SUPPLEMENT
Outdoor Air Pollution A Global Perspective Yuh-Chin T. Huang, MD, MHS
Although the air quality in Western countries has continued to improve over the past decades, rapid economic growth in developing countries has left air quality in many cities notoriously poor. The World Health Organization estimates that urban outdoor air pollution is estimated to cause 1.3 million deaths worldwide per year. The primary health concerns of outdoor air pollution come from particulate matter less than 2.5 μm (PM2.5) and ozone (O3 ). Short-term exposure to PM2.5 increases cardiopulmonary morbidity and mortality. Long-term exposure to PM2.5 has been linked to adverse perinatal outcomes and lung cancer. Excessive O3 exposure is known to increase respiratory morbidity. Patients with chronic cardiopulmonary diseases are more susceptible to the adverse effects of air pollution. Counseling these patients about air pollution and the associated risks should be part of the regular management plans in clinical practice.
A
ir pollution is a global problem. The World Health Organization recently estimated that, in 2012, approximately 3.7 million people died as a result of exposure to ambient air pollution (http: //www.who.int/phe/health topics/outdoorair/databases/en/). Worldwide ambient air pollution contributes to 6.7% of all deaths. Lowand middle-income countries in the Southeast Asia and Western Pacific regions where the air pollution is most severe had the largest air pollution-related disease burden. The disease burden remains significant even in the developed countries where the levels of air pollutants are generally much lower because of the constant exposure of the large number of people to the air pollutants (http: //www.who.int/gho/phe/outdoor air pollution/burden/en/). This review discusses the global burden of air pollution and focuses on the health effects associated with two most prevalent air pollutants, ozone (O3 ) and particulate matter (PM). The review is intended for clinicians and anyone who is interested in the clinical aspect of air pollution.
Q: WHAT IS THE GLOBAL BURDEN OF AIR POLLUTION? Urban air pollution was first noted in AD 1272 by King Edward I who described a coal smoke event.1 Both Greek and Roman societies noted that air pollution was a potential source of health problems. After industrialization in the late nineteenth century, many severe air pollution episodes were documented. These episodes had been attributed to coal burning and were associated with a major increase in mortality and morbidity, including the notorious London smog of 1952, which resulted in more than 4000 deaths. Efforts to reduce air pollution ensued in the 1960s and 1970s, which led to a marked improvement in air quality in Western countries. Despite these efforts, new epidemiological studies in the 1980s and 1990s
From the Department of Medicine, Duke University Medical Center, Durham, NC. The author declares no conflict of interest. Address correspondence to: Yuh-Chin T. Huang, MD, MHS, Department of Medicine, Duke University Medical Center, 1821 Hillandale Rd, Suite 25A, Durham, NC 27705 ([email protected]). C 2014 by American College of Occupational and Environmental Copyright Medicine DOI: 10.1097/JOM.0000000000000240
using time series analysis continued to show associations between adverse health effects and particulate matter less than 2.5 μm (PM2.5) at levels much lower than those encountered in earlier air pollution disasters, and in some studies at concentrations near or below the national standards. Currently, there is no evidence of a safe level of exposure or a threshold for PM2.5 below which no adverse health effects occur. Although the air quality in Western countries has continued to improve, in developing countries, rapid economic growth over the past decades has left air quality in many cities notoriously poor. For example, in January 2013, heavy smog smothered Beijing, China, for many days. “The air tasted of coal dust and car fumes” (http: //www.bbc.com/news/world-asia-china-20998147). The smog was so thick that one could only see a few hundred meters in the city center in the afternoon. The PM2.5 level was more than 400 μg/m3 (http: //www.bbc.co.uk/news/world-asia-china-20998147). Natural disasters, such as forest fires and volcanic eruptions, also contributed to poor air quality. For example, in June 2013, forest fires in Riau, Indonesia, caused thick haze in the neighboring countries. Malaysia declared a state of emergency whereas Singapore urged people to remain indoors due to “hazardous” levels of pollution. Sudden eruption of the Icelandic volcano, Eyjafjallaj¨okull, in April 2010 disrupted air travel across western and northern Europe for a week. Recent studies have shown increased symptoms of upper airway irritation and exacerbation of preexisting asthma for residents in the exposed area,2,3 although the effects on mortality are inconclusive.4 With global warming, it is predicted that natural disasters such as forest fires will occur with increasing frequency. Although the relative risk for air pollution-related health effects tends to be low, the attributable risk is significant because of the large population exposed to air pollutants. According to the World Health Organization, urban outdoor air pollution is estimated to cause 1.3 million deaths worldwide per year. Worldwide, outdoor air pollution contributes to 5% of all cardiopulmonary deaths (http://www.who.int/gho/phe/outdoor air pollution/en/index.html). Exposure to air pollution depends upon many variables. Ambient concentrations of pollutants are affected by seasonal and meteorological conditions (eg, hot, dry air increases O3 production). The concentrations of air pollutants also have significant spatial and geographic variations. Proximity to a source of emissions (eg, power plant, major road, or highway), as well as time-activity patterns, will influence exposure to pollution. The level of some air pollutants near a busy highway may be several times higher than those measured by a monitor station located away from the road. There is a strong association between the traffic intensity near a home and cardiorespiratory mortality with relative risks of 1.05 to 1.10.5 In the United States, approximately 16% of the housing units (approximately 48 million people, mostly nonwhite and economically disadvantaged) are located within 300 ft of a major highway, railroad, or airport. With urbanization globally, the near-road air pollution has and will become a major public health issue.
Q: WHAT IS AIR POLLUTION? Air pollution is a complex mixture of particles and gases that originate from both anthropogenic (eg, combustion of fossil fuels) and natural (eg, soil resuspension) sources, with secondary
JOEM r Volume 56, Number 10S, October 2014 Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
S3
JOEM r Volume 56, Number 10S, October 2014
Huang
physicochemical modifications in the atmosphere. Primary air pollutants include particulate patter (PM) and nitrogen oxides (NOx), whereas secondary air pollutants include O3 . In an urban environment, outdoor air pollutants are generated primarily by emissions from sources, such as large stationary fuel combustion sources (eg, electric utility plants), industrial emissions (eg, smelters and oil refineries), and transportation modalities (eg, automobiles, aircraft, and locomotives). Particulate matter is a mixture of sulfate, nitrate, elemental (black) carbon, organic carbon, and crustal material. It also contains metals in the forms of oxides and soluble salts. The specific composition and relative abundance of these constituents depend on the sources and vary from place to place. For example, PM from combustion of fossil fuel contains a large amount of soluble transition metals. This is in contrast with PM derived from soil, (eg, Mount St Helen dust), which has almost no metals. The US Environmental Protection Agency (EPA) has set standards for six air pollutants that are associated with health effects, called criteria pollutants, including ground level O3 , PM, lead, NO2 , CO, and SO2 (http://www .epa.gov/air/criteria.html). Ambient PM is commonly categorized by size fraction on the basis of its mass median aerodynamic diameter (MMAD). Coarse PM has MMAD between 2.5 and 10 μm (PM10 and PM2.5) and fine PM has MMAD less than 2.5 μm (PM2.5). The ultrafine PM (particles with MMAD ≤0.1 μm) is a subset of fine PM. Each size fraction possesses unique physical and chemical properties. Coarse PM mainly derives from natural sources, including resuspended crustal material, suspended residues from brake pads, tire ware and road usage, sea spray and biological materials (eg, pollen, mold, spores, and other plant parts). Fine PM derives primarily from fuel burning, such as power plants and automobiles. Ultrafine PM also primarily derives from fuel combustion; however, these particles are highly unstable and tend to grow through coagulation and/or condensation after a few hours to form larger complex aggregates. Fine PM tends to travel a longer distance from the source than coarse PM. There is a significant spatial variability in PM concentrations. The inhomogeneous spatial distribution is particularly important for PM from mobile sources. People who live near a busy highway may be exposed to higher concentrations of PM than that shown by the local PM monitor station. PM concentration and composition also show significant seasonal variation.
Q: WHAT ARE THE ADVERSE HEALTH EFFECTS OF AIR POLLUTION? Exposure to air pollution is associated with adverse effects on human health. The following section focuses on PM and O3 that have drawn the most attention because of their impact on cardiopulmonary mortality and morbidity globally. Exposure to other air pollutants, such as CO, NO2 , SO2 , and toxic air pollutants, is also associated with health effects. Interested readers are referred to EPA Web sites for more information (http://www.epa.gov/air/urbanair/; http://www. epa.gov/ttn/atw/3_90_024.html).
