Associations between paediatric obesity, chemical mixtures and environmental factors, in a national cross-sectional study of Canadian children.

BACKGROUND: Whilst single chemical exposures are suspected to be obesogenic, the combined role of chemical mixtures in paediatric obesity is not well understood. OBJECTIVES: We aimed to evaluate the potential associations between chemical mixtures and obesity in a population-based sample of Canadian children. METHODS: We ascertained biomonitoring and health data for children aged 3-11 from the cross-sectional Canadian Health Measures Survey from 2007 to 2019. Several chemicals of interest were measured in blood or urine and paediatric obesity was defined based on measured anthropometrics. Using quantile-based G computational analysis, we quantified the effects of three chemical mixtures selected a priori. Models were adjusted for sociodemographic and environmental factors identified through a directed acyclic graph. Results are presented through adjusted relative risks (RR) with 95% confidence intervals (95% CI). RESULTS: We included 9147 children. Of these, 24.1% were overweight or obese. Exposure to the mixture of bisphenol A, acrylamide, glycidamide, metals, parabens and arsenic increased the risk of childhood overweight or obesity by 45% (95% CI 1.09, 1.93), obesity by 109% (95% CI 1.27, 3.42) and central obesity by 82% (95% CI 1.30, 2.56). CONCLUSIONS: Our findings support the role of early childhood chemical exposures in paediatric obesity and the potential combined effects of chemicals.

Harmonizing the assessment of allostatic load across cycles of the Canadian Health Measures Survey: Variable selection and calculation method.

Background: The availability of measures to operationalize allostatic load - the cumulative toll on the body of responding to stressor demands - in population health surveys may differ across years or surveys, hampering analyses on the entire sampled population. Here, impacts of variable selection and calculation method were evaluated to generate an allostatic load index applicable across all cycles of the Canadian Health Measures Survey (CHMS). Methods: Data from CHMS cycles 1 to 4 were used to compare allostatic load scores when replacing the most prevalent risk factor, waist-to-hip ratio - available in cycles 1 to 4 but not 5 and 6 - with body mass index (BMI), waist circumference, waist circumference within BMI groups (classified as normal, overweight, or obese), or waist-to-height ratio. Indexes were generated using clinical or sex-specific empirically defined risk thresholds and as count-based or continuous scores. Logistic regression models that included age and sex were used to relate each potential index to socioeconomic indicators (educational attainment, household income). Results: Of the variables assessed, waist-to-height ratio and waist circumference were closest to waist-to-hip ratio according to an individual's percentile ranking and in classifying "at risk" using either clinical or empirically defined cut-offs. Allostatic load profiles generated using waist-to-height ratios most closely resembled profiles constructed using waist-to-hip ratios. Sex-dependent associations with educational attainment and household income were maintained across constructs whether indexes were count-based or continuous. Interpretation: Allostatic load profiles and associations with socioeconomic indicators were robust to variable substitution and method of calculation, supporting the use of a harmonized index across survey cycles to assess the cumulative toll on health of stressor exposure.

Concordance between In Vitro and In Vivo Relative Toxic Potencies of Diesel Exhaust Particles from Different Biodiesel Blends.

