| 41. |
- Kogevinas, Manolis, et al.
(author)
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Exposure to substances in the workplace and new-onset asthma : an international prospective population-based study (ECRHS-II)
- 2007
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 370:9584, s. 336-341
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Journal article (peer-reviewed)abstract
- Background The role of exposure to substances in the workplace in new-onset asthma is not well characterised in population-based studies. We therefore aimed to estimate the relative and attributable risks of new-onset asthma in relation to occupations, work-related exposures, and inhalation accidents. Methods We studied prospectively 6837 participants from 13 countries who previously took part in the European Community Respiratory Health Survey (1990-95) and did not report respiratory symptoms or a history of asthma at the time of the first study. Asthma was assessed by methacholine challenge test and by questionnaire data on asthma symptoms. Exposures were defined by high-risk occupations, an asthma-specific job exposure matrix with additional expert judgment, and through self-report of acute inhalation events. Relative risks for new onset asthma were calculated with log-binomial models adjusted for age, sex, smoking, and study Centre. Findings A significant excess asthma risk was seen after exposure to substances known to cause occupational asthma (Relative risk=1.6, 95% CI 1.1-2.3, p=0.017). Risks were highest for asthma defined by bronchial hyper-reactivity in addition to symptoms (2.4,1.3-4.6, p=0.008). Of common occupations, a significant excess risk of asthma was seen for nursing (2.2,1.3-4.0, p=0.007). Asthma risk was also increased in participants who reported an acute symptomatic inhalation event such as fire, mixing cleaning products, or chemical spills (RR=3.3, 95% CI 1.0-11.1, p=0.051). The population-attributable risk for adult asthma due to occupational exposures ranged from 10% to 25%, equivalent to an incidence of new-onset occupational asthma of 250-300 cases per million people per year. Interpretation Occupational exposures account for a substantial proportion of adult asthma incidence. The increased risk of asthma after inhalation accidents suggests that workers who have such accidents should be monitored closely.
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| 42. |
- Künzli, Nino, et al.
(author)
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Comparison of oxidative properties, light absorbance, total and elemental mass concentration of ambient PM2.5 collected at 20 European sites.
- 2006
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In: Environ Health Perspect. - 0091-6765. ; 114:5, s. 684-90
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Journal article (peer-reviewed)abstract
- BACKGROUND: Body mass, as well as distribution of body fat, are predictors of both diabetes and cardiovascular disease. In Northern Sweden, despite a marked increase in average body mass, prevalence of diabetes was stagnant and myocardial infarctions decreased. A more favourable distribution of body fat is a possible contributing factor.This study investigates the relative importance of individual food items for time trends in waist circumference (WC) and hip circumference (HC) on a population level. METHODS: Independent cross-sectional surveys conducted in 1986, 1990, 1994 and 1999 in the two northernmost counties of Sweden with a common population of 250,000. Randomly selected age stratified samples, altogether 2982 men and 3087 women aged 25-64 years. Questionnaires were completed and anthropometric measurements taken. For each food item, associations between frequency of consumption and waist and hip circumferences were estimated. Partial regression coefficients for every level of reported intake were multiplied with differences in proportion of the population reporting the corresponding levels of intake in 1986 and 1999. The sum of these product terms for every food item was the respective estimated impact on mean circumference. RESULTS: Time trends in reported food consumption associated with the more favourable gynoid distribution of adipose tissue were increased use of vegetable oil, pasta and 1.5% fat milk. Trends associated with abdominal obesity were increased consumption of beer in men and higher intake of hamburgers and French fried potatoes in women. CONCLUSION: Food trends as markers of time trends in body fat distribution have been identified. The method is a complement to conventional approaches to establish associations between food intake and disease risk on a population level.
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| 43. |
- Lemonnier, Nathanaël, et al.
