2016 Section 5 Green Book

the eosinophilic fungal mucin with post-operative topical steroid irrigation reduces the recurrence rate of AFS to a minimum. One factor to consider in AFS is the coexis- tence of fungal and bacterial biofilms that can persist after the inflammatory process to fungus in AFS is removed. 26 Cystic Fibrosis CF patients are probably the most difficult CRS patients to manage. On nasal endoscopy, thick tenacious mucus and purulence is characteristic of the CF sinus- nasal cavities. CT scores are high and often demonstrate underdeveloped sinuses. On histopathology, CF tissue samples demonstrate subepithelial cell distribution that is consistent with an infectious pattern. Cystic fibrosis had the highest ratio of PMN, which also points to an in- fectious process. Even though CF is most likely an infectious process like NASsA, CF tissue samples were different than NASsA. Cystic fibrosis tissues were hyper- cellular with a high number of mast cells, which was also seen among eosinophilic-based CRS such as AERD, AFS, AScA, and ASsA. Cystic fibrosis CRS had the highest quantity of mast cells, and it was statistically higher than all of the other CRS subclasses. Mast cells were higher in CRS subclasses with intrinsic mucosal inflammatory CRS subclasses such as asthmatic sinusitis and aspirin triad. This is an expected result, because the mast cell is sec- ond only to eosinophil as a potent inflammatory cell. CF tissue was expected to have low mast cells and low cellu- larity, because it was thought to be predominantly an infectious sinusitis. Cystic fibrosis did have low eosino- phil counts as expected but then had the highest mast cell count. Even though CF has traits that are consistent with an infectious process, CF CRS is not mediated by Th1 cells like NASsA. CF did not have statistical difference in CD4 cells or IFN- c to control like NASsA. The most likely explanation to solidify the data for CF is that CF has an infectious inflammatory process that is associated with mast cells. Cystic fibrosis involves an infectious or external inflammation that is associated with mast cell, LTB4, and IL6. In a study examining LTB4 and IL6 in breath condensate, LTB4 and IL6 were measured between CF and a control group. 27 Cystic fibrosis had elevated LTB4 and IL6 compared to the control group ( P < .01). Also, when the CF patients were given antibiotics for their infections, there was a significant drop in the LTB4 and IL6 ( P < .01). Another interesting finding in the study was that an active Pseudomonas aeruginosa infection increased LTB4 and IL6 production in comparison to other bacterial infections in CF patients. The most likely source for the LTB4 in CF patients is the mast cells that were very high in CF. Leukotriene B4 is a strong PMN chemoattractant and therefore accounts for the high PMN count in CF patients. 28 The high PMN count in CF sinus tissue is also likely respon- sible for the destruction of the epithelium and goblet cells as seen in our study. Another interesting finding

desensitization has not been clearly defined, but one pos- sible explanation is that aspirin inhibits IL4 transcription in peripheral T cells. 21 In a study examin- ing IL4 after aspirin desensitization in AERD patients, IL4 levels were significantly decreased after 6 months of daily aspirin maintenance. 22 Allergic Fungal Sinusitis AFS is well defined in the literature. 23 It has been described as a IgE-mediated Th2 process, much like AScA or unified airway CRS. Even though AFS has an intrinsic inflammatory process like AScA, AFS does not share the same attributes as AScA. In a broad sense, the difference between AFS and AScA is that the AFS is a localized disease process, whereas AScA is more of a sys- temic issue. Allergic fungal sinusitis patients rarely have asthma as a confounding variable, but for AScA, asthma is part of it identity. Also, AFS has a specific allergic reac- tion to a fungus, whereas in AScA it has a more undifferentiated response to any sensitized inhalant aller- gens. Allergic fungal sinusitis is mostly a unilateral disease, whereas AScA commonly involves bilateral sinuses. In severe cases, allergic fungal sinusitis can have bilateral involvement (Fig. 11). Both AFS and AScA can have eosinophilic mucin deposited in the sinuses. However, AFS has fungus within the mucin detected with Grocott’s silver stain, and AScA does not stain for fungus. Although the presence of purulence between AFS and AScA was not statistically different in our study, pu- rulence is commonly seen in AFS and less so in AScA. Interestingly, CD4 was not elevated in AFS as it was demonstrated in AScA. Even though CD4 was not higher than the control group for AFS, AFS is likely a Th2-medi- ated inflammatory process, because AFS had a significantly higher amount of Th2 cytokines expression such as IL5. Even though AScA and AFS are both medi- ated by an IgE inflammatory pathway, AScA and AFS do not have the same immunologic pathway. Interleukin 4 and IL13 are more likely to play a role in AScA, whereas AFS likely has IL4, IL5, and IL13 involved. In a study by Upadhyaya et al., Th2 cells were divided into two subpo- pulations. 24 One group of Th2 cells expressed IL4 and IL13 but not IL5, whereas another group of Th2 cells expressed IL4, IL5, and IL13. IL4 and IL13 can be coex- pressed without IL5, because their genes are adjacent, and the IL5 gene is in the opposite orientation. Also, the expression of IL5 demonstrates a more differentiated Th2 inflammatory pathway. 25 The fact that IL5 is strongly expressed in AFS and not in AScA appears to be consist- ent, that AFS may be a more differentiated eosinophilic disease than AScA. Another interesting finding for AFS was that AFS had elevated CD19 and plasma cells in comparison to the control group. Having elevated CD19 and plasma cells in AFS is coherent, because B cells (CD19) develop into plasma cells. A possible explanation that both CD19 and plasma cells were high for AFS is that immunoglob- ulin may play a large role in this disease process. Fortunately, the inflammatory drive in AFS is not as severe as AERD or AScA, so complete evacuation of

Han: Subclassification of Chronic Sinusitis

Laryngoscope 123: March 2013

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