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Genetics and Genomics of Aspirin Exacerbated Respiratory Disease (AERD)

2020-02-12 17:40:59 | BioPortfolio

Summary

Aspirin Exacerbated Respiratory Disease (AERD) is a relatively homogeneous disease characterized by adult-onset severe asthma, development of non-cancerous growths in the nasal canal (i.e. nasal polyps) and aspirin allergy. The cause of AERD is unknown, although likely results from environmental insults in combination with genetic susceptibility. AERD disease homogeneity increases the possibility of discovering narrowly-defined genetic contributors, and makes it an ideal population to study the genetic and epigenetic changes that cause asthma. Researchers recently discovered that gene expression of epithelial growth and repair (EGR) genes are substantially decreased in bronchial airway epithelial cells of severe asthmatics compared to less severe asthmatics and healthy controls. This new finding indicates that epithelial integrity and related processes may be of primary importance to the development of severe asthma, and potentially the severe asthma subtype, AERD. This finding was later supported in a subsequent lab model, which showed that blocking a central epithelial repair and differentiation gene, human epidermal growth factor receptor 2 (ERBB2), decreased healing time of bronchial epithelial cells after injury. Thus, the objective of the proposed study is to determine whether EGR gene are also down-regulated in AERD, a homogeneous severe asthma subtype. As an extension, the researchers will also determine whether genetic mutations and/or epigenetic changes relate to and potentially explain this down-regulation of EGR genes. Specifically, the researchers plan to obtain gene expression of freshly brushed nasal airway epithelial cells of 140 AERD patients, 70 non-aspirin sensitive asthma patients, and 35 healthy controls, noting that nasal epithelial gene expression has recently been shown to mirror lung epithelial changes in asthmatic airways. Swabbing the nasal canal for epithelial cells allows to evaluate airway epithelial cell gene expression non-invasively. Our experimental design contrasts AERD gene expression profiles against healthy controls, and determines whether EGR genes are depressed in AERD relative to health controls. As a corollary, the researchers look to discover an AERD-specific gene expression profile which may one-day aid in diagnosis and expand current knowledge of disease mechanisms. As an extension, the researchers will correlate gene expression changes, specifically any finding of down-regulated EGR genes, with methylation changes (i.e. epigenetic changes) and genetic mutations.

Study Design

Conditions

Aspirin Exacerbated Respiratory Disease

Location

National Jewish Health
Denver
Colorado
United States
80206

Status

Recruiting

Source

National Jewish Health

Results (where available)

View Results

Links

Published on BioPortfolio: 2020-02-12T17:40:59-0500

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Medical and Biotech [MESH] Definitions

A non-steroidal anti-inflammatory agent that is less effective than equal doses of ASPIRIN in relieving pain and reducing fever. However, individuals who are hypersensitive to ASPIRIN may tolerate sodium salicylate. In general, this salicylate produces the same adverse reactions as ASPIRIN, but there is less occult gastrointestinal bleeding. (From AMA Drug Evaluations Annual, 1992, p120)

Asthmatic adverse reaction (e.g., BRONCHOCONSTRICTION) to conventional NSAIDS including aspirin use.

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The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)

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