Barbara Hoffmann

Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE)

BACKGROUND Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations. METHODS This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 μm (PM10), less than 2·5 μm (PM2·5), and between 2·5 and 10 μm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses. FINDINGS The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03-1·45] per 10 μg/m(3)). For PM2·5 the HR was 1·18 (0·96-1·46) per 5 μg/m(3). The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10-2·08) and 1·55 (1·05-2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99-1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95-1·07] per 20 μg/m(3)) or traffic intensity on the nearest street (HR 1·00 [0·97-1·04] per 5000 vehicles per day). INTERPRETATION Particulate matter air pollution contributes to lung cancer incidence in Europe. FUNDING European Communitys Seventh Framework Programme.

Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project

BACKGROUND Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants. METHODS We used data from 22 European cohort studies, which created a total study population of 367,251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 μm (PM2.5), less than 10 μm (PM10), and between 10 μm and 2.5 μm (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buffer. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis. FINDINGS The total study population consisted of 367,251 participants who contributed 5,118,039 person-years at risk (average follow-up 13.9 years), of whom 29,076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 μg/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I(2) p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 μg/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 μg/m(3) (1.07, 1.01-1.13). INTERPRETATION Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value. FUNDING European Communitys Seventh Framework Program (FP7/2007-2011).

Residential Exposure to Traffic Is Associated With Coronary Atherosclerosis

Background— Long-term exposure to fine-particulate-matter (PM2.5) air pollution may accelerate the development and progression of atherosclerosis. We investigated the associations of long-term residential exposure to traffic and fine particulate matter with the degree of coronary atherosclerosis. Methods and Results— We used baseline data on 4494 participants (age 45 to 74 years) from the German Heinz Nixdorf Recall Study, a population-based, prospective cohort study that started in 2000. To assess exposure differences, distances between residences and major roads were calculated, and annual fine particulate matter concentrations, derived from a small-scale dispersion model, were assigned to each address. The main outcome was coronary artery calcification (CAC) assessed by electron-beam computed tomography. We evaluated the association between air pollution and CAC with logistic and linear regression analyses, controlling for individual level risk factors of coronary atherosclerosis. Compared with participants living >200 m away from a major road, participants living within 50, 51 to 100, and 101 to 200 m had odds ratios of 1.63 (95% CI, 1.14 to 2.33), 1.34 (95% CI, 1.00 to 1.79), and 1.08 (95% CI, 0.85 to 1.39), respectively, for a high CAC (CAC above the age- and gender-specific 75th percentile). A reduction in the distance between the residence and a major road by half was associated with a 7.0% (95% CI, 0.1 to 14.4) higher CAC. Fine particulate matter exposure was associated with CAC only in subjects who had not been working full-time for at least 5 years. Conclusions— Long-term residential exposure to high traffic is associated with the degree of coronary atherosclerosis.

Development of Land Use Regression Models for PM2.5, PM2.5 Absorbance, PM10 and PMcoarse in 20 European Study Areas; Results of the ESCAPE Project

Land Use Regression (LUR) models have been used increasingly for modeling small-scale spatial variation in air pollution concentrations and estimating individual exposure for participants of cohort studies. Within the ESCAPE project, concentrations of PM(2.5), PM(2.5) absorbance, PM(10), and PM(coarse) were measured in 20 European study areas at 20 sites per area. GIS-derived predictor variables (e.g., traffic intensity, population, and land-use) were evaluated to model spatial variation of annual average concentrations for each study area. The median model explained variance (R(2)) was 71% for PM(2.5) (range across study areas 35-94%). Model R(2) was higher for PM(2.5) absorbance (median 89%, range 56-97%) and lower for PM(coarse) (median 68%, range 32- 81%). Models included between two and five predictor variables, with various traffic indicators as the most common predictors. Lower R(2) was related to small concentration variability or limited availability of predictor variables, especially traffic intensity. Cross validation R(2) results were on average 8-11% lower than model R(2). Careful selection of monitoring sites, examination of influential observations and skewed variable distributions were essential for developing stable LUR models. The final LUR models are used to estimate air pollution concentrations at the home addresses of participants in the health studies involved in ESCAPE.

