Effects of functional endoscopic sinus surgery on asthma control in patients with comorbid chronic rhinosinusitis and asthma: A national database study.

KEY POINTS: In patients with chronic rhinosinusitis and comorbid asthma, patients with surgical intervention required less asthma rescue medication, as compared to those who did not undergo surgery. Following sinus surgery, patients with chronic rhinosinusitis and asthma required more asthma medication, as compared to the time period prior to surgery.

Invasive fungal rhinosinusitis: current evidence and research opportunities.

PURPOSE OF REVIEW: To summarize the evidence surrounding diagnosis, treatment, prognosis, and surveillance of patients with acute invasive fungal sinusitis (AIFS) and discuss future research needs. RECENT FINDINGS: New risk factors for AIFS such as COVID have been identified, and a new prognostic staging system has been developed. SUMMARY: Most patients who develop AIFS are immunocompromised, with the majority having a history of diabetes or a hematologic malignancy. Unfortunately, there are not any highly sensitive and specific diagnostic tools. Therefore, a combination of signs and symptoms, imaging, endoscopy, biopsy, and labs should be used to diagnosis AIFS. Although surgery and systemic antifungals are known to improve outcomes, there is limited data on time to intervention, duration of antifungals, and surveillance patterns. There is also limited information on factors that can predict outcomes in AIFS patients. However, sensory/perceptual changes, prolonged neutropenia duration, and comorbidity burden may be associated with a poor prognosis.

Chief Complaint: Nasal Congestion.

Nasal obstruction is the subjective perception and objective state of insufficient airflow through the nose. Nasal congestion, conversely, describes a state of not just inadequate airflow or obstructive phenomena but also pressure- and mucus-related states to the patient. Nasal receptors belonging to the transient receptor potential (TRP) protein family mediate the sense of nasal patency via the trigeminal nerve. The transient receptor potential melastatin-8 (TRPM8) responds to temperatures around 8°C to 22°C, and is stimulated by menthol and other cooling agents. The radiant effects of airflow create heat loss to activate these receptors and humans perceive this as nasal patency rather than the direct detection of airflow. The thermovascular state of the mucosa, in conditions such as rhinitis, influence TRPM8 activation. Nasal endoscopy can show signs of rhinitis and should be considered an essential part of the workup of nasal congestion. Efforts to relieve nasal congestion need to manage the mucosal state and surgery needs to ensures that the nasal cavity mucosa is exposed to the cooling effects of airflow rather than simply creating a passage to the nasopharynx.

Prognostic Factors for Survival Using a Clinical Severity Staging System Among Patients With Acute Invasive Fungal Sinusitis.

Importance: Despite the aggressive progression of fulminant acute invasive fungal sinusitis (AIFS), data on prognostic factors have been disparate, hindering the development of a staging system. A composite staging system may improve prognostication for patient counseling and conduct of clinical research. Objective: To identify prognostically important factors in AIFS and to incorporate the factors into a comprehensive Functional Severity Staging System and Clinical Severity Staging System. Design, Setting, and Participants: This retrospective cohort study included adult patients diagnosed with pathology-proven AIFS from June 1, 1992, to December 31, 2022, at Washington University Medical Center and Barnes-Jewish Hospital, a tertiary care center in St Louis, Missouri. Data were analyzed from April to July 2023. Main Outcome and Measures: Sequential sequestration and conjunctive consolidation was used to develop a composite staging system to predict 6-month overall survival. Results: Of 71 patients with pathology-proven AIFS over the 30-year period, the median (range) age of the cohort was 56 (19-63) years, and there were 47 (66%) male patients. The median (range) follow-up time was 2 (0-251) months. There were 28 patients alive within 6 months, for a 39% survival rate. Symptoms, comorbidity burden, and presence and duration of severe neutropenia were associated with 6-month survival and were consolidated into a 3-category Clinical Severity Staging System with 6-month survival of 75% for stage A (n = 16), 41% for stage B (n = 27), and 18% for stage C (n = 28). The discriminative power of the composite staging system was moderate (C statistic, 0.63). Conclusion and Relevance: This cohort study supports the clinical importance of symptomatology, comorbidity burden, and prolonged severe neutropenia at the time of AIFS presentation. The composite clinical staging system may be useful for clinicians when counseling patients with AIFS and conducting clinical research.

