Histoblood Group Antigens as a Risk Factor of Asthma
Histoblood Group Antigens, Viruses and Asthma
Study Overview
Detailed Description
BACKGROUND:
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).
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
California
-
San Francisco, California, United States, 94143
- University of California, San Francisco
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Diagnosis of asthma, as confirmed by methacholine responsiveness less than 8 mg/mL
- History of asthma exacerbation in the 2 years prior to study entry requiring treatment with oral corticosteroids
Exclusion Criteria:
- Cigarette smoking in the 10 years prior to study entry or total pack per year history greater than 10
- History of asthma exacerbations requiring treatment with oral corticosteroids since age 12 (control group)
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Exacerbation resistant asthma
Control group
|
Characterization tests including blood group typing, measures of lung function, measures of allergy, and collection of DNA.
|
|
Exacerbation prone asthma
Cases
|
Characterization tests including blood group typing, measures of lung function, measures of allergy, and collection of DNA.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Asthma exacerbations requiring prednisone
Time Frame: Prior 2 years
|
Prior 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Lung fuction
Time Frame: Current
|
FEV1% predicted
|
Current
|
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: John V. Fahy, University of California, San Francisco
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Respiratory Tract Diseases
- Bronchial Diseases
- Lung Diseases, Obstructive
- Respiratory Hypersensitivity
- Hypersensitivity, Immediate
- Hypersensitivity
- Lung Diseases
- Asthma
- Health Care Quality, Access, and Evaluation
- Investigative Techniques
- Epidemiologic Methods
- Diagnostic Techniques and Procedures
- Diagnosis
- Data Collection
- Health Care Evaluation Mechanisms
- Quality of Health Care
- Public Health
- Environment and Public Health
- Health Services
- Health Care Facilities Workforce and Services
- Preventive Health Services
- Diagnostic Services
- Health Surveys
- Surveys and Questionnaires
- Public Health Practice
- Mass Screening
Other Study ID Numbers
- 283
- R01HL080414 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.