Diesel exhaust particles (DEPs) contribute to air pollution exposure-related adverse health impacts. Here, we examined in vitro, and in vivo toxicities of DEPs from a Caterpillar C11 heavy-duty diesel engine emissions using ultra-low-sulfur diesel (ULSD) and biodiesel blends (20% v/v) of canola (B20C), soy (B20S), or tallow-waste fry oil (B20T) in ULSD. The in vitro effects of DEPs (DEPULSD, DEPB20C, DEPB20S, and DEPB20T) in exposed mouse monocyte/macrophage cells (J774A.1) were examined by analyzing the cellular cytotoxicity endpoints (CTB, LDH, and ATP) and secreted proteins. The in vivo effects were assessed in BALB/c mice (n = 6/group) exposed to DEPs (250 µg), carbon black (CB), or saline via intratracheal instillation 24 h post-exposure. Bronchoalveolar lavage fluid (BALF) cell counts, cytokines, lung/heart mRNA, and plasma markers were examined. In vitro cytotoxic potencies (e.g., ATP) and secreted TNF-α were positively correlated (p < 0.05) with in vivo inflammatory potency (BALF cytokines, lung/heart mRNA, and plasma markers). Overall, DEPULSD and DEPB20C appeared to be more potent compared to DEPB20S and DEPB20T. These findings suggested that biodiesel blend-derived DEP potencies can be influenced by biodiesel sources, and inflammatory process- was one of the potential underlying toxicity mechanisms. These observations were consistent across in vitro and in vivo exposures, and this work adds value to the health risk analysis of cleaner fuel alternatives.

Modulation of insulin signaling pathway genes by ozone inhalation and the role of glucocorticoids: A multi-tissue analysis.

Air pollution is associated with increased risk of metabolic diseases including type 2 diabetes, of which dysregulation of the insulin-signaling pathway is a feature. While studies suggest pollutant exposure alters insulin signaling in certain tissues, there is a lack of comparison across multiple tissues needed for a holistic assessment of metabolic effects, and underlying mechanisms remain unclear. Air pollution increases plasma levels of glucocorticoids, systemic regulators of metabolic function. The objectives of this study were to 1) determine effects of ozone on insulin-signaling genes in major metabolic tissues, and 2) elucidate the role of glucocorticoids. Male Fischer-344 rats were treated with metyrapone, a glucocorticoid synthesis inhibitor, and exposed to 0.8 ppm ozone or clean air for 4 h, with tissue collected immediately or 24 h post exposure. Ozone inhalation resulted in distinct mRNA profiles in the liver, brown adipose, white adipose and skeletal muscle tissues, including effects on insulin-signaling cascade genes (Pik3r1, Irs1, Irs2) and targets involved in glucose metabolism (Hk2, Pgk1, Slc2a1), cell survival (Bcl2l1), and genes associated with diabetes and obesity (Serpine1, Retn, Lep). Glucocorticoid-dependent regulation was observed in the liver and brown and white adipose tissues, while effects in skeletal muscle were largely unaffected by metyrapone treatment. Gene expression changes were accompanied by altered phosphorylation states of insulin-signaling proteins (BAD, GSK, IR-ß, IRS-1) in the liver. The results show that systemic effects of ozone inhalation include tissue-specific regulation of insulin-signaling pathway genes via both glucocorticoid-dependent and independent mechanisms, providing insight into mechanisms underlying adverse effects of pollutants.

Randomized Cross-Over Study of In-Vehicle Cabin Air Filtration, Air Pollution Exposure, and Acute Changes to Heart Rate Variability, Saliva Cortisol, and Cognitive Function.

To determine how traffic-related air pollution (TRAP) exposures affect commuter health, and whether cabin air filtration (CAF) can mitigate exposures, we conducted a cross-over study of 48 adults exposed to TRAP during two commutes with and without CAF. Measurements included particulate air pollutants (PM2.5, black carbon [BC], ultrafine particles [UFPs]), volatile organic compounds, and nitrogen dioxide. We measured participants' heart rate variability (HRV), saliva cortisol, and cognitive function. On average, CAF reduced concentrations of UFPs by 26,232 (95%CI: 11,734, 40,730) n/cm3, PM2.5 by 6 (95%CI: 5, 8) µg/m3, and BC by 1348 (95%CI: 1042, 1654) ng/m3, or 28, 30, and 32%, respectively. Each IQR increase in PM2.5 was associated with a 28% (95%CI: 2, 60) increase in high-frequency power HRV at the end of the commute and a 22% (95%CI: 7, 39) increase 45 min afterward. IQR increases in UFPs were associated with increased saliva cortisol in women during the commute (18% [95%CI: 0, 40]). IQR increases in UFPs were associated with strong switching costs (19% [95%CI: 2, 39]), indicating a reduced capacity for multitasking, and PM2.5 was associated with increased reaction latency, indicating slower responses (5% [95%CI: 1, 10]). CAF can reduce particulate exposures by almost a third.

