Mortality-Air Pollution Associations in Low Exposure Environments (MAPLE): Phase 2.

INTRODUCTION: Mortality is associated with long-term exposure to fine particulate matter (particulate matter ≤2.5 µm in aerodynamic diameter; PM2.5), although the magnitude and form of these associations remain poorly understood at lower concentrations. Knowledge gaps include the shape of concentration-response curves and the lowest levels of exposure at which increased risks are evident and the occurrence and extent of associations with specific causes of death. Here, we applied improved estimates of exposure to ambient PM2.5 to national population-based cohorts in Canada, including a stacked cohort of 7.1 million people who responded to census year 1991, 1996, or 2001. The characterization of the shape of the concentration-response relationship for nonaccidental mortality and several specific causes of death at low levels of exposure was the focus of the Mortality-Air Pollution Associations in Low Exposure Environments (MAPLE) Phase 1 report. In the Phase 1 report we reported that associations between outdoor PM2.5 concentrations and nonaccidental mortality were attenuated with the addition of ozone (O3) or a measure of gaseous pollutant oxidant capacity (Ox), which was estimated from O3 and nitrogen dioxide (NO2) concentrations. This was motivated by our interests in understanding both the effects air pollutant mixtures may have on mortality and also the role of O3 as a copollutant that shares common sources and precursor emissions with those of PM2.5. In this Phase 2 report, we further explore the sensitivity of these associations with O3 and Ox, evaluate sensitivity to other factors, such as regional variation, and present ambient PM2.5 concentration-response relationships for specific causes of death. METHODS: PM2.5 concentrations were estimated at 1 km2 spatial resolution across North America using remote sensing of aerosol optical depth (AOD) combined with chemical transport model (GEOS-Chem) simulations of the AOD:surface PM2.5 mass concentration relationship, land use information, and ground monitoring. These estimates were informed and further refined with collocated measurements of PM2.5 and AOD, including targeted measurements in areas of low PM2.5 concentrations collected at five locations across Canada. Ground measurements of PM2.5 and total suspended particulate matter (TSP) mass concentrations from 1981 to 1999 were used to backcast remote-sensing-based estimates over that same time period, resulting in modeled annual surfaces from 1981 to 2016.Annual exposures to PM2.5 were then estimated for subjects in several national population-based Canadian cohorts using residential histories derived from annual postal code entries in income tax files. These cohorts included three census-based cohorts: the 1991 Canadian Census Health and Environment Cohort (CanCHEC; 2.5 million respondents), the 1996 CanCHEC (3 million respondents), the 2001 CanCHEC (3 million respondents), and a Stacked CanCHEC where duplicate records of respondents were excluded (Stacked CanCHEC; 7.1 million respondents). The Canadian Community Health Survey (CCHS) mortality cohort (mCCHS), derived from several pooled cycles of the CCHS (540,900 respondents), included additional individual information about health behaviors. Follow-up periods were completed to the end of 2016 for all cohorts. Cox proportional hazard ratios (HRs) were estimated for nonaccidental and other major causes of death using a 10-year moving average exposure and 1-year lag. All models were stratified by age, sex, immigrant status, and