Long-Term Exposure to Air Pollution and Risk of Acute Lower Respiratory Infections in the Danish Nurse Cohort.

RATIONALE: Air pollution is a major risk factor for chronic cardiorespiratory diseases, affecting both the immune and respiratory systems' functionality, while the epidemiological evidence on respiratory infections remains sparse. OBJECTIVE: We aimed to assess the association of long-term exposure to ambient air pollution with risk of developing new and recurrent ALRIs that characterized by persistently severe symptoms necessitating hospital contact, and identify the potential susceptible populations by socio-economic status (SES), smoking, physical activity status, overweight, and co-morbidity with chronic lung disease. METHODS: We followed 23,912 female nurses from the Danish Nurse Cohort (> 44 years) from baseline (1993 or 1999) until 2018 for the incident and recurrent ALRIs defined by hospital contact (in-, outpatient, and emergency room) data from the National Patient Register. Residential annual mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) were modelled using Danish DEHM/UBM/AirGIS system. We used marginal Cox models with time-varying exposures to assess the association of 3-year running-mean air pollution with incident and recurrent ALRIs and examine effect modification by age, socio-economic status (SES), smoking, physical activity, body mass index, and comorbidity with asthma or chronic obstructive pulmonary disease (COPD). RESULTS: During a 21.3 years mean follow-up, 4,746 ALRIs were observed, of which 2,553 were incident. We observed strong positive associations of all three pollutants with incident ALRIs, with hazard ratios and 95% confidence intervals of 1.19 (1.08-1.31) per 2.5 µg/m3 for PM2.5, 1.17 (1.11-1.24) per 8.0 µg/m3 for NO2, and 1.09 (1.05-1.12) per 0.3 µg/m3 for BC, and slightly stronger associations with recurrent ALRIs. Associations were strongest in COPD patients and nurses with low physical activity. CONCLUSION: Long-term exposure to air pollution at low levels was associated with risk of new and recurrent ALRIs, with COPD patients and physically inactive subjects most vulnerable. Primary Source of Funding: This study was supported by the Novo Nordisk Foundation Challenge Programme (NNF17OC0027812).

Relationship between rest-activity rhythms and cardiorespiratory fitness in middle-aged workers: a cross-sectional study with non-parametric analysis using accelerometers worn on the thigh.

BACKGROUND: Rest-activity rhythms are directly related to health risks, but there are limited objective methods to assess them. This study aimed to investigate the relationship between rest-activity rhythms and cardiorespiratory fitness (CRF) in middle-aged workers. METHODS: Peak oxygen uptake was measured on a treadmill to assess CRF in 254 middle-aged workers who were divided into low, medium, and high-CRF groups based on tertiles. Participants were asked to wear an accelerometer (activPAL) on their thighs for 1 week, and the logarithmically transformed acceleration data were used for the analysis of a 24-hour rest-activity rhythm. Sex, age, body mass index, occupation, smoking status, and alcohol consumption were used as covariates in Model 1, with Model 2 also including walking count on non-workdays. Repeated measures analysis of variance was used to compare time course of rest-activity rhythms changes on workdays between groups, and post-hoc tests were conducted using Bonferroni's correlation. RESULTS: Higher CRF correlated with increased physical activity. In model 1, higher CRF showed improved interdaily stability, but the significant difference disappeared in model 2 after adjusting for non-workday walking counts. A time-course group comparison showed that the high group had significantly higher activity levels than those of the low group from 6:00 to 8:59 and 17:00 to 17:59 and the medium group from 6:00 to 7:59 and 19:00 to 19:59. CONCLUSIONS: Workers who have better rest-activity rhythms and engage in higher levels of physical activity on workdays tend to have higher CRF levels. Regular daily routines, influenced by physical activity during holidays, can positively impact cardiopulmonary endurance.

Multiple myeloma risk in relation to long-term air pollution exposure - A pooled analysis of four European cohorts.

