Correlation between chronic sinusitis subtypes and basophil levels in peripheral blood / 临床耳鼻咽喉头颈外科杂志

Objective:To explore the clinical correlation between peripheral blood basophil levels and chronic sinusitis （CRS） subtypes. Methods:One hundred and twenty-six patients with CRS and 103 healthy cases from physical examination admitted to the First Affiliated Hospital of Soochow University from January 2021 to October 2022 were retrospectively analyzed. According to the histopathological classification, CRS patients were divided into eosinophilic chronic sinusitis （eCRS） group （47 cases） and non eosinophilic chronic sinusitis （non-eCRS） group （79 cases）. The differences among the three groups in peripheral blood inflammation cell counts, eosinophils-to-basophils ratio（bEBR）, basophils-to-neutrophils ratio（BNR）, basophils-to-lymphocytes ratio（BLR）, basophils-to-monocytes ratio（BMR） were compared, and study the correlation between each index and Lund-Mackay score, and the correlation between basophils in peripheral blood and other inflammatory cells. Results:The counts of basophils in the peripheral blood of the healthy control group, eCRS group and non-eCRS group were 0.03±0.01, 0.04±0.02, 0.03±0.02, respectively, the eosinophils-to-basophils ratio（bEBR） were 5.64±4.22, 8.38±5.95, 4.55±3.90, the basophils-to-neutrophils ratio（BNR） were 0.01±0, 0.01±0.01, 0.01±0.01, and the basophils-to-lymphocytes ratio（BLR） were 0.01±0.01, 0.02±0.01, and 0.02±0.01, respectively, the basophils-to-monocytes ratio（BMR） were 0.08±0.04, 0.11±0.06, and 0.08 ±0.04 respectively. There was a statistically significant difference between eCRS group and healthy control group, non-eCRS group（P<0.01）, while there was no statistically significant difference between non-eCRS group and healthy control group（P>0.05）. Basophil counts （r=0.185 5, P<0.05）, BLR（r=0.226 9, P<0.05）, BMR（r=0.228 1, P<0.01） in patients with CRS were positively correlated with Lund Makey score. In addition, basophils were also positively correlated with eosinophils（r=0.479 2, P<0.01）, lymphocytes（r=0.259 4, P<0.01）, and monocytes（r=0.256 4, P<0.01） in patients with CRS. Conclusion:The peripheral blood basophil count, BLR and BMR were significantly increased in eCRS, and were significantly positively correlated with Lund -Makey score. It has the potential to develop into disease biomarkers and new therapeutic targets of eCRS.

Association between plasma inflammatory mediators and histological endotypes of nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective: To compare the clinical characteristics and plasma inflammatory markers levels in different endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP), and to explore the plasma biomarkers associated with endotypes of CRSwNP. Methods: A total of 74 CRSwNP patients (male/female: 41/33; average age: 40 years) and 40 control subjects underwent septoplasty in Tongji Hospital from January 2015 to December 2017 were enrolled in this study. The demographic and clinical features of all subjects including age, gender, past history, visual analogue scale (VAS) and CT scores were recorded. Patients with CRSwNP were divided into EoshighNeuhigh, EoshighNeulow, EoslowNeuhigh and EoslowNeulow four endotypes according to the eosinophil (Eos) percentage and neutrophil (Neu) count of nasal polyps tissue. Preoperative blood routine was performed and the levels of 27 biomarkers in plasma were measured by Bio-Plex suspension chip method. The clinical characteristics and the level of serum biomarkers of patients with different endotypes were compared. SPSS 18.0 software was used for statistical analysis. Results: There was no difference in the clinical features including gender ratio, age, course of disease, VAS score, endoscopy and CT score among EoshighNeuhigh, EoshighNeulow, EoslowNeuhigh and EoslowNeulow CRSwNP patients. Compared with EoslowNeuhigh and EoslowNeulow CRSwNP patients, patients with EoshighNeuhigh and EoshighNeulow endotype demonstrated a higher prevalence of atopy, allergic rhinitis and asthma comorbidity, and increased peripheral blood eosinophil absolute count and percentage (all P<0.05). However, there was no significant difference between EoshighNeuhigh and EoshighNeulow CRSwNP. Plasma levels of all 27 mediators including type 1 cytokines (IL-12 and IFN-γ), type 2 cytokines (IL-4, IL-5 and IL-13), type 3 cytokines (IL-17A), pro-inflammatory cytokines (IL-6 and TNF-α) and tissue remodeling-related markers (bFGF, VEGF and PDGF-BB) demonstrated no significant difference among all endotypes of CRSwNP (all P>0.05). Conclusions: Eoshigh and Eoslow CRSwNP patients display significant differences regarding the prevalence of atopy, allergic rhinitis and asthma comorbidity, peripheral blood eosinophil absolute count and percentage, but the clinical characteristics, blood cellular and biological markers can not effectively distinguish four endotypes of CRSwNP. Further studies are warranted to dig out the potential objective, convenient and reliable markers associated with endotypes in patients with CRSwNP.