where appropriate, census year or survey cycle. Models were further adjusted for income adequacy quintile, visible minority status, Indigenous identity, educational attainment, labor-force status, marital status, occupation, and ecological covariates of community size, airshed, urban form, and four dimensions of the Canadian Marginalization Index (Can-Marg; instability, deprivation, dependency, and ethnic concentration). The mCCHS analyses were also adjusted for individual-level measures of smoking, alcohol consumption, fruit and vegetable consumption, body mass index (BMI), and exercise behavior.In addition to linear models, the shape of the concentration-response function was investigated using restricted cubic splines (RCS). The number of knots were selected by minimizing the Bayesian Information Criterion (BIC). Two additional models were used to examine the association between nonaccidental mortality and PM2.5. The first is the standard threshold model defined by a transformation of concentration equaling zero if the concentration was less than a specific threshold value and concentration minus the threshold value for concentrations above the threshold. The second additional model was an extension of the Shape Constrained Health Impact Function (SCHIF), the eSCHIF, which converts RCS predictions into functions potentially more suitable for use in health impact assessments. Given the RCS parameter estimates and their covariance matrix, 1,000 realizations of the RCS were simulated at concentrations from the minimum to the maximum concentration, by increments of 0.1 µg/m3. An eSCHIF was then fit to each of these RCS realizations. Thus, 1,000 eSCHIF predictions and uncertainty intervals were determined at each concentration within the total range.Sensitivity analyses were conducted to examine associations between PM2.5 and mortality when in the presence of, or stratified by tertile of, O3 or Ox. Additionally, associations between PM2.5 and mortality were assessed for sensitivity to lower concentration thresholds, where person-years below a threshold value were assigned the mean exposure within that group. We also examined the sensitivity of the shape of the nonaccidental mortality-PM2.5 association to removal of person-years at or above 12 µg/m3 (the current U.S. National Ambient Air Quality Standard) and 10 µg/m3 (the current Canadian and former [2005] World Health Organization [WHO] guideline, and current WHO Interim Target-4). Finally, differences in the shapes of PM2.5-mortality associations were assessed across broad geographic regions (airsheds) within Canada. RESULTS: The refined PM2.5 exposure estimates demonstrated improved performance relative to estimates applied previously and in the MAPLE Phase 1 report, with slightly reduced errors, including at lower ranges of concentrations (e.g., for PM2.5 <10 µg/m3).Positive associations between outdoor PM2.5 concentrations and nonaccidental mortality were consistently observed in all cohorts. In the Stacked CanCHEC analyses (1.3 million deaths), each 10-µg/m3 increase in outdoor PM2.5 concentration corresponded to an HR of 1.084 (95% confidence interval [CI]: 1.073 to 1.096) for nonaccidental mortality. For an interquartile range (IQR) increase in PM2.5 mass concentration of 4.16 µg/m3 and for a mean annual nonaccidental death rate of 92.8 per 10,000 persons (over the 1991-2016 period for cohort participants ages 25-90), this HR corresponds to an additional 31.62 deaths per 100,000 people, which is equivalent to an additional 7,848 deaths per year in Canada, based on the 2016 population. In RCS models, mean HR