(author)
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A novel whole blood gene expression signature for asthma, dermatitis, and rhinitis multimorbidity in children and adolescents
- 2020
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY. - 0105-4538 .- 1398-9995. ; 75:12, s. 3248-3260
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Journal article (peer-reviewed)abstract
- Background: Allergic diseases often occur in combination (multimorbidity). Human blood transcriptome studies have not addressed multimorbidity. Large-scale gene expression data were combined to retrieve biomarkers and signaling pathways to disentangle allergic multimorbidity phenotypes.Methods: Integrated transcriptomic analysis was conducted in 1233 participants with a discovery phase using gene expression data (Human Transcriptome Array 2.0) from whole blood of 786 children from three European birth cohorts (MeDALL), and a replication phase using RNA Sequencing data from an independent cohort (EVA-PR, n = 447). Allergic diseases (asthma, atopic dermatitis, rhinitis) were considered as single disease or multimorbidity (at least two diseases), and compared with no disease.Results: Fifty genes were differentially expressed in allergic diseases. Thirty-two were not previously described in allergy. Eight genes were consistently overexpressed in all types of multimorbidity for asthma, dermatitis, and rhinitis (CLC, EMR4P, IL5RA, FRRS1, HRH4, SLC29A1, SIGLEC8, IL1RL1). All genes were replicated the in EVA-PR cohort. RT-qPCR validated the overexpression of selected genes. In MeDALL, 27 genes were differentially expressed in rhinitis alone, but none was significant for asthma or dermatitis alone. The multimorbidity signature was enriched in eosinophil-associated immune response and signal transduction. Protein-protein interaction network analysis identified IL5/JAK/STAT and IL33/ST2/IRAK/TRAF as key signaling pathways in multimorbid diseases. Synergistic effect of multimorbidity on gene expression levels was found.Conclusion: A signature of eight genes identifies multimorbidity for asthma, rhinitis, and dermatitis. Our results have clinical and mechanistic implications, and suggest that multimorbidity should be considered differently than allergic diseases occurring alone.
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| 44. |
- Leynaert, Benedicte, et al.
(author)
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Gender differences in prevalence, diagnosis and incidence of allergic and non-allergic asthma : a population-based cohort
- 2012
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In: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 67:7, s. 625-631
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Journal article (peer-reviewed)abstract
- Background Although women with severe non-allergic asthma may represent a substantial proportion of adults with asthma in clinical practice, gender differences in the incidence of allergic and non-allergic asthma have been little investigated in the general population. Methods Gender differences in asthma prevalence, reported diagnosis and incidence were investigated in 9091 men and women randomly selected from the general population and followed up after 8-10 years as part of the European Community Respiratory Health Survey. The protocol included assessment of bronchial responsiveness, IgE specific to four common allergens and skin tests to nine allergens. Results Asthma was 20% more frequent in women than in men over the age of 35 years. Possible under-diagnosis of asthma appeared to be particularly frequent among non-atopic individuals, but was as frequent in women as in men. The follow-up of subjects without asthma at baseline showed a higher incidence of asthma in women than in men (HR 1.94; 95% CI 1.40 to 2.68), which was not explained by differences in smoking, obesity or lung function. More than 60% of women and 30% of men with new-onset asthma were non-atopic. The incidence of non-allergic asthma was higher in women than in men throughout all the reproductive years (HR 3.51; 95% CI 2.21 to 5.58), whereas no gender difference was observed for the incidence of allergic asthma. Conclusions This study shows that female sex is an independent risk factor for non-allergic asthma, and stresses the need for more careful assessment of possible non-allergic asthma in clinical practice, in men and women.
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| 45. |
- Llop, Sabrina, et al.
(author)
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CYP3A genes and the association between prenatal methylmercury exposure and neurodevelopment
- 2017
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In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 105, s. 34-42
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Journal article (peer-reviewed)abstract
- Background Results on the association between prenatal exposure to methylmercury (MeHg) and child neuropsychological development are heterogeneous. Underlying genetic differences across study populations could contribute to this varied response to MeHg. Studies in Drosophila have identified the cytochrome p450 3A (CYP3A) family as candidate MeHg susceptibility genes. Objectives We evaluated whether genetic variation in CYP3A genes influences the association between prenatal exposure to MeHg and child neuropsychological development. Methods The study population included 2639 children from three birth cohort studies: two subcohorts in Seychelles (SCDS) (n = 1160, 20 and 30 months of age, studied during the years 2001–2012), two subcohorts from Spain (INMA) (n = 625, 14 months of age, 2003–2009), and two subcohorts from Italy and Greece (PHIME) (n = 854, 18 months of age, 2006–2011). Total mercury, as a surrogate of MeHg, was analyzed in maternal hair and/or cord blood samples. Neuropsychological development was evaluated using Bayley Scales of Infant Development (BSID). Three functional polymorphisms in the CYP3A family were analyzed: rs2257401 (CYP3A7), rs776746 (CYP3A5), and rs2740574 (CYP3A4). Results There was no association between CYP3A polymorphisms and cord mercury concentrations. The scores for the BSID mental scale improved with increasing cord blood mercury concentrations for carriers of the most active alleles (β[95% CI]: = 2.9[1.53,4.27] for CYP3A7 rs2257401 GG + GC, 2.51[1.04,3.98] for CYP3A5 rs776746 AA + AG and 2.31[0.12,4.50] for CYP3A4 rs2740574 GG + AG). This association was near the null for CYP3A7 CC, CYP3A5 GG and CYP3A4 AA genotypes. The interaction between the CYP3A genes and total mercury was significant (p < 0.05) in European cohorts only. Conclusions Our results suggest that the polymorphisms in CYP3A genes may modify the response to dietary MeHg exposure during early life development.
