Air pollution and human health: a phenome-wide association study.

OBJECTIVES: To explore the associations of long-term exposure to air pollution with onset of all human health conditions. DESIGN: Prospective phenome-wide association study. SETTING: Denmark. PARTICIPANTS: All Danish residents aged ≥30 years on 1 January 2000 were included (N=3 323 612). After exclusion of individuals with missing geocoded residential addresses, 3 111 988 participants were available for the statistical analyses. MAIN OUTCOME MEASURE: First registered diagnosis of every health condition according to the International Classification of Diseases, 10th revision, from 2000 to 2017. RESULTS: Long-term exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were both positively associated with the onset of more than 700 health conditions (ie, >80% of the registered health conditions) after correction for multiple testing, while the remaining associations were inverse or insignificant. As regards the most common health conditions, PM2.5 and NO2 were strongest positively associated with chronic obstructive pulmonary disease (PM2.5: HR 1.06 (95% CI 1.05 to 1.07) per 1 IQR increase in exposure level; NO2: 1.14 (95% CI 1.12 to 1.15)), type 2 diabetes (PM2.5: 1.06 (95% CI 1.05 to 1.06); NO2: 1.12 (95% CI 1.10 to 1.13)) and ischaemic heart disease (PM2.5: 1.05 (95% CI 1.04 to 1.05); NO2: 1.11 (95% CI 1.09 to 1.12)). Furthermore, PM2.5 and NO2 were both positively associated with so far unexplored, but highly prevalent outcomes relevant to public health, including senile cataract, hearing loss and urinary tract infection. CONCLUSIONS: The findings of this study suggest that air pollution has a more extensive impact on human health than previously known. However, as this study is the first of its kind to investigate the associations of long-term exposure to air pollution with onset of all human health conditions, further research is needed to replicate the study findings.

Early-life air pollution and green space exposures as determinants of stunting among children under age five in Sub-Saharan Africa.

BACKGROUND: Childhood malnutrition is a major public health issue in Sub-Saharan Africa (SSA) and 61.4 million children under the age of five years in the region are stunted. Although insight from existing studies suggests plausible pathways between ambient air pollution exposure and stunting, there are limited studies on the effect of different ambient air pollutants on stunting among children. OBJECTIVE: Explore the effect of early-life environmental exposures on stunting among children under the age of five years. METHODS: In this study, we used pooled health and population data from 33 countries in SSA between 2006 and 2019 and environmental data from the Atmospheric Composition Analysis Group and NASA's GIOVANNI platform. We estimated the association between early-life environmental exposures and stunting in three exposure periods - in-utero (during pregnancy), post-utero (after pregnancy to current age) and cumulative (from pregnancy to current age), using Bayesian hierarchical modelling. We also visualise the likelihood of stunting among children based on their region of residence using Bayesian hierarchical modelling. RESULTS: The findings show that 33.6% of sampled children were stunted. In-utero PM2.5 was associated with a higher likelihood of stunting (OR = 1.038, CrI = 1.002-1.075). Early-life exposures to nitrogen dioxide and sulphate were robustly associated with stunting among children. The findings also show spatial variation in a high and low likelihood of stunting based on a region of residence. IMPACT STATEMENT: This study explores the effect of early-life environmental exposures on child growth or stunting among sub-Saharan African children. The study focuses on three exposure windows - pregnancy, after birth and cumulative exposure during pregnancy and after birth. The study also employs spatial analysis to assess the spatial burden of stunted growth in relation to environmental exposures and socioeconomic factors. The findings suggest major air pollutants are associated with stunted growth among children in sub-Saharan Africa.

Stiripentol for Drug-Resistant Epilepsy Treatment in Tuberous Sclerosis Complex.

BACKGROUND: Drug-resistant epilepsy (DRE) is common in tuberous sclerosis complex (TSC). The role of stiripentol (STP) in seizure treatment in this population is not well understood. This study evaluates the efficacy and tolerability of STP in patients with TSC with DRE. METHODS: We performed a retrospective review of patients with TSC with DRE. Seizure frequencies at 1 month before (baseline) and 1, 3, 6, and 12 months after STP initiation were collected. RESULTS: Of the 1492 patients, 13 received STP and the number of patients with ≥50% seizure reduction at 1, 3, 6, and 12 months was 6/13 (46.2%), 4/13 (30.8%), 8/13 (61.5%), and 6/13 (46.2%), respectively. Six patients (46.2%) had favorable outcomes with persistent seizure reduction through 12 months. Their mean (±S.D.) percentage of seizure reduction at 1, 3, 6, and 12 months was 68.1 (±22.0), 71.3 (±23.2), 75.7 (±23.5), and 75.7 (±23.5), respectively. One patient had worsening seizures throughout the STP course. Three patients did not have seizure reduction until after 6 months, and 2 had initial seizure reduction before worsening. Younger age (P value <0.001), early STP treatment (P value <0.001), higher doses (P value = 0.004), and higher baseline seizure frequency (P value = 0.01) were associated with favorable outcomes. Side effects were seen in 85% of our cohort. CONCLUSIONS: About 46% of the patients had favorable outcomes. Younger age, early STP treatment, higher doses, and higher baseline seizure frequency were significantly associated with favorable outcomes.

