title: Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis.
abstract: BACKGROUND
  Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified 5 asthma subphenotypes that represent the severity spectrum of early-onset allergic asthma, late-onset severe asthma, and severe asthma with chronic obstructive pulmonary disease characteristics. Analysis of induced sputum from a subset of SARP subjects showed 4 sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophil (≥2%) and neutrophil (≥40%) percentages had characteristics of very severe asthma.
  
  
  OBJECTIVE
  To better understand interactions between inflammation and clinical subphenotypes, we integrated inflammatory cellular measures and clinical variables in a new cluster analysis.
  
  
  METHODS
  Participants in SARP who underwent sputum induction at 3 clinical sites were included in this analysis (n = 423). Fifteen variables, including clinical characteristics and blood and sputum inflammatory cell assessments, were selected using factor analysis for unsupervised cluster analysis.
  
  
  RESULTS
  Four phenotypic clusters were identified. Cluster A (n = 132) and B (n = 127) subjects had mild-to-moderate early-onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of cluster C (n = 117) and D (n = 47) subjects who had moderate-to-severe asthma with frequent health care use despite treatment with high doses of inhaled or oral corticosteroids and, in cluster D, reduced lung function. The majority of these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophil percentages were the most important variables determining cluster assignment.
  
  
  CONCLUSIONS
  This multivariate approach identified 4 asthma subphenotypes representing the severity spectrum from mild-to-moderate allergic asthma with minimal or eosinophil-predominant sputum inflammation to moderate-to-severe asthma with neutrophil-predominant or mixed granulocytic inflammation.
authors: Wake Forest School of Medicine, Center for Genomics and Personalized Medicine Research and the Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Winston-Salem, NC. Electronic address: wmoore@wakehealth.edu.
authors: Wendy C
authors: WC
authors: Moore
authors: Wake Forest School of Medicine, Center for Genomics and Personalized Medicine Research and the Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Winston-Salem, NC.
authors: Annette T
authors: AT
authors: Hastie
authors: Wake Forest School of Medicine, Center for Genomics and Personalized Medicine Research and the Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Winston-Salem, NC.
authors: Xingnan
authors: X
authors: Li
authors: Wake Forest School of Medicine, Center for Genomics and Personalized Medicine Research and the Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Winston-Salem, NC.
authors: Huashi
authors: H
authors: Li
authors: University of Wisconsin School of Medicine and Public Health, Allergy, Pulmonary and Critical Care Division, Madison, Wis.
authors: William W
authors: WW
authors: Busse
authors: University of Wisconsin School of Medicine and Public Health, Allergy, Pulmonary and Critical Care Division, Madison, Wis.
authors: Nizar N
authors: NN
authors: Jarjour
authors: University of Pittsburgh School of Medicine, Pulmonary, Allergy and Critical Care Medicine, Pittsburgh, Pa.
authors: Sally E
authors: SE
authors: Wenzel
authors: Wake Forest School of Medicine, Center for Genomics and Personalized Medicine Research and the Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Winston-Salem, NC.
authors: Stephen P
authors: SP
authors: Peters
authors: Wake Forest School of Medicine, Center for Genomics and Personalized Medicine Research and the Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Winston-Salem, NC.
authors: Deborah A
authors: DA
authors: Meyers
authors: Wake Forest School of Medicine, Center for Genomics and Personalized Medicine Research and the Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Winston-Salem, NC.
authors: Eugene R
authors: ER
authors: Bleecker
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001249:Asthma / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D016000:Cluster Analysis; D005260:Female; D006098:Granulocytes; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D010641:Phenotype; D012129:Respiratory Function Tests; D012307:Risk Factors; D012720:Severity of Illness Index; D013183:Sputum / Q000166:cytology*; D055815:Young Adult
keywords: Severe Asthma Research Program; cluster analysis; eosinophils; neutrophils; phenotype; severe asthma; sputum