The association between maternal urinary phthalate metabolites concentrations and pregnancy induced hypertension: Results from the EDEN Mother-Child Cohort.

BACKGROUND: Studies have suggested that exposure to endocrine disruptors such as phthalates that are widely used in our daily life (food wrapping, cosmetics, toys, medical devices, polyvinyl chloride flooring, and building materials) might be related to raised blood pressure and increased risk of cardiovascular diseases. Phthalates might induce a pro-inflammatory response and increased oxidative stress and may be a cause of pregnancy induced hypertension. METHODS: We evaluated the association between maternal exposure to phthalates during pregnancy and pregnancy induced hypertension. 604 pregnant women were included and eleven phthalate metabolites were quantified in spot maternal urine samples collected between the 23rd and 28th week of gestation in a French EDEN mother-child cohort. The associations were assessed by applying multiple logistic regression analysis. RESULTS: Twenty nine (4,8%) mothers developed pregnancy induced hypertension. Two low molecular weight phthalate metabolites: Monoethyl phthalate (MEP) and Mono-n­butyl phthalate (MBP) were positively associated with pregnancy induced hypertension in crude (Odds Ratio: 1.43, 95% Confidence Interval: 1.04-1.96, p-value = 0.02 and 1.48, 1.10-2.01, p-value =0.01) and in adjusted (1.47, 1.01-2.14, p-value = 0.04 and 1.66, 1.11-2.47, p-value = 0.01) models respectively. CONCLUSION: Our data suggest that prenatal exposure to some phthalates, including MEP and MBP, might play a role in pregnancy induced hypertension.

Do gene-environment interactions play a role in COVID-19 distribution? The case of Alpha-1 Antitrypsin, air pollution and COVID-19.

BACKGROUND: Gene-environment interactions are relevant for several respiratory diseases. This communication raises the hypothesis that the severity of COVID-19, a complex disease where the individual response to the infection may play a significant role, could partly result from a gene-environment interaction between air-pollution and Alpha-1 Antitrypsin (AAT) genes. METHODS: To evaluate the impact of the AAT and air pollution interaction on COVID-19, we introduced an AAT*air pollution global risk score summing together, in each country, an air pollution score (ozone, nitrogen dioxide and fine particulate matter) and an AAT score (which sums the ranked frequency of MZ, SZ, MS). We compared this global score with the ranking of European countries in terms of death number per million persons. RESULTS: The ranking of the AAT*air pollution global risk score matched the ranking of the countries in terms of the observed COVID-19 deaths per 1M inhabitants, namely in the case of the first European countries: Belgium, UK, Spain, Italy, Sweden, France. We observed parallelism between the number of COVID deaths and the AAT*air pollution global risk in Europe. AAT anti-protease, immune-modulating and coagulation-modulating activities may explain this finding, although very speculatively. CONCLUSIONS: Even if further studies taking into account genetic background, population density, temporal dynamics of individual epidemics, access to healthcare, social disparities and immunological response to SARS-CoV2 are needed, our preliminary observation urges to open a discussion on gene-environment interactions in COVID-19.

The impact of outdoor air pollution on COVID-19: a review of evidence from in vitro, animal, and human studies.

Studies have pointed out that air pollution may be a contributing factor to the coronavirus disease 2019 (COVID-19) pandemic. However, the specific links between air pollution and severe acute respiratory syndrome-coronavirus-2 infection remain unclear. Here we provide evidence from in vitro, animal and human studies from the existing literature. Epidemiological investigations have related various air pollutants to COVID-19 morbidity and mortality at the population level, however, those studies suffer from several limitations. Air pollution may be linked to an increase in COVID-19 severity and lethality through its impact on chronic diseases, such as cardiopulmonary diseases and diabetes. Experimental studies have shown that exposure to air pollution leads to a decreased immune response, thus facilitating viral penetration and replication. Viruses may persist in air through complex interactions with particles and gases depending on: 1) chemical composition; 2) electric charges of particles; and 3) meteorological conditions such as relative humidity, ultraviolet (UV) radiation and temperature. In addition, by reducing UV radiation, air pollutants may promote viral persistence in air and reduce vitamin D synthesis. Further epidemiological studies are needed to better estimate the impact of air pollution on COVID-19. In vitro and in vivo studies are also strongly needed, in particular to more precisely explore the particle-virus interaction in air.

