Giota Touloumi

Confounding and Effect Modification in the Short-term Effects of Ambient Particles on Total Mortality: Results from 29 European Cities within the Aphea2 Project

We present the results of the Air Pollution and Health: A European Approach 2 (APHEA2) project on short-term effects of ambient particles on mortality with emphasis on effect modification. We used daily measurements for particulate matter less than 10 &mgr;m in aerodynamic diameter (PM10) and/or black smoke from 29 European cities. We considered confounding from other pollutants as well as meteorologic and chronologic variables. We investigated several variables describing the cities’ pollution, climate, population, and geography as potential effect modifiers. For the individual city analysis, generalized additive models extending Poisson regression, using a smoother to control for seasonal patterns, were applied. To provide quantitative summaries of the results and explain remaining heterogeneity, we applied second-stage regression models. The estimated increase in the daily number of deaths for all ages for a 10 &mgr;g/m3 increase in daily PM10 or black smoke concentrations was 0.6% [95% confidence interval (CI) = 0.4–0.8%], whereas for the elderly it was slightly higher. We found important effect modification for several of the variables studied. Thus, in a city with low average NO2, the estimated increase in daily mortality for an increase of 10 &mgr;g/m3 in PM10 was 0.19 (95% CI = 0.00–0.41), whereas in a city with high average NO2 it was 0.80% (95% CI = 0.67–0.93%); in a relatively cold climate the corresponding effect was 0.29% (95% CI = 0.16–0.42), whereas in a warm climate it was 0.82% (95% CI = 0.69–0.96); in a city with low standardized mortality rate it was 0.80% (95% CI = 0.65–0.95%), and in one with a high rate it was 0.43% (95% CI = 0.24–0.62). Our results confirm those previously reported on the effects of ambient particles on mortality. Furthermore, they show that the heterogeneity found in the effect parameters among cities reflects real effect modification, which is explained by specific city characteristics.

Air pollution and daily admissions for chronic obstructive pulmonary disease in 6 European cities: results from the APHEA project

We investigated the short-term effects of air pollution on hospital admissions for chronic obstructive pulmonary disease (COPD) in Europe. As part of a European project (Air Pollution and Health, a European Approach (APHEA)), we analysed data from the cities of Amsterdam, Barcelona, London, Milan, Paris and Rotterdam, using a standardized approach to data eligibility and statistical analysis. Relative risks for daily COPD admissions were obtained using Poisson regression, controlling for: seasonal and other cycles; influenza epidemics; day of the week; temperature; humidity and autocorrelation. Summary effects for each pollutant were estimated as the mean of each citys regression coefficients weighted by the inverse of the variance, allowing for additional between-cities variance, as necessary. For all ages, the relative risks (95% confidence limits (95% CL)) for a 50 microg x m(-3) increase in daily mean level of pollutant (lagged 1-3 days) were (95% CL): sulphur dioxide 1.02 (0.98, 1.06); black smoke 1.04 (1.01, 1.06); total suspended particulates 1.02 (1.00, 1.05), nitrogen dioxide 1.02 (1.00, 1.05) and ozone (8 h) 1.04 (1.02, 1.07). The results confirm that air pollution is associated with daily admissions for chronic obstructive pulmonary disease in European cities with widely varying climates. The results for particles and ozone are broadly consistent with those from North America, though the coefficients for particles are substantially smaller. Overall, the evidence points to a causal relationship but the mechanisms of action, exposure response relationships and pollutant interactions remain unclear.

Methodological issues in studies of air pollution and daily counts of deaths or hospital admissions.

STUDY OBJECTIVE: To review the issues and methodologies in epidemiologic time series studies of daily counts of mortality and hospital admissions and illustrate some of the methodologies. DESIGN: This is a review paper with an example drawn from hospital admissions of the elderly in Cleveland, Ohio, USA. MAIN RESULTS: The central issue is control for seasonality. Both over and under control are possible, and the use of diagnostics, including plots, is necessary. Weather dependence is probably non-linear, and adequate methods are necessary to adjust for this. In Cleveland, the use of categorical variables for weather and sinusoidal terms for filtering season are illustrated. After control for season, weather, and day of the week effects, hospital admission of persons aged 65 and older in Cleveland for respiratory illness was associated with ozone (RR = 1.09, 95% CI 1.02, 1.16) and particulates (PM10 (RR = 1.12, 95% CI 1.01, 1.24), and marginally associated with sulphur dioxide (SO2) (RR = 1.03, 95% CI = 0.99, 1.06). All of the relative risks are for a 100 micrograms/m3 increase in the pollutant. CONCLUSIONS: Several adequate methods exist to control for weather and seasonality while examining the associations between air pollution and daily counts of mortality and morbidity. In each case, care and judgement are required.

Acute Effects of Ambient Particulate Matter on Mortality in Europe and North America : Results from the APHENA Study

