C. Arden Pope

Health Effects of Fine Particulate Air Pollution: Lines that Connect

INTRODUCTION Herein is the discussion of the 2006 A&WMA Critical Review1,2 on “Health Effects of Fine Particulate Air Pollution: Lines that Connect.” In the review, Drs. C. Arden Pope III and Douglas Dockery addressed the epidemiological evidence for the effects of particulate matter (PM) on human health indicators. The review documents substantial progress since the 1997 Critical Review3 in the areas of: (1) short-term exposure and mortality; (2) long-term exposure and mortality; (3) time scales of exposure; (4) the shape of the concentration-response function; (5) cardiovascular disease; and (6) biological plausibility. Invited and contributing discussants agree and disagree with points made in the review. Each discussion is self-contained and adds information relevant to the topic. Joint authorship of this article does not imply that a discussant subscribes to the opinions expressed by others. Commentaries are the opinions of the author only and do not necessarily reflect the positions of their respective organizations. In particular, Dr. Costa’s comments have not been reviewed by U.S. Environmental Protection Agency (EPA) and do not reflect official positions or policies of the agency. CRITICAL REVIEW DISCUSSION ISSN 1047-3289 J. Air & Waste Manage. Assoc. 56:1368–1380

Particulate Matter Air Pollution and Cardiovascular Disease An Update to the Scientific Statement From the American Heart Association

In 2004, the first American Heart Association scientific statement on “Air Pollution and Cardiovascular Disease” concluded that exposure to particulate matter (PM) air pollution contributes to cardiovascular morbidity and mortality. In the interim, numerous studies have expanded our understanding of this association and further elucidated the physiological and molecular mechanisms involved. The main objective of this updated American Heart Association scientific statement is to provide a comprehensive review of the new evidence linking PM exposure with cardiovascular disease, with a specific focus on highlighting the clinical implications for researchers and healthcare providers. The writing group also sought to provide expert consensus opinions on many aspects of the current state of science and updated suggestions for areas of future research. On the basis of the findings of this review, several new conclusions were reached, including the following: Exposure to PM <2.5 &mgr;m in diameter (PM2.5) over a few hours to weeks can trigger cardiovascular disease–related mortality and nonfatal events; longer-term exposure (eg, a few years) increases the risk for cardiovascular mortality to an even greater extent than exposures over a few days and reduces life expectancy within more highly exposed segments of the population by several months to a few years; reductions in PM levels are associated with decreases in cardiovascular mortality within a time frame as short as a few years; and many credible pathological mechanisms have been elucidated that lend biological plausibility to these findings. It is the opinion of the writing group that the overall evidence is consistent with a causal relationship between PM2.5 exposure and cardiovascular morbidity and mortality. This body of evidence has grown and been strengthened substantially since the first American Heart Association scientific statement was published. Finally, PM2.5 exposure is deemed a modifiable factor that contributes to cardiovascular morbidity and mortality.

Cardiovascular Mortality and Long-Term Exposure to Particulate Air Pollution Epidemiological Evidence of General Pathophysiological Pathways of Disease

Background—Epidemiologic studies have linked long-term exposure to fine particulate matter air pollution (PM) to broad cause-of-death mortality. Associations with specific cardiopulmonary diseases might be useful in exploring potential mechanistic pathways linking exposure and mortality. Methods and Results—General pathophysiological pathways linking long-term PM exposure with mortality and expected patterns of PM mortality with specific causes of death were proposed a priori. Vital status, risk factor, and cause-of-death data, collected by the American Cancer Society as part of the Cancer Prevention II study, were linked with air pollution data from United States metropolitan areas. Cox Proportional Hazard regression models were used to estimate PM-mortality associations with specific causes of death. Long-term PM exposures were most strongly associated with mortality attributable to ischemic heart disease, dysrhythmias, heart failure, and cardiac arrest. For these cardiovascular causes of death, a 10-&mgr;g/m3 elevation in fine PM was associated with 8% to 18% increases in mortality risk, with comparable or larger risks being observed for smokers relative to nonsmokers. Mortality attributable to respiratory disease had relatively weak associations. Conclusions—Fine particulate air pollution is a risk factor for cause-specific cardiovascular disease mortality via mechanisms that likely include pulmonary and systemic inflammation, accelerated atherosclerosis, and altered cardiac autonomic function. Although smoking is a much larger risk factor for cardiovascular disease mortality, exposure to fine PM imposes additional effects that seem to be at least additive to if not synergistic with smoking.