Long-term exposure to air pollution and mortality from dementia, psychiatric disorders, and suicide in a large pooled European cohort: ELAPSE study.

Ambient air pollution is an established risk factor for premature mortality from chronic cardiovascular, respiratory and metabolic diseases, while evidence on neurodegenerative diseases and psychiatric disorders remains limited. We examined the association between long-term exposure to air pollution and mortality from dementia, psychiatric disorders, and suicide in seven European cohorts. Within the multicenter project 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE), we pooled data from seven European cohorts from six countries. Based on the residential addresses, annual mean levels of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), ozone (O3), and 8 PM2.5 components were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and mortality from dementia, psychiatric disorders, and suicide. Of 271,720 participants, 900 died from dementia, 241 from psychiatric disorders, and 164 from suicide, during a mean follow-up of 19.7 years. In fully adjusted models, we observed positive associations of NO2 (hazard ratio [HR] = 1.38; 95 % confidence interval [CI]: 1.13, 1.70 per 10 µg/m3), PM2.5 (HR = 1.29; 95 % CI: 0.98, 1.71 per 5 µg/m3), and BC (HR = 1.37; 95 % CI: 1.11, 1.69 per 0.5 × 10-5/m) with psychiatric disorders mortality, as well as with suicide (NO2: HR = 1.13 [95 % CI: 0.92, 1.38]; PM2.5: HR = 1.19 [95 % CI: 0.76, 1.87]; BC: HR = 1.08 [95 % CI: 0.87, 1.35]), and no association with dementia mortality. We did not detect any positive associations of O3 and 8 PM2.5 components with any of the three mortality outcomes. Long-term exposure to NO2, PM2.5, and BC may lead to premature mortality from psychiatric disorders and suicide.

Stringency of COVID-19 Containment Response Policies and Air Quality Changes: A Global Analysis across 1851 Cities.

The COVID-19 containment response policies (CRPs) had a major impact on air quality (AQ). These CRPs have been time-varying and location-specific. So far, despite having numerous studies on the effect of COVID-19 lockdown on AQ, a knowledge gap remains on the association between stringency of CRPs and AQ changes across the world, regions, nations, and cities. Here, we show that globally across 1851 cities (each more than 300 000 people) in 149 countries, after controlling for the impacts of relevant covariates (e.g., meteorology), Sentinel-5P satellite-observed nitrogen dioxide (NO2) levels decreased by 4.9% (95% CI: 2.2, 7.6%) during lockdowns following stringent CRPs compared to pre-CRPs. The NO2 levels did not change significantly during moderate CRPs and even increased during mild CRPs by 2.3% (95% CI: 0.7, 4.0%), which was 6.8% (95% CI: 2.0, 12.0%) across Europe and Central Asia, possibly due to population avoidance of public transportation in favor of private transportation. Among 1768 cities implementing stringent CRPs, we observed the most NO2 reduction in more populated and polluted cities. Our results demonstrate that AQ improved when and where stringent COVID-19 CRPs were implemented, changed less under moderate CRPs, and even deteriorated under mild CRPs. These changes were location-, region-, and CRP-specific.

Impact of hypothetical improvements in the psychosocial work environment on sickness absence rates: a simulation study.

