Chronic rhinosinusitis as a multifactorial inflammatory disorder

Abstract

Chronic rhinosinusitis (CRS) is a prevalent health condition characterized by sinonasal mucosal inflammation lasting at least 12 weeks. Heterogeneous in clinical presentation, histopathology, and therapeutic response, CRS represents a spectrum of disease entities with variable pathophysiology. Increased knowledge of cellular and molecular derangements in CRS suggests potential etiologies and targets for therapy. Microbial elements including fungi, staphylococcal enterotoxin, and biofilms have been implicated as inflammatory stimuli, along with airborne irritants and allergens. Defects in innate immunity have gained increased attention as contributors to the chronic inflammatory state. A combination of host susceptibility and environmental exposure is widely believed to underlie CRS, although direct evidence is lacking. Presently, without precise disease definitions and identifiable universal triggers, CRS pathogenesis is broadly described as multifactorial. Current research is beginning to unravel complex and diverse effects of chronic inflammation on sinonasal mucosal homeostasis, but dysfunctional pathways of inflammatory regulation and resolution require further elucidation.

Fig 1

Pathophysiologic pathways of chronic rhinosinusitis. CRSwNP—chronic rhinosinusitis with nasal polyps; CRSsNP— chronic rhinosinusitis without nasal polyps.

Fig 2

Innate immunity of the sinonasal tract. The primary mechanism of sinonasal innate immune defense is orderly mucociliary clearance. The mucus blanket, which contains many secreted antimicrobials and opsonins, is continuously propelled to the nasopharynx, providing constitutive, nonspecific protection of the sinonasal mucosal surface. In addition, sinonasal epithelial cells actively participate in innate immunity, using pattern-recognition receptors to detect luminal pathogens and responding directly with selective expression of targeted antimicrobial effectors. At the same time, epithelial cells signal to adaptive immune cells through cytokines and costimulatory molecules to coordinate a vigorous defense of the mucosal surface. Emerging evidence suggests that predominance of certain T-helper populations (Th1, Th2, and Th17) in the mucosa, as well as the presence of T-regulatory cells (Tregs) may play a role in chronic rhinosinusitis pathogenesis. Epithelial cells guide the recruitment of adaptive immune cells by producing signaling molecules that interact locally with resident dendritic cells and T cells. Cytokines produced by specific T-cell subclasses modulate the innate immune responses of epithelial cells by influencing the pattern of antimicrobial gene expression. Chronic sinonasal inflammatory disease may result from the loss of mucosal homeostasis due to dysregulation of these innate immune pathways. (From Lane [3].)