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

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• 作者：Wendy C. Moore ; MD^a ; ^{wmoore@wakehealth.edu" class="auth_mail} ; Annette T. Hastie ; PhD^a ; Xingnan Li ; PhD ; MS^a ; Huashi Li ; MS^a ; William W. Busse ; MD^b ; Nizar N. Jarjour ; MD^b ; Sally E. Wenzel ; MD^c ; Stephen P. Peters ; MD ; PhD^a ; Deborah A. Meyers ; PhD^a ; Eugene R. Bleecker ; MD^a ; for the National Heart ; Lung ; Blood Institute's Severe Asthma Research Program d
• 关键词：Severe Asthma Research Program ; severe asthma ; sputum ; eosinophils ; neutrophils ; phenotype ; cluster analysis
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：June 2014
• 年：2014
• 卷：133
• 期：6
• 页码：1557-1563.e5
• 全文大小：552 K

文摘

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.