| 1. |
- Beelen, Rob, et al.
(författare)
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Effects of long-term exposure to air pollution on natural-cause mortality : an analysis of 22 European cohorts within the multicentre ESCAPE project
- 2014
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 383:9919, s. 785-795
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Tidskriftsartikel (refereegranskat)abstract
- 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 mu m (PM2.5), less than 10 mu m (PM10), and between 10 mu m and 2.5 mu m (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 buff er. 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 mu g/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 mu g/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 mu g/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.
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| 2. |
- Beelen, Rob, et al.
(författare)
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Long-term Exposure to Air Pollution and Cardiovascular Mortality An Analysis of 22 European Cohorts
- 2014
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Ingår i: Epidemiology. - : Lippincott Williams & Wilkins. - 1044-3983 .- 1531-5487. ; 25:3, s. 368-378
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Tidskriftsartikel (refereegranskat)abstract
- Background: Air pollution has been associated with cardiovascular mortality, but it remains unclear as to whether specific pollutants are related to specific cardiovascular causes of death. Within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE), we investigated the associations of long-term exposure to several air pollutants with all cardiovascular disease (CVD) mortality, as well as with specific cardiovascular causes of death. Methods: Data from 22 European cohort studies were used. Using a standardized protocol, study area-specific air pollution exposure at the residential address was characterized as annual average concentrations of the following: nitrogen oxides (NO2 and NOx); particles with diameters of less than 2.5 mu m (PM2.5), less than 10 mu m (PM10), and 10 mu m to 2.5 mu m (PMcoarse); PM2.5 absorbance estimated by land-use regression models; and traffic indicators. We applied cohort-specific Cox proportional hazards models using a standardized protocol. Random-effects meta-analysis was used to obtain pooled effect estimates. Results: The total study population consisted of 367,383 participants, with 9994 deaths from CVD (including 4,992 from ischemic heart disease, 2264 from myocardial infarction, and 2484 from cerebrovascular disease). All hazard ratios were approximately 1.0, except for particle mass and cerebrovascular disease mortality; for PM2.5, the hazard ratio was 1.21 (95% confidence interval = 0.87-1.69) per 5 mu g/m(3) and for PM10, 1.22 (0.91-1.63) per 10 mu g/m(3). Conclusion: In a joint analysis of data from 22 European cohorts, most hazard ratios for the association of air pollutants with mortality from overall CVD and with specific CVDs were approximately 1.0, with the exception of particulate mass and cerebrovascular disease mortality for which there was suggestive evidence for an association.
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| 3. |
- Beelen, Rob, et al.
(författare)
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Natural-Cause Mortality and Long-Term Exposure to Particle Components : An Analysis of 19 European Cohorts within the Multi-Center ESCAPE Project
- 2015
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 525-533
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Forskningsöversikt (refereegranskat)abstract
- 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 mu m (PM2.5) and <= 10 mu m (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 200ng/m(3)). 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.
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| 4. |
- Cai, Yutong, et al.
(författare)
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Cross-sectional associations between air pollution and chronic bronchitis : an ESCAPE meta-analysis across five cohorts
- 2014
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 69:11, s. 1005-1014
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study aimed to assess associations of outdoor air pollution on prevalence of chronic bronchitis symptoms in adults in five cohort studies (Asthma-E3N, ECRHS, NSHD, SALIA, SAPALDIA) participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE) project.METHODS: Annual average particulate matter (PM10, PM2.5, PMabsorbance, PMcoarse), NO2, nitrogen oxides (NOx) and road traffic measures modelled from ESCAPE measurement campaigns 2008-2011 were assigned to home address at most recent assessments (1998-2011). Symptoms examined were chronic bronchitis (cough and phlegm for ≥3 months of the year for ≥2 years), chronic cough (with/without phlegm) and chronic phlegm (with/without cough). Cohort-specific cross-sectional multivariable logistic regression analyses were conducted using common confounder sets (age, sex, smoking, interview season, education), followed by meta-analysis.RESULTS: 15 279 and 10 537 participants respectively were included in the main NO2 and PM analyses at assessments in 1998-2011. Overall, there were no statistically significant associations with any air pollutant or traffic exposure. Sensitivity analyses including in asthmatics only, females only or using back-extrapolated NO2 and PM10 for assessments in 1985-2002 (ECRHS, NSHD, SALIA, SAPALDIA) did not alter conclusions. In never-smokers, all associations were positive, but reached statistical significance only for chronic phlegm with PMcoarse OR 1.31 (1.05 to 1.64) per 5 µg/m(3) increase and PM10 with similar effect size. Sensitivity analyses of older cohorts showed increased risk of chronic cough with PM2.5abs (black carbon) exposures.CONCLUSIONS: Results do not show consistent associations between chronic bronchitis symptoms and current traffic-related air pollution in adult European populations.
