Sphenoid Sinus Fungal Ball and Reestablishing Sinus Function.

OBJECTIVES: The aim was to assess the developmental attributes of sphenoid sinuses affected by fungal balls and describe a surgical approach which reestablishes gravity-dependent drainage to compensate for any mucociliary dysfunction. METHODS: A within-patient case-control analysis was performed on sphenoid sinus dimensions from patients with sphenoid sinus fungal ball (SSFB). Radiological dimensions were assessed to determine the dominant or larger sinus by volume and width. Pneumatization in the sagittal and lateral extent was assessed. The influence of sinus size and pneumatization variants within a patient was analyzed. Patency and the presence of mucostasis from radical reshaping of the sinus cavity were documented at least 3 months after surgery. Complications (bleeding, cerebrospinal fluid leak, and cranial nerve palsy) were recorded. RESULTS: Twenty-three patients (59 ± 19 years, 86% female, 46 sphenoid sinuses) were assessed. Fungal ball was more common in the smaller (non-dominant) sinus, by width (78% vs. 22%, p < 0.01) and by proportion of total sphenoid volume (0.39 ± 0.16 vs. 0.61 ± 0.16, p < 0.01). Pneumatization variants did not influence the development of SSFB within a patient. All patients had patency and the absence of mucostasis or persistent inflammation at last follow-up. No complications were reported. CONCLUSION: The smaller or nondominant sphenoid sinus is more affected by SSFB. Surgical reshaping of the sphenoid to prevent mucostasis is favorable in managing the smaller affected sinus cavity. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Headache in Patients with Sellar Disease: Clinicomorphological Predictors of Headache and the Outcome of Endoscopic Transsphenoidal Surgery.

Objectives Sellar pathologies are frequently found on imaging performed to investigate headache. However, both headache and incidental sellar lesions are common. Hence, this study prospectively examined headache prevalence, phenotype, and severity in patients with sellar pathologies and the impact of transsphenoidal surgery on headache. Methods Patients undergoing transsphenoidal resection of sellar lesions were consecutively recruited. At baseline, participants were defined as having headache or not and headache phenotype was characterized using validated questionnaires. Headache severity was assessed at baseline and 6 months postoperatively using the Headache Impact Test-6 (HIT-6) and Migraine Disability Assessment Score (MIDAS). Tumor characteristics were defined using radiological, histological, and endocrine factors. Primary outcomes included baseline headache prevalence and severity and headache severity change at 6 months postoperatively. Correlation between headache and radiological, histological, and endocrine characteristics was also of interest. Results Sixty participants (62% female, 47.1 ± 18.6 years) were recruited. Sixty-three percent possessed baseline headache. HIT-6 scores were higher in patients with primary headache risk factors, including younger age (R 2 = -0.417, p = 0.010), smoking history (63.31 ± 7.93 vs 54.44 ± 9.21, p = 0.0060), and family headache history (68.13 ± 7.01 vs 54.94 ± 9.11, p = 0.0030). Headaches were more common in patients with dural invasion (55.70 ± 12.14 vs 47.18 ± 10.15, p = 0.027) and sphenoid sinus invasion (58.87 ± 8.97 vs 51.29 ± 10.97, p = 0.007). Postoperative severity scores improved more with higher baseline headache severity (HIT-6: R 2 = -0.682, p < 0.001, MIDAS: R 2 = -0.880, p < 0.0010) and dural invasion (MIDAS: -53.00 ± 18.68 vs 12.00 ± 17.54, p = 0.0030). Conclusion Headaches in sellar disease are likely primary disorders triggered or exacerbated by sellar pathology. These may respond to surgery, particularly in patients with severe headache and dural invasion.

Preservation or removal of the lateral nasal wall in endoscopic management of maxillary sinus neoplasia: A comparison of approach related morbidity.

