RESUMO
BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.
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Asma , Produtos Biológicos , Pólipos Nasais , Rinite , Sinusite , Humanos , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Doença Crônica , Consenso , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Omalizumab/uso terapêutico , Qualidade de Vida , Rinite/complicações , Rinite/tratamento farmacológico , Sinusite/complicações , Sinusite/tratamento farmacológico , Esteroides/uso terapêuticoRESUMO
BACKGROUND: Cellulose powder (CP) has been reported as a safe and effective complementary treatment for allergic rhinitis (AR). Currently, CP has gained increasing application for clinical management worldwide, particularly in China. However, studies focusing on the effect of CP on normal human nasal epithelial cells (hNECs) and ciliary function are lacking. Here, we aimed to explore the adverse effects of CP on the activity and ciliary function of hNECs. METHODS: We biopsied ethmoid sinus or middle turbinate tissues during surgical resection from control subjects who underwent endoscopic sinus surgery for diseases other than AR. Cells were isolated and passaged, followed by differentiation in an air-liquid interface (ALI). Flow cytometry and cell viability test (cell counting kit-8) were performed to detect the cytotoxicity of CP (effects on cell proliferation) on normal hNECs. By using the ALI culture model, we investigated the effects of CP on ciliary beat frequency (CBF). RESULTS: There was a significant reduction in hNEC count at high concentrations of CP (2.5 mg/mL) at days 3 and 7 (both p < 0.05). As the concentration increased, cell death increased progressively from day 3 to day 7. However, these effects were not evident at low concentrations (0.25 mg/mL, p > 0.05). High-dose CP (2.5 mg) significantly reduced the CBF (p < 0.05). At lower concentrations (0.25-2.5 mg/mL), CP initially increased but subsequently reduced the CBF of hNECs compared with control group. CONCLUSIONS: Cytotoxicity and the suppression of ciliary beat at high concentrations justify more prudent use of CP for the management of AR.
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Celulose/farmacologia , Cílios/efeitos dos fármacos , Mucosa Nasal/efeitos dos fármacos , Adulto , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Celulose/efeitos adversos , Celulose/uso terapêutico , Cílios/fisiologia , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Feminino , Humanos , Masculino , Pós , Rinite Alérgica/tratamento farmacológicoRESUMO
BACKGROUND: Glucocorticoids are the first-line medical treatment for chronic rhinosinusitis with nasal polyps (CRSwNP), whose local metabolism is catalyzed by 11ß-HSD1 and 11ß-HSD2. This study investigates the role of 11ß-HSD1 and 11ß-HSD2 on the glucocorticoid response of CRSwNP patients and the pathogenic mechanism of these polyps. METHODS: Forty-three adult CRSwNP patients were enrolled in this study. We evaluated the endoscopic scores by a nasal polyp grading system before and after treatment. We estimated the response to glucocorticoids by the total endoscopic scores. The logistic regression models and inflammatory characteristic curves were conducted to explore the prediction of the response to glucocorticoid in CRSwNP. The expression of 11ß-HSD1 and 11ß-HSD2 on human sinonasal epithelial cells (HSECS) was measured under the stimulation of toll-like receptor agonists and dexamethasone. RESULTS: The endoscopic scores in the CRSwNP group declined, the expression of 11ß-HSD1/11ß-HSD2 increased (r = 0.5276, P = 0.0011), and the cutoff value of the ratio of 11ß-HSD1/11ß-HSD2 was 0.4654 (sensitivity 79.17%, specificity 88.89%). Dexamethasone induced a decrease in the ratio of 11ß-HSD1/11ß-HSD2 (P = 0.049) by the stimulation of PGN-BS. CONCLUSION: We found a strong correlation between the response to glucocorticoids and the ratio of 11ß-HSD1/11ß-HSD2, which could be used as a marker in predicting the level of tissue response to glucocorticoid therapy in CRSwNP. In addition, PGN-BS could also be a therapeutic target, as it is the negative factor that will decrease the sensitivity of glucocorticoids by reducing the ratio of 11ß-HSD1/11ß-HSD2.
