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Background Allergic fungal rhinosinusitis (AFRS) is an endotype of chronic rhinosinusitis (CRS) with nasal polyps characterized by eosinophilic mucin laden with fungal hyphae entrapped in expanded sinus cavities with an exaggerated hypersensitivity to fungal elements. The last decade has elucidated fungi-driven inflammatory pathways contributing to the pathophysiology of chronic inflammatory respiratory diseases. In addition, novel therapeutic biologic options have become available for CRS over the last several years. Objective To review the current literature examining AFRS, focusing on recent developments in our understanding of its pathophysiology and implications for treatment options. Methods Review article. Results Fungi-driven respiratory inflammation has been linked to fungal proteinases and toxin activity. In addition, AFRS patients demonstrate a local sinonasal immunodeficiency in antimicrobial peptides and hence limited antifungal activity, along with an exaggerated type 2 inflammatory response, highlighting a possible imbalanced type 1, type 2, and type 3 profile. The elucidation of these dysregulated molecular pathways has highlighted novel potential therapeutic targets. As such, the clinical management of AFRS, which once included surgery and extended courses of oral corticosteroids, is transitioning away from long courses of oral corticosteroids to incorporate novel delivery mechanisms of topical therapeutic targets and biologics for recalcitrant disease. Conclusion AFRS is an endotype of CRS with nasal polyps (CRSwNP) for which the molecular pathways leading to its inflammatory dysfunction are beginning to be illuminated. In addition to affecting treatment options, these understandings may shape necessary changes to diagnostic criteria and the extrapolated effects of environmental changes on AFRS. More critically, a better appreciation of fungi-driven inflammatory pathways may have implications for the understanding of broader CRS inflammation.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a significant disease burden. The optimal use of and administration route for intranasal corticosteroids (INCS) when managing CRSwNP are unclear.We systematically synthesized the evidence addressing INCS for CRSwNP.We searched studies archived in Medline, Embase, and Central from database inception until September 1, 2021, for randomized controlled trials comparing INCS using any delivery method to placebo or other INCS administration types. Paired reviewers screened records, abstracted data, and rated risk of bias (CLARITY revision of Cochrane Risk of Bias version 1 tool) independently and in duplicate. We synthesized the evidence for each outcome using random effects network meta-analyses. We critically appraised the evidence following the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) approach.We analyzed 61 randomized controlled trials (7176 participants, 8 interventions). Sinusitis-related quality of life might improve with INCS rinse (mean difference [MD] -6.83, 95% confidence interval [CI] -11.94 to -1.71) and exhalation delivery system (EDS) (MD -7.86, 95% CI -14.64 to -1.08) compared to placebo (both low certainty evidence). Nasal obstruction symptoms are likely improved when receiving INCS via stent/dressing (MD -0.31, 95% CI -0.54 to -0.08), spray (MD -0.51, 95% CI -0.61 to -0.41), and EDS (MD -0.35, 95% CI -0.51 to -0.18) (all moderate to high certainty) compared to placebo. We found no important differences in adverse effects among interventions (moderate certainty for INCS spray, very low to low certainty for others).Multiple delivery forms of INCS are viable therapeutic options for CRSwNP, resulting in improvement of patient-important outcomes. INCS via stent, spray, and EDS appear to be beneficial across the widest range of considered outcomes.

The European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), latest version EPOS2020, and the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS), latest version ICAR-RS-2021, assimilate thousands of articles on the topic of rhinosinusitis. Encompassing scores of subtopics and relying on the perspectives of many international experts, EPOS2020 and ICAR-RS-2021 reduce the existing data into consumable formats and create evidence-based recommendations. The approaches and findings are similar in many respects but have significant differences. This clinical commentary, authored by some of the principal authors of these documents, compares and contrasts EPOS2020 and ICAR-RS-2021, examining methodology, diagnostic and treatment recommendations, and each document's emphases. This commentary demonstrates that, through somewhat differing methodologies, the 2 documents arrive at largely similar conclusions. Those who care for patients suffering from rhinosinusitis will find the documents complementary and valuable in their differences as much as in their similarities.

