The association between the Canadian active living environments index and glucose metabolism in a Canadian national population study.

Biomarkers of glucose metabolism may reflect insulin resistance, a risk factor for diabetes and cardiovascular disease (CVD). Neighborhoods conducive to a physically active lifestyle have the potential to improve these biomarkers. We examined cross-sectional associations between walkability and blood biomarkers of glucose metabolism in 29,649 Canadian Health Measures Survey (CHMS) participants. We used generalized linear mixed models with sampling weights adjusted for province, participants' age, sex, annual household income and educational attainment, cigarette smoking, environmental tobacco smoke, alcohol consumption, and exposure to ambient fine particulate air pollution (PM2.5). A higher value of the Canadian Active Living Environments Index, a measure of neighborhood walkability, equivalent to the magnitude of its interquartile range (IQR) of 2.4 was significantly associated with percentage differences of -0.48 (95% confidence interval (CI): 0.63, -0.32), -3.17 (95%CI: 5.27, -1.08), -3.88 (95%CI: 6.38, -1.38), and -3.36 (95%CI: 5.25, -1.47) in HbA1C, fasting insulin, HOMA-IR, and HOMA-ß, respectively, for all CHMS participants. No significant effects were observed in those ≤16 years old. Canadians living in neighborhoods that facilitate active living have more favorable biomarkers of glucose metabolism, suggesting that the built environment has the potential to improve risk factors for diabetes and CVD in adults.

Do blood metals influence lipid profiles? Findings of a cross-sectional population-based survey.

Dyslipidemia, an imbalance of lipids and a major risk factor for cardiovascular disease, has been associated with elevated blood and urine levels of several heavy metals. Using data from a Canadian Health Measures Survey (CHMS), we tested associations between blood levels of cadmium, copper, mercury, lead, manganese, molybdenum, nickel, selenium, and zinc, and the lipids triglycerides (TG), total cholesterol (TC), low density lipoproteins (LDL), high density lipoproteins (HDL) and apolipoproteins A1 (APO A1), and B (APO B). All adjusted associations between single metals and lipids were positive and significant, except for APO A1 and HDL. The joint effect of an interquartile range increase in heavy metals was positively associated with percentage increases of TC, LDL and APO B of 8.82% (95%CI: 7.06, 10.57), 7.01% (95%CI: 2.51, 11.51) and 7.15% (95%CI: 0.51, 13.78), respectively. Future studies are warranted to determine if reducing environmental exposure to heavy metals favorably influences lipid profiles and the risk of cardiovascular disease.

Activity-related dyspnea in older adults participating in the Canadian Longitudinal Study on Aging.

BACKGROUND: Dyspnea is associated with functional impairment and impaired quality of life. There is limited information on the potential risk factors for dyspnea in an older adult population. OBJECTIVES: Among older adults aged 45 to 85 years of age, what sociodemographic, environmental, and disease related factors are correlated with dyspnea? DESIGN: We used cross-sectional questionnaire data collected on 28,854 participants of the Canadian Longitudinal Study of Aging (CLSA). Multinomial regression was used to assess the independent effect of individual variables adjusting for the other variables of interest. KEY RESULTS: The adjusted odds ratios for dyspnea "walking on flat surfaces" were highest for obesity (OR, 5.71; 95%CI, 4.71-6.93), lung disease (OR, 3.91; 95%CI, 3.41-4.49), and depression (OR, 3.68; 95%CI, 3.15-4.29), and were greater than 2 for lower income, and heart disease. The effect of diabetes remained significant after adjusting for sociodemographics, heart disease and BMI (OR, 1.61; 95%CI, 1.39-1.86). Those with both respiratory disease and depression had a 12.78-fold (95%CI, 10.09-16.19) increased odds of exertional dyspnea, while the corresponding OR for the combination of heart disease and depression was 18.31 (95%CI, 13.4-25.01). CONCLUSIONS: In a community sample of older adults, many correlates of dyspnea exist which have significant independent and combined effects. These factors should be considered in the clinical context where dyspnea is out of proportion to the degree of heart and lung disease. Whether or not diabetes may possibly be a risk factor for dyspnea merits further investigation.