Hair cortisol as a viable tool for the assessment of an association between environmental noise exposure and chronic stress.

Entrenched in the well-established link between stress and health, noise exposure as a potential contributor to stress-related health effects receives tremendous attention. Indeed, exposure to noise can act as a stressor as evidenced through increased heart rate, blood pressure, adrenaline, epinephrine, and cortisol. Cortisol is secreted from the adrenal glands in response to stressor-induced activation of the hypothalamic-pituitary-adrenal axis. For assessment of environmental noise and stress, repeated sampling in blood, saliva, or urine is necessary to evaluate the association between environmental noise exposure and protracted changes in cortisol. Controlling for the many variables that influence the secretion of cortisol at discrete sampling intervals is challenging. Studies suggest that systemically produced cortisol integrates and remains in hair as it grows, providing a measure that integrates a cortisol response over a longer period, circumventing several limitations associated with multiple sampling. Robust evidence supports the integration of cortisol into hair, yet recent studies call into question the notion that cortisol is retained with growth. The current paper discusses the strengths and limitations of hair cortisol analysis with an emphasis on its utility as a measure of chronic stress in environmental noise studies.

Establishing an air-liquid interface exposure system for exposure of lung cells to gases.

OBJECTIVE: Growing interest in non-animal-based models has led to the development of devices to expose cells to airborne substances. Cells/tissues grown at the air-liquid interface (ALI) are more representative of lung cells/tissues in vivo compared to submerged cell cultures. Additionally, airborne exposures should allow for closer modeling of human lung toxicity. However, such exposures present technical challenges, including maintaining optimal cell health, and establishing consistent exposure monitoring and control. We aimed to establish a reliable system and procedures for cell exposures to gases at the ALI. METHODS: We tested and adapted a horizontal-flow ALI-exposure system to verify and optimize temperature, humidity/condensation, and control of atmosphere delivery. We measured temperature and relative humidity (RH) throughout the system, including at the outlet (surrogate measures) and at the well, and evaluated viability of lung epithelial A549 cells under control conditions. Exposure stability, dosimetry, and toxicity were tested using ozone. RESULTS: Temperatures measured directly above wells vs. outflow differed; using above-well temperature enabled determination of near-well RH. Under optimized conditions, the viability of A549 cells exposed to clean air (2 h) in the ALI system was unchanged from incubator-grown cells. In-well ozone levels, determined through reaction with potassium indigotrisulfonate, confirmed dosing. Cells exposed to 200 ppb ozone at the ALI presented reduced viability, while submerged cells did not. CONCLUSION: Our results emphasize the importance of monitoring near-well conditions rather than relying on surrogate measures. Rigorous assessment of ALI exposure conditions led to procedures for reproducible exposure of cells to gases.

Acute cardiovascular effects of inhaled ambient particulate matter: Chemical composition-related oxidative stress, endothelin-1, blood pressure, and ST-segment changes in Wistar rats.