Endoscopic sinus surgery (ESS) and septoplasty are commonly performed procedures without standardized postoperative pain regimens. There is reluctance to prescribe opioids for postoperative pain given their potential for abuse. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been demonstrated to reduce or even obviate the need for opioid pain medications after otolaryngologic surgeries, but prospective validation is lacking.A randomized, controlled study comparing the efficacy of diclofenac sodium to hydrocodone/acetaminophen (APAP) after ESS with or without septoplasty was performed. Participants were given a 100-mm visual analog pain scale (VAS) at postoperative days (PODs) 1, 2, 3, and 5 after ESS. Two-sample t tests were used to compare pain scores between groups.One hundred patients enrolled, and 74 patients provided pain scores to the survey. Pain was greatest for both groups on POD 1. Treatment with diclofenac sodium vs hydrocodone/APAP did not statistically impact pain scores at PODs 1, 2, 3, or 5. No cases of epistaxis requiring an emergency room visit or return to the operating room were noted during the study period.Diclofenac sodium may be non-inferior to hydrocodone/APAP in treating pain after ESS with or without septoplasty in opioid naive patients without pre-existing pain conditions. Further studies with larger samples are warranted to investigate the potential superiority of diclofenac to hydrocodone/APAP in certain patients after ESS and septoplasty.

The etiologic role of fungi in chronic rhinosinusitis remains controversial. The purpose of this review is to further our understanding of molecular immunologic pathways activated by fungi and clinical trials of antifungals in severe subtypes of asthma and allergic fungal rhinosinusitis.Various fungal components such as protease and chitin are capable of eliciting a type 2 innate and adaptive immune response. However, definitive studies on the etiologic role of fungi in chronic rhinosinusitis (CRS) is dependent on the development of a fungi-induced murine model of CRS. Short of this model, extrapolations of observations and results from clinical trials in fungi-induced asthma subtypes support a key role of fungi in the pathophysiology of allergic fungal rhinosinusitis and possibly other CRS endotypes.Fungi plays a key role in the pathophysiology of several subtypes of chronic inflammatory respiratory diseases. However, a fungi-induced murine model of CRS is needed to explicitly investigate the molecular pathways and potential therapeutic targets.

Unified airway disease describes the shared epidemiologic and pathophysiologic relationship among the chronic inflammatory diseases of the upper and lower airways including allergic rhinitis, chronic rhinosinusitis, asthma, and chronic otitis media. This concept proposes that these diseases are manifestations of a single inflammatory process and require an integrated diagnostic and therapeutic approach to achieve global disease control. Future directions to further establish this entity should focus on pathophysiology, diagnostic markers, flora microbes with particular emphasis on fungi, the role of type 3 inflammation, and targeted therapeutics including biologics, JAK inhibitors, and synthetic peptides.

These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline, nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases. Systematic reviews for each management option informed the guideline. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to inform and develop recommendations. The guideline panel reached consensus on the following statements: (1) In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation, low certainty of evidence) (2) In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation, moderate certainty of evidence) (3) In people with aspirin (nonsteroidal anti-inflammatory drug) exacerbated respiratory disease, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). The conditions for each recommendation are discussed in the guideline.

The allergic airway diseases chronic rhinosinusitis (CRS), allergic fungal rhinosinusitis (AFRS), asthma, allergic bronchopulmonary mycosis/aspergillosis (ABPM/A), and cystic fibrosis (CF) share a common immunological signature marked by T H 2 and TH 17 cell predominant immune responses, the production of IgE antibody, and atypical inflammatory cell infiltrate that includes eosinophils and other innate immune effector cells. Severe forms of these disorders have long been recognized as being related to hypersensitivity reactions to environmental fungi. Increasingly however,environmental fungi are assuming a more primary role in the etiology of these disorders, with airway mycosis, a type of non-invasive airway fungal infection,recognized as an essential driving factor in at least severe subsets of allergic airway diseases. In this review, we consider recent progress made in understanding the immune mechanisms that drive airway mycosis-related diseases, improvements in immune-based diagnostic strategies, and therapeutic approaches that target key immune pathways.

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.

