Urban environment and health: a cross-sectional multiregional project based on population health surveys in Spain (DAS-EP project) - study protocol.

INTRODUCTION: The European Environment Agency estimates that 75% of the European population lives in cities. Despite the many advantages of city life, the risks and challenges to health arising from urbanisation need to be addressed in order to tackle the growing burden of disease and health inequalities in cities. This study, Urban environment and health: a cross-sectional multiregional project based on population health surveys in Spain (DAS-EP project), aims to investigate the complex association between the urban environmental exposures (UrbEEs) and health. METHODS AND ANALYSIS: DAS-EP is a Spanish multiregional cross-sectional project that combines population health surveys (PHS) and geographical information systems (GIS) allowing to collect rich individual-level data from 17 000 adult citizens participating in the PHS conducted in the autonomous regions of the Basque Country, Andalusia, and the Valencian Community, and the city of Barcelona in the years 2021-2023. This study focuses on the population living in cities or metropolitan areas with more than 100 000 inhabitants. UrbEEs are described by objective estimates at participants' home addresses by GIS, and subjective indicators present in PHS. The health outcomes included in the PHS and selected for this study are self-perceived health (general and mental), prevalence of chronic mental disorders, health-related quality of life, consumption of medication for common mental disorders and sleep quality. We aim to further understand the direct and indirect effects between UrbEEs and health, as well as to estimate the impact at the population level, taking respondents' sociodemographic and socioeconomic characteristics, and lifestyle into consideration. ETHICS AND DISSEMINATION: The study was approved by the regional Research Ethics Committee of the Basque Country (Ethics Committee for Research Involving Medicinal Products in the Basque Country; PI2022138), Andalusia (Biomedical Research Ethics Committee of the Province of Granada; 2078-N-22), Barcelona (CEIC-PSMar; 2022/10667) and the Valencian Community (Ethics Committee for Clinical Research of the Directorate General of Public Health and Center for Advanced Research in Public Health; 20221125/04). The results will be communicated to the general population, health professionals, and institutions through conferences, reports and scientific articles.

Estimating ambient air pollution mortality and disease burden and its economic cost in Barcelona.

BACKGROUND: The new WHO air quality guidelines indicate that the air pollution disease burden is greater than previously reported. We aimed to estimate the air pollution disease burden and its economic cost in Barcelona to inform local action. METHODS: We used a quantitative health impact assessment to estimate the non-accidental mortality and incidence of childhood asthma and lung cancer attributable to long-term air pollution exposure in the city of Barcelona (Spain) in 2018-2019. We used the population weighted mean of PM2.5 and NO2 assigned at the geocoded address during the study period and the 2021 WHO air quality guidelines as counterfactual scenario to estimate new annual cases attributable to each pollutant separately and combined. We estimated the social cost of attributable deaths and the health care cost of childhood asthma and lung cancer attributable cases. We also estimated attributable mortality by city district and the mortality avoidable by achieving the WHO air quality interim targets. RESULTS: Mean exposure was 17 µg/m3 for PM2.5 and 39 µg/m3 for NO2. Total combined air pollution attributable mortality was 13% (95%CI = 9%-17%), corresponding to 1,886 deaths (95%CI = 1,296-2,571) and a social cost of €1,292 million (95%CI = 888-1,762) annually. Fifty-one percent (95%CI = 21%-71%) and 17% (95%CI = 7%-29%) of new cases of childhood asthma and lung cancer were attributable to air pollution with a health care cost of €4.3 and €2.7 million, respectively. Achieving the first unmet WHO air quality interim targets for PM2.5 and for NO2 would avoid 410 deaths and €281 million annually. CONCLUSION: Air pollution in Barcelona represents a huge disease and economic burden, which is greater than previous estimates. Much stronger measures to reduce PM2.5 and NO2 levels are urgently needed. Until the WHO air quality guidelines are met in the city, achieving each WHO air quality interim targets would avoid hundreds of deaths each year.

Implantación de una prueba rápida de infección estreptocócica: ¿su uso también mejora la adherencia antibiótica? / Introduction of rapid streptococcal antigen test: can its use improve adherence to antibiotic therapy?

