Epidemiological studies likely need to consider PM2.5 composition even if total outdoor PM2.5 mass concentration is the exposure of interest.

Background: Outdoor fine particulate air pollution, <2.5 µm (PM2.5) mass concentrations can be constructed through many different combinations of chemical components that have varying levels of toxicity. This poses a challenge for studies interested in estimating the health effects of total outdoor PM2.5 (i.e., how much PM2.5 mass is present in the air regardless of composition) because we must consider possible confounders of the version of treatment-outcome relationships. Methods: We evaluated the extent of possible bias in mortality hazard ratios for total outdoor PM2.5 by examining models with and without adjustment for sulfate and nitrate in PM2.5 as examples of potential confounders of version of treatment-outcome relationships. Our study included approximately 3 million Canadians and Cox proportional hazard models were used to estimate hazard ratios for total outdoor PM2.5 adjusting for sulfate and/or nitrate and other relevant covariates. Results: Hazard ratios for total outdoor PM2.5 and nonaccidental, cardiovascular, and respiratory mortality were overestimated due to the confounding version of treatment-outcome relationships, and associations for lung cancer mortality were underestimated. Sulfate was most strongly associated with nonaccidental, cardiovascular, and respiratory mortality suggesting that regulations targeting this specific component of outdoor PM2.5 may have greater health benefits than interventions targeting total PM2.5. Conclusions: Studies interested in estimating the health impacts of total outdoor PM2.5 (i.e., how much PM2.5 mass is present in the air) need to consider potential confounders of the version of treatment-outcome relationships. Otherwise, health risk estimates for total PM2.5 will reflect some unknown combination of how much PM2.5 mass is present in the air and the kind of PM2.5 mass that is present.

Fine particulate matter components and interstitial lung disease in rheumatoid arthritis.

BACKGROUND: Exposure to ambient fine particulate matter with an aerodynamic diameter <2.5 µg·m-3 (PM2.5) is a risk factor for pulmonary and systemic autoimmune diseases; however, evidence on which PM2.5 chemical components are more harmful is still scant. Our goal is to investigate potential associations between major PM2.5 components and interstitial lung disease (ILD) onset in rheumatoid arthritis (RA). METHODS: New-onset RA subjects identified from a US healthcare insurance database (MarketScan) were followed for new onset of RA-associated ILD (RA-ILD) from 2011 to 2018. Annual concentrations of ambient PM2.5 chemical components (i.e. sulfate, nitrate, ammonium, organic matter, black carbon, mineral dust and sea salt) were estimated by combining satellite retrievals with chemical transport modelling and refined by geographically weighted regression. Exposures from 2006 up to 1 year before ILD onset or end of study were assigned to subjects based on their core-based statistical area or metropolitan division codes. A novel time-to-event quantile-based g (generalised)-computation approach was used to estimate potential associations between RA-ILD onset and the exposure mixture of all seven PM2.5 chemical components adjusting for age, sex and prior chronic obstructive pulmonary disease (as a proxy for smoking). RESULTS: We followed 280 516 new-onset RA patients and detected 2194 RA-ILD cases across 1 394 385 person-years. The adjusted hazard ratio for RA-ILD onset was 1.54 (95% CI 1.47-1.63) per every decile increase in all seven exposures. Ammonium, mineral dust and black carbon contributed more to ILD risk than the other PM2.5 components. CONCLUSION: Exposure to components of PM2.5, particularly ammonium, increases ILD risk in RA.

Estimating Intra-Urban Inequities in PM2.5-Attributable Health Impacts: A Case Study for Washington, DC.

Air pollution levels are uneven within cities, contributing to persistent health disparities between neighborhoods and population sub-groups. Highly spatially resolved information on pollution levels and disease rates is necessary to characterize inequities in air pollution exposure and related health risks. We leverage recent advances in deriving surface pollution levels from satellite remote sensing and granular data in disease rates for one city, Washington, DC, to assess intra-urban heterogeneity in fine particulate matter (PM2.5)- attributable mortality and morbidity. We estimate PM2.5-attributable cases of all-cause mortality, chronic obstructive pulmonary disease, ischemic heart disease, lung cancer, stroke, and asthma emergency department (ED) visits using epidemiologically derived health impact functions. Data inputs include satellite-derived annual mean surface PM2.5 concentrations; age-resolved population estimates; and statistical neighborhood-, zip code- and ward-scale disease counts. We find that PM2.5 concentrations and associated health burdens have decreased in DC between 2000 and 2018, from approximately 240 to 120 cause-specific deaths and from 40 to 30 asthma ED visits per year (between 2014 and 2018). However, remaining PM2.5-attributable health risks are unevenly and inequitably distributed across the District. Higher PM2.5-attributable disease burdens were found in neighborhoods with larger proportions of people of color, lower household income, and lower educational attainment. Our study adds to the growing body of literature documenting the inequity in air pollution exposure levels and pollution health risks between population sub-groups, and highlights the need for both high-resolution disease rates and concentration estimates for understanding intra-urban disparities in air pollution-related health risks.

