Search

Introduction: Mortality is associated with long-term exposure to fine particulate matter (particulate matter ≤2.5 μm in aerodynamic diameter; PM 2.5 ), 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 PM 2.5 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 PM 2.5 concentrations and nonaccidental mortality were attenuated with the addition of ozone (O 3 ) or a measure of gaseous pollutant oxidant capacity (O x ), which was estimated from O 3 and nitrogen dioxide (NO 2 ) concentrations. This was motivated by our interests in understanding both the effects air pollutant mixtures may have on mortality and also the role of O 3 as a copollutant that shares common sources and precursor emissions with those of PM 2.5 . In this Phase 2 report, we further explore the sensitivity of these associations with O 3 and O x , evaluate sensitivity to other factors, such as regional variation, and present ambient PM 2.5 concentration-response relationships for specific causes of death., Methods: PM 2.5 concentrations were estimated at 1 km 2 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 PM 2.5 mass concentration relationship, land use information, and ground monitoring. These estimates were informed and further refined with collocated measurements of PM 2.5 and AOD, including targeted measurements in areas of low PM 2.5 concentrations collected at five locations across Canada. Ground measurements of PM 2.5 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 PM 2.5 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 PM 2.5 . 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/m 3 . 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 PM 2.5 and mortality when in the presence of, or stratified by tertile of, O 3 or O x . Additionally, associations between PM 2.5 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-PM 2.5 association to removal of person-years at or above 12 μg/m 3 (the current U.S. National Ambient Air Quality Standard) and 10 μg/m 3 (the current Canadian and former [2005] World Health Organization [WHO] guideline, and current WHO Interim Target-4). Finally, differences in the shapes of PM 2.5 -mortality associations were assessed across broad geographic regions (airsheds) within Canada., Results: The refined PM 2.5 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 PM 2.5 <10 μg/m 3 )., Positive associations between outdoor PM 2.5 concentrations and nonaccidental mortality were consistently observed in all cohorts. In the Stacked CanCHEC analyses (1.3 million deaths), each 10-μg/m 3 increase in outdoor PM 2.5 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 PM 2.5 mass concentration of 4.16 μg/m 3 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/m 3 to 4.5 μg/m 3 , flattened from 4.5 μg/m 3 to 8.0 μg/m 3 , then increased for concentrations above 8.0 μg/m 3 . The threshold model results reflected this pattern with -2 log-likelihood values being equal at 2.5 μg/m 3 and 8.0 μg/m 3 . However, mean threshold model predictions monotonically increased over the concentration range with the lower 95% CI equal to one from 2.5 μg/m 3 to 8.0 μg/m 3 . 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-PM 2.5 association to removal of person-years at or above the current U.S. and Canadian standards of 12 μg/m 3 and 10 μg/m 3 , respectively. In the full cohort and in both restricted cohorts, a steep increase was observed from the minimum concentration of 2.5 μg/m 3 to 5 μg/m 3 . For the full cohort and the <12 μg/m 3 cohort the relationship flattened over the 5 to 9 μg/m 3 range and then increased above 9 μg/m 3 . A similar increase was observed for the <10 μg/m 3 cohort followed by a clear decline in the magnitude of predictions over the 5 to 9 μg/m 3 range and an increase above 9 μg/m 3 . Together these results suggest that a positive association exists for concentrations >9 μg/m 3 with indications of adverse effects on mortality at concentrations as low as 2.5 μg/m 3 ., Among the other causes of death examined, PM 2.5 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 PM 2.5 for heart failure, lung cancer, and kidney failure., In sensitivity analyses, the addition of O 3 and O x attenuated associations between PM 2.5 and mortality. When analyses were stratified by tertiles of copollutants, associations between PM 2.5 and mortality were only observed in the highest tertile of O 3 or O x . 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 PM 2.5 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 in concentration-mortality relationships, specifically the flattening of the concentration-mortality relationship over the 5 to 9 μg/m 3 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 PM 2.5 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 PM 2.5 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/m 3 , and there was no clear evidence in the observed data of a lower threshold, below which PM 2.5 was not associated with nonaccidental mortality., (© 2022 Health Effects Institute. All rights reserved.)

