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).
Keywords: ambient pollutants; ozone; pulmonary function; effect modification.