Ozone Exposure and Mortality: An Empiric Bayes Metaregression Analysis
Levy, Jonathan I.; Chemerynski, Susan M.; Sarnat, Jeremy A.
From the Exposure, Epidemiology and Risk Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA.
Submitted 12 August 2004; final version accepted 4 March 2005.
Funding provided by the U.S. Environmental Protection Agency, Office of Air Quality Planning and Standards, RFQ #RT-03-00322.
Publication costs for this paper have been paid by EPA.
Editors’ note: An editorial and commentaries on this article appears on pages 425–435.
Correspondence: Jonathan I. Levy, Harvard School of Public Health, Landmark Center Room 404K, P.O. Box 15677, Boston, MA 02215. E-mail: firstname.lastname@example.org.
Background: Results from time-series epidemiologic studies evaluating the relationship between ambient ozone concentrations and premature mortality vary in their conclusions about the magnitude of this relationship, if any, making it difficult to estimate public health benefits of air pollution control measures. We conducted an empiric Bayes metaregression to estimate the ozone effect on mortality, and to assess whether this effect varies as a function of hypothesized confounders or effect modifiers.
Methods: We gathered 71 time-series studies relating ozone to all-cause mortality, and we selected 48 estimates from 28 studies for the metaregression. Metaregression covariates included the relationship between ozone concentrations and concentrations of other air pollutants, proxies for personal exposure–ambient concentration relationships, and the statistical methods used in the studies. For our metaregression, we applied a hierarchical linear model with known level-1 variances.
Results: We estimated a grand mean of a 0.21% increase (95% confidence interval = 0.16–0.26%) in mortality per 10-μg/m3 increase of 1-hour maximum ozone (0.41% increase per 10 ppb) without controlling for other air pollutants. In the metaregression, air-conditioning prevalence and lag time were the strongest predictors of between-study variability. Air pollution covariates yielded inconsistent findings in regression models, although correlation analyses indicated a potential influence of summertime PM2.5.
Conclusions: These findings, coupled with a greater relative risk of ozone in the summer versus the winter, demonstrate that geographic and seasonal heterogeneity in ozone relative risk should be anticipated, but that the observed relationship between ozone and mortality should be considered for future regulatory impact analyses.
Although ozone exposure has well-documented influences on respiratory health, including increased airway resistance and lung function decrements,1,2 determining and quantifying its causal effect on premature mortality remains a challenge. In recent regulatory impact analyses of air pollution control measures,3–5 the U.S. Environmental Protection Agency (EPA) excluded the ozone–mortality relationship from primary benefits estimates, stating that the epidemiologic literature was too uncertain to infer causality and provide reasonable quantitative estimates.
For ozone–mortality time-series studies, there are a few primary concerns. First, ozone concentrations are frequently correlated with concentrations of other air pollutants, which themselves have been causally linked with mortality. Because of the strong and consistent epidemiologic literature linking particulate matter (PM) and mortality,6–9 any observed relationship between ozone and mortality could simply reflect PM effects that were not adequately captured in the analysis. Other air pollutants such as carbon monoxide (CO), sulfur dioxide (SO2), or nitrogen dioxide (NO2) may be influential as well. Second, because ozone formation is greatest on hot and humid days, which are independently associated with increased mortality,10,11 proper statistical controls for weather in the analysis are crucial (and often difficult to model).
In addition, because ozone is highly reactive in indoor environments (where people spend most of their time), ambient ozone concentrations tend to be higher than personal ozone exposures.12,13 This makes epidemiologic findings based on central site monitors difficult to interpret. Air conditioning further reduces indoor ozone concentrations, especially on the hot and humid days when ozone concentrations are generally highest.12–14 Finally, annually averaged ozone–mortality risks are hard to interpret due to seasonal differences in ozone levels, an inadequate dynamic range during the winter, and differences among personal exposure–ambient concentration or ambient pollutant relationships by season.
Because of these factors, as well as differences in the analytical methods used to address them, simply pooling the results of the published literature has limited interpretability. An alternative approach is to exclude studies that did not adequately address all potentially influential factors. However, given the current literature, this would result in the exclusion of most studies. For example, the U.S. EPA3 evaluated 31 published studies and chose 4 studies in the United States15–18 that were potentially applicable for regulatory impact analyses. None of these studies controlled for fine particulate matter (PM2.5), because monitoring data were not available at the times of the analyses. Similarly, an evaluation of 50 published estimates19 yielded 6 estimates (4 in the United States and 2 in Europe) that met basic screening criteria for a pooled estimate. These pooled estimates are therefore hard to interpret or to apply in regulatory impact analyses, and substantial uncertainties remain.
One approach for dealing with a varied and uncertain literature is to conduct a metaregression, controlling for site or study characteristics that could account for between-study variability. Known confounders or effect modifiers can be characterized external to the study, thus increasing the number of studies eligible for the analysis and allowing insight about the relationship between ozone and mortality. In this study, we identified the published literature on short-term effects of ozone on mortality and conducted a metaregression to determine the influence of other air pollutants, concentration–exposure relationships, weather, and study design on the magnitude of this relationship.
We constructed our database by identifying time-series studies from recent meta-analyses,19,20 the EPA PM criteria document,9 a database provided by the U.S. EPA (Lisa Conner, U.S. EPA, personal communication, 2003), and a Medline search in October 2003 using the keywords “ozone” and “mortality.” We excluded studies that were not time-series studies of all-cause, all-age mortality risks or were not peer-reviewed and publicly available.
