Maternal smoking during pregnancy increases the risk of gut microbiome-associated childhood overweight and obesity.

Childhood obesity is linked to maternal smoking during pregnancy. Gut microbiota may partially mediate this association and could be potential targets for intervention; however, its role is understudied. We included 1,592 infants from the Canadian Healthy Infants Longitudinal Development Cohort. Data on environmental exposure and lifestyle factors were collected prenatally and throughout the first three years. Weight outcomes were measured at one and three years of age. Stool samples collected at 3 and 12 months were analyzed by sequencing the V4 region of 16S rRNA to profile microbial compositions and magnetic resonance spectroscopy to quantify the metabolites. We showed that quitting smoking during pregnancy did not lower the risk of offspring being overweight. However, exclusive breastfeeding until the third month of age may alleviate these risks. We also reported that maternal smoking during pregnancy significantly increased Firmicutes abundance and diversity. We further revealed that Firmicutes diversity mediates the elevated risk of childhood overweight and obesity linked to maternal prenatal smoking. This effect possibly occurs through excessive microbial butyrate production. These findings add to the evidence that women should quit smoking before their pregnancies to prevent microbiome-mediated childhood overweight and obesity risk, and indicate the potential obesogenic role of excessive butyrate production in early life.

Evidence Synthesis of Observational Studies in Environmental Health: Lessons Learned from a Systematic Review on Traffic-Related Air Pollution.

BACKGROUND: There is a long tradition in environmental health of using frameworks for evidence synthesis, such as those of the U.S. Environmental Protection Agency for its Integrated Science Assessments and the International Agency for Research on Cancer Monographs. The framework, Grading of Recommendations Assessment, Development, and Evaluation (GRADE), was developed for evidence synthesis in clinical medicine. The U.S. Office of Health Assessment and Translation (OHAT) elaborated an approach for evidence synthesis in environmental health building on GRADE. METHODS: We applied a modified OHAT approach and a broader "narrative" assessment to assess the level of confidence in a large systematic review on traffic-related air pollution and health outcomes. DISCUSSION: We discuss several challenges with the OHAT approach and its implementation and suggest improvements for synthesizing evidence from observational studies in environmental health. We consider the determination of confidence using a formal rating scheme of up- and downgrading of certain factors, the treatment of every factor as equally important, and the lower initial confidence rating of observational studies to be fundamental issues in the OHAT approach. We argue that some observational studies can offer high-confidence evidence in environmental health. We note that heterogeneity in magnitude of effect estimates should generally not weaken the confidence in the evidence, and consistency of associations across study designs, populations, and exposure assessment methods may strengthen confidence in the evidence. We mention that publication bias should be explored beyond statistical methods and is likely limited when large and collaborative studies comprise most of the evidence and when accrued over several decades. We propose to identify possible key biases, their most likely direction, and their potential impacts on the results. We think that the OHAT approach and other GRADE-type frameworks require substantial modification to align better with features of environmental health questions and the studies that address them. We emphasize that a broader, "narrative" evidence assessment based on the systematic review may complement a formal GRADE-type evaluation. https://doi.org/10.1289/EHP11532.

Assessing secondhand and thirdhand tobacco smoke exposure in Canadian infants using questionnaires, biomarkers, and machine learning.

BACKGROUND: As smoking prevalence has decreased in Canada, particularly during pregnancy and around children, and technological improvements have lowered detection limits, the use of traditional tobacco smoke biomarkers in infant populations requires re-evaluation. OBJECTIVE: We evaluated concentrations of urinary nicotine biomarkers, cotinine and trans-3'-hydroxycotinine (3HC), and questionnaire responses. We used machine learning and prediction modeling to understand sources of tobacco smoke exposure for infants from the CHILD Cohort Study. METHODS: Multivariable linear regression models, chosen through a combination of conceptual and data-driven strategies including random forest regression, assessed the ability of questionnaires to predict variation in urinary cotinine and 3HC concentrations of 2017 3-month-old infants. RESULTS: Although only 2% of mothers reported smoking prior to and throughout their pregnancy, cotinine and 3HC were detected in 76 and 89% of the infants' urine (n = 2017). Questionnaire-based models explained 31 and 41% of the variance in cotinine and 3HC levels, respectively. Observed concentrations suggest 0.25 and 0.50 ng/mL as cut-points in cotinine and 3HC to characterize SHS exposure. This cut-point suggests that 23.5% of infants had moderate or regular smoke exposure. SIGNIFICANCE: Though most people make efforts to reduce exposure to their infants, parents do not appear to consider the pervasiveness and persistence of secondhand and thirdhand smoke. More than half of the variation in urinary cotinine and 3HC in infants could not be predicted with modeling. The pervasiveness of thirdhand smoke, the potential for dermal and oral routes of nicotine exposure, along with changes in public perceptions of smoking exposure and risk warrant further exploration.

