Changes in the temperature-mortality relationship in France: Limited evidence of adaptation to a new climate.

CONTEXT: Documenting trends in the health impacts of ambient temperature is key to supporting adaptation strategies to climate change. This paper explores changes in the temperature-related mortality in 18 French urban centers between 1970 and 2015. METHOD: A multicentric time-series design with time-varying distributed lag nonlinear models was adopted to model the shape of the relationship and assess temporal changes in risks and impacts. RESULTS: The general shape of the temperature-mortality relationship did not change over time, except for an increasing risk at very low percentiles and a decreasing risk at very high percentiles. The relative risk at the 99.9th percentile compared to the 50th percentile of the 1970-2015 temperature distribution decreased from 2.33 [95% confidence interval (CI): 1.95:2.79] in 1975 to 1.33 [95% CI: 1.14:1.55] in 2015. Between 1970 and 2015, 302,456 [95% CI: 292,723:311,392] deaths were attributable to non-optimal temperatures, corresponding to 5.5% [95% CI: 5.3:5.6] of total mortality. This burden decreased progressively, representing 7.2% [95% CI: 6.7:7.7] of total mortality in the 1970s to 3.4% [95% CI: 3.2:3.6] in the 2000s. However, the contribution of hot temperatures to this burden (higher than the 90th percentile) increased. DISCUSSION: Despite the decreasing relative risk, the fraction of mortality attributable to extreme heat increased between 1970 and 2015, thus highlighting the need for proactive adaptation.

On the supra-linearity of the relationship between air pollution, mortality and hospital admission in 18 French cities.

PURPOSE: Understanding the relationship between an environmental determinant and a given health outcome is key to inform public health policies. The short-term mortality and morbidity responses to outdoor air pollutants are traditionally assessed as a log-linear relationship, but few studies suggest a possible deviation from linearity. This paper investigates the shape of the relationship between ozone, NO2 and fine particulate matter (PM10 and PM2.5), mortality and hospital admissions in 18 French cities between 2000 and 2017. METHOD: A multi-centric time series design, using quasi-Poisson generalized additive models, was used. Four approaches were compared to model concentration-response curves (log-linear, piecewise-linear with a priori defined breakpoints, piecewise-linear with no a priori breakpoint and cubic spline). RESULTS: All the models indicated evidence of supra-linearity between PM10, PM2.5, NO2, mortality and hospital admissions. For instance, with a log-linear model, a 10 µg/m3 increase in PM2.5 was associated with a 0.4% [95% CI 0.2; 0.7] increase in non-accidental mortality. When using a piecewise model with a priori set breakpoint at 10 µg/m3, the mortality increase was 3.8% [4.4; 6.3] below 10 µg/m3, and 0.3% [0; 0.6] above. Non-significant impacts of ozone were found for concentrations below 90 µg/m3 to 120 µg/m3, with some variability in the identified threshold across the heath indicator studied. CONCLUSION: The supra-linearity of the relationship between PM10, PM2.5, NO2, mortality and hospital admissions supports the need to further reduce air pollution concentrations well below regulatory values.

Influence of temperature on mortality in the French overseas regions: a pledge for adaptation to heat in tropical marine climates.

CONTEXT: Tropical areas and small islands are identified as highly vulnerable to climate change, and already experiencing shifts in their temperature distribution. However, the knowledge on the health impacts of temperatures under tropical marine climate is limited. We explored the influence of temperature on mortality in four French overseas regions located in French Guiana, French West Indies, and in the Indian Ocean, between 2000 and 2015. METHOD: Distributed lag non-linear generalized models linking temperature and mortality were developed in each area, and relative risks were combined through a meta-analysis. Models were used to estimate the fraction of mortality attributable to non-optimal temperatures. The role of humidity was also investigated. RESULTS: An increased risk of mortality was observed when the temperature deviated from median. Results were not modified when introducing humidity. Between 2000 and 2015, 979 deaths [confidence interval (CI) 95% 531:1359] were attributable to temperatures higher than the 90th percentile of the temperature distribution, and 442 [CI 95% 178:667] to temperature lower than the 10th percentile. DISCUSSION: Heat already has a large impact on mortality in the French overseas regions. Results suggest that adaptation to heat is relevant under tropical marine climate.

