Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otorhinolaryngology Head & Neck Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
J Allergy Clin Immunol. 2019 Dec;144(6):1566-1574.e6. doi: 10.1016/j.jaci.2019.08.040. Epub 2019 Sep 25.
Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease subdivided based on the presence or absence of nasal polyps (NPs). Histologic features of chronic rhinosinusitis with nasal polyps (CRSwNP) include inflammatory cell infiltration and excessive fibrin deposition in NPs. Thrombin-activatable fibrinolysis inhibitor (TAFI) is an enzyme that plays an antifibrinolytic role in the body. The significance of TAFI has been documented in patients with chronic inflammatory diseases, including chronic lung disease; however, it has not been evaluated in the pathogenesis of NPs.
The objective of this study was to evaluate the potential role of TAFI in the pathogenesis of NPs.
Nasal lavage fluid was collected from control subjects and patients with CRS. We measured levels of thrombin/anti-thrombin complex (TATc) and TAFI protein using an ELISA.
TATc levels in nasal lavage fluid were significantly increased in patients with CRSwNP and patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared with control subjects, and TAFI levels in nasal lavage fluid were also significantly increased in patients with CRSwNP compared with those in control subjects and patients with CRSsNP. There was a significant correlation between TATc and TAFI levels in nasal lavage fluid. Interestingly, patients with CRS and asthma showed increased TATc and TAFI levels in nasal lavage fluid compared with those in patients with CRS without asthma, especially patients with CRSwNP.
Increased TATc and TAFI levels in nasal passages of patients with CRSwNP might participate in fibrin deposition in NPs and might play a role in the pathogenesis of CRSwNP and asthma.
慢性鼻-鼻窦炎(CRS)是一种异质性慢性炎症性疾病,根据是否存在鼻息肉(NPs)进行细分。伴有鼻息肉的慢性鼻-鼻窦炎(CRSwNP)的组织学特征包括炎症细胞浸润和 NPs 中纤维蛋白过度沉积。凝血酶激活的纤溶抑制物(TAFI)是一种在体内发挥抗纤溶作用的酶。TAFI 在包括慢性肺部疾病在内的慢性炎症性疾病患者中的意义已得到证实,但尚未在 NPs 的发病机制中进行评估。
本研究旨在评估 TAFI 在 NPs 发病机制中的潜在作用。
从对照受试者和 CRS 患者中采集鼻冲洗液。我们使用 ELISA 测量凝血酶/抗凝血酶复合物(TATc)和 TAFI 蛋白的水平。
与对照受试者相比,CRSwNP 患者和无鼻息肉的慢性鼻-鼻窦炎(CRSsNP)患者的鼻冲洗液 TATc 水平显著升高,CRSwNP 患者的 TAFI 水平也显著高于对照受试者和 CRSsNP 患者。鼻冲洗液中 TATc 和 TAFI 水平之间存在显著相关性。有趣的是,与无哮喘的 CRS 患者相比,患有 CRS 和哮喘的患者的鼻冲洗液中 TATc 和 TAFI 水平升高,尤其是 CRSwNP 患者。
CRSwNP 患者鼻腔中 TATc 和 TAFI 水平的升高可能参与 NPs 中的纤维蛋白沉积,并可能在 CRSwNP 和哮喘的发病机制中发挥作用。