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Platelet-activating factor (PAF) is a phospholipid-derived inflammatory mediator that triggers various inflammatory conditions, including eosinophil activation and recruitment. This study aimed to evaluate the expressions of PAF-metabolism-associated genes, namely genes coding the enzymes involved in PAF synthesis (LPCAT1, LPCAT2, LPCAT3, and LPCAT4), PAF degradation (PAFAH1B2, PAFAH1B3, and PAFAH2), and the gene for the PAF receptor (PTAFR) in subtypes of CRSwNP classified by clinical- or hierarchal-analysis-based classifications. Transcriptomic analysis using bulk RNA barcoding and sequencing (BRB-seq) was performed with CRSwNP, including eosinophilic CRS (ECRS) ( n = 9), nonECRS (n = 8), ECRS with aspirin-exacerbated respiratory disease (Asp) ( n = 3), and controls with a normal uncinate process mucosa ( n = 6). PTAFR was only upregulated in ECRS and nonECRS. In the hierarchical cluster analysis with clusters 1 and 2 reflecting patients with low-to-moderate and high levels of type 2 inflammation, respectively, cluster 1 exhibited a significant downregulation of LPCAT2 and an upregulation of PTAFR expression, while cluster 2 showed an upregulation of LPCAT1, PAFAH1B2, and PTAFR and downregulation of PAFAH2 expression. Understanding this strong PAF-associated pathophysiology in the severe type 2 inflammation group could provide valuable insights into the treatment and management of CRSwNP.

Objectives : Olfactory dysfunction is a clinical sign that is important to detect with coexistent upper airway comorbidities in patients with asthma. This study aimed to investigate the etiology of olfactory dysfunction in patients with asthma and the relationship between fractional exhaled nitric oxide (FeNO) levels. Materials and Methods : This study included 47 asthma patients who were evaluated for olfactory dysfunction at Hiroshima University Hospital between 2012 and 2020. The etiologies of olfactory dysfunction were evaluated, and they were classified according to the FeNO levels of patients with asthma. Results : Olfactory dysfunction was observed in 30 patients with asthma, with chronic rhinosinusitis (77%) being the most prevalent etiology. Eosinophilic chronic rhinosinusitis (ECRS) was the most prevalent etiology of olfactory dysfunction in asthma patients with high FeNO levels (≥25 ppb), while non-eosinophilic chronic rhinosinusitis (NCRS) was the most prevalent etiology in asthma patients with low FeNO levels (<25 ppb). Additionally, the prevalence of ECRS was significantly higher in asthma patients with olfactory dysfunction and high FeNO levels (74%) than in those with either high FeNO levels or olfactory dysfunction and those with low FeNO levels and no olfactory dysfunction (12% and 9%, respectively). Conclusions : We found that ECRS was the predominant cause of olfactory dysfunction in patients with high FeNO levels, while NCRS was more common in those with low FeNO levels. The present study showed that both ECRS and NCRS are common etiologies of olfactory dysfunction in patients with asthma. Additionally, this study supports the link between upper and lower airway inflammation in patients with asthma complicated with olfactory dysfunction.

The bitter taste receptors (T2Rs) expressed in human sinonasal mucosae are known to elicit innate immune responses involving the release of nitric oxide (NO). We investigated the expression and distribution of two T2Rs, T2R14 and T2R38, in patients with chronic rhinosinusitis (CRS) and correlated the results with fractional exhaled NO (FeNO) levels and genotype of the T2R38 gene (TAS2R38). Using the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) phenotypic criteria, we identified CRS patients as either eosinophilic (ECRS, n = 36) or non-eosinophilic (non-ECRS, n = 56) patients and compared these groups with 51 non-CRS subjects. Mucosal specimens from the ethmoid sinus, nasal polyps, and inferior turbinate were collected from all subjects, together with blood samples, for RT-PCR analysis, immunostaining, and single nucleotide polymorphism (SNP) typing. We observed significant downregulation of T2R38 mRNA levels in the ethmoid mucosa of non-ECRS patients and in the nasal polyps of ECRS patients. No significant differences in T2R14 or T2R38 mRNA levels were found among the inferior turbinate mucosae of the three groups. Positive T2R38 immunoreactivity was localized mainly in epithelial ciliated cells, whereas secretary goblet cells generally showed lack of staining. The patients in the non-ECRS group showed significantly lower oral and nasal FeNO levels compared with the control group. There was a trend towards higher CRS prevalence in the PAV/AVI and AVI/AVI genotype groups as compared to the PAV/PAV group. Our findings reveal complex but important roles of T2R38 function in ciliated cells associated with specific CRS phenotypes, suggesting the T2R38 pathway as a potential therapeutic target for promotion of endogenous defense mechanisms.

