November 2007

by Michelle Hofmann, MD, MPH and Charles Langelier, MD, PhD cand.

Background

At certain times of the year, Utah has some of the worst air quality in the nation. According to the American Lung Association’s State of the Air report for 2007, three of Utah’s major metropolitan areas ranked among the top 25 most polluted by short term particle pollution (PM2.5), including Logan (5th), Salt Lake City-Ogden-Clearfield (7th), and Provo-Orem (19th). Poor air quality not only compromises the aesthetics of our beautiful state, it also significantly endangers the health of Utah’s citizens. An extensive body of scientific evidence now indicates that air pollution is responsible for signifi cant morbidity and mortality; thus, physicians should be aware of these fi ndings in order to optimally protect the health of their patients. The following brief review aims to discuss the most contemporary fi ndings on this subject and address the relevance of these studies to the Utah medical community. Air pollution is composed of a variety of substances, including fine particles (PM2.5), ozone, volatile organic compounds, nitrogen oxides, sulfur dioxide, and toxic metals such as mercury. These pollutants are responsible for significant health problems, including cardiovascular and pulmonary disease, increased susceptibility to respiratory infection, and ultimately premature death. Certain hazardous air pollutants, including benzene and polycyclic aromatic hydrocarbons, are well established carcinogens and reproductive toxins, while others, such as the heavy metals mercury and lead, are potent neurotoxins. The majority of air pollution in Utah can be attributed to automobiles and power plants, as well as emissions from industrial sources such as refineries. The combustion of fossil fuels, in particular coal, for electricity generation is the single greatest source of air pollution in the United States.

In the United States, air pollution is regulated by the Environmental Protection Agency under the Clean Air Act. Health based standards are set for criteria pollutants, including ozone, nitrogen dioxide, particulate matter, and sulfur dioxide. Areas that are out of compliance with these standards are known as non-attainment areas. For extended periods throughout the past several years, the Wasatch Front and Cache Valley have experienced some of the unhealthiest air in the country and Salt Lake City is now poised to violate the EPA standards for PM2.5 and ozone, signifi cantly compromising public health. Unhealthy ozone levels occur most frequently in Utah during the summer, while high particulate levels tend to occur during winter temperature inversions1. Particulate Air Pollution From a public health standpoint, fi ne particulate matter (particles <2.5uM in diameter or PM2.5) is one of the most signifi cant air pollutants in our region. An extensive array of scientifi c work has examined PM2.5 pathology from both an epidemiological and molecular perspective. Short-term increases (over hours to days) in particle pollution have been linked to death from respiratory and cardiovascular causes, including strokes2,3,4, increased numbers of heart attacks, especially among the elderly and in people with heart conditions5, infl ammation of lung tissue in young, healthy adults 6, increased hospitalization for cardiovascular disease, including strokes7,8, increased emergency room visits for patients suffering from acute respiratory ailments9, increased hospitalization for asthma among children10,11,12, and increased severity of asthma attacks in children13. Long-term exposure to particle pollution results in increased hospitalization for asthma attacks14, slowed lung function growth in children and teenagers15,16, signifi cant damage to the small airways of the lungs17, increased risk of dying from lung cancer, and18 increased risk of death from cardiovascular disease19. Epidemiological and toxicological studies demonstrate a clear link between both short- and long-term exposure to PM2.5 and cardiovascular disease. Air pollution, like smoking, adversely affects the vasculature and circulation and results in vascular infl ammation with an increased risk of blood clot formation, vasoconstriction and rupture of atherosclerotic plaque. Many of the classic and contemporary studies on particulate air pollution have been conducted in Utah by the internationally recognized BYU professor of economics, C. Arden Pope. A recent study of 12,000 patients conducted along the Wasatch Front over eight years found that every 10 µg/m3 rise in PM2.5 resulted in a 4.5% increase in the risk of unstable angina or myocardial infarction20. A study of 65,000 women conducted over four years found that a 10 µg/m3 rise in PM2.5 resulted in a 24% increase in the risk of cardiovascular events, a 76% increase in the risk of death from cardiovascular disease, a 35% increase in the risk of stroke, and an 83% increase in the risk of death from stroke21. To put these values in perspective, during winter inversions, the valleys in Utah may routinely experience a 40 µg/m3 increase in PM2.5 levels. Despite the fact that the precise pathological and molecular mechanisms of air pollution cardiovascular toxicity are still being