2016 Section 5 Green Book

either bench or clinical research study, the research data will hopefully become coherent and produce better research outcomes.

TABLE VI. Average Percentage of CD45 1 Cells, CD45 1 CD4 1 Cells, and CD45 1 CD4 2 Cells With Positive Intracellular Markers.

CRS Subclass

IFN

IL4

IL5

IL13

IL17

DISCUSSION Physicians, from primary care physicians to otolar- yngologists, can differentiate the proposed division of CRS. The subclasses of CRS can be easily determined from clinical history and readily accessible laboratory or office testing (Fig. 6). Diagnosis for CF, allergic fungal si- nusitis, and aspirin triad are well described in the literature. Patients with allergy and asthma can be diag- nosed with office or laboratory testing, and CRS can then be divided as described in Figure 6. The proposed subclassification of CRS does not require difficult and expensive laboratory testing such as proteomics or microarray. The general characteristics of the CRS sub- classes are described in Figure 7 . By dividing CRS into this subclassification, effective targeted management can be developed for each category of CRS. Also, by defining the type of CRS that is being evaluated in Average % of CD45 1 cells with positive intracellular marker AERD 3.9 1.8 0.2 0.3 0.7 AFS 3.1 1 1.3 1.5 2.4 CF 14.6 0.2 0.8 2 2.7 AScA 12.1 1.3 0.04 0.1 1.3 ASsA 9 3.2 0.2 0.5 2.2 NAScA 14 1.2 0.4 0.3 0.7 NASsA 15.5 0.8 0.1 1.8 1.9 Control 4.4 1.2 0.3 0.4 1.8 Total 9.6 1.2 0.4 0.8 1.6 Average % of CD45 1 CD4 1 cells with positive intracellular marker AERD 2.6 1.4 0.3 0.4 1.7 AFS 2.3 0.9 2.4 3.2 4 CF 8.6 0.4 0.5 0.3 3.9 AScA 9.7 1.8 0.04 0.2 3.4 ASsA 11.9 3.2 0.2 0.6 2.9 NAScA 22.1 1.3 0.6 0.4 1.9 NASsA 24.4 3 0.2 2.4 2.8 Control 4.1 1.2 0.2 0.6 3.1 Total 11.6 1.7 0.5 0.9 2.9 Average % of CD45 1 CD4 2 cells with positive intracellular marker AERD 6.5 1.9 0.4 0.6 0.4 AFS 3.6 1.2 0.7 0.6 1.7 CF 17.7 0.04 0.9 2.7 0.9 AScA 10.5 1 0.02 0.1 1.2 ASsA 10 2.5 0.02 0.2 0.6 NAScA 12.9 0.3 0.3 0.3 0.6 NASsA 14.7 0.7 0.07 0.3 1.2 Control 4.8 0.9 0.3 0.4 1.1 Total 9.7 1 0.4 0.6 0.9 AERD 5 aspirin exacerbated respiratory disease also known as aspirin triad; AFS 5 allergic fungal sinusitis; AScA 5 asthmatic sinusitis with allergy; ASsA 5 asthmatic sinusitis without allergy; CF 5 cystic fibrosis; CRS 5 chronic rhinosinusitis; IFN 5 interferon; IL 5 interleukin; NAScA 5 nonasthmatic sinusi- tis with allergy; NASsA 5 nonasthmatic sinusitis without allergy.

Nonasthmatic Sinusitis Without Allergy Typically, NASsA patients have purulence on their nasal endoscopy and do not have high CT scores (Fig. 8). The biopsy of the sinus mucosa is not hypercellular and does not have an abundant amount of eosinophils in the mucosa. Structural abnormality due to anatomic var- iants may be a factor in these patients, such as concha bullosa, infraorbital ethmoid air cell, and deviated sep- tum, that predisposes them to persistent bacterial sinus infections. 7 These sinus infections can occur after a viral exacerbation that leads to persistent cyclical bacterial infections (Fig. 9). NASsA is similar to noneosinophilic sinusitis, which has been previously described. 8 NASsA has an extrinsic mucosal inflammation that is steered through T helper cells, CD3 1 CD4 1 . The inflammation in NASsA is termed extrinsic, because the inflammation is not derived from the mucosa but rather from an external source such as an infection that has been distinguished with elevated levels of IFN- c . IFN- c is a Th1 cytokine commonly representing an infectious process. NASsA patients have elevated levels of IL6 or IL8, similar to noneosinophilic sinusitis and may benefit from long- term macrolide therapy. 8 It is possible that innate im- munity may be involved in NASsA patients, but it was not evaluated in this study. Hypoxia is also likely to be a factor in these NASsA patients due to sinus ostium obstruction. 9 NASsA patients can often improve with a combina- tion of oral antibiotics and steroids. For those NASsA patients who do not improve with medical management, ESS is a good subsequent treatment. However, there are NASsA patients who have recalcitrant bacterial sinus infections that persist despite properly opening the sinuses and being treated with culture-directed antibiot- ics. The most likely explanation for the obstinate low- grade bacterial infection causing localized inflammation is bony bacterial infection or biofilm. Bacterial biofilm in CRS has been shown to be a Th1-mediated process. 10 Management of bacterial biofilm is difficult, and multi- modality treatment may be necessary to improve these patients. Multimodality treatment will likely include high-dose topical antibiotics with or without topical sur- factant after mechanical irritation such as ESS or high- pressure irrigation of the sinuses. Nonasthmatic Sinusitis With Allergy If an inflammatory pathway continuum existed with NASsA on one end and AScA on the other spec- trum, then NAScA would be between them. NAScA inflammatory pathway is also likely to be directed by T helper cells, because CD3 1 CD4 1 was higher in this group versus the control group. Even though NAScA had significantly higher levels of IFN- c than the control group, NAScA is likely a combination of an infectious

Han: Subclassification of Chronic Sinusitis

Laryngoscope 123: March 2013

53