Background: Endoscopic sinus surgery presents significant visuospatial challenges to surgical trainees. We tested the utility of novel 3D printed models to simulate sinus surgery tasks to improve endoscopic skillsets in resident trainees. Methods: This was a prospective quality improvement study of 10 ENT residents (PGY1-5). Participants rotated through 4 stations with different 3D simulation training modules designed to enhance endoscopic skillsets in the axial, sagittal and coronal planes (e.g., straight forceps to grasp a bead from a ledge, angled instruments to cannulate openings). Participants completed a self-assessment survey on the subjective sinus surgical skills using a visual analog scale before and after tasks. Two- tailed paired T-tests were used to analyze the data. Results: All residents rated their post-intervention “overall sinus surgery skills” higher than pre-intervention. They rated simulations to provide more significant utility as an adjunct to surgical education after the intervention. All but one participant reported improved spatial awareness working with the endoscopes and surgical instruments. There was subjectively improved proficiency in using 0-degree and angled endoscopes as well as cutting, grasping, and curved instruments after the intervention. The simulations led to subjective improvements in spatial awareness, bimanual dexterity, and increased confidence in selecting correct surgical instruments. Conclusion: Our set of novel 3D printed models to improve sinus surgery skillset was well accepted by the resident cohort. The 3D models can serve as an adjunct tool to traditional residency education.

Allergic fungal rhinosinusitis (AFRS) is a noninvasive subtype of chronic rhinosinusitis with nasal polyps (CRSwNP) that usually develops in immunocompetent atopic individuals and is more common in geographic regions characterized by warm temperatures and high humidity, conducive to higher environmental fungal presence. Allergic fungal rhinosinusitis usually presents with unique computed tomography findings and significant polyp burden, yet patients often report minimal sinus symptoms. Patients with AFRS often have extremely elevated serum total and fungal-specific IgE levels. Treatment almost always requires surgery, in which adjuvant medical therapy is critical to success. However, until recently the choice of adjuvant therapy has consisted primarily of either oral and/or topical steroids. Although oral corticosteroids decrease recurrence after surgery, data for the effectiveness of other adjunctive pharmacologic agents, including topical and oral antifungal agents and immunotherapy, have remained unclear and hence are not recommended in recent guidelines including the International Consensus of Allergy and Rhinology. Three biologics, omalizumab, dupilumab, and mepolizumab, have recently been approved for treating CRSwNP in general, but clinical trials to date with these biologics did not involve AFRS patients. Recently published case reports and smaller prospective studies have shown good efficacy of these biologics on the AFRS subgroup of patients. This article provides an overview of the understanding of the pathophysiology of AFRS, implications of this understanding on the possible role of biologics, and clinical reports on the use of biologics in treating AFRS. Because biologics are indicated for treating CRSwNP, follow up real-world evidence studies are needed for AFRS.

I. Executive summary BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document. Methods ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided. Conclusion This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.

To identify differences in inpatient otolaryngology consultations and interventions for patients based on COVID-19.Records were reviewed for all patients for whom otolaryngology was consulted at a high-volume tertiary care hospital from April 30, 2020 to October 1, 2020. Demographic information, length of stay, COVID-19 status, indication for consultation, and otolaryngology interventions were recorded. Statistical analysis was performed using R software.Bleeding composed a significantly higher proportion of otolaryngology consults in COVID-19 positive patients (28% vs. 8.4%, p0.0001). Management of bleeding was the most common procedure performed in positive patients (n=37, 35%), and they had a higher median number of interventions performed when compared to bleeding patients who tested negative (1, IQR 1-2 vs. 1, IQR 0-1, p=0.04). COVID-19 positive patients with bleeding were more likely to expire than those with other indications for otolaryngology consultation (50% vs. 7%, p0.001).Bleeding and associated interventions comprised the predominant discrepancy between COVID-19 positive and negative patients in our cohort. We encourage routine use of simple and cost-effective methods to decrease risk of bleeding.

