寡细胞型哮喘的异质性：前瞻性队列研究的层次聚类分析
2021/02/09
摘要
背景：哮喘是一种异质性疾病，根据诱导痰细胞计数可分为四种炎症表型：嗜酸粒细胞性哮喘（EA）、中性粒细胞性哮喘（NA）、混合粒细胞性哮喘（MGA）和寡细胞性哮喘（PGA）。虽然研究主要集中在EA和NA，但对PGA知之甚少。
目的：研究寡细胞性哮喘（PGA）的异质性，找出可能的PGA簇，指导临床治疗。
方法：采用分层聚类分析对PGA患者进行分组，并纳入前瞻性队列研究，以验证这些聚类与现实环境中哮喘未来急性加重风险的相关性。在一个单独的群体中通过树分析来验证聚类。最后，我们探讨了PGA的稳定性。
结果：对145例PGA患者进行聚类分析，发现3个聚类：聚类1（n=110，75.9%）为“轻度PGA”，聚类2（n=20，13.8%）为“伴有心理障碍和鼻炎等过敏性疾病的PGA”，聚类3（n=15，10.3%为“吸烟相关PGA”。第3组急性加重（RR=6.43，P=0.01）、急诊（RR=8.61，P=0.03）和住院（RR=12.94，P<0.01）风险显著增加。聚类分析的结果在一个独立的PGA群体中得到了验证。虽然PGA可以转化成其他表型或从其他表型发展而来，但70%的PGA随着时间的推移是稳定的。
结论：在三个确定的PGA簇中，簇3有更高的急性加重风险。PGA异质性表明需要新的有针对性的干预措施。
Heterogeneity of paucigranulocytic asthma: A prospective cohort study with hierarchical cluster analysis
Ke Deng, Xin Zhang, Ying Liu, Li Zhang, Gang Wang, Min Feng, Brian G Oliver, Lei Wang, Philip M Hansbro, Lin Qin, Min Xie, Zhi Hong Chen, Jodie Simpson, Jie Zhang, Wei Min Li, Gang Wang, Peter Gerard Gibson
Abstract
Background: Asthma, a heterogeneous disease, can be divided into four inflammatory phenotypes using induced sputum cell counts -eosinophilic asthma (EA), neutrophilic asthma (NA), mixed granulocytic asthma (MGA), and paucigranulocytic asthma (PGA). While research has focused on EA and NA, there is little known on 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 three 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 (RR = 6.43, P = 0.01), emergency visit (RR = 8.61, P = 0.03), and hospitalization (RR = 12.94, P < 0.01). 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 three identified PGA clusters, Cluster 3 had a higher risk of severe exacerbation. PGA heterogeneity indicates the requirement of novel targeted interventions.
背景：哮喘是一种异质性疾病，根据诱导痰细胞计数可分为四种炎症表型：嗜酸粒细胞性哮喘（EA）、中性粒细胞性哮喘（NA）、混合粒细胞性哮喘（MGA）和寡细胞性哮喘（PGA）。虽然研究主要集中在EA和NA，但对PGA知之甚少。
目的：研究寡细胞性哮喘（PGA）的异质性，找出可能的PGA簇，指导临床治疗。
方法：采用分层聚类分析对PGA患者进行分组，并纳入前瞻性队列研究，以验证这些聚类与现实环境中哮喘未来急性加重风险的相关性。在一个单独的群体中通过树分析来验证聚类。最后，我们探讨了PGA的稳定性。
结果：对145例PGA患者进行聚类分析，发现3个聚类：聚类1（n=110，75.9%）为“轻度PGA”，聚类2（n=20，13.8%）为“伴有心理障碍和鼻炎等过敏性疾病的PGA”，聚类3（n=15，10.3%为“吸烟相关PGA”。第3组急性加重（RR=6.43，P=0.01）、急诊（RR=8.61，P=0.03）和住院（RR=12.94，P<0.01）风险显著增加。聚类分析的结果在一个独立的PGA群体中得到了验证。虽然PGA可以转化成其他表型或从其他表型发展而来，但70%的PGA随着时间的推移是稳定的。
结论：在三个确定的PGA簇中，簇3有更高的急性加重风险。PGA异质性表明需要新的有针对性的干预措施。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(7.574 J Allergy Clin Immunol Pract. 2021 Jan 19;S2213-2198(21)00060-X. doi: 10.1016/j.jaip.2021.01.004.)
(7.574 J Allergy Clin Immunol Pract. 2021 Jan 19;S2213-2198(21)00060-X. doi: 10.1016/j.jaip.2021.01.004.)
Heterogeneity of paucigranulocytic asthma: A prospective cohort study with hierarchical cluster analysis
Ke Deng, Xin Zhang, Ying Liu, Li Zhang, Gang Wang, Min Feng, Brian G Oliver, Lei Wang, Philip M Hansbro, Lin Qin, Min Xie, Zhi Hong Chen, Jodie Simpson, Jie Zhang, Wei Min Li, Gang Wang, Peter Gerard Gibson
Abstract
Background: Asthma, a heterogeneous disease, can be divided into four inflammatory phenotypes using induced sputum cell counts -eosinophilic asthma (EA), neutrophilic asthma (NA), mixed granulocytic asthma (MGA), and paucigranulocytic asthma (PGA). While research has focused on EA and NA, there is little known on 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 three 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 (RR = 6.43, P = 0.01), emergency visit (RR = 8.61, P = 0.03), and hospitalization (RR = 12.94, P < 0.01). 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 three identified PGA clusters, Cluster 3 had a higher risk of severe exacerbation. PGA heterogeneity indicates the requirement of novel targeted interventions.
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嗜酸粒细胞性重症哮喘和嗜酸粒细胞性COPD患者2型气道炎症的分子标志物相似
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Caspase-11促进过敏性气道炎症
