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Objective: Structured histopathology (SHP) is a method of analyzing sinonasal tissue to characterize endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP). Allergic fungal rhinosinusitis (AFRS) shares several features with certain endotypes of CRSwNP. Our objective was to compare the histopathology of AFRS and eosinophilic CRSwNP to further understand whether they are separate endotypes or disease entities altogether., Methods: A retrospective review of AFRS and CRSwNP patients undergoing endoscopic sinus surgery was performed. Data were collected on demographics, comorbidities, subjective and objective severity scores, and 13-variable SHP reports. CRSwNP patients with >10 eosinophils per high-power field (eCRSwNP) were included. Chi-squared and t-tests were used for statistical analysis., Results: A total of 29 AFRS and 108 eCRSwNP patients were identified. AFRS patients were younger and more often Black. Symptom severity scores (SNOT-22, Lund-MacKay, and Lund-Kennedy) were uniform between groups. AFRS patients had a higher rate of Charcot-Leyden crystals (41.4% vs. 10.2%; p < 0.001). Severe degree of inflammation, eosinophilic inflammatory predominance, eosinophil aggregates, subepithelial edema, and basement membrane thickening were common in both groups, and their rates were not statistically significantly different between groups. Metaplasia, ulceration, fibrosis, and hyperplastic/papillary change rates were low (<30%) and similar between groups., Conclusion: The SHP of eCRSwNP and AFRS are highly consistent, which suggests AFRS is a severe subtype of CRSwNP overall rather than a separate disease entity. This also lends credence to AFRS belonging on the endotypic spectrum of CRSwNP., Level of Evidence: 3 Laryngoscope, 134:2617-2621, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Biologics are effective for chronic rhinosinusitis with nasal polyposis (CRSwNP) by reducing type 2 inflammation. Nonresponders often require functional endoscopic sinus surgery (FESS) and represent a challenging population potentially due to non-type 2 pathophysiology. This study characterizes the histopathologic features of biologic nonresponders., Methods: A retrospective review of 257 CRSwNP patients undergoing FESS was conducted. The biologic nonresponder group included patients with prior biologic therapy who exhibited persistent symptoms and polyp burden. Those with CRSwNP not prescribed biologic therapy were selected as controls. Demographics, comorbidities, and structured histopathology consisting of 13 variables were collected., Results: Of 257 CRSwNP patients, 20 were on biologics prior to FESS. Fourteen patients (70.0%) received dupilumab, one (5.0%) received mepolizumab, one (5.0%) received omalizumab, and four (20.0%) tried multiple biologics. The mean age for the biologic nonresponder group was 45.8 years compared to 50.4 years for the controls. Nonresponders had a significantly increased incidence of reduced tissue eosinophilia, defined as <5 per high power field (55% vs. 31.2%, p = 0.044) and increased basement membrane thickening (100% vs. 78.1%, p = 0.019). The remaining 11 variables did not reach statistical significance., Conclusion: Histopathologic analysis of biologic nonresponders demonstrates decreased eosinophilia and thickened basement membranes. These findings, particularly low tissue eosinophils, are consistent with a non-type 2 CRSwNP that may be recalcitrant to biologic therapies. Histopathologic analysis done in conjunction with FESS may aid clinicians in understanding response to biologic therapies in patients with CRSwNP who have persistent symptom burden necessitating FESS., (© 2023 ARS‐AAOA, LLC.)