Expert position paper on air pollution and cardiovascular disease

Air pollution has wide-ranging and deleterious effects on human health and is a major issue for the global community. The Global Burden of Disease study has described the worldwide impact of air pollution with as many as 3.1 million of 52.8 million all-cause and all-age deaths being attributable to ambient air pollution in the year 2010.1 Moreover, ambient air pollution ranked ninth among the modifiable disease risk factors, being listed above other commonly recognized factors, such as low physical activity, a high-sodium diet, high cholesterol, and drug use. Finally, air pollution accounts for 3.1% of global disability-adjusted life years, an index that measures the time spent in states of reduced health.1 Although it is intuitive that air pollution is an important stimulus for the development and exacerbation of respiratory diseases, such as asthma, chronic obstructive pulmonary disease, and lung cancer, there is generally less public awareness of its substantial impact on cardiovascular disease. Historically, the 1952 Great Smog of London led to an increase in cardiovascular death as well as deaths due to respiratory disease. Subsequent studies in the 1990s, such as the Harvard Six Cities2 and American Cancer Society cohort studies,2,3 established an enduring positive association between long-term exposure to air pollution and total and cardiovascular mortality, mainly due to coronary artery disease.4 In Europe, the first study that supported this association between long-term exposure and mortality was the Netherlands Cohort Study on Diet and Cancer.5 Associations with cardiovascular morbidity and mortality are also seen with short-term (e.g. day-to-day fluctuations) pollutant exposures of residents in large urban areas worldwide, including the United States of America6 …

Long term exposure to ambient air pollution and incidence of acute coronary events: prospective cohort study and meta-analysis in 11 European cohorts from the ESCAPE Project

Objectives To study the effect of long term exposure to airborne pollutants on the incidence of acute coronary events in 11 cohorts participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Design Prospective cohort studies and meta-analysis of the results. Setting Cohorts in Finland, Sweden, Denmark, Germany, and Italy. Participants 100 166 people were enrolled from 1997 to 2007 and followed for an average of 11.5 years. Participants were free from previous coronary events at baseline. Main outcome measures Modelled concentrations of particulate matter <2.5 μm (PM2.5), 2.5-10 μm (PMcoarse), and <10 μm (PM10) in aerodynamic diameter, soot (PM2.5 absorbance), nitrogen oxides, and traffic exposure at the home address based on measurements of air pollution conducted in 2008-12. Cohort specific hazard ratios for incidence of acute coronary events (myocardial infarction and unstable angina) per fixed increments of the pollutants with adjustment for sociodemographic and lifestyle risk factors, and pooled random effects meta-analytic hazard ratios. Results 5157 participants experienced incident events. A 5 μg/m3 increase in estimated annual mean PM2.5 was associated with a 13% increased risk of coronary events (hazard ratio 1.13, 95% confidence interval 0.98 to 1.30), and a 10 μg/m3 increase in estimated annual mean PM10 was associated with a 12% increased risk of coronary events (1.12, 1.01 to 1.25) with no evidence of heterogeneity between cohorts. Positive associations were detected below the current annual European limit value of 25 μg/m3 for PM2.5 (1.18, 1.01 to 1.39, for 5 μg/m3 increase in PM2.5) and below 40 μg/m3 for PM10 (1.12, 1.00 to 1.27, for 10 μg/m3 increase in PM10). Positive but non-significant associations were found with other pollutants. Conclusions Long term exposure to particulate matter is associated with incidence of coronary events, and this association persists at levels of exposure below the current European limit values.

Air Pollution Exposure and Lung Function in Children: The ESCAPE Project.