BACKGROUND: Air pollution is a growing concern worldwide, with significant impacts on human health. Multiple myeloma is a type of blood cancer with increasing incidence. Studies have linked air pollution exposure to various types of cancer, including leukemia and lymphoma, however, the relationship with multiple myeloma incidence has not been extensively investigated. METHODS: We pooled four European cohorts (N = 234,803) and assessed the association between residential exposure to nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), and ozone (O3) and multiple myeloma. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS: During 4,415,817 person-years of follow-up (average 18.8 years), we observed 404 cases of multiple myeloma. The results of the fully adjusted linear analyses showed hazard ratios (95% confidence interval) of 0.99 (0.84, 1.16) per 10 µg/m³ NO2, 1.04 (0.82, 1.33) per 5 µg/m³ PM2.5, 0.99 (0.84, 1.18) per 0.5 10-5 m-1 BCE, and 1.11 (0.87, 1.41) per 10 µg/m³ O3. CONCLUSIONS: We did not observe an association between long-term ambient air pollution exposure and incidence of multiple myeloma.

Long-term air pollution exposure and malignant intracranial tumours of the central nervous system: a pooled analysis of six European cohorts.

BACKGROUND: Risk factors for malignant tumours of the central nervous system (CNS) are largely unknown. METHODS: We pooled six European cohorts (N = 302,493) and assessed the association between residential exposure to nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), ozone (O3) and eight elemental components of PM2.5 (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) and malignant intracranial CNS tumours defined according to the International Classification of Diseases ICD-9/ICD-10 codes 192.1/C70.0, 191.0-191.9/C71.0-C71.9, 192.0/C72.2-C72.5. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS: During 5,497,514 person-years of follow-up (average 18.2 years), we observed 623 malignant CNS tumours. The results of the fully adjusted linear analyses showed a hazard ratio (95% confidence interval) of 1.07 (0.95, 1.21) per 10 µg/m³ NO2, 1.17 (0.96, 1.41) per 5 µg/m³ PM2.5, 1.10 (0.97, 1.25) per 0.5 10-5m-1 BC, and 0.99 (0.84, 1.17) per 10 µg/m³ O3. CONCLUSIONS: We observed indications of an association between exposure to NO2, PM2.5, and BC and tumours of the CNS. The PM elements were not consistently associated with CNS tumour incidence.

Long-term exposure to air pollution and risk of SARS-CoV-2 infection and COVID-19 hospitalisation or death: Danish nationwide cohort study.

BACKGROUND: Early ecological studies have suggested links between air pollution and risk of coronavirus disease 2019 (COVID-19), but evidence from individual-level cohort studies is still sparse. We examined whether long-term exposure to air pollution is associated with risk of COVID-19 and who is most susceptible. METHODS: We followed 3 721 810 Danish residents aged ≥30 years on 1 March 2020 in the National COVID-19 Surveillance System until the date of first positive test (incidence), COVID-19 hospitalisation or death until 26 April 2021. We estimated residential annual mean particulate matter with diameter ≤2.5 µm (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone (O3) in 2019 by the Danish DEHM/UBM model, and used Cox proportional hazards regression models to estimate the associations of air pollutants with COVID-19 outcomes, adjusting for age, sex, individual- and area-level socioeconomic status, and population density. RESULTS: 138 742 individuals were infected, 11 270 were hospitalised and 2557 died from COVID-19 during 14 months. We detected associations of PM2.5 (per 0.53 µg·m-3) and NO2 (per 3.59 µg·m-3) with COVID-19 incidence (hazard ratio (HR) 1.10 (95% CI 1.05-1.14) and HR 1.18 (95% CI 1.14-1.23), respectively), hospitalisations (HR 1.09 (95% CI 1.01-1.17) and HR 1.19 (95% CI 1.12-1.27), respectively) and death (HR 1.23 (95% CI 1.04-1.44) and HR 1.18 (95% CI 1.03-1.34), respectively), which were strongest in the lowest socioeconomic groups and among patients with chronic respiratory, cardiometabolic and neurodegenerative diseases. We found positive associations with BC and negative associations with O3. CONCLUSION: Long-term exposure to air pollution may contribute to increased risk of contracting severe acute respiratory syndrome coronavirus 2 infection as well as developing severe COVID-19 disease requiring hospitalisation or resulting in death.

Association between exposure to multiple air pollutants, transportation noise and cause-specific mortality in adults in Switzerland.

