Early life multiple exposures and child cognitive function: A multi-centric birth cohort study in six European countries.

Epidemiological studies mostly focus on single environmental exposures. This study aims to systematically assess associations between a wide range of prenatal and childhood environmental exposures and cognition. The study sample included data of 1298 mother-child pairs, children were 6-11 years-old, from six European birth cohorts. We measured 87 exposures during pregnancy and 122 cross-sectionally during childhood, including air pollution, built environment, meteorology, natural spaces, traffic, noise, chemicals and life styles. The measured cognitive domains were fluid intelligence (Raven's Coloured Progressive Matrices test, CPM), attention (Attention Network Test, ANT) and working memory (N-Back task). We used two statistical approaches to assess associations between exposure and child cognition: the exposome-wide association study (ExWAS) considering each exposure independently, and the deletion-substitution-addition algorithm (DSA) considering all exposures simultaneously to build a final multiexposure model. Based on this multiexposure model that included the exposure variables selected by ExWAS and DSA models, child organic food intake was associated with higher fluid intelligence (CPM) scores (beta = 1.18; 95% CI = 0.50, 1.87) and higher working memory (N-Back) scores (0.23; 0.05, 0.41), and child fast food intake (-1.25; -2.10, -0.40), house crowding (-0.39; -0.62, -0.16), and child environmental tobacco smoke (ETS) (-0.89; -1.42, -0.35), were all associated with lower CPM scores. Indoor PM2.5 exposure was associated with lower N-Back scores (-0.09; -0.16, -0.02). Additional associations in the unexpected direction were found: Higher prenatal mercury levels, maternal alcohol consumption and child higher perfluorooctane sulfonic acid (PFOS) levels were associated with better cognitive performance; and higher green exposure during pregnancy with lower cognitive performance. This first comprehensive and systematic study of many prenatal and childhood environmental risk factors suggests that unfavourable child nutrition, family crowdedness and child indoor air pollution and ETS exposures adversely and cross-sectionally associate with cognitive function. Unexpected associations were also observed and maybe due to confounding and reverse causality.

Early-Life Environmental Exposures and Childhood Obesity: An Exposome-Wide Approach.

BACKGROUND: Chemical and nonchemical environmental exposures are increasingly suspected to influence the development of obesity, especially during early life, but studies mostly consider single exposure groups. OBJECTIVES: Our study aimed to systematically assess the association between a wide array of early-life environmental exposures and childhood obesity, using an exposome-wide approach. METHODS: The HELIX (Human Early Life Exposome) study measured child body mass index (BMI), waist circumference, skinfold thickness, and body fat mass in 1,301 children from six European birth cohorts age 6-11 y. We estimated 77 prenatal exposures and 96 childhood exposures (cross-sectionally), including indoor and outdoor air pollutants, built environment, green spaces, tobacco smoking, and biomarkers of chemical pollutants (persistent organic pollutants, metals, phthalates, phenols, and pesticides). We used an exposure-wide association study (ExWAS) to screen all exposure-outcome associations independently and used the deletion-substitution-addition (DSA) variable selection algorithm to build a final multiexposure model. RESULTS: The prevalence of overweight and obesity combined was 28.8%. Maternal smoking was the only prenatal exposure variable associated with higher child BMI (z-score increase of 0.28, 95% confidence interval: 0.09, 0.48, for active vs. no smoking). For childhood exposures, the multiexposure model identified particulate and nitrogen dioxide air pollution inside the home, urine cotinine levels indicative of secondhand smoke exposure, and residence in more densely populated areas and in areas with fewer facilities to be associated with increased child BMI. Child blood levels of copper and cesium were associated with higher BMI, and levels of organochlorine pollutants, cobalt, and molybdenum were associated with lower BMI. Similar results were found for the other adiposity outcomes. DISCUSSION: This first comprehensive and systematic analysis of many suspected environmental obesogens strengthens evidence for an association of smoking, air pollution exposure, and characteristics of the built environment with childhood obesity risk. Cross-sectional biomarker results may suffer from reverse causality bias, whereby obesity status influenced the biomarker concentration. https://doi.org/10.1289/EHP5975.

Predictors of personal exposure to black carbon among women in southern semi-rural Mozambique.