When inflammation is not just inflammation-A review of systemic diseases of the nose and sinuses part 2: Granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Chronic rhinosinusitis is a very common condition. Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (eGPA) are systemic diseases which can contribute to the development of chronic rhinosinusitis in select patients. OBJECTIVE: Characterize the presenting features, diagnostic criteria, workup, and management of granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis as they are encountered in otolaryngology clinics. METHODS: Full length manuscripts published 2000 or later were reviewed. A separate search was conducted for each disease. Pertinent clinical features related to sinonasal manifestations of GPA and eGPA were collected and reported in this review. RESULTS: 467 references were discovered during literature review process. In total, 42 references for GPA and 35 references for eGPA were included in this review. CONCLUSION: GPA and eGPA are vasculitis syndromes which commonly present in the context of multisystem disease. For GPA, pulmonary and renal disease are common; for eGPA a history of asthma is nearly ubiquitous. Sinonasal disease is a very common feature for both disease processes and may precede the development of systemic symptoms in many patients. Clinical work up and diagnosis is complex and generally requires multidisciplinary care. Treatment primarily consists of immunosuppressive agents, and a number of steroids, steroid sparing agents, and biologics have been shown to be effective. The role of sinus surgery includes tissue biopsy for diagnosis, functional surgery for symptom management in select cases, and reconstruction of cosmetic and functional defects.

When inflammation is not just inflammation-A review of systemic diseases of the nose and sinuses part 1: IgG4-related disease and sarcoidosis.

BACKGROUND: Chronic rhinosinusitis is a very common condition. IgG4-related disease (IgG4-RD) and sarcoidosis are systemic diseases which can contribute to the development of chronic rhinosinusitis in select patients. OBJECTIVE: Characterize the presenting features, diagnostic criteria, workup, and management of sinonasal IgG4-RD and sarcoidosis as they are encountered in otolaryngology clinics. METHODS: Full length manuscripts published 2000 or later were reviewed. A separate search was conducted for each disease. Pertinent clinical features related to sinonasal manifestations of IgG4-RD and sarcoidosis were collected and reported in this review. RESULTS: 404 references were discovered during literature review process. In total, 42 references for IgG4-RD and 34 references for sarcoidosis were included in this review. CONCLUSION: IgG4-RD and sarcoidosis are autoimmune inflammatory conditions that can affect many systems of the body. For both disease entities, sinonasal disease is a less common presentation which can lead to delayed diagnosis. Sinonasal IgG4-RD commonly presents in the setting of multisystem disease. All with other clinical features, biopsy plays a key role in the diagnosis for both diseases. Treatment for IgG4-RD consists primarily of steroids and rituximab which can lead to excellent and durable remission. A variety of immunosuppressive agents are used in the management of sarcoidosis. Surgery for IgG4-RD is primarily utilized for tissue biopsy, although resection or debulking may be considered. For sarcoidosis, surgery can be used for tissue biopsy and functional sinus surgery can offer symptomatic relief in many patients.

Stellate Ganglion Block for the Treatment of COVID-19-Induced Olfactory Dysfunction: A Prospective Pilot Study.

