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OBJECTIVES: Chronic rhinosinusitis (CRS) endotypes have demonstrated clinical value in guiding treatment decisions. Bacterial lysates are immunomodulators that have shown beneficial effects in various respiratory inflammatory diseases. This study aimed to evaluate the effect of postoperative bacterial lysate therapy on different CRS endotypes. METHODS: Patients diagnosed with CRS who underwent endoscopic sinus surgery were recruited. Bacterial lysates were administered postoperatively for 10 days per month for 3 months to the experimental group comprising patients with a history of frequent upper respiratory infections without adverse reactions. The remaining participants were allocated to the control group. The results of the postoperative 3-, 6-, and 12-month assessments, including the modified Lund-Kennedy (mLK) endoscopic and Sinonasal Outcome Test (SNOT) 22 scores, for the groups were compared. The tissue samples obtained from the participants were evaluated to detect the presence of relevant inflammatory mediators. RESULTS: Among the 92 participants, 47 started bacterial lysate therapy 2 weeks after the surgery. The tissue cytokine profiles and clinical parameters, such as the disease severity and blood eosinophil percentage, of the bacterial lysate and control groups were comparable before treatment. The mLK endoscopic and SNOT-22 scores did not differ after 3, 6, and 12 months of follow-up. The subgroup analysis revealed that the bacterial lysate group had significantly lower mLK endoscopic scores than the control group for CRS without nasal polyps, while there was a tendency toward significance for the interleukin (IL)-5 negative group after 6 months. CONCLUSION: Postoperative bacterial lysate therapy has some beneficial effects on the endoscopic findings of patients with CRS without nasal polyps or those who are negative for IL-5.
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Endoscopia , Rinite , Sinusite , Humanos , Sinusite/cirurgia , Sinusite/terapia , Doença Crônica , Rinite/cirurgia , Rinite/terapia , Rinite/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Fenótipo , Extratos Celulares , Pólipos Nasais/cirurgia , Pólipos Nasais/metabolismo , Pólipos Nasais/complicações , Teste de Desfecho Sinonasal , Interleucina-5/metabolismo , Cuidados Pós-Operatórios/métodos , Citocinas/metabolismo , Resultado do Tratamento , Lisados Bacterianos , RinossinusiteRESUMO
Objective: To analyze changes in olfactory function after endoscopic endonasal skull base surgery and compare performance of the olfactory questionnaire with those of conventional psychophysical tests. Methods: Patients were classified into 5 categories for olfactory function evaluation (normal, mild hyposmia, moderate hyposmia, severe hyposmia, and anosmia) based on a self-assessment. Patients also underwent the butanol threshold test (BTT), Cross-Cultural Smell Identification Test (CCSIT), and 11-item olfactory questionnaire. Subjects with normosmia preoperatively and who were followed up at least 6 months after surgery were analyzed. Receiver operating characteristic curves and confusion matrix analysis were performed for BTT, CCSIT, and olfactory questionnaire to compare their diagnostic abilities. The effects of age, preoperative olfaction, septal flap, tumor pathology, and tumor size on postoperative olfaction were evaluated using multivariate linear regression analysis. Results: Data from 108 patients were analyzed. Postoperative changes in the olfactory questionnaire were significantly associated with changes in the BTT and CCSIT. The area under the curve for postoperative self-olfactory function classification was highest for olfactory questionnaire (0.894), followed by BTT (0.767) and CCSIT (0.688). Patient age at the time of surgery and preoperative BTT score were significantly related to postoperative olfactory outcomes. Conclusion: The olfactory questionnaire correlated well with conventional psychosomatic olfactory function tests. In combination with clinical parameters and preoperative psychosomatic olfactory function tests, the olfactory questionnaire is suitable for assessing subjective olfactory function after endoscopic endonasal skull base surgery.
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Fungus ball is the most common form of non-invasive fungal sinusitis, and maxillary sinus is the most commonly involved site. Maxillary sinus fungus ball (MFB) accounts for a considerable proportion of unilateral maxillary sinusitis. The prevalence of MFB has recently increased; however, its contributing factors are unclear. This study analyzed the association between MFB and dental implants. One hundred one patients who underwent unilateral maxillary sinus surgery were divided into two groups based on surgical biopsy results: unilateral bacterial sinusitis (UBS, n = 45) and MFB (n = 56). Stratified random sampling of 30 patients from each group was performed to adjust for age. The number of dental implants on maxillary teeth and degree of penetration into the maxillary sinus was radiologically evaluated. The number of patients with dental implants was greater (P = 0.085) and the number of implants was significantly higher (P = 0.031) in the MFB group. Dental implant can be a potential risk factor for MFB development. Therefore, dental implant surgeons should take caution in penetrating the maxillary sinus floor during implant insertion and otolaryngologists should consider the possibility of fungus ball when assessing patients with sinusitis who have dental implants.