Objetivo: Evaluar la influencia del resultado de la prueba rápida de diagnóstico para la identificación del antígeno estreptocócico en infecciones faringoamigdalares pediátricas, en términos de mejora de la adherencia a la terapia antibiótica. Diseño: Ensayo clínico comunitario de dos grupos de estudio con asignación aleatoria. Emplazamiento: Centros de atención primaria de Cataluña Central. Participantes: En el estudio se incluyeron a pacientes de tres a 15 años por muestreo consecutivo, que fueron atendidos por sospecha de infección faringoamigdalar en las consultas pediátricas entre noviembre del 2010 y febrero del 2011. De 557 pacientes que satisficieron los criterios de inclusión, se hizo seguimiento a 519. Intervención: El grupo control siguió el algoritmo diagnóstico y terapéutico habitual. Al grupo de intervención, se le realizó adicionalmente la prueba diagnóstica rápida de detección del antígeno estreptocócico y se indicó tratamiento según el resultado. Mediciones principales: Evaluación de la adherencia, los motivos de no adherencia y los factores de riesgo sociodemográficos mediante una encuesta telefónica. Resultados: Se prescribió antibiótico al 65,6% y los pediatras del grupo control fueron más propensos a recetar antibióticos que los del grupo intervención (88,5 vs. 45,5%, p< 0,001). El 64,8% de los pacientes siguió las indicaciones del tratamiento, siendo la causa principal de no adherencia no cumplir el horario (25,6%). La adherencia terapéutica fue superior en el grupo de intervención (68%) que en el de control (62,9%), no existiendo una diferencia significativa. Conclusiones: La prueba rápida del diagnóstico para la identificación de estreptococo, complementaria al uso de los criterios Centor evita la prescripción innecesaria de tratamiento antibiótico, aunque no ha demostrado mejorar la adherencia terapéutica.(AU)

Objective: To evaluate the influence of the result of a rapid streptococcal antigen test in paediatric pharyngotonsillitis infections, in terms of improvement of antibiotic therapy adherence. Design: Randomized community clinical trial with two study groups. Location: Primary Care Centers in Central Catalonia. Participants: Patients aged from 3 to 15 years, who were attended at paediatric consultations on suspicion of pharyngotonsillitis caused by an infection between November 2010 and February 2011 (both included), were included in the study on a consecutive basis. 557 patients met the inclusion criteria and 519 were evaluated. Intervention: The control group received the usual diagnostic-therapeutic algorithm. Rapid streptococcal antigen test was additionally performed to experimental group participants and it was indicated the more convenient treatment. Main measurements: Antibiotic adherence, non-adherence causes and socio-demographic risk factors were evaluated via telephone survey. Results: Antibiotics were prescribed to 65.6% and paediatricians of the control group were more likely to prescribe antibiotic than the ones in the intervention group (88.5% vs 45.5%, p< 0.0001). 64.8% followed doctor's treatment orders, being failure following medication scheduling the main cause of non-adherence (25.6%). Medication adherence was higher in the experimental group (68%) than in the control group (62.9%) but no significant differences were found. Conclusion: Rapid strep test, complementing the use of Centor Criteria avoids unnecessary antibiotics prescriptions, but had not been proven to be effective in increasing medication adherence.(AU)

[Introduction of rapid streptococcal antigen test: can its use improve adherence to antibiotic therapy?] / Implantación de una prueba rápida de infección estreptocócica: ¿su uso también mejora la adherencia antibiótica?

OBJECTIVE: To evaluate the influence of the result of a rapid streptococcal antigen test in paediatric pharyngotonsillitis infections, in terms of improvement of antibiotic therapy adherence. DESIGN: Randomized community clinical trial with two study groups. LOCATION: Primary Care Centers in Central Catalonia. PARTICIPANTS: Patients aged from 3 to 15 years, who were attended at paediatric consultations on suspicion of pharyngotonsillitis caused by an infection between November 2010 and February 2011 (both included), were included in the study on a consecutive basis. 557 patients met the inclusion criteria and 519 were evaluated. INTERVENTION: The control group received the usual diagnostic-therapeutic algorithm. Rapid streptococcal antigen test was additionally performed to experimental group participants and it was indicated the more convenient treatment. MAIN MEASUREMENTS: Antibiotic adherence, non-adherence causes and socio-demographic risk factors were evaluated via telephone survey. RESULTS: Antibiotics were prescribed to 65.6% and paediatricians of the control group were more likely to prescribe antibiotic than the ones in the intervention group (88.5% vs 45.5%, p< 0.0001). 64.8% followed doctor's treatment orders, being failure following medication scheduling the main cause of non-adherence (25.6%). Medication adherence was higher in the experimental group (68%) than in the control group (62.9%) but no significant differences were found. CONCLUSION: Rapid strep test, complementing the use of Centor Criteria avoids unnecessary antibiotics prescriptions, but had not been proven to be effective in increasing medication adherence.

Study Protocol for the Evaluation of the Health Effects of Superblocks in Barcelona: The "Salut Als Carrers" (Health in the Streets) Project.

