Airborne Nanoparticle Concentrations Are Associated with Increased Mortality Risk in Canada's Two Largest Cities.

RATIONALE: Outdoor fine particulate air pollution (PM2.5) contributes to millions of deaths around the world each year, but much less is known about the long-term health impacts of other particulate air pollutants including ultrafine particles (a.k.a. nanoparticles) which are in the nanometer size range (<100 nm), widespread in urban environments, and not currently regulated. OBJECTIVES: Estimate the associations between long-term exposure to outdoor ultrafine particles and mortality. METHODS: Outdoor air pollution levels were linked to the residential addresses of a large, population-based cohort from 2001 - 2016. Associations between long-term exposure to outdoor ultrafine particles and nonaccidental and cause-specific mortality were estimated using Cox proportional hazards models. MEASUREMENTS: An increase in long-term exposure to outdoor ultrafine particles was associated with an increased risk of nonaccidental mortality (Hazard Ratio = 1. 073, 95% Confidence Interval = 1. 061, 1. 085) and cause-specific mortality, the strongest of which was respiratory mortality (Hazard Ratio = 1.174, 95% Confidence Interval = 1.130, 1.220). MAIN RESULTS: Long-term exposure to outdoor ultrafine particles was associated with increased risk of mortality. We estimated the mortality burden for outdoor ultrafine particles in Montreal and Toronto, Canada to be approximately 1100 additional nonaccidental deaths every year. Furthermore, we observed possible confounding by particle size which suggests that previous studies may have underestimated or missed important health risks associated with ultrafine particles. CONCLUSIONS: As outdoor ultrafine particles are not currently regulated, there is great potential for future regulatory interventions to improve population health by targeting these common outdoor air pollutants.

Impact of lowering fine particulate matter from major emission sources on mortality in Canada: A nationwide causal analysis.

Emissions of fine particulate matter (PM2.5) from human activities have been linked to substantial disease burdens, but evidence regarding how reducing PM2.5 at its sources would improve public health is sparse. We followed a population-based cohort of 2.7 million adults across Canada from 2007 through 2016. For each participant, we estimated annual mean concentrations of PM2.5 and the fractional contributions to PM2.5 from the five leading anthropogenic sources at their residential address using satellite observations in combination with a global atmospheric chemistry transport model. For each source, we estimated the causal effects of six hypothetical interventions on 10-y nonaccidental mortality risk using the parametric g-formula, a structural causal model. We conducted stratified analyses by age, sex, and income. This cohort would have experienced tangible health gains had contributions to PM2.5 from any of the five sources been reduced. Compared with no intervention, a 10% annual reduction in PM2.5 contributions from transportation and power generation, Canada's largest and fifth-largest anthropogenic sources, would have prevented approximately 175 (95%CI: 123-226) and 90 (95%CI: 63-117) deaths per million by 2016, respectively. A more intensive 50% reduction per year in PM2.5 contributions from the two sources would have averted 360 and 185 deaths per million, respectively, by 2016. The potential health benefits were greater among men, older adults, and low-income earners. In Canada, where PM2.5 levels are among the lowest worldwide, reducing PM2.5 contributions from anthropogenic sources by as little as 10% annually would yield meaningful health gains.

Daily Summer Temperatures and Hospitalization for Acute Cardiovascular Events: Impact of Outdoor PM 2.5 Oxidative Potential on Observed Associations Across Canada.

BACKGROUND: Oxidative stress plays an important role in the health impacts of both outdoor fine particulate air pollution (PM 2.5 ) and thermal stress. However, it is not clear how the oxidative potential of PM 2.5 may influence the acute cardiovascular effects of temperature. METHODS: We conducted a case-crossover study of hospitalization for cardiovascular events in 35 cities across Canada during the summer months (July-September) between 2016 and 2018. We collected three different metrics of PM 2.5 oxidative potential each month in each location. We estimated associations between lag-0 daily temperature (per 5ºC) and hospitalization for all cardiovascular (n = 44,876) and ischemic heart disease (n = 14,034) events across strata of monthly PM 2.5 oxidative potential using conditional logistical models adjusting for potential time-varying confounders. RESULTS: Overall, associations between lag-0 temperature and acute cardiovascular events tended to be stronger when outdoor PM 2.5 oxidative potential was higher. For example, when glutathione-related oxidative potential (OP GSH ) was in the highest tertile, the odds ratio (OR) for all cardiovascular events was 1.040 (95% confidence intervals [CI] = 1.004, 1.074) compared with 0.980 (95% CI = 0.943, 1.018) when OP GSH was in the lowest tertile. We observed a greater difference for ischemic heart disease events, particularly for older subjects (age >70 years). CONCLUSIONS: The acute cardiovascular health impacts of summer temperature variations may be greater when outdoor PM 2.5 oxidative potential is elevated. This may be particularly important for ischemic heart disease events.

