Candida albicans elicits protective allergic responses via platelet mediated T helper 2 and T helper 17 cell polarization.

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.

Allergic fungal rhinosinusitis linked to other hyper-IgE syndromes through defective TH17 responses.

BACKGROUND: In a gene expression analysis comparing sinus mucosa samples from allergic fungal rhinosinusitis (AFRS) patients with samples from non-AFRS chronic rhinosinusitis with nasal polyp (CRSwNP) patients, the antimicrobial peptide (AMP) histatin 1 (HTN1) was found to be the most differentially downregulated gene in AFRS. OBJECTIVE: We sought to identify the molecular etiology of the downregulated expression of HTN1. METHODS: We used RT-PCR to compare the expression of AMPs and a fungistasis assay to evaluate the antifungal activity of sinus secretions. Using flow cytometry, we characterized the presence of TH17/TH22 cells and signal transducer and activator of transcription (STAT) signaling from AFRS patients, non-AFRS CRSwNP patients, and healthy controls. RESULTS: We confirmed decreased expression of AMPs in AFRS sinus mucosa with concordant decrease in antifungal activity in sinus secretions. IL-22 and IL-22-producing T cells were deficient within sinus mucosa of AFRS patients. In vitro studies demonstrated a defect in IL-6/STAT3 signaling critical for TH17/TH22 differentiation. Epithelial cells from AFRS patients could express AMPs when stimulated with exogenous IL-22/IL-17 and circulating TH17 cell abundance was normal. CONCLUSIONS: Similar to other hyper-IgE syndromes, but distinct from CRSwNP, AFRS patients express a defect in STAT3 activation limited to IL-6-dependent STAT3 phosphorylation that is critical for TH17/TH22 differentiation. This defect leads to a local deficiency of IL-17/IL-22 cytokines and deficient AMP expression within diseased sinus mucosa of AFRS patients. Our findings support evaluation of therapeutic approaches that enhance airway AMP production in AFRS.

EUFOREA/EPOS2020 statement on the clinical considerations for chronic rhinosinusitis with nasal polyps care.

Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP.

The Joint Task Force on Practice Parameters GRADE guidelines for the medical management of chronic rhinosinusitis with nasal polyposis.

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. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation 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.

Update on allergic fungal rhinosinusitis.

Allergic fungal rhinosinusitis (AFRS) is a unique clinical entity that falls under the broader umbrella of chronic rhinosinusitis with nasal polyps with type 2 inflammation. It is characterized by nasal polyposis, production of characteristic thick eosinophilic mucin, and expansile change of involved sinus cavities. The diagnosis is classically made using the Bent and Kuhn criteria. However, recent studies have indicated the lack of specificity of some major criteria. The need to fulfill all 5 criteria before diagnosing AFRS partially mitigates this but renders the criteria cumbersome to use, and highlights the need to develop more specific criteria. Our understanding of AFRS pathophysiology has advanced significantly and has helped elucidate the lack of histatins contributing to the inability to clear fungal spores, consequently leading to fungi-induced disruption of the epithelial barrier and stimulation of sinonasal epithelial cells. These trigger a cascade of type 2 inflammatory cytokines driven by both the adaptive and innate immune system. Although more research is needed, these findings could hypothetically point to a limited type 3 immune response at the sinus mucosa, resulting in a compensatory overstimulation of type 2 inflammatory processes. Treatment for AFRS remains centered on surgery and topical corticosteroids. Short courses of systemic corticosteroids may be used with caution, and fungal-specific immunotherapy and systemic antifungals are options in recalcitrant disease. Biologics show early promise, as we await data from randomized controlled trials under way. Finally, new insights into AFRS pathology provide opportunities for novel therapeutic strategies.

Topical corticosteroids for chronic rhinosinusitis with nasal polyposis: GRADE systematic review and network meta-analysis.

BACKGROUND: 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. OBJECTIVE: We systematically synthesized the evidence addressing INCS for CRSwNP. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Computer-Assisted Analysis of Oral Antifungal Therapy in Chronic Rhinosinusitis with Airway Mycosis: a Retrospective Cohort Analysis.

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.

The role of CT and endoscopy in the evaluation of patients referred for intranasal Cryoablation.

