Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis.
Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis.
复制标题
DOI：
10.1016/j.jaci.2013.10.011
复制
发表时间：
2014-06
影响因子：
14.2
通讯作者：
Bleecker, Eugene R.
中科院分区：
文献类型：
--
作者：
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.
关键词：
来自严重哮喘研究计划（SARP）的临床聚类分析确定了5种哮喘亚表型，它们代表了早发性过敏性哮喘、晚发性严重哮喘和伴COPD特征的严重哮喘的严重程度谱。对一部分SARP受试者的诱导痰进行分析，发现四种痰炎细胞模式。嗜酸性粒细胞（≥2%）和中性粒细胞（≥40%）同时升高的受试者具有非常严重哮喘的特征。为了更好地理解炎症和临床亚表型之间的相互作用，我们在一个新的聚类分析中整合了炎症细胞测量和临床变量。在三个临床地点进行痰诱导的SARP参与者被纳入本分析（n=423）。通过因子分析选择临床特征、血痰炎症细胞评估等15个变量进行无监督聚类分析。鉴定出四个表型簇。A组（n=132）和B组（n=127）患者为轻中度早发型过敏性哮喘，痰中炎症细胞类型为少粒细胞或嗜酸性粒细胞。相比之下，这些炎症模式仅存在于C组（117）和D组（47）中7%的中重度哮喘患者中，这些患者尽管接受了高剂量吸入或口服皮质类固醇治疗，但仍经常使用医疗保健服务，并且在D组中，肺功能降低。这些受试者中的大多数（约83%）单独或并发嗜中性粒细胞增多。基线肺功能和痰中性粒细胞是决定聚类分配的最重要变量。这种多变量方法确定了四种哮喘亚表型，代表了从轻度或嗜酸性痰炎症为主的轻中度过敏性哮喘到以嗜中性粒细胞或混合粒细胞炎症为主的中重度哮喘的严重程度。
Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified five asthma subphenotypes that represent the severity spectrum of early onset allergic asthma, late onset severe asthma and severe asthma with COPD characteristics. Analysis of induced sputum from a subset of SARP subjects showed four sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophils (≥2%) and neutrophils (≥40%) 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 at three clinical sites who underwent sputum induction were included in this analysis (n=423). Fifteen variables including clinical characteristics and blood and sputum inflammatory cell assessments were selected by factor analysis for unsupervised cluster analysis. Four phenotypic clusters were identified. Cluster A (n=132) and B (n=127) subjects had mild-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-severe asthma with frequent health care utilization despite treatment with high doses of inhaled or oral corticosteroids, and in Cluster D, reduced lung function. The majority these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophils were the most important variables determining cluster assignment. This multivariate approach identified four asthma subphenotypes representing the severity spectrum from mild-moderate allergic asthma with minimal or eosinophilic predominant sputum inflammation to moderate-severe asthma with neutrophilic predominant or mixed granulocytic inflammation.
登录
查看更多内容
影响因子：
6.1
作者：
Nair, P.;Gaga, M.;Chanez, P.
通讯作者：
Chanez, P.
DOI：
10.1164/rccm.200805-737oc
发表时间：
2009-01-01
影响因子：
24.7
作者：
Denning, David W.;O'Driscoll, B. Ronan;Niven, Robert M.
通讯作者：
Niven, Robert M.
DOI：
10.1164/rccm.201109-1640oc
发表时间：
2012-03-15
影响因子：
24.7
作者：
McGrath, Kelly Wong;Icitovic, Nikolina;Fahy, John V.
通讯作者：
Fahy, John V.
影响因子：
3
作者：
KAISER, HF
通讯作者：
KAISER, HF
DOI：
10.1164/rccm.200707-1134oc
发表时间：
2008-01-15
影响因子：
24.7
作者：
Simpson, Jodie L.;Powell, Heather;Gibson, Peter G.
通讯作者：
Gibson, Peter G.