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11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , Dexametasona/farmacologia , Pólipos Nasais/enzimologia , Adulto , Biomarcadores/metabolismo , Células Epiteliais/enzimologia , Feminino , Glucocorticoides/farmacologia , Humanos , Masculino , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/patologiaAssuntos
Rinite Alérgica Sazonal , Rinite Alérgica , Celulose , Células Epiteliais , Humanos , NarizRESUMO
BACKGROUND: Chronic rhinosinusitis (CRS) is tightly linked to airway hyperresponsiveness (AHR) and asthma. However, the practical surrogate parameters for evaluating AHR in patients with CRS remain unclear. OBJECTIVE: To evaluate the diagnostic values of sinus computed tomography for AHR in patients with CRS. METHODS: We performed a prospective, single-blinded study of 125 consecutive patients with CRS. These patients were subdivided into AHR and non-AHR (NAHR) groups based on histamine provocation test results. The following parameters were compared between 2 groups of CRS patients: Lund-Mackay scores, olfactory cleft (OC) scores, and serum eosinophil counts. RESULTS: Fifty-seven patients (45.4%) presented with AHR. The OC scores, the ratio of OC scores to total scores, and the eosinophil counts in the AHR group were significantly higher than those in the NAHR group (P < .001). Multivariate logistic regression revealed that OC scores and eosinophil counts were independent risk factors for asymptomatic AHR (OC scores P < .001 and eosinophil counts P = .010). The OC score had a higher predictive value for AHR (area under curve, 0.800) than eosinophil counts (area under the curve, 0.637). When the OC score was 3 or higher, the sensitivity was 75.0%, specificity was 77.9%, and positive predictive value was 68.8%. CONCLUSION: The findings validate a prospective assessment of sinus computed tomography as a screening tool for AHR in patients with CRS.
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Asma/diagnóstico por imagem , Hiper-Reatividade Brônquica/diagnóstico por imagem , Rinite/diagnóstico por imagem , Sinusite/diagnóstico por imagem , Adulto , Asma/complicações , Asma/diagnóstico , Asma/imunologia , Hiper-Reatividade Brônquica/complicações , Hiper-Reatividade Brônquica/diagnóstico , Hiper-Reatividade Brônquica/imunologia , Testes de Provocação Brônquica , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seios Paranasais , Estudos Prospectivos , Rinite/complicações , Rinite/diagnóstico , Rinite/imunologia , Índice de Gravidade de Doença , Método Simples-Cego , Sinusite/complicações , Sinusite/diagnóstico , Sinusite/imunologia , Tomografia Computadorizada por Raios XRESUMO
The surrogate markers for subclassifying eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS remain elusive. We herein performed a cross-sectional study to assess the clinical implication of clinical symptoms, CT findings, blood eosinophil (EOS) examination based on histological examination of tissue eosinophilia in 105 adult CRS patients (including 72 with nasal polyps and 33 without nasal polyps) in southern China. We found the mean score of smell loss was significantly higher in ECRS subgroup than those in non-ECRS subgroup (p < 0.05), whereas the average ethmoid osteitis index in non-ECRS subgroup was significantly higher than that in ECRS subgroup (p < 0.05). Moreover, we found both the mean blood EOS number and ratio were significantly higher in ECRS subgroup than those in non-ECRS subgroup (p < 0.05). By applying receiver operating characteristic (ROC) curve analysis, we found blood EOS number had a sensitivity of 84.9 % and specificity of 84.4 % [area under the curve (AUC): 0.873] at the cutoff level of 0.16 × 10(9)/L, and blood EOS ratio had a sensitivity of 89.0 % and specificity of 84.4 % (AUC: 0.863) at the cutoff level of 2.05 % in this cohort. Our findings indicated that smell loss score, ethmoid osteitis index and blood EOS number and ratio may be used for the differential diagnosis of ECRS as the surrogate markers.
