Ole Raaschou-Nielsen

Exposure to Ultrafine Particles from Ambient Air and Oxidative Stress–Induced DNA Damage

Background Particulate matter, especially ultrafine particles (UFPs), may cause health effects through generation of oxidative stress, with resulting damage to DNA and other macromolecules. Objective We investigated oxidative damage to DNA and related repair capacity in peripheral blood mononuclear cells (PBMCs) during controlled exposure to urban air particles with assignment of number concentration (NC) to four size modes with average diameters of 12, 23, 57, and 212 nm. Design Twenty-nine healthy adults participated in a randomized, two-factor cross-over study with or without biking exercise for 180 min and with exposure to particles (NC 6169-15362/cm3) or filtered air (NC 91-542/cm3) for 24 hr. Methods The levels of DNA strand breaks (SBs), oxidized purines as formamidopyrimidine DNA glycolase (FPG) sites, and activity of 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGG1) in PBMCs were measured by the Comet assay. mRNA levels of OGG1, nucleoside diphosphate linked moiety X-type motif 1 (NUDT1), and heme oxygenase-1 (HO1) were determined by real-time reverse transcriptase–polymerase chain reaction. Results Exposure to UFPs for 6 and 24 hr significantly increased the levels of SBs and FPG sites, with a further insignificant increase after physical exercise. The OGG1 activity and expression of OGG1, NUDT1, and HO1 were unaltered. There was a significant dose–response relationship between NC and DNA damage, with the 57-nm mode as the major contributor to effects. Concomitant exposure to ozone, nitrogen oxides, and carbon monoxide had no influence. Conclusion Our results indicate that UFPs, especially the 57-nm soot fraction from vehicle emissions, causes systemic oxidative stress with damage to DNA and no apparent compensatory up-regulation of DNA repair within 24 hr.

Chronic Obstructive Pulmonary Disease and Long-Term Exposure to Traffic-related Air Pollution: A Cohort Study

RATIONALEnShort-term exposure to air pollution has been associated with exacerbation of chronic obstructive pulmonary disease (COPD), whereas the role of long-term exposures on the development of COPD is not yet fully understood.nnnOBJECTIVESnWe assessed the effect of exposure to traffic-related air pollution over 35 years on the incidence of COPD in a prospective cohort study.nnnMETHODSnWe followed 57,053 participants in the Danish Diet, Cancer, and Health cohort in the Hospital Discharge Register for their first hospital admission for COPD between 1993 and 2006. We estimated the annual mean levels of nitrogen dioxide (NO₂) and nitrogen oxides (NO(x)) at all residential addresses of the cohort participants since 1971 to an event or 2006 and used indicators of traffic near the residential address at recruitment. We assessed the association between exposure to air pollution and COPD incidence by Cox regression analyses for the full cohort, and for participants with and without comorbid conditions, including asthma, diabetes, or cardiovascular disease.nnnMEASUREMENTS AND MAIN RESULTSnA first hospital admission for COPD was recorded for 1,786 (3.4%) of 52,799 eligible subjects between recruitment (1993-1997) and 2006. COPD incidence was associated with the 35-year mean NO₂ level (hazard ratio, 1.08; 95% confidence interval, 1.02-1.14, per interquartile range of 5.8 μg/m³), with stronger associations in subjects with diabetes (1.29; 1.05-1.50) and asthma (1.19; 1.03-1.38).nnnCONCLUSIONSnLong-term exposure to traffic-related air pollution may contribute to the development of COPD with possibly enhanced susceptibility in people with diabetes and asthma.

Association between short-term exposure to ultrafine particles and hospital admissions for stroke in Copenhagen, Denmark

AIMSnThe relevance of ultrafine particles (UFPs, particles <0.1 microm diameter), the smallest fraction of ambient particulate matter, on stroke morbidity has not been documented. We studied the effects of short-term changes in exposure to these particles on stroke, separately for ischaemic and haemorrhagic strokes, mild and severe strokes, and ischaemic strokes with (likely embolic) and without (likely thrombotic) atrial fibrillation (AF).nnnMETHODS AND RESULTSnWe used a time-stratified case-crossover design to study the association between short-term exposure to UFPs, particulate matter <10 microm in diameter (PM(10)), nitrogen oxides (NO(x)) and carbon monoxide (CO) (measured at single background station) and hospital admissions for stroke in Copenhagen (2003-2006). Of 7485 stroke admissions, 6798 were ischaemic and 687 haemorrhagic, 3485 mild, and 2248 severe. Of the ischaemic stroke cases, 1204 had AF and 5273 did not. We found significant positive association with exposure to UFPs, NO(x) and CO, and ischaemic strokes, and UFPs and NO(x) and mild strokes, 4 days before admission. The strongest associations were with UFPs. Exposure to UFPs lead to a 21% increase in hospital admissions (per interquartile range of 5-day averages; 95% confidence interval 4-41%) for mild ischaemic stroke of without AF (likely thrombotic origin).nnnCONCLUSIONnOur results indicate possible effects of traffic-related air pollution, mainly UFPs, on hospital admissions for ischaemic stroke, especially for mild ischaemic stroke of likely thrombotic origin (without AF). These are novel findings regarding the relevance of UFPs and the heterogeneous effect of air pollution on the severity and origin of stroke, and need confirmation by other data.

