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Increasing Fine Particulate Air Pollution in China and the Potential Use of Exposure and Biomarker Data in Disease Prevention Chris H. Wendt,*,†,∥ Gurumurthy Ramachandran,‡ Charles Lo,§ Marshall Hertz,∥ and Jeffrey H. Mandel‡ †
Veteran’s Administration Hospital, ‡University of Minnesota School of Public Health, §Mechanical Engineering Department, and University of Minnesota Medical School, University of Minnesota, Minneapolis, Minnesota 55455, United States
∥
ABSTRACT: Increased industrialization and urbanization have led to marked increases in air pollutants in China over the last decade. Pollutant levels in the north and eastern regions are often four times higher than current daily levels in the United States. Recent reports indicate a higher incidence of lung cancer and mortality in men and urban dwellers, but the contribution of air pollution to these findings remains unknown. Future studies that define individual exposures, combined with biomarkers linked to disease, will be essential to the understanding of risk posed by air pollution in China.
1. BACKGROUND
Adverse health effects have been linked with air pollution in numerous epidemiological investigations in China and elsewhere. Air-pollution-associated diseases described in China include increases in asthma, COPD, ischemic heart disease, lung cancer, and others.9−14 Recent reports in China suggest increased mortality from cardiac disease5 as well as increased emergency room visits during high pollutant levels.9,13,15 Outside of China, exposure to PM 2.5 has also been associated with disease excess, most of which relate to premature mortality; cardiovascular and respiratory disease, including lung cancer;16−19 and neurologic conditions including dementia.20 We have reviewed more recent exposure patterns to fine particulates in China along with estimates of lung cancer and have identified knowledge gaps and potential research directions that could help manage the impact of this problem.
China is in the midst of economic expansion with dramatic increases in energy use, resulting in noticeable changes in air quality. Questions have arisen as to the impact on human health subsequent to this. Air-pollution-related health problems are not new; reports have suggested various disease excess dating as far back as the 1948 air pollution in Donora, Pennsylvania that resulted in 20 deaths,1 and, in 1952, the welldocumented “London Fog” that resulted in pollution levels so high that 4000 deaths were ascribed to it.2 The recent economic changes in China are exemplified by its total industrial production, which, according to United Nations data, increased from 62% that of the United States in 2007 to 120% that of the United States in 2011. Coal has been the main source of energy in China and accounts for roughly 50% of the world’s usage.3 In 2000, China’s energy consumption was 1.455 billion tons of Standard Coal Equivalent (SCE) (China Statistical Yearbook, 2013).4 By 2011, consumption increased 139% to 3.48 billion tons of SCE. The industrial sector consumption increased from 1.037 billion tons of SCE to 2.46 billion tons of SCE, about 70% of the country’s total consumption. The sources of China’s air pollutants are mainly attributable to coal-fired power plants, automobile emissions, biomass burning, and other industrial sources.5−7 Pollutant levels vary from city to city due to such factors as the sources of the pollutants, geography, climate, and the type and size of particles generated. Especially of concern is the rapid increase in particulate matter of 2.5 μm or less in aerodynamic diameter (PM 2.5) since 2000. This sized pollutant has known deleterious health effects, especially in regard to cardiovascular and respiratory disease.7,8 © XXXX American Chemical Society
2. EXPOSURE TRENDS It is known that different parts of China have different types and amounts of air contaminants. Pollution levels, in general, appear to be higher in the north and eastern regions, corresponding to areas of greater industrialization and urbanization. In a 2003 research study, PM 2.5 levels were recorded in major Chinese cities, with daily averages as high as 182 μg/ m3 in some locations.21 The average daily exposures measured in the Chinese Six-City study ranged from 55 to 177 μg/m3.22 From these data, it is clear that pollutant levels appear to be comparable to or even higher than levels in southern California Special Issue: Chemical Toxicology in China Received: November 5, 2014
A
