National Heart and Lung Institute, Imperial College London, and Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK.
Department of Computing & Data Science Institute, Imperial College London.
Clin Transl Med. 2022 Apr;12(4):e816. doi: 10.1002/ctm2.816.
Exacerbation-prone asthma is a feature of severe disease. However, the basis for its persistency remains unclear.
To determine the clinical and transcriptomic features of frequent exacerbators (FEs) and persistent FEs (PFEs) in the U-BIOPRED cohort.
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.
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.
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.
易恶化哮喘是严重疾病的一个特征。然而，其持续性的基础仍不清楚。
在 U-BIOPRED 队列中确定频繁恶化者（FE）和持续性频繁恶化者（PFEs）的临床和转录组特征。
我们比较了 FE（过去一年中≥2 次恶化）与非频繁恶化者（IE，<2 次恶化）以及 PFE 与次年再次出现≥2 次恶化与持续性 IE（PIE）的特征。通过基因集变异分析对 103 个基因特征分析了血液、支气管和鼻上皮刷取物、支气管活检和痰细胞中的转录组数据。
在 317 名患者中，62.4%为 FE，其中 63.6%为 PFE，而 37.6%为 IE，其中 61.3%为 PIE。使用多变量分析，FE 与短效β-激动剂使用、鼻窦炎和每日口服皮质类固醇使用相关，而 PFE 与特应性皮炎、短效β-激动剂使用和哮喘控制指数相关。CEA 细胞黏附分子 5（CEACAM5）是支气管活检中 PE 和 IE 之间唯一差异表达的转录物。在其他四个隔室中没有差异表达的基因。与 IE 相比，FE 患者支气管活检中 2 型、辅助性 T 细胞 17 型和 1 型途径特征以及与病毒感染相关的基因表达评分更高，而 PFE 患者支气管活检中 2 型、1 型和类固醇不敏感途径特征的表达评分更高。
FE 组及其 PFE 亚组与较差的哮喘控制相关，与 IE 和 PIE 相比，分别表现出更高的 1 型和 2 型激活途径。