Fugitive Emissions of Volatile Organic Compounds from a Tailings Pond in the Oil Sands Region of Alberta.

Tailings ponds in the oil sands (OS) region in Alberta, Canada, have been associated with fugitive emissions of volatile organic compounds (VOCs) and other pollutants to the atmosphere. However, the contribution of tailings ponds to the total fugitive emissions of VOCs from OS operations remains uncertain. To address this knowledge gap, a field study was conducted in the summer of 2017 at Suncor's Pond 2/3 to estimate emissions of a suite of pollutants including 68 VOCs using a combination of micrometeorological methods and measurements from a flux tower. The results indicate that in 2017, Pond 2/3 was an emission source of 3322 ± 727 tons of VOCs including alkanes, aromatics, and oxygenated and sulfur-containing organics. While the total VOC emissions were approximately a factor of 2 higher than those reported by Suncor, the individual VOC species emissions varied by up to a factor of 12. A chemical mass balance (CMB) receptor model was used to estimate the contribution of the tailings pond to VOC pollution events in a nearby First Nations and Metis community in Fort McKay. CMB results indicate that Suncor Pond 2/3 contributed up to 57% to the total mass of VOCs measured at Fort McKay, reinforcing the importance of accurate VOC emission estimation methods for tailings ponds.

An ecological analysis of long-term exposure to PM2.5 and incidence of COVID-19 in Canadian health regions.

BACKGROUND: Ambient fine particulate matter (PM2.5) is associated with a wide range of acute and chronic health effects, including increased risk of respiratory infection. However, evidence specifically related to novel coronavirus disease (COVID-19) is limited. METHODS: COVID-19 case counts for 111 Canadian health regions were obtained from the COVID-19 Canada Open Data portal. Annual PM2.5 data for 2000-2016 were estimated from a national exposure surface based on remote sensing, chemical transport modelling and ground observations, and minimum and maximum temperature data for 2000-2015 were based on a national interpolated surface derived from thin-plate smoothing splines. Population counts and sociodemographic data by health region were obtained from the 2016 census, and health data (self-rated health and prevalence of smoking, obesity, and selected chronic diseases) by health region, were obtained from the Canadian Community Health Survey. Data on total number of COVID-19 tests and changes in mobility comparing post-vs. pre-introduction of social distancing measures were available by province. Data were analyzed using negative binomial regression models. RESULTS: After controlling for province, temperature, demographic and health characteristics and days since peak incidence by health region, long-term PM2.5 exposure exhibited a positive association with COVID-19 incidence (incidence rate ratio 1.07, 95% confidence interval 0.97-1.18 per µg/m3). This association was larger in magnitude and statistically significant in analyses excluding provinces that reported cases only for aggregated health regions, excluding health regions with less than median population density, and restricted to the most highly affected provinces (Quebec and Ontario). CONCLUSIONS: We observed a positive association between COVID-19 incidence and long-term PM2.5 exposure in Canadian health regions. The association was larger in magnitude and statistically significant in more highly affected health regions and those with potentially less exposure measurement error. While our results generate hypotheses for further testing, they should be interpreted with caution and require further examination using study designs less prone to bias.

Disease assimilation: The mortality impacts of fine particulate matter on immigrants to Canada.

BACKGROUND: Immigrants make up 20% of the Canadian population; however, little is known about the mortality impacts of fine particulate matter (PM2.5) air pollution on immigrants compared with non-immigrants, or about how impacts may change with duration in Canada. DATA AND METHODS: This study used the 2001 Canadian Census Health and Environment Cohort, a longitudinal cohort of 3.5 million individuals, of which 764,000 were classified as immigrants (foreign-born). Postal codes from annual income tax files were used to account for mobility among respondents and to assign annual PM2.5 concentrations from 1998 to 2016. Exposures were estimated as a three-year moving average prior to the follow-up year. Cox survival models were used to determine hazard ratios (HRs) for cause-specific mortality, comparing the Canadian and foreign-born populations, with further stratification by year of immigration grouped into 10-year cohorts. RESULTS: Differences in urban-rural settlement patterns resulted in greater exposure to PM2.5 for immigrants compared with non-immigrants (mean = 9.3 vs. 7.5 µg/m3), with higher exposures among more recent immigrants. In fully adjusted models, immigrants had higher HRs per 10 µg/m3 increase in PM2.5 concentration compared with Canadian-born individuals for cardiovascular mortality (HR [95% confidence interval] = 1.22 [1.12 to 1.34] vs. 1.12 [1.07 to 1.18]) and cerebrovascular mortality (HR = 1.25 [1.03 to 1.52] vs. 1.03 [0.93 to 1.15]), respectively. However, tests for differences between the two groups were not significant when Cochran's Q test was used. No significant associations were found for respiratory outcomes, except for lung cancer in non-immigrants (HR = 1.10 [1.02 to 1.18]). When stratified by year of immigration, differences in HRs across varied by cause of death. DISCUSSION: In Canada, PM2.5 is an equal-opportunity risk factor, with immigrants experiencing similar if not higher mortality risks compared with non-immigrants for cardiovascular-related causes of death. Some notable differences also existed with cerebrovascular and lung cancer deaths. Continued reductions in air pollution, particularly in urban areas, will improve the health of the Canadian population as a whole.