PM HEALTH EFFECTS The primary health concerns from exposure to air pollution come from PM, in particular PM2.5. Numerous epidemiological studies have demonstrated an association between PM and adverse cardiopulmonary health effects.6–9 The association is remarkably consistent across the different geographic regions. Although healthy individuals may experience symptoms from exposure to elevated levels of PM, subjects with heart or lung diseases, children and older adults, subjects with certain genetic polymorphism and subjects in low socioeconomic status are particularly susceptible. The EPA has recently updated the health effects associated with PM exposure (http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=216546). Short-term exposure to PM2.5 increases respiratory morbidity that includes respiratory symptoms, decreased pulmonary funcS4
tion, increased medication use, and respiratory-related hospital admissions and emergency department visits for asthma, chronic obstructive pulmonary disease (COPD), and respiratory infection.10–12 The risk is approximately 2.0% to 6.0% per 10 μg/m3 increases in PM2.5 for all respiratory diseases combined as well as COPD admissions.10–12 The excessive risk was also observed in children with asthma. For example, exposure to PM2.5 was associated with severe respiratory symptoms and decreased lung function in asthmatic children, particularly those who were not taking anti-inflammatory medications.13,14 Controlled human exposure studies using adult volunteers have demonstrated increased markers of pulmonary inflammation after exposure to a variety of different particles, including concentrated ambient air pollution particles (PM drawn from ambient air and concentrated by cascade impactor), woodsmoke, and diesel exhaust.15–17 Other acute respiratory effects associated with PM2.5 exposure include desaturation of hemoglobin by oxygen in patients with COPD, oxidative stress, lung function decline, and airway hyper responsiveness in allergic and nonallergic patients.12,18–21 Exposure to PM2.5 also increases cardiovascular morbidity, in particular ischemic heart disease, congestive heart failure, and malignant arrhythmias.6 A recent study that analyzed 57,908 Women’s Health Initiative clinical trial participants from 1999 to 2003 showed a 4% and 5% increase in the odds of ST abnormality and T abnormality, respectively, for each 10-μg/m3 increase in PM2.5 on days 0 to 2.22 The average PM2.5 concentration on days 0 to 2 in this study was 13.9 μg/m3 , well within the current national safety standard for PM2.5. Controlled human exposure studies have demonstrated that acute exposure to PM2.5 induced changes in various measures of cardiovascular functions, including heart rate variability, endothelial dysfunction, and myocardial ischemia, especially in patients with cardiovascular diseases.15,23–25 The strongest effects were found after exposure to diesel exhaust. Whether or not these effects were caused solely by PM2.5 remains unclear because the subjects were also exposed to gaseous copollutants, such as CO and NO2 . Other extrapulmonary effects associated with PM2.5 exposure include systemic oxidative stress, insulin resistance, and hemostasis.18,26 Exposure to PM2.5 increases the risk of mortality from all causes and cardiopulmonary diseases.5,27–29 The risks for cardiovascular and respiratory mortality were approximately 0.60% and 1.68% per 10 μg/m3 increase in PM2.5, respectively. Long-term exposure to PM2.5 also has been linked to adverse perinatal outcomes and lung cancer. It is notable that most of the adverse health effects associated with PM exposure have been seen with cigarette smoking also, indicating the two pollutants may share common pathophysiologic mechanisms. More recently, ultrafine PM has received increased attention because of its large reactive surface area and the putative ability to permeate the alveolar–capillary barrier.30 It has been hypothesized that many of the health effects observed with PM2.5 exposure may be due to its ultrafine fraction. To date, controlled human exposure studies have provided the majority of the evidence for health effects in response to short-term exposure to ultrafine PM, especially to diesel exhaust that typically contains a large number of ultrafine particles. These studies have consistently demonstrated changes after exposure to relatively high concentrations of ultrafine particles in healthy adults as well as patients with cardiopulmonary diseases.15,23 Epidemiological and panel studies found an association between ultrafine particles and hospital admissions for cardiovascular disease, asthma/COPD, subclinical cardiovascular measures (ie, arrhythmias and supraventricular beats), respiratory symptoms, decline in respiratory function, and mortality.31,32 These health effects described by controlled exposure and observational studies were similar to those seen with PM2.5 exposure. There are, however, several factors that make it more difficult to ascertain that these observations are specific to ultrafine PM. National monitoring stations are not in place to measure ultrafine PM. The number concentrations of ultrafine PM are highly spatially variable (eg, concentrations drop off quickly as
C 2014 American College of Occupational and Environmental Medicine
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
JOEM r Volume 56, Number 10S, October 2014
Outdoor Air Pollution
one increases the distance from the road). Therefore, the errors in exposure estimates may be greater. In addition, ultrafine PM tends to form aggregates when inhaled and loses its physical characteristics. Thus, it is unclear whether the effects are due to ultrafine particles themselves, larger particles (ie, PM2.5), or the gaseous components (in diesel exhaust studies). Although there were epidemiological studies showing health effects of PM10 and PM2.5 on mortality and cardiopulmonary morbidity, others failed to substantiate them. One reason for the variability may be that PM10 and PM2.5 are not directly monitored in the national network, and thus ambient concentrations of PM10 and PM2.5 have to be estimated by the subtraction of PM10 and PM2.5 measurements using various methods. The errors introduced by the procedures may lead to a greater uncertainty and misclassification of health effects associated with PM10 and PM2.5. In positive studies, the relative risks associated with PM10 and PM2.5 were similar to those with PM2.5 at concentrations near or below current national standards. The relatively few controlled human exposure studies have observed alterations in heart rate variability and mild pulmonary inflammation in young healthy individuals and older patients with coronary artery disease.33,34
level of O3 below which there are no detrimental health effects. One recent controlled exposure study showed no acute effect at 0.04 ppm but a small FEV1 decrement at 0.06 ppm.46 If true, this indicates that the health effects would continue to be present even at exposure levels below the current EPA standards. Patients with asthma show similar or increased functional and inflammatory airway response to O3 exposure. Repeated exposure to O3 at 0.2 ppm enhanced both FEV1 decrement and sputum eosinophilia to inhaled allergen in subjects with asthma. The O3 response does not seem to correlate with the severity of asthma. The health effects of exposure to O3 on children are of particular concern because their lungs are growing. Studies have linked long-term O3 exposure to increased prevalence of childhood asthma and reduced lung function and increased asthma symptoms in schoolchildren. Patients with COPD did not show excessive sensitivity to acute (1-hour) exposure to low levels O3 up to 0.3 ppm; however, when the exposure is more prolonged (4-hour) combining with exercise, patients with COPD did show FEV1 decrement two to three times greater than that in control subjects. The health effects associated with O3 have recently been updated by the EPA (http://cfpub.epa.gov/ncea/isa/recordisplay.cfm?deid=149923).
O3 HEALTH EFFECTS
Q: WHAT ARE THE METHODS THAT CAN MINIMIZE THE HEALTH IMPACT OF AIR POLLUTION?