OBJECTIVE: The objective of this study was to explore the safety and feasibility of stellate ganglion blocks (SGBs) to treat persistent COVID-19-induced olfactory dysfunction (OD). Secondarily, the goal was to determine effect sizes to plan a future randomized clinical trial. STUDY DESIGN: Prospective case series. SETTING: Quaternary Care Academic Medical Center. METHODS: In this single-arm pilot trial, adult participants with a COVID-19 diagnosis ≥ 12 months prior to enrollment with OD underwent bilateral SGBs. Subjects were followed for 1 month after completion of SGB. The primary outcome measure was the change in the Clinical Global Impression-Improvement Scale for smell loss. Secondary outcome measures included changes in the University of Pennsylvania Smell Identification Test (UPSIT) and Olfactory Dysfunction Outcomes Rating (ODOR). RESULTS: Twenty participants were enrolled with a mean (SD) age of 46 (11) years and a mean (SD) duration of OD of 21 (5) months. At 1 month, 10 (50%) participants experienced at least slight subjective improvement in their OD, 11 (55%) attained a clinically meaningful improvement in smell identification using the UPSIT, and 7 (35%) achieved a clinically meaningful improvement in olfactory-specific quality of life (QoL) measured by the ODOR. The median difference between UPSIT scores at baseline and 1 month was 6 (95% confidence interval: 3-11), exceeding the minimal clinically important difference of 4. There were no serious adverse events. CONCLUSION: Sequential SGBs for COVID-19-associated OD were safe and associated with modest improvements in subjective olfaction, odor identification, and olfactory-specific QoL. A placebo-controlled trial is warranted to determine the efficacy of SGBs for COVID-19-associated OD.

Invasive fungal sinusitis risk factors among immunosuppressed hematopoietic stem cell transplant recipients.

KEY POINTS: Invasive fungal sinusitis (IFS) rate and risk factors in transplant recipients were explored IFS rate is higher in allogeneic recipients with prior transplants and worse comorbidity scores The at-risk timeframes for IFS development were identified.

Diagnosis, Prognosticators, and Management of Acute Invasive Fungal Rhinosinusitis: Multidisciplinary Consensus Statement and Evidence-Based Review with Recommendations.

BACKGROUND: Acute invasive fungal sinusitis (AIFS) is an aggressive disease that requires prompt diagnosis and multidisciplinary treatment given its rapid progression. However, there is currently no consensus on diagnosis, prognosis, and management strategies for AIFS, with multiple modalities routinely employed. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on AIFS, summarize the existing evidence, and provide recommendations on the management of AIFS. METHODS: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through January 2022. Studies evaluating management for orbital, non-sinonasal head and neck, and intracranial manifestations of AIFS were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on management principles for AIFS were generated. RESULTS: A review and evaluation of published literature was performed on 12 topics surrounding AIFS (signs and symptoms, laboratory and microbiology diagnostics, endoscopy, imaging, pathology, surgery, medical therapy, management of extrasinus extension, reversing immunosuppression, and outcomes and survival). The aggregate quality of evidence was varied across reviewed domains. CONCLUSION: Based on the currently available evidence, judicious utilization of a combination of history and physical examination, laboratory and histopathologic techniques, and endoscopy provide the cornerstone for accurate diagnosis of AIFS. In addition, AIFS is optimally managed by a multidisciplinary team via a combination of surgery (including resection whenever possible), antifungal therapy, and correcting sources of immunosuppression. Higher quality (i.e., prospective) studies are needed to better define the roles of each modality and determine diagnosis and treatment algorithms.

RNA Sequencing and Gene Ontology Analysis in Acute Invasive Fungal Sinusitis.