Traffic-Related Air Pollution and Carotid Plaque Burden in a Canadian City With Low-Level Ambient Pollution.

Background The association between fine particulate matter and cardiovascular disease has been convincingly demonstrated. The role of traffic-related air pollutants is less clear. To better understand the role of traffic-related air pollutants in cardiovascular disease development, we examined associations between NO2, carotid atherosclerotic plaque, and cardiometabolic disorders associated with cardiovascular disease. Methods and Results Cross-sectional analyses were conducted among 2227 patients (62.9±13.8 years; 49.5% women) from the Stroke Prevention and Atherosclerosis Research Centre (SPARC) in London, Ontario, Canada. Total carotid plaque area measured by ultrasound, cardiometabolic disorders, and residential locations were provided by SPARC medical records. Long-term outdoor residential NO2 concentrations were generated by a land use regression model. Associations between NO2, total carotid plaque area, and cardiometabolic disorders were examined using multiple regression models adjusted for age, sex, smoking, and socioeconomic status. Mean NO2 was 5.4±1.6 ppb in London, Ontario. NO2 was associated with a significant increase in plaque (3.4 mm2 total carotid plaque area per 1 ppb NO2), exhibiting a linear dose-response. NO2 was also positively associated with triglycerides, total cholesterol, and the ratio of low- to high-density lipoprotein cholesterol (P<0.05). Diabetes mellitus mediated the relationship between NO2 and total carotid plaque area (P<0.05). Conclusions Our results demonstrate that even low levels of traffic-related air pollutants are linked to atherosclerotic plaque burden, an association that may be partially attributable to pollution-induced diabetes mellitus. Our findings suggest that reducing ambient concentrations in cities with NO2 below current standards would result in additional health benefits. Given the billions of people exposed to traffic emissions, our study supports the global public health significance of reducing air pollution.

Low concentrations of fine particle air pollution and mortality in the Canadian Community Health Survey cohort.

BACKGROUND: Approximately 2.9 million deaths are attributed to ambient fine particle air pollution around the world each year (PM2.5). In general, cohort studies of mortality and outdoor PM2.5 concentrations have limited information on individuals exposed to low levels of PM2.5 as well as covariates such as smoking behaviours, alcohol consumption, and diet which may confound relationships with mortality. This study provides an updated and extended analysis of the Canadian Community Health Survey-Mortality cohort: a population-based cohort with detailed PM2.5 exposure data and information on a number of important individual-level behavioural risk factors. We also used this rich dataset to provide insight into the shape of the concentration-response curve for mortality at low levels of PM2.5. METHODS: Respondents to the Canadian Community Health Survey from 2000 to 2012 were linked by postal code history from 1981 to 2016 to high resolution PM2.5 exposure estimates, and mortality incidence to 2016. Cox proportional hazard models were used to estimate the relationship between non-accidental mortality and ambient PM2.5 concentrations (measured as a three-year average with a one-year lag) adjusted for socio-economic, behavioural, and time-varying contextual covariates. RESULTS: In total, 50,700 deaths from non-accidental causes occurred in the cohort over the follow-up period. Annual average ambient PM2.5 concentrations were low (i.e. 5.9 µg/m3, s.d. 2.0) and each 10 µg/m3 increase in exposure was associated with an increase in non-accidental mortality (HR = 1.11; 95% CI 1.04-1.18). Adjustment for behavioural covariates did not materially change this relationship. We estimated a supra-linear concentration-response curve extending to concentrations below 2 µg/m3 using a shape constrained health impact function. Mortality risks associated with exposure to PM2.5 were increased for males, those under age 65, and non-immigrants. Hazard ratios for PM2.5 and mortality were attenuated when gaseous pollutants were included in models. CONCLUSIONS: Outdoor PM2.5 concentrations were associated with non-accidental mortality and adjusting for individual-level behavioural covariates did not materially change this relationship. The concentration-response curve was supra-linear with increased mortality risks extending to low outdoor PM2.5 concentrations.

