Daniel L. Crouse

Long-Term Ozone Exposure and Mortality in a Large Prospective Study

RATIONALE Tropospheric ozone (O3) is potentially associated with cardiovascular disease risk and premature death. Results from long-term epidemiological studies on O3 are scarce and inconclusive. OBJECTIVES In this study, we examined associations between chronic ambient O3 exposure and all-cause and cause-specific mortality in a large cohort of U.S. adults. METHODS Cancer Prevention Study II participants were enrolled in 1982. A total of 669,046 participants were analyzed, among whom 237,201 deaths occurred through 2004. We obtained estimates of O3 concentrations at the participants residence from a hierarchical Bayesian space-time model. Estimates of fine particulate matter (particulate matter with an aerodynamic diameter of up to 2.5 μm [PM2.5]) and NO2 concentrations were obtained from land use regression. Cox proportional hazards regression models were used to examine mortality associations adjusted for individual- and ecological-level covariates. MEASUREMENTS AND MAIN RESULTS In single-pollutant models, we observed significant positive associations between O3, PM2.5, and NO2 concentrations and all-cause and cause-specific mortality. In two-pollutant models adjusted for PM2.5, significant positive associations remained between O3 and all-cause (hazard ratio [HR] per 10 ppb, 1.02; 95% confidence interval [CI], 1.01-1.04), circulatory (HR, 1.03; 95% CI, 1.01-1.05), and respiratory mortality (HR, 1.12; 95% CI, 1.08-1.16) that were unchanged with further adjustment for NO2. We also observed positive mortality associations with both PM2.5 (both near source and regional) and NO2 in multipollutant models. CONCLUSIONS Findings derived from this large-scale prospective study suggest that long-term ambient O3 contributes to risk of respiratory and circulatory mortality. Substantial health and environmental benefits may be achieved by implementing further measures aimed at controlling O3 concentrations.

Associations of Pregnancy Outcomes and PM2.5 in a National Canadian Study

Background Numerous studies have examined associations between air pollution and pregnancy outcomes, but most have been restricted to urban populations living near monitors. Objectives We examined the association between pregnancy outcomes and fine particulate matter in a large national study including urban and rural areas. Methods Analyses were based on approximately 3 million singleton live births in Canada between 1999 and 2008. Exposures to PM2.5 (particles of median aerodynamic diameter ≤ 2.5 μm) were assigned by mapping the mother’s postal code to a monthly surface based on a national land use regression model that incorporated observations from fixed-site monitoring stations and satellite-derived estimates of PM2.5. Generalized estimating equations were used to examine the association between PM2.5 and preterm birth (gestational age < 37 weeks), term low birth weight (< 2,500 g), small for gestational age (SGA; < 10th percentile of birth weight for gestational age), and term birth weight, adjusting for individual covariates and neighborhood socioeconomic status (SES). Results In fully adjusted models, a 10-μg/m3 increase in PM2.5 over the entire pregnancy was associated with SGA (odds ratio = 1.04; 95% CI 1.01, 1.07) and reduced term birth weight (–20.5 g; 95% CI –24.7, –16.4). Associations varied across subgroups based on maternal place of birth and period (1999–2003 vs. 2004–2008). Conclusions This study, based on approximately 3 million births across Canada and employing PM2.5 estimates from a national spatiotemporal model, provides further evidence linking PM2.5 and pregnancy outcomes. Citation Stieb DM, Chen L, Beckerman BS, Jerrett M, Crouse DL, Omariba DW, Peters PA, van Donkelaar A, Martin RV, Burnett RT, Gilbert NL, Tjepkema M, Liu S, Dugandzic RM. 2016. Associations of pregnancy outcomes and PM2.5 in a National Canadian Study. Environ Health Perspect 124:243–249; http://dx.doi.org/10.1289/ehp.1408995

A national study of the association between traffic-related air pollution and adverse pregnancy outcomes in Canada, 1999-2008.

