Biomarkers of exposure to environmental contaminants in French pregnant women from the Elfe cohort in 2011.

BACKGROUND: As part of the perinatal component of the French Human Biomonitoring (HBM) program, biomarkers levels of various chemicals have been described among pregnant women having given birth in continental France in 2011 and who have been enrolled in the Elfe cohort (French Longitudinal Study since Childhood). This paper describes the design of the study and provides main descriptive results regarding exposure biomarkers levels. METHODS: Exposure biomarkers were measured in biological samples collected at delivery from pregnant women randomly selected among the participants in the clinical and biological component of the Elfe cohort (n=4145). The geometric mean and percentiles of the levels distribution were estimated for each biomarker. The sampling design was taken into account in order to obtain estimates representative of the French pregnant women in 2011. RESULTS: Results provide a nation-wide representative description of biomarker levels for important environmental contaminants among pregnant women who gave birth in France in 2011. Bisphenol A (BPA), and some metabolites of phthalates, pesticides (mainly pyrethroids), dioxins, furans, polychlorobiphenyls (PCBs), brominated flame retardants (BFRs), perfluorinated compounds (PFCs) and metals (except uranium) were quantified in almost 100% of the pregnant women. Some compounds showed a downward trend compared to previous studies (lead, mercury), but others did not (pyrethroids) and should be further monitored. CONCLUSION AND PERSPECTIVES: The present results show that French pregnant women are exposed to a wide variety of pollutants, including some that have been banned or restricted in France.

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.

A time series study of gastroenteritis and tap water quality in the Nantes area, France, 2002-2007.

In the Nantes area, 410,000 inhabitants are supplied with water pumped from the Loire River. The treatment of this water is carried out through a process of complete clarification and disinfection. During the study period (2002-07), the quality of drinking water complied with European microbial standards and mean turbidity in finished water was 0.05 NTU (nephelometric turbidity units). We aimed to characterize the link between produced water turbidity and other operational data and the incidence of acute gastroenteritis (AGE) in the Nantes area. The daily number of medical prescriptions for AGE was drawn from the French national health insurance system's drug reimbursement data. We modeled this time series using Poisson regression within the framework of a Generalized Additive Model. We showed that an interquartile range turbidity degradation (0.042-0.056 NTU) was connected to a 4.2% (CI95=(1.5%; 6.9%)) increase in the risk of AGE in children and a 2.9% (CI95=(0.5%; 5.4%)) increase in adults. The slope of the turbidity risk function was higher during both high- and low-water conditions of the river. High values of daily flow of produced water were also associated with higher endemic levels of AGE.

Effects of heat waves on mortality: effect modification and confounding by air pollutants.

BACKGROUND: Heat waves and air pollution are both associated with increased mortality. Their joint effects are less well understood. METHODS: We explored the role of air pollution in modifying the effects of heat waves on mortality, within the EuroHEAT project. Daily mortality, meteorologic, and air pollution data from nine European cities for the years 1990-2004 were assembled. We defined heat waves by taking both intensity and duration into account. The city-specific effects of heat wave episodes were estimated using generalized estimating equation models, adjusting for potential confounders with and without inclusion of air pollutants (particles, ozone, nitrogen dioxide, sulphur dioxide, carbon monoxide). To investigate effect modification, we introduced an interaction term between heat waves and each single pollutant in the models. Random effects meta-analysis was used to summarize the city-specific results. RESULTS: The increase in the number of daily deaths during heat wave episodes was 54% higher on high ozone days compared with low, among people age 75-84 years. The heat wave effect on high PM10 days was increased by 36% and 106% in the 75-84 year and 85+ year age groups, respectively. A similar pattern was observed for effects on cardiovascular mortality. Effect modification was less evident for respiratory mortality, although the heat wave effect itself was greater for this cause of death. The heat wave effect was smaller (15-30%) after adjustment for ozone or PM10. CONCLUSIONS: The heat wave effect on mortality was larger during high ozone or high PM10 days. When assessing the effect of heat waves on mortality, lack of adjustment for ozone and especially PM10 overestimates effect parameters. This bias has implications for public health policy.