The association between air pollution and hospitalization for patients with systemic lupus erythematosus in Chile: A daily time series analysis.

Genetic and environmental factors are thought to influence the activity of systemic lupus erythematosus (SLE), but relatively little is known about the effects of ambient air pollution. Using pollution data from air monitoring stations in the urban centers in Santiago Chile, along with daily patient hospitalization data from 2001 to 2012, an association between ambient air pollution and daily hospital admissions for SLE was tested using generalized linear models. Averaged over all regions pollutant mean 24 h concentrations were: 0.96 ppm carbon monoxide (CO), 64 ppb ozone (O3), 43 ppb nitrogen dioxide (NO2), 9 ppb sulphur dioxide (SO2), 29 µg/m3 particulate matter ≤ 2.5 µm in mean aerodynamic diameter (PM2.5), and 67 µg/m3 particulate matter ≤ 10 µm in diameter (PM10). The relative risk estimates in single pollutant models for an interquartile range (IQR) increase in pollutant were: RR = 1.34 (95% CI: 1.06-1.83) for SO2, RR = 1.60 (95% CI: 1.15-2.24) for CO, and RR = 1.41 (95% CI: 1.14-1.86) for PM2.5. In two-pollutant models, the significance of SO2 and PM2.5 persisted despite adjustments for each of the other measured pollutants. These findings suggest that acute increases in air pollution increase the risk of hospitalization with a primary diagnosis of SLE.

The association between air pollution and COVID-19 related mortality in Santiago, Chile: A daily time series analysis.

BACKGROUND: Exposure to ambient air pollution is a risk factor for morbidity and mortality from lung and heart disease. RESEARCH QUESTION: Does short term exposure to ambient air pollution influence COVID-19 related mortality? STUDY DESIGN AND METHODOLOGY: Using time series analyses we tested the association between daily changes in air pollution measured by stationary monitors in and around Santiago, Chile and deaths from laboratory confirmed or suspected COVID-19 between March 16 and August 31, 2020. Results were adjusted for temporal trends, temperature and humidity, and stratified by age and sex. RESULTS: There were 10,069 COVID-19 related deaths of which 7659 were laboratory confirmed. Using distributed lags, the cumulative relative risk (RR) (95% CI) of mortality for an interquartile range (IQR) increase in CO, NO2 and PM2.5 were 1.061 (1.033-1.089), 1.067 (1.023-1.103) and 1.058 (1.034-1.082), respectively There were no significant differences in RR by sex.. In those at least 85 years old, an IQR increase in NO2 was associated with a 12.7% (95% CI 4.2-22.2) increase in daily mortality. CONCLUSION: This study provides evidence that daily increases in air pollution increase the risk of dying from COVID-19, especially in the elderly.

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.

Do acute changes in ambient air pollution increase the risk of potentially fatal cardiac arrhythmias in patients with implantable cardioverter defibrillators?

BACKGROUND: Daily changes in ambient air pollution have been associated with cardiac morbidity and mortality. Precipitating a cardiac arrhythmia in susceptible individuals may be one mechanism. We investigated the influence of daily changes in air pollution in the Province of Ontario, Canada on the frequency of discharges from implantable cardio defibrillators (ICDs) which occur in response to potentially life threatening arrhythmias. METHODS: Using a case- crossover design, we compared ambient air pollution concentrations on the day of an ICD discharge to other days in the same month and year in 1952 patients. We adjusted for weather, lagged the exposure data from 0 to 3 days, and stratified the results by several patient-related characteristics. RESULTS: Median (interquartile range) for ozone (O3), fine particulate matter (PM2.5), sulphur dioxide (SO2) and nitrogen dioxide (NO2) were 26.0 ppb (19.4, 33.0), 6.6 µg/m3 (4.3, 10.6), 1.00 ppb (0.4,2.1), 10.0 ppb (6.0,15.3) respectively. Unlagged odds ratios (95%) for an ICD discharge associated with an interquartile range increase in pollutant were 0.97 (0.86, 1.09) for O3, 0.99 (0.92, 1.06) for PM2.5, 0.97 (0.91, 1.03) for SO2, and 1.00 (0.89, 1.12) for NO2. CONCLUSION: We found no evidence that the concentrations of ambient air pollution observed in our study were a risk factor for potentially fatal cardiac arrhythmias in patients with ICDs.