A comparative study of artificial intelligence nasal polyp classification based on whole-slide imaging and JESREC diagnostic criteria / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the types and clinical characteristics of chronic rhinosinusitis with nasal polyps (CRSwNP) based on artificial intelligence and whole-slide imaging (WSI), and to explore the consistency of the diagnostic criteria of the Japanese epidemiological survey of refractory eosinophilic chronic rhinosinusitis (JESREC) in Chinese CRSwNP patients. Methods: The data of 136 patients with CRSwNP (101 males and 35 females, aging 14 to 70 years) who underwent endoscopic sinus surgery from 2018 to 2019 in the Department of Otorhinolaryngology Head and Neck Surgery, the Third Affiliated Hospital of Sun Yat-sen University were analysed retrospectively. The preoperative clinical characteristics of patients were collected, such as visual analogue scale (VAS) of nasal symptoms, peripheral blood inflammatory cell count, total immunoglobulin E (IgE), Lund-Kennedy score and Lund-Mackay score. The proportion of inflammatory cells such as eosinophils, lymphocytes, plasma cells and neutrophils were calculated on the WSI of each patient through artificial intelligence chronic rhinosinusitis evaluation platform 2.0 (AICEP 2.0), and the specific type of nasal polyps was then obtained as eosinophilic CRSwNP (eCRSwNP) or non-eosinophilic CRSwNP (non-eCRSwNP). In addition, the JESREC diagnostic criteria was used to classify the nasal polyps, and the classification results were compared with the current gold standard for nasal polyps diagnosis (pathological diagnosis based on WSI). The accuracy, sensitivity and specificity of the diagnostic criteria of JESREC were evaluated. The data were expressed in M (Q1, Q3) and statistically analyzed by SPSS 17.0. Results: There was no significant difference between eCRSwNP and non-eCRSwNP in age distribution, gender, time of onset, total VAS score, Lund-Kennedy score or Lund-Mackay score. However, there was a significant difference in the ratio of nasal polyp inflammatory cells (eosinophils 40.5% (22.8%, 54.7%) vs 2.5% (1.0%, 5.3%), neutrophils 0.3% (0.1%, 0.7%) vs 1.3% (0.5%, 3.6%), lymphocytes 49.9% (39.3%, 65.9%) vs 82.0% (72.8%, 87.5%), plasma cells 5.1% (3.6%, 10.5%) vs 13.0% (7.4%, 16.3%), χ2 value was 9.91, 4.66, 8.28, 5.06, respectively, all P<0.05). In addition, eCRSwNP had a significantly higher level of proportion of allergic symptoms (nasal itching and sneezing), asthma, peripheral blood eosinophil and total IgE (all P<0.05). The overall accuracy, sensitivity and specificity of the JESREC diagnostic criteria was 74.3%, 81.3% and 64.3%, respectively. Conclusions: The eCRSwNP based on artificial intelligence and WSI has significant high level of allergic symptoms, asthma, peripheral blood eosinophils and total IgE, and the percentages of inflammatory cells in nasal polyps are different from that of non-eCRSwNP. The JESREC diagnostic criteria has good consistency in our research.

Different concentrations of specialized pro-resolving mediators in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the difference of concentrations of specialized pro-resolving mediators (SPMs) derived from fatty acids in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP). Methods: A total of 36 patients with bilateral chronic rhinosinusitis with nasal polyps (CRSwNP) who underwent endoscopic nasal surgeries in Peking Union Medical College Hospital from May 2019 to September 2020 were enrolled, including 27 males and 9 females, with the age from 13 to 67 years. There were 23 cases of ECRSwNP and 13 cases of nECRSwNP. At the same time, 12 control subjects were enrolled. The concentrations of multiple SPMs, including lipoxins (LXA4 and LXB4), resolvins (RvD1, RvD2, RvD3, RvD5 and RvE1), protectins (PDX) and maresins (Mar-1) in nasal polyps with different histological subtypes and normal nasal mucosa were analyzed using liquid chromatography-tandem mass spectrometry. The concentrations of SPMs between groups were compared using Mann-Whitney U test. Spearman's rank correlation coefficient was used to measure the correlation between the concentrations of SPMs in nasal polyps and tissue eosinophil counts. Results: The concentrations of RvD2, RvD3, RvD5, LXA4, LXB4, Mar-1 and PDX in ECRSwNP group were significantly higher than that in controls (Z value was -2.276, -2.313, -3.371, -2.094, -2.051, -3.104 and -2.294, respectively, all P<0.05). The concentrations of RvD2, RvD5, Mar-1 and PDX in ECRSwNP group were significantly higher than those in nECRSwNP group (Z value was -2.175, -2.289, -2.243 and -2.124, respectively, all P<0.05). There was no significant difference in all these SPMs between nECRSwNP and controls (all P>0.05). The concentrations of RvD2, RvD3, RvD5, LXB4, Mar-1 and PDX in nasal polyps correlated positively with tissue eosinophil counts (r value was 0.443, 0.436, 0.371, 0.502, 0.340 and 0.386, respectively, all P<0.05). Conclusions: A varienty of SPMs are elevated in ECRSwNP. Dysregulation of fatty acid metabolism might play an important role in the chronic inflammation of ECRSwNP.