Background: Extended endoscopic transsphenoidal (EET) approaches can include complete resection of both superior turbinate (ST) for wider exposure. Moreover, ST resection has been associated with postoperative olfactory impairment. Objective: We sought to determine the impact of bilateral ST resection on olfaction during a transsphenoidal approach. Method: A prospective observational study was conducted on 29 patients undergoing endoscopic skull base surgery sparing the olfactory tracts at a tertiary academic center. Olfactory function was measured with Sniffin’ Sticks at the preoperative visit, 2-weeks and 6 to 8 weeks postoperatively. All components: odor threshold (OT), odor discrimination (OD), odor identification (OI) and composite scores (TDI = OT+OD+OI) were evaluated. Result: Study was completed in 15 patients with 14 excluded due to a variety of reasons. At 2 weeks, a significant decrease was noted in composite scores (32.3 ± 5.4 vs. 23.8 ± 5.8, P Conclusion: Patients undergoing bilateral ST resection during EET procedures experience transient hyposmia postoperatively. However, the olfactory function normalizes to preoperative levels at 6 to 8 weeks. The resection of the bilateral superior turbinate does not appear to decrease olfactory function.

Background Nonallergic rhinitis (NAR) is currently a diagnosis of exclusion with an unclear pathophysiologic mechanism and limited treatment options. In patients diagnosed with NAR based on symptoms, negative skin testing and positive optical rhinometry (ORM), the study's objective was to evaluate the therapeutic action of intranasal capsaicin in the management of rhinitic symptoms and the effect on ORM readings. Methods Patients with a history of NAR underwent screening by a diagnostic intranasal capsaicin challenge with ORM and skin-prick testing. Twenty-two NAR patients were enrolled and randomized to either treatment with 0.1mM capsaicin (n = 11) or placebo (n = 11). Treatment consisted of 5 consecutive intranasal applications separated by 1 hour with follow-up at 4 and 12 weeks. At each visit, subjects underwent intranasal capsaicin challenge with ORM reading and a visual analog scale scoring of rhinitis symptoms. Results Treatment with intranasal capsaicin resulted in a median change with improvement in total symptom score (TSS) of -5 from baseline vs an increase of 2 with placebo at 4 weeks, which remained significantly different between the groups at 12 weeks (p = 0.03). At 12 weeks posttreatment, 60% of the intervention group vs 80% of placebo-treated patients still met objective criteria for NAR by ORM. Conclusion Using ORM in the objective diagnosis of NAR, this trial showed that intranasal 0.1mM capsaicin not only improved rhinitic symptoms but also objectively reduced nasal reactivity and nasal congestion with a 40% responder rate at 12 weeks as noted by ORM.

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.

Allergic fungal rhinosinusitis (AFRS) represents a subtype of chronic rhinosinusitis with nasal polyposis that exhibits a unique, often striking clinical presentation. Since its initial description more than a quarter century ago, a more sophisticated understanding of the pathophysiology of AFRS has been achieved and significant advancements in improving clinical outcomes made. This review focuses on the latest developments involving the pathophysiology and clinical management of this fascinating disease.

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with

Environmental fungi are etiologically related to chronic rhinosinusitis (CRS) with airway mycosis, but their infectious role remains uncertain, in part because of potentially inadequate methods of disease quantitation. Our objective was to determine objective radiographic and symptomatic outcomes of oral antifungal therapy in adult patients with CRS and airway mycosis by using computer-assisted analysis. We conducted a retrospective study of 65 patients with CRS and culture-proven airway mycosis in a single-center referral-based academic practice, comparing paired sinus computed tomography (CT) scans and symptom scores prior to and during chronic oral antifungal therapy using computer-assisted analysis of sino-mucosal area (CAASMA). A comparator group received standard therapy without antifungals. Administration of antifungals was associated with significantly reduced sinus mucosal thickening as assessed by CAASMA (-6.85% absolute reduction; 95% confidence interval [CI], -11.8283 to -1.8717; P < 0.005), but not by Lund-Mackay score. In contrast, standard care alone was linked by CAASMA to enhanced mucosal thickening (4.14% absolute increase; 95% CI, -1.8066 to 10.0866; P < 0.005). Thirty of the 41 antifungal-treated patients (73%) showed decreased sinus mucosal burdens, while only 21 patients (43%) receiving standard therapy showed improved imaging (odds ratio [OR], 11.65; 95% CI, 3.2 to 42.2; P < 0.05). Nineteen patients (50%) noted improved symptoms at the time of a follow-up CT scan, while only 8 patients (20%) on standard therapy improved (OR, 6.21; 95% CI, 1.7 to 22.7; P < 0.05). These retrospective findings indicate that oral antifungals can reduce mucosal thickening and improve symptoms in CRS with airway mycosis. Randomized clinical trials are warranted to verify these findings.

