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1.
Mol Med Rep ; 23(6)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33899116

RESUMO

In the process of nasal tissue remodeling, nasal fibroblasts serve an important role via myofibroblast differentiation and the production of extracellular matrix (ECM). Nasal fibroblast abnormalities can lead to conditions such as chronic rhinosinusitis. Salvianolic acid B (Sal B), a water-soluble active pharmaceutical compound extract from the root of the traditional Chinese medicine Salvia miltiorrhiza, displays antioxidative, antiproliferative and antifibrosis properties. The present study aimed to investigate the mechanism underlying the effects of Sal B on nasal polyp fibroblast (NPF) myofibroblast differentiation and ECM accumulation. Primary NPFs were obtained from nasal polyps of patients with chronic sinusitis. The proliferative and cytotoxic effects of Sal B on NPFs were evaluated by performing the Cell Counting Kit-8 assay. The Transwell assay was conducted to assess cell migration. α-smooth muscle actin (α-SMA), TGF-ß1 receptor (TßR)-I, TßR-II, Smad2/3 mRNA and protein expression levels and (p)-Smad2/3 phosphorylation levels were measured via reverse transcription-quantitative PCR and western blotting, respectively. Type III collagen and fibronectin levels were analyzed by ELISA. The results indicated that Sal B significantly downregulated TGF-ß1-induced α-SMA, fibronectin and collagen III expression levels in NPFs. Similarly, Sal B significantly decreased TGF-ß1-induced TßR-I, TßR-II, p-Smad2/3, MMP-2 and MMP-9 mRNA and protein expression levels in NPFs. Furthermore, Sal B significantly decreased TGF-ß1-induced NPF migration. Therefore, the present study indicated that Sal B inhibited myofibroblast differentiation and ECM accumulation in nasal fibroblasts, suggesting that Sal B may inhibit nasal polyp formation via certain mechanisms.


Assuntos
Benzofuranos/farmacologia , Diferenciação Celular , Matriz Extracelular/metabolismo , Miofibroblastos/efeitos dos fármacos , Pólipos Nasais/metabolismo , Transdução de Sinais , Actinas/metabolismo , Adulto , Proliferação de Células , Células Cultivadas , Matriz Extracelular/efeitos dos fármacos , Feminino , Humanos , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Miofibroblastos/citologia , Miofibroblastos/metabolismo , Pólipos Nasais/patologia , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/metabolismo
2.
Artigo em Chinês | MEDLINE | ID: mdl-33794605

RESUMO

Objective:To investigate the roles of nasal nitric oxide(nNO) in diagnosis and endotypes of CRSwNP. Methods:Eighty-two CRSwNP patients and thirty healthy volunteers were recruited for this study. The patients were classified into eosinophilic CRSwNP (Eos CRSwNP) and non-eosinophilic CRSwNP (non-Eos CRSwNP) endotypes by tissue eosinophil percentage. nNO levels were measured with an electrochemical sensor-based device. nNO levels and clinical factors were compared among the groups. Receiver-operating characteristic (ROC) curve and logistic regression analyses were performed to evaluate the predictive ability of the nNO for diagnosis and endotypes of CRSwNP. Results:Eos CRSwNP patients(143.9±106.2) ×10-9 had lower nNO levels than non-Eos CRSwNP[(228.3±109.2) ×10-9, P=0.000 9) and healthy subjects(366.5±88.0) ×10-9, P<0.000 1). Patients with atopy exhibited significantly higher levers of nNO compared with patients without atopy(P<0.05). For Eos CRSwNP diagnosis, nNO had the highest predictive value(AUC: 0.939; sensitivity: 76.74%; specificity: 96.67%; cut-off value: 231×10-9, P<0.001). Furthermore, nNO levels were associated with CRSwNP endotypes(odds ratio: 1.010; 95% confidence interval: 1.003%, 1.016%; P=0.002). When the nNO concentration was 158 ×10-9, we could discriminate Eos CRSwNP from non-Eos CRSwNP(AUC=0.710, sensitivity: 76.92%; specificity, 60.47%, P=0.001). After it was combinated by nNO, periphera blood eosinophil count(PEAC) and VAS score, the AUC was increased to 0.894(95%CI=0.807 to 0.951, P<0.000 1, sensitivity: 76.74%, specificity: 89.74%). Conclusion:nNO may has potential for non-invasive diagnosis and endotype of CRSwNP. nNO combined with PEAC and VAS score may be an ideal diagnostic tool for endotyps of Eos CRSwNP. However, the atopic status of the patients influenced the levels of nNO.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Doença Crônica , Eosinófilos/patologia , Humanos , Pólipos Nasais/diagnóstico , Pólipos Nasais/patologia , Óxido Nítrico , Rinite/diagnóstico , Rinite/patologia , Sinusite/diagnóstico , Sinusite/patologia
3.
Artigo em Chinês | MEDLINE | ID: mdl-33730810

RESUMO

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.


