Although ozone has been documented to have respiratory effects, MOSES was designed to test a question which has been less well understood: whether ozone has short-term cardiovascular effects at present-day ambient levels (70 parts per billion is the current US National Ambient Air Quality 8-hour Standard).

Possible pathways by which ozone may cause adverse health effects. Pathways evaluated in MOSES are shown in bold- face; the number of endpoints evaluated is shown in brackets. Source: HEI. Click to enlarge.

The three centers successfully recruited and tested 87 participants (ages 55–70 years) who completed all visits. Analyses of the primary cardiovascular endpoints showed no statistically significant effects of ozone exposure at 70 or 120 ppb on autonomic nervous system function, cardiac electrical repolarization, or cardiac arrhythmia. In addition, ozone exposure did not lead to statistically significant changes in oxidative stress or in markers of systemic inflammation, vascular function, or prothrombotic status. The only changes associated with ozone exposure seen in cardiovascular endpoints were an increase in the secondary endpoint plasma endothelin‑1 (a marker of vascular function) and a decrease in nitrotyrosine (a marker of oxidative stress) after exposure to 120 ppb, but not 70 ppb, ozone.

On the other hand, the MOSES study confirmed that ozone has effects on the respiratory system even at these low concentrations, even though cardiac effects were not observed. In these older volunteers, moderate exercise during clean air exposure (0 ppb) led to an increased forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) 15 minutes after exposure compared with pre-exposure values, and they remained significantly higher after 22 hours. However, these improvements in lung function were attenuated after ozone exposure in a dose–response manner at 70 and 120 ppb. In addition, ozone exposure at 120 ppb significantly increased the percentage of polymorphonuclear leukocytes (a marker of lung inflammation; also referred to as “neutrophils”) in sputum as well as of club cell 16 (a marker of airway epithelial cell injury) in blood 22 hours later, compared with clean air exposure.

In contrast, changes in sputum concentrations of the inflammatory markers interleukin-6, interleukin-8, and tumor necrosis factor-alpha were not statistically significant. There was no evidence of statistically significant interactions between sex, age, or GSTM1 status and the observed changes in lung function, sputum polymorphonuclear leukocytes, or plasma club cell 16 after ozone exposure.

—“HEI Synopsis of Research Report 192, Part 1”

Led by Dr. John Balmes (University of California San Francisco), Dr. Phil Bromberg (University of North Carolina), and Dr. Mark Frampton (University of Rochester), and conducted in the largest number of volunteers ever tested, the study followed rigorous, standardized protocols, and all statistical analyses were conducted at a central data center.

It was subjected to detailed oversight by the HEI Research Committee and staff, the MOSES Data Monitoring Board, separate data quality audits, and intensive independent peer review by the HEI MOSES Review Panel.

The Review Panel concluded, in its Commentary accompanying the Investigators’ report, that:

• There was no convincing evidence that ozone exposure in this large study of older, healthy adults affected the primary cardiovascular endpoints identified by the investigators. Also, no responder subgroups could be identified in which ozone elicited cardiovascular effects that were not evident in the group as a whole.

• The observed lack of cardiovascular effects may not be generalizable to the overall adult population, which includes people who are less healthy and who are exposed to multiple pollutants for long periods of time.

• There were moderate effects on lung function and on two markers of lung injury and inflammation in these healthy, older adults (a population that had not often been studied in the past), a result that provides confirmation of ozone effects on the lung at concentrations similar to the current air quality standard.

The MOSES study adds substantially to our understanding of the potential effects of ozone exposure in healthy older adults. It importantly did not find cardiovascular effects in this population, but did confirm effects on the lung, even at the low levels of ozone exposure at which the study was conducted.

— HEI President Dan Greenbaum

The Health Effects Institute is an independent, nonprofit research institute funded jointly by the US Environmental Protection Agency, industry, foundations, and development banks to provide credible, high-quality science on air pollution and health for air quality decisions.

Resources

• Frampton MW, Balmes JR, Bromberg PA, Stark P, Arjomandi M, Hazucha MJ, et al. (2017) “Multicenter Ozone Study in oldEr Subjects (MOSES): Part 1. Effects of Exposure to Low Concentrations of Ozone on Respiratory and Cardiovascular Outcomes.” Research Report 192, Pt 1. Boston, MA:Health Effects Institute.