Transglutaminase (TGM) isoform catalyze the cross-linking reaction of identical or different substrate proteins. Eosinophil has been recognized in chronic rhinosinusitis with nasal polyps (CRSwNP) forming tissue eosinophil in nasal polyp (NP), and TGM isoforms are suggested to be associated with a critical role in asthma and other allergic conditions. The aim of this study was to reveal the association of specific TGM isoform with both the tissue eosinophil infiltration deeply concerning with the intractable severity of CRSwNP and the fibrin polymerization ability of TGM isoform associated with the tissue eosinophil infiltration, which lead to NP formation and/or maintenance in CRSwNP. NP tissues (CRSwNP group) and uncinate process (UP) (control group) were collected from patients with CRSwNP and control subjects. We examined: (1) the expression level of TGM isoforms by using a real-time polymerase chain reaction (PCR) and the comparison to the issue eosinophil count in the CRSwNP group, (2) the location of specific TGM isoform in the mucosal tissue using immunohistochemistry, (3) the inflammatory cell showing the colocalization of specific TGM isoform in Laser Scanning Confocal Microscopy (LSCM) imaging, and (4) the fibrin polymerase activity of specific TGM isoform using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). A certain level of TGM 1, 2, 3, 5 expression was present in both the CRSwNP group and the control group. Only TGM 1 expression showed a positive significant correlation with the tissue eosinophil count in the CRSwNP group. The localization of TGM 1 in NP (CRSwNP) laid mainly in a submucosal layer as inflammatory cells and was at the cytoplasm in the tissue eosinophil. Fibrin polymerase activity of TGM 1 showed the same polymerase ability of factor XIIIA. TGM 1 might influence the NP formation and/or maintenance in CRSwNP related to the tissue eosinophil infiltration, which formed fibrin mesh composing NP stroma.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease with a high symptom burden, including nasal congestion and smell disorders. This study performed a detailed transcriptomic analysis in CRSwNP classified as eosinophilic CRS (ECRS), nonECRS according to the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) criteria, and a group of ECRS with comorbid aspirin intolerant asthma (Asp). Gene expression profiles of nasal polyps and the uncinate process in CRSwNP patients and normal subjects (controls) were generated by bulk RNA barcoding and sequencing (BRB-seq). A differentially expressed genes (DEGs) analysis was performed using DESeq2 software in iDEP to clarify any relationship between gene expression and disease backgrounds. A total of 3004 genes were identified by DEGs analysis to be associated with ECRS vs control, nonECRS vs control, and Asp vs control. A pathway analysis showed distinct profiles between the groups. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) showed distinct phenotype-specific pathways of expressed genes. In the specific pathway of "cytokine-cytokine receptor interaction", the differentially expressed genes were widely distributed. This study indicates that transcriptome analysis using BRB-seq may be a valuable tool to explore the pathogenesis of type 2 inflammation in CRSwNP.