Assuntos
Pólipos Nasais , Rinite , Adulto , China , Doença Crônica , Células Epiteliais , Feminino , Humanos , Hipóxia/patologia , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Rinite/patologia
4.
BMJ Case Rep ; 14(1)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431532

RESUMO

Woakes' syndrome (WS) is a rare entity, defined as severe recalcitrant nasal polyposis with consecutive deformity of the nasal pyramid. WS occurs mainly in childhood and its aetiology remains unclear. We report a case of a 68-year old woman, with aspirin-exacerbated respiratory disease, who presented with recurrent nasal polyposis and progressive broadening of the nasal dorsum. CT scan revealed extensive bilateral nasal polyposis and diffuse osteitis, with anterior ethmoidal calcified lesions. The patient underwent revision endoscopic sinus surgery and nasal pyramid deformity was successfully managed without osteotomies.


Assuntos
Sinusite Etmoidal/diagnóstico , Pólipos Nasais/diagnóstico , Deformidades Adquiridas Nasais/etiologia , Administração Intranasal , Idoso , Biópsia , Endoscopia , Seio Etmoidal/diagnóstico por imagem , Seio Etmoidal/patologia , Seio Etmoidal/cirurgia , Sinusite Etmoidal/complicações , Sinusite Etmoidal/patologia , Sinusite Etmoidal/terapia , Feminino , Glucocorticoides , Humanos , Mucosa Nasal/diagnóstico por imagem , Mucosa Nasal/patologia , Mucosa Nasal/cirurgia , Pólipos Nasais/complicações , Pólipos Nasais/patologia , Pólipos Nasais/terapia , Recidiva , Síndrome , Tomografia Computadorizada por Raios X
5.
Am J Otolaryngol ; 42(1): 102795, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33128996

RESUMO

In chronic rhinosinusitis (CRS), endotyping, being based on the pathogenic mechanism, provides a precise picture appropriate for use in clinical practice. Structured histopathological examination of CRS is considered a necessary step in efforts to establish its pathogenesis and improve our endotyping capabilities. Herein we discuss the associations between histopathology and clinical characteristics of CRS patients to assist medical and surgical treatment choices.


Assuntos
Planejamento de Assistência ao Paciente , Rinite/patologia , Rinite/cirurgia , Sinusite/patologia , Sinusite/cirurgia , Corticosteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Asma , Doença Crônica , Endoscopia/métodos , Eosinófilos/patologia , Humanos , Hipersensibilidade , Inflamação , Mucosa Nasal/patologia , Pólipos Nasais/diagnóstico , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/patologia , Pólipos Nasais/cirurgia , Procedimentos Cirúrgicos Nasais/métodos , Rinite/diagnóstico , Rinite/tratamento farmacológico , Sinusite/diagnóstico , Sinusite/tratamento farmacológico
6.
Artigo em Chinês | MEDLINE | ID: mdl-32610404