This approach yielded 71 potential studies,6,8,15–18,21–85 with some studies reporting multiple city-specific estimates. We removed estimates in which city-specific relative risks or their variances were not reported by the authors,8,27,44,51,53,56,64,71,72,82,85 estimates that were exact duplicates (same authors, cities, study years, and estimates) or superseded by more recent work by the same authors,23,34,40,46,56,60,68,76 and studies that lacked all-age, year-round relative risks.30,32,36,63,66,77,83 We also omitted publications from the National Morbidity and Mortality Air Pollution Study (NMMAPS),6,70 because these data were being reanalyzed separately by other investigators, and we omitted studies for which we were unable to obtain air pollution data necessary for the metaregression.31,42,43,49,50,57,61,73,74,80,81 Because only 2 of the remaining studies were in developing countries,24,25 we excluded these studies to avoid highly influential observations but tested the sensitivity of our findings to their inclusion. Twenty-eight studies remained, from which 48 city-specific relative risk estimates were available. When possible, we also extracted season-specific relative risk estimates, yielding 14 summer/ozone season values16,21,22,37,39,41,55,58,75,77,78,83 and 10 winter/nonozone season values.16,21,22,37,39,41,55,75,77
We selected ozone relative risk estimates that were derived without controlling for other air pollutants. In studies that presented estimates with numerous lag times and averaging times, we selected same-day ozone concentrations when available. This approach was consistent with the majority of the literature, although it did not always yield the primary estimate reported by the authors. All relative risks were converted into percentage increases in mortality per 10 μg/m3 of 1-hour maximum ozone. Estimates that were based on ozone measured in parts per billion were converted to μg/m3, assuming standard temperature and pressure (1 ppb = 1.96 μg/m3). We applied conversion factors to move among 1-hour maximum, 8-hour maximum, and 24-hour average concentrations, with a ratio of 4:3:2 assumed at all sites based on the difference between the median and 95th percentile concentrations across sites for 1996–2000 monitoring data in the United States.86 Because these conversions could vary across sites and years, we evaluated indicator variables within the regression models to ensure that neither conversion was influential.
We categorized studies as GAM-affected or not, in which GAM-affected means that a study used generalized additive models without updating the default convergence criteria, an approach that could influence effect estimates and standard errors.87 We also classified studies by their approach for temperature control using categories proposed elsewhere20: 1) studies that used a linear term for temperature (potentially missing the U-shaped relationship between temperature and mortality), 2) those that added dummy variables for extreme hot/cold days to the linear term, or 3) those that incorporated nonlinear temperature terms.
To capture the relationship between ozone concentrations and concentrations of other criteria pollutants (PM10, PM2.5, CO, SO2, and NO2) for each study, we constructed univariate regressions with ozone as the independent variable at each study site. This approach will yield the magnitudes of concentration changes associated with changes in ozone concentrations rather than providing only the correlations. Because we did not have access to the raw data used within the studies, we relied on publicly available monitoring data gathered from the U.S. EPA Air Quality System,88 the European Environmental Agency Air Base,89 the U.K. National Air Quality Information Archive,90 and the Canadian National Air Pollution Surveillance System.91 When data were available for the years of the epidemiologic studies within the cities or counties studied, those data were used. If those data were unavailable, we first expanded the years surrounding the study dates, followed by the counties surrounding the study site. PM2.5 data were not available for European cities. We used 1-hour maximum concentrations for ozone and CO, and daily average concentrations for all other pollutants. Regressions were run across the entire year as well as restricted to ozone season (May through October) and nonozone season (November through April). In addition, we calculated annual average 1-hour maximum ozone concentrations to capture potential nonlinear concentration–response relationships.
We considered 2 variables as proxies for the ozone personal exposure–ambient concentration relationship. Cooling degree days theoretically captures changes in activity patterns and ventilation used to reduce exposure to high temperatures, and residential central air-conditioning prevalence indicates whether climate control is likely to be based primarily on air-conditioning use (which would decrease indoor ozone levels) or on open windows (which would increase indoor ozone levels). Because daily temperature data were not available for all sites, we estimated cooling degree days using monthly mean temperatures.92 For the cities where daily data were available,93,94 the estimated cooling degree days were highly correlated with the actual (r = 0.99).
Air-conditioning prevalence data for the years approximately corresponding to the epidemiologic studies were obtained for U.S. cities95 and Canadian provinces.96,97 Data were available for selected cities in Canada and all provinces in 2001,98 and the ratio between city and province prevalence was used to adjust the earlier province data when available. Air-conditioning prevalence data for Europe were not available. Because there is no theoretical reason to suspect a linear relationship between cooling degree days and ozone–mortality relative risk, we used an indicator variable for cooling degree days above or below the median across sites. We similarly used an indicator variable for air-conditioning prevalence above or below the median among the sites with data, assuming all sites in Europe have prevalence below the median. We used actual air-conditioning prevalence for analyses on subsets of the data.
For our metaregression, we applied a hierarchical linear model as derived by Raudenbush and Bryk99 and applied in a previous air pollution meta-analysis.100 For this application, the level-1 model is defined as βi = μi + εi, where βi is the reported effect for study i, μi is the true effect, and εi is ∼N(0,si2), where si2 is the reported variance of the effect estimate. In the second-level model, μi = Wi′γ + δi, where Wi is a vector of site or study characteristics (ie, air-conditioning prevalence, GAM-affected), γ is a vector of regression coefficients to be determined, and δi represents the unexplained between-study variability, which is ∼ N(0,τ2). τ2 is derived by maximizing the log of the likelihood function, which is proportional to
where γ* is the maximum likelihood estimate for the vector of derived coefficients, defined as (Σ λiWiWi′)−1 Σ λiWiβi, where λi is τ2/(si2 + τ2).99,100 Posterior empiric Bayes estimates can be calculated as weighted averages of the reported effect βi and the best-fit model output σ̂i, where βi is weighted by τ2/(τ2 + si2) and σ̂i is weighted by si2/(τ2 + si2). Thus, as the regression model explains more between-study variability, the posterior estimate is more heavily weighted toward the model output rather than the observed value, but studies with greater statistical power have posterior estimates closer to the reported values. The metaregression analysis was conducted using HLM (version 5.05; Scientific Software International, Lincolnwood, IL).
Equation (Uncited)Image Tools
For the regression models, given a relatively small sample size and large number of potential covariates, we used an approach similar to forward regression in which the empiric Bayes residuals are linearly regressed against the remaining predictors and the most significant terms are entered sequentially,101 with a threshold of t = 1.7 (corresponding to P = 0.10).
Single-pollutant central effect estimates ranged from a 1.1% decrease in daily mortality per 10-μg/m3 increase of 1-hour maximum ozone to a 1.7% increase, with many estimates between 0.1% and 0.5% (Table 1). Figure 1 shows that a clear “funnel”-shaped trend occurs with increasing sample size, suggesting that many extreme effect estimates are due to small sample size.