Superblocks are currently being introduced in Barcelona to respond to the city's scarcity of green spaces and high levels of air pollution, traffic injuries, and sedentariness. The aim is to calm the streets by reducing the number of square meters dedicated to private vehicles and to reclaim part of this public space for people. Salut als Carrers (Health in the Streets) is a project to evaluate the potential environmental and health effects of the superblock model with an equity perspective in Barcelona. This study aims to explain the various interventions implemented in different neighborhoods in Barcelona and the methods that will be used to evaluate them in a quasi-experimental and health impact assessment (HIA) approaches. Given the complexity of the intervention evaluated, the project employs mixed methodologies. Quantitative methods include: (a) a pre-post health survey of 1200 people randomly selected from the municipal register asked about self-perceived health and quality of life, social support, mental health, mobility, physical activity, neighborhood characteristics, and housing; (b) pre-post environmental measurements, mainly of nitrogen dioxide (NO2), particulate matter of less than 10 µm (PM10), and particulate matter of less than 2.5 µm (PM2.5) and black carbon; (c) pre-post environmental walkability measures using the Microscale Audit of Pedestrian Streetscapes (MAPS) tool; (d) use of public space and physical activity levels using the System for Observing Play and Recreation in Communities (SOPARC), a validated observation tool; (e) pre-post traffic injury measures with a comparison group; and (f) the comparison and integration of pre-post assessment with previous HIAs and the improvement of future HIAs. Qualitative studies will be performed to analyze residents' perception of these effects by using: (a) various focus groups according to different participant characteristics who are more or less likely to use the superblocks; and (b) a guerrilla ethnography, which is a method that combines ethnographic observation and semi-structured interviews. This study, which evaluates the impact of an ambitious urban-renewal program on health, will help to assess the effectiveness of public policy in terms of health and health inequalities.

Trihalomethanes in Drinking Water and Bladder Cancer Burden in the European Union.

BACKGROUND: Trihalomethanes (THMs) are widespread disinfection by-products (DBPs) in drinking water, and long-term exposure has been consistently associated with increased bladder cancer risk. OBJECTIVE: We assessed THM levels in drinking water in the European Union as a marker of DBP exposure and estimated the attributable burden of bladder cancer. METHODS: We collected recent annual mean THM levels in municipal drinking water in 28 European countries (EU28) from routine monitoring records. We estimated a linear exposure-response function for average residential THM levels and bladder cancer by pooling data from studies included in the largest international pooled analysis published to date in order to estimate odds ratios (ORs) for bladder cancer associated with the mean THM level in each country (relative to no exposure), population-attributable fraction (PAF), and number of attributable bladder cancer cases in different scenarios using incidence rates and population from the Global Burden of Disease study of 2016. RESULTS: We obtained 2005-2018 THM data from EU26, covering 75% of the population. Data coverage and accuracy were heterogeneous among countries. The estimated population-weighted mean THM level was 11.7µg/L [standard deviation (SD) of 11.2]. The estimated bladder cancer PAF was 4.9% [95% confidence interval (CI): 2.5, 7.1] overall (range: 0-23%), accounting for 6,561 (95% CI: 3,389, 9,537) bladder cancer cases per year. Denmark and the Netherlands had the lowest PAF (0.0% each), while Cyprus (23.2%), Malta (17.9%), and Ireland (17.2%) had the highest among EU26. In the scenario where no country would exceed the current EU mean, 2,868 (95% CI: 1,522, 4,060; 43%) annual attributable bladder cancer cases could potentially be avoided. DISCUSSION: Efforts have been made to reduce THM levels in the European Union. However, assuming a causal association, current levels in certain countries still could lead to a considerable burden of bladder cancer that could potentially be avoided by optimizing water treatment, disinfection, and distribution practices, among other possible measures. https://doi.org/10.1289/EHP4495.

Exposure to disinfection by-products in swimming pools and biomarkers of genotoxicity and respiratory damage - The PISCINA2 Study.