Background: There is evidence for adverse effects of outdoor air pollution on lung function of children. Quantitative summaries of the effects of air pollution on lung function, however, are lacking due to large differences among studies. Objectives: We aimed to study the association between residential exposure to air pollution and lung function in five European birth cohorts with a standardized exposure assessment following a common protocol. Methods: As part of the European Study of Cohorts for Air Pollution Effects (ESCAPE) we analyzed data from birth cohort studies situated in Germany, Sweden, the Netherlands, and the United Kingdom that measured lung function at 6–8 years of age (n = 5,921). Annual average exposure to air pollution [nitrogen oxides (NO2, NOx), mass concentrations of particulate matter with diameters < 2.5, < 10, and 2.5–10 μm (PM2.5, PM10, and PMcoarse), and PM2.5 absorbance] at the birth address and current address was estimated by land-use regression models. Associations of lung function with estimated air pollution levels and traffic indicators were estimated for each cohort using linear regression analysis, and then combined by random effects meta-analysis. Results: Estimated levels of NO2, NOx, PM2.5 absorbance, and PM2.5 at the current address, but not at the birth address, were associated with small decreases in lung function. For example, changes in forced expiratory volume in 1 sec (FEV1) ranged from –0.86% (95% CI: –1.48, –0.24%) for a 20-μg/m3 increase in NOx to –1.77% (95% CI: –3.34, –0.18%) for a 5-μg/m3 increase in PM2.5. Conclusions: Exposure to air pollution may result in reduced lung function in schoolchildren. Citation: Gehring U, Gruzieva O, Agius RM, Beelen R, Custovic A, Cyrys J, Eeftens M, Flexeder C, Fuertes E, Heinrich J, Hoffmann B, de Jongste JC, Kerkhof M, Klümper C, Korek M, Mölter A, Schultz ES, Simpson A, Sugiri D, Svartengren M, von Berg A, Wijga AH, Pershagen G, Brunekreef B. 2013. Air pollution exposure and lung function in children: the ESCAPE project. Environ Health Perspect 121:1357–1364; http://dx.doi.org/10.1289/ehp.1306770

Chronic Residential Exposure to Particulate Matter Air Pollution and Systemic Inflammatory Markers

Background Long-term exposure to urban air pollution may accelerate atherogenesis, but mechanisms are still unclear. The induction of a low-grade systemic inflammatory state is a plausible mechanistic pathway. Objectives: We analyzed the association of residential long-term exposure to particulate matter (PM) and high traffic with systemic inflammatory markers. Methods We used baseline data from the German Heinz Nixdorf Recall Study, a population-based, prospective cohort study of 4,814 participants that started in 2000. Fine PM [aerodynamic diameter ≤ 2.5 μm (PM2.5)] exposure based on a small-scale dispersion and chemistry transport model was assigned to each home address. We calculated distances between residences and major roads. Long-term exposure to air pollution (annual PM2.5 and distance to high traffic) and concentration of inflammatory markers [high-sensitivity C-reactive protein (hs-CRP) and fibrinogen] on the day of the baseline visit were analyzed with sex-stratified multiple linear regression, controlling for individual-level risk factors. Results In the adjusted analysis, a cross-sectional exposure difference of 3.91 μg/m3 in PM2.5 (interdecile range) was associated with increases in hs-CRP of 23.9% [95% confidence interval (CI), 4.1 to 47.4%] and fibrinogen of 3.9% (95% CI, 0.3 to 7.7%) in men, whereas we found no association in women. Chronic traffic exposure was not associated with inflammatory markers. Short-term exposures to air pollutants and temperature did not influence the results markedly. Conclusions Our study indicates that long-term residential exposure to high levels of PM2.5 is associated with systemic inflammatory markers in men. This might provide a link between air pollution and coronary atherosclerosis.

Distribution and prevalence of reflux in the superficial and deep venous system in the general population--results from the Bonn Vein Study, Germany.

