鼻气道转录组可反映下气道中部分哮喘相关基因特征
2026/03/30
摘要
背景：支气管刷检转录组分析可揭示与哮喘相关的基因特征，但由于支气管镜检查具有侵入性，其临床应用受到一定限制。基于“统一气道”假说，本研究旨在评估鼻腔刷检样本是否以及在多大程度上能够反映下气道中与哮喘相关的转录组学改变。
方法：本研究基于ARMS队列开展，共纳入26例哮喘患者和28例健康对照，所有受试者均完成了系统的临床表型评估。研究者采集鼻腔及支气管刷检样本并进行RNA测序。采用edgeR及加权基因共表达网络分析（WGCNA）鉴定支气管刷检样本中与哮喘相关的基因及基因模块，随后分析其在ARMS队列鼻腔刷检样本中的表达模式，并在独立的ATLANTIS队列（n = 427）中进行验证。
结果：研究在下气道中共鉴定出51个与哮喘相关的基因，其中与健康对照相比，哮喘患者有40个基因上调、11个基因下调。在这40个上调基因中，有7个基因在ARMS队列的鼻腔刷检样本中同样呈上调表达，并在ATLANTIS队列中得到验证，分别为CLCA1、FETUB、CST1、NTRK2、CDH26、TPSAB1和DHX35。WGCNA分析进一步显示，在ARMS队列的支气管与鼻腔刷检样本中，有2个基因模块在哮喘中持续升高，且该结果在ATLANTIS队列中获得证实。其中一个模块主要表征IL-13驱动的炎症反应，另一个模块则主要反映肥大细胞活化状态。
结论：尽管上下气道中哮喘相关基因特征仅有有限重叠，但其重叠部分具有明确的生物学意义，表现为7个基因及2个基因模块在哮喘中持续上调。这些共同的分子特征表明，2型炎症至少包含IL-13驱动的炎症反应和肥大细胞活化两个相对独立的组成部分。该研究提示，特定鼻腔基因特征可望作为无创性标志物，用于识别不同分子机制驱动的哮喘内表型。
关键词：IL-13相关炎症；哮喘；无创性；2型炎症；联合气道
Abstract
Background: Transcriptomic analysis of bronchial brushes reveals asthma-associated gene signatures but is limited by the invasiveness of bronchoscopy. Based on the "united airways" hypothesis, we evaluated whether and to what extent nasal brushes reflect asthma-associated transcriptomic changes in the lower airways.
Methods:In the ARMS study, we included 26 asthma patients and 28 healthy controls, all fully clinically characterized. Nasal and bronchial brushes were collected for RNA sequencing. We used edgeR and WGCNA to identify asthma-associated genes and modules in bronchial brushes. We assessed their expression patterns in ARMS nasal brushes and validated the findings in the independent ATLANTIS study (n = 427).
Results:We identified 51 asthma-associated genes in the lower airways, of which 40 were up-regulated and 11 were down-regulated in asthma compared to healthy controls. Seven of the 40 up-regulated genes were also up-regulated in ARMS nasal brushes and validated in ATLANTIS: CLCA1, FETUB, CST1, NTRK2, CDH26, TPSAB1, and DHX35. WGCNA revealed two modules that were consistently elevated in asthma across bronchial and nasal brushes in ARMS and confirmed in ATLANTIS. One module represents IL-13 related inflammation, whereas the other represents mast cell activity.
Conclusion:The asthma-associated gene signatures of the lower and upper airways show a limited but biologically coherent overlap, with seven genes and two gene modules consistently elevated in asthma. The shared gene signatures reflect two separate components of type 2 inflammation: IL-13 related inflammation and mast cell activity. Selected nasal gene signatures offer a non-invasive tool to identify asthma endotypes with distinct molecular mechanisms driving underlying disease biology.
Keywords:IL‐13 related inflammation; asthma; non‐invasive; type 2 inflammation; united airways.
