This multisite time-series study of 95 large US urban communities through-out a 14-year period provides strong evidence of an association between mortality and short-term exposure to ozone. On average across the 95 communities, we estimated a 0.52% (95% PI, 0.27%-0.77%) increase in daily mortality for a 10-ppb increase in the previous week’s ozone concentration. We found that the community-specific estimates were heterogeneous. Air pollution effect estimates may be heterogeneous because of many factors, including city-specific differences in pollution characteristics, the use of air conditioning, time spent indoors vs out-doors, and socioeconomic factors.
The estimated effect was relatively robust to estimation with several statistical models and to the degree of confounding adjustment for seasonality, long-term trends, and temperature. The results indicate a substantial health burden from ozone pollution. For example, according to our national average estimate from the constrained distributed-lag model, a 10-ppb increase in daily ozone would correspond to an additional 319 (95% PI, 168-472) annual premature deaths for New York City and 3767 (95% PI, 1976-5562) premature deaths annually for the 95 urban communities, based on mortality data from 2000. This value is probably an underestimate of the total mortality burden from such an increase in ozone because it accounts for only the short-term effects. Further, we found a relationship between mortality and ozone at pollution levels below the current regulatory standard. Our analysis focused on 95 large urbanized areas, although rural communities may also experience elevated ozone levels, especially because of large biogenic emissions of volatile organic compounds and the movement of ozone and ozone precursors from other regions.
Our study resolves inconsistencies in the findings of previous time-series studies of ozone and mortality. The national average estimate was comparable to those from other pooled analyses, including meta-analyses and other, smaller multicity studies. To compare results across these studies, which have used diverse metrics for ozone exposure, we converted the estimates from all of the studies to a common metric, the daily average. Although the relationship between different ozone concentration metrics can vary by location, we used ratios of 2.5 and 1.33 to convert estimates according to the daily 1-hour maximum and 8-hour maximum, respectively, to the daily average, as has been done by others.46,47
Earlier multicity time-series studies of ozone and mortality have estimated a broad range of effects. A 10-ppb increase in daily ozone was associated with estimated increases in daily mortality of 2.84% (95% PI, 0.95%-4.77%) for 4 European cities,48
0.61% (95% PI, −0.38% to 1.60%) for 7 Spanish cities,49
1.40% (95% PI, 0.68%-2.12%) for 6 French cities,50
and 0.43% (95% PI, 0.23%-0.63%) for 80 US urban centers from 1987 to 199422
; however, a negative, non-statistically significant association was reported for 7 major Korean cities for 1991-1997.51
Recent meta-analyses were reported by Thurston and Ito,47
who combined results of 16 studies and considered differences in their approaches to the modeling of weather; Levy et al,46
who used 4 US studies based in Cook County, Illinois, and Philadelphia; Stieb et al,52,53
who extracted results from 109 single- and multicity studies for random effects pooling; and Anderson et al,54
who conducted a meta-analysis of ozone and PM as part of a World Health Organization project. The overall estimates from the meta-analysis studies, expressed as the percentage increase in daily mortality for a 10-ppb increase in daily ozone, are 0.89% (95% CI, 0.56%-1.22%)47
; 1.37% (95% CI, 0.78%-1.96%),47
considering only studies that allow nonlinear associations between temperature and mortality; 0.98% (95% CI, 0.59%-1.38%)46
; 1.12% (95% CI, 0.32%-1.92%)52,53
; and 0.78% (95% CI, 0.39%-1.18%).54
Our distributed-lag model’s estimate was 0.52% (95% PI, 0.27%-0.77%) for a 10-ppb increase in the previous week’s ozone levels, whereas our estimates for a single day’s lag was 0.25% (95% PI, 0.12%-0.39%) and 0.18% (95% PI, 0.06%-0.30%) for a 10-ppb increase in the same day’s and previous day’s ozone concentrations, respectively. The lower value estimated by our model could be due to publication bias in the single-city studies that are incorporated into the meta-analyses. Because the same statistical approach was applied to time-series data from the 95 large US urban communities, our results are not subject to publication bias.
A key advance in our study is the use of distributed-lag models, rather than models that estimate the effect of a single day or several days at a particular lag. Using single-day lagged models and the distributed-lag approach, we found statistically significant associations between ozone levels on the preceding days (primarily the current day and 2 previous days) and daily mortality. This temporal pattern of effect would be anticipated for ozone, which produces acute inflammatory responses in the lung; adaptation of this inflammatory response with several days of repeated exposure has been demonstrated.55,56
Although the temporal dynamics of the underlying processes linking ozone exposure to increased mortality may differ from those of the inflammatory response, inflammation has been postulated as having a central role in the increased mortality and morbidity associated with ozone.
Several groups within the population have been considered at increased risk from ozone exposure, including older persons and those with underlying chronic heart and lung diseases. We did not find evidence of significantly greater risk for these 2 groups; the estimated increments in risk were similar across age groups and for total mortality and cardiorespiratory mortality. However, this lack of evidence for increased susceptibility should be interpreted in the context of effect modification on the relative risk scale in the statistical models that were used. In these models, higher underlying mortality rates are increased multiplicatively by the effect of ozone, implying a substantially greater absolute effect of ozone in older persons or those with cardiac or pulmonary diseases. Because the older population has a larger baseline mortality rate than the general population, the same relative rate estimate for the older and the general populations leads to a larger number of extra deaths for the elderly.
One critical concern is the extent to which effect estimates may be confounded by either temperature or other pollutants. In the communities included in the present analysis, the concentration of ozone was not correlated with concentrations of PM10. This lack of correlation and the stability of the ozone estimate with inclusion of PM10, and vice versa, in the models provide strong evidence against confounding of the effects of these 2 pollutants. The ozone and mortality results do not appear to be confounded by temperature, as evidenced by analyses using subsets of the data at various temperature levels and periods.
However, the estimated effect of ozone, although robust to the adjustment for PM10
, may still reflect the risk from the photochemical pollution mixture more generally. Atmospheric photochemistry produces several hazardous pollutants, in addition to ozone, such as peroxyacyl nitrates.18
Ozone may act as a surrogate indicator for this highly complex and geographically variable mixture and is likely to be an imperfect measure of potential toxicity. The degree to which ozone functions as a surrogate for other pollutants or the pollutant mixture in general, and thereby misclassifies toxicity, may vary across locations and depend on the mix of sources and meteorologic factors. Although statistically significant relationships were identified for all ozone concentration metrics considered, the analysis did not identify a particular metric as the optimum predictor of mortality.
Ozone pollution is now widespread in urban areas in the United States and many other countries. Its rise reflects primarily increased numbers of motor vehicles and miles traveled; vehicle emissions are a major source of precursor hydro carbons and nitrogen oxides. In the United States, more than a hundred areas are not in compliance with the 8-hour NAAQS for ozone, with the most extreme violations in California.2
Our findings, interpreted in the context of the already extensive epidemiologic and toxicologic evidence on ozone toxicity, indicate that this widespread pollutant adversely affects mortality, in addition to other health effects that have been associated with ozone.4-6
The consequences of control strategies for public health can be tracked with the methods and databases described in this report.