The maximum and minimum effect estimates have central estimates approximately 4 standard deviations from the mean, whereas all other values are within 2 standard deviations of the mean. Because these outliers might skew estimates of heterogeneity and influence regression results, we removed those estimates for the primary analyses. Of the 46 remaining estimates, 18 were reported by the authors to be “statistically significant” (P < 0.05). When rank-ordered by total number of deaths (the product of the length of the time-series and number of daily deaths), only 2 of 16 estimates in the lowest tertile are statistically significant, versus 4 of 15 in the second tertile and 12 of 15 in the highest tertile.
There is significant heterogeneity among the effect estimates as determined using Cochran's Q-statistic (P < 0.001), even after removing the 2 outliers. With no covariates in the metaregression, the resulting single-pollutant grand mean is a 0.21% increase in daily mortality per 10-μg/m3 increase of 1-hour maximum ozone (95% confidence interval [CI] = 0.16% to 0.26%). The grand mean is unchanged by inclusion of the outliers or 2 Mexico City estimates.24,25
The magnitude of the ozone–mortality relationship differs substantially across seasons (Fig. 2). The single-pollutant grand mean for summer estimates is a 0.43% increase in daily mortality per 10-μg/m3 increase of 1-hour maximum ozone (95% confidence interval = 0.29% to 0.56%) versus a grand mean for winter estimates of −0.02% (−0.17% to 0.14%).
Although univariate relationships between predictive variables and the ozone–mortality relationship have limited interpretability given correlations among predictors, we present selected stratified values in Table 2. Most predictors do not substantially influence the estimates, although same-day effects appear somewhat greater than lagged effects, and effects appear greater at sites with lower annual average ozone concentrations. Effect estimates are higher for studies using nonlinear temperature terms, as hypothesized, although only 3 of 46 estimates were derived using linear temperature terms. There is a modest inverse relationship between effect estimates and air-conditioning prevalence, although few estimates were available in locations with high central air-conditioning prevalence (Fig. 3).
There is a broad distribution across sites in the regression relationships between ozone and other pollutants, with only limited evidence of a correlation with the ozone–mortality effect estimate (Fig. 4). Positive slopes, which might indicate potential confounding, are seen only for annual and summer PM2.5, although the relationships are weak. For the gaseous pollutants, the regression coefficients at many sites are negative, indicating that higher ozone concentrations are associated with lower levels of these pollutants. The relationship between PM and ozone is generally positive, especially during the summer (Fig. 4). However, these univariate relationships must be interpreted with caution given the influence of other factors.
Applying our hierarchical linear model to the full set of estimates, the 3 predictors entering the forward regression model for the ozone–mortality effect estimate are the lag time (in days), the residential central air-conditioning prevalence (above or below the median), and the ozone–NO2 regression coefficient (all year) (Table 3). This model indicates that ozone has a greater effect in cities with less air conditioning and where there is a positive relationship between ozone and NO2. Also, same-day ozone effects are greater than lagged effects. This model yields posterior city-specific effect estimates that range from −0.1% to 0.4% (Fig. 5).
Clearly, our regression findings could be sensitive to many factors. First, to determine the influence of the assumed conversion factors, we evaluated whether indicator variables for reported units (ppb vs. μg/m3) or measurement time (1-hour maximum, 8-hour maximum, 24-hour average) were significant if added to the final multivariate model. Only the 8-hour dummy variable was statistically significant (P = 0.01), indicating that studies using 8-hour maxima had slightly lower estimates than studies using 1-hour maxima or 24-hour averages.
To get a better sense of the influence of both air conditioning and PM2.5, we restricted the analysis to the 27 U.S. and Canadian estimates for which data on these variables were available. Applying the model from Table 3 yields nearly identical results, with coefficients close to the original values. Using our forward regression approach, there is no evidence of a positive effect from the ozone–PM2.5 regression coefficient, and using the actual air-conditioning prevalence does not change our model findings.
Given concern about influential points, we tested whether the ozone–NO2 regression coefficient changed when extreme values were deleted. If the minimum value is deleted, the optimal forward regression model includes only lag time and air-conditioning prevalence, and the coefficient for the ozone–NO2 regression coefficient decreases from 0.77 to 0.48.
Our final sensitivity analysis considers only studies with number of deaths above the median to determine whether studies with limited statistical power might be influential. Applying the regression model defined in Table 3, the coefficients for lag time and air-conditioning prevalence are similar, whereas the coefficient for the ozone–NO2 regression coefficient decreases from 0.77 to 0.22. Only the lag time enters into the forward regression model (P = 0.08).
Results from our primary model imply that between-study variability in ozone-related mortality can be partially explained by differences in the lag time, air-conditioning prevalence, and relationship between ambient ozone and nitrogen dioxide concentrations. For lag time and air conditioning, the results are robust and intuitive, and suggest that same-day ozone effects exceed lagged effects and that the ambient ozone–mortality relationship might be lower in cities with greater prevalence of residential central air conditioning (and therefore lower personal exposure to ozone).
The less robust influence of NO2, along with the weak effect of PM2.5, is harder to interpret. Given the evidence demonstrating a relationship between ambient PM2.5 and mortality, a stronger association for the PM2.5–ozone regression coefficient may have been anticipated. Furthermore, univariate relationships (Fig. 4) appear stronger for PM2.5 than for NO2, and correlation analyses show that summertime PM2.5 has the strongest mean correlation with ambient ozone among the criteria pollutants and seasons (Fig. 6). Our findings could be related to difficulties in identifying causal factors in a multivariate context, limitations in our ambient pollution data, or might indicate that the use of air pollution regression coefficients in hierarchical linear models is not the optimal approach for evaluating confounding. Although the magnitude of the relationship between ozone and copollutants is influential, so is the strength of the correlation, and the latter might better capture confounding. However, repeating our primary analysis using correlations rather than regression coefficients yielded identical findings.
Beyond the regression findings, we can reach some broad conclusions about the ozone–mortality relationship. Fewer than half of the studies in our analysis reported “statistically significant” findings, which is largely a function of the statistical power of the studies. This observation provides justification for a meta-analytic approach, which helps to combine evidence from individual studies lacking statistical power. In addition, we documented a substantial difference in the ozone–mortality relationship between the summer and winter (Fig. 2).
Clearly, our metaregression has many limitations. Although we attempted to capture the crucial dimensions of methodologic heterogeneity, there are many factors either difficult to quantify or unreported by the authors that could influence effect estimates. This is exemplified by the fact that estimates sometimes differed for studies conducted within the same city, although many of the regression covariates were identical (a factor that limited the predictive power of our regressions). More complex terms reflecting the degrees of freedom used in temperature spline models, for example, might capture some of this uncertainty. More broadly, our pooled estimates depend on the statistical methods applied in the past. For example, recent time-series studies have applied distributed lag models to evaluate the influence of longer time windows,7,102,103 something that cannot be done in a metaregression if the original studies did not follow this approach.