BACKGROUND: Swimming in pools is a healthy activity that entails exposure to disinfection by-products (DBPs), some of which are irritant and genotoxic. OBJECTIVES: We evaluated exposure to DBPs during swimming in a chlorinated pool and the association with short-term changes in genotoxicity and lung epithelium permeability biomarkers. METHODS: Non-smoker adults (N = 116) swimming 40 min in an indoor pool were included. We measured a range of biomarkers before and at different times after swimming: trihalomethanes (THMs) in exhaled breath (5 min), trichloroacetic acid (TCAA) in urine (30 min), micronuclei in lymphocytes (1 h), serum club cell protein (CC16) (1 h), urine mutagenicity (2 h) and micronuclei in reticulocytes (4 days in a subset, N = 19). Several DBPs in water and trichloramine in air were measured, and physical activity was extensively assessed. We estimated interactions with polymorphisms in genes related to DBP metabolism. RESULTS: Median level of chloroform, brominated and total THMs in water was 37.3, 9.5 and 48.5, µg/L, respectively, and trichloramine in air was 472.6 µg/m3. Median exhaled chloroform, brominated and total THMs increased after swimming by 10.9, 2.6 and 13.4, µg/m3, respectively. Creatinine-adjusted urinary TCAA increased by 3.1 µmol/mol. Micronuclei in lymphocytes and reticulocytes, urine mutagenicity and serum CC16 levels remained unchanged after swimming. Spearman correlation coefficients showed no association between DBP exposure and micronuclei in lymphocytes, urine mutagenicity and CC16. Moderate associations were observed for micronuclei in reticulocytes and DBP exposure. CONCLUSIONS: The unchanged levels of the short-term effect biomarkers after swimming and null associations with personal estimates of exposure to DBPs suggest no measurable effect on genotoxicity in lymphocytes, urine mutagenicity and lung epithelium permeability at the observed exposure levels. The moderate associations with micronuclei in reticulocytes require cautious interpretation given the reduced sample size.

A multivariate approach to investigate the combined biological effects of multiple exposures.

Epidemiological studies provide evidence that environmental exposures may affect health through complex mixtures. Formal investigation of the effect of exposure mixtures is usually achieved by modelling interactions, which relies on strong assumptions relating to the identity and the number of the exposures involved in such interactions, and on the order and parametric form of these interactions. These hypotheses become difficult to formulate and justify in an exposome context, where influential exposures are numerous and heterogeneous. To capture both the complexity of the exposome and its possibly pleiotropic effects, models handling multivariate predictors and responses, such as partial least squares (PLS) algorithms, can prove useful. As an illustrative example, we applied PLS models to data from a study investigating the inflammatory response (blood concentration of 13 immune markers) to the exposure to four disinfection by-products (one brominated and three chlorinated compounds), while swimming in a pool. To accommodate the multiple observations per participant (n=60; before and after the swim), we adopted a multilevel extension of PLS algorithms, including sparse PLS models shrinking loadings coefficients of unimportant predictors (exposures) and/or responses (protein levels). Despite the strong correlation among co-occurring exposures, our approach identified a subset of exposures (n=3/4) affecting the exhaled levels of 8 (out of 13) immune markers. PLS algorithms can easily scale to high-dimensional exposures and responses, and prove useful for exposome research to identify sparse sets of exposures jointly affecting a set of (selected) biological markers. Our descriptive work may guide these extensions for higher dimensional data.

Long-term exposure to trihalomethanes in drinking water and breast cancer in the Spanish multicase-control study on cancer (MCC-SPAIN).

BACKGROUND: Exposure to trihalomethanes (THMs) in drinking water has consistently been associated with an increased risk of bladder cancer, but evidence on other cancers including the breast is very limited. OBJECTIVES: We assessed long-term exposure to THMs to evaluate the association with female breast cancer (BC) risk. METHODS: A multi case-control study was conducted in Spain from 2008 to 2013. We included 1003 incident BC cases (women 20-85years old) recruited from 14 hospitals and 1458 population controls. Subjects were interviewed to ascertain residential histories and major recognized risk factors for BC. Mean residential levels of chloroform, brominated THMs (Br-THMs) and the sum of both as total THM (TTHMs) during the adult-lifetime were calculated. RESULTS: Mean adult-lifetime residential levels ranged from 0.8 to 145.7µg/L for TTHM (median=30.8), from 0.2 to 62.4µg/L for chloroform (median=19.7) and from 0.3 to 126.0µg/L for Br-THMs (median=9.7). Adult-lifetime residential chloroform was associated with BC (adjusted OR=1.47; 95%CI=1.05, 2.06 for the highest (>24µg/L) vs. lowest (<8µg/L) quartile; p-trend=0.024). No association was detected for residential Br-THMs (OR=0.91; 95%CI=0.68, 1.23 for >31µg/L vs. <6µg/L) or TTHMs (OR=1.14; 95%CI=0.83, 1.57 for >48µg/L vs. <22µg/L). CONCLUSIONS: At common levels in Europe, long-term residential total THMs were not related to female breast cancer. A moderate association with chloroform was suggested at the highest exposure category. This large epidemiological study with extensive exposure assessment overcomes several limitations of previous studies but further studies are needed to confirm these results.

Effects of exposure to water disinfection by-products in a swimming pool: A metabolome-wide association study.

