Modelling the spatial risk pattern of dementia in Denmark using residential location data: A registry-based national cohort.

Dementia is a major global public health concern that is increasingly leading to morbidity and mortality among older adults. While studies have focused on the risk factors and care provision, there is currently limited knowledge about the spatial risk pattern of the disease. In this study, we employ Bayesian spatial modelling with a stochastic partial differential equation (SPDE) approach to model the spatial risk using complete residential history data from the Danish population and health registers. The study cohort consisted of 1.6 million people aged 65 years and above from 2005 to 2018. The results of the spatial risk map indicate high-risk areas in Copenhagen, southern Jutland and Funen. Individual socioeconomic factors and population density reduce the intensity of high-risk patterns across Denmark. The findings of this study call for the critical examination of the contribution of place of residence in the susceptibility of the global ageing population to dementia.

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.

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.

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 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.

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.

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.

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 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.

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 air pollution and liver cancer incidence in six European cohorts.

Particulate matter air pollution and diesel engine exhaust have been classified as carcinogenic for lung cancer, yet few studies have explored associations with liver cancer. We used six European adult cohorts which were recruited between 1985 and 2005, pooled within the "Effects of low-level air pollution: A study in Europe" (ELAPSE) project, and followed for the incidence of liver cancer until 2011 to 2015. The annual average exposure to nitrogen dioxide (NO2 ), particulate matter with diameter <2.5 µm (PM2.5 ), black carbon (BC), warm-season ozone (O3 ), and eight elemental components of PM2.5 (copper, iron, zinc, sulfur, nickel, vanadium, silicon, and potassium) were estimated by European-wide hybrid land-use regression models at participants' residential addresses. We analyzed the association between air pollution and liver cancer incidence by Cox proportional hazards models adjusting for potential confounders. Of 330 064 cancer-free adults at baseline, 512 developed liver cancer during a mean follow-up of 18.1 years. We observed positive linear associations between NO2 (hazard ratio, 95% confidence interval: 1.17, 1.02-1.35 per 10 µg/m3 ), PM2.5 (1.12, 0.92-1.36 per 5 µg/m3 ), and BC (1.15, 1.00-1.33 per 0.5 10-5 /m) and liver cancer incidence. Associations with NO2 and BC persisted in two-pollutant models with PM2.5 . Most components of PM2.5 were associated with the risk of liver cancer, with the strongest associations for sulfur and vanadium, which were robust to adjustment for PM2.5 or NO2 . Our study suggests that ambient air pollution may increase the risk of liver cancer, even at concentrations below current EU standards.

Long-term air pollution and road traffic noise exposure and COPD: the Danish Nurse Cohort.

BACKGROUND: While air pollution has been linked to the development of chronic obstructive pulmonary disease (COPD), evidence on the role of environmental noise is just emerging. We examined the associations of long-term exposure to air pollution and road traffic noise with COPD incidence. METHODS: We defined COPD incidence for 24 538 female nurses from the Danish Nurse Cohort (age >44 years) as the first hospital contact between baseline (1993 or 1999) and 2015. We estimated residential annual mean concentrations of particulate matter with an aerodynamic diameter <2.5 µm (PM2.5) since 1990 and nitrogen dioxide (NO2) since 1970 using the Danish Eulerian Hemispheric Model/Urban Background Model/Air Geographic Information System modelling system, and road traffic noise (Lden) since 1970 using the Nord2000 model. Time-varying Cox regression models were applied to assess the associations of air pollution and road traffic noise with COPD incidence. RESULTS: 977 nurses developed COPD during a mean of 18.6 years' follow-up. We observed associations with COPD for all three exposures with HRs and 95% CIs of 1.19 (1.01-1.41) per 6.26 µg·m-3 for PM2.5, 1.13 (1.05-1.20) per 8.19 µg·m-3 for NO2 and 1.15 (1.06-1.25) per 10 dB for Lden. Associations with NO2 and Lden attenuated slightly after mutual adjustment, but were robust to adjustment for PM2.5. Associations with PM2.5 were attenuated to null after adjustment for either NO2 or Lden. No potential interaction effect was observed between air pollutants and noise. CONCLUSION: Long-term exposure to air pollution, especially traffic-related NO2, and to road traffic noise were independently associated with COPD.

Long-term exposure to ambient air pollution and road traffic noise and asthma incidence in adults: The Danish Nurse cohort.