Long-term exposure to ambient air pollution and incidence of cerebrovascular events: results from 11 European cohorts within the ESCAPE project.

Background: Few studies have investigated effects of air pollution on the incidence of cerebrovascular events. Objectives: We assessed the association between long-term exposure to multiple air pollutants and the incidence of stroke in European cohorts. Methods: Data from 11 cohorts were collected, and occurrence of a first stroke was evaluated. Individual air pollution exposures were predicted from land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE). The exposures were: PM2.5 [particulate matter (PM) ≤ 2.5 μm in diameter], coarse PM (PM between 2.5 and 10 μm), PM10 (PM ≤ 10 μm), PM2.5 absorbance, nitrogen oxides, and two traffic indicators. Cohort-specific analyses were conducted using Cox proportional hazards models. Random-effects meta-analysis was used for pooled effect estimation. Results: A total of 99,446 study participants were included, 3,086 of whom developed stroke. A 5-μg/m3 increase in annual PM2.5 exposure was associated with 19% increased risk of incident stroke [hazard ratio (HR) = 1.19, 95% CI: 0.88, 1.62]. Similar findings were obtained for PM10. The results were robust to adjustment for an extensive list of cardiovascular risk factors and noise coexposure. The association with PM2.5 was apparent among those ≥ 60 years of age (HR = 1.40, 95% CI: 1.05, 1.87), among never-smokers (HR = 1.74, 95% CI: 1.06, 2.88), and among participants with PM2.5 exposure < 25 μg/m3 (HR = 1.33, 95% CI: 1.01, 1.77). Conclusions: We found suggestive evidence of an association between fine particles and incidence of cerebrovascular events in Europe, even at lower concentrations than set by the current air quality limit value. Citation: Stafoggia M, Cesaroni G, Peters A, Andersen ZJ, Badaloni C, Beelen R, Caracciolo B, Cyrys J, de Faire U, de Hoogh K, Eriksen KT, Fratiglioni L, Galassi C, Gigante B, Havulinna AS, Hennig F, Hilding A, Hoek G, Hoffmann B, Houthuijs D, Korek M, Lanki T, Leander K, Magnusson PK, Meisinger C, Migliore E, Overvad K, Östenson CG, Pedersen NL, Pekkanen J, Penell J, Pershagen G, Pundt N, Pyko A, Raaschou-Nielsen O, Ranzi A, Ricceri F, Sacerdote C, Swart WJ, Turunen AW, Vineis P, Weimar C, Weinmayr G, Wolf K, Brunekreef B, Forastiere F. 2014. Long-term exposure to ambient air pollution and incidence of cerebrovascular events: results from 11 European cohorts within the ESCAPE project. Environ Health Perspect 122:919–925;u2002http://dx.doi.org/10.1289/ehp.1307301

Air pollution from traffic and risk for lung cancer in three Danish cohorts.

Background: Air pollution is suspected to cause lung cancer. The purpose was to investigate whether the concentration of nitrogen oxides (NOx) at the residence, used as an indicator of air pollution from traffic, is associated with risk for lung cancer. Methods: We identified 679 lung cancer cases in the Danish Cancer Registry from the members of three prospective cohorts and selected a comparison group of 3,481 persons from the same cohorts in a case-cohort design. Residential addresses from January 1, 1971, were traced in the Central Population Registry. The NOx concentration at each address was calculated by dispersion models, and the time-weighted average concentration for all addresses was calculated for each person. We used Cox models to estimate incidence rate ratios after adjustment for smoking (status, duration, and intensity), educational level, body mass index, and alcohol consumption. Results: The incidence rate ratios for lung cancer were 1.30 [95% confidence interval (95% CI), 1.07-1.57] and 1.45 (95% CI, 1.12-1.88) for NOx concentrations of 30 to 72 and >72 μg/m3, respectively, when compared with <30 μg/m3. This corresponds to a 37% (95% CI, 6-76%) increase in incidence rate ratio per 100 μg/m3 NOx. The results showed no significant heterogeneity in the incidence rate ratio for lung cancer between cohorts or between strata defined by gender, educational level, or smoking status. Conclusion: The study showed a modest association between air pollution from traffic and the risk for lung cancer. Impact: This study points at traffic as a source of carcinogenic air pollution and stresses the importance of strategies for reduction of population exposure to traffic-related air pollution. Cancer Epidemiol Biomarkers Prev; 19(5); 1284–91. ©2010 AACR.

