Department of Otorhinolaryngology Head and Neck Surgery, Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China.
Upper Airways Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium.
J Allergy Clin Immunol. 2023 Feb;151(2):458-468. doi: 10.1016/j.jaci.2022.10.010. Epub 2022 Oct 19.
Previous studies on the endotyping of chronic rhinosinusitis (CRS) that were based on inflammatory factors have broadened our understanding of the disease. However, the endotype of CRS combined with inflammatory and remodeling features has not yet been clearly elucidated.
We sought to identify the endotypes of patients with CRS according to inflammatory and remodeling factors.
Forty-eight inflammatory and remodeling factors in the nasal mucosal tissues of 128 CRS patients and 24 control subjects from northern China were analyzed by Luminex, ELISA, and ImmunoCAP. Sixteen factors were used to perform the cluster analysis. The characteristics of each cluster were analyzed using correlation analysis and validated by immunofluorescence staining.
Patients were classified into 5 clusters. Clusters 1 and 2 showed non-type 2 signatures with low biomarker concentrations, except for IL-19 and IL-27. Cluster 3 involved a low type 2 endotype with the highest expression of neutrophil factors, such as granulocyte colony-stimulating factor, IL-8, and myeloperoxidase, and remodeling factors, such as matrix metalloproteinases and fibronectin. Cluster 4 exhibited moderate type 2 inflammation. Cluster 5 exhibited high type 2 inflammation, which was associated with relatively higher levels of neutrophil and remodeling factors. The proportion of CRS with nasal polyps, asthma, allergies, anosmia, aspirin sensitivity, and the recurrence of CRS increased from clusters 1 to 5.
Diverse inflammatory mechanisms result in distinct CRS endotypes and remodeling profiles. The explicit differentiation and accurate description of these endotypes will guide targeted treatment decisions.
基于炎症因子的慢性鼻-鼻窦炎(CRS)分型研究拓宽了我们对该疾病的认识。然而,结合炎症和重塑特征的 CRS 表型尚未得到明确阐明。
我们旨在根据炎症和重塑因子来确定 CRS 患者的表型。
采用 Luminex、ELISA 和 ImmunoCAP 技术分析了来自中国北方的 128 例 CRS 患者和 24 例对照者的鼻黏膜组织中的 48 种炎症和重塑因子。使用 16 种因子进行聚类分析。通过相关性分析和免疫荧光染色验证来分析每个聚类的特征。
患者被分为 5 个聚类。聚类 1 和 2 表现为非 2 型表型,生物标志物浓度较低,除了 IL-19 和 IL-27。聚类 3 涉及低 2 型表型,具有最高表达的中性粒细胞因子,如粒细胞集落刺激因子、IL-8 和髓过氧化物酶,以及重塑因子,如基质金属蛋白酶和纤维连接蛋白。聚类 4 表现为中度 2 型炎症。聚类 5 表现为高 2 型炎症,与相对较高水平的中性粒细胞和重塑因子有关。伴有鼻息肉、哮喘、过敏、嗅觉丧失、阿司匹林敏感性和 CRS 复发的 CRS 患者比例从聚类 1 到 5 逐渐增加。
不同的炎症机制导致不同的 CRS 表型和重塑特征。这些表型的明确区分和准确描述将指导靶向治疗决策。