When expressed in terms of V-P/VD, the absorption distribution of the men and women was indistinguishable, Moreover, an interpretation of the O-3 distribution in terms of an intrinsic mass transfer parameter (K alpha) indicated that differences between the O-3 dosimetry in all subjects, whether men or women, could be explained by a unique correlation with anatomic dead space: K alpha (in s(-1)) = 610 VD-1.05 (in ml). Application of this result to measurements of O-3 exposure response indicated that previously reported gender differences may be due to a failure in properly accounting for tissue surface within the conducting airways.