Numerous epidemiological studies have reported an association between excessive O3 in the air and respiratory morbidity, primarily hospital admissions and emergency department visits in patients with respiratory diseases during the warm season.35 O3 exposure also is associated with increased mortality, especially from respiratory causes.36–39 A study on 95 large urban communities in the United States showed that a 10-ppb increase in the previous week’s O3 was associated with a 0.52% increase in daily mortality and a 0.64% increase in cardiovascular and respiratory mortality.36 Another recent study estimated that each 10-ppb increase in daily O3 is associated with a 0.87% increase in total mortality.40 Panel studies, which make individual-level exposure assessment feasible, generally confirm the adverse effects of O3 on respiratory symptoms, lung function, and use of asthma medication in individual patients.35,41 In human controlled exposure studies, short-term exposure to O3 at 0.08 ppm or more consistently showed an acute but reversible decrement in lung function, induction of respiratory symptoms (cough, chest pain), and increases in nonspecific airway reactivity.35 The responses are generally accentuated by exercise or increased duration of exposure. The acute pulmonary response has considerable individual variability. About 20% to 50% of the individuals showed a decrement of forced expiratory volume in 1 second (FEV1 ) more than 10% at 0.08 to 0.12 ppm of O3 . The variability decreased at lower O3 concentration. Children and obese subjects tend to have a greater response to O3 .35 Children breathe at a greater respiratory rate and a greater volume of air per body weight than adults. Their airways and alveolar surface are smaller. They also spend more time outdoors engaged in vigorous activities. Therefore, children tend to be exposed to a relative greater dose of O3 in the lung. In addition, the fact that their lung is still developing makes children even more vulnerable to the toxic effects of O3 . The physiological mechanisms underlying the greater responsiveness to O3 in obese individuals are unclear, but a different breathing pattern (more rapid and shallower breathing) that could increase relative O3 dose to lung tissues. An increase in obesityspecific circulating hormones and inflammatory factors (eg, leptin, adiponectin, and plasminogen activator inhibitor) might also play a role. Individuals carrying certain genetic polymorphism may have increased sensitivity to O3 exposure. These genotypes include GSTP1 105Val variant, the HMOX1 long (GT)n repeat, GSTM1-null/NQO1 Pro187Pro-combination genotype, NQO1wt, GSTM1null, and TNF308G/G.42–45 Individuals seem to develop some tolerance in lung function and symptoms to O3 after repeated exposures, but not in the inflammation response. It is unclear whether there is a threshold
Recognition of outdoor air pollution as a significant contributor to respiratory health is important in clinical practice. As described above, exposure to specific air pollutants, such as O3 and PM, may provoke respiratory symptoms and exacerbate existing chronic pulmonary diseases. Long-term exposure to air pollution has also been suggested as a risk factor for incident asthma in both children and adults, the development of COPD, and allergic rhinitis.47–57 Acute and chronic exposure to air pollution may also increase the risk for respiratory infections.58–60 One small cohort study of cystic fibrosis patients demonstrated an increased risk of pulmonary exacerbations with increased levels of O3 , PM2.5, and PM10, and a decrease in FEV1 with increased PM2.5.61 Finally, air pollution has been positively associated with lung cancer in nonsmokers, although direct causation requires further inquiry.62–64 Patients with chronic pulmonary disease, such as asthma and COPD, are more susceptible to the respiratory effects of air pollution. Therefore, it is important to identify these susceptible patients in clinical practice. Monitoring air quality and environmental disasters (eg, forest fires) can be a way for both the physicians and the patients to anticipate potential respiratory complications and adjust medications. The current and forecasted air quality index can be obtained from the EPA Web site (http://www.airnow.gov/). The air quality index uses concentrations of the five criteria pollutants that impact cardiopulmonary health and calculate an index value. The calculated value has a range from 0 to 500. A value less than 100 is generally considered satisfactory air quality for all people; above this, symptoms may occur for sensitive populations initially, followed by greater numbers of the population affected as the index increases. Air quality is also reported on-line, with local weather reports, on the Weather Channel, and in the national newspaper, USA Today.65 It may also be helpful to identify the primary residence and its distance to major roadways, power plants, or other industrial facilities as part of the exposure assessment. This may be particularly important in patients whose respiratory symptoms are poorly controlled or who have frequent exacerbations. Counseling patients with chronic cardiopulmonary diseases about air pollution and the associated risks should be part of the regular management plans. Shofer et al65 recommend an approach that includes the mnemonic AIR (ask, inform, react). Ask patients with chronic respiratory illnesses whether they know air pollution can exacerbate their symptoms, cause acute illness, and even be fatal. Inform patients that general respiratory symptoms such as
C 2014 American College of Occupational and Environmental Medicine
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
S5
JOEM r Volume 56, Number 10S, October 2014
Huang
cough, wheeze, phlegm, shortness of breath, or chest discomfort may be related to air pollution. Educate patients about how to measure air quality using the air quality index and where to find it. Finally, patients should have a plan to react to air quality information. If the air quality level is unhealthy, sensitive patients should avoid prolonged or heavy exertion outdoors. Patients should also carry a short-acting β-agonist rescue inhaler for use should symptoms arise. Dosage of inhaled steroids may be increased preemptively when environmental disasters occur near the patient’ residence. Medication compliance should be reinforced, especially during the high pollution times, in an effort to decrease the exacerbation of symptoms. Corticosteroids should be recommended early if exacerbations are not sufficiently managed by rescue albuterol inhaler or nebulizer at home. Clinicians should also advise their patients not to travel to regions during the time when the air quality is reported to be poor because of winter smog or natural disasters, such as forest fires. People living in or near the areas affected by poor air quality should remain indoors to minimize inhalation of hazardous pollutants (eg, smoke and PM). If one has to be outdoors for a prolonged period, special masks with true HEPA filters would be preferred because ordinary dust masks, which are designed to filter out large particles, will still allow the more dangerous smaller particles to pass through.
REFERENCES 1. Stern AC, Boubel RW, Turner DB, Fox DL. Fundamentals of Air Pollution. Orlando, FL: Academic Press; 1984. 2. Carlsen HK, Gislason T, Benediktsdottir B, et al. A survey of early health effects of the Eyjafjallajokull 2010 eruption in Iceland: a population-based study. BMJ Open. 2012;2:e000343. 3. Carlsen HK, Hauksdottir A, Valdimarsdottir UA, et al. Health effects following the Eyjafjallajokull volcanic eruption: a cohort study. BMJ Open. 2012;2. 4. Oudin A, Carlsen HK, Forsberg B, Johansson C. Volcanic ash and daily mortality in Sweden after the Icelandic volcano eruption of May 2011. Int J Environ Res Public Health. 2013;10:6909–6919. 5. Brunekreef B, Beelen R, Hoek G, et al. Effects of long-term exposure to traffic-related air pollution on respiratory and cardiovascular mortality in the Netherlands: the NLCS-AIR study. Res Rep Health Eff Inst. 2009:5–71; discussion 73–89. 6. Brook RD. Cardiovascular effects of air pollution. Clin Sci (Lond). 2008;115:175–187. 7. Dominici F, McDermott A, Daniels M, Zeger SL, Samet JM. Revised analyses of the National Morbidity, Mortality, and Air Pollution Study: mortality among residents of 90 cities. J Toxicol Environ Health A. 2005;68:1071–1092. 8. Krewski D, Burnett R, Jerrett M, et al. Mortality and long-term exposure to ambient air pollution: ongoing analyses based on the American Cancer Society cohort. J Toxicol Environ Health A. 2005;68:1093–1109. 9. Schulz H, Harder V, Ibald-Mulli A, et al. Cardiovascular effects of fine and ultrafine particles. J Aerosol Med. 2005;18:1–22. 10. Schwartz J, Neas LM. Fine particles are more strongly associated than coarse particles with acute respiratory health effects in schoolchildren. Epidemiology. 2000;11:6–10. 11. Englert N. Fine particles and human health—a review of epidemiological studies. Toxicol Lett. 2004;149:235–242. 12. McCreanor J, Cullinan P, Nieuwenhuijsen MJ, et al. Respiratory effects of exposure to diesel traffic in persons with asthma. N Engl J Med. 2007;357:2348– 2358. 13. Delfino RJ, Zeiger RS, Seltzer JM, Street DH, McLaren CE. Association of asthma symptoms with peak particulate air pollution and effect modification by anti-inflammatory medication use. Environ Health Perspect. 2002;110:A607–617. 14. Liu L, Poon R, Chen L, et al. Acute effects of air pollution on pulmonary function, airway inflammation, and oxidative stress in asthmatic children. Environ Health Perspect. 2009;117:668–674. 15. Ghio AJ, Huang YC. Exposure to concentrated ambient particles (CAPs): a review. Inhal Toxicol. 2004;16:53–59. 16. Nightingale JA, Maggs R, Cullinan P, et al. Airway inflammation after controlled exposure to diesel exhaust particulates. Am J Respir Crit Care Med. 2000;162:161–166.
