Klea Katsouyanni

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 lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE)

BACKGROUND Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations. METHODS This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses. FINDINGS The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03-1·45] per 10 μg/m(3)). For PM2·5 the HR was 1·18 (0·96-1·46) per 5 μg/m(3). The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10-2·08) and 1·55 (1·05-2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99-1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95-1·07] per 20 μg/m(3)) or traffic intensity on the nearest street (HR 1·00 [0·97-1·04] per 5000 vehicles per day). INTERPRETATION Particulate matter air pollution contributes to lung cancer incidence in Europe. FUNDING European Communitys Seventh Framework Programme.

Heat effects on mortality in 15 European cities

BACKGROUND Higher incidence rates of childhood cancer and particularly leukemia have been observed in regions with higher radon levels, but case-control studies have given inconsistent results. We tested the hypothesis that domestic radon exposure increases the risk for childhood cancer. METHODS We identified 2400 incident cases of leukemia, central nervous system tumor, and malignant lymphoma diagnosed in children between 1968 and 1994 in the Danish Cancer Registry. Control children (n = 6697) were selected from the Danish Central Population Registry. Radon levels in residences of children and the cumulated exposure of each child were calculated as the product of exposure level and time, for each address occupied during childhood. RESULTS Cumulative radon exposure was associated with risk for acute lymphoblastic leukemia (ALL), with rate ratios of 1.21 (95% confidence interval = 0.98-1.49) for levels of 0.26 to 0.89 x 10(3) Bq/m3-years and 1.63 (1.05-2.53) for exposure to >0.89 x 10(3) Bq/m3-years, when compared with <0.26 x 10(3) Bq/m3-years. A linear dose-response analysis showed a 56% increase in the rate of ALL per 10(3) Bq/m3-years increase in exposure. The association with ALL persisted in sensitivity analyses and after adjustment for potential confounders. No association was found with the other types of childhood cancer. CONCLUSIONS This study suggests that domestic radon exposure increases the risk for ALL during childhood but not for other childhood cancers.Background: Epidemiologic studies show that high temperatures are related to mortality, but little is known about the exposure-response function and the lagged effect of heat. We report the associations between daily maximum apparent temperature and daily deaths during the warm season in 15 European cities. Methods: The city-specific analyses were based on generalized estimating equations and the city-specific results were combined in a Bayesian random effects meta-analysis. We specified distributed lag models in studying the delayed effect of exposure. Time-varying coefficient models were used to check the assumption of a constant heat effect over the warm season. Results: The city-specific exposure-response functions have a V shape, with a change-point that varied among cities. The meta-analytic estimate of the threshold was 29.4°C for Mediterranean cities and 23.3°C for north-continental cities. The estimated overall change in all natural mortality associated with a 1°C increase in maximum apparent temperature above the city-specific threshold was 3.12% (95% credibility interval = 0.60% to 5.72%) in the Mediterranean region and 1.84% (0.06% to 3.64%) in the north-continental region. Stronger associations were found between heat and mortality from respiratory diseases, and with mortality in the elderly. Conclusions: There is an important mortality effect of heat across Europe. The effect is evident from June through August; it is limited to the first week following temperature excess, with evidence of mortality displacement. There is some suggestion of a higher effect of early season exposures. Acclimatization and individual susceptibility need further investigation as possible explanations for the observed heterogeneity among cities.

Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project

BACKGROUND Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants. METHODS We used data from 22 European cohort studies, which created a total study population of 367,251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 μm (PM2.5), less than 10 μm (PM10), and between 10 μm and 2.5 μm (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buffer. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis. FINDINGS The total study population consisted of 367,251 participants who contributed 5,118,039 person-years at risk (average follow-up 13.9 years), of whom 29,076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 μg/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I(2) p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 μg/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 μg/m(3) (1.07, 1.01-1.13). INTERPRETATION Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value. FUNDING European Communitys Seventh Framework Program (FP7/2007-2011).

Short-term effects of particulate air pollution on cardiovascular diseases in eight European cities

Study objective: As part of the APHEA project this study examined the association between airborne particles and hospital admissions for cardiac causes (ICD9 390–429) in eight European cities (Barcelona, Birmingham, London, Milan, the Netherlands, Paris, Rome, and Stockholm). All admissions were studied, as well as admissions stratified by age. The association for ischaemic heart disease (ICD9 410–413) and stroke (ICD9 430–438) was also studied, also stratified by age. Design: Autoregressive Poisson models were used that controlled for long term trend, season, influenza epidemics, and meteorology to assess the short-term effects of particles in each city. The study also examined confounding by other pollutants. City specific results were pooled in a second stage regression to obtain more stable estimates and examine the sources of heterogeneity. Main results: The pooled percentage increases associated with a 10 μg/m3 increase in PM10 and black smoke were respectively 0.5% (95% CI: 0.2 to 0.8) and 1.1% (95% CI: 0.4 to 1.8) for cardiac admissions of all ages, 0.7% (95% CI: 0.4 to 1.0) and 1.3% (95% CI: 0.4 to 2.2) for cardiac admissions over 65 years, and, 0.8% (95% CI: 0.3 to 1.2) and 1.1% (95% CI: 0.7 to 1.5) for ischaemic heart disease over 65 years. The effect of PM10 was little changed by control for ozone or SO2, but was substantially reduced (CO) or eliminated (NO2) by control for other traffic related pollutants. The effect of black smoke remained practically unchanged controlling for CO and only somewhat reduced controlling for NO2. Conclusions: These effects of particulate air pollution on cardiac admissions suggest the primary effect is likely to be mainly attributable to diesel exhaust. Results for ischaemic heart disease below 65 years and for stroke over 65 years were inconclusive.

