Chronic rhinosinusitis (CRS) is an inflammatory condition of the paranasal mucosa and nasal cavity that persists longer than 3 months. Typically medical or surgical treatments offer very little assistance to these patients, a reflection of the general morbidity caused by this disorder. There has been much controversy regarding the specific pathogenesis of CRS in the literature, as there are currently several competing theories as to what the mechanism of disease might be. Additionally, all studies have been analyzed with different parameters and with different methods, adding a great deal of discrepancy to the field, and not allowing all work to be directly comparable.
Histopathology reveals inflammation of the mucosal lining, goblet cell hyperplasia, subepithelial edema, and mononuclear cell infiltration as hallmarks of CRS (Bachert et al., 2004). The major leukocyte affiliated with inflammation in CRS is the eosinophil, differing from the invasive forms of sinusitis where neutrophils (PMNs) are predominantly seen (Harlin et al., 1988; Wei et al., 2003). However an increase in IL-8 (a PMN chemokine) has been seen in CRS patients, suggesting neutrophils may aid in the local immunity of the nasal cavity, but are not the primary effector cells in this condition (Suzuki et al., 1996). In addition to IL-8, other proinflammatory mediators such as IL-1P, IL-6, MCP-1, TNF-a, and the eicosanoid PGE2 have all been seen in CRS and appear to play a role in the persistence of inflammation (Kuehnemund et al., 2004). In CRS patients, histopathology reveals inflammation of the mucosal lining, goblet cell hyperplasia, subepithelial edema, and mononuclear cell infiltration (Bachert et al., 2004).
Another direct symptom of CRS is the development of polyposis that is almost always correlated with the disease (Ferguson, 2000a). Polyps form from ede-matous tissue stemming from the middle meatus and can cause disruption of respiration, or, in severe cases, facial deformity (Moloney, 1977; Drake-Lee, 1997; Setti-paine, 1994). The polyps are usually pale in color due to poor blood supply, but in the presence of inflammation can appear more reddish. One theory on the early formation of polyps is the "epithelial rupture theory" put forward by Tos (1997). He posits that formation starts with a rupture along the nasal epithelium caused by pressure from edematous and infiltrated lamina propria. The lamina propria projects beyond the fault and is slowly covered by expanding epithelial cells. As the polyp grows in length, it starts to become vascularized and eventually is completely enveloped by nasal epithelium. Another hypothesis based on work from Bernstein and others, builds upon the ulceration and re-epitheliazation proposed by Tos, and explains polyp formation and persistence begins with the upregulation of GM-CSF and G-CSF by macrophages within the nasosinal cavity (Bernstein, 1997). These cytokines are responsible for the recruitment of eosinophils, mast cells, and PMNs to the site of inflammation, resulting in the release of various inflammatory intermediates such as prostaglandins, leukotrienes, and major basic protein (MBP) (Bernstein, 1997). This eventually leads to a further amplification of the response, altering ion transport (Na+ and Ca2+), and resulting in water retention within the epithelium and lamina propria. This water retention results in edema and aids in the growth of the polyps themselves.
Though the mechanism of chronicity behind CRS is unknown, recent work by Ponikau et al. (1999) suggests that a hypersensitive reaction to a fungal etiological agent may be responsible. In a sample of 210 CRS patients, they found 96% (202/210) tested positive for the presence of fungi in their nasal samples. The predominant fungi isolated were species of Aspergillus, Alternaría, Candida, and Penicillium (Table 1.1). Additionally the study also found 100% (14/14) of healthy volunteers tested positive for fungal colonies. This suggests that while the fungi themselves are probably not the sole mediator of CRS, the hypersensitive response demonstrated by CRS patients may be caused by the fungi. This etiology is parallel to the known disease allergic fungal rhinosinusitis (AFRS, discussed later in the chapter), though Ponikau et al. failed to find significant levels of IgE in the study, traditionally a characteristic of AFRS. Thus the authors suggest the term "eosinophilic fungal rhinosinusitis" be used in lieu of AFRS so as to describe the onset of eosinophilia, without the foundation of IgE being a mechanistic process in the disease (Ponikau et al., 1999). This work was supported by Braun and others who used similar techniques and found comparable results (Braun et al., 2003).
Contrasted against this theory is the work done by Ferguson who suggests that CRS be divided into two distinct subcategories; those patients with AFRS and those with a similar, but distinct clinicopathologi-cal entity, eosinophilic mucin rhinosinusitis (EMRS) (Ferguson, 2000b). EMRS is described as histopathologically similar to AFRS with the distinct absence of fungi in the samples. In a review of the literature and from patient studies, Ferguson compared 431 patients with AFRS to 69 with EMRS and found that patients with AFRS tended to have a lower incidence of asthma (41% vs. 93%), decreased aspirin sensitivity (13% vs. 54%), and increased total IgE levels. Additionally AFRS patients were more likely to have allergic rhinitis (84% vs. 63%) and were also younger in age (30.7 vs. 48.0). All values were found to have statistical significance. Ferguson concluded these disorders were different enough from one another and that their characteristics should denote these distinctions; AFRS should be characterized by fungal isolation and is mediated by IgE hypersensitivity (Type 1), and EMRS be characterized by the presence of allergic mucus, lack of fungal isolation, and mediated by general immune dysregulation.
While the exact pathogenesis of CRS is unclear, it is understood that the altered nasal environment lends itself to frequent acute bacterial and viral co-infections (Davis and Kita, 2004). In this scenario microbes are able to act as opportunists and take advantage of the host's weakened immune state. The inflammatory response responsible for altering the nasal environment (interruption of mucociliary beat, remodeling of nasal architecture, obstruction of sinonasal ostia, etc.) is believed to be a key factor in contributing to the persistence of CRS.
Was this article helpful?