Associations of neighborhood greenspace, and active living environments with autism spectrum disorders: A matched case-control study in Ontario, Canada.

BACKGROUND: Increasing evidence links early life residential exposure to natural urban environmental attributes and positive health outcomes in children. However, few studies have focused on their protective effects on the risk of autism spectrum disorder (ASD). The aim of this study was to investigate the associations of neighborhood greenspace, and active living environments during pregnancy with ASD in young children (≤6 years). METHODS: We conducted a population-based matched case-control study of singleton term births in Ontario, Canada for 2012-2016. The ASD and environmental data was generated using the Ontario Autism Spectrum Profile, the Better Outcomes Registry & Network Ontario, and Canadian Urban Environmental Health Research Consortium. We employed conditional logistic regressions to estimate the odds ratio (OR) between ASD and environmental factors characterizing selected greenspace metrics and neighborhoods conducive to active living (i.e., green view index (GVI), normalized difference vegetation index (NDVI), tree canopy, park proximity and active living environments index (ALE)). RESULTS: We linked 8643 mother-child pairs, including 1554 cases (18%). NDVI (OR 1.034, 0.944-1.024, per Inter Quartile Range [IQR] = 0.08), GVI (OR 1.025, 95% CI 0.953-1.087, per IQR = 9.45%), tree canopy (OR 0.992, 95% CI 0.903-1.089, per IQR = 6.24%) and the different categories of ALE were not associated with ASD in adjusted models for air pollution. In contrast, living closer to a park was protective (OR 0.888, 0.833-0.948, per 0.06 increase in park proximity index), when adjusted for air pollution. CONCLUSIONS: This study reported mixed findings showing both null and beneficial effects of green spaces and active living environments on ASD. Further investigations are warranted to elucidate the role of exposure to greenspaces and active living environments on the development of ASD.

Multi-pollutant case-crossover models of all-cause and cause-specific mortality and hospital admissions by age group in 47 Canadian cities.

Most of the existing epidemiological studies have investigated adverse health effects of multiple air pollutants for a limited number of cities, thus the evidence of the health impacts is limited and it is challenging to compare these results because of different modeling approaches and potential publication bias. In this paper, we expand the number of Canadian cities, with the use of the most recent available health data. A multi-pollutant model in a case-crossover design is used to investigate the short-term impacts of air pollution on various health outcomes in 47 Canadian main cities, comparing three age groups (all-age, senior (age 66+), non-senior). The main findings are that a 14 ppb increase of O3 was associated with a 0.17%-2.78% (0.62%-1.46%) increase in the odds of all-age respiratory mortality (hospitalization). A 12.8 ppb increase of NO2 was associated with a 0.57%-1.47% (0.68%-1.86%) increase in the odds of all-age (non-senior) respiratory hospitalization. A 7.6 µgm-3 increase of PM2.5 was associated with a 0.19%-0.69% (0.33%-1.1%) increase in the odds of all-age (non-senior) respiratory hospitalization.

Critical Time Windows for Air Pollution Exposure and Birth Weight in a Multicity Canadian Pregnancy Cohort.

BACKGROUND: Maternal prenatal exposure to air pollution has been associated with adverse birth outcomes. However, previous studies focused on a priori time intervals such as trimesters reported inconsistent associations. OBJECTIVES: We investigated time-varying vulnerability of birth weight to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) using flexible time intervals. METHODS: We analyzed 1,300 live, full-term births from Maternal-Infant Research on Environmental Chemicals, a Canadian prospective pregnancy cohort spanning 10 cities (2008-2011). Daily PM2.5 and NO2 concentrations were estimated from ground-level monitoring, satellite models, and land-use regression, and assigned to participants from pre-pregnancy through delivery. We developed a flexible two-stage modeling method-using a Bayesian Metropolis-Hastings algorithm and empirical density threshold-to identify time-dependent vulnerability to air pollution without specifying exposure periods a priori. This approach identified critical windows with varying lengths (2-363 days) and critical windows that fell within, or straddled, predetermined time periods (i.e., trimesters). We adjusted the models for detailed infant and maternal covariates. RESULTS: Critical windows associated with reduced birth weight were identified during mid- to late-pregnancy for both PM2.5 and NO2: -6 g (95% credible interval: -11, -1 g) and -5 g (-10, -0.1 g) per µg/m3 PM2.5 during gestational days 91-139 and 249-272, respectively; and -3 g (-5, -1 g) per ppb NO2 during days 55-145. DISCUSSION: We used a novel, flexible selection method to identify critical windows when maternal exposures to air pollution were associated with decrements in birth weight. Our results suggest that air pollution impacts on fetal development may not be adequately captured by trimester-based analyses.