S6
17. Barregard L, Sallsten G, Andersson L, et al. Experimental exposure to wood smoke: effects on airway inflammation and oxidative stress. Occup Environ Med. 2008;65:319–324. 18. Romieu I, Castro-Giner F, Kunzli N, Sunyer J. Air pollution, oxidative stress and dietary supplementation: a review. Eur Respir J. 2008;31:179–197. 19. Sorensen M, Daneshvar B, Hansen M, et al. Personal PM2.5 exposure and markers of oxidative stress in blood. Environ Health Perspect. 2003;111:161– 166. 20. Wei Y, Han IK, Shao M, Hu M, Zhang OJ, Tang X. PM2.5 constituents and oxidative DNA damage in humans. Environ Sci Technol. 2009;43:4757–4762. 21. Gong H, Jr, Linn WS, Clark KW, Anderson KR, Geller MD, Sioutas C. Respiratory responses to exposures with fine particulates and nitrogen dioxide in the elderly with and without COPD. Inhal Toxicol. 2005;17:123–132. 22. Zhang ZM, Whitsel EA, Quibrera PM, et al. Ambient fine particulate matter exposure and myocardial ischemia in the Environmental Epidemiology of Arrhythmogenesis in the Women’s Health Initiative (EEAWHI) study. Environ Health Perspect. 2009;117:751–756. 23. Huang YC, Ghio AJ. Controlled human exposures to ambient pollutant particles in susceptible populations. Environ Health. 2009;8:33. 24. Huang YC, Ghio AJ. Vascular effects of ambient pollutant particles and metals. Curr Vasc Pharmacol. 2006;4:199–203. 25. Mills NL, Tornqvist H, Gonzalez MC, et al. Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. N Engl J Med. 2007;357:1075–1082. 26. Kelly FJ, Sandstrom T. Air pollution, oxidative stress, and allergic response. Lancet. 2004;363:95–96. 27. Chen H, Goldberg MS, Villeneuve PJ. A systematic review of the relation between long-term exposure to ambient air pollution and chronic diseases. Rev Environ Health. 2008;23:243–297. 28. Krewski D, Jerrett M, Burnett RT, et al. Extended follow-up and spatial analysis of the American Cancer Society study linking particulate air pollution and mortality. Res Rep Health Eff Inst. 2009:5–114; discussion 115–136. 29. Franklin M, Zeka A, Schwartz J. Association between PM2.5 and all-cause and specific-cause mortality in 27 US communities. J Expo Sci Environ Epidemiol. 2007;17:279–287. 30. Frampton MP, Brauer M, Kleeman M, Kreiling WG, Ntziachristos L, Sarnat SE. HEI Review Panel on Ultrafine Particles. Understanding the health effects of ambient ultrafine particles. HEI Perspectives 3. Health Effects Institute, Boston, MA; 2013. 31. Rundell KW, Slee JB, Caviston R, Hollenbach AM. Decreased lung function after inhalation of ultrafine and fine particulate matter during exercise is related to decreased total nitrate in exhaled breath condensate. Inhal Toxicol. 2008;20:1–9. 32. Wichmann HE, Spix C, Tuch T, et al. Daily mortality and fine and ultrafine particles in Erfurt, Germany part I: role of particle number and particle mass. Res Rep Health Eff Inst. 2000:5–86; discussion 87–94. 33. Graff DW, Cascio WE, Rappold A, Zhou H, Huang YC, Devlin RB. Exposure to concentrated coarse air pollution particles causes mild cardiopulmonary effects in healthy young adults. Environ Health Perspect. 2009;117:1089– 1094. 34. Lipsett MJ, Tsai FC, Roger L, Woo M, Ostro BD. Coarse particles and heart rate variability among older adults with coronary artery disease in the Coachella Valley, California. Environ Health Perspect. 2006;114:1215–1220. 35. McClellan RO, Frampton MW, Koutrakis P, et al. Critical considerations in evaluating scientific evidence of health effects of ambient ozone: a conference report. Inhal Toxicol. 2009;21(suppl 2):1–36. 36. Bell ML, McDermott A, Zeger SL, Samet JM, Dominici F. Ozone and short-term mortality in 95 US urban communities, 1987–2000. JAMA. 2004;292:2372–2378. 37. Levy JI, Chemerynski SM, Sarnat JA. Ozone exposure and mortality: an empiric bayes metaregression analysis. Epidemiology. 2005;16:458–468. 38. Jerrett M, Burnett RT, Pope CA, 3rd, et al. Long-term ozone exposure and mortality. N Engl J Med. 2009;360:1085–1095. 39. Samoli E, Zanobetti A, Schwartz J, et al. The temporal pattern of mortality responses to ambient ozone in the APHEA project. J Epidemiol Community Health. 2009;63:960–966. 40. Bell ML, Dominici F, 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. 41. Chan CC, Wu TH. Effects of ambient ozone exposure on mail carriers’ peak expiratory flow rates. Environ Health Perspect. 2005;113:735–738. 42. Alexeeff SE, Litonjua AA, Wright RO, et al. Ozone exposure, antioxidant genes, and lung function in an elderly cohort: VA normative aging study. Occup Environ Med. 2008;65:736–742.
C 2014 American College of Occupational and Environmental Medicine
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
JOEM r Volume 56, Number 10S, October 2014
43. Chen C, Arjomandi M, Tager IB, Holland N, Balmes JR. Effects of antioxidant enzyme polymorphisms on ozone-induced lung function changes. Eur Respir J. 2007;30:677–683. 44. Bergamaschi E, De Palma G, Mozzoni P, et al. Polymorphism of quinonemetabolizing enzymes and susceptibility to ozone-induced acute effects. Am J Respir Crit Care Med. 2001;163:1426–1431. 45. Yang IA, Fong KM, Zimmerman PV, Holgate ST, Holloway JW. Genetic susceptibility to the respiratory effects of air pollution. Thorax. 2008;63:555– 563. 46. Adams WC. Comparison of chamber 6.6-h exposures to 0.04–0.08 PPM ozone via square-wave and triangular profiles on pulmonary responses. Inhal Toxicol. 2006;18:127–136. 47. Brauer M, Hoek G, Smit HA, et al. Air pollution and development of asthma, allergy and infections in a birth cohort. Eur Respir J. 2007;29:879–888. 48. Morgenstern V, Zutavern A, Cyrys J, et al. Atopic diseases, allergic sensitization, and exposure to traffic-related air pollution in children. Am J Respir Crit Care Med. 2008;177:1331–1337. 49. Nordling E, Berglind N, Melen E, et al. Traffic-related air pollution and childhood respiratory symptoms, function and allergies. Epidemiology. 2008;19:401–408. 50. Gehring U, Wijga AH, Brauer M, et al. Traffic-related air pollution and the development of asthma and allergies during the first 8 years of life. Am J Respir Crit Care Med. 2010;181:596–603. 51. McConnell R, Berhane K, Gilliland F, et al. Asthma in exercising children exposed to ozone: a cohort study. Lancet. 2002;359:386–391. 52. Gauderman WJ, Avol E, Gilliland F, et al. The effect of air pollution on lung development from 10 to 18 years of age. N Engl J Med. 2004;351:1057–1067. 53. McConnell R, Islam T, Shankardass K, et al. Childhood incident asthma and traffic-related air pollution at home and school. Environ Health Perspect. 2010;118:1021–1026. 54. Kunzli N, Bridevaux PO, Liu LJ, et al. Traffic-related air pollution correlates with adult-onset asthma among never-smokers. Thorax. 2009;64:664–670.
Outdoor Air Pollution
55. Modig L, Jarvholm B, Ronnmark E, et al. Vehicle exhaust exposure in an incident case-control study of adult asthma. Eur Respir J. 2006;28:75–81. 56. Modig L, Toren K, Janson C, Jarvholm B, Forsberg B. Vehicle exhaust outside the home and onset of asthma among adults. Eur Respir J. 2009;33:1261– 1267. 57. Andersen ZJ, Hvidberg M, Jensen SS, et al. Chronic obstructive pulmonary disease and long-term exposure to traffic-related air pollution: a cohort study. Am J Respir Crit Care Med. 2011;183:455–461. 58. Dockery DW, Speizer FE, Stram DO, Ware JH, Spengler JD, Ferris BG, Jr. Effects of inhalable particles on respiratory health of children. Am Rev Respir Dis. 1989;139:587–594. 59. Schwartz J. PM10, ozone, and hospital admissions for the elderly in Minneapolis-St. Paul, Minnesota. Arch Environ Health. 1994;49:366– 374. 60. Wong TW, Lau TS, Yu TS, et al. Air pollution and hospital admissions for respiratory and cardiovascular diseases in Hong Kong. Occup Environ Med. 1999;56:679–683. 61. Goss CH, Newsom SA, Schildcrout JS, Sheppard L, Kaufman JD. Effect of ambient air pollution on pulmonary exacerbations and lung function in cystic fibrosis. Am J Respir Crit Care Med. 2004;169:816–821. 62. Pope CA, 3rd, Burnett RT, Turner MC, et al. Lung cancer and cardiovascular disease mortality associated with ambient air pollution and cigarette smoke: shape of the exposure-response relationships. Environ Health Perspect. 2011;119:1616–1621. 63. Villeneuve PJ, Parent ME, Sahni V, Johnson KC. Occupational exposure to diesel and gasoline emissions and lung cancer in Canadian men. Environ Res. 2011;111:727–735. 64. Katanoda K, Sobue T, Satoh H, et al. An association between long-term exposure to ambient air pollution and mortality from lung cancer and respiratory diseases in Japan. J Epidemiol. 2011;21:132–143. 65. Shofer S, Chen TM, Gokhale J, Kuschner WG. Outdoor air pollution: counseling and exposure risk reduction. Am J Med Sci. 2007;333:257–260.