Short-term increases in particulate matter (PM) are associated with heightened morbidity and mortality from cardiovascular causes. Inhalation of PM is known to increase endothelin (ET)-1 levels. Yet, less is known about particle composition-related changes at the molecular level including the endothelinergic system and relationship with cardiovascular function changes. In this work, adult Wistar male rats were exposed for 4 h by nose-only inhalation to clean air, Ottawa urban particles (EHC-93, 48 mg/m3) and water-leached (EHC-93L, 49 mg/m3) particles, to examine the effect of particle compositional changes on oxidative stress, circulating ETs, blood pressure, and heart electrophysiology. Particle deposition in the respiratory compartment was estimated at 85 µg (25 ng/cm2). Lung cell proliferation was low in both treatment groups, indicating absence of acute injury. Inhalation of EHC-93 caused statistically significant elevations (p < 0.05) of oxidative stress markers, ET-1, ET-3, blood pressure, and a decrease of ST-segment duration in the ECG at 1.5 days post-exposure. Leached particles (EHC-93L) caused rapid but transient elevation (p < 0.05) of oxidative stress, ET-1, ET-2, and ET-3 at earlier time points, with no changes in blood pressure or ST-segment. These results demonstrate that inhalation of urban particles at an internal dose inadequate to cause acute lung injury can induce oxidative stress, enhance vasoactive endothelins, leading to vasopressor response, affecting cardiac electrophysiology in Wistar rats, consistent with the cardiovascular impacts of ambient particles in human populations. Change in particle potency after removal of soluble species, notably cadmium, zinc and polar organics suggests that the toxicodynamics of cardiovascular effects can be modified by physicochemical properties of particles.

Sex-difference in air pollution-related acute circulatory and respiratory mortality and hospitalization.

BACKGROUND: Numerous studies have estimated adverse effects of short-term exposure to ambient air pollution on public health. Few have focused on sex-differences, and results have been inconsistent. The purpose of this study was three-fold: to identify sex-differences in air pollution-related health outcomes; to examine sex-differences by cause and season; and to examine time trends in sex-differences. METHODS: Daily data were collected on circulatory- and respiratory-related mortality (for 29 years) and cause-specific hospitalization (for 17 years) with hourly concentrations of ozone (O3), nitrogen dioxide (NO2), and fine particulate matter (PM2.5). For hospitalization, more specific causes were examined: ischemic heart disease (IHD), other heart disease (OHD), cerebrovascular disease (CEV), chronic lower respiratory diseases (CLRD), and Influenza/Pneumonia (InfPn). Generalized Poisson models were applied to 24 Canadian cities, and the city-specific estimates were combined for nationwide estimates for each sex using Bayesian hierarchical models. Finally, sex-differences were tested statistically based on their interval estimates, considering the correlation between sex-specific national estimates. RESULTS: Sex-differences were more frequently observed for hospitalization than mortality, respiratory than circulatory health outcomes, and warm than cold season. For hospitalization, males were at higher risk (M > F) for warm season (OHD and InfPn from O3; IHD from NO2; and InfPn from PM2.5), but F > M for cold season (CEV from O3 and OHD from NO2). For mortality, we found F > M only for circulatory diseases from ozone during the warm season. Among the above-mentioned sex-differences, three cases showed consistent time trends over the years: while M > F for OHD from O3 and IHD from NO2, F > M for OHD from NO2. CONCLUSIONS: We found that sex-differences in effect of ambient air pollution varied over health outcome, cause, season and time. In particular, the consistent trends (either F > M or M > F) across 17 years provide stronger evidence of sex-differences in hospitalizations, and warrant investigation in other populations.

Modulation by Ozone of Glucocorticoid-Regulating Factors in the Lungs in Relation to Stress Axis Reactivity.

Exposure to air pollutants increases levels of circulating glucocorticoid stress hormones that exert profound effects relevant to health and disease. However, the nature and magnitude of tissue-level effects are modulated by factors that regulate local glucocorticoid activity; accordingly, inter-individual differences could contribute to susceptibility. In the present study, we characterized effects of ozone (O3) inhalation on glucocorticoid-regulating factors in the lungs of rat strains with contrasting hypothalamic-pituitary-adrenal stress axis responses. Hyper-responsive Fischer (F344) and less responsive Lewis (LEW) rats were exposed to air or 0.8 ppm O3 for 4 h by nose-only inhalation. Levels of the high-specificity and -affinity corticosteroid-binding globulin protein increased in the lungs of both strains proportional to the rise in corticosterone levels following O3 exposure. Ozone reduced the ratio of 11ß-hydroxysteroid dehydrogenase type 1 (HSDB1)/HSDB2 mRNA in the lungs of F344 but not LEW, indicating strain-specific transcriptional regulation of the major glucocorticoid metabolism factors that control tissue-level action. Intercellular adhesion molecule (ICAM)-1 and total elastase activity were increased by O3 in both strains, consistent with extravasation and tissue remodeling processes following injury. However, mRNA levels of inflammatory markers were significantly higher in the lungs of O3-exposed LEW compared to F344. The data show that strain differences in the glucocorticoid response to O3 are accompanied by corresponding changes in regulatory factors, and that these effects are collectively associated with a differential inflammatory response to O3. Innate differences in glucocorticoid regulatory factors may modulate the pulmonary effects of inhaled pollutants, thereby contributing to differential susceptibility.