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| 5. |
- Gehring, Ulrike, et al.
(författare)
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Air Pollution Exposure and Lung Function in Children : The ESCAPE Project
- 2013
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 121:11-12, s. 1357-1364
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Tidskriftsartikel (refereegranskat)abstract
- 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 mu m (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-mu g/m(3) increase in NOx to -1.77% (95% CI: -3.34, -0.18%) for a 5-mu g/m(3) increase in PM2.5. CONCLUSIONS: Exposure to air pollution may result in reduced lung function in schoolchildren.
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| 6. |
- Hugentobler, Katharina Gloria, et al.
(författare)
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Lipid Composition Affects the Efficiency in the Functional Reconstitution of the Cytochrome c Oxidase
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:19
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Tidskriftsartikel (refereegranskat)abstract
- The transmembrane protein cytochrome c oxidase (CcO) is the terminal oxidase in the respiratory chain of many aerobic organisms and catalyzes the reduction of dioxygen to water. This process maintains an electrochemical proton gradient across the membrane hosting the oxidase. CcO is a well-established model enzyme in bioenergetics to study the proton-coupled electron transfer reactions and protonation dynamics involved in these processes. Its catalytic mechanism is subject to ongoing intense research. Previous research, however, was mainly focused on the turnover of oxygen and electrons in CcO, while studies reporting proton turnover rates of CcO, that is the rate of proton uptake by the enzyme, are scarce. Here, we reconstitute CcO from R. sphaeroides into liposomes containing a pH sensitive dye and probe changes of the pH value inside single proteoliposomes using fluorescence microscopy. CcO proton turnover rates are quantified at the single-enzyme level. In addition, we recorded the distribution of the number of functionally reconstituted CcOs across the proteoliposome population. Studies are performed using proteoliposomes made of native lipid sources, such as a crude extract of soybean lipids and the polar lipid extract of E. coli, as well as purified lipid fractions, such as phosphatidylcholine extracted from soybean lipids. It is shown that these lipid compositions have only minor effects on the CcO proton turnover rate, but can have a strong impact on the reconstitution efficiency of functionally active CcOs. In particular, our experiments indicate that efficient functional reconstitution of CcO is strongly promoted by the addition of anionic lipids like phosphatidylglycerol and cardiolipin.
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| 7. |
- Jacquemin, Benedicte, et al.