Evaluating the aerosolization of droplets from surgical instruments to assess the implications of surgery in SARS-CoV-2 transmission for both patients and providers. Cadaver study. Outpatient surgery center. Aerosolized particles between 0.3 and 25 microns were measured. Instruments tested included monopolar cautery with and without suction, bipolar cautery, a bipolar vessel sealing device, and tissue scissors. Each trial was compared to a background reading. Monopolar cautery without suction, Ligasure used continuously and Bipolar cautery produced the most aerosols. Monopolar cautery with simultaneous suction produced no detectable aerosols. Ligasure used for a single cycle produced notably fewer aerosols than during continuous use. Most aerosols produced were

Background: Reliable use of surgical navigation depends upon the registration process. The gold standard is paired-point registration with bone-anchored fiducials, but contour-map registration is more practical. Surgeons may employ variable contour maps and less experienced team members often perform this critical step. The impact of these practices on target registration error (TRE) is not well-studied. Methods: A dry lab set-up consisting of a navigation system (Fusion ENT, Medtronic, Jacksonville, FL) and a sinus phantom with 2 mm radiopaque spheres in the sphenoid and ethmoid regions was developed. A CT (0.625 mm slice thickness) was obtained. Registration was performed with a contour-based protocol. Accuracy was determined using the software’s distance measurement tool. Registration was performed with narrow-field (NF; forehead points medial to the mid-pupillary line) and wide field (WF; entire forehead) contour maps. An experienced rhinologist and a resident surgeon performed each registration in triplicate and TRE at the sphenoid and ethmoid markers was measured in triplicate. Results: WF mapping had a lower TRE than NF (1.09 mm [95% Confidence Interval (CI) 0.96-1.22] vs 1.68 mm [95% CI 1.50-1.86]). The experienced surgeon had a lower TRE compared to the resident (1.21 mm [95% CI 1.08-1.34] vs 1.54 mm [95% CI 1.35-1.74]). Conclusions: In this navigation model, wide field mapping offers better accuracy than narrow-field mapping, and an experienced surgeon seemed to achieve better accuracy than a resident surgeon. These observations have potential implications for the use of this technology in the operating room.

In the last two decades, the development of culture-independent genomic techniques has facilitated an increased appreciation of the microbiota-immunity interactions and their role in a multitude of chronic inflammatory diseases such as chronic rhinosinusitis (CRS), asthma, inflammatory bowel disease and dermatitis. While the pathologic role of bacteria in chronic inflammatory diseases is generally accepted, the understanding of the role of fungi remains controversial. Chronic rhinosinusitis, specifically the phenotype linked to nasal polyps, represents a spectrum of chronic inflammatory diseases typically characterized by a type 2 immune response. Studies on the microbiota within sinus cavities from healthy and diseased patients have focused on the bacterial community, mainly highlighting the loss of diversity associated with sinus inflammation. Within the various CRS with nasal polyps (CRSwNP) phenotypes, allergic fungal rhinosinusitis presents an opportunity to investigate the role of fungi in chronic type 2 immune responses as well as the antifungal immune pathways designed to prevent invasive fungal diseases. In this review, we examine the spectrum of fungi-associated sinus diseases highlighting the interaction between fungal species and host immune status on disease presentation. With a focus on fungi and type 2 immune response, we highlight the current knowledge and its limitations of the sinus mycobiota along with cellular interactions and activated molecular pathways linked to fungi.

Chronic rhinosinusitis (CRS) has been associated with comorbid depression, yet the prevalence of depression among all patients with CRS is not well described. The Patient Health Questionnaire-9 (PHQ-9), a validated instrument for diagnosing depression, has been used to assess depression in a variety of clinical settings. PHQ-9 scores ≥10 are the threshold for a depression diagnosis. The purpose of this study was to assess the prevalence of depression in a rhinology practice and compare the PHQ-9 with the 22-item Sinonasal Outcome Test (SNOT-22).Retrospective chart review.Tertiary rhinology practice.During the 2-month period ending April 30, 2018, all rhinology patients were asked to complete the PHQ-9 and SNOT-22.Among 216 patients, 46 (21.3%) had a self-reported history of depression, and 39 (18.1%) had a PHQ-9 score ≥10. Of the 39 patients screening positive for depression, 18 (41.9%) had no history of depression. Comparison of PHQ-9 with overall SNOT-22 score had a Pearson's coefficient of 0.632 (Depression rates (estimated by PHQ-9 responses) among rhinology patients are similar to chronic disease populations; depression may be underdiagnosed in rhinology patients. Higher SNOT-22 scores were associated with higher PHQ-9 scores. Further studies are warranted to understand the impact of comorbid conditions of depression and CRS in patient quality of life.