BACKGROUND: The endoscopic modified medial maxillectomy (MMM) and prelacrimal approach (PLA) are two routinely performed endoscopic approaches to the maxillary sinus when access via a middle meatal antrostomy is insufficient. However, there is no data in the literature that has compared outcomes and complication profile between the two procedures to determine which approach is superior. OBJECTIVE: To compare the approach related morbidity of PLA and MMM. METHODS: A retrospective cohort study of all consecutive adult patients undergoing either MMM or PLA from 2009 to 2023 were identified. The primary outcome was development of epistaxis, paraesthesia, lacrimal injury, iatrogenic sinus dysfunction within a minimum of 3 months post-operative follow up. RESULTS: 39 patients (44 sides) underwent PLA and 96 (96 sides) underwent MMM. There were no statistically significant differences between the rates of paraesthesia (9.1 % vs 14.6 %, p = 0.367) or prolonged paraesthesia (2.3 % vs 5.2 %, p = 0.426), iatrogenic maxillary sinus dysfunction (2.3 % vs 5.2 %, p = 0.426) or adhesions requiring removal (4.5 % vs 4.2 %, p = 0.918). No cases of epiphora or nasal cavity stenosis occurred in either arm in our study. CONCLUSIONS: According to our data, the endoscopic modified medial maxillectomy and prelacrimal approach are both equally safe approaches with their own benefits to access.

Comparison of Allergen Immunotherapy Alone and in Conjunction With Turbinate Surgery for Nasal Obstruction in Perennial Allergic Rhinitis Patients.

BACKGROUND: Nasal obstruction, triggered by allergic rhinitis, often does not resolve with allergen-specific immunotherapy (AIT) alone, thus inferior turbinate reduction surgery (ITR) may be required. This study aims to investigate the impact of combined treatment on nasal obstruction, as evidence is currently limited. METHODOLOGY/PRINCIPAL: A retrospective cohort study of perennial allergic rhinitis patients experiencing nasal obstruction and undergoing ≥12 months AIT was conducted. Two groups were derived, those undergoing AIT-with or without an ITR. Patient reported nasal obstruction (evaluated with questionnaires) and nasal airway function (Nasal Peak Inspiratory Flow [NPIF] and Nasal Airflow Resistance [NAR]) were monitored. The change from baseline to 12 months post-treatment in each group were compared. RESULTS: A total of 118 patients (33.71 ± 14.43 years, 41.5% female) were recruited, 72% had AIT and 28% AIT&ITR. At baseline, the AIT&ITR group had a higher level of nasal obstruction (>moderate%; 63.6% vs 52.9%, P = .048). Post treatment, AIT&ITR group reported greater reduction in nasal obstruction (>1 category change: 75.8% vs 48.2%, P = .002). Similarly, the AIT&ITR group had greater improvement in nasal function by NPIF (-13.9 ± 110.3 L/minute vs -3.4 ± 78.1 L/minute, P = .049) and NAR (-0.120 ± 0.342 Pa/cm³/second vs -0.093 ± 0.224 Pa/cm³/second, P = .050). CONCLUSIONS: Allergic rhinitis patients, with moderate to severe nasal obstruction, who undergo combined AIT&ITR have greater relief of nasal obstruction and improved airflow analysis compared to AIT alone.

Long-term treatment outcomes in refractory rhinitis medicamentosa managed with nasal surgery.

