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

Bush, Michele L., Patrick T. Asplund, Kristen A. Miles,Abdellaziz Ben-Jebria, and James S. Ultman. Longitudinaldistribution of O₃ absorption inthe lung: gender differences and intersubject variability.J. Appl. Physiol. 81(4):1651-1657, 1996.Because the National Ambient Air QualityStandard for ozone (O₃) isintended to protect the most sensitive individuals in the generalpopulation, it is necessary to identify sources of intersubjectvariation in the exposure-dose-response cascade. We hypothesize thatdifferences in lung anatomy can modulate exposure-dose relationshipsbetween individuals, and this results in differences between theirresponsiveness to O₃ at a fixedexposure condition. During quiet breathing, the conducting airwaysremove the majority of inhaled O₃,so the volume of this region should have an important impact onO₃ dose distribution. Employingthe bolus inhalation method, we measured the distribution ofO₃ absorption with respect topenetration volume (V_P), and using the Fowler single-breath N₂washout method, we determined the dead space volume(VD) in the lungs of 10 menand 10 women at a fixed respiratory flow of 250 ml/s. On average, thewomen absorbed O₃ at smallerV_P than the men, and the women hadsmaller VD than the men. Whenexpressed in terms ofV_P/ VD,the absorption distribution of the men and women was indistinguishable.Moreover, an interpretation of theO₃ distribution in terms of anintrinsic mass transfer parameter(Ka) indicated that differencesbetween the O₃ dosimetry in allsubjects, whether men or women, could be explained by a uniquecorrelation with anatomic dead space: Ka (ins¹) = 610 VD^1.05(in ml). Application of this result to measurements ofO₃ exposure response indicatedthat previously reported gender differences may be due to a failure inproperly accounting for tissue surface within the conducting airways.

     

Kinetics of ozone reaction with uric acid, ascorbic acid, and glutathione at physiologically relevant conditions

This study quantified the reaction kinetics of O3 with three low molecular weight antioxidants-uric acid (UA), ascorbic acid (AH2), and glutathione (GSH)-found in respiratory mucous. Using a semi-batch reactor in which a 500 ml/min flow of air containing 1-5 parts per million of O3 contacted 3 ml of well-stirred physiological saline solution containing 100-200 microM antioxidant, we found that: (1) mass transfer resistances in the gas and liquid phases were successfully eliminated by the reactor design; (2) the reaction of O3 with UA, AH2 and GSH had stoichiometries of 1:1, 1:1, and 1:2.5, respectively; (3) the reactivity between O3 and antioxidants was in the order UA approximately AH2>GSH. Simulating the measured amounts of O3 absorbed and antioxidant consumed with a mathematical model, reaction rate constants of O(3) with UA, AH2, and GSH were found to be 5.83 x 10(4) M(-1) s(-1), 5.5 x 10(4) M(-1) s(-1), and 57.5 M(-0.75) s(-1), respectively.