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Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is known to have 2 phenotypes in East Asia. Eosinophilic CRSwNP (ECRSwNP), defined as tissue eosinophilia and easily recurrent, is distinguished from other non-eosinophilic CRSwNP (NECRSwNP) types. However, the pathogenesis of each remains unclear., Methods: Nasal polyp tissues from ECRS (ECRSwNP) and NECRS (NECRSwNP) patients were obtained, and their comprehensive gene expression profiles were investigated by microarray analysis. Bioinformatics approaches (eg, Ingenuity Pathway Analysis [IPA]) were used to interrogate the data sets., Results: Hierarchical clustering and principal component analysis (PCA) collectively showed that ECRSwNP and NECRSwNP had distinct gene expression patterns. Of note, these genes could be divided into 8 distinctive clusters having different expression patterns and functions. Upstream Regulator Analysis revealed that not only T-helper 2 (Th2) and the eosinophilia-related molecules (interleukin 4 [IL4], IL5, and colony stimulating factor 2 [CSF2]) reported so far, but also cell cycle regulators (cyclin dependent kinase inhibitor 1A [CDKNA1] and cyclin D1 [CCND1]) and a tissue fibrosis-related molecule (transforming growth factor β [TGFβ]) were identified in ECRSwNP. On the other hand, mainly interferons (IFNs) and acute inflammatory cytokines (IL1 and IL6) were predicted as upstream regulators in NECRSwNP., Conclusion: These results are useful for understanding the molecular basis of the mechanisms of CRSwNP and point to new targets for developing specific biomarkers and personalized therapeutic strategies for CRSwNP., (© 2018 ARS-AAOA, LLC.)

Background: The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS)., Methods: Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus., Results: The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS., Conclusion: As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed., (© 2016 ARS-AAOA, LLC.)

Background: Total and specific immunoglobulin E (IgE) in nasal polyps (NP) is related to local eosinophilic inflammation. However, it remains unclear which antigens cause a stronger accumulation of eosinophils in NP. We investigated whether local IgEs to specific antigens correlated with local eosinophil accumulation., Methods: Total IgE, antigen-specific IgEs [5 species of fungi, staphylococcal enterotoxins A and B (SEA and SEB), cedar pollen, ragweed pollen and house-dust mites] and eosinophil cationic protein (ECP) were measured in sinus mucosa homogenates and serum from 29 patients with chronic rhinosinusitis with NP (CRSwNP), 8 patients with allergic fungal rhinosinusitis (AFRS) and 8 control subjects without CRS. The level of ECP in NP was analyzed for correlations with the total and specific IgE levels in the serum and NP., Results: In CRSwNP, antigen-specific IgEs [Alternaria > mite (Dp) > Aspergillus > SEB > Penicillium > mite (Df), but not the other fungi, SEA or pollens] in the sinus mucosa correlated significantly with the local ECP. In AFRS, antigen-specific IgEs [Penicillium > mite (Df) > Alternaria, but not the other fungi, SEs or pollens] in the sinus mucosa correlated significantly with the local ECP., Conclusions: Local total IgE and antigen (fungi, mites and SEs)-specific IgEs in NP are related to the local eosinophilic inflammation of AFRS and CRSwNP., (Copyright © 2013 S. Karger AG, Basel.)

Background: The pathophysiology of chronic rhinosinusitis (CRS) is not fully understood. In Europe and the United States, major subsets of CRS classification are based on the presence or absence of polyps. Although nasal polyps (NPs) are a critical factor, many other factors also contribute to the pathogenesis of CRS. The aim of this study was to investigate diverse CRS phenotypes using cluster analysis., Methods: This was a multicenter study examining clinical data from CRS patients treated at five hospitals. The study design was a retrospective analysis of prospectively collected data. Complete data were available for 425/496 patients. Data were subjected to k-means cluster analysis in an attempt to identify the different phenotypes involved in CRS., Results: CRS was divided into four clusters. Cluster 1 (n = 180) and cluster 2 (n = 129) comprised patients with low peripheral eosinophil and mucosal eosinophil counts. However, polyp scores in cluster 2 were higher than cluster 1. Cluster 3 (n = 50) comprised patients with very high mucosal eosinophil counts but low polyp and symptom scores. Finally, subjects in cluster 4 (n = 66) showed severe polyposis. Polyp score and mucosal eosinophil count were the strongest predictors of clustering by discriminant analysis., Conclusion: The results of this study identified distinct clinical CRS phenotypes. CRS was classified into four phenotypes based on NPs and mucosal eosinophil counts. Cutoff points for these factors were identified by tree analysis. Additional studies are needed to establish clinical significance of the phenotypes.

