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Sökning: WFRF:(Postma DS)

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  • Bousquet, J, et al. (författare)
  • Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper
  • 2012
  • Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 158:3, s. 216-231
  • Tidskriftsartikel (refereegranskat)abstract
    • Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.
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  • Dijk, FN, et al. (författare)
  • Genetic regulation of IL1RL1 methylation and IL1RL1-a protein levels in asthma
  • 2018
  • Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 51:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Interleukin-1 receptor–like 1 (IL1RL1) is an important asthma gene. (Epi)genetic regulation of IL1RL1 protein expression has not been established. We assessed the association between IL1RL1 single nucleotide polymorphisms (SNPs), IL1RL1 methylation and serum IL1RL1-a protein levels, and aimed to identify causal pathways in asthma.Associations of IL1RL1 SNPs with asthma were determined in the Dutch Asthma Genome-wide Association Study cohort and three European birth cohorts, BAMSE (Children/Barn, Allergy, Milieu, Stockholm, an Epidemiological survey), INMA (Infancia y Medio Ambiente) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy), participating in the Mechanisms of the Development of Allergy study. We performed blood DNA IL1RL1 methylation quantitative trait locus (QTL) analysis (n=496) and (epi)genome-wide protein QTL analysis on serum IL1RL1-a levels (n=1462). We investigated the association of IL1RL1 CpG methylation with asthma (n=632) and IL1RL1-a levels (n=548), with subsequent causal inference testing. Finally, we determined the association of IL1RL1-a levels with asthma and its clinical characteristics (n=1101).IL1RL1 asthma-risk SNPs strongly associated with IL1RL1 methylation (rs1420101; p=3.7×10−16) and serum IL1RL1-a levels (p=2.8×10−56). IL1RL1 methylation was not associated with asthma or IL1RL1-a levels. IL1RL1-a levels negatively correlated with blood eosinophil counts, whereas there was no association between IL1RL1-a levels and asthma.In conclusion, asthma-associated IL1RL1 SNPs strongly regulate IL1RL1 methylation and serum IL1RL1-a levels, yet neither these IL1RL1-methylation CpG sites nor IL1RL1-a levels are associated with asthma.
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  • Joos, GF, et al. (författare)
  • Indirect airway challenges
  • 2003
  • Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 21:6, s. 1050-1068
  • Tidskriftsartikel (refereegranskat)
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  • Marenholz, I, et al. (författare)
  • Meta-analysis identifies seven susceptibility loci involved in the atopic march
  • 2015
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6, s. 8804-
  • Tidskriftsartikel (refereegranskat)abstract
    • Eczema often precedes the development of asthma in a disease course called the ‘atopic march’. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10−8) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10−9). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.
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