BACKGROUND: Ambient air pollution is likely a risk factor for asthma, and recent evidence suggests the possible relevance of road traffic noise. OBJECTIVES: We examined the associations of long-term exposure to air pollution and road traffic noise with adult-asthma incidence. METHODS: We followed 28,731 female nurses (age > 44 years) from the Danish Nurse Cohort, recruited in 1993 and 1999, for first hospital contact for asthma from 1977 until 2015. We estimated residential annual mean concentrations of particulate matter with diameter < 2.5 µm (PM2.5) since 1990 and nitrogen dioxide (NO2) since 1970 with the Danish DEHM/UBM/AirGIS modeling system, and road traffic noise (Lden) since 1970 with the Nord2000 model. Time-varying Cox regression models were used to associate air pollution and road traffic noise exposure with asthma incidence. RESULTS: During 18.6 years' mean follow-up, 528 out of 23,093 participants had hospital contact for asthma. The hazard ratios (HR) and 95% confidence intervals for asthma incidence associated with 3-year moving average exposures were 1.29 (1.03, 1.61) per 6.3 µg/m3 for PM2.5, 1.16 (1.07, 1.27) per 8.2 µg/m3 for NO2, and 1.12 (1.00, 1.25) per 10 dB for Lden. The HR for NO2 remained unchanged after adjustment for either PM2.5 or Lden, while the HRs for PM2.5 and Lden attenuated to unity after adjustment for NO2. CONCLUSIONS: Long-term exposure to air pollution was associated with adult-asthma incidence independently of road traffic noise, with NO2 most relevant. Road traffic noise was not independently associated with adult-asthma incidence.

Cumulative Occupational Exposures and Lung-Function Decline in Two Large General-Population Cohorts.

Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up.Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults).Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking.Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV1 = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV1/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts.Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.

Long-term exposure to low levels of air pollution and mortality adjusting for road traffic noise: A Danish Nurse Cohort study.

BACKGROUND: The association between air pollution and mortality is well established, yet some uncertainties remain: there are few studies that account for road traffic noise exposure or that consider in detail the shape of the exposure-response function for cause-specific mortality outcomes, especially at low-levels of exposure. OBJECTIVES: We examined the association between long-term exposure to particulate matter [(PM) with a diameter of <2.5 µm (PM2.5), <10 µm (PM10)], and nitrogen dioxide (NO2) and total and cause-specific mortality, accounting for road traffic noise. METHODS: We used data on 24,541 females (age > 44 years) from the Danish Nurse Cohort, who were recruited in 1993 or 1999, and linked to the Danish Causes of Death Register for follow-up on date of death and its cause, until the end of 2013. Annual mean concentrations of PM2.5, PM10, and NO2 at the participants' residences since 1990 were estimated using the Danish DEHM/UBM/AirGIS dispersion model, and annual mean road traffic noise levels (Lden) were estimated using the Nord2000 model. We examined associations between the three-year running mean of PM2.5, PM10, and NO2 with total and cause-specific mortality by using time-varying Cox Regression models, adjusting for individual characteristics and residential road traffic noise. RESULTS: During the study period, 3,708 nurses died: 843 from cardiovascular disease (CVD), 310 from respiratory disease (RD), and 64 from diabetes. In the fully adjusted models, including road traffic noise, we detected associations of three-year running mean of PM2.5 with total (hazard ratio; 95% confidence interval: 1.06; 1.01-1.11), CVD (1.14; 1.03-1.26), and diabetes mortality (1.41; 1.05-1.90), per interquartile range of 4.39 µg/m3. In a subset of the cohort exposed to PM2.5 < 20 µg/m3, we found even stronger association with total (1.19; 1.11-1.27), CVD (1.27; 1.01-1.46), RD (1.27; 1.00-1.60), and diabetes mortality (1.44; 0.83-2.48). We found similar associations with PM10 and none with NO2. All associations were robust to adjustment for road traffic noise. DISCUSSION: Long-term exposure to low-levels of PM2.5 and PM10 is associated with total mortality, and mortality from CVD, RD, and diabetes. Associations were even stronger at the PM2.5 levels below EU limit values and were independent of road traffic noise.

Occupational exposures and incidence of chronic bronchitis and related symptoms over two decades: the European Community Respiratory Health Survey.

OBJECTIVES: Chronic bronchitis (CB) is an important chronic obstructive pulmonary disease (COPD)-related phenotype, with distinct clinical features and prognostic implications. Occupational exposures have been previously associated with increased risk of CB but few studies have examined this association prospectively using objective exposure assessment. We examined the effect of occupational exposures on CB incidence in the European Community Respiratory Health Survey. METHODS: Population samples aged 20-44 were randomly selected in 1991-1993, and followed up twice over 20 years. Participants without chronic cough or phlegm at baseline were analysed. Coded job histories during follow-up were linked to the ALOHA Job Exposure Matrix, generating occupational exposure estimates to 12 categories of chemical agents. Their association with CB incidence over both follow-ups was examined with Poisson models using generalised estimating equations. RESULTS: 8794 participants fulfilled the inclusion criteria, contributing 13 185 observations. Only participants exposed to metals had a higher incidence of CB (relative risk (RR) 1.70, 95% CI 1.16 to 2.50) compared with non-exposed to metals. Mineral dust exposure increased the incidence of chronic phlegm (RR 1.72, 95% CI 1.43 to 2.06). Incidence of chronic phlegm was increased in men exposed to gases/fumes and to solvents and in women exposed to pesticides. CONCLUSIONS: Occupational exposures are associated with chronic phlegm and CB, and the evidence is strongest for metals and mineral dust exposure. The observed differences between men and women warrant further investigation.