Cellular Reactions in Allergic Provocation-Testing Visualized by Confocal Laser Endomicroscopy
Nina K. Wenda, MD (Presenter); Christop Striedter; Ralf Kiesslich; Jan Gosepath
Introduction: Reactions occurring in allergic rhinitis have been intensively studied, especially on an immunological level. We used endonasal probe-based confocal laser endomicroscopy to visualize acute effects of allergic nasal provocation testing and to evaluate a potential value of this methodology in quantifying the clinical response.
Method: We examined 20 patients with known inhalant allergies against housedust mite or grass pollen. After mapping and documenting the normal mucosa of the inferior turbinate, nasal provocation was performed and effects were observed using probe-based confocal laser endomicroscopy under endoscopic vision. With intravenous fluorescein used as contrast agent, the occurring reactions were observed over a period of 10 minutes. We established criteria of cellular events in correlation to clinical symptoms over time to develop a morphological grading of the occurring provocation induced response.
Results: Visualization of endonasal mucosa as well as its alterations occurring after allergen challenge in acute allergic rhinitis was well feasible using confocal laser endomicroscopy. Reactions included vascular dilation as well as widespread loss of cellular junctions and loss of cellular integrity. The onset of detectable changes as well as number and extent of cellular alterations reproducibly correlated with the severity of symptoms and allowed for establishing a grading system for the allergic response over time.
Conclusion: Endonasal confocal laser endomicroscopy is a promising method for real-time in vivo investigation of mucosal allergic patterns on a cellular level. The results of this study suggest that it might be useful to clinicians to add a visual grading of the individual intensity of clinical response in nasal provocation testing and highlight interindividual variations within this well-established diagnostic tool.
Comparison of Steroid Regimens in Management of CRSsNP
Hector A. Perez, MD (Presenter); Ethan Miles; Christopher Vuong; Christopher Church; Kristin Seiberling
Introduction: Topical nasal steroids and oral antibiotics are a mainstay in treatment of patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP). Oral steroids are commonly given for both of these variants; however, their role in CRSsNP is less well delineated. The purpose of this research study is to determine if there is a role for oral steroids in patients who have CRSsNP and compare their impact in patients who receive only antibiotic therapy.
Method: This is a prospective randomized trial with patients divided into 3 different arms. The treatment arms consisted of amoxicillin clavulanate with steroid nasal spray (group 1); amoxicillin clavulanate, steroid nasal spray, with a 6-day prednisone course (group 2); and amoxicillin clavulanate, steroid nasal spray, with a 20-day prednisone course (group 3). Patients presenting to an outpatient rhinology clinic with history of CRS with Lund-Mackay scores of 6 or greater and no evidence of polyps on nasal endoscopy were enrolled in the study and randomized. Sinonasal Outcome Test–22 (SNOT-22) questionnaires were administered on the day of enrollment. SNOT-22 questionnaires, computed tomography scans, and nasal endoscopy were repeated at the 4-week follow-up visit.
Results: A total of 33 patients were enrolled as part of the study. SNOT-22, Lund-Mackay, and Lund-Kennedy groups were not significantly different in the pretreatment analysis of the 3 groups (P value .62, .72, .57). After the 4 weeks of treatment, SNOT-22 score averages among the 3 groups decreased from 46.6, 49.8, and 41.3 to 40.3, 32.2, and 29.4, respectively, for groups 1, 2, and 3; however, no changes were considered statistically significant between groups (P value .52). Lund-Mackay scores were significantly decreased in group 2, with a mean decrease of 1.7 points (P value .07). There was no significant difference in the posttreatment Lund-Mackay score (P value .98) or in the percentage of patients requiring sinus surgery within 1 year of study enrollment (P value .82).
Conclusion: In adults with CRSsNP, the cohorts of patients who had the addition of oral steroids had the greatest reported symptomatic improvement, with no appreciated difference between a 6-day and a 20-day steroid course.
Effect of p16 Status on Survival Outcomes in Sinonasal Squamous Cell Carcinoma
Aarti Agarwal, MD (Presenter); Gurston Nyquist, MD; Ramez Philips, MD; Chandala Chitguppi, MD; Marc R. Rosen, MD; Mindy R. Rabinowitz, MD
Introduction: We analyze the effect of p16 positivity on recurrence patterns, disease-free survival (DFS), and overall survival (OS) in sinonasal mass (SNM); elucidate the role of p16 status on survival for sinonasal squamous cell carcinoma (SCC); and examine the role of p16 in treatment for sinonasal malignancy. This is an analysis on the effect of p16 positivity on recurrence patterns, disease-free survival (DFS), and overall survival (OS) in SNM.