Numerous studies have examined the association of air pollution with preterm birth and birth weight outcomes. Traffic-related air pollution has also increasingly been identified as an important contributor to adverse health effects of air pollution. We employed a national nitrogen dioxide (NO2) exposure model to examine the association between NO2 and pregnancy outcomes in Canada between 1999 and 2008. National models for NO2 (and particulate matter of median aerodynamic diameter <2.5µm (PM2.5) as a covariate) were developed using ground-based monitoring data, estimates from remote-sensing, land use variables and, for NO2, deterministic gradients relative to road traffic sources. Generalized estimating equations were used to examine associations with preterm birth, term low birth weight (LBW), small for gestational age (SGA) and term birth weight, adjusting for covariates including infant sex, gestational age, maternal age and marital status, parity, urban/rural place of residence, maternal place of birth, season, year of birth and neighbourhood socioeconomic status and per cent visible minority. Associations were reduced considerably after adjustment for individual covariates and neighbourhood per cent visible minority, but remained significant for SGA (odds ratio 1.04, 95%CI 1.02-1.06 per 20ppb NO2) and term birth weight (16.2g reduction, 95% CI 13.6-18.8g per 20ppb NO2). Associations with NO2 were of greater magnitude in a sensitivity analysis using monthly monitoring data, and among births to mothers born in Canada, and in neighbourhoods with higher incomes and a lower proportion of visible minorities. In two pollutant models, associations with NO2 were less sensitive to adjustment for PM2.5 than vice versa, and there was consistent evidence of a dose-response relationship for NO2 but not PM2.5. In this study of approximately 2.5 million Canadian births between 1999 and 2008, we found significant associations of NO2 with SGA and term birth weight which remained significant after adjustment for PM2.5, suggesting that traffic may be a particularly important source with respect to the role of air pollution as a risk factor for adverse pregnancy outcomes.

Ambient air pollution and adverse birth outcomes: Differences by maternal comorbidities

BACKGROUND Prenatal exposure to ambient air pollution has been associated with adverse birth outcomes, but the potential modifying effect of maternal comorbidities remains understudied. Our objective was to investigate whether associations between prenatal air pollution exposures and birth outcomes differ by maternal comorbidities. METHODS A total of 818,400 singleton live births were identified in the province of Ontario, Canada from 2005 to 2012. We assigned exposures to fine particulate matter (PM2.5), nitrogen dioxide (NO2) and ozone (O3) to maternal residences during pregnancy. We evaluated potential effect modification by maternal comorbidities (i.e. asthma, hypertension, pre-existing diabetes mellitus, heart disease, gestational diabetes and preeclampsia) on the associations between prenatal air pollution and preterm birth, term low birth weight and small for gestational age. RESULTS Interquartile range (IQR) increases in PM2.5 (2μg/m(3)), NO2 (9ppb) and O3 (5ppb) over the entire pregnancy were associated with a 4% (95% CI: 2.4-5.6%), 8.4% (95% CI: 5.5-10.3%) and 2% (95% CI: 0.5-4.1%) increase in the odds of preterm birth, respectively. Increases of 10.6% (95% CI: 0.2-2.1%) and 23.8% (95% CI: 5.5-44.8%) in the odds of preterm birth were observed among women with pre-existing diabetes while the increases were of 3.8% (95% CI: 2.2-5.4%) and 6.5% (95% CI: 3.7-8.4%) among women without this condition for pregnancy exposure to PM2.5 and NO2, respectively (Pint<0.01). The increase in the odds of preterm birth for exposure to PM2.5 during pregnancy was higher among women with preeclampsia (8.3%, 95% CI: 0.8-16.4%) than among women without (3.6%, 95% CI: 1.8-5.3%) (Pint=0.04). A stronger increase in the odds of preterm birth was found for exposure to O3 during pregnancy among asthmatic women (12.0%, 95% CI: 3.5-21.1%) compared to non-asthmatic women (2.0%, 95% CI: 0.1-3.5%) (Pint<0.01). We did not find statistically significant effect modification for the other outcomes investigated. CONCLUSIONS Findings of this study suggest that associations of ambient air pollution with preterm birth are stronger among women with pre-existing diabetes, asthma, and preeclampsia.