BACKGROUND: Cryoablation (CA) of the posterior nasal nerves has garnered increasing interest as an office-based procedure for chronic rhinitis (CR). Standardized preoperative evaluation, specifically the role of computed tomography (CT) and nasal endoscopy, has yet to be defined. We report a series of patients who underwent CT and endoscopy as part of CR work-up in patients referred for CA. OBJECTIVE: Highlight the importance of both nasal endoscopy and CT scan in the evaluation of CR given significant overlap of symptoms and common occurrence of related sinonasal conditions. METHODS: Retrospective analysis of all patients referred to a single tertiary rhinology practice for CA was performed. RESULTS: Fifteen patients were sent for CA by medical allergists. Five patients were deemed CA candidates, and 1 patient received only medical CR treatment. Four patients had evidence of incomplete prior sinus surgery and/or continued chronic rhinosinusitis on endoscopic exam. These 4 patients received a combination of medical and surgical management with either complete resolution or improvement in CR symptoms. In 3 patients, CT confirmed chronic rhinosinusitis that was not apparent on endoscopy, and received a combination of medical and surgical management with symptom improvement. In the last two patients, final diagnoses were nasal valve collapse and recurrent acute rhinosinusitis. CONCLUSIONS: Referrals for CA are becoming more common and the optimal preoperative work up remains unclear. In this limited retrospective review, 67% of patients had diagnoses other than CR and thus were not deemed candidates for CA. Both CT and endoscopy are complementary to a detailed history and physical examination and can aid in CA candidate selection.

N95 respirator reuse, decontamination methods, and microbial burden: A randomized controlled trial.

PURPOSE: To evaluate the effectiveness and ease of N95 respirator decontamination methods in a clinic setting and to identify the extent of microbial colonization on respirators associated with reuse. METHODS: In a prospective fashion, N95 respirators (n = 15) were randomized to a decontamination process (time, dry heat, or ultraviolet C light [UVC]) in outpatient clinics. Each respirator was re-used up to 5 separate clinic sessions. Swabs on each respirator for SARS-CoV-2, bacteria, and fungi were obtained before clinic, after clinic and post-treatment. Mask integrity was checked after each treatment (n = 68). Statistical analyses were performed to determine factors for positive samples. RESULTS: All three decontamination processes reduced bacteria counts similarly. On multivariate mixed model analysis, there were an additional 8.1 colonies of bacteria (95% CI 5.7 to 10.5; p < 0.01) on the inside compared to the outside surface of the respirators. Treatment resulted in a decrease of bacterial load by 8.6 colonies (95% CI -11.6 to -5.5; p < 0.01). Although no decontamination treatment affected the respirator filtration efficiency, heat treatments were associated with the breakdown of thermoplastic elastomer straps. Contamination with fungal and SARS-CoV-2 viral particles were minimal to non-existent. CONCLUSIONS: Time, heat and UVC all reduced bacterial load on reused N95 respirators. Fungal contamination was minimal. Heat could permanently damage some elastic straps making the respirators nonfunctional. Given its effectiveness against microbes, lack of damage to re-treated respirators and logistical ease, UVC represents an optimal decontamination method for individual N95 respirators when reuse is necessary.

The international sinonasal microbiome study: A multicentre, multinational characterization of sinonasal bacterial ecology.

The sinonasal microbiome remains poorly defined, with our current knowledge based on a few cohort studies whose findings are inconsistent. Furthermore, the variability of the sinus microbiome across geographical divides remains unexplored. We characterize the sinonasal microbiome and its geographical variations in both health and disease using 16S rRNA gene sequencing of 410 individuals from across the world. Although the sinus microbial ecology is highly variable between individuals, we identify a core microbiome comprised of Corynebacterium, Staphylococcus, Streptococcus, Haemophilus and Moraxella species in both healthy and chronic rhinosinusitis (CRS) cohorts. Corynebacterium (mean relative abundance = 44.02%) and Staphylococcus (mean relative abundance = 27.34%) appear particularly dominant in the majority of patients sampled. Amongst patients suffering from CRS with nasal polyps, a statistically significant reduction in relative abundance of Corynebacterium (40.29% vs 50.43%; P = .02) was identified. Despite some measured differences in microbiome composition and diversity between some of the participating centres in our cohort, these differences would not alter the general pattern of core organisms described. Nevertheless, atypical or unusual organisms reported in short-read amplicon sequencing studies and that are not part of the core microbiome should be interpreted with caution. The delineation of the sinonasal microbiome and standardized methodology described within our study will enable further characterization and translational application of the sinus microbiota.

