Davis Joseph

Abstract:

Chronic rhinosinusitis with eosinophilic infiltration (ECRS) is a severe and refractory form of rhinosinusitis, often coexisting with asthma. Eosinophilic infiltration and macrophages play a crucial role in the pathophysiology of severe asthma. This paper is configured to cover both the biochemical and clinical aspects of ECRS. 

In the biochemical facet, a detailed and exhaustive characterization of all the main molecular signaling pathways linked to ECRS was carried out based on the critical analysis of the scientific literature. Based on this characterization, the following flowsheets of ECRS immunology, oxidative stress and inflammation have been developed for the first time: (1) an electron delocalization chemical flowsheet of the mechanism of superoxide radical conversion into H₂O₂ and the subsequent breakdown of H₂O₂ into water and oxygen, (2) a biochemical flowsheet of the main molecular pathways involving carbon monoxide (CO) as well as inflammation, and (3) a biochemical flowsheet of the main signaling pathways involved in the inflammatory processes described in this paper. Furthermore, the main therapeutic targets for ECRS as a group and as a unified signaling pathway were identified for the first time based on the molecular characterization of the aforementioned signaling pathways and the critical analysis of the scientific literature related to (1) Interleukin-17A (IL-17A), (2) superoxide dismutase (SOD), (3) heme-oxygenase-1 (HO-1), (4) protein tyrosine phosphatase non-receptor type 2 (PTPN2), (5) NOD-like receptor protein 3 (NLRP3), (6) the inflammasome and (7) B cells.

In the clinical facet, a thorough review of ECRS patient studies was conducted to determine new potential effective treatments against the disease. The three most important conclusions of the clinical review are the following:     (1) The loss of Cu,Zn-SOD in ECRS epithelium may contribute to an increase in IL-17A, macrophage infiltration in the subepithelial tissue, and MUC5AC overproduction in the epithelium, thereby exacerbating inflammation and mucus hypersecretion, (2) a reduction of HO-1 expression in the epithelium and macrophage infiltration are associated with epithelial damage in CRS with eosinophilic infiltration, and (3) overall, antioxidants may play a critical role in elucidating the pathogenesis of intractable diseases like ECRS and may offer new therapeutic strategies.