Changes in exposure to ambient fine particulate matter after relocating and long term survival in Canada: quasi-experimental study.

OBJECTIVE: To investigate the association between changes in long term residential exposure to ambient fine particulate matter (PM2.5) and premature mortality in Canada. DESIGN: Population based quasi-experimental study. SETTING: Canada. PARTICIPANTS: 663 100 respondents to the 1996, 2001, and 2006 Canadian censuses aged 25-89 years who had consistently lived in areas with either high or low PM2.5 levels over five years preceding census day and moved during the ensuing five years. INTERVENTIONS: Changes in long term exposure to PM2.5 arising from residential mobility. MAIN OUTCOME MEASURES: The primary outcome was deaths from natural causes. Secondary outcomes were deaths from any cardiometabolic cause, any respiratory cause, and any cancer cause. All outcomes were obtained from the national vital statistics database. RESULTS: Using a propensity score matching technique with numerous personal, socioeconomic, health, and environment related covariates, each participant who moved to a different PM2.5 area was matched with up to three participants who moved within the same PM2.5 area. In the matched groups that moved from high to intermediate or low PM2.5 areas, residential mobility was associated with a decline in annual PM2.5 exposure from 10.6 µg/m3 to 7.4 and 5.0 µg/m3, respectively. Conversely, in the matched groups that moved from low to intermediate or high PM2.5 areas, annual PM2.5 increased from 4.6 µg/m3 to 6.7 and 9.2 µg/m3. Five years after moving, individuals who experienced a reduction in exposure to PM2.5 from high to intermediate levels showed a 6.8% (95% confidence interval 1.7% to 11.7%) reduction in mortality (2510 deaths in 56 025 v 4925 deaths in 101 960). A greater decline in mortality occurred among those exposed to a larger reduction in PM2.5. Increased mortality was found with exposure to PM2.5 from low to high levels, and to a lesser degree from low to intermediate levels. Furthermore, the decreases in PM2.5 exposure were most strongly associated with reductions in cardiometabolic deaths, whereas the increases in PM2.5 exposure were mostly related to respiratory deaths. No strong evidence was found for the changes in PM2.5 exposure with cancer related deaths. CONCLUSIONS: In Canada, decreases in PM2.5 were associated with lower mortality, whereas increases in PM2.5 were associated with higher mortality. These results were observed at PM2.5 levels considerably lower than many other countries, providing support for continuously improving air quality.

Association of fine particulate matter air pollution and its constituents with lung function: The China Pulmonary Health study.

The associations of long-term exposure to various constituents of fine particulate matter (≤2.5 µm in aerodynamic diameter, PM2.5) air pollution with lung function were not clearly elucidated in developing countries. The aim was to evaluate the associations of long-term exposure to main constituents of PM2.5 with lung function in China. This is a nationwide, cross-sectional analysis among 50,991 study participants from the China Pulmonary Health study. Multivariable linear regression models were used to obtain differences of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow at 25-75% of exhaled FVC (FEF25-75%) associated with an interquartile range (IQR) change of PM2.5 or its constituents. Residential annual PM2.5 levels varied from 26 µg/m3 to 92 µg/m3 (average: 53 µg/m3). An IQR increase of PM2.5 concentrations was associated with lower FEV1 (19.82 mL, 95% CI: 11.30-28.33), FVC (17.45 mL, 95% CI: 7.16-27.74), PEF (86.64 mL/s, 95% CI: 59.77-113.52), and FEF25-75% (31.93 mL/s, 95% CI: 16.64-47.22). Black carbon, organic matter, ammonium, sulfate, and nitrate were negatively associated with most lung function indicators, with organic matter and nitrate showing consistently larger magnitude of associations than PM2.5 mass. This large-scale study provides first-hand epidemiological evidence that long-term exposure to ambient PM2.5 and some constituents, especially organic matter and nitrate, were associated with lower large- and small- airway function.

