Associations between ambient air pollution and daily mortality in a cohort of congestive heart failure: Case-crossover and nested case-control analyses using a distributed lag nonlinear model.

BACKGROUND: Persons with congestive heart failure may be at higher risk of the acute effects related to daily fluctuations in ambient air pollution. To meet some of the limitations of previous studies using grouped-analysis, we developed a cohort study of persons with congestive heart failure to estimate whether daily non-accidental mortality were associated with spatially-resolved, daily exposures to ambient nitrogen dioxide (NO2) and ozone (O3), and whether these associations were modified according to a series of indicators potentially reflecting complications or worsening of health. METHODS: We constructed the cohort from the linkage of administrative health databases. Daily exposure was assigned from different methods we developed previously to predict spatially-resolved, time-dependent concentrations of ambient NO2 (all year) and O3 (warm season) at participants' residences. We performed two distinct types of analyses: a case-crossover that contrasts the same person at different times, and a nested case-control that contrasts different persons at similar times. We modelled the effects of air pollution and weather (case-crossover only) on mortality using distributed lag nonlinear models over lags 0 to 3 days. We developed from administrative health data a series of indicators that may reflect the underlying construct of "declining health", and used interactions between these indicators and the cross-basis function for air pollutant to assess potential effect modification. RESULTS: The magnitude of the cumulative as well as the lag-specific estimates of association differed in many instances according to the metric of exposure. Using the back-extrapolation method, which is our preferred exposure model, we found for the case-crossover design a cumulative mean percentage changes (MPC) in daily mortality per interquartile increment in NO2 (8.8 ppb) of 3.0% (95% CI: -0.4, 6.6%) and for O3 (16.5 ppb) 3.5% (95% CI: -4.5, 12.1). For O3 there was strong confounding by weather (unadjusted MPC = 7.1%; 95% CI: 1.7, 12.7%). For the nested case-control approach the cumulative MPC for NO2 in daily mortality was 2.9% (95% CI: -0.9, 6.9%) and for O3 7.3% (95% CI: 3.0, 11.9%). We found evidence of effect modification between daily mortality and cumulative NO2 and O3 according to the prescribed dose of furosemide in the nested case-control analysis, but not in the case-crossover analysis. CONCLUSIONS: Mortality in congestive heart failure was associated with exposure to daily ambient NO2 and O3 predicted from a back-extrapolation method using a land use regression model from dense sampling surveys. The methods used to assess exposure can have considerable influence on the estimated acute health effects of the two air pollutants

Complex relationships between greenness, air pollution, and mortality in a population-based Canadian cohort

Background: Epidemiological studies have consistently demonstrated that exposure to fine particulate matter (PM 2.5 )is associated with increased risks of mortality. To a lesser extent, a series of studies suggest that living in greener areas is associated with reduced risks of mortality. Only a handful of studies have examined the interplay between PM 2.5 , greenness, and mortality. Methods: We investigated the role of residential greenness in modifying associations between long-term exposures to PM 2.5 and non-accidental and cardiovascular mortality in a national cohort of non-immigrant Canadian adults (i.e., the 2001 Canadian Census Health and Environment Cohort). Specifically, we examined associations between satellite-derived estimates of PM 2.5 exposure and mortality across quintiles of greenness measured within 500 m of individual's place of residence during 11 years of follow-up. We adjusted our survival models for many personal and contextual measures of socioeconomic position, and residential mobility data allowed us to characterize annual changes in exposures. Results: Our cohort included approximately 2.4 million individuals at baseline, 194,270 of whom died from non-accidental causes during follow-up. Adjustment for greenness attenuated the association between PM 2.5 and mortality (e.g., hazard ratios (HRs)and 95% confidence intervals (CIs)per interquartile range increase in PM 2.5 in models for non-accidental mortality decreased from 1.065 (95% CI: 1.056–1.075)to 1.041 (95% CI: 1.031–1.050)). The strength of observed associations between PM 2.5 and mortality decreased as greenness increased. This pattern persisted in models restricted to urban residents, in models that considered the combined oxidant capacity of ozone and nitrogen dioxide, and within neighbourhoods characterised by high or low deprivation. We found no increased risk of mortality associated with PM 2.5 among those living in the greenest areas. For example, the HR for cardiovascular mortality among individuals in the least green areas was 1.17 (95% CI: 1.12–1.23)compared to 1.01 (95% CI: 0.97–1.06)among those in the greenest areas. Conclusions: Studies that do not account for greenness may overstate the air pollution impacts on mortality. Residents in deprived neighbourhoods with high greenness benefitted by having more attenuated associations between PM 2.5 and mortality than those living in deprived areas with less greenness. The findings from this study extend our understanding of how living in greener areas may lead to improved health outcomes