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| 46. |
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| 47. |
- Macsali, Ferenc, et al.
(author)
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Early Age at Menarche, Lung Function, and Adult Asthma
- 2011
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In: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 183:1, s. 8-14
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Journal article (peer-reviewed)abstract
- Rationale: Hormonal and metabolic status appears to influence lung health in women, and there are findings suggesting that early menarche may be related to asthma, cardiovascular disease, diabetes, and breast cancer. Objectives: This study investigates whether age at menarche is related to adult lung function and asthma. Methods: Among participants in the European Community Respiratory Health Survey II, 3,354 women aged 27-57 years from random population samples in 21 centers responded to a questionnaire concerning women's health (1998-2002). Of these women, 2,873 had lung function measurements, 2,136 had measurements of bronchial hyperreactivity, and 2,743 had IgE measurements. Logistic, linear, and negative binomial regression analyses included adjustment for age, height, body mass index, education, smoking, family size, and center. Measurements and Main Results: FEV1 and FVC were lower and asthma was more common in women with early menarche. Women reporting menarche at age 10 years or less, as compared with women with menarche at age 13 years (reference category), had lower FEV1 (adjusted difference, -113 ml; 95% confidence interval [CI], -196 to -33 ml) and FVC (-126 ml; 95% CI, -223 to -28 ml); also lower FEV1 expressed as a percentage of the predicted value (-3.28%; 95% CI, -6.25 to -0.30%) and FVC expressed as a percentage of the predicted value (-3.63%; 95% CI, -6.64 to -0.62%). Women with early menarche more often had asthma symptoms (odds ratio, 1.80; 95% CI, 1.09-2.97), asthma with bronchial hyperreactivity (odds ratio, 2.79; 95% CI, 1.06-7.34), and higher asthma symptom score (mean ratio, 1.58; 95% CI, 1.12-2.21). Conclusions: Women with early menarche had lower lung function and more asthma in adulthood. This supports a role for metabolic and hormonal factors in women's respiratory health.
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| 48. |
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| 49. |
- Matheson, Melanie Claire, et al.
(author)
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Early-life risk factors and incidence of rhinitis : Results from the European Community Respiratory Health Study - an international population-based cohort study
- 2011
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In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 128:4, s. 816-823.e5
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Journal article (peer-reviewed)abstract
- Background: Rhinitis is an increasingly common condition with a heavy health care burden, but relatively little is known about its risk factors. Objective: To examine the association between early-life factors and the development of rhinitis in the European Community Respiratory Health Study (ECRHS). Methods: In 1992-1994, community-based samples of 20-44-year-old people were recruited from 48 centers in 22 countries. On average, 8.9 years later, 28 centers reinvestigated their samples. Onset of rhinitis was reported by 8486 participants in interviewer-led questionnaires. Cox regression was used to assess independent predictors of rhinitis at ages <= 5, 6-10, 11-20, and >= 21 years. Results: The crude lifelong incidence of rhinitis was 7.00/1000/year (men) and 7.95/1000/year (women) (P = .002). Women developed less rhinitis in later childhood (hazard ratios [HR], 0.63; 95% CI, 0.47-0.85) and more rhinitis in adulthood (HR, 1.36; 95% CI, 1.11-1.66) than did men. In atopic subjects, siblings were associated with lower risk of rhinitis throughout life (pooled HR, 0.94; 95% CI, 0.91-0.98 per 1 sibling). Early contact with children in the family or day care was associated with less incidence of rhinitis, predominantly before age 5 years (HR, 0.84; 95% CI, 0.72-0.99). Early childhood pets or growing up on a farm was associated with less incidence of rhinitis in adolescence (HR, 0.50; 95% CI, 0.37-0.68). Combining these factors showed evidence of a dose-response relationship (trend P = .0001). Conclusions: Gender is a strong risk factor for rhinitis, with age patterns varying according to atopic status. Protective effects of early contact with children and animals were suggested for incident rhinitis, with risk patterns varying by age window and atopic status.
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| 50. |
- Merid, Simon Kebede, et al.
(author)
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Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
- 2020
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In: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
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Journal article (peer-reviewed)abstract
- Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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