Ozone-dependent increases in lung glucocorticoids and macrophage response: Effect modification by innate stress axis function.

Although considerable inter-individual variability exists in health effects associated with air pollutant exposure, underlying reasons remain unclear. We examined whether innate differences in stress axis function modify lung glucocorticoid and macrophage responses to ozone (O3). Highly-stress responsive Fischer (F344) and less responsive Lewis (LEW) rats were exposed for 4 h by nose-only inhalation to air or O3 (0.8 ppm). Ozone increased corticosterone recovered by bronchoalveolar lavage in both strains (F344 > LEW). Higher corticosterone in F344 was associated with a blunted response to O3 of macrophage pro-inflammatory genes compared to LEW. Pharmacological inhibition of O3-dependent corticosterone production in F344 enhanced the inflammatory gene response to O3, mimicking the LEW phenotype. Examination of potential impacts of glucocorticoids on macrophage function using a human monocyte-derived macrophage cell line (THP-1) showed that cortisol modified phagocytosis in a macrophage phenotype-dependent manner. Overall, our data implicate endogenous glucocorticoids in the regulation of pulmonary macrophage responses to O3.

Exposure Load: Using biomonitoring data to quantify multi-chemical exposure burden in a population.

People are often concurrently exposed to numerous chemicals. Here we sought to leverage existing large biomonitoring datasets to improve our understanding of multi-chemical exposures in a population. Using nationally-representative data from the 2012-2015 Canadian Health Measures Survey (CHMS), we developed Exposure Load, a metric that counts the number of chemicals measured in people above a defined concentration threshold. We calculated Exposure Loads based on five concentration thresholds: the analytical limit of detection (LOD) and the 50th, 75th, 90th and 95th percentiles. Our analysis considered 44 analyte biomarkers representing 26 chemicals from the 2012-2015 CHMS; complete biomarker data were available for 1858 participants aged 12-79 years following multiple imputation of results that were missing due to sample loss. Chemicals may have one or more biomarkers, and for the purposes of Exposure Load calculation, participants were considered to be exposed to a chemical if at least one biomarker was above the threshold. Distributions of Exposure Loads are reported for the total population, as well as by age group, sex and smoking status. Canadians had an Exposure Load between 9 and 21 (out of 26) when considering LOD as the threshold, with the majority between 13 and 18. At higher thresholds, such as the 95th percentile, the majority of Canadians had an Exposure Load between 0 and 3, although some people had an Exposure Load of up to 15, indicating high exposures to multiple chemicals. Adolescents aged 12-19 years had significantly lower Exposure Loads than adults aged 40-79 years at all thresholds and adults aged 20-39 years at the 50th and 75th percentiles. Smokers had significantly higher Exposure Loads than nonsmokers at all thresholds except the LOD, which was expected given that tobacco smoke is a known source of certain chemicals included in our analysis. No differences in Exposure Loads were observed between males and females at any threshold. These findings broadly suggest that Canadians are concurrently exposed to many chemicals at lower concentrations and to fewer chemicals at high concentrations. They should assist in identifying vulnerable subpopulations disproportionately exposed to numerous chemicals at high concentrations. Future work will use Exposure Loads to identify prevalent chemical combinations and their link with adverse health outcomes in the Canadian population. The Exposure Load concept can be applied to other large datasets, through collaborative efforts in human biomonitoring networks, in order to further improve our understanding of multiple chemical exposures in different populations.