Epidemiological description of an outbreak of dermatitis related to dimethylfumarate, France, 2008.

Following similar events in other European countries, some cases of dermatitis related to contact with China-imported furniture possibly treated with dimethyl(E)-butenedioate (dimethylfumarate [DMF]) were reported to the French institute for public health surveillance at the beginning of September 2008. An active multisource case collection was conducted in order to provide an epidemiological description of this outbreak. Results of this investigation show that, in France, mainly during the 4th quarter of 2008, a large number of people presented dermatological symptoms at least plausibly due to a contact with DMF-treated consumer products. The products involved were mostly shoes and sofa (94% of cases). This work offers an example of a multipartner investigation in the field of environmental health. It also shows how the results obtained contributed to decision-making and resulted in the limitation of DMF-treated products in France and in Europe.

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

BACKGROUND: The 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. METHODS: Heat 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. RESULTS: The 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. CONCLUSIONS: Climate 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.

Are the short-term effects of air pollution restricted to cardiorespiratory diseases?

Short-term effects of air pollution on common morbidity are largely unknown. The authors explored links between daily levels of air pollution (nitrogen dioxide, ozone, and particulate matter less than 10 microm in diameter (PM(10))) and medical home visits made for diverse reasons in Bordeaux, France, during 2000-2006. Daily numbers of visits were obtained from a network of general practitioners. The excess relative risk (ERR) of a visit for each indicator associated with increased pollutant levels was estimated by fitting a Poisson regression model, controlling for well-known confounding factors and temporal trends. Positive and significant associations were found between air pollution and most health indicators. A 10-microg/m(3) increase in PM(10) levels was associated with increases in visits for upper and lower respiratory diseases (ERRs were 1.5% (95% confidence interval (CI): 0.3, 2.7) and 2.5% (95% CI: 0.5, 4.4), respectively), headache and asthenia (ERR = 3.5%, 95% CI: 1.3, 5.9), and skin rash and conjunctivitis (ERR = 3.2%, 95% CI: -0.2, 6.8). Significant associations were also found between nitrogen dioxide and ozone and several health indicators. Distributed-lag models showed no harvesting effect, and some effects persisted up to 15 days after exposure increased. These results suggest that considering only the most severe effects of air pollution leads to underestimation of its impact on public health.

Influence of socioeconomic deprivation on the relation between air pollution and beta-agonist sales for asthma.

BACKGROUND: Air pollution triggers asthma attacks hours to days after exposure. It remains unclear whether socioeconomic deprivation modulates these effects. Investigation of these interactions requires adequate statistical power, obtainable by using either a sufficient number of observations or very sensitive indicators of asthma attacks. Using a small-area temporal ecologic approach, we studied the short-term relations between ambient air pollution and sales of short-acting beta-agonist (SABA) drugs, a frequent and specific treatment for control of asthma attacks in children and young adults, and then tested the influence of deprivation on these relations. METHODS: The study took place in Strasbourg, France in 2004. Health insurance funds provided data on 15,121 SABA sales for patients aged 0 to 39 years. Deprivation was estimated by small geographic areas using an index constructed from census data. Daily average ambient concentrations of particulate matter (particles with an aerodynamic diameter < 10 microm [PM(10)]), nitrogen dioxide (NO(2)), and ozone (O(3)) were modeled on a small-area level. Adjusted case-crossover models were used for statistical analysis. RESULTS: Increased of 10 microg/m(3) in ambient PM(10), NO(2), and O(3) concentrations were associated, respectively, with increases of 7.5% (95% confidence interval [CI], 4 to 11.2%), 8.4% (95% CI, 5 to 11.9%), and 1% (95% CI, - 0.3 to 2.2%) in SABA sales. Deprivation had no influence on these relations. CONCLUSION: The associations observed are consistent with those reported by studies focusing on SABA use. Similar studies in other settings should confirm whether the lack of interaction with deprivation is due to specific local conditions.