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cancer in China in the 1970s was reported at 5.47/100,000. During the early 1990s, the death rate from lung cancer was reported at 17.27/100,000, a 3-fold increase.28 More recent mortality rates have increased from the 1990s but have been stable from 2006 to 2010 (Table 1).29−33 One needs to also take into account the high prevalence of smoking in China, especially in men, when determining the contribution of PM 2.5 to mortality. In 2010, an estimated 52.9% of men smoked compared to only 2.4% of women.34 This is particularly important since the exposure rate is orders of magnitude higher in smokers. Several cohort studies in the U.S. and Europe have shown a clear link between long-term exposure to fine particulate matter (aerodynamic diameter ≤100 nm) and risk of cardiovascular events and mortality.25,35−41 Individuals with coronary heart disease have demonstrated an increase in inflammatory markers, C-reactive protein and coagulation factors, that correlate with ultrafine particulate matter exposure. Recent reports from China relate similar increases in cardiovascular hospital emergency room visits related to ambient PM 2.5 levels.9,15 Although further studies are necessary to define the link in fine air particulate exposure and noncancer-related respiratory mortality,42 there is growing evidence that chronic obstructive pulmonary disease (COPD) prevalence is strongly linked to air pollution exposure.43,44 In China, the prevalence of COPD is significantly higher in those that smoke, as expected, but also in those with poor ventilation in the kitchen consistent with biomass and/or coal burning exposures.45 Ambient pollution levels, particularly NO2, PM 10, PM 2.5, and ozone have also been associated with increased hospital admissions for children with asthma in Hong Kong.46
in the United States during the smoggy 1970s and are over four times higher than the current daily standards of 35 μg/m3 in the U.S.23 In comparison, 24-h averages reported from U.S. Embassy sites for Beijing, Chengdu, Shenyang, Guangzhou, and Shanghai were 101.7; 97.1; 96; 55.3; and 58.9 μg/m3, respectively, in 2013, compared to 14 μg/m3 in Los Angeles. Recent news reports indicate that daily PM 2.5 levels in some major cities have frequently exceeded the recommended air quality standards in the U.S. of 35 μg/m3, with hourly levels as high as 800 μg/m3 in Beijing. The composition of the PM 2.5 pollution in China also varies by city and season. The main component of PM 2.5 measured in China’s 14 largest cities consists of organic carbon, followed by SO42−, NO3−, and NH4+. Ammonia nitrate was particularly prevalent in the winter months when cold temperatures shifted it from its gas form to particulate matter. Lead also remained high in several cities correlating with arsenic and sulfate, consistent with coal combustion. Lastly, 20% of the PM 2.5 correlated with fugitive dust, i.e., particulate matter not attributable to human activities such as soil dust. This highlights the complexity of the different components that contribute to air pollution in China, including coal and biomass combustion, engine exhaust along with fugitive dust.21
3. MORTALITY TRENDS AND DISEASE-SPECIFIC EFFECTS OF PM China’s general crude rates of overall mortality have been stable from 2009 to 2012, at approximately 7/1000 people (World Bank, 2014). The health effects of the increasing PM 2.5 pollution is less studied in China compared to Europe and the U.S. A recent meta-analysis of 33 time-series studies revealed significant associations among air pollution with increased total respiratory and cardiovascular mortality linked to PM exposure.22 Epidemiologic studies have demonstrated associations between both short- and long-term PM exposures and increased risk of lung cancer mortality.24,25,19,26,27 In China, new cancer cases have been increasing since 2006, corresponding to the increase in the number of registries reporting, although the overall cancer incidence has not been increasing (Table 1). These five years of reports suggest higher lung cancer incidence and mortality in men vs women and in urban vs rural areas. This is consistent with urban areas having greater degrees of air pollution, but the exact explanation for this finding has not been determined. The death rate for lung