Gender differences in respiratory health outcomes among farming cohorts around the globe: findings from the AGRICOH consortium.

Purpose: Respiratory hazards of farming have been identified for centuries, with little focus on gender differences. We used data from the AGRICOH consortium, a collective of prospective cohorts of agricultural workers, to assess respiratory disease prevalence among adults in 18 cohorts representing over 200,000 farmers, farm workers, and their spouses from six continents.Methods: Cohorts collected data between 1992 and 2016 and ranged in size from 200 to >128,000 individuals; 44% of participants were female. Farming practices varied from subsistence farming to large-scale industrial agriculture. All cohorts provided respiratory outcome information for their cohort based on their study definitions. The majority of outcomes were based on self-report using standard respiratory questionnaires; the greatest variability in assessment methods was associated with chronic obstructive pulmonary disease (COPD).Results: For all three respiratory symptoms (cough, phlegm, and wheeze), the median prevalence in men was higher than in women, with the greatest difference for phlegm (17% vs. 10%). For asthma, women had a higher prevalence (7.8% vs 6.5%), with the difference associated with allergic asthma. The relative proportion of allergic asthma varied among cohorts. In two of eight cohorts for women and two of seven cohorts for men, allergic asthma was more common than non-allergic asthma.Conclusions: These findings indicate that respiratory outcomes are common among farmers around the world despite differences in agricultural production. As women in the general population are at higher risk of asthma, exploring gender differences in occupational studies is critical for a deeper understanding of respiratory disease among agricultural workers.

Foetal exposure to heavy metals and risk of atopic diseases in early childhood.

BACKGROUND: Accumulating evidence suggests that in utero exposures can influence the development of the immune system and thus contribute to disease development. Studies investigating the association between prenatal exposures to heavy metals and atopic diseases, however, are scarce. METHODS: Children from the EDEN birth cohort were prospectively followed up using parental questionnaires with validated questions on asthma, allergic rhinitis, eczema, and food allergy symptoms. The questionnaires were administered every 4 months during the children's first year, and then every year until the age of 5, with a final survey at the age of 8. Serum concentrations of lead (Pb), cadmium (Cd), and manganese (Mn) were assessed in maternal blood samples collected during mid-pregnancy and in cord blood of 651 mother-children pairs. Hazard ratios (HR) for the incidence of each atopic disease in relation to the exposure to metals were calculated using Cox proportional hazard models. RESULTS: Levels of Cd in cord blood were associated with greater risk of asthma (hazard ratio [95% confidence interval] for upper vs lower quartile: 1.81 [1.00-3.29]), eczema (1.60 [1.09-2.35]), and food allergy (3.17 [1.36-7.38]), while Mn levels in maternal serum were associated with eczema (1.55 [1.05-2.28]). These associations were similar in males and females and were confirmed using log concentrations of metals as exposures. CONCLUSIONS: Our results support the hypothesis that fetal exposure to heavy metals may affect the development of asthma, eczema, and food allergy in childhood and suggest that timing of exposure in utero may have a role in these associations.

Indoor air pollution, physical and comfort parameters related to schoolchildren's health: Data from the European SINPHONIE study.

Substantial knowledge is available on the association of the indoor school environment and its effect among schoolchildren. In the same context, the SINPHONIE (School indoor pollution and health: Observatory network in Europe) conducted a study to collect data and determine the distribution of several indoor air pollutants (IAPs), physical and thermal parameters and their association with eye, skin, upper-, lower respiratory and systemic disorder symptoms during the previous three months. Finally, data from 115 schools in 54 European cities from 23 countries were collected and included 5175 schoolchildren using a harmonized and standardized protocol. The association between exposures and the health outcomes were examined using logistic regression models on the environmental stressors assessed in classroom while adjusting for several confounding factors; a VOC (volatile organic compound) score defined as the sum of the number of pollutants to which the children were highly exposed (concentration > median of the distribution) in classroom was also introduced to evaluate the multiexposure - outcome association. Schoolchildren while adjusting for several confounding factors. Schoolchildren exposed to above or equal median concentration of PM2.5, benzene, limonene, ozone and radon were at significantly higher odds of suffering from upper, lower airways, eye and systemic disorders. Increased odds were also observed for any symptom (sick school syndrome) among schoolchildren exposed to concentrations of limonene and ozone above median values. Furthermore, the risks for upper and lower airways and systemic disorders significantly increased with the VOCs score. Results also showed that increased ventilation rate was significantly associated with decreased odds of suffering from eye and skin disorders whereas similar association was observed between temperature and upper airways symptoms. The present study provides evidence that exposure to IAPs in schools is associated with various health problems in children. Further investigations are needed to confirm our findings.