Air pollution and the sequelae of COVID-19 patients: A multistate analysis.

IMPORTANCE: Recent evidence links air pollution to the severity COVID-19 symptoms and to death from the disease. To date, however, few studies have assessed whether air pollution affects the sequelae to more severe states or recovery from COVID-19 in a cohort with individual data. OBJECTIVE: To assess how air pollution affects the transition to more severe COVID-19 states or to recovery from COVID-19 infection in a cohort with detailed patient information. DESIGN AND OUTCOMES: We used a cohort design that followed patients admitted to hospital in the Kaiser Permanente Southern California (KPSC) Health System, which has 4.7 million members with characteristics similar to the general population. Enrollment began on 06/01/2020 and ran until 01/30/2021 for all patients admitted to hospital while ill with COVID-19. All possible states of sequelae were considered, including deterioration to intensive care, to death, discharge to recovery, or discharge to death. Transition risks were estimated with a multistate model. We assessed exposure using chemical transport model that predicted ambient concentrations of nitrogen dioxide, ozone, and fine particulate matter (PM2.5) at a 1 km scale. RESULTS: Each increase in PM2.5 concentration equivalent to the interquartile range was associated with increased risk of deterioration to intensive care (HR of 1.16; 95% CI: 1.12-1.20) and deterioration to death (HR of 1.11; 95% CI: 1.04-1.17). Results for ozone were consistent with PM2.5 effects, but ozone also affected the transition from recovery to death: HR of 1.24 (95% CI: 1.01-1.51). NO2 had weaker effects but displayed some elevated risks. CONCLUSIONS: PM2.5 and ozone were significantly associated with transitions to more severe states while in hospital and to death after discharge from hospital. Reducing air pollution could therefore lead to improved prognosis for COVID-19 patients and a sustainable means of reducing the health impacts of coronaviruses now and in the future.

Air Pollution and Pediatric Respiratory Hospitalizations: Effect Modification by Particle Constituents and Oxidative Potential.

Rationale: Outdoor particulate and gaseous air pollutants impair respiratory health in children, and these associations may be influenced by particle composition. Objectives: To examine whether associations between short-term variations in fine particulate air pollution, oxidant gases, and respiratory hospitalizations in children are modified by particle constituents (metals and sulfur) or oxidative potential. Methods: We conducted a case-crossover study of 10,500 children (0-17 years of age) across Canada. Daily fine particle mass concentrations and oxidant gases (nitrogen dioxide and ozone) were collected from ground monitors. Monthly estimates of fine particle constituents (metals and sulfur) and oxidative potential were also measured. Conditional logistic regression models were used to estimate associations between air pollutants and respiratory hospitalizations, above and below median values for particle constituents and oxidative potential. Measurements and Main Results: Lag-1 fine particulate matter mass concentrations were not associated with respiratory hospitalizations (odds ratio and 95% confidence interval per 10 µg/m3 increase in fine particulate matter: 1.004 [0.955-1.056]) in analyses ignoring particle constituents and oxidative potential. However, when models were examined above or below median metals, sulfur, and oxidative potential, positive associations were observed above the median. For example, the odds ratio and 95% confidence interval per 10 µg/m3 increase in fine particulate matter were 1.084 (1.007-1.167) when copper was above the median and 0.970 (0.929-1.014) when copper was below the median. Similar trends were observed for oxidant gases. Conclusions: Stronger associations were observed between outdoor fine particles, oxidant gases, and respiratory hospitalizations in children when metals, sulfur, and particle oxidative potential were elevated.

Long-term Exposure to Oxidant Gases and Mortality: Effect Modification by PM 2.5 Transition Metals and Oxidative Potential.