BACKGROUND: Long-term exposure to air pollution and noise is detrimental to health; but studies that evaluated both remain limited. This study explores associations with natural and cause-specific mortality for a range of air pollutants and transportation noise. METHODS: Over 4 million adults in Switzerland were followed from 2000 to 2014. Exposure to PM2.5, PM2.5 components (Cu, Fe, S and Zn), NO2, black carbon (BC) and ozone (O3) from European models, and transportation noise from source-specific Swiss models, were assigned at baseline home addresses. Cox proportional hazards models, adjusted for individual and area-level covariates, were used to evaluate associations with each exposure and death from natural, cardiovascular (CVD) or non-malignant respiratory disease. Analyses included single and two exposure models, and subset analysis to study lower exposure ranges. RESULTS: During follow-up, 661,534 individuals died of natural causes (36.6% CVD, 6.6% respiratory). All exposures including the PM2.5 components were associated with natural mortality, with hazard ratios (95% confidence intervals) of 1.026 (1.015, 1.038) per 5 µg/m3 PM2.5, 1.050 (1.041, 1.059) per 10 µg/m3 NO2, 1.057 (1.048, 1.067) per 0.5 × 10-5/m BC and 1.045 (1.040, 1.049) per 10 dB Lden total transportation noise. NO2, BC, Cu, Fe and noise were consistently associated with CVD and respiratory mortality, whereas PM2.5 was only associated with CVD mortality. Natural mortality associations persisted < 20 µg/m3 for PM2.5 and NO2, < 1.5 10-5/m BC and < 53 dB Lden total transportation noise. The O3 association was inverse for all outcomes. Including noise attenuated all outcome associations, though many remained significant. Across outcomes, noise was robust to adjustment to air pollutants (e.g. natural mortality 1.037 (1.033, 1.042) per 10 dB Lden total transportation noise, after including BC). CONCLUSION: Long-term exposure to air pollution and transportation noise in Switzerland contribute to premature mortality. Considering co-exposures revealed the importance of local traffic-related pollutants such as NO2, BC and transportation noise.

Long-term exposure to elemental components of fine particulate matter and all-natural and cause-specific mortality in a Danish nationwide administrative cohort study.

BACKGROUND: Fine particulate matter (PM2.5) is a well-recognized risk factor for premature death. However, evidence on which PM2.5 components are most relevant is unclear. METHODS: We evaluated the associations between mortality and long-term exposure to eight PM2.5 elemental components [copper (Cu), iron (Fe), zinc (Zn), sulfur (S), nickel (Ni), vanadium (V), silicon (Si), and potassium (K)]. Studied outcomes included death from diabetes, chronic kidney disease (CKD), dementia, and psychiatric disorders as well as all-natural causes, cardiovascular disease (CVD), respiratory diseases (RD), and lung cancer. We followed all residents in Denmark (aged ≥30 years) from January 1, 2000 to December 31, 2017. We used European-wide land-use regression models at a 100 × 100 m scale to estimate the residential annual mean levels of exposure to PM2.5 components. The models were developed with supervised linear regression (SLR) and random forest (RF). The associations were evaluated by Cox proportional hazard models adjusting for individual- and area-level socioeconomic factors and total PM2.5 mass. RESULTS: Of 3,081,244 individuals, we observed 803,373 death from natural causes during follow-up. We found significant positive associations between all-natural mortality with Si and K from both exposure modeling approaches (hazard ratios; 95% confidence intervals per interquartile range increase): SLR-Si (1.04; 1.03-1.05), RF-Si (1.01; 1.00-1.02), SLR-K (1.03; 1.02-1.04), and RF-K (1.06; 1.05-1.07). Strong associations of K and Si were detected with most causes of mortality except CKD and K, and diabetes and Si (the strongest associations for psychiatric disorders mortality). In addition, Fe was relevant for mortality from RD, lung cancer, CKD, and psychiatric disorders; Zn with mortality from CKD, RD, and lung cancer, and; Ni and V with lung cancer mortality. CONCLUSIONS: We present novel results of the relevance of different PM2.5 components for different causes of death, with K and Si seeming to be most consistently associated with mortality in Denmark.

Long-term air pollution exposure and Parkinson's disease mortality in a large pooled European cohort: An ELAPSE study.

BACKGROUND: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson's Disease (PD) remains limited. OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. METHODS: Within the project 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. RESULTS: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01-1.55), NO2 (1.13; 0.95-1.34 per 10 µg/m3), and BC (1.12; 0.94-1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58-0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95-1.62) or BC (1.28; 0.96-1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5. CONCLUSION: Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality.

Breast Cancer Incidence in Relation to Long-Term Low-Level Exposure to Air Pollution in the ELAPSE Pooled Cohort.