Daylight and School Performance in European Schoolchildren.

: Aims and objectives: Lighting constitutes a critical issue in school design because of its importance as a strong enabler of performance, which is crucial for child development. However, data on light impacts on school performance are scarce. The main objective of this study was to assess the relationship between daylighting conditions in classrooms and mathematical and logical test scores. METHODS: The population-based SINPHONIE (Schools Indoor Pollution and Heath: Observatory Network in Europe) study provides information on relationships between lighting conditions and school performance for 2670 elementary schoolchildren, aged 8-13 years from 155 classrooms in 53 schools across 12 European countries. These data were acquired through direct physical assessments and questionnaires completed by teachers, schoolchildren, and their parents, allowing for estimations of multiple objective daylight indicators, as well as subjective parameters such as the perception of lighting. Schoolchildren performed an attention/concentration exam that included simple mathematical exercises in addition to a logical ciphering test. The corresponding performance scores were compared against multiple daylighting parameters. RESULTS: A positive relationship was found between performance scores and type of window shading, latitude, percentage of window facing south, and window glazing, with the highest impact due to the window-to-floor area ratio. CONCLUSION: Data collected in the SINPHONIE study across 12 European countries indicate that daylighting parameters are relevant to schoolchildren's performance. As SINPHONIE was not designed specifically with lighting in mind, dedicated studies covering a wide range of classroom configurations would be enlightening.

Influence of residential land cover on childhood allergic and respiratory symptoms and diseases: Evidence from 9 European cohorts.

INTRODUCTION: Recent research focused on the interaction between land cover and the development of allergic and respiratory disease has provided conflicting results and the underlying mechanisms are not fully understood. In particular, green space, which confers an overall positive impact on general health, may be significantly contributing to adverse respiratory health outcomes. This study evaluates associations between surrounding residential land cover (green, grey, agricultural and blue space), including type of forest cover (deciduous, coniferous and mixed), and childhood allergic and respiratory diseases. METHODS: Data from 8063 children, aged 3-14 years, were obtained from nine European population-based studies participating in the HEALS project. Land-cover exposures within a 500 m buffer centred on each child's residential address were computed using data from the Coordination of Information on the Environment (CORINE) program. The associations of allergic and respiratory symptoms (wheeze, asthma, allergic rhinitis and eczema) with land coverage were estimated for each study using logistic regression models, adjusted for sex, age, body mass index, maternal education, parental smoking, and parental history of allergy. Finally, the pooled effects across studies were estimated using meta-analyses. RESULTS: In the pooled analyses, a 10% increase in green space coverage was significantly associated with a 5.9%-13.0% increase in the odds of wheezing, asthma, and allergic rhinitis, but not eczema. A trend of an inverse relationship between agricultural space and respiratory symptoms was observed, but did not reach statistical significance. In secondary analyses, children living in areas with surrounding coniferous forests had significantly greater odds of reporting wheezing, asthma and allergic rhinitis. CONCLUSION: Our results provide further evidence that exposure to green space is associated with increased respiratory disease in children. Additionally, our findings suggest that coniferous forests might be associated with wheezing, asthma and allergic rhinitis. Additional studies evaluating both the type of green space and its use in relation to respiratory conditions should be conducted in order to clarify the underlying mechanisms behind associated adverse impacts.

Indoor exposure to particulate matter and volatile organic compounds in dwellings and workplaces and respiratory health in French farmers.