Air pollution exposure during pregnancy and childhood and brain morphology in preadolescents.

BACKGROUND: Studies investigating the relationship between exposure to air pollution and brain development using magnetic resonance images are emerging. However, most studies have focused only on prenatal exposures, and have included a limited selection of pollutants. Here, we aim to expand the current knowledge by studying pregnancy and childhood exposure to a wide selection of pollutants, and brain morphology in preadolescents. METHODS: We used data from 3133 preadolescents from a birth cohort from Rotterdam, the Netherlands (enrollment: 2002-2006). Concentrations of nitrogen oxides, coarse, fine, and ultrafine particles, and composition of fine particles were estimated for participant's home addresses in pregnancy and childhood, using land use regression models. Structural brain images were obtained at age 9-12 years. We assessed the relationships of air pollution exposure, with brain volumes, and surface-based morphometric data, adjusting for socioeconomic and life-style characteristics, using single as well as multi-pollutant approach. RESULTS: No associations were observed between air pollution exposures and global volumes of total brain, and cortical and subcortical grey matter. However, we found associations between higher pregnancy and childhood air pollution exposures with smaller corpus callosum, smaller hippocampus, larger amygdala, smaller nucleus accumbens, and larger cerebellum (e.g. -69.2mm3 hippocampal volume [95%CI -129.1 to -9.3] per 1ng/m3 increase in pregnancy exposure to polycyclic aromatic hydrocarbons). Higher pregnancy exposure to air pollution was associated with smaller cortical thickness while higher childhood exposure was associated with predominantly larger cortical surface area. CONCLUSION: Higher pregnancy or childhood exposure to several air pollutants was associated with altered volume of several brain structures, as well as with cortical thickness and surface area. Associations showed some similarity to delayed maturation and effects of early-life stress.

Residential greenness and indicators of stress and mental well-being in a Canadian national-level survey.

BACKGROUND: Residential proximity to greenness in urban areas has been shown to confer a number of health benefits, including improved mental health. We investigated whether greenness was associated with self-reported stress, distress, and mental health among adult participants of multiple cycles of a national Canadian health survey, and whether these associations varied by sex, age, income, and neighbourhood characteristics. METHODS: Our study population included 397,900 participants of the Canadian Community Health Survey, 18 years of age or older, who lived in census metropolitan areas between 2000 and 2015. We used the Normalized Difference Vegetation Index (NDVI) to characterize participants' exposure to greenness within 250 m, 500 m, and 1 km buffers from a representative location of their postal code. Health outcomes included: self-reported perceptions of life stress, psychological distress, and self-rated mental health. We used multiple regression models, adjusted for relevant individual and neighbourhood-level variables to estimate associations (and 95% confidence intervals) between each outcome and exposure to greenness. FINDINGS: In models with all participants, we observed 6% lower odds of poor self-rated mental health per increase in the interquartile range (i.e., 0.12) of NDVI within a 500 m buffer. Across the three outcomes, we found substantial heterogeneity in effect size across categories of sex, age, and community-level indicators of deprivation and urban form. For example, each incremental increase in greenness exposure was associated with a reduction of 0.61 (95% CI: 0.81 to -0.51) on the K10 psychological distress score among those living in the active core of cities, and with an increase of 0.07 (95% CI: 0.03-0.12) on this score among those living in the most suburban areas. CONCLUSIONS: Our results indicate that the potential benefits of residential greenness on mental health vary across personal and neighbourhood-level characteristics and are sensitive to how the outcome is measured. Additional research is needed to understand which features of greenness are most relevant to different sub-groups of the population to maximize these health benefits.