Factors associated with morbidity during the 2003 heat wave in two population-based cohorts of elderly subjects: PAQUID and Three City.

INTRODUCTION: France was affected in early August 2003 by a heat wave with an exceptional health impact. Many studies on mortality were conducted but few data are available on morbidity. The objectives of this study were to describe the impact of the 2003 heat wave in the general population of elderly people and to determine individual factors associated with morbidity. METHODS: A cross-sectional study nested in two prospective cohorts, the PAQUID and the Three-City (3C) studies, was performed. The sample included 2295 subjects from the general population, aged 67 and over who were interviewed by a phone questionnaire to complete data available in the database of the two cohorts. Two variables assessing morbidity (felt by the person and objectively observed) were created. Relationship between morbidity and individual factors were explored in univariate analyses; then multiple logistic regressions were conducted. RESULTS: During the heat wave, 8.8% of the subjects felt a deterioration of their health, and 7.8% declared an objective morbid outcome. In the univariate analyses, many factors were associated with morbidity. After multiple adjustments, few associations were still observed but some factors were associated with a decreased risk (presence of a bathroom, dressing lighter than usually) or an increased risk (stopping usual activities, presence of chronic diseases). CONCLUSION: This study showed a non-negligible impact of the 2003 heat wave in term of felt and objective morbidity. Several individual factors were shown to be associated with morbidity and should be taken into account for the elaboration of prevention plans.

Sensitivity analysis in summary measure of population health in France.

BACKGROUND: The aim of this study is to provide estimates of the French burden of disease, using the WHO Global Burden of Disease methodology and to perform sensitivity analysis on different set of mortality data. METHODS: The burden of disease is measured by disability-adjusted life years (DALYs) that take into account both mortality and morbidity data. Results were obtained using French mortality data for the years 2000 and 2001 and morbidity data estimated by WHO for France. Sensitivity analyses were conducted using different mortality data sets and various life tables as mortality norms. Calculations were also performed with and without discounting and age-weighting. RESULTS: In France, the annual burden of disease was about 12.4 million DALYs. Depending on the mortality data set and the choice of social values used for calculation, results could be quite different. The use of WHO estimates for mortality resulted in an underestimation of 2.6% of total DALYs with respect to French data. Changes of the mortality norm imply changes in the number of years of life lost (YLLs), whereas the use of discounting and age-weighting mainly modifies the ranking of diseases. CONCLUSION: DALYs constitute a summary measure of population health, which is a powerful tool for the grading of health problems, allowing to compare fatal and non-fatal diseases. Nevertheless, the validity of results obtained depends primarily on the validity of the input data. Collecting morbidity data (mainly incidence) at the national level is hence an important step in order to assess more accurately the specific burden of diseases in France.

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.

Air pollution and doctors' house calls for respiratory diseases in the Greater Paris area (2000-3).

This study describes the short-term relationships between the daily levels of PM10, PM2.5, NO2 and the number of doctors' house calls for asthma, upper respiratory diseases (URD) and lower respiratory diseases (LRD) in Greater Paris for the years 2000-3. Doctors' house calls are a relevant health indicator for the study of short-term health effects of air pollution. Indeed, it is potentially more sensitive than indicators such as general hospital admissions due to the severity of diseases motivating the call. In this study, time-series analysis was used. The daily numbers of doctor's house calls were adjusted for time trends, seasonal factors, day of the week, influenza, weather and pollen. Up to 15 days of lag between exposure and health effects was considered using distributed lag models. A total of about 1,760,000 doctors' house calls for all causes occurred during the study period, among which 8027 were for asthma, 52,928 for LRD and 74,845 for URD. No significant increase in risk was found between air pollution and doctors' house calls for asthma. No significant association was found between NO2 and doctors' house calls. An increase of 10 microg/m3 in the mean levels of PM10 and PM2.5 encountered during the 3 previous days was associated with an increase of 3% (0.8% and 5.3%) and 5.9% (2.9% and 9.0%) in the number of doctor's house calls for URD and LRD, respectively. Considering up to 15 days between exposure and health outcomes, effects persist until 4 days after exposure and then decrease progressively. No morbidity displacement was observed. This study shows a significant heath effect of ambient particles (PM2.5 and PM10). When compared to the RRs obtained for mortality or hospital admissions in the same area, the values of the RRs obtained in this study confirm the higher sensibility of doctor's house calls for respiratory diseases as a health indicator.

