Johan Nilsson Sommar

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.

Arterial Blood Pressure and Long-Term Exposure to Traffic-Related Air Pollution: An Analysis in the European Study of Cohorts for Air Pollution Effects (ESCAPE)

Background: Long-term exposure to air pollution has been hypothesized to elevate arterial blood pressure (BP). The existing evidence is scarce and country specific. Objectives: We investigated the cross-sectional association of long-term traffic-related air pollution with BP and prevalent hypertension in European populations. Methods: We analyzed 15 population-based cohorts, participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE). We modeled residential exposure to particulate matter and nitrogen oxides with land use regression using a uniform protocol. We assessed traffic exposure with traffic indicator variables. We analyzed systolic and diastolic BP in participants medicated and nonmedicated with BP-lowering medication (BPLM) separately, adjusting for personal and area-level risk factors and environmental noise. Prevalent hypertension was defined as ≥ 140 mmHg systolic BP, or ≥ 90 mmHg diastolic BP, or intake of BPLM. We combined cohort-specific results using random-effects meta-analysis. Results: In the main meta-analysis of 113,926 participants, traffic load on major roads within 100 m of the residence was associated with increased systolic and diastolic BP in nonmedicated participants [0.35 mmHg (95% CI: 0.02, 0.68) and 0.22 mmHg (95% CI: 0.04, 0.40) per 4,000,000 vehicles × m/day, respectively]. The estimated odds ratio (OR) for prevalent hypertension was 1.05 (95% CI: 0.99, 1.11) per 4,000,000 vehicles × m/day. Modeled air pollutants and BP were not clearly associated. Conclusions: In this first comprehensive meta-analysis of European population-based cohorts, we observed a weak positive association of high residential traffic exposure with BP in nonmedicated participants, and an elevated OR for prevalent hypertension. The relationship of modeled air pollutants with BP was inconsistent. Citation: Fuks KB, Weinmayr G, Foraster M, Dratva J, Hampel R, Houthuijs D, Oftedal B, Oudin A, Panasevich S, Penell J, Sommar JN, Sørensen M, Tittanen P, Wolf K, Xun WW, Aguilera I, Basagaña X, Beelen R, Bots ML, Brunekreef B, Bueno-de-Mesquita HB, Caracciolo B, Cirach M, de Faire U, de Nazelle A, Eeftens M, Elosua R, Erbel R, Forsberg B, Fratiglioni L, Gaspoz JM, Hilding A, Jula A, Korek M, Krämer U, Künzli N, Lanki T, Leander K, Magnusson PK, Marrugat J, Nieuwenhuijsen MJ, Östenson CG, Pedersen NL, Pershagen G, Phuleria HC, Probst-Hensch NM, Raaschou-Nielsen O, Schaffner E, Schikowski T, Schindler C, Schwarze PE, Søgaard AJ, Sugiri D, Swart WJ, Tsai MY, Turunen AW, Vineis P, Peters A, Hoffmann B. 2014. Arterial blood pressure and long-term exposure to traffic-related air pollution: an analysis in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Environ Health Perspect 122:896–905; http://dx.doi.org/10.1289/ehp.1307725

End-stage renal disease and low level exposure to lead, cadmium and mercury; a population-based, prospective nested case-referent study in Sweden.

BackgroundCadmium (Cd), lead (Pb), and mercury (Hg) cause toxicological renal effects, but the clinical relevance at low-level exposures in general populations is unclear. The objective of this study is to assess the risk of developing end-stage renal disease in relation to Cd, Pb, and Hg exposure.MethodsA total of 118 cases who later in life developed end-stage renal disease, and 378 matched (sex, age, area, and time of blood sampling) referents were identified among participants in two population-based prospective cohorts (130,000 individuals). Cd, Pb, and Hg concentrations were determined in prospectively collected samples.ResultsErythrocyte lead was associated with an increased risk of developing end-stage renal disease (mean in cases 76 μg/L; odds ratio (OR) 1.54 for an interquartile range increase, 95% confidence interval (CI) 1.18-2.00), while erythrocyte mercury was negatively associated (2.4 μg/L; OR 0.75 for an interquartile range increase, CI 0.56-0.99). For erythrocyte cadmium, the OR of developing end-stage renal disease was 1.15 for an interquartile range increase (CI 0.99-1.34; mean Ery-Cd among cases: 1.3 μg/L). The associations for erythrocyte lead and erythrocyte mercury, but not for erythrocyte cadmium, remained after adjusting for the other two metals, smoking, BMI, diabetes, and hypertension. Gender-specific analyses showed that men carried almost all of the erythrocyte lead and erythrocyte cadmium associated risks.ConclusionsErythrocyte lead is associated with end-stage renal disease but further studies are needed to evaluate causality. Gender-specific analyses suggest potential differences in susceptibility or in exposure biomarker reliability.