Correction to: Systematic review and meta-analysis of case-crossover and time-series studies of short term outdoor nitrogen dioxide exposure and ischemic heart disease morbidity.

An amendment to this paper has been published and can be accessed via the original article.

Systematic review and meta-analysis of case-crossover and time-series studies of short term outdoor nitrogen dioxide exposure and ischemic heart disease morbidity.

BACKGROUND: Nitrogen dioxide (NO2) is a pervasive urban pollutant originating primarily from vehicle emissions. Ischemic heart disease (IHD) is associated with a considerable public health burden worldwide, but whether NO2 exposure is causally related to IHD morbidity remains in question. Our objective was to determine whether short term exposure to outdoor NO2 is causally associated with IHD-related morbidity based on a synthesis of findings from case-crossover and time-series studies. METHODS: MEDLINE, Embase, CENTRAL, Global Health and Toxline databases were searched using terms developed by a librarian. Screening, data extraction and risk of bias assessment were completed independently by two reviewers. Conflicts between reviewers were resolved through consensus and/or involvement of a third reviewer. Pooling of results across studies was conducted using random effects models, heterogeneity among included studies was assessed using Cochran's Q and I2 measures, and sources of heterogeneity were evaluated using meta-regression. Sensitivity of pooled estimates to individual studies was examined using Leave One Out analysis and publication bias was evaluated using Funnel plots, Begg's and Egger's tests, and trim and fill. RESULTS: Thirty-eight case-crossover studies and 48 time-series studies were included in our analysis. NO2 was significantly associated with IHD morbidity (pooled odds ratio from case-crossover studies: 1.074 95% CI 1.052-1.097; pooled relative risk from time-series studies: 1.022 95% CI 1.016-1.029 per 10 ppb). Pooled estimates for case-crossover studies from Europe and North America were significantly lower than for studies conducted elsewhere. The high degree of heterogeneity among studies was only partially accounted for in meta-regression. There was evidence of publication bias, particularly for case-crossover studies. For both case-crossover and time-series studies, pooled estimates based on multi-pollutant models were smaller than those from single pollutant models, and those based on older populations were larger than those based on younger populations, but these differences were not statistically significant. CONCLUSIONS: We concluded that there is a likely causal relationship between short term NO2 exposure and IHD-related morbidity, but important uncertainties remain, particularly related to the contribution of co-pollutants or other concomitant exposures, and the lack of supporting evidence from toxicological and controlled human studies.

The association between ambient air pollution concentrations and psychological distress.

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

Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015.