Gene transcriptome analysis of nasal epithelial cells in chronic rhinosinusitis with nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective: To identify the differentially expressed genes in nasal epithelial cells from chronic rhinosinusitis with nasal polyps (CRSwNP), and to analyze related genes which are involved in deficiency of nasal epithelial barrier in CRSwNP patients by analyzing the datasets download from the gene expression omnibus(GEO) database. Methods: The mRNA expression microarray data numbered GSE107624 (7 CRSwNP and 7 controls) and GSE69093 (13 CRSwNP and 11 controls) were downloaded from the publicly available GEO database. These two datasets were jointly analyzed to screen the differentially expressed genes in nasal epithelial cells of controls and CRSwNP patients. In the meanwhile, we further evaluated the function annotation and regulatory pathways of the differentially expressed genes. To further confirmed what we have observed, sinus tissues were collected from patients with CRSwNP (14 cases, 46.8±17.9 years) and uncinate process tissues were collected from patients with nasal septum deviation (7 cases, 23.4±2.3 years) as control group. The primary epithelial cells of nasal mucosa were cultured and the mRNA level of screened genes were measured by Q-PCR. SPSS 22.0 software was used to for statistical analysis. Results: GSE107624 dataset showed that there were 3 856 differentially genes in nasal epithelial cells between CRSwNP and control group, while there were 771 differentially expressed genes in GSE69093 dataset. Finally, 55 up-regulated genes and 3 down-regulated genes were noticed in nasal epithelial cells of CRSwNP patients in the two datasets. GO gene functional annotation analysis showed that SPTBN1, FNBP1L, VAPB and SNX1 were involved in cell adhesion function, MAP1B was participated in the formation of microtubule related complex. KEGG pathway enrichment analysis indicated that BAMBI and SIAH1 were involved in regulation of Wnt pathway, COL6A1 and EIF4E were involved in the regulation of PI3K-AKT pathway. String protein interaction network analysis assumed that MAP1B and VAPB were the core functional proteins. Among top 3 differentially expressed genes COL6A1, MAP1B and BAMBI, only MAP1B gene was increased in nasal epithelial cells of CRSwNP patients in comparison to controls. Conclusion: The increased MAP1B gene in epithelial cells of CRSwNP, as well as abnormal regulation of Wnt and PI3K-AKT signal pathways may mediate the barrier dysfunction in CRSwNP.

Hypoxic stimulation leads to the changes of inflammatory factors in mucosal epithelial cells of nasal polyps / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the roles of hypoxic stimulation in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) by comparing the variation and differences of inflammatory factors secreted from epithelial cells of nasal polyps and normal nasal mucosa under hypoxic stimulation. Methods: Sixty-eight patients who were diagnosed with CRSwNP from June 2015 to January 2018 at China-Japan Union Hospital of Jilin University were analyzed, including 36 males and 32 females, aged (45.2±12.5) years. Nasal polyps mucosa was included in CRS-NP group and inferior turbinate mucosa was included in CRS-IT group. According to the degree of eosinophil infiltration in histopathologic results, each of these two groups was further divided into eosinophil infiltration and non-eosinophil infiltration as Eos-NP group (n=34), Non-Eos-NP group (n=34), Eos-IT group (n=20) and Non-Eos-IT group (n=20). The inferior turbinate mucosa of twenty-five patients who were diagnosed with cyst of paranasal sinus or deviation of nasal septum was classified as control group (n=25), including 14 males and 11 females, aged (42.8±10.2) years. The expression of interleukin 17A (IL-17A), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and hypoxia-inducible factor 1α (HIF-1α) in each group was analyzed by immunohistochemical staining. After 0, 24 and 48 h hypoxic stimulation, the secretion of IL-17A, IFN-γ, TNF-α in primary nasal mucosa epithelial cells of each group was tested by enzyme-linked immune sorbent assay (ELISA) experiment; the expression of HIF-1α was tested by immunofluorescent staining and imaging and Western blot. SPSS 17.0 software and two-way ANOVA were used for statistical analysis. Results: Immunohistochemical staining showed that the expression of IL-17A and TNF-α was much higher in control group (optical density (OD) value was 0.37±0.03, 0.53±0.02, respectively) and the expression of IFN-γ and HIF-1α was much higher in Eos-IT group (OD value was 0.47±0.03, 0.39±0.02, respectively). The secretion of IL-17A and TNF-α was much lower in control group than that in other groups under normal condition. After 48 h hypoxic stimulation, the secretion of IL-17A and TNF-α was much higher in control group compared with other groups. The secretion of IFN-γ in Eos-NP group was much higher than that in control group under normal condition ((13.7±1.3) pg/ml vs (11.1±1.6) pg/ml, P<0.05). After 48 h hypoxic stimulation, there was no difference of IFN-γ between control group and Eos-NP group. The expression of HIF-1α decreased in Eos-NP group and Non-Eos-NP group while increased in CRS-IT group and control group upon prolonged exposure to hypoxia. HIF-1α was mostly located at cytoplasm of epithelial cells in control and CRS-IT group while mainly located at nucleus of epithelial cells in CRS-NP group. Conclusions: The secretion of IL-17A, TNF-α, IFN-γ and the expression of HIF-1α show significant difference between normal nasal mucosa, polyps and inferior turbinate of CRSwNP under hypoxic stimulation, presenting different subcellular localization. This illustrates the proteins above are involved in transcription and regulation of the gene responsible for the pathogenesis of CRSwNP.

