HEI study finds no heart effects of ozone exposure in healthy older adults; lungs affected at relatively low exposures
7 July 2017
The largest systematic study ever conducted of human volunteers exposed to ozone air pollution has found no evidence of effects on the heart in its healthy, older participants, but did find effects on the volunteers’ ability to breathe, even at low ambient levels.
HEI Research Report 192, Multicenter Ozone Study in oldEr Subjects (MOSES): Part 1. Effects of Exposure to Low Concentrations of Ozone on Respiratory and Cardiovascular Outcomes—published by the Health Effects Institute—measured a large number of cardiovascular and respiratory endpoints in 87 healthy, older participants who were exposed to 0, 70, or 120 parts per billion ozone for 3 hours while exercising moderately.
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
—“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.