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Eosinofilia , Pólipos Nasais , Rinite , Sinusite , Adulto , Biomarcadores/análise , China/epidemiologia , Doença Crônica , Estudos Transversais , Diagnóstico Diferencial , Eosinofilia/sangue , Eosinofilia/complicações , Eosinofilia/diagnóstico , Eosinofilia/epidemiologia , Eosinofilia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/etiologia , Pólipos Nasais/patologia , Transtornos do Olfato/etiologia , Curva ROC , Rinite/sangue , Rinite/complicações , Rinite/diagnóstico , Rinite/epidemiologia , Rinite/fisiopatologia , Índice de Gravidade de Doença , Sinusite/sangue , Sinusite/complicações , Sinusite/diagnóstico , Sinusite/epidemiologia , Sinusite/fisiopatologiaRESUMO
OBJECTIVE: To evaluate the necessity of nerve sheath incision for the treatment of patients with traumatic optic neuropathy (TON) during endoscopic optic nerve decompression. METHODS: Seventy-four TON patients were enrolled and subjected to endoscopic optic nerve decompression. In 31 TON patients (group A), osseous decompression and nerve sheath incision were performed, and in 43 TON patients (group B), osseous decompression alone was carried out. Visual acuity was evaluated postoperatively. RESULTS: After surgery, visual acuity was improved in 47 of 74 patients, with a total effectiveness ratio of 63.5%. The total ratio of improvement in groups A and B was 61.2 and 65.1%, respectively, and no significant difference was observed (p > 0.05). As to the patients with residual vision preoperatively, the ratio of improvement in groups A and B was 64.2 and 71.4%, respectively (p > 0.05), not favoring nerve sheath incision during endoscopic optic nerve decompression. CONCLUSION: Our preliminary results suggest that during endoscopic optic nerve decompression for the treatment of TON patients, nerve sheath incision is not obligatory for the improvement of visual acuity.
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Endoscopia/métodos , Bainha de Mielina , Procedimentos Neurocirúrgicos/métodos , Traumatismos do Nervo Óptico/cirurgia , Nervo Óptico/cirurgia , Adolescente , Adulto , Descompressão Cirúrgica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Acuidade VisualRESUMO
OBJECTIVE: To evaluate the regulatory effect of corticosteroid on occludin expression in polyp tissues of chronic rhinosinusitis with nasal polyps (CRSwNP) patients and in vitro. METHODS: Twenty CRSwNP patients were enrolled and subjected to prednisone (30 mg/day for 14 days). The expression of occludin in polyp tissues was examined before and after treatment using immunohistochemical staining and quantitative reverse transcription polymerase chain reaction. Moreover, the expression of occludin in polyp-derived epithelial cells (PECs) and human bronchial epithelial cells (BECs) was examined using Western blot analysis in the presence of corticosteroid and/or MKP-1 siRNA, respectively. RESULTS: mRNA and protein expression of occludin in polyp tissues was significantly upregulated after prednisone administration (p < 0.05). Corticosteroids significantly increased MKP-1 and occludin expression in cultured PECs (p < 0.05), and MKP-1 siRNA significantly decreased occludin expression in cultured BECs (p < 0.05). CONCLUSION: Our findings suggest that corticosteroid can promote epithelial occludin expression in nasal polyps through a MKP-1-dependent pathway.
