Do Ambient Ozone or Other Pollutants Modify Effects of Controlled Ozone Exposure on Pulmonary Function?

Rationale: In a previous trial (MOSES [Multicenter Ozone Study of oldEr Subjects]), 3 hours of controlled ozone (O₃) exposure caused concentration-related reductions in lung function with evidence of airway inflammation and injury, but without convincing evidence of effects on cardiovascular function. However, the subjects' exposures to indoor and outdoor air pollution in the hours and days before each controlled O₃ exposure may have modified biomarker responses to the controlled O₃ exposures.Objectives: We sought to determine whether personal measures of nitrogen dioxide (NO₂) and O₃, or ambient concentrations of O₃, particulate matter ≤2.5 μm in aerodynamic diameter, NO₂, carbon monoxide (CO), and sulfur dioxide (SO₂) in the 72 and 96 hours before the exposure visit modified biomarker responses to controlled O₃ exposure.Methods: MOSES subjects were exposed for 3 hours in random order to clean air containing 0 ppb O₃, 70 ppb O₃, or 120 ppm O₃, alternating 15 minutes of moderate exercise with 15 minutes of rest. Cardiovascular and pulmonary endpoints (biomarkers of autonomic function, repolarization, ST segment change, arrhythmia, prothrombotic vascular status, systemic inflammation, vascular function, pulmonary function, oxidative stress, and lung injury) were measured on the day before, the day of, and up to 22 hours after each exposure. We evaluated whether ambient pollutant concentrations in the 96 hours before the pre-exposure visit modified pre- to post-exposure lung function biomarker responses to the controlled O₃ exposures, using tertiles of passive personal exposure samplers (PES) of O₃ and NO₂, ambient air pollutant concentrations, and mixed effects linear regression. We also similarly explored the effect modification of controlled O₃ effects on biomarkers of other MOSES outcome groups in the same way. Although we used P < 0.01 to define statistical significance, we did not formally correct for multiple comparisons.Results: The effects of MOSES controlled O₃ exposures on forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC) were modified by ambient NO₂ and CO, and PES NO₂. Reductions in FEV₁ and FVC were observed only when these concentrations were in the "medium" or "high" tertile in the 72 hours before the pre-exposure visit. There was no such modification of the effect of controlled O₃ exposure on any other cardiopulmonary outcome group.Conclusions: Reductions in markers of lung function, but not other pathways, by the MOSES controlled O₃ exposure were modified by ambient NO₂ and CO, and PES NO₂, and these reductions were observed only when these pollutant concentrations were elevated in the hours and days before the pre-exposure visit.Clinical trial registered with ClinicalTrials.gov (NCT01487005).