Samer Fakhri

IL-33–Responsive Innate Lymphoid Cells Are an Important Source of IL-13 in Chronic Rhinosinusitis with Nasal Polyps

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. MEASUREMENTS AND MAIN RESULTS Elevated expression of ST2, the ligand-binding chain of the IL-33 receptor, was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP and healthy control subjects. An increased percentage of innate lymphoid cells was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP. ST2(+) innate lymphoid cells are a consistent source of IL-13 in response to IL-33 stimulation. Significant induction of IL-33 was observed in epithelial cells derived from patients with CRSwNP compared with patients with CRSsNP in response to stimulation with Aspergillus fumigatus extract. CONCLUSIONS These data suggest a role for sinonasal epithelial cell-derived IL-33 and an IL-33-responsive innate lymphoid cell population in the pathophysiology of CRSwNP demonstrating the functional importance of innate lymphoid cells in Th2-mediated inflammatory disease.

Esthesioneuroblastoma: 25-year experience at a single institution

Objectives To evaluate outcomes for patients with esthesioneuroblastoma treated at a single institution during a 25-year period. Design Eighteen patients with pathologic diagnosis of esthesioneuroblastoma between 1980 and 2004 were retrospectively identified. Results Two patients had Kadish A, seven had Kadish B, and nine had Kadish C disease. The mean follow-up was 71 months. Treatment regimens consisted of surgery alone (four patients), surgery followed by postoperative radiation (six patients), surgery followed by postoperative chemoradiotherapy (three patients), preoperative radiotherapy (two patients), preoperative chemoradiotherapy (one patient), chemoradiotherapy (one patient), and surgery plus chemotherapy (one patient). Surgical approaches (n = 17) consisted of 13 traditional craniofacial resections, one endoscopic-assisted cranionasal resection, and three minimally invasive endoscopic resections. The 10-year disease-specific survival was 80%. The overall recurrence-free survival at five and 10 years was 62% and 46%, respectively. Positive surgical margins and TNM staging predicted survival. Conclusion 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.

Isolated sphenoid sinus disease : Etiology and management

OBJECTIVE: To evaluate the diagnosis and management of isolated sphenoid sinus disease by using the current rhinologic standard of care. STUDY DESIGN: Retrospective chart review. RESULTS: Fifty sequential, symptomatic patients were studied. Presenting symptoms included headache or facial pain (88%), rhinorrhea (46%), and nasal congestion (26%). All patients underwent CT imaging, demonstrating bony changes or dehiscences (42%), a mass (24%), or complete opacification of the sphenoid sinus (22%). Eighty percent required surgical intervention. The most frequent diagnoses were as follows: sinusitis (38%), fungal ball (20%), neoplasm (16%), and mucocele (12%). Treatment resulted in clinical or endoscopic improvement or resolution in 87% of the patients. CONCLUSION: 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.

Transnasal endoscopic resection of lesions of the clivus: a preliminary report.

Objective: To review our experience with transnasal endoscopic resection of clival lesions.

Balloon catheter dilatation for frontal sinus ostium stenosis in the office setting

Background Frontal sinus ostium stenosis (FSOS) is problematic even for expert surgeons. Balloon catheter (BC) technology has been recently introduced to rhinology. The aim of this study is to assess technical feasibility and effectiveness of BC dilatation of FSOS in the office setting. Methods This retrospective, multi-institutional case series describes all patients who underwent BC dilatation of FSOS in the office setting in the year ending December 31, 2007. Results Six adult patients underwent a total of seven BC dilatations of FSOS in the clinical setting. The pretreatment ostium size was 1-2 mm. Four of the dilatations were performed with a 5-mm lacrimal BC (LacriCATH, Quest Medical, Allen, TX) and three dilatations were executed with a 7-mm sinus BC (SinuCATH, Quest Medical). All procedures were performed using topical anesthesia only. No complications occurred. Five of the six dilated FSOS dilatations were deemed successful after one BC dilatation. One ostium contracted >50% and required repeat BC dilatation. All ostia have remained patent with a follow-up range of 4-9 months. No subject has required formal surgical revision. Conclusion This preliminary report describes BC of FSOS in the office setting. The technique may serve as a safe and feasible alternative, potentially avoiding formal revision sinus surgery in select patients.

Airway surface mycosis in chronic TH2-associated airway disease

BACKGROUND Environmental fungi have been linked to TH2 cell-related airway inflammation and the TH2-associated chronic airway diseases asthma, chronic rhinosinusitis (CRS) 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 patients with TH2-associated and non-TH2-associated airway disease. METHODS Sinus lavage fluid and blood were collected from sinus surgery patients (n = 118) including patients with CRSwNP, patients with CRS without nasal polyps, patients with AFRS, and non-CRS/nonasthmatic control patients. Asthma status was determined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. PBMCs were restimulated with fungal antigens in an enzyme-linked immunocell spot assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared with fungus-specific IgE levels measured from plasma by ELISA. RESULTS Filamentous fungi were significantly more commonly cultured in patients with TH2-associated airway disease (asthma, CRSwNP, or AFRS: n = 68) than in control patients with non-TH2-associated disease (n = 31): 74% vs 16%, respectively (P < .001). Both fungus-specific IL-4 enzyme-linked immunocell spot (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.

Increased percentage of mast cells within sinonasal mucosa of chronic rhinosinusitis with nasal polyp patients independent of atopy

Initial attention on the pathophysiology of chronic rhinosinusitis (CRS) has focused on eosinophils. Other immune cells such as mast cells (MCs) have been identified and appear to be elevated in CRS with nasal polyp (NP) patients. MCs are commonly linked to immunoglobulin E (IgE)‐mediated inflammatory changes characterized by elevated T helper 2 cytokines. Although atopy is a common comorbid condition with CRS, the objective of this study was to determine if elevated MCs are linked primarily to atopic status in CRS patients and to understand the significance of MCs in the pathophysiology of CRS.

A meta-analysis of topical amphotericin B for the treatment of chronic rhinosinusitis.

Fungal species have been implicated in the pathophysiology of chronic rhinosinusitis (CRS). Based on this observation, some clinicians have employed topical antifungal therapy with amphotericin B (AMB); however, its efficacy has not been consistently supported by the literature.

Prevalence of confirmed asthma varies in chronic rhinosinusitis subtypes

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 polyposis (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.

Staphylococcus aureus prevalence in allergic fungal rhinosinusitis vs other subsets of chronic rhinosinusitis with nasal polyps.

The pathogenesis of allergic fungal rhinosinusitis (AFRS) is thought to represent an immunological reaction to fungal antigens. Recent studies have implicated superantigens and non‐immunoglobulin E (IgE)‐mediated mechanisms in the development of AFRS. The objective of this study is to assess the prevalence of Staphylococcus aureus in AFRS vs other subsets of chronic rhinosinusitis with polyps (CRSwNP, also termed non‐AFRS).