Background: Strong eosinophil infiltration in chronic rhinosinusitis with nasal polyp (CRSwNP) is highly associated with recalcitrance and higher nasal polyp recurrence rate after surgery. The prevalence of eosinophilic CRSwNP (ECRS) is increasing in Asian countries including Japan. Benralizumab is a humanized anti-IL-5R alpha monoclonal antibody that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity., Objective: To assess the efficacy and safety of benralizumab in patients with ECRS., Methods: This phase II, randomized, double-blind, placebo-controlled study was conducted in Japan. Patients were randomized 1:2:2 to placebo, a single administration of benralizumab 30 mg, or benralizumab 30 mg every 4 weeks (q4w) for a total of three doses. The primary endpoint was the change in nasal polyp score from baseline at Week 12., Results: Overall, 56 patients were enrolled (placebo, n = 11; benralizumab single dose, n = 22; benralizumab q4w, n = 23). Although the mean total nasal polyp score began to decrease after the initiation of benralizumab treatment, there were no statistically significant differences in change in nasal polyp score from baseline at Week 12 between benralizumab and placebo (placebo, -0.5 ± 0.8; benralizumab single, -0.3 ± 0.8; benralizumab q4w, -0.5 ± 1.5). Post-hoc analysis showed that the administration of benralizumab decreased nasal polyp scores ≥2 points in 42.2% of ECRS patients and that patients with high blood eosinophil levels had a greater tendency to respond to benralizumab treatment. The safety profile was similar to that in previous studies and no unexpected adverse events were noted., Conclusion: Although benralizumab did not meet the primary efficacy endpoint, reductions of nasal polyp scores were seen in the benralizumab group compared with the placebo group over the whole study period, especially in patients with high levels of blood eosinophils.

Objective: Severe acute respiratory syndrome coronavirus-2 uses angiotensin-converting enzyme-2 as a primary receptor for invasion. This study investigated angiotensin-converting enzyme-2 expression in the sinonasal mucosa of patients with chronic rhinosinusitis, as this could be linked to a susceptibility to severe acute respiratory syndrome coronavirus-2 infection., Methods: Ethmoid sinus specimens were obtained from 27 patients with eosinophilic chronic rhinosinusitis, 18 with non-eosinophilic chronic rhinosinusitis and 18 controls. The angiotensin-converting enzyme-2 and other inflammatory cytokine and chemokine messenger RNA levels were assessed by quantitative reverse transcription polymerase chain reaction. Angiotensin-converting enzyme-2 positive cells were examined immunohistologically., Results: The eosinophilic chronic rhinosinusitis patients showed a significant decrease in angiotensin-converting enzyme-2 messenger RNA expression. In the chronic rhinosinusitis patients, angiotensin-converting enzyme-2 messenger RNA levels were positively correlated with tumour necrosis factor-α and interleukin-1β (r = 0.4971 and r = 0.3082, respectively), and negatively correlated with eotaxin-3 (r = -0.2938). Angiotensin-converting enzyme-2 immunoreactivity was mainly localised in the ciliated epithelial cells., Conclusion: Eosinophilic chronic rhinosinusitis patients with type 2 inflammation showed decreased angiotensin-converting enzyme-2 expression in their sinus mucosa. Angiotensin-converting enzyme-2 regulation was positively related to pro-inflammatory cytokines, especially tumour necrosis factor-α production, in chronic rhinosinusitis patients.

The human paranasal sinuses are the major source of intrinsic nitric oxide (NO) production in the human airway. NO plays several roles in the maintenance of physiological homeostasis and the regulation of airway inflammation through the expression of three NO synthase (NOS) isoforms. Measuring NO levels can contribute to the diagnosis and assessment of allergic rhinitis (AR) and chronic rhinosinusitis (CRS). In symptomatic AR patients, pro-inflammatory cytokines upregulate the expression of inducible NOS (iNOS) in the inferior turbinate. Excessive amounts of NO cause oxidative damage to cellular components, leading to the deposition of cytotoxic substances. CRS phenotype and endotype classifications have provided insights into modern treatment strategies. Analyses of the production of sinus NO and its metabolites revealed pathobiological diversity that can be exploited for useful biomarkers. Measuring nasal NO based on different NOS activities is a potent tool for specific interventions targeting molecular pathways underlying CRS endotype-specific inflammation. We provide a comprehensive review of the functional diversity of NOS isoforms in the human sinonasal system in relation to these two major nasal disorders' pathologies. The regulatory mechanisms of NOS expression associated with the substrate bioavailability indicate the involvement of both type 1 and type 2 immune responses.

