Health and respirable particulate (PM10) air pollution: a causal or statistical association?

Numerous studies have reported weak but statistically significant acute health effects of particulate air pollution. The associations are observed at levels below the current U.S. standard of 150 micrograms/m3 (24 hr). Health effects include acute increased mortality from cardiopulmonary conditions and acute morbidity such as hospital admissions for related diseases. We reviewed recent epidemiology studies to evaluate whether criteria for causality are met, and we conclude that they are not. The weak associations are as likely to be due to confounding by weather, copollutants, or exposure misclassification as by ambient particulate matter (PM). The results from the same metropolitan areas are inconsistent, and PM explains such a small amount of the variability in mortality/morbidity that the association has little practical significance. Finally, experimental chamber studies of susceptible individuals exposed to PM concentrations well above 150 micrograms/m3 provide no evidence to support the morbidity/mortality findings. None of the criteria for establishing causality of the PM/mortality hypothesis are clearly met at ambient concentrations common in many U.S. cities.     

可吸入颗粒物的健康效应机制

流行病学的研究表明,大气颗粒物的浓度水平与呼吸系统和心肺疾病的发病率、住院率和死亡率呈显著的正相关关系,但其生物和毒理学机制尚不清楚.根据可吸入颗粒物的特征和成分,国外的学者提出了各种不同的假说,包括以物理为基础的假说、有害有机组分假说、生物质假说、酸性气溶胶假说和氧化性损伤假说等.该文主要对可吸入颗粒物如何影响人体健康、对健康影响的主要毒理学机制(尤其是氧化性损伤假说)及毒理学评价方法的研究进展进行了综述.并针对中国可吸入颗粒物污染现状及其对人体健康的影响,提出研究方向,认为我国应加强大气颗粒物毒理学及评价方法的研究,从而揭示其对人体健康的影响机制.     

Mechanisms mediating adverse effects of air pollution on cardiovascular hemodynamic function and vulnerability to cardiac arrhythmias

Epidemiologic studies indicate an association between airborne particulate matter and cardiovascular morbidity and mortality. However, the underlying pathophysiologic mechanisms require further investigation. This review examines insights derived from large animal inhalation studies on systemic and coronary hemodynamic function and susceptibility to cardiac arrhythmias. We present evidence of acute cardiovascular alterations in chronically instrumented or anesthetized large animals exposed to concentrated ambient particles. Significant changes were observed in a number of clinically relevant variables. These included elevations in arterial blood pressure and reductions in myocardial perfusion during coronary occlusion that resulted in the exacerbation of ischemic parameters, such as ST-segment elevation and vasoconstriction. The involvement of sympathetic nerve activity was implicated by the fact that alpha-adrenergic blockade with prazosin significantly blunted the vasoconstrictor effects. Alterations in baroreceptor function during air particulate exposure were also substantial. Enhanced susceptibility to both atrial and ventricular arrhythmias was demonstrated. These studies with clinically relevant large animal models underscore the importance of the role of air particulate pollution in inducing adverse effects on cardiovascular function and warrant further exploration of specific components of air pollution as well as the physiologic triggers that lead to cardiovascular events. New clinically applicable research tools have evolved, particularly heart rate turbulence, a noninvasive measure of baroreceptor function, and T-wave alternans, an index of susceptibility to life-threatening arrhythmias, which can be employed clinically to evaluate the impact of air pollution on cardiovascular risk.     

Mortality and ambient fine particles in southwest Mexico City, 1993-1995.

++Epidemiologic studies have focused attention on the health effects of fine particulate air pollutants <2.5 microm in diameter (PM2.5). To further characterize the potential effects of fine particles, we investigated the relationship of air pollution to mortality in Mexico City during 1993-1995. The concentration of PM2.5 was measured on a 24-hr integrated basis; concentrations of NO2 and ozone were measured hourly and reduced to 24-hr means. Daily mortality was determined from death registration records, and Poisson regression was used to model daily death counts as a function of air pollutant levels on the same and previous days, while controlling for temperature and periodic cycles. Without taking other air pollutants into account, a 10 microg/m3 increase in the level of PM2.5 was associated with a 1.4% increase in total mortality, both on the current day and 4 days after exposure [95% confidence interval (CI), 0.2-2.5]. An equivalent increase in PM2.5 was also associated with somewhat larger excesses of deaths among people over 65 years of age and from cardiovascular and respiratory causes, which occurred after a lag of 4 days. The mean concentration of ozone over a 2-day period was associated with a 1.8% increase in mortality from cardiovascular diseases. NO2 was not consistently related to mortality. Fine particles had an independent effect on mortality when modeled simultaneously with other pollutants, and the association of ozone with cardiovascular mortality was strengthened after adjusting for NO2 and PM2.5. These results support previous findings that urban air pollution at current levels leads to excess mortality and suggest that fine particles may play a causal role in producing that excess.     