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Glucocorticoides/uso terapêutico , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/metabolismo , Ocludina/metabolismo , Prednisona/uso terapêutico , Adulto , Western Blotting , Brônquios/metabolismo , Células Cultivadas , Células Epiteliais/metabolismo , Feminino , Humanos , Técnicas Imunoenzimáticas , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para CimaRESUMO
Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease ï¼N-ERDï¼ is a chronic respiratory disease characterized by eosinophilic inflammation, featuring chronic rhinosinusitis ï¼CRSï¼, asthma, and intolerance to cyclooxygenase 1 ï¼COX-1ï¼ inhibitors. The use of these medications can lead to an acute worsening of rhinitis and asthma symptoms. This condition has not yet received sufficient attention in China, with a high rate of misdiagnosis and a lack of related research. The Chinese Rhinology Research Group convened a group of leading young experts in otolaryngology from across the country, based on the latest domestic and international evidence-based medical practices to formulate this consensus.The consensus covers the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies for N-ERD, including pharmacotherapy, surgery, biologic treatments, and desensitization therapy. The goal is to improve recognition of N-ERD, reduce misdiagnosis, and enhance treatment outcomes.
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Anti-Inflamatórios não Esteroides , Humanos , Anti-Inflamatórios não Esteroides/efeitos adversos , China , Rinite/diagnóstico , Rinite/terapia , Rinite/induzido quimicamente , Sinusite/diagnóstico , Sinusite/terapia , Sinusite/tratamento farmacológico , Consenso , Asma/diagnóstico , Asma/tratamento farmacológico , Doença CrônicaRESUMO
OBJECTIVE: To evaluate the efficacy of long-term clarithromycin (CAM) treatment in adult Chinese patients suffering from chronic rhinosinusitis without nasal polyps (CRSnNP). METHODS: Thirty-three CRSnNP patients were enrolled and subjected to CAM treatment for 12 weeks (250 mg daily). The total nasal symptom scores (TNSS), nasal resistance and inflammatory mediators including interleukin (IL)-8 and myeloperoxidase (MPO) were evaluated at weeks 0 and 12. Quality of life (QoL) was assessed in all patients by using the Sinonasal Outcome Test 20 and Short Form 36 questionnaires. RESULTS: CAM treatment significantly improved TNSS, nasal resistance and QoL, and it inhibited IL-8 and MPO production in CRSnNP patients (p < 0.05). CAM treatment was more effective for IL-8(high) CRSnNP patients than for IL-8(low) CRSnNP patients (p < 0.05). CONCLUSION: Long-term, low-dose CAM treatment is effective and safe for the treatment of CRSnNP in Chinese patients.
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Claritromicina/uso terapêutico , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , China/epidemiologia , Doença Crônica , Claritromicina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Masculino , Pólipos Nasais , Prevalência , Rinite/complicações , Rinite/epidemiologia , Sinusite/complicações , Sinusite/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Nowadays, the heterogeneity of chronic rhinosinusitis (CRS) has attracted extensive attention. The histological patterns and clinical characteristics may vary greatly in different areas and among different groups of people. Prior studies found a shift from the neutrophilic inflammatory pattern to the eosinophilic inflammatory pattern in Asian cities. This study set out with the aim of investigating the changes that have occurred in the past 18 years of southern China and exploring the causes. METHODS: Tissues, clinical, and demographic characteristics were obtained from 473 patients (91 in 2000-2001, 170 in 2010-2011, 212 in 2017-2018) who satisfied the criteria of diffuse (bilateral) chronic rhinosinusitis. The clinical characteristics, including the previous history of allergic rhinitis and asthma, and the major symptoms of rhinosinusitis, were collected. Formalin-fixed nasal tissue was obtained from each patient for calculating inflammatory cells. We also performed immunohistochemistry to evaluate the expression levels of eosinophilic cationic protein (ECP), IgE, myeloperoxidase (MPO), and other Type 1, Type 2, and Type 3 related inflammatory cytokines. RESULTS: The comorbidity of asthma and atopic disease was higher in 2017-2018 compared to 2000-2001. The histological characteristics revealed a significant increase in tissue eosinophils and decrease in neutrophils in 2017-2018 as compared with 2000-2001. Meanwhile, the proportion of eosinophilic CRS (eCRS) increased significantly from 2000 to 2001 to 2017-2018 (P = 0.03). The tissue eosinophil increase was higher in overweight patients (Body Mass Index, BMI≥24) as compared with non-overweight. There was an increasing trend of ECP, IL-13 and IL-17. Besides, IFN-γ and TNF-α decreased. CONCLUSIONS: There was an eosinophilic shift of diffuse rhinosinusitis inflammatory pattern in southern China over the last 18 years. The proportion of eCRS and difficult-to-treat rhinosinusitis has steadily increased, which is associated with the increase of Type 2, Type 3 cytokines and the decrease of Type 1 cytokines. This study also provided firstly evidence of a strong relationship between overweight and eosinophil shift in the southern Chinese population.