Nasal polyposis: more than a chronic inflammatory disorder-a disease of mechanical dysfunction - the São paulo position

Introduction: The importance of our study lies in the fact that we have demonstrated the occurrence ofmechanical dysfunction within polypoid tissues, which promotes the development of polyps in the nasal cavity. Objective: To change the paradigm of nasal polyposis (NP). In this new conception, the chronic nasal inflammatory process that occurs in response to allergies, to pollution, to changes in the epithelial barrier, or to other factors is merely the trigger of the development of the disease in individuals with a genetic predisposition to an abnormal tissue remodeling process, which leads to a derangement of the mechanical properties of the nasal mucosa and, consequently, allows it to grow unchecked. Data: Synthesis We propose a fundamentally new approach to intervening in the pathological process of NP, addressing biomechanical properties, fluid dynamics, and the concept of surface tension. Conclusion: The incorporation of biomechanical knowledge into our understanding of NP provides a new perspective to help elucidate the physiology and the pathology of nasal polyps, and new avenues for the treatment and cure of NP (AU)

Nasal polyposis in cystic fibrosis: follow-up of children and adolescents for a 3-year period / Polipose nasal em fibrose cística: seguimento em crianças e adolescentes durante um período de 3 anos

Abstract Introduction: Nasal polyposis is often found in patients with cystic fibrosis. Objective: To assess the incidence of nasal polyposis, the response to medical treatment, recurrence and the need for surgical intervention in children and adolescents with cystic fibrosis during a three-year follow-up. Methods: Clinical symptoms (pulmonary, pancreatic insufficiency, malnutrition, nasal obstruction), two positive sweat chloride tests, and genotype findings in 23 patients with cystic fibrosis were analyzed. All patients underwent nasal endoscopy every 12 months from January 2005 to December 2007, to assess the presence and grade of Nasal Polyps. Nasal polyposis, when present, were treated with topical corticosteroids for 6-12 months, with progress being evaluated within the 3 years of follow-up. Results: In the first evaluation, nasal polyposis was diagnosed in 30.43% of patients (3 bilateral and 4 unilateral), recurrent pneumonia in 82.6%, pancreatic insufficiency in 87%, and malnutrition in 74%. The presence of nasal polyposis was not associated with chloride values in the sweat, genotype, clinical signs of severity of cystic fibrosis, or nasal symptoms. In the three-year period of follow up, 13 patients (56.52%) had at least one event of polyposis, with the youngest being diagnosed at 32 months of age. Only one patient underwent surgery (polypectomy), and there was one diagnosis of nasopharyngeal carcinoma. Conclusion: The study showed a high incidence of nasal polyposis. Monitoring through routine endoscopy in patients with cystic fibrosis, even in the absence of nasal symptoms, is highly recommended. The therapy with topical corticosteroids achieved good results. Thus, an interaction between pediatricians and otolaryngologists is necessary.

Resumo Introdução: A polipose nasal é frequentemente encontrada em pacientes portadores de fibrose cística. Objetivo: Avaliar a incidência de polipose nasal, a resposta ao tratamento clínico, a recorrência e a necessidade de intervenção cirúrgica em crianças e adolescentes com fibrose cística durante um seguimento de 3 anos. Método: Os sintomas clínicos (pulmonar, insuficiência pancreática, desnutrição, obstrução nasal), duas pesquisas de cloro no suor positivas e genótipo de 23 pacientes com fibrose cística foram descritos. Todos os pacientes foram submetidos à endoscopia nasal a cada 12 meses de janeiro de 2005 a dezembro de 2007, para avaliação de presença e grau de polipose nasal. A polipose nasal, quando presente, foi tratada com corticosteroide tópico de 6 a 12 meses e avaliada a evolução nos 3 anos de seguimento. Resultados: Na primeira avaliação, a polipose nasal foi diagnosticada em 30,43% dos pacientes (três bilaterais e quatro unilaterais), pneumonia recorrente em 82,6%, insuficiência pancreática em 87% e a desnutrição em 74%. A presença de polipose nasal não se associou aos valores de cloro no suor, genótipo, sinais clínicos de gravidade da fibrose cística ou sintomas nasais. Nos três anos de seguimento, 13 pacientes (56,52%) apresentaram pelo menos um evento de polipose, o mais jovem foi diagnosticado aos 32 meses. Apenas um paciente foi submetido à cirurgia (polipectomia) e houve um diagnóstico de carcinoma da nasofaringe. Conclusão: O estudo mostrou alta incidência de polipose nasal. O acompanhamento por meio de exames endoscópicos de rotina em pacientes fibrocisticos, mesmo na ausência de sintomas nasais, é altamente recomendado. A terapia com corticoide tópico mostrou bons resultados. Assim, faz-se necessária a interação entre pediatras e otorrinolaringologistas.

Distinct characteristics of nasal polyps with and without eosinophilia / Diferenças nas características de pólipos nasais com e sem eosinofilia

Abstract Introduction Eosinophilic and noneosinophilic Nasal polyps (NPs) are different subtypes of NPs and require different treatment methods. Objective To compare the histologic characteristics, mRNA and protein expression between Nasal Polyps with and without eosinophilia. Methods NPs tissues were obtained from eighty-six NPs patients during surgery. Eosinophilic and noneosinophilic NPs were distinguished according to immunochemical results of the specimen. The histological, mRNA and protein expression features were compared between the two groups. Results In eosinophilic NPs, we observed a significantly higher GATA-3, IL-5, IL-4, IL-13 mRNA and protein expression. In noneosinophilic NPs, IL-17, IL-23 and RORc mRNA and protein expression were increased. Immunohistochemistry tests showed, more mast cells and less neutrophils in eosinophilic NPs compared with noneosinophilic NPs. Eosinophilic NPs patient presented more severe symptom scores when compared to noneosinophilic NPs. Conclusion We demonstrate for the first time that Th2 is the predominant reaction in eosinophilic NPs while Th17 is the predominant reaction in noneosinophilic NPs. Our study may provide new treatment strategy for NPs.