BACKGROUND: The association between psychosocial working environments and sickness absence is well-known. However, the potential for reducing sickness absences of different lengths through improvements in psychosocial work factors is not fully understood. We aim to quantify the potential for reducing short-, intermediate- and long-term sickness absence rates, respectively, through hypothetical improvements in several psychosocial work factors. METHODS: This longitudinal study includes 24 990 public hospital employees from the 2014 wave of the Well-being in Hospital Employees study. The 1-year sickness absence rate was divided into short- (1-3 days), intermediate- (4-28 days) and long-term (29 days or more) periods. We simulated hypothetical scenarios with improvements in 17 psychosocial work factors using the parametric g-formula and estimated resulting changes in sickness absence rate ratios (RRs) with 95% confidence intervals (95% CIs). RESULTS: Setting all 17 psychosocial work factors to their most desirable levels (vs. least desirable levels) was associated with an overall 54% lower rate of sickness absence (95% CI: 48-60%). Reducing bullying (no vs. yes RR: 0.86, 95% CI: 0.83-0.90) and perceived stress (low vs. high RR: 0.90, 95% CI: 0.87-0.92), and increasing skill discretion (high vs. low RR: 0.91, 95% CI: 0.89-0.94) held the largest potential for reducing the total sickness absence rate. Overall, associations were similar for short-, intermediate- and long-term sickness absence. CONCLUSIONS: The psychosocial working environment was strongly associated with sickness absence. Improving the working environment may have a great impact on short-, intermediate- and long-term sickness absence rates.

Chronic disorders, work-unit leadership quality and long-term sickness absence among 33 025 public hospital employees.

OBJECTIVE: This study aimed to examine the association between work-unit level leadership quality and individual-level long-term sickness absence (LTSA) in the hospital sector and effect modification by chronic disorders. METHODS: This longitudinal analysis included 33 025 Danish public hospital employees who were followed-up for one year after baseline in March 2014. Leadership quality was assessed by questionnaire with mean responses aggregated by work-unit and characterized in tertiles. LTSA during follow-up was determined from employer records. Chronic disorders at baseline was assessed from the Danish hospital and prescription registers. We performed multilevel logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for potential confounders. We evaluated interaction between chronic illness and low leadership quality on multiplicative and additive scales. RESULTS: We identified employees as healthy (60.8%) or with somatic (31.6%), mental (3.3%), or both somatic and mental (4.3%) disorders. During follow-up, 6% of employees registered a LTSA. Medium and high leadership quality were associated with lower risk of LTSA with OR of 0.84 (95% CI 0.76-0.94) and 0.73 (95% CI 0.65-0.82) respectively, compared to low leadership quality. Associations were similar for healthy employees and employees with only somatic disorders, whereas no association was observed for employees with mental disorders (in presence or absence of somatic disorders). No statistically significant (α=0.05) interactions between leadership quality and chronic disorders on LTSA were observed. CONCLUSION: The findings suggest that the quality of leadership in work units is associated with risk of long-term sick leave in the Danish public hospital sector and that strong leadership protects employees against LTSA.

Long-term exposure to air pollution and mortality in a Danish nationwide administrative cohort study: Beyond mortality from cardiopulmonary disease and lung cancer.

BACKGROUND: The association between long-term exposure to air pollution and mortality from cardiorespiratory diseases is well established, yet the evidence for other diseases remains limited. OBJECTIVES: To examine the associations of long-term exposure to air pollution with mortality from diabetes, dementia, psychiatric disorders, chronic kidney disease (CKD), asthma, acute lower respiratory infection (ALRI), as well as mortality from all-natural and cardiorespiratory causes in the Danish nationwide administrative cohort. METHODS: We followed all residents aged ≥ 30 years (3,083,227) in Denmark from 1 January 2000 until 31 December 2017. Annual mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (warm season) were estimated using European-wide hybrid land-use regression models (100 m × 100 m) and assigned to baseline residential addresses. We used Cox proportional hazard models to evaluate the association between air pollution and mortality, accounting for demographic and socioeconomic factors. We additionally applied indirect adjustment for smoking and body mass index (BMI). RESULTS: During 47,023,454 person-years of follow-up, 803,881 people died from natural causes. Long-term exposure to PM2.5 (mean: 12.4 µg/m3), NO2 (20.3 µg/m3), and/or BC (1.0 × 10-5/m) was statistically significantly associated with all studied mortality outcomes except CKD. A 5 µg/m3 increase in PM2.5 was associated with higher mortality from all-natural causes (hazard ratio 1.11; 95% confidence interval 1.09-1.13), cardiovascular disease (1.09; 1.07-1.12), respiratory disease (1.11; 1.07-1.15), lung cancer (1.19; 1.15-1.24), diabetes (1.10; 1.04-1.16), dementia (1.05; 1.00-1.10), psychiatric disorders (1.38; 1.27-1.50), asthma (1.13; 0.94-1.36), and ALRI (1.14; 1.09-1.20). Associations with long-term exposure to ozone (mean: 80.2 µg/m3) were generally negative but became significantly positive for several endpoints in two-pollutant models. Generally, associations were attenuated but remained significant after indirect adjustment for smoking and BMI. CONCLUSION: Long-term exposure to PM2.5, NO2, and/or BC in Denmark were associated with mortality beyond cardiorespiratory diseases, including diabetes, dementia, psychiatric disorders, asthma, and ALRI.

