The H antigen at epithelial surfaces is associated with susceptibility to asthma exacerbation.

rationaleAcute asthma exacerbations, precipitated by viral infections, are a significant cause of morbidity, but not all patients with asthma are equally susceptible.

objectivesTo explore susceptibility factors for asthma exacerbations, we considered a role for histoblood group antigens because they are implicated in mechanisms of gastrointestinal viral infection, specifically the O-secretor mucin glycan phenotype. We investigated if this phenotype is associated with susceptibility to asthma exacerbation.

methodsWe performed two consecutive case-control studies in subjects with asthma who were either prone or resistant to asthma exacerbations. Exacerbation-prone cases had frequent use of prednisone for an asthma exacerbation and frequent asthma-related healthcare utilization, whereas exacerbation-resistant control subjects had rarely reported asthma exacerbations. The frequency of different mucin glycan phenotypes, defined by the presence or absence of H (O), A, B, or AB antigens, was compared in cases and control subjects. MEASUREMENTS AND MAIN

resultsIn an initial study consisting of 49 subjects with asthma (23 cases and 26 control subjects), we found that having the O-secretor phenotype was associated with a 5.8-fold increase in the odds of being a case (95% confidence interval, 1.7-21.0; P = 0.006). In a replication study consisting of 204 subjects with asthma (101 cases and 103 control subjects), we found that having the O-secretor phenotype was associated with a 2.3-fold increased odds of being a case (95% confidence interval, 1.2-4.4; P = 0.02).

conclusionsThe O-secretor mucin glycan phenotype is associated with susceptibility to asthma exacerbation. Clinical trial registered at www.clinicaltrials.gov (NCT00201266).