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OBJECTIVE: This study was designed to determine whether nasal saline irrigation improved the symptoms and signs of allergic rhinitis (AR) and whether nasal saline irrigation could be used as a complementary management of AR in children while less steroids were used. METHOD: 26 children with AR were divided into three groups and were given nasal saline irrigation and/or topical steroid. Symptoms and signs of AR and mucociliary clearance (MCC) were evaluated, and concentration of soluble intercellular adhesion molecule (sICAM)-1 in nasal secretion was detected. RESULTS: In AR children treated with nasal irrigation and tapered topical steroid at week 8 and week 12, a significant improvement in symptoms and signs was observed, and a significant decrease in the mean values of MCC and the mean concentrations of sICAM-1 in nasal secretions was also detected. CONCLUSION: Nasal saline irrigation can be viewed as a good adjunctive treatment option for AR. It permitted the use of less topical steroids for controlling AR in children, which will contribute to fewer side effects and less economic burden.
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Anti-Inflamatórios/administração & dosagem , Budesonida/administração & dosagem , Glucocorticoides/administração & dosagem , Lavagem Nasal , Cloreto de Sódio/administração & dosagem , Administração Tópica , Adolescente , Aerossóis , Criança , Relação Dose-Resposta a Droga , Esquema de Medicação , Sinergismo Farmacológico , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Depuração Mucociliar , Mucosa Nasal/metabolismo , Concentração Osmolar , Rinite Alérgica Perene/tratamento farmacológico , Rinite Alérgica Perene/fisiopatologia , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the outcome of transnasal endoscopic optic nerve decompression (TEOND) for traumatic optic neuropathy (TON). METHODS: The clinical data of 155 consecutive patients with TON treated with TEOND after failure of mega-dose steroid therapy were retrospectively analyzed, their outcomes were summarized after follow-up, and then Logistic regression was used to analyze the prognosis-related information to explore the factors influencing prognosis. RESULTS: Patients were followed up for 3 - 60 months. The total effective rate of the 155 patients was 44.5%. The effective rate of the patients with light perception or better vision was 87.5%, much higher than that of the patients without light perception (29.6%). Eyesight was improved, mostly occurring 1 - 5 days after operation and lasting for 1 - 3 months, in 69 patients. Residual vision degree after trauma (OR = 0.04) and the interval between injury and surgery (OR = 4.62) were significant prognostic factors of the general effect (P < 0.01), and the gradual or immediate visual loss history (OR = 0.22) and the interval between injury and surgery (OR = 6.34) were significant to the outcomes of the patients with no light perception (P < 0.05). Sex, age, duration of coma after trauma, pre- and post-operative duration of steroid treatment, operators, fracture site of optic canal, and nerve sheath incision were not correlated to the outcomes of patients (all P > 0.05). Intraoperative cerebrospinal fluid rhinorrhea and postoperative transient visual loss occurred in one and the other two cases, respectively, but these conditions were resolved successfully. CONCLUSION: TEOND is effective and safe for TON patients, but the visual outcome is poor for the immediate blindness cases. The surgery is indicated for the patients with some residual vision or with a gradual visual loss and is suggested to perform early within seven days after injury.