背景：支气管刷检转录组分析可揭示与哮喘相关的基因特征，但由于支气管镜检查具有侵入性，其临床应用受到一定限制。基于“统一气道”假说，本研究旨在评估鼻腔刷检样本是否以及在多大程度上能够反映下气道中与哮喘相关的转录组学改变。
方法：本研究基于ARMS队列开展，共纳入26例哮喘患者和28例健康对照，所有受试者均完成了系统的临床表型评估。研究者采集鼻腔及支气管刷检样本并进行RNA测序。采用edgeR及加权基因共表达网络分析（WGCNA）鉴定支气管刷检样本中与哮喘相关的基因及基因模块，随后分析其在ARMS队列鼻腔刷检样本中的表达模式，并在独立的ATLANTIS队列（n = 427）中进行验证。
结果：研究在下气道中共鉴定出51个与哮喘相关的基因，其中与健康对照相比，哮喘患者有40个基因上调、11个基因下调。在这40个上调基因中，有7个基因在ARMS队列的鼻腔刷检样本中同样呈上调表达，并在ATLANTIS队列中得到验证，分别为CLCA1、FETUB、CST1、NTRK2、CDH26、TPSAB1和DHX35。WGCNA分析进一步显示，在ARMS队列的支气管与鼻腔刷检样本中，有2个基因模块在哮喘中持续升高，且该结果在ATLANTIS队列中获得证实。其中一个模块主要表征IL-13驱动的炎症反应，另一个模块则主要反映肥大细胞活化状态。
结论：尽管上下气道中哮喘相关基因特征仅有有限重叠，但其重叠部分具有明确的生物学意义，表现为7个基因及2个基因模块在哮喘中持续上调。这些共同的分子特征表明，2型炎症至少包含IL-13驱动的炎症反应和肥大细胞活化两个相对独立的组成部分。该研究提示，特定鼻腔基因特征可望作为无创性标志物，用于识别不同分子机制驱动的哮喘内表型。
关键词：IL-13相关炎症；哮喘；无创性；2型炎症；联合气道
（南方医科大学南方医院 凌嘉骏 朱邦 樊可可 赵海金）
（Wen H, Kole T, et, al. Nasal Airway Transcriptome Reflects Selected Asthma-Associated Gene Signatures in the Lower Airways. Allergy. 2026 Mar 10. doi: 10.1111/all.70283. Epub ahead of print. PMID: 41805075.）
（Wen H, Kole T, et, al. Nasal Airway Transcriptome Reflects Selected Asthma-Associated Gene Signatures in the Lower Airways. Allergy. 2026 Mar 10. doi: 10.1111/all.70283. Epub ahead of print. PMID: 41805075.）
Abstract
Background: Transcriptomic analysis of bronchial brushes reveals asthma-associated gene signatures but is limited by the invasiveness of bronchoscopy. Based on the "united airways" hypothesis, we evaluated whether and to what extent nasal brushes reflect asthma-associated transcriptomic changes in the lower airways.
Methods:In the ARMS study, we included 26 asthma patients and 28 healthy controls, all fully clinically characterized. Nasal and bronchial brushes were collected for RNA sequencing. We used edgeR and WGCNA to identify asthma-associated genes and modules in bronchial brushes. We assessed their expression patterns in ARMS nasal brushes and validated the findings in the independent ATLANTIS study (n = 427).
Results:We identified 51 asthma-associated genes in the lower airways, of which 40 were up-regulated and 11 were down-regulated in asthma compared to healthy controls. Seven of the 40 up-regulated genes were also up-regulated in ARMS nasal brushes and validated in ATLANTIS: CLCA1, FETUB, CST1, NTRK2, CDH26, TPSAB1, and DHX35. WGCNA revealed two modules that were consistently elevated in asthma across bronchial and nasal brushes in ARMS and confirmed in ATLANTIS. One module represents IL-13 related inflammation, whereas the other represents mast cell activity.
Conclusion:The asthma-associated gene signatures of the lower and upper airways show a limited but biologically coherent overlap, with seven genes and two gene modules consistently elevated in asthma. The shared gene signatures reflect two separate components of type 2 inflammation: IL-13 related inflammation and mast cell activity. Selected nasal gene signatures offer a non-invasive tool to identify asthma endotypes with distinct molecular mechanisms driving underlying disease biology.
Keywords:IL‐13 related inflammation; asthma; non‐invasive; type 2 inflammation; united airways.
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