Evaluation of a method to indirectly adjust for unmeasured covariates in the association between fine particulate matter and mortality.

BACKGROUND: Indirect adjustment via partitioned regression is a promising technique to control for unmeasured confounding in large epidemiological studies. The method uses a representative ancillary dataset to estimate the association between variables missing in a primary dataset with the complete set of variables of the ancillary dataset to produce an adjusted risk estimate for the variable in question. The objective of this paper is threefold: 1) evaluate the method for non-linear survival models, 2) formalize an empirical process to evaluate the suitability of the required ancillary matching dataset, and 3) test modifications to the method to incorporate time-varying exposure data, and proportional weighting of datasets. METHODS: We used the association between fine particle air pollution (PM2.5) with mortality in the 2001 Canadian Census Health and Environment Cohort (CanCHEC, N = 2.4 million, 10-years follow-up) as our primary dataset, and the 2001 cycle of the Canadian Community Health Survey (CCHS, N = 80,630) as the ancillary matching dataset that contained confounding risk factor information not available in CanCHEC (e.g., smoking). The main evaluation process used a gold-standard approach wherein two variables (education and income) available in both datasets were excluded, indirectly adjusted for, and compared to true models with education and income included to assess the amount of bias correction. An internal validation for objective 1 used only CanCHEC data, whereas an external validation for objective 2 replaced CanCHEC with the CCHS. The two proposed modifications were applied as part of the validation tests, as well as in a final indirect adjustment of four missing risk factor variables (smoking, alcohol use, diet, and exercise) in which adjustment direction and magnitude was compared to models using an equivalent longitudinal cohort with direct adjustment for the same variables. RESULTS: At baseline (2001) both cohorts had very similar PM2.5 distributions across population characteristics, although levels for CCHS participants were consistently 1.8-2.0 µg/m3 lower. Applying sample-weighting largely corrected for this discrepancy. The internal validation tests showed minimal downward bias in PM2.5 mortality hazard ratios of 0.4-0.6% using a static exposure, and 1.7-3% when a time-varying exposure was used. The external validation of the CCHS as the ancillary dataset showed slight upward bias of -0.7 to -1.1% and downward bias of 1.3-2.3% using the static and time-varying approaches respectively. CONCLUSIONS: The CCHS was found to be fairly well representative of CanCHEC and its use in Canada for indirect adjustment is warranted. Indirect adjustment methods can be used with survival models to correct hazard ratio point estimates and standard errors in models missing key covariates when a representative matching dataset is available. The results of this formal evaluation should encourage other cohorts to assess the suitability of ancillary datasets for the application of the indirect adjustment methodology to address potential residual confounding.

Carbonaceous aerosol sampling of gasoline direct injection engine exhaust with an integrated organic gas and particle sampler.

Positive and negative artifacts of particle-phase organic carbon (p-OC) and the polycyclic aromatic hydrocarbons (PAHs) in gasoline direct injection (GDI) engine exhaust particulate matter (PM) were assessed using an integrated organic gas and particle sampler (IOGAPS). Three configurations (denuder + sorbent impregnated filters (SIFs), upstream Zefluor filter + denuder + SIFs, and standard filter pack + SIFs) were used to collect GDI exhaust samples at cold start and highway cruise operating conditions with no aftertreatment. Approximately 35% of the measured GDI p-OC was attributed to positive artifacts; negative artifacts were not detectable due to low overall SVOC concentrations. GDI engine exhaust PAH concentrations were approximately 10 times higher during cold start than highway cruise. At highway cruise, pyrene and fluoranthene were the dominant PAHs in the undenuded filter pack; downstream of the denuder benzo(a)anthracene was the dominant PAH. From a comparison of our findings to published PAH emission factors we estimate that three-way catalyst conversion efficiencies of PAHs were approximately 80% for 3 of the 15 PAHs measured during highway cruise operation. These conversion efficiencies may be considerably lower during cold start operation when the three-way catalyst has not reached its operating temperature. Our previous work showed that adverse biological responses to GDI engine exhaust exposure may be dominated by the particle phase when measured downstream of a Teflon filter. Understanding the partitioning characteristics of PAHs may help elucidate specific PAHs contributing to this effect.

Metals and oxidative potential in urban particulate matter influence systemic inflammatory and neural biomarkers: A controlled exposure study.