Fine-Particulate Air Pollution and Life Expectancy in the United States

BACKGROUND Exposure to fine-particulate air pollution has been associated with increased morbidity and mortality, suggesting that sustained reductions in pollution exposure should result in improved life expectancy. This study directly evaluated the changes in life expectancy associated with differential changes in fine particulate air pollution that occurred in the United States during the 1980s and 1990s. METHODS We compiled data on life expectancy, socioeconomic status, and demographic characteristics for 211 county units in the 51 U.S. metropolitan areas with matching data on fine-particulate air pollution for the late 1970s and early 1980s and the late 1990s and early 2000s. Regression models were used to estimate the association between reductions in pollution and changes in life expectancy, with adjustment for changes in socioeconomic and demographic variables and in proxy indicators for the prevalence of cigarette smoking. RESULTS A decrease of 10 microg per cubic meter in the concentration of fine particulate matter was associated with an estimated increase in mean (+/-SE) life expectancy of 0.61+/-0.20 year (P=0.004). The estimated effect of reduced exposure to pollution on life expectancy was not highly sensitive to adjustment for changes in socioeconomic, demographic, or proxy variables for the prevalence of smoking or to the restriction of observations to relatively large counties. Reductions in air pollution accounted for as much as 15% of the overall increase in life expectancy in the study areas. CONCLUSIONS A reduction in exposure to ambient fine-particulate air pollution contributed to significant and measurable improvements in life expectancy in the United States.

Spatial analysis of air pollution and mortality in Los Angeles.

Background: The assessment of air pollution exposure using only community average concentrations may lead to measurement error that lowers estimates of the health burden attributable to poor air quality. To test this hypothesis, we modeled the association between air pollution and mortality using small-area exposure measures in Los Angeles, California. Methods: Data on 22,905 subjects were extracted from the American Cancer Society cohort for the period 1982–2000 (5,856 deaths). Pollution exposures were interpolated from 23 fine particle (PM2.5) and 42 ozone (O3) fixed-site monitors. Proximity to expressways was tested as a measure of traffic pollution. We assessed associations in standard and spatial multilevel Cox regression models. Results: After controlling for 44 individual covariates, all-cause mortality had a relative risk (RR) of 1.17 (95% confidence interval = 1.05–1.30) for an increase of 10 &mgr;g/m3 PM2.5 and a RR of 1.11 (0.99–1.25) with maximal control for both individual and contextual confounders. The RRs for mortality resulting from ischemic heart disease and lung cancer deaths were elevated, in the range of 1.24–1.6, depending on the model used. These PM results were robust to adjustments for O3 and expressway exposure. Conclusion: Our results suggest the chronic health effects associated with within-city gradients in exposure to PM2.5 may be even larger than previously reported across metropolitan areas. We observed effects nearly 3 times greater than in models relying on comparisons between communities. We also found specificity in cause of death, with PM2.5 associated more strongly with ischemic heart disease than with cardiopulmonary or all-cause mortality.

REVIEW OF EPIDEMIOLOGICAL EVIDENCE OF HEALTH EFFECTS OF PARTICULATE AIR POLLUTION

AbstractThis article summarizes epidemiological evidence of health effects of particulate air pollution. Acute exposure to elevated levels of particulate air pollution has been associated with increased cardiopulmonary mortality, increased hospitalization for respiratory disease, exacerbation of asthma, increased incidence and duration of respiratory symptoms, declines in lung function, and restricted activity. Small deficits in lung function, higher risk of chronic respiratory disease and symptoms, and increased mortality have also been associated with chronic exposure to respirable particulate air pollution. Health effects have been observed at levels common to many U.S. cites and at levels below current US. National Ambient Air Quality Standards. Although the biological mechanisms involved are poorly understood, recent epidemiological evidence supports the hypothesis that respirable particulate air pollution is an important risk factor for respiratory disease and cardiopulmonary mortality.

Long-Term Ozone Exposure and Mortality

BACKGROUND Although many studies have linked elevations in tropospheric ozone to adverse health outcomes, the effect of long-term exposure to ozone on air pollution-related mortality remains uncertain. We examined the potential contribution of exposure to ozone to the risk of death from cardiopulmonary causes and specifically to death from respiratory causes. METHODS Data from the study cohort of the American Cancer Society Cancer Prevention Study II were correlated with air-pollution data from 96 metropolitan statistical areas in the United States. Data were analyzed from 448,850 subjects, with 118,777 deaths in an 18-year follow-up period. Data on daily maximum ozone concentrations were obtained from April 1 to September 30 for the years 1977 through 2000. Data on concentrations of fine particulate matter (particles that are < or = 2.5 microm in aerodynamic diameter [PM(2.5)]) were obtained for the years 1999 and 2000. Associations between ozone concentrations and the risk of death were evaluated with the use of standard and multilevel Cox regression models. RESULTS In single-pollutant models, increased concentrations of either PM(2.5) or ozone were significantly associated with an increased risk of death from cardiopulmonary causes. In two-pollutant models, PM(2.5) was associated with the risk of death from cardiovascular causes, whereas ozone was associated with the risk of death from respiratory causes. The estimated relative risk of death from respiratory causes that was associated with an increment in ozone concentration of 10 ppb was 1.040 (95% confidence interval, 1.010 to 1.067). The association of ozone with the risk of death from respiratory causes was insensitive to adjustment for confounders and to the type of statistical model used. CONCLUSIONS In this large study, we were not able to detect an effect of ozone on the risk of death from cardiovascular causes when the concentration of PM(2.5) was taken into account. We did, however, demonstrate a significant increase in the risk of death from respiratory causes in association with an increase in ozone concentration.