BACKGROUND: Established risk factors for breast cancer include genetic disposition, reproductive factors, hormone therapy, and lifestyle-related factors such as alcohol consumption, physical inactivity, smoking, and obesity. More recently a role of environmental exposures, including air pollution, has also been suggested. The aim of this study, was to investigate the relationship between long-term air pollution exposure and breast cancer incidence. METHODS: We conducted a pooled analysis among six European cohorts (n = 199,719) on the association between long-term residential levels of ambient nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), and ozone in the warm season (O3) and breast cancer incidence in women. The selected cohorts represented the lower range of air pollutant concentrations in Europe. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS: During 3,592,885 person-years of follow-up, we observed a total of 9,659 incident breast cancer cases. The results of the fully adjusted linear analyses showed a HR (95% confidence interval) of 1.03 (1.00-1.06) per 10 µg/m³ NO2, 1.06 (1.01-1.11) per 5 µg/m³ PM2.5, 1.03 (0.99-1.06) per 0.5 10-5 m-1 BC, and 0.98 (0.94-1.01) per 10 µg/m³ O3. The effect estimates were most pronounced in the group of middle-aged women (50-54 years) and among never smokers. CONCLUSIONS: The results were in support of an association between especially PM2.5 and breast cancer. IMPACT: The findings of this study suggest a role of exposure to NO2, PM2.5, and BC in development of breast cancer.

Association of cardiorespiratory fitness with the risk factors of cardiovascular disease: Evaluation using the Japan step test from the National Institute of Occupational Safety and Health.

OBJECTIVE: Cardiorespiratory fitness (CRF) is an important factor for evaluating cardiovascular disease (CVD) risk. We recently developed a novel method (National Institute of Occupational Safety and Health, Japan step test [JST]) for evaluating CRF in workers; its criterion validity has been investigated. However, its association with health risk must be confirmed before its application in the workplace. Therefore, we aimed to determine the association of JST-evaluated CRF with the prevalence of CVD risk among Japanese workers. METHODS: For CRF evaluation, working adults completed the JST, which comprised a 3-minute stepping exercise and a 2-minute recovery period. Data on CVD risk factors and clinical history were collected through medical certification within 1 year from the date of the JST measurements. Participants were divided into three groups for multiple logistic regression analyses based on the JST values (low, moderate, and high). Odds ratios (ORs) for the prevalence of CVD risk were calculated. RESULTS: We recruited 885 working adults (46.4% women). The prevalence of CVD risk in the total population was 18.6%. When compared to the reference group (low CRF), the ORs for CVD risk prevalence after adjustments for lifestyle factors (smoking status, alcohol consumption status, and exercise habits) were 0.42 (95% confidence interval [CI], 0.28-0.63) and 0.29 (95% CI, 0.18-0.45) for the moderate and high groups, respectively. CONCLUSION: An inverse association was noted between the JST-evaluated CRF and CVD risk prevalence. JST may be helpful for identifying workers at risk for CVD development.

Long term exposure to air pollution and kidney parenchyma cancer - Effects of low-level air pollution: a Study in Europe (ELAPSE).

BACKGROUND: Particulate matter (PM) is classified as a group 1 human carcinogen. Previous experimental studies suggest that particles in diesel exhaust induce oxidative stress, inflammation and DNA damage in kidney cells, but the evidence from population studies linking air pollution to kidney cancer is limited. METHODS: We pooled six European cohorts (N = 302,493) to assess the association of residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC), warm season ozone (O3) and eight elemental components of PM2.5 (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) with cancer of the kidney parenchyma. The main exposure model was developed for year 2010. We defined kidney parenchyma cancer according to the International Classification of Diseases 9th and 10th Revision codes 189.0 and C64. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS: The participants were followed from baseline (1985-2005) to 2011-2015. A total of 847 cases occurred during 5,497,514 person-years of follow-up (average 18.2 years). Median (5-95%) exposure levels of NO2, PM2.5, BC and O3 were 24.1 µg/m3 (12.8-39.2), 15.3 µg/m3 (8.6-19.2), 1.6 10-5 m-1 (0.7-2.1), and 87.0 µg/m3 (70.3-97.4), respectively. The results of the fully adjusted linear analyses showed a hazard ratio (HR) of 1.03 (95% confidence interval [CI]: 0.92, 1.15) per 10 µg/m³ NO2, 1.04 (95% CI: 0.88, 1.21) per 5 µg/m³ PM2.5, 0.99 (95% CI: 0.89, 1.11) per 0.5 10-5 m-1 BCE, and 0.88 (95% CI: 0.76, 1.02) per 10 µg/m³ O3. We did not find associations between any of the elemental components of PM2.5 and cancer of the kidney parenchyma. CONCLUSION: We did not observe an association between long-term ambient air pollution exposure and incidence of kidney parenchyma cancer.