Is air pollution a cause of cardiovascular disease? Updated review and controversies

Particulate matter (PM) air pollution is associated with an increased risk of cardiovascular morbidity and mortality. The focus of this review will be on the role that both acute and chronic exposure to PM plays in causing cardiovascular disease and on the latest major new findings and controversies in this field of research. Even short-term exposure to PM2.5 over a few hours can trigger myocardial infarctions, cardiac ischemia, arrhythmias, heart failure, stroke, exacerbation of peripheral arterial disease, and sudden death. Chronic exposure to moderately elevated levels also enhances the risk for developing a variety of cardiovascular diseases, possibly including hypertension and systemic atherosclerosis. Recent epidemiologic studies have furthered our understanding of the linkage between air pollutants and human health, with a multitude of plausible mechanistic explanations having been demonstrated experimentally during the past few years. Although a number of finer details relating to both the epidemiology and the mechanisms involved require more investigation, the overall weight of evidence is now sufficient to implicate PM exposure as a cause of cardiovascular disease. Without doubt, exposure to particulate matter can play a causal role in triggering a host of acute cardiovascular events via many mechanisms. Although long-term air pollution exposure has been shown to promote the development of atherosclerosis, the clinical significance of this relation requires more investigation.     

Health effects of particles in ambient air

A summary of a critical review by a working group of the German commission on Air Pollution Prevention of VDI and DIN of the actual data on exposure and health effects (excluding cancer) of fine particulate air pollution is presented. EXPOSURE: Typical ambient particle concentrations for PM10 (PM2.5) in Germany are in the range of 10-45 (10-30) microg/m3 as annual mean and 50-200 (40-150) microg/m3 as maximum daily mean. The ratio of PM2.5/PM10 generally amounts between 0.7 and 0.9. HEALTH EFFECTS: During the past 10 years many new epidemiological and toxicological studies on health effects of particulate matter (PM) have been published. In summary, long-term exposure against PM for years or decades is associated with elevated total, cardiovascular, and infant mortality. With respect to morbidity, respiratory symptoms, lung growth, and function of the immune system are affected. Short-term studies show consistant associations of exposure to daily concentrations of PM with mortality and morbidity on the same day or the subsequent days. Patients with asthma, COPD, pneumonia, and other respiratory diseases as well as patients with cardio-vascular diseases and diabetes are especially affected. The strongest associations are found for PM2.5 followed by PM10, with no indication of a threshold value for the health effects. The data base for ultra fine particles is too small for final conclusions. The available toxicological data support the epidemiological findings and give hints as to the mechanisms of the effects. CONCLUSION: The working group concludes that a further reduction of the limit values proposed for 2005 will substantially reduce health risks due to particulate air pollution. Because of the strong correlation of PM10 with PM2.5 at most German sites there is no specific need for limit values of PM2.5 for Germany in addition to those of PM10.     

A time-series analysis of acidic particulate matter and daily mortality and morbidity in the Buffalo, New York, region

A component of particulate matter (PM) air pollution that may provide one biologically plausible pathway for the observed PM air pollution-health effect associations is aerosol acidity (H(+)). An increasing number of observational studies have demonstrated associations between H(+) and increased adverse health effects in the United States and abroad. Although studies have shown significant H(+) associations with increased morbidity in the United States, similar associations have yet to be shown with daily mortality. We considered a 2.5-year record of daily H(+) and sulfate measurements (May 1988-October 1990) collected in the Buffalo, New York, region in a time-series analysis of respiratory, circulatory, and total daily mortality and hospital admissions. Other copollutants considered included particulate matter [less than/equal to] 10 microm in aerodynamic diameter, coefficient of haze, ozone, carbon monoxide, sulfur dioxide, and nitrogen dioxide. Various modeling techniques were applied to control for confounding of effect estimates due to seasonality, weather, and day-of-week effects. We found multiple significant pollutant-health effect associations--most strongly between SO(4)(2-) and respiratory hospital admissions (as indicated by its t-statistic). Additionally, H(+) and SO(4)(2-) demonstrated the most coherent associations with both respiratory hospital admissions [H(+): relative risk (RR) = 1. 31; 95% confidence interval (CI), 1.14-1.51; and SO(4)(2-): RR = 1. 18, CI, 1.09-1.28] and respiratory mortality (H(+): RR = 1.55, CI, 1. 09-2.20; and SO(4)(2-): RR = 1.24, CI, 1.01-1.52). Thus, acidic sulfate aerosols represent a component of PM air pollution that may contribute to the previously noted adverse effects of PM mass on human health, and the associations demonstrated in this study support the need for further investigations into the potential health effects of acidic aerosols.     