Furthermore, if the ozone–mortality relationship varies geographically, then studies included in the metaregression must be spatially representative to yield generalizable results. Although air conditioning appeared to modify the ozone effect, it is difficult to evaluate potential effect modification given few studies in settings and time periods with high central air-conditioning prevalence. Of our 46 estimates, only 4 were in settings with air-conditioning prevalence above 50%.33,47,59 All 4 of these estimates lacked statistical power, with 3 based on only 1 year of data.33,47 It is therefore difficult to make definitive conclusions about the influence of residential air conditioning on the ozone–mortality relationship. Further time-series studies should be conducted in warm settings with high air-conditioning prevalence to determine the importance of this factor, and studies such as NMMAPS should examine potential effect modification by air-conditioning prevalence. Given the growth of air-conditioning use in many locations, especially in the United States, understanding this influence would be crucial in developing concentration–response functions for prospective regulatory impact analyses. Furthermore, air-conditioning prevalence is only a rough surrogate of residential ventilation and personal exposure patterns, and so more refined indicators should be investigated.
Another limitation is the fact that multiple studies found that ozone was “statistically insignificant” without reporting quantitative estimates.53,56,71,72,82 Other time-series mortality studies may not have mentioned small ozone effects because the results did not reach statistical significance, and in general, such findings may be less likely to be published. Omitting all 3 categories of studies potentially biases our pooled estimates. To bound the influence of this factor, we follow an approach adopted previously19 and calculate the grand mean with no covariates, assuming that omitted studies have a central estimate of zero and the minimum variance among included studies. Adding 5 such estimates would reduce our pooled estimate to 0.17% (95% CI = 0.12% to 0.21%). Although the addition of more studies with no ozone effects would further reduce the central estimate, it would take 161 studies of minimum variance (and many more studies of greater variance) before the pooled estimate became statistically insignificant.
Finally, even if our metaregression accurately captures the relationship between ambient ozone concentrations and mortality risk, this may not reflect the actual exposure–risk relationship. Each of the studies in the current analysis used ambient ozone measurements as surrogates of personal ozone exposures. However, personal ozone exposures have consistently been much lower than corresponding ambient ozone levels of 12- and 24-hour durations.14,105–110 Hence, observed relative risk estimates from studies using ambient concentrations may be underestimating true risks associated with exposure to ozone, presuming that these are the health-relevant averaging times or that these relationships hold for shorter time periods.
Furthermore, exposure assessment studies have not provided conclusive evidence that ambient ozone concentrations are, in fact, strongly correlated with personal ozone exposures. Although only a limited number of exposure assessment studies have examined personal–ambient ozone associations, results suggest that the associations are stronger during the summer, when people spend more time outdoors and within well-ventilated indoor environments.14,105,106,110 The only study to examine hourly relationships between ambient and personal ozone showed weak personal–ambient ozone correlations indoors (r = 0.05) and stronger correlations outdoors (r = 0.8).111 Thus, the amount of exposure error between ambient ozone measurements and corresponding personal exposures may be greater during the winter as compared with the summer, which may contribute to the observed differences in the season-specific risk estimates. Together these results provide some evidence that ambient ozone monitors serve as better surrogates of actual exposure to ozone during warm seasons than during cold seasons.
Despite these limitations, we can draw some conclusions that are useful for public policy. First, our grand mean estimate appears comparable to estimates from previous meta-analyses. Thurston and Ito20 concluded that 6 studies with appropriate temperature characterization had a pooled relative risk of 1.056 per 100 ppb of 1-hour maximum ozone, corresponding to a 0.27% increase in daily mortality per 10-μg/m3 increase of 1-hour maximum ozone. The U.S. EPA estimated a 2.9% increase in deaths per 100-ppb increase in 1-hour maximum ozone4 or an approximate 0.15% increase in daily mortality per 10-μg/m3 increase of 1-hour maximum ozone. These values bound our central estimate of a 0.21% increase.
In addition, the relationship between ozone and mortality appears lower in settings with high residential central air-conditioning prevalence, in agreement with past ozone exposure studies12,13,107 and PM epidemiology.112 Finally, the robustness of the ozone–mortality relationship, even when controlling for key confounders and effect modifiers, indicates that inclusion of ozone-related mortality in future regulatory impact analyses may be warranted, although further investigation is needed into potential PM2.5 confounding in the summer and the personal exposure–ambient concentration relationships by season. Future studies should also explicitly incorporate air-conditioning prevalence or other personal exposure surrogates into the estimation of an appropriate national average ozone–mortality relationship.
We thank Michelle Bell, Francesca Dominici, Kaz Ito, and their colleagues for their participation in this joint effort.
1. Mudway IS, Kelly FJ. Ozone and the lung: a sensitive issue. Mol Aspects Med
2. Hazucha MJ, Bates DV, Bromberg PA, et al. Mechanism of action of ozone on the human lung. J Appl Physiol
3. US Environmental Protection Agency. The Benefits and Costs of the Clean Air Act: 1990 to 2010
. Washington, DC: Office of Air and Radiation; 1999.
4. US Environmental Protection Agency. Regulatory Impact Analysis—Control of Air Pollution from New Motor Vehicles: Tier 2 Motor Vehicle Emissions Standards and Gasoline Sulfur Control Requirements
. Washington, DC: Office of Air and Radiation; 1999.
5. US Environmental Protection Agency. Draft Regulatory Impact Analysis: Control of Emissions from Nonroad Diesel Engines
. Washington, DC: Assessment and Standards Division, Office of Transportation and Air Quality; 2003.
6. Samet JM, Dominici F, Curriero FC, et al. Fine particulate air pollution and mortality in 20 US cities, 1987–1994. N Engl J Med
7. Schwartz J. Is there harvesting in the association of airborne particles with daily deaths and hospital admissions? Epidemiology
8. Schwartz J. Airborne particles and daily deaths in 10 US cities. In: Revised Analyses of Time-Series Studies of Air Pollution and Health
. Boston: Health Effects Institute; 2003:211–218.
