Chronic rhinosinusitis pathogenesis

Whitney W Stevens,Robert J Lee,Robert P Schleimer,Noam A Cohen

doi:10.1016/j.jaci.2015.10.009

Abstract

There are a variety of medical conditions associated with chronic sinonasal inflammation, including chronic rhinosinusitis (CRS) and cystic fibrosis. In particular, CRS can be divided into 2 major subgroups based on whether nasal polyps are present or absent. Unfortunately, clinical treatment strategies for patients with chronic sinonasal inflammation are limited, in part because the underlying mechanisms contributing to disease pathology are heterogeneous and not entirely known. It is hypothesized that alterations in mucociliary clearance, abnormalities in the sinonasal epithelial cell barrier, and tissue remodeling all contribute to the chronic inflammatory and tissue-deforming processes characteristic of CRS. Additionally, the host innate and adaptive immune responses are also significantly activated and might be involved in pathogenesis. Recent advancements in the understanding of CRS pathogenesis are highlighted in this review, with special focus placed on the roles of epithelial cells and the host immune response in patients with cystic fibrosis, CRS without nasal polyps, or CRS with nasal polyps.

Highlights

Chronic rhinosinusitis pathogenesisSinonasal epithelial cells express the 1-a-hydroxylase enzyme, which is important for synthesis of bioactive vitamin D; when sinonasal epithelial cells are exposed to inactive vitamin D precursors, they synthesize bioactive vitamin D and increase LL-37 production.[66] vitamin D might contribute to airway innate immunity,[67] including in patients with CRS and allergic rhinitis.[68,69]
From athe Division of Allergy-Immunology, Department of Medicine, dthe Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago; bthe Departments of Otorhinolaryngology–Head and Neck Surgery and cPhysiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia; ethe Philadelphia Veterans Affairs Medical Center, Surgical Service; and fthe Monell Chemical Senses Center, Philadelphia
Another concept that has emerged is that the correct balance of microbes within the local microbiome might be immunomodulatory and that an imbalance shifts an important regulator of local inflammation.[11]

Summary

Chronic rhinosinusitis pathogenesis

Sinonasal epithelial cells express the 1-a-hydroxylase enzyme, which is important for synthesis of bioactive vitamin D; when sinonasal epithelial cells are exposed to inactive vitamin D precursors, they synthesize bioactive vitamin D and increase LL-37 production.[66] vitamin D might contribute to airway innate immunity,[67] including in patients with CRS and allergic rhinitis.[68,69]. Thiocyanate is oxidized through lactoperoxidase to hypothiocyanite, a compound with antibacterial, antifungal, and antiviral effects.[85] Both CFTR and pendrin can regulate thiocyanate transport, linking ion transport with host defense.[86] CFTR defects that reduce thiocyanate secretions might impair airway innate defense mechanisms in patients with CF.[87] An increase in pendrin levels in patients with CRS can influence thiocyanate transport.[29]. A diagnostic, prognostic, or efficacy indicator in patients with sinonasal disease.[94]

REGULATION OF ANTIMICROBIAL COMPOUND PRODUCTION AND SECRETION

Findings

CONCLUSIONS