predictions increased from the minimum concentration of 2.5 µg/m3 to 4.5 µg/m3, flattened from 4.5 µg/m3 to 8.0 µg/m3, then increased for concentrations above 8.0 µg/m3. The threshold model results reflected this pattern with -2 log-likelihood values being equal at 2.5 µg/m3 and 8.0 µg/m3. However, mean threshold model predictions monotonically increased over the concentration range with the lower 95% CI equal to one from 2.5 µg/m3 to 8.0 µg/m3. The RCS model was a superior predictor compared with any of the threshold models, including the linear model.In the mCCHS cohort analyses inclusion of behavioral covariates did not substantially change the results for both linear and nonlinear models. We examined the sensitivity of the shape of the nonaccidental mortality-PM2.5 association to removal of person-years at or above the current U.S. and Canadian standards of 12 µg/m3 and 10 µg/m3, respectively. In the full cohort and in both restricted cohorts, a steep increase was observed from the minimum concentration of 2.5 µg/m3 to 5 µg/m3. For the full cohort and the <12 µg/m3 cohort the relationship flattened over the 5 to 9 µg/m3 range and then increased above 9 µg/m3. A similar increase was observed for the <10 µg/m3 cohort followed by a clear decline in the magnitude of predictions over the 5 to 9 µg/m3 range and an increase above 9 µg/m3. Together these results suggest that a positive association exists for concentrations >9 µg/m3 with indications of adverse effects on mortality at concentrations as low as 2.5 µg/m3.Among the other causes of death examined, PM2.5 exposures were consistently associated with an increased hazard of mortality due to ischemic heart disease, respiratory disease, cardiovascular disease, and diabetes across all cohorts. Associations were observed in the Stacked CanCHEC but not in all other cohorts for cerebrovascular disease, pneumonia, and chronic obstructive pulmonary disease (COPD) mortality. No significant associations were observed between mortality and exposure to PM2.5 for heart failure, lung cancer, and kidney failure.In sensitivity analyses, the addition of O3 and Ox attenuated associations between PM2.5 and mortality. When analyses were stratified by tertiles of copollutants, associations between PM2.5 and mortality were only observed in the highest tertile of O3 or Ox. Across broad regions of Canada, linear HR estimates and the shape of the eSCHIF varied substantially, possibly reflecting underlying differences in air pollutant mixtures not characterized by PM2.5 mass concentrations or the included gaseous pollutants. Sensitivity analyses to assess regional variation in population characteristics and access to healthcare indicated that the observed regional differences inconcentration-mortality relationships, specifically the flattening of the concentration-mortality relationship over the 5 to 9 µg/m3 range, was not likely related to variation in the makeup of the cohort or its access to healthcare, lending support to the potential role of spatially varying air pollutant mixtures not sufficiently characterized by PM2.5 mass concentrations. CONCLUSIONS: In several large, national Canadian cohorts, including a cohort of 7.1 million unique census respondents, associations were observed between exposure to PM2.5 with nonaccidental mortality and several specific causes of death. Associations with nonaccidental mortality were observed using the eSCHIF methodology at concentrations as low as 2.5 µg/m3, and there was no clear evidence in the observed data of a lower threshold, below which PM2.5 was not associated with nonaccidental mortality.