9. US Environmental Protection Agency. Fourth External Review Draft of Air Quality Criteria for Particulate Matter
. Research Triangle Park, NC: National Center for Environmental Assessment, Office of Research and Development; 2003.
10. O'Neill MS, Zanobetti A, Schwartz J. Modifiers of the temperature and mortality association in seven US cities. Am J Epidemiol
11. Kalkstein LS, Greene JS. An evaluation of climate/mortality relationships in large U.S. cities and the possible impacts of a climate change. Environ Health Perspect
12. Zhang J, Lioy PJ. Ozone in residential air: concentrations, I/O ratios, indoor chemistry, and exposures. Indoor Air
13. Avol EL, Navidi WC, Colome SD. Modeling ozone levels in and around Southern California homes. Environ Sci Technol
14. Liu L-JS, Delfino R, Koutrakis P. Ozone exposure assessment in a Southern California community. Environ Health Perspect
15. Ito K, Thurston GD. Daily PM10/mortality associations: an investigation of at-risk subpopulations. J Expo Anal Environ Epidemiol
16. Moolgavkar SH, Luebeck EG, Hall TA, et al. Air pollution and daily mortality in Philadelphia. Epidemiology
17. Kinney PL, Ito K, Thurston GD. A sensitivity analysis of mortality/PM10 associations in Los Angeles. Inhal Toxicol
18. Samet JM, Zeger SL, Kelsall JE, et al. Particulate Air Pollution and Daily Mortality: Analysis of the Effects of Weather and Multiple Air Pollutants. The Phase 1.B Report of the Particle Epidemiology Evaluation Project
. Cambridge, MA: Health Effects Institute; 1997.
19. Levy JI, Carrothers TJ, Tuomisto JT, et al. Assessing the public health benefits of reduced ozone concentrations. Environ Health Perspect
20. Thurston GD, Ito K. Epidemiological studies of acute ozone exposures and mortality. J Expo Anal Environ Epidemiol
21. Anderson HR, Bremner SA, Atkinson RW, et al. Particulate matter and daily mortality and hospital admissions in the west midlands conurbation of the United Kingdom: associations with fine and coarse particles, black smoke and sulphate. Occup Environ Med
22. Anderson HR, deLeon AP, Bland JM, et al. Air pollution and daily mortality in London: 1987–92. BMJ
23. Baxter LA, Finch SJ, Lipfert FW, et al. Comparing estimates of the effects of air pollution on human mortality obtained using different regression methodologies. Risk Anal
24. Borja-Aburto VH, Castillejos M, Gold DR, et al. Mortality and ambient fine particles in southwest Mexico City, 1993–1995. Environ Health Perspect
25. Borja-Aburto VH, Loomis DP, Bangdiwala SI, et al. Ozone, suspended particulates, and daily mortality in Mexico City. Am J Epidemiol
26. Bremner SA, Anderson HR, Atkinson RW, et al. Short-term associations between outdoor air pollution and mortality in London 1992–4. Occup Environ Med
27. Burnett RT, Brook J, Dann T, et al. Association between particulate- and gas-phase components of urban air pollution and daily mortality in eight Canadian cities. Inhal Toxicol
. 2000;12(suppl 4):15–39.
28. Burnett RT, Cakmak S, Brook JR. The effect of the urban ambient air pollution mix on daily mortality rates in 11 Canadian cities. Can J Public Health
29. Burnett RT, Cakmak S, Raizenne ME, et al. The association between ambient carbon monoxide levels and daily mortality in Toronto, Canada. J Air Waste Manag Assoc
30. Chock DP, Winkler SL, Chen C. A study of the association between daily mortality and ambient air pollutant concentrations in Pittsburgh, Pennsylvania. J Air Waste Manag Assoc
31. Cifuentes LA, Vega J, Kopfer K, et al. Effect of the fine fraction of particulate matter versus the coarse mass and other pollutants on daily mortality in Santiago, Chile. J Air Waste Manag Assoc
32. Diaz J, Garcia R, Ribera P, et al. Modeling of air pollution and its relationship with mortality and morbidity in Madrid, Spain. Int Arch Occup Environ Health
33. Dockery DW, Schwartz J, Spengler JD. Air pollution and daily mortality: associations with particulates and acid aerosols. Environ Res
34. Fairley D. Daily mortality and air pollution in Santa Clara County, California: 1989–1996. Environ Health Perspect
35. Fairley D. Mortality and air pollution for Santa Clara County, California, 1989–1996. Revised Analyses of Time-Series Studies of Air Pollution and Health
. Boston: Health Effects Institute; 2003;97–106.
36. Fischer P, Hoek G, Brunekreef B, et al. Air pollution and mortality in The Netherlands: are the elderly more at risk? Eur Respir J Suppl
37. Goldberg MS, Burnett RT, Brook J, et al. Associations between daily cause-specific mortality and concentrations of ground-level ozone in Montreal, Quebec. Am J Epidemiol
38. Gwynn RC, Burnett RT, Thurston GD. A time-series analysis of acidic particulate matter and daily mortality and morbidity in the Buffalo, New York, region. Environ Health Perspect
39. Hoek G. Daily mortality and air pollution in The Netherlands. Revised Analyses of Time-Series Studies of Air Pollution and Health
. Boston: Health Effects Institute; 2003;133–142.