BACKGROUND: Exposure to ambient air pollution increases morbidity and mortality, and is a leading contributor to global disease burden. We explored spatial and temporal trends in mortality and burden of disease attributable to ambient air pollution from 1990 to 2015 at global, regional, and country levels. METHODS: We estimated global population-weighted mean concentrations of particle mass with aerodynamic diameter less than 2·5 µm (PM2·5) and ozone at an approximate 11 km × 11 km resolution with satellite-based estimates, chemical transport models, and ground-level measurements. Using integrated exposure-response functions for each cause of death, we estimated the relative risk of mortality from ischaemic heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, lung cancer, and lower respiratory infections from epidemiological studies using non-linear exposure-response functions spanning the global range of exposure. FINDINGS: Ambient PM2·5 was the fifth-ranking mortality risk factor in 2015. Exposure to PM2·5 caused 4·2 million (95% uncertainty interval [UI] 3·7 million to 4·8 million) deaths and 103·1 million (90·8 million 115·1 million) disability-adjusted life-years (DALYs) in 2015, representing 7·6% of total global deaths and 4·2% of global DALYs, 59% of these in east and south Asia. Deaths attributable to ambient PM2·5 increased from 3·5 million (95% UI 3·0 million to 4·0 million) in 1990 to 4·2 million (3·7 million to 4·8 million) in 2015. Exposure to ozone caused an additional 254 000 (95% UI 97 000-422 000) deaths and a loss of 4·1 million (1·6 million to 6·8 million) DALYs from chronic obstructive pulmonary disease in 2015. INTERPRETATION: Ambient air pollution contributed substantially to the global burden of disease in 2015, which increased over the past 25 years, due to population ageing, changes in non-communicable disease rates, and increasing air pollution in low-income and middle-income countries. Modest reductions in burden will occur in the most polluted countries unless PM2·5 values are decreased substantially, but there is potential for substantial health benefits from exposure reduction. FUNDING: Bill & Melinda Gates Foundation and Health Effects Institute.

Meta-Analysis Methods to Estimate the Shape and Uncertainty in the Association Between Long-Term Exposure to Ambient Fine Particulate Matter and Cause-Specific Mortality Over the Global Concentration Range.

Estimates of excess mortality associated with exposure to ambient concentrations of fine particulate matter have been obtained from either a single cohort study or pooling information from a small number of studies. However, standard frequentist methods of pooling are known to underestimate statistical uncertainty in the true risk distribution when the number of studies pooled is small. Alternatively, Bayesian pooling methods using noninformative priors yield unrealistically large amounts of uncertainty in this case. We present a new hybrid frequentist-bayesian framework for meta-analysis that incorporates features of both frequentist and Bayesian approaches, yielding estimated uncertainty distributions that are more useful for burden estimation. We also present an example of mortality risk due to long-term exposure to ambient fine particulate matter obtained from a small number of cohort studies conducted in the United States and Europe. We compare our new risk uncertainty distribution to that obtained by the integrated exposure-response (IER) model used in the Global Burden of Disease 2010 project for which risk was modeled over the entire global concentration range. We suggest a method to incorporate our new risk uncertainty distribution based on the relatively low concentrations observed in the United States and western Europe into the IER model, thus extending risk estimation to the global concentration range.

Approximations for Estimating Change in Life Expectancy Attributable to Air Pollution in Relation to Multiple Causes of Death Using a Cause Modified Life Table.

There is considerable debate as to the most appropriate metric for characterizing the mortality impacts of air pollution. Life expectancy has been advocated as an informative measure. Although the life-table calculus is relatively straightforward, it becomes increasingly cumbersome when repeated over large numbers of geographic areas and for multiple causes of death. Two simplifying assumptions were evaluated: linearity of the relation between excess rate ratio and change in life expectancy, and additivity of cause-specific life-table calculations. We employed excess rate ratios linking PM2.5 and mortality from cerebrovascular disease, chronic obstructive pulmonary disease, ischemic heart disease, and lung cancer derived from a meta-analysis of worldwide cohort studies. As a sensitivity analysis, we employed an integrated exposure response function based on the observed risk of PM2.5 over a wide range of concentrations from ambient exposure, indoor exposure, second-hand smoke, and personal smoking. Impacts were estimated in relation to a change in PM2.5 from 19.5 µg/m(3) estimated for Toronto to an estimated natural background concentration of 1.8 µg/m(3) . Estimated changes in life expectancy varied linearly with excess rate ratios, but at higher values the relationship was more accurately represented as a nonlinear function. Changes in life expectancy attributed to specific causes of death were additive with maximum error of 10%. Results were sensitive to assumptions about the air pollution concentration below which effects on mortality were not quantified. We have demonstrated valid approximations comprising expression of change in life expectancy as a function of excess mortality and summation across multiple causes of death.

