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- Castro-Giner, F., et al.
(författare)
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Positionally cloned genes and age-specific effects in asthma and atopy : an international population-based cohort study (ECRHS)
- 2010
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 65:2, s. 124-131
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Tidskriftsartikel (refereegranskat)abstract
- Background Several genes identified by positional cloning have been associated with asthma and atopy, but few findings have been replicated. Age at onset of asthma has been associated with different phenotypic characteristics, and with variants at chromosome 17q21 identified through genome-wide association. This study examined the associations and age-specific effects on asthma, atopy and bronchial hyper-responsiveness (BHR) of five candidate genes previously identified by positional cloning (ADAM33, PHF11, NPSR1, DPP10, SPINK5). Methods 51 polymorphisms from 2474 participants from 13 countries who took part in the European Community Respiratory Health Survey (1990-2000) were studied. Asthma and age at onset of asthma were assessed by questionnaire data, BHR by methacholine challenge and atopy by specific immunoglobulin E to four common allergens. Results Significant associations with asthma, atopy and particularly for asthma with atopy were observed for a large region of 47 kb in the NPSR1 gene, even after Bonferroni correction for multiple comparisons (p < 0.001). The associations with NPSR1 were stronger in those reporting a first attack of asthma before the age of 15, with statistically significant interactions with age of onset found for three SNPs. The evidence for ADAM33 and BHR and for an age-specific effect of two SNPs in DPP10 and asthma was weaker. Conclusion This study provides further evidence for an effect of NPSR1 on asthma, atopy and atopic asthma. In addition, this analysis suggests a role for NPSR1 in early-onset asthma driven by the strong effect of this gene on atopic asthma.
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- Anto, J. M., et al.
(författare)
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Risk factors of new-onset asthma in adults : a population-based international cohort study
- 2010
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 65:8, s. 1021-1030
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Tidskriftsartikel (refereegranskat)abstract
- P>Background: The occurrence of new-onset asthma during adulthood is common, but there is insufficient understanding of its determinants including the role of atopy. Objective: To assess the risk factors for the development of new-onset asthma in middle-aged adults and to compare them according to atopy. Methods: A longitudinal analysis of 9175 young adults who participated in two surveys of the European Community Respiratory Health Survey (ECRHS) conducted 9 years apart. Findings: We observed 179 cases of new-onset asthma among 4588 participants who were free of asthma and reported at the beginning of the follow-up that they had never had asthma (4.5 per 1000 person-years). In a logistic regression, the following risk factors were found to increase the risk of new-onset asthma: female gender (OR: 1.97; 95% confidence interval (CI): 1.38,2.81), bronchial hyperresponsiveness (3.25; 2.19,4.83), atopy (1.55;1.08,2.21), FEV1 < 100 % predicted (1.87;1.34,2.62), nasal allergy (1.98;1.39,2.84) and maternal asthma (1.91;1.13;3.21). Obesity, respiratory infections in early life and high-risk occupations increased the risk of new-onset asthma although we had limited power to confirm their role. Among the atopics, total IgE and sensitization to cat were independently related to the risk of new-onset asthma. The proportion of new-onset asthma attributable to atopy varied from 12% to 21%. Conclusion: Adults reporting that they had never had asthma were at a substantial risk of new-onset asthma as a result of multiple independent risk factors including lung function. Atopy explains a small proportion of new-onset adult asthma.
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- Bakolis, I, et al.
(författare)
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Respiratory health and endotoxin : associations and modification by CD14/-260 genotype
- 2012
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 39:3, s. 573-581
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to endotoxin has been associated with increased respiratory symptoms and decrements in lung function in occupational settings but little is known about health effects of domestic exposure in adults. We describe the association of respiratory disease, IgE sensitisation, bronchial reactivity and lung function with mattress endotoxin levels in adults and determine whether these associations are modified by polymorphisms in CD14.Endotoxin levels in mattress dust from a population based sample of 972 adults were measured. Associations were examined using generalized linear mixed models, adjusting for individual and household confounders. Effect modification of these associations by CD14/-260 (rs2569190) was assessed.Mattress endotoxin levels varied from 0.1 to 402.6 EU·mg(-1). Although there was no overall association of lung function with endotoxin exposure, there was evidence that the association of FEV1 and FVC with endotoxin was modified by CD14/-260 genotype (p for interaction 0.005 and 0.013 respectively). There was no evidence that symptoms, IgE sensitisation or bronchial reactivity was associated with mattress endotoxin levels.In this large epidemiological study of adults there was no evidence that mattress endotoxin level was associated with respiratory symptoms or IgE sensitisation but the association of lung function with endotoxin levels may be modified by CD14-genotype.
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