Current knowledge on the prevalence and clinical features of antrochoanal polyps (ACPs), benign lesions arising in the maxillary sinus and extending into the choana, is very limited in Japan. We prospectively evaluated prevalence and clinical features in 15 subjects with ACPs from among 728 undergoing endoscopic endonasal sinus surgery between April 2007 and March 2008, and prospectively enrolled in this study. The 15 subjects, who accounted for 2.1% of the total, had nasal obstruction, rhinorrhea, and postnasal drip. Symptoms significantly reduced postoperatively. Maxillary-sinus-origin ACP distribution was 40% from the maxillary sinus floor to the posterior wall, 26.7% from maxillary sinus floor, and 20% from the maxillary sinus floor to the internal wall. Postoperative recurrence was 13.3%. Endoscopic endonasal sinus surgery for ACPs was most effective for polyp is originating in the maxillary sinus determined carefully and excised as completely as possible, followed by appropriate postoperative treatment.

Background: The prevalence of patients with chronic rhinosinusitis (CRS) refractory to traditional therapy appears to be on the increase. In these cases, CRS tends to be associated with bronchial asthma (BA), especially, aspirin-intolerant asthma (AIA). On the other hand, arachidonic acid metabolites have been extensively investigated in the pathogenesis of BA. We sought to assess the role of prostaglandin D(2) (PGD(2)) and prostaglandin E(2) (PGE(2)) in the recalcitrant pathophysiology of CRS., Methods: Samples were prepared from the nasal polyps and mucosa of 40 patients undergoing endoscopic sinus surgery (ESS) at our hospital. The nasal polyp specimens obtained from the patients with CRS were divided into three groups, as follows: the CRS-AIA group, consisting of specimens obtained from patients with CRS complicated by AIA, the CRS-ATA group, consisting of specimens obtained from patients with CRS associated with aspirin-tolerant asthma (ATA), and the CRS-NA group, consisting of specimens obtained from CRS patients without BA. PGD(2) and PGE(2) were extracted from the specimens and quantified., Results: The concentrations of PGD(2) were significantly higher in the nasal polyps of the CRS-ATA group. The concentrations of PGE(2) were lowest in the nasal polyps of the CRS-AIA group. The PGD(2)/PGE(2) ratio was highest in the CRS-AIA group., Conclusions: It has previously been reported that CRS complicated by AIA is most likely to be characterized by repeated remissions and relapses, and is thus the most intractable. We may therefore say that the PGD(2)/PGE(2) ratio reflects the intractable nature of CRS.

Background: Myofibroblasts are related to airway remodeling and may play an important role in the pathogenesis of the histological features of nasal polyps associated with asthma. The aim of this study was to analyze and compare the eosinophilic cationic protein, transforming growth factor (TGF) beta, and myofibroblasts in the nasal polyps of patients with chronic sinusitis associated with and without asthma., Methods: Nasal polyp samples were obtained during endoscopic sinus surgery and were classified into asthma and nonasthma groups. Immunohistochemistry was performed using antibodies against activated eosinophils, TGF-beta, and myofibroblasts., Results: The asthma group showed an increased number of activated eosinophils, TGF-beta, and myofibroblasts compared with the nonasthma and control groups. We found no correlation of asthma and aspirin intolerance with the immunohistochemical findings., Conclusion: The increased number of myofibroblasts in the nasal polyps of the asthma group may be responsible for the extracellular matrix accumulation, polyp formation, and polyp recurrence.

Two interleukin 13 receptors (IL-13Rs) have been identified as IL-13Ralpha1 and IL-13Ralpha2. IL-13Ralpha1 is composed of a heterodimer consisting of IL-13Ralpha1 and IL-4 receptor alpha (IL-4Ralpha) as a signaling subunit. In contrast, IL-13Ralpha2 is known as a decoy receptor for IL-13. In this study, we investigated the expression of IL-13Rs on human fibroblasts. IL-13Ralpha2 was significantly up-regulated after stimulation with tumor necrosis factor-alpha (TNF-alpha) and/or IL-4. In contrast, IL-13Ralpha1 was constitutively detectable and was not up-regulated. After the induction of IL-13alpha2 by IL-4, STAT6 phosphorylation through IL-13Ralpha1 by IL-13 was inhibited. We also detected large intracellular pools of IL-13Ralpha2 in fibroblasts quantitatively. Furthermore, mobilization of the IL-13Ralpha2 protein stores from the cytoplasm to the cell surface was prevented by an inhibitor of protein transport, brefeldin-A. These results indicate that TNF-alpha and IL-4 synergistically up-regulate the expression of IL-13Ralpha2 decoy receptor on human fibroblasts by inducing gene expression and mobilizing intracellular receptors, and thus may down-regulate the IL-13 signaling.

