Aspergillus Enhances Eosinophil and Neutrophil Extracellular DNA Trap Formation in Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is characterized by inflammatory cell infiltration in the sinonasal mucosa. Eosinophil and neutrophil extracellular traps (EETs and NETs, respectively) are prominently found in CRS. This study aimed to investigate the effect of airborne fungi, Alternaria alternata and Aspergillus fumigatus, on EET and NET formation. Nasal epithelial cells, eosinophils, and neutrophils were isolated from eosinophilic CRS (ECRS), non-ECRS (NECRS), and healthy control. We determined eosinophil and neutrophil transepithelial migration after fungal treatment. We then determined the release of EETs and NETs by fungi using Sytox Green staining and determined the role of reactive oxygen species (ROS) using ROS inhibitors. We identified more abundant EETs and NETs in ECRS than in NECRS. A. alternata and A. fumigatus enhanced eosinophil and neutrophil transepithelial migration. A. fumigatus strongly induced EET and NET formation in CRS and, simultaneously, suppressed fungal metabolic activity. EET formation in CRS is associated with nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and NET formation with NADPH-oxidase and mitochondrial ROS. A. fumigatus, but not A. alternata, induced EET and NET formation, and peripheral blood eosinophils and neutrophils exhibited different immune responses against A. fumigatus following the inflammatory status of the host. Aspergillus-fumigatus-induced EET and NET formation plays a crucial role in CRS pathogenesis.

Effects of Lidocaine-Derived Organic Compounds on Eosinophil Activation and Survival.

Lidocaine, a local anesthetic, is known to possess anti-inflammatory properties. However, its clinical use is limited by inconveniences, such as its local synesthetic effects. This study evaluated lidocaine analogs designed and synthesized to overcome the disadvantages of lidocaine, having anti-inflammatory properties. Interleukin 5 (IL-5)-induced eosinophil activation and survival were evaluated using 36 lidocaine analogs with modified lidocaine structure on the aromatic or the acyl moiety or both. Eosinophil survival was evaluated using a CellTiter 96® aqueous cell proliferation assay kit. Superoxide production was determined using the superoxide dismutase-inhibitable reduction of cytochrome C method. Eosinophil cationic protein (ECP), IL-8, and transcription factor expression were determined using enzyme-linked immunosorbent assay. The platelet-activating factor (PAF)-induced migration assay was performed using a Transwell insert system. Compounds EI137 and EI341 inhibited IL-5-induced eosinophil survival and superoxide and ECP production in a concentration-dependent manner. These compounds also significantly reduced IL-8 production. Although compounds EI137 and EI341 significantly reduced phosphorylated ERK 1/2 expression, they did not influence other total and phosphorylated transcription factors. Moreover, 1000 µM of compound EI341 only inhibited PAF-induced migration of eosinophils. Lidocaine analogs EI137 and EI341 inhibited IL-5-mediated activation and survival of eosinophils. These compounds could be new therapeutic agents to treat eosinophilic inflammatory diseases.

Inflammatory Endotypes of Chronic Rhinosinusitis in the Korean Population: Distinct Expression of Type 3 Inflammation.