Influence of exposure assessment methods on associations between long-term exposure to outdoor fine particulate matter and risk of cancer in the French cohort Gazel.

BACKGROUND: Many studies investigated the relationship between outdoor fine particulate matter (PM2.5) and cancer. While they generally indicated positive associations, results have not been fully consistent, possibly because of the diversity of methods used to assess exposure. OBJECTIVES: To investigate how using different PM2.5 exposure assessment methods influences risk estimates in the large French general population-based Gazel cohort (20,625 participants at enrollment) with a 26-year follow-up with complete residential histories. METHODS: We focused on two cancer incidence outcomes: all-sites combined and lung. We used two distinct exposure assessment methods: a western European land use regression (LUR), and a chemistry-dispersion model (Gazel-Air) for France, each with a time series ≥20-years annual concentrations. Spearman correlation coefficient between the two estimates of PM2.5 was 0.71 across all person-years; the LUR tended to provide higher exposures. We used extended Cox models with attained age as time-scale and time-dependent cumulative exposures, adjusting for a set of confounders including sex and smoking, to derive hazard ratios (HRs) and their 95% confidence interval, implementing a 10-year lag between exposure and incidence/censoring. RESULTS: We obtained similar two-piece linear associations for all-sites cancer (3711 cases), with a first slope of HRs of 1.53 (1.24-1.88) and 1.43 (1.19-1.73) for one IQR increase of cumulative PM2.5 exposure for the LUR and the Gazel-Air models respectively, followed by a plateau at around 1.5 for both exposure assessments. For lung cancer (349 cases), the HRs from the two exposure models were less similar, with largely overlapping confidence limits. CONCLUSION: Our findings using long-term exposure estimates from two distinct exposure assessment methods corroborate the association between air pollution and cancer risk.

Greening is a promising but likely insufficient adaptation strategy to limit the health impacts of extreme heat.

BACKGROUND: Adapting the urban environment to heat is a public health priority in the context of climate change. Cities are now considering interventions on specific urban characteristics known to contribute to the urban heat island (UHI) such as vegetation and imperviousness. OBJECTIVES: To explore how these urban characteristics influence the temperature-mortality relationship in the Paris region. METHODS: We modeled the temperature-mortality relationship for the 1300 municipalities of the region from 1990 to 2015, while including an interaction with indicators that summarize the municipalities' main urban characteristics. Four indicators were tested: lack of green spaces, lack of trees, proportion of impervious surface, and overexposed population to a potential night UHI. RESULTS: The shape of the temperature-mortality relationship was similar across all municipalities, but with a higher slope at the highest temperatures in municipalities with less green spaces, less trees, and more impervious soil. For instance, in Paris and its close suburbs, the relative risk associated with a temperature in the 99th percentile of the temperature distribution (compared to the 50th percentile) was 2.17 [IC95% 1.98:2.38] in municipalities with 40% of their surface covered by trees compared to 2.57 [IC 95% 2.47:2.68] in municipalities with only 3% of their surface covered by trees. DISCUSSION: A lack of vegetation and a high degree of imperviousness were associated with a higher risk of heat-related mortality in the Paris region. Therefore, we can assume that interventions targeting these characteristics could reduce the health impacts of extreme heat. Such interventions should be coupled with other initiatives such as protecting the most vulnerable and promoting appropriate behaviors.

Heat and cold related-mortality in 18 French cities.

OBJECTIVES: Understanding the dynamics of the temperature-mortality relationship is an asset to support public health interventions. We investigated the lag structure of the mortality response to cold and warm temperatures in 18 French cities between 2000 and 2010. METHODS: A distributed lag non-linear generalized model using a quasi-Poisson distribution and controlling for classical confounding factors was built in each city. A fitted meta-analytical model combined the city-specific models to derive the best linear unbiased prediction of the association, and a meta-regression explored the influence of background characteristics of the cities. The fraction of mortality attributable to cold and heat was estimated with reference to the minimum mortality temperature. RESULTS: Between 2000 and 2010, 3.9% [CI 95% 3.2:4.6] of the total mortality was attributed to cold, and 1.2% [1.1:1.2] to heat. The immediate increase in mortality following high temperatures was partly compensated by a harvesting effect when temperatures were below the 99.2 percentiles of the mean temperature distributions. DISCUSSION: Cold represents a significant public health burden, mostly driven by moderate temperatures (between percentiles 2.5 and 25). The population is better adapted to warm temperatures, up to a certain intensity when heat becomes an acute environmental health emergency (above percentile 99). The rapid increase in mortality risk at very high temperatures percentiles calls for an active adaptation in a context of climate change.