Objectives/hypothesis: Dupilumab, which blocks the shared receptor component for interleukin-4 and interleukin-13, reduced polyp size, sinus opacification, and symptom severity, and was well tolerated in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) in the SINUS-52 study (NCT02898454). We assessed dupilumab in patients enrolled at Japanese centers., Methods: Patients on a background of mometasone furoate nasal spray, received dupilumab 300 mg every 2 weeks (q2w) for 52 weeks (Arm A); dupilumab 300 mg q2w for 24 weeks, followed by every 4 weeks (q4w) for 28 weeks (Arm B); or placebo (Arm C). Co-primary endpoints were week 24 nasal polyp score (NPS), nasal congestion (NC) score, and sinus Lund-Mackay CT (LMK-CT) scores. Symptoms, sense of smell, health-related quality of life, and safety were assessed during the 52-week treatment period., Results: Of 49 patients enrolled in Japan, 45 completed the study. Week 24 least squares (LS) mean improvement versus placebo were as follows: NPS (Arm A: -3.1, P < .0001; Arm B: -2.1, P = .0011); NC score (Arm A: -1.2, P < .0001; Arm B: -0.9, P < .0001); and LMK-CT (Arm A: -5.1, P = .0005; Arm B: -2.8, P = .0425). The most common treatment-emergent adverse event in dupilumab and placebo-treated patients was nasopharyngitis., Conclusion: Dupilumab provided rapid, significant, and clinically meaningful improvements for patients with CRSwNP in Japan. Dupilumab was well tolerated, and safety and efficacy were consistent with the overall study population., Level of Evidence: 2 Laryngoscope, 131:E1770-E1777, 2021., (© 2020 Sanofi. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

The guidance deals with the recommended applications, procedures, and safety management of nebulizer therapy for acute rhinosinusitis. In Japan, nebulizer therapy for sinusitis has been covered by public health insurance since 1958 and has been commonly carried out nationwide. The Japan Society for Infection and Aerosol in Otorhinolaryngology and the Oto-Rhino-Laryngological Society of Japan set up a working group to draw up a consensus guidance on nebulizer therapy for acute rhinosinusitis. The device for nebulizer therapy are classified into jet, ultrasound, and mesh types. In Japan, cefmenoxime hydrochloride (CMX) was approved for use in nebulizer therapy since 1996. The widening of the obstructed lesions such as large polyps prior to nebulizer therapy were recommended. The numbers of times of nebulizer therapy is recommended for three times in a week for at least for 2 weeks (cure rate: 68%, eradication ratio: 48%). Concerns should be pay for the changes of activity of medicine due to the mixing and bacterial contamination. Pseudomonas cepacia growing in a short even in both saline and distilled water leads to contamination at high concentrations by 2 days. Nebulizer therapy is an effective treatment based on a drug delivery system (DDS) to the nasal and paranasal cavities. The therapy effectively increases the local drug concentration by promptly and uniformly delivering drugs to a targeted local site. The therapy is safe with less systemic absorption and with few adverse reactions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Although human paranasal sinuses are critical organs for nitric oxide production, little information is available regarding the role of arginase in alterations of arginine metabolism and nasal nitric oxide levels that may be informative for classifying chronic rhinosinusitis subtypes., Methods: The expression and localisation of arginase and nitric oxide synthase isoforms in paranasal sinus mucosa were examined, and the fractional exhaled nitric oxide was measured in chronic rhinosinusitis without nasal polyps (n=18) and chronic rhinosinusitis with nasal polyps (n = 27) patients., Results: Increased arginase-2 activities in chronic rhinosinusitis without nasal polyps patients were associated with significantly lower levels of nasal fractional exhaled nitric oxide. Chronic rhinosinusitis with nasal polyps patients showed significant NOS2 messenger RNA upregulation with concomitant higher levels of oral and nasal fractional exhaled nitric oxide., Conclusion: These results indicate that fractional exhaled nitric oxide is a valid marker for differentiating chronic rhinosinusitis phenotypes based on a delicate balance between arginase and nitric oxide synthase activities in nitric oxide production.