PURPOSE: Cluster analyses on inflammatory markers of chronic rhinosinusitis (CRS) in Asians from multicenter data are lacking. This multicenter study aimed to identify the endotypes of CRS in Koreans and to evaluate the relationship between the endotypes and clinical parameters. METHODS: Nasal tissues were obtained from patients with CRS and controls who underwent surgery. The endotypes of CRS were investigated by measuring interleukin (IL)-5, interferon (IFN)-γ, IL-17A, IL-22, IL-1ß, IL-6, IL-8, matrix metalloproteinase-9, eotaxin-3, eosinophil cationic protein, myeloperoxidase (MPO), human neutrophil elastase (HNE), periostin, transforming growth factor-ß1, total immunoglobulin E (IgE), and staphylococcal enterotoxin (SE)-specific IgE. We performed hierarchical cluster analysis and evaluated the phenotype, comorbidities, and Lund-Mackay computed tomography (LM CT) score in each cluster. RESULTS: Five clusters and 3 endotypes were extracted from 244 CRS patients: cluster 1 had no upregulated mediators compared to the other clusters (mild mixed inflammatory CRS); clusters 2, 3, and 4 had higher concentrations of neutrophil-associated mediators including HNE, IL-8, IL-17A, and MPO (T3 CRS); and cluster 5 had higher levels of eosinophil-associated mediators (T2 CRS). SE-specific IgE was undetectable in T3 CRS and had low detectable levels (6.2%) even in T2 CRS. The CRS with nasal polyps (CRSwNP) phenotype and LM CT scores showed no significant differences between T2 and T3 CRS, while the incidence of comorbid asthma was higher in T2 CRS than T3 CRS. In T3 clusters, higher levels of neutrophilic markers were associated with disease severity and CRSwNP phenotype. CONCLUSIONS: In Koreans, there is a distinct T3 CRS endotype showing a high proportion of CRSwNP and severe disease extent, along with T2 CRS.

Transoral thyroidectomy implemented by a novice surgeon: Efforts for safe implementation.

Background: This study aimed to evaluate the feasibility, safety, and early surgical outcomes of transoral robotic and endoscopic thyroidectomy conducted by a novice surgeon. Methods: We analyzed 27 patients who underwent transoral thyroidectomy between December 2018 and November 2021. All the surgeries were performed by a novice surgeon without prior endoscopic or robotic surgery experience; the surgeon had experienced 12 cases of transcervical thyroidectomy before adopting transoral thyroidectomy. Results: Of the 27 cases, 1 was converted to the transcervical approach due to poor bleeding control. Four cases had transient recurrent laryngeal nerve palsy, and three had transient hypoparathyroidism. Most of the patients were very satisfied with the postoperative cosmetic outcome. Conclusions: Transoral robotic and endoscopic thyroidectomies are feasible for the novice surgeon, with reasonable results in the early adoption stage if preparations are according to the suggested framework. Level of Evidence: Level 4.

Immunopathologic Role of Fungi in Chronic Rhinosinusitis.

Airborne fungi are ubiquitous in the environment and are commonly associated with airway inflammatory diseases. The innate immune defense system eliminates most inhaled fungi. However, some influence the development of chronic rhinosinusitis. Fungal CRS is thought of as not a common disease, and its incidence increases over time. Fungi are present in CRS patients and in healthy sinonasal mucosa. Although the immunological mechanisms have not been entirely explained, CRS patients may exhibit different immune responses than healthy people against airborne fungi. Fungi can induce Th1 and Th2 immune responses. In CRS, Th2-related immune responses against fungi are associated with pattern recognition receptors in nasal epithelial cells, the production of inflammatory cytokines and chemokines from nasal epithelial cells, and interaction with innate type 2 cells, lymphocytes, and inflammatory cells. Fungi also interact with neutrophils and eosinophils and induce neutrophil extracellular traps (NETs) and eosinophil extracellular traps (EETs). NETs and EETs are associated with antifungal properties and aggravation of chronic inflammation in CRS by releasing intracellular granule proteins. Fungal and bacterial biofilms are commonly found in CRS and may support chronic and recalcitrant CRS infection. The fungal-bacterial interaction in the sinonasal mucosa could affect the survival and virulence of fungi and bacteria and host immune responses. The interaction between the mycobiome and microbiome may also influence the host immune response, impacting local inflammation and chronicity. Although the exact immunopathologic role of fungi in the pathogenesis of CRS is not completely understood, they contribute to the development of sinonasal inflammatory responses in CRS.