Sub-Saharan Africa (SSA) has the highest proportion of people using unclean fuels for household energy, which can result in products of incomplete combustion that are damaging for health. Black carbon (BC) is a useful marker of inefficient combustion-related particles; however, ambient air quality data and temporal patterns of personal exposure to BC in SSA are scarce. We measured ambient elemental carbon (EC), comparable to BC, and personal exposure to BC in women of childbearing age from a semi-rural area of southern Mozambique. We measured ambient EC over one year (2014-2015) using a high-volume sampler and an off-line thermo-optical-transmission method. We simultaneously measured 5-min resolved 24-h personal BC using a portable MicroAeth (AE51) in 202 women. We used backwards stepwise linear regression to identify predictors of log-transformed 24-h mean and peak (90th percentile) personal BC exposure. We analyzed data from 187 non-smoking women aged 16-46 years. While daily mean ambient EC reached moderate levels (0.9 µg/m3, Standard Deviation, SD: 0.6 µg/m3), daily mean personal BC reached high levels (15 µg/m3, SD: 19 µg/m3). Daily patterns of personal exposure revealed a peak between 6 and 7 pm (>35 µg/m3), attributable to kerosene-based lighting. Key determinants of mean and peak personal exposure to BC were lighting source, kitchen type, ambient EC levels, and temperature. This study highlights the important contribution of lighting sources to personal exposure to combustion particles in populations that lack access to clean household energy.

Human Early Life Exposome (HELIX) study: a European population-based exposome cohort.

PURPOSE: Essential to exposome research is the collection of data on many environmental exposures from different domains in the same subjects. The aim of the Human Early Life Exposome (HELIX) study was to measure and describe multiple environmental exposures during early life (pregnancy and childhood) in a prospective cohort and associate these exposures with molecular omics signatures and child health outcomes. Here, we describe recruitment, measurements available and baseline data of the HELIX study populations. PARTICIPANTS: The HELIX study represents a collaborative project across six established and ongoing longitudinal population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the UK). HELIX used a multilevel study design with the entire study population totalling 31 472 mother-child pairs, recruited during pregnancy, in the six existing cohorts (first level); a subcohort of 1301 mother-child pairs where biomarkers, omics signatures and child health outcomes were measured at age 6-11 years (second level) and repeat-sampling panel studies with around 150 children and 150 pregnant women aimed at collecting personal exposure data (third level). FINDINGS TO DATE: Cohort data include urban environment, hazardous substances and lifestyle-related exposures for women during pregnancy and their offspring from birth until 6-11 years. Common, standardised protocols were used to collect biological samples, measure exposure biomarkers and omics signatures and assess child health across the six cohorts. Baseline data of the cohort show substantial variation in health outcomes and determinants between the six countries, for example, in family affluence levels, tobacco smoking, physical activity, dietary habits and prevalence of childhood obesity, asthma, allergies and attention deficit hyperactivity disorder. FUTURE PLANS: HELIX study results will inform on the early life exposome and its association with molecular omics signatures and child health outcomes. Cohort data are accessible for future research involving researchers external to the project.

Impact of commuting exposure to traffic-related air pollution on cognitive development in children walking to school.

A few studies have found associations between the exposure to traffic-related air pollution at school and/or home and cognitive development. The impact on cognitive development of the exposure to air pollutants during commuting has not been explored. We aimed to assess the role of the exposure to traffic-related air pollutants during walking commute to school on cognitive development of children. We performed a longitudinal study of children (n = 1,234, aged 7-10 y) from 39 schools in Barcelona (Catalonia, Spain) who commuted by foot to school. Children were tested four times during a 12-month follow-up to characterize their developmental trajectories of working memory (d' of the three-back numbers test) and inattentiveness (hit reaction time standard error of the Attention Network Test). Average particulate matter ≤2.5 µm (PM2.5), Black Carbon (BC) and NO2 concentrations were estimated using Land Use Regression for the shortest walking route to school. Differences in cognitive growth were evaluated by linear mixed effects models with age-by-pollutant interaction terms. Exposure to PM2.5 and BC from the commutes by foot was associated with a reduction in the growth of working memory (an interquartile range increase in PM2.5 and BC concentrations decreased the annual growth of working memory by 5.4 (95% CI [-10.2, -0.6]) and 4.6 (95% CI [-9.0, -0.1]) points, respectively). The findings for NO2 were not conclusive and none of the pollutants were associated with inattentiveness. Efforts should be made to implement pedestrian school pathways through low traffic streets in order to increase security and minimize children's exposure to air pollutants.

