| 21. |
- Imboden, Medea, et al.
(författare)
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Epigenome-wide association study of lung function level and its change
- 2019
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 54:1
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Tidskriftsartikel (refereegranskat)abstract
- Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, 6-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10-7) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute β-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and their ratio (FEV1/FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96×10-21 and pcombined=7.22×10-50). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV1/FVC: p=2.65×10-20).Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children.
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| 22. |
- 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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| 23. |
- Temam, Sofia, et al.
(författare)
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Socioeconomic position and outdoor nitrogen dioxide (NO2) exposure in Western Europe : a multi-city analysis
- 2017
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 101, s. 117-124
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Inconsistent associations between socioeconomic position (SEP) and outdoor air pollution have been reported in Europe, but methodological differences prevent any direct between-study comparison.OBJECTIVES: Assess and compare the association between SEP and outdoor nitrogen dioxide (NO2) exposure as a marker of traffic exhaust, in 16 cities from eight Western European countries.METHODS: Three SEP indicators, two defined at individual-level (education and occupation) and one at neighborhood-level (unemployment rate) were assessed in three European multicenter cohorts. NO2 annual concentration exposure was estimated at participants' addresses with land use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE; http://www.escapeproject.eu/). Pooled and city-specific linear regressions were used to analyze associations between each SEP indicator and NO2. Heterogeneity across cities was assessed using the Higgins' I-squared test (I(2)).RESULTS: The study population included 5692 participants. Pooled analysis showed that participants with lower individual-SEP were less exposed to NO2. Conversely, participants living in neighborhoods with higher unemployment rate were more exposed. City-specific results exhibited strong heterogeneity (I(2)>76% for the three SEP indicators) resulting in variation of the individual- and neighborhood-SEP patterns of NO2 exposure across cities. The coefficients from a model that included both individual- and neighborhood-SEP indicators were similar to the unadjusted coefficients, suggesting independent associations.CONCLUSIONS: Our study showed for the first time using homogenized measures of outcome and exposure across 16 cities the important heterogeneity regarding the association between SEP and NO2 in Western Europe. Importantly, our results showed that individual- and neighborhood-SEP indicators capture different aspects of the association between SEP and exposure to air pollution, stressing the importance of considering both in air pollution health effects studies.
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| 24. |
- Thun, Gian Andri, et al.
(författare)
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Causal and Synthetic Associations of Variants in the SERPINA Gene Cluster with Alpha1-antitrypsin Serum Levels
- 2013
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:8, s. e1003585-
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Tidskriftsartikel (refereegranskat)abstract
- Several infrequent genetic polymorphisms in the SERPINA1 gene are known to substantially reduce concentration of alpha1-antitrypsin (AAT) in the blood. Since low AAT serum levels fail to protect pulmonary tissue from enzymatic degradation these polymorphisms also increase the risk for early onset chronic obstructive pulmonary disease (COPD). The role of more common SERPINA1 single nucleotide polymorphisms (SNPs) in respiratory health remains poorly understood. We present here an agnostic investigation of genetic determinants of circulating AAT levels in a general population sample by performing a genome-wide association study (GWAS) in 1392 individuals of the SAPALDIA cohort. Five common SNPs defined by showing minor allele frequencies (MAFs) >5% reached genome-wide significance all located in the SERPINA gene cluster at 14q32.13. The top-ranking genotyped SNP rs4905179 was associated with an estimated effect of beta = 20.068 g/L per minor allele (P = 1.20*10(-12)). But denser SERPINA1 locus genotyping in 5569 participants with subsequent stepwise conditional analysis as well as exon-sequencing in a subsample (N = 410) suggested that AAT serum level is causally determined at this locus by rare (MAF<1%) and low-frequent (MAF 1-5%) variants only in particular by the well-documented protein inhibitor S and Z (PI S PI Z) variants. Replication of the association of rs4905179 with AAT serum levels in the Copenhagen City Heart Study (N = 8273) was successful (P<0.0001) as was the replication of its synthetic nature (the effect disappeared after adjusting for PI S and Z P = 0.57). Extending the analysis to lung function revealed a more complex situation. Only in individuals with severely compromised pulmonary health (N = 397) associations of common SNPs at this locus with lung function were driven by rarer PI S or Z variants. Overall our meta-analysis of lung function in ever-smokers does not support a functional role of common SNPs in the SERPINA gene cluster in the general population.