(författare)
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Ambient Air Pollution and Adult Asthma Incidence in Six European Cohorts (ESCAPE)
- 2015
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 613-621
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Short-term exposure to air pollution has adverse effects among patients with asthma, but whether long-term exposure to air pollution is a cause of adult-onset asthma is unclear. OBJECTIVE: We aimed to investigate the association between air pollution and adult onset asthma. METHODS: Asthma incidence was prospectively assessed in six European cohorts. Exposures studied were annual average concentrations at home addresses for nitrogen oxides assessed for 23,704 participants (including 1,257 incident cases) and particulate matter (PM) assessed for 17,909 participants through ESCAPE land-use regression models and traffic exposure indicators. Meta-analyses of cohort-specific logistic regression on asthma incidence were performed. Models were adjusted for age, sex, overweight, education, and smoking and included city/area within each cohort as a random effect. RESULTS: In this longitudinal analysis, asthma incidence was positively, but not significantly, associated with all exposure metrics, except for PMcoarse. Positive associations of borderline significance were observed for nitrogen dioxide [adjusted odds ratio (OR) = 1.10; 95% CI: 0.99, 1.21 per 10 mu g/m(3); p = 0.10] and nitrogen oxides (adjusted OR = 1.04; 95% CI: 0.99, 1.08 per 20 mu g/m(3); p = 0.08). Nonsignificant positive associations were estimated for PM10 (adjusted OR = 1.04; 95% CI: 0.88, 1.23 per 10 mu g/m(3)), PM2.5 (adjusted OR = 1.04; 95% CI: 0.88, 1.23 per 5 mu g/m(3)), PM2.5absorbance (adjusted OR = 1.06; 95% CI: 0.95, 1.19 per 10(-5)/m), traffic load (adjusted OR = 1.10; 95% CI: 0.93, 1.30 per 4 million vehicles x meters/day on major roads in a 100-m buffer), and traffic intensity (adjusted OR = 1.10; 95% CI: 0.93, 1.30 per 5,000 vehicles/day on the nearest road). A nonsignificant negative association was estimated for PMcoarse (adjusted OR = 0.98; 95% CI: 0.87, 1.14 per 5 mu g/m(3)). CONCLUSIONS: Results suggest a deleterious effect of ambient air pollution on asthma incidence in adults. Further research with improved personal-level exposure assessment (vs. residential exposure assessment only) and phenotypic characterization is needed.
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| 8. |
- Mathey, Carina M, et al.
(författare)
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Molecular Genetic Screening in Patients With ACE Inhibitor/Angiotensin Receptor Blocker-Induced Angioedema to Explore the Role of Hereditary Angioedema Genes
- 2022
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Ingår i: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Angioedema is a relatively rare but potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As with hereditary forms of angioedema (HAE), this adverse reaction is mediated by bradykinin. Research suggests that ACEi/ARB-induced angioedema has a multifactorial etiology. In addition, recent case reports suggest that some ACEi/ARB-induced angioedema patients may carry pathogenic HAE variants. The aim of the present study was to investigate the possible association between ACEi/ARB-induced angioedema and HAE genes via systematic molecular genetic screening in a large cohort of ACEi/ARB-induced angioedema cases. Targeted re-sequencing of five HAE-associated genes (SERPING1, F12, PLG, ANGPT1, and KNG1) was performed in 212 ACEi/ARB-induced angioedema patients recruited in Germany/Austria, Sweden, and Denmark, and in 352 controls from a German cohort. Among patients, none of the identified variants represented a known pathogenic variant for HAE. Moreover, no significant association with ACEi/ARB-induced angioedema was found for any of the identified common [minor allele frequency (MAF) >5%] or rare (MAF < 5%) variants. However, several non-significant trends suggestive of possible protective effects were observed. The lowest p-value for an individual variant was found in PLG (rs4252129, p.R523W, p = 0.057, p.adjust > 0.999, Fisher's exact test). Variant p.R523W was found exclusively in controls and has previously been associated with decreased levels of plasminogen, a precursor of plasmin which is part of a pathway directly involved in bradykinin production. In addition, rare, potentially functional variants (MAF < 5%, Phred-scaled combined annotation dependent depletion score >10) showed a nominally significant enrichment in controls both: 1) across all five genes; and 2) in the F12 gene alone. However, these results did not withstand correction for multiple testing. In conclusion, our results suggest that HAE-associated mutations are, at best, a rare cause of ACEi/ARB-induced angioedema. Furthermore, we were unable to identify a significant association between ACEi/ARB-induced angioedema and other variants in the investigated genes. Further studies with larger sample sizes are warranted to draw more definite conclusions concerning variants with limited effect sizes, including protective variants.
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| 9. |
- Wang, Meng, et al.