Urinary levels of pyrethroid pesticides and determinants in pregnant French women from the Elfe cohort.

Pyrethroids are insecticides which are widely used for agricultural and domestic purposes. The general population can be exposed to them. Given the suspected effects of pesticides on the development of the foetus, exposure to pyrethroids during pregnancy is a major public health concern. The objective of this paper is to describe the urinary levels of the following five pyrethroid metabolites and their associated determinants among pregnant French women in 2011 enrolled in the Elfe cohort (n = 1077): a) 3-phenoxy benzoic (3-PBA), b) 4­fluoro­3­phenoxy benzoic acid (4-F-3-PBA), c) Cis­3­(2,2dibromovinyl)­2,2­dimethyl cyclopropane-carboxylic acid (Cis-DBCA); d) Cis­3­(2,2dichlorovinyl)­2,2­dimethyl cyclopropane-carboxylic acid (Cis-DCCA) and e) Trans-3­(2,2dichlorovinyl)­2,2­dimethyl cyclopropane-carboxylic acid (Trans-DCCA). The distribution levels were estimated for each pyrethroid metabolite. Multivariable analyses helped determine the predictors of these levels. All metabolites except 4-F-3-PBA were detected in all the urine samples. The mean urinary concentration of the sum of the metabolites (3-PBA, Cis-DBCA, Cis-DCCA, Trans-DCCA) was 1.18 µg/L, with the highest concentrations observed for 3-PBA. A comparison of these levels with other studies showed that pregnant French women tend to be more exposed to pyrethroids than their American counterparts, less exposed than Chinese and Caribbean mothers, and have similar exposure to Japanese mothers. In our study, urinary levels of pyrethroid metabolites were positively related to smoking during pregnancy, consuming fish and alcohol, domestic pesticide use and living in the vicinity of crops during pregnancy. These findings highlight the importance of non-dietary pathways when evaluating exposure to pyrethroids.

Prenatal exposure to lead in France: Cord-blood levels and associated factors: Results from the perinatal component of the French Longitudinal Study since Childhood (Elfe).

BACKGROUND: As a result of the ban on lead in gasoline on 2nd January 2000, the French population's exposure to lead has decreased in recent years. However, because of the acknowledged harmful cognitive effects of lead even at low levels, lead exposure remains a major public health issue. In France, few biomonitoring data are available for exposure to lead in pregnant women and newborn. The purpose of the perinatal component of the French human biomonitoring (HBM) program was to describe levels of various biomarkers of exposure to several environmental pollutants, including lead, among mother-baby pairs. In this paper, we aimed to describe the distribution of cord blood lead levels (CBLL) in French mother-baby pairs, and to estimate the contribution of the main lead exposure risk factors to these levels. METHOD: A total of 1968 mother-baby pairs selected from the participants of the perinatal component of the French HBM program were included in the study on lead. Lead levels were analyzed in cord blood collected at child delivery by inductively coupled plasma-mass spectrometry (ICP-MS). The data collected included biological sample, socio-demographic characteristics, environmental and occupational exposure, and information on dietary factors. RESULTS: CBLL were quantified for 99.5% of the sample. The CBLL geometric mean was 8.30 µg/l (95% CI [7.94-8.68]) with a 95th percentile of 24.3 µg/l (95% CI [20.7-27.1]). Factors significantly associated with CBLL were tap water consumption, alcohol consumption, shellfish consumption, vegetable consumption, bread consumption, smoking, and the mother being born in countries where lead is often used. CONCLUSION: This study provides the first reference value for CBLL in a random sample of mother-baby pairs not particularly exposed to high levels of lead (24.3 µg/l). A substantial decrease in CBLL over time was observed, which confirms the decrease of exposure to lead among the general population. CBLL observed in this French study were in the range of those found in recent surveys conducted in other countries.