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Implantes Dentários , Levantamento do Assoalho do Seio Maxilar , Sinusite , Humanos , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/cirurgia , Implantes Dentários/efeitos adversos , Fatores de Risco , FungosRESUMO
OBJECTIVES: Several criteria exist for classifying chronic rhinosinusitis with nasal polyps (CRSwNP) as eosinophilic or non-eosinophilic. This study attempted to evaluate several criteria for defining eosinophilic CRSwNP from clinical and immunological perspectives. METHODS: A cohort of 84 patients (73 patients with CRSwNP and 11 control patients) was retrospectively analyzed. Patients were divided into eosinophilic and non-eosinophilic CRSwNP based on four different criteria: eosinophils (EOS) accounting for more than 20% of the total inflammatory cells; ≥70 EOS per high-power field (HPF); >55 EOS/HPF; and ≥10 EOS/HPF. Preoperative clinical characteristics, the immunological profiles of 14 cytokines from nasal tissue, and postoperative outcomes were compared between eosinophilic and non-eosinophilic CRSwNP based on each criterion. These criteria were immunologically validated by using 14 cytokines to predict the performance of tissue eosinophilia with a random forest model. RESULTS: Patients with eosinophilic CRSwNP were significantly older when the criterion of ≥10 EOS/HPF or EOS >20% was used. The number of patients with aspirin intolerance was significantly higher in eosinophilic CRSwNP based on the criterion of EOS >20%. From an immunological perspective, non-type 2 inflammatory cytokines were significantly higher in non-eosinophilic CRSwNP with the criterion of EOS >20% of the total inflammatory cells. In addition, the criterion of EOS >20% of the total inflammatory cells resulted in the best prediction of eosinophilic CRSwNP, with an accuracy of 88.10% and area under the curve of 0.94. CONCLUSION: Clinical and immunological characteristics were different between eosinophilic and non-eosinophilic CRSwNP depending on a variety of criteria, and the. RESULTS: of this study should be taken into account when choosing the criterion for defining eosinophilic CRSwNP and interpreting the data accordingly.
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BACKGROUND: Fractional exhaled nitric oxide (FeNO) is useful in the management of asthma and predicting the efficacy of standard corticosteroids and biologics. However, the diagnostic value of FeNO in asthmatic chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. OBJECTIVE: We assessed FeNO levels in patients with CRSwNP and evaluated the diagnostic value of FeNO for screening type 2 CRSwNP (T2-CRSwNP) with asthma. METHODS: We enrolled 94 patients who were diagnosed with CRSwNP and underwent functional endoscopic sinus surgery. FeNO levels, the blood eosinophil percentage, total IgE, spirometry tests (FEV1/FVC), Lund-Mackay CT score, and percentage of patients with comorbid asthma were compared among CRSwNP subgroups. Spearman rank correlation test was used to assess the degree of association between variables. ROC curve analysis was conducted to evaluate the diagnostic capability to differentiate T2-CRSwNP based on clinical and histological classifications. RESULTS: FeNO levels and the blood eosinophil percentage were significantly higher in patients with T2-CRSwNP(h) based on histological data (P < .05). FeNO was correlated with the blood eosinophil percentage (r = 0.420, P < .001) and FEV1/FVC (r = -0.324, P = .001). A FeNO level of 27â ppb had a good ability to discriminate patients with asthmatic T2-CRSwNP(h) (AUC = 0.848; 95% CI = 0.7602-0.9361; sensitivity = 90.9%; specificity = 63.9%). The optimal cutoff values for FeNO and the blood eosinophil percentage for diagnosing asthmatic T2-CRSwNP(h) were 68â ppb and 5.6% (sensitivity = 95.5%; specificity = 86.1%; AUC = 0.931; 95% CI = 0.8832-0.9791). In the diagnosis of severe T2-CRSwNP(c) based on clinical data, a FeNO level of 36â ppb showed the highest AUC (0.816; 95% CI = 0.7173-0.914; sensitivity = 72.7%; specificity = 79.2%). CONCLUSION: FeNO is a useful marker for screening asthmatic T2-CRSwNP even prior to biopsy or asthma evaluation and may assist in selecting a proper treatment.