Outdoor fine particles and nonfatal strokes: systematic review and meta-analysis.

BACKGROUND: Epidemiologic studies find that long- and short-term exposure to fine particles (PM2.5) is associated with adverse cardiovascular outcomes, including ischemic and hemorrhagic strokes. However, few systematic reviews or meta-analyses have synthesized these results. METHODS: We reviewed epidemiologic studies that estimated the risks of nonfatal strokes attributable to ambient PM2.5. To pool risks among studies we used a random-effects model and 2 Bayesian approaches. The first Bayesian approach assumes a normal prior that allows risks to be zero, positive or negative. The second assumes a gamma prior, where risks can only be positive. This second approach is proposed when the number of studies pooled is small, and there is toxicological or clinical literature to support a causal relation. RESULTS: We identified 20 studies suitable for quantitative meta-analysis. Evidence for publication bias is limited. The frequentist meta-analysis produced pooled risk ratios of 1.06 (95% confidence interval = 1.00-1.13) and 1.007 (1.003-1.010) for long- and short-term effects, respectively. The Bayesian meta-analysis found a posterior mean risk ratio of 1.08 (95% posterior interval = 0.96-1.26) and 1.008 (1.003-1.013) from a normal prior, and of 1.05 (1.02-1.10) and 1.008 (1.004-1.013) from a gamma prior, for long- and short-term effects, respectively, per 10 µg/m PM2.5. CONCLUSIONS: Sufficient evidence exists to develop a concentration-response relation for short- and long-term exposures to PM2.5 and stroke incidence. Long-term exposures to PM2.5 result in a higher risk ratio than short-term exposures, regardless of the pooling method. The evidence for short-term PM2.5-related ischemic stroke is especially strong.

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.

Circulatory health risks from additive multi-pollutant models: short-term exposure to three common air pollutants in Canada.

Numerous studies have reported adverse health effects of ambient air pollution on circulatory health outcomes mainly based on single-pollutant models. However, limited studies have focused on adjusted effect of multi-pollutant exposures on public health. This study aimed to examine short-term effects of three common air pollutants-ground-level ozone (ozone), nitrogen dioxide (NO2), and fine particulate matter (PM2.5)-through multi-pollutant models for mixed effect of adjustment. Daily data (circulatory hospitalization and mortality) and hourly data (air pollutants and temperature) were collected for 24 Canadian cities for 2001-2012. We applied generalized additive over-dispersion Poisson regression models with 1, 2, or 3 pollutants for city-specific risks, and Bayesian hierarchical models for national risks. This study found little mixed effect of adjustment through multi-pollutant models (ozone and/or NO2 and/or PM2.5) for circulatory hospitalization or mortality in Canada for 2001-2012, indicating that the 1-pollutant model did not result in considerable under- or over-estimates. It seemed weak-to-moderate correlations among air pollutants did not change the significant effect of one air pollutant after accounting for others. Inconsistent findings between other previous studies and this study indicate the need of comparable study design for multi-pollutant effect analysis.

Tracking national and regional spatial-temporal mortality risk associated with NO2 concentrations in Canada: a Bayesian hierarchical two-level model.

The association between daily variations in urban air quality and mortality has been well documented using time series statistical methods. This approach assumes a constant association over time. We develop a space-time dynamic model that relaxes this assumption, thus more directly examining the hypothesis that improvements in air quality translate into improvements in public health. We postulate a Bayesian hierarchical two-level model to estimate annual mortality risks at regional and national levels and to track both risk and heterogeneity of risk within and between regions over time. We illustrate our methods using daily nitrogen dioxide concentrations (NO2) and nonaccidental mortality data collected for 1984-2004 in 24 Canadian cities. Estimates of risk and heterogeneity are compared by cause of mortality (cardio-pulmonary [CP] versus non-CP) and season, respectively. Over the entire period, the NO2 risk for CP mortality was slightly lower but with a narrower credible interval than that for non-CP mortality, mainly due to an unusually low risk for a single year (1998). Warm season NO2 risk was higher than cold season risk for both CP and non-CP mortality. For 21 years overall there were no significant differences detected among the four regional NO2 risks. We found overall that there was no strong evidence for time trends in NO2 risk at national or regional levels. However, an increasing linear time trend in the annual between-region heterogeneities was detected, which suggests the differences in risk among the four regions are getting larger, and further studies are necessary to understand the increasing heterogeneity.