4. KNOWLEDGE GAPS IN UNDERSTANDING AIR POLLUTION HEALTH EFFECTS 4.1. Exposure Assessment Issues. Most studies of air pollution to date have involved the use of ambient monitoring data, often in combination with death or disease information obtained from public databases. These studies have defined exposure−disease associations based on average contaminant levels in the environment. While valuable insights have been provided with this approach, these types of studies are limited in the understanding of individual risk associated with air pollution. The relationship between exposure and disease might be better understood using personal exposures and individual disease measures. It is important that this approach also account for contaminants in various microenvironments as well as known confounders, including other common lung toxicants and smoking. Determination and use of the most appropriate metric is critical in the exposure assessment process. While the gravimetric measure of PM 2.5 has been used most commonly for regulatory and population-based epidemiological purposes, other metrics have been proposed. Because the three main PM sources in China (vehicular exhaust, power plant emissions, and biomass burning) are combustion-related, we would expect particles less than 1 μm in aerodynamic diameter to predominate. Using PM 1.0 as a metric would exclude some of the noncombustion-related aerosols and would be a more source-specific metric. PM 1.0 may give a more realistic indication of air pollution, better correlated with health effects and thus used for targeted pollution reduction methods that focus on automobile and industrial emissions.7
Table 1. China’s Overall Cancer Mortality and Lung Cancer Mortality by Gender in Urban and Rural Areas 2006−2010a year
overall cancerb
lung cancer
urban menc
urban womenc
rural menc
rural womenc
200621 200722 200823 200924 201025
273 276 299 285 235
44.15 45.50 46.07 45.57 37.00
63.44 65.71 65.62 67.61 56.72d 41.0
30.84 33.05 31.66 28.39 27.04d 17.31
46.19 46.51 50.79 48.58 43.26d 38.09
19.59 NA 20.18 22.56 19.56d 15.64
a
Crude mortality is presented expressed as a rate (cases/100,000). Rates are a reflection of urban and rural-based cancer registry reports. b Rates are a crude incidence for all cancers per 100,000 individuals, unadjusted for age or gender. cRates are unadjusted incidences specifically for lung cancer. dThe top number represents the genderadjusted rate; the bottom number represents the gender- and ageadjusted rate standardized to the Chinese population in 2000. B
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daily exposure, linking disease to long-term air pollution exposure is time- and resource-intensive due to the inability to identify individuals at risk and the relative lag of disease onset following exposure. A method to better identify individuals at risk is to develop biomarkers that indicate exposure and/or a biological effect of the exposure. 4.3.1. Exposure Biomarkers. Biomarkers that are linked to PM exposure, especially those linked to disease occurrence and mechanisms, can serve as outcome surrogates, identify the physiological effect of the exposure, and give insight into causalities. Exposure biomarkers can be as simple as directly measuring the exogenous substance or its metabolites in individuals as evidence of exposure. Some particulate matter can also be detected on key target molecules, such as adducts on proteins or DNA. This is particularly true for particles containing the carcinogenic polycyclic aromatic hydrocarbons (PAH) that are known to form DNA adducts through covalent binding.51 If these substances can be quantified, then a relationship between environmental levels and internal exposure can be estimated. 4.3.2. Effect Biomarkers. Effect biomarkers reflect the influence PM have on the organism, at the cellular or organ level, and are quantified by measuring physiological or biochemical responses. One use for effect biomarkers is the determination of threshold response. While direct measurements of the PM can determine exposure, not all exposures result in a physiological response. This was evident in populations exposed to PM in urban, rural, and occupational settings where low to moderate exposures demonstrated a linear response in the formation of DNA adducts, whereas at higher exposure concentrations this relationship became nonlinear.52 Understanding the dose−response and threshold relationships is important in determining the physiological response and may be helpful in establishing policy regarding threshold limit values. One example of an effect biomarker is in relation to lung cancer, which, by incidence rates, is higher in recent years compared to the 1990 rates. Several studies have linked DNA adducts as well as markers of early DNA damage, including mutagenicity, with ambient fine particulate air pollution exposure.51,53−58 In an evaluative review of 524 publications, Demetriou et al. identified 1-hydroxypyrene, DNA adducts, chromosomal aberrations, micronuclei, nucleobase oxidative damage, and methylation as putative biomarkers for lung cancer associated with PM exposure.59 These biomarkers have the potential to define susceptible populations and exposure thresholds while also yielding insights into the mechanism of disease.