examined, it is generally well accepted that inhalation of particulate air pollution creates and induces both pulmonary and systemic infl ammation and oxidative stress, leading to direct vascular injury, atherosclerosis, and autonomic dysfunction22. Particulate air pollution exposure accelerates atherosclerosis in both human and animal studies, and the buildup of atherosclerotic plaque, measured by the carotid intima–media thickness, is higher in communities with higher mean PM2.5 concentrations23. Particulate air pollution has been found to lead to rapid and signifi cant increases in fi brinogen, plasma viscosity, platelet activation, and release of endothelins, a family of potent vasoconstrictor molecules. In animal models, particulate air pollution and a high fat diet synergistically interact to raise cholesterol and accelerate atherosclerosis24. In summary, PM2.5 air pollution is responsible for signifi cant disease both in Utah and worldwide, with some of the most signifi cant pathology occurring in the cardiovascular system. Ozone Air Pollution Ozone is a second key air pollutant of public health signifi – cance in Utah. While ozone high in the stratosphere is essential in protecting biological organisms from the damaging effects of UV radiation, tropospheric or “ground-level” ozone is quite harmful to human health. Troposhperic ozone, the major constituent of summertime smog, is formed from a chemical reaction involving nitrogen oxides, volatile organic compounds and sunlight. Higher temperatures promote ozone formation and record temperatures in Utah this summer resulted in an unprecedented number of days during which Wasatch Front communities experienced unhealthy levels of ozone air pollution. Ozone is a powerful oxidant and the pathology of this pollutant can largely be attributed to the oxidation, infl ammation, and subsequent destruction of epithelial tissues, primarily in the lung. New research has confi rmed that ozone exposure increases the risk of premature death25 and well established studies have found that acute clinical effects of exposure include shortness of breath, chest pain, wheezing, coughing and increased susceptibility to respiratory infections. The pronounced infl ammation of the lungs and airways induced by ozone results in an increased risk of asthma attacks and an increased need for medical treatment and hospital admission for individuals with asthma, chronic obstructive pulmonary disease and cystic fi brosis26. Animal toxicology studies have also shown that long-term exposure to high levels of ozone induces permanent structural changes to the lungs27. Protecting Health The combined impact of air pollution on public health in both Utah and throughout the world is exceedingly signifi – cant. Studies estimate that the nationwide death toll attributed to air pollution exceeds tens of thousands annually28 and considerable evidence now demonstrates that no safe level of exposure for either PM2.5 or ozone exists18-20. Identifying the most sensitive individuals and developing optimal intervention strategies are ongoing scientifi c and clinical challenges. While improving air quality is likely to benefi t everyone, a growing body of research suggests that children and seniors are uniquely susceptible to the adverse effects of air pollution. In addition, individuals with preexisting chronic lung or cardiovascular disease, including coronary artery disease, previous stroke or heart attack, or diabetes may be especially sensitive to air pollution toxicity. On high pollution days, it is advisable for susceptible individuals to avoid exercising outdoors. Exposure to ozone can be minimized in the summertime by exercising during early morning hours before sunlight and high temperatures have had the chance to induce pollution formation. During winter inversions or at other times of high air pollution, exercising in the mountains or inside (indoor gym or walking in a shopping mall) can be encouraged. Parents should be advised to limit the amount of time their children spend playing outdoors during periods of unhealthy air quality. Given the overwhelming evidence demonstrating the adverse effects of air pollution, it is reasonable to assume that signifi cant benefi t would result if Utah physicians were aware of daily pollution levels and air quality forecasts and could advise susceptible patients. Furthermore, as key advocates for the health of not only individual patients but also the general populace, it might follow that physicians should be actively engaged in supporting policies aimed at safeguarding and improving regional air quality. Reliable current and forecasted air pollution levels throughout Utah are available from several sources, including the Utah Division of Air Quality at www.airquality.utah.gov and the EPA at http://airnow.gov, and can also be obtained via local radio, television and newspapers. Several medical organizations are currently engaged in advocating for more protective state and federal air pollution legislation, including the American Lung Association (www.lungusa.org), the American Heart Association (www.americanheart.org), Physicians for Social Responsibility (www.psr.org) and Utah Physicians for a Healthy Environment (www.uphe.org).

