Relationship of leukaemias with long-term ambient air pollution exposures in the adult Danish population

Background Few population-based epidemiological studies of adults have examined the relationship between air pollution and leukaemias. Methods Using Danish National Cancer Registry data and Danish DEHM-UBM-AirGIS system-modelled air pollution exposures, we examined whether particulate matter (PM2.5), black carbon (BC), nitrogen dioxide (NO2) and ozone (O3) averaged over 1, 5 or 10 years were associated with adult leukaemia in general or by subtype. In all, 14,986 adult cases diagnosed 1989–2014 and 51,624 age, sex and time-matched controls were included. Separate conditional logistic regression models, adjusted for socio-demographic factors, assessed exposure to each pollutant with leukaemias. Results Fully adjusted models showed a higher risk of leukaemia with higher 1-, 5- and 10-year-average exposures to PM2.5 prior to diagnosis (e.g. OR per 10 µg/m3 for 10-year average: 1.17, 95% CI: 1.03, 1.32), and a positive relationship with 1-year average BC. Results were driven by participants 70 years and older (OR per 10 µg/m3 for 10-year average: 1.35, 95% CI: 1.15–1.58). Null findings for younger participants. Higher 1-year average PM2.5 exposures were associated with higher risks for acute myeloid and chronic lymphoblastic leukaemia. Conclusion Among older adults, higher risk for leukaemia was associated with higher residential PM2.5 concentrations averaged over 1, 5 and 10 years prior to diagnosis.</p

Dabigatran use in Danish atrial fibrillation patients in 2011: a nationwide study

OBJECTIVE: Dabigatran was recently approved for anticoagulation in patients with atrial fibrillation (AF); data regarding real-world use, comparative effectiveness and safety are sparse. DESIGN: Pharmacoepidemiological cohort study. METHODS/SETTINGS: From nationwide registers, we identified patients with an in-hospital or outpatient-clinic AF diagnosis who claimed a prescription of dabigatran 110 or 150 mg, or vitamin K antagonist (VKA), between 22 August and 31 December 2011. HRs of thromboembolic events (ischaemic stroke, transitory ischaemic attack and peripheral artery embolism) and bleedings were estimated using Cox regression analyses in all patients and stratified by previous VKA use. RESULTS: Overall, 1612 (3.1%) and 1114 (2.1%) patients claimed a prescription of dabigatran 110 and 150 mg, and 49640 (94.8%) of VKA. Patients treated with dabigatran 150 mg were younger with less comorbidity than those treated with dabigatran 110 mg and VKA, as were VKA naïve patients compared with previous VKA users. Recommendations set by the European Medicine Agency (EMA) for dabigatran were met in 90.3% and 55.5% of patients treated with 110 and 150 mg. Patients treated with 150 mg dabigatran, who did not fulfil the recommendations by EMA, were >80 years, patients with liver or kidney disease, patients with previous bleeding. Compared with VKA, the thromboembolic risk associated with dabigatran 110 and 150 mg was HR 3.52 (1.40 to 8.84) and 5.79 (1.81 to 18.56) in previous VKA users, and HR 0.95(0.47 to 1.91) and 1.14(0.60 to 2.16) in VKA naïve patients. Bleeding risk was increased in previous VKA users receiving dabigatran 110 mg, but not in patients with 150 mg dabigatran, nor in the VKA naïve users. CONCLUSIONS: Deviations from the recommended use of dabigatran were frequent among patients treated with 150 mg. With cautious interpretation, dabigatran use in VKA naïve patients seems safe. Increased risk of thromboembolism and bleeding with dabigatran among previous VKA users was unexpected and may reflect patient selection and ‘drug switching’ practices

Alcohol Intake and Risk of Coronary Heart Disease in Younger, Middle-Aged, and Older Adults

BACKGROUND: Light-to-moderate alcohol consumption is associated with a reduced risk of coronary heart disease (CHD). This protective effect of alcohol, however, may be confined to middle-aged or older individuals. CHD Incidence is low in men younger than 40 and in women younger than 50 years and for this reason, study cohorts rarely have the power to investigate effects of alcohol on CHD risk in younger adults. This study examined whether the beneficial effect of alcohol on CHD depends on age. METHODS AND RESULTS: A pooled analysis of eight prospective studies from North America and Europe including 192,067 women and 74,919 men free of cardiovascular diseases, diabetes, and cancers at baseline. Average daily alcohol intake was assessed at baseline using a food frequency or diet history questionnaire. An inverse association between alcohol and risk of coronary heart disease was observed in all age groups: hazard ratios among moderately drinking men (5.0–29.9 g/day) aged 39–50, 50–59, and 60+ years were 0.58 (95% C.I. 0.36 to 0.93), 0.72 (95% C.I. 0.60–0.86), and 0.85 (95% C.I. 0.75 to 0.97) compared with abstainers. However, the analyses indicated a smaller incidence rate difference (IRD) between abstainers and moderate consumers in younger adults (IRD=45 per 100,000; 90% C.I. 8 to 84), than in middle-aged (IRD=64 per 100,000; 90% C.I. 24 to 102) and older adults (IRD=89 per 100,000; 90% C.I. 44 to 140). Similar results were observed in women. CONCLUSIONS: Alcohol is also associated with a decreased risk of CHD in younger adults; however, the absolute risk was small compared with middle-aged and older adults