Ambient particulate air pollution, heart rate variability, and blood markers of inflammation in a panel of elderly subjects

Epidemiologic studies report associations between particulate air pollution and cardiopulmonary morbidity and mortality. Although the underlying pathophysiologic mechanisms remain unclear, it has been hypothesized that altered autonomic function and pulmonary/systemic inflammation may play a role. In this study we explored the effects of air pollution on autonomic function measured by changes in heart rate variability (HRV) and blood markers of inflammation in a panel of 88 elderly subjects from three communities along the Wasatch Front in Utah. Subjects participated in multiple sessions of 24-hr ambulatory electrocardiographic monitoring and blood tests. Regression analysis was used to evaluate associations between fine particulate matter [aerodynamic diameter less than or equal to 2.5 microm (PM2.5)] and HRV, C-reactive protein (CRP), blood cell counts, and whole blood viscosity. A 100- microg/m3 increase in PM2.5 was associated with approximately a 35 (SE = 8)-msec decline in standard deviation of all normal R-R intervals (SDNN, a measure of overall HRV); a 42 (SE = 11)-msec decline in square root of the mean of the squared differences between adjacent normal R-R intervals (r-MSSD, an estimate of short-term components of HRV); and a 0.81 (SE = 0.17)-mg/dL increase in CRP. The PM2.5-HRV associations were reasonably consistent and statistically robust, but the CRP association dropped to 0.19 (SE = 0.10) after excluding the most influential subject. PM2.5 was not significantly associated with white or red blood cell counts, platelets, or whole-blood viscosity. Most short-term variability in temporal deviations of HRV and CRP was not explained by PM2.5; however, the small statistically significant associations that were observed suggest that exposure to PM2.5 may be one of multiple factors that influence HRV and CRP.     

PM(10) exposure, gaseous pollutants, and daily mortality in Inchon, South Korea.

To evaluate the relative importance of various measures of particulate and gaseous air pollution as predictors of daily mortality in Inchon, South Korea, the association between total daily mortality and air pollution was investigated for a 20-month period (January 1995 through August 1996). Poisson regression was used to regress daily death counts on each air pollutant, controlling for time trends, season, and meteorologic influences such as temperature and relative humidity. Regression coefficients of a 5-day moving average of particulate matter less than or = to 10 microm in aerodynamic diameter (PM(10)) on total mortality were positively significant when considered separately and simultaneously with other pollutants in the model. PM(10) remained significant when the models were confined to cardiovascular or respiratory mortality. Sulfur dioxide (SO(2)) and carbon monoxide (CO) were significantly related to respiratory mortality in the single-pollutant model. Ozone exposure was not statistically significant with regard to mortality in the above models, and graphic analysis showed that the relationship was nonlinear. A combined index of PM(10), nitrogen dioxide, SO(2), and CO seemed to better explain the exposure-response relationship with total mortality than an individual air pollutant. Pollutants should be considered together in the risk assessment of air pollution, as opposed to measuring the risk of individual pollutants.     

Does particulate matter modify the association between temperature and cardiorespiratory diseases?