BACKGROUND: Populations are simultaneously exposed to outdoor concentrations of oxidant gases (i.e., O 3 and NO 2 ) and fine particulate air pollution (PM 2.5 ). Since oxidative stress is thought to be an important mechanism explaining air pollution health effects, the adverse health impacts of oxidant gases may be greater in locations where PM 2.5 is more capable of causing oxidative stress. METHODS: We conducted a cohort study of 2 million adults in Canada between 2001 and 2016 living within 10 km of ground-level monitoring sites for outdoor PM 2.5 components and oxidative potential. O x exposures (i.e., the redox-weighted average of O 3 and NO 2 ) were estimated using a combination of chemical transport models, land use regression models, and ground-level data. Cox proportional hazards models were used to estimate associations between 3-year moving average O x and mortality outcomes across strata of transition metals and sulfur in PM 2.5 and three measures of PM 2.5 oxidative potential adjusting for possible confounding factors. RESULTS: Associations between O x and mortality were consistently stronger in regions with elevated PM 2.5 transition metal/sulfur content and oxidative potential. For example, each interquartile increase (6.27 ppb) in O x was associated with a 14.9% (95% CI = 13.0, 16.9) increased risk of nonaccidental mortality in locations with glutathione-related oxidative potential (OP GSH ) above the median whereas a 2.50% (95% CI = 0.600, 4.40) increase was observed in regions with OP GSH levels below the median (interaction P value <0.001). CONCLUSION: Spatial variations in PM 2.5 composition and oxidative potential may contribute to heterogeneity in the observed health impacts of long-term exposures to oxidant gases.

Differential Mortality Risks Associated With PM2.5 Components: A Multi-Country, Multi-City Study.

BACKGROUND: The association between fine particulate matter (PM2.5) and mortality widely differs between as well as within countries. Differences in PM2.5 composition can play a role in modifying the effect estimates, but there is little evidence about which components have higher impacts on mortality. METHODS: We applied a 2-stage analysis on data collected from 210 locations in 16 countries. In the first stage, we estimated location-specific relative risks (RR) for mortality associated with daily total PM2.5 through time series regression analysis. We then pooled these estimates in a meta-regression model that included city-specific logratio-transformed proportions of seven PM2.5 components as well as meta-predictors derived from city-specific socio-economic and environmental indicators. RESULTS: We found associations between RR and several PM2.5 components. Increasing the ammonium (NH4+) proportion from 1% to 22%, while keeping a relative average proportion of other components, increased the RR from 1.0063 (95% confidence interval [95% CI] = 1.0030, 1.0097) to 1.0102 (95% CI = 1.0070, 1.0135). Conversely, an increase in nitrate (NO3-) from 1% to 71% resulted in a reduced RR, from 1.0100 (95% CI = 1.0067, 1.0133) to 1.0037 (95% CI = 0.9998, 1.0077). Differences in composition explained a substantial part of the heterogeneity in PM2.5 risk. CONCLUSIONS: These findings contribute to the identification of more hazardous emission sources. Further work is needed to understand the health impacts of PM2.5 components and sources given the overlapping sources and correlations among many components.

Cardiopulmonary Mortality and Fine Particulate Air Pollution by Species and Source in a National U.S. Cohort.

The purpose of this study was to estimate cardiopulmonary mortality associations for long-term exposure to PM2.5 species and sources (i.e., components) within the U.S. National Health Interview Survey cohort. Exposures were estimated through a chemical transport model for six species (i.e., elemental carbon (EC), primary organic aerosols (POA), secondary organic aerosols (SOA), sulfate (SO4), ammonium (NH4), nitrate (NO3)) and five sources of PM2.5 (i.e., vehicles, electricity-generating units (EGU), non-EGU industrial sources, biogenic sources (bio), "other" sources). In single-pollutant models, we found positive, significant (p < 0.05) mortality associations for all components, except POA. After adjusting for remaining PM2.5 (total PM2.5 minus component), we found significant mortality associations for EC (hazard ratio (HR) = 1.36; 95% CI [1.12, 1.64]), SOA (HR = 1.11; 95% CI [1.05, 1.17]), and vehicle sources (HR = 1.06; 95% CI [1.03, 1.10]). HRs for EC, SOA, and vehicle sources were significantly larger in comparison to those for remaining PM2.5 (per unit µg/m3). Our findings suggest that cardiopulmonary mortality associations vary by species and source, with evidence that EC, SOA, and vehicle sources are important contributors to the PM2.5 mortality relationship. With further validation, these findings could facilitate targeted pollution regulations that more efficiently reduce air pollution mortality.