Comparison of tris(2-ethylhexyl) phosphate and di(2-ethylhexyl) phosphoric acid toxicities in a rat 28-day oral exposure study.

Tris(2-ethylhexyl) phosphate (TEHP, CAS no. 78-42-2) is a plasticizer and a flame retardant, while di(2-ethylhexyl) phosphoric acid (DEHPA, CAS no. 298-07-7) is an oil additive and extraction solvent. Publicly-available information on repeated exposure to these two related organophosphate compounds is fragmentary. Hence, adult male and female Fischer rats were exposed to TEHP (300, 1000 and 3000 mg/kg body weight [BW]/day) or DEHPA (20, 60 and 180 mg/kg BW/day) by gavage for 28 consecutive days, to assess and compare their toxicities. Although significantly impaired BW gains and evidence of TEHP enzymatic hydrolysis to DEHPA were observed only in males, exposures to the highest TEHP and DEHPA doses often resulted in similar alterations of hematology, serum clinical chemistry and liver enzymatic activities in both males and females. The squamous epithelial hyperplasia and hyperkeratosis observed in the non-glandular forestomach of rats exposed to the middle and high DEHPA doses were most likely caused by the slightly corrosive nature of this chemical. Although tubular degeneration and spermatid retention were observed only in the testes of males exposed to the highest TEHP dose, numerous periodic acid-Schiff stained crystalline inclusions were observed in testis interstitial cells at all TEHP dose levels. No-observed-adverse-effect levels for TEHP and DEHPA are proposed, but the lower serum pituitary hormone levels resulting from TEHP and DEHPA exposures and the perturbations of testicular histology observed in TEHP-treated males deserve further investigation. Improved characterization of the toxicity of flame retardants will contribute to better informed substitution choices for legacy flame retardants phased-out over health concerns.

Effect modification of perinatal exposure to air pollution and childhood asthma incidence.

Perinatal exposure to ambient air pollution has been associated with childhood asthma incidence, however, less is known regarding the potential effect modifiers in this association. We examined whether maternal and infant characteristics modified the association between perinatal exposure to air pollution and development of childhood asthma.761 172 births occurring between 2006 and 2012 were identified in the province of Ontario, Canada. Associations between exposure to ambient air pollutants and childhood asthma incidence (up to age 6) were estimated using Cox regression models.110,981 children with asthma were identified. In models adjusted for postnatal exposures, second trimester exposures to particulate matter with a diameter ≤2.5 µm (PM2.5) (Hazard Ratio (HR) per interquartile (IQR) increase=1.07, 95% CI: 1.06-1.09) and nitrogen dioxide (NO2) (HR per IQR increase=1.06, 95% CI: 1.03-1.08) were associated with childhood asthma development. Enhanced impacts were found among children born to mothers with asthma, those who smoked during pregnancy, boys, those born preterm, of low birth weight and among those born to mothers living in urban areas during pregnancy.Prenatal exposure to air pollution may have a differential impact on the risk of asthma development according to maternal and infant characteristics.

Cardiovascular and inflammatory mechanisms in healthy humans exposed to air pollution in the vicinity of a steel mill.