BACKGROUND: Acute invasive fungal sinusitis (AIFS) is an aggressive and dangerous disease of the paranasal sinuses with high morbidity and mortality. The immune response at the level of the nasal mucosa, the site of entry, has not been previously evaluated. OBJECTIVE: To evaluate differential gene expression in the sinonasal mucosa of AIFS patients as compared to control patients using RNA sequencing. METHODS: Sinonasal tissue samples were prospectively obtained from consenting patients undergoing surgery between November, 2020 and November, 2021. RNA extraction and sequencing were performed and differential expression was analyzed to detect transcriptional differences between patient groups. RESULTS: Tissue samples were collected from 4 patients with active AIFS diagnoses, 2 patients with recovered AIFS, 1 patient with a diagnosis of non-invasive fungal ball, and 4 healthy controls. 255 genes were differentially expressed in AIFS patients as compared to control patients. Specific Gene Ontology (GO) biological processes that were identified as differentially expressed in AIFS patients as compared to controls included the following: 1. GO:0007155 (cell adhesion), 2. GO:0030199 (collagen fibril organization) and 3. GO:0001525 (angiogenesis). CONCLUSION: Transcriptional differences were noted between AIFS and control patients in sinonasal tissue samples. Future work is necessary to determine causes of the differential gene expressions between AIFS and control patients, specifically those who are immunosuppressed, or with preexisting non-invasive forms of fungal sinusitis, to guide treatment and prevention strategies.

Intermediate Invasive Fungal Sinusitis, a Distinct Entity From Acute Fulminant and Chronic Invasive Fungal Sinusitis.

BACKGROUND: The current classification system of invasive fungal sinusitis (IFS) includes acute (aIFS) and chronic (cIFS) phenotypes. Both phenotypes display histopathologic evidence of tissue necrosis, but differ by presence of angioinvasion, extent of necrosis, and disease progression. aIFS is defined by a rapid onset of symptoms, while cIFS slowly progresses over ≥12 weeks. However, a subset of IFS patients do not fit into the clinical presentation and histopathologic characteristics of either aIFS or cIFS. OBJECTIVES: To investigate the demographic, clinical, and histopathologic characteristics of a distinct subset of IFS. METHODS: Retrospective review of patients with IFS from a single tertiary-care institution (2010-2020). Patients with symptoms for ≤4 weeks were classified as aIFS if they displayed endoscopic evidence of mucosal necrosis or fungal angioinvasion on pathology. Patients with slowly progressive IFS for ≥12 weeks were classified as cIFS. Patients with symptom duration between 4 and 12 weeks with evidence of invasive fungal disease were classified as a new entity and were further investigated. RESULTS: Of the 8 patients identified, 50% were immunosuppressed at presentation. The mean symptom duration prior to presentation was 50.5 days (SD 16.8), and common symptoms included facial pain (100%), vision change (87.5%), and blindness (37.5%). Two patients (25%) died of their disease. Sites of fungal involvement confirmed by histopathology included sphenoid (62.5%) and ethmoid sinuses (12.5%), orbital apex (25%), optic nerve (12.5%), pterygopalatine fossa (12.5%), and clivus (12.5%). Fungal elements but without obvious angioinvasion, were identified in all specimens, and fungus balls (50%), granulomas (37.5%), and giant cells (25%) were also observed on histopathology. CT and MRI radiographic imaging showed findings consistent with orbital, intracranial, or skull base involvement in all patients. CONCLUSION: We propose intermediate IFS as a new subgroup of patients with IFS who do not fit into the standard classification of aIFS or cIFS.

Biologics for chronic rhinosinusitis with nasal polyps: Economics and ethics.

Biologics have recently been approved for use in chronic rhinosinusitis with nasal polyps patients. While effective in controlling disease on subjective and objective short-term outcome measures, limited data suggest that biologics have the potential to be used long term. The current wholesale acquisition costs for biologics are quite high. Widespread, prolonged use of these medications may create a large burden to our healthcare system. Cost-effectiveness analyses, particularly for specific patient cohorts, are needed to determine appropriate use of these medications. The ethics of patient preference of various treatment options, counseling regarding side effect profiles, and healthcare economics also need to be addressed.

Computed Tomography as a Predictor of Sinonasal Inverted Papilloma Origin, Skull Base Involvement, and Stage.