BACKGROUND: Oxidative stress and inflammation are considered to be important pathways leading to particulate matter (PM)-associated disease. In this exploratory study, we examined the effects of metals and oxidative potential (OP) in urban PM on biomarkers of systemic inflammation, oxidative stress and neural function. METHODS: Fifty-three healthy non-smoking volunteers (mean age 28 years, twenty-eight females) were exposed to coarse (2.5-10 µm, mean 213 µg/m3), fine (0.15-2.5 µm, 238 µg/m3), and/or ultrafine concentrated ambient PM (<0.3 µm, 136 µg/m3). Exposures lasted 130 min, separated by ≥2 weeks. Metal concentrations and OP (measured by ascorbate and glutathione depletion in synthetic airway fluid) in PM were analyzed. Blood and urine samples were collected pre-exposure, and 1-h and 21-h post exposure for assessment of biomarkers. We used mixed-regression models to analyze associations adjusting for PM size and mass concentration. RESULTS: Results for metals were expressed as change (%) from daily pre-exposure biomarker levels after exposure to a metal at a level equivalent to the mean concentration. Exposure to various metals (silver, aluminum, barium, copper, iron, potassium, lithium, nickel, tin, and/or vanadium) was significantly associated with increased levels of various blood or urinary biomarkers. For example, the blood inflammatory marker vascular endothelia growth factor (VEGF) increased 5.3% (95% confidence interval: 0.3%, 10.2%) 1-h post exposure to nickel; the traumatic brain injury marker ubiquitin C-terminal hydrolase L1 (UCHL1) increased 11% (1.2%, 21%) and 14% (0.3%, 29%) 1-h and 21-h post exposure to barium, respectively; and the systemic stress marker cortisol increased 1.5% (0%, 2.9%) and 1.5% (0.5%, 2.8%) 1-h and 21-h post exposure to silver, respectively. Urinary DNA oxidation marker 8­hydroxy­deoxy­guanosine increased 14% (6.4%, 21%) 1-h post exposure to copper; urinary neural marker vanillylmandelic acid increased 29% (3%, 54%) 1-h post exposure to aluminum; and urinary cortisol increased 88% (0.9%, 176%) 1-h post exposure to vanadium. Results for OP were expressed as change (%) from daily pre-exposure biomarker levels after exposure to ascorbate-related OP at a level equivalent to the mean concentration, or for exposure to glutathione-related OP at a level above the limit of detection. Exposure to ascorbate- or glutathione-related OP was significantly associated with increased inflammatory and neural biomarkers including interleukin-6, VEGF, UCHL1, and S100 calcium-binding protein B in blood, and malondialdehyde and 8-hydroxy-deoxy-guanosine in urine. For example, UCHL1 increased 9.4% (1.8%, 17%) in blood 21-h post exposure to ascorbate-related OP, while urinary malondialdehyde increased 19% (3.6%, 35%) and 8-hydroxy-deoxy-guanosine increased 24% (2.9%, 48%) 21-h post exposure to ascorbate- and glutathione-related OP, respectively. CONCLUSION: Our results from this exploratory study suggest that metal constituents and OP in ambient PM may influence biomarker levels associated with systemic inflammation, oxidative stress, perturbations of neural function, and systemic physiological stress.

Associations between fine particulate matter and mortality in the 2001 Canadian Census Health and Environment Cohort.

BACKGROUND: Large cohort studies have been used to characterise the association between long-term exposure to fine particulate matter (PM2.5) air pollution with non-accidental, and cause-specific mortality. However, there has been no consensus as to the shape of the association between concentration and response. METHODS: To examine the shape of this association, we developed a new cohort based on respondents to the 2001 Canadian census long-form. We applied new annual PM2.5 concentration estimates based on remote sensing and ground measurements for Canada at a 1km spatial scale from 1998 to 2011. We followed 2.4 million respondents who were non-immigrants aged 25-90 years and did not reside in an institution over a 10 year period for mortality. Exposures were assigned as a 3-year mean prior to the follow-up year. Income tax files were used to account for residential mobility among respondents using postal codes, with probabilistic imputation used for missing postal codes in the tax data. We used Cox survival models to determine hazard ratios (HRs) for cause-specific mortality. We also estimated Shape Constrained Health Impact Functions (a concentration-response function) for selected causes of death. RESULTS: In models stratified by age, sex, airshed, and population centre size, and adjusted for individual and neighbourhood socioeconomic variables, HR estimates for non-accidental mortality were HR = 1.18 (95% CI: 1.15-1.21) per 10µg/m3 increase in concentration. We observed higher HRs for cardiovascular disease (HR=1.25; 95% CI: 1.19-1.31), cardio-metabolic disease (HR = 1.27; 95% CI: 1.21-1.33), ischemic heart disease (HR = 1.36; 95% CI: 1.28-1.44) and chronic obstructive pulmonary disease (COPD) mortality (HR = 1.24; 95% CI: 1.11-1.39) compared to HR for all non-accidental causes of death. For non-accidental, cardio-metabolic, ischemic heart disease, respiratory and COPD mortality, the shape of the concentration-response curve was supra-linear, with larger differences in relative risk for lower concentrations. For both pneumonia and lung cancer, there was some suggestion that the curves were sub-linear. CONCLUSIONS: Associations between ambient concentrations of fine particulate matter and several causes of death were non-linear for each cause of death examined.