RESUMO

Objective: To investigate the expression and cellular provenance of interleukin 17A (IL-17A) in non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP), and to analyze the possible reasons for its different expression. Methods: Samples were collected from 14 patients with eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and 28 patients with nECRSwNP, who underwent functional endoscopic sinus surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to May 2018, including 33 males and 9 females, with the age ranging from 18 to 65 years old. Enzyme linked immune sorbent assay (ELISA) and flow cytometry were used to investigate the expression and cellular origins of IL-17A in the nasal tissue of ECRSwNP and nECRSwNP groups. Then the difference of quantity and differentiation ability of the major cells producing IL-17A between ECRSwNP and nECRSwNP groups were analyzed by flow cytometry. Finally, the expressions of IL-6, transforming growth factor-ß(TGF-ß), and IL-23, which were considered as the important factors in promoting Th17/Tc17 differentiation in CRSwNP and their correlation with IL-17A, were analyzed by ELISA. Statistical analysis was performed using IBM SPSS 20. Results: The IL-17A protein levels and IL-17A(+)lymphocyte percentages were higher in nECRSwNP group compared with that of the ECRSwNP group (158.56 (167.76) pg/ml (M(QR)) vs. 9.42 (11.33) pg/ml, 10.21%±1.54% (x±s) vs. 3.93%±0.80%, Z=2.95, t=3.62, all P<0.01). Tc17 cells (CD8(+)T cells producing IL-17A) and Th17 cells (CD4(+)T cells producing IL-17A) were major IL-17A producers in both ECRSwNP and nECRSwNP group. Further analysis revealed that there was no significant difference in quantity of CD8(+)and CD4(+)T cells between ECRSwNP and nECRSwNP group, but the differentiation ability about CD8(+)and CD4(+)T cells differentiating into Tc17 and Th17 in nECRSwNP group was stronger than that in ECRSwNP. The high expressions of IL-6 and TGF-ß, which were considered as the important factors in promoting Th17/Tc17 differentiation were also found in nECRSwNP group compared with ECRSwNP (56.07 (234.25) pg/ml vs. 8.27 (12.51) pg/ml, (5.44±0.34) pg/ml vs. (4.17±0.22) pg/ml, Z=2.426, t=2.29, all P<0.05). But the difference in expression of IL-23 was not significant difference between the two groups. Moreover, the expression of IL-17A showed significantly positive correlation with IL-6 (r=0.615, P=0.009). No positive correlation between IL-17A and TGF-ß or IL-23 was observed. Conclusions: The expression of IL-17A in nasal mucosa of nECRSwNP patients is significantly higher than that of ECRSwNP, which is due to the increase of expression and differentiation of Tc17/Th17 cells. IL-17A shows positive correlation with IL-6 in CRSwNP, which is the important factor in promoting Th17/Tc17 differentiation.


Assuntos
Interleucina-17 , Pólipos Nasais , Rinite , Sinusite , Adolescente , Adulto , Idoso , Doença Crônica , Feminino , Humanos , Interleucina-17/metabolismo , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Pólipos Nasais/metabolismo , Pólipos Nasais/patologia , Rinite/metabolismo , Rinite/patologia , Sinusite/metabolismo , Sinusite/patologia , Adulto Jovem
7.
Ann Allergy Asthma Immunol ; 125(3): 304-310.e1, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32387168

RESUMO

BACKGROUND: Predicting postoperative olfactory decline in patients with chronic rhinosinusitis (CRS) remains a considerable challenge. OBJECTIVE: To evaluate patterns of postoperative olfactory function in patients with CRS and explore potential predictors of postoperative olfactory decline. METHODS: A total of 76 patients with CRS electing endoscopic sinus surgery (ESS) were enrolled in this prospective study. Olfaction was assessed with Sniffin' Sticks preoperatively and 3 months postoperatively. Preoperative peripheral venous blood and superior turbinate at surgery were collected for eosinophil quantification. Olfactory cleft was evaluated by computed tomography and endoscopy. Postoperative olfactory decline was defined by a decrease in threshold-discrimination-identification (TDI) score more than 0 point. Multivariable logistic regression analysis was conducted to identify potential predictors associated with postoperative olfactory decline in TDI score. RESULTS: A total of 30.26% of patients with CRS (23/76) presented with olfactory decline 3 months post-ESS. Patients with CRS with olfactory decline showed significantly higher preoperative tissue eosinophils (P < .001), blood eosinophil count (P = .002), blood eosinophil percentage (P = .009), and preoperative TDI scores (P = .017) than patients with CRS without olfactory decline. After adjusting for patient demographics and comorbidities, the preoperative tissue eosinophilia was significantly associated with patients with CRS with postoperative olfactory decline (odds ratio = 1.103; P = .038). An absolute count of 23.5 eosinophils per high-power field in superior turbinate was the best predictor of olfactory decline with the highest area under the receiver operating characteristic curve of 0.901. CONCLUSION: Superior turbinate eosinophilia is highly associated with olfactory decline in patients with CRS 3 months after ESS.