BACKGROUND: There is a paucity of mechanistic information that is central to the understanding of the adverse health effects of source emission exposures. To identify source emission-related effects, blood and saliva samples from healthy volunteers who spent five days near a steel plant (Bayview site, with and without a mask that filtered many criteria pollutants) and at a well-removed College site were tested for oxidative stress, inflammation and endothelial dysfunction markers. METHODS: Biomarker analyses were done using multiplexed protein-array, HPLC-Fluorescence, EIA and ELISA methods. Mixed effects models were used to test for associations between exposure, biological markers and physiological outcomes. Heat map with hierarchical clustering and Ingenuity Pathway Analysis (IPA) were used for mechanistic analyses. RESULTS: Mean CO, SO2 and ultrafine particles (UFP) levels on the day of biological sampling were higher at the Bayview site compared to College site. Bayview site exposures "without" mask were associated with increased (p < 0.05) pro-inflammatory cytokines (e.g IL-4, IL-6) and endothelins (ETs) compared to College site. Plasma IL-1ß, IL-2 were increased (p < 0.05) after Bayview site "without" compared to "with" mask exposures. Interquartile range (IQR) increases in CO, UFP and SO2 were associated with increased (p < 0.05) plasma pro-inflammatory cytokines (e.g. IL-6, IL-8) and ET-1(1-21) levels. Plasma/saliva BET-1 levels were positively associated (p < 0.05) with increased systolic BP. C-reactive protein (CRP) was positively associated (p < 0.05) with increased heart rate. Protein network analyses exhibited activation of distinct inflammatory mechanisms after "with" and "without" mask exposures at the Bayview site relative to College site exposures. CONCLUSIONS: These findings suggest that air pollutants in the proximity of steel mill site can influence inflammatory and vascular mechanisms. Use of mask and multiple biomarker data can be valuable in gaining insight into source emission-related health impacts.

Maternal Exposure to Aeroallergens and the Risk of Early Delivery.

BACKGROUND: Daily changes in aeroallergens during pregnancy could trigger early labor, but few investigations have evaluated this issue. This study aimed to investigate the association between exposure to aeroallergens during the week preceding birth and the risk of early delivery among preterm and term pregnancies. METHODS: We identified data on 225,234 singleton births that occurred in six large cities in the province of Ontario, Canada, from 2004 to 2011 (April to October) from a birth registry. We obtained daily counts of pollen grains and fungal spores from fixed-site monitoring stations in each city and assigned them to pregnancy period of each birth. Associations between exposure to aeroallergens in the preceding week and risk of delivery among preterm (<37 gestational weeks), early-term (37-38 weeks), and full-term (≥39 weeks) pregnancies were evaluated with Cox regression models, adjusting for maternal characteristics, meteorologic parameters, and air pollution concentrations, and pooled across the six cities. RESULTS: The risk of delivery increased by 3% per interquartile range width (IQRw = 22.1 grains/m) increase in weed pollen the day before birth among early-term (hazard ratio [HR] = 1.03; 95% confidence interval [CI]: 1.01, 1.05) and full-term pregnancies (HR = 1.03; 95% CI: 1.01, 1.04). Exposure to fungal spores cumulated over 0 to 2 lagged days was associated with increased risk of delivery among full-term pregnancies only (HR = 1.07; 95% CI: 1.01, 1.12). We observed no associations among preterm deliveries. CONCLUSIONS: Increasing concentrations of ambient weed pollen and fungal spores may be associated with earlier delivery among term births.

Exposure to air pollution near a steel plant is associated with reduced heart rate variability: a randomised crossover study.

