Anna Páldy

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.

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.

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.

Impact of high temperatures on mortality: is there an added heat wave effect?

Background: Mortality during sustained periods of hot weather is generally regarded as being in excess of what would be predicted from smooth temperature-mortality gradients estimated using standard time-series regression models. However, the evidence for an effect of continuous days of exceptional heat (“heat wave effect”) is indirect. In addition, because some interventions may be triggered only during forecasted heat waves, it would be helpful to know what fraction of all heat-related deaths falls during these specific periods and what fraction occurs throughout the remainder of the summer. Methods: Extended time-series data sets of daily mortality counts in 3 major European cities (London, 28 years of data; Budapest, 31 years; Milan, 18 years) were examined in relation to hot weather using a generalized estimating equations approach. We modeled temperature and specific heat wave terms using a variety of specifications. Results: With a linear effect of same-day temperature above an identified threshold, an additional “heat wave” effect of 5.5% was observed in London (95% confidence interval = 2.2 to 8.9), 9.3% in Budapest (5.8 to 13.0), and 15.2% in Milan (5.7 to 22.5). Heat wave effects were reduced slightly when we relaxed the linear assumption and these effects were reduced substantially when temperature was modeled as an average value of lags 0 to 2 days. In London, fewer than half of all heat-related deaths could be attributed to identified heat wave periods. In Milan and Budapest, the fraction was less than one fifth. Conclusions: Heat wave effects were apparent in simple time-series models but were reduced in multilag nonlinear models and small when compared with the overall summertime mortality burden of heat. Reduction of the overall heat burden requires preventive measures in addition to those that target warnings and responses uniquely to heat waves.

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.

Changes to Airborne Pollen Counts across Europe

A progressive global increase in the burden of allergic diseases has affected the industrialized world over the last half century and has been reported in the literature. The clinical evidence reveals a general increase in both incidence and prevalence of respiratory diseases, such as allergic rhinitis (common hay fever) and asthma. Such phenomena may be related not only to air pollution and changes in lifestyle, but also to an actual increase in airborne quantities of allergenic pollen. Experimental enhancements of carbon dioxide (CO) have demonstrated changes in pollen amount and allergenicity, but this has rarely been shown in the wider environment. The present analysis of a continental-scale pollen data set reveals an increasing trend in the yearly amount of airborne pollen for many taxa in Europe, which is more pronounced in urban than semi-rural/rural areas. Climate change may contribute to these changes, however increased temperatures do not appear to be a major influencing factor. Instead, we suggest the anthropogenic rise of atmospheric CO levels may be influential.

An ecological time-series study of heat-related mortality in three European cities

BackgroundEurope has experienced warmer summers in the past two decades and there is a need to describe the determinants of heat-related mortality to better inform public health activities during hot weather. We investigated the effect of high temperatures on daily mortality in three cities in Europe (Budapest, London, and Milan), using a standard approach.MethodsAn ecological time-series study of daily mortality was conducted in three cities using Poisson generalized linear models allowing for over-dispersion. Secular trends in mortality and seasonal confounding factors were controlled for using cubic smoothing splines of time. Heat exposure was modelled using average values of the temperature measure on the same day as death (lag 0) and the day before (lag 1). The heat effect was quantified assuming a linear increase in risk above a cut-point for each city. Socio-economic status indicators and census data were linked with mortality data for stratified analyses.ResultsThe risk of heat-related death increased with age, and females had a greater risk than males in age groups ≥65 years in London and Milan. The relative risks of mortality (per °C) above the heat cut-point by gender and age were: (i) Male 1.10 (95%CI: 1.07–1.12) and Female 1.07 (1.05–1.10) for 75–84 years, (ii) M 1.10 (1.06–1.14) and F 1.08 (1.06–1.11) for ≥85 years in Budapest (≥24°C); (i) M 1.03 (1.01–1.04) and F 1.07 (1.05–1.09), (ii) M 1.05 (1.03–1.07) and F 1.08 (1.07–1.10) in London (≥20°C); and (i) M 1.08 (1.03–1.14) and F 1.20 (1.15–1.26), (ii) M 1.18 (1.11–1.26) and F 1.19 (1.15–1.24) in Milan (≥26°C). Mortality from external causes increases at higher temperatures as well as that from respiratory and cardiovascular disease. There was no clear evidence of effect modification by socio-economic status in either Budapest or London, but there was a seemingly higher risk for affluent non-elderly adults in Milan.ConclusionWe found broadly consistent determinants (age, gender, and cause of death) of heat related mortality in three European cities using a standard approach. Our results are consistent with previous evidence for individual determinants, and also confirm the lack of a strong socio-economic gradient in heat health effects currently in Europe.

Short-term effects of ambient particles on mortality in the elderly: results from 28 cities in the APHEA2 project

Within the framework of the APHEA2 (Air Pollution on Health: a European Approach) project, the effects of ambient particles on mortality among persons ≥65 yrs were investigated. Daily measurements for particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10) and black smoke (BS), as well as the daily number of deaths among persons ≥65 yrs of age, from 29 European cities, have been collected. Data on other pollutants and meteorological variables, to adjust for confounding effects and data on city characteristics, to investigate potential effect modification, were also recorded. For individual city analysis, generalised additive models extending Poisson regression, using a locally weighted regression (LOESS) smoother to control for seasonal effects, were applied. To combine individual city results and explore effect modification, second stage regression models were applied. The per cent increase (95% confidence intervals), associated with a 10 µg·m−3 increase in PM10, in the elderly daily number of deaths was 0.8% (0.7–0.9%) and the corresponding number for BS was 0.6% (0.5–0.8%). The effect size was modified by the long-term average levels of nitrogen dioxide (higher levels were associated with larger effects), temperature (larger effects were observed in warmer countries), and by the proportion of the elderly in each city (a larger proportion was associated with higher effects). These results indicate that ambient particles have effects on mortality among the elderly, with relative risks comparable or slightly higher than those observed for total mortality and similar effect modification patterns. The effects among the older persons are of particular importance, since the attributable number of events will be much larger, compared to the number of deaths among the younger population.

Association Between the Clastogenic Effect in Peripheral Lymphocytes and Human Exposure to Arsenic Through Drinking Water

We describe the association between structural chromosome aberrations (CAs) and parameters of exposure to arsenic among 42 individuals exposed to arsenic through well waters in Finland. The median concentration of arsenic in the wells was 410 μg/l, the total arsenic concentrations in urine (As‐tot) was 180 μg/l, and in hair 1.3 μg/g, for current users (n = 32) of contaminated wells. Urinary arsenic species and CAs were also analyzed in eight control individuals from the same village who consumed water which contained arsenic <1.0 μg/l (detection limit). Increased arsenic exposure, indicated best by increased concentrations of arsenic species (inorganic arsenic, methylarsonic acid (MMA), dimethylarsinic acid (DMA)) in urine, was associated with increased frequency of CAs. The increased urinary ratio of MMA/As‐tot and the decreased ratio of DMA/As‐tot were associated with increased CAs when all aberration types, including gaps, were considered. Associations between CAs and arsenic exposure indicators were stronger among current users than among persons who had stopped using the contaminated well water for 2–4 months before sampling (ex‐users, n = 10). Furthermore, there was a positive but not statistically significant association between CAs and arsenic in hair among the current users, but not among the ex‐users, who still had relatively high arsenic concentrations in hair. The results suggest that the effect observed in the present study reflects relatively recent arsenic exposure. Environ. Mol. Mutagen. 32: 301–313, 1998