Assuntos
Eosinofilia/etiologia , Transtornos do Olfato/etiologia , Complicações Cognitivas Pós-Operatórias/etiologia , Rinite/etiologia , Sinusite/complicações , Conchas Nasais/patologia , Doença Crônica , Endoscopia/métodos , Eosinofilia/patologia , Eosinófilos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/patologia , Transtornos do Olfato/patologia , Complicações Cognitivas Pós-Operatórias/patologia , Período Pré-Operatório , Rinite/patologia , Sinusite/patologia , Sinusite/cirurgia , Olfato/fisiologia
8.
J Allergy Clin Immunol ; 145(3): 740-750, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32145873

RESUMO

Chronic rhinosinusitis (CRS) is one of the most common chronic diseases worldwide. It is a heterogeneous disease, and geographical or ethnic differences in inflammatory pattern in nasal mucosa are major issues. Tissue eosinophilia in CRS is highly associated with extensive sinus disease, recalcitrance, and a higher nasal polyp (NP) recurrence rate after surgery. The prevalence of eosinophilic CRS (ECRS) is increasing in Asian countries within the last 2 decades, and this trend appears to be occurring across the world. International consensus criteria for ECRS are required for the accurate understanding of disease pathology and precision medicine. In a multicenter large-scale epidemiological survey, the "Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis study," ECRS was definitively defined when the eosinophil count in nasal mucosa is greater than or equal to 70 eosinophils/hpf (magnification, ×400), and this study proposed an algorithm that classifies CRS into 4 groups according to disease severity. The main therapeutic goal with ECRS is to eliminate or diminish the bulk of NP tissue. NPs are unique abnormal lesions that grow from the lining of the nasal and paranasal sinuses, and type 2 inflammation plays a critical role in NP development in patients with ECRS. An imbalance between protease and endogenous protease inhibitors might play a pivotal role in the initiation and exacerbation of type 2 inflammation in ECRS. Intraepithelial mast cells in NPs, showing a tryptase+, chymase- phenotype, may also enhance type 2 inflammation. Intense edema and reduced fibrosis are important histological features of eosinophilic NPs. Mucosal edema mainly consists of exuded plasma protein, and excessive fibrin deposition would be expected to contribute to the retention of proteins from capillaries and thereby perpetuate mucosal edema that may play an etiological role in NPs. Upregulation of the coagulation cascade and downregulation of fibrinolysis strongly induce abnormal fibrin deposition in nasal mucosa, and type 2 inflammation plays a central role in the imbalance of coagulation and fibrinolysis.


Assuntos
Fibrina/metabolismo , Inflamação/imunologia , Inflamação/patologia , Pólipos Nasais/imunologia , Pólipos Nasais/patologia , Doença Crônica , Eosinófilos/imunologia , Eosinófilos/patologia , Humanos , Imunidade Inata/imunologia , Inflamação/metabolismo , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Pólipos Nasais/metabolismo , Rinite/imunologia , Rinite/metabolismo , Rinite/patologia , Sinusite/imunologia , Sinusite/metabolismo , Sinusite/patologia
9.
Respir Med ; 162: 105871, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32056672

RESUMO

BACKGROUND: Nasal polyps are a significantly associated pathology of chronic rhinosinusitis (CRS) whose mechanisms of pathogenesis are not fully elucidated, especially the interaction of the polyp with its environment that allows its growth on the nasal epithelial lining. Exosomes are nanovesicles that serve important biological functions, including cell-to-cell signaling and communication. OBJECTIVE: Hence, we sought to explore the roles of the epithelial-derived exosomal proteome obtained from the human nasal epithelium in the modulation of CRS with nasal polyp (CRSwNP) pathogenesis. METHODS: We sampled exosomes from nasal lavage fluid and primary human nasal epithelial cells (hNECs) from healthy controls and patients with CRSwNP with and without coexisting asthma. The presence of exosomes was confirmed using a NanoSight assay, transmission electron microscopy and western blotting. The exosomal proteome was profiled with mass spectrometry. The Cell Counting Kit-8 was used to confirm the roles of exosomes in mediating cellular proliferation. RESULTS: The hNEC-derived exosomes from diseased epithelium contained differentially expressed proteins that were mainly involved in epithelial remodeling via pathways such as p53. An in vitro study further demonstrated that epithelial-derived exosomes from patients with CRSwNP (with and without coexisting asthma) significantly reduced the rate of proliferation of control hNECs at an effective concentration of ≥10 µg/ml. CONCLUSIONS: Exosomes secreted by hNECs from patients with CRSwNP, regardless of their coexistence with asthma, are laden with proteins that influence cell proliferation pathways, potentially leading to remodeling of the sinonasal mucosa.