Evaluation of AirGIS: a GIS-based air pollution and human exposure modelling system

This study describes in brief the latest extensions of the Danish Geographic Information System (GIS)-based air pollution and human exposure modelling system (AirGIS), which has been developed in Denmark since 2001 and gives results of an evaluation with measured air pollution data. The system shows, in general, a good performance for both long-term averages (annual and monthly averages), short-term averages (hourly and daily) as well as when reproducing spatial variation in air pollution concentrations. Some shortcomings and future perspectives of the system are discussed too.

Long-term exposure to low-level arsenic in drinking water and diabetes incidence: a prospective study of the diet, cancer and health cohort.

Background: Established causes of diabetes do not fully explain the present epidemic. High-level arsenic exposure has been implicated in diabetes risk, but the effect of low-level arsenic exposure in drinking water remains unclear. Objective: We sought to determine whether long-term exposure to low-level arsenic in drinking water in Denmark is associated with an increased risk of diabetes using a large prospective cohort. Methods: During 1993–1997, we recruited 57,053 persons. We followed each cohort member for diabetes occurrence from enrollment until 31 December 2006. We traced and geocoded residential addresses of the cohort members and used a geographic information system to link addresses with water-supply areas. We estimated individual exposure to arsenic using all addresses from 1 January 1971 until the censoring date. Cox proportional hazards models were used to model the association between arsenic exposure and diabetes incidence, separately for two definitions of diabetes: all cases and a more strict definition in which cases of diabetes based solely on blood glucose results were excluded. Results: Over a mean follow-up period of 9.7 years for 52,931 eligible participants, there were a total of 4,304 (8.1%) diabetes cases, and 3,035 (5.8%) cases of diabetes based on the more strict definition. The adjusted incidence rate ratios (IRRs) per 1-μg/L increment in arsenic levels in drinking water were as follows: IRR = 1.03 (95% CI: 1.01, 1.06) and IRR = 1.02 (95% CI: 0.99, 1.05) for all and strict diabetes cases, respectively. Conclusions: Long-term exposure to low-level arsenic in drinking water may contribute to the development of diabetes. Citation: Bräuner EV, Nordsborg RB, Andersen ZJ, Tjønneland A, Loft S, Raaschou-Nielsen O. 2014. Long-term exposure to low-level arsenic in drinking water and diabetes incidence: a prospective study of the Diet, Cancer and Health cohort. Environ Health Perspect 122:1059–1065;u2002http://dx.doi.org/10.1289/ehp.1408198

Natural-Cause Mortality and Long-Term Exposure to Particle Components: An Analysis of 19 European Cohorts within the Multi-Center ESCAPE Project

Background Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality. Objectives Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter. Methods Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori–selected components of particulate matter (PM) was characterized following a strictly standardized protocol. Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions ≤ 2.5 μm (PM2.5) and ≤ 10 μm (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis. Results The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 sulfur (1.14; 95% CI: 1.06, 1.23 per 200 ng/m3). In a two-pollutant model, the association with PM2.5 sulfur was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced. Conclusions Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality. This association was robust to adjustment for other pollutants and PM2.5. Citation Beelen R, Hoek G, Raaschou-Nielsen O, Stafoggia M, Andersen ZJ, Weinmayr G, Hoffmann B, Wolf K, Samoli E, Fischer PH, Nieuwenhuijsen MJ, Xun WW, Katsouyanni K, Dimakopoulou K, Marcon A, Vartiainen E, Lanki T, Yli-Tuomi T, Oftedal B, Schwarze PE, Nafstad P, De Faire U, Pedersen NL, Östenson C-G, Fratiglioni L, Penell J, Korek M, Pershagen G, Eriksen KT, Overvad K, Sørensen M, Eeftens M, Peeters PH, Meliefste K, Wang M, Bueno-de-Mesquita HB, Sugiri D, Krämer U, Heinrich J, de Hoogh K, Key T, Peters A, Hampel R, Concin H, Nagel G, Jaensch A, Ineichen A, Tsai MY, Schaffner E, Probst-Hensch NM, Schindler C, Ragettli MS, Vilier A, Clavel-Chapelon F, Declercq C, Ricceri F, Sacerdote C, Galassi C, Migliore E, Ranzi A, Cesaroni G, Badaloni C, Forastiere F, Katsoulis M, Trichopoulou A, Keuken M, Jedynska A, Kooter IM, Kukkonen J, Sokhi RS, Vineis P, Brunekreef B. 2015. Natural-cause mortality and long-term exposure to particle components: an analysis of 19 European cohorts within the Multi-Center ESCAPE Project. Environ Health Perspect 123:525–533;u2002http://dx.doi.org/10.1289/ehp.1408095