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Descompressão Cirúrgica/métodos , Endoscopia , Traumatismos do Nervo Óptico/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemAssuntos
Asma/epidemiologia , Eosinofilia/epidemiologia , Osteopontina/sangue , Rinite Alérgica Perene/epidemiologia , Rinite Alérgica Sazonal/epidemiologia , Adulto , Asma/sangue , Asma/diagnóstico , Biomarcadores/sangue , Circulação Sanguínea , Degranulação Celular , Células Cultivadas , China , Comorbidade , Eosinofilia/sangue , Feminino , Humanos , Interleucina-5/sangue , Masculino , Pessoa de Meia-Idade , Rinite Alérgica Perene/sangue , Rinite Alérgica Sazonal/sangue , Adulto JovemAssuntos
Asma/epidemiologia , Rinite/complicações , Sinusite/complicações , Adulto , China/epidemiologia , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
Damage to the mucociliary clearance system is a typical change in the pathogenesis in chronic rhinosinusitis. However, the mechanisms underlying cilia loss remain unclear. WDPCP is a key protein essential for ciliogenesis, and is also an effector of the planar cell polarity signaling system. In this study, we sought to determine the role of WDPCP in cilia loss in patients with chronic rhinosinusitis. We demonstrated the expression of WDPCP in human sinonasal epithelium from patients with chronic rhinosinusitis and control subjects. We also used air-liquid interface to culture primary human sinonasal epithelial cells in-vitro model and to investigate WDPCP function. We then explored links between rhinosinusitis, WDPCP and inflammation. Accompanied with cilia loss, expression of WDPCP in human sinonasal epithelium from patients with chronic rhinosinusitis was decreased significantly compared with control subjects. In vitro study, we found that WDPCP level increased at first, and then decreased. Inhibiting WDPCP expression could lead to the poor quantity and length of cilia with reduced expression of Septin7. Also, Th1 type inflammatory mediators could decrease the expression of WDPCP. In conclusion, inflammatory cytokines cause reduced WDPCP expression, which contributes to impaired ciliogenesis in human rhinosinusitis.
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Cílios/metabolismo , Glicoproteínas/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adulto , Doença Crônica , Cílios/patologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Glicoproteínas/biossíntese , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Pessoa de Meia-Idade , Rinite/patologia , Sinusite/patologiaRESUMO
OBJECTIVE: To evaluate the expression and possible modulation of heme oxygenase-1 (HO-1) in nasal polyps of patients with chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Nasal polyps and uncinate process tissues were collected from 25 CRSwNP patients and 19 healthy controls with nasal septal deviation. HO-1 expression was examined using qRT-PCR, immunohistochemistric staining and Western blot analysis. Moreover, additional uncinate process mucosal samples of 15 healthy controls with nasal septal deviation were harvested for nasal explant culture experiments. HO-1 expression was measured in cultured nasal explant in response to specific inflammatory and glucocorticoid stimulation. SPSS 20.0 software was used to analyze the data. RESULTS: The mRNA and protein expression of HO-1 was significantly increased in polyp tissues, 1.220±0.397 in mRNA and 1.409±0.701 in protein, compared with healthy controls 0.464±0.318 in mRNA and 0.017±0.1147 in protein (U=22.00 in mRNA and U=1.00 in protein, both P< 0.05). The immunohistochemical results showed that HO-1 was mainly distributed in the epithelial layer, submucosal glands and inflammatory cells in nasal tissues. Nasal explant culture experiments demonstrated that HO-1 mRNA was upregulated by IL-17A. The HO-1 mRNA level before the stimulation was 1.000, and 17.264±4.275 after the stimulation of 1 ng/ml IL-17A (U=0, P<0.05), 19.128±4.605 after the stimulation of 10 ng/ml IL-17A (U=0, P<0.05), but was significantly suppressed after stimulation with glucocorticoids (dexamethasone, DEX). The mRNA level after the glucocorticoids stimulation was 0.370±0.101 (U=0, P<0.05) and 0.316±0.167 (U=0, P<0.05) respectively. Furthermore, the HO-1 mRNA was inhibited by TGF-ß1, the mRNA level was 0.217±0.322 (U=0, P<0.05), 0.070±0.070 (U=0, P<0.05), respectively. CONCLUSION: Increased HO-1 expression may play a role in the pathogenesis of CRSwNP, which may be considered as the therapeutic target.