Assuntos
Proliferação de Células , Exossomos/fisiologia , Pólipos Nasais/etiologia , Pólipos Nasais/patologia , Proteômica , Transdução de Sinais/fisiologia , Asma/complicações , Comunicação Celular , Células Epiteliais , Exossomos/genética , Humanos , Espectrometria de Massas , Mucosa Nasal/citologia , Pólipos Nasais/complicações
10.
Indian J Pathol Microbiol ; 63(1): 106-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32031135

RESUMO

Monotypic angiomyolipoma is usually found in the kidneys and is composed predominantly of epithelioid cells which show positivity for melanocyte and smooth muscle markers. It can pose a diagnostic challenge due to a range of differential diagnosis. We report the second case of monotypic angiomyolipoma of nasal cavity and first from India in a 54-year-old male who presented with a nasal polyp. Grossly the tumor was well circumscribed and un-encapsulated. Microscopy showed a large number of epithelioid cells mixed with a few spindle cells, varying sized blood vessels, and focal areas of adipose tissue. Immunohistochemistry was positive for smooth muscle actin (SMA) and human melanoma black (HMB-45) stains. It is important to identify this tumor as it can sometimes be mistaken for malignancy and only needs endoscopic resection.


Assuntos
Angiomiolipoma/diagnóstico por imagem , Epistaxe/etiologia , Cavidade Nasal/patologia , Neoplasias Nasais/diagnóstico por imagem , Biomarcadores Tumorais , Diagnóstico Diferencial , Técnicas Histológicas , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/diagnóstico por imagem , Pólipos Nasais/patologia , Neoplasias Nasais/cirurgia , Tomografia Computadorizada por Raios X
11.
Ann Allergy Asthma Immunol ; 124(4): 333-341, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32007569

RESUMO

OBJECTIVE: To review the latest discoveries on airway epithelial cell diversity and remodeling in type 2 inflammation, including nasal polyposis. DATA SOURCES: Reviews and primary research manuscripts were identified from PubMed, Google, and Bioarchives, using the search words airway epithelium, nasal polyposis, or chronic rhinosinusitis with nasal polyposis AND basal cell, ciliated cell, secretory cell, goblet cell, neuroendocrine cell, pulmonary neuroendocrine cell, ionocyte, brush cell, solitary chemosensory cell, microvillus cell, or tuft cell. STUDY SELECTIONS: Studies were selected based on novelty and likely relevance to airway epithelial innate immune functions or the pathobiology of type 2 inflammation. RESULTS: Airway epithelial cells are more diverse than previously appreciated, with specialized subsets, including ionocytes, solitary chemosensory cells, and neuroendocrine cells that contribute to important innate immune functions. In chronic rhinosinusitis with nasal polyposis, the composition of the epithelium is significantly altered. Loss of ciliated cells and submucosal glands and an increase in basal airway epithelial progenitors leads to loss of innate immune functions and an expansion of proinflammatory potential. Type 2 cytokines play a major role in driving this process. CONCLUSION: Airway epithelial remodeling in chronic rhinosinusitis is extensive, leading to loss of innate immune function and enhanced proinflammatory potential. The mechanisms driving airway remodeling and its sequelae deserve further attention before restitution of epithelial differentiation can be considered a reasonable therapeutic target.


Assuntos
Remodelação das Vias Aéreas , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Rinite/patologia , Sinusite/patologia , Doença Crônica , Humanos , Inflamação/imunologia , Inflamação/patologia , Mucosa Nasal/imunologia , Pólipos Nasais/imunologia , Rinite/imunologia , Sinusite/imunologia
12.
Eur J Histochem ; 64(1)2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31988531

