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

• Published in: Journal of allergy and clinical immunology Vol. 133; no. 6; pp. 1557 - 1563.e5
• Main Authors: Moore, Wendy C., Hastie, Annette T., Li, Xingnan, Li, Huashi, Busse, William W., Jarjour, Nizar N., Wenzel, Sally E., Peters, Stephen P., Meyers, Deborah A., Bleecker, Eugene R.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2014; Elsevier; Elsevier Limited
• Subjects: Adolescent; Adult; Age; Age Factors; Allergy and Immunology; Asthma; Asthma - blood; Asthma - diagnosis; Asthma - physiopathology; Biological and medical sciences; Body mass index; Cluster Analysis; Colleges & universities; Discriminant analysis; eosinophils; Family medical history; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granulocytes; Humans; Immunopathology; Leukocyte Count; Male; Medical sciences; Middle Aged; Multivariate analysis; Neutrophils; Phenotype; Respiratory Function Tests; Risk Factors; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; severe asthma; Severe Asthma Research Program; Severity of Illness Index; sputum; Sputum - cytology; Statistical methods; Young Adult; phenotype; ATS; eosinophils; sputum; SARP; Severe Asthma Research Program; FVC; severe asthma; ICS; HCU; cluster analysis; neutrophils; OCS; BMI; Forced vital capacity; Inhaled corticosteroid; Oral corticosteroid; American Thoracic Society; Body mass index; Health care utilization; Immunopathology; Granulocyte; Eosinophil; Numeration; Phenotype; Association; Immunology; Research program; Sputum; Neutrophil; Severe asthma
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2013.10.011

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. To better understand interactions between inflammation and clinical subphenotypes, we integrated inflammatory cellular measures and clinical variables in a new cluster analysis. 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. 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. 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.