RATIONALE: Acute asthma exacerbations, precipitated by viral infections, are a significant cause of morbidity, but not all patients with asthma are equally susceptible. OBJECTIVES: To 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. METHODS: We 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 RESULTS: In 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). CONCLUSIONS: The O-secretor mucin glycan phenotype is associated with susceptibility to asthma exacerbation. Clinical trial registered at www.clinicaltrials.gov (NCT00201266).
RATIONALE: Acute asthma exacerbations, precipitated by viral infections, are a significant cause of morbidity, but not all patients with asthma are equally susceptible. OBJECTIVES: To 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. METHODS: We 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 RESULTS: In 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). CONCLUSIONS: The O-secretor mucin glycan phenotype is associated with susceptibility to asthma exacerbation. Clinical trial registered at www.clinicaltrials.gov (NCT00201266).
Authors: R Pellegrino; G Viegi; V Brusasco; R O Crapo; F Burgos; R Casaburi; A Coates; C P M van der Grinten; P Gustafsson; J Hankinson; R Jensen; D C Johnson; N MacIntyre; R McKay; M R Miller; D Navajas; O F Pedersen; J Wanger Journal: Eur Respir J Date: 2005-11 Impact factor: 16.671
Authors: Lisa Lindesmith; Christine Moe; Severine Marionneau; Nathalie Ruvoen; Xi Jiang; Lauren Lindblad; Paul Stewart; Jacques LePendu; Ralph Baric Journal: Nat Med Date: 2003-04-14 Impact factor: 53.440
Authors: S L Johnston; P K Pattemore; G Sanderson; S Smith; F Lampe; L Josephs; P Symington; S O'Toole; S H Myint; D A Tyrrell Journal: BMJ Date: 1995-05-13
Authors: Peter W Heymann; Holliday T Carper; Deborah D Murphy; Thomas A E Platts-Mills; James Patrie; Anne P McLaughlin; Elizabeth A Erwin; Marcus S Shaker; Martha Hellems; Jehanna Peerzada; Frederick G Hayden; Tina K Hatley; Rachel Chamberlain Journal: J Allergy Clin Immunol Date: 2004-08 Impact factor: 10.793
Authors: Christopher M Evans; Tasha E Fingerlin; Marvin I Schwarz; David Lynch; Jonathan Kurche; Laura Warg; Ivana V Yang; David A Schwartz Journal: Physiol Rev Date: 2016-10 Impact factor: 37.312
Authors: Ian J Welsby; Barbara Phillips-Bute; Joseph P Mathew; Mark F Newman; Richard Becker; Sunil Rao; Carmelo A Milano; Mark Stafford-Smith Journal: J Thromb Thrombolysis Date: 2014-10 Impact factor: 2.300
Authors: Christopher M Evans; Dorota S Raclawska; Fani Ttofali; Deborah R Liptzin; Ashley A Fletcher; Daniel N Harper; Maggie A McGing; Melissa M McElwee; Olatunji W Williams; Elizabeth Sanchez; Michelle G Roy; Kristen N Kindrachuk; Thomas A Wynn; Holger K Eltzschig; Michael R Blackburn; Michael J Tuvim; William J Janssen; David A Schwartz; Burton F Dickey Journal: Nat Commun Date: 2015-02-17 Impact factor: 14.919