The prospective effects of long-term exposure to ambient PM2.5 and constituents on mortality in rural East China.

Few cohort studies explored the associations of long-term exposure to ambient fine particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) and its chemical constituents with mortality risk in rural China. We conducted a 12-year prospective study of 28,793 adults in rural Deqing, China from 2006 to 2018. Annual mean PM2.5 and its constituents, including black carbon (BC), organic carbon (OC), ammonium (NH4+), nitrate (NO3-), sulfate (SO42-), and soil dust were measured at participants' addresses at enrollment from a satellite-based exposure predicting model. Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) of long-term exposure to PM2.5 for mortality. A total of 1960 deaths were identified during the follow-up. We found PM2.5, BC, OC, NH4+, NO3-, and SO42- were significantly associated with an increased risk of non-accidental mortality. The HR for non-accidental mortality was 1.17 (95%CI: 1.07, 1.28) for each 10 µg/m3 increase in PM2.5. As for constituents, the strongest association was found for BC (HR = 1.21, 95%CI: 1.11, 1.33), followed by NO3-, NH4+, SO42-, and OC (HR = 1.14-1.17 per interquartile range). A non-linear relationship was found between PM2.5 and non-accidental mortality. Similar associations were found for cardio-cerebrovascular and cancer mortality. Associations were stronger among men and ever smokers. Conclusively, we found long-term exposure to ambient PM2.5 and its chemical constituents (especially BC and NO3-) increased mortality risk. Our results suggested the importance of adopting effective targeted emission control to improve air quality for health protection in rural East China.

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.

Ambient ultrafine particle concentrations and incidence of childhood cancers.

BACKGROUND: Ambient air pollution has been associated with childhood cancer. However, little is known about the possible impact of ambient ultrafine particles (<0.1 µm) (UFPs) on childhood cancer incidence. OBJECTIVE: This study aimed to evaluate the association between prenatal and childhood exposure to UFPs and development of childhood cancer. METHODS: We conducted a population-based cohort study of within-city spatiotemporal variations in ambient UFPs across the City of Toronto, Canada using 653,702 singleton live births occurring between April 1, 1998 and March 31, 2017. Incident cases of 13 subtypes of paediatric cancers among children up to age 14 were ascertained using a cancer registry. Associations between ambient air pollutant concentrations and childhood cancer incidence were estimated using random-effects Cox proportional hazards models. We investigated both single- and multi-pollutant models accounting for co-exposures to PM2.5 and NO2. RESULTS: A total of 1,066 childhood cancers were identified. We found that first trimester exposure to UFPs (Hazard Ratio (HR) per 10,000/cm3 increase = 1.13, 95% CI: 1.03-1.22) was associated with overall cancer incidence diagnosed before 6 years of age after adjusting for PM2.5, NO2, and for personal and neighborhood-level covariates. Association between UFPs and overall cancer incidence exhibited a linear shape. No statistically significant associations were found for specific cancer subtypes. CONCLUSION: Ambient UFPs may represent a previously unrecognized risk factor in the aetiology of cancers in children. Our findings reinforce the importance of conducting further research on the effects of UFPs given their high prevalence of exposure in urban areas.

Evaluating the Sensitivity of PM2.5-Mortality Associations to the Spatial and Temporal Scale of Exposure Assessment.

BACKGROUND: The temporal and spatial scales of exposure assessment may influence observed associations between fine particulate air pollution (PM2.5) and mortality, but few studies have systematically examined this question. METHODS: We followed 2.4 million adults in the 2001 Canadian Census Health and Environment Cohort for nonaccidental and cause-specific mortality between 2001 and 2011. We assigned PM2.5 exposures to residential locations using satellite-based estimates and compared three different temporal moving averages (1, 3, and 8 years) and three spatial scales (1, 5, and 10 km) of exposure assignment. In addition, we examined different spatial scales based on age, employment status, and urban/rural location, and adjustment for O3, NO2, or their combined oxidant capacity (Ox). RESULTS: In general, longer moving averages resulted in stronger associations between PM2.5 and mortality. For nonaccidental mortality, we observed a hazard ratio of 1.11 (95% CI = 1.08, 1.13) for the 1-year moving average compared with 1.23 (95% CI = 1.20, 1.27) for the 8-year moving average. Respiratory and lung cancer mortality were most sensitive to the spatial scale of exposure assessment with stronger associations observed at smaller spatial scales. Adjustment for oxidant gases attenuated associations between PM2.5 and cardiovascular mortality and strengthened associations with lung cancer. Despite these variations, PM2.5 was associated with increased mortality in nearly all of the models examined. CONCLUSIONS: These findings support a relationship between outdoor PM2.5 and mortality at low concentrations and highlight the importance of longer-exposure windows, more spatially resolved exposure metrics, and adjustment for oxidant gases in characterizing this relationship.