The mortality impacts of fine particles in France.

INTRODUCTION: Worldwide, air pollution has become a main environmental cause of premature mortality. This burden is largely due to fine particles. Recent cohort studies have confirmed the health risks associated with chronic exposure to PM2.5 for European and French populations. We assessed the mortality impact of PM2.5 in continental France using these new results. METHODS: Based on a meta-analysis of French and European cohorts, we computed a shrunken estimate of PM2.5-mortality relationship for the French population (RR 1.15 [1.05:1.25] for a 10µg/m(3) increase in PM2.5). This RR was applied to PM2.5 annual concentrations estimated at a fine spatial scale, using a classical health impacts assessment method. The health benefits associated with alternative scenarios of improving air quality were computed for 36,219 French municipalities for 2007-2008. RESULTS: 9% of the total mortality in continental France is attributable to anthropogenic PM2.5. This represents >48,000 deaths per year, and 950,000years of life lost per year, more than half occurring in urban areas larger than 100,000 inhabitants. If none of the municipalities exceeded the World Health Organization guideline value for PM2.5 (10µg/m(3)), the total mortality could be decreased by 3%, corresponding to 400,000years of life saved per year. CONCLUSION: Results were consistent with previous estimates of the long-term mortality impacts of fine particles in France. These findings show that further actions to improve air quality in France would substantially improve health.

How to estimate exposure when studying the temperature-mortality relationship? A case study of the Paris area.

Time series studies assessing the effect of temperature on mortality generally use temperatures measured by a single weather station. In the Paris region, there is a substantial measurement network, and a variety of exposure indicators created from multiple stations can be tested. The aim of this study is to test the influence of exposure indicators on the temperature-mortality relationship in the Paris region. The relationship between temperature and non-accidental mortality was assessed based on a time series analysis using Poisson regression and a generalised additive model. Twenty-five stations in Paris and its three neighbouring departments were used to create four exposure indicators. These indicators were (1) the temperature recorded by one reference station, (2) a simple average of the temperatures of all stations, (3) an average weighted on the departmental population and (4) a classification of the stations based on land use and an average weighted on the population in each class. The relative risks and the Akaike criteria were similar for all the exposure indicators. The estimated temperature-mortality relationship therefore did not appear to be significantly affected by the indicator used, regardless of study zone (departments or region) or age group. The increase in temperatures from the 90(th) to the 99(th) percentile of the temperature distribution led to a significant increase in mortality over 75 years (RR = 1.10 [95% CI, 1.07; 1.14]). Conversely, the decrease in temperature between the 10(th) and 1(st) percentile had a significant effect on the mortality under 75 years (RR = 1.04 [95% CI, 1.01; 1.06]). In the Paris area, there is no added value in taking multiple climatic stations into account when estimating exposure in time series studies. Methods to better represent the subtle temperature variations in densely populated areas in epidemiological studies are needed.

Association between long-term exposure to air pollution and mortality in France: A 25-year follow-up study.

INTRODUCTION: Long-term exposure to air pollution (AP) has been shown to have an impact on mortality in numerous countries, but since 2005 no data exists for France. OBJECTIVES: We analyzed the association between long-term exposure to air pollution and mortality at the individual level in a large French cohort followed from 1989 to 2013. METHODS: The study sample consisted of 20,327 adults working at the French national electricity and gas company EDF-GDF. Annual exposure to PM10, PM10­2.5, PM2.5, NO2, O3, SO2, and benzene was assessed for the place of residence of participants using a chemistry-transport model and taking residential history into account. Hazard ratios were estimated using a Cox proportional-hazards regression model, adjusted for selected individual and contextual risk factors. Hazard ratios were computed for an interquartile range (IQR) increase in air pollutant concentrations. RESULTS: The cohort recorded 1967 non-accidental deaths. Long-term exposures to b aseline PM2.5, PM10-25, NO2 and benzene were associated with an increase in non-accidental mortality (Hazard Ratio, HR = 1.09; 95% CI: 0.99, 1.20 per 5.9 µg/m3, PM10-25; HR=1.09; 95% CI: 1.04, 1.15 per 2.2 µg/m3, NO2: HR=1.14; 95% CI: 0.99, 1.31 per 19.3 µg/m3 and benzene: HR=1.10; 95% CI: 1.00, 1.22 per 1.7 µg/m3).The strongest association was found for PM10: HR = 1.14; 95% CI: 1.05, 1.25 per 7.8 µg/m3. PM10, PM10-25 and SO2 were associated with non-accidental mortality when using time varying exposure. No significant associations were observed between air pollution and cardiovascular and respiratory mortality. CONCLUSION: Long-term exposure to fine particles, nitrogen dioxide, sulfur dioxide and benzene is associated with an increased risk of non-accidental mortality in France. Our results strengthen existing evidence that outdoor air pollution is a significant environmental risk factor for mortality. Due to the limited sample size and the nature of our study (occupational), further investigations are needed in France with a larger representative population sample.