Background: Chronic rhinosinusitis (CRS) can be classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays more intense eosinophilic infiltration and the presence of Th2 cytokines. Mucosal eosinophilia is associated with more severe symptoms and often requires multiple surgeries because of recurrence; however, even in eosinophilic CRS (ECRS), clinical course is variable. In this study, we wanted to set objective clinical criteria for the diagnosis of refractory CRS., Methods: This was a retrospective study conducted by 15 institutions participating in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC). We evaluated patients with CRS treated with endoscopic sinus surgery (ESS), and risk of recurrence was estimated using Cox proportional hazard models. Multiple logistic regression models and receiver operating characteristics curves were constructed to create the diagnostic criterion for ECRS., Results: We analyzed 1716 patients treated with ESS. To diagnose ECRS, the JESREC scoring system assessed unilateral or bilateral disease, the presence of nasal polyps, blood eosinophilia, and dominant shadow of ethmoid sinuses in computed tomography (CT) scans. The cutoff value of the score was 11 points (sensitivity: 83%, specificity: 66%). Blood eosinophilia (>5%), ethmoid sinus disease detected by CT scan, bronchial asthma, aspirin, and nonsteroidal anti-inflammatory drugs intolerance were associated significantly with recurrence., Conclusion: We subdivided CRSwNP in non-ECRS, mild, moderate, and severe ECRS according to our algorithm. This classification was significantly correlated with prognosis. It is notable that this algorithm may give useful information to clinicians in the refractoriness of CRS before ESS or biopsy., (© 2015 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Objective: Monitoring of fractional concentrations of exhaled nitric oxide (FeNO) has become a reliable marker of inflammation in human nose and paranasal sinuses. However, it is still unknown to what extent nasal NO levels contribute to the pathology of chronic rhinosinusitis (CRS). In the present study, we aimed to examine FeNO levels and the underlying mechanism of NO production and metabolism in patients with eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS., Methods: Thirty-three untreated ECRS patients, 16 non-ECRS patients, and 38 normal subjects were enrolled in this cross-sectional study of FeNO levels. Oral and nasal FeNO levels were measured before treatment using an electrochemical NO analyzer (NObreath(®)) with a nose adaptor. The mRNA expression of three nitric oxide synthase (NOS) isoforms, interleukin-5 (IL-5), and transforming growth factor-beta (TGF-β) in the ethmoid sinus mucosa and nasal polyps were analyzed by real-time PCR. Immunohistological localization of inducible NOS (iNOS) and nitrotyrosine (NT), a marker for oxidized NO metabolites, was also examined., Results: ECRS patients showed significantly higher oral FeNO levels compared to non-ECRS patients and normal subjects (mean values, 47.6, 13.5, and 15.3ppb, respectively). Nasal FeNO levels of the non-ECRS patients (30.5ppb) were significantly lower than those of the ECRS patients (53.9ppb) and normal subjects (45.5ppb). Positive correlations existed between the blood eosinophil percentage and FeNO levels in ECRS patients. Histologically, ECRS patients showed higher eosinophil accumulation in the ethmoid mucosa than non-ECRS patients (103.1 vs. 16.3cells/HPF). Real-time PCR analysis showed significant upregulation of iNOS and IL-5 mRNA expression in the ethmoid mucosa of the ECRS patients compared to those of non-ECRS patients. Positive iNOS immunoreactivity was observed in ciliated epithelial cells, submucosal glands and associated inflammatory cells in both groups. NT immunoreactivity was detected in the epithelium and around inflammatory cells. Intense NT staining was co-localized with eosinophil accumulation and ECRS patients showed significantly higher rates of NT-positive cells than non-ECRS patients., Conclusion: A combination of oral and nasal FeNO measurement is a valid marker for the classification and definition of different CRS subtypes in Japan. Higher levels of oral and nasal FeNO in ECRS patients may reflect the persistence of eosinophilic inflammation in sinus mucosa with concomitant iNOS upregulation and accompanying deposition of oxidized NO metabolites., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: We aimed to examine the effect of different therapeutic modalities on levels of fractional concentrations of exhaled nitric oxide (FeNO) in patients with eosinophilic chronic rhinosinusitis (ECRS)., Methods: Thirty-six ECRS patients with nasal polyps were treated either medically or surgically. Oral and nasal FeNO levels were measured using an electrochemical NO analyzer initially and at 1 and 6 months. The mRNA expression and localization of nitric oxide synthase (NOS) isoforms in sinus mucosa and nasal polyps were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemistry., Results: The mean oral FeNO levels in the surgical group had decreased significantly from 50.9 to 36.8 ppb 6 months after endoscopic sinus surgery. All patients in this group showed significantly higher nasal FeNO levels after treatment. The mean nasal FeNO levels were 62.3 ppb at 1 month and 93.6 ppb at 6 months. Mean oral and nasal FeNO levels in the medical group after treatment remained unchanged when compared with the baseline levels. Positive immunoreactivity of inducible NOS (iNOS) was observed in both epithelial cells and submucosal inflammatory cells. Real-time PCR analysis showed significant up-regulation of iNOS and IL-5 mRNA expression., Conclusion: A combination of oral and nasal FeNO measurements is useful to monitor the extent of inflammation in CRS patients. The increase in nasal FeNO in the surgical group indicates prompt recovery of NO release from healed sinus mucosa through the opened sinus ostia. Reduction of oral FeNO levels may reflect a cessation of the underlying lower airway inflammation that is characteristic of ECRS.

