Respiratory Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
Janssen Research and Development, Johnson & Johnson, Spring House, Pa.
J Allergy Clin Immunol. 2018 Apr;141(4):1280-1290. doi: 10.1016/j.jaci.2017.06.037. Epub 2017 Jul 26.
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.
We sought to identify gene profiles associated with adult-onset severe asthma.
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.
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.
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.
成人起病的严重哮喘的特征是尽管接受高强度的哮喘治疗，但疾病仍高度症状性。为了开发靶向治疗，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用于识别异质样本中基因谱的统计技术。
我们旨在确定与成人起病严重哮喘相关的基因谱。
这是一项横断面观察性研究，在该研究中，我们从 U-BIOPRED 队列中选择了成人起病哮喘（定义为 18 岁及以上起病）的成年患者与儿童起病严重哮喘（<18 岁）进行比较。使用诱导痰（n=83）、鼻刷（n=41）、支气管刷检（n=65）和活检（n=47）（Affymetrix HT HG-U133+PM）的总 RNA 评估基因表达。使用基因集变异分析来识别白细胞谱系、炎症和诱导性肺损伤途径中差异富集的预定义基因特征。
在与儿童起病严重哮喘相比，在成人起病严重哮喘患者中鉴定出了在鼻刷（5 个特征）、痰（3 个特征）和支气管刷检（6 个特征）中差异显著富集的基因特征。与嗜酸性气道炎症、肥大细胞和第 3 组固有淋巴细胞相关的特征在成人起病严重哮喘中更为丰富，而与诱导性肺损伤相关的特征在成人起病严重哮喘中则不那么丰富。
成人起病的严重哮喘的特征是涉及嗜酸性粒细胞、肥大细胞和第 3 组固有淋巴细胞的炎症途径。这些途径可能成为治疗成人起病严重哮喘的有用靶点。