BACKGROUND: A number of studies have shown that both temperature and air pollution are associated with health outcomes. In assessing air pollution effects, temperature is usually considered a confounder. However, only a few recent studies considered air pollution as confounders while assessing temperature effects. Few studies are available on whether or not air pollution modifies the temperature-disease relationship. METHODS: In this study, we used three parallel Poisson generalized additive models to examine whether particulate matter < 10 mum in aerodynamic diameter (PM10) modified the effects of minimum temperature on cardiorespiratory morbidity and mortality in Brisbane, Australia. RESULTS: Results show that PM10 statistically significantly modified the effects of temperature on respiratory and cardiovascular hospital admissions, all nonexternal-cause mortality, and cardiovascular mortality at different lags. The enhanced adverse temperature effects were found at higher levels of PM10, but no clear evidence emerged for interactive effects on respiratory and cardiovascular emergency visits. Three parallel models produced similar results, which strengthened the validity of findings. CONCLUSION: We conclude that it is important to evaluate the modification role of air pollution in the assessment of temperature-related health impacts.     

Seasonal variation of chemical species associated with short-term mortality effects of PM(2.5) in Xi'an, a Central City in China

The authors conducted a time-series analysis to examine seasonal variation of mortality risk in association with particulate matter less than 2.5 μm in aerodynamic diameter (PM(2.5)) and chemical species in Xi'an, China, using daily air pollution and all-cause and cause-specific mortality data (2004-2008). Poisson regression incorporating natural splines was used to estimate mortality risks of PM(2.5) and its chemical components, adjusting for day of the week, time trend, and meteorologic effects. Increases of 2.29% (95% confidence interval: 0.83, 3.76) for all-cause mortality and 3.08% (95% confidence interval: 0.94, 5.26) for cardiovascular mortality were associated with an interquartile range increase of 103.0 μg/m(3) in lagged 1-2 day PM(2.5) exposure. Stronger effects were observed for the elderly (≥65 years), males, and cardiovascular diseases groups. Secondary components (sulfate and ammonium), combustion species (elemental carbon, sulfur, chlorine), and transition metals (chromium, lead, nickel, and zinc) appeared most responsible for increased risk, particularly in the cold months. The authors concluded that differential association patterns observed across species and seasons indicated that PM(2.5)-related effects might not be sufficiently explained by PM(2.5) mass alone. Future research is needed to examine spatial and temporal varying factors that might play important roles in modifying the PM(2.5)-mortality association.     

Potential role of ultrafine particles in associations between airborne particle mass and cardiovascular health

Numerous epidemiologic time-series studies have shown generally consistent associations of cardiovascular hospital admissions and mortality with outdoor air pollution, particularly mass concentrations of particulate matter (PM) < or = 2.5 or < or = 10 microm in diameter (PM2.5, PM10). Panel studies with repeated measures have supported the time-series results showing associations between PM and risk of cardiac ischemia and arrhythmias, increased blood pressure, decreased heart rate variability, and increased circulating markers of inflammation and thrombosis. The causal components driving the PM associations remain to be identified. Epidemiologic data using pollutant gases and particle characteristics such as particle number concentration and elemental carbon have provided indirect evidence that products of fossil fuel combustion are important. Ultrafine particles < 0.1 microm (UFPs) dominate particle number concentrations and surface area and are therefore capable of carrying large concentrations of adsorbed or condensed toxic air pollutants. It is likely that redox-active components in UFPs from fossil fuel combustion reach cardiovascular target sites. High UFP exposures may lead to systemic inflammation through oxidative stress responses to reactive oxygen species and thereby promote the progression of atherosclerosis and precipitate acute cardiovascular responses ranging from increased blood pressure to myocardial infarction. The next steps in epidemiologic research are to identify more clearly the putative PM casual components and size fractions linked to their sources. To advance this, we discuss in a companion article (Sioutas C, Delfino RJ, Singh M. 2005. Environ Health Perspect 113:947-955) the need for and methods of UFP exposure assessment.     

Cardiovascular health and particulate vehicular emissions: a critical evaluation of the evidence

