Role of type 2 inflammation and imbalance between fibrinolysis and fibrin deposition in nasal polyp formation in eosinophilic chronic rhinosinusitis

Abstract

The most common endotype-based chronic rhinosinusitis (CRS) classification includes the eosinophilic CRS (ECRS) and non-eosinophilic CRS (non-ECRS) subtypes. ECRS is characterized by severe type 2 inflammation and is therapeutically challenging. Moreover, nasal polyp (NP) recurrences are frequent in patients with ECRS, despite medical treatment and surgical interventions. Comorbid asthma, including aspirin/non-steroidal anti-inflammatory drug intolerance is also common in ECRS. Therefore, the main therapeutic target in patients with ECRS is to completely eliminate or diminish the bulk of the NP tissue. An accurate understanding of the pathogenesis of NP is important to improve the effectiveness of therapy for ECRS.

NPs are histopathologically characterized by intense edematous stroma filled with plasma proteins, mainly albumin, and minimal fibrosis, owing to decreased levels of collagen production. We previously reported that excessive fibrin deposition was observed in NP tissue. Excessive fibrin deposition contributes to the retention of plasma proteins exuded from capillaries and thereby perpetuates mucosal edema, which could be implicated in the etiopathogenesis of NPs. Fibrin, an end product of the coagulation cascade, plays a major role in blood clotting at the site of vascular injury. However, disturbances in fibrin turnover result in abnormal fibrin deposition and can produce detrimental effects owing to its pro-inflammatory properties. Tissue fibrin is generated by the coagulation cascade and broken down by the fibrinolysis cascade. Recent studies have reported disturbances in both coagulation and fibrinolysis cascades in ECRS.

Mucosal edema and excessive fibrin deposition are known to contribute to retention of exuded plasma proteins from capillaries and thereby perpetuate mucosal edema that may participate in the etiopathogenesis of NPs. Up-regulation of the coagulation cascade and down-regulation of fibrinolysis are strongly associated with abnormal fibrin deposition in the nasal mucosa, and type 2 inflammation plays a key role in the imbalance between coagulation and fibrinolysis.