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Glucocorticoides/farmacologia , Heme Oxigenase-1/metabolismo , Pólipos Nasais/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Western Blotting , Estudos de Casos e Controles , Doença Crônica , Dexametasona/farmacologia , Humanos , Interleucina-17/farmacologia , Pólipos Nasais/complicações , RNA Mensageiro/metabolismo , Rinite/complicações , Sinusite/complicações , Técnicas de Cultura de Tecidos , Fator de Crescimento Transformador beta1/metabolismoRESUMO
BACKGROUND: Cysteinyl leukotriene (LT) has been proposed in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). This study sought to examine the expression of the LT receptor (LTR) in CRSwNP patients and evaluate the potential role of LTR antagonist (LTRA) in the management of eosinophilic CRSwNP (ECRS) patients. METHODS: Nasal polyps and uncinate process tissues were collected from 18 ECRS patients, 13 non-eosinophilic CRSwNP (non-ECRS) patients, and 16 control subjects. The messenger RNA (mRNA) and protein expression of LTR (cysteinyl leukotriene receptor 1 [CysLT1R] and cysteinyl leukotriene receptor 2 [CysLT2R]) was examined using quantitative reverse-transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, and Western blot analysis. Moreover, the effects of LTRA and steroids on total nasal symptom scores (TNSS) of uncontrolled ECRS patients were evaluated. RESULTS: The mRNA and protein expression of CysLT1R and CysLT2R was significantly increased in polyp tissues compared with healthy controls (p < 0.05). Compared with the non-ECRS subset, the ECRS subset showed significantly increased expression of CysLT1R and CysLT2R, as well as leukotriene C4 (LTC4) and leukotriene D4 (LTC4) levels (p < 0.05). Moreover, combined LTRA and steroids significantly decreased TNSS more than steroids alone in uncontrolled ECRS patients (p < 0.01). CONCLUSION: Our findings indicate that LTR was differentially expressed between ECRS and non-ECRS patients, and that LTRA may be used as an additional therapy for ECRS patients.
Assuntos
Acetatos/uso terapêutico , Antagonistas de Leucotrienos/uso terapêutico , Leucotrienos/metabolismo , Pólipos Nasais/metabolismo , Quinolinas/uso terapêutico , Receptores de Leucotrienos/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adulto , Anti-Inflamatórios/uso terapêutico , Biomarcadores/metabolismo , Western Blotting , Budesonida/uso terapêutico , Estudos de Casos e Controles , Doença Crônica , Ciclopropanos , Quimioterapia Combinada , Eosinófilos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rinite/complicações , Rinite/tratamento farmacológico , Sinusite/complicações , Sinusite/tratamento farmacológico , Sulfetos , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the application of Chinese guideline for the diagnosis and treatment of chronic rhinosinusitis (2008, Nanchang) on a national scale. METHODS: The contents of the guideline and its relevant applied indicators were designed into an initial questionnaire and, after a pre-survey, revised into a formal questionnaire. Then a stratified sampling was selected out of otolaryngology practitioners in the different level hospitals across the country. After a uniform training, the investigators were sent to these different hospitals to conduct questionnaire survey by face to face interview with otolaryngology respondents. Based on the summarized data, statistical analyses on the awareness and practice status of the guideline, together with their influencing factors, were made. SPSS 16.0 software was used to analyze the data. RESULTS: Issuing and withdrawing questionnaires were performed from December 2012 to June 2013 and 1 240 respondents in 350 hospitals from 30 different provinces, municipalities or autonomous regions were effectively investigated. An average awareness and practice rate of 48.7% and 40.8% upon the guideline was acquired, respectively. There was a significant correlation (r = 0.280, P = 0.000) between the two indicators. With linear regression, county-level hospitals, junior practitioners, non-rhino professionals were the risk factors of poor guideline adherence. In addition, respondents form western region showed lower awareness and practice rate than that of ones from central and eastern region. CONCLUSION: The adherence on Chinese guideline for the diagnosis and treatment of chronic rhinosinusitis is nationally low, so popularization of activities should be urgently strengthened, especially in focus areas, focus hospitals, and focus groups.