C 2014 American College of Occupational and Environmental Medicine
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
S7
Outdoor Air Pollution A Global Perspective Yuh-Chin T. Huang, MD, MHS
Although the air quality in Western countries has continued to improve over the past decades, rapid economic growth in developing countries has left air quality in many cities notoriously poor. The World Health Organization estimates that urban outdoor air pollution is estimated to cause 1.3 million deaths worldwide per year. The primary health concerns of outdoor air pollution come from particulate matter less than 2.5 μm (PM2.5) and ozone (O3 ). Short-term exposure to PM2.5 increases cardiopulmonary morbidity and mortality. Long-term exposure to PM2.5 has been linked to adverse perinatal outcomes and lung cancer. Excessive O3 exposure is known to increase respiratory morbidity. Patients with chronic cardiopulmonary diseases are more susceptible to the adverse effects of air pollution. Counseling these patients about air pollution and the associated risks should be part of the regular management plans in clinical practice.
A
ir pollution is a global problem. The World Health Organization recently estimated that, in 2012, approximately 3.7 million people died as a result of exposure to ambient air pollution (http: //www.who.int/phe/health topics/outdoorair/databases/en/). Worldwide ambient air pollution contributes to 6.7% of all deaths. Lowand middle-income countries in the Southeast Asia and Western Pacific regions where the air pollution is most severe had the largest air pollution-related disease burden. The disease burden remains significant even in the developed countries where the levels of air pollutants are generally much lower because of the constant exposure of the large number of people to the air pollutants (http: //www.who.int/gho/phe/outdoor air pollution/burden/en/). This review discusses the global burden of air pollution and focuses on the health effects associated with two most prevalent air pollutants, ozone (O3 ) and particulate matter (PM). The review is intended for clinicians and anyone who is interested in the clinical aspect of air pollution.
Q: WHAT IS THE GLOBAL BURDEN OF AIR POLLUTION? Urban air pollution was first noted in AD 1272 by King Edward I who described a coal smoke event.1 Both Greek and Roman societies noted that air pollution was a potential source of health problems. After industrialization in the late nineteenth century, many severe air pollution episodes were documented. These episodes had been attributed to coal burning and were associated with a major increase in mortality and morbidity, including the notorious London smog of 1952, which resulted in more than 4000 deaths. Efforts to reduce air pollution ensued in the 1960s and 1970s, which led to a marked improvement in air quality in Western countries. Despite these efforts, new epidemiological studies in the 1980s and 1990s
From the Department of Medicine, Duke University Medical Center, Durham, NC. The author declares no conflict of interest. Address correspondence to: Yuh-Chin T. Huang, MD, MHS, Department of Medicine, Duke University Medical Center, 1821 Hillandale Rd, Suite 25A, Durham, NC 27705 ([email protected]). C 2014 by American College of Occupational and Environmental Copyright Medicine DOI: 10.1097/JOM.0000000000000240
using time series analysis continued to show associations between adverse health effects and particulate matter less than 2.5 μm (PM2.5) at levels much lower than those encountered in earlier air pollution disasters, and in some studies at concentrations near or below the national standards. Currently, there is no evidence of a safe level of exposure or a threshold for PM2.5 below which no adverse health effects occur. Although the air quality in Western countries has continued to improve, in developing countries, rapid economic growth over the past decades has left air quality in many cities notoriously poor. For example, in January 2013, heavy smog smothered Beijing, China, for many days. “The air tasted of coal dust and car fumes” (http: //www.bbc.com/news/world-asia-china-20998147). The smog was so thick that one could only see a few hundred meters in the city center in the afternoon. The PM2.5 level was more than 400 μg/m3 (http: //www.bbc.co.uk/news/world-asia-china-20998147). Natural disasters, such as forest fires and volcanic eruptions, also contributed to poor air quality. For example, in June 2013, forest fires in Riau, Indonesia, caused thick haze in the neighboring countries. Malaysia declared a state of emergency whereas Singapore urged people to remain indoors due to “hazardous” levels of pollution. Sudden eruption of the Icelandic volcano, Eyjafjallaj¨okull, in April 2010 disrupted air travel across western and northern Europe for a week. Recent studies have shown increased symptoms of upper airway irritation and exacerbation of preexisting asthma for residents in the exposed area,2,3 although the effects on mortality are inconclusive.4 With global warming, it is predicted that natural disasters such as forest fires will occur with increasing frequency. Although the relative risk for air pollution-related health effects tends to be low, the attributable risk is significant because of the large population exposed to air pollutants. According to the World Health Organization, urban outdoor air pollution is estimated to cause 1.3 million deaths worldwide per year. Worldwide, outdoor air pollution contributes to 5% of all cardiopulmonary deaths (http://www.who.int/gho/phe/outdoor air pollution/en/index.html). Exposure to air pollution depends upon many variables. Ambient concentrations of pollutants are affected by seasonal and meteorological conditions (eg, hot, dry air increases O3 production). The concentrations of air pollutants also have significant spatial and geographic variations. Proximity to a source of emissions (eg, power plant, major road, or highway), as well as time-activity patterns, will influence exposure to pollution. The level of some air pollutants near a busy highway may be several times higher than those measured by a monitor station located away from the road. There is a strong association between the traffic intensity near a home and cardiorespiratory mortality with relative risks of 1.05 to 1.10.5 In the United States, approximately 16% of the housing units (approximately 48 million people, mostly nonwhite and economically disadvantaged) are located within 300 ft of a major highway, railroad, or airport. With urbanization globally, the near-road air pollution has and will become a major public health issue.
Q: WHAT IS AIR POLLUTION? Air pollution is a complex mixture of particles and gases that originate from both anthropogenic (eg, combustion of fossil fuels) and natural (eg, soil resuspension) sources, with secondary
JOEM r Volume 56, Number 10S, October 2014 Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
S3
JOEM r Volume 56, Number 10S, October 2014
Huang
physicochemical modifications in the atmosphere. Primary air pollutants include particulate patter (PM) and nitrogen oxides (NOx), whereas secondary air pollutants include O3 . In an urban environment, outdoor air pollutants are generated primarily by emissions from sources, such as large stationary fuel combustion sources (eg, electric utility plants), industrial emissions (eg, smelters and oil refineries), and transportation modalities (eg, automobiles, aircraft, and locomotives). Particulate matter is a mixture of sulfate, nitrate, elemental (black) carbon, organic carbon, and crustal material. It also contains metals in the forms of oxides and soluble salts. The specific composition and relative abundance of these constituents depend on the sources and vary from place to place. For example, PM from combustion of fossil fuel contains a large amount of soluble transition metals. This is in contrast with PM derived from soil, (eg, Mount St Helen dust), which has almost no metals. The US Environmental Protection Agency (EPA) has set standards for six air pollutants that are associated with health effects, called criteria pollutants, including ground level O3 , PM, lead, NO2 , CO, and SO2 (http://www .epa.gov/air/criteria.html). Ambient PM is commonly categorized by size fraction on the basis of its mass median aerodynamic diameter (MMAD). Coarse PM has MMAD between 2.5 and 10 μm (PM10 and PM2.5) and fine PM has MMAD less than 2.5 μm (PM2.5). The ultrafine PM (particles with MMAD ≤0.1 μm) is a subset of fine PM. Each size fraction possesses unique physical and chemical properties. Coarse PM mainly derives from natural sources, including resuspended crustal material, suspended residues from brake pads, tire ware and road usage, sea spray and biological materials (eg, pollen, mold, spores, and other plant parts). Fine PM derives primarily from fuel burning, such as power plants and automobiles. Ultrafine PM also primarily derives from fuel combustion; however, these particles are highly unstable and tend to grow through coagulation and/or condensation after a few hours to form larger complex aggregates. Fine PM tends to travel a longer distance from the source than coarse PM. There is a significant spatial variability in PM concentrations. The inhomogeneous spatial distribution is particularly important for PM from mobile sources. People who live near a busy highway may be exposed to higher concentrations of PM than that shown by the local PM monitor station. PM concentration and composition also show significant seasonal variation.
Q: WHAT ARE THE ADVERSE HEALTH EFFECTS OF AIR POLLUTION? Exposure to air pollution is associated with adverse effects on human health. The following section focuses on PM and O3 that have drawn the most attention because of their impact on cardiopulmonary mortality and morbidity globally. Exposure to other air pollutants, such as CO, NO2 , SO2 , and toxic air pollutants, is also associated with health effects. Interested readers are referred to EPA Web sites for more information (http://www.epa.gov/air/urbanair/; http://www. epa.gov/ttn/atw/3_90_024.html).