The Kingston Allergy Birth Cohort: Exploring parentally reported respiratory outcomes through the lens of the exposome.

BACKGROUND: The Kingston Allergy Birth Cohort (KABC) is a prenatally recruited cohort initiated to study the developmental origins of allergic disease. Kingston General Hospital was chosen for recruitment because it serves a population with notable diversity in environmental exposures relevant to the emerging concept of the exposome. OBJECTIVE: To establish a profile of the KABC using the exposome framework and examine parentally reported respiratory symptoms to 2 years of age. METHODS: Data on phase 1 of the cohort (n = 560 deliveries) were compiled, and multivariate Cox proportional hazards regression models were used to determine associations with respiratory symptoms. RESULTS: The KABC exhibits diversity within the 3 exposome domains of general external (socioeconomic status, rural or urban residence), specific external (cigarette smoke, breastfeeding, mold or dampness), and internal (respiratory health, gestational age), as well as significant associations between exposures from different domains. Significant associations emerged between parental reports of wheeze or cough without a cold and prenatal cigarette smoke exposure, mold or dampness in the home, and the use of air fresheners in the early-life home environment. Breastfeeding, older siblings, and increased gestational age were associated with decreased respiratory symptoms. CONCLUSION: The KABC is a unique cohort with diversity that can be leveraged for exposomics-based studies. This study found that all 3 domains of the exposome had effects on the respiratory health of KABC children. Ongoing studies using phase 1 of the KABC continue to explore the internal exposome through allergy skin testing and epigenetic analyses and the specific external domain through in-home environmental analyses, air pollution modeling, and ultimately potential convergences within and among domains.

Maternal exposure to ambient air pollution and risk of early childhood cancers: A population-based study in Ontario, Canada.

BACKGROUND: There are increasing concerns regarding the role of exposure to ambient air pollution during pregnancy in the development of early childhood cancers. OBJECTIVE: This population based study examined whether prenatal and early life (<1year of age) exposures to ambient air pollutants, including nitrogen dioxide (NO2) and particulate matter with aerodynamic diameters ≤2.5µm (PM2.5), were associated with selected common early childhood cancers in Canada. METHODS: 2,350,898 singleton live births occurring between 1988 and 2012 were identified in the province of Ontario, Canada. We assigned temporally varying satellite-derived estimates of PM2.5 and land-use regression model estimates of NO2 to maternal residences during pregnancy. Incident cases of 13 subtypes of pediatric cancers among children up to age 6 until 2013 were ascertained through administrative health data linkages. Associations of trimester-specific, overall pregnancy and first year of life exposures were evaluated using Cox proportional hazards models, adjusting for potential confounders. RESULTS: A total of 2044 childhood cancers were identified. Exposure to PM2.5, per interquartile range increase, over the entire pregnancy, and during the first trimester was associated with an increased risk of astrocytoma (hazard ratio (HR) per 3.9µg/m3=1.38 (95% CI: 1.01, 1.88) and, HR per 4.0µg/m3=1.40 (95% CI: 1.05-1.86), respectively). We also found a positive association between first trimester NO2 and acute lymphoblastic leukemia (ALL) (HR=1.20 (95% CI: 1.02-1.41) per IQR (13.3ppb)). CONCLUSIONS: In this population-based study in the largest province of Canada, results suggest an association between exposure to ambient air pollution during pregnancy, especially in the first trimester and an increased risk of astrocytoma and ALL. Further studies are required to replicate the findings of this study with adjustment for important individual-level confounders.

Influence of exposure to coarse, fine and ultrafine urban particulate matter and their biological constituents on neural biomarkers in a randomized controlled crossover study.