Methods: Retrospective chart review was conducted at a tertiary care center. Patients with sinonasal SCC treated with curative intent from 2012 to 2018 were identified. The independent variable of interest was p16 status, which was assessed using immunohistochemistry with a 70% staining cutoff for positivity. Kaplan-Meier survival curve was plotted to assess correlation between p16 status and DFS and OS. The association between recurrence patterns and p16 status was conducted using chi-square and Fisher exact tests. Multivariable Cox proportional hazard analysis was conducted to assess the association between independent variables and DFS.
Results: A total of 55 patients with sinonasal SCC met inclusion criteria. Patients were p16 positive in 32 of 55 (58%) of cases. Kaplan-Meier survival curve revealed no statistically significant association between p16 status and DFS or OS survival (P = .402, P = .416). There was no difference in recurrence patterns in patients with p16-positive vs -negative tumors.
Conclusion: p16 status did not have prognostic value on DFS and OS in our cohort of patients with sinonasal SCC undergoing treatment with curative intent. There was no difference in recurrence patterns between the 2 populations. Based on the results of this study, p16 status should not affect counseling of patients as it relates to their prognosis from SNM.
The Impact of Biologics on Sinonasal Outcomes in Patients Treated for AERD
Glen D’Souza, MD (Presenter); Elina Toskala, MD; Mindy R. Rabinowitz, MD; Gurston Nyquist, MD; Marc Rosen, MD; Jessica Most, MD
Introduction: We recognize demographic factors predictive of treatment failure in aspirin-exacerbated respiratory disease (AERD); analyze the impact of sinonasal and asthma variables on treatment failure in AERD; and demonstrate the complexity of managing patients with AERD. As biologics have only recently been approved for use in polyps, the study needed more follow-up data to be robust.
Methods: This is a retrospective chart review conducted at a tertiary care hospital between 2011 to 2021 by performing a search through the electronic medical record for patients with an ICD code diagnosis of 2 out of 3 AERD criteria: asthma, aspirin, and nonsteroidal anti-inflammatory drug sensitivity and sinonasal polyposis. This was followed by a manual chart review to include patients with all 3 criteria. They were grouped into patients whose symptoms were adequately managed by single treatment modality (group A) or needed change in treatment modality (group B). Demographic data were analyzed.
Results: Of the 72 (N) patients in the study, 36% (26) required change in treatment modality. The mean age and body mass index were 44.48 years (SD 15.11, range 18.9 to 73.24 [group A vs group B, 46.82 vs 41.17 years, P = .16] and 29.83 (SD 7.99, range 18.9 to 56 29 [group A vs group B, 58 vs 30.29, P = .72]), respectively. Overall, 65% were women, with no significant gender differences between the groups (group A vs group B = 68% vs 58%, P = .26). While 58% of the population was Caucasian, a significantly higher number of African Americans required change in treatment modality (group A vs group B [24% vs 50%, P = .043]), 61.5% (16) changed from AD to B, of which 44% (7) had their symptoms controlled by a single biologic agent while 56% required more than 1 change in biologic agent.
Conclusion: Racial factors may play a role in predicting adequate management of AERD as shown by our study, while the role played by other demographic factors may not be statistically significant. The role of sinonasal and asthma variables in predicting response to therapy is being studied.
Inflammatory Cytokine Signature in Allergic Fungal Sinusitis
William C. Scott, MD (Presenter); Katherine Hill, MD; Rakesh Chandra, MD; Naweed Chowdhury, MD; Justin H. Turner, MD, PhD
Introduction: Allergic fungal sinusitis (AFS) is a clinically challenging subtype of chronic rhinosinusitis with nasal polyps (CRSwNP). Although most CRSwNP is associated with primarily type 2 inflammation, the inflammatory signature of AFS specifically has not been well characterized.
Method: During endoscopic sinus surgery, mucus was collected from 109 patients with CRSwNP, 25 patients with AFS, and 63 non-CRS controls. Seventeen inflammatory mediators and cytokines were measured from these samples. The patterns of inflammatory marker expression were compared between groups. Markers of disease severity including preoperative Sinonasal Outcome Test–22 (SNOT-22) scores, number of prior surgeries, and radiographic Lund-McKay scores were also collected for both groups.
Results: Both AFS and CRSwNP were distinguished from non-CRS controls by significantly elevated levels of interleukin (IL)–5, IL-6, IL-7, IL-8, IL-13, and tumor necrosis factor-α. AFS could be distinguished from CRSwNP by elevated levels of IL-5 (P = .002), IL-6 (P = .01), IL-9 (P = .01), and IL-13 (P < .001). When compared with CRSwNP, patients with AFS had higher Lund-McKay scores (P < .001) and a higher average number of prior surgeries (P = .005) but had lower preoperative SNOT-22 scores, although this result was not statistically significant.
Conclusion: AFS and CRSwNP were found to have a predominantly type 2 inflammatory signature, consistent with their eosinophilic presentation. AFS was characterized by an even more marked elevation in type 2 cytokines when compared with CRSwNP. Better defining the inflammatory signature of AFS will help us better understand its pathophysiology and may help elucidate the role for biologic medications in managing this disease.
