Sputum Transcriptomic Analysis and Clustering Reveals Insight Into Asthma Heterogeneity.

IF 3.9 2区医学 Q1 RESPIRATORY SYSTEM

Lung Pub Date : 2025-08-20 DOI:10.1007/s00408-025-00843-1

Janne Goossens, Anne-Charlotte Jonckheere, Sien De Boodt, Ellen Dilissen, Nora Marain, Tatjana Decaesteker, Alvaro Cortes, Jeroen A Vanoirbeek, Sven F Seys, Lieven Dupont, Dominique M A Bullens

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引用次数: 0

Abstract

Introduction: Asthma is a heterogenous disease shaped by different inflammatory pathways. 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.

Clinical trial: ClinicalTrials.gov Identifier: NCT01224938 registered on 19 October 2010.

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痰转录组学分析和聚类揭示哮喘异质性。

简介：哮喘是一种由不同炎症途径形成的异质性疾病。目的是研究哮喘患者的转录组谱，并将其与炎症、气道损伤和肺功能联系起来。方法：在我们三级中心门诊肺炎门诊就诊的成年哮喘患者，进行了诊断性痰诱导，经同意后，将剩余的痰RNA用于批量RNA测序（n = 56）并结合无监督聚类。对合并症进行回顾性分析。通过qPCR检测痰液细胞因子mRNA水平。结果：无监督聚类将所有哮喘患者细分为三个聚类之一。聚类1包含大多数缺氧粒细胞性哮喘患者，氧化应激上调，tlr信号通路和几种细胞因子通路下调。簇2表达上调S100家族信号通路基因，主要与2型炎症相关，包括痰嗜酸性粒细胞升高、上皮细胞损伤、IL-4 mRNA水平升高和过敏。类群3哮喘患者肺功能较差，炎症基因上调，痰中性粒细胞和钙保护蛋白水平升高。结论：在经典的2型/非2型分类上，可以识别出3种不同的哮喘类型。临床试验：ClinicalTrials.gov标识符：NCT01224938，注册于2010年10月19日。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lung 医学-呼吸系统

CiteScore

9.10

自引率

10.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Lung publishes original articles, reviews and editorials on all aspects of the healthy and diseased lungs, of the airways, and of breathing. Epidemiological, clinical, pathophysiological, biochemical, and pharmacological studies fall within the scope of the journal. Case reports, short communications and technical notes can be accepted if they are of particular interest.