Ambient PM₂.₅, O₃, and NO₂ Exposures and Associations with Mortality over 16 Years of Follow-Up in the Canadian Census Health and Environment Cohort (CanCHEC)

Background: Few studies examining the associations between long-term exposure to ambient air pollution and mortality have considered multiple pollutants when assessing changes in exposure due to residential mobility during follow-up. Objective: We investigated associations between cause-specific mortality and ambient concentrations of fine particulate matter (≤ 2.5 μm; PM₂.₅), ozone (O₃), and nitrogen dioxide (NO₂) in a national cohort of about 2.5 million Canadians. Methods: We assigned estimates of annual concentrations of these pollutants to the residential postal codes of subjects for each year during 16 years of follow-up. Historical tax data allowed us to track subjects’ residential postal code annually. We estimated hazard ratios (HRs) for each pollutant separately and adjusted for the other pollutants. We also estimated the product of the three HRs as a measure of the cumulative association with mortality for several causes of death for an increment of the mean minus the 5th percentile of each pollutant: 5.0 μg/m³ for PM₂.₅, 9.5 ppb for O₃, and 8.1 ppb for NO₂. Results: PM₂.₅, O₃, and NO₂ were associated with nonaccidental and cause-specific mortality in single-pollutant models. Exposure to PM₂.₅ alone was not sufficient to fully characterize the toxicity of the atmospheric mix or to fully explain the risk of mortality associated with exposure to ambient pollution. Assuming additive associations, the estimated HR for nonaccidental mortality corresponding to a change in exposure from the mean to the 5th percentile for all three pollutants together was 1.075 (95% CI: 1.067, 1.084). Accounting for residential mobility had only a limited impact on the association between mortality and PM₂.₅ and O₃, but increased associations with NO₂. Conclusions: In this large, national-level cohort, we found positive associations between several common causes of death and exposure to PM₂.₅, O₃, and NO₂

The Impact of Rural Hospital Closures and Health Service Restructuring on Provincial- and Community-Level Patterns of Hospital Admissions in New Brunswick

In the early 2000s, the Province of New Brunswick, Canada, undertook health system restructuring, including closing some rural hospitals. We examined whether changes in geographic access to hospitals and primary care were associated with changes in patterns of hospital use. We described three measures of hospital use for ambulatory care sensitive conditions (ACSCs) among adults 75 years and younger annually during the period 2004–2013 overall, and at the community scale. We described spatial and temporal patterns in: age-standardized hospitalization rates, age-standardized incidence of hospital admissions, and rates of admissions via ambulance. Overall, rates and incidence of hospitalizations for ACSCs declined while admissions via ambulance remained largely unchanged. We observed considerable regional variation in rates between communities in 2004. This regional variation decreased over time, with rural areas demonstrating the sharpest declines. Changes in hospital service provision within individual communities had little impact on rates of ACSC admissions. Results were consistent across urban and rural communities and were robust to analyses that included older patients and those admitted for reasons other than ACSCs. Our results suggest that the restructuring and hospital closures did not result in substantial changes to regional patterns or rates of service use

Double burden of deprivation and high concentrations of ambient air pollution at the neighbourhood scale in Montreal, Canada