Resumo Introdução Pólipos nasais (PNs) eosinofílicos e não eosinofílicos são diferentes subtipos de PNs e requerem diferentes métodos de tratamento. Objetivo Comparar as características histológicas e a expressão de mRNAs e proteínas entre PNs com e sem eosinofilia. Método Amostras de PNs foram obtidos de 86 pacientes durante a cirurgia. PNs eosinofílicos e não eosinofílicos foram diferenciados segundo os resultados imunoistoquímicos de cada amostra. As características histológicas e de expressão de mRNAs e de proteínas foram comparadas entre os dois grupos. Resultados Em PNs eosinofílicos, observamos uma expressão significativamente maior dos mRNAs e proteínas GATA-3, IL-5, IL-4 e IL-13. Nos PNs não eosinofílicos, aumentou a expressão dos mRNAs e das proteínas IL-17, IL-23 e RORc. Nos testes imunoistoquímicos, observamos maior número de mastócitos e menor número de neutrófilos nos PNs eosinofílicos, em comparação com PNs não eosinofílicos. Os pacientes com PNs eosinofílicos obtiveram escores de sintomas mais graves vs. PNs não eosinofílicos. Conclusão Demonstramos, pela primeira vez, uma reação Th2 predominante em PNs eosinofílicos e uma reação Th17 predominante em PNs não eosinofílicos. Nosso estudo pode proporcionar novas estratégias terapêuticas para a rinossinusite crônica.

The human leukocyte antigen G molecule (HLA-G) expression in patients with nasal polyposis / A expressão do antígeno humano leucocitário G (HLA-G) em pacientes com polipose nasossinusal

INTRODUCTION: Sinonasal polyposis (NP) is a chronic inflammatory pathology of the nasal/paranasal cavities which affects from 1%-4% of the population. Although polyps seem to be a manifestation of chronic inflammation in both allergic and non-allergic subjects, the pathogenesis of nasal polyposis remains unknown. HLA-G molecules are a kind of no classic class I antigen with anti-inflammatory and tolerogenic properties. Little attention has been paid to the role of HLA-G chronic inflammatory disorders. OBJECTIVE: The aim of this study is to investigate the expression of HLA-G in the NP. MATERIALS AND METHODS: Prospective study involving samples of patients presenting with nasal polyposis that were subjected to the immunohistochemistry technique. After a skin prick test, all patients were divided into atopic and nonatopic groups and classified as asthmatic or non-asthmatic. RESULTS: Immunohistochemical staining demonstrated a higher expression of the HLA-G molecule in samples from nonatopic than in those from atopic patients, and was significantly lower in the non-asthmatic patients. CONCLUSION: These results indicate that HLA-G may play an important role in the pathology of nasal polyposis. Considering the anti-inflammatory properties of HLA-G, this study suggests that it could reduce susceptibility to atopy and asthma. .

INTRODUÇÃO: Polipose nasossinusal (PNS) é uma patologia inflamatória crônica das cavidades nasais/paranasais que afeta 1%-4% da população. Embora os pólipos pareçam ser uma manifestação de inflamação crônica em ambos os indivíduos alérgicos e não alérgicos, a patogênese da polipose nasal permanece desconhecida. Moléculas HLA-G são antígenos não clássicos da classe I com propriedades anti-inflamatórias e tolerogênicas. Pouca atenção tem sido dada ao papel do HLA-G em doenças inflamatórias crônicas. OBJETIVO: Investigar a expressão de HLA-G na PNS. MATERIAIS E MÉTODOS: Estudo prospectivo de pacientes com polipose nasal que foram submetidas à técnica de imuno-histoquímica. Após realizarem teste cutâneo, os pacientes foram divididos em grupos atópicos e não atópicos e classificados como asmáticos ou não asmáticos. RESULTADO: A coloração imuno-histoquímica mostrou uma maior expressão da molécula HLA-G em pacientes não atópicos do que naqueles atópicos e foi significativamente inferior nos pacientes não asmáticos. CONCLUSÃO: Os resultados indicam que o HLA-G pode ter um papel importante na patologia da polipose nasal. Considerando as propriedades anti-inflamatórias do HLA-G, este estudo sugere que ele poderia reduzir a susceptibilidade a atopia e asma. .

Apoptose em pólipos nasais eosinofílicos submetidos in vitro ao tratamento com mitomicina C / Apoptosis in eosinophilic nasal polyps treated in vitro with mitomycin C

A etiopatogênese da polipose nasal eosinofílica ainda não foi esclarecida. Os eosinófilos constituem as principais células do infiltrado inflamatório e estão relacionados com a perpetuação do processo inflamatório na rinossinusite crônica com pólipos nasais. OBJETIVO: Avaliar a ação in vitro da mitomicina no índice apoptótico de pólipos nasais eosinofílicos. MATERIAL E MÉTODO: Estudo prospectivo experimental autopareado com amostra de biópsia de 15 pacientes com polipose nasal eosinofílica. Cada fragmento foi dividido em dois grupos. No grupo experimental aplicou-se mitomicina por cinco minutos, na dosagem de 400 µg/ml. O grupo controle foi submetido às mesmas manipulações, mas utilizando-se somente meio de cultura. Os fragmentos contidos nos dois primeiros compartimentos, controle e experimento, foram imediatamente submetidas ao preparo para histopatologia. O outro par de amostra, contendo controle e experimento, foi incubado por 12 horas. Após 12 horas, os fragmentos foram retirados para exame histopatológico. O índice apoptótico foi determinado pela morfometria na coloração hematoxilina-eosina e pela análise da fragmentação do DNA. RESULTADO: A comparação do dois grupos demonstrou diferença significativa (p < 0,001) no índice apoptótico das culturas incubadas por 12 horas. CONCLUSÃO: A mitomicina induz in vitro o aumento do índice apoptótico dos eosinófilos dos pólipos nasais eosinofílicos.