BACKGROUND: Epidemiological studies have shown that as ambient air pollution (AP) increases the risk of cardiovascular mortality also increases. The mechanisms of this effect may be linked to alterations in autonomic nervous system function. We wished to examine the effects of industrial AP on heart rate variability (HRV), a measure of subtle changes in heart rate and rhythm representing autonomic input to the heart. METHODS: Sixty healthy adults were randomized to spend five consecutive 8-h days outdoors in one of two locations: (1) adjacent to a steel plant in the Bayview neighbourhood in Sault Ste Marie Ontario or (2) at a College campus, several kilometers from the plant. Following a 9-16 day washout period, participants spent five consecutive days at the other site. Ambient AP levels and ambulatory electrocardiogram recordings were collected daily. HRV analysis was undertaken on a segment of the ambulatory ECG recording during a 15 min rest period, near the end of the 8-h on-site day. Standard HRV parameters from both time and frequency domains were measured. Ambient AP was measured with fixed site monitors at both sites. Statistical analysis was completed using mixed-effects models. RESULTS: Compared to the College site, HRV was statistically significantly reduced at the Bayview site by 13% (95%CI 3.6,19.2) for the standard deviation of normal to normal, 8% (95%CI 0.1, 4.9) for the percent normal to normal intervals differing by more than 50 ms, and 15% (95%CI 74.9, 571.2) for low frequency power. Levels of carbon monoxide, sulphur dioxide, nitrogen dioxide, and fine and ultrafine particulates were slightly, but statistically significantly, elevated at Bayview when compared to College. Interquartile range changes in individual air pollutants were significantly associated with reductions in HRV measured on the same day. The patterns of effect showed a high degree of consistency, with nearly all pollutants significantly inversely associated with at least one measure of HRV. CONCLUSIONS: The significant associations between AP and changes in HRV suggest that ambient AP near a steel plant may impact autonomic nervous system control of the heart.

Infant birth weight and third trimester maternal plasma markers of vascular integrity: the MIREC study.

BACKGROUND: There is paucity of information on mechanisms constituting adverse birth outcomes. We assessed here the relationship between vascular integrity and adverse birth effects. METHODS AND RESULTS: Third trimester maternal plasma (n = 144) from the Maternal-Infant Research on Environmental Chemicals Study (MIREC) was analysed for vascular, inflammatory and oxidative stress markers by HPLC-fluorescence, protein array and EIA method. Analysis of the <25th and >75th percentile birth weight subgroups revealed markers associated with birth weight (ETs, MMP-9, VEGF, and 8-isoPGF-2α) and gestational age (ET-1, MMP-2, and VEGF). CONCLUSIONS: Mechanistic insights into adverse birth outcome pathways can be achieved by integrating information on multiple biomarkers, physiology using systems biology approach.

Development of an integrated approach for comparison of in vitro and in vivo responses to particulate matter.

BACKGROUND: Association of particulate matter with adverse health effects has been established in epidemiological studies and animal experiments. Epidemiological studies are difficult to undertake while animal studies are impractical for high-throughput toxicity testing. The ease and rapidity of in vitro tests emphasizes their potential for use in risk assessment of chemicals and particles. We examined the association between in vitro and in vivo responses to ambient particles, to determine the potential of cell-based assays as standalone toxicity screening tools. METHODS: Assays of cytotoxicity and key inflammatory mediators were applied to determine the in vitro biological potency of a panel of urban and mineral particles in J774A.1 macrophages and A549 lung epithelial cells. The particles were also screened for the presence of AhR agonists using the Ah receptor-dependent gene induction assay and for endotoxin using the Limulus amebocyte lysate assay. A subset of the particles with a contrasting in vitro toxicity profile was delivered intratracheally in BALB/c mice to assess their in vivo biological potency. Results from various bioassays were combined within the in vitro and in vivo models. The combined potency measures were examined for associations. RESULTS: Overall, J774A.1 cells were more sensitive to particle effects than A549 cells. Whereas the combined cytotoxicity estimates were highly correlated between the two cell lines, the combined in vitro inflammatory potency estimates were not, emphasizing functional differences of the two cell types. Secretion of inflammatory markers by J774A.1 cells was correlated with AhR ligand binding profile and endotoxin levels of particles. Particle instillation led to an acute toxicity response in BALB/c mice, with neutrophilia and release of inflammatory mediators. While the combined toxicity estimates were not correlated between in vitro and in vivo models, the combined inflammatory and integrated potency estimates (toxicity and inflammation) approached the threshold for significance (p = 0.052) in a correlation within in vitro and in vivo models, with a ranking of fine particle (DWR1), minerals (TiO2, CRI) and coarse particles (SRM-, EHC-type) from low to high potency. CONCLUSION: Integration of in vitro endpoints shows promise in determining adverse outcomes of particle exposures in vivo. The devised data reduction and computational approach will prove useful in the development of models for assessment of hazard potential of particles; however, distinct models may be needed for particles of different type, such as urban particles vs. mineral particles, nanomaterials.