Long-term Exposure to Fine Particulate Matter Air Pollution and Mortality Among Canadian Women.

Background: Long-term exposure to fine particulate matter (PM2.5) has been associated with increased mortality, especially from cardiovascular disease. There are, however, uncertainties about the nature of the exposure–response relation at lower concentrations. In Canada, where ambient air pollution levels are substantially lower than in most other countries, there have been few attempts to study associations between long-term exposure to PM2.5 and mortality. Methods: We present a prospective cohort analysis of 89,248 women who enrolled in the Canadian National Breast Screening Study between 1980 and 1985, and for whom residential measures of PM2.5 could be assigned. We derived individual-level estimates of long-term exposure to PM2.5 from satellite observations. We linked cohort records to national mortality data to ascertain mortality between 1980 and 2005. We used Cox proportional hazards models to characterize associations between PM2.5 and several causes of death. The hazard ratios (HRs) and 95% confidence intervals (CIs) computed from these models were adjusted for several individual and neighborhood-level characteristics. Results: The cohort was composed predominantly of Canadian-born (82%) and married (80%) women. The median residential concentration of PM2.5 was 9.1 &mgr;g/m3 (standard deviation = 3.4). In fully adjusted models, a 10 &mgr;g/m3 increase in PM2.5 exposure was associated with elevated risks of nonaccidental (HR: 1.12; 95% CI = 1.04, 1.19), and ischemic heart disease mortality (HR: 1.34; 95% CI = 1.09, 1.66). Conclusions: The findings from this study provide additional support for the hypothesis that exposure to very low levels of ambient PM2.5 increases the risk of cardiovascular mortality.

Data Resource Profile: 1991 Canadian Census Cohort

The 1991 Canadian Census Cohort is the largest population-based cohort in Canada (N=2,734,835). Prior to the creation of this Cohort, no national population-based Canadian cohort was available to examine mortality by socioeconomic indicators. The 1991 Canadian Census Cohort was created via the linkage of a sub-sample of respondents from the mandatory 1991 Canadian Census long-form to historical tax summary files, Canadian Mortality Database, Canadian Cancer Database, 1991 Health and Activity Limitation Survey and a sub-sample of the Longitudinal Worker File. Overall ascertainment of mortality and cancer is anticipated to be nearly complete and the Cohort is broadly representative of most groups in the Canadian population. The Cohort has been used to examine mortality outcomes by different indicators of socioeconomic status, occupational categories, ethnic groups, educational attainment, and for exposure to ambient air pollution. Results have shown that the estimated remaining years of life at age 25 differed substantially by income adequacy quintile, educational attainment, housing type and Aboriginal ancestry.

Oxidative burden of fine particulate air pollution and risk of cause-specific mortality in the Canadian Census Health and Environment Cohort (CanCHEC).