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Asma , Pólipos Nasais , Rinite , Sinusite , Humanos , Teste da Fração de Óxido Nítrico Exalado , Rinite/diagnóstico , Rinite/patologia , Pólipos Nasais/diagnóstico , Pólipos Nasais/patologia , Sinusite/diagnóstico , Sinusite/patologia , Asma/diagnóstico , Doença Crônica , Óxido Nítrico/análise , Testes RespiratóriosRESUMO
PURPOSE: To check the change in growth-for-age after adenotonsillectomy in pre-pubertal children and investigate the affecting factors. METHODS: Two hundred and six pediatric patients who underwent adenotonsillectomy by a single surgeon between January 2011 and December 2014 were included for the retrospective cohort study. The z-scores of height-, weight-, and body mass index (BMI)-for-age were measured before adenotonsillectomy and 1 year after the operation. The Korean version of the obstructive sleep apnea-18 questionnaire (OSA-18), symptom questionnaire, physical examinations, demographic data, and pre-operative z-scores were used to analyze the factors affecting z-score change. RESULTS: Among 206 pediatric patients, 167 patients were normal growth; 19 were undergrowth; and 20 were obese. After the operation, height, weight, and BMI z-scores all increased both in 167 normal-growth patients and 19 undergrowth patients (p value < 0.05). However, in 20 obese patients, only height z-score significantly increased (p value = 0.028). The multiple regression test showed that the sleep disturbance domain of OSA-18 was positively correlated with height z-score change (p value = 0.041), and age was negatively correlated with weight z-score change (p value = 0.016). Pre-operative BMI z-score was negatively correlated (p value = 0.019) and adenoid grade was positively correlated (p value = 0.023) with BMI z-score change. CONCLUSIONS: These findings suggest that adenotonsillectomy may positively affect growth in pre-pubertal children, without undesirable weight gain. Additionally, the sleep disturbance domain of OSA-18 may play a role in predicting post-operative height increase in pre-pubertal children.
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Apneia Obstrutiva do Sono , Tonsilectomia , Criança , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Adenoidectomia , Tonsilectomia/efeitos adversos , Obesidade , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/cirurgiaRESUMO
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease treated with medication or surgery. For recalcitrant type 2 CRSwNP, biological agents have been effectively used to improve nasal polyp score, nasal congestion score, daily symptoms related to CRSwNP, and time to systemic corticosteroid use or revision surgery. Although general guidelines for using biologics to treat CRSwNP were proposed by the European Position Paper on Rhinosinusitis and Nasal Polyps in 2020 and various studies have tested their efficacy, there is much more to learn about biologics-specific indication and choice of biologics based on the endotypes, for instance. Understanding the vascular distribution of monoclonal antibodies and the differences in the vascularity of the non-polyp mucosa and nasal polyp tissue will not only aid understanding of each biologic's clinical effect but also provide insights to establishing a more personalized approach to treating recalcitrant CRSwNP with biologics.
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This study aimed to investigate the effect of age in patients with chronic rhinosinusitis with nasal polyp (CRSwNP). 269 patients were divided into eosinophilic and non-eosinophilic groups based on tissue eosinophilia, defined by eosinophils accounting for more than 20% of the total inflammatory cells. Patients were then further divided into younger and older groups based on the age of 35 years. Clinical characteristics including blood eosinophil, Lund Mackay score, and modified Lund-Kennedy (mLK) scores were compared. Levels of 14 cytokines from nasal tissues of an additional 78 patients were analyzed. Tissue eosinophilia was significantly associated with age and the proportion of non-eosinophilic CRSwNP was significantly higher in younger patients as compared to older patients (79.2% vs 56.6%). There was no difference in clinical characteristics and cytokine levels between the younger and older patients with eosinophilic CRSwNP. In contrast, in patients with non-eosinophilic CRSwNP, younger patients had significantly lower preoperative blood eosinophils and higher mLK scores at three and six months, postoperatively, compared to older patients. Alpha-1 antitrypsin and IL-5 levels were significantly lower in younger patients than in older patients in non-eosinophilic CRSwNP. This study suggests a potential association between age, non-type 2 inflammation and treatment outcome in CRSwNP.
