Study Results
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Basic Information
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COMPLETED
126 participants
OBSERVATIONAL
2005-07-31
Brief Summary
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Detailed Description
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The purpose of this study is to explore the role of histoblood group antigens in virus-induced asthma exacerbations. These antigens (ABH and Lewis) decorate O- and N-linked glycans on mucin and epithelial glycoproteins, respectively. Glycan synthesis involves glycosyltransferases, including fucosyltransferases (FUT) encoded by FUT genes. Glycan degradation involves glycosidases, including fucosidase. "Secretor status" is defined by FUT2 activity in epithelial cells, which forms the H antigen and allows subsequent synthesis and secretion of A, B, and Lewis B antigens. In preliminary studies it was found that: 1) asthmatic patients with frequent exacerbations are more likely than non-exacerbated patients to be secretors; 2) secretors report more frequently that a cold causes asthma; and 3) sputum in stable asthma has abnormally high fucosidase activity. These findings suggest that airway glycans are subjected to the following two competing homoeostatic influences: 1) the diversity and activity of glycosyltransferases within cells that synthesize glycans; and 2) the diversity and activity of glycosidases that turn over and remodel glycans in the airway lumen. This study will test the hypothesis that secretor positive asthmatic patients are susceptible to virus-induced asthma exacerbation and that abnormal glycosidase activity in secretions modifies the glycan coat and promotes virus-induced exacerbation.
DESIGN NARRATIVE:
Secretor status will be studied in order to determine whether it is a risk factor for asthma exacerbations precipitated by viruses. Preliminary studies suggest that secretor positive asthmatics are prone to asthma exacerbations and that asthmatic patients have abnormal glycosidase activity in their airway secretions. This study will explore these findings further in the following two ways: 1) a case-control study will compare secretor status and frequency of viral airway infection in 50 asthmatic patients hospitalized for management of acute severe asthma to 50 asthmatic subjects in the outpatient setting without a history of severe asthma exacerbation. Sputum samples or tracheal aspirates (from intubated patients) will be collected from all patients. In these samples, DNA will be used as a microarray to detect viruses; and 2) epithelial brushings and bronchial biopsies from a tissue bank will be used to establish the relationship between secretor status (erythrocyte Lea and Leb phenotyping) and airway epithelial cell activity of FUT genes (real time RT-PCR), and expression of Lea, Leb, A, B, and H antigens (immunohistochemistry).
Conditions
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Study Design
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CASE_CONTROL
PROSPECTIVE
Study Groups
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Exacerbation resistant asthma
Control group
Screening
Characterization tests including blood group typing, measures of lung function, measures of allergy, and collection of DNA.
Exacerbation prone asthma
Cases
Screening
Characterization tests including blood group typing, measures of lung function, measures of allergy, and collection of DNA.
Interventions
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Screening
Characterization tests including blood group typing, measures of lung function, measures of allergy, and collection of DNA.
Eligibility Criteria
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Inclusion Criteria
* History of asthma exacerbation in the 2 years prior to study entry requiring treatment with oral corticosteroids
Exclusion Criteria
* History of asthma exacerbations requiring treatment with oral corticosteroids since age 12 (control group)
18 Years
75 Years
ALL
No
Sponsors
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National Heart, Lung, and Blood Institute (NHLBI)
NIH
University of California, San Francisco
OTHER
Responsible Party
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Principal Investigators
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John V. Fahy
Role: STUDY_CHAIR
University of California, San Francisco
Locations
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University of California, San Francisco
San Francisco, California, United States
Countries
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References
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Innes AL, McGrath KW, Dougherty RH, McCulloch CE, Woodruff PG, Seibold MA, Okamoto KS, Ingmundson KJ, Solon MC, Carrington SD, Fahy JV. The H antigen at epithelial surfaces is associated with susceptibility to asthma exacerbation. Am J Respir Crit Care Med. 2011 Jan 15;183(2):189-94. doi: 10.1164/rccm.201003-0488OC. Epub 2010 Aug 23.
Other Identifiers
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283
Identifier Type: -
Identifier Source: org_study_id
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