Impact of personal and ambient-level exposures to nitrogen dioxide and particulate matter on cardiovascular function.

This work explored the association between nitrogen dioxide (NO(2)) and PM(2.5) components with changes in cardiovascular function in an adult non-smoking cohort. The cohort consisted of 65 volunteers participating in the US EPA's Detroit Exposure and Aerosol Research Study (DEARS) and a University of Michigan cardiovascular sub-study. Systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), brachial artery diameter (BAD), brachial artery flow-mediated dilatation (FMD) and nitroglycerin-mediated arterial dilatation (NMD) were collected by in-home examinations. A maximum of 336 daily environmental and health effect observations were obtained. Daily potassium air concentrations were associated with significant decreases in DBP (-0.0447 mmHg/ng/m(3) ± 0.0132, p = 0.0016, lag day 0) among participants compliant with the personal monitoring protocol. Personal NO(2) exposures resulted in significant changes in BAD (e.g., 0.0041 mm/ppb ± 0.0019, p = 0.0353, lag day 1) and FMD (0.0612 ± 0.0235, p = 0.0103, lag day 0) among other findings.

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

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

Differences in blood pressure and vascular responses associated with ambient fine particulate matter exposures measured at the personal versus community level.

BACKGROUND: Higher ambient fine particulate matter (PM2.5) levels can be associated with increased blood pressure and vascular dysfunction. OBJECTIVES: To determine the differential effects on blood pressure and vascular function of daily changes in community ambient- versus personal-level PM2.5 measurements. METHODS: Cardiovascular outcomes included vascular tone and function and blood pressure measured in 65 non-smoking subjects. PM2.5 exposure metrics included 24 h integrated personal- (by vest monitors) and community-based ambient levels measured for up to 5 consecutive days (357 observations). Associations between community- and personal-level PM2.5 exposures with alterations in cardiovascular outcomes were assessed by linear mixed models. RESULTS: Mean daily personal and community measures of PM2.5 were 21.9±24.8 and 15.4±7.5 µg/m³, respectively. Community PM2.5 levels were not associated with cardiovascular outcomes. However, a 10 µg/m³ increase in total personal-level PM2.5 exposure (TPE) was associated with systolic blood pressure elevation (+1.41 mm Hg; lag day 1, p<0.001) and trends towards vasoconstriction in subsets of individuals (0.08 mm; lag day 2 among subjects with low secondhand smoke exposure, p=0.07). TPE and secondhand smoke were associated with elevated systolic blood pressure on lag day 1. Flow-mediated dilatation was not associated with any exposure. CONCLUSIONS: Exposure to higher personal-level PM2.5 during routine daily activity measured with low-bias and minimally-confounded personal monitors was associated with modest increases in systolic blood pressure and trends towards arterial vasoconstriction. Comparable elevations in community PM2.5 levels were not related to these outcomes, suggesting that specific components within personal and background ambient PM2.5 may elicit differing cardiovascular responses.

Pollutant-sex specific differences in respiratory hospitalization and mortality risk attributable to short-term exposure to ambient air pollution.