Background: Patients undergoing endoscopic sinus surgery (ESS) are at risk of complications because of the close proximity of the sinuses to the orbit and anterior skull base. The aim of this study was to evaluate the complications of ESS and to identify patient characteristics that were risk factors for the complications. Methods: We conducted a prospective study of 706 patients who underwent ESS for chronic rhinosinusitis. Patients completed preoperative examinations that included computed tomography, endoscopic observation for nasal polyps, and tests for comorbidities including asthma and vascular disease. Perioperative complications were evaluated based on information provided by the surgeons. Multivariate analysis was performed to identify patient characteristics that were risk factors for complications. Results: Overall, perioperative complications occurred in 41 patients (5.8%). A major complication, cerebrospinal fluid leakage, occurred in one patient (0.1%). Minor complications occurred in 40 patients (5.7%), with the most common being intraoperative hemorrhage (n = 18). Multivariate analysis indicated that presence of asthma and the total polyp score correlated significantly with the occurrence of complications. Conclusion: The risk factors for perioperative complications were asthma and the polyp score. We conclude that the surgeon should confirm whether the patient has lower airway disease, especially asthma, before operating. The surgeon should also determine the grade of nasal polyps. [ABSTRACT FROM AUTHOR]

Background: The olfactory cleft (OC) is the most important anatomical site for the maintenance of olfactory function. Obstruction of airflow in the OC by various conditions, such as inflammation, leads to poor olfactory function. Therefore, it is important to increase OC airflow while performing endoscopic sinus surgery (ESS). However, no technique to increase airflow has yet been established.We designed a superior turbinate lateralization (STL) procedure that displaces the entire ST bone laterally by eliminating the connection between the posterior ST and the anterior wall of the sphenoid sinus. The effect of the STL procedure was investigated in terms of anatomy and olfactory function.ESS with the STL procedure was performed on seven patients with chronic rhinosinusitis and nasal polyps. The cross-sectional area of the OC at 3 months postoperatively was significantly larger than that before ESS. In addition, the Open Essence test and questionnaires revealed significantly improvements in sense of smell. Airflow in the OC was significantly higher in STL procedure group than in the non-STL procedure group.The STL procedure enlarges the bony framework of the OC, and by increasing OC airflow, facilitates the transport of odorants to the olfactory epithelium, thereby improving olfactory perception.Methods: The olfactory cleft (OC) is the most important anatomical site for the maintenance of olfactory function. Obstruction of airflow in the OC by various conditions, such as inflammation, leads to poor olfactory function. Therefore, it is important to increase OC airflow while performing endoscopic sinus surgery (ESS). However, no technique to increase airflow has yet been established.We designed a superior turbinate lateralization (STL) procedure that displaces the entire ST bone laterally by eliminating the connection between the posterior ST and the anterior wall of the sphenoid sinus. The effect of the STL procedure was investigated in terms of anatomy and olfactory function.ESS with the STL procedure was performed on seven patients with chronic rhinosinusitis and nasal polyps. The cross-sectional area of the OC at 3 months postoperatively was significantly larger than that before ESS. In addition, the Open Essence test and questionnaires revealed significantly improvements in sense of smell. Airflow in the OC was significantly higher in STL procedure group than in the non-STL procedure group.The STL procedure enlarges the bony framework of the OC, and by increasing OC airflow, facilitates the transport of odorants to the olfactory epithelium, thereby improving olfactory perception.Results: The olfactory cleft (OC) is the most important anatomical site for the maintenance of olfactory function. Obstruction of airflow in the OC by various conditions, such as inflammation, leads to poor olfactory function. Therefore, it is important to increase OC airflow while performing endoscopic sinus surgery (ESS). However, no technique to increase airflow has yet been established.We designed a superior turbinate lateralization (STL) procedure that displaces the entire ST bone laterally by eliminating the connection between the posterior ST and the anterior wall of the sphenoid sinus. The effect of the STL procedure was investigated in terms of anatomy and olfactory function.ESS with the STL procedure was performed on seven patients with chronic rhinosinusitis and nasal polyps. The cross-sectional area of the OC at 3 months postoperatively was significantly larger than that before ESS. In addition, the Open Essence test and questionnaires revealed significantly improvements in sense of smell. Airflow in the OC was significantly higher in STL procedure group than in the non-STL procedure group.The STL procedure enlarges the bony framework of the OC, and by increasing OC airflow, facilitates the transport of odorants to the olfactory epithelium, thereby improving olfactory perception.Conclusion: The olfactory cleft (OC) is the most important anatomical site for the maintenance of olfactory function. Obstruction of airflow in the OC by various conditions, such as inflammation, leads to poor olfactory function. Therefore, it is important to increase OC airflow while performing endoscopic sinus surgery (ESS). However, no technique to increase airflow has yet been established.We designed a superior turbinate lateralization (STL) procedure that displaces the entire ST bone laterally by eliminating the connection between the posterior ST and the anterior wall of the sphenoid sinus. The effect of the STL procedure was investigated in terms of anatomy and olfactory function.ESS with the STL procedure was performed on seven patients with chronic rhinosinusitis and nasal polyps. The cross-sectional area of the OC at 3 months postoperatively was significantly larger than that before ESS. In addition, the Open Essence test and questionnaires revealed significantly improvements in sense of smell. Airflow in the OC was significantly higher in STL procedure group than in the non-STL procedure group.The STL procedure enlarges the bony framework of the OC, and by increasing OC airflow, facilitates the transport of odorants to the olfactory epithelium, thereby improving olfactory perception. [ABSTRACT FROM AUTHOR]

