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.

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.

Does ambient air pollution influence biochemical markers of liver injury? Findings of a cross-sectional population-based survey.

BACKGROUND: There is limited evidence supporting an adverse effect of ambient air pollution on the liver. OBJECTIVES: To test the association between exposure to residential air pollution and serum biochemical indicators of liver injury. METHODS: We used a nationally representative sample of 32,989 participants aged 3-79 years old who participated in the Canadian Health Measures Survey between 2007 and 2019. Cross-sectional associations were assessed by generalized linear mixed models incorporating survey-specific sampling weights. RESULTS: The joint effect of an interquartile range (IQR) increase in nitrogen dioxide (NO2), ozone (O3) and fine particulate matter (PM2.5) was positively and significantly associated with all measures of liver injury adjusting for age, sex, education, income, smoking, alcohol consumption, body mass index (BMI), total cholesterol, diabetes, hypertension, and physical activity. The ranking of effect sizes from largest to smallest percent increases were 8.72% (95% confidence interval [CI] 7.56, 9.88) for alanine aminotransferase (ALT), 5.54% (95%CI 3.31, 7.77) for gamma-glutamyl transferase (GGT), 4.81% (95%CI 3.87, 5.74) for aspartate aminotransferase (AST), 2.46% (95%CI 0.26, 4.65) for total bilirubin (TBIL) and 1.18% (95%CI 0.62, 1.75) for alkaline phosphatase (ALP). Findings were not significantly different when stratified by age (≤16, >16 yr), sex, smoking (current, other), cholesterol (≤6.18, >6.18 mmol/l) and BMI (<30, ≥30 kg/m2). DISCUSSION: These findings suggest that ambient air pollution may have a relatively small impact on the liver, but these changes may have significant impact from a population health perspective, considering the ubiquitous nature of air pollution, or for individuals exposed to very high levels of air pollution.

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.

Biomonitoring of DEET and DCBA in Canadian children following typical protective insect repellent use.

N,N-diethyl-m-toluamide (DEET) is an ingredient found in many consumer insect repellents and its use is recommended to Canadians by government agencies, including Health Canada, for protection against insect bites including mosquitos and ticks. The majority of research on DEET exposure and toxicokinetics in humans has focused on adult populations with little information from vulnerable populations, including children. We aimed to fill this knowledge gap by examining real-world exposure data for DEET and its metabolite 3-diethylcarbamoyl benzoic acid (DCBA) in a sample population of Canadian children. We conducted a 24-h observational exposure human biomonitoring study at three overnight summer camps in Ontario, Canada through July and August 2019. Participating children aged 7-13 years provided multiple spot urine samples over a 24-h period and completed a journal to document insect repellent use and factors that could influence absorption of DEET. Children were instructed to use insect repellent as they usually would while attending a summer camp. Exposure was quantified using the information from the participant's journal and the change in the mass of their insect repellent containers over the course of the study. A total of 389 urine samples were collected from 124 children. Among participants using insect repellent, urinary levels of DEET were elevated between 2 and 8 h post-application and decreased thereafter but remained qualitatively higher than concentrations in participants who did not use insect repellent on the study day, even at 18-22 h post-application. DCBA was the predominant metabolite of DEET exposure in urine. DCBA was elevated between 8 and 14 h post-application, and declined thereafter, but not to the level observed among those who did not use insect repellent on the study day. Children who used more insect repellent, or used higher concentration insect repellent (10%-30% DEET) excreted higher levels of DEET and DCBA. Excreted DEET and DCBA accounted for 0.001% (median) and 1.3% (median) of the estimated applied DEET, respectively. Children did not reach an undetectable level of DEET or DCBA in urine, even among those not using insect repellent during the study day, indicating a potentially complex multi-route exposure to insect repellents in a real world scenario. This work provides targeted biomonitoring data for children intentionally using DEET-based insect repellents for normal protective use, and will support the risk re-evaluation of DEET by Health Canada.

Development of an observational exposure human biomonitoring study to assess Canadian children's DEET exposure during protective use.