BACKGROUND: Exposure to disinfection by-products (DBPs) in drinking water and chlorinated swimming pools are associated with adverse health outcomes, but biological mechanisms remain poorly understood. OBJECTIVES: Evaluate short-term changes in metabolic profiles in response to DBP exposure while swimming in a chlorinated pool. MATERIALS AND METHODS: The PISCINA-II study (EXPOsOMICS project) includes 60 volunteers swimming 40min in an indoor pool. Levels of most common DBPs were measured in water and in exhaled breath before and after swimming. Blood samples, collected before and 2h after swimming, were used for metabolic profiling by liquid-chromatography coupled to high-resolution mass-spectrometry. Metabolome-wide association between DBP exposures and each metabolic feature was evaluated using multivariate normal (MVN) models. Sensitivity analyses and compound annotation were conducted. RESULTS: Exposure levels of all DBPs in exhaled breath were higher after the experiment. A total of 6,471 metabolic features were detected and 293 features were associated with at least one DBP in exhaled breath following Bonferroni correction. A total of 333 metabolic features were associated to at least one DBP measured in water or urine. Uptake of DBPs and physical activity were strongly correlated and mutual adjustment reduced the number of statistically significant associations. From the 293 features, 20 could be identified corresponding to 13 metabolites including compounds in the tryptophan metabolism pathway. CONCLUSION: Our study identified numerous molecular changes following a swim in a chlorinated pool. While we could not explicitly evaluate which experiment-related factors induced these associations, molecular characterization highlighted metabolic features associated with exposure changes during swimming.

Blood transcriptional and microRNA responses to short-term exposure to disinfection by-products in a swimming pool.

BACKGROUND: Swimming in a chlorinated pool results in high exposure levels to disinfection by-products (DBPs), which have been associated with an increased risk of bladder cancer. OBJECTIVES: By studying molecular responses at the blood transcriptome level we examined the biological processes associated with exposure to these compounds. METHODS: Whole-genome gene expression and microRNA analysis was performed on blood samples collected from 43 volunteers before and 2h after 40min swimming in an indoor chlorinated pool (PISCINAII study). Exposure to THMs was measured in exhaled breath. Heart rate and kcal expenditure were measured as proxies for physical activity. Associations between exposure levels and gene expression were assessed using multivariate normal models (MVN), correcting for age, body mass index and sex. A Bonferroni threshold at 5% was applied. RESULTS: MVN-models for the individual exposures identified 1778 genes and 23 microRNAs that were significantly associated with exposure to at least one DBP. Due to co-linearity it was not possible to statistically disentangle responses to DBP exposure from those related to physical activity. However, after eliminating previously reported transcripts associated with physical activity a large number of hits remained associated with DBP exposure. Among those, 9 were linked with bladder and 31 with colon cancer. Concordant microRNA/mRNA expressions were identified in association with DBP exposure for hsa-mir-22-3p and hsa-miR-146a-5p and their targets RCOR1 and TLR4, both related to colon cancer in association with DBP exposure. CONCLUSIONS: Short-term exposure to low levels of DBPs shows genomics responses that may be indicative of increased cancer risk.

Gene expression changes in blood RNA after swimming in a chlorinated pool.

Exposure to disinfection by-products (DBP) such as trihalomethanes (THM) in swimming pools has been linked to adverse health effects in humans, but their biological mechanisms are unclear. We evaluated short-term changes in blood gene expression of adult recreational swimmers after swimming in a chlorinated pool. Volunteers swam 40min in an indoor chlorinated pool. Blood samples were drawn and four THM (chloroform, bromodichloromethane, dibromochloromethane and bromoform) were measured in exhaled breath before and after swimming. Intensity of physical activity was measured as metabolic equivalents (METs). Gene expression in whole blood mRNA was evaluated using IlluminaHumanHT-12v3 Expression-BeadChip. Linear mixed models were used to evaluate the relationship between gene expression changes and THM exposure. Thirty-seven before-after pairs were analyzed. The median increase from baseline to after swimming were: 0.7 to 2.3 for MET, and 1.4 to 7.1µg/m3 for exhaled total THM (sum of the four THM). Exhaled THM increased on average 0.94µg/m3 per 1 MET. While 1643 probes were differentially expressed post-exposure. Of them, 189 were also associated with exhaled levels of individual/total THM or MET after False Discovery Rate. The observed associations with the exhaled THM were low to moderate (Log-fold change range: -0.17 to 0.15). In conclusion, we identified short-term gene expression changes associated with swimming in a pool that were minor in magnitude and their biological meaning was unspecific. The high collinearity between exhaled THM levels and intensity of physical activity precluded mutually adjusted models with both covariates. These exploratory results should be validated in future studies.

Trihalomethane concentrations in tap water as determinant of bottled water use in the city of Barcelona.