RESUMO

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent sinonasal mucosa inflammatory disease with still unclear pathophysiologic mechanisms that imply events of tissue repair and structural remodelling. Several cascades seem to have a considerable role in the onset and progression of mucosa hyperproliferation in nasal polyps including transforming growth factor ß/Small mother against decapentaplegic (TGFß/Smads), mitogenactivated protein kinases (MAPKs), advanced glycosylation end-products (AGEs) together with epithelial-tomesenchymal transition (EMT). Since many inflammatory mediators are reported to play important roles in the development of nasal polyps (NP) disease, this study aimed to analyse the correlation between the AGEs/receptor of advanced glycosylation end-products (RAGE)/extracellular signal-regulated kinase (ERK) signalling pathway and the main markers of EMT to better understand the influence that they exert on the remodelling of nasal mucous membranes in patients affected by CRSwNP vs normal controls. A total of 30 patients were enrolled in this study. Immunohistochemical analysis, using AGE, RAGE, p-ERK, MMP-3, TGF-ß1, Smad2/3, Collagen I-III, α-SMA, E-cadherin, IL-6 and Vimentin antibodies, was performed. AGE, RAGE, ERK, p-ERK and MMP3 were also evaluated using western blot analysis. We observed an overexpression of the AGE/RAGE/p-ERK and the main mesenchymal markers of EMT (Vimentin and IL-6) in CRSwNP vs controls whereas the TGF-ß/Smad3 pathway did not show any significant differences between the two groups of patients. These observations suggest a complex network of processes in the pathogenesis of NP, and the AGE/RAGE/ERK pathway and EMT might work together in promoting tissue remodelling in the formation of CRSwNP.


Assuntos
Transição Epitelial-Mesenquimal/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Pólipos Nasais/etiologia , Sinusite/etiologia , Adulto , Doença Crônica , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Imuno-Histoquímica , Interleucina-6/metabolismo , Masculino , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Pólipos Nasais/fisiopatologia , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Sinusite/patologia , Sinusite/fisiopatologia , Vimentina/metabolismo
14.
Isr Med Assoc J ; 22(1): 48-52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31927806

RESUMO

BACKGROUND: Nasal polyps are three-dimensional structures arising from the mucosa of the upper airway. Due to their complexity, the reliability of single-layer cell cultures and animal systems as research models is limited. OBJECTIVES: To evaluate the feasibility of an ex vivo organ culture of human polyps, preserving tissue structure and function. METHODS: Nasal polyps were excised during routine endoscopic sinus surgery for chronic rhinosinusitis and polyposis. Fresh tissue samples were used for pathological evaluation and for the preparation of 250-500 µm sections, which were incubated in culture media. Tissue viability was assessed by visualisation of cilia motility, measurement of glucose uptake, and an infectivity assay. Cytokine secretion was evaluated by enzyme-linked immunosorbent assay and real-time polymerase chain reaction before and after the introduction of steroids. RESULTS: Polyp tissue viability was retained for 2-3 days as demonstrated by cilia motility, glucose uptake and preserved cellular composition. Tissue samples maintained their capacity to respond to infection by herpes simplex virus 1 and adenovirus. Introduction of dexamethasone to cultured tissue samples led to suppression of interferon-g production. CONCLUSIONS: The ex vivo nasal polyp organ culture reproduces the physiological, metabolic, and cellular features of nasal polyps. Furthermore, it shows a preserved capacity for viral infection and response to drugs. This system is a useful tool for the investigation nasal-polyps and for the development of novel therapies.


Assuntos
Pólipos Nasais/diagnóstico , Técnicas de Cultura de Órgãos/métodos , Adulto , Quimiocinas/metabolismo , Citocinas/metabolismo , Glucose/metabolismo , Humanos , Pólipos Nasais/metabolismo , Pólipos Nasais/patologia , Pólipos Nasais/cirurgia , Reação em Cadeia da Polimerase em Tempo Real
15.
Int Forum Allergy Rhinol ; 10(1): 23-28, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31794110

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) is a frequently observed condition in patients with immunodeficiency secondary to tumor necrosis factor alpha inhibitors (TNFαis). The histologic features of CRS caused by TNFαis have yet to be determined and may have important implications in understanding the pathophysiology of the disease process. METHODS: A structured histopathology report was used to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). These structured histopathology variables were compared among patients with CRS on TNFαi (CRSαi), CRS without nasal polyps (CRSsNP) patients, and CRS with nasal polyps (CRSwNP) patients. RESULTS: Eighteen CRSαi, 91 CRSwNP, and 113 CRSsNP patients undergoing FESS were analyzed. Compared to CRSsNP, CRSαi patients exhibited increased mucosal ulceration (16.7% vs 0.9%, p < 0.008), increased fibrosis (100% vs 34.5%, p < 0.001), and increased presence of Charcot-Leiden crystals (16.7% vs 0%, p < 0.002). Compared to CRSwNP, CRSαi patients demonstrated increased fibrosis (100% vs 54.9%, p < 0.001), decreased presence of subepithelial edema (44.4% vs 69.2% p < 0.043), decreased eosinophil aggregates (22.2% vs 47.3% p < 0.042), and fewer eosinophils per high-power field (44.4% vs 73.6%, p < 0.017). CONCLUSION: CRSαi exhibits structured histopathology more similar to CRSsNP. In the appropriate clinical context, it may be reasonable that the medical regimen for these patients be focused on a more antineutrophilic, macrolide-based approach. This study provides insight into the inflammatory environment of patients with CRSαi and may have implications for disease management.