The exposure metrics discussed above are all time-averaged over 24 or 48 h. However, PM levels are known to exhibit significant short-term variability. A systematic assessment of short-term variability in indoor and outdoor values requires suitable real-time PM monitors, both mass-based and surface area- or number-based. It has been hypothesized that these short-term variations may be relevant to health and may potentially explain some of the excess mortality and morbidity attributed to ambient PM.47,48 4.2. Study Design Issues. To better understand the health risks of PM 2.5 and other atmospheric pollutants, improved understanding is needed regarding which individuals are at highest risk. If this were known, efforts could be focused on minimizing future exposure in these individuals, in hopes of enhancing both primary and secondary disease prevention. The type of information required to enhance our understanding of individual risk begins with the use of the appropriate study designs, namely, cohort and case-control studies. In these circumstances, the investigation of an occupational cohort may be helpful, particularly one with comparable quantities and composition of PM 2.5 as experienced in segments of the general population. Although exposures in the occupational setting are generally higher than what the general population would encounter, they typically provide a spectrum of exposure possibilities. These often range from very high exposures over long time periods to lower exposures over short times, allowing the opportunity for multiple exposure comparisons within the work setting. Determination of a cumulative exposure estimate is a common method used in this setting. This estimate combines the average exposure concentration to which a worker is exposed with the duration of time worked at that exposure. The subsequent cumulative exposure metric is expressed in concentration-years (e.g., mg/ m3/years). When a workplace process has been stable over time, it may be possible to use current exposure measures to estimate past exposures. The cumulative exposure metric makes sense biologically, as it reflects chronic exposure that fits best with how dust-related lung diseases occur. Cumulative exposure is also helpful in assessing health effects in younger worker populations, as exist in China, where age itself may not be associated with much disease. The use of an individual risk approach is an important complement to ambient monitoring for several reasons. First, when done properly the individual risk approach can provide insights into the exposure−response relationship and may be key to understanding how successful lowering of ambient levels really is.49 This can then be used to support the regulatory process generated from ambient monitoring. Second, from a preventive view, it is critical to understand individual risk when environmental pollution is likely to be long lasting. Also, this approach is needed to utilize individual biomarker data since ultimately the biomarker has to be tied to a response and/or disease process. In effect, this creates the potential for minimizing the risk, through the identification of a related biomarker, for diseases that would otherwise result from longer exposures. 4.3. Biomarkers and PM Exposure. Studies have demonstrated that individual susceptibility to the adverse health effects of PM 2.5 is variable. It is highly likely that individual susceptibility exists for the adverse effects of PM 2.5; examples of individual susceptibility include specific polymorphisms demonstrating biological links to ozone responses.50 While daily mortality can be correlated directly to
5. FUTURE DIRECTIONS China’s air pollution levels are consistently elevated, often higher than levels experienced in the United States several decades ago, prior to the 1970 Clean Air Act that led to marked reductions in air pollution levels in the U.S. This air pollution problem is not likely to be resolved quickly, given the current magnitude of pollution levels and the Chinese government’s preference for economic expansion, industrialization, and urbanization. Obtaining and refining better insights into the public health repercussions of air pollution in China and in other air pollution environments will require additional investigations. These investigations need to include improved public reporting of mortality rates and rates of key morbidities including lung cancer, nonmalignant lung diseases, and heart C