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.

Low concentrations of fine particle air pollution and mortality in the Canadian Community Health Survey cohort.

BACKGROUND: Approximately 2.9 million deaths are attributed to ambient fine particle air pollution around the world each year (PM2.5). In general, cohort studies of mortality and outdoor PM2.5 concentrations have limited information on individuals exposed to low levels of PM2.5 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 PM2.5 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 PM2.5. 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 PM2.5 exposure estimates, and mortality incidence to 2016. Cox proportional hazard models were used to estimate the relationship between non-accidental mortality and ambient PM2.5 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 PM2.5 concentrations were low (i.e. 5.9 µg/m3, s.d. 2.0) and each 10 µg/m3 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/m3 using a shape constrained health impact function. Mortality risks associated with exposure to PM2.5 were increased for males, those under age 65, and non-immigrants. Hazard ratios for PM2.5 and mortality were attenuated when gaseous pollutants were included in models. CONCLUSIONS: Outdoor PM2.5 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 PM2.5 concentrations.

Evaluation of a method to indirectly adjust for unmeasured covariates in the association between fine particulate matter and mortality.

BACKGROUND: Indirect adjustment via partitioned regression is a promising technique to control for unmeasured confounding in large epidemiological studies. The method uses a representative ancillary dataset to estimate the association between variables missing in a primary dataset with the complete set of variables of the ancillary dataset to produce an adjusted risk estimate for the variable in question. The objective of this paper is threefold: 1) evaluate the method for non-linear survival models, 2) formalize an empirical process to evaluate the suitability of the required ancillary matching dataset, and 3) test modifications to the method to incorporate time-varying exposure data, and proportional weighting of datasets. METHODS: We used the association between fine particle air pollution (PM2.5) with mortality in the 2001 Canadian Census Health and Environment Cohort (CanCHEC, N = 2.4 million, 10-years follow-up) as our primary dataset, and the 2001 cycle of the Canadian Community Health Survey (CCHS, N = 80,630) as the ancillary matching dataset that contained confounding risk factor information not available in CanCHEC (e.g., smoking). The main evaluation process used a gold-standard approach wherein two variables (education and income) available in both datasets were excluded, indirectly adjusted for, and compared to true models with education and income included to assess the amount of bias correction. An internal validation for objective 1 used only CanCHEC data, whereas an external validation for objective 2 replaced CanCHEC with the CCHS. The two proposed modifications were applied as part of the validation tests, as well as in a final indirect adjustment of four missing risk factor variables (smoking, alcohol use, diet, and exercise) in which adjustment direction and magnitude was compared to models using an equivalent longitudinal cohort with direct adjustment for the same variables. RESULTS: At baseline (2001) both cohorts had very similar PM2.5 distributions across population characteristics, although levels for CCHS participants were consistently 1.8-2.0 µg/m3 lower. Applying sample-weighting largely corrected for this discrepancy. The internal validation tests showed minimal downward bias in PM2.5 mortality hazard ratios of 0.4-0.6% using a static exposure, and 1.7-3% when a time-varying exposure was used. The external validation of the CCHS as the ancillary dataset showed slight upward bias of -0.7 to -1.1% and downward bias of 1.3-2.3% using the static and time-varying approaches respectively. CONCLUSIONS: The CCHS was found to be fairly well representative of CanCHEC and its use in Canada for indirect adjustment is warranted. Indirect adjustment methods can be used with survival models to correct hazard ratio point estimates and standard errors in models missing key covariates when a representative matching dataset is available. The results of this formal evaluation should encourage other cohorts to assess the suitability of ancillary datasets for the application of the indirect adjustment methodology to address potential residual confounding.