40. Hoek G, Brunekreef B, Verhoeff A, et al. Daily mortality and air pollution in The Netherlands. J Air Waste Manag Assoc
41. Hoek G, Schwartz JD, Groot B, et al. Effects of ambient particulate matter and ozone on daily mortality in Rotterdam, The Netherlands. Arch Environ Health
42. Hong YC, Leem JH, Ha EH. Air pollution and daily mortality in Inchon, Korea. J Korean Med Sci
43. Hong YC, Leem JH, Ha EH, et al. PM(10) exposure, gaseous pollutants, and daily mortality in Inchon, South Korea. Environ Health Perspect
44. Katsouyanni K, Touloumi G, Spix C, et al. Short term effects of ambient sulphur dioxide and particulate matter on mortality in 12 European cities: results from time series data from the APHEA project. BMJ
45. Kelsall JE, Samet JM, Zeger SL, et al. Air pollution and mortality in Philadelphia, 1974–1988. Am J Epidemiol
46. Kinney PL, Ozkaynak H. Associations of daily mortality and air-pollution in Los-Angeles-County. Environ Res
47. Klemm RJ, Mason RM Jr. Aerosol Research and Inhalation Epidemiological Study (ARIES): air quality and daily mortality statistical modeling—interim results. J Air Waste Manag Assoc
48. Kotesovec F, Skorkovsky J, Brynda J, et al. Daily mortality and air pollution in northern Bohemia: different effects for men and women. Cent Eur J Public Health
49. Lee JT, Kim H, Hong YC, et al. Air pollution and daily mortality in seven major cities of Korea, 1991–1997. Environ Res
50. Lee JT, Shin D, Chung Y. Air pollution and daily mortality in Seoul and Ulsan, Korea. Environ Health Perspect
51. Lipfert FW, Morris SC, Wyzga RE. Daily mortality in the Philadelphia metropolitan area and size-classified particulate matter. J Air Waste Manag Assoc
52. Lippmann M, Ito K, Nadas A, et al. Association of particulate matter components with daily mortality and morbidity in urban populations. Research Report Health Effects Institute
53. Mar TF, Norris GA, Koenig JQ, et al. Associations between air pollution and mortality in Phoenix, 1995–1997. Environ Health Perspect
54. Michelozzi P, Forastiere F, Fusco D, et al. Air pollution and daily mortality in Rome, Italy. Occup Environ Med
55. Moolgavkar SH. Air pollution and daily mortality in two US counties: season-specific analyses and exposure–response relationships. Inhal Toxicol
56. Moolgavkar SH. Air pollution and daily mortality in three US counties. Environ Health Perspect
57. Morgan G, Corbett S, Wlodarczyk J, et al. Air pollution and daily mortality in Sydney, Australia, 1989 through 1993. Am J Public Health
58. Ostro B. Fine particulate air pollution and mortality in two Southern California counties. Environ Res
59. Ostro BD, Broadwin R, Lipsett MJ. Coarse and fine particles and daily mortality in the Coachella Valley, California: a follow-up study. J Expo Anal Environ Epidemiol
60. Ostro BD, Hurley S, Lipsett MJ. Air pollution and daily mortality in the Coachella Valley, California: a study of PM10 dominated by coarse particles. Environ Res
61. Ostro BD, Sanchez JM, Aranda C, et al. Air pollution and mortality: results from a study of Santiago, Chile. J Expo Anal Environ Epidemiol
62. Peters A, Skorkovsky J, Kotesovec F, et al. Associations between mortality and air pollution in central Europe. Environ Health Perspect
63. Ponka A, Savela M, Virtanen M. Mortality and air pollution in Helsinki. Arch Environ Health
64. Pope CA III, Schwartz J, Ransom MR. Daily mortality and PM10 pollution in Utah Valley. Arch Environ Health
65. Prescott GJ, Cohen GR, Elton RA, et al. Urban air pollution and cardiopulmonary ill health: a 14.5 year time series study. Occup Environ Med
66. Rahlenbeck SI, Kahl H. Air pollution and mortality in East Berlin during the winters of 1981–1989. Int J Epidemiol
67. Roemer WH, van Wijnen JH. Daily mortality and air pollution along busy streets in Amsterdam, 1987–1998. Epidemiology
68. Ito K, Kinney P, Thurston GD. Variations in PM10 concentrations within two metropolitan areas and their implications for health effects analyses. Inhal Toxicol
69. Saez M, Ballester F, Barcelo MA, et al. A combined analysis of the short-term effects of photochemical air pollutants on mortality within the EMECAM project. Environ Health Perspect
70. Samet J, Zeger S, Dominici F, et al. The National Morbidity, Mortality, and Air Pollution Study Part II: Morbidity, Mortality, and Air Pollution in the United States
. Cambridge, MA: Health Effects Institute; 2000.
71. Schwartz J. Particulate air pollution and daily mortality in Detroit. Environ Res
72. Shumway RH, Azari AS, Pawitan T. Modeling mortality fluctuations in Los Angeles as a function of pollution and weather effects. Environ Res
73. Simpson R, Denison L, Petroeschevsky A, et al. Effects of ambient particle pollution on daily mortality in Melbourne, 1991–1996. J Expo Anal Environ Epidemiol
74. Simpson RW, Williams G, Petroeschevsky A, et al. Associations between outdoor air pollution and daily mortality in Brisbane, Australia. Arch Environ Health
75. Sunyer J, Castellsague J, Saez M, et al. Air pollution and mortality in Barcelona. J Epidemiol Community Health
. 1996;50(suppl 1):s76–80.
76. Touloumi G, Katsouyanni K, Zmirou D, et al. Short-term effects of ambient oxidant exposure on mortality: a combined analysis within the APHEA project. Air pollution and health: a European approach. Am J Epidemiol
77. Vedal S, Brauer M, White R, et al. Air pollution and daily mortality in a city with low levels of pollution. Environ Health Perspect
78. Verhoeff AP, Hoek G, Schwartz J, et al. Air pollution and daily mortality in Amsterdam. Epidemiology
79. Wietlisbach V, Pope CA, Ackermann-Liebrich U. Air pollution and daily mortality in three Swiss urban areas. Soz Praventivmed
80. Wong CM, Ma S, Hedley AJ, et al. Effect of air pollution on daily mortality in Hong Kong. Environ Health Perspect
81. Wong TW, Tam WS, Yu TS, et al. Associations between daily mortalities from respiratory and cardiovascular diseases and air pollution in Hong Kong, China. Occup Environ Med
82. Wordley J, Walters S, Ayres JG. Short term variations in hospital admissions and mortality and particulate air pollution. Occup Environ Med
83. Zeghnoun A, Czernichow P, Beaudeau P, et al. Short-term effects of air pollution on mortality in the cities of Rouen and Le Havre, France, 1990–1995. Arch Environ Health
84. Zmirou D, Barumandzadeh T, Balducci F, et al. Short term effects of air pollution on mortality in the city of Lyon, France, 1985–90. J Epidemiol Community Health
. 1996;50(suppl 1):S30–35.
85. Li Y, Roth HD. Daily mortality analysis by using different regression models in Philadelphia County, 1973–1990. Inhal Toxicol
86. Pinto J. Percentiles of 1996–2000 ozone concentrations. US Environmental Protection Agency memorandum, September 2003.