BACKGROUND: Limited treatment options exist for refractory Rhinitis Medicamentosa (RM). The role of surgery after failed medical management is not well defined. Mucosal contact points and restricted airflow often perpetuate decongestant use. This study assessed the long-term outcomes of nasal surgery in patients with refractory RM. METHODS: A prospective cohort study of refractory RM treated with nasal surgery was performed with ≥12 months follow-up. Refractory RM was defined as nasal decongestant use once per day continuously for ≥4 weeks despite medical therapy. Patients with concomitant sinus disease and nonrhinitis conditions were excluded. Sinonasal Outcome Test (SNOT22), Nasal Symptom Score (NSS), and nasal medication use were assessed. Patients who ceased decongestants were compared with ongoing users. RESULTS: A total of 56 patients (age 48.4 [5.0] years, 50% female) were assessed. Median follow-up was 3.4(1.6-6.2) years. Total cessation of decongestants was achieved in 91.1%, while 5.4% had intermittent use, and 3.6% reported daily use. Ongoing users had higher odds of concomitant asthma (40.0% vs. 3.9%; odds ratio [OR], 16.33 [1.7-159.75]; p = 0.036), reduced symptom improvement (ΔSNOT22, -4.6 [15.7] vs. 27.1 [17], p = 0.009 and ΔNSS, -1.0 [4.2] vs. -6.6 [5.1], p = 0.025), and greater ongoing use of nasal corticosteroid (60.0% vs. 5.9%; OR 24.0 [2.8-203.1]) and saline sprays (40% vs. 3.9%; OR 16.3 [1.7-159.8]) but showed no difference in allergy status (OR, 0.7[0.1-7.1]), previous surgery (OR, 1.0[0.1-10.2]), gastroesophageal reflux (OR 1.0[0.1-10.2], or underlying anxiety/depression (OR 6.1[0.8-45.9]) compared with those who ceased. CONCLUSION: Surgically re-establishing a nasal airway was associated with long-term decongestant cessation and symptom improvement in medically refractory RM.

Predictors of persistent disease in biologic treated type 2 diffuse/eosinophilic chronic rhinosinusitis undergoing surgery.

BACKGROUND: Biologic therapy targeting type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) has greatly improved disease control but nonresponders exist in a proportion of patients in phase 3 trials and clinical practice. This study explores the serum and histologic changes in biologic treated CRSwNP that predict disease control. METHODS: A cross-sectional study was performed of patients with CRSwNP on biologics for their asthma, who underwent endoscopic sinus surgery while on biologic therapy. At the 6-month postoperative assessment, patients with poorly controlled CRSwNP while on biologic therapy were compared to patients who were controlled. Blood and mucosal samples taken at the time of surgery 6 months prior were assessed to predict disease control. RESULTS: A total of 37 patients were included (age 47.8 ± 12.4 years, 43.2% female). Those with poorly controlled disease had reduced tissue eosinophils (% >100 cells/high-powered field: 8.3% vs. 50.0%, p < 0.001) and increased serum neutrophils (5.2 ± 2.7 vs. 3.7 ± 1.1 × 109 cells/L, p = 0.02). Logistic regression analysis demonstrated that reduced tissue eosinophil was predictive for poorly controlled disease (OR = 0.21, 95% CI [0.05, 0.83], p = 0.03). Receiver-operating characteristic analysis showed that need for rescue systemic corticosteroid was predicted at a serum neutrophil cut-off level of 5.75 × 109 cells/L (sensitivity = 80.0%, specificity = 96.9%, AUC = 0.938, p = 0.002). CONCLUSION: Low tissue eosinophils and increased serum neutrophils while on biologics predict for poor response in the biological treatment of with CRSwNP. A serum neutrophil level of ≥5.75 × 109 cells/L predicts for poor response to current biologic therapy.

Recreating the microscopic direct access Draf 2a frontal sinusotomy in the endoscopic era and comparison to an angled instrument approach.