Background: Adult and elderly patients with chronic rhinosinusitis (CRS) undergo similar therapeutic management. Few studies have undertaken sinonasal tissue-level comparisons of these groups. This study examines histopathological differences between adults (>18, <65 years) and the elderly (≥65 years) with CRS, with the goal of optimizing medical management., Methods: In a retrospective cohort analysis, demographic factors, comorbidities, and a structured histopathological report of 13 variables were compared across adult and elderly patients with CRS who underwent functional endoscopic sinus surgery. These cohorts of adult and elderly patients included patients with and without nasal polyps (NP)., Results: Three hundred adult (158 aCRSsNP, 142 aCRSwNP) and 77 elderly (38 eCRSsNP, 39 eCRSwNP) patients were analyzed. Mean age of the adult cohort was 44.4 ± 12.4 years, while that of the elderly cohort was 71.9 ± 5.9 years ( P   <   .001 ). Significantly more adults compared to elderly individuals demonstrated a positive atopic status (79.7% vs 64.0%, P   =   .004 ). Elderly patients exhibited higher rates of comorbid diabetes mellitus than adult patients (21.6% vs 10.3%, P   =   .009 ). Adults exhibited more tissue eosinophilia (43.4% vs 28.6%, P   =   .012 ) and presence of eosinophil aggregates (25.0% vs 14.3%, P   =   .029 ) compared to elderly patients, regardless of NP status. Conversely, the elderly demonstrated significantly more fungal elements (11.7% vs 3.0%, P   =   .004 ), and trended toward increased overall inflammation (63.6% vs 55.3%, P   =   .118 ) and tissue neutrophilia (35.1% vs 27.3%, P   =   .117 ), compared to adults., Conclusion: Sinonasal tissue of adult and elderly patients with CRS demonstrates clear histopathological differences. Patient comorbidities, in addition to histopathological characterizations, may provide further context for management optimization., Level of Evidence: 2., Short Summary: Sinonasal tissue samples from adult and elderly patients with CRS demonstrate clear histopathological differences. These patient populations also exhibit unique comorbidities. These distinctions have the potential to inform and optimize management of this condition.

Objective: To explore how diabetes mellitus impacts chronic rhinosinusitis clinically and on structured histopathology to provide insights on new potential chronic rhinosinusitis endotypes., Study Design: Retrospective cohort study., Setting: Tertiary academic center., Methods: A retrospective study of chronic rhinosinusitis patients who underwent functional endoscopic sinus surgery from 2015 to 2020 was performed. Structured 13-variable histopathology reports were generated from intraoperative sinonasal specimens. These variables were compared against demographic factors, comorbidities, culture data, and preoperative Lund-Mackay and SNOT-22 scores using logistic regression., Results: There were 411 patients, including 52 diabetics. Diabetes was associated with higher mean body mass index (34.9 vs 29.2; p < .001), age (57.8 vs 48.0; p < .001), and Gram-negative (40.2% vs 22.7%; p < .030) and coagulase-negative Staphylococcus (49.0% vs 28.5%; p = .008) culture rates. Black (23.1% vs 18.7%) and Hispanic (23.1% vs 8.6%) races were more common with diabetes (p = .026). Gender, smoking, polyp status, and Lund-Mackay and SNOT-22 scores did not differ between groups. Diabetics had more fungal elements (13.5% vs 3.3%, p = .018); no other histopathological differences were seen. When controlling for demographic variables and comorbidities, diabetes independently predicted the presence of fungal elements (HR 4.38, p = .018)., Conclusion: Diabetic chronic rhinosinusitis patients demonstrated increased fungal elements on structured histopathology. Other histopathological features were unaffected by diabetes. These findings may have important implications on the medical and surgical management of diabetic chronic rhinosinusitis patients in which early fungal disease assessment is paramount., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: Adult and pediatric patients with chronic rhinosinusitis (CRS) may have differing philosophies in therapeutic management. Few studies have examined sinonasal tissue-level comparisons of these groups. This study examines histopathologic differences between children and adults with CRS, with the goal of understanding disease pathogenesis and optimizing medical management for both populations., Methods: In a retrospective cohort of CRS patients who underwent functional endoscopic sinus surgery (FESS), demographic factors, pertinent comorbidities, and a structured histopathologic report of 13 variables were compared across pediatric and adult CRS patients with and without nasal polyps (pCRSwNP, pCRSsNP, aCRSwNP, aCRSsNP, respectively)., Results: A total of 378 adult (181 aCRSsNP, 197 aCRSwNP) and 50 pediatric (28 pCRSsNP, 22 pCRSwNP) patients were analyzed. Significantly more children compared with adults had a comorbid asthma diagnosis (64.5% vs. 37.2%, p = 0.003). Adults with CRS exhibited significantly more tissue neutrophilia (28.9% vs. 12.0%, p = 0.006), basement membrane thickening (70.3% vs. 44.0%, p < 0.001), subepithelial edema (61% vs. 30.0%, p < 0.001), squamous metaplasia (22.0% vs. 4.0%, p < 0.001), and eosinophil aggregates (22.8% vs. 4.0%, p < 0.001) than children with CRS. The majority (66.5%) of adult CRS patients exhibited a lymphoplasmacytic-predominant inflammatory background, whereas the majority (57.8%) of children with CRS exhibited a lymphocyte-predominant inflammatory background., Conclusions: Sinonasal tissue of adult and pediatric CRS patients demonstrates clear histopathologic differences. Our findings provide insight into differing pathophysiology, which may enable optimization of targeted therapies for patients in each of these unique clinical groups., (© 2022 ARS-AAOA, LLC.)

