Background

Adult-onset severe asthma is characterized by highly symptomatic disease despite high-intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease is needed for the development of targeted treatments. Gene set variation analysis is a statistical technique used to identify gene profiles in heterogeneous samples.

Objective

We sought to identify gene profiles associated with adult-onset severe asthma.

Methods

This was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at age ≥18 years) as compared with childhood-onset severe asthma (<18 years) were selected from the U-BIOPRED cohort. Gene expression was assessed on the total RNA of induced sputum (n = 83), nasal brushings (n = 41), and endobronchial brushings (n = 65) and biopsies (n = 47) (Affymetrix HT HG-U133+ PM). Gene set variation analysis was used to identify differentially enriched predefined gene signatures of leukocyte lineage, inflammatory and induced lung injury pathways.

Results

Significant differentially enriched gene signatures in patients with adult-onset as compared with childhood-onset severe asthma were identified in nasal brushings (5 signatures), sputum (3 signatures), and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells, and group 3 innate lymphoid cells were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung injury were less enriched in adult-onset severe asthma.

Conclusions

Adult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells, and group 3 innate lymphoid cells. These pathways could represent useful targets for the treatment of adult-onset severe asthma.

中文翻译：

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在成人发作的严重哮喘中使用转录组谱发现通路

背景

尽管进行了高强度哮喘治疗，但成人发作的重度哮喘仍以高度症状为特征。开发靶向治疗需要了解这种异质性疾病的潜在途径。基因集变异分析是一种统计技术，用于识别异质样本中的基因谱。

客观的

我们试图确定与成人严重哮喘相关的基因谱。

方法

这是一项横断面、观察性研究，其中从 U-BIOPRED 队列中选择了成年哮喘（定义为 ≥18 岁开始）与儿童期严重哮喘（<18 岁）的成年患者. 在诱导痰 (n = 83)、鼻刷 (n = 41) 和支气管内刷 (n = 65) 和活检 (n = 47) (Affymetrix HT HG-U133+ PM) 的总 RNA 上评估基因表达。基因集变异分析用于识别白细胞谱系、炎症和诱导肺损伤途径的差异富集的预定义基因特征。

结果

在鼻刷（5 个特征）、痰液（3 个特征）和支气管内刷（6 个特征）中鉴定出成人发病的重度哮喘患者与儿童发病的严重哮喘患者的显着差异富集的基因特征。与嗜酸性气道炎症、肥大细胞和第 3 组先天淋巴细胞相关的特征在成人发作的重症哮喘中更为丰富，而与诱导性肺损伤相关的特征在成人发作的重症哮喘中则较少。

结论

成人重度哮喘的特征是炎症通路涉及嗜酸性粒细胞、肥大细胞和第 3 组先天性淋巴细胞。这些途径可以代表治疗成人严重哮喘的有用靶点。