High-throughput DNA sequencing of the paranasal sinus microbiome has potential in the diagnosis and treatment of sinusitis. The objective of this study is to evaluate the use of high-throughput DNA sequencing to diagnose sinusitis of odontogenic origin.Case series with chart review.Single tertiary care academic medical center.A chart review was performed of DNA sequencing results from the sinus aspirates obtained under endoscopic visualization in 142 patients with sinusitis. The identification of any potentially pathogenic bacteria associated with oral flora in a sample was classified as a positive result for sinusitis of odontogenic etiology. The sensitivity, specificity, and predictive values of using high-throughput DNA sequencing to diagnose sinusitis of odontogenic etiology were determined, with the patient's computed tomography sinus scan as the reference standard. On computed tomography scans, an odontogenic source was determined by the presence of a periapical lucency perforating the schneiderian membrane.Seven of the 142 patients enrolled in this study had an odontogenic source based on computed tomography scans. Relative to this reference standard, high-throughput DNA sequencing produced a sensitivity of 85.7% (95% CI, 42.1%-99.6%), a specificity of 81.5% (95% CI, 73.9%-87.6%), a positive predictive value of 19.4% (95% CI, 13.1%-27.7%), and a negative predictive value of 99.1% (95% CI, 94.7%-99.9%).This study supports the use of high-throughput DNA sequencing in supplementing other methods of investigation for identifying an odontogenic etiology of sinusitis.

Objective: In the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP), Aspergillus fumigatus (A. fumigatus) can upregulate IL-33 from human sinonasal epithelial cells (SNECs), which then activates innate lymphoid cells causing release of IL-13, an important driver of allergic inflammation. However, the mechanism by which A. fumigatus mediates the induction of IL-33 expression remains to be elucidated. The objectives of this study were to determine the specific fungal component(s) and the receptor responsible for mediating the A. fumigatus induced increase in IL-33 expression in SNECs from patients with CRSwNP. Methods: SNECs from CRSwNP patients were cultured and stimulated with various fungal components in the absence or presence of 4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride, an irreversible serine protease inhibitor, or GB83, a reversible protease activated receptor 2 (PAR2) inhibitor. IL-33 expression was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). PAR2 expression was examined in inflamed mucosa from nonatopic control and CRSwNP patients. Results: Elevation of IL-33 expression in primary SNECs was found in response to fungal protease but not fungal cell wall components. PAR2 expression was elevated in inflamed mucosa from CRSwNP patients in comparison to controls. The A. fumigatus fungal protease-mediated elevation in IL-33 expression by human SNECs was serine protease- and PAR2-dependent. Conclusion: These data suggest that serine protease activity of A. fumigatus is capable of inducing IL-33 expression in CRSwNP SNECs via PAR2, a potential therapeutic target in the treatment of CRSwNP. Level of evidence: NA Laryngoscope, 129:2230-2235, 2019.

CXCR5 mediates homing of both B and follicular helper T (TFH) cells into follicles of secondary lymphoid organs. We found that CXCR5+CD8+ T cells are present in human tonsils and follicular lymphoma, inhibit TFH-mediated B cell differentiation, and exhibit strong cytotoxic activity. Consistent with these findings, adoptive transfer of CXCR5+CD8+ T cells into an animal model of lymphoma resulted in significantly greater antitumor activity than CXCR5-CD8+ T cells. Furthermore, RNA-Seq-based transcriptional profiling revealed 77 differentially expressed genes unique to CXCR5+CD8+ T cells. Among these, a signature comprised of 33 upregulated genes correlated with improved survival in follicular lymphoma patients. We also showed that CXCR5+CD8+ T cells could be induced and expanded ex vivo using IL-23 plus TGF-β, suggesting a possible strategy to generate these cells for clinical application. In summary, our study identified CXCR5+CD8+ T cells as a distinct T cell subset with ability to suppress TFH-mediated B cell differentiation, exert strong antitumor activity, and confer favorable prognosis in follicular lymphoma patients.