Mortality-Air Pollution Associations in Low-Exposure Environments (MAPLE): Phase 1.

INTRODUCTION: Fine particulate matter (particulate matter ≤2.5 µm in aerodynamic diameter, or PM2.5) is associated with mortality, but the lower range of relevant concentrations is unknown. Novel satellite-derived estimates of outdoor PM2.5 concentrations were applied to several large population-based cohorts, and the shape of the relationship with nonaccidental mortality was characterized, with emphasis on the low concentrations (<12 µg/m3) observed throughout Canada. METHODS: Annual satellite-derived estimates of outdoor PM2.5 concentrations were developed at 1-km2 spatial resolution across Canada for 2000-2016 and backcasted to 1981 using remote sensing, chemical transport models, and ground monitoring data. Targeted ground-based measurements were conducted to measure the relationship between columnar aerosol optical depth (AOD) and ground-level PM2.5. Both existing and targeted ground-based measurements were analyzed to develop improved exposure data sets for subsequent epidemiological analyses.Residential histories derived from annual tax records were used to estimate PM2.5 exposures for subjects whose ages ranged from 25 to 90 years. About 8.5 million were from three Canadian Census Health and Environment Cohort (CanCHEC) analytic files and another 540,900 were Canadian Community Health Survey (CCHS) participants. Mortality was linked through the year 2016. Hazard ratios (HR) were estimated with Cox Proportional Hazard models using a 3-year moving average exposure with a 1-year lag, with the year of follow-up as the time axis. All models were stratified by 5-year age groups, sex, and immigrant status. Covariates were based on directed acyclical graphs (DAG), and included contextual variables (airshed, community size, neighborhood dependence, neighborhood deprivation, ethnic concentration, neighborhood instability, and urban form). A second model was examined including the DAG-based covariates as well as all subject-level risk factors (income, education, marital status, indigenous identity, employment status, occupational class, and visible minority status) available in each cohort. Additional subject-level behavioral covariates (fruit and vegetable consumption, leisure exercise frequency, alcohol consumption, smoking, and body mass index [BMI]) were included in the CCHS analysis.Sensitivity analyses evaluated adjustment for covariates and gaseous copollutants (nitrogen dioxide [NO2] and ozone [O3]), as well as exposure time windows and spatial scales. Estimates were evaluated across strata of age, sex, and immigrant status. The shape of the PM2.5-mortality association was examined by first fitting restricted cubic splines (RCS) with a large number of knots and then fitting the shape-constrained health impact function (SCHIF) to the RCS predictions and their standard errors (SE). This method provides graphical results indicating the RCS predictions, as a nonparametric means of characterizing the concentration-response relationship in detail and the resulting mean SCHIF and accompanying uncertainty as a parametric summary.Sensitivity analyses were conducted in the CCHS cohort to evaluate the potential influence of unmeasured covariates on air pollution risk estimates. Specifically, survival models with all available risk factors were fit and compared with models that omitted covariates not available in the CanCHEC cohorts. In addition, the PM2.5 risk estimate in the CanCHEC cohort was indirectly adjusted for multiple individual-level risk factors by estimating the association between PM2.5 and these covariates within the CCHS. RESULTS: Satellite-derived PM2.5 estimates were low and highly correlated with ground monitors. HR estimates (per 10-µg/m3 increase in PM2.5) were similar for the 1991 (1.041, 95% confidence interval [CI]: 1.016-1.066) and 1996 (1.041, 1.024-1.059) CanCHEC cohorts with a larger estimate observed for the 2001 cohort (1.084, 1.060-1.108). The pooled cohort HR estimate was 1.053 (1.041-1.065). In the CCHS an analogous model indicated a HR of 1.13 (95% CI: 1.06-1.21), which was reduced slightly with the addition of behavioral covariates (1.11, 1.04-1.18). In each of the CanCHEC cohorts, the RCS increased rapidly over lower concentrations, slightly declining between the 25th and 75th percentiles and then increasing beyond the 75th percentile. The steepness of the increase in the RCS over lower concentrations diminished as the cohort start date increased. The SCHIFs displayed a supralinear association in each of the three CanCHEC cohorts and in the CCHS cohort.In sensitivity analyses conducted with the 2001 CanCHEC, longer moving averages (1, 3, and 8 years) and smaller spatial scales (1 km2 vs. 10 km2) of exposure assignment resulted in larger associations between PM2.5 and mortality. In both the CCHS and CanCHEC analyses, the relationship between nonaccidental mortality and PM2.5 was attenuated when O3 or a weighted measure of oxidant gases was included in models. In the CCHS analysis, but not in CanCHEC, PM2.5 HRs were also attenuated by the inclusion of NO2. Application of the indirect adjustment and comparisons within the CCHS analysis suggests that missing data on behavioral risk factors for mortality had little impact on the magnitude of PM2.5-mortality associations. While immigrants displayed improved overall survival compared with those born in Canada, their sensitivity to PM2.5 was similar to or larger than that for nonimmigrants, with differences between immigrants and nonimmigrants decreasing in the more recent cohorts. CONCLUSIONS: In several large population-based cohorts exposed to low levels of air pollution, consistent associations were observed between PM2.5 and nonaccidental mortality for concentrations as low as 5 µg/m3. This relationship was supralinear with no apparent threshold or sublinear association.

Cause-specific mortality by occupational skill level in Canada: a 16-year follow-up study.

