Student Research: Samantha Erb

, Environmental Toxicology (Tox), 2011
Faculty Advisor: Joel D. Kaufman

Inhalation of Diesel Exhaust in Human Subjects and Gene Expression in Peripheral Blood Leukocytes


Abstract

Introduction

Particulate Matter & Cardiovascular Disease

Exposure to ambient air pollution has been known to be associated with adverse health effects and increased mortality for decades. Extreme air pollution events, such as in 1930 in Meuse Valley of Belgium and the 1952 London fog incident, led to sharp increases in mortality and led to increased research into the association between air pollution and disease. Epidemiologically, ambient air pollution has been identified as a risk factor for cardiovascular disease (CVD). Environmental Protection Agency-designated increased levels of criteria pollutants including sulfur dioxide, nitrogen dioxide, ozone, carbon monoxide, and particulate matter (PM) with an aerodynamic diameter less than 2.5 µm have been looked at with special interest. All six criteria pollutants are hazardous to human health, but PM in particular has been associated with increased morbidity and mortality at concentrations present frequently in the ambient environment. Large-scale epidemiological studies in the United States and in Europe have found a strong association between low to moderate levels of PM exposure and adverse health outcomes, as well as between short-term increased PM and mortality.

Particulate matter is composed of complex mixture of very small particles and liquid droplets. It can include dust particles, metals, organic chemicals, acids, and soil. PM is categorized by size; PM with a diameter between 2.5 and 10 µm are considered inhalable coarse particles (PM10) while PM with a diameter below 2.5 µm (PM2.5) are classified as fine particles. Sources of PM vary widely; coarse particles are generally derived from resuspension of dust, soil, spores, pollen, and materials from mining. In contrast, PM2.5 is largely formed from combustion or emission from industrial processes, burning, or motor vehicle operations [and atmospheric processes on emissions from those sources]. Ultrafine particulate matter is generally generated by combustion processes. PM10 largely deposits in the tracheobronchial tree, while PM2.5 can more readily reach the bronchioles and alveoli. PM2.5 is more toxicologically relevant as smaller particles are more respirable, remain suspended for a longer period of time, and may have toxic chemicals including sulfates, nitrates, organics, and acids adsorbed to their surfaces.

Particulate matter has been associated with adverse health effects including overall increased mortality due to ischemic heart disease, dysrhythmias, cardiac arrest, and heart failure. Cardiovascular disease is the leading cause of death in the United States. It was responsible for over 831,000 deaths in 2006, or 34.3 percent of all deaths. The American Heart Association estimates that 81.1 million individuals had at lease one form of heart disease in the same year, including coronary hearth disease, high blood pressure, stroke, and/or heart failure.

Evidence points to a relationship between both short-term and long-term exposures to PM2.5 and adverse health outcomes. According to the National Morality and Morbidity Air Pollution study, which gathered data from 90 U.S. cities, each 24-hour-average 10 µg/m3 increase in PM10 concentration relates to an increase of 0.21% in daily total mortality and 0.31% in daily cardiopulmonary mortality. The American Cancer Society cohort study showed that an annual-average 10 µg/m3 increase in annual PM10 concentration related to a 4% and 6% increase in all-cause and pulmonary mortality, respectively. Studies have typically involved epidemiologic assessments of ambient air pollution and long-term effects and clinical endpoints, such as mortality, hospitalization, or specific diagnoses; panel or clinical studies have utilized subclinical endpoints, including systemic inflammation and oxidative stress, endothelial dysfunction, changes in blood pressure, and altered heart rate variability. Investigation of subclinical endpoints will help elucidate the mechanisms underlying the relationship between PM and CVD. The effects of the relationship are unknown, but likely include direct myocardium effects, disturbances of the cardiac autonomic nervous system, inflammation, endothelial dysfunction, coagulation and thrombosis, and pulmonary systematic oxidative stress.