The etiopathogenesis of eosinophilic nasal polyps is yet to be explained. Eosinophils are key components in the inflammatory infiltrate and are related to the perpetuation of the inflammatory process in chronic rhinosinusitis with nasal polyps. OBJECTIVE: This paper aims to evaluate the in vitro action of mitomycin upon the apoptotic index of nasal polyps. MATERIALS AND METHODS: This is a self-paired prospective experimental study using biopsy fragments from 15 patients with eosinophilic nasal polyps. Biopsy fragments were divided into two groups. In the case group, the fragments were treated with 400 µg/ml of mitomycin for five minutes. The control group fragments were treated with culture medium. The pair of fragments contained in the two first compartments - control and case - were immediately sent to the histopathologist. The other pair of samples containing control and case fragments was incubated for 12 hours. The fragments were then taken to the histopathologist for testing. The apoptotic index was determined by the morphometry in hematoxylin and eosin staining and DNA fragmentation analysis (TUNEL reaction). RESULTS: The comparison between the two groups showed a statistically significant difference (p < 0,001) in the apoptotic index of the 12-hour incubated cultures. CONCLUSION: Mitomycin acts in vitro upon the eosinophilic nasal polyps inducing the rise of the eosinophilic apoptotic index.

In vitro effect of glucocorticoids on nasal polyps / Efeito in vitro de glicocorticosteróides sobre pólipos nasais

Glucocorticoids are considered the main treatment option for nasal polyps, but their effect is only recently being understood. AIM: To evaluate whether fluticasone propionate (FP) inhibits the inflammatory process induced by TNF-alpha in vitro, and to assess if NF-kappaB is associated to this inhibition. STUDY DESIGN: Experimental in vitro study. MATERIALS AND METHODS: Nasal polyp fibroblasts were cultured during 24 hours. Three different concentrations of FP (1, 10 and 100 nM, added to TNF-alpha) were compared to negative (without additive) and positive (TNF-alpha) controls. Gene expression (RTQ-PCR) and protein concentration (ELISA) of VCAM-1, ICAM-1, eotaxin and RANTES were measured, as well as the nuclear translocation of NF-kappaB. RESULTS: TNF-alpha significantly increased protein concentration and RNA expression of all the studied molecules, as well as the nuclear translocation of NF-kappaB, when compared to the negative control. FP decreased these parameters in a dose-dependent manner, statistically different from positive control up to 100nM. CONCLUSIONS: FP extensively inhibited inflammatory recruiters, at both protein and RNA levels, confirming the ability of glucocorticoids to modulate the inflammatory process in nasal polyps. This inhibition was associated to decreased NF-kappaB nuclear translocation, demonstrating that this is an important mechanism of glucocorticoids action for nasal polyps.

Glicocorticoides são considerados a principal opção terapêutica para polipose nasossinusal, mas seus efeitos estão sendo descobertos apenas recentemente. OBJETIVO: Avaliar se proprionato de fluticasona (FP) inibe in vitro o processo inflamatório induzido por TNF-alfa, e se NF-kappaB está associado a esta inibição. FORMA DE ESTUDO: Experimental in vitro. MATERIAIS E MÉTODOS: Fibroblastos de pólipos nasais foram cultivados por 24 horas. Três concentrações diferentes de FP (1, 10 e 100nM, além do TNF-alfa) foram comparados a controles negativo (sem aditivo) e positivo (TNF-alfa). Expressão gênica (RTQ-PCR) concentração proteica (ELISA) de VCAM-1, ICAM-1, eotaxin e RANTES foram medidos, assim como a translocação nuclear de NF-kappaB. RESULTADOS: TNF-alfa aumentou significativamente a concentração proteica e expressão gênica de todas molé¬culas estudadas, assim como a translocação nuclear de NF-kappaB, quando comparado ao controle negativo. O FP diminuiu estes parâmetros numa forma dose-dependente, diferente estatisticamente do controle positivo até 100nM. CONCLUSÕES: O FP extensivamente inibiu os recrutadores inflamatórios, em níveis proteicos e gênicos, confirmando a habilidade dos glicocorticoides em modular o processo inflamatório na polipose nasossinusal. Esta inibição esteve associada à diminuição da translocação nuclear de NF-kappaB, demonstrando que este é um importante mecanismo de ação dos glicocorticoide na polipose nasossinusal.