BACKGROUND A recent analysis suggested potential narrowing of the gender gap in research productivity in the field of rhinology. This analysis did not, however, provide insight into how the genders are represented in the rhinologic literature. This study aimed to evaluate 11 years of literature to evaluate for gender differences in authorship position, collaborations, category and content of research, citations, and funding to gain perspective on how gender and authorship has changed over time. METHODS Authorship data for all articles on rhinologic subject matter published between January 1, 2008 and December 31, 2018 in four otolaryngology journals was collected. The gender of authors was determined by protocol. Category and content of research and funding status/source were additionally obtained. RESULTS Data were collected from 2666 articles. Gender of 14,510 authors was determined. Female authors accounted for 23% of the overall authors and male authors accounted for 77%. Female first authorship increased significantly over time, but there was no change in female senior authorship. The percentage of female authors steadily increased over time, whereas male authorship decreased slightly. Mixed gender teams were shown to be increasing in frequency. Women published more than expected in basic science and allergy and less than expected in skull base. On funded studies, women were significantly underrepresented as senior authors. CONCLUSION This study represents the first assessment of gender differences in the rhinology literature. Areas where female representation can improve include senior authorship, increased involvement in skull base publications, and increased funding.

Summary Fungal airway infection (airway mycosis) is an important cause of allergic airway diseases such as asthma, but the mechanisms by which fungi trigger asthmatic reactions are poorly understood. Here, we leverage wild-type and mutant Candida albicans to determine how this common fungus elicits characteristic Th2 and Th17 cell-dependent allergic airway disease in mice. We demonstrate that rather than proteinases that are essential virulence factors for molds, C. albicans instead promoted allergic airway disease through the peptide toxin candidalysin. Candidalysin activated platelets through the Von Willebrand factor (VWF) receptor GP1bα to release the Wnt antagonist Dickkopf-1 (Dkk-1) to drive Th2 and Th17 cell responses that correlated with reduced lung fungal burdens. Platelets simultaneously precluded lethal pulmonary hemorrhage resulting from fungal lung invasion. Thus, in addition to hemostasis, platelets promoted protection against C. albicans airway mycosis through an antifungal pathway involving candidalysin, GP1bα, and Dkk-1 that promotes Th2 and Th17 responses.

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal “microbiotypes” or “states”: the first is Corynebacterium-dominated, the second is Staphylococcus-dominated, and the third dominated by the other core genera of the sinonasal microbiome (Streptococcus, Haemophilus, Moraxella, and Pseudomonas). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based on geography. We also describe a potential reciprocal relationship between Corynebacterium species and Staphylococcus aureus, suggesting that a certain microbial equilibrium between various players is reached in the sinuses. We validate our approach by applying it to a separate 16S rRNA gene sequence dataset of 97 sinus swabs from a different patient cohort. Sinonasal microbiotyping may prove useful in reducing the complexity of describing sinonasal microbiota. It may drive future studies aimed at modeling microbial interactions in the sinuses and in doing so may facilitate the development of a tailored patient-specific approach to the treatment of sinus disease in the future.

BACKGROUND Bioabsorbable steroid-releasing implants (mometasone furoate, 370 μg) are effective for improving postsurgical outcomes in the frontal sinus ostia (FSO). In this study we evaluated the effect of these implants on frontal outcomes in various patient subgroups with chronic rhinosinusitis (CRS) using pooled data from 2 randomized, controlled trials (RCTs). METHODS A total of 160 subjects were enrolled in 2 RCTs. After surgery, subjects were randomized to receive an implant in 1 FSO with the contralateral side as control. Data through day 90 from the 2 studies were pooled and subgroup analyses were performed. RESULTS At day 30, relative to controls, steroid-releasing implants significantly reduced the need for postoperative interventions by 46.8% (95% confidence interval [CI], -60.7 to -27.9), for surgical interventions by 51.2% (95% CI, -68.2 to -25.2), and for oral steroid interventions by 37.2% (95% CI, -54.6 to -13.1) in the pooled data set. At day 90, statistically significant reductions (p < 0.05) in the need for postoperative interventions (relative reduction [RR], 30.2%), restenosis/occlusion rate (RR, 31.7%), and inflammation score (absolute difference, -6.0), and increase in estimated FSO diameter (absolute difference, 1 mm), favoring the treated side, were observed. Subgroup analyses of the pooled data showed statistically significant improvements (p < 0.05) at day 90 in restenosis/occlusion rate, and estimated FSO diameter, favoring the treated side across subgroups, with no statistically significant subgroup-by-treatment interactions. CONCLUSION Bioabsorbable steroid-releasing sinus implants improve outcomes of frontal sinus surgery through 90 days, irrespective of asthma status, previous endoscopic sinus surgery, extent of surgery, extent of polyps, or Lund-Mackay computed tomography stage in the FSO.