Immunopathologic Role of Eosinophils in Eosinophilic Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is a diverse chronic inflammatory disease of the sinonasal mucosa. CRS manifests itself in a variety of clinical and immunologic patterns. The histological hallmark of eosinophilic CRS (ECRS) is eosinophil infiltration. ECRS is associated with severe disease severity, increased comorbidity, and a higher recurrence rate, as well as thick mucus production. Eosinophils play an important role in these ECRS clinical characteristics. Eosinophils are multipotential effector cells that contribute to host defense against nonphagocytable pathogens, as well as allergic and nonallergic inflammatory diseases. Eosinophils interact with Staphylococcus aureus, Staphylococcal enterotoxin B, and fungi, all of which were found in the tissue of CRS patients. These interactions activate Th2 immune responses in the sinonasal mucosa and exacerbate local inflammation. Activated eosinophils were discovered not only in the tissue but also in the sinonasal cavity secretion. Eosinophil extracellular traps (EETs) are extracellular microbes trapping and killing structures found in the secretions of CRS patients with intact granule protein and filamentous chromatic structures. At the same time, EET has a negative effect by causing an epithelial barrier defect. Eosinophils also influence the local tissue microenvironment by exchanging signals with other immune cells and structural cells. As a result, eosinophils are multifaceted leukocytes that contribute to various physiologic and pathologic processes of the upper respiratory mucosal immune system. The goal of this review is to summarize recent research on the immunopathologic properties and immunologic role of eosinophils in CRS.

Fibrous dysplasia of the maxillary bone secondary to sinus surgery in an elderly patient: A case report.

Fibrous dysplasia (FD) is a rare benign disease that replaces a normal bone with abnormal fibrous and weak osseous tissue. It is usually detected in childhood and rarely occurs in old age. Although the disease is known to be caused by a genetic mutation, only a single case of FD secondary to surgery is reported in the literature. We report a case of monostotic FD of the maxillary sinus in a 70-year-old Asian woman who presented with incidental calcific lesion in the maxillary sinus on a brain computed tomography scan. At 32 months prior to presentation, the patient had undergone an endoscopic sinus surgery for a fungal ball of the same sinus. The lesion was removed by endoscopic surgery, and the histopathological evidence was consistent with FD. To the best of our knowledge, this is the second case of a postsurgical craniofacial FD, and a rare case that occurred in old age.

Apnea-hypopnea Index is Correlated with Pulse Rate in Patients with Sleep-related Breathing Disorder without Hypertension, Cardiovascular Disease, or Diabetes Mellitus.

Objective: This study aimed to compare the mean pulse rate (PR) and mean blood pressure (BP) between patients with obstructive sleep apnea (OSA) and those with simple snoring (SS) during a 24-hour period, and to investigate the correlation between apnea-hypopnea index (AHI), PR, and BP in sleep-related breathing disorder (SRBD) patients with and without hypertension, diabetes mellitus (DM), and cardiovascular diseases (CVDs). Methods: Ninety SRBD patients underwent full-night polysomnography, and ambulatory BP and PR were monitored for 24 hours. Participants were classified into OSA (AHI ≥ 5) and control (SS) (AHI < 5) groups, and BP and PR were compared. Participants were also divided into groups with and without hypertension, CVDs, or DM to analyze the correlation between AHI, BP, and PR in each group. Results: Mean PRs during the daytime period and during the whole 24-hour period in the OSA group were significantly higher than those in the SS group after controlling for potential confounders. No significant difference was observed in mean BP between the groups. Partial correlation analysis after controlling for confounders showed significant correlation between AHI and PR during daytime and the 24-hour period in participants without hypertension, DM, or CVDs, but not in participants with these conditions. Conclusion: The significant differences and correlations only in PR (not in BP) found in this study suggest that PR could be an early marker for SRBD in individuals without comorbidities, and that an increased sympathetic tone could be responsible for future occurrence of CVD.

Korean Red Ginseng and Ginsenoside Rg3 Suppress Asian Sand Dust-Induced Epithelial-Mesenchymal Transition in Nasal Epithelial Cells.

