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Effects of ozone in human volunteers exposed to low levels of ozone in a laboratory

Principal Investigators: 

University of California - San Francisco


University of North Carolina–Chapel Hill


University of Rochester

This multi-center study focused on the effects of ozone in human volunteers, aged 55 to 70 years, who were exposed in chambers to near ambient levels of ozone with intermittent exercise. Effects on the cardiovascular system, along with changes in pulmonary function, inflammation and oxidative stress were studied. Part 1 has been published (see link below). Part 2 of the study is ongoing, to further analyze the participant's prior exposures to ambient air pollutants and conduct additional analyses of the rich dataset.  

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In review

Abstract for HEI Annual Conference 2018

Multicenter Ozone Study In Elderly Subjects (MOSES) - Part 2: Impacts of Personal and Ambient Concentrations of Ozone and Other Pollutants on Cardiopulmonary Biomarkers

Rich DQ, Frampton M, Thurston SW, Thevenet-Morrison K, and Zareba W, University of Rochester Medical Center, Rochester, NY; Balmes J, Arjomandi M, and Ganz P, University of California, San Francisco, CA; Bromberg P, Hazucha M, and Alexis N, University of North Carolina at Chapel Hill, NC

Background: The Multi-center Ozone Study of Elderly Subjects (MOSES) was a multi-center study evaluating whether short-term controlled exposure of older, healthy individuals to low levels of ozone induced acute changes in cardiovascular biomarkers. In MOSES Part 1, ozone exposure caused concentration-related reductions in lung function with evidence for airway inflammation and injury, without convincing evidence for effects on cardiovascular function. However, pollutant exposures before the study may have independently impacted the study biomarkers, and/or modified biomarker responses to controlled ozone exposures.  

Study Design: In MOSES Part 2, we used a longitudinal panel study design, cardiopulmonary biomarker data from MOSES Part 1, and passively collected personal exposure samples (PES) of ozone and NO2, and ambient air pollution and weather measurements in the 96 hours before the pre-exposure visit. Using mixed effects linear regression, we evaluated whether PES concentrations and ambient pollutant concentrations in the previous 96 hours were associated with pre- to post-exposure biomarker changes, independent of the controlled ozone exposures (Aim 1); modified biomarker responses to the MOSES controlled ozone exposures (Aim 2); and were associated with changes in biomarkers measured at the pre-exposure visit (Aim 3).

Results: As hypothesized for Aim 3, increased ambient ozone concentrations were associated with decreased pre-exposure heart rate variability (HRV). For example, High Frequency (HF) HRV decreased in association with increased ambient ozone concentrations in the previous 96 hours (-0.460 ln of ms2; 95% CI, -0.743, to -0.177 for each 10.35 ppb increase in ozone; p=0.002). However, these increases in ambient ozone were also associated with increases in HF and LF from pre- to post-exposure (Aim 1), likely reflecting a ‘recovery’ of HRV during the MOSES ozone exposure sessions. Similar patterns were observed for FEV1 and FVC and increased ambient PM2.5, CO, and NO2 in the previous 96 hours. However, increased pollutant concentrations were not associated with adverse changes in other cardiopulmonary biomarkers. In Aim 2, effects of MOSES controlled ozone exposures on FEV1 and FVC (but not other biomarkers) were modified by ambient NO2 and CO, and PES NO2, with reductions in FEV1 and FVC observed only when these concentrations were “High” in the 72 hours before the pre-exposure visit.

Conclusions: Increased ambient ozone concentrations were associated with reduced HRV, with “recovery” during exposure visits. Increased ambient PM2.5, NO2, and CO (markers of traffic pollution), were associated with reduced pulmonary function, independent of the MOSES controlled ozone exposures. Pulmonary responses to the experimental ozone exposures were modified by ambient NO2 and CO concentrations, and PES NO2 concentrations, with adverse changes in FEV1 occurring only when ambient and PES pollutant levels were high.


Poster by MOSES Investigators' Team, 2018 HEI Annual Conference


Arjomandi M, Balmes JR, Frampton MW, Bromberg P, Rich DQ, Stark P, Alexis NE, Costantini M, Hollenbeck-Pringle D, Dagincourt N, Hazucha MJ. Respiratory Responses to Ozone Exposure. MOSES (The Multicenter Ozone Study in Older Subjects). Am J Respir Crit Care Med. 2018 May 15;197(10):1319-1327. doi: 10.1164/rccm.201708-1613OC. PMID: 29232153

Rich DQ, Balmes JR, Frampton MW, Zareba W, Stark P, Arjomandi M, Hazucha MJ, Costantini MG, Ganz P, Hollenbeck-Pringle D, Dagincourt N, Bromberg PA. Cardiovascular function and ozone exposure: The Multicenter Ozone Study in oldEr Subjects (MOSES). Environ Int. 2018 Jun 29;119:193-202. doi: 10.1016/j.envint.2018.06.014. PMID: 29980042


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