Variability in and agreement between modeled and personal continuously measured black carbon levels using novel smartphone and sensor technologies.

Novel technologies, such as smartphones and small personal continuous air pollution sensors, can now facilitate better personal estimates of air pollution in relation to location. Such information can provide us with a better understanding about whether and how personal exposures relate to residential air pollution estimates, which are normally used in epidemiological studies. The aims of this study were to examine (1) the variability in personal air pollution levels during the day and (2) the relationship between modeled home and school estimates and continuously measured personal air pollution exposure levels in different microenvironments (e.g., home, school, and commute). We focused on black carbon as an indicator of traffic-related air pollution. We recruited 54 school children (aged 7-11) from 29 different schools around Barcelona as part of the BREATHE study, an epidemiological study of the relation between air pollution and brain development. For 2 typical week days during 2012-2013, the children were given a smartphone with CalFit software to obtain information on their location and physical activity level and a small sensor, the micro-aethalometer model AE51, to measure their black carbon levels simultaneously and continuously. We estimated their home and school exposure to PM2.5 filter absorbance, which is well-correlated with black carbon, using a temporally adjusted PM2.5 absorbance land use regression (LUR) model. We found considerable variation in the black carbon levels during the day, with the highest levels measured during commuting periods (geometric mean = 2.8 µg/m(3)) and the lowest levels at home (geometric mean = 1.3 µg/m(3)). Hourly temporally adjusted LUR model estimates for the home and school showed moderate to good correlation with measured personal black carbon levels at home and school (r = 0.59 and 0.68, respectively) and lower correlation with commuting trips (r = 0.32 and 0.21, respectively). The correlation between modeled home estimates and overall personal black carbon levels was 0.62. Personal black carbon levels vary substantially during the day. The correlation between modeled and measured black carbon levels was generally good, with the exception of commuting times. In conclusion, novel technologies, such as smartphones and sensors, provide insights in personal exposure to air pollution.

Lifetime occupational exposure to dusts, gases and fumes is associated with bronchitis symptoms and higher diffusion capacity in COPD patients.

BACKGROUND: Occupational exposure to dusts, gases and fumes has been associated with reduced FEV1 and sputum production in COPD patients. The effect of occupational exposure on other characteristics of COPD, especially those reflecting emphysema, has not been studied in these patients. METHODS: We studied 338 patients hospitalized for a first exacerbation of COPD in 9 Spanish hospitals, obtaining full occupational history in a face-to-face interview; job codes were linked to a job exposure matrix for semi-quantitative estimation of exposure to mineral/biological dust, and gases/fumes for each job held. Patients underwent spirometry, diffusing capacity testing and analysis of gases in stable conditions. Quality of life, dyspnea and chronic bronchitis symptoms were determined with a questionnaire interview. A high- resolution CT scan was available in 133 patients. RESULTS: 94% of the patients included were men, with a mean age of 68(8.5) years and a mean FEV1% predicted 52 (16). High exposure to gases or fumes was associated with chronic bronchitis, and exposure to mineral dust and gases/fumes was associated with higher scores for symptom perception in the St. George's questionnaire. No occupational agent was associated with a lower FEV1. High exposure to all occupational agents was associated with better lung diffusion capacity, in long-term quitters. In the subgroup with CT data, patients with emphysema had 18% lower DLCO compared to those without emphysema. CONCLUSIONS: In our cohort of COPD patients, high exposure to gases or fumes was associated with chronic bronchitis, and high exposure to all occupational agents was consistently associated with better diffusion capacity in long-term quitters.

Cured meat consumption increases risk of readmission in COPD patients.

Recent studies have shown that a high dietary intake of cured meat increases the risk of chronic obstructive pulmonary disease (COPD) development. However, its potential effects on COPD evolution have not been tested. We aimed to assess the association between dietary intake of cured meat and risk of COPD readmission in COPD patients. 274 COPD patients were recruited during their first COPD admission between 2004 and 2006, provided information on dietary intake of cured meat during the previous 2 yrs, and were followed until December 31, 2007 (median follow-up 2.6 yrs). Associations between cured meat intake and COPD admissions were assessed using parametric regression survival-time models. Mean ± SD age was 68 ± 8 yrs, 93% of patients were male, 42% were current smokers, mean post-bronchodilator forced expiratory volume in 1 s (FEV(1)) was 53 ± 16% predicted, and median cured meat intake was 23 g · day(-1). After adjusting for age, FEV(1), and total caloric intake, high cured meat intake (more than median value) increased the risk of COPD readmission (adjusted HR 2.02, 95% CI 1.31-3.12; p=0.001). High cured meat consumption increases the risk of COPD readmission in COPD patients. The assessment of the effectiveness of healthy diet advice should be considered in the future.

