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RATIONALE Previously, in the Multi-center Ozone Study of oldEr Subjects (MOSES), 3 hours of controlled ozone (O3) exposure caused concentration-related reductions in lung function with evidence for airway inflammation and injury, but without convincing evidence for effects on cardiovascular function. However, 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. OBJECTIVE We examined whether personal measures of NO2 and O3, or ambient concentrations of O3, PM2.5, NO2, CO, and 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, and 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 samples (PES) of O3 and NO2, ambient air pollutant concentrations, and mixed effects linear regression. We also similarly explored effect modification of controlled ozone effects on biomarkers of other MOSES outcome groups in the same way. Although p<0.01 was used to define statistical significance, we did not formally correct for multiple comparisons. RESULTS Effects of MOSES controlled O3 exposures on FEV1 and FVC were modified by ambient NO2 and CO, and PES NO2, with reductions in FEV1 and FVC 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, with reductions 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).