A Prospective Study of Organochlorines in Adipose Tissue and Risk of Non-Hodgkin Lymphoma

Background: Exposure to organochlorines has been examined as a potential risk factor for non-Hodgkin lymphoma (NHL), with inconsistent results that may be related to limited statistical power or to imprecise exposure measurements. Objective: Our purpose was to examine associations between organochlorine concentrations in prediagnostic adipose tissue samples and the risk of NHL. Methods: We conducted a case–cohort study using a prospective Danish cohort of 57,053 persons enrolled between 1993 and 1997. Within the cohort we identified 256 persons diagnosed with NHL in the population-based nationwide Danish Cancer Registry and randomly selected 256 subcohort persons. We measured concentrations of 8 pesticides and 10 polychlorinated biphenyl (PCB) congeners in adipose tissue collected upon enrollment. Associations between the 18 organochlorines and NHL were analyzed in Cox regression models, adjusting for body mass index. Results: Incidence rate ratios and confidence intervals (CIs) for interquartile range increases in concentrations of dichlorodiphenyltrichlorethane (DDT), cis-nonachlor, and oxychlordane were 1.35 (95% CI: 1.10, 1.66), 1.13 (95% CI: 0.94, 1.36), and 1.11 (95% CI: 0.89, 1.38), respectively, with monotonic dose–response trends for DDT and cis-nonachlor based on categorical models. The relative risk estimates were higher for men than for women. In contrast, no clear association was found between NHL and PCBs. Conclusion: We found a higher risk of NHL in association with higher adipose tissue levels of DDT, cis-nonachlor, and oxychlordane, but no association with PCBs. This is the first study of organochlorines and NHL using prediagnostic adipose tissue samples in the exposure assessment and provides new environmental health evidence that these organochlorines contribute to NHL risk.

A study of the combined effects of physical activity and air pollution on mortality in elderly urban residents: the Danish diet, cancer, and health cohort

Background Physical activity reduces, whereas exposure to air pollution increases, the risk of premature mortality. Physical activity amplifies respiratory uptake and deposition of air pollutants in the lung, which may augment acute harmful effects of air pollution during exercise. Objectives We aimed to examine whether benefits of physical activity on mortality are moderated by long-term exposure to high air pollution levels in an urban setting. Methods A total of 52,061 subjects (50–65 years of age) from the Danish Diet, Cancer, and Health cohort, living in Aarhus and Copenhagen, reported data on physical activity in 1993–1997 and were followed until 2010. High exposure to air pollution was defined as the upper 25th percentile of modeled nitrogen dioxide (NO2) levels at residential addresses. We associated participation in sports, cycling, gardening, and walking with total and cause-specific mortality by Cox regression, and introduced NO2 as an interaction term. Results In total, 5,534 subjects died: 2,864 from cancer, 1,285 from cardiovascular disease, 354 from respiratory disease, and 122 from diabetes. Significant inverse associations of participation in sports, cycling, and gardening with total, cardiovascular, and diabetes mortality were not modified by NO2. Reductions in respiratory mortality associated with cycling and gardening were more pronounced among participants with moderate/low NO2 [hazard ratio (HR) = 0.55; 95% CI: 0.42, 0.72 and 0.55; 95% CI: 0.41, 0.73, respectively] than with high NO2 exposure (HR = 0.77; 95% CI: 0.54, 1.11 and HR = 0.81; 95% CI: 0.55, 1.18, p-interaction = 0.09 and 0.02, respectively). Conclusions In general, exposure to high levels of traffic-related air pollution did not modify associations, indicating beneficial effects of physical activity on mortality. These novel findings require replication in other study populations. Citation Andersen ZJ, de Nazelle A, Mendez MA, Garcia-Aymerich J, Hertel O, Tjønneland A, Overvad K, Raaschou-Nielsen O, Nieuwenhuijsen MJ. 2015. A study of the combined effects of physical activity and air pollution on mortality in elderly urban residents: the Danish Diet, Cancer, and Health cohort. Environ Health Perspect 123:557–563;u2002http://dx.doi.org/10.1289/ehp.1408698