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Eosinofilia/cirurgia , Pólipos Nasais/cirurgia , Rinite/cirurgia , Sinusite/cirurgia , Adulto , Fatores Etários , Doença Crônica , Estudos Transversais , Eosinofilia/diagnóstico , Eosinofilia/imunologia , Eosinofilia/metabolismo , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-5/metabolismo , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/diagnóstico , Pólipos Nasais/imunologia , Pólipos Nasais/metabolismo , República da Coreia , Estudos Retrospectivos , Rinite/diagnóstico , Rinite/imunologia , Rinite/metabolismo , Sinusite/diagnóstico , Sinusite/imunologia , Sinusite/metabolismo , Fatores de Tempo , Resultado do Tratamento , alfa 1-Antitripsina/metabolismoRESUMO
OBJECTIVES: The aim of this study was to analyze the risk of malignancy in salivary gland tumors on the basis of the Milan System for Reporting Salivary Gland Cytopathology. METHODS: A retrospective review was performed of the charts of patients with salivary gland tumors in whom the final diagnosis was confirmed by surgical excision. Preoperative fine needle aspiration results were categorized according to the Milan System for Reporting Salivary Gland Cytopathology: non-diagnostic (category I), nonneoplastic (category II), atypia of undetermined significance (category III), neoplasm (category IV), suspicious for malignancy (category V), and malignant (category VI). Fine needle aspiration and final diagnosis were compared, and the risk of malignancy and operative/oncological outcomes were analyzed. RESULTS: A total of 288 patients were enrolled in this study. Postoperative histopathologic salivary gland malignancies were found in 30 (10.4%) patients. Risk of malignancy was 7.1%, 0%, 48.0%, 4.8%, 88.7%, and 100% in categories I, II, III, IV, V, and VI, respectively. The most common malignant tumor in category III was salivary duct carcinoma (37.5%), followed by acinic cell carcinoma (25.0%), mucoepidermoid carcinoma (25.0%), and squamous cell carcinoma (12.5%). The 5-year survival rate of patients with malignant tumors showed no statistical difference between category III and category V/VI (P = .140). Risk of malignancy was 88.9% and 100% in category V and VI, respectively. CONCLUSIONS: A half of atypia of undetermined significance (category III) cases were malignant. Once diagnosed, the prognosis of malignant tumor in category III was similar with that in category V/VI.
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Carcinoma/patologia , Doenças das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologia , Adulto , Idoso , Biópsia por Agulha Fina , Carcinoma/epidemiologia , Diagnóstico Diferencial , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Doenças das Glândulas Salivares/mortalidade , Doenças das Glândulas Salivares/cirurgia , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/cirurgia , Taxa de SobrevidaRESUMO
PURPOSE: Various immune cells, including eosinophils and neutrophils, are known to contribute to the development of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the current understanding of the role of neutrophils in the development of CRSwNP still remains unclear. Therefore, we investigated risk factors for refractoriness of CRSwNP in an Asian population. METHODS: Protein levels of 17 neutrophil-related mediators in nasal polyps (NPs) were determined by multiplex immunoassay, and exploratory factor analysis using principal component analysis was performed. Immunofluorescence analysis was conducted to detect human neutrophil elastase (HNE) or myeloperoxidase (MPO)-positive cells. Tissue eosinophilic nasal polyp (ENP) and tissue neutrophilia (Neuhigh) were defined as greater than 70 eosinophils and 20 HNE-positive cells, otherwise was classified into non-eosinophilic nasal polyp (NENP) and absence of tissue neutrophilia (Neulow). RESULTS: In terms of disease control status, NENP-Neulow patients showed the higher rate of disease control than NENP-Neuhigh and ENP-Neuhigh patients. Linear by linear association demonstrated the trend in refractoriness from NENP-Neulow to NENP-Neuhigh or ENP-Neulow to ENP-Neuhigh. When multiple logistic regression was performed, tissue neutrophilia (hazard ratio, 4.38; 95% confidence interval, 1.76-10.85) was found as the strongest risk factor for CRSwNP refractoriness. Additionally, exploratory factor analysis revealed that interleukin (IL)-18, interferon-γ, IL-1Ra, tumor necrosis factor-α, oncostatin M, and MPO were associated with good disease control status, whereas IL-36α and IL-1α were associated with refractory disease control status. In subgroup analysis, HNE-positive cells and IL-36α were significantly upregulated in the refractory group (P = 0.0132 and P = 0.0395, respectively), whereas MPO and IL-18 showed higher expression in the controlled group (P = 0.0002 and P = 0.0009, respectively). Moreover, immunofluorescence analysis revealed that IL-36RâºHNEâº-double positive cells were significantly increased in the refractory group compared to the control group. We also found that the ratio of HNE-positive cells to α1 anti-trypsin was increased in the refractory group. CONCLUSIONS: Tissue neutrophilia had an influence on treatment outcomes in the Asian CRSwNP patients. HNE-positive cells and IL-36α may be biomarkers for predicting refractoriness in Asians with CRSwNP. Additionally, imbalances in HNE and α1 anti-trypsin may be associated with pathophysiology of neutrophilic chronic rhinosinusitis.