Objective: Patients with eosinophilic chronic rhinosinusitis (ECRS) show a high percentage of eosinophilic infiltration in the paranasal sinus mucosa. It is well documented that topical steroids have a beneficial effect in ECRS with nasal polyposis. We investigated mucosal distribution and cellular localization of glucocorticoid receptor (GR) isoform expression in human paranasal sinuses in relation to the clinical characteristics of eosinophilic chronic rhinosinusitis (ECRS) patients., Methods: Mucosal specimens were obtained from 20 sinusitis patients by endoscopic sinus surgery (ESS). Quantitative fluorescence immunohistochemical analysis was employed to examine the degree of glucocorticoid receptor (GR) isoform expression in sinus mucosa specimens. An RT-PCR procedure was performed to determine the relative quantities of mRNA for the human GRalpha and GRbeta genes., Results: Patients in the ECRS group showed significant increases in peripheral blood eosinophils as compared to the non-ECRS group (16.98% vs. 2.31%). Positive immunoreactivity of GRbeta expression was predominantly found to be positive in inflammatory cells. The absolute number of GRbeta-positive cells in the ECRS group was increased in comparison with that in the non-ECRS group. The difference was statistically significant both in the maxillary (179.7 cells/mm(2) vs. 82.5 cells/mm(2)) and ethmoid sinus (302.0 cells/mm(2) vs. 61.5 cells/mm(2)) mucosa. The GRbeta/GRalpha cell ratio in the ECRS group was elevated when compared with that in the non-ECRS group both in the maxillary and the ethmoid sinus mucosa, with the latter difference being significant., Conclusions: The presence of high peripheral eosinophilia indicates a high likelihood of ECRS disease. Our results support the association of GRbeta expression with ECRS. The expression of GRbeta immunoreactivity, an endogenous inhibitor of steroid action previously associated with steroid insensitivity, may be one of major contributing factors in ECRS., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

The overall pathological view of paranasal sinus inflammation in the Japanese population has profoundly changed in recent years. Eosinophilic chronic rhinosinusitis (ECRS) is a clinical entity of intractable chronic sinus inflammation accompanied by numerous infiltrations of activated eosinophils in the paranasal sinus mucosa and/or nasal polyps. Several pathologic processes are considered to act in concert to promote the accumulation of eosinophils in ECRS. They include infiltration of progenitor cells, increase in local IL-3, IL-5, IL-13, GM-CSF and eotaxin production, and upregulation of adhesion molecules. The role of nasal allergen sensitization and innate immunity responses in the sinus mucosa has also been proposed in the development of ECRS. Various pathogens including TLRs ligands may trigger an abnormal immune response at the mucosal surface. The objectives of ECRS management should focus directly on inhibition of local eosinophil infiltration. Surgical procedures include widely opening the bony wall septum of every affected sinus and mechanical removal of diseased mucosal lesion. The use of local and/or systemic steroids, leukotriene receptor antagonists, and Th2 cytokine antagonists is recommended. Local administration of steroids is a potent treatment strategy for preventing relapse of nasal polyposis and is considered to be the first-line treatment for ECRS patients.

Schizophillum commune (S. commune) is a rare type of basidiomycetous fungus that has being reported as a cause of allergic fungal rhinosinusitis (AFRS), invasive type of fungal sinusitis and allergic bronchopulmonary mycosis (ABPM). However, it is believed that S. commune was often misdiagnosed to Aspergillus sp. We report a case of bilateral nasal polyps and maxillary, ethmoidal and sphenoidal involvement within the context of S. commune and Aspergillus niger associated AFRS. Our patient was suffering from a chronic disease with periods of remission and exacerbation and was treated successfully by a combination of surgical and antifungal treatment. In our experience, S. commune may be found frequently in patients with AFRS. AFRS, including the S. commune-associated type, usually runs a prolonged course and can affect any paranasal sinus. Surgical treatment alone is not sufficient and must be combined with medical treatment.