PM HEALTH EFFECTS The primary health concerns from exposure to air pollution come from PM, in particular PM2.5. Numerous epidemiological studies have demonstrated an association between PM and adverse cardiopulmonary health effects.6–9 The association is remarkably consistent across the different geographic regions. Although healthy individuals may experience symptoms from exposure to elevated levels of PM, subjects with heart or lung diseases, children and older adults, subjects with certain genetic polymorphism and subjects in low socioeconomic status are particularly susceptible. The EPA has recently updated the health effects associated with PM exposure (http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=216546). Short-term exposure to PM2.5 increases respiratory morbidity that includes respiratory symptoms, decreased pulmonary funcS4
tion, increased medication use, and respiratory-related hospital admissions and emergency department visits for asthma, chronic obstructive pulmonary disease (COPD), and respiratory infection.10–12 The risk is approximately 2.0% to 6.0% per 10 μg/m3 increases in PM2.5 for all respiratory diseases combined as well as COPD admissions.10–12 The excessive risk was also observed in children with asthma. For example, exposure to PM2.5 was associated with severe respiratory symptoms and decreased lung function in asthmatic children, particularly those who were not taking anti-inflammatory medications.13,14 Controlled human exposure studies using adult volunteers have demonstrated increased markers of pulmonary inflammation after exposure to a variety of different particles, including concentrated ambient air pollution particles (PM drawn from ambient air and concentrated by cascade impactor), woodsmoke, and diesel exhaust.15–17 Other acute respiratory effects associated with PM2.5 exposure include desaturation of hemoglobin by oxygen in patients with COPD, oxidative stress, lung function decline, and airway hyper responsiveness in allergic and nonallergic patients.12,18–21 Exposure to PM2.5 also increases cardiovascular morbidity, in particular ischemic heart disease, congestive heart failure, and malignant arrhythmias.6 A recent study that analyzed 57,908 Women’s Health Initiative clinical trial participants from 1999 to 2003 showed a 4% and 5% increase in the odds of ST abnormality and T abnormality, respectively, for each 10-μg/m3 increase in PM2.5 on days 0 to 2.22 The average PM2.5 concentration on days 0 to 2 in this study was 13.9 μg/m3 , well within the current national safety standard for PM2.5. Controlled human exposure studies have demonstrated that acute exposure to PM2.5 induced changes in various measures of cardiovascular functions, including heart rate variability, endothelial dysfunction, and myocardial ischemia, especially in patients with cardiovascular diseases.15,23–25 The strongest effects were found after exposure to diesel exhaust. Whether or not these effects were caused solely by PM2.5 remains unclear because the subjects were also exposed to gaseous copollutants, such as CO and NO2 . Other extrapulmonary effects associated with PM2.5 exposure include systemic oxidative stress, insulin resistance, and hemostasis.18,26 Exposure to PM2.5 increases the risk of mortality from all causes and cardiopulmonary diseases.5,27–29 The risks for cardiovascular and respiratory mortality were approximately 0.60% and 1.68% per 10 μg/m3 increase in PM2.5, respectively. Long-term exposure to PM2.5 also has been linked to adverse perinatal outcomes and lung cancer. It is notable that most of the adverse health effects associated with PM exposure have been seen with cigarette smoking also, indicating the two pollutants may share common pathophysiologic mechanisms. More recently, ultrafine PM has received increased attention because of its large reactive surface area and the putative ability to permeate the alveolar–capillary barrier.30 It has been hypothesized that many of the health effects observed with PM2.5 exposure may be due to its ultrafine fraction. To date, controlled human exposure studies have provided the majority of the evidence for health effects in response to short-term exposure to ultrafine PM, especially to diesel exhaust that typically contains a large number of ultrafine particles. These studies have consistently demonstrated changes after exposure to relatively high concentrations of ultrafine particles in healthy adults as well as patients with cardiopulmonary diseases.15,23 Epidemiological and panel studies found an association between ultrafine particles and hospital admissions for cardiovascular disease, asthma/COPD, subclinical cardiovascular measures (ie, arrhythmias and supraventricular beats), respiratory symptoms, decline in respiratory function, and mortality.31,32 These health effects described by controlled exposure and observational studies were similar to those seen with PM2.5 exposure. There are, however, several factors that make it more difficult to ascertain that these observations are specific to ultrafine PM. National monitoring stations are not in place to measure ultrafine PM. The number concentrations of ultrafine PM are highly spatially variable (eg, concentrations drop off quickly as
C 2014 American College of Occupational and Environmental Medicine
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
JOEM r Volume 56, Number 10S, October 2014
Outdoor Air Pollution
one increases the distance from the road). Therefore, the errors in exposure estimates may be greater. In addition, ultrafine PM tends to form aggregates when inhaled and loses its physical characteristics. Thus, it is unclear whether the effects are due to ultrafine particles themselves, larger particles (ie, PM2.5), or the gaseous components (in diesel exhaust studies). Although there were epidemiological studies showing health effects of PM10 and PM2.5 on mortality and cardiopulmonary morbidity, others failed to substantiate them. One reason for the variability may be that PM10 and PM2.5 are not directly monitored in the national network, and thus ambient concentrations of PM10 and PM2.5 have to be estimated by the subtraction of PM10 and PM2.5 measurements using various methods. The errors introduced by the procedures may lead to a greater uncertainty and misclassification of health effects associated with PM10 and PM2.5. In positive studies, the relative risks associated with PM10 and PM2.5 were similar to those with PM2.5 at concentrations near or below current national standards. The relatively few controlled human exposure studies have observed alterations in heart rate variability and mild pulmonary inflammation in young healthy individuals and older patients with coronary artery disease.33,34
level of O3 below which there are no detrimental health effects. One recent controlled exposure study showed no acute effect at 0.04 ppm but a small FEV1 decrement at 0.06 ppm.46 If true, this indicates that the health effects would continue to be present even at exposure levels below the current EPA standards. Patients with asthma show similar or increased functional and inflammatory airway response to O3 exposure. Repeated exposure to O3 at 0.2 ppm enhanced both FEV1 decrement and sputum eosinophilia to inhaled allergen in subjects with asthma. The O3 response does not seem to correlate with the severity of asthma. The health effects of exposure to O3 on children are of particular concern because their lungs are growing. Studies have linked long-term O3 exposure to increased prevalence of childhood asthma and reduced lung function and increased asthma symptoms in schoolchildren. Patients with COPD did not show excessive sensitivity to acute (1-hour) exposure to low levels O3 up to 0.3 ppm; however, when the exposure is more prolonged (4-hour) combining with exercise, patients with COPD did show FEV1 decrement two to three times greater than that in control subjects. The health effects associated with O3 have recently been updated by the EPA (http://cfpub.epa.gov/ncea/isa/recordisplay.cfm?deid=149923).
O3 HEALTH EFFECTS
Q: WHAT ARE THE METHODS THAT CAN MINIMIZE THE HEALTH IMPACT OF AIR POLLUTION?
