Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis

Wendy C. Moore, Annette T. Hastie, Xingnan Li, Huashi Li, William W. Busse, Nizar N. Jarjour, Sally E. Wenzel, Stephen P. Peters, Deborah A. Meyers, Eugene R. Bleecker

Research output: Contribution to journalArticlepeer-review

461 Scopus citations


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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)1557-1563.e5
JournalJournal of Allergy and Clinical Immunology
Issue number6
StatePublished - Jun 2014
Externally publishedYes


  • Severe Asthma Research Program
  • cluster analysis
  • eosinophils
  • neutrophils
  • phenotype
  • severe asthma
  • sputum

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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