Long-term Air Pollution Exposure and Pneumonia-related Mortality in a Large Pooled European Cohort.

Rationale: Ambient air pollution exposure has been linked to mortality from chronic cardiorespiratory diseases, while evidence on respiratory infections remains more limited. Objectives: We examined the association between long-term exposure to air pollution and pneumonia-related mortality in adults in a pool of eight European cohorts. Methods: Within the multicenter project ELAPSE (Effects of Low-Level Air Pollution: A Study in Europe), we pooled data from eight cohorts among six European countries. Annual mean residential concentrations in 2010 for fine particulate matter, nitrogen dioxide (NO2), black carbon (BC), and ozone were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and pneumonia, influenza, and acute lower respiratory infections (ALRI) mortality. Measurements and Main Results: Of 325,367 participants, 712 died from pneumonia and influenza combined, 682 from pneumonia, and 695 from ALRI during a mean follow-up of 19.5 years. NO2 and BC were associated with 10-12% increases in pneumonia and influenza combined mortality, but 95% confidence intervals included unity (hazard ratios, 1.12 [0.99-1.26] per 10 µg/m3 for NO2; 1.10 [0.97-1.24] per 0.5 10-5m-1 for BC). Associations with pneumonia and ALRI mortality were almost identical. We detected effect modification suggesting stronger associations with NO2 or BC in overweight, employed, or currently smoking participants compared with normal weight, unemployed, or nonsmoking participants. Conclusions: Long-term exposure to combustion-related air pollutants NO2 and BC may be associated with mortality from lower respiratory infections, but larger studies are needed to estimate these associations more precisely.

Long-term exposure to road traffic noise and all-cause and cause-specific mortality: a Danish Nurse Cohort study.

BACKGROUND: Long-term road traffic noise exposure is linked to cardio-metabolic disease morbidity, whereas evidence on mortality remains limited. OBJECTIVES: We investigated association of long-term exposure to road traffic noise with all-cause and cause-specific mortality. METHODS: We linked 22,858 females from the Danish Nurse Cohort (DNC), recruited into the Danish Register of Causes of Death up to 2014. Road traffic noise levels since 1970 were modelled by Nord2000 as the annual mean of a weighted 24 h average (Lden). Cox regression models examined the associations between Lden (5-year and 23-year means) and all-cause and cause-specific mortalities, adjusting for lifestyle and exposure to PM2.5 (particulate matter with diameter < 2.5 µm) and NO2 (nitrogen dioxide). RESULTS: During follow-up (mean 17.4 years), 3902 nurses died: 1622 from cancer, 922 from CVDs (289 from stroke), 338 from respiratory diseases (186 from chronic obstructive pulmonary disease, 114 from lower respiratory tract infections [ALRIs]), 234 from dementia, 95 from psychiatric disorders, and 79 from diabetes. Hazard ratios (95% confidence intervals) for all-cause mortality from fully-adjusted models were 1.06 (1.01, 1.11) and 1.09 (1.03, 1.15) per 10 dB of 5-year and 23-year mean Lden, respectively, which attenuated slightly in our main model (fully-adjusted plus PM2.5: 1.04 [1.00, 1.10]; 1.08 [1.02, 1.13]). Main model estimates suggested the strongest associations between 5-year mean Lden and diabetes (1.14: 0.81, 1.61), ALRIs (1.13: 0.84, 1.54), dementia (1.12: 0.90, 1.38), and stroke (1.10: 0.91, 1.31), whereas associations with 23-year mean Lden were suggested for respiratory diseases (1.15: 0.95, 1.39), psychiatric disorders (1.11: 0.78, 1.59), and all cancers (1.08: 0.99, 1.17). DISCUSSION: Among the female nurses from the DNC, we observed that long-term exposure to road traffic noise led to premature mortality, independently of air pollution, and its adverse effects may extend well beyond those on the cardio-metabolic system to include respiratory diseases, cancer, neurodegenerative and psychiatric disorders.

Long-term exposure to low ambient air pollution concentrations and mortality among 28 million people: results from seven large European cohorts within the ELAPSE project.