Contributions of Innate Lymphoid Cells in Chronic Rhinosinusitis.

PURPOSE OF REVIEW: To review innate lymphoid cells (ILCs) and their role in chronic rhinosinusitis (CRS). RECENT FINDINGS: The immune system consists of the innate and adaptive response. Until the recognition of ILCs, chronic inflammatory diseases were characterized by cytokines linked only to T helper cells. However, these immune responses are now described more broadly to include contributions from both the innate and adaptive immunity. In CRS, focus had been on ILC2s in CRS with nasal polyps. These studies also highlight the importance of epithelial cell-derived cytokines in coordinating these responses. In addition to indirect crosstalk via cytokines, ILCs and T helper cells can utilize the OX40/OX40 ligand and major histocompatibility complex class II pathways to directly interact and coordinate responses. In addition to T helper cells, ILCs contribute to the inflammatory response associated with CRS. The understanding of these cells along with pathways that activate and perpetuate these cells leads to new potential therapeutic targets for CRS treatment.

Update on the Role of Fungus in Allergy, Asthma, and the Unified Airway.

The united airway refers to the combined upper and lower airways and their interconnected pathophysiologic relationships. Inflammatory airway diseases (chronic rhinosinusitis, asthma, and so forth) have been linked to fungal species through type 2 immune responses. These type 2 immune responses involve the cytokines interleukin (IL)-4, IL-5, IL-13, and a myriad of other inflammatory processes that lead to a spectrum of diseases from allergic bronchopulmonary mycosis to chronic rhinosinusitis. Historically, these diseases have been managed primarily with corticosteroids but recent revelations in the molecular pathophysiology provide opportunities for more diverse treatment options for patients with uncontrolled disease.

New Developments in Allergic Fungal Rhinosinusitis Pathophysiology and Treatment.

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.

Unified Airway Disease: Future Directions.

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.

Otolaryngology consultations for COVID-19 patients: A retrospective cohort study of indications, interventions, and considerations.

OBJECTIVE: To identify differences in inpatient otolaryngology consultations and interventions for patients based on COVID-19. METHODS: 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. RESULTS: Bleeding composed a significantly higher proportion of otolaryngology consults in COVID-19 positive patients (28% vs. 8.4%, p<0.0001). 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%, p<0.001). CONCLUSION: 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.

Dural sinus narrowing in patients with spontaneous anterior skull base cerebrospinal fluid leak.

Objectives: Current evidence suggests a link between idiopathic intracranial hypertension (IIH) and spontaneous cerebrospinal fluid (sCSF) leak, as well as between IIH and dural venous sinus (DVS) narrowing. However, there are limited data linking DVS narrowing and sCSF leak. This study aims to determine the prevalence of DVS narrowing in patients with sCSF leak. Methods: A retrospective review of all patients with sCSF leak that presented to a tertiary academic center from 2008 to 2019. Preoperative imaging was independently reviewed by two neuroradiologists to evaluate for DVS narrowing. Available literature was used to estimate the prevalence of DVS narrowing in the general population to allow for comparison. Data were analyzed using Exact binomial test. Results: Analysis of 25 patients with appropriate imaging revealed the majority were women (21/25, 84%) with a mean age of 51.89 years (SD 13.96). The majority of these patients were found to have narrowing of the DVS (20/25, 80%). In patient with sCSF leaks, there was a significantly higher proportion of patients with DVS narrowing compared with published literature examining this condition in the general population (80% vs. 40%, CI 0.59-0.93, p < .001). Conclusion: The prevalence of DVS narrowing in patients with sCSF leaks is substantial and likely greater than the general population. Moreover, there appears to be narrowing in most patients with sCSF leak. Preoperative radiological evaluation of the DVS using MR venography may be useful in patients with sCSF leaks as DVS stenosis may be an underdiagnosed etiology. Further study is needed to evaluate this. Level of Evidence: IV.

Evaluation and treatment of rhinosinusitis with primary antibody deficiency in adults: Evidence-based review with recommendations.