Assuntos
Sinusite/terapia , Doença Crônica/terapia , Fidelidade a Diretrizes , Humanos , Guias de Prática Clínica como Assunto , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To evaluate the efficacy of clarithromycin (CAM) treatment in adult Chinese patients suffering from chronic rhinosinusitis with nasal polyps (CRSwNP) or without nasal polyps (CRSsNP). METHODS: A prospective, open and self-controlled clinical trial on patients with CRS was conducted. Fifty patients met inclusion criteria. Of 50 patients, there were 33 patients with CRSsNP and 17 patients with CRSwNP. CAM was administered at 250 mg/d and the duration of administration was 12 weeks. Outcome measures included assessments of visual analogue scale (VAS), the sino-nasal outcome test-20(SNOT-20), the medical outcomes study short-form 36 items(SF-36), Lund-Kennedy endoscopy score, and Lund-Mackay computed tomography score. Before starting the treatment, 2 months after treatment and at the end of treatment, each patient had to complete all the measures except Lund-Mackay computed tomography score, which was only conducted before and after treatment. In order to evaluate the safety of CAM, liver function and renal function in all patients were detected before and after treatment. SPSS 16.0 software was used to analyze the data. RESULTS: Forty-five patients completed 3 months follow-up and 5 patients withdrew due to different reasons. The results were as follows: (1) Thirty-three patients with CRSsNP's VAS scores of four time point were 5.81 ± 1.69, 3.76 ± 1.94, 2.98 ± 1.95, 2.06 ± 2.13, respectively, there were statistically significant improvements in turn (t values were 5.910, 8.090, 8.932, all P < 0.05). Endoscopy score of four time point were 6.28 ± 1.28, 5.00 ± 1.67, 4.12 ± 1.76, 3.12 ± 2.19, respectively, there were statistically significant improvements in turn compared with before treatment (t values were 6.662, 9.161, 9.936, all P < 0.05). The CT scores before and after treatment were 10.33 ± 4.65 and 4.67 ± 4.59, respectively (t = 7.226, P = 0.000) . (2) Seventeen patients with CRSwNP's VAS scores of four time point were 6.07 ± 2.02, 4.87 ± 2.61, 4.06 ± 2.85, 4.08 ± 2.80, respectively, there were statistically significant improvements after 2 or 3 months (t values were 3.285, 3.468, both P < 0.05) except after one month (t = 1.846, P > 0.05). Endoscopy score of four time point were 10.65 ± 1.77, 9.35 ± 1.93, 8.65 ± 2.76, 8.47 ± 2.76, respectively, there were statistically significant improvements in turn(t values were 4.068, 4.863, 5.156, all P < 0.05). The CT scores before and after treatment were 13.82 ± 4.94 and 11.41 ± 5.12, respectively (t = 3.975, P = 0.001). (3) During the period of CAM treatment, 1 patient reported a tolerable headache and weakness and 1 patient had abdominal pain after two months treatment, all the symptoms disappeared while they were asked to stop the drug. Liver function and renal function were detected in 40 patients, the differences before and after treatment were not significant statistically. CONCLUSIONS: Long-term, low-dose CAM treatment is effective in the treatment of CRSsNP and CRSwNP in Chinese patients. Meanwhile, the efficacy of CAM is more significant in polyp-free group compared with polyp group. Low does CAM therapy is safe, and the liver function and renal function does not worsen after 3 months treatment.