BACKGROUND: Long-term exposure to ambient air pollution has been associated with premature mortality, but associations at concentrations lower than current annual limit values are uncertain. We analysed associations between low-level air pollution and mortality within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE). METHODS: In this multicentre longitudinal study, we analysed seven population-based cohorts of adults (age ≥30 years) within ELAPSE, from Belgium, Denmark, England, the Netherlands, Norway, Rome (Italy), and Switzerland (enrolled in 2000-11; follow-up until 2011-17). Mortality registries were used to extract the underlying cause of death for deceased individuals. Annual average concentrations of fine particulate matter (PM2·5), nitrogen dioxide (NO2), black carbon, and tropospheric warm-season ozone (O3) from Europe-wide land use regression models at 100 m spatial resolution were assigned to baseline residential addresses. We applied cohort-specific Cox proportional hazard models with adjustment for area-level and individual-level covariates to evaluate associations with non-accidental mortality, as the main outcome, and with cardiovascular, non-malignant respiratory, and lung cancer mortality. Subset analyses of participants living at low pollutant concentrations (as per predefined values) and natural splines were used to investigate the concentration-response function. Cohort-specific effect estimates were pooled in a random-effects meta-analysis. FINDINGS: We analysed 28 153 138 participants contributing 257 859 621 person-years of observation, during which 3 593 741 deaths from non-accidental causes occurred. We found significant positive associations between non-accidental mortality and PM2·5, NO2, and black carbon, with a hazard ratio (HR) of 1·053 (95% CI 1·021-1·085) per 5 µg/m3 increment in PM2·5, 1·044 (1·019-1·069) per 10 µg/m3 NO2, and 1·039 (1·018-1·059) per 0·5 × 10-5/m black carbon. Associations with PM2·5, NO2, and black carbon were slightly weaker for cardiovascular mortality, similar for non-malignant respiratory mortality, and stronger for lung cancer mortality. Warm-season O3 was negatively associated with both non-accidental and cause-specific mortality. Associations were stronger at low concentrations: HRs for non-accidental mortality at concentrations lower than the WHO 2005 air quality guideline values for PM2·5 (10 µg/m3) and NO2 (40 µg/m3) were 1·078 (1·046-1·111) per 5 µg/m3 PM2·5 and 1·049 (1·024-1·075) per 10 µg/m3 NO2. Similarly, the association between black carbon and non-accidental mortality was highest at low concentrations, with a HR of 1·061 (1·032-1·092) for exposure lower than 1·5× 10-5/m, and 1·081 (0·966-1·210) for exposure lower than 1·0× 10-5/m. INTERPRETATION: Long-term exposure to concentrations of PM2·5 and NO2 lower than current annual limit values was associated with non-accidental, cardiovascular, non-malignant respiratory, and lung cancer mortality in seven large European cohorts. Continuing research on the effects of low concentrations of air pollutants is expected to further inform the process of setting air quality standards in Europe and other global regions. FUNDING: Health Effects Institute.

The plasticity of late-onset dementia: A nationwide cohort study in Denmark.

INTRODUCTION: The determinants of the secular decline in the incidence of dementia are not clear. The aim of this study was to investigate the influences of four factors-education, wealth, cerebrovascular health, and general health-on the secular decline. METHODS: A cohort study was conducted of all individuals aged ≥65 years in Denmark from 2005 through 2018 (N = 1,757,168). Annual incidence rates of dementia and population attributable risks of the four factors were calculated and birth cohort trends were examined. RESULTS: The incidence of dementia declined by 22.5% in men and 34.2% in women from 2005 through 2018. Population attributable risks of lower education, lower wealth, and stroke likewise declined. Independent of these improvements, the incidence of dementia fell across successive birth cohorts. DISCUSSION: Most of the observed plasticity in late-onset dementia is associated with a risk decline across successive birth cohorts that is independent of improvements in traditional risk factors.

Variability in the association between long-term exposure to ambient air pollution and mortality by exposure assessment method and covariate adjustment: A census-based country-wide cohort study.