A major public health goal is to determine linkages between specific pollution sources and adverse health outcomes. This paper provides an integrative evaluation of the database examining effects of vehicular emissions, such as black carbon (BC), carbonaceous gasses, and ultrafine PM, on cardiovascular (CV) morbidity and mortality. Less than a decade ago, few epidemiological studies had examined effects of traffic emissions specifically on these health endpoints. In 2002, the first of many studies emerged finding significantly higher risks of CV morbidity and mortality for people living in close proximity to major roadways, vs. those living further away. Abundant epidemiological studies now link exposure to vehicular emissions, characterized in many different ways, with CV health endpoints such as cardiopulmonary and ischemic heart disease and circulatory-disease-associated mortality; incidence of coronary artery disease; acute myocardial infarction; survival after heart failure; emergency CV hospital admissions; and markers of atherosclerosis. We identify numerous in vitro, in vivo, and human panel studies elucidating mechanisms which could explain many of these cardiovascular morbidity and mortality associations. These include: oxidative stress, inflammation, lipoperoxidation and atherosclerosis, change in heart rate variability (HRV), arrhythmias, ST-segment depression, and changes in vascular function (such as brachial arterial caliber and blood pressure). Panel studies with accurate exposure information, examining effects of ambient components of vehicular emissions on susceptible human subjects, appear to confirm these mechanisms. Together, this body of evidence supports biological mechanisms which can explain the various CV epidemiological findings. Based upon these studies, the research base suggests that vehicular emissions are a major environmental cause of cardiovascular mortality and morbidity in the United States. As a means to reduce the public health consequences of such emissions, it may be desirable to promulgate a black carbon (BC) PM_2.5 standard under the National Ambient Air Quality Standards, which would apply to both on and off-road diesels. Two specific critical research needs are identified. One is to continue research on health effects of vehicular emissions, gaseous as well as particulate. The second is to utilize identical or nearly identical research designs in studies using accurate exposure metrics to determine whether other major PM pollutant sources and types may also underlie the specific health effects found in this evaluation for vehicular emissions.     

Effects of particulate air pollution on hemostasis

Exposure to particulate air pollution is associated with acute and chronic cardiovascular morbidity and mortality. The mechanisms involved in these effects are not fully elucidated. Research has proved that fine particles, principally the ultrafine fraction, which are predominantly derived from combustion of fossil fuel, are the most toxic. Recent clinical and experimental studies have reported mechanistic observations linking fine and ultrafine particles to the coagulation cascade, platelet function, and subsequent development of atherosclerosis and thrombosis. These effects have been explained either by release of soluble mediators by the lungs, which affect blood coagulation parameters, or by the direct translocation of ultrafine particles into the systemic circulation or the alteration of autonomic cardiac control. Despite recent advances, additional studies are needed to investigate the pathophysiologic mechanisms linking particulate air pollution and hemostasis.     

Relationship between particulate matter measured by optical particle counter and mortality in Seoul, Korea, during 2001

This study was performed to examine the relationship between particulate matter exposure and mortality in Seoul, Korea, during the year 2001. Particulate matter data were collected using an optical particle counter (OPC) and national monitoring stations in Seoul. The size-resolved aerosol number concentrations of particles 0.3-25 microm in diameter and mass concentrations of PM10 (particulate matter less than 10 microm in diameter) and PM2.5 (less than 2.5 microm in diameter) were measured. Meteorological data such as air temperature and relative humidity were provided by the Korea Meteorological Administration. Daily mortality was analyzed using a generalized additive Poisson model, with adjustment for the effects of seasonal trend, air temperature, humidity, and day of the week as confounders, in a nonparametric approach. We used S-Plus for all analyses. Model fitness, using loess smoothing, was based on stringent convergence criteria to minimize the default convergence criteria in the S-Plus generalized additive models module. The IQR (interquartile range) increase of fine particle (10.21 number/cm3 [the total number of particles per cubic centimeter]) and respiratory particle (10.38 number/cm3) number concentration were associated with a 5.73% (5.03%-6.45%) and a 5.82% (5.13%-6.53%) increase in respiratory disease-associated mortality, respectively. Mortality effects in the elderly (aged over 65 years) were increased by more than 0.51% to 2.59%, and the relative risks of respiratory-related and cardiovascular-related mortality were increased by 0.51% to 1.06% compared with all-cause mortality. These findings support the hypothesis that air pollution is harmful to sensitive subjects, such as the elderly, and has a greater effect on respiratory- and cardiovascular-related mortality than all-cause mortality. However, our results using OPC data did not support the hypothesis that PM2.5 would have more adverse health effects than PM10 in number concentration but not in mass concentration.     

