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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:133

Article

Moore, Wendy C.^1,2  Hastie, Annette T.^1,2  Li, Xingnan^1,2  Li, Huashi^1,2  Busse, William W.³  Jarjour, Nizar N.³  Wenzel, Sally E.⁴  Peters, Stephen P.^1,2  Meyers, Deborah A.^1,2  Bleecker, Eugene R.^1,2 

[1] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA

[2] Sect Pulm Crit Care Allergy & Immunol Dis, Winston Salem, NC USA

[3] Univ Wisconsin, Sch Med & Publ Hlth, Allergy Pulm & Crit Care Div, Madison, WI 53706 USA

[4] Univ Pittsburgh, Sch Med Pulm Allergy & Crit Care Med, Bethesda, MD USA

[5] NHLBI, Severe Asthma Res Program, Bethesda, MD 20892 USA

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

DOI  :  10.1016/j.jaci.2013.10.011

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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