Asthma, chronic rhinosinusitis, and related incurable allergic afflictions of the upper and lower airways are medically important because of their association with the disabling symptom of dyspnea and, at least for asthma, the potential to cause fatal asphyxiation. Extensive research over the past two decades has uncovered both the physiological basis of airway obstruction in asthma and key governing molecular pathways. Exaggerated airway constriction in response to diverse provocative stimuli, termed airway hyperresponsiveness, is mediated through the cytokines interleukin 4 (IL-4) and IL-13 and the transcription factor signal transducer and activator of transcription 6 (STAT6). Overproduction of mucus has long been known to be an essential second component of airway obstruction and is also mediated in part through the IL-4/IL-13/STAT6 pathway. In this review, we discuss a second major signaling pathway which underlies mucus production that is mediated through proteinase-cleaved fibrinogen signaling through Toll-like receptor 4. Unexpectedly, our analysis of human sputum and paranasal sinus fluid indicates that in most cases of severe allergic airway disease, a unique type of airway fungal infection, termed airway mycosis, is pathogenically linked to these conditions. We further discuss how fungal and endogenous proteinases mediate the fibrinogenolysis that is essential to both Toll-like receptor 4 signaling and fibrin deposition that, together with mucus, contribute to airway obstruction.

Studying the pathophysiology of allergic fungal rhinosinusitis (AFRS) has proved challenging. While this clinical entity is easily distinguishable based on the clinical criteria set forth by Bent and Kuhn twenty-five years ago, studies examining type 2 inflammatory profiles in AFRS can make it seem more alike other CRS subtypes than it is different. Still, evolving research seems to clearly delineate this subtype from others in CRS. This review will critically evaluate the evolution of research examining the pathophysiology of AFRS and will conclude with a summary of the special considerations in the management of this fascinating disease. Keywords: Allergic fungal rhinosinusitis (AFRS), Chronic rhinosinusitis (CRS), Nasal polyps, Type 2 inflammation, Allergic sinusitis, Fungal sinusitis, Fungal allergy, Eosinophilic mucin rhinosinusitis, Nasal polyposis

Intra-arterial embolization of juvenile nasopharyngeal angiofibroma (JNA) prior to surgical resection is the preferred approach to minimize blood loss during surgical resection of the tumor. However, the presence of external carotid artery-internal carotid artery (ECA-ICA) anastomoses may hinder complete tumor embolization due to the associated risk for embolic complications. Here, we evaluate the use of a balloon-assisted embolization (BAE) technique in the treatment of JNA. We conducted a retrospective review of JNA patients who underwent tumor embolization with injection of Onyx in a single session between 2013-2018. All cases displayed tumor arterial supply from ECA and ICA circulations on 2-D catheter angiograms. Procedural and surgical outcome data were analyzed. Results are given as mean±standard deviation (range). Among 9 patients with JNA, all were males and mean age was 14.1±6.3 years (range, 9-29 years). The mean tumor volume embolization was 84.4±12.4% (range, 60-100%) and in 89% patients ≥80% of tumor volume embolization was achieved. There were no embolization-related complications reported. During surgical resection of the tumor there was a low average surgical blood loss of 722±651.5 mL (range, 50-2,000 mL) and the mean procedure time was 282.6±85.4 mins (range, 151-403 mins). In this series, the BAE technique showed to be a safe and effective approach to achieve successful tumor embolization while avoiding embolic complications and effectively reducing the risk for blood loss during surgical resection.