Chronic rhinosinusitis (CRS) is characterized by chronic inflammation of the sinonasal mucosa with epithelial dedifferentiation toward the mesenchymal phenotype, known as the epithelial-mesenchymal transition (EMT). Asian sand dust (ASD) can induce nasal mucosal inflammation and cause the development of EMT. Korean red ginseng (KRG) and ginsenoside Rg3 have been used as traditional herbal medicines to treat various diseases. The aim of this study was to investigate their effect on ASD-induced EMT in nasal epithelial cells. Primary nasal epithelial cells were incubated with ASD with or without KRG or Rg3, and the production of transforming growth factor-ß1 (TGF-ß1) and interleukin (IL)-8 was measured. EMT markers were determined by RT-PCR, Western blot analysis, and confocal microscopy, and transcription factor expression by Western blot analysis. The effect on cell migration was evaluated using the wound scratch assay. Results showed ASD-induced TGF-ß1 production, downregulation of E-cadherin, and upregulation of fibronectin in nasal epithelial cells. KRG and Rg3 suppressed TGF-ß1 production (31.7% to 43.1%), upregulated the expression of E-cadherin (26.4% to 88.3% in mRNA), and downregulated that of fibronectin (14.2% to 46.2% in mRNA and 52.3% to 70.2% in protein). In addition, they suppressed the ASD-induced phosphorylation of ERK, p38, and mTOR, as well as inhibiting the ASD-induced migration of nasal epithelial cells (25.2% to 41.5%). The results of this study demonstrate that KRG and Rg3 inhibit ASD-induced EMT by suppressing the activation of ERK, p38, and mTOR signaling pathways in nasal epithelial cells.

Asian Sand Dust Particles Enhance the Development of Aspergillus fumigatus Biofilm on Nasal Epithelial Cells.

BACKGROUND: Asian sand dust (ASD) and Aspergillus fumigatus are known risk factors for airway mucosal inflammatory diseases. Bacterial and fungal biofilms commonly coexist in chronic rhinosinusitis and fungus balls. We evaluated the effects of ASD on the development of A. fumigatus biofilm formation on nasal epithelial cells. METHODS: Primary nasal epithelial cells were cultured with A. fumigatus conidia with or without ASD for 72 h. The production of interleukin (IL)-6, IL-8, and transforming growth factor (TGF)-ß1 from nasal epithelial cells was determined by the enzyme-linked immunosorbent assay. The effects of ASD on A. fumigatus biofilm formation were determined using crystal violet, concanavalin A, safranin staining, and confocal scanning laser microscopy. RESULTS: ASD and A. fumigatus significantly enhanced the production of IL-6 and IL-8 from nasal epithelial cells. By coculturing A. fumigatus with ASD, the dry weight and safranin staining of the fungal biofilms significantly increased in a time-dependent manner. However, the increased level of crystal violet and concanavalin A stain decreased after 72 h of incubation. CONCLUSIONS: ASD and A. fumigatus induced the production of inflammatory chemical mediators from nasal epithelial cells. The exposure of A. fumigatus to ASD enhanced the formation of biofilms. The coexistence of ASD and A. fumigatus may increase the development of fungal biofilms and fungal inflammatory diseases in the sinonasal mucosa.

Fabrication and Characterization of In0.53Ga0.47As/InAs/In0.53Ga0.47As Composite Channel Metamorphic HEMTs (mHEMTs) on a GaAs Substrate.

In this work, we successfully demonstrated In0.53Ga0.47As/InAs/In0.53Ga0.47As composite channel metamorphic high electron mobility transistors (mHEMTs) on a GaAs substrate. The fabricated mHEMTs with a 100 nm gate length exhibited excellent DC and logic characteristics such as VT = -0.13 V, gm,max = 949 mS/mm, subthreshold swing (SS) = 84 mV/dec, drain-induced barrier lowering (DIBL) = 89 mV/V, and Ion/Ioff ratio = 9.8 × 103 at a drain-source voltage (VDS) = 0.5 V. In addition, the device exhibited excellent high-frequency characteristics, such as fT/fmax = 261/304 GHz for the measured result and well-matched modeled fT/fmax = 258/309 GHz at VDS = 0.5 V, which is less power consumption compared to other material systems. These high-frequency characteristics are a well-balanced demonstration of fT and fmax in the mHEMT structure on a GaAs substrate.