PURPOSE: Microscopic Draf 2a frontal sinusotomy relied on direct access. However, the modern-day endoscopic approach is hindered by the anterior-posterior dimensions of the frontal recess. The nasofrontal beak, angled endoscopes, and variable frontal recess anatomy make the surgery challenging. Carolyn's window frontal sinusotomy removes the limitation of anterior-posterior dimensions and is an endoscopic version of the microscopic Draf 2a. This study aims to compare the perioperative outcomes and morbidity from endoscopic direct access Draf 2a compared to angled access Draf 2a. METHODS: Consecutive adult patients (> 18 years) seen at a tertiary referral clinic who underwent Draf 2a frontal sinus surgery using either endoscopic direct access (Carolyn's window) or endoscopic angled instrumentation were included. Patients who underwent Carolyn's window were compared to those with angled Draf 2a frontal sinusotomy. RESULTS: One hundred patients (age 51.96 ± 15.85 years, 48.0% female, follow-up 60.75 ± 17.34 months) were included. 44% of patients used Carolyn's window approach. 100% [95% CI 98.2-100%] of patients achieved successful frontal sinus patency. Both groups were comparable for early morbidities (bleeding, pain, crusting, and adhesions) and late morbidities (retained frontal recess partitions). There were no other morbidities in the early and late postoperative periods. CONCLUSION: The endoscopic direct access Draf 2a, or Carolyn's window, removes the anteroposterior diameter limitation. The frontal sinus patency and early and late surgical morbidities of direct access Draf 2a were comparable with the angled Draf 2a frontal sinusotomy. Surgical modifications, often with drills and bone removal, can be successfully made to enhance access in endoscopic sinus surgery without concern for additional morbidity.

Endoscopic-Modified Medial Maxillectomy for the Nonfunctioning Maxillary Sinus.

BACKGROUND: Middle meatal antrostomy (MMA) is the traditional intervention for chronic maxillary sinusitis but often fails to correct a nonfunctioning maxillary sinus that has lost its capability for mucociliary clearance. Endoscopic-modified medial maxillectomy (EMMM) can reshape the maxillary sinus and avoid a "sumping" effect, preventing secondary bacterial colonization, encouraging dependent drainage, and promoting effective nasal irrigation. OBJECTIVES: We describe a modification of the EMMM surgical technique in patients with recalcitrant maxillary sinusitis and perioperative outcomes. METHODS: Consecutive adult patients with nonfunctioning maxillary sinuses managed with EMMM were assessed. Primary outcomes were the resolution of the presenting symptom and the absence of mucostasis. Secondary outcomes were early (<90 days) and late (>90 days) morbidity. RESULTS: Fifty-seven patients (51.7 ± 17.5 years, 56.1% female) were assessed. Fifty-two patients had complete resolution of their presenting symptom (91.2% [95% CI: 80.7-97.1]) and 52 patients had an absence of mucostasis (91.2% [95% CI: 80.7-97.1]). Those with persistent crusting were also those with symptoms. Early morbidities included temporary dysesthesia (3.2%), bleeding (1.1%), and pain (3.2%), with no late morbidities. CONCLUSION: EMMM is a robust approach for salvaging a nonfunctioning maxillary sinus. The procedure enhances nasal irrigation, supplants mucociliary clearance, and discourages dependent mucus retention.

The Modified Medial Maxillectomy as a Radical or Extended,-yet Still Functional,-Technique in Sinus Surgery.

BACKGROUND: Endoscopic sinus surgery with a middle meatal antrostomy is a common intervention in the treatment algorithm for maxillary sinus pathologies. However, this procedure has its origins in a time when simple ventilation of the sinus cavity was the primary (and only often) goal of surgery. In some patients, persistent mucociliary dysfunction occurs despite ventilatory surgery. Although the endoscopic modified medial maxillectomy (MMM) was originally described for tumour surgery, it provides a radical yet still functional option to overcome chronic sinus dysfunction. OBJECTIVE: The goal of this study was to describe the functional status of a post-MMM sinus cavity. METHODS: A consecutive series of patients who underwent at least a unilateral MMM by three tertiary rhinologists were retrospectively reviewed. Prospectively collected data included patient demographics (including age, gender, smoking status and comorbidities), disease-specific factors, microbiology, and preoperative patient-reported symptoms based on the 22-item Sinonasal Outcome Test-22 (SNOT-22) and radiology. The primary outcome of the study was the presence of sinus dysfunction, defined by mucostasis or pooling on endoscopic examination at the last follow-up. Secondary outcomes included the need for revision surgery as a result of sinus dysfunction and the improvement in SNOT-22 score. RESULTS: A total of 551 medial maxillectomies (47.0% female, 52.9 ± 16.8 years) were performed. Very few patients experienced post-operative sustained mucostasis following MMM (10.2%) and even fewer required revision surgery (5.0%). Chronic obstructive pulmonary disease (odds ratio (OR) = 6.82, P < 0.002.) and asthma (OR = 2.48, P = 0.03) were associated with mucostasis. Patients who underwent an MMM experienced a notable postoperative improvement in SNOT-22 score (45.9 ± 23.7 (pre-op) vs. 23.6 ± 19.4 (post-op); paired t-test, P < 0.0001). CONCLUSION: The MMM, whether performed for access to pathology or with the intent to avoid mucous 'sumping' with the sinus, can provide a long-term functional maxillary sinus cavity with minimal morbidity.