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| 25. |
- Boudier, Anne, et al.
(författare)
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Ten-Year Follow-up of Cluster-based Asthma Phenotypes in Adults A Pooled Analysis of Three Cohorts
- 2013
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 188:5, s. 550-560
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The temporal stability of adult asthma phenotypes identified using clustering methods has never been addressed. Longitudinal cluster-based methods may provide novel insights in the study of the natural history of asthma. Objectives: To compare the stability of cluster-based asthma phenotype structures a decade apart in adults and to address the individuals' phenotypic transition across these asthma phenotypes. Methods: The latent transition analysis was applied on longitudinal data (twice, 10 yr apart) from 3,320 adults with asthma who took part in the European Community Respiratory Health Survey, the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults, or the Epidemiological Study on Genetics and Environment of Asthma. Nine variables covering personal and phenotypic characteristics measured twice, 10 years apart, were simultaneously considered. Measurements and Main Results: Latent transition analysis identifies seven asthma phenotypes (prevalence range, 8.4-20.8%), mainly [GRAPHICS] characterized by the level of asthma symptoms ( low, moderate, high), the allergic status, and pulmonary function. Phenotypes observed 10 years apart showed strong similarities. The probability of membership in the same asthma phenotype at both times varied across phenotypes from 54 to 88%. Different transition patterns were observed across phenotypes. Transitions toward increased asthma symptoms were more frequently observed among nonallergic phenotypes as compared with allergic phenotypes. Results showed a strong stability of the allergic status over time. Conclusions: Adult asthma phenotypes identified by a clustering approach, 10 years apart, were highly consistent. This study is the first to model the probabilities of transitioning over time between comprehensive asthma phenotypes.
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| 26. |
- Carsin, Anne-Elie, et al.
(författare)
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Restrictive spirometry pattern is associated with low physical activity levels : A population based international study
- 2019
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Ingår i: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 146, s. 116-123
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Restrictive spirometry pattern is an under-recognised disorder with a poor morbidity and mortality prognosis. We compared physical activity levels between adults with a restrictive spirometry pattern and with normal spirometry.Methods: Restrictive spirometry pattern was defined as a having post-bronchodilator FEV1/FVC ≥ Lower Limit of Normal and a FVC<80% predicted in two population-based studies (ECRHS-III and SAPALDIA3). Physical activity was measured using the International Physical Activity Questionnaire. The odds of having low physical activity (<1st study-specific tertile) was evaluated using adjusted logistic regression models.Results: Subjects with a restrictive spirometry pattern (n = 280/4721 in ECRHS, n = 143/3570 in SAPALDIA) reported lower levels of physical activity than those with normal spirometry (median of 1770 vs 2253 MET·min/week in ECRHS, and 3519 vs 3945 MET·min/week in SAPALDIA). Subjects with a restrictive spirometry pattern were more likely to report low physical activity (meta-analysis odds ratio: 1.41 [95%CI 1.07–1.86]) than those with a normal spirometry. Obesity, respiratory symptoms, co-morbidities and previous physical activity levels did not fully explain this finding.Conclusion: Adults with a restrictive spirometry pattern were more likely to report low levels of physical activity than those with normal spirometry. These results highlight the need to identify and act on this understudied but prevalent condition.
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| 27. |
- de Marco, Roberto, et al.
(författare)
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Asthma, COPD and overlap syndrome : a longitudinal study in young European adults
- 2015
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 46:3, s. 671-679
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Tidskriftsartikel (refereegranskat)abstract
- We compared risk factors and clinical characteristics, 9-year lung function change and hospitalisation risk across subjects with the asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), asthma or COPD alone, or none of these diseases. Participants in the European Community Respiratory Health Survey in 1991-1993 (aged 20-44 years) and 1999-2001 were included. Chronic airflow obstruction was defined as pre-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity
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| 28. |
- Fuks, Kateryna B., et al.