References
1. U.S. Environmental Protection Agency. Air Quality Criteria for Particulate Matter.
2004. At www.epa.gov/ttn/naaqs/standards/pm/s_pm_cr_cd.html.
2. Dominici F, McDermott A, Zeger SL, Samet JM. On the Use of Generalized Additive
Models in Time-Series Studies of Air Pollution and Health. Am. J. Epidemiol 2002;
156:193-203.
3. Hong, Y.-C., Lee J.-T., Kim, H., Ha, E.-H., Schwartz, J., and Christiani, D.C. Effects
of Air Pollutants on Acute Stroke Mortality. Environ. Health Perspect. Vol. 110, pp.
187-191, 2002.
4. Tsai SS, Goggins WB, Chiu HF, Yang CY. Evidence for an Association Between Air
Pollution and Daily Stroke Admissions in Kaohsiung, Taiwan. Stroke. 2003; 34:
2612-6. Epub 2003 Oct 09.
5. D’Ippoliti D, Forastiere F, Ancona C, Agabity N, Fusco D, Michelozzi P, Perucci
CA. Air Pollution and Myocardial Infarction in Rome: a case-crossover analysis.
Epidemiology 2003;14:528-535.
6. Ghio AJ, Kim C, Devlin RB. Concentrated Ambient Air Particles Induce Mild
Pulmonary Infl ammation in Healthy Human Volunteers. Am J Respir Crit Care Med
2000; 162(3 Pt 1):981-8.
7. Metzger KB, Tolbert PE, Klein M, Peel JL, Flanders WD, Todd K, Mulholland
JA, Ryan PB, Frumkin H. Ambient Air Pollution and Cardiovascular Emergency
Department Visits in Atlanta, Georgia, 1993-2000. Epidemiology 2004;15: 46-56.
8. Tsai SS, Goggins WB, Chiu HF, Yang CY. Evidence for an Association Between
Air Pollution and Daily Stroke Admissions in Kaohsiung, Taiwan. Stroke. 2003;
34:2612-6. Epub 2003 Oct 09.
9. Van Den Eeden SK, Quesenberry CP Jr, Shan J, Lurmann F. Particulate Air Pollution
and Morbidity in the California Central Valley: a high particulate pollution region. Final
Report to the California Air Resources Board, Contract 97-303, July 12, 2002.
10. Lin M, Chen Y, Burnett RT, Villeneuve PJ, Kerwski D. The Infl uence of Ambient
Coarse Particulate Matter on Asthma Hospitalization in Children: case-crossover
and time-series analyses. Environ. Health Perspet 2002;110:575-581.
11. Norris G, YoungPong SN, Koenig JQ, Larson TV, Sheppard L, Stout JW. An
Association Between Fine Particles and Asthma Emergency Department Visits for
Children in Seattle. Environ Health Perspect 1999;107:489-493
12. Tolbert PE, Mulholland JA, MacIntosh DD, Xu F, Daniels D, Devine OJ, Carlin BP,
Klein M, Dorley J, Butler AJ, Nordenberg DF, Frumkin H, Ryan PB, White MC. Air
Quality and Pediatric Emergency Room Visits for Asthma in Atlanta, Georgia. Am J
Epidemiol 2000; 151:798-810.
13. Slaughter JC, Lumley T, Sheppard L, Koenig JQ, Shapiro, GG. Effects of Ambient Air
Pollution on Symptom Severity and Medication Use in Children with Asthma. Ann
Allergy Asthma Immunol 2003; 91:346-53.
14. Lin S, Munsie JP, Hwang SA, Fitzerald E, Cayo MR. Childhood Asthma Hospitalization
and Residential Exposure to State Route Traffi c. Environ Res 2002; 88:73-81.
15. Gauderman WJ, Gilliland GF, Vora H, Avol E, Stram D, McConnell R, Thomas
D, Lurmann F, Margolis HG, Rappaport EB, Berhane K, Peters JM. Association
between Air Pollution and Lung Function Growth in Southern California Children:
results from a second cohort. Am J Respir Crit Care Med 2002;166:76-84.
