title: Exacerbation risk in severe asthma is stratified by inflammatory phenotype using longitudinal measures of sputum eosinophils.
abstract: Airway inflammatory phenotyping is increasingly applied to subjects with asthma. However, its relationship to clinical outcomes in difficult asthma is incompletely elucidated.
  
  
  
  The goal of our study was to determine the relationship between exacerbation rates and phenotypes of difficult asthma based on the longitudinal measures of sputum eosinophils and neutrophils.
  
  
  
  Subjects in the longitudinal observational study from two tertiary care centres that completed 1 year of observation and provided at least three sputum samples were classified by inflammatory phenotypes using previously established thresholds. Kaplan-Meier curves and univariable and multivariable Cox proportional hazard models were used to determine the association between inflammatory phenotypes and exacerbation rate.
  
  
  
  During the study, 115 exacerbations occurred in 73 severe asthmatic subjects. Subjects with the persistently eosinophilic phenotype had a significantly shorter time to first exacerbation and greater risk of exacerbation over a 1-year period than those with the non-eosinophilic phenotype based on the univariable and multivariable Cox proportional hazard model (hazard ratio [HR], 3.24; 95% confidence interval [CI], 1.35-7.72; adjusted HR, 3.90; 95% CI, 1.34-11.36). No significant differences in time to first exacerbation or exacerbation risk over a 1-year period were observed among the neutrophilic phenotypes.
  
  
  
  The persistent eosinophilic phenotype is associated with increased exacerbation risk compared with the non-eosinophilic phenotype in severe asthma. No differences in time to first exacerbation or exacerbation risk over a 1-year period were detected among neutrophilic phenotypes.
authors.affiliation: Department of Medicine, Institute of Medical Sciences, Keenan Centre for Biomedical Research, Li Ka Shing Knowledge institute, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: C J
authors.initials: CJ
authors.lastname: Walsh
authors.affiliation: Department of Mathematics, SUNY-Brockport, Brockport, NY, USA.
authors.forename: T
authors.initials: T
authors.lastname: Zaihra
authors.affiliation: Respiratory Epidemiology and Clinical Research Unit, McGill University Health Centre, Montreal, QC, Canada.|Department of Medicine, McGill University, Montreal, QC, Canada.|Department of Epidemiology, Biostatistics and Occupational health, McGill University, Montreal, QC, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Benedetti
authors.affiliation: Montreal Chest Institute and the Meakins-Christie Laboratories, Montreal, QC, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Fugère
authors.affiliation: Montreal Chest Institute and the Meakins-Christie Laboratories, Montreal, QC, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Olivenstein
authors.affiliation: Research Centre, Hôpital du Sacré-Cœur de, Montreal, QC, Canada.|Faculty of Medicine, University de Montreal, Montreal, QC, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Lemière
authors.affiliation: Montreal Chest Institute and the Meakins-Christie Laboratories, Montreal, QC, Canada.
authors.forename: Q
authors.initials: Q
authors.lastname: Hamid
authors.affiliation: Department of Medicine, McGill University, Montreal, QC, Canada. james.martin@mcgill.ca.
authors.forename: J G
authors.initials: JG
authors.lastname: Martin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D018450:Disease Progression; D004804:Eosinophils / Q000473:pathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D010641:Phenotype; D011446:Prospective Studies; D012129:Respiratory Function Tests; D012307:Risk Factors; D012720:Severity of Illness Index; D013183:Sputum / Q000166:cytology* / Q000276:immunology*; D055815:Young Adult
chemical_list: D018927:Anti-Asthmatic Agents
keywords: asthma exacerbation; biomarkers; longitudinal study; severe asthma