Bacterial colonization differences between central compartment atopic disease and eosinophilic chronic rhinosinusitis.

KEY POINTS: Culturable bacterial colonization is similar between type 2 CRS phenotypes Staphylococcus aureus coinfection is similar between eosinophilic CRS and CCAD Patients with CCAD were younger, consistent with current knowledge of the disease.

A Scoping Review of Artificial Intelligence Research in Rhinology.

BACKGROUND: A considerable volume of possible applications of artificial intelligence (AI) in the field of rhinology exists, and research in the area is rapidly evolving. OBJECTIVE: This scoping review aims to provide a brief overview of all current literature on AI in the field of rhinology. Further, it aims to highlight gaps in the literature for future rhinology researchers. METHODS: OVID MEDLINE (1946-2022) and EMBASE (1974-2022) were searched from January 1, 2017 until May 14, 2022 to identify all relevant articles. The Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews checklist was used to guide the review. RESULTS: A total of 2420 results were identified of which 62 met the eligibility criteria. A further 17 articles were included through bibliography searching, for a total of 79 articles on AI in rhinology. Each year resulted in an increase in the number of publications, from 3 articles published in 2017 to 31 articles published in 2021. Articles were produced by authors from 22 countries with a relative majority coming from the USA (19%), China (19%), and South Korea (13%). Articles were placed into 1 of 5 categories: phenotyping/endotyping (n = 12), radiological diagnostics (n = 42), prognostication (n = 10), non-radiological diagnostics (n = 7), surgical assessment/planning (n = 8). Diagnostic or prognostic utility of the AI algorithms were rated as excellent (n = 29), very good (n = 25), good (n = 7), sufficient (n = 1), bad (n = 2), or was not reported/not applicable (n = 15). CONCLUSIONS: AI is experiencing an increasingly significant role in rhinology research. Articles are showing high rates of diagnostic accuracy and are being published at an almost exponential rate around the world. Utilizing AI in radiological diagnosis was the most published topic of research, however, AI in rhinology is still in its infancy and there are several topics yet to be thoroughly explored.

CCAD or eCRS: Defining Eosinophilic Subpopulations in Chronic Rhinosinusitis.