Semen quality trends in French regions are consistent with a global change in environmental exposure.

A retrospective study carried out recently in a large sample of men, close to the general population, has reported a significant and strong decline in sperm concentration and morphology in the whole of France between 1989 and 2005. We studied these trends within each region of France. Data were obtained from the Fivnat database. The study sample comprised male partners of sterile women in whom both tubes were absent or blocked. They were located at the assisted reproductive technology center. A Bayesian spatio-temporal model with parametric time trends, adjusted for age, was used to model overall time trends for each region. The results show that sperm concentration decreased in almost all regions of France. Among them, Aquitaine showed the highest decrease and Midi-Pyrénées had the lowest average for the whole period. Regarding total motility, most regions showed a slight increase while Bourgogne showed a steep and significant decrease. While considering sperm morphology, there was a decrease in most of the regions. The decrease in Aquitaine and Midi-Pyrénées was stronger when compared with the overall trend. In conclusion, a decrease in sperm concentration and morphology, already shown at the French metropolitan territory level, was observed in most regions of France. This is consistent with a global change in environmental exposure, according to the endocrine disruptor hypothesis especially. Indeed, ubiquitary exposure to chemicals has been growing in the general population of France since the 1950s, and the results do not appear to support the lifestyle hypothesis. The highest decreases and lowest values are consistently observed in two proximate regions that are both highly agricultural and densely populated.

A review of the epidemiological methods used to investigate the health impacts of air pollution around major industrial areas.

We performed a literature review to investigate how epidemiological studies have been used to assess the health consequences of living in the vicinity of industries. 77 papers on the chronic effects of air pollution around major industrial areas were reviewed. Major health themes were cancers (27 studies), morbidity (25 studies), mortality (7 studies), and birth outcome (7 studies). Only 3 studies investigated mental health. While studies were available from many different countries, a majority of papers came from the United Kingdom, Italy, and Spain. Several studies were motivated by concerns from the population or by previous observations of an overincidence of cases. Geographical ecological designs were largely used for studying cancer and mortality, including statistical designs to quantify a relationship between health indicators and exposure. Morbidity was frequently investigated through cross-sectional surveys on the respiratory health of children. Few multicenter studies were performed. In a majority of papers, exposed areas were defined based on the distance to the industry and were located from <2 km to >20 km from the plants. Improving the exposure assessment would be an asset to future studies. Criteria to include industries in multicenter studies should be defined.

A simple indicator to rapidly assess the short-term impact of heat waves on mortality within the French heat warning system.

We propose a simple method to provide a rapid and robust estimate of the short-term impacts of heat waves on mortality, to be used for communication within a heat warning system. The excess mortality during a heat wave is defined as the difference between the observed mortality over the period and the observed mortality over the same period during the N preceding years. This method was tested on 19 French cities between 1973 and 2007. In six cities, we compared the excess mortality to that obtained using a modelling of the temperature-mortality relationship. There was a good agreement between the excess mortalities estimated by the simple indicator and by the models. Major differences were observed during the most extreme heat waves, in 1983 and 2003, and after the implementation of the heat prevention plan in 2006. Excluding these events, the mean difference between the estimates obtained by the two methods was of 13 deaths [1:45]. A comparison of mortality with the previous years provides a simple estimate of the mortality impact of heat waves. It can be used to provide early and reliable information to stakeholders of the heat prevention plan, and to select heat waves that should be further investigated.

