Histoblood Group Antigens as a Risk Factor of Asthma

Asthma Clinical Trial

Official title:

Histoblood Group Antigens, Viruses and Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00201266
• Other study ID #: 283
• Secondary ID: R01HL080414
• Status: Completed
• Phase: N/A
• First received: September 16, 2005
• Last updated: March 11, 2013
• Start date: July 2005

Study information

• Verified date: March 2013
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

This study will evaluate the link between blood group antigens and asthma exacerbations.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 126
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Asthma
• Lung Diseases

Intervention

Procedure:
• Screening
Characterization tests including blood group typing, measures of lung function, measures of allergy, and collection of DNA.

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Asthma exacerbations requiring prednisone		Prior 2 years	Yes
Secondary	Lung fuction	FEV1% predicted	Current	Yes