The modifying effect of socioeconomic status on the relationship between traffic, air pollution and respiratory health in elementary schoolchildren.

The volume and type of traffic and exposure to air pollution have been found to be associated with respiratory health, but few studies have considered the interaction with socioeconomic status at the household level. We investigated the relationships of respiratory health related to traffic type, traffic volume, and air pollution, stratifying by socioeconomic status, based on household income and education, in 3591 schoolchildren in Windsor, Canada. Interquartile range changes in traffic exposure and pollutant levels were linked to respiratory symptoms and objective measures of lung function using generalised linear models for three levels of income and education. In 95% of the relationships among all cases, the odds ratios for reported respiratory symptoms (a decrease in measured lung function), based on an interquartile range change in traffic exposure or pollutant, were greater in the lower income/education groups than the higher, although the odds ratios were in most cases not significant. However, in up to 62% of the cases, the differences between high and low socioeconomic groups were statistically significant, thus indicating socioeconomic status (SES) as a significant effect modifier. Our findings indicate that children from lower socioeconomic households have a higher risk of specific respiratory health problems (chest congestion, wheezing) due to traffic volume and air pollution exposure.

Assessment of urinary metabolite excretion after rat acute exposure to perfluorooctanoic acid and other peroxisomal proliferators.

Perfluorooctanoic acid (PFOA) is a persistent environmental contaminant. Activation of the peroxisome proliferator activated receptor alpha (PPARα) resulting from exposure to PFOA has been extensively studied in rodents. However, marked differences in response to peroxisome proliferators prevent extrapolation of rodent PPARα activation to human health risks and additional molecular mechanisms may also be involved in the biological response to PFOA exposure. To further explore the potential involvement of such additional pathways, the effects of PFOA exposure on urinary metabolites were directly compared with those of other well-known PPARα agonists. Male rats were administered PFOA (10, 33, or 100 mg/kg/d), fenofibrate (100 mg/kg/d), or di(2-ethylhexyl) phthalate (100 mg/kg/d) by gavage for 3 consecutive days and allowed to recover for 4 days, and overnight urine was collected. Greater urinary output was observed exclusively in PFOA-treated rats as the total fraction of PFOA excreted in urine increased with the dose administered. Assessment of urinary metabolites (ascorbic acid, quinolinic acid, 8-hydroxy-2'-deoxyguanosine, and malondialdehyde) provided additional information on PFOA's effects on hepatic glucuronic acid and tryptophan-nicotinamide adenine dinucleotide (NAD) pathways and on oxidative stress, whereas increased liver weight and palmitoyl-CoA oxidase activity indicative of PPARα activation and peroxisomal proliferation persisted up to day five after the last exposure.

Indirect adjustment for multiple missing variables applicable to environmental epidemiology.

OBJECTIVES: Develop statistical methods for survival models to indirectly adjust hazard ratios of environmental exposures for missing risk factors. METHODS: A partitioned regression approach for linear models is applied to time to event survival analyses of cohort study data. Information on the correlation between observed and missing risk factors is obtained from ancillary data sources such as national health surveys. The relationship between the missing risk factors and survival is obtained from previously published studies. We first evaluated the methodology using simulations, by considering the Weibull survival distribution for a proportional hazards regression model with varied baseline functions, correlations between an adjusted variable and an adjustment variable as well as selected censoring rates. Then we illustrate the method in a large, representative Canadian cohort of the association between concentrations of ambient fine particulate matter and mortality from ischemic heart disease. RESULTS: Indirect adjustment for cigarette smoking habits and obesity increased the fine particulate matter-ischemic heart disease association by 3%-123%, depending on the number of variables considered in the adjustment model due to the negative correlation between these two risk factors and ambient air pollution concentrations in Canada. The simulations suggested that the method yielded small relative bias (<40%) for most cohort designs encountered in environmental epidemiology. CONCLUSIONS: This method can accommodate adjustment for multiple missing risk factors simultaneously while accounting for the associations between observed and missing risk factors and between missing risk factors and health endpoints.