BACKGROUND: Many studies have reported associations of individual pollutants with respiratory hospitalization and mortality based on different populations, which makes it difficult to directly compare adverse health effects among multiple air pollutants. OBJECTIVES: The study goal is to compare acute respiratory-related hospitalization and mortality associated with short-term exposure to three ambient air pollutants and analyze differences in health risks by season, age and sex. METHODS: Hourly measurements of air pollutants (ozone, NO2, PM2.5) and temperature were collected from ground-monitors for 24 cities along with daily hospitalization (1996-2012) and mortality (1984-2012) data. National associations between air pollutant and health outcome were estimated for season (warm, cold vs. year-round), age (base ≥ 1, seniors > 65), and sex (females ≥ 1 and males ≥ 1) using Bayesian hierarchical models. RESULTS: Overall, the three air pollutants were significantly associated with acute respiratory health outcomes at different lag-days. For respiratory hospitalization, the increased risks in percent changes with 95% posterior intervals for a 10-unit increase in each pollutant were: ozone (lag1, 0.7% (0.4, 0.9)), NO2 (lag0, 0.7% (0.1, 1.4)), and PM2.5 (lag1, 1.3% (0.7, 1.9)). For respiratory mortality: ozone (lag2, 1.2% (0.4, 1.9)), NO2 (lag1, 2.1% (0.6, 3.5)), and PM2.5 (lag1, 0.6% (-1.0, 2.2)). While some differences in risk were observed by season and age group, sex-specific differences were more pronounced. Compared with males, females had a higher respiratory mortality risk (1.8% (0.6, 2.9) vs 0.5% (-0.3, 1.3)) from ozone, a higher respiratory hospitalization risk (0.9% (0.0, 1.8) vs 0.6% (-0.3, 1.4)) but lower mortality risk (1.4% (-1.0, 3.7) vs 2.2% (0.4, 4.0)) from NO2, and a lower hospitalization risk (0.7% (-0.2, 1.7) vs 1.8% (1.0, 2.6)) from PM2.5. CONCLUSION: This study reports significant health effects of short-term exposure to three ambient air pollutants on respiratory hospitalization (ozone≈NO2 < PM2.5 per-10 unit; ozone>NO2 ≈ PM2.5 per-IQR) and mortality (ozone≈NO2 > PM2.5) in Canada. Pollutant-sex-specific differences were found, but inconclusive due to limited biological and physiological explanations. Further studies are warranted to understand the pollutant-sex specific differences.

Comparison of hospitalization and mortality associated with short-term exposure to ambient ozone and PM2.5 in Canada.

BACKGROUND: Hospitalization and mortality (H-M) have been linked to air pollution separately. However, previous studies have not adequately compared whether air pollution is a stronger risk factor for hospitalization or mortality. This study aimed to investigate differences in H-M risk from short-term ozone and PM2.5 exposures, and determine whether differences are modified by season, age, and sex. METHODS: Daily ozone, PM2.5, temperature, and all-cause H-M counts (ICD-10, A00-R99) were collected for 22-24 Canadian cities for up to 29 years. Generalized additive Poisson models were employed to estimate associations between each pollutant and health outcome, which were compared across season (warm, cold, or year-round), age (all ages or seniors > 65), and sex. RESULTS: Overall, ozone and PM2.5 showed higher season-specific risk of mortality than hospitalization: warm-season ozone: 0.54% (95% credible interval, 0.20, 0.85) vs. 0.14% (0.02, 0.27) per 10 ppb; and year-round PM2.5: 0.90% (0.33, 1.41) vs. 0.29% (0.03, 0.56) per 10 µg/m3. While age showed little H-M difference, sex appeared to be a modifier of H-M risk. While females had higher mortality risk, males had higher hospitalization risk: for females, ozone 0.87% (0.36, 1.35) vs. -0.03% (-0.18, 0.11) and PM2.5 1.19% (0.40, 1.90) vs. 0.19% (-0.10, 0.47); and for males ozone 0.20% (-0.28, 0.65) vs. 0.35% (0.18, 0.51). CONCLUSION: This study found H-M differences attributable to ozone and PM2.5, suggesting that both are stronger risk factors for mortality than hospitalization. In addition, there were clear H-M differences by sex: specifically, females showed higher mortality risk and males showed higher hospitalization risk.