Biomonitoring data of N,N-diethyl-meta-toluamide (DEET) in children is scarce and limited to controlled exposure and surveillance studies. We conducted a 24-hour observational exposure and human biomonitoring study designed to estimate use of and exposure to DEET-based insect repellents by Canadian children in an overnight summer camp setting. Here, we present our study design and methodology. In 2019, children between the ages of 7 and 13 took part in the study (n = 126). Children controlled their use of DEET-based insect repellents, and provided an account of their activities at camp that could impact insect repellent absorption. Children provided a total of 389 urine samples throughout the study day, and reported the time that they applied insect repellent, which allowed us to contextualize urinary DEET and metabolite concentrations with respect to the timing of insect repellent application. DEET (2.3%

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.

Urban air pollution and emergency department visits related to central nervous system diseases.

Ambient air pollution has been associated with adverse neurological health outcomes. Ambient pollutants are thought to trigger oxidative stress and inflammation to which vulnerable populations, such as elderly may be particularly susceptible. Our study investigated the possible association between concentrations of ambient air pollutants and the number of emergency department (ED) visits for nervous system disorders among people residing in a large Canadian city. A time-stratified case-crossover study design combining data from the National Ambulatory Care Reporting System (NACRS) and the National Air Pollution Surveillance (NAPS) between 2004 and 2015 was used. Two air quality health indices were considered in additional to specific pollutants, including carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3) and fine particulate matter (PM2.5). Weather condition data were included in the models. ED visits with a discharge diagnosis were identified using ICD-10 codes (G00-G99). The analysis was stratified by sex and age, also by seasons. The associations were investigated in arrays organized as 18 strata and 15 time lags (in days) for each pollutant. Overall, 140,511 ED visits were included for the analysis. Most ED visits were related to episodic and paroxysmal diagnoses (G40-G47, 64%), with a majority of visits for migraines (G43, 39%). Among females, an increase of 0.1ppm ambient CO was associated with an increased risk of paroxysmal diagnoses at day 1 (RR = 1.019 (95%CI 1.004-1.033)), day 6 (1.024 (1.010-1.039)) and day 7 (1.022 (1.007-1.036). PM2.5 and SO2, and air quality indices were similarly associated with ED visits for episodic and paroxysmal disorders in days 6 and 7. Findings highlight that ambient air pollution is associated with an increased number of ED visits for nervous system disorders, particularly visits for paroxysmal diagnoses.

Urban Air Pollution and Emergency Department Visits for Neoplasms and Outcomes of Blood Forming and Metabolic Systems.

This study focused on investigating possible associations between exposure to urban air pollution and the number of emergency department (ED) visits for various health outcomes. The outcomes were grouped into four chapters of the International Classification of Diseases Tenth Revision (ICD-10) system (i.e., Chapter II-IV: "Neoplasms", "Diseases of the blood", "Endocrine, nutritional and metabolic diseases", and XVIII: "Symptoms, signs and abnormal clinical and laboratory findings"). The data were collected for the city of Toronto, Canada, (2004-2015, 4292 days). Four gaseous air pollutants (carbon monoxide (CO), nitrogen dioxide (NO2), ground level ozone (O3), and sulfur dioxide (SO2)) and fine particulate matter (PM2.5), and two calculated air quality health indexes (AQHI) based on Toronto were used. The statistical models were constructed by applying the conditional Poisson regression. The exposure was assessed over a maximum of 15 days (time lags 0-14 days). An analysis was performed with the following strata: sex, age, and seasons. Relative risks (RR) and their 95% confidence intervals (95%CI) were estimated for an increase in concentration by a one interquartile range (IQR). For the AQHI (composed of NO2, O3, and PM2.5), IQR = 1, the estimations for lag 1 and all patients, are RR = 1.023 (95%CI: 1.008, 1.038), 1.026 (1.012, 1.040), 1.013 (1.003, 1.024), and 1.007 (1.003, 1.010) for Chapters II-IV and XVIII, respectively. The results show that in the four large, analyzed health groups, the impact of air quality mainly occurs over a short period (from current day to a maximum of 3 days after exposure).

The association between blood PFAS concentrations and clinical biochemical measures of organ function and metabolism in participants of the Canadian Health Measures Survey (CHMS).