Recently, the YAMIK sinus catheter (YAMIK) has been reported to be a useful therapeutic device in the treatment of sinusitis. The present study was conducted to compare its delivery of either a normal saline (NS) or a betamethasone solution (0.4 mg/ml) into the paranasal sinuses of 25 patients (39 sides) with chronic sinusitis. The following parameters were evaluated: (1) subjective nasal clinical symptoms (nasal discharge, nasal obstruction, postnasal drip and headache), (2) X-ray photographs (ethmoid and maxillary sinuses) and (3) cytokine levels (IL-1beta, IL-8 and TNF-alpha) by enzyme-linked immunosorbent assay. The total nasal symptom scores significantly decreased after the first therapy, and the total X-ray photograph scores significantly decreased after therapy with either NS or the betamethasone solution. In both NS and betamethasone patients, the levels of IL-1beta and IL-8 had significantly decreased by the 3rd and 2nd weeks after therapy, respectively. In contrast, the TNF-alpha level decreased after the first therapy with betamethasone solution and remained unchanged after therapy with NS. These findings suggest that evacuation of the pathological effusions in sinuses may exert a beneficial effect by reducing the levels of IL-1beta and IL-8, and we speculate that removal of pathological effusions from the sinuses may provide treatment through different mechanisms than those that occur in treatment with betamethasone.

The purpose of this study was to compare the expression of cytokines and nuclear factor-kappa B (NF-kappa B) subunits in cultured sinus mucosal cells by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in chronic sinusitis patients with allergic rhinitis (abbreviated as AR patients) versus patients without AR (abbreviated as non-AR patients). The localization of p50 in cultured sinus mucosal cells was also observed by immunocytochemistry. The expression of messenger RNAs (mRNA) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-8, p50 and p65 subunits, and inhibitory kappa B-alpha (I kappa B-alpha) were analyzed by RT-PCR. The proportion of active NF-kappa B-positive cells in the epithelial layer was analyzed using a laser-scanning confocal microscope image system. The levels of GM-CSF, IL-6, IL-8, and p50 mRNAs in AR patients were significantly higher than those in non-AR patients (p < 0.01, p < 0.01, p < 0.01, and p < 0.001, respectively). Immunocytochemical reaction for p50 in sinus mucosal cells in AR patients showed more intense nuclear staining compared to non-AR patients. These findings could support the hypothesis that the increase of cytokines from sinus mucosal cells in AR patients was associated with augmented NF-kappa B mRNA expression, resulting in the modification of the cytokine network.

This study examines the immunohistological localization of proliferating cell nuclear antigen in the nasal and paranasal sinus epithelium from a group of patients undergoing sinus surgery for chronic sinusitis. PCNA immunoreactivity as determined by fluorescence intensity and the density of labeled cells as assessed by confocal laser scanning microscopy. The control group consisted of seven specimens taken from patients with post operative maxillary cyst and optic nerve canal fracture. In this group, most of the labeled cells were located on the basal cell layers with a few on the intermediate cell layers. The average labeled cell densities were 57.3 cells/mm2 on the basal cell layers and 15.9 cells/mm2 on the intermediate cell layer. The sinusitis group consisted of eleven patients. In contrast with the control group, the sinusitis epithelium displayed a significantly high proportion of goblet and intermediate cells positively stained for PCNA. The average densities were 84.9 cells/mm2 on the basal cell layers and 133.1 cells/mm2 on the intermediate cell layers in this group, the latter being nearly ten fold greater than that in the control group. Epithelial PCNA expression was correlated with the degree of inflammatory cell infiltration assessed by serial sections for each sample. A positive correlation was observed between these two factors (R = 0.63, Pearson). We believe that epithelial cell turnover is accelerated in chronic rhinosinusitis due to continuous exposure to various pathogens and host immune interventions. In those cases, goblet and intermediate cells would play the major role in enhanced epithelial proliferation.