Bottled water consumption is increasing worldwide, despite its huge economic and environmental cost. We aim to describe personal and tap water quality determinants of bottled water use in the city of Barcelona. This cross-sectional study used data from the Health Survey of Barcelona in 2006 (N=5417 adults). The use of bottled water to drink and to cook was evaluated in relation to age, gender, educational level, district and levels of trihalomethanes (THMs), free chlorine, conductivity, chloride, sodium, pH, nitrate and aluminium in municipal tap water using Robust Poisson Regression. The prevalence of bottled water use to drink and cook was 53.9% and 6.7%, respectively. Chemical parameters in water had a large variability (interquartile range of THMs concentrations: 83.2-200.8µg/L) and were correlated between them, except aluminium. Drinking bottled water increased with educational level, while cooking with bottled water was higher among men than among women and decreased with age. After adjusting by these personal determinants, a dose-response relationship was found between concentrations of all chemicals except aluminium in tap water and bottled water use. The highest association was found for THMs, with a Prevalence Ratio of 2.00 (95%CI=1.86, 2.15) for drinking bottled water and 2.80 (95%CI=1.72, 4.58) for cooking with bottled water, among those with >150µg/L vs. <100µg/L THMs in tap water. CONCLUSION: More than half of Barcelona residents regularly drank bottled water, and the main determinant was the chemical composition of tap water, particularly THM level.

Acute changes in serum immune markers due to swimming in a chlorinated pool.

BACKGROUND: Exposure to disinfectants and disinfection byproducts (DBPs) due to swimming in chlorinated water has been associated with allergic and respiratory health effects, including asthma. OBJECTIVES: Biological mechanisms contributing to these associations are largely unknown. We hypothesized a potential pathway involving modulation of the immune system. METHODS: We assessed levels of immune markers (CCL11, CCL22, CXCL10, CRP, EGF, GCSF, IL-8, IL-17, IL-1RA, MPO, VEGF, Periostin) in serum collected from 30 women and 29 men before and after 40min of swimming in a chlorinated pool. Exposure to DBPs was assessed by measuring bromodichloromethane, bromoform, chloroform, and dibromochloromethane in exhaled breath before and after swimming. Covariate data including information on physical activity was available through questionnaires and measurements. We assessed the association between indicators of swimming in a chlorinated pool and changes in serum immune marker concentrations using linear regression with bivariate normal distributions and adjusted for multiple comparisons by applying the Benjamini-Hochberg procedure. RESULTS: We observed a significant decrease in serum concentrations of IL-8 (-12.53%; q=2.00e-03), CCL22 (-7.28%; q=4.00e-04), CCL11 (-7.15%; q=9.48e-02), CRP (-7.06%; q=4.68e-05), and CXCL10 (-13.03%; q=6.34e-14) and a significant increase in IL-1RA (20.16%; q=4.18e-06) from before to after swimming. Associations with quantitative measurements of DBPs or physical activity were similar in direction and strength. Most of the observed associations became non-significant when we adjusted the effects of exposure to DBPs for physical activity or vice-versa. CONCLUSIONS: Our study indicates that swimming in a chlorinated pool induces perturbations of the immune response through acute alterations of patterns of cytokine and chemokine secretion. The observed effects could not be uniquely attributed to either exposure to DBPs or physical activity. Evidence in the literature suggests that observed decreases in immune markers are possibly due to an immunosuppressive effect of DBPs, while the increase in IL-1RA might be due to physical activity.

Environmental and personal determinants of the uptake of disinfection by-products during swimming.

BACKGROUND: Trihalomethanes (THMs) in exhaled breath and trichloroacetic acid (TCAA) in urine are internal dose biomarkers of exposure to disinfection by-products (DBPs) in swimming pools. OBJECTIVE: We assessed how these biomarkers reflect the levels of a battery of DBPs in pool water and trichloramine in air, and evaluated personal determinants. METHODS: A total of 116 adults swam during 40min in a chlorinated indoor pool. We measured chloroform, bromodichloromethane, dibromochloromethane and bromoform in exhaled breath and TCAA in urine before and after swimming, trichloramine in air and several DBPs in water. Personal determinants included sex, age, body mass index (BMI), distance swum, energy expenditure, heart rate and 12 polymorphisms in GSTT1, GSTZ1 and CYP2E1 genes. RESULTS: Median level of exhaled total THMs and creatinine adjusted urine TCAA increased from 0.5 to 14.4µg/m(3) and from 2.5 to 5.8µmol/mol after swimming, respectively. The increase in exhaled brominated THMs was correlated with brominated THMs, haloacetic acids, haloacetonitriles, haloketones, chloramines, total organic carbon and total organic halogen in water and trichloramine in air. Such correlations were not detected for exhaled chloroform, total THMs or urine TCAA. Exhaled THM increased more in men, urine TCAA increased more in women, and both were affected by exercise intensity. Genetic variants were associated with differential increases in exposure biomarkers. CONCLUSION: Our findings suggest that, although affected by sex, physical activity and polymorphisms in key metabolizing enzymes, brominated THMs in exhaled breath could be used as a non-invasive DBP exposure biomarker in swimming pools with bromide-containing source waters. This warrants confirmation with new studies.

