Rationale: Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP) are associated with Th1 and Th2 cytokine polarization, respectively; however, the pathophysiology of CRS remains unclear. The importance of innate lymphoid cells in Th2-mediated inflammatory disease has not been clearly defined. Objectives: The objective of this study was to investigate the role of the epithelial cell-derived cytokine IL-33 and IL-33-responsive innate lymphoid cells in the pathophysiology of CRS. Methods: Relative gene expression was evaluated using quantitative real-time polymerase chain reaction. Innate lymphoid cells in inflamed ethmoid sinus mucosa from patients with CRSsNP and CRSwNP were characterized using flow cytometry. Cytokine production from lymphoid cells isolated from inflamed mucosa of patients with CRS was examined using ELISA and intracellular cytokine staining. Chronic rhinosinusitis (CRS) is a chronic inflammatory process of the nasal and paranasal sinus mucosa affecting more than 30 million people annually, resulting in significant direct healthcare costs (1). CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP) are associated with Th1 and Th2 cytokine polarization, respectively (2, 3), although the cellular and molecular mechanisms driving the Th2-mediated inflammation in CRSwNP are not clearly understood (4, 5). Due largely to a lack of understanding of the pathophysiology of CRS, current treatment options, including high-dose glucocorticosteroids and surgeries, remain noncurative, generic, and largely unchanged over the past decade.IL-33, a member of the IL-1 family of cytokines, is expressed by epithelial cells, endothelial cells, fibroblasts, smooth muscle cells, macrophages, and dendritic cells (6-8). The IL-33 receptor, a heterodimeric complex composed of ST2 and IL-1 receptor accessory protein (IL1RAP), is expressed on numerous immune cells, including Th2 cells, mast cells, basophils, eosinophils, and macrophages (7-9). IL-33 is a chemoattractant for Th2 cells (10) and promotes Th2 polarization of naive CD4 1 T cells, enhancing production of IL-5 and IL-13 independent of IL-4 (11). IL-33 can also induce proinflammatory cytokine and chemokine production by mast cells and enhance degranulation (12), stimulate basophils and eosinophils (13), and enhance IL-13-driven polarization of alternatively activated macrophages (14). More recently, an important role for IL-33 in regulating the development and function of type 2 innate lymphoid cells (ILC) was described (15, 16). The epithelial cell-derived cytokine IL-33 is known to play a key role in the development and regulation of a Th2 immune response, mediated in part by an IL-33-responsive innate lymphoid cell population. However, there is little direct evidence of an important role for these cells in Th2-mediated inflammatory disease in humans. What This Study Adds to the FieldHere we show that the percentage of innate lymphoid cells is significantly elevated in diseased mucosa in chronic rhinosinusitis w...

Background Chronic rhinosinusitis (CRS) and asthma describe inflammation of the upper and lower airway, respectively. Not surprisingly, the prevalence of CRS and asthma has been linked, with up to 50% asthma prevalence in CRS with nasal polyps (CRSwNP) patients. However, these prevalence rates do not address subtypes of CRSwNP including allergic fungal rhinosinusitis (AFRS). This study sets out to objectively determine asthma prevalence in CRS subtypes prospectively. Methods A prospective prevalence study of adult CRS patients was conducted over a 1 year period at a tertiary care center. Patients were grouped into CRSwNP, CRS without nasal polyps (CRSsNP), or AFRS. Patients were administered an Asthma Screening Questionnaire (ASQ) and confirmed by pulmonary function testing (PFT) if positive on the ASQ. Chi squared analysis was performed to compare the asthma prevalence among the CRS subtypes. Results A total of 410 patients (age 48.1 ± 16.4, 53.5% male) were included. Of these, 178 (43.4%) had CRSwNP, 166 (40.5%) had CRSsNP, and 66 (16.1%) met criteria for AFRS. Analysis revealed that 48.3% of CRSwNP patients, 16.5% of CRSsNP patients, and 23.6% of AFRS patients had asthma confirmed by PFTs. Chi squared analysis showed a significant difference in asthma prevalence between CRSwNP and AFRS (p=0.0016) and CRSwNP and CRSsNP (p=0.0000), but no significant difference between CRSsNP and AFRS (p=0.2380). Conclusion There is a significant difference in the prevalence of asthma between CRSwNP and AFRS, suggesting a fundamental distinction in their etiologies despite similar immunologic profiles. Further efforts to delineate these biological disparities are underway.

The presenting symptoms of isolated sphenoid sinus disease can be nonspecific and may result in an inordinate delay in diagnosis. Nasal endoscopy and radiologic imaging are central to making an accurate and timely diagnosis. Medical treatment or minimally invasive surgical techniques can successfully manage the majority of patients with persistent or refractory symptoms.

Both endoscopic and open surgical approaches have been successful in treating a small number of esthesioneuroblastoma patients with high survival and low rate of surgical complications.

Background Environmental fungi have been linked to T helper type 2 (Th2) cell-related airway inflammation and the Th2-associated chronic airway diseases asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. Objective To determine the frequency of fungus isolation and fungus-specific immunity in Th2-associated and non-associated airway disease patients. Methods Sinus lavage fluid and blood were collected from sinus surgery patients (n=118) including CRS patients with and without nasal polyps and AFRS and non-CRS/non-asthmatic control patients. Asthma status was deteremined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. Peripheral blood mononuclear cells were restimulated with fungal antigens in an enzyme linked immunocell spot (ELISpot) assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared to fungus-specific IgE levels measured from plasma by ELISA. Results Filamentous fungi were significantly more commonly cultured from Th2-associated airway disease subjects (asthma, CRSwNP, or AFRS: n=68) compared to non-Th2-associated control patients (n=31); 74% vs 16% respectively, p<0.001. Both fungus-specific IL-4 ELISpot (n=48) and specific IgE (n=70) data correlated with Th2-associated diseases (sensitivity 73% and specificity 100% vs. 50% and 77%, respectively). Conclusions The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with Th2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients. Clinical Implications Airway fungi may contribute to the expression of sinusitis with nasal polyps and asthma, suggesting that efforts to eradicate fungi from the airways and environments of these patients should be considered.