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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 the 2019 HEI Annual Conference

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

David Q. Rich1, Mark Frampton1, Sally W. Thurston1, Kelly Thevenet-Morrison1, Wojciech Zareba1, John Balmes2, Mehrdad Arjomandi2, Peter Ganz2, Philip Bromberg3, Milan Hazucha3, and Neil Alexis3

1University of Rochester Medical Center, Rochester, NY, USA; 2University of California, San Francisco, CA, USA; 3University of North Carolina, Chapel Hill, NC, USA

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-1, ozone exposure caused concentration-related reductions in lung function with evidence for airway inflammation and injury, without effects on cardiovascular function. However, other pollutant exposures before the study may have confounded or modified these effects.

Study Design. In MOSES-2, we used a longitudinal panel study design, MOSES-1 cardiopulmonary biomarker data, and passive personal exposure samplers (PES) for ozone and NO2, and ambient air pollution measurements in the 96 hours before the pre-exposure visit. Using mixed effects linear regression, we evaluated whether pollutant concentrations confounded the MOSES-1 controlled ozone exposure effects on pre- to post-exposure biomarker changes (Aim 1), modified these biomarker responses to the controlled ozone exposures (Aim 2), were associated with changes in biomarkers measured at the pre-exposure visit or morning of the exposure session (Aim 3); and whether they were associated with differences in the pre- to post-exposure biomarker changes independent of the controlled ozone exposures (Aim 4).

Results. Controlled ozone exposure effects on pre- to post-exposure biomarker differences were little changed when including PES or ambient pollutant concentrations in the model (Aim 1). Controlled O3 exposure effects on FEV1 and FVC were modified by ambient NO2 and CO, and PES NO2, with reductions observed only when pollutant concentrations were “Medium” or “High” in the 72 hours before the pre-exposure visit. There was no modification of the controlled O3 exposure effect on any other pollutant/biomarker association (Aim 2). Increased ambient O3, PM2.5, CO, and NO2 concentrations were associated with decreased pre-exposure heart rate variability (HRV; Aim 3), but also associated with increases in HRV from pre- to post-exposure (Aim 4), likely reflecting a ‘recovery’ during the MOSES O3 exposure sessions. A similar pattern was observed for FEV1 and FVC and ambient PM2.5, CO, and NO2. Increased pollutant concentrations were not associated with adverse changes in other biomarker groups.

Conclusions. Our MOSES-1 findings of controlled ozone exposure effects on pulmonary function, but effects on cardiovascular biomarkers, were not confounded by ambient or personal pollutant exposures before the pre-exposure visit. MOSES-1 ozone effects on pulmonary function were modified by ambient NO2 and CO, and PES NO2, with reductions observed only when these pollutant concentrations were elevated in the hours/days before the pre-exposure visit. Increased ambient O3, PM2.5, NO2, and CO concentrations were associated with reduced HRV and pulmonary function, with “recovery” during exposure visits. Increased pollutant concentrations were not associated with changes in other cardiopulmonary biomarkers.


Poster by MOSES Investigators' Team, 2019 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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