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 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.

Hepatoprotective effect of Centella asiatica 50% ethanol extract against acetaminophen-induced acute liver injury in BALB/c mice.

N-acetyl-p-aminophenol (acetaminophen, APAP) is a well-known component of analgesic and antipyretic monotherapy products. However, exceeding the recommended dose can lead to serious injury to the liver. We conducted this study to determine the potential of Centella asiatica as a natural substance to protect against APAP-induced liver injury. When acute hepatotoxicity was induced in mice by APAP overdose, their liver weight decreased significantly (p < 0.05). However, mice treated with C. asiatica 50% ethanol extract (CA-HE50, 200 mg/kg) for a week before induction of hepatotoxicity by APAP had similar liver weights to those of mice in which hepatotoxicity was not induced. In particular, levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, which are biomarkers of liver injury, were significantly increased by APAP and dose-dependently decreased by CA-HE50 (p < 0.05). Glutathione and malondialdehyde, indicators of oxidative stress, were significantly changed by APAP and CA-HE50 (p < 0.05). In addition, hepatic necrosis and expression of genes encoding pro-inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1ß, and IL-4) induced by APAP were inhibited by CA-HE50, and these results were dose-dependent. Through our in vivo studies, we found that CA-HE50 can help prevent APAP-induced hepatic tissue injury in BALB/c mice. Furthermore, CA-HE50 was effective at protecting RAW 264.7 cells from lipopolysaccharide-induced cytotoxicity and inhibiting the release of nitric oxide from these cells; in particular, asiaticoside was found to be a key component of CA-HE50 responsible for these effects. Therefore, we suggest that CA-HE50 has potential applications in functional health foods and drugs.

Multioside, an active ingredient from adonis amurensis, displays anti-cancer activity through autophagosome formation.

BACKGROUND: Adonis amurensis Regel & Radde, commonly found in East Asia, has been traditionally used to treat cardiac insufficiency and edema. Although this plant extract has been shown to regulate cell growth and neovascularization, the anti-cancer mechanism of A. amurensis has not been fully investigated. PURPOSE: In this study, we aimed to examine the anti-cancer activity of A. amurensis and identify its underlying mechanism. METHODS: The growth of cancer cells was evaluated by MTT and hollow fiber assays. A cancer xenograft nude mouse model was used to assess the anti-cancer activities in vivo. Autophagic activity was measured by the detection of autophagosome formation and by performing a monodansylcadaverine (MDC) assay. RESULT: A. amurensis extract showed potent anti-cancer activity both in vitro and in vivo. Importantly, the treatment of cancer cells with A. amurensis extract dramatically increased the formation of autophagosomes and was involved in the activation of multiple signaling components including AKT, ERK, and MAPK. Furthermore, we isolated an active ingredient, Multioside, which exhibited strong anti-cancer activity through autophagy. CONCLUSION: A. amurensis displays anti-cancer activity that is mediated by the activation of autophagy, suggesting that A. amurensis could be a useful therapeutic anti-cancer agent.

Which cytokine is the most related to weight loss-induced decrease in arterial stiffness in overweight and obese men?

Obesity and increased arterial stiffness are risk factors for cardiovascular disease. A well-known characteristic of obesity is the chronic low-grade inflammatory state, and it causes elevation of arterial stiffness. Weight-loss reduces arterial stiffness and inflammatory level in obese individuals. However, it is unclear which inflammatory factor is most related to weight loss-induce decreases in arterial stiffness in overweight and obese men. Thus, the aim of this study was to determine which circulating cytokine level has the most effect on decreasing arterial stiffness after lifestyle modification. Twenty overweight and obese men completed a 12-week period of lifestyle modifications (combination of aerobic exercise training and dietary modification). We measured brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness, and circulating cytokine levels using comprehensive analysis. After the 12-week lifestyle modifications, body mass was markedly decreased. Also, baPWV and the levels of several circulating cytokines significantly decreased after the lifestyle modifications. We observed a positive correlation between changes in baPWV and circulating interleukin-6 (IL-6) levels. Furthermore, multiple liner regression analysis revealed that change in baPWV was significantly associated with that in IL-6 levels after consideration of changes in systolic blood pressure and body mass index. These results suggest that for overweight and obese men, a 12-week period of lifestyle modifications-induced a decrease in circulating cytokine levels (especially IL-6 levels), leads to decreased baPWV.