BACKGROUND: Central compartment atopic disease (CCAD) and eosinophilic chronic rhinosinusitis (eCRS) are two clinical phenotypes of primary diffuse type 2 chronic rhinosinusitis (CRS) defined in the European Position Paper on Rhinosinusitis 2020 classification. Currently, the distinction between these subtypes relies on phenotypic features alone. OBJECTIVE: This study aimed to investigate whether eosinophil activation differed between CCAD and eCRS. METHODS: A cross-sectional study was conducted of adult patients presenting with CCAD and eCRS who had undergone functional endoscopic sinus surgery. Routine pathology results were obtained from clinical records. Eosinophils were counted on haematoxylin and eosin-stained formalin-fixed paraffin-embedded sinonasal tissue. Eotaxin-3, eosinophil peroxidase and immunoglobulin E levels were assessed using immunohistochemistry. RESULTS: 38 participants were included (51.7 ± 15.6 years, 47.4% female), of whom 36.8% were diagnosed with CCAD and 63.2% with eCRS. The eCRS group was characterised by older age (55.8 ± 16.3 vs 44.5 ± 11.8 years, p = 0.029), and on histology exhibited a higher degree of tissue inflammation (τb = 0.409, p = 0.011), greater proportion of patients with >100 eosinophils/high power field (87.5% vs 50%, p = 0.011), and higher absolute tissue eosinophil count (2141 ± 1947 vs 746 ± 519 cells/mm2, p = 0.013). Eotaxin-3 scores were higher in the eCRS group (5.00[5.00-6.00] vs 6.00[6.00-6.75], p = 0.015). Other outcomes were similar. CONCLUSIONS: Eosinophil and eotaxin-3 levels were elevated in eCRS compared with CCAD, suggesting a greater degree of eosinophil stimulation and chemotaxis. Patients with CCAD were younger. Future investigation and biomarkers may better distinguish CRS subpopulations.

Carolyn's Window Approach to Unilateral Frontal Sinus Surgery.

OBJECTIVES: Due to the complexity and variety of the frontal recess and sinus anatomy, traditional Draf 2a frontal sinus surgery is challenging. The thickness of the nasofrontal beak and anterior-posterior dimensions of the frontal recess contribute to this complexity. Carolyn's window technique eliminates the limitation of anterior-posterior depth to facilitate a Draf 2a frontal sinusotomy. The approach is a 0° endoscope technique and provides an excellent view of the frontal sinus and recess. We describe Carolyn's window approach to frontal sinus surgery and the perioperative outcomes. METHODS: Consecutive adult patients in whom Carolyn's window technique was applied for frontal sinus dissection as part of the endoscopic management of both inflammatory and neoplastic disease were assessed. The primary outcome was frontal sinus patency. Secondary outcomes were surgical morbidity, defined as early (<90 days) or late (>90 days). RESULTS: Forty-five patients (49.1 ± 17.9 years, 48.9% Female) were assessed. All patients had successful frontal sinus patency (100% [95CI: 92.1%-100%]). Morbidities were adhesion (4.8%), crusting (2.4%), pain (1.2%), and bleeding (1.2%) in the early postoperative period. There were no other morbidities in the early and late postoperative periods. CONCLUSION: Carolyn's window approach to frontal sinusotomy is a technique that evolves from previously described approaches. Successful frontal sinus patency with very low morbidities is achieved while still working with a 0° endoscope. The "axillectomy" performed simplifies frontal recess surgery by removing the anteroposterior diameter limitation and the dexterity required in angled endoscopy and instrumentation. The inferior-based lateral wall mucosal flap and free mucosal grafting expedite the mucosal healing process. Laryngoscope, 133:2496-2501, 2023.

Prelacrimal Approach to Maxillary Sinus Pathology.

BACKGROUND: Access to the anterior, lateral, inferior, and inferomedial maxillary sinus has been a limitation of the middle meatal antrostomy. Expanded techniques such as the modified medial maxillectomy provide access to many of these areas but require remucosalization, and crusting can occur during the recovery phase. The prelacrimal approach (PLA) offers direct 0° endoscope access to these areas. Additionally, PLA can preserve the nasolacrimal duct and mucosal coverage. OBJECTIVES: We describe the current surgical technique and outcomes of PLA patients. METHODS: Consecutive adult patients with pathology addressed by PLA to the maxillary sinus were assessed. The primary outcome was the restoration of the lateral wall, and the secondary outcomes were early (< 90 days) and late morbidity (> 90 days). RESULTS: Forty patients (52.8 ± 17 years, 62.5% female) were assessed. All patients had successful restoration of the lateral nasal wall (100% [95CI: 91.2%-100%]). The complications reported were primarily dysesthesia (early 10% and late 2.5%). CONCLUSION: The PLA provides robust access to the anterior, lateral, inferior, and inferomedial maxilla. PLA offers rapid mucosal recovery while preserving the normal physiology and the lacrimal systems with low morbidity.