Background The APHENA (Air Pollution and Health: A Combined European and North American Approach) study is a collaborative analysis of multicity time-series data on the effect of air pollution on population health, bringing together data from the European APHEA (Air Pollution and Health: A European Approach) and U.S. NMMAPS (National Morbidity, Mortality and Air Pollution Study) projects, along with Canadian data. Objectives The main objective of APHENA was to assess the coherence of the findings of the multicity studies carried out in Europe and North America, when analyzed with a common protocol, and to explore sources of possible heterogeneity. We present APHENA results on the effects of particulate matter (PM) ≤ 10 μm in aerodynamic diameter (PM10) on the daily number of deaths for all ages and for those < 75 and ≥ 75 years of age. We explored the impact of potential environmental and socioeconomic factors that may modify this association. Methods In the first stage of a two-stage analysis, we used Poisson regression models, with natural and penalized splines, to adjust for seasonality, with various degrees of freedom. In the second stage, we used meta-regression approaches to combine time-series results across cites and to assess effect modification by selected ecologic covariates. Results Air pollution risk estimates were relatively robust to different modeling approaches. Risk estimates from Europe and United States were similar, but those from Canada were substantially higher. The combined effect of PM10 on all-cause mortality across all ages for cities with daily air pollution data ranged from 0.2% to 0.6% for a 10-μg/m3 increase in ambient PM10 concentration. Effect modification by other pollutants and climatic variables differed in Europe and the United States. In both of these regions, a higher proportion of older people and higher unemployment were associated with increased air pollution risk. Conclusions Estimates of the increased mortality associated with PM air pollution based on the APHENA study were generally comparable with results of previous reports. Overall, risk estimates were similar in Europe and in the United States but higher in Canada. However, PM10 effect modification patterns were somewhat different in Europe and the United States.

Estimating the Exposure–Response Relationships between Particulate Matter and Mortality within the APHEA Multicity Project

Several studies have reported significant health effects of air pollution even at low levels of air pollutants, but in most of theses studies linear nonthreshold relations were assumed. We investigated the exposure–response association between ambient particles and mortality in the 22 European cities participating in the APHEA (Air Pollution and Health—A European Approach) project, which is the largest available European database. We estimated the exposure–response curves using regression spline models with two knots and then combined the individual city estimates of the spline to get an overall exposure–response relationship. To further explore the heterogeneity in the observed city-specific exposure–response associations, we investigated several city descriptive variables as potential effect modifiers that could alter the shape of the curve. We conclude that the association between ambient particles and mortality in the cities included in the present analysis, and in the range of the pollutant common in all analyzed cities, could be adequately estimated using the linear model. Our results confirm those previously reported in Europe and the United States. The heterogeneity found in the different city-specific relations reflects real effect modification, which can be explained partly by factors characterizing the air pollution mix, climate, and the health of the population.

Short-term effects of ambient particles on cardiovascular and respiratory mortality

Background: Particulate air pollution is associated with increased mortality. There is a need for European results from multicountry databases concerning cause-specific mortality to obtain more accurate effect estimates. Methods: We report the estimated effects of ambient particle concentrations (black smoke and particulate matter less than 10 μm [PM10]) on cardiovascular and respiratory mortality, from 29 European cities, within the Air Pollution and Health: a European Approach (APHEA2) project. We applied a 2-stage hierarchical modeling approach assessing city-specific effects first and then overall effects. City characteristics were considered as potential effect modifiers. Results: An increase in PM10 by 10 μg/m3 (lag 0 + 1) was associated with increases of 0.76% (95% confidence interval = 0.47 to 1.05%) in cardiovascular deaths and 0.58% (0.21 to 0.95%) in respiratory deaths. The same increase in black smoke was associated with increases of 0.62% (0.35 to 0.90%) and 0.84% (0.11 to 1.57%), respectively. Conclusions: These effect estimates are appropriate for health impact assessment and standard-setting procedures.

Short-term effects of nitrogen dioxide on mortality: an analysis within the APHEA project

The short-term effects of nitrogen dioxide (NO2) on total, cardiovascular and respiratory mortality in 30 European cities participating in the Air Pollution on Health: a European Approach (APHEA)-2 project were investigated. The association was examined using hierarchical models implemented in two stages. In the first stage, data from each city were analysed separately, whereas in the second stage, the city-specific air pollution estimates were regressed on city-specific covariates to obtain overall estimates and to explore sources of possible heterogeneity. A significant association of NO2 with total, cardiovascular and respiratory mortality was found, with stronger effects on cause-specific mortality. There was evidence of confounding in respiratory mortality with black smoke and sulphur dioxide. The effect of NO2 on total and cardiovascular mortality was observed mainly in western and southern European cities, and was larger when smoking prevalence was lower and household gas consumption was higher. The effect of NO2 on respiratory mortality was higher in cities with a larger proportion of elderly persons in the population and higher levels of particulate matter with a 50% cut-off aerodynamic diameter of 10 μm. The results of this large study are consistent with an independent effect of nitrogen dioxide on mortality, but the role of nitrogen dioxide as a surrogate of other unmeasured pollutants cannot be completely ruled out.

Time-series analysis of air pollution and cause-specific mortality

Ten large European cities provided data on daily air pollution as well as mortality from respiratory and cardiovascular mortality. We used Poisson autoregressive models that controlled for trend, season, influenza epidemics, and meteorologic influences to assess the short-term effects of air pollution at each city. We then compared and pooled the city-specific results in a meta-analysis. The pooled relative risks of daily deaths from cardiovascular conditions were 1.02 [95% confidence interval (CI) = 1.01–1. 04] for a 50

Short-term effects of air pollution on hospital admissions of respiratory diseases in Europe: A quantitative summary of APHEA study results

g/m3 increment in the concentration of black smoke and 1.04 (95% CI = 1.01–1.06) for an increase in sulfur dioxide levels in western European cities. For respiratory diseases, these figures were 1.04 (95% CI = 1.021.07) and 1.05 (95% CI = 1.03–1.07), respectively. These associations were not found in the five central European cities. Eight-hour averages of ozone were also moderately associated with daily mortality in western European cities (relative risk = 1.02; 95% CI = 1.00–1.03 for cardiovascular conditions and relative risk = 1.06; 95% CI = 1.02–1.10 for respiratory conditions). Nitrogen dioxide did not show consistent relations with daily mortality. These results are similar to previously published data and add credence to the causal interpretation of these associations at levels of air pollution close to or lower than current European standards. (Epidemiology 1998; 9:495–503)