Longitudinal distribution of O3 absorption in the lung: gender differences and intersubject variability

Because the National Ambient Air Quality Standard for ozone (O3) 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 O3 at a fixed exposure condition. During quiet breathing, the conducting airways remove the majority of inhaled O3, so the volume of this region should have an important impact on O3 dose distribution. Employing the bolus inhalation method, we measured the distribution of O3 absorption with respect to penetration volume (Vp), and using the Fowler single-breath N2 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 O3 at smaller Vp than the men, and the women had smaller VD than the men. When expressed in terms of Vp/VD, the absorption distribution of the men and women was indistinguishable. Moreover, an interpretation of the O3 distribution in terms of an intrinsic mass transfer parameter (Ka) indicated that differences between the O3 dosimetry in all subjects, whether men or women, could be explained by a unique correlation with anatomic dead space: Ka (in s-1) = 610 VD-105 (in ml). Application of this result to measurements of O3 exposure response indicated that previously reported gender differences may be due to a failure in properly accounting for tissue surface within the conducting airways.