Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, University of Fukui, Fukui, Japan.
Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Japan; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
J Allergy Clin Immunol. 2020 Mar;145(3):740-750. doi: 10.1016/j.jaci.2020.01.027.
Chronic rhinosinusitis (CRS) is one of the most common chronic diseases worldwide. It is a heterogeneous disease, and geographical or ethnic differences in inflammatory pattern in nasal mucosa are major issues. Tissue eosinophilia in CRS is highly associated with extensive sinus disease, recalcitrance, and a higher nasal polyp (NP) recurrence rate after surgery. The prevalence of eosinophilic CRS (ECRS) is increasing in Asian countries within the last 2 decades, and this trend appears to be occurring across the world. International consensus criteria for ECRS are required for the accurate understanding of disease pathology and precision medicine. In a multicenter large-scale epidemiological survey, the "Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis study," ECRS was definitively defined when the eosinophil count in nasal mucosa is greater than or equal to 70 eosinophils/hpf (magnification, ×400), and this study proposed an algorithm that classifies CRS into 4 groups according to disease severity. The main therapeutic goal with ECRS is to eliminate or diminish the bulk of NP tissue. NPs are unique abnormal lesions that grow from the lining of the nasal and paranasal sinuses, and type 2 inflammation plays a critical role in NP development in patients with ECRS. An imbalance between protease and endogenous protease inhibitors might play a pivotal role in the initiation and exacerbation of type 2 inflammation in ECRS. Intraepithelial mast cells in NPs, showing a tryptase+, chymase- phenotype, may also enhance type 2 inflammation. Intense edema and reduced fibrosis are important histological features of eosinophilic NPs. Mucosal edema mainly consists of exuded plasma protein, and excessive fibrin deposition would be expected to contribute to the retention of proteins from capillaries and thereby perpetuate mucosal edema that may play an etiological role in NPs. Upregulation of the coagulation cascade and downregulation of fibrinolysis strongly induce abnormal fibrin deposition in nasal mucosa, and type 2 inflammation plays a central role in the imbalance of coagulation and fibrinolysis.
慢性鼻-鼻窦炎（CRS）是全球最常见的慢性疾病之一。它是一种异质性疾病，鼻腔黏膜的炎症模式存在地域或种族差异是主要问题。CRS 组织嗜酸性粒细胞增多与广泛的鼻窦疾病、难治性和手术后鼻息肉（NP）复发率高高度相关。在过去的 20 年中，亚洲国家 ECRS 的患病率呈上升趋势，这种趋势似乎正在全球范围内发生。需要有 ECRS 的国际共识标准，才能准确了解疾病病理和精准医学。在一项多中心大规模流行病学调查中，即“日本难治性嗜酸性慢性鼻-鼻窦炎的流行病学调查研究”中，当鼻黏膜中的嗜酸性粒细胞计数大于或等于 70 个/高倍视野（放大倍数×400）时，明确定义了 ECRS，该研究提出了一种根据疾病严重程度将 CRS 分为 4 组的算法。治疗 ECRS 的主要目标是消除或减少 NP 组织的体积。NP 是一种独特的异常病变，从鼻腔和副鼻窦的衬里生长，2 型炎症在 ECRS 患者 NP 发育中起关键作用。蛋白酶和内源性蛋白酶抑制剂之间的失衡可能在 ECRS 中 2 型炎症的启动和加剧中起关键作用。NP 中的上皮内肥大细胞表现出类胰蛋白酶+、类糜蛋白酶-表型，也可能增强 2 型炎症。强烈的水肿和减少的纤维化是嗜酸性 NP 的重要组织学特征。黏膜水肿主要由渗出的血浆蛋白组成，过多的纤维蛋白沉积预计会导致毛细血管中的蛋白质滞留，从而使黏膜水肿持续存在，这可能在 NP 中起病因作用。凝血级联的上调和纤维蛋白溶解的下调强烈诱导鼻黏膜中异常的纤维蛋白沉积，2 型炎症在凝血和纤维蛋白溶解的失衡中起核心作用。