Associations of Long-Term Exposure to Ultrafine Particles and Nitrogen Dioxide With Increased Incidence of Congestive Heart Failure and Acute Myocardial Infarction.

Although long-term exposure to traffic-related air pollutants such as nitrogen dioxide has been linked to cardiovascular disease (CVD) mortality, little is known about the association between ultrafine particles (UFPs), defined as particles less than or equal to 0.1 µm in diameter, and incidence of major CVD events. We conducted a population-based cohort study to assess the associations of chronic exposure to UFPs and nitrogen dioxide with incident congestive heart failure (CHF) and acute myocardial infarction. Our study population comprised all long-term Canadian residents aged 30-100 years who lived in Toronto, Ontario, Canada, during the years 1996-2012. We estimated annual concentrations of UFPs and nitrogen dioxide by means of land-use regression models and assigned these estimates to participants' postal-code addresses in each year during the follow-up period. We estimated hazard ratios for the associations of UFPs and nitrogen dioxide with incident CVD using random-effects Cox proportional hazards models. We controlled for smoking and obesity using an indirect adjustment method. Our cohorts comprised approximately 1.1 million individuals at baseline. In single-pollutant models, each interquartile-range increase in UFP exposure was associated with increased incidence of CHF (hazard ratio for an interquartile-range increase (HRIQR) = 1.03, 95% confidence interval (CI): 1.02, 1.05) and acute myocardial infarction (HRIQR = 1.05, 95% CI: 1.02, 1.07). Adjustment for fine particles and nitrogen dioxide did not materially change these estimated associations. Exposure to nitrogen dioxide was also independently associated with higher CHF incidence (HRIQR = 1.04, 95% CI: 1.03, 1.06).

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.

Ambient air pollution and the prevalence of rhinoconjunctivitis in adolescents: a worldwide ecological analysis.

Whether exposure to outdoor air pollution increases the prevalence of rhinoconjunctivitis in children is unclear. Using data from Phase Three of the International Study of Asthma and Allergies in childhood (ISAAC), we investigated associations of rhinoconjunctivitis prevalence in adolescents with model-based estimates of ozone, and satellite-based estimates of fine (diameter < 2.5 µm) particulate matter (PM2.5) and nitrogen dioxide (NO2). Information on rhinoconjunctivitis (defined as self-reported nose symptoms without a cold or flu accompanied by itchy watery eyes in the past 12 months) was available on 505,400 children aged 13-14 years, in 183 centres in 83 countries. Centre-level prevalence estimates were calculated and linked geographically with estimates of long-term average concentrations of NO2, ozone and PM2.5. Multi-level models were fitted adjusting for population density, climate, sex and gross national income. Information on parental smoking, truck traffic and cooking fuel was available for a restricted set of centres (77 in 36 countries). Between centres within countries, the estimated change in rhinoconjunctivitis prevalence per 100 children was 0.171 (95% confidence interval: - 0.013, 0.354) per 10% increase in PM2.5, 0.096 (- 0.003, 0.195) per 10% increase in NO2 and - 0.186 (- 0.390, 0.018) per 1 ppbV increase in ozone. Between countries, rhinoconjunctivitis prevalence was significantly negatively associated with both ozone and PM2.5. In the restricted dataset, the latter association became less negative following adjustment for parental smoking and open fires for cooking. In conclusion, there were no significant within-country associations of rhinoconjunctivitis prevalence with study pollutants. Negative between-country associations with PM2.5 and ozone require further investigation.

Long-term exposure to ambient ultrafine particles and respiratory disease incidence in in Toronto, Canada: a cohort study.