Prognostic factors and outcomes in minimal access resections of skull base and sinonasal epithelial malignancy.

BACKGROUND: Sinonasal epithelial malignancies are uncommon tumours but represent a challenge to treatment given their close proximity to the orbit, brain and cranial nerves. Traditional external surgical approaches have potential for significant functional and cosmetic morbidity. An endoscopic approach provides the surgeon with good access for tumour removal and enables surveillance postoperatively. This study aimed to assess outcomes of an endoscopic approach to sinonasal epithelial malignancy and evaluate factors that may influence its utility. METHODS: A case series was performed involving consecutive patients treated with endoscopic or endoscopic-assisted surgery for epithelial sinonasal malignancy. Stratification included TNM staging, histopathology, surgical approach, margin status, perineural involvement and adjuvant or neoadjuvant therapy. At follow-up, complications, local control, nodal status and evidence of distant metastases were recorded. Statistical analyses to identify risk factors for developing recurrence and survival differences were performed. RESULTS: Thirty-five patients were assessed in this study (59.2 ± 11.4 years, 42.9% female). T stage at presentation was T1 in 11.4%, T2 in 17.1%, T3 in 22.9% and T4 in 48.6%. The 3 and 5 year disease specific survival were 91.3% (SE 5) and 71.1% (SE 10). The only factors to influence survival outcomes were perineural invasion of tumour and positive margins at the time of initial surgery. Large tumours did not limit the utility of an endoscopic approach. CONCLUSION: Endoscopic approach is a safe and oncologically equitable treatment approach to external approaches in the management of epithelial sinonasal malignancy. As with external approaches, perineural invasion of malignance is a poor prognostic factor.

Mepolizumab decreases tissue eosinophils while increasing type-2 cytokines in eosinophilic chronic rhinosinusitis.

BACKGROUND: Eosinophilic chronic rhinosinusitis is an often treatment-resistant inflammatory disease mediated by type-2 cytokines, including interleukin (IL)-5. Mepolizumab, a monoclonal antibody drug targeting IL-5, has demonstrated efficacy and safety in inflammatory airway disease, but there is negligible evidence on direct tissue response. The study's aim was to determine the local effect of mepolizumab on inflammatory biomarkers in sinonasal tissue of eosinophilic chronic rhinosinusitis patients. METHODS: Adult patients with eosinophilic chronic rhinosinusitis received 100mg mepolizumab subcutaneously at four-weekly intervals for 24 weeks in this prospective phase 2 clinical trial. Tissue eosinophil counts, eosinophil degranulation (assessed as submucosal eosinophil peroxidase deposition by immunohistochemistry) and cytokine levels (measured in homogenates by immunoassay) were evaluated in ethmoid sinus tissue biopsies collected at baseline and at weeks 4, 8, 16 and 24. RESULTS: Twenty patients (47.7 ± 11.7 years, 50% female) were included. Sinonasal tissue eosinophil counts decreased after 24 weeks of treatment with mepolizumab (101.64 ± 93.80 vs 41.74 ± 53.76 cells per 0.1 mm2 ; p = .035), eosinophil degranulation remained unchanged (5.79 ± 2.08 vs 6.07 ± 1.20, p = .662), and type-2 cytokine levels increased in sinonasal tissue for IL-5 (10.84 ± 18.65 vs 63.98 ± 50.66, p = .001), IL-4 (4.48 ± 3.77 vs 9.38 ± 7.56, p = .004), IL-13 (4.02 ± 2.57 vs 6.46 ± 3.99, p = .024) and GM-CSF (1.51 ± 1.74 vs 4.50 ± 2.97, p = .001). CONCLUSION: Mepolizumab reduced eosinophils in sinonasal tissue, demonstrating that antagonism of IL-5 suppresses eosinophil trafficking. With reduced tissue eosinophils, a local type-2 inflammatory feedback loop may occur. The study exposes mechanistic factors which may explain incomplete treatment response.