INTRODUCTION: Few investigations have related objective assessments of indoor air pollutants to respiratory health in farmers, in spite of the many rural environmental hazards to which they are exposed. Chemical air pollution has been particularly neglected. OBJECTIVE: We investigated the relationships of indoor exposure to particulate matter (PM) and volatile organic compounds (VOCs) to respiratory health in farmers. METHODS: Nineteen VOCs (5 families) and PM (from ultrafine to total suspended particles (TSP)) were objectively assessed in dwellings and workplaces in 109 French farmers during a week. To take into account multiple exposures, scores of exposure were computed for total VOCs and VOCs families. Individuals filled a standardized questionnaire and underwent spirometry with bronchodilation test. RESULTS: On average, VOCs concentrations were higher in dwellings than in workplaces. The reverse was observed for PM. When considering the mean concentrations of air pollutants for the whole farm (dwellings + workplaces), asthma (9.3%) was positively associated with elevated exposure to benzene (adjusted odds-ratio (ORa) = 6.64, 95%CI: 1.56-28.27), trichloroethylene (4.80, 1.00-23.30) and halogenated hydrocarbons score (2.9, 95% 1.3-6.8). Early airway obstruction (FEF25-75 < 80%, with normal FEV1 and FVC and FEV/FVC ≥ 70%) (29.8%) was related to elevated exposure to 2-butoxyetylacetate (11.49, 1.55-85.37) and glycol ethers score (2.0; 1.0-4.1) in the whole farm and to PM2.5 (ORa = 5.26, 95% CI: 1.09-25.28) in the granary/stable. The risk of Chronic Obstructive Pulmonary Diseases (FEV/FVC < 70%) (COPD) (4.26%) was found to be larger with elevated exposure to aldehydes (OR = 3.95, 1.09-14.26). CONCLUSION: Indoor chemical air pollution is detrimental to farmers' respiratory health. More epidemiological investigations with detailed exposure assessments and clinical measures of respiratory effects are needed in rural settings to corroborate these findings.

A model for estimating the lifelong exposure to PM2.5 and NO2 and the application to population studies.

Numerous epidemiological studies have confirmed the negative influences of air pollutants on human health, where fine particles (PM2.5) and nitrogen dioxide (NO2) cause the highest health risks. However, the traditional studies have only involved the ambient concentration for a short to medium time period, which ignores the influence of indoor sources, the individual time-activity pattern, and the fact that the health status is impacted by the long-term accumulated exposure. The aim of this paper is to develop a methodology to simulate the lifelong exposure (rather than outdoor concentration) to PM2.5 and NO2 for individuals in Europe. This method is realized by developing a probabilistic model that integrates an outdoor air quality model, a model estimating indoor air pollution, an exposure model, and a life course trajectory model for predicting retrospectively the employment status. This approach has been applied to samples of two population studies in the frame of the European Commission FP7-ENVIRONMENT research project HEALS (Health and Environment-wide Associations based on Large Population Surveys), where socioeconomic data of the participants have been collected. Results show that the simulated exposures to both pollutants for the samples are influenced by socio-demographic characteristics, including age, gender, residential location, employment status and smoking habits. Both outdoor concentrations and indoor sources play an important role in the total exposure. Moreover, large variances have been observed among countries and cities. The application of this methodology provides valuable insights for the exposure modelling, as well as important input data for exploring the correlation between exposure and health impacts.

Lifelong exposure to multiple stressors through different environmental pathways for European populations.

Traditional exposure studies provide valuable insights for epidemiology, toxicology, and risk assessment. Throughout their lives, individuals are exposed to thousands of stressors in the environment which are not static, but influenced by environmental, temporal, spatial, and even socio-demographic factors. Existing exposure studies have usually focused on specific stressors for a constrained period of time. In response, the concept of the exposome has been raised, which is defined as the totality of exposure experienced from conception until death. The EU FP7-ENVIRONMENT research project HEALS was launched with the aim of incorporating a series of novel technologies, data analysis, and modelling tools to efficiently support exposome studies in Europe. The authors have developed a framework of modelling tools for estimating the long-term external exposure of selected population groups to multiple stressors through different pathways. As the starting point, the stressors, including electromagnetic fields (EMF) and ultraviolet light (UV) through dermal uptake, phthalates (DEHP, DIDP, and DINP) through inhalation, as well as chromium, mercury, and lead through food intake, have been selected. The simulation for multiple stressors has been realised by developing a probabilistic model that integrates the micro-environment approach, time-activity patterns, and a life course trajectory model. The methodology has been applied to a selected sample of subjects enrolled in the Italian Twin Registry (ITR). The results show that long-term exposures to multiple stressors are affected by factors including age, gender, geographical location, and education level. The methods developed in this paper extended the temporal and spatial scales of exposure modelling in Europe. Moreover, the application of our methods provided a novel approach and crucial input data for future work on environment-wide association studies.