BACKGROUND: Epidemiological studies have reported associations between air pollution and neuro-psychological conditions. Biological mechanisms behind these findings are still not clear. OBJECTIVES: We examined changes in blood and urinary neural biomarkers following exposure to concentrated ambient coarse, fine and ultrafine particles. METHODS: Fifty healthy non-smoking volunteers, mean age 28years, were exposed to coarse (2.5-10µm, mean 213µg/m3) and fine (0.15-2.5µm, mean 238µg/m3) concentrated ambient particles (CAPs), and filtered ambient and/or medical air. Twenty-five participants were exposed to ultrafine CAP (mean size 59.6nm, range 47.0-69.8nm), mean (136µg/m3) and filtered medical air. Exposures lasted 130min, separated by ≥2weeks, and the biological constituents endotoxin and ß-1,3-d-glucan of each particle size fraction were measured. Blood and urine samples were collected pre-exposure, and 1-hour and 21-hour post-exposure to determine neural biomarker levels. Mixed-model regressions assessed associations between exposures and changes in biomarker levels. RESULTS: Results were expressed as percent change from daily pre-exposure biomarker levels. Exposure to coarse CAP was significantly associated with increased urinary levels of the stress-related biomarkers vanillylmandelic acid (VMA) and cortisol when compared with exposure to filtered medical air [20% (95% confidence interval: 1.0%, 38%) and 64% (0.2%, 127%), respectively] 21hours post-exposure. However exposure to coarse CAP was significantly associated with decreases in blood cortisol [-26.0% (-42.4%, -9.6%) and -22.4% (-43.7%, -1.1%) at 1h and 21h post-exposure, respectively]. Biological molecules present in coarse CAP were significantly associated with blood biomarkers indicative of blood brain barrier integrity. Endotoxin content was significantly associated with increased blood ubiquitin C-terminal hydrolase L1 [UCHL1, 11% (5.3%, 16%) per ln(ng/m3+1)] 1-hour post-exposure, while ß-1,3-d-glucan was significantly associated with increased blood S100B [6.3% (3.2%, 9.4%) per ln(ng/m3+1)], as well as UCHL1 [3.1% (0.4%, 5.9%) per ln(ng/m3+1)], one-hour post-exposure. Fine CAP was marginally associated with increased blood UCHL1 when compared with exposure to filtered medical air [17.7% (-1.7%, 37.2%), p=0.07] 21hours post-exposure. Ultrafine CAP was not significantly associated with changes in any blood and urinary neural biomarkers examined. CONCLUSION: Ambient coarse particulate matter and its biological constituents may influence neural biomarker levels that reflect perturbations of blood-brain barrier integrity and systemic stress response.

Oil sands operations as a large source of secondary organic aerosols.

Worldwide heavy oil and bitumen deposits amount to 9 trillion barrels of oil distributed in over 280 basins around the world, with Canada home to oil sands deposits of 1.7 trillion barrels. The global development of this resource and the increase in oil production from oil sands has caused environmental concerns over the presence of toxic compounds in nearby ecosystems and acid deposition. The contribution of oil sands exploration to secondary organic aerosol formation, an important component of atmospheric particulate matter that affects air quality and climate, remains poorly understood. Here we use data from airborne measurements over the Canadian oil sands, laboratory experiments and a box-model study to provide a quantitative assessment of the magnitude of secondary organic aerosol production from oil sands emissions. We find that the evaporation and atmospheric oxidation of low-volatility organic vapours from the mined oil sands material is directly responsible for the majority of the observed secondary organic aerosol mass. The resultant production rates of 45-84 tonnes per day make the oil sands one of the largest sources of anthropogenic secondary organic aerosols in North America. Heavy oil and bitumen account for over ten per cent of global oil production today, and this figure continues to grow. Our findings suggest that the production of the more viscous crude oils could be a large source of secondary organic aerosols in many production and refining regions worldwide, and that such production should be considered when assessing the environmental impacts of current and planned bitumen and heavy oil extraction projects globally.

Cytotoxic and inflammatory potential of size-fractionated particulate matter collected repeatedly within a small urban area.