INTRODUCTION: Mortality data by occupation are not routinely available in Canada, so we analyzed census-linked data to examine cause-specific mortality rates across groups of occupations ranked by skill level. METHODS: A 15% sample of 1991 Canadian Census respondents aged 25 years or older was previously linked to 16 years of mortality data (1991-2006). The current analysis is based on 2.3 million people aged 25 to 64 years at cohort inception, among whom there were 164 332 deaths during the follow-up period. Occupations coded according to the National Occupation Classification were grouped into five skill levels. Age-standardized mortality rates (ASMRs), rate ratios (RRs), rate differences (RDs) and excess mortality were calculated by occupational skill level for various causes of death. RESULTS: ASMRs were clearly graded by skill level: they were highest among those employed in unskilled jobs (and those without an occupation) and lowest for those in professional occupations. All-cause RRs for men were 1.16, 1.40, 1.63 and 1.83 with decreasing occupational skill level compared with professionals. For women the gradient was less steep: 1.23, 1.24, 1.32 and 1.53. This gradient was present for most causes of death. Rate ratios comparing lowest to highest skill levels were greater than 2 for HIV/AIDS, diabetes mellitus, suicide and cancer of the cervix as well as for causes of death associated with tobacco use and excessive alcohol consumption. CONCLUSION: Mortality gradients by occupational skill level were evident for most causes of death. These results provide detailed cause-specific baseline indicators not previously available for Canada.

TITRE: Mortalité par cause en fonction du niveau de compétence professionnelle au Canada : une étude de suivi sur 16 ans. INTRODUCTION: Les données sur la mortalité par profession n'étant pas facilement accessibles au Canada, nous avons analysé des données issues du recensement pour étudier les taux de mortalité par cause au sein de différents groupes de professions hiérarchisés par niveaux de compétence. MÉTHODOLOGIE: Un échantillon de 15 % des répondants de 25 ans et plus au recensement du Canada de 1991 avait été précédemment couplé avec 16 années de données sur la mortalité (1991-2006). Notre analyse est fondée sur une cohorte de 2,3 millions de personnes âgées de 25 à 64 ans au début de l'étude, au sein de laquelle 164 332 décès ont été enregistrés au cours de la période de suivi. Les professions ont été classées conformément à la Classification nationale des professions et ont été réparties en cinq groupes de niveaux de compétence. Les taux de mortalité normalisés selon l'âge (TMNA), les rapports de taux (RT), les différences de taux (DT) et la surmortalité ont été calculés par niveau de compétence professionnelle pour différentes causes de décès. RÉSULTATS: Les TMNA variaient clairement selon le niveau de compétence : ils étaient plus élevés chez les personnes occupant un poste non spécialisé (et chez celles sans emploi) et moins élevés chez celles occupant un poste professionnel. Chez les hommes, les RT toutes causes confondues étaient de 1,16, 1,40, 1,63 et 1,83 à mesure que le niveau de compétence professionnelle diminuait et en référence au groupe des professionnels. Chez les femmes, le gradient était moins prononcé : 1,23, 1,24, 1,32 et 1,53. Nous avons observé ce gradient pour la plupart des causes de décès. Les RT concernant les niveaux de compétence les plus faibles par rapport aux plus élevés étaient supérieurs à 2 pour le VIH/sida, le diabète sucré, le suicide et le cancer du col de l'utérus, ainsi que pour les causes de décès associées au tabagisme et à la consommation excessive d'alcool. CONCLUSION: Les gradients de la mortalité par niveau de compétence professionnelle étaient clairs pour la plupart des causes de décès. Ces résultats fournissent des indicateurs de référence détaillés sur la mortalité par cause qui n'étaient pas disponibles au Canada auparavant.

Cardiovascular disease mortality among First Nations people in Canada, 1991-2001.

OBJECTIVE: To compare cardiovascular disease mortality patterns between First Nations people and non-Aboriginal adults by sex and by income adequacy quintile and level of educational attainment. METHODS: A 15% sample of 1991 Canadian census respondents aged 25 years or older was previously linked to 11 years of mortality data. In this study, First Nations people were defined by North American Indian ethnic origin (ancestry), registration under the Indian Act, and/or membership in an Indian band or First Nation. The cohort included 62 400 First Nations people and 2 624 300 non-Aboriginal people. RESULTS: Compared to non-Aboriginal cohort members, the age-standardized cardiovascular disease mortality rate was 30% higher for First Nations men and 76% higher for First Nations women. This represented an excess of 58 deaths and 71 deaths per 100 000 person-years at risk, for First Nations men and women, respectively. Within each income adequacy quintile (adjusted for family size and region of residence) and level of educational attainment, the risk of dying from cardiovascular disease was higher for First Nations people compared to their non-Aboriginal counterparts. CONCLUSION: First Nations people had higher rates of death from cardiovascular disease than non-Aboriginal Canadians within each income quintile and level of education. Income and education accounted for 67% and 25% of the excess mortality of First Nations men and women respectively.