Risk Model Establishment of Endoscopic Sinus Surgery for Patients with Chronic Rhinosinusitis: a Multicenter Study in Korea.

BACKGROUND: Endoscopic sinus surgery (ESS) is the mainstay treatment for refractory chronic rhinosinusitis (CRS). Since various factors may contribute to the surgical outcome, it is challenging for physicians to predict surgical outcomes. The aim of study was to analyze the prognostic factors of postoperative outcomes and to establish the prediction model with the risk factors that impact the postoperative outcomes. METHODS: Medical records of CRS patients who underwent ESS at 9 institutions in 2005, 2010, and 2016 were retrospectively reviewed. We classified the patients into 2 groups based on postoperative objective endoscopic outcomes. Demographics, nose-specific symptoms, olfactory function, eosinophil counts in blood (EoB) and nasal tissue (EoT), and Lund-Mackay CT score (LMS) were collected. Univariate and multivariate analyses were performed and established a prediction equation for postoperative endoscopic objective outcomes. RESULTS: In total (n = 1,249), 27.0% were not satisfied under postoperative endoscopic examination. Of 10 variables, LMS (> 5), sinus dominancy (maxillary sinus and ethmoid sinus), EoB (> 210), and EoT (> 100) were statistically significant in univariate analysis (P < 0.05, all). In multivariate analysis, EoT (> 100) and LMS (> 5) were significantly associated with poor postoperative outcome. Furthermore, 5 significant variables were employed to establish the risk model of postoperative outcomes and P (the value of prediction probability) = 1 / (1 + exp [-0.392 + 1.088 × EoT (> 100) + 0.123 × mean LMS (> 5) - 0.366 × sinus dominancy (maxillary) + 0.064 × sinus dominancy (similar) + 0.200 × EoB (4%) + 0.344 × EoB (> 210)] was developed. CONCLUSION: Tissue eosinophil count and radiographic severity predispose to a poorer outcome of ESS and the risk model established may be helpful to predict postoperative outcomes of ESS.

Effect of Korean Red Ginseng and Rg3 on Asian Sand Dust-Induced MUC5AC, MUC5B, and MUC8 Expression in Bronchial Epithelial Cells.

Korean Red ginseng (KRG), commonly used in traditional medicine, has anti-inflammatory, anti- oxidative, and anti-tumorigenic properties. Asian sand dust (ASD) is known to aggravate upper and lower airway inflammatory responses. BEAS-2B cells were exposed to ASD with or without KRG or ginsenoside Rg3. Mucin 5AC (MUC5AC), MUC5B, and MUC8 mRNA and protein expression levels were determined using quantitative RT-PCR and enzyme-linked immunosorbent assay. Nuclear factor kappa B (NF-κB), activator protein 1, and mitogen-activated protein kinase expression and activity were determined using western blot analysis. ASD induced MUC5AC, MUC5B, and MUC8 mRNA and protein expression in BEAS-2B cells, which was significantly inhibited by KRG and Rg3. Although ASD-induced mucin expression was associated with NF-κB and p38 mitogen-activated protein kinase (MAPK) activity, KRG and Rg3 significantly suppressed only ASD-induced NF-κB expression and activity. KRG and Rg3 inhibited ASD-induced mucin gene expression and protein production from bronchial epithelial cells. These results suggest that KRG and Rg3 have potential for treating mucus-producing airway inflammatory diseases.

Chamaecyparis obtusa Essential Oil Inhibits House Dust Mite Induced Nasal Epithelial Cell Activation and Immune Responses.

