U-BIOPRED队列中持续恶化的严重哮喘的临床和转录组特征
2022/05/17
摘要
背景：容易恶化的哮喘是严重疾病的一个特征。然而，其持续存在的基础仍不清楚。
目的：确定U-BIOPRED队列中频繁恶化者（FEs）和持续恶化者（PFEs）的临床和转录组特征。
方法：我们比较了FE（过去一年中≥2次恶化）与不经常恶化者（IE，<2次恶化）的特征，以及第二年中重复≥2次恶化的PFE与持续性IE（PIE）的特征。通过基因组变异分析，对血液、支气管和鼻腔上皮刷毛、支气管活检和痰液细胞中的转录组数据进行分析，得出103个基因特征。
结果：在317名患者中，62.4%有FE，其中63.6%有PFE；而37.6%有IE，其中61.3%有PIE。采用多变量分析，FE与短效β-激动剂的使用、鼻窦炎和每日口服皮质类固醇的使用有关，而PFE则与湿疹、短效β-激动剂的使用和哮喘控制指数有关。CEA细胞粘附分子5（CEACAM5）是PE和IE之间支气管活检中唯一不同表达的转录物。在其他四个区间没有差异表达的基因。与IE相比，FE的支气管活检中2型、T-helper 17型和1型通路信号以及与病毒感染有关的信号的表达分数较高，而与PIE相比，PFE的支气管活检中2型、1型和类固醇不敏感通路信号的表达分数较高。
结论：与IE和PIE相比，FE组及其PFE亚组与哮喘控制不佳有关，同时分别表达较高的1型和2型激活途径。
Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort
Uruj Hoda, Stelios Pavlidis, Aruna T. Bansal et al.
Abstract
BACKGROUND:Exacerbation-prone asthma is a feature of severe disease. However, the basis for its persistency remains unclear.
OBJECTIVES:To determine the clinical and transcriptomic features of frequent exacerbators (FEs) and persistent FEs (PFEs) in the U-BIOPRED cohort.
METHODS:We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE, <2 exacerbations) and of PFE with repeat ≥2 exacerbations during the following year to persistent IE (PIE). Transcriptomic data in blood, bronchial and nasal epithelial brushings, bronchial biopsies and sputum cells were analysed by gene set variation analysis for 103 gene signatures.
RESULTS:Of 317 patients, 62.4% had FE, of whom 63.6% had PFE, while 37.6% had IE, of whom 61.3% had PIE. Using multivariate analysis, FE was associated with short-acting beta-agonist use, sinusitis and daily oral corticosteroid use, while PFE was associated with eczema, short-acting beta-agonist use and asthma control index. CEA cell adhesion molecule 5 (CEACAM5) was the only differentially expressed transcript in bronchial biopsies between PE and IE. There were no differentially expressed genes in the other four compartments. There were higher expression scores for type 2, T-helper type-17 and type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while there were higher expression scores of type 2, type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE.
CONCLUSION:The FE group and its PFE subgroup are associated with poor asthma control while expressing higher type 1 and type 2 activation pathways compared to IE and PIE, respectively.
背景：容易恶化的哮喘是严重疾病的一个特征。然而，其持续存在的基础仍不清楚。
目的：确定U-BIOPRED队列中频繁恶化者（FEs）和持续恶化者（PFEs）的临床和转录组特征。
方法：我们比较了FE（过去一年中≥2次恶化）与不经常恶化者（IE，<2次恶化）的特征，以及第二年中重复≥2次恶化的PFE与持续性IE（PIE）的特征。通过基因组变异分析，对血液、支气管和鼻腔上皮刷毛、支气管活检和痰液细胞中的转录组数据进行分析，得出103个基因特征。
结果：在317名患者中，62.4%有FE，其中63.6%有PFE；而37.6%有IE，其中61.3%有PIE。采用多变量分析，FE与短效β-激动剂的使用、鼻窦炎和每日口服皮质类固醇的使用有关，而PFE则与湿疹、短效β-激动剂的使用和哮喘控制指数有关。CEA细胞粘附分子5（CEACAM5）是PE和IE之间支气管活检中唯一不同表达的转录物。在其他四个区间没有差异表达的基因。与IE相比，FE的支气管活检中2型、T-helper 17型和1型通路信号以及与病毒感染有关的信号的表达分数较高，而与PIE相比，PFE的支气管活检中2型、1型和类固醇不敏感通路信号的表达分数较高。
结论：与IE和PIE相比，FE组及其PFE亚组与哮喘控制不佳有关，同时分别表达较高的1型和2型激活途径。
(中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校)
(Clin Transl Med. 2022 Apr;12(4):e816. DOI: 10.1002/ctm2.816)
(Clin Transl Med. 2022 Apr;12(4):e816. DOI: 10.1002/ctm2.816)
Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort
Uruj Hoda, Stelios Pavlidis, Aruna T. Bansal et al.
Abstract
BACKGROUND:Exacerbation-prone asthma is a feature of severe disease. However, the basis for its persistency remains unclear.
OBJECTIVES:To determine the clinical and transcriptomic features of frequent exacerbators (FEs) and persistent FEs (PFEs) in the U-BIOPRED cohort.
METHODS:We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE, <2 exacerbations) and of PFE with repeat ≥2 exacerbations during the following year to persistent IE (PIE). Transcriptomic data in blood, bronchial and nasal epithelial brushings, bronchial biopsies and sputum cells were analysed by gene set variation analysis for 103 gene signatures.
RESULTS:Of 317 patients, 62.4% had FE, of whom 63.6% had PFE, while 37.6% had IE, of whom 61.3% had PIE. Using multivariate analysis, FE was associated with short-acting beta-agonist use, sinusitis and daily oral corticosteroid use, while PFE was associated with eczema, short-acting beta-agonist use and asthma control index. CEA cell adhesion molecule 5 (CEACAM5) was the only differentially expressed transcript in bronchial biopsies between PE and IE. There were no differentially expressed genes in the other four compartments. There were higher expression scores for type 2, T-helper type-17 and type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while there were higher expression scores of type 2, type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE.
CONCLUSION:The FE group and its PFE subgroup are associated with poor asthma control while expressing higher type 1 and type 2 activation pathways compared to IE and PIE, respectively.
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贝那利珠单抗、美泊利单抗与奥马珠单抗治疗与鼻息肉相关的严重过敏性哮喘的实际疗效
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重症哮喘患者对生物制剂家庭给药的看法：一项国际定性研究