BACKGROUND: There is clear evidence that the prevalence of primary antibody deficiency (PAD) is higher in patients with recurrent and chronic rhinosinusitis (CRS) than in the general population. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on rhinosinusitis with PAD, summarize the existing evidence, and provide recommendations on the evaluation and management of rhinosinusitis in patients with PAD. METHODS: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through August 2022. Studies on the evaluation and management of rhinosinusitis in PAD patients were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on the evaluation and management principles for PAD were generated. RESULTS: A total of 42 studies were included in this evidence-based review. These studies were evaluated on incidence of PAD in rhinosinusitis patients, incidence of rhinosinusitis in PAD patients, and on the different treatment modalities used and their outcome. The aggregate quality of evidence was varied across reviewed domains. CONCLUSION: Based on the currently available evidence, PAD can occur in up to 50% of patients with recalcitrant CRS. Despite the presence of multiple studies addressing rhinosinusitis and PAD, the level of evidence supporting different treatment options continues to be lacking. Optimal management requires a multidisciplinary approach through collaboration with clinical immunology. There is need for higher-level studies that compare different treatments in patients with PAD and rhinosinusitis.

The Unified Airway Hypothesis: Evidence From Specific Intervention With Anti-IL-5 Biologic Therapy.

The unified airway hypothesis proposes that upper and lower airway diseases reflect a single pathological process manifesting in different locations within the airway. Functional, epidemiological, and pathological evidence has supported this well-established hypothesis for some time. However, literature on the pathobiologic roles/therapeutic targeting of eosinophils and IL-5 in upper and lower airway diseases (including asthma, chronic rhinosinusitis with nasal polyps [CRSwNP], and nonsteroidal anti-inflammatory drug-exacerbated respiratory disease) has recently emerged. This narrative review revisits the unified airway hypothesis by searching the scientific literature for recent learnings and clinical trial/real-world data that provide a novel perspective on its relevance for clinicians. According to the available literature, eosinophils and IL-5 have important pathophysiological roles in both the upper and lower airways, although the impact of eosinophils and IL-5 may vary in asthma and CRSwNP. Some differential effects of anti-IL-5 and anti-IL-5-receptor therapies in CRSwNP have been observed, requiring further investigation. However, pharmaceutical targeting of eosinophils and IL-5 in patients with upper, lower, and comorbid upper and lower airway inflammation has led to clinical benefit, supporting the hypothesis that these are linked conditions manifesting in different locations. Consideration of this approach may improve patient care and aid clinical decision making.

Acoustic resonance therapy is safe and effective for the treatment of nasal congestion in rhinitis: A randomized sham-controlled trial.

BACKGROUND: Acoustic resonance therapy (ART) is a novel vibrational treatment that delivers patient-specific resonant frequency acoustic energy to the sinonasal cavities. In a pilot study, ART was effective for the acute treatment of nasal congestion. We conducted a sham-controlled randomized trial to validate the efficacy of ART when administered daily for 2 weeks. METHODS: A total of 52 adult patients were enrolled in a multi-center, randomized, double-blinded, sham-controlled, interventional study evaluating ART administered by a vibrational headband. Patients received either active treatment or a non-therapeutic sham treatment twice daily over 2 weeks. Clinical endpoints were the average change in nasal congestion sub-score of the Total Nasal Symptom Score (TNSS) and the average change in composite TNSS. RESULTS: ART resulted in a significantly greater mean change in the nasal congestion sub-score compared to sham (-0.87 [95% confidence interval [CI] -1.11, -0.62] vs. -0.44 [95% CI -0.64, -0.23], p = 0.008). ART also resulted in a significantly greater reduction in the composite TNSS versus sham, (-2.85 [95% CI -3.85, -1.85], vs. -1.32 [95% CI -2.27, -0.36], p = 0.027). The response rate, determined by a nasal congestion sub-score minimal clinically important difference of 0.23, was 80.8% for ART and 46.2% for sham, with an adjusted risk ratio of 1.95 (95% CI 1.26, 3.02, p = 0.003) in favor of ART. Safety endpoints showed no adverse events. CONCLUSION: ART is a safe and effective non-pharmacologic alternative for the treatment of nasal congestion.

The role of fungus in the pathogenesis of chronic rhinosinusitis.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.