Heart rate variability associated with particulate air pollution

BACKGROUND Epidemiologic studies have linked fine particulate air pollution with cardiopulmonary mortality, yet underlying biologic mechanisms remain unknown. Changes in heart rate variability (HRV) may reflect changes in cardiac autonomic function and risk of sudden cardiac death. This study evaluated changes in mean heart rate and HRV in human beings associated with changes in exposure to particulate air pollution. METHODS Repeated ambulatory electrocardiographic monitoring was conducted on 7 subjects for a total of 29 person-days before, during, and after episodes of elevated pollution. Mean HR, the standard deviation of normal-to-normal (NN) intervals (SDNN), the standard deviation of the averages of NN intervals in all 5-minute segments of the recording (SDANN), and the square root of the mean of squared differences between adjacent NN intervals (r-MSSD) were calculated for 24-hour and 6-hour time segments. Associations of HRV with particulate pollution levels were evaluated with fixed-effects regression models. RESULTS After controlling for differences across patients, elevated particulate levels were associated with (1) increased mean HR, (2) decreased SDNN, a measure of overall HRV, (3) decreased SDANN, a measure that corresponds to ultralow frequency variability, and (4) increased r-MSSD, a measure that corresponds to high-frequency variability. The associations between HRV and particulates were small but persisted even after controlling for mean HR. CONCLUSIONS This study suggests that changes in cardiac autonomic function reflected by changes in mean HR and HRV may be part of the pathophysiologic mechanisms or pathways linking cardiovascular mortality and particulate air pollution.

Daily Mortality and PM10 Pollution in Utah Valley

The association between daily mortality and respirable particulate pollution (PM10) in Utah County was assessed from April 1985 through December 1989. Poisson regression analysis was used to regress daily death counts on PM10 pollution levels, controlling for variability in the weather. A significant positive association between nonaccidental mortality and PM10 pollution was observed. The strongest association was with 5-d moving average PM10 levels, including the concurrent day and the preceding 4 d. An increase in 5-d moving average PM10 levels, equal to 100 micrograms/m3, was associated with an estimated increase in deaths per day equal to 16%. The association with mortality and PM10 was largest for respiratory disease deaths, next largest for cardiovascular deaths, and smallest for all other deaths. Mean PM10 concentrations during the study period equaled 47 micrograms/m3. The maximum 24-h and 5-d moving average PM10 levels equaled 365 and 297 micrograms/m3, respectively. Relatively low levels of sulfur dioxide, aerosol acidity, and ozone suggested an independent association between mortality and PM10. The relative risk of death increased monotonically with PM10, and the relationship was observed at PM10 levels that were well below the current National Ambient Air Quality Standard of 150 micrograms/m3.

Cardiovascular Mortality and Exposure to Airborne Fine Particulate Matter and Cigarette Smoke Shape of the Exposure-Response Relationship

Background— Fine particulate matter exposure from both ambient air pollution and secondhand cigarette smoke has been associated with larger risks of cardiovascular mortality than would be expected on the basis of linear extrapolations of the relative risks from active smoking. This study directly assessed the shape of the exposure-response relationship between cardiovascular mortality and fine particulates from cigarette smoke and ambient air pollution. Methods and Results— Prospective cohort data for >1 million adults were collected by the American Cancer Society as part of the Cancer Prevention Study II in 1982. Cox proportional hazards regression models that included variables for increments of cigarette smoking and variables to control for education, marital status, body mass, alcohol consumption, occupational exposures, and diet were used to describe the mortality experience of the cohort. Adjusted relative risks of mortality were plotted against estimated average daily dose of fine particulate matter from cigarette smoke along with comparison estimates for secondhand cigarette smoke and air pollution. There were substantially increased cardiovascular mortality risks at very low levels of active cigarette smoking and smaller but significant excess risks even at the much lower exposure levels associated with secondhand cigarette smoke and ambient air pollution. Conclusions— Relatively low levels of fine particulate exposure from either air pollution or secondhand cigarette smoke are sufficient to induce adverse biological responses increasing the risk of cardiovascular disease mortality. The exposure-response relationship between cardiovascular disease mortality and fine particulate matter is relatively steep at low levels of exposure and flattens out at higher exposures.