Designing health impact functions to assess marginal changes in outdoor fine particulate matter.

Estimating health benefits from improvements in ambient air quality requires the characterization of the magnitude and shape of the association between marginal changes in exposure and marginal changes in risk, and its uncertainty. Several attempts have been made to do this, each requiring different assumptions. These include the Log-Linear(LL), IntegratedExposure-Response(IER), and GlobalExposureMortalityModel(GEMM). In this paper we develop an improved relative risk model suitable for use in health benefits analysis that incorporates features of existing models while addressing limitations in each model. We model the derivative of the relative risk function within a meta-analytic framework; a quantity directly applicable to benefits analysis, incorporating a Fusion of algebraic functions used in previous models. We assume a constant derivative in concentration over low exposures, like the LL model, a declining derivative over moderate exposures observed in cohort studies, and a derivative declining as the inverse of concentration over high global exposures in a similar manner to the GEMM. The model properties are illustrated with examples of fitting it to data for the six specific causes of death previously examined by the GlobalBurdenofDisease program with ambient fine particulate matter (PM2.5). In a test case analysis assuming a 1% (benefits analysis) or 100% (burden analysis), reduction in country-specific fine particulate matter concentrations, corresponding estimated global attributable deaths using the Fusion model were found to lie between those of the IER and LL models, with the GEMM estimates similar to those based on the LL model.

Ambient air pollution and the risk of acute myocardial infarction and stroke: A national cohort study.

We used a large national cohort in Canada to assess the incidence of acute myocardial infarction (AMI) and stroke hospitalizations in association with long-term exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3). The study population comprised 2.7 million respondents from the 2006 Canadian Census Health and Environment Cohort (CanCHEC), followed for incident hospitalizations of AMI or stroke between 2006 and 2016. We estimated 10-year moving average estimates of PM2.5, NO2, and O3, annually. We used Cox proportional hazards models to examine the associations adjusting for various covariates. For AMI, each interquartile range (IQR) increase in exposure was found to be associated with a hazard ratio of 1.026 (95% CI: 1.007-1.046) for PM2.5, 1.025 (95% CI: 1.001-1.050) for NO2, and 1.062 (95% CI: 1.041-1.084) for O3, respectively. Similarly, for stroke, an IQR increase in exposure was associated with a hazard ratio of 1.078 (95% CI: 1.052-1.105) for PM2.5, 0.995 (95% CI: 0.965-1.030) for NO2, and 1.055 (95% CI: 1.028-1.082) for O3, respectively. We found consistent evidence of positive associations between long-term exposures to PM2.5, and O3, and to a lesser degree NO2, with incident AMI and stroke hospitalizations.

Within-City Variation in Reactive Oxygen Species from Fine Particle Air Pollution and COVID-19.

Rationale: Evidence linking outdoor air pollution with coronavirus disease (COVID-19) incidence and mortality is largely based on ecological comparisons between regions that may differ in factors such as access to testing and control measures that may not be independent of air pollution concentrations. Moreover, studies have yet to focus on key mechanisms of air pollution toxicity such as oxidative stress. Objectives: To conduct a within-city analysis of spatial variations in COVID-19 incidence and the estimated generation of reactive oxygen species (ROS) in lung lining fluid attributable to fine particulate matter (particulate matter with an aerodynamic diameter ⩽2.5 µm [PM2.5]). Methods: Sporadic and outbreak-related COVID-19 case counts, testing data, population data, and sociodemographic data for 140 neighborhoods were obtained from the City of Toronto. ROS estimates were based on a mathematical model of ROS generation in lung lining fluid in response to iron and copper in PM2.5. Spatial variations in long-term average ROS were predicted using a land-use regression model derived from measurements of iron and copper in PM2.5. Data were analyzed using negative binomial regression models adjusting for covariates identified using a directed acyclic graph and accounting for spatial autocorrelation. Measurements and Main Results: A significant positive association was observed between neighborhood-level ROS and COVID-19 incidence (incidence rate ratio = 1.07; 95% confidence interval, 1.01-1.15 per interquartile range ROS). Effect modification by neighborhood-level measures of racialized group membership and socioeconomic status was also identified. Conclusions: Examination of neighborhood characteristics associated with COVID-19 incidence can identify inequalities and generate hypotheses for future studies.