BACKGROUND: Ambient air pollution exposure has been associated with higher mortality risk in numerous studies. We assessed potential variability in the magnitude of this association for non-accidental, cardiovascular disease, respiratory disease, and lung cancer mortality in a country-wide administrative cohort by exposure assessment method and by adjustment for geographic subdivisions. METHODS: We used the Belgian 2001 census linked to population and mortality register including nearly 5.5 million adults aged ≥30 (mean follow-up: 9.97 years). Annual mean concentrations for fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone (O3) were assessed at baseline residential address using two exposure methods; Europe-wide hybrid land use regression (LUR) models [100x100m], and Belgium-wide interpolation-dispersion (RIO-IFDM) models [25x25m]. We used Cox proportional hazards models with age as the underlying time scale and adjusted for various individual and area-level covariates. We further adjusted main models for two different area-levels following the European Nomenclature of Territorial Units for Statistics (NUTS); NUTS-1 (n = 3), or NUTS-3 (n = 43). RESULTS: We found no consistent differences between both exposure methods. We observed most robust associations with lung cancer mortality. Hazard Ratios (HRs) per 10 µg/m3 increase for NO2 were 1.060 (95%CI 1.042-1.078) [hybrid LUR] and 1.040 (95%CI 1.022-1.058) [RIO-IFDM]. Associations with non-accidental, respiratory disease and cardiovascular disease mortality were generally null in main models but were enhanced after further adjustment for NUTS-1 or NUTS-3. HRs for non-accidental mortality per 5 µg/m3 increase for PM2.5 for the main model using hybrid LUR exposure were 1.023 (95%CI 1.011-1.035). After including random effects HRs were 1.044 (95%CI 1.033-1.057) [NUTS-1] and 1.076 (95%CI 1.060-1.092) [NUTS-3]. CONCLUSION: Long-term air pollution exposure was associated with higher lung cancer mortality risk but not consistently with the other studied causes. Magnitude of associations varied by adjustment for geographic subdivisions, area-level socio-economic covariates and less by exposure assessment method.

Organizational Justice and Long-term Metabolic Trajectories: A 25-Year Follow-up of the Whitehall II Cohort.

CONTEXT: Organizational justice has been linked to lower risk of several chronic conditions among employees, but less is known about the long-term mechanisms underlying this risk reduction. OBJECTIVE: To assess whether self-reported organizational justice is associated with individual and composite long-term metabolic trajectories. DESIGN: Twenty-five-year follow-up of the Whitehall II prospective cohort study. SETTING: Middle-aged public servants from the United Kingdom. PARTICIPANTS: Data on 8182 participants were used. MAIN OUTCOME MEASURES: Levels of 11 anthropometric, glycemic, lipid, and blood pressure biomarkers were measured at 5 timepoints (1991-2013). We used generalized estimating equations and group-based trajectory modeling to investigate the relationship between organizational justice and biomarker trajectories. RESULTS: High vs low organizational justice were associated with lower waist (-1.7 cm) and hip (-1 cm) circumference, body mass index (-0.6 kg/m2), triglycerides (-1.07 mmol/L), and fasting insulin (-1.08 µIU/mL) trajectories. Two latent metabolic trajectory clusters were identified: a high- and a low-risk cluster. High organizational justice (vs low) were associated with belonging to the low-risk cluster (pooled odds ratio = 1.47). The low-risk cluster demonstrated lower baseline levels of most biomarkers and better glycemic control, whereas the high-risk cluster showed higher baseline levels of most biomarkers, glycemic deterioration, but also greater improvements in lipid levels over time. CONCLUSIONS: People with high organizational justice had more favorable long-term cardiometabolic biomarker patterns than those with low organizational justice, indicating a potential mechanism contributing to the lower risk of chronic diseases in the first group. Further intervention studies are warranted to determine whether improvement of organizational justice might improve long-term health.

Long-term exposure to fine particle elemental components and mortality in Europe: Results from six European administrative cohorts within the ELAPSE project.

Evidence for the association between long-term exposure to ambient particulate matter components and mortality from natural causes is sparse and inconsistent. We evaluated this association in six large administrative cohorts in the framework of the Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) project. We analyzed data from country-wide administrative cohorts in Norway, Denmark, the Netherlands, Belgium, Switzerland and in Rome (Italy). Annual 2010 mean concentrations of copper (Cu), iron (Fe), potassium (K), nickel (Ni), sulfur (S), silicon (Si), vanadium (V) and zinc (Zn) in fine particulate matter (PM2.5) were estimated using 100 × 100 m Europe-wide hybrid land use regression models assigned to the participants' residential addresses. We applied cohort-specific Cox proportional hazard models controlling for area- and individual-level covariates to evaluate associations with natural mortality. Two pollutant models adjusting for PM2.5 total mass or nitrogen dioxide (NO2) were also applied. We pooled cohort-specific estimates using a random effects meta-analysis. We included almost 27 million participants contributing more than 240 million person-years. All components except Zn were significantly associated with natural mortality [pooled Hazard Ratios (HRs) (95% CI): 1.037 (1.014, 1.060) per 5 ng/m3 Cu; 1.069 (1.031, 1.108) per 100 ng/m3 Fe; 1.039 (1.018, 1.062) per 50 ng/m3 K; 1.024 (1.006, 1.043) per 1 ng/m3 Ni; 1.036 (1.016, 1.057) per 200 ng/m3 S; 1.152 (1.048, 1.266) per 100 ng/m3 Si; 1.020 (1.006, 1.034) per 2 ng/m3 V]. Only K and Si were robust to PM2.5 or NO2 adjustment [pooled HRs (95% CI) per 50 ng/m3 in K: 1.025 (1.008, 1.044), 1.020 (0.999, 1.042) and per 100 ng/m3 in Si: 1.121 (1.039, 1.209), 1.068 (1.022, 1.117) adjusted for PM2.5 and NO2 correspondingly]. Our findings indicate an association of natural mortality with most components, which was reduced after adjustment for PM2.5 and especially NO2.