16. Gauderman WJ, Avol E, Gilliland F, Vora H, Thomas D, Berhane K, McConnell R, Kuenzli
N, Lurmann F, Rappaport E, Margolis H, Bates D, Peters J. The effect of air pollution on
lung development from 10 to 18 years of age. NEJM 2004;351:1057-67
17. Churg, A Brauer, M, Avila-Casado, MdC, Fortoul TI, Wright JL. Chronic Exposure
to High Levels of Particulate Air Pollution and Small Airway Remodeling. Environ
Health Perspect 2003; 111: 714-718.
18. Pope CA, Burnett RT, Thun MJ, Calle EE, Krewski D, Ito K, Thurston GD. Lung
Cancer, Cardiopulmonary Mortality, and Long-Term Exposure to Fine Particulate
Air Pollution, JAMA 2002;287:9.
19. Pope CA III, Burnett RT, Thurston GD, Thun MJ, Calle EE, Krewski D, Godleski JJ.
Cardiovascular Mortality and Year-round Exposure to Particulate Air Pollution:
epidemiological evidence of general pathophysiological pathways of disease.
Circulation. 2004; 109:71-77.
20. Pope A et al. Ischemic heart disease triggered by short-term exposure to fi ne particulate
air pollution. Circulation. 2006 (114): 2443–2448.
21. Miller KA, Siscovick DS, Sheppard L, et al. Long-term exposure to air pollution and
incidence of cardiovascular events in women. N Engl J Med 2007;356:447-458.
[Free Full Text]
22. Brook RD, Franklin B, Cascio W, et al. Air pollution and cardiovascular disease: a
statement for healthcare professionals from the Expert Panel on Population and
Prevention Science of the American Heart Association. Circulation 2004;109:2655-
2671. [CrossRef][ISI][Medline]
23. Kunzli N, Jerrett M, Mack WJ, et al. Ambient air pollution and atherosclerosis in
Los Angeles. Environ Health Perspect 2005;113:201-206. [ISI][Medline]
24. Sun Q et al. Long term air pollution exposure and acceleration of atherosclerosis
and vascular infl ammation in the animal model. JAMA. Dec. 21, 2005, Vol. 294:
p 3003–10.
25. Bell ML, Dominici F, and Samet JM. A Meta-Analysis of Time-Series Studies of
Ozone and Mortality with Comparison to the National Morbidity, Mortality, and
Air Pollution Study. Epidemiology 2005; 16:436-445. Levy JI, Chermerynski
SM, Sarnat JA. Ozone Exposure and Mortality: an empiric Bayes metaregression
analysis. Epidemiology 2005; 16:458-468. Ito K, De Leon SF, Lippmann
M. Associations Between Ozone and Daily Mortality: analysis and meta-analysis.
Epidemiology 2005; 16:446-429.
26. Gent JF, Triche EW, Holford TR, Belanger K, Bracken MB, Beckett WS, Leaderer BP.
Association of Low-Level Ozone and Fine Particles with Respiratory Symptoms in
Children with Asthma. JAMA 2003; 290:1859-1867. Desqueyroux H, Pujet JC, Prosper
M, Squinazi F, Momas I. Short-Term Effects of Low-Level Air Pollution on Respiratory
Health of Adults Suffering from Moderate to Severe Asthma. Environ Res 2002;89:29-37;
Burnett RT, Brook JR, Yung WT, Dales RE, Krewski D. Association between Ozone
and Hospitalization for Respiratory Diseases in 16 Canadian Cities. Environ Res
1997;72:24-31. Medina-Ramón M, Zanobetti A, Schwartz J. The Effect of Ozone and
PM10 on Hospital Admissions for Pneumonia and Chronic Obstructive Pulmonary
Disease: a national multicity study. Am J Epidemiol 2006; 163(6):579-588.
27. Fanucchi MV, Plopper CG, Evans MJ, Hyde DM, Van Winkle LS, Gershwin LJ,
Schelegle ES. Cyclic Exposure to Ozone Alters Distal Airway Development in Infant
Rhesus Monkeys. Am J Physiol Lung Cell Mol Physiol 2006; 291:644-650.
28. Abt Associates. The Particulate-Related Health Benefi ts of Reducing Power Plant
Emissions. October 2000. Available at www.catf.us/publications/view/4. ; U. S.
Environmental Protection Agency. Fact Sheet: Clean Air Interstate Rule, March 10