(författare)
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Long-term exposure to elemental constituents of particulate matter and cardiovascular mortality in 19 European cohorts : Results from the ESCAPE and TRANSPHORM projects
- 2014
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 66, s. 97-106
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Tidskriftsartikel (refereegranskat)abstract
- Background: Associations between long-term exposure to ambient particulate matter (PM) and cardiovascular (CVD) mortality have been widely recognized. However, health effects of long-term exposure to constituents of PM on total CVD mortality have been explored in a single study only. Aims: The aim of this study was to examine the association of PM composition with cardiovascular mortality. Methods: We used data from 19 European ongoing cohorts within the framework of the ESCAPE (European Study of Cohorts for Air Pollution Effects) and TRANSPHORM (Transport related Air Pollution and Health impacts Integrated Methodologies for Assessing Particulate Matter) projects. Residential annual average exposure to elemental constituents within particle matter smaller than 2.5 and 10 pm (PM2.5 and PM10) was estimated using Land Use Regression models. Eight elements representing major sources were selected a priori (copper, iron, potassium, nickel, sulfur, silicon, vanadium and zinc). Cohort-specific analyses were conducted using Cox proportional hazards models with a standardized protocol. Random-effects metaanalysis was used to calculate combined effect estimates. Results: The total population consisted of 322,291 participants, with 9545 CVD deaths. We found no statistically significant associations between any of the elemental constituents in PM2.5 or PM10 and CVD mortality in the pooled analysis. Most of the hazard ratios (HRs) were close to unity, e.g. for PM10 Fe the combined HR was 0.96 (0.84-1.09). Elevated combined HRs were found for PM2.5 Si (1.17, 95% Cl: 0.93-1.47), and S in PM2.5 (1.08,95% Cl: 0.95-1.22) and PM10 (1.09,95% Cl: 0.90-132). Conclusion: In a joint analysis of 19 European cohorts, we found no statistically significant association between long-term exposure to 8 elemental constituents of particles and total cardiovascular mortality.
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| 10. |
- Wang, Meng, et al.
(författare)
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Performance of multi-city land use regression models for nitrogen dioxide and fine particles
- 2014
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Ingår i: Journal of Environmental Health Perspectives. - : Public Health Services, US Dept of Health and Human Services. - 0091-6765 .- 1552-9924. ; 122:8, s. 843-849
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Land use regression (LUR) models have been developed mostly to explain intraurban variations in air pollution based on often small local monitoring campaigns. Transferability of LUR models from city to city has been investigated, but little is known about the performance of models based on large numbers of monitoring sites covering a large area.OBJECTIVES: We aimed to develop European and regional LUR models and to examine their transferability to areas not used for model development.METHODS: We evaluated LUR models for nitrogen dioxide (NO2) and particulate matter (PM; PM2.5, PM2.5 absorbance) by combining standardized measurement data from 17 (PM) and 23 (NO2) ESCAPE (European Study of Cohorts for Air Pollution Effects) study areas across 14 European countries for PM and NO2. Models were evaluated with cross-validation (CV) and hold-out validation (HV). We investigated the transferability of the models by successively excluding each study area from model building.RESULTS: The European model explained 56% of the concentration variability across all sites for NO2, 86% for PM2.5, and 70% for PM2.5 absorbance. The HV R2s were only slightly lower than the model R2 (NO2, 54%; PM2.5, 80%; PM2.5 absorbance, 70%). The European NO2, PM2.5, and PM2.5 absorbance models explained a median of 59%, 48%, and 70% of within-area variability in individual areas. The transferred models predicted a modest-to-large fraction of variability in areas that were excluded from model building (median R2: NO2, 59%; PM2.5, 42%; PM2.5 absorbance, 67%).CONCLUSIONS: Using a large data set from 23 European study areas, we were able to develop LUR models for NO2 and PM metrics that predicted measurements made at independent sites and areas reasonably well. This finding is useful for assessing exposure in health studies conducted in areas where no measurements were conducted.
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