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BACKGROUND: Evidence of osteitis is frequently observed in patients with chronic rhinosinusitis (CRS), especially in recalcitrant cases. However, studies focusing on biological markers of osteitis are limited and it remains unclear whether osteitis is associated with different phenotypes of CRS. This study aimed to analyze the expression and assess the roles of receptor activator of nuclear factor κB ligand (RANKL) in patients with CRS and osteitis. METHODS: CRS patients with nasal polyps (CRSwNP, n = 63), CRS patients without nasal polyps (CRSsNP, n = 8), and control subjects (n = 12) were enrolled. Histologic phenotypes, clinical information, and computed tomography (CT) scores were investigated. The Global Osteitis Scoring Scale (GOSS) and RANKL, a molecular marker of bone remodeling, were analyzed in each type of CRS. CRS mouse models were treated with anti-RANKL. RESULTS: GOSS values were significantly higher in all CRS patients than in the control group. The GOSS value in non-eosinophilic CRSwNP was higher than in eosinophilic CRSwNP. RANKL was upregulated whereas decoy receptor osteoprotegerin (OPG) was downregulated in CRS. RANKL messenger RNA (mRNA) and protein levels were positively correlated with GOSS. RANKL/OPG was increased in recurrent cases compared with primary cases. Multiple inflammatory mediators were positively correlated with the protein level of RANKL in CRS tissues. In the mouse CRSwNP model, anti-RANKL treatment abrogated mucosal inflammation and bone remodeling. CONCLUSION: RANKL expression is associated with clinical osteitis and disease severity in CRSwNP. These findings shed light on the importance of RANKL as a potential biomarker of CRS and a key player in CRS pathogenesis.
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Osteíte/metabolismo , Ligante RANK/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adulto , Animais , Biomarcadores/metabolismo , Doença Crônica , Citocinas/metabolismo , Modelos Animais de Doenças , Eosinofilia , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Pólipos Nasais/metabolismo , Pólipos Nasais/patologia , Osteíte/complicações , Osteíte/tratamento farmacológico , Osteíte/patologia , Osteoprotegerina/metabolismo , Ligante RANK/antagonistas & inibidores , Rinite/complicações , Rinite/patologia , Sinusite/complicações , Sinusite/patologiaRESUMO
PURPOSE: To evaluate the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) classification, a clinical scoring system, for predicting disease control status in chronic rhinosinusitis with nasal polyps (CRSwNP) and to investigate prognostic factors. MATERIALS AND METHODS: In total, 134 CRSwNP patients who underwent functional endoscopic sinus surgery after maximal medical treatment were enrolled. These patients were categorized into four groups according to JESREC classification: 1) non-eosinophilic CRSwNP (non-ECRSwNP), 2) mild eosinophilic CRSwNP (ECRSwNP), 3) moderate ECRSwNP, and 4) severe ECRSwNP. Disease control status among the patients was evaluated at 1 year after surgery, and the patients were divided into two groups (disease-controlled and disease-uncontrolled groups) for the investigation of prognostic factors. RESULTS: There was no significant difference in disease control status between non-ECRSwNP and ECRSwNP groups (p=0.970). Age, Lund-Mackay CT scores, global osteitis scores, tissue neutrophil count, and tissue eosinophil count were associated with disease control status. In subgroup analysis of the non-ECRSwNP group, only high tissue neutrophil count was related with disease control status, whereas for the ECRSwNP group, young age, high Lund-Mackay CT scores, high global osteitis scores, and high tissue and blood eosinophil counts were associated with disease control status. CONCLUSION: No difference in disease control status was identified between non-ECRSwNP and ECRSwNP cases. Tissue neutrophilia, however, appeared to be associated with disease control status in non-ECRSwNP cases, whereas tissue and blood eosinophilia was associated with ECRSwNP cases.