Reprodutibilidade do estadiamento endoscópico tridimensional da polipose nasal / Reproducibility of the three-dimensional endoscopic staging system for nasal polyposis

A polipose nasossinusal é um processo inflamatório crônico da mucosa nasal, caracterizado pela presença de pólipos nasais múltiplos e bilaterais. Vários tipos de medicações têm sido usados no seu tratamento. Para estudar o resultado de diferentes formas de tratamento, é preciso alguma forma de estadiamento. OBJETIVOS: Apresentar um novo método endoscópico de estadiamento, baseado na endoscopia nasal e na avaliação tridimensional dos pólipos, comparar sua reprodutibilidade entre outros dois métodos já difundidos. Forma de estudo: Estudo de coorte histórica com corte transversal. Material e método: Três examinadores avaliaram exames de 20 pacientes portadores de polipose nasossinusal em diferentes momentos, antes e 15 e 30 dias após o início de um tratamento com prednisona, na dose de 1 mg/kg/dia por 7 dias. Foi avaliado o grau de concordância entre os examinadores para cada método, utilizando-se o Kappa múltiplo para análise estatística. Resultados: Os três métodos mostraram-se reprodutíveis, sendo que o método proposto apresentou menor concordância entre os examinadores. Conclusão: O estadiamento proposto mostrou-se reprodutível, apesar de apresentar menor concordância do que os outros dois estadiamentos.

Nasal Polyposis is a chronic inflammatory process of the nasal mucosa, characterized by multiple and bilateral nasal polyps. Different drugs have been used in its treatment. In order to study the results of different treatment modalities it is necessary to have some kind of staging. AIM: to present a new endoscopic staging method, based on nasal endoscopy and on the three-dimensional nasal polyp assessment; and compare its reproducibility with that from two other systems already established in the literature. Study design: Cohort study. Material and methods: Three experts assessed the exams of 20 patients with nasal polyposis at different times, before, at 15 and at 30 days after the start of oral prednisone, 1 mg/kg/day, during 7 days. We assessed the agreement rate among the experts, using Kappa for statistic analysis. Results: The three methods were reproducible, and the method hereby proposed had the least agreement among the examiners. Conclusions: the three-dimensional staging system proposed proved reproducible, despite showing less agreement among the examiners than the other as the other two methods.

Clinicopathological evaluation of nasal biopsy specimens- and afip experience

To evaluate the presence and frequency of clinically significant microscopic diagnosis in cases under going nasal polypectomy/biopsy. Cases of nasal polypectomy/biopsy reported from department of histopathology during last five years [2004-2008] were retrieved from records and evaluated microscopically for detailed histological diagnosis. A total of 383 cases were reviewed. Most frequent age was 5[th] decade. Nasal polepectomy comprised 54.73% [n=214]. Nasal Biopsy not otherwise specified comprised 21.99% [n=86]. Suspicious of growth was indicated in 23.27% [n=84] cases. Among all types of biopsy, 60.04% [n=230] were inflammatory nasal polyps, 10.44% [n=40] malignant neoplasm, 5.48% [n=21] were inverted papilloma. Rest of the cases [24.03%] showed benign inflammatory changes and benign neoplastic lesions. Although frequency of neoplastic lesion in routine polypectomy specimen as mentioned in literature is low. Our study reveals significant number of malignant cases. Considering the prognostic significant of early histological diagnosis and appropriate post considered essential. Large scale studies are required to evaluate clinicopathological correction of nasal biopsy specimens in our setup

Characteristics of antrochoanal polyps in the pediatric age group

To evaluate and compare the clinical and the pathological characteristics of antrochoanal polyps [ACPS] in adults and children. Medical records of 35 patients [19 children, 16 adults] operated upon for ACPS between 1995 and 2005 at an academic tertiary center were reviewed retrospectively. Demographic characteristics, clinical presentation, surgical management, histological findings and recurrence rate were compared. Of the 35 patients, 19 [54%] were children [mean age, 12.6 years] and 16 [46%] were adults [mean age, 31.4 years]. Nasal obstruction was the most common presenting symptom in both groups. The incidence of snoring and/or obstructive sleep apnea was statistically significant, more common among the pediatric age group as compared to the adult group [P =.001]. Epistaxis was also found to be more common among the pediatric age group [P =.027], while sinusitis was noted to be significantly more common among the adult group [P =.019].Transnasal endoscopic removal of ACPS was performed in 12 [63.1%] children and 11 [68.7%] adults. A combined open/endoscopic approach was required in 36.9% of children and 31.3% of adults. On histologic examination, allergic ACPS [the mucosal surface is respiratory epithelium, no mucus glands, abundant eosinophils] was more common than inflammatory ACPS [the mucosal surface is respiratory epithelium, no mucus glands, abundant neutrophils] in children [2.8:1] as compared to adults [0.8:1] [P =.045]. All of our patients were followed with endoscopic examination for a period ranging from 9 to 42 months [mean, 24 months]. Recurrence of ACPS was identified in 2 children and 1 adult. Antrochoanal polyps are a rare clinical entity. Children have unique clinical and pathological features as compared to adults. Endoscopic excision is safe and effective in the pediatric age group and has the capability to ensure complete removal and lower recurrence rate

Manifestações otorrinolaringológicas da fibrose cística: revisão da literatura / Otorhinolaryngologic manifestations of cystic fibrosis: literature review

Introdução: A Fibrose Cística é a doença genética autossômica recessiva mais comum entre caucasianos. Ocorre devido a mutações no gene que codifica proteína reguladora de condução transmembrana, acarretando deficiência transporte de cloro. Objetivo: Realizar revisão da literatura sobre Fibrose Cística, enfatizando manifestações otorrinolaringológicas. Método: Utilizou-se consulta do banco de dados on line do Pub Med, aplicando a pesquisa dos termos Fibrosis Cystic and Sinusitis e Mucoviscidosis and Sinusitis. Considerações Finais: Embora não seja a principal causa de morte, as manifestações otorrinolaringológicas da Fibrose Cística trazem importante morbidade para estes pacientes.