BACKROUND Fine particulate air pollution (PM2.5) is known to contribute to cardiorespiratory mortality but it is not clear how PM2.5 oxidative burden (i.e. the ability of PM2.5 to cause oxidative stress) may influence long-term mortality risk. METHODS We examined the relationship between PM2.5 oxidative burden and cause-specific mortality in Ontario, Canada. Integrated PM2.5 samples were collected from 30 provincial monitoring sites between 2012 and 2013. The oxidative potential (% depletion/µg) of regional PM2.5 was measured as the ability of filter extracts to deplete antioxidants (glutathione and ascorbate) in a synthetic respiratory tract lining fluid. PM2.5oxidative burden was calculated as the product of PM2.5 mass concentrations and regional estimates of oxidative potential. In total, this study included 193,300 people who completed the Canadian long-form census in 1991 and who lived within 5km of a site where oxidative potential was measured. Deaths occurring between 1991 and 2009 were identified through record linkages and Cox proportional hazard models were used to estimate hazard ratios (and 95% confidence intervals) for interquartile changes in exposure adjusting for individual-level covariates and indirect-adjustment for smoking and obesity. RESULTS Glutathione-related oxidative burden was associated with cause-specific mortality. For lung cancer specifically, this metric was associated with a 12% (95% CI: 5.0-19) increased risk of mortality whereas a 5.0% (95% CI: 0.1, 10) increase was observed for PM2.5. Indirect adjustment for smoking and obesity decreased the lung cancer hazard ratio for glutathione-related oxidative burden but it remained significantly elevated (HR=1.07, 95% CI: 1.005, 1.146). Ascorbate-related oxidative burden was not associated with mortality. CONCLUSIONS Our findings suggest that glutathione-related oxidative burden may be more strongly associated with lung cancer mortality than PM2.5 mass concentrations.

A class of non-linear exposure-response models suitable for health impact assessment applicable to large cohort studies of ambient air pollution

The effectiveness of regulatory actions designed to improve air quality is often assessed by predicting changes in public health resulting from their implementation. Risk of premature mortality from long-term exposure to ambient air pollution is the single most important contributor to such assessments and is estimated from observational studies generally assuming a log-linear, no-threshold association between ambient concentrations and death. There has been only limited assessment of this assumption in part because of a lack of methods to estimate the shape of the exposure-response function in very large study populations. In this paper, we propose a new class of variable coefficient risk functions capable of capturing a variety of potentially non-linear associations which are suitable for health impact assessment. We construct the class by defining transformations of concentration as the product of either a linear or log-linear function of concentration multiplied by a logistic weighting function. These risk functions can be estimated using hazard regression survival models with currently available computer software and can accommodate large population-based cohorts which are increasingly being used for this purpose. We illustrate our modeling approach with two large cohort studies of long-term concentrations of ambient air pollution and mortality: the American Cancer Society Cancer Prevention Study II (CPS II) cohort and the Canadian Census Health and Environment Cohort (CanCHEC). We then estimate the number of deaths attributable to changes in fine particulate matter concentrations over the 2000 to 2010 time period in both Canada and the USA using both linear and non-linear hazard function models.

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.

Spatial associations between socioeconomic groups and NO2 air pollution exposure within three large Canadian cities.

Previous studies of environmental justice in Canadian cities have linked lower socioeconomic status to greater air pollution exposures at coarse geographic scales, (i.e., Census Tracts). However, studies that examine these associations at finer scales are less common, as are comparisons among cities. To assess differences in exposure to air pollution among socioeconomic groups, we assigned estimates of exposure to ambient nitrogen dioxide (NO2), a marker for traffic-related pollution, from city-wide land use regression models to respondents of the 2006 Canadian census long-form questionnaire in Toronto, Montreal, and Vancouver. Data were aggregated at a finer scale than in most previous studies (i.e., by Dissemination Area (DA), which includes approximately 400-700 persons). We developed simultaneous autoregressive (SAR) models, which account for spatial autocorrelation, to identify associations between NO2 exposure and indicators of social and material deprivation. In Canadas three largest cities, DAs with greater proportions of tenants and residents who do not speak either English or French were characterised by greater exposures to ambient NO2. We also observed positive associations between NO2 concentrations and indicators of social deprivation, including the proportion of persons living alone (in Toronto), and the proportion of persons who were unmarried/not in a common-law relationship (in Vancouver). Other common measures of deprivation (e.g., lone-parent families, unemployment) were not associated with NO2 exposures. DAs characterised by selected indicators of deprivation were associated with higher concentrations of ambient NO2 air pollution in the three largest cities in Canada.