BACKGROUND: Exposure to coarse, fine, and ultrafine particles is associated with adverse population health impacts. We investigated whether size-fractionated particles collected repeatedly in the vicinity of industrial (steel mills and associated coking operations, wastewater treatment), high traffic, and residential areas display systematic differences in biological potency. METHODS: Particulate matter (PM<0.1, PM0.1-0.5, PM0.5-2.5, PM2.5-10, PM>10) samples collected at sites within Windsor, Ontario, were screened for biological potency in human A549 lung epithelial and murine J774A.1 macrophage-like cells using cytotoxicity bioassays (cellular ATP, resazurin reduction, lactate dehydrogenase (LDH) release), cytokine production, and transcript profiles. Potency was determined from the slope of each dose-effect relationship. RESULTS: Cytotoxic potency varied across size fractions and within a fraction across sites and sampling periods, suggesting that particle composition, in addition to size and mass, affected particle toxicity. While ATP and LDH profiles showed some similarity, resazurin reduction (a measure of metabolic activity) exhibited a unique pattern of response, indicating that the cytotoxicity assays were sensitive to distinct particle characteristics. Chemical speciation varied in relation to prevailing winds, consistent with enrichment of source emissions (e.g. higher metal and polycyclic aromatic hydrocarbon content downwind of the industrial site). Notwithstanding this variability, site-dependent differences in particle toxicity were evident, including greater potency of coarse fractions at the industrial site and of ultrafine particles at the traffic site (Site × Size interactions, p < 0.05). Regression of potency against particle constituents revealed correlations between resazurin reduction, induction of metal-responsive genes, and metal content, which were particularly strong for the coarse fraction, and between cytokine release and endotoxin, suggesting that these factors were important drivers of biological effects that explain, at least in part, the contrasting potencies of particles compared on an equivalent mass basis. CONCLUSIONS: The data show that 1) particle potency and composition can exhibit significant temporal variation in relation to source contributions; 2) sources may differentially impact the potency of specific size fractions; and 3) particle constituents, notably metals and endotoxin, may elicit distinct biological responses. Together, the data are consistent with the notion that sources and composition, in addition to size and mass concentration, are relevant to particle toxicity.

Personal black carbon exposure influences ambulatory blood pressure: air pollution and cardiometabolic disease (AIRCMD-China) study.

Few prospective studies have assessed the blood pressure effect of extremely high air pollution encountered in Asia's megacities. The objective of this study was to evaluate the association between combustion-related air pollution with ambulatory blood pressure and autonomic function. During February to July 2012, personal black carbon was determined for 5 consecutive days using microaethalometers in patients with metabolic syndrome in Beijing, China. Simultaneous ambient fine particulate matter concentration was obtained from the Beijing Municipal Environmental Monitoring Center and the US Embassy. Twenty-four-hour ambulatory blood pressure and heart rate variability were measured from day 4. Arterial stiffness and endothelial function were obtained at the end of day 5. For statistical analysis, we used generalized additive mixed models for repeated outcomes and generalized linear models for single/summary outcomes. Mean (SD) of personal black carbon and fine particulate matter during 24 hours was 4.66 (2.89) and 64.2 (36.9) µg/m(3). Exposure to high levels of black carbon in the preceding hours was associated significantly with adverse cardiovascular responses. A unit increase in personal black carbon during the previous 10 hours was associated with an increase in systolic blood pressure of 0.53 mm Hg and diastolic blood pressure of 0.37 mm Hg (95% confidence interval, 0.17-0.89 and 0.10-0.65 mm Hg, respectively), a percentage change in low frequency to high frequency ratio of 5.11 and mean interbeat interval of -0.06 (95% confidence interval, 0.62-9.60 and -0.11 to -0.01, respectively). These findings highlight the public health effect of air pollution and the importance of reducing air pollution.

Spatial association between ambient fine particulate matter and incident hypertension.

BACKGROUND: Laboratory studies suggest that exposure to fine particulate matter (≤2.5 µm in diameter) (PM2.5) can trigger a combination of pathophysiological responses that may induce the development of hypertension. However, epidemiological evidence relating PM2.5 and hypertension is sparse. We thus conducted a population-based cohort study to determine whether exposure to ambient PM2.5 is associated with incident hypertension. METHODS AND RESULTS: We assembled a cohort of 35 303 nonhypertensive adults from Ontario, Canada, who responded to 1 of 4 population-based health surveys between 1996 and 2005 and were followed up until December 31, 2010. Incident diagnoses of hypertension were ascertained from the Ontario Hypertension Database, a validated registry of persons diagnosed with hypertension in Ontario (sensitivity=72%, specificity=95%). Estimates of long-term exposure to PM2.5 at participants' postal-code residences were derived from satellite observations. We used Cox proportional hazards models, adjusting for various individual and contextual risk factors including body mass index, smoking, physical activity, and neighbourhood-level unemployment rates. We conducted various sensitivity analyses to assess the robustness of the effect estimate, such as investigating several time windows of exposure and controlling for potential changes in the risk of hypertension over time. Between 1996 and 2010, we identified 8649 incident cases of hypertension and 2296 deaths. For every 10-µg/m(3) increase of PM2.5, the adjusted hazard ratio of incident hypertension was 1.13 (95% confidence interval, 1.05-1.22). Estimated associations were comparable among all sensitivity analyses. CONCLUSIONS: This study supports an association between PM2.5 and incident hypertension.