Background: Atopy has a strong association with chronic rhinosinusitis (CRS)., Objective: To understand whether patients with atopy and CRS can be defined by markers of tissue histopathology, systemic biomarkers, and clinical factors, which may guide their response to new pharmacologic agents., Methods: In a retrospective cohort of CRS patients who underwent functional endoscopic sinus surgery, a structured histopathology report consisting of 12 variables, comorbid conditions, preoperative total serum IgE levels, and preoperative modified Lund-Kennedy endoscopic and sinonasal outcome test (SNOT-22) scores were compared between atopic CRS (aCRS) and non-aCRS control patients in a multivariable model., Results: A total of 380 CRS patients were enrolled, 286 of whom had comorbid atopy (aCRS). Compared with non-aCRS, aCRS patients had significantly higher preoperative total SNOT-22 scores (40.45 ± 22.68 vs 29.70 ± 20.68, P = .015) and symptom-specific SNOT-22 scores in all domains except psychological dysfunction. Relative to non-aCRS, aCRS patients had increased tissue eosinophilia (P < .0001), eosinophil aggregates (P < .0001), Charcot-Leyden crystals (P < .04), fibrosis (P < .02), total serum IgE levels (P < .04), polyploid disease (P < .001), and a prevalence of comorbid asthma (P < .0001) and aspirin exacerbated respiratory disease (AERD) (P < .003). Patients with aCRS demonstrated increased tissue eosinophilia compared with non-aCRS patients even after controlling for polypoid disease, asthma, and AERD., Conclusion: In the context of CRS, atopy appears to be a specific predictor of CRS severity linked to specific histopathologic variables, including enhanced eosinophilic aggregates. Moving forward, allergic status may be a useful way to identify an atopic endotype of CRS patients. Furthermore, after surgery, patients are often maintained on intranasal corticosteroids. In patients whose disease is unresponsive to steroids, we may look to atopic status to identify another management therapy. Atopic CRS patients, irrespective of polyp and asthmatic status, could be optimal candidates for biologic agents such as T-helper cell, eosinophil, and/or IgE-targeted therapies., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic rhinosinusitis (CRS) is a frequently observed condition in patients with immunodeficiency secondary to immunosuppressive medications. The histologic features of CRS among patients undergoing immunosuppressive treatment have yet to be determined and may have important implications on understanding the pathophysiology of the disease process., Methods: A structured histopathology report was utilized to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). Histopathology variables, Lund-Mackay score (LMS), and sinonasal outcome test 22 scores were compared among patients with CRS on immunosuppressive therapy (CRSi), CRS without nasal polyps (CRSsNP) patients, and CRS with nasal polyps (CRSwNP) patients., Results: Fifteen CRSi, 36 CRSwNP, and 56 CRSsNP patients undergoing FESS were analyzed. Compared to CRSsNP, CRSi patients exhibited a trend toward increased moderate-severe inflammation (66.7% vs 42.1%, P < .080), increased neutrophil infiltrate (40.0% vs 24.6%, P < .192), and decreased fibrosis (26.7% vs 43.9%, P < .182). Compared to CRSwNP, CRSi patients demonstrated decreased fibrosis (26.7% vs 66.7%, P < .010), decreased eosinophil aggregates (13.3% vs 44.4%, P < .032), and a trend toward fewer eosinophils per high-power field (46.7% vs 66.7%, P < .154). CRSi cases had significantly lower mean LMS (8.20 ± 4.30 vs 12.78 ± 6.56, P < .017) compared to CRSwNP., Conclusion: CRSi patients exhibit histopathology and disease severity more similar to CRSsNP with trends toward increased neutrophilia and reduced fibrosis. In the appropriate clinical context, discontinuing or changing a patient's immunosuppressive regimen may be a valid treatment option in patients with CRSi. This study provides initial insight into understanding the propensity for chronic sinusitis in patients undergoing immunosuppressive treatment which may have implications on disease management.