Air Pollution as a Risk Factor for Incident Chronic Obstructive Pulmonary Disease and Asthma. A 15-Year Population-based Cohort Study.

Rationale: Current evidence on the relationship between long-term exposure to air pollution and new onset of chronic lung disease is inconclusive.Objectives: To examine associations of incident chronic obstructive pulmonary disease (COPD) and adult-onset asthma with past exposure to fine particulate matter ≤ 2.5 µm in diameter (PM2.5), nitrogen dioxide (NO2), ozone (O3), and the redox-weighted average of NO2 and O3 (Ox) and characterize the concentration-response relationship.Methods: We conducted a population-based cohort study of all Ontarians, aged 35-85 years, from 2001 to 2015. A 3-year moving average of residential exposures to selected pollutants with a 1-year lag were estimated during follow-up. We used Cox proportional hazard models and Aalen additive-hazard models to quantify the pollution-disease associations and characterized the shape of these relationships using newly developed nonlinear risk models.Measurements and Main Results: Among 5.1 million adults, we identified 340,733 and 218,005 incident cases of COPD and asthma, respectively. We found positive associations of COPD with PM2.5 per interquartile-range (IQR) increase of 3.4 µg/m3 (hazard ratio, 1.07; 95% confidence interval, 1.06-1.08), NO2 per IQR increase of 13.9 ppb (1.04; 1.02-1.05), O3 per IQR increase of 6.3 ppb (1.04; 1.03-1.04), and Ox per IQR increase of 4.4 ppb (1.03; 1.03-1.03). By contrast, we did not find strong evidence linking these pollutants to adult-onset asthma. In addition, we quantified that each IQR increase in pollution exposure yielded 3.0 (2.4-3.6), 3.2 (2.0-4.3), 1.9 (1.3-2.5), and 2.3 (1.7-2.9) excess cases of COPD per 100,000 adults for PM2.5, NO2, O3, and Ox, respectively. Furthermore, most pollutant-COPD relationships exhibited supralinear shapes.Conclusions: Air pollution was associated with a higher incidence of COPD but was not associated with a higher incidence of adult-onset asthma.

A Population-Based Cohort Study of Respiratory Disease and Long-Term Exposure to Iron and Copper in Fine Particulate Air Pollution and Their Combined Impact on Reactive Oxygen Species Generation in Human Lungs.

Metal components in fine particulate matter (PM2.5) from nontailpipe emissions may play an important role in underlying the adverse respiratory effects of PM2.5. We investigated the associations between long-term exposure to iron (Fe) and copper (Cu) in PM2.5 and their combined impact on reactive oxygen species (ROS) generation in human lungs, and the incidence of asthma, chronic obstructive pulmonary disease (COPD), COPD mortality, pneumonia mortality, and respiratory mortality. We conducted a population-based cohort study of ∼0.8 million adults in Toronto, Canada. Land-use regression models were used to estimate the concentrations of Fe, Cu, and ROS. Outcomes were ascertained using validated health administrative databases. We found positive associations between long-term exposure to Fe, Cu, and ROS and the risks of all five respiratory outcomes. The associations were more robust for COPD, pneumonia mortality, and respiratory mortality than for asthma incidence and COPD mortality. Stronger associations were observed for ROS than for either Fe or Cu. In two-pollutant models, adjustment for nitrogen dioxide somewhat attenuated the associations while adjustment for PM2.5 had little influence. Long-term exposure to Fe and Cu in PM2.5 and estimated ROS concentration in lung fluid was associated with increased incidence of respiratory diseases, suggesting the adverse respiratory effects of nontailpipe emissions.

Predicting Spatial Variations in Multiple Measures of Oxidative Burden for Outdoor Fine Particulate Air Pollution across Canada.