Assuntos
Imunossupressores/efeitos adversos , Rinite/induzido quimicamente , Sinusite/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Doença Crônica , Endoscopia , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/patologia , Pólipos Nasais/cirurgia , Seios Paranasais/patologia , Fenótipo , Rinite/patologia , Rinite/cirurgia , Sinusite/patologia , Sinusite/cirurgia
16.
Occup Med (Lond) ; 70(1): 72-74, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-31587045

RESUMO

BACKGROUND: Possible factors for cell atypia in nasal mucosa include noxious chemicals: ammonia, formaldehyde and heavy metals. AIMS: Case presentation of a nasal polyp with epithelial dysplasia in a worker exposed to nickel and copper salt dust. CASE REPORT: A 27-year-old man complained of impaired nasal breathing and mild right-sided epistaxis. He was exposed to copper and nickel salt dust for 6 years. Clinical examination showed a polypoid lesion arising from the right middle turbinate. Histopathological examination of the excised lesion showed high-grade epithelial dysplasia. Duration of exposure and concentration of heavy metals in serum suggest the biological plausibility of exposure to these factors and development of epithelial dysplasia in the nasal mucosa. CONCLUSIONS: Epithelial dysplasia may occasionally be noted in inflammatory nasal polyps, especially in workers exposed to heavy metals.


Assuntos
Cobre/efeitos adversos , Pólipos Nasais/induzido quimicamente , Níquel/efeitos adversos , Exposição Ocupacional/efeitos adversos , Adulto , Cobre/sangue , Humanos , Masculino , Metalurgia , Mucosa Nasal/citologia , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Níquel/sangue
17.
Int Forum Allergy Rhinol ; 10(1): 128-132, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31589812

RESUMO

BACKGROUND: Lymphatic dysfunction is hypothesized to be an underlying factor in the pathophysiology of yellow nail syndrome (YNS) (yellow nails, lymphedema, pleural effusions, and frequently chronic rhinosinusitis [CRS]). It is unclear why some YNS patients develop CRS. We quantified lymphatic and total vasculature of sinonasal mucosa in YNS patients and compared it to controls from CRS patients with (CRSwNP) or without polyps (CRSsNP). METHODS: Immunohistochemistry was performed on archival sinonasal mucosal samples from 5 patients with YNS and 14 controls with antibodies against podoplanin and CD31, markers of lymphatics. Morphometric assessment was performed on digital images using ImageJ software. RESULTS: In YNS, the number of lymphatics/mm2 ranged from 7 to 18/mm2 (controls: 6 to 43/mm2 , p = 0.343), with a mean perimeter between 92 and 201 µm (controls: 42 to 280 µm, p = 0.482). Total vasculature density was higher than lymphatics, ranging between 189 and 1159 vessels/mm2 , average 669 (controls: 139 to 1467/mm2 , average 503, p = 0.257) with smaller average perimeter, 40 to 117 µm, mean 64.8 µm (controls: 42 to 92 µm, mean 65.3 µm, p = 0.965). Lymphatics constituted only a small fragment of the total vasculature, ranging from 1.15% to 4.76%, average 2.34% (controls: 0.81% to 10.58%, average 4.88%, p = 0.156). CRSwNP patients had significantly higher lymphatic density (p = 0.011) and ratio of lymphatics to total vasculature (p = 0.045) than patients with YNS or CRSsNP. CONCLUSION: This is the first histological analysis of sinus mucosa in patients with YNS. Vascular type, density, size, and distribution in the sinonasal mucosa of YNS patients are not statistically significantly different from those of the CRSsNP group. Lymphatic density and ratio to total vasculature is higher in CRSwNP patients.


Assuntos
Mucosa Nasal/irrigação sanguínea , Pólipos Nasais/patologia , Rinite/patologia , Sinusite/patologia , Síndrome das Unhas Amareladas/patologia , Idoso , Biomarcadores/metabolismo , Vasos Sanguíneos/patologia , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo
19.
Histopathology ; 76(2): 296-307, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31408