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A., and Tracy, R. P. (2012) Prospective study of particulate air pollution exposures, subclinical atherosclerosis, and clinical cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). Am. J. Epidemiol. 176, 825−837. (13) Qiao, L., Cai, J., Wang, H., Wang, W., Zhou, M., Lou, S., Chen, R., Dai, H., Chen, C., and Kan, H. (2014) PM2.5 constituents and hospital emergency-room visits in Shanghai, China. Environ. Sci. Technol. 48, 10406−10414. (14) Lee S, W, W., and Lau, Y. (2006) Association between air pollution and asthma admission among children in Hong Kong. Clin. Exp. Allergy 36, 1138−1146. (15) Guo, Y., Jia, Y., Pan, X., Liu, L., and Wichmann, H. E. (2009) The association between fine particulate air pollution and hospital emergency room visits for cardiovascular diseases in Beijing, China. Sci. Total Environ. 407, 4826−4830. (16) Beelen, R., Stafoggia, M., Raaschou-Nielsen, O., Andersen, Z. J., Xun, W. W., Katsouyanni, K., Dimakopoulou, K., Brunekreef, B., Weinmayr, G., Hoffmann, B., Wolf, K., Samoli, E., Houthuijs, D., Nieuwenhuijsen, M., Oudin, A., Forsberg, B., Olsson, D., Salomaa, V., Lanki, T., Yli-Tuomi, T., Oftedal, B., Aamodt, G., Nafstad, P., De Faire, U., Pedersen, N. L., Ostenson, C. G., Fratiglioni, L., Penell, J., Korek, M., Pyko, A., Eriksen, K. T., Tjonneland, A., Becker, T., Eeftens, M., Bots, M., Meliefste, K., Wang, M., Bueno-de-Mesquita, B., Sugiri, D., Kramer, U., Heinrich, J., de Hoogh, K., Key, T., Peters, A., Cyrys, J., Concin, H., Nagel, G., Ineichen, A., Schaffner, E., Probst-Hensch, N., Dratva, J., Ducret-Stich, R., Vilier, A., Clavel-Chapelon, F., Stempfelet, M., Grioni, S., Krogh, V., Tsai, M. Y., Marcon, A., Ricceri, F., Sacerdote, C., Galassi, C., Migliore, E., Ranzi, A., Cesaroni, G., Badaloni, C., Forastiere, F., Tamayo, I., Amiano, P., Dorronsoro, M., Katsoulis, M., Trichopoulou, A., Vineis, P., and Hoek, G. (2014) Longterm exposure to air pollution and cardiovascular mortality: an analysis of 22 European cohorts. Epidemiol. 25, 368−378. (17) Yorifuji, T., Suzuki, E., and Kashima, S. (2014) Outdoor air pollution and out-of-hospital cardiac arrest in Okayama, Japan. J. Occup. Environ. Med. 56, 1019−1023. (18) Franklin, M., Zeka, A., and Schwartz, J. (2007) Association between PM2.5 and all-cause and specific-cause mortality in 27 US communities. J. Exposure Sci. Environ. Epidemiol. 17, 279−287. (19) Raaschou-Nielsen, O., Andersen, Z. J., Beelen, R., Samoli, E., Stafoggia, M., Weinmayr, G., Hoffmann, B., Fischer, P., Nieuwenhuijsen, M. J., Brunekreef, B., Xun, W. W., Katsouyanni, K., Dimakopoulou, K., Sommar, J., Forsberg, B., Modig, L., Oudin, A., Oftedal, B., Schwarze, P. E., Nafstad, P., De Faire, U., Pedersen, N. L., Ostenson, C. G., Fratiglioni, L., Penell, J., Korek, M., Pershagen, G., Eriksen, K. T., Sorensen, M., Tjonneland, A., Ellermann, T., Eeftens, M., Peeters, P. H., Meliefste, K., Wang, M., Bueno-de-Mesquita, B., Key, T. J., de Hoogh, K., Concin, H., Nagel, G., Vilier, A., Grioni, S., Krogh, V., Tsai, M. Y., Ricceri, F., Sacerdote, C., Galassi, C., Migliore, E., Ranzi, A., Cesaroni, G., Badaloni, C., Forastiere, F., Tamayo, I., Amiano, P., Dorronsoro, M., Trichopoulou, A., Bamia, C., Vineis, P., and Hoek, G. (2013) Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE). Lancet Oncol. 14, 813− 822. (20) Ailshire, J. A., and Crimmins, E. M. (2014) Fine particulate matter air pollution and cognitive function among older US adults. Am. J. Epidemiol. 180, 359−366. (21) Cao, J. J., Shen, Z. X., Chow, J. C., Watson, J. G., Lee, S. C., Tie, X. X., Ho, K. F., Wang, G. H., and Han, Y. M. (2012) Winter and summer PM2.5 chemical compositions in fourteen Chinese cities. J. Air Waste Manage. Assoc. 62, 1214−1226. (22) Shang, Y., Sun, Z., Cao, J., Wang, X., Zhong, L., Bi, X., Li, H., Liu, W., Zhu, T., and Huang, W. (2013) Systematic review of Chinese studies of short-term exposure to air pollution and daily mortality. Environ. Int. 54, 100−111. (23) Parrish, D. D., Singh, H. B., Molina, L., and Madronich, S. (2011) Air quality progress in North American megacities: A review. Atmos. Environ. 45, 7015−7025.
disease. Equally essential is to establish monitoring and reporting of both ambient and individual air pollution exposures, especially at the level of PM 2.5. Although large epidemiology studies are important to link ambient air pollution to certain morbidities and mortalities, these studies do not elucidate individual risk, nor do these studies evaluate the role of outdoor versus indoor pollution. In this regard, an occupational cohort can provide detailed exposure estimates and better define individual risk. Lastly, validated biomarkers have the potential to define individuals at highest risk; to link exposure to disease causality; and to function as surrogates for disease susceptibility. This approach would allow continuous monitoring to detect response to interventions, which will shorten the time needed to complete studies essential to the development of new policies that minimize exposure and risk.
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AUTHOR INFORMATION
Corresponding Author
*University of Minnesota, VAMC 1 Veterans Dr., Minneapolis, MN 55417. Phone: (612) 467-4860. Fax: (612) 727-5634. Email:
[email protected]. Notes
The authors declare no competing financial interest.
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ABBREVIATIONS SCE, Standard Coal Equivalent; COPD, chronic obstructive pulmonary disease; PM, particulate matter; PAH, polycyclic aromatic hydrocarbons
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REFERENCES
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