Intracranial tumors of the central nervous system and air pollution - A nationwide case-control study from Denmark

Background: Inconclusive evidence has suggested a possible link between air pollution and central nervous system (CNS) tumors. We investigated a range of air pollutants in relation to types of CNS tumors. Methods: We identified all (n = 21,057) intracranial tumors in brain, meninges and cranial nerves diagnosed in Denmark between 1989 and 2014 and matched controls on age, sex and year of birth. We established personal 10- year mean residential outdoor exposure to particulate matter < 2.5 μm (PM2.5), nitrous oxides (NOX), primary emitted black carbon (BC) and ozone. We used conditional logistic regression to calculate odds ratios (OR) linearly (per interquartile range (IQR)) and categorically. We accounted for personal income, employment, marital status, use of medication as well as socio-demographic conditions at area level. Results: Malignant tumors of the intracranial CNS was associated with BC (OR: 1.034, 95%CI: 1.005–1.065 per IQR. For NOx the OR per IQR was 1.026 (95%CI: 0.998–1.056). For malignant non-glioma tumors of the brain we found associations with PM2.5 (OR: 1.267, 95%CI: 1.053–1.524 per IQR), BC (OR: 1.049, 95%CI: 0.996–1.106) and NOx (OR: 1.051, 95% CI: 0.996–1.110). Conclusion: Our results suggest that air pollution is associated with malignant intracranial CNS tumors and malignant non-glioma of the brain. However, additional studies are needed

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

Long-term exposure to low-level air pollution and incidence of chronic obstructive pulmonary disease: The ELAPSE project.

BACKGROUND: Air pollution has been suggested as a risk factor for chronic obstructive pulmonary disease (COPD), but evidence is sparse and inconsistent. OBJECTIVES: We examined the association between long-term exposure to low-level air pollution and COPD incidence. METHODS: Within the 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE) study, we pooled data from three cohorts, from Denmark and Sweden, with information on COPD hospital discharge diagnoses. Hybrid land use regression models were used to estimate annual mean concentrations of particulate matter with a diameter < 2.5 µm (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) in 2010 at participants' baseline residential addresses, which were analysed in relation to COPD incidence using Cox proportional hazards models. RESULTS: Of 98,058 participants, 4,928 developed COPD during 16.6 years mean follow-up. The adjusted hazard ratios (HRs) and 95% confidence intervals for associations with COPD incidence were 1.17 (1.06, 1.29) per 5 µg/m3 for PM2.5, 1.11 (1.06, 1.16) per 10 µg/m3 for NO2, and 1.11 (1.06, 1.15) per 0.5 10-5m-1 for BC. Associations persisted in subset participants with PM2.5 or NO2 levels below current EU and US limit values and WHO guidelines, with no evidence for a threshold. HRs for NO2 and BC remained unchanged in two-pollutant models with PM2.5, whereas the HR for PM2.5 was attenuated to unity with NO2 or BC. CONCLUSIONS: Long-term exposure to low-level air pollution is associated with the development of COPD, even below current EU and US limit values and possibly WHO guidelines. Traffic-related pollutants NO2 and BC may be the most relevant

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 (PM 2.5), nitrogen dioxide (NO 2), black carbon (BC), and ozone (O 3), as well as 8 PM 2.5 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 PM 2.5 (hazard ratio per 5 µg/m 3: 1.25; 95% confidence interval: 1.01-1.55), NO 2 (1.13; 0.95-1.34 per 10 µg/m 3), and BC (1.12; 0.94-1.34 per 0.5 × 10 -5m -1), and a negative association with O 3 (0.74; 0.58-0.94 per 10 µg/m 3). Associations of PM 2.5, NO 2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM 2.5 remained robust when adjusted for NO 2 (1.24; 0.95-1.62) or BC (1.28; 0.96-1.71), whereas associations with NO 2 or BC attenuated to null. O 3 associations remained negative, but no longer statistically significant in models with PM 2.5. We detected suggestive positive associations with the potassium component of PM 2.5. CONCLUSION: Long-term exposure to PM 2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality

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 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