Long-Term Effect of Outdoor Air Pollution on Mortality and Morbidity: A 12-Year Follow-Up Study for Metropolitan France.

BACKGROUND: Short-term effects of air pollution are documented more than long-term effects. OBJECTIVE: We investigated 12-year impacts of ambient air pollutants on cardiovascular and respiratory morbidity and mortality at the departmental level in metropolitan France. METHODS: Daily air pollution data at 2-km resolution, including concentrations of particulate matter of 10 µm or 2.5 µm in diameter or less (PM10 and PM2.5), nitrogen dioxide (NO2), and ozone (O3), were accrued from the CHIMERE database for 1999 and 2000. Simultaneously, morbidity (hospitalizations) and mortality data were collected in 2012 using the ESPS (Enquête Santé et Protection Sociale/Health, Health Care and Insurance Survey) survey data and the CepiDc (Centre d'Épidémiologie sur les Causes Médicales de Décès/French Epidemiology Centre on Medical Causes of Death) database. Based on Poisson regression analyses, the long-term effect was estimated. A higher risk of all-cause mortality was observed using CépiDc database, with a relative risk of 1.024 (95% CI: 1.022, 1.026) and 1.029 (95% CI: 1.027, 1.031) for a 10 µg/m³ increase in PM2.5 and PM10, respectively. Mortality due to cardiovascular and respiratory diseases likewise exhibited long-term associations with both PM2.5 and PM10. Using ESPS survey data, a significant risk was observed for both PM2.5 and PM10 in all-cause mortality and all-cause morbidity. Although a risk for higher all-cause mortality and morbidity was also present for NO2, the cause-specific relative risk due to NO2 was found to be lesser, as compared to PM. Nevertheless, cardiovascular and respiratory morbidity were related to NO2, along with PM2.5 and PM10. However, the health effect of O3 was seen to be substantially lower in comparison to the other pollutants. CONCLUSION: Our study confirmed that PM has a long-term impact on mortality and morbidity. Exposure to NO2 and O3 could also lead to increased health risks.

Prenatal Exposure to Phthalates and the Development of Eczema Phenotypes in Male Children: Results from the EDEN Mother-Child Cohort Study.

BACKGROUND: Contradictory results exist regarding the importance of early-life exposure to phthalates for development of childhood eczema. OBJECTIVES: We evaluated the association between maternal urinary concentrations of phthalate metabolites between the 24th and 28th week of gestation and occurrence of eczema in their sons up to 5 y of age, according to allergic sensitization as assessed by total immunoglobulin E (IgE) in a subsample of individuals. METHODS: Data on health outcomes and background factors were collected using five standardized annual questionnaires completed by parents at the children's ages of 1-5 y, and their associations with phthalate metabolite urinary concentrations were assessed in 604 mother-son pairs with adjusted multiple logistic regression and Cox's survival model. Several eczema phenotypes were considered. Atopic status was assessed at 5 y of age in 293 boys through total IgE assessment. RESULTS: At 5 y of age, the prevalence of ever eczema was 30.4%. Metabolites of di-isobutyl phthalate (DiBP) and di-isononyl phthalate (DiNP) were positively associated with early-onset (0-24 mo of age) eczema (15.7%) and late-onset (24-60 mo of age) eczema (14.7%). Applying the Cox's model showed a significant association of occurrence of eczema in the first 5 y of life with DiBP and DiNP metabolites. Among IgE-sensitized boys, metabolites of di-n-butyl phthalate (DBP) and DiBP were significantly associated with ever eczema {hazard ratio (HR)=1.67 [95% confidence interval (CI): 1.10, 2.54], p=0.01 and HR=1.87 (95% CI: 1.01, 3.48), p=0.04, respectively}. CONCLUSIONS: Occurrence of eczema in early childhood may be influenced by prenatal exposure to certain phthalates in boys. Further investigations are needed to confirm this observation. https://doi.org/10.1289/EHP1829.