Long-term exposure to road traffic noise and stroke incidence: a Danish Nurse Cohort study.

BACKGROUND: Road traffic noise has been linked to increased risk of ischemic heart disease, yet evidence on stroke shows mixed results. We examine the association between long-term exposure to road traffic noise and incidence of stroke, overall and by subtype (ischemic or hemorrhagic), after adjustment for air pollution. METHODS: Twenty-five thousand six hundred and sixty female nurses from the Danish Nurse Cohort recruited in 1993 or 1999 were followed for stroke-related first-ever hospital contact until December 31st, 2014. Full residential address histories since 1970 were obtained and annual means of road traffic noise (Lden [dB]) and air pollutants (particulate matter with diameter < 2.5 µm and < 10 µm [PM2.5 and PM10], nitrogen dioxide [NO2], nitrogen oxides [NOx]) were determined using validated models. Time-varying Cox regression models were used to estimate hazard ratios (HR) (95% confidence intervals [CI]) for the associations of one-, three-, and 23-year running means of Lden preceding stroke (all, ischemic or hemorrhagic), adjusting for stroke risk factors and air pollutants. The World Health Organization and the Danish government's maximum exposure recommendations of 53 and 58 dB, respectively, were explored as potential Lden thresholds. RESULTS: Of 25,660 nurses, 1237 developed their first stroke (1089 ischemic, 148 hemorrhagic) during 16 years mean follow-up. For associations between a 1-year mean of Lden and overall stroke incidence, the estimated HR (95% CI) in the fully adjusted model was 1.06 (0.98-1.14) per 10 dB, which attenuated to 1.01 (0.93-1.09) and 1.00 (0.91-1.09) in models further adjusted for PM2.5 or NO2, respectively. Associations for other exposure periods or separately for ischemic or hemorrhagic stroke were similar. There was no evidence of a threshold association between Lden and stroke. CONCLUSIONS: Long-term exposure to road traffic noise was suggestively positively associated with the risk of overall stroke, although not after adjusting for air pollution.

Long-Term Exposure to Air Pollution, Road Traffic Noise, and Heart Failure Incidence: The Danish Nurse Cohort.

Background We examined the association of long-term exposure to air pollution and road traffic noise with incident heart failure (HF). Methods And Results Using data on female nurses from the Danish Nurse Cohort (aged >44 years), we investigated associations between 3-year mean exposures to air pollution and road traffic noise and incident HF using Cox regression models, adjusting for relevant confounders. Incidence of HF was defined as the first hospital contact (inpatient, outpatient, or emergency) between cohort baseline (1993 or 1999) and December 31, 2014, based on the Danish National Patient Register. Annual mean levels of particulate matter with a diameter <2.5 µm since 1990 and NO2 and road traffic noise since 1970 were estimated at participants' residences. Of the 22 189 nurses, 484 developed HF. We detected associations with all 3 pollutants, with hazard ratios (HRs) of 1.17 (95% CI, 1.01-1.36), 1.10 (95% CI, 0.99-1.22), and 1.12 (95% CI, 0.99-1.26) per increase of 5.1 µg/m3 in particulate matter with a diameter <2.5 µm, 8.6 µg/m3 in NO2, and 9.3 dB in road traffic noise, respectively. We observed an enhanced risk of HF incidence for those exposed to high levels of the 3 pollutants; however, the effect modification of coexposure was not statistically significant. Former smokers and nurses with hypertension showed the strongest associations with particulate matter with a diameter <2.5 µm (Peffect modification<0.05). Conclusions We found that long-term exposures to air pollution and road traffic noise were independently associated with HF.

