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Nasal epithelial gene expression identifies relevant asthma endotypes in the ATLANTIS study
Thorax ( IF 9.0 ) Pub Date : 2024-07-15 , DOI: 10.1136/thorax-2023-221230 Tatiana Karp , Alen Faiz , Jos van Nijnatten , Huib A M Kerstjens , Ilse Boudewijn , Monica Kraft , Judith M Vonk , Martijn C Nawijn , Irene H Heijink , Bianca Beghé , Klaus F Rabe , Alberto Papi , Chris Brightling , Dave Singh , Thys van der Molen , Salman Siddiqui , Stephanie Christenson , Victor Guryev , Maarten van den Berge
Thorax ( IF 9.0 ) Pub Date : 2024-07-15 , DOI: 10.1136/thorax-2023-221230 Tatiana Karp , Alen Faiz , Jos van Nijnatten , Huib A M Kerstjens , Ilse Boudewijn , Monica Kraft , Judith M Vonk , Martijn C Nawijn , Irene H Heijink , Bianca Beghé , Klaus F Rabe , Alberto Papi , Chris Brightling , Dave Singh , Thys van der Molen , Salman Siddiqui , Stephanie Christenson , Victor Guryev , Maarten van den Berge
Introduction Asthma is an inflammatory airways disease encompassing multiple phenotypes and endotypes. Several studies suggested gene expression in nasal epithelium to serve as a proxy for bronchial epithelium, being a non-invasive approach to investigate lung diseases. We hypothesised that molecular differences in upper airway epithelium reflect asthma-associated differences in the lower airways and are associated with clinical expression of asthma. Methods We analysed nasal epithelial gene expression data from 369 patients with asthma and 58 non-asthmatic controls from the Assessment of Small Airways Involvement in Asthma study. Unsupervised hierarchical clustering was performed on asthma-associated genes. Asthma-associated gene signatures were replicated in independent cohorts with nasal and bronchial brushes data by comparing Gene Set Variation Analysis scores between asthma patients and non-asthmatic controls. Results We identified 67 higher expressed and 59 lower expressed genes in nasal epithelium from asthma patients compared with controls (false discovery rate<0.05), including CLCA1, CST1 and POSTN , genes well known to reflect asthma in bronchial airway epithelium. Hierarchical clustering revealed several molecular asthma endotypes with distinct clinical characteristics, including an endotype with higher blood and sputum eosinophils, high fractional exhaled nitric oxide, and more severe small airway dysfunction, as reflected by lower forced expiratory flow at 50%. In an independent cohort, we demonstrated that genes higher expressed in the nasal epithelium reflect asthma-associated changes in the lower airways. Conclusion Our results show that the nasal epithelial gene expression profile reflects asthma-related processes in the lower airways. We suggest that nasal epithelium may be a useful non-invasive tool to identify asthma endotypes and may advance personalised management of the disease. Data are available on reasonable request. For code used in the manuscript, see [https://github.com/TatiKarp/gene\_expression\_thorax][1]. [1]: https://github.com/TatiKarp/gene_expression_thorax
中文翻译:
ATLANTIS 研究中鼻上皮基因表达识别相关哮喘内型
简介 哮喘是一种炎症性气道疾病,包含多种表型和内型。几项研究表明鼻上皮中的基因表达可以作为支气管上皮的替代物,是研究肺部疾病的非侵入性方法。我们假设上气道上皮的分子差异反映了下气道中与哮喘相关的差异,并且与哮喘的临床表现相关。方法 我们分析了哮喘小气道参与评估研究中 369 名哮喘患者和 58 名非哮喘对照者的鼻上皮基因表达数据。对哮喘相关基因进行无监督的层次聚类。通过比较哮喘患者和非哮喘对照之间的基因集变异分析评分,在具有鼻和支气管刷数据的独立队列中复制了哮喘相关基因特征。结果 与对照组相比,我们在哮喘患者的鼻上皮中鉴定出了 67 个高表达基因和 59 个低表达基因(错误发现率<0.05),包括 CLCA1、CST1 和 POSTN,这些基因是众所周知的反映支气管气道上皮哮喘的基因。层次聚类揭示了几种具有不同临床特征的分子哮喘内型,包括血液和痰液嗜酸性粒细胞较高的内型、呼出一氧化氮分数较高以及更严重的小气道功能障碍(如 50% 时用力呼气流量较低所反映的)。在一个独立的队列中,我们证明鼻上皮中表达较高的基因反映了下呼吸道中与哮喘相关的变化。结论 我们的结果表明鼻上皮基因表达谱反映了下呼吸道哮喘相关过程。 我们认为鼻上皮可能是识别哮喘内型的有用的非侵入性工具,并可能促进该疾病的个性化管理。可根据合理要求提供数据。有关手稿中使用的代码,请参阅 [https://github.com/TatiKarp/gene\_expression\_thorax][1]。 [1]:https://github.comcom/TatiKarp/gene_express_thorax
更新日期:2024-07-16
中文翻译:
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ATLANTIS 研究中鼻上皮基因表达识别相关哮喘内型
简介 哮喘是一种炎症性气道疾病,包含多种表型和内型。几项研究表明鼻上皮中的基因表达可以作为支气管上皮的替代物,是研究肺部疾病的非侵入性方法。我们假设上气道上皮的分子差异反映了下气道中与哮喘相关的差异,并且与哮喘的临床表现相关。方法 我们分析了哮喘小气道参与评估研究中 369 名哮喘患者和 58 名非哮喘对照者的鼻上皮基因表达数据。对哮喘相关基因进行无监督的层次聚类。通过比较哮喘患者和非哮喘对照之间的基因集变异分析评分,在具有鼻和支气管刷数据的独立队列中复制了哮喘相关基因特征。结果 与对照组相比,我们在哮喘患者的鼻上皮中鉴定出了 67 个高表达基因和 59 个低表达基因(错误发现率<0.05),包括 CLCA1、CST1 和 POSTN,这些基因是众所周知的反映支气管气道上皮哮喘的基因。层次聚类揭示了几种具有不同临床特征的分子哮喘内型,包括血液和痰液嗜酸性粒细胞较高的内型、呼出一氧化氮分数较高以及更严重的小气道功能障碍(如 50% 时用力呼气流量较低所反映的)。在一个独立的队列中,我们证明鼻上皮中表达较高的基因反映了下呼吸道中与哮喘相关的变化。结论 我们的结果表明鼻上皮基因表达谱反映了下呼吸道哮喘相关过程。 我们认为鼻上皮可能是识别哮喘内型的有用的非侵入性工具,并可能促进该疾病的个性化管理。可根据合理要求提供数据。有关手稿中使用的代码,请参阅 [https://github.com/TatiKarp/gene\_expression\_thorax][1]。 [1]:https://github.comcom/TatiKarp/gene_express_thorax