Pulmonary Function Changes in Cigarette Smokers Exposed to Ozone

Open Access
Bates, Melissa Lowe
Graduate Program:
Doctor of Philosophy
Document Type:
Date of Defense:
March 04, 2008
Committee Members:
  • James S Ultman, Committee Chair
  • Abdellaziz Ben Jebria, Committee Member
  • James Anthony Pawelczyk, Committee Member
  • Rebecca Bascom, Committee Member
  • Ozone
  • Pulmonary Function
  • Dose Response
  • Carbon Dioxide Expirogram
  • Cigarette Smokers
  • Nasal Lavage
PURPOSE: The acute inhalation of ozone (O3) by healthy nonsmokers compromises conducting airway function during exercise, as measured by forced expiratory volume in one second (FEV1). Paradoxically, cigarette smokers have exhibited little to no decrement in FEV1. We hypothesized that smoking-induced changes in the epithelial lining layer, such as increased thickness or lower antioxidant capacity, may allow O3 to penetrate deeper into the lungs of smokers versus non-smokers, thereby reducing the conducting airway responsiveness. If O3 penetrates deeper longitudinally, O3 may alter markers of distal airway function in smokers, notably the normalized slope (SN) of the CO2 expirogram. METHODS: We recruited 30 smokers (19M, 11F, 24 ± 4 years, 6 ± 4 total years smoking, 4 ± 2 packs/wk) and 30 non-smokers (17M, 13F, 25 ± 6 years) with clinically normal lung function, who had no history of respiratory or cardiovascular disease. Volunteers participated in two research sessions where they exercised for one hour on a cycle ergometer while breathing either filtered air or 0.30 ppm O3 at a workload sufficient to elicit a minute volume equal to 15 liters per minute times body surface area (m2). Exposure gases were delivered through a Hans Rudolph mask that allowed for oral breathing only. Breath-by-breath measures of tidal volume, breathing frequency, and the dose of O3 retained by the lung were made. Before and after each exposure, subjects completed lung function tests, a symptom questionnaire, and a series of breaths during which the CO2 expirograms were recorded. From the CO2 expirograms, we calculated values of conducting airway volume (VD) and SN. Additionally, pre- and post- exposure we sampled the nasal epithelial lining fluid (ELF) via nasal lavage and measured the ELF antioxidant capacity. Pre-O3 exposure, we obtained blood plasma and quantified circulating uric and ascorbic acid concentrations. Uric and ascorbic acid concentrations were quantified by high performance liquid chromatography and the total antioxidant capacity was determined using the oxygen radical absorbance capacity (ORAC) assay. In order to test our hypothesis, we developed a mathematical model which describes the longitudinal partitioning of the inhaled dose of O3 to the conducting airways and alveolar airspaces. This model relates the fraction of the total O3 dose reaching the alveolar region to the rate of transport of O3 to the ELF in the conducting airways (Ka) and the ratio of the VD to tidal volume (VD/VT) during exercise. Ka is determined largely by the availability of ELF antioxidants. RESULTS: Both smokers and non-smokers experienced no significant changes in FEV1, VD, or SN with air exposure. However, with O3 exposure, we found smokers and non-smokers to be equally responsive in terms of FEV1 (-9.5 ± 1.8% versus -8.7 ± 1.9%). While smokers were responsive in terms of VD (-6.1 ± 1.2%) and SN (9.1 ± 3.4%), non-smokers were not. We compared pre-and post-O3 exposure values of VD with values of VT measured in the 10th and 55th minute of exposure and found that in the 10th minute of exposure, smokers and non-smokers had similar values of VD/VT. However, in the 55th minute of exposure, non-smokers increased VD/VT (16.4 ± 2.8%) while smokers did not (8.4 ± 4.2%). Post-O3 exposure, smokers experienced fewer respiratory-related symptoms (shortness of breath, cough, and chest burning) compared to non-smokers. In terms of antioxidant status, smokers and non-smokers were not different in terms of plasma or nasal ELF ascorbic or uric acids. The ELF of both smokers and non-smokers had similar ORAC values. This led us to conclude that, because ELF antioxidant capacities were similar between both groups, Ka is not different. In applying our findings to our model, we concluded that, because Ka and initial VD/VT were not different in non-smokers and smokers, initial differences in longitudinal dose distribution are not responsible for the increased changes in SN experienced by the smokers. However, because smokers fail to increase VD/VT over the course of the exposure, they receive a higher cumulative dose to the peripheral airspaces compared to non-smokers. CONCLUSIONS: Young cigarette smokers retain their responsiveness to O3 in terms of FEV1. Uniquely, these smokers experience changes in VD that lead to heterogeneity in airway morphometry. This conclusion is supported by the observed increase in SN. We have determined that changes in the expirogram are not a result of initial differences in the dose penetrating to the peripheral airways. However, a decrease in VD/VT over the course of the exposure increases the dose to which the peripheral lung is exposed relative to the conducting airways. These findings demonstrate that young smokers are more sensitive to the health effects of O3 than non-smokers. Because we have identified that this population of young smokers responds differently to O3 in terms of FEV1 than the populations of older smokers reported in the literature, future studies of the health effects of airborne pollutants in smokers should include a cohort of young smokers.