Genetics and Genomics of Aspirin Exacerbated Respiratory Disease (AERD)

NCT04261582 | Suspended

• 1 other identifier: HS-3200sIRB
• Study Type: observational
• Target: 245
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Aspirin Exacerbated Respiratory Disease; Aspirin-Sensitive Asthma; Nasal Polyps

Outcome Measures

Primary Outcomes (1)

• Evaluation of EGR related gene expression in AERD

  Researchers will obtain global gene expression of freshly brushed nasal airway epithelial cells of AERD patients, non-aspirin sensitive asthma patients, and healthy patients using nasal swab samples and running RNAseq on the collected cells. Researchers will contrast AERD gene profiles against non-aspirin sensitive asthma patients and healthy patients and determine whether down-regulation of EGR genes is found in AERD.

  Through study completion, 3 years

Secondary Outcomes (2)

• Relation of EGR gene expression to epigenetic gene methylation

  Through study completion, 3 years

• Influence of Genetic variation on EGR related gene expression

  Through study completion, 3 years

Study Arms (3)

AERD participants

Participants with aspirin exacerbated respiratory disease. Adults with aspirin allergy, nasal polyps and adult-onset severe asthma.

Healthy controls

Healthy participants that do not have asthma.

Non-aspirin sensitive asthma participants

Participants with asthma, but that do not have a sensitivity to aspirin.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

AERD participants, a subtype of severe asthma characterized by inflammation of the nasal cavity, development of non-cancerous growths, and an allergy to aspirin; 35 healthy control participants. Populations will be recruited from clinic visits or clinical research inquiries, all volunteers.

You may qualify if:

• Physician diagnosis of asthma
• Physician diagnosis of chronic nasal disease featuring nasal polyps
• Sensitivity to aspirin verified by an aspirin provocative challenge in clinic
• Healthy control participant

You may not qualify if:

• Active smoking
• Pregnancy
• History of greater than or equal to 10 pack-years of smoking
• Any significant comorbid conditions that could inadvertently interfere with study results
• Conditions that require bursts of oral corticosteroids
• Other significant lung diseases
• Other disease in the view of the investigator prohibits participation in the study

Sponsors & Collaborators

• National Jewish Health: lead
• The Scripps Research Institute: collaborator

Study Sites (1)

National Jewish Health

Denver, Colorado, 80206, United States

Location

MeSH Terms

Conditions

Nasal Polyps

Condition Hierarchy (Ancestors)

Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: February 10, 2020
• Study Start: November 6, 2018
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2022
• Last Updated: September 1, 2021

Record last verified: 2021-08

Locations

US (1)