Introduction: Cystic Fibrosis is the most common recessive autosomic genetic disease among Caucasians. It's caused by mutations in the gene that decodes regulatory protein for transmembrane conductance, resulting in defective transport of chlorine. Objective: Review the literature about Cystic Fibrosis, with emphasis on otorhinolaryngologic manifestations. Method: The online Pub Med databases were researched and we applied the following search terms Fibrosis Cystic and Sinusitis, and Mucoviscidosis and Sinusitis. Conclusions: Although it is not the main cause of death, the otorhinolaryngologic manifestations of the Cystic Fibrosis bring important morbidity to these patients.

Efeito da mitomicina C na secreção de fator estimulador de granulócitos macrófagos e interleucina-5 em cultura de estroma de pólipos nasais eosinofílicos / Effect of mitomycin C on the secretion of granulocyte macrophages colonies stimulating factor and interleukin-5 in eosinophilic nasal polyps stromal culture

O estudo de fatores teciduais, como a concentração de fator estimulador de colônias de macrófagos (GM-CSF) e interleucina 5 (IL-5), aponta para os mecanismos envolvidos na manutenção da eosinofilia em pólipos nasossinusais eosinofílicos. A mitomicina C (MMC) tem sido utilizada com bons resultados em otorrinolaringologia. OBJETIVO: Este estudo teve como objetivo avaliar a ação da Mitomicina C sobre a secreção de GM-CSF e IL-5 em pólipos eosinofílicos. FORMA DE ESTUDO: caso-controle. MATERIAL E MÉTODO: O estudo foi comparativo experimental autopareado, com amostras de pólipos biopsiados de pacientes portadores de polipose nasossinusal eosinofílica. Os fragmentos semeados como grupo experimental receberam mitomicina C por 5 minutos na dosagem de 400microg/ml e então lavadas em meio RPMI. Nos tempos zero, 12 e 24 horas, o sobrenadante foi retirado para determinação dos níveis de GM-CSF em 22 pacientes e IL-5, em 19 pacientes, utilizando o método de ELISA. RESULTO: Diminuição de secreção de GM-CSF nos grupos tratados com mitomicina C no tempo 24h (p<= 0,05); no grupo tratado houve expressão significativa de GM-CSF entre zero e 12 horas (p=0,013) demonstrando a viabilidade da cultura igualmente ao grupo não tratado; tendência à queda dos níveis de IL-5 no grupo tratado em 24h. CONCLUSÃO: O estudo demonstrou que a mitomicina C foi capaz de inibir a síntese de GM-CSF em culturas de pólipos nasais eosinofílicos e com provável ação sobre a secreção de IL-5, necessitando de estudos complementares.

Eosinophil Inflammation of Nasal Polyp Tissue: Relationships with Matrix Metalloproteinases, Tissue Inhibitor of Metalloproteinase-1, and Transforming Growth Factor-beta1

Eosinophil and mast cell infiltrations are consistent findings in nasal polyp tissue. Previous studies have shown that matrix metalloproteinases (MMPs) may be involved in eosinophil infiltration in airway mucosa of asthmatic patients, and that transforming growth factor-beta1 (TGF-beta1) induces extracellular matrix deposition in nasal polyp tissue. The aim of this study was to evaluate the role of MMPs and tissue-inhibitor of metalloproteinase-1 (TIMP-1) in association with TGF-beta1, eosinophils and mast cell activation in nasal polyp tissue. Nasal polyp tissues from 20 patients who underwent polypectomies were collected and prepared into tissue homogenate. Eosinophil cationic protein (ECP) and tryptase levels were measured by CAP system (Pharmacia, Sweden). MMP-2, MMP-9, TIMP-1 and TGF-beta1 levels were measured by enzyme-liked immunosorbent assay. MMP-2 was the predominant form of MMPs, followed by MMP-9 and TIMP-1. There were significant correlations between ECP, and MMP-9, MMP-2, TGF-beta1 and tryptase, but not with TIMP-1. Significant correlations were noted between tryptase, and MMP-2, MMP-9, and TGF-beta1, but not with TIMP-1. Close correlations were noted between TGF-beta1, and MMP-9 and MMP-2, but not with TIMP-1. MMP-2, MMP-9, and TGF-beta1 may contribute to eosinophil and mast cell migrations into nasal polyp tissue.

Langerhan's cell histiocytosis presenting as bilateral bleeding nasal polypi

Langerhan's cell histiocytosis is a rare clinical entity. Cases have been described in medical literature affecting head and neck region. In this first reported case, a 40 years old male presented with recurrent epistaxis. On examination he had bilateral bleeding nasal polypi originating from the lateral nasal wall in the middle meatus region, proceeding backward towards the nasopharynx as well as anteriorly, filling the nasal cavity completely with bilateral submandibular lymphadenopathy: Diagnosis was made on histopatohlogy and using special immunohistochemical stains [S-100 positive]. Surgical curettage, steroids, cytotoxic chemotherapy and low dose radiotherapy, 7x2 Gy in 4 fractions to the head and neck region achieved local control of the disease fairly rapidly