痰转录组学分析和聚类揭示哮喘异质性
2025/08/31
摘要
背景：哮喘是一种由不同炎症途径形成的异质性疾病。
目的：本研究旨在研究哮喘患者的转录组谱，并分析其与炎症、气道损伤和肺功能之间的相关性。
方法：本研究纳入就诊于本三级医院呼吸科门诊的成年哮喘患者，所有患者均接受诊断性诱导痰检验，在获得其同意后使用剩余痰RNA进行批量RNA测序（n=56），并进行无监督聚类。同时本研究对受试者合并症进行回顾性分析。通过qPCR测定痰液细胞因子mRNA水平，并测定痰液上清液中的气道损伤标志物。
结果：无监督聚类将所有哮喘患者分为三个聚类。第1组包含大多数寡粒细胞哮喘患者，其特征为氧化应激上调，TLR信号传导和细胞因子途径下调；第2组中S100家族信号通路基因上调，主要与2型炎症相关，伴痰嗜酸性粒细胞增多、上皮损伤、IL-4 mRNA水平升高和过敏；第3组哮喘患者肺功能较差，炎症基因上调，嗜中性粒细胞和钙卫蛋白水平升高。
结论：除经典的2型/非2型分类外，本研究提出新的分类方法，可将哮喘分为三种不同集群。
Sputum Transcriptomic Analysis and Clustering Reveals Insight Into Asthma Heterogeneity.
Goossens J, Jonckheere AC, De Boodt S, Dilissen E, Marain N, Decaesteker T, Cortes A, Vanoirbeek JA, Seys SF, Dupont L, Bullens DMA.
Abstract
BACKGROUND:Asthma is a heterogenous disease shaped by different inflammatory pathways.
OBJECTIVES:The aim is to investigate transcriptomic profiles in asthmatic patients and associate these with inflammation, airway damage and lung function.
METHODS:Adult asthma patients attending the outpatient pneumology clinic in our tertiary center, underwent diagnostic sputum induction and upon consent remaining sputum RNA was used for bulk RNA-sequencing (n = 56) coupled with unsupervised clustering. A retrospective analysis of comorbidities was performed. Sputum cytokine mRNA levels were determined via qPCR. Airway damage markers were determined in sputum supernatant.
RESULTS:Unsupervised clustering subdivided all asthmatic patients in one of three clusters. Cluster 1 contained most of the pauci-granulocytic asthma patients in whom oxidative stress was upregulated and TLR-signalling and several cytokine pathways down-regulated. Cluster 2 had upregulated S100 family signalling pathway genes, was mostly associated to type 2 inflammation with elevated sputum eosinophils, epithelial damage, IL-4 mRNA levels and allergy. Asthma patients in cluster 3 had worse lung function, upregulated inflammatory genes, increased sputum neutrophils and calprotectin levels.
CONCLUSION: Three different asthma clusters could be identified bridging over the classical type 2/non-type 2 classification.
背景：哮喘是一种由不同炎症途径形成的异质性疾病。
目的：本研究旨在研究哮喘患者的转录组谱，并分析其与炎症、气道损伤和肺功能之间的相关性。
方法：本研究纳入就诊于本三级医院呼吸科门诊的成年哮喘患者，所有患者均接受诊断性诱导痰检验，在获得其同意后使用剩余痰RNA进行批量RNA测序（n=56），并进行无监督聚类。同时本研究对受试者合并症进行回顾性分析。通过qPCR测定痰液细胞因子mRNA水平，并测定痰液上清液中的气道损伤标志物。
结果：无监督聚类将所有哮喘患者分为三个聚类。第1组包含大多数寡粒细胞哮喘患者，其特征为氧化应激上调，TLR信号传导和细胞因子途径下调；第2组中S100家族信号通路基因上调，主要与2型炎症相关，伴痰嗜酸性粒细胞增多、上皮损伤、IL-4 mRNA水平升高和过敏；第3组哮喘患者肺功能较差，炎症基因上调，嗜中性粒细胞和钙卫蛋白水平升高。
结论：除经典的2型/非2型分类外，本研究提出新的分类方法，可将哮喘分为三种不同集群。
（中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校）
（Lung. 2025 Aug 20;203(1):89. doi: 10.1007/s00408-025-00843-1.）
Sputum Transcriptomic Analysis and Clustering Reveals Insight Into Asthma Heterogeneity.
Goossens J, Jonckheere AC, De Boodt S, Dilissen E, Marain N, Decaesteker T, Cortes A, Vanoirbeek JA, Seys SF, Dupont L, Bullens DMA.
Abstract
BACKGROUND:Asthma is a heterogenous disease shaped by different inflammatory pathways.
OBJECTIVES:The aim is to investigate transcriptomic profiles in asthmatic patients and associate these with inflammation, airway damage and lung function.
METHODS:Adult asthma patients attending the outpatient pneumology clinic in our tertiary center, underwent diagnostic sputum induction and upon consent remaining sputum RNA was used for bulk RNA-sequencing (n = 56) coupled with unsupervised clustering. A retrospective analysis of comorbidities was performed. Sputum cytokine mRNA levels were determined via qPCR. Airway damage markers were determined in sputum supernatant.
RESULTS:Unsupervised clustering subdivided all asthmatic patients in one of three clusters. Cluster 1 contained most of the pauci-granulocytic asthma patients in whom oxidative stress was upregulated and TLR-signalling and several cytokine pathways down-regulated. Cluster 2 had upregulated S100 family signalling pathway genes, was mostly associated to type 2 inflammation with elevated sputum eosinophils, epithelial damage, IL-4 mRNA levels and allergy. Asthma patients in cluster 3 had worse lung function, upregulated inflammatory genes, increased sputum neutrophils and calprotectin levels.
CONCLUSION: Three different asthma clusters could be identified bridging over the classical type 2/non-type 2 classification.
上一篇：
没有了
下一篇：
没有了