Long term exposure to low level air pollution and mortality in eight European cohorts within the ELAPSE project: pooled analysis.

OBJECTIVE: To investigate the associations between air pollution and mortality, focusing on associations below current European Union, United States, and World Health Organization standards and guidelines. DESIGN: Pooled analysis of eight cohorts. SETTING: Multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) in six European countries. PARTICIPANTS: 325 367 adults from the general population recruited mostly in the 1990s or 2000s with detailed lifestyle data. Stratified Cox proportional hazard models were used to analyse the associations between air pollution and mortality. Western Europe-wide land use regression models were used to characterise residential air pollution concentrations of ambient fine particulate matter (PM2.5), nitrogen dioxide, ozone, and black carbon. MAIN OUTCOME MEASURES: Deaths due to natural causes and cause specific mortality. RESULTS: Of 325 367 adults followed-up for an average of 19.5 years, 47 131 deaths were observed. Higher exposure to PM2.5, nitrogen dioxide, and black carbon was associated with significantly increased risk of almost all outcomes. An increase of 5 µg/m3 in PM2.5 was associated with 13% (95% confidence interval 10.6% to 15.5%) increase in natural deaths; the corresponding figure for a 10 µg/m3 increase in nitrogen dioxide was 8.6% (7% to 10.2%). Associations with PM2.5, nitrogen dioxide, and black carbon remained significant at low concentrations. For participants with exposures below the US standard of 12 µg/m3 an increase of 5 µg/m3 in PM2.5 was associated with 29.6% (14% to 47.4%) increase in natural deaths. CONCLUSIONS: Our study contributes to the evidence that outdoor air pollution is associated with mortality even at low pollution levels below the current European and North American standards and WHO guideline values. These findings are therefore an important contribution to the debate about revision of air quality limits, guidelines, and standards, and future assessments by the Global Burden of Disease.

Long-term exposure to low-level ambient air pollution and incidence of stroke and coronary heart disease: a pooled analysis of six European cohorts within the ELAPSE project.

BACKGROUND: Long-term exposure to outdoor air pollution increases the risk of cardiovascular disease, but evidence is unclear on the health effects of exposure to pollutant concentrations lower than current EU and US standards and WHO guideline limits. Within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we investigated the associations of long-term exposures to fine particulate matter (PM2·5), nitrogen dioxide (NO2), black carbon, and warm-season ozone (O3) with the incidence of stroke and acute coronary heart disease. METHODS: We did a pooled analysis of individual data from six population-based cohort studies within ELAPSE, from Sweden, Denmark, the Netherlands, and Germany (recruited 1992-2004), and harmonised individual and area-level variables between cohorts. Participants (all adults) were followed up until migration from the study area, death, or incident stroke or coronary heart disease, or end of follow-up (2011-15). Mean 2010 air pollution concentrations from centrally developed European-wide land use regression models were assigned to participants' baseline residential addresses. We used Cox proportional hazards models with increasing levels of covariate adjustment to investigate the association of air pollution exposure with incidence of stroke and coronary heart disease. We assessed the shape of the concentration-response function and did subset analyses of participants living at pollutant concentrations lower than predefined values. FINDINGS: From the pooled ELAPSE cohorts, data on 137 148 participants were analysed in our fully adjusted model. During a median follow-up of 17·2 years (IQR 13·8-19·5), we observed 6950 incident events of stroke and 10 071 incident events of coronary heart disease. Incidence of stroke was associated with PM2·5 (hazard ratio 1·10 [95% CI 1·01-1·21] per 5 µg/m3 increase), NO2 (1·08 [1·04-1·12] per 10 µg/m3 increase), and black carbon (1·06 [1·02-1·10] per 0·5 10-5/m increase), whereas coronary heart disease incidence was only associated with NO2 (1·04 [1·01-1·07]). Warm-season O3 was not associated with an increase in either outcome. Concentration-response curves indicated no evidence of a threshold below which air pollutant concentrations are not harmful for cardiovascular health. Effect estimates for PM2·5 and NO2 remained elevated even when restricting analyses to participants exposed to pollutant concentrations lower than the EU limit values of 25 µg/m3 for PM2·5 and 40 µg/m3 for NO2. INTERPRETATION: Long-term air pollution exposure was associated with incidence of stroke and coronary heart disease, even at pollutant concentrations lower than current limit values. FUNDING: Health Effects Institute.