Self-rated stress, distress, mental health, and health as modifiers of the association between long-term exposure to ambient pollutants and mortality.

BACKGROUND: Individual and neighbourhood-scale socioeconomic characteristics modify associations between exposure to air pollution and mortality. The role of stress, which may integrate effects of social and environmental exposures on health, is unknown. We examined whether an individual's perspective on their own well-being, as assessed using self-rated measures of stress and health, modifies the pollutant-mortality relationship. METHODS: The Canadian Community Health Survey (CCHS)-mortality cohort includes respondents from surveys administered between 2001 and 2012 linked to vital statistics and postal codes from 1981 until 2016. Annual fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) exposure estimates were attached to a sample of cohort members aged 30-89 years (n = 398,300 respondents/3,848,400 person-years). We examined whether self-rated stress, distress, mental health, and general health modified associations between long-term exposure to each pollutant (three-year moving average with one-year lag) and non-accidental mortality using Cox survival models, adjusted for individual- (i.e. socioeconomic and behavioural) and neighbourhood-scale covariates. RESULTS: In fully-adjusted models, the relationship between exposure to pollutants and mortality was stronger among those with poor self-rated mental health, including a significant difference for NO2 (hazard ratio (HR) = 1.15, 95% CI 1.06-1.25 per IQR) compared to those with very good/excellent mental health (HR = 1.05, 95% CI 1.01-1.08; Cochran's Q = 4.01; p < 0.05). Poor self-rated health was similarly associated with higher pollutant-associated HRs, but only in unadjusted models. Stress and distress did not modify pollutant-mortality associations. CONCLUSIONS: Poor self-rated mental and general health were associated with increased mortality attributed to exposure to ambient pollutants.

The association between ambient air pollution concentrations and psychological distress.

BACKGROUND: A growing number of epidemiological studies have linked air pollution exposure to psychological conditions. Laboratory studies indicate that air pollutants can activate the neuroendocrine stress axis and modulate stress hormone levels, which could contribute to the development or exacerbation of psychological distress. The present study examined the spatial associations between air pollutants (fine particulate matter [PM2.5], nitrogen dioxide [NO2] and ground-level ozone [O3]) and psychological distress among subjects in the most populous provinces in Canada. DATA AND METHODS: Subjects were sampled from the Canadian Community Health Survey in three regions (Quebec in 2005 [n=25,800], British Columbia and Alberta in 2005 [n=23,000], and Ontario in 2011 [n=36,000]), and were assigned estimates of annual exposure to three ambient air pollutants (PM2.5, NO2 and O3) for the same years. Individual psychological distress was assessed using the Kessler Psychological Distress Scale (K10), based on anxiety and depressive symptoms in the past month. Regression models (both ordinary least squares and simultaneous autoregressive models) were applied to estimate associations between K10 distress scores and each air pollutant, after adjusting for individual (demographic, socioeconomic and behavioural) and neighbourhood covariates.. RESULTS: Psychological distress was positively associated with PM2.5 and NO2 in all three regions, and with O3 in Quebec. However, after further adjusting for individual and neighbourhood covariates, the associations between distress and air pollution remained statistically significant only in Quebec. DISCUSSION: Some evidence for positive associations between psychological distress and ambient air pollution after adjusting for spatial autocorrelation was found.

Ozone increases plasma kynurenine-tryptophan ratio and impacts hippocampal serotonin receptor and neurotrophic factor expression: Role of stress hormones.