OBJECTIVE Venous diseases are among the most frequent diseases in the general population of industrialized countries. The aim of this article is to investigate the population-based prevalence of pathologic reflux in superficial and deep leg veins, taking into account factors as gender, age, and clinical classification of venous disease. METHODS In a population-based cross-sectional study, 3072 subjects aged 18 to 79 years (1350 male, 1722 female, response 59%) were enrolled from October 2000 through November 2001. A standardized interview was conducted to document phlebological history and clinical examinations including duplex sonography of selected superficial and deep leg veins. Pathological reflux was defined as being >500 ms. All participants where classified according to the CEAP classification. RESULTS Using the highest clinical stage per participant, 9.6% where classified C0, 59.0% C1, 14.3% C2, 13.5% C3, 2.9% C4, and 0.7% C5-C6. A pathological reflux (>500 ms) was found in 35.3% (95% confidence interval [CI] 33.6-37.1) of subjects with 21.0% (95% CI 19.5-22.5) showing reflux in at least one superficial vein and 20.0% (95% CI 18.6-21.5) showing reflux in at least one deep vein. We observed significantly higher reflux prevalence for the superficial veins in women while for the deep veins reflux prevalence were significantly higher in men. Prevalence of reflux in the superficial veins markedly increases with age. In the deep venous system, no clear changes in reflux prevalence with age can be observed. For superficial veins, reflux prevalence is markedly higher with higher C-stages. For the deep veins, the proportion of refluxes is relatively constant in stages C0-C3 with a distinct increase of prevalence from stage C4 onward. CONCLUSION Our results show a high prevalence of reflux both for the superficial and the deep venous system. Reflux prevalence is associated with gender, age, and the clinical stage as measured by the CEAP classification. Further longitudinal studies are needed to clarify the relevance of pathological reflux in subjects with otherwise healthy veins.

Association between ambient air pollution and diabetes mellitus in Europe and North America: systematic review and meta-analysis.

Background Air pollution is hypothesized to be a risk factor for diabetes. Epidemiological evidence is inconsistent and has not been systematically evaluated. Objectives We systematically reviewed epidemiological evidence on the association between air pollution and diabetes, and synthesized results of studies on type 2 diabetes mellitus (T2DM). Methods We systematically searched electronic literature databases (last search, 29 April 2014) for studies reporting the association between air pollution (particle concentration or traffic exposure) and diabetes (type 1, type 2, or gestational). We systematically evaluated risk of bias and role of potential confounders in all studies. We synthesized reported associations with T2DM in meta-analyses using random-effects models and conducted various sensitivity analyses. Results We included 13 studies (8 on T2DM, 2 on type 1, 3 on gestational diabetes), all conducted in Europe or North America. Five studies were longitudinal, 5 cross-sectional, 2 case–control, and 1 ecologic. Risk of bias, air pollution assessment, and confounder control varied across studies. Dose–response effects were not reported. Meta-analyses of 3 studies on PM2.5 (particulate matter ≤ 2.5 μm in diameter) and 4 studies on NO2 (nitrogen dioxide) showed increased risk of T2DM by 8–10% per 10-μg/m3 increase in exposure [PM2.5: 1.10 (95% CI: 1.02, 1.18); NO2: 1.08 (95% CI: 1.00, 1.17)]. Associations were stronger in females. Sensitivity analyses showed similar results. Conclusion Existing evidence indicates a positive association of air pollution and T2DM risk, albeit there is high risk of bias. High-quality studies assessing dose–response effects are needed. Research should be expanded to developing countries where outdoor and indoor air pollution are high. Citation Eze IC, Hemkens LG, Bucher HC, Hoffmann B, Schindler C, Künzli N, Schilowski T, Probst-Hensch NM. 2015. Association between ambient air pollution and diabetes mellitus in Europe and North America: systematic review and meta-analysis. Environ Health Perspect 123:381–389; http://dx.doi.org/10.1289/ehp.1307823