87. Health Effects Institute. Revised Analyses of Time-Series Studies of Air Pollution and Health. Special Report
. Boston: Health Effects Institute; 2003.
96. Statistics Canada. Household Income, Facilities, and Equipment Survey, 1982
. Ottawa, Ontario, Canada; 1983.
97. Natural Resources Canada. 1993 Survey of Household Energy Use: Provincial Results
. Ottawa, Ontario: Energy Demand Branch; 1995.
98. Statistics Canada. Survey of Household Spending in 2001.
Ottawa, Ontario, Canada; 2002.
99. Raudenbush SW, Bryk AS. Empirical Bayes meta-analysis. J Educ Stat
100. Levy JI, Hammitt JK, Spengler JD. Estimating the mortality impacts of particulate matter: what can be learned from between-study variability? Environ Health Perspect
101. Bryk AS, Raudenbush SW. Hierarchical Linear Models
. Newbury Park, CA: Sage Publications; 1992.
102. Schwartz J. Harvesting and long term exposure effects in the relation between air pollution and mortality. Am J Epidemiol
103. Bell ML, McDermott A, Zeger SL, et al. Ozone and short-term mortality in 95 US urban communities, 1987–2000. JAMA
104. Sarnat JA, Schwartz J, Catalano PJ, et al. Gaseous pollutants in particulate matter epidemiology: confounders or surrogates? Environ Health Perspect
105. Sarnat JA, Koutrakis P, Suh HH. Assessing the relationship between personal particulate and gaseous exposures of senior citizens living in Baltimore, MD. J Air Waste Manag Assoc
106. O'Neill MS, Ramirez-Aguilar M, Meneses-Gonzalez F, et al. Ozone exposure among Mexico City outdoor workers. J Air Waste Manag Assoc
107. Liu LJ, Koutrakis P, Leech J, et al. Assessment of ozone exposures in the greater metropolitan Toronto area. J Air Waste Manag Assoc
108. Liu LJ, Koutrakis P, Suh HH, et al. Use of personal measurements for ozone exposure assessment: a pilot study. Environ Health Perspect
109. Brauer M, Brook JR. Personal and fixed-site ozone measurements with a passive sampler. J Air Waste Manag Assoc
110. Liard R, Zureik M, Le Moullec Y, et al. Use of personal passive samplers for measurement of NO(2), NO, and O(3) levels in panel studies. Environ Res
111. Chang LT, Suh HH, Wolfson JM, et al. Laboratory and field evaluation of measurement methods for one-hour exposures to O3, PM2.5, and CO. J Air Waste Manag Assoc
112. Janssen NA, Schwartz J, Zanobetti A, et al. Air conditioning and source-specific particles as modifiers of the effect of PM(10) on hospital admissions for heart and lung disease. Environ Health Perspect
This article has been cited 73 time(s).
Environmental Science & TechnologyImpact of Human Presence on Secondary Organic Aerosols Derived from Ozone-Initiated Chemistry in a Simulated Office EnvironmentEnvironmental Science & Technology
Journal of Toxicology and Environmental Health-Part A-Current IssuesAir pollution risk estimates: Determinants of heterogeneityJournal of Toxicology and Environmental Health-Part A-Current Issues
Environmental HealthAncillary human health benefits of improved air quality resulting from climate change mitigationEnvironmental Health
Inhalation ToxicologyChemicals present in automobile traffic tunnels and the possible community health hazards: A review of the literatureInhalation Toxicology
Inhalation ToxicologyCritical considerations in evaluating scientific evidence of health effects of ambient ozone: a conference reportInhalation Toxicology
Atmospheric EnvironmentSpatial variability of summertime tropospheric ozone over the continental United States: Implications of an evaluation of the CMAQ modelAtmospheric Environment
LancetEnergy and Health 2 - Electricity generation and healthLancet
Journal of the Air & Waste Management Association
The health benefits of reduced tropospheric ozone in California
Journal of the Air & Waste Management Association, 56(7):
American Journal of Respiratory and Critical Care MedicineMortality displacement in the association of ozone with mortality - An analysis of 48 cities in the United StatesAmerican Journal of Respiratory and Critical Care Medicine
Archives of Environmental & Occupational Health
Temperature Enhanced Effects of Ozone on Cardiovascular Mortality in 95 Large US Communities, 1987-2000: Assessment Using the NMMAPS Data
Archives of Environmental & Occupational Health, 64(3):
European Respiratory JournalClimate change and respiratory disease: European Respiratory Society position statementEuropean Respiratory Journal
New England Journal of Medicine
Long-Term Ozone Exposure and Mortality
New England Journal of Medicine, 360():
Journal of the Air & Waste Management AssociationUsing Backup Generators for Meeting Peak Electricity Demand: A Sensitivity Analysis on Emission Controls, Location, and Health EndpointsJournal of the Air & Waste Management Association
Environmental Science & TechnologyIntercontinental Impacts of Ozone Pollution on Human MortalityEnvironmental Science & Technology
Journal of Epidemiology and Community HealthThe temporal pattern of mortality responses to ambient ozone in the APHEA projectJournal of Epidemiology and Community Health
Environment InternationalUsing air quality modeling to study source-receptor relationships between nitrogen oxides emissions and ozone exposures over the United StatesEnvironment International
Environmental Health PerspectivesThe impact of secondary particles on the association between ambient ozone and mortalityEnvironmental Health Perspectives
American Journal of Preventive MedicineClimate Change, Air Quality, and Human HealthAmerican Journal of Preventive Medicine
Occupational and Environmental MedicineAir pollution and asthma severity in adultsOccupational and Environmental Medicine
Revue Des Maladies RespiratoiresShort-term health effects of air pollution on mortalityRevue Des Maladies Respiratoires
Inhalation ToxicologyReassessing the relationship between ozone and short-term mortality in US urban communitiesInhalation Toxicology
American Journal of Respiratory and Critical Care MedicineTLR4 Is Necessary for Hyaluronan-mediated Airway Hyperresponsiveness after Ozone InhalationAmerican Journal of Respiratory and Critical Care Medicine
Environmental HealthIs there adaptation in the ozone mortality relationship: A multi-city case-crossover analysisEnvironmental Health
Atmospheric Chemistry and Physics
Effect of regional precursor emission controls on long-range ozone transport - Part 2: Steady-state changes in ozone air quality and impacts on human mortality
Atmospheric Chemistry and Physics, 9():
Revue Francaise D AllergologieShort-term health effects of air pollution on mortalityRevue Francaise D Allergologie
