FeNO区分上皮基因表达簇：来自MESOS随机对照试验的探索性分析
2022/06/17
摘要
背景：了解哮喘生物标志物与基因表达特征的关系有助于确定发病的驱动因素。
目的：对II期tralokinumab单抗试验MESOS（NCT02449473）进行事后探索性分析，旨在分析中重度哮喘患者的基线气道炎症。
方法：通过基线支气管刷检样品的转录组学分析计算T2和T17基因表达特征，3-和5-基因平均值（3-和5GM）。使用这些特征的聚类分析确定了三个不同的炎症亚组：T2LOW/T17HIGH（n=33）、T2HIGH/T17LOW（n=10）和T2LOW/T17LOW（n=27）。
结果：呼气一氧化氮（FeNO）分数在T2HIGH/T17LOW组最高，T2LOW/T17HIGH组最低（中位数[范围]：52.0 [42.5-116.3]和18.8 [6.6-128.6]ppb）；P=0.003）。高FeNO水平与高T2基因表达密切相关（Spearman ρ=0.5537；P<0.001）。研究了FeNO、血液和支气管粘膜下嗜酸性粒细胞水平以及IgE升高患者的个体差异表达基因，，其中Cystatin SN（CST1）是所有亚组中上调最多的基因（在临床定义的生物标记物高表达亚组中上调4.49-34.42倍）。
结论：FeNO有助于鉴别T2或T17基因表达的患者。FeNO水平升高与CST1高表达相关。
背景：了解哮喘生物标志物与基因表达特征的关系有助于确定发病的驱动因素。
目的：对II期tralokinumab单抗试验MESOS（NCT02449473）进行事后探索性分析，旨在分析中重度哮喘患者的基线气道炎症。
方法：通过基线支气管刷检样品的转录组学分析计算T2和T17基因表达特征，3-和5-基因平均值（3-和5GM）。使用这些特征的聚类分析确定了三个不同的炎症亚组：T2LOW/T17HIGH（n=33）、T2HIGH/T17LOW（n=10）和T2LOW/T17LOW（n=27）。
结果：呼气一氧化氮（FeNO）分数在T2HIGH/T17LOW组最高，T2LOW/T17HIGH组最低（中位数[范围]：52.0 [42.5-116.3]和18.8 [6.6-128.6]ppb）；P=0.003）。高FeNO水平与高T2基因表达密切相关（Spearman ρ=0.5537；P<0.001）。研究了FeNO、血液和支气管粘膜下嗜酸性粒细胞水平以及IgE升高患者的个体差异表达基因，，其中Cystatin SN（CST1）是所有亚组中上调最多的基因（在临床定义的生物标记物高表达亚组中上调4.49-34.42倍）。
结论：FeNO有助于鉴别T2或T17基因表达的患者。FeNO水平升高与CST1高表达相关。
(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)
(J Allergy Clin Immunol. 2022 May 7;S0091-6749(22)00620-0. doi: 10.1016/j.jaci.2022.04.024.)
(J Allergy Clin Immunol. 2022 May 7;S0091-6749(22)00620-0. doi: 10.1016/j.jaci.2022.04.024.)
FeNO differentiates epithelial gene expression clusters: exploratory analysis from the MESOS randomised controlled trial
Sarah Diver, Sriram Sridhar, Latifa C Khalfaoui, Richard J Russell, Claire Emson, Janet M Griffiths, Melissa de Los Reyes, Da Yin, Gene Colice, Christopher E Brightling
Abstract
Background：Understanding how asthma biomarkers relate to gene expression signatures could help identify drivers of pathogenesis.
Objective：This post hoc exploratory analysis of the phase II tralokinumab trial, MESOS (NCT02449473), aimed to profile baseline airway inflammation in patients with moderate-to-severe asthma.
Methods：The T2 and T17 gene expression signatures, 3- and 5- gene mean (3- and 5GM) were calculated through transcriptomic analysis of baseline bronchial brushing samples. Clustering analysis using these signatures identified three distinct inflammatory subgroups: T2LOW/T17HIGH (n = 33), T2HIGH/T17LOW (n = 10) and T2LOW/T17LOW (n = 27).
Results：Fractional exhaled nitric oxide (FeNO) levels were highest for T2HIGH/T17LOW and lowest for T2LOW/T17HIGH (median [range], 52.0 [42.5-116.3] and 18.8 [6.6-128.6] parts per billion (ppb), respectively; P = 0.003). High FeNO levels strongly correlated with high T2 gene expression (Spearman ρ = 0.5537; P < 0.001). Individual genes differentially expressed in patients with elevated levels of FeNO, blood and bronchial submucosal eosinophils, and IgE were explored, with Cystatin SN (CST1) the most up-regulated gene in all subgroups (4.49-34.42-fold upregulation across clinically defined subgroups with high biomarker expression).
Conclusion：FeNO may be useful to differentiate patients with T2 or T17 gene expression. Elevated FeNO levels were associated with high CST1 expression.
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短效β2-激动剂处方与哮喘的不良临床结果有关：多国、横断面SABINA Ⅲ 研究
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儿童肥胖相关哮喘的内分型：人体测量、代谢、营养和CD4+淋巴细胞对肺功能的影响