Background: The prevalence of patients with chronic rhinosinusitis (CRS) refractory to traditional therapy appears to be on the increase. In these cases, CRS tends to be associated with bronchial asthma (BA), especially, aspirin-intolerant asthma (AIA). On the other hand, arachidonic acid metabolites have been extensively investigated in the pathogenesis of BA. We sought to assess the role of prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2) in the recalcitrant pathophysiology of CRS. Methods: Samples were prepared from the nasal polyps and mucosa of 40 patients undergoing endoscopic sinus surgery (ESS) at our hospital. The nasal polyp specimens obtained from the patients with CRS were divided into three groups, as follows: the CRS-AIA group, consisting of specimens obtained from patients with CRS complicated by AIA, the CRS-ATA group, consisting of specimens obtained from patients with CRS associated with aspirin-tolerant asthma (ATA), and the CRS-NA group, consisting of specimens obtained from CRS patients without BA. PGD2 and PGE2 were extracted from the specimens and quantified. Results: The concentrations of PGD2 were significantly higher in the nasal polyps of the CRS-ATA group. The concentrations of PGE2 were lowest in the nasal polyps of the CRS-AIA group. The PGD2/PGE2 ratio was highest in the CRS-AIA group. Conclusions: It has previously been reported that CRS complicated by AIA is most likely to be characterized by repeated remissions and relapses, and is thus the most intractable. We may therefore say that the PGD2/ PGE2 ratio reflects the intractable nature of CRS. [ABSTRACT FROM AUTHOR]

Objective: Although sleep impairment is reported by patients with chronic rhinosinusitis, the associated factors have not been well studied. Therefore, we determined the associated risk factors for sleep impairment in patients with chronic rhinosinusitis (CRS).Methods: This study was a prospective cohort study. A total of 572 adult patients (171 women, 401 men; mean age, 49.0 years; range, 18-64 years) who completed a questionnaire, had a clinical examination, and underwent endoscopic sinus surgery were analyzed using stepwise multiple linear regression.Results: With regard to subjective symptoms, nasal obstruction (beta coef., 0.27; p<0.001), anterior nasal drainage (beta coef., 0.13; p=0.004), facial pain/pressure (beta coef., 0.09; p=0.048), headache (beta coef., 0.10; p=0.010), and cough (beta coef., 0.14; p<0.001) were predictors of an increased risk of sleep impairment of CRS (adjusted R(2), 0.240; p=0.048). In the matter of background parameters, total polyp score (polyp grading system) (beta coef., 0.16; p<0.001) and allergic rhinitis (beta coef., 0.09; p=0.034) were predictors of an increased risk of sleep impairment of CRS (adjusted R(2), 0.029; p=0.034).Conclusion: These results suggest that sleep impairment in these patients is caused by the various mechanisms associated with nasal symptoms themselves, CRS and allergic rhinitis. However, the specific pathophysiology has not been clarified yet; further studies are expected to elucidate that of sleep impairment in patients with CRS. [ABSTRACT FROM AUTHOR]