Comparison of Sinonasal Histopathological Changes in Biological Treatment of Eosinophilic Chronic Rhinosinusitis.

BACKGROUND: Biologic therapies such as mepolizumab and benralizumab are currently utilised in the treatment of eosinophilic asthma, and are emerging in the management of eosinophilic chronic rhinosinusitis (eCRS). These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytokine signalling and eosinophil inflammation. Mepolizumab does so by targeting IL-5, whereas benralizumab targets the α chain of the IL-5 receptor. This study compares the sinonasal tissue response to anti-IL-5 biologic therapies in patients with eCRS. METHODS: A cross-sectional study of adult eCRS patients who had completed at least 2 cycles of biologic therapy and underwent endoscopic sinus surgery as part of their management were included. Sinonasal mucosal tissue biopsies were obtained intraoperatively and assessed with structured histopathological examination. Comparisons of tissue histopathology outcomes following treatment with mepolizumab or benralizumab were performed. RESULTS: 18 patients (age 49.6 ± 14.2 years, 47% female, 100% co-morbid asthma) were included in this study, comprising 10 patients managed with mepolizumab and 8 patients managed with benralizumab. Even after mepolizumab, the tissue had predominantly eosinophilic inflammation compared to benralizumab (90% v 0%, p < 0.01), which demonstrated a greater lymphoplasmacytic inflammation (10% v 75%, χ2(2) = 14.53, p < 0.01). Compared with benralizumab, mepolizumab had increased tissue eosinophil count (100% v 37.5% >10 eosinophils/HPF, τb = -8.47, p < 0.001) and more severe subepithelial oedema (80% v 37.5% severe, τb = -2.37, p = 0.02). CONCLUSION: Tissue histopathologic outcomes reflect the differing mechanism of action of mepolizumab and benralizumab in eCRS. Further analysis at the tissue level will provide further information to guide application of mAbs in type 2 inflammatory diseases.

Empty Nose Syndrome Pathophysiology: A Systematic Review.

OBJECTIVE: The pathophysiology of empty nose syndrome (ENS) remains unclear despite significant research. The pathophysiologic mechanism of ENS was systematically reviewed. DATA SOURCES: MEDLINE and Embase. REVIEW METHODS: Data were systematically reviewed for studies that provided original data on pathophysiology. RESULTS: A total of 2476 studies were screened, and 19 met the inclusion criteria: 13 case-control and 6 cross-sectional. Nine pathophysiologic themes were identified.• Demographics: ENS symptoms had no relationship with climatic factors.• Symptomatology: ENS patients demonstrated high symptom severity.• Mental health: Anxiety and depression including hyperventilation were reported in >50% of ENS patients and correlated with ENS symptom severity.• Anatomic features: Structural changes in response to turbinate surgery were similar between ENS and non-ENS patients.• Airflow analysis: Airflow parameters were similar between ENS and non-ENS patients after turbinate surgery. On computational fluid dynamic analysis, differences were found on multiple outcomes.• Diagnostic testing: The menthol detection test was impaired in ENS, and cotton placement in the airway improved ENS symptoms.• Cognitive function: Functional magnetic resonance imaging showed activation in emotional processing area during breathing.• Olfactory function: Subjective impairment was reported in ENS, but quantitative measures were similar to non-ENS patients.• Mucosal physiology/innate immunity: Turbinate histopathology in ENS showed a tissue-remodeling pattern. Nasal nitric oxide level was lower in ENS patients. CONCLUSION: There is evidence of high comorbid mental health disorders in ENS patients. An abnormal trigeminal-thermoreceptor response may be present in some patients. The influence of altered airflow and the evidence of surgery as the cause for ENS are unclear.