Numerous epidemiological studies have reported an association between excessive O3 in the air and respiratory morbidity, primarily hospital admissions and emergency department visits in patients with respiratory diseases during the warm season.35 O3 exposure also is associated with increased mortality, especially from respiratory causes.36–39 A study on 95 large urban communities in the United States showed that a 10-ppb increase in the previous week’s O3 was associated with a 0.52% increase in daily mortality and a 0.64% increase in cardiovascular and respiratory mortality.36 Another recent study estimated that each 10-ppb increase in daily O3 is associated with a 0.87% increase in total mortality.40 Panel studies, which make individual-level exposure assessment feasible, generally confirm the adverse effects of O3 on respiratory symptoms, lung function, and use of asthma medication in individual patients.35,41 In human controlled exposure studies, short-term exposure to O3 at 0.08 ppm or more consistently showed an acute but reversible decrement in lung function, induction of respiratory symptoms (cough, chest pain), and increases in nonspecific airway reactivity.35 The responses are generally accentuated by exercise or increased duration of exposure. The acute pulmonary response has considerable individual variability. About 20% to 50% of the individuals showed a decrement of forced expiratory volume in 1 second (FEV1 ) more than 10% at 0.08 to 0.12 ppm of O3 . The variability decreased at lower O3 concentration. Children and obese subjects tend to have a greater response to O3 .35 Children breathe at a greater respiratory rate and a greater volume of air per body weight than adults. Their airways and alveolar surface are smaller. They also spend more time outdoors engaged in vigorous activities. Therefore, children tend to be exposed to a relative greater dose of O3 in the lung. In addition, the fact that their lung is still developing makes children even more vulnerable to the toxic effects of O3 . The physiological mechanisms underlying the greater responsiveness to O3 in obese individuals are unclear, but a different breathing pattern (more rapid and shallower breathing) that could increase relative O3 dose to lung tissues. An increase in obesityspecific circulating hormones and inflammatory factors (eg, leptin, adiponectin, and plasminogen activator inhibitor) might also play a role. Individuals carrying certain genetic polymorphism may have increased sensitivity to O3 exposure. These genotypes include GSTP1 105Val variant, the HMOX1 long (GT)n repeat, GSTM1-null/NQO1 Pro187Pro-combination genotype, NQO1wt, GSTM1null, and TNF308G/G.42–45 Individuals seem to develop some tolerance in lung function and symptoms to O3 after repeated exposures, but not in the inflammation response. It is unclear whether there is a threshold
Recognition of outdoor air pollution as a significant contributor to respiratory health is important in clinical practice. As described above, exposure to specific air pollutants, such as O3 and PM, may provoke respiratory symptoms and exacerbate existing chronic pulmonary diseases. Long-term exposure to air pollution has also been suggested as a risk factor for incident asthma in both children and adults, the development of COPD, and allergic rhinitis.47–57 Acute and chronic exposure to air pollution may also increase the risk for respiratory infections.58–60 One small cohort study of cystic fibrosis patients demonstrated an increased risk of pulmonary exacerbations with increased levels of O3 , PM2.5, and PM10, and a decrease in FEV1 with increased PM2.5.61 Finally, air pollution has been positively associated with lung cancer in nonsmokers, although direct causation requires further inquiry.62–64 Patients with chronic pulmonary disease, such as asthma and COPD, are more susceptible to the respiratory effects of air pollution. Therefore, it is important to identify these susceptible patients in clinical practice. Monitoring air quality and environmental disasters (eg, forest fires) can be a way for both the physicians and the patients to anticipate potential respiratory complications and adjust medications. The current and forecasted air quality index can be obtained from the EPA Web site (http://www.airnow.gov/). The air quality index uses concentrations of the five criteria pollutants that impact cardiopulmonary health and calculate an index value. The calculated value has a range from 0 to 500. A value less than 100 is generally considered satisfactory air quality for all people; above this, symptoms may occur for sensitive populations initially, followed by greater numbers of the population affected as the index increases. Air quality is also reported on-line, with local weather reports, on the Weather Channel, and in the national newspaper, USA Today.65 It may also be helpful to identify the primary residence and its distance to major roadways, power plants, or other industrial facilities as part of the exposure assessment. This may be particularly important in patients whose respiratory symptoms are poorly controlled or who have frequent exacerbations. Counseling patients with chronic cardiopulmonary diseases about air pollution and the associated risks should be part of the regular management plans. Shofer et al65 recommend an approach that includes the mnemonic AIR (ask, inform, react). Ask patients with chronic respiratory illnesses whether they know air pollution can exacerbate their symptoms, cause acute illness, and even be fatal. Inform patients that general respiratory symptoms such as
C 2014 American College of Occupational and Environmental Medicine
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
S5
JOEM r Volume 56, Number 10S, October 2014
Huang
cough, wheeze, phlegm, shortness of breath, or chest discomfort may be related to air pollution. Educate patients about how to measure air quality using the air quality index and where to find it. Finally, patients should have a plan to react to air quality information. If the air quality level is unhealthy, sensitive patients should avoid prolonged or heavy exertion outdoors. Patients should also carry a short-acting β-agonist rescue inhaler for use should symptoms arise. Dosage of inhaled steroids may be increased preemptively when environmental disasters occur near the patient’ residence. Medication compliance should be reinforced, especially during the high pollution times, in an effort to decrease the exacerbation of symptoms. Corticosteroids should be recommended early if exacerbations are not sufficiently managed by rescue albuterol inhaler or nebulizer at home. Clinicians should also advise their patients not to travel to regions during the time when the air quality is reported to be poor because of winter smog or natural disasters, such as forest fires. People living in or near the areas affected by poor air quality should remain indoors to minimize inhalation of hazardous pollutants (eg, smoke and PM). If one has to be outdoors for a prolonged period, special masks with true HEPA filters would be preferred because ordinary dust masks, which are designed to filter out large particles, will still allow the more dangerous smaller particles to pass through.
REFERENCES 1. Stern AC, Boubel RW, Turner DB, Fox DL. Fundamentals of Air Pollution. Orlando, FL: Academic Press; 1984. 2. Carlsen HK, Gislason T, Benediktsdottir B, et al. A survey of early health effects of the Eyjafjallajokull 2010 eruption in Iceland: a population-based study. BMJ Open. 2012;2:e000343. 3. Carlsen HK, Hauksdottir A, Valdimarsdottir UA, et al. Health effects following the Eyjafjallajokull volcanic eruption: a cohort study. BMJ Open. 2012;2. 4. Oudin A, Carlsen HK, Forsberg B, Johansson C. Volcanic ash and daily mortality in Sweden after the Icelandic volcano eruption of May 2011. Int J Environ Res Public Health. 2013;10:6909–6919. 5. Brunekreef B, Beelen R, Hoek G, et al. Effects of long-term exposure to traffic-related air pollution on respiratory and cardiovascular mortality in the Netherlands: the NLCS-AIR study. Res Rep Health Eff Inst. 2009:5–71; discussion 73–89. 6. Brook RD. Cardiovascular effects of air pollution. Clin Sci (Lond). 2008;115:175–187. 7. Dominici F, McDermott A, Daniels M, Zeger SL, Samet JM. Revised analyses of the National Morbidity, Mortality, and Air Pollution Study: mortality among residents of 90 cities. J Toxicol Environ Health A. 2005;68:1071–1092. 8. Krewski D, Burnett R, Jerrett M, et al. Mortality and long-term exposure to ambient air pollution: ongoing analyses based on the American Cancer Society cohort. J Toxicol Environ Health A. 2005;68:1093–1109. 9. Schulz H, Harder V, Ibald-Mulli A, et al. Cardiovascular effects of fine and ultrafine particles. J Aerosol Med. 2005;18:1–22. 10. Schwartz J, Neas LM. Fine particles are more strongly associated than coarse particles with acute respiratory health effects in schoolchildren. Epidemiology. 2000;11:6–10. 11. Englert N. Fine particles and human health—a review of epidemiological studies. Toxicol Lett. 2004;149:235–242. 12. McCreanor J, Cullinan P, Nieuwenhuijsen MJ, et al. Respiratory effects of exposure to diesel traffic in persons with asthma. N Engl J Med. 2007;357:2348– 2358. 13. Delfino RJ, Zeiger RS, Seltzer JM, Street DH, McLaren CE. Association of asthma symptoms with peak particulate air pollution and effect modification by anti-inflammatory medication use. Environ Health Perspect. 2002;110:A607–617. 14. Liu L, Poon R, Chen L, et al. Acute effects of air pollution on pulmonary function, airway inflammation, and oxidative stress in asthmatic children. Environ Health Perspect. 2009;117:668–674. 15. Ghio AJ, Huang YC. Exposure to concentrated ambient particles (CAPs): a review. Inhal Toxicol. 2004;16:53–59. 16. Nightingale JA, Maggs R, Cullinan P, et al. Airway inflammation after controlled exposure to diesel exhaust particulates. Am J Respir Crit Care Med. 2000;162:161–166.