The relation between temperature, ozone, and mortality in nine French cities during the heat wave of 2003.

BACKGROUND: During August 2003, record high temperatures were observed across Europe, and France was the country most affected. During this period, elevated ozone concentrations were measured all over the country. Questions were raised concerning the contribution of O3 to the health impact of the summer 2003 heat wave. METHODS: We used a time-series design to analyze short-term effects of temperature and O3 pollution on mortality. Counts of deaths were regressed on temperatures and O3 levels, controlling for possible confounders: long-term trends, season, influenza outbreaks, day of the week, and bank holiday effects. For comparison with previous results of the nine cities, we calculated pooled excess risk using a random effect approach and an empirical Bayes approach. FINDINGS: For the nine cities, the excess risk of death is significant (1.01% ; 95% confidence interval, 0.58-1.44) for an increase of 10 microg/m3 in O3 level. For the 3-17 August 2003 period, the excess risk of deaths linked to O3 and temperatures together ranged from 10.6% in Le Havre to 174.7% in Paris. When we compared the relative contributions of O3 and temperature to this joint excess risk, the contribution of O3 varied according to the city, ranging from 2.5% in Bordeaux to 85.3% in Toulouse. INTERPRETATION: We observed heterogeneity among the nine cities not only for the joint effect of O3 and temperatures, but also for the relative contribution of each factor. These results confirmed that in urban areas O3 levels have a non-negligible impact in terms of public health.

Impact of the 2003 heatwave on all-cause mortality in 9 French cities.

BACKGROUND: A heatwave occurred in France in August 2003, with an accompanying excess of all-cause mortality. This study quantifies this excess mortality and investigates a possible harvesting effect in the few weeks after the heatwave. METHODS: A time-series study using a Poisson regression model with regression splines to control for nonlinear confounders was used to analyze the correlation between heatwave variable and mortality in 9 French cities. RESULTS: After controlling for long-term and seasonal time trends and the usual effects of temperature and air pollution, we estimated that 3,096 extra deaths resulted from the heatwave. The maximum daily relative risk of mortality during the heatwave (compared with expected deaths at that time of year) ranged from 1.16 in Le Havre to 5.00 in Paris. There was little evidence of mortality displacement in the few weeks after the heatwave, with an estimated deficit of 253 deaths at the end of the period. CONCLUSIONS: The heatwave in France during August 2003 was associated with a large increase in the number of deaths. The impact estimated using a time-series design was consistent with crude previous estimates of the impact of the heatwave. This finding suggests that neither air pollution nor long-term and seasonal trends confounded previous estimates. There was no evidence to suggest that the extras deaths associated with the heatwave were simply brought forward in time.

Mechanotransduction in root gravity sensing cells.

The analysis of the dose-response curve of the gravitropic reaction of lentil seedling roots has shown that these organs are more sensitive when they have been grown in microgravity than when they have been grown on a 1 g centrifuge in space before gravistimulation. This difference of gravisensitivity is not due to the volume or the density of starch grains of statoliths, which are about the same in both conditions (1 g or microgravity). However, the distribution of statoliths within the statocyte may be responsible for this differential sensitivity, since the dispersion of these organelles is greater in microgravity than in 1 g. When lentil roots grown in microgravity or in 1 g are stimulated at 0.93 g for 22 min, the amyloplasts sediment following two different trajectories. They move from the proximal half of the statocytes toward the lower longitudinal wall in the microgravity grown sample and from the distal half toward the longitudinal wall in the 1 g grown sample. At the end of the stimulation, they reach a similar position within the statocytes. If the roots of both samples are left in microgravity for 3 h, the amyloplasts move toward the cell centre in a direction that makes an average angle of 40 degrees with respect to the lower longitudinal wall. The actin filaments, which are responsible for this movement, may have an overall orientation of 40 degrees with respect to this wall. Thus, when roots grown in microgravity are stimulated on the minicentrifuge the amyloplasts slide on the actin filaments, whereas they move perpendicular to them in 1 g grown roots. Our results suggest that greater sensitivity of seedling roots grown in microgravity should be due to greater dispersion of statoliths, to better contacts between statoliths and the actin network and to greater number of activated mechanoreceptors. One can hypothesize that stretch activated ion channels (SACs) located in the plasma membrane are responsible for the transduction of gravistimulus. These SACs may be connected together by elements of the cytoskeleton lining the plasma membrane and to the actin filaments. They could be stimulated by the action of statoliths on the actin network and/or on these elements of the cytoskeleton which link the mechanoreceptors (SACs).

