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.

BACKGROUND: A study was undertaken to assess the combined association between urban air pollution and emergency admissions for asthma during the years 1986-92 in Barcelona, Helsinki, Paris and London. METHODS: Daily counts were made of asthma admissions and visits to the emergency room in adults (age range 15-64 years) and children (< 15 years). Covariates were short term fluctuations in temperature and humidity, viral epidemics, day of the week effects, and seasonal and secular trends. Estimates from all the cities were obtained for the entire period and separately by warm or cold seasons using Poisson time-series regression models. Combined associations were estimated using meta-analysis techniques. RESULTS: Daily admissions for asthma in adults increased significantly with increasing ambient levels of nitrogen dioxide (NO2) (relative risk (RR) per 50 micrograms/m3 increase 1.029, 95% CI 1.003 to 1.055) and non-significantly with particles measured as black smoke (RR 1.021, 95% CI 0.985 to 1.059). The association between asthma admissions and ozone (O3) was heterogeneous among cities. In children, daily admissions increased significantly with sulphur dioxide (SO2) (RR 1.075, 95% CI 1.026 to 1.126) and non-significantly with black smoke (RR 1.030, 95% CI 0.979 to 1.084) and NO2, though the latter only in cold seasons (RR 1.080, 95% CI 1.025 to 1.140). No association was observed for O3. The associations between asthma admissions and NO2 in adults and SO2 in children were independent of black smoke. CONCLUSIONS: The evidence of an association between air pollution at current urban levels and emergency room visits for asthma has been extended to Europe. In addition to particles, NO2 and SO2--by themselves or as a constituent of a pollution mixture--may be important in asthma exacerbations in European cities.

Objective : To investigate whether outdoor air pollution levels in London influence daily mortality. Design : Poisson regression analysis of daily counts of deaths, with adjustment for effects of secular trend, seasonal and other cyclical factors, day of the week, holidays, influenza epidemic, temperature, humidity, and autocorrelation, from April 1987 to March 1992. Pollution variables were particles (black smoke), sulphur dioxide, ozone, and nitrogen dioxide, lagged 0-3 days. Setting : Greater London. Outcome measures : Relative risk of death from all causes (excluding accidents), respiratory disease, and cardiovascular disease. Results : Ozone levels (same day) were associated with a significant increase in all cause, cardiovascular, and respiratory mortality; the effects were greater in the warm season (April to September) and were independent of the effects of other pollutants. In the warm season an increase of the eight hour ozone concentration from the 10th to the 90th centile of the seasonal range (7-36 ppb) was associated with an increase of 3.5% (95% confidence interval 1.7 to 5.3), 3.6% (1.04 to 6.1), and 5.4% (0.4 to 10.7) in all cause, cardiovascular, and respiratory mortality respectively. Black smoke concentrations on the previous day were significantly associated with all cause mortality, and this effect was also greater in the warm season and was independent of the effects of other pollutants. For black smoke an increase from the 10th to 90th centile in the warm season (7-19 µg/m ³ ) was associated with an increase of 2.5% (0.9 to 4.1) in all cause mortality. Significant but smaller and less consistent effects were also observed for nitrogen dioxide and sulphur dioxide. Conclusion : Daily variations in air pollution within the range currently occurring in London may have an adverse effect on daily mortality. Key messages: Evidence from other countries suggests that similar levels of pollution may be associated with short term health effects This study suggests that air pollution due to particles and ozone may be associated with increased daily mortality in London The evidence is less convincing for nitrogen dioxide and sulphur dioxide It would be prudent to assume that these associations are causal and to reduce air pollution levels with the help of appropriate abate- ment policies

The Air Pollution and Health: a European Approach (APHEA) project is a coordinated study of the short-term effects of air pollution on mortality and hospital admissions using data from 15 European cities, with a wide range of geographic, sociodemographic, climatic, and air quality patterns. The objective of this paper is to summarize the results of the short-term effects of ambient oxidants on daily deaths from all causes (excluding accidents). Within the APHEA project, six cities spanning Central and Western Europe provided data on daily deaths and NO₂ and/or O₃ levels. The data were analyzed by each center separately following a standardized methodology to ensure comparability of results. Poisson autoregressive models allowing for overdispersion were fitted. Fixed effects models were used to pool the individual regression coefficients when there was no evidence of heterogeneity among the cities and random effects models otherwise. Factors possibly correlated with heterogeneity were also investigated. Significant positive associations were found between daily deaths and both NO₂ and O₃. Increases of 50 μg/m³ in NO₂ (1-hour maximum) or O₃ (1-hour maximum) were associated with a 1.3% (95% confidence interval 0.9–1.8) and 2.9% (95% confidence interval 1.0–4.9) increase in the daily number of deaths, respectively. Stratified analysis of NO₂ effects by low and high levels of black smoke or O₃ showed no significant evidence for an interaction within each city. However, there was a tendency for larger effects of NO₂ in cities with higher levels of black smoke. The pooled estimate for the O₃ effect was only slightly reduced, whereas the one for NO₂ was almost halved (although it remained significant) when two pollutant models including black smoke were applied. The internal validity (consistency across cities) as well as the external validity (similarities with other published studies) of our results on the O₃ effect support the hypothesis of a causal relation between O₃ and all cause daily mortality. However, the short-term effects of NO₂ on mortality may be confounded by other vehicle-derived pollutants. Thus, the issue of independent NO₂ effects requires additional investigation. Am J Epidemiol 1997;146:177-85.