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J Allergy Clin Immunol. 2014 Jun;133(6):1557-63.e5. doi: 10.1016/j.jaci.2013.10.011. Epub 2013 Dec 9.

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

Author information

1
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.
2
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.
3
University of Wisconsin School of Medicine and Public Health, Allergy, Pulmonary and Critical Care Division, Madison, Wis.
4
University of Pittsburgh School of Medicine, Pulmonary, Allergy and Critical Care Medicine, Pittsburgh, Pa.

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.

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.

KEYWORDS:

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

PMID:
24332216
PMCID:
PMC4040309
DOI:
10.1016/j.jaci.2013.10.011
[Indexed for MEDLINE]
Free PMC Article

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