Objective To investigate the diagnostic performance of computed tomography (CT) to determine the origin, skull base involvement, and stage of sinonasal inverted papilloma (IP). Design This is a retrospective cohort study. Setting This is set at a tertiary care medical center. Participants Patients with preoperative CT imaging who underwent extirpative surgery for histologically confirmed sinonasal IP between January 2005 and October 2019. Main Outcome Measures The likely sites of tumor origin, skull base involvement, and radiographic tumor stage were determined by two board-certified neuroradiologists after re-reviewing preoperative CT imaging. These radiologic findings were then compared with intraoperative and pathologic findings. Results Of 86 patients, 74% (64/86) had IP lesions with correctly classified sites of origin on CT. CT was not sensitive for diagnosing ethmoid sinus origin (48%, 52%), frontal sinus origin (80%, 40%), and skull base origin (17%, 17%). CT was not sensitive (62%, 57%) but specific (86%, 98%) for identifying any skull base involvement. There was substantial-to-near perfect agreement between radiographic and pathologic Cannady stages (weighted κ = 0.61 for rater 1; weighted κ = 0.81 for rater 2). Interrater agreement was substantial for identifying tumor origin (κ = 0.75) and stage (weighted κ = 0.62) and moderate for identifying skull base involvement (κ = 0.43). Conclusion Interrater agreement on CT findings was substantial except on skull base involvement. CT correctly predicted site of tumor origin in up to 74% of subjects. CT was not sensitive for diagnosing skull base involvement but had substantial-to-near perfect agreement with pathologic tumor staging. CT is a useful but albeit limited adjunct for tumor localization and surgical planning for sinonasal IP.

Knowledge Gaps and Research Needs for Biologic Therapy in Rhinology Practice.

Biologic agents are emerging for chronic rhinosinusitis with nasal polyposis (CRSwNP) patients with recalcitrant disease. Although early work has shown promise, and several trials are ongoing, there is significant work to be done in this field. CRS patients form a heterogeneous group, and identification of appropriate patients for the use of biologic agents is critical. The determination of endotype-specific biomarkers will help define patient selection and predict treatment response. As more biologic agents become approved, head-to-head trials will be needed to compare them with similar products. Ultimately, cost-effectiveness analyses and further quality of life studies will guide treatment recommendations.

Pedicle Corridors and Vessel Options for Free Flap Reconstruction following Endoscopic Endonasal Skull Base Surgery: A Systematic Review.

Introduction Microvascular free flaps offer an alternative to local and regional flaps for coverage of complex or large skull base defects. Routes and approaches to these reconstructive options are complicated and require an understanding of complex head and neck anatomy. Methods A systematic review of the literature was performed using a set of search terms with the help of a qualified librarian. Articles were reviewed and selected for inclusion based on relevance. We were interested in reporting possible routes for free flap accessibility to the skull base as well as microvascular vessel options, as this choice may affect the geometry and accessibility to the defect. Results A total of 1,917 articles were obtained from a comprehensive search and 11 articles were ultimately found to be relevant to this review. Published options for vessel anastomosis and corridors to the skull base following endoscopic endonasal surgery are reviewed, including Caldwell-Luc/transbuccal space, prevertebral space, transpterygoid/parapharyngeal, and transmaxillary approaches. Conclusion The field of endoscopic surgery has continued to advance and provide options for tumors of the skull base. This has led to a need for creative routes to the skull base for free flap reconstruction.

Guidance for contemporary use of biologics in management of chronic rhinosinusitis with nasal polyps: discussion from a National Institutes of Health-sponsored workshop.

BACKGROUND: Biologic medications are emerging as options for treating chronic rhinosinusitis with nasal polyps (CRSwNP). Several questions remain regarding patient selection, indications, clinical efficacy, and cost effectiveness. METHODS: In November 2019, a group of physicians and scientists gathered to consider strategies for future studies regarding biologics. During the discussion, gaps in knowledge highlighted a need for a consensus on the present day use of biologics in polyp patients. RESULTS: The goal of this guideline is to propose recommendations for the current use of biologics in CRSwNP as new evidence continues to emerge and inform practice. CONCLUSION: We suggest that physicians evaluate patients on an individual basis and closely monitor for improvement due to the high cost and unknown long-term effects of biologics.