| 1. |
- Castro-Giner, F., et al.
(författare)
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Joint effect of obesity and TNFA variability on asthma : two international cohort studies
- 2009
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 33:5, s. 1003-1009
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a risk factor for asthma. Adipose tissue expresses pro-inflammatory molecules including tumour necrosis factor (TNF), and levels of TNF are also related to polymorphisms in the TNF-alpha (TNFA) gene. The current authors examined the joint effect of obesity and TNFA variability on asthma in adults by combining two population-based studies. The European Community Respiratory Health Survey and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults used comparable protocols, questionnaires and measures of lung function and atopy. DNA samples from 9,167 participants were genotyped for TNFA -308 and lymphotoxin-alpha (LTA) +252 gene variants. Obesity and TNFA were associated with asthma when mutually adjusting for their independent effects (odds ratio (OR) for obesity 2.4, 95% confidence interval (CI) 1.7-3.2; OR for TNFA -308 polymorphism 1.3, 95% CI 1.1-1.6). The association of obesity with asthma was stronger for subjects carrying the G/A and A/A TNFA -308 genotypes compared with the more common G/G genotype, particularly among nonatopics (OR for G/A and A/A genotypes 6.1, 95% CI 2.5-14.4; OR for G/G genotype 1.7, 95% CI 0.8-3.3). The present findings provide, for the first time, evidence for a complex pattern of interaction between obesity, a pro-inflammatory genetic factor and asthma.
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| 2. |
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| 3. |
- Castro-Giner, F, et al.
(författare)
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TNFA -308G>A in two international population-based cohorts and risk of asthma
- 2008
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Ingår i: European Respiratory Journal. - Sheffield : European respiratory society journals. - 0903-1936 .- 1399-3003. ; 32:2, s. 350-361
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Tidskriftsartikel (refereegranskat)abstract
- Genetic association studies have related the tumour necrosis factor-alpha gene (TNFA) guanine to adenine substitution of nucleotide -308 (-308G>A) polymorphism to increased risk of asthma, but results are inconsistent. The aim of the present study was to test whether two single-nucleotide polymorphisms, of TNFA and of the lymphotoxin-alpha gene (LTA), are associated with asthma, bronchial hyperresponsiveness and atopy in adults, by combining the results of two large population-based multicentric studies and conducting a meta-analysis of previously published studies. The European Community Respiratory Health Survey (ECRHS) and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) used comparable protocols, including questionnaires for respiratory symptoms and measures of lung function and atopy. DNA samples from 11,136 participants were genotyped at TNFA -308 and LTA 252. Logistic regression employing fixed and random effects models and nonparametric techniques were used. The prevalence of asthma was 6%. The TNFA -308G>A polymorphism was associated with increased asthma prevalence and with bronchial hyperresponsiveness. No consistent association was found for atopy. The LTA 252A>G polymorphism was not associated with any of the outcomes. A meta-analysis of 17 studies showed an increased asthma risk for the TNFA -308 adenine allele. The tumour necrosis factor-alpha gene nucleotide -308 polymorphism is associated with a moderately increased risk of asthma and bronchial hyperresponsiveness, but not with atopy. These results are supported by a meta-analysis of previously published studies.
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| 4. |
- Gudbjartsson, Daniel F., et al.
(författare)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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| 5. |
- Harrop, J., et al.
(författare)
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Eczema, atopy and allergen exposure in adults : a population-based study
- 2007
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 37:4, s. 526-535
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are few published studies on geographical variation in prevalence of eczema in adults or its association with recognised risk factors for allergic disease. Objective: To describe the geographical variation in prevalence of eczema in adults, assess the associations with sociodemographic risk factors, serum-specific IgE and IgG, and exposure to allergen. Methods: A community-based sample of 8206 adults aged 27-56 years, in 25 European centres and Portland, USA, provided questionnaire information on symptoms of eczema. Serum-specific IgE to house dust mite (HDM), cat, grass and Cladosporium, and IgG and IgG4 to HDM and cat were measured. Mattress levels of mite and cat allergen were assessed. Results: Overall prevalence of eczema was 7.1% (range between countries of 2.2-17.6%). Eczema was associated with female gender [odds ratio (OR) 1.25; 95% confidence interval (CI) (1.01-1.55)], family history of atopic disease (OR 1.43; 95% CI 1.18-1.74), IgE sensitization to at least one allergen (OR 1.50; 95% CI 1.19-1.90), particularly Cladosporium (OR 3.65; 95% CI 1.81-7.37), and total IgE. Eczema was negatively associated with age and no clear associations were observed with sibship size, mattress mite and cat allergen levels or with cat and HDM-specific IgG or IgG4. Conclusions: There is geographical variation in the prevalence of eczema in adults both within and between countries. Although the disease is associated with IgE sensitization, in this study it was not related to mattress mite or cat allergen levels.