Per- and poly-fluoroalkyl substances (PFAS) are ubiquitous and may persist in human tissue for several years. Only a small proportion of PFAS have been studied for human health effects. We tested the association between human blood levels of six PFAS and several clinical measures of organ and metabolic function in a nationally representative sample of 6768 participants aged 3-79 years old who participated in the Canadian Health Measures Survey. Cross-sectional associations were assessed by generalized linear mixed models incorporating survey-specific sampling weights. An increase in perfluorooctanoic acid (PFOA) equivalent to the magnitude of its geometric mean (GM) of 2.0 µg/L was associated with percentage (95% CI) increases in serum enzymes reflecting liver function: aspartate aminotransferase (AST) 3.7 (1.1, 6.4), gamma-glutamyl transferase (GGT) 11.8 (2.5, 21.8), alanine aminotransferase (ALT) 3.2 (0.5, 5.9), and bilirubin 3.6 (2.7, 4.5). A GM increase in perfluorodecanoic acid (PFDA) of 0.2 µg/L was positively associated with percentage increases in GGT, triglycerides, low-density lipoprotein (LDL) cholesterol, total cholesterol, and calcium with respective increases of 15.5 (2.2, 30.4), 7.0 (1.0, 13.2), 10.7 (5.5, 16.1), 2.8 (0.2, 5.3), and 0.8 (0.3, 1.3). PFOA, perfluorooctane sulfonate (PFOS), PFDA and perfluorononanoic acid (PFNA) were positively associated with GGT. All six congeners were positively associated with at least one biomarker of lipid metabolism, and 5 of 6, PFOA, PFOS, PFDA, perfluorohexane sulfonate (PFHxS) and PFNA were positively associated with serum calcium. Exposure to selected PFAS is associated with clinical blood tests reflecting metabolism and the function of several organ systems. These relatively small changes may possibly indicate early pathology that is clinically inapparent and may possibly be of significance in a general population or in individuals exposed to very high levels of PFAS.

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.

Temporal variation of total mercury levels in the hair of pregnant women from the Maternal-Infant Research on Environmental Chemicals (MIREC) study.

Prenatal exposure to total mercury (T-Hg) comes from both natural and anthropogenic sources. T-Hg can cross the blood-brain and placental barriers, and may be associated with future neurological and physiological dysfunctions. Scalp hair is an optimal and non-invasive indicator of chronic T-Hg exposure. As part of the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, hair samples from 350 women were collected within weeks after giving birth, to determine temporal variations in T-Hg levels from preconception to delivery, and to compare these levels to corresponding levels measured in other matrices (maternal and umbilical cord blood, and infant's meconium). A maximum of 12 one-cm hair segments were cut starting at the scalp; segments closer to the scalp reflected recent exposure (within the last month). For proper comparison, the hair segments were matched with the collection dates for other matrices. GM hair T-Hg levels greatly decreased during pregnancy, from 0.26 µg g-1 (preconception or full-length hair) to 0.18 µg g-1 (at delivery or segments closer to the scalp). A similar decreasing trend was found for T-Hg in maternal blood: 1st trimester (0.60 µg L-1) to 3rd trimester (0.47 µg L-1). The median hair-to-blood ratios of T-Hg levels varied from 364 (1st trimester), to 408 (3rd trimester), to 229 (cord blood). Very low T-Hg levels were detected in meconium. Mercury levels in blood and hair correlated with consumption of large predatory fish.

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.

Decomposition of reactive oxygen species by copper(II) bis(1-pyrazolyl)methane complexes.

Two bis(1-pyrazolyl)alkane ligands, bis(3,5-dimethyl-1-pyrazolyl)methane and bis(4-iodo-3,5-dimethyl-1-pyrazolyl)methane, and their copper(II) complexes, bis(3,5-dimethyl-1-pyrazolyl)methanedinitratocopper(II) [CuL1(NO3)2] and bis(4-iodo-3,5-dimethyl-1-pyrazolyl)methanedinitratocopper(II) [CuL2(NO3)2] x 2H2O, were prepared. Physiochemical properties of the copper(II) complexes were studied by spectroscopic (UV-vis, IR, EPR) techniques and cyclic voltammetry. Spectroscopic analysis revealed a 1:1 stoichiometry of ligand:copper(II) ion and a bidentate coordination mode for the nitrate ions in both of the complexes. According to experimental and theoretical ab initio data, the copper(II) ion is located in an octahedral hexacoordinated environment. Both complexes were able to catalyze the dismutation of superoxide anion (O2*-) (pH 7.5) and decomposition of H2O2 (pH 7.5) and peroxynitrite (pH 10.9). In addition, both complexes exhibited superoxide dismutase (SOD) like activity toward extracellular and intracellular reactive oxygen species produced by activated human neutrophils in whole blood. Thus, these complexes represent useful SOD mimetics with a broad range of antioxidant activity toward a variety of reactive oxidants.