Serum cytokine levels related to exposure to volatile organic compounds and PM2.5 in dwellings and workplaces in French farmers - a mechanism to explain nonsmoking COPD.

Although French farmers smoke less on average than individuals from the general population, they suffer more from COPD. Exposure to biological and chemical air pollutants in the farm may be the cause of these higher COPD rates. This study investigates the role of bio-contaminants, including the relationship of exposure to volatile organic compounds (VOCs) and fine particulate matter (of diameter of 2.5 µm [PM2.5]) objectively measured in the farm settings (dwellings and workplaces) to serum cytokines involved in COPD, in a sample of 72 farmers from 50 farms in the Auvergne region, France. Mean concentrations of VOCs were highest inside the home, while levels of PM2.5 were highest in workplaces (stables and granaries). After adjusting for confounders, high exposure to PM2.5 was significantly associated with a decreased level of serum cytokines (among others, IL13: ß: -0.94, CI: -1.5 to -0.2, P-value =0.004; IL8: ß: -0.82, CI: -1.4 to -0.2, P-value =0.005) and high exposure to VOCs according to a VOC global score with a decreased IL13 level (ß: -0.5, CI: -0.9 to -0.1, P-value =0.01). Moreover, respiratory symptoms and diseases, including COPD, were associated with a decreased level of serum cytokines significantly in the case of IL5. An alteration of immune response balance in terms of cytokine levels in relation to indoor chemical air pollution exposure may contribute to respiratory health impairment in farmers.

Short-Term Health Impact Assessment of Urban PM10 in Bejaia City (Algeria).

We used Health Impact Assessment (HIA) to analyze the impact on a given population's health outcomes in terms of all-causes mortality and respiratory and cardiovascular hospitalizations attributable to short-term exposure to particulate matter less than 10 µm diameter (PM10) in Bejaia city, for which health effects of air pollution have never been investigated. Two scenarios of PM10 reduction were considered: first, a scenario where the PM10 annual mean is decreased by 5 µg/m(3), and then a scenario where this PM10 mean is decreased to 20 µg/m(3) (World Health Organization annual air quality guideline (WHO-AQG)). Annual mean level of PM10 (81.7 µg/m(3)) was calculated from objective measurements assessed in situ. Each year, about 4 and 55 deaths could be postponed with the first and the second scenarios successfully. Furthermore, decreasing PM10 annual mean by 5 µg/m(3) would avoid 5 and 3 respiratory and cardiac hospitalizations, respectively, and not exceeding the PM10 WHO-AQG (20 µg/m(3)) would result in a potential gain of 36 and 23 per 100000 respiratory and cardiac hospitalizations, respectively. Lowering in current levels of PM10 has a nonnegligible impact in terms of public health that it is expected to be higher in the case of long-term effects.

Non-accidental health impacts of wildfire smoke.

Wildfires take a heavy toll on human health worldwide. Climate change may increase the risk of wildfire frequency. Therefore, in view of adapted preventive actions, there is an urgent need to further understand the health effects and public awareness of wildfires. We conducted a systematic review of non-accidental health impacts of wildfire and incorporated lessons learned from recent experiences. Based on the literature, various studies have established the relationship between one of the major components of wildfire, particulate matter (particles with diameter less than 10 µm (PM10) and less than 2.5 µm (PM2.5)) and cardiorespiratory symptoms in terms of Emergency Rooms visits and hospital admissions. Associations between wildfire emissions and various subclinical effects have also been established. However, few relationships between wildfire emissions and mortality have been observed. Certain segments of the population may be particularly vulnerable to smoke-related health risks. Among them, people with pre-existing cardiopulmonary conditions, the elderly, smokers and, for professional reasons, firefighters. Potential action mechanisms have been highlighted. Overall, more research is needed to better understand health impact of wildfire exposure.