Residual oil combustion: a major source of airborne nickel in New York City

On the basis of previous observations that: (1) both the nickel (Ni) concentration in ambient air fine particulate matter (PM(2.5)) and daily mortality rates in New York City (NYC) were much higher than in any other US city; and (2) that peaks in Ni concentration was strongly associated with cardiac function in a mouse model of atherosclerosis, we initiated a study of the spatial and seasonal distributions of Ni in NYC and vicinity to determine the feasibility of productive human population-based studies of the extent to which ambient fine particle Ni may account for cardiovascular health effects. Using available speciation data from previous studies at The New York University, Environmental Protection Agency's Speciation Trends Network; and the Interagency Monitoring of Protected Visual Environments network, we determined that Ni in NYC is on average 2.5 times higher in winter than in summer. This apparent seasonal gradient is absent, or much less pronounced, at NJ and CT speciation sites. Ni concentrations at a site on the east side of Manhattan and at two sites in the western portion of the Bronx were a factor of two higher than at a site on the west side of Manhattan, or at one at Queens College in eastern Queens County, indicating a strong spatial gradient within NYC. We conclude that the winter peaks of fine particle Ni indicate that space heating, which involves the widespread reliance on residual oil combustion in many older residential and commercial buildings in NYC, is a major source of ambient air Ni. Epidemiologic studies based on data generated by a network of speciation sites throughout NYC could effectively test the hypothesis that Ni could account for a significant portion of the excess mortality and morbidity that have been associated with elevated mass concentrations of PM(2.5).     

Air pollution and daily mortality in a city with low levels of pollution

The concentration-response relationship between daily ambient inhalable particle (particulate matter less than or equal to 10 micro m; PM(10)) concentrations and daily mortality typically shows no evidence of a threshold concentration below which no relationship is observed. However, the power to assess a relationship at very low concentrations of PM(10) has been limited in studies to date. The concentrations of PM(10) and other air pollutants in Vancouver, British Columbia, Canada, from January 1994 through December 1996 were very low: the 50th and 90th percentiles of daily average PM(10) concentrations were 13 and 23 micro g/m(3), respectively, and 27 and 39 ppb, respectively, for 1-hr maximum ozone. Analyses of 3 years of daily pollution (PM(10), ozone, sulfur dioxide, nitrogen dioxide, and carbon monoxide) concentrations and mortality counts showed that the dominant associations were between ozone and total mortality and respiratory and cardiovascular mortality in the summer, and between nitrogen dioxide and total mortality in the winter, although some association with PM(10) may also have been present. We conclude that increases in low concentrations of air pollution are associated with increased daily mortality. These findings may support the notion that no threshold pollutant concentrations are present, but they also raise concern that these effects may not be effects of the measured pollutants themselves, but rather of some other factor(s) present in the air pollution-meteorology mix.     

Season, sex, age, and education as modifiers of the effects of outdoor air pollution on daily mortality in Shanghai, China: The Public Health and Air Pollution in Asia (PAPA) Study

BACKGROUND: Various factors can modify the health effects of outdoor air pollution. Prior findings about modifiers are inconsistent, and most of these studies were conducted in developed countries. OBJECTIVES: We conducted a time-series analysis to examine the modifying effect of season, sex, age, and education on the association between outdoor air pollutants [particulate matter < 10 microm in aerodynamic diameter (PM(10)), sulfur dioxide, nitrogen dioxide, and ozone] and daily mortality in Shanghai, China, using 4 years of daily data (2001-2004). METHODS: Using a natural spline model to analyze the data, we examined effects of air pollution for the warm season (April-September) and cool season (October-March) separately. For total mortality, we examined the association stratified by sex and age. Stratified analysis by educational attainment was conducted for total, cardiovascular, and respiratory mortality. RESULTS: Outdoor air pollution was associated with mortality from all causes and from cardiorespiratory diseases in Shanghai. An increase of 10 mug/m(3) in a 2-day average concentration of PM(10), SO(2), NO(2), and O(3) corresponds to increases in all-cause mortality of 0.25% [95% confidence interval (CI), 0.14-0.37), 0.95% (95% CI, 0.62-1.28), 0.97% (95% CI, 0.66-1.27), and 0.31% (95% CI, 0.04-0.58), respectively. The effects of air pollutants were more evident in the cool season than in the warm season, and females and the elderly were more vulnerable to outdoor air pollution. Effects of air pollution were generally greater in residents with low educational attainment (illiterate or primary school) compared with those with high educational attainment (middle school or above). CONCLUSIONS: Season, sex, age, and education may modify the health effects of outdoor air pollution in Shanghai. These findings provide new information about the effects of modifiers on the relationship between daily mortality and air pollution in developing countries and may have implications for local environmental and social policies.