Genetic and Epigenetic Changes in AERD
Research type
Research Study
Full title
Genetic and local respiratory epithelial/polyp epigenetic variants associated with aspirin-exacerbated respiratory disease (AERD)\n
IRAS ID
197923
Contact name
Glenis Scadding
Contact email
Sponsor organisation
University College London
Duration of Study in the UK
2 years, 5 months, 20 days
Research summary
Aspirin- exacerbated respiratory disease (AERD) is an asthma phenotype of unknown aetiology characterised by concomitant nasal polyposis with persistent eosinophilic inflammation of the whole respiratory tract, exacerbated by aspirin /NSAIDs. AERD patients require more medical therapy and surgery than aspirin-tolerant asthmatics and comprise 25% of all intensive-care asthma admissions.\n\nThe adult onset suggests the importance of environmental factors in driving the risk of AERD. To this end, We hypothesise that an interplay between a genetically susceptible background exposed to accumulating environmental triggers increases the risk of AERD in adulthood. In support of this hypothesis, a number of genetic studies and a recent small epigenetic study has found genetic and epigenetic differences (i. e. changes in the degree of DNA methylation at specific sites in the genome which affect the degree of expression of genes) in polyps from aspirin – sensitive and tolerant Korean patients, but no differences in blood samples.\n\nIn order to test the above hypotheses in Caucasians, we propose to undertake a genetic and local epigenetic analysis of two easily accessible and implicated tissues in AERD pathogenesis - nasal epithelium and polyp – in Caucasian AERD patients and controls, using the largest and most deeply phenotyped case-series collection in Europe, already the subject of genetic investigation. \n\nIf epithelium can be used as a reliable alternative to polyp, then repeated investigation would allow evaluation of the emergence of aspirin sensitivity, changes in gene expression in response to aspirin challenge, local aspirin desensitisation and other treatments, leading to a much better understanding of the aetiology and control of this largely ignored adult-onset asthmatic disease.\n
REC name
London - Brent Research Ethics Committee
REC reference
17/LO/1345
Date of REC Opinion
9 Oct 2017
REC opinion
Further Information Favourable Opinion