Essential oils extracted from plants contain protective volatile compounds and are known to processes antibacterial, antifungal, anti-oxidative, and anti-inflammatory effects. This study was conducted to explore the immunomodulatory effects of essential oil extracted from Chamaecyparis obtusa (EOCO) on house dust mite-induced mucosal inflammation. Cultured primary nasal epithelial cells were stimulated with Dermatophagoides pteronyssinus (DP), and Dermatophagoides farina (DF) for 48 h. The production of interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) was measured by enzyme-linked immunosorbent assay, and the expression levels of nuclear factor (NF)-κB, activator protein (AP)-1, and mitogen-activated protein kinase (MAPK) were determined by western blot analysis. To examine the effect of EOCO on the production of chemical mediators and the expression of transcription factors, epithelial cells were pretreated with EOCO for 1 h before stimulation. Peripheral blood mononuclear cells (PBMCs) were cultured in nasal epithelial cell conditioned media (NECM) for 72 h, after which the levels of IL-5, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were measured. DP and DF enhanced the production of IL-25, IL-33, and TSLP, and EOCO pretreatment inhibited their production from nasal epithelial cells. EOCO pretreatment also significantly suppressed the expression of NF-κB and AP-1. NECM induced the production of IL-5, IFN- γ, and TNF-α from PBMCs, and only TNF-α production was significantly inhibited by EOCO pretreatment. EOCO pretreatment inhibited the DP and DF induced nasal epithelial cell derived cytokine production and TNF-α production from PBMCs. These results indicate the potential value of EOCO in the treatment of airway inflammatory or immunological diseases.

Immunomodulative Effects of Chamaecyparis obtusa Essential Oil in Mouse Model of Allergic Rhinitis.

The present study aims to investigate the immunomodulatory effects of essential oil from Chamaecyparis obtusa (EOCO) in an ovalbumin (OVA)-induced allergic rhinitis (AR) mouse model. BALB/c mice were intraperitoneally sensitized and stimulated with OVA. From day 22 to 35, 0.01% and 0.1% ECOC was intranasally administered 1 h before OVA stimulation. Nasal symptoms, as well as serum total and OVA-specific immunoglobulin (Ig) E levels, were measured. Interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels in nasal lavage fluid (NLF) and their production by activated splenocytes were measured. Histological changes in the sinonasal mucosa were evaluated through hematoxylin and eosin and periodic acid-Schiff staining procedure. Th cytokines and their transcription factor mRNA expressions were determined using reverse-transcription polymerase chain reaction. Intranasal EOCO administration significantly suppressed allergic symptoms, OVA-specific IgE level, sinonasal mucosal inflammatory cell infiltration, and mucus-producing periodic acid-Schiff (PAS) positive cell count. EOCO also significantly inhibited IL-4, IL-10, and TNF-α levels in NLF and activated splenocytes. Th2 and Treg related cytokines and their transcription factors in sinonasal mucosa were significantly suppressed through intransal EOCO instillation. In conclusion, repetitive EOCO intranasal instillation showed anti-inflammatory and anti-allergic effects by suppressing nasal symptoms and inhibiting the production and expression of inflammatory mediators in the OVA-induced AR mouse model.

Development and immunopathological characteristics of an Alternaria-induced chronic rhinosinusitis mouse model.

Airborne fungi are associated with upper and lower airway inflammatory diseases. Alternaria is commonly found in nasal secretions and induces the production of chemical mediators from sinonasal mucosa. This study aimed to establish an Alternaria-induced chronic rhinosinusitis (CRS) mouse model and determine the influence of host allergic background on the immunopathological characteristics of CRS. BALB/c mice were used for establishing the CRS model. Alternaria was intranasally instilled for 8 or 16 weeks with or without ovalbumin (OVA) presensitization. Total serum IgE and Alternaria-specific IgE levels were measured by enzyme-linked immunosorbent assay (ELISA). Interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels in nasal lavage fluid (NLF) and splenocytes were measured by ELISA and their mRNAs and levels of associated transcription factors in sinonasal mucosa were determined with quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Hematoxylin-eosin staining and periodic acid-Schiff staining were performed to evaluate histological changes. Total serum IgE was increased in both allergic and non-allergic CRS. IL-4 was strongly expressed in NLF in both allergic and non-allergic CRS at 16 weeks and not only eosinophils but also neutrophils were increased in NLF of non-allergic CRS mice. The levels of Th1, Th2, and Treg cytokines and transcription factor mRNAs were significantly increased in sinonasal mucosa of non-allergic CRS mice. Both inflammatory cell infiltration and goblet cell hyperplasia were increased in CRS mice. Repeated intranasal instillation of Alternaria results in sinonasal inflammation with inflammatory cell infiltration. The sinonasal mucosal immune responses against Alternaria were shown to differ depending on the host allergic background.