Lead concentration in plasma as a biomarker of exposure and risk, and modification of toxicity by delta-aminolevulinic acid dehydratase gene polymorphism

UNLABELLED Blood lead concentration (B-Pb), the main biomarker of lead exposure and risk, is curvi-linearily related to exposure. We assessed plasma lead (P-Pb) as a marker for both lead exposure and toxic effects. We examined claims that δ-aminolevulinic acid dehydratase genotype (ALAD) can modify lead toxicity. In 290 lead-exposed and 91 unexposed Chinese workers, we determined P-Pb, B-Pb, urinary lead (U-Pb), ALAD polymorphism (rs1800435, ALAD1/2; TaqMan assay), and also toxic effects on heme synthesis (blood zinc protoporphyrin and hemoglobin, urinary δ-aminolevulic acid), on the kidneys (urinary albumin, β2-microglobulin and N-acetyl-β-d-glucosaminidase) and on the peripheral nervous system (sensory and motor conduction velocities). In exposed workers, median P-Pb was 4.10 (range 0.35-27)μg/L, B-Pb 401 (110-950)μg/L, and U-Pb 188 (22-590)μg/g creatinine. P-Pb had a higher ratio between exposed and unexposed workers (median 39, range 18-110) than B-Pb (19, 15-36; p<0.001) and U-Pb (28, 15-36; p<0.001). All three biomarkers were associated with all toxic effects (P-Pb: rS=-0.10 to 0.79; B-Pb: rS=-0.08 to 0.75; all p<0.05). In the exposed workers, B-Pb and U-Pb were significantly higher (p=0.04) in ALAD2 carriers (7% in the exposed population) than in ALAD1 homozygotes. P-Pb values were similar; ALAD1 homozygotes suffered higher kidney toxicity at the same P-Pb. CONCLUSIONS (i) P-Pb has advantages over B-Pb as a biomarker of high Pb exposure, but it was not significantly better as an index of risk of toxicity. (ii) The ALAD genotype modifies toxicokinetics and toxicodynamics.

Investigation of lead concentrations in whole blood, plasma and urine as biomarkers for biological monitoring of lead exposure

Lead in blood is a major concept in biomonitoring of exposure but investigations of its alternatives are scarce. The aim of the study was to describe different lead biomarkers’ variances, day-to-day and between individuals, estimating their fraction of the total variance. Repeated sampling of whole blood, plasma and urine were conducted for 48 lead-exposed men and 20 individuals under normal environmental lead exposure, in total 603 measurements. For lead workers, the fraction of the total variance attributed to differences between individuals was 91% for whole-blood lead (geometric mean 227 μg/l; geometric standard deviation (GSD): 1.55 μg/l); plasma 78% (0.57 μg/l; GSD: 1.84 μg/l); density-adjusted urine 82%; and unadjusted urine 75% (23.7 μg/l; GSD: 2.48 μg/l). For the individuals under normal lead exposure, the corresponding fractions were 95% of the total variance for whole blood (20.7 μg/l; GSD: 8.6 μg/l), 15% for plasma (0.09 μg/l; GSD: 0.04 μg/l), 87% for creatinine-adjusted urine and 34% for unadjusted (10.8 μg/l; GSD: 6.7 μg/l). Lead concentration in whole blood is the biomarker with the best ability to discriminate between individuals with different mean concentration. Urinary and plasma lead also performed acceptably in lead workers, but at low exposures plasma lead was too imprecise. Urinary adjustments appear not to increase the between-individual fraction of the total variance among lead workers but among those with normal lead exposure.

Outdoor air pollution and risk for kidney parenchyma cancer in 14 European cohorts

Several studies have indicated weakly increased risk for kidney cancer among occupational groups exposed to gasoline vapors, engine exhaust, polycyclic aromatic hydrocarbons and other air pollutants, although not consistently. It was the aim to investigate possible associations between outdoor air pollution at the residence and the incidence of kidney parenchyma cancer in the general population. We used data from 14 European cohorts from the ESCAPE study. We geocoded and assessed air pollution concentrations at baseline addresses by land‐use regression models for particulate matter (PM10, PM2.5, PMcoarse, PM2.5 absorbance (soot)) and nitrogen oxides (NO2, NOx), and collected data on traffic. We used Cox regression models with adjustment for potential confounders for cohort‐specific analyses and random effects models for meta‐analyses to calculate summary hazard ratios (HRs). The 289,002 cohort members contributed 4,111,908 person‐years at risk. During follow‐up (mean 14.2 years) 697 incident cancers of the kidney parenchyma were diagnosed. The meta‐analyses showed higher HRs in association with higher PM concentration, e.g. HR = 1.57 (95%CI: 0.81–3.01) per 5 μg/m3 PM2.5 and HR = 1.36 (95%CI: 0.84–2.19) per 10−5m−1 PM2.5 absorbance, albeit never statistically significant. The HRs in association with nitrogen oxides and traffic density on the nearest street were slightly above one. Sensitivity analyses among participants who did not change residence during follow‐up showed stronger associations, but none were statistically significant. Our study provides suggestive evidence that exposure to outdoor PM at the residence may be associated with higher risk for kidney parenchyma cancer; the results should be interpreted cautiously as associations may be due to chance.