Fine particulate air pollution (PM2.5) is a leading contributor to the overall global burden of disease. Traditionally, outdoor PM2.5 has been characterized using mass concentrations which treat all particles as equally harmful. Oxidative potential (OP) (per µg) and oxidative burden (OB) (per m3) are complementary metrics that estimate the ability of PM2.5 to cause oxidative stress, which is an important mechanism in air pollution health effects. Here, we provide the first national estimates of spatial variations in multiple measures (glutathione, ascorbate, and dithiothreitol depletion) of annual median outdoor PM2.5 OB across Canada. To do this, we combined a large database of ground-level OB measurements collected monthly prospectively across Canada for 2 years (2016-2018) with PM2.5 components estimated using a chemical transport model (GEOS-Chem) and satellite aerosol observations. Our predicted ground-level OB values of all three methods were consistent with ground-level observations (cross-validation R2 = 0.63-0.74). We found that forested regions and urban areas had the highest OB, predicted primarily by black carbon and organic carbon from wildfires and transportation sources. Importantly, the dominant components associated with OB were different than those contributing to PM2.5 mass concentrations (secondary inorganic aerosol); thus, OB metrics may better indicate harmful components and sources on health than the bulk PM2.5 mass, reinforcing that OB estimates can complement the existing PM2.5 data in future national-level epidemiological studies.

Global estimates of mortality associated with long-term exposure to outdoor fine particulate matter.

Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries-the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5-10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9-8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3-4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations.

Exposure to ambient air pollution and the incidence of lung cancer and breast cancer in the Ontario Population Health and Environment Cohort.

Lung and female breast cancers are highly prevalent worldwide. Although the association between exposure to ambient fine particulate matter (PM2.5 ) and lung cancer has been recognized, there is less evidence for associations with other common air pollutants such as nitrogen dioxide (NO2 ) and ozone (O3 ). Even less is known about potential associations between these pollutants and breast cancer. We conducted a population-based cohort study to investigate the associations of chronic exposure to PM2.5 , NO2 , O3 and redox-weighted average of NO2 and O3 (Ox ) with incident lung and breast cancer, using the Ontario Population Health and Environment Cohort (ONPHEC), which includes all long-term residents aged 35-85 years who lived in Ontario, Canada, 2001-2015. Incident lung and breast cancers were ascertained using the Ontario Cancer Registry. Annual estimates of exposures were assigned to the residential postal codes of subjects for each year during follow-up. We used Cox proportional-hazards models adjusting for personal- and neighborhood-level covariates. Our cohorts for lung and breast cancer analyses included ~4.9 million individuals and ~2.5 million women, respectively. During follow-up, 100,146 incident cases of lung cancer and 91,146 incident cases of breast cancer were diagnosed. The fully adjusted analyses showed positive associations of lung cancer incidence with PM2.5 (hazard ratio [HR] = 1.02 [95% CI: 1.01-1.05] per 5.3 µg/m3 ) and NO2 (HR = 1.05 [95% CI: 1.03-1.07] per 14 ppb). No associations with lung cancer were observed for O3 or Ox . Relationships between PM2.5 and NO2 with lung cancer exhibited a sublinear shape. We did not find compelling evidence linking air pollution to breast cancer.

Cancer mortality risk, fine particulate air pollution, and smoking in a large, representative cohort of US adults.

PURPOSE: Air pollution and smoking are associated with various types of mortality, including cancer. The current study utilizes a publicly accessible, nationally representative cohort to explore relationships between fine particulate matter (PM2.5) exposure, smoking, and cancer mortality. METHODS: National Health Interview Survey and mortality follow-up data were combined to create a study population of 635,539 individuals surveyed from 1987 to 2014. A sub-cohort of 341,665 never-smokers from the full cohort was also created. Individuals were assigned modeled PM2.5 exposure based on average exposure from 1999 to 2015 at residential census tract. Cox Proportional Hazard models were utilized to estimate hazard ratios for cancer-specific mortality controlling for age, sex, race, smoking status, body mass, income, education, marital status, rural versus urban, region, and survey year. RESULTS: The risk of all cancer mortality was adversely associated with PM2.5 (per 10 µg/m3 increase) in the full cohort (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.08-1.22) and the never-smokers' cohort (HR 1.19, 95% CI 1.06-1.33). PM2.5-morality associations were observed specifically for lung, stomach, colorectal, liver, breast, cervix, and bladder, as well as Hodgkin lymphoma, non-Hodgkin lymphoma, and leukemia. The PM2.5-morality association with lung cancer in never-smokers was statistically significant adjusting for multiple comparisons. Cigarette smoking was statistically associated with mortality for many cancer types. CONCLUSIONS: Exposure to PM2.5 air pollution contributes to lung cancer mortality and may be a risk factor for other cancer types. Cigarette smoking has a larger impact on cancer mortality than PM2.5 , but is associated with similar cancer types.