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.

Effects of Cold Weather on Mortality: Results From 15 European Cities Within the PHEWE Project

Weather-related health effects have attracted renewed interest because of the observed and predicted climate change. The authors studied the short-term effects of cold weather on mortality in 15 European cities. The effects of minimum apparent temperature on cause- and age-specific daily mortality were assessed for the cold season (October-March) by using data from 1990-2000. For city-specific analysis, the authors used Poisson regression and distributed lag models, controlling for potential confounders. Meta-regression models summarized the results and explored heterogeneity. A 1 degrees C decrease in temperature was associated with a 1.35% (95% confidence interval (CI): 1.16, 1.53) increase in the daily number of total natural deaths and a 1.72% (95% CI: 1.44, 2.01), 3.30% (95% CI: 2.61, 3.99), and 1.25% (95% CI: 0.77, 1.73) increase in cardiovascular, respiratory, and cerebrovascular deaths, respectively. The increase was greater for the older age groups. The cold effect was found to be greater in warmer (southern) cities and persisted up to 23 days, with no evidence of mortality displacement. Cold-related mortality is an important public health problem across Europe. It should not be underestimated by public health authorities because of the recent focus on heat-wave episodes.

The impact of heat waves on mortality in 9 European cities: results from the EuroHEAT project

BackgroundThe present study aimed at developing a standardized heat wave definition to estimate and compare the impact on mortality by gender, age and death causes in Europe during summers 1990-2004 and 2003, separately, accounting for heat wave duration and intensity.MethodsHeat waves were defined considering both maximum apparent temperature and minimum temperature and classified by intensity, duration and timing during summer. The effect was estimated as percent increase in daily mortality during heat wave days compared to non heat wave days in people over 65 years. City specific and pooled estimates by gender, age and cause of death were calculated.ResultsThe effect of heat waves showed great geographical heterogeneity among cities. Considering all years, except 2003, the increase in mortality during heat wave days ranged from + 7.6% in Munich to + 33.6% in Milan. The increase was up to 3-times greater during episodes of long duration and high intensity. Pooled results showed a greater impact in Mediterranean (+ 21.8% for total mortality) than in North Continental (+ 12.4%) cities. The highest effect was observed for respiratory diseases and among women aged 75-84 years. In 2003 the highest impact was observed in cities where heat wave episode was characterized by unusual meteorological conditions.ConclusionsClimate change scenarios indicate that extreme events are expected to increase in the future even in regions where heat waves are not frequent. Considering our results prevention programs should specifically target the elderly, women and those suffering from chronic respiratory disorders, thus reducing the impact on mortality.

High temperature and hospitalizations for cardiovascular and respiratory causes in 12 European cities.

RATIONALE Episode analyses of heat waves have documented a comparatively higher impact on mortality than on morbidity (hospital admissions) in European cities. The evidence from daily time series studies is scarce and inconsistent. OBJECTIVES To evaluate the impact of high environmental temperatures on hospital admissions during April to September in 12 European cities participating in the Assessment and Prevention of Acute Health Effects of Weather Conditions in Europe (PHEWE) project. METHODS For each city, time series analysis was used to model the relationship between maximum apparent temperature (lag 0-3 days) and daily hospital admissions for cardiovascular, cerebrovascular, and respiratory causes by age (all ages, 65-74 age group, and 75+ age group), and the city-specific estimates were pooled for two geographical groupings of cities. MEASUREMENTS AND MAIN RESULTS For respiratory admissions, there was a positive association that was heterogeneous between cities. For a 1 degrees C increase in maximum apparent temperature above a threshold, respiratory admissions increased by +4.5% (95% confidence interval, 1.9-7.3) and +3.1% (95% confidence interval, 0.8-5.5) in the 75+ age group in Mediterranean and North-Continental cities, respectively. In contrast, the association between temperature and cardiovascular and cerebrovascular admissions tended to be negative and did not reach statistical significance. CONCLUSIONS High temperatures have a specific impact on respiratory admissions, particularly in the elderly population, but the underlying mechanisms are poorly understood. Why high temperature increases cardiovascular mortality but not cardiovascular admissions is also unclear. The impact of extreme heat events on respiratory admissions is expected to increase in European cities as a result of global warming and progressive population aging.

PSYCHOLOGICAL STRESS AND FATAL HEART-ATTACK - THE ATHENS (1981) EARTHQUAKE NATURAL EXPERIMENT

The effects of acute and subacute psychological stress caused by a sudden general disaster on mortality from atherosclerotic heart disease (underlying cause) and cardiac events (proximate cause) were investigated by comparing total and cause-specific mortality during the days after a major earthquake in Athens in 1981 with the mortality during the surrounding month and the corresponding periods of 1980 and 1982. There was an excess of deaths from cardiac and external causes on the days after the major earthquake, but no excess of deaths from cancer and little, if any, excess of deaths from other causes. The excess mortality was more evident when atherosclerotic heart disease was considered as the underlying cause (5, 7, and 8 deaths on the first three days, respectively; background mean deaths per day 2.6; upper 95th centile 5) than when cardiac events in general were considered as the proximate cause (9, 11, and 14 deaths on the first three days, respectively; background mean 7.1, upper 95th centile 12).