Nasal Epithelial Cells Activated with Alternaria and House Dust Mite Induce Not Only Th2 but Also Th1 Immune Responses.

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by mucosal inflammation. Airborne allergens are associated with upper and lower airway inflammatory disease. We investigated the effects of airborne allergen stimulation in the nasal epithelial cells and their effect on the peripheral blood mononuclear cells' (PBMCs) Th immune polarization. Interleukin (IL)-10, IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels were determined using the enzyme-linked immunosorbent assay (ELISA) in nasal polyp tissues. Cultured primary nasal epithelial cells were stimulated with Alternaria alternata, Aspergillus fumigatus, Dermatophagoides pteronyssinus (DP), and Dermatophagoides farina (DF) for 48 hours. IL-6, IL-25, IL-33, and TSLP production were measured by ELISA, and the nuclear factor-κB (NF-κB), activator protein 1 (AP-1), and mitogen-activated protein kinase (MAPK) expression were determined by western blot analyses. PBMCs were cultured with nasal epithelial cell-conditioned media (NECM), and IL-5, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were measured. Innate lymphoid type2 cells (ILC2) were analyzed with flowcytometry. IL-25, IL-33, and TSLP levels were significantly higher in eosinophilic nasal polyps. Alternaria, DP, and DF enhanced IL-33 and TSLP production from the nasal epithelial cells through the NF-κB, AP-1, and MAPK pathway. NECM induced IL-5, IFN-γ, and TNF-α production from PBMCs, without increasing ILC2 expression. Alternaria and house dust mites enhanced the chemical mediator production from nasal epithelial cells and these allergens may induce not only Th2 inflammatory responses but also Th1 inflammatory responses in the nasal mucosa.

Clinicopathologic characteristics of paranasal sinus fungus ball: retrospective, multicenter study in Korea.

PURPOSE: Fungus ball (FB) is the most common type of fungal rhinosinusitis and the prevalence of FB has increased over the past 10 years. The aim of this study was to compare the clinical characteristics of Korean adult patients with FB and chronic rhinosinusitis (CRS) without FB. METHODS: We retrospectively analyzed data on 1362 patients (147 FB and 1215 CRS) who underwent endoscopic sinus surgery at nine Korean medical centers in 2005, 2010, and 2016. We evaluated the prevalence of FB and compared the clinical characteristics of FB and CRS. Medical records, computed tomography (CT) findings, atopic status, concomitant diseases, tissue, and blood eosinophil count were assessed. RESULTS: The prevalence of FB was significantly higher in 2016 (15.9%) than in the other years (7.8% in 2005 and 7.5% in 2010). The FB patients were more likely to be female, older, have unilateral disease and less likely to have allergy compared to the CRS patients. The most common main complaint related to CRS and FB was nasal obstruction. CT determined that unilateral disease and maxillary sinus dominancy were common in patients with FB. The incidence of concomitant diseases was much higher in FB, with lower tissue and blood eosinophilia. CONCLUSION: FB is commonly encountered in older women with the increased prevalence. FB had a different clinical presentation, radiological findings, and prognosis than CRS. Further studies are needed to understand the pathophysiologic mechanisms underlying the development of FB.