Simultaneously elevated exhaled nitric oxide and serum-eosinophil cationic protein relate to recent asthma events in asthmatics in a cross-sectional population-based study

We have reported that increased fraction of exhaled nitric oxide (FeNO), a measure of TH2‐driven airway inflammation, and blood eosinophil count, a marker of systemic eosinophil inflammation, correlated with asthma attacks in a population‐based study.

Impacts on air pollution and health by changing commuting from car to bicycle

Our study is based on individual data on peoples home and work addresses, as well as their age, sex and physical capacity, in order to establish realistic bicycle-travel distances. A transport model is used to single out data on commuting preferences in the County Stockholm. Our analysis shows there is a very large potential for reducing emissions and exposure if all car drivers living within a distance corresponding to a maximum of a 30min bicycle ride to work would change to commuting by bicycle. It would result in >111,000 new cyclists, corresponding to an increase of 209% compared to the current situation. Mean population exposure would be reduced by about 7% for both NOx and black carbon (BC) in the most densely populated area of the inner city of Stockholm. Applying a relative risk for NOx of 8% decrease in all-cause mortality associated with a 10μgm-3 decrease in NOx, this corresponds to >449 (95% CI: 340-558) years of life saved annually for the Stockholm county area with 2.1 million inhabitants. This is more than double the effect of the reduced mortality estimated for the introduction of congestion charge in Stockholm in 2006. Using NO2 or BC as indicator of health impacts, we obtain 395 (95% CI: 172-617) and 185 (95% CI: 158-209) years of life saved for the population, respectively. The calculated exposure of BC and its corresponding impacts on mortality are likely underestimated. With this in mind the estimates using NOx, NO2 and BC show quite similar health impacts considering the 95% confidence intervals.

Quality of life in relation to the traffic pollution indicators NO2 and NOx: results from the Swedish GA2LEN survey

Background Asthma is a chronic disease that may affect daily activities and quality of life. Asthmatics have higher incidence of chronic rhinosinusitis (CRS) and asthma is associated with sinonasal inflammation and nasal symptoms, that all impair quality of life. Worsening of asthma has been found associated with levels of nitrogen dioxide as traffic indicator. Aims The aim of the study was to evaluate the impact of traffic pollution indicated by nitrogen oxides (NO2 and NOx) on quality of life in asthmatic persons, individuals with CRS and controls. Methods Within the Swedish Ga2len (Global Allergy and Asthma European Network), 605 asthmatics with and without CRS, 110 individuals with CRS only and 226 controls from four cities were surveyed. The mini Asthma Quality of life Questionnaire (mAQLQ) and the Euro Quality of Life (EQ-5D) health questionnaire were used. Air pollution concentrations at the home address were modelled using dispersion models. Results Levels of NO2 (geometric mean 10.1 μg/m3 (95% CI 9.80 to 10.5) and NOx (12.1 μg/m3, 11.7 to 12.6) were similar among conditions (controls, asthmatics, individuals with CRS and asthmatics with CRS). The mAQLQ overall score was not found associated with levels of NO2 or NOx, with or without adjustments, and neither was scores within each of the four domains of mAQLQ: symptoms, activity limitations, emotional functions and effects of environmental stimuli. The mean EQ-5D index value, based on the five dimensions mobility, self-care, usual activities, pain/discomfort and anxiety depression, was also found unrelated to NO2 and NOx. Conclusions At moderate exposure levels traffic pollution appears not to affect quality of life.

Important non-disease-related determinants of exhaled nitric oxide levels in mild asthma – results from the Swedish GA2LEN study

Fractional exhaled nitric oxide (FeNO) has a potential clinical role in asthma management. Constitutive factors such as age, height and gender, as well as individual characteristics, such as IgE sensitization and smoking, affect the levels of FeNO in population‐based studies. However, their effect on FeNO in subjects with asthma has been scarcely studied.