Systematic review and meta-analysis of cohort studies of long term outdoor nitrogen dioxide exposure and mortality.

OBJECTIVE: To determine whether long term exposure to outdoor nitrogen dioxide (NO2) is associated with all-cause or cause-specific mortality. METHODS: MEDLINE, Embase, CENTRAL, Global Health and Toxline databases were searched using terms developed by a librarian. Screening, data extraction and risk of bias assessment were completed independently by two reviewers. Conflicts were resolved through consensus and/or involvement of a third reviewer. Pooling of results across studies was conducted using random effects models, heterogeneity among included studies was assessed using Cochran's Q and I2 measures, and sources of heterogeneity were evaluated using meta-regression. Sensitivity of pooled estimates to individual studies was examined and publication bias was evaluated using Funnel plots, Begg's and Egger's tests, and trim and fill. RESULTS: Seventy-nine studies based on 47 cohorts, plus one set of pooled analyses of multiple European cohorts, met inclusion criteria. There was a consistently high degree of heterogeneity. After excluding studies with probably high or high risk of bias in the confounding domain (n = 12), pooled hazard ratios (HR) indicated that long term exposure to NO2 was significantly associated with mortality from all/ natural causes (pooled HR 1.047, 95% confidence interval (CI), 1.023-1.072 per 10 ppb), cardiovascular disease (pooled HR 1.058, 95%CI 1.026-1.091), lung cancer (pooled HR 1.083, 95%CI 1.041-1.126), respiratory disease (pooled HR 1.062, 95%CI1.035-1.089), and ischemic heart disease (pooled HR 1.111, 95%CI 1.079-1.144). Pooled estimates based on multi-pollutant models were consistently smaller than those from single pollutant models and mostly non-significant. CONCLUSIONS: For all causes of death other than cerebrovascular disease, the overall quality of the evidence is moderate, and the strength of evidence is limited, while for cerebrovascular disease, overall quality is low and strength of evidence is inadequate. Important uncertainties remain, including potential confounding by co-pollutants or other concomitant exposures, and limited supporting mechanistic evidence. (PROSPERO registration number CRD42018084497).

Temporal trends in associations between ozone and circulatory mortality in age and sex in Canada during 1984-2012.

BACKGROUND: Considerable research has been conducted on the association between ground-level ozone (ozone) and various causes of mortality, but the relationships by age and sex (biological) have been inconsistent, and temporal trends remain unexplored. OBJECTIVES: The study goals are to investigate the adverse health effects of short-term exposure to ozone on circulatory mortality by age and sex, and to examine trends in annual health effects. METHODS: Daily ozone, temperature, and circulatory mortality counts (ICD I00-I99) were collected for 24 urban cities for 29 years (1984-2012). Associations between ozone and circulatory mortality were estimated using generalized additive Poisson models for season (warm vs. cold), age [base (≥1) vs. seniors (>65)], and sex, accounting for confounders (calendar-time, temperature, day of the week). City-specific estimates were pooled to represent national associations through Bayesian hierarchical models. RESULTS: While the cold season returned insignificant estimates, the warm season showed statistically significant associations: a 10 ppb increase in ozone was associated with 0.7% increase in circulatory mortality with a 95% posterior interval of 0.2%, 1.1%. One-day lagged ozone in the warm season showed little age differences [0.7% (0.23%, 1.12%) vs. 0.8% (0.22%, 1.27%)], but visible sex differences: females were at a higher circulatory mortality risk than males [1.1% (0.31%, 1.71%) vs. 0.3% (-0.46%, 0.98%)]. Annual estimates suggest overall up-down temporal changes; a slightly increasing trend until 2002-2004, and a generally decreasing trend thereafter. CONCLUSION: This study found noticeable sex-related differences in circulatory mortality attributable to short-term exposure to ozone. Further research is warranted to understand whether sex alone, or unknown interactions with other factors derived the differences, and to clarify the specific biological mechanisms underlying differences in risk estimates between females and males.