Occupational and Environmental MedicineOzone exposure, antioxidant genes, and lung function in an elderly cohort: VA normative aging studyOccupational and Environmental Medicine
NeurotoxicologyNeurobehavioral effects of ambient air pollution on cognitive performance in US adultsNeurotoxicology
Environmental HealthModifiers of short-term effects of ozone on mortality in eastern Massachusetts - A case-crossover analysis at individual levelEnvironmental Health
Proceedings of the National Academy of Sciences of the United States of America
Global health benefits of mitigating ozone pollution with methane emission controls
Proceedings of the National Academy of Sciences of the United States of America, 103():
Environmental Science & TechnologyAdjoint sensitivity analysis of ozone nonattainment over the continental United StatesEnvironmental Science & Technology
Environmental Health PerspectivesOzone and daily mortality in Shanghai, ChinaEnvironmental Health Perspectives
Environmental Health PerspectivesPotential confounding of particulate matter on the short-term association between ozone and mortality in multisite time-series studiesEnvironmental Health Perspectives
Seasonal Forecasts, Climatic Change and Human Health
Impacts of heat and ozone on mortality risk in the New York City metropolitan region under a changing climate
Seasonal Forecasts, Climatic Change and Human Health, 30():
Journal of Epidemiology and Community HealthAir pollution and cardiovascular admissions association in Spain: results within the EMECAS projectJournal of Epidemiology and Community Health
Ozone exposure and lung function - Effect modified by obesity and airways hyperresponsiveness in the VA normative aging study
Atmospheric Chemistry and Physics
The influence of European pollution on ozone in the Near East and northern Africa
Atmospheric Chemistry and Physics, 8(8):
Ecology Law Quarterly
The Ozone Saga
Ecology Law Quarterly, 35(3):
Journal of Biological ChemistryHyaluronan Mediates Ozone-induced Airway Hyperresponsiveness in MiceJournal of Biological Chemistry
Journal of Occupational and Environmental HygieneClimate Change and Occupational Safety and Health: Establishing a Preliminary FrameworkJournal of Occupational and Environmental Hygiene
LancetHealth and Climate Change 5 Public health benefits of strategies to reduce greenhouse-gas emissions: health implications of short-lived greenhouse pollutantsLancet
Indoor AirOzone-surface reactions in five homes: surface reaction probabilities, aldehyde yields, and trendsIndoor Air
Environmental Science & TechnologyIntegrated assessment of the spatial variability of ozone impacts from emissions of nitrogen oxidesEnvironmental Science & Technology
Neurochemical ResearchPrenatal exposure to ozone disrupts cerebellar monoamine contents in newborn ratsNeurochemical Research
Journal of Exposure Science and Environmental EpidemiologyA scripted activity study of the impact of protective advice on personal exposure to ultra-fine and fine particulate matter and volatile organic compoundsJournal of Exposure Science and Environmental Epidemiology
Journal of Exposure Science and Environmental EpidemiologySummary and findings of the EPA and CDC symposium on air pollution exposure and healthJournal of Exposure Science and Environmental Epidemiology
Environment InternationalDoes temperature modify short-term effects of ozone on total mortality in 60 large eastern US communities? An assessment using the NMMAPS dataEnvironment International
Risk AnalysisIs Epidemiology the Key to Cumulative Risk Assessment ?Risk Analysis
Toxicology and Applied PharmacologyIs it true that ozone is always toxic? The end of a dogmaToxicology and Applied Pharmacology
Resource and Energy EconomicsDose response functions and the harvesting effectResource and Energy Economics
Comptes Rendus GeoscienceHuman mortality effects of future concentrations of tropospheric ozoneComptes Rendus Geoscience
American Journal of EpidemiologyEffect modification by community characteristics on the short-term effects of ozone exposure and mortality in 98 US communitiesAmerican Journal of Epidemiology
American Journal of EpidemiologyAmbient Ozone Concentrations and Cardiac Mortality in Southern California 1983-2000: Application of a New Marginal Structural Model ApproachAmerican Journal of Epidemiology
Journal of Environmental MonitoringBiological monitoring of ozone: the twenty-year Italian experienceJournal of Environmental Monitoring
Epidemiologia & Prevenzione
Health impact of ozone in 13 Italian cities
Epidemiologia & Prevenzione, 31(6):
Science of the Total EnvironmentFactors influencing relationships between personal and ambient concentrations of gaseous and particulate pollutantsScience of the Total Environment
Journal of Epidemiology and Community HealthAir pollution and emergency admissions in Boston, MAJournal of Epidemiology and Community Health
Environmental Health PerspectivesOzone's impact on public health: Contributions from indoor exposures to ozone and products of ozone-initiated chemistryEnvironmental Health Perspectives
Atmospheric EnvironmentWhich metric of ambient ozone to predict daily mortality?Atmospheric Environment
Atmospheric EnvironmentImpact of cement renders on airborne ozone and carbon dioxide concentrationsAtmospheric Environment
European Respiratory JournalImpact of climate change on ozone-related mortality and morbidity in EuropeEuropean Respiratory Journal
Environmental Health PerspectivesTime-Series Analyses of Air Pollution and Mortality in the United States: A Subsampling ApproachEnvironmental Health Perspectives
Environmental Science & TechnologyPreparation Methods to Optimize the Performance of Sensor Discs for Fast Chemiluminescence Ozone AnalyzersEnvironmental Science & Technology
BiogeosciencesMeasurements of nitrogen oxides and ozone fluxes by eddy covariance at a meadow: evidence for an internal leaf resistance to NO2Biogeosciences
Air Quality Atmosphere and HealthThe public health context for PM2.5 and ozone air quality trendsAir Quality Atmosphere and Health
Environmental Monitoring and AssessmentSeasonal variation in the acute effects of ozone on premature mortality among elderly JapaneseEnvironmental Monitoring and Assessment
Atmospheric Chemistry and PhysicsAir pollution and associated human mortality: the role of air pollutant emissions, climate change and methane concentration increases from the preindustrial period to presentAtmospheric Chemistry and Physics
EpidemiologyAmbient Ozone and MortalityEpidemiology
EpidemiologyThe Methodologic Ozone EffectEpidemiology
© 2005 Lippincott Williams & Wilkins, Inc.