Some neighbourhoods in urban areas are characterised by concentrations of socially and materially deprived populations. Additionally, levels of ambient air pollution in a city can be variable at the local scale and can create disparities in air quality between neighbourhoods. Socioeconomic and physical characteristics of neighbourhood environments can affect the health and well-being of local residents. In this paper we identify whether neighbourhoods in Montreal, Canada characterised by social and material deprivation have higher levels of ambient air pollution than do others. We collected two-week integrated samples of nitrogen dioxide (NO2) at 133 sites in Montreal during three seasons between 2005 and 2006. We used these data in a geographic information system, along with data describing characteristics of land use, roads, and traffic, to create a spatial model of predicted mean annual concentrations of NO2 across Montreal. Next, we collected neighbourhood socioeconomic information for 501 census tracts and overlaid their boundaries on the pollution surface. We calculated Pearson correlation coefficients and 95% confidence intervals (CI) between neighbourhood-level indicators of deprivation and levels of ambient NO2. We found associations between concentrations of NO2 and neighbourhood-level indicators of material deprivation, including median household income, and with indicators of social deprivation, including proportion of people living alone. We identified specific neighbourhoods that were characterised by a double burden of high levels of deprivation and high concentrations of ambient NO2. Because of the particular social geography in Montreal, we found that not all deprived neighbourhoods had high levels of pollution and that some affluent neighbourhoods in the downtown core had high levels. Our results underscore the importance of considering social contexts in interpreting general associations between social and environmental risks to population health.Canada Air pollution Neighbourhoods Socioeconomic position Geographic information systems (GIS)

Individual Exposure To Traffic Related Air Pollution Across Land-Use Clusters

In this study, we estimated the transportation-related emissions of nitrogen oxides (NOx) at an individual level for a sample of the Montreal population. Using linear regression, we quantified the associations between NOx emissions and selected individual attributes. We then investigated the relationship between individual emissions of NOx and exposure to nitrogen dioxide (NO2) concentrations derived from a land-use regression model. Factor analysis and clustering of land-uses were used to test the relationships between emissions and exposures in different Montreal areas. We observed that the emissions generated per individual are positively associated with vehicle ownership, gender, and employment status. We also noted that individuals who live in the suburbs or in peripheral areas generate higher emissions of NOx but are exposed to lower NO2 concentrations at home and throughout their daily activities. Finally, we observed that for most individuals, NO2 exposures based on daily activity locations were often slightly more elevated than NO2 concentrations at the home location. We estimated that between 20% and 45% of individuals experience a daily exposure that is largely different from the concentration at their home location. Our findings are relevant to the evaluation of equity in the generation of transport emissions and exposure to traffic-related air pollution. We also shed light on the effect of accounting for daily activities when estimating air pollution exposure

Inferring cell-type-specific causal gene regulatory networks during human neurogenesis

Abstract Background Genetic variation influences both chromatin accessibility, assessed in chromatin accessibility quantitative trait loci (caQTL) studies, and gene expression, assessed in expression QTL (eQTL) studies. Genetic variants can impact either nearby genes (cis-eQTLs) or distal genes (trans-eQTLs). Colocalization between caQTL and eQTL, or cis- and trans-eQTLs suggests that they share causal variants. However, pairwise colocalization between these molecular QTLs does not guarantee a causal relationship. Mediation analysis can be applied to assess the evidence supporting causality versus independence between molecular QTLs. Given that the function of QTLs can be cell-type-specific, we performed mediation analyses to find epigenetic and distal regulatory causal pathways for genes within two major cell types of the developing human cortex, progenitors and neurons. Results We find that the expression of 168 and 38 genes is mediated by chromatin accessibility in progenitors and neurons, respectively. We also find that the expression of 11 and 12 downstream genes is mediated by upstream genes in progenitors and neurons. Moreover, we discover that a genetic locus associated with inter-individual differences in brain structure shows evidence for mediation of SLC26A7 through chromatin accessibility, identifying molecular mechanisms of a common variant association to a brain trait. Conclusions In this study, we identify cell-type-specific causal gene regulatory networks whereby the impacts of variants on gene expression were mediated by chromatin accessibility or distal gene expression. Identification of these causal paths will enable identifying and prioritizing actionable regulatory targets perturbing these key processes during neurodevelopment