Income disparities in life expectancy in the City of Toronto and Region of Peel, Ontario.

INTRODUCTION: To understand the lack of a gradient in mortality by neighbourhood income in a previous study, we used individual-level data from the 1991-2001 Canadian census mortality follow-up study to examine income-related disparities in life expectancy and probability of survival to age 75 years in the City of Toronto and Region of Peel. METHODS: We calculated period life tables for each sex and income adequacy quintile, overall and separately for immigrants and non-immigrants. RESULTS: For all cohort members of both sexes, including both immigrants and non-immigrants, there was a clear gradient across the income quintiles, with higher life expectancy in each successively richer quintile. However, the disparities by income were much greater when the analysis was restricted to non-immigrants. The lesser gradient for immigrants appeared to reflect the higher proportion of recent immigrants in the lower income quintiles. CONCLUSION: These findings highlight the importance of using individual-level ascertainment of income whenever possible, and of including immigrant status and period of immigration in assessments of health outcomes, especially for areas with a high proportion of immigrants.

Mortality of urban Aboriginal adults in Canada, 1991-2001.

OBJECTIVE: To compare mortality patterns for urban Aboriginal adults with those of urban non-Aboriginal adults. METHODS: Using the 1991-2001 Canadian census mortality follow-up study, our study tracked mortality to December 31, 2001, among a 15% sample of adults, including 16 300 Aboriginal and 2 062 700 non-Aboriginal persons residing in urban areas on June 4, 1991. The Aboriginal population was defined by ethnic origin (ancestry), Registered Indian status and/or membership in an Indian band or First Nation, since the 1991 census did not collect information on Aboriginal identity. RESULTS: Compared to urban non-Aboriginal men and women, remaining life expectancy at age 25 years was 4.7 years and 6.5 years shorter for urban Aboriginal men and women, respectively. Mortality rate ratios for urban Aboriginal men and women were particularly elevated for alcohol-related deaths, motor vehicle accidents and infectious diseases, including HIV/AIDS. For most causes of death, urban Aboriginal adults had higher mortality rates compared to other urban residents. Socio-economic status played an important role in explaining these disparities. CONCLUSION: Results from this study help fill a data gap on mortality information of urban Aboriginal people of Canada.

Mortality of urban Aboriginal adults in Canada, 1991-2001.

OBJECTIVE: To compare mortality patterns for urban Aboriginal adults with those of urban non-Aboriginal adults. METHODS: Using the 1991-2001 Canadian census mortality follow-up study, our study tracked mortality to December 31, 2001, among a 15% sample of adults, including 16 300 Aboriginal and 2 062 700 non-Aboriginal persons residing in urban areas on June 4, 1991. The Aboriginal population was defined by ethnic origin (ancestry), Registered Indian status and/or membership in an Indian band or First Nation, since the 1991 census did not collect information on Aboriginal identity. RESULTS: Compared to urban non-Aboriginal men and women, remaining life expectancy at age 25 years was 4.7 years and 6.5 years shorter for urban Aboriginal men and women, respectively. Mortality rate ratios for urban Aboriginal men and women were particularly elevated for alcohol-related deaths, motor vehicle accidents and infectious diseases, including HIV/AIDS. For most causes of death, urban Aboriginal adults had higher mortality rates compared to other urban residents. Socio-economic status played an important role in explaining these disparities. CONCLUSION: Results from this study help fill a data gap on mortality information of urban Aboriginal people of Canada.