Lifestyle modification decreases arterial stiffness in overweight and obese men: dietary modification vs. exercise training.

Obesity and increased arterial stiffness are independent risk factors for cardiovascular disease. Arterial stiffness is increased in obese individuals than in age-matched nonobese individuals. We demonstrated that dietary modification and exercise training are effective in reducing arterial stiffness in obese persons. However, the differences in the effect on arterial stiffness between dietary modification and exercise training are unknown. The purpose of the current study was to compare the effect of dietary modification and aerobic exercise training on arterial stiffness and endothelial function in overweight and obese persons. Forty-five overweight and obese men (48 ± 1 year) completed either a dietary modification (well-balanced nutrient, 1680 kcal/day) or an exercise-training program (walking, 40-60 min/day, 3 days/week) for 12 weeks. Before and after the intervention, all participants underwent anthropometric measurements. Arterial stiffness was measured based on carotid arterial compliance, brachial-ankle pulse wave velocity (baPWV), and endothelial function was determined by circulating level of endothelin-1 (ET-1) and nitric oxide metabolite (nitrites/nitrate as metabolite: NOx). Body mass and waist circumference significantly decreased after both intervention programs. Weight loss was greater after dietary modification than after exercise training (-10.1 ± 0.6 kg vs. -3.6 ± 0.5 kg, p < .01). Although arterial stiffness and the plasma levels of ET-1 and NOx were improved after dietary modification or exercise training, there were no differences in those improvements between the 2 types of interventions. Exercise training improves arterial function in obese men without as much weight loss as after dietary modification.

Abdominal obesity: causal factor or simply a symptom of obesity-related health risk.

BACKGROUND: Abdominal fat (AF) reduction is advocated in the treatment of obesity-related diseases. Nonetheless, recent studies have shown additional beneficial effects against obesity-related health risks, independent of AF reduction. Therefore it is important to determine whether AF plays a causal role in promoting metabolic disorders or is simply a symptom of increased obesity-related health risk factors. Clarification of the primary role of AF in the pathogenesis of obesity-related disease is also important. OBJECTIVE: This retrospective study was conducted with the objectives of 1) comparison between groups exhibiting equivalent amounts of AF loss that resulted from distinct treatments (exercise and dietary restriction) with respect to degrees of improvement in obesity-related health risk factors and 2) determination of definite differences in the outcomes of obesity-related health risk in subjects receiving identical treatment (exercise) but exhibiting a remarkable difference in AF reduction. DESIGN: In 66 subjects who completed a 12-week exercise or dietary restriction program, 17 parameters (systolic blood pressure [SBP] and diastolic blood pressure [DBP]; high-sensitivity C-reactive protein [hs-CRP]; leptin, adiponectin, tumor necrosis factor [TNF]-α, interleukin [IL]-6; alanine aminotransferase [ALT], gamma glutamyl transpeptidase [γGT]; lipid profile: high-density lipoprotein cholesterol [HDLC], triglyceride [TG]; fasting plasma glucose [FPG], hemoglobin A1c [HbA1c], homeostasis model assessment of insulin resistance (HOMA-IR); creatinine, uric acid; and maximal aerobic capacity [VO2 max]) were examined as indicators of obesity-related health risk. RESULTS: Despite equivalent magnitudes of AF reduction (-29.5% versus -30.1%) in subjects in the exercise and dietary restriction groups (objective 1), ten parameters (SBP, DBP, HDLC, HOMA-IR, uric acid, creatinine, hs-CRP, adiponectin, IL-6, and VO2 max) showed significant differences. However, for large AF reduction differences (-30.1% versus -2.8%) between groups of subjects in the same exercise program (objective 2), only creatinine and VO2 max were different. CONCLUSION: It is likely that AF reduction alone is not directly linked to improvement in obesity-related health risk factors, indicating the need for reexamination of the management for AF reduction (ie, lifestyle modification) rather than simply targeting reduction of AF.