Histoblood Group Antigens as a Risk Factor of Asthma
Condition: Asthma; Lung Diseases
MeSH terms: Asthma; Lung Diseases
Study type: Observational

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

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).
    

Intervention name(s): Screening
Intervention type(s): Procedure
Intervention description(s): Characterization tests including blood group typing, measures of lung function, measures of allergy, and collection of DNA.
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Asthmatics of two types: 1. Exacerbation resistant asthma (no requirement for prednisone
        for asthma since age 12). 2. Exacerbation prone asthma (requirement for prednisone for
        asthma in the past 2 years).
      
Biospecimen description: 
      DNA, plasma, saliva, induced sputum.