(författare)
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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)
- 2014
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Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences (NIEHS). - 0091-6765 .- 1552-9924. ; 122:9, s. 896-905
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Long-term exposure to air pollution is 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: Fifteen population-based cohorts, participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE), were analysed. Residential exposure to particulate matter and nitrogen oxides was modelled with land use regression using a uniform protocol. Traffic exposure was assessed with traffic indicator variables. We analysed systolic and diastolic BP in participants medicated and non-medicated 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, 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 non-medicated 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 for prevalent hypertension was 1.05 [95% CI: 0.99-1.11] per 4,000,000 vehicles × m/day. Modelled 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 non-medicated participants, and an elevated OR for prevalent hypertension. The relationship of modelled air pollutants with BP was inconsistent.
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| 29. |
- Guerra, Stefano, et al.
(författare)
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Health-related quality of life and risk factors associated with spirometric restriction
- 2017
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Ingår i: European Respiratory Journal. - : The European Respiratory Society. - 0903-1936 .- 1399-3003. ; 49:5
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Tidskriftsartikel (refereegranskat)abstract
- The restrictive spirometric pattern is associated with a substantial morbidity and mortality burden. We sought to determine to what extent spirometric restriction is associated with impaired quality of life.We used data from two large population-based European cohorts: 6698 European Community Respiratory Health Survey (ECRHS) and 6069 Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) adult participants. The restrictive pattern was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥lower limit of normal (LLN) and FVC 1/FVC In both cohorts, the restrictive pattern was associated with heavy smoking, being underweight or obese and the coexistence of respiratory symptoms. In univariate analyses, compared with the normal group, both the restrictive and obstructive pattern had significant Physical Component Summary deficits (−2.77 and −2.08, respectively, in ECRHS; −3.25 and −2.14, respectively, in SAPALDIA; all p-values <0.001). However, in models adjusted for sex, age, education, body mass index, smoking, comorbidities and respiratory symptoms, only the restrictive pattern remained significantly associated with Physical Component Summary deficits (p=0.004 in ECRHS; p=0.001 in SAPALDIA).The restrictive spirometric pattern is associated with deficits in the physical component of quality of life that are partly independent of the presence of respiratory symptoms.
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| 30. |
- Jarvis, Debbie, et al.
(författare)
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Prevalence of asthma-like symptoms with ageing
- 2018
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Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 73:1, s. 37-48
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Change in the prevalence of asthma-like symptoms in populations of ageing adults is likely to be influenced by smoking, asthma treatment and atopy.METHODS: The European Community Respiratory Health Survey collected information on prevalent asthma-like symptoms from representative samples of adults aged 20-44 years (29 centres in 13 European countries and Australia) at baseline and 10 and 20 years later (n=7844). Net changes in symptom prevalence were determined using generalised estimating equations (accounting for non-response through inverse probability weighting), followed by meta-analysis of centre level estimates.FINDINGS: Over 20 years the prevalence of 'wheeze' and 'wheeze in the absence of a cold' decreased (-2.4%, 95% CI -3.5 to -1.3%; -1.5%, 95% CI -2.4 to -0.6%, respectively) but the prevalence of asthma attacks, use of asthma medication and hay fever/nasal allergies increased (0.6%, 95% CI 0.1 to 1.11; 3.6%, 95% CI 3.0 to 4.2; 2.7%, 95% CI 1.7 to 3.7). Changes were similar in the first 10 years compared with the second 10 years, except for hay fever/nasal allergies (increase seen in the first 10 years only). Decreases in these wheeze-related symptoms were largely seen in the group who gave up smoking, and were seen in those who reported hay fever/nasal allergies at baseline.INTERPRETATION: European adults born between 1946 and 1970 have, over the last 20 years, experienced less wheeze, although they were more likely to report asthma attacks, use of asthma medication and hay fever. Decrease in wheeze is largely attributable to smoking cessation, rather than improved treatment of asthma. It may also be influenced by reductions in atopy with ageing.
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