Ingested Nitrate and Breast Cancer in the Spanish Multicase-Control Study on Cancer (MCC-Spain).

BACKGROUND: Ingested nitrate leads to endogenous formation of N-nitroso compounds that are breast carcinogens in animals, but human evidence is limited. OBJECTIVE: We evaluated ingested nitrate as a risk factor for breast cancer (BC) in a multicase-control study. METHODS: Hospital-based incident BC cases and population-based controls were recruited in eight Spanish regions in 2008-2013; participants provided residential and water consumption from 18 years of age and information on known BC risk factors. Long-term nitrate levels (1940-2010) were estimated and linked with residential histories and water consumption to calculate waterborne ingested nitrate (milligrams/day). Dietary ingested nitrate (milligrams/day) was calculated using food frequency questionnaires and published dietary nitrate contents. Interactions with endogenous nitrosation factors and other variables were evaluated. A total of 1,245 cases and 1,520 controls were included in the statistical analysis. RESULTS: Among the study regions, average ± SD waterborne ingested nitrate ranged from 2.9 ± 1.9 to 13.5 ± 7.5 mg/day, and dietary ingested nitrate ranged from 88.5 ± 48.7 to 154 ± 87.8 mg/day. Waterborne ingested nitrate was not associated with BC overall, but among postmenopausal women, those with both high nitrate (> 6 vs. < 2.6 mg/day) and high red meat intake (≥ 20 vs. < 20 g/day) were more likely to be cases than women with low nitrate and low red meat intake (adjusted odds ratio = 1.64; 95% confidence interval: 1.08, 2.49; overall interaction p-value = 0.17). No association was found with dietary nitrate. CONCLUSIONS: Waterborne ingested nitrate was associated with BC only among postmenopausal women with high red meat consumption. Dietary nitrate was not associated with BC regardless of the animal or vegetable source or of menopausal status. CITATION: Espejo-Herrera N, Gracia-Lavedan E, Pollan M, Aragonés N, Boldo E, Perez-Gomez B, Altzibar JM, Amiano P, Zabala AJ, Ardanaz E, Guevara M, Molina AJ, Barrio JP, Gómez-Acebo I, Tardón A, Peiró R, Chirlaque MD, Palau M, Muñoz M, Font-Ribera L, Castaño-Vinyals G, Kogevinas M, Villanueva CM. 2016. Ingested nitrate and breast cancer in the Spanish Multicase-Control Study on Cancer (MCC-Spain). Environ Health Perspect 124:1042-1049; http://dx.doi.org/10.1289/ehp.1510334.

Overview of Disinfection By-products and Associated Health Effects.

The presence of chemical compounds formed as disinfection by-products (DBPs) is widespread in developed countries, and virtually whole populations are exposed to these chemicals through ingestion, inhalation, or dermal absorption from drinking water and swimming pools. Epidemiological evidence has shown a consistent association between long-term exposure to trihalomethanes and the risk of bladder cancer, although the causal nature of the association is not conclusive. Evidence concerning other cancer sites is insufficient or mixed. Numerous studies have evaluated reproductive implications, including sperm quality, time to pregnancy, menstrual cycle, and pregnancy outcomes such as fetal loss, fetal growth, preterm delivery, and congenital malformation. The body of evidence suggests only minor effects from high exposure during pregnancy on fetal growth indices such as small for gestational age (SGA) at birth. Populations highly exposed to swimming pools such as pool workers and professional swimmers show a higher prevalence of respiratory symptoms and asthma, respectively, although the direction of the association, and thus causality, is not clear among professional swimmers. The risk of asthma, wheezing, eczema, and other respiratory outcomes among children attending swimming pools has been the object of extensive research. Early studies suggested a positive association, while subsequent larger studies found no correlations or showed a protective association. Future research should develop methods to evaluate the effects of the DBP mixture and the interaction with personal characteristics (e.g., genetics, lifestyle), clarify the association between swimming pools and respiratory health, evaluate the occurrence of DBPs in low- and middle-income countries, and evaluate outcomes suggested by animal studies that have not been considered in epidemiological investigations.

Water hardness and eczema at 1 and 4 y of age in the INMA birth cohort.