Quantitative Characterization of Uncertainty in the Concentration-Response Relationship between Long-Term PM2.5 Exposure and Mortality at Low Concentrations.

Extensive epidemiologic evidence supports a linear, no-threshold concentration-response (C-R) relationship between long-term exposure to fine particles (PM2.5) and mortality in the United States. While examinations of the C-R relationship are designed to assess the shape of the C-R curve, they do not provide the information needed to quantitatively characterize uncertainty at specific PM2.5 concentrations, which is often needed in the context of risk assessments and benefits analyses. We developed a novel approach, using information that is typically available in published epidemiologic studies, to quantitatively characterize uncertainty at different concentrations along the PM2.5 concentration distribution. Our approach utilizes the annual mean PM2.5 concentration and corresponding standard deviation from a published epidemiologic study to estimate the standard deviation of hypothetical PM2.5 concentration distributions defined at 0.1 µg/m3 increments. The hypothetical distributions are then used to derive adjusted uncertainty estimates in the reported effect estimate at low concentrations (i.e., concentrations lower than the annual mean observed in the study). We demonstrate the application of this method in six individual epidemiologic studies that examined the relationship between long-term PM2.5 exposure and mortality and were conducted in different geographic locations worldwide and at different PM2.5 concentrations. This new method allows for a more comprehensive quantitative evaluation of uncertainty in the shape of the C-R relationship between long-term PM2.5 exposure and mortality at concentrations below the mean annual concentrations observed in current studies.

Understanding the Joint Impacts of Fine Particulate Matter Concentration and Composition on the Incidence and Mortality of Cardiovascular Disease: A Component-Adjusted Approach.

Past health impact assessments of ambient fine particulate matter (particles with an aerodynamic diameter ≤2.5 µm; PM2.5) have generally considered mass concentration only, despite PM2.5 being a heterogeneous mixture. Given constant changes in the concentration and the composition of atmospheric aerosol, uncertainty exists as to whether the current focus on PM2.5 mass or individual components may fully characterize the health burden of PM2.5. We proposed a component-adjusted method that jointly estimates the health impacts of PM2.5 and its major components while allowing for a potential nonlinear PM2.5-outcome relationship. Using this method, we quantified the effects of PM2.5 on the risks of developing acute myocardial infarction (AMI) and dying from cardiovascular causes in comparison to three traditional approaches in the entire adult population across Ontario, Canada. We observed that PM2.5 was positively associated with AMI incidence and cardiovascular mortality with all four methods. Compared to the traditional approaches, however, the new component-adjusted approach demonstrated a significant improvement in explaining the health impacts of PM2.5, especially in the presence of a nonlinear PM2.5-outcome relationship. Using the new approach, we found that the effects of PM2.5 on AMI incidence and cardiovascular mortality may be 10% to 27% higher than what would be estimated from the conventional approaches examining PM2.5 alone.

Fine particulate air pollution and human mortality: 25+ years of cohort studies.

Much of the key epidemiological evidence that long-term exposure to fine particulate matter air pollution (PM2.5) contributes to increased risk of mortality comes from survival studies of cohorts of individuals. Although the first two of these studies, published in the mid-1990s, were highly controversial, much has changed in the last 25 + years. The objectives of this paper are to succinctly compile and summarize the findings of these cohort studies using meta-analytic tools and to address several of the key controversies. Independent reanalysis and substantial extended analysis of the original cohort studies have been conducted and many additional studies using a wide variety of cohorts, including cohorts constructed from public data and leveraging natural experiments have been published. Meta-analytic estimates of the mean of the distribution of effects from cohort studies that are currently available, provide substantial evidence of adverse air pollution associations with all-cause, cardiopulmonary, and lung cancer mortality.