BACKGROUND: Little is known about the long-term health effects of ambient ultrafine particles (<0.1 µm) (UFPs) including their association with respiratory disease incidence. In this study, we examined the relationship between long-term exposure to ambient UFPs and the incidence of lung cancer, adult-onset asthma, and chronic obstructive pulmonary disease (COPD). METHODS: Our study cohort included approximately 1.1 million adults who resided in Toronto, Canada and who were followed for disease incidence between 1996 and 2012. UFP exposures were assigned to residential locations using a land use regression model. Random-effect Cox proportional hazard models were used to estimate hazard ratios (HRs) describing the association between ambient UFPs and respiratory disease incidence adjusting for ambient fine particulate air pollution (PM2.5), NO2, and other individual/neighbourhood-level covariates. RESULTS: In total, 74,543 incident cases of COPD, 87,141 cases of asthma, and 12,908 cases of lung cancer were observed during follow-up period. In single pollutant models, each interquartile increase in ambient UFPs was associated with incident COPD (HR = 1.06, 95% CI: 1.05, 1.09) but not asthma (HR = 1.00, 95% CI: 1.00, 1.01) or lung cancer (HR = 1.00, 95% CI: 0.97, 1.03). Additional adjustment for NO2 attenuated the association between UFPs and COPD and the HR was no longer elevated (HR = 1.01, 95% CI: 0.98, 1.03). PM2.5 and NO2 were each associated with increased incidence of all three outcomes but risk estimates for lung cancer were sensitive to indirect adjustment for smoking and body mass index. CONCLUSIONS: In general, we did not observe clear evidence of positive associations between long-term exposure to ambient UFPs and respiratory disease incidence independent of other air pollutants. Further replication is required as few studies have evaluated these relationships.

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

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

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.

Comparing the Health Effects of Ambient Particulate Matter Estimated Using Ground-Based versus Remote Sensing Exposure Estimates.

BACKGROUND: Remote sensing (RS) is increasingly used for exposure assessment in epidemiological and burden of disease studies, including those investigating whether chronic exposure to ambient fine particulate matter (PM2.5) is associated with mortality. OBJECTIVES: We compared relative risk estimates of mortality from diseases of the circulatory system for PM2.5 modeled from RS with that for PM2.5 modeled using ground-level information. METHODS: We geocoded the baseline residence of 668,629 American Cancer Society Cancer Prevention Study II (CPS-II) cohort participants followed from 1982 to 2004 and assigned PM2.5 levels to all participants using seven different exposure models. Most of the exposure models were averaged for the years 2002-2004, and one RS estimate was for a longer, contemporaneous period. We used Cox proportional hazards regression to estimate relative risks (RRs) for the association of PM2.5 with circulatory mortality and ischemic heart disease. RESULTS: Estimates of mortality risk differed among exposure models. The smallest relative risk was observed for the RS estimates that excluded ground-based monitors for circulatory deaths [RR = 1.02, 95% confidence interval (CI): 1.00, 1.04 per 10 µg/m3 increment in PM2.5]. The largest relative risk was observed for the land-use regression model that included traffic information (RR = 1.14, 95% CI: 1.11, 1.17 per 10 µg/m3 increment in PM2.5). CONCLUSIONS: We found significant associations between PM2.5 and mortality in every model; however, relative risks estimated from exposure models using ground-based information were generally larger than those estimated using RS alone.

Long-term exposure to fine particulate matter air pollution and the risk of lung cancer among participants of the Canadian National Breast Screening Study.

Recently, air pollution has been classified as a carcinogen largely on the evidence of epidemiological studies of lung cancer. However, there have been few prospective studies that have evaluated associations between fine particulate matter (PM2.5 ) and cancer at lower concentrations. We conducted a prospective analysis of 89,234 women enrolled in the Canadian National Breast Screening Study between 1980 and 1985, and for whom residential measures of PM2.5 could be assigned. The cohort was linked to the Canadian Cancer Registry to identify incident lung cancers through 2004. Surface PM2.5 concentrations were estimated using satellite data. Cox proportional hazards models were used to characterize associations between PM2.5 and lung cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) computed from these models were adjusted for several individual-level characteristics, including smoking. The cohort was composed predominantly of Canadian-born (82%), married (80%) women with a median PM2.5 exposure of 9.1 µg/m(3) . In total, 932 participants developed lung cancer. In fully adjusted models, a 10 µg/m(3) increase in PM2.5 was associated with an elevated risk of lung cancer (HR: 1.34; 95% CI = 1.10, 1.65). The strongest associations were observed with small cell carcinoma (HR: 1.53; 95% CI = 0.93, 2.53) and adenocarcinoma (HR: 1.44; 95% CI = 1.06, 1.97). Stratified analyses suggested increased PM2.5 risks were limited to those who smoked cigarettes. Our findings are consistent with previous epidemiological investigations of long-term exposure to PM2.5 and lung cancer. Importantly, they suggest associations persist at lower concentrations such as those currently found in Canadian cities.