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| 7. |
- Cerveri, I, et al.
(författare)
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What defines airflow obstruction in asthma?
- 2009
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 34:3, s. 568-573
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Tidskriftsartikel (refereegranskat)abstract
- Asthma guidelines from the Global Initiative for Asthma (GINA) and from the National Heart, Lung, and Blood Institute provide conflicting definitions of airflow obstruction, suggesting a fixed forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) cut-off point and the lower limit of normality (LLN), respectively. The LLN was recommended by the recent American Thoracic Society/European Respiratory Society guidelines on lung function testing. The problem in using fixed cut-off points is that they are set regardless of age and sex in an attempt to simplify diagnosis at the expense of misclassification. The sensitivity and specificity of fixed FEV(1)/FVC ratios of 0.70, 0.75 and 0.80 versus the LLN were evaluated in 815 subjects (aged 20-44 yrs) with a diagnosis of asthma within the framework of the European Community Respiratory Health Survey. In males, the 0.70 ratio showed 76.5% sensitivity and 100.0% specificity, the 0.75 ratio 100.0% sensitivity and 92.4% specificity, and the 0.80 ratio 100.0% sensitivity but 58.1% specificity. In females, the 0.70 ratio showed 57.3% sensitivity and 100.0% specificity, the 0.75 ratio 91.5% sensitivity and 95.9% specificity, and the 0.80 ratio 100.0% sensitivity but 72.9% specificity. The fixed cut-off points cause a lot of misidentification of airflow obstruction in young adults, with overestimation with the 0.80 ratio and underestimation with the 0.70 ratio. In conclusion, the GINA guidelines should change their criteria for defining airflow obstruction.
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| 10. |
- Svanes, C, et al.
(författare)
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Long-term reliability in reporting of childhood pets by adults interviewed twice, 9 years apart. Results from the European Community Respiratory Health Survey I and II
- 2008
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Ingår i: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 18:2, s. 84-92
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Tidskriftsartikel (refereegranskat)abstract
- Investigation of long-term effects of childhood pet exposure is usually based on retrospective information provided by adults, while there is little knowledge about the reliability in adult reporting of childhood events. We analyzed 8287 adults interviewed about childhood pets twice, on average nine years apart, in the European Community Respiratory Health Survey. Agreement between the surveys in reporting of childhood cats, dogs and birds were investigated with kappa statistics, and potential effects of disease status on agreement were analyzed with kappa statistics and multiple logistic regressions. Cats, dogs and birds in childhood were reported by 44, 41 and 38%, respectively. Cohen's kappa for agreement in adult reporting of childhood pets was 0.714 (95% CI=0.698-0.729) for cat, 0.709 (0.691-0.722) for dog, and 0.606 (0.591-0.626) for bird. Thus, agreement was significantly higher for reporting of cat and dog than for bird. Adult wheeze, asthma or atopy did not influence agreement. Neither did adult cat sensitization influence agreement in adult reporting of childhood cat. Childhood factors such as moving house <5 years, or growing up as a single child, in a large family or in a rural area, were associated with poorer agreement, while adult factors were unrelated to agreement. PRACTICAL IMPLICATIONS: Long-term reliability in adult reporting of childhood pets was substantial, and not influenced by disease status. Thus, collection of information about childhood pets from adults appears to be reliable for the purpose of studying adult allergic disease. Future studies should consider that the reliability was higher for a more important childhood event and influenced by childhood rather than adult characteristics. Imperfect reliability contributed to underestimation of the effects of pets on adult allergy; i.e. with a kappa of 0.71, a true odds ratio (OR) of 0.80 would be attenuated to 0.86. Future studies should account for non-differential misclassification error.
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