Background: Approximately 2.9 million deaths are attributed to ambient fine particle air pollution around the world each year (PM 2.5 ). In general, cohort studies of mortality and outdoor PM 2.5 concentrations have limited information on individuals exposed to low levels of PM 2.5 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 PM 2.5 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 PM 2.5 ., 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 PM 2.5 exposure estimates, and mortality incidence to 2016. Cox proportional hazard models were used to estimate the relationship between non-accidental mortality and ambient PM 2.5 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 PM 2.5 concentrations were low (i.e. 5.9 μg/m 3 , s.d. 2.0) and each 10 μg/m 3 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/m 3 using a shape constrained health impact function. Mortality risks associated with exposure to PM 2.5 were increased for males, those under age 65, and non-immigrants. Hazard ratios for PM 2.5 and mortality were attenuated when gaseous pollutants were included in models., Conclusions: Outdoor PM 2.5 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 PM 2.5 concentrations.

Background: Ambient fine particulate air pollution with aerodynamic diameter ≤ 2.5   μ m ( PM 2.5 ) is an important contributor to the global burden of disease. Information on the shape of the concentration-response relationship at low concentrations is critical for estimating this burden, setting air quality standards, and in benefits assessments., Objectives: We examined the concentration-response relationship between PM 2.5 and nonaccidental mortality in three Canadian Census Health and Environment Cohorts (CanCHECs) based on the 1991, 1996, and 2001 census cycles linked to mobility and mortality data., Methods: Census respondents were linked with death records through 2016, resulting in 8.5 million adults, 150 million years of follow-up, and 1.5 million deaths. Using annual mailing address, we assigned time-varying contextual variables and 3-y moving-average ambient PM 2.5 at a 1 × 1   km spatial resolution from 1988 to 2015. We ran Cox proportional hazards models for PM 2.5 adjusted for eight subject-level indicators of socioeconomic status, seven contextual covariates, ozone, nitrogen dioxide, and combined oxidative potential. We used three statistical methods to examine the shape of the concentration-response relationship between PM 2.5 and nonaccidental mortality., Results: The mean 3-y annual average estimate of PM 2.5 exposure ranged from 6.7 to 8.0   μ g / m 3 over the three cohorts. We estimated a hazard ratio (HR) of 1.053 [95% confidence interval (CI): 1.041, 1.065] per 10 - μ g / m 3 change in PM 2.5 after pooling the three cohort-specific hazard ratios, with some variation between cohorts (1.041 for the 1991 and 1996 cohorts and 1.084 for the 2001 cohort). We observed a supralinear association in all three cohorts. The lower bound of the 95% CIs exceeded unity for all concentrations in the 1991 cohort, for concentrations above 2   μ g / m 3 in the 1996 cohort, and above 5   μ g / m 3 in the 2001 cohort., Discussion: In a very large population-based cohort with up to 25 y of follow-up, PM 2.5 was associated with nonaccidental mortality at concentrations as low as 5   μ g / m 3 . https://doi.org/10.1289/EHP5204.

Outdoor fine particulate air pollution (PM 2.5 ) is known to increase mortality risk and is recognized as an important contributor to global disease burden. However, less is known about how oxidant gases may modify the chronic health effects of PM 2.5 . In this study, we examined how the oxidant capacity of O 3 and NO 2 (using a redox-weighted average, O x ) may modify the relationship between PM 2.5 and mortality in the 2001 Canadian Census Health and Environment Cohort. In total, 2,448,500 people were followed over a 10.6-year period. Each 3.86 µg/m 3 increase in PM 2.5 was associated with nonaccidental (Hazard Ratio (HR) = 1.095, 95% CI: 1.077, 1.112), cardiovascular (HR = 1.088, 95% CI: 1.059, 1.118), and respiratory mortality (HR = 1.110, 95% CI: 1.051, 1.171) in the highest tertile of O x whereas weaker/null associations were observed in the middle and lower tertiles. Analysis of joint non-linear concentration-response relationships for PM 2.5 and O x suggested threshold concentrations between approximately 23 and 25 ppb with O x concentrations above these values strengthening PM 2.5 -mortality associations. Overall, our findings suggest that oxidant gases enhance the chronic health risks of PM 2.5 . In some areas, reductions in O x concentrations may have the added benefit of reducing the public health impacts of PM 2.5 even if mass concentrations remain unchanged.