Journal Article

Ozone effects on blood biomarkers of systemic inflammation, oxidative stress, endothelial function, and thrombosis: The Multicenter Ozone Study in oldEr Subjects (MOSES)

Dagincourt, Nicholas, Hazucha, Milan J., Frampton, Mark W., Balmes, John R., Costantini, Maria G., Bromberg, Philip A., Rich, David Q., Hollenbeck-Pringle, Danielle, Arjomandi, Mehrdad, Stark, Paul

2019

Overview

The evidence that exposure to ozone air pollution causes acute cardiovascular effects is mixed. We postulated that exposure to ambient levels of ozone would increase blood markers of systemic inflammation, prothrombotic state, oxidative stress, and vascular dysfunction in healthy older subjects, and that absence of the glutathione S-transferase Mu 1 (GSTM1) gene would confer increased susceptibility. This double-blind, randomized, crossover study of 87 healthy volunteers 55-70 years of age was conducted at three sites using a common protocol. Subjects were exposed for 3 h in random order to 0 parts per billion (ppb) (filtered air), 70 ppb, and 120 ppb ozone, alternating 15 min of moderate exercise and rest. Blood was obtained the day before, approximately 4 h after, and approximately 22 h after each exposure. Linear mixed effect and logistic regression models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. The definition of statistical significance was p<0.01. There were no effects of ozone on the three primary markers of systemic inflammation and a prothrombotic state: C-reactive protein, monocyte-platelet conjugates, and microparticle-associated tissue factor activity. However, among the secondary endpoints, endothelin-1, a potent vasoconstrictor, increased from pre- to post-exposure with ozone concentration (120 vs 0 ppb: 0.07 pg/mL, 95% confidence interval [CI] 0.01, 0.14; 70 vs 0 ppb: -0.03 pg/mL, CI -0.09, 0.04; p = 0.008). Nitrotyrosine, a marker of oxidative and nitrosative stress, decreased with increasing ozone concentrations, with marginal significance (120 vs 0 ppb: -41.5, CI -70.1, -12.8; 70 vs 0 ppb: -14.2, CI -42.7, 14.2; p = 0.017). GSTM1 status did not modify the effect of ozone exposure on any of the outcomes. These findings from healthy older adults fail to identify any mechanistic basis for the epidemiologically described cardiovascular effects of exposure to ozone. The findings, however, may not be applicable to adults with cardiovascular disease.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adults / Aged / Air Pollutants - adverse effects / Air pollution / Asthma / Atherosclerosis / Biological markers / Biology and Life Sciences / Biomarkers / Biomarkers - blood / Blood / C-reactive protein / C-Reactive Protein - analysis / Cardiovascular disease / Cardiovascular diseases / Care and treatment / Confidence intervals / Cross-Over Studies / Disease susceptibility / Dose-Response Relationship, Drug / Double-Blind Method / Earth Sciences / Ecology and Environmental Sciences / Elderly / Endothelin / Endothelin 1 / Endothelins / Endothelium / Endothelium, Vascular - drug effects / Environmental health / Epidemiology / Exposure / Factor VII / Female / Genes / Genetic research / Glutathione / Glutathione transferase / GSTM1 protein / Health aspects / Health care / Health sciences / Humans / Inflammation / Inflammation - blood / Inflammation - chemically induced / Inhalation Exposure - adverse effects / Male / Medicine / Medicine and Health Sciences / Microparticles / Middle Aged / Monocytes / Morbidity / Mortality / Nitrotyrosine / Older people / Outdoor air quality / Oxidative stress / Oxidative Stress - drug effects / Ozone / Ozone - adverse effects / Ozone concentration / Ozone effects / Patient outcomes / Physical Sciences / Platelet Activation - drug effects / Pollutants / Pollution / Pollution effects / Pollution monitoring / Public health / Regression analysis / Regression models / Risk factors / Statistical analysis / Studies / Thromboembolism / Thrombosis / Thrombosis - chemically induced / Tissue factor / Young adults