Extreme ambient temperatures and cardiorespiratory emergency room visits: assessing risk by comorbid health conditions in a time series study.

BACKGROUND: Extreme ambient temperatures are an increasing public health concern. The aim of this study was to assess if persons with comorbid health conditions were at increased risk of adverse cardiorespiratory morbidity during temperature extremes. METHODS: A time series study design was applied to 292,666 and 562,738 emergency room (ER) visits for cardiovascular and respiratory diseases, respectively, that occurred in Toronto area hospitals between April 1st 2002 and March 31st 2010. Subgroups of persons with comorbid health conditions were identified. Relative risks (RRs) and their corresponding 95% confidence intervals (CIs) were estimated using a Poisson regression model with distributed lag non-linear model, and were adjusted for the confounding influence of seasonality, relative humidity, day-of-the-week, outdoor air pollutants and daily influenza ER visits. Effect modification by comorbid health conditions was tested using the relative effect modification (REM) index. RESULTS: Stronger associations of cardiovascular disease ER visits were observed for persons with diabetes compared to persons without diabetes (REM = 1.12; 95% CI: 1.01 - 1.27) with exposure to the cumulative short term effect of extreme hot temperatures (i.e. 99th percentile of temperature distribution vs. 75th percentile). Effect modification was also found for comorbid respiratory disease (REM = 1.17; 95% CI: 1.02 - 1.44) and cancer (REM = 1.20; 95% CI: 1.02 - 1.49) on respiratory disease ER visits during short term hot temperature episodes. The effect of extreme cold temperatures (i.e. 1st percentile of temperature distribution vs. 25th percentile) on cardiovascular disease ER visits were stronger for individuals with comorbid cardiac diseases (REM = 1.47; 95% CI: 1.06 - 2.23) and kidney diseases (REM = 2.43; 95% CI: 1.59 - 8.83) compared to those without these conditions when cumulated over a two-week period. CONCLUSIONS: The identification of those most susceptible to temperature extremes is important for public health officials to implement adaptation measures to manage the impact of extreme temperatures on population health.

Ambient air pollution exposure and COVID-19 related hospitalizations in Santiago, Chile.

Morbidity and mortality from several diseases are increased on days of higher ambient air pollution. We carried out a daily time-series analysis with distributive lags to study the influence of short-term air pollution exposure on COVID-19 related hospitalization in Santiago, Chile between March 16 and August 31, 2020. Analyses were adjusted for temporal trends, ambient temperature, and relative humidity, and stratified by age and sex. 26,579 COVID-19 hospitalizations were recorded of which 24,501 were laboratory confirmed. The cumulative percent change in hospitalizations (95% confidence intervals) for an interquartile range increase in air pollutants were: 1.1 (0.2, 2.0) for carbon monoxide (CO), 0.30 (0.0, 0.50) for nitrogen dioxide (NO2), and 2.7 (1.9, 3.0) for particulate matter of diameter ≤ 2.5 microns (PM2.5). Associations with ozone (O3), particulate matter of diameter ≤ 10 microns (PM10) and sulfur dioxide (SO2) were not significant. The observed effect of PM2.5 was significantly greater for females and for those individuals ≥ 65 years old. This study provides evidence that daily increases in air pollution, especially PM2.5, result in a higher observed risk of hospitalization from COVID-19. Females and the elderly may be disproportionately affected.

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.