Definition of temperature thresholds: the example of the French heat wave warning system.

Heat-related deaths should be somewhat preventable. In France, some prevention measures are activated when minimum and maximum temperatures averaged over three days reach city-specific thresholds. The current thresholds were computed based on a descriptive analysis of past heat waves and on local expert judgement. We tested whether a different method would confirm these thresholds. The study was set in the six cities of Paris, Lyon, Marseille, Nantes, Strasbourg and Limoges between 1973 and 2003. For each city, we estimated the excess in mortality associated with different temperature thresholds, using a generalised additive model, controlling for long-time trends, seasons and days of the week. These models were used to compute the mortality predicted by different percentiles of temperatures. The thresholds were chosen as the percentiles associated with a significant excess mortality. In all cities, there was a good correlation between current thresholds and the thresholds derived from the models, with 0°C to 3°C differences for averaged maximum temperatures. Both set of thresholds were able to anticipate the main periods of excess mortality during the summers of 1973 to 2003. A simple method relying on descriptive analysis and expert judgement is sufficient to define protective temperature thresholds and to prevent heat wave mortality. As temperatures are increasing along with the climate change and adaptation is ongoing, more research is required to understand if and when thresholds should be modified.

How to use near real-time health indicators to support decision-making during a heat wave: the example of the French heat wave warning system.

Introduction The French warning system for heat waves is based on meteorological forecasts. Near real-time health indicators are used to support decision-making, e.g. to extend the warning period, or to choose the most appropriate preventive measures. They must be analysed rapidly to provide decision-makers useful and in-time information. The objective of the study was to evaluate such health indicators. Methods A literature review identified a range of possible mortality and morbidity indicators. A reduced number were selected, based on several criteria including sensitivity to heat, reactivity, representativity and data quality. Two methods were proposed to identify indicator-based statistical alarms: historical limits or control charts, depending on data availability. The use of the indicators was examined using the 2006 and 2009 heat waves. Results Out of 25 possible indicators, 5 were selected: total mortality, total emergency calls, total emergency visits, emergency visits for people aged 75 and over and emergency visits for causes linked to heat. In 2006 and 2009, no clear increases were observed during the heat waves. The analyses of real-time health indicators showed there was no need to modify warning proposals based on meteorological parameters. Discussion These findings suggest that forecasted temperatures can be used to anticipate heat waves and promote preventive actions. Health indicators may not be needed to issue a heat wave alert, but daily surveillance of health indicators may be useful for decision-makers to adapt prevention measures.

Short term effects of air pollution on hospitalizations for cardiovascular diseases in eight French cities: the PSAS program.

INTRODUCTION: Short term associations between air pollution indicators and hospitalizations for cardiovascular diseases have been suggested by epidemiological and clinical studies. The present study aims at estimating the association between particles with diameter <10 microm (PM(10)), nitrogen dioxide (NO(2)) and ozone and hospitalizations for cardiovascular diseases in eight French cities during the 1998-2003 period. METHODS: The daily number of hospitalizations in each city was extracted from the French hospital information system (PMSI) for cardiovascular diseases, cardiac diseases, ischemic heart diseases and stroke. Excess relative risks (ERRs) of hospitalization associated with a 10 microg/m(3) increase in pollutant levels were estimated in each city by fitting a Poisson regression model, controlling for well-known confounding factors and temporal trends. City-specific results were then combined by inverse variance weighting. RESULTS: Daily number of hospitalizations for cardiovascular diseases was associated with PM(10) levels (for a 10 microg/m(3) increase, ERR=0.8%, 95% CI: [0.2, 1.5]), with NO(2) (1.1%, [0.6, 1.6]) but not with ozone (0.1% [-0.2%, 0.5%]). Associations were stronger in people aged 65 years and over, and when only hospitalizations for ischemic heart diseases were considered. No association was found between strokes and air pollution levels. DISCUSSION: Our study suggests that the ambient levels of air pollutants currently experienced in the eight French cities, which are close to European air quality guidelines, are yet linked to a short term increase of hospitalizations for cardiovascular diseases. These results are consistent with epidemiological and toxicological data on the cardiovascular effects of air pollution.