Background: Chronic rhinosinusitis (CRS) is commonly classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Structured histopathologic reporting has the potential to identify salient histologic markers to differentiate subtypes and provide insights into pathophysiologic mechanisms in CRS., Methods: A structured histopathology report of 13 variables was prospectively employed to analyze ethmoid sinus tissue removed during endoscopic sinus surgery for 99 patients, including 43 CRSsNP and 56 CRSwNP. These variables were compared in association with presence of nasal polyps, radiographic computed tomography scores (Lund-Mackay Score [LMS]), subjective symptoms scores (SNOT-22), duration of CRS, comorbid asthma, and atopy., Results: Overall inflammation did not differentiate between CRSsNP and CRSwNP (p < 0.26). Compared to CRSsNP, CRSwNP had statistically significant increase in basement membrane thickening (76.8% vs 48.8%, p < 0.004), subepithelial edema (19.6% vs 2.3%, p < 0.01), fibrosis (58.9% vs 27.9%, p < 0.002), hyperplastic/papillary changes (12.5% vs 0.0%, p < 0.016), eosinophilia (41.1% vs 18.6%, p < 0.047), and eosinophilic aggregates (30.4% vs 11.6%, p < 0.022). Higher LMS was associated with increased eosinophilia (p < 0.001), eosinophil aggregates (p < 0.000), inflammation (p < 0.023), basement membrane thickening (p < 0.037), hyperplastic/papillary changes (p < 0.040) and fibrosis (p < 0.000). SNOT-22 scores were not associated with any histologic parameters., Conclusion: Significant histopathologic differences were evident in patients with CRSwNP and CRSsNP. No single feature reliably differentiated between the 2 subtypes, underscoring the heterogeneity of CRS and limitation of this phenotypic classification system. Eosinophilic aggregates were associated with significantly worse disease, possibly signifying a unique subtype. Further studies are needed to understand the relationship of histopathologic features to disease outcome., (© 2017 ARS-AAOA, LLC.)

Background: Sinusitis complicated by intracranial or orbital extension can be life-threatening and require emergent intervention. Histologic features of complicated sinusitis have yet to be determined and may have significant implications for understanding pathophysiology. Methods: A structured histopathology report was utilized to analyze sinus tissue extracted during functional endoscopic sinus surgery (FESS). A total of 13 histopathology variables were compared between patients with complicated sinusitis (CS), CRS without nasal polyps (CRSsNP), and CRS with nasal polyps (CRSwNP). Results: About 24 CS, 149 uncomplicated CRSsNP, and 191 uncomplicated CRSwNP patients were analyzed. Nasal tissue from CS and CRSwNP patients demonstrated similar levels of overall inflammation (66.7% vs. 69.6% with moderate/severe inflammation, P =.466). Relative to CRSsNP, CS patients showed significantly greater overall inflammation (66.7% vs. 41.6%, P =.019). CS patients demonstrated significantly fewer eosinophils per high power field (eos/HPF) and eosinophil aggregates compared to CRSwNP patients (20.8% vs. 70.7% with 5+eos/HPF, P <.0001 ; 4.2% vs. 33.5%, P <.0001). Relative to CRSsNP patients, CS patients demonstrated enhanced neutrophil infiltration (45.8% vs. 28.0%, P =.011). About 91.7% of CS patients demonstrated a lymphoplasmacytic predominant inflammatory infiltrate, compared to 69.8% of CRSsNP and 62.8% of CRSwNP patients (P <.0001). Conclusion: Significant histopathological differences were evident in patients with CS, CRSsNP, and CRSwNP. CS patients did not perfectly fit either a CRSsNP or CRSwNP profile, underscoring the importance of delineating the histopathological features of CS. This study offers insight into the histologic aspects of CS, providing initial evidence that it is an aggressive neutrophilic inflammatory process. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Failure after sinus surgery is multifactorial, but often due to recurrence of inflammatory mucosal disease. Postoperative steroid requirements for controlling mucosal inflammation may provide insight into predicting which patients require more aggressive medical therapy to prevent disease relapse.Study Design: Retrospective chart review.Methods: A review was performed of patients who underwent functional endoscopic sinus surgery (FESS) for refractory chronic rhinosinusitis (CRS). Sino-Nasal Outcome Test-22 scores and cumulative prednisone dose (milligrams) requirements at 1, 3, and 6 months postoperatively were reviewed. A structured histopathology report of 11 variables was accessed to correlate histopathology with postoperative steroid requirements.Results: One hundred one patients were reviewed including 42 CRS with nasal polyps and 59 CRS without nasal polyps patients. CRS patients with eosinophilia required greater cumulative steroids to control disease at 1-, 3-, and 6-month postoperative intervals (P < .026, P < .007, P < .013, respectively) compared to patients without eosinophilia. Patients with tissue eosinophil aggregates required the highest cumulative steroids at 1-, 3-, and 6-month postoperative intervals (P < .003, P < .001, P < .001, respectively). When removing patients with eosinophil aggregates from the eosinophilia group, no difference persisted between patients with eosinophilia and those without eosinophilia at all intervals (P = .664, P = .735, P = .800, respectively). No other histopathology variable correlated with postoperative steroid requirement.Conclusions: Tissue eosinophil aggregates appear to be the largest driving factor for increased prednisone requirements after sinus surgery to control mucosal disease than mere presence of eosinophils. This key finding may identify patients at high risk for failure after sinus surgery and guide more proactive postoperative management.Level Of Evidence: 4 Laryngoscope, 129:794-799, 2019. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis (CRS) is a heterogeneous disease process that can arise in the context of odontogenic disease from the maxillary teeth. The histopathologic features of odontogenic CRS (CRSo) have yet to be determined and may have important implications on disease management and need for escalation of therapy. Objectives The objectives of this study are to characterize the histopathologic features of CRSo and determine whether the inflammatory profile of CRSo contributes to its recalcitrance to medical therapy and need for surgery in a subset of patients with this disease. Methods A structured histopathology report was used to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). Histopathology variables, Lund–Mackay scores (LMS), and Sinonasal Outcome Test-22 scores were compared among CRSo patients, CRS without nasal polyps (CRSsNP) patients, and CRS with nasal polyps (CRSwNP) patients. Results Twenty-three CRSo, 38 CRSwNP, and 53 CRSsNP patients who underwent FESS were analyzed. Compared to CRSsNP, CRSo exhibited increased moderate–severe inflammation (73.9% vs 41.5%, P < .009). Compared to CRSwNP, CRSo had decreased squamous metaplasia (0.0% vs 18.4%, P < .03) and decreased fibrosis (26.1% vs 63.2%, P < .005). Eosinophilia was prevalent in CRSo but to a lesser extent than in CRSwNP (39.1% vs 63.2%, P < .05). CRSo cases had significantly lower mean LMS compared to CRSwNP (7.83 ± 2.77 vs12.18 ± 6.77, P < .005). Conclusion CRSo exhibits histopathologic features similar to those of CRSsNP with more severe inflammation. Moreover, eosinophilia, which is not typically considered to coexist with CRSo, was present in a large portion of CRSo patients. These findings may help explain at the inflammatory level why select cases of CRSo may be recalcitrant to medical and dental therapy. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis (CRS) is a commonly observed sequela after radiation therapy to the paranasal sinuses. The histopathologic features of radiation-induced CRS have yet to be determined and may have major implications in disease management. Methods A structured histopathology report was utilized to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). Histopathology variables, Lund-Mackay score (LMS), and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were compared among patients with radiation-induced CRS (CRSr), CRS without nasal polyps (CRSsNP), and CRS with nasal polyps (CRSwNP). Results Fifteen CRSr, 43 CRSsNP, and 56 CRSwNP patients who underwent FESS were analyzed. Compared with CRSsNP, CRSr cases had increased squamous metaplasia (40.0% vs 9.3%, p < 0.013) and subepithelial edema (53.3% vs. 2.3%, p < 0.001). Compared with CRSwNP, CRSr cases had fewer eosinophils per high-power field (20.0% vs 50.0%, p < 0.034), less basement membrane thickening (33.3% vs 76.8%, p < 0.002), and fewer eosinophil aggregates (0.0% vs 30.4%, p < 0.009). CRSr had significantly greater mean LMS (13.47 ± 5.13 vs 7.07 ± 4.79, p < 0.001) compared with CRSsNP. Conclusion Radiation-induced CRS patients exhibited greater squamous metaplasia and subepithelial edema when compared with a cohort of patients with CRSsNP, and decreased eosinophilia and basement membrane thickening compared with a cohort of CRSwNP patients. CRSr cases demonstrated no difference in eosinophilia or neutrophilia compared with CRSsNP, and decreased eosinophilia compared with CRSwNP, lending further credence to the unique nature of radiation in the development of CRS in this patient group. These findings may have major implications with regard to extent of surgical intervention and medical management. [ABSTRACT FROM AUTHOR]

Background: Medically refractory chronic rhinosinusitis (CRS) is often treated with functional endoscopic sinus surgery (FESS) and high‐volume steroid nasal irrigation. While budesonide is the most common steroid irrigation for this indication, mometasone has a superior pharmacokinetic profile, which may allow dose escalation. The safety and efficacy of mometasone at higher concentrations than previously used in treating CRS have not been explored. Methods: Patients were recruited from a tertiary level clinic between June 2018 and December 2019. Inclusion criteria included adults (>18 years); CRS diagnosis; previous FESS; pre‐treatment morning cortisol within normal range; minimum of twice daily high‐volume sinonasal mometasone irrigations (total dose of 4 mg) for 12 weeks; and post‐treatment morning cortisol measured within 2 weeks following the study period. Patients with potential for endogenous or exogenous disruption of the HPA axis were excluded. Results: 14 patients were enrolled in this prospective cohort study. In all but one patient, pre‐ and post‐treatment morning cortisol levels were not significantly different and were within normal limits (6.7‐25.4 μg/dL). Following an uninterrupted 12‐week treatment course, no evidence of HPA axis suppression was found (P = 0.915). The single patient who was found to have a low (1.3 μg/dL) post‐treatment morning serum cortisol level reportedly received an intraarticular steroid shot several days prior to the blood draw. She remained asymptomatic and her rechecked serum cortisol was within normal limits at 12.3 μg/dL. Conclusions: High‐volume 2 mg twice daily sinonasal mometasone irrigations did not cause HPA axis suppression in a representative sample of patients with refractory CRS post‐FESS with normal baseline cortisol levels. [ABSTRACT FROM AUTHOR]

Patients with post-functional endoscopic sinus surgery CRS treated with intranasal low- and high-dose mometasone exhibited improved endoscopic sinus disease relative to postoperative patients whose disease was not managed with corticosteroids. Keywords: chronic rhinosinusitis; corticosteroids; endoscopic sinus surgery; medical therapy; patient reported outcome measure; quality of life; SNOT-22; topical irrigations EN chronic rhinosinusitis corticosteroids endoscopic sinus surgery medical therapy patient reported outcome measure quality of life SNOT-22 topical irrigations 955 957 3 06/21/22 20220701 NES 220701 INTRODUCTION The most commonly accepted cause of chronic rhinosinusitis (CRS) is inflammation of the upper airway, specifically the nose and paranasal sinuses.1 Treatment is aimed at decreasing mucosal inflammation, overcoming associated hypersecretory mucin, and suppressing reactivity to environmental triggers. Improved sinonasal symptom and endoscopy sinus scores with dose-escalated intranasal mometasone irrigation in patients with refractory chronic rhinosinusitis. [Extracted from the article]