BACKGROUND: Exposure to hard water has been suggested as a risk factor for eczema in childhood, based on limited evidence from two ecologic and two cross-sectional studies. OBJECTIVES: We evaluate this hypothesis for the first time in early infancy using prospective data from a mother-child cohort study. METHODS: We used data from the INMA cohorts in Gipuzkoa, Sabadell and Valencia, Spain (N=1638). Current and ever eczema, bathing frequency and duration and covariables were collected by questionnaires at 14 months (14 m) and 4 years (4 y). Calcium carbonate (CaCO3) level in municipal water was assigned to home addresses at birth, 14 m and 4 y. We calculated Odds Ratio (OR) of eczema related to CaCO3 at home, bath exposure and a combination of both. RESULTS: Prevalence of eczema ever was 18.4% at 14 m and 33.4% at 4 y. Mean CaCO3 ranged from 51.6 to 272.8 mg/L among areas. No association was detected between water hardness at home and current or ever eczema. Adjusted OR was 0.79 (95%CI=0.45, 1.39) at 14 m and 0.93 (0.56, 1.52) at 4 y among children in the highest vs. lowest tertiles of CaCO3. Bath exposure alone or in combination with water hardness did not increase the OR of eczema at 14 m or 4 y either. CONCLUSIONS: We did not find an association between eczema and water hardness at home or bathing exposure during the first four years of life. This first cohort study in a critical age period with improved exposure assessment does not confirm the association suggested among children by previous studies.

Influence of physical activity in the intake of trihalomethanes in indoor swimming pools.

This study describes the relationship between physical activity and intake of trihalomethanes (THMs), namely chloroform (CHCl3), bromodichloromethane (CHCl2Br), dibromochloromethane (CHClBr2) and bromoform (CHBr3), in individuals exposed in two indoor swimming pools which used different disinfection agents, chlorine (Cl-SP) and bromine (Br-SP). CHCl3 and CHBr3 were the dominant compounds in air and water of the Cl-SP and Br-SP, respectively. Physical exercise was assessed from distance swum and energy expenditure. The changes in exhaled breath concentrations of these compounds were measured from the differences after and before physical activity. A clear dependence between distance swum or energy expenditure and exhaled breath THM concentrations was observed. The statistically significant relationships involved higher THM concentrations at higher distances swum. However, air concentration was the major factor determining the CHCl3 and CHCl2Br intake in swimmers whereas distance swum was the main factor for CHBr3 intake. These two causes of THM incorporation into swimmers concurrently intensify the concentrations of these compounds into exhaled breath and pointed to inhalation as primary mechanism for THM uptake. Furthermore, the rates of THM incorporation were proportionally higher as higher was the degree of bromination of the THM species. This trend suggested that air-water partition mechanisms in the pulmonary system determined higher retention of the THM compounds with lower Henry's Law volatility constants than those of higher constant values. Inhalation is therefore the primary mechanisms for THM exposure of swimmers in indoor buildings.

Risks and benefits of green spaces for children: a cross-sectional study of associations with sedentary behavior, obesity, asthma, and allergy.

BACKGROUND: Green spaces have been associated with both health benefits and risks in children; however, available evidence simultaneously investigating these conflicting influences, especially in association with different types of greenness, is scarce. OBJECTIVES: We aimed to simultaneously evaluate health benefits and risks associated with different types of greenness in children, in terms of sedentary behavior (represented by excessive screen time), obesity, current asthma, and allergic rhinoconjunctivitis. METHODS: We conducted a cross-sectional study of a population-based sample of 3,178 schoolchildren (9-12 years old) in Sabadell, Spain, in 2006. Information on outcomes and covariates was obtained by questionnaire. We measured residential surrounding greenness as the average of satellite-derived Normalized Difference Vegetation Index (NDVI) in buffers of 100 m, 250 m, 500 m, and 1,000 m around each home address. Residential proximity to green spaces was defined as living within 300 m of a forest or a park, as separate variables. We used logistic regression models to estimate associations separately for each exposure-outcome pair, adjusted for relevant covariates. RESULTS: An interquartile range increase in residential surrounding greenness was associated with 11-19% lower relative prevalence of overweight/obesity and excessive screen time, but was not associated with current asthma and allergic rhinoconjunctivitis. Similarly, residential proximity to forests was associated with 39% and 25% lower relative prevalence of excessive screen time and overweight/obesity, respectively, but was not associated with current asthma. In contrast, living close to parks was associated with a 60% higher relative prevalence of current asthma, but had only weak negative associations with obesity/overweight or excessive screen time. CONCLUSION: We observed two separable patterns of estimated health benefits and risks associated with different types of greenness.