[Validation of the Yale Physical Activity Survey in chronic obstructive pulmonary disease patients]. / Validación del cuestionario de actividad física de Yale en pacientes con enfermedad pulmonar obstructiva crónica.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) perform limited physical activity. Surprisingly, there is a lack of research in COPD about the validity of physical activity questionnaires. Our aim was to validate the Yale Physical Activity Survey in COPD patients in order to quantify and classify their levels of physical activity. METHODS: 172 COPD patients from 8 university hospitals in Spain wore an accelerometer (SenseWear(®)Pro(2)Armband) for 8 days and answered the questionnaire 15 days later. Statistical analyses used to compare both tools measures included: (i) Spearman's correlation coefficient, (ii) intraclass correlation coefficient (ICC) and Bland-Altman plots, (iii) distribution of accelerometer measurements according to tertiles of the questionnaire, and (iv) receiver operating characteristic (ROC) curves to detect sedentary patients. RESULTS: 94% of participants were men, 28% were active smokers and 7% were currently working. Mean (standard deviation) age was 70 (8) years, mean post-bronchodilator FEV(1) was 52 (15)% predicted, and median (p25-p75) steps taken was 5,702 (3,273-9,253) steps per day(-1). Spearman correlations were low to moderate (from 0.29 to 0.52, all P<.001). ICCs showed weak agreement (from 0.34 to 0.40, all P<.001). A wide variability in agreement was observed in the Bland-Altman plots. Significant differences in accelerometer measurements were found according to questionnaire tertiles (all P<.001). The area under the ROC for identifying sedentarism was 0.71 (95% CI: 0.63-0.79). CONCLUSIONS: The Yale Physical Activity Survey may be a valid tool to classify, but not to quantify, physical activity performed by COPD patients. The summary index of this questionnaire, based on seven short questions, shows the best validity properties. This suggests that it should be considered a screening tool to identify patients at risk for sedentarism.

Physical activity and clinical and functional status in COPD.

BACKGROUND: The mechanisms underlying the benefits of regular physical activity in the evolution of COPD have not been established. Our objective was to assess the relationship between regular physical activity and the clinical and functional characteristics of COPD. METHODS: Three hundred forty-one patients were hospitalized for the first time because of a COPD exacerbation in nine teaching hospitals in Spain. COPD diagnosis was confirmed by spirometry under stable conditions. Physical activity before the first COPD hospitalization was measured using the Yale questionnaire. The following outcome variables were studied under stable conditions: dyspnea, nutritional status, complete lung function tests, respiratory and peripheral muscle strength, bronchial colonization, and systemic inflammation. RESULTS: The mean age was 68 years (SD, 9 years), 93% were men, 43% were current smokers, and the mean postbronchodilator FEV(1) was 52% predicted (SD, 16% predicted). Multivariate linear regression models were built separately for each outcome variable and adjusted for potential confounders (including remaining outcomes if appropriate). When patients with the lowest quartile of physical activity were compared to patients in the other quartiles, physical activity was associated with significantly higher diffusing capacity of the lung for carbon monoxide (Dlco) [change in the second, third, and fourth quartiles of physical activity, compared with first quartile (+ 6%, + 6%, and + 9% predicted, respectively; p = 0.012 [for trend])], expiratory muscle strength (maximal expiratory pressure [Pemax]) [+ 7%, + 5%, and + 9% predicted, respectively; p = 0.081], 6-min walking distance (6MWD) [+ 40, + 41, and + 45 m, respectively; p = 0.006 (for trend)], and maximal oxygen uptake (Vo(2)peak) [+ 55, + 185, and + 81 mL/min, respectively; p = 0.110 (for trend)]. Similarly, physical activity reduced the risk of having high levels of circulating tumor necrosis factor alpha (odds ratio, 0.78, 0.61, and 0.36, respectively; p = 0.011) and C-reactive protein (0.70, 0.51, and 0.52, respectively; p = 0.036) in multivariate logistic regression. CONCLUSIONS: More physically active COPD patients show better functional status in terms of Dlco, Pemax, 6MWD, Vo(2)peak, and systemic inflammation.