Air pollution is associated with adverse impacts on the brain, including cognitive decline and increased incidence of dementia, depression and anxiety; however, underlying mechanisms remain unclear. We have shown that both ozone and particulate matter activate the hypothalamic-pituitary-adrenal (HPA) axis, increasing plasma glucocorticoids and altering mRNA profiles in multiple tissues including the brain. HPA axis dysregulation has been associated with central nervous system impacts, including key effects in the hippocampus; accordingly, we hypothesized that pollutant-dependent increases in glucocorticoid levels impact biological pathways relevant to brain health. Fischer-344 rats were treated with metyrapone (0 or 50 mg/kg), a glucocorticoid synthesis inhibitor, and exposed to ozone (0 or 0.8 ppm) for 4 h (n = 5/group) to investigate the role of glucocorticoids in ozone-dependent effects on tryptophan metabolism and expression of serotonin receptors and neurotrophic factors. Ozone increased plasma levels of the tryptophan metabolite kynurenine (~2-fold) and decreased tryptophan levels (~1.2 fold). Hippocampal expression of serotonin receptors exhibited differential regulation following exposure, and expression of key neurotrophic factors (brain-derived neurotrophic factor, vascular endothelial growth factor A, insulin-like growth factor-1, tyrosine kinase receptor B, b-cell lymphoma 2) was decreased. Some, but not all effects were abrogated by metyrapone treatment, suggesting both glucocorticoid-dependent and -independent regulation. Exposure to exogenous corticosterone (10 mg/kg) followed by clean air reproduced the ozone effects that were blocked with metyrapone, confirming the specificity of effects to glucocorticoids. These results indicate that ozone can modify pathways relevant to brain health and establish a role for the HPA axis in mediating these effects.

Association of urinary polycyclic aromatic hydrocarbons and obesity in children aged 3-18: Canadian Health Measures Survey 2009-2015.

Polycyclic aromatic hydrocarbons (PAHs) may contribute to obesity. Childhood obesity is a strong predictor of adult obesity and morbidity; however, the relationship between PAHs and obesity in young children (e.g., aged 3-5) has not been studied. We examined the association between urinary PAH metabolites and measures of obesity in children. We analyzed data from 3667 children aged 3-18 years who participated in the Canadian Health Measures Survey (CHMS, 2009-2015). We ran separate multivariable linear models to estimate the association between quartiles of PAH metabolites and each of body mass index (BMI) percentile, waist circumference (WC), and waist-to-height ratio (WHtR) in the total population, as well as in the age subgroups 3-5, 6-11, and 12-18, adjusting for age, sex, ethnicity, education, income quintile, diet, creatinine, and exposure to environmental tobacco smoke. A multinomial logistic regression model estimated adjusted odds ratios for risk of central obesity. BMI, WC, and WHtR were positively associated with total PAH and naphthalene metabolites in the total population aged 3-18 and in age groups 6-11 and 12-18. In 3-5 year olds, WHtR, but not BMI, was significantly associated with total PAH, naphthalene, and phenanthrene metabolites. Overall, those in the highest quartile for naphthalene or total PAH metabolites had three times greater odds of having central obesity compared with those in the lowest quartile. Urinary PAH metabolites are associated with WHtR, an indicator of central obesity and predictor of health risks associated with obesity, in children as young as 3-5.

Effect of industrial point-source air pollutants on fractional exhaled nitric oxide in healthy volunteers.

BACKGROUND: Few studies have examined the effects of industrial, fixed-site sources of air pollution on lung inflammation in nearby residents. We investigated the effects of short-term exposure to ambient air near a steel plant on the fractional exhaled concentration of nitric oxide (FeNO), a measure of airway inflammation, in healthy volunteers. METHODS: A cross-over study design was used. Fifty-nine non-smoking participants (mean age 24 years) were randomly assigned to each of two 5-day exposure scenarios: breathing ambient air adjacent to a steel plant or 5 km away at a college campus site. FeNO and on-site air pollutants were measured daily. Mixed effects linear regression models were used for data analysis, adjusting for sex, temperature, humidity and day of week. RESULTS: Compared with the college site, PM 2.5, ultrafine PM, SO2, NO2 and CO levels were significantly greater near the steel plant. FeNO was 15.3% (95% CI, 6.6%, 24.8%) higher near the plant compared to the college site. CONCLUSIONS: Exposure to ambient air near a steel plant was associated with increased airway inflammation as measured by exhaled nitric oxide.