A polarized cell: the root statocyte.

In the gravity-perceiving cells (statocytes), located in the centre of the root cap, polarity is expressed in the arrangement of the organelles since, in most genera, the nucleus and the endoplasmic reticulum are maintained at the opposite ends of each cell by actin. Polarity is also evident in the distribution of plasmodesmata, which are more numerous in the transverse walls than in the longitudinal walls. The centre of each statocyte is depleted of microtubules (they are only located at the periphery) but is occupied by numerous amyloplasts (statoliths), denser than the cytoplasm. The amyloplasts do not contribute to the inherent structural polarity since their position is dependent upon the gravity vector. This article focuses on new microscopic analyses and on data obtained from experiments performed in microgravity, which have contributed to our better understanding of the architecture of the actin web implicated in the perception of gravity. Depending upon the plant, the actin network seems to be formed of single filaments arranged in various ways, or, of thin bundles of actin filaments. The amyloplasts are enmeshed in this web of actin and their envelopes are associated with it, but they can have autonomous movement via myosin in the absence of gravity. From calculations of the value of the force necessary to move one amyloplast in the lentil root, and from videomicroscopy performed with living statocytes of maize roots, it is hypothesized that actin microfilaments could be orientated in an overall diagonal direction in the statocyte. These observations could help in understanding how slight amyloplast movements may trigger and transmit the gravitropic signal.

The dose-response curve of the gravitropic reaction: a re-analysis.

The dose-response curve of the gravitropic reaction is often used to evaluate the gravisensing of plant organs. It has been proposed (Larsen 1957) that the response (curvature) varies linearly as a function of the logarithm of the dose of gravistimulus. As this model fitted correctly most of the data obtained in the literature, the presentation time (tp, minimal duration of stimulation in the gravitational field to induce a response) or the presentation dose (dp, minimal quantity in g.s of stimulation to induce a response) were estimated by extrapolating down to zero curvature the straight line representing the response as a function of the logarithm of the stimulus. This method was preferred to a direct measurement of dp or tp with minute stimulations, since very slight gravitropic response cannot be distinguished from the background oscillations of the extremity of the organs. In the present review, it is shown that generally the logarithmic model (L) does not fit the experimental data published in the literature as well as the hyperbolic model (H). The H model in its simplest form is related to a response in which a ligand-receptor system is the limiting phase in the cascade of events leading to the response (Weyers et al. 1987). However, it is demonstrated that the differential growth, responsible for the curvature (and the angle of curvature), would vary as a hyperbolic function of the dose of stimulation, even if several steps involving ligand-receptor systems are responsible for the gravitropic curvature. In the H model, there is theoretically no presentation time (or presentation dose) since the curve passes through the origin. The value of the derivative of the H function equals a/b and represents the slope of the cune at the origin. It could be therefore used to estimate gravisensitivity. This provides a measurement of graviresponsiveness for threshold doses of stimulation. These results imply that the presentation time (or presentation dose) derived from the L model cannot be used anymore as an estimate of gravisensitivity. On the contrary, the perception time (minimal duration of a repeated stimulation which induces a response), which is less than 1 s, should be related to the perception of gravity. The consequences of these results on the mode of action and the nature of graviperception are discussed.