S6
17. Barregard L, Sallsten G, Andersson L, et al. Experimental exposure to wood smoke: effects on airway inflammation and oxidative stress. Occup Environ Med. 2008;65:319–324. 18. Romieu I, Castro-Giner F, Kunzli N, Sunyer J. Air pollution, oxidative stress and dietary supplementation: a review. Eur Respir J. 2008;31:179–197. 19. Sorensen M, Daneshvar B, Hansen M, et al. Personal PM2.5 exposure and markers of oxidative stress in blood. Environ Health Perspect. 2003;111:161– 166. 20. Wei Y, Han IK, Shao M, Hu M, Zhang OJ, Tang X. PM2.5 constituents and oxidative DNA damage in humans. Environ Sci Technol. 2009;43:4757–4762. 21. Gong H, Jr, Linn WS, Clark KW, Anderson KR, Geller MD, Sioutas C. Respiratory responses to exposures with fine particulates and nitrogen dioxide in the elderly with and without COPD. Inhal Toxicol. 2005;17:123–132. 22. Zhang ZM, Whitsel EA, Quibrera PM, et al. Ambient fine particulate matter exposure and myocardial ischemia in the Environmental Epidemiology of Arrhythmogenesis in the Women’s Health Initiative (EEAWHI) study. Environ Health Perspect. 2009;117:751–756. 23. Huang YC, Ghio AJ. Controlled human exposures to ambient pollutant particles in susceptible populations. Environ Health. 2009;8:33. 24. Huang YC, Ghio AJ. Vascular effects of ambient pollutant particles and metals. Curr Vasc Pharmacol. 2006;4:199–203. 25. Mills NL, Tornqvist H, Gonzalez MC, et al. Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. N Engl J Med. 2007;357:1075–1082. 26. Kelly FJ, Sandstrom T. Air pollution, oxidative stress, and allergic response. Lancet. 2004;363:95–96. 27. Chen H, Goldberg MS, Villeneuve PJ. A systematic review of the relation between long-term exposure to ambient air pollution and chronic diseases. Rev Environ Health. 2008;23:243–297. 28. Krewski D, Jerrett M, Burnett RT, et al. Extended follow-up and spatial analysis of the American Cancer Society study linking particulate air pollution and mortality. Res Rep Health Eff Inst. 2009:5–114; discussion 115–136. 29. Franklin M, Zeka A, Schwartz J. Association between PM2.5 and all-cause and specific-cause mortality in 27 US communities. J Expo Sci Environ Epidemiol. 2007;17:279–287. 30. Frampton MP, Brauer M, Kleeman M, Kreiling WG, Ntziachristos L, Sarnat SE. HEI Review Panel on Ultrafine Particles. Understanding the health effects of ambient ultrafine particles. HEI Perspectives 3. Health Effects Institute, Boston, MA; 2013. 31. Rundell KW, Slee JB, Caviston R, Hollenbach AM. Decreased lung function after inhalation of ultrafine and fine particulate matter during exercise is related to decreased total nitrate in exhaled breath condensate. Inhal Toxicol. 2008;20:1–9. 32. Wichmann HE, Spix C, Tuch T, et al. Daily mortality and fine and ultrafine particles in Erfurt, Germany part I: role of particle number and particle mass. Res Rep Health Eff Inst. 2000:5–86; discussion 87–94. 33. Graff DW, Cascio WE, Rappold A, Zhou H, Huang YC, Devlin RB. Exposure to concentrated coarse air pollution particles causes mild cardiopulmonary effects in healthy young adults. Environ Health Perspect. 2009;117:1089– 1094. 34. Lipsett MJ, Tsai FC, Roger L, Woo M, Ostro BD. Coarse particles and heart rate variability among older adults with coronary artery disease in the Coachella Valley, California. Environ Health Perspect. 2006;114:1215–1220. 35. McClellan RO, Frampton MW, Koutrakis P, et al. Critical considerations in evaluating scientific evidence of health effects of ambient ozone: a conference report. Inhal Toxicol. 2009;21(suppl 2):1–36. 36. Bell ML, McDermott A, Zeger SL, Samet JM, Dominici F. Ozone and short-term mortality in 95 US urban communities, 1987–2000. JAMA. 2004;292:2372–2378. 37. Levy JI, Chemerynski SM, Sarnat JA. Ozone exposure and mortality: an empiric bayes metaregression analysis. Epidemiology. 2005;16:458–468. 38. Jerrett M, Burnett RT, Pope CA, 3rd, et al. Long-term ozone exposure and mortality. N Engl J Med. 2009;360:1085–1095. 39. Samoli E, Zanobetti A, Schwartz J, et al. The temporal pattern of mortality responses to ambient ozone in the APHEA project. J Epidemiol Community Health. 2009;63:960–966. 40. Bell ML, Dominici F, 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. 41. Chan CC, Wu TH. Effects of ambient ozone exposure on mail carriers’ peak expiratory flow rates. Environ Health Perspect. 2005;113:735–738. 42. Alexeeff SE, Litonjua AA, Wright RO, et al. Ozone exposure, antioxidant genes, and lung function in an elderly cohort: VA normative aging study. Occup Environ Med. 2008;65:736–742.
C 2014 American College of Occupational and Environmental Medicine
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
JOEM r Volume 56, Number 10S, October 2014
43. Chen C, Arjomandi M, Tager IB, Holland N, Balmes JR. Effects of antioxidant enzyme polymorphisms on ozone-induced lung function changes. Eur Respir J. 2007;30:677–683. 44. Bergamaschi E, De Palma G, Mozzoni P, et al. Polymorphism of quinonemetabolizing enzymes and susceptibility to ozone-induced acute effects. Am J Respir Crit Care Med. 2001;163:1426–1431. 45. Yang IA, Fong KM, Zimmerman PV, Holgate ST, Holloway JW. Genetic susceptibility to the respiratory effects of air pollution. Thorax. 2008;63:555– 563. 46. Adams WC. Comparison of chamber 6.6-h exposures to 0.04–0.08 PPM ozone via square-wave and triangular profiles on pulmonary responses. Inhal Toxicol. 2006;18:127–136. 47. Brauer M, Hoek G, Smit HA, et al. Air pollution and development of asthma, allergy and infections in a birth cohort. Eur Respir J. 2007;29:879–888. 48. Morgenstern V, Zutavern A, Cyrys J, et al. Atopic diseases, allergic sensitization, and exposure to traffic-related air pollution in children. Am J Respir Crit Care Med. 2008;177:1331–1337. 49. Nordling E, Berglind N, Melen E, et al. Traffic-related air pollution and childhood respiratory symptoms, function and allergies. Epidemiology. 2008;19:401–408. 50. Gehring U, Wijga AH, Brauer M, et al. Traffic-related air pollution and the development of asthma and allergies during the first 8 years of life. Am J Respir Crit Care Med. 2010;181:596–603. 51. McConnell R, Berhane K, Gilliland F, et al. Asthma in exercising children exposed to ozone: a cohort study. Lancet. 2002;359:386–391. 52. Gauderman WJ, Avol E, Gilliland F, et al. The effect of air pollution on lung development from 10 to 18 years of age. N Engl J Med. 2004;351:1057–1067. 53. McConnell R, Islam T, Shankardass K, et al. Childhood incident asthma and traffic-related air pollution at home and school. Environ Health Perspect. 2010;118:1021–1026. 54. Kunzli N, Bridevaux PO, Liu LJ, et al. Traffic-related air pollution correlates with adult-onset asthma among never-smokers. Thorax. 2009;64:664–670.
Outdoor Air Pollution
55. Modig L, Jarvholm B, Ronnmark E, et al. Vehicle exhaust exposure in an incident case-control study of adult asthma. Eur Respir J. 2006;28:75–81. 56. Modig L, Toren K, Janson C, Jarvholm B, Forsberg B. Vehicle exhaust outside the home and onset of asthma among adults. Eur Respir J. 2009;33:1261– 1267. 57. Andersen ZJ, Hvidberg M, Jensen SS, et al. Chronic obstructive pulmonary disease and long-term exposure to traffic-related air pollution: a cohort study. Am J Respir Crit Care Med. 2011;183:455–461. 58. Dockery DW, Speizer FE, Stram DO, Ware JH, Spengler JD, Ferris BG, Jr. Effects of inhalable particles on respiratory health of children. Am Rev Respir Dis. 1989;139:587–594. 59. Schwartz J. PM10, ozone, and hospital admissions for the elderly in Minneapolis-St. Paul, Minnesota. Arch Environ Health. 1994;49:366– 374. 60. Wong TW, Lau TS, Yu TS, et al. Air pollution and hospital admissions for respiratory and cardiovascular diseases in Hong Kong. Occup Environ Med. 1999;56:679–683. 61. Goss CH, Newsom SA, Schildcrout JS, Sheppard L, Kaufman JD. Effect of ambient air pollution on pulmonary exacerbations and lung function in cystic fibrosis. Am J Respir Crit Care Med. 2004;169:816–821. 62. Pope CA, 3rd, Burnett RT, Turner MC, et al. Lung cancer and cardiovascular disease mortality associated with ambient air pollution and cigarette smoke: shape of the exposure-response relationships. Environ Health Perspect. 2011;119:1616–1621. 63. Villeneuve PJ, Parent ME, Sahni V, Johnson KC. Occupational exposure to diesel and gasoline emissions and lung cancer in Canadian men. Environ Res. 2011;111:727–735. 64. Katanoda K, Sobue T, Satoh H, et al. An association between long-term exposure to ambient air pollution and mortality from lung cancer and respiratory diseases in Japan. J Epidemiol. 2011;21:132–143. 65. Shofer S, Chen TM, Gokhale J, Kuschner WG. Outdoor air pollution: counseling and exposure risk reduction. Am J Med Sci. 2007;333:257–260.
C 2014 American College of Occupational and Environmental Medicine
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
S7
