少粒细胞性哮喘的异质性：一项采用层次聚类分析的前瞻性队列研究。

Heterogeneity of Paucigranulocytic Asthma: A Prospective Cohort Study with Hierarchical Cluster Analysis.

机构信息

Department of Respiratory and Critical Care Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Laboratory of Pulmonary Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu, Sichuan, China.

Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

J Allergy Clin Immunol Pract. 2021 Jun;9(6):2344-2355. doi: 10.1016/j.jaip.2021.01.004. Epub 2021 Jan 20.

DOI:10.1016/j.jaip.2021.01.004

PMID:33482419

Abstract

BACKGROUND

Asthma, a heterogeneous disease, can be divided into 4 inflammatory phenotypes using induced sputum cell counts-eosinophilic asthma (EA), neutrophilic asthma (NA), mixed granulocytic asthma, and paucigranulocytic asthma (PGA). Although research has focused on EA and NA, there is little known about PGA.

OBJECTIVE

To study the heterogeneity of PGA and identify possible PGA clusters to guide clinical treatment.

METHODS

Patients with PGA were grouped by hierarchical cluster analysis and enrolled into a prospective cohort study to validate the clusters, relative to future risk of asthma exacerbations in a real-world setting. Clusters were validated by tree analysis in a separate population. Finally, we explored PGA stability.

RESULTS

Cluster analysis of 145 patients with PGA identified 3 clusters: cluster 1 (n = 110, 75.9%) was "mild PGA," cluster 2 (n = 20, 13.8%) was "PGA with psychological dysfunction and rhinoconjunctivitis and other allergic diseases," and cluster 3 (n = 15, 10.3%) was "smoking-associated PGA." Cluster 3 had significantly increased risk of severe exacerbation (relative risk [RR] = 6.43, P = .01), emergency visit (RR = 8.61, P = .03), and hospitalization (RR = 12.94, P < .01). Results of the cluster analysis were successfully validated in an independent PGA population classified using decision tree analysis. Although PGA can transform into or develop from other phenotypes, 70% were stable over time.

CONCLUSIONS

Among 3 identified PGA clusters, cluster 3 had a higher risk of severe exacerbation. PGA heterogeneity indicates the requirement of novel targeted interventions.

摘要

背景

哮喘是一种异质性疾病，可以根据诱导痰细胞计数将其分为 4 种炎症表型-嗜酸性粒细胞性哮喘（EA）、中性粒细胞性哮喘（NA）、混合粒细胞性哮喘和少粒细胞性哮喘（PGA）。虽然研究集中在 EA 和 NA 上，但对 PGA 知之甚少。

目的

研究 PGA 的异质性，并确定可能的 PGA 聚类，以指导临床治疗。

方法

通过层次聚类分析将 PGA 患者分组，并将其纳入前瞻性队列研究，以验证聚类在真实环境中未来哮喘加重的风险，在另一个人群中通过树分析验证聚类。最后，我们探讨了 PGA 的稳定性。

结果

对 145 例 PGA 患者的聚类分析发现了 3 个聚类：聚类 1（n=110，75.9%）为“轻度 PGA”，聚类 2（n=20，13.8%）为“PGA 伴有心理功能障碍和鼻结膜炎及其他过敏性疾病”，聚类 3（n=15，10.3%）为“与吸烟相关的 PGA”。聚类 3 发生严重加重的风险显著增加（相对风险 [RR] = 6.43，P =.01）、急诊就诊（RR = 8.61，P =.03）和住院治疗（RR = 12.94，P <.01）。使用决策树分析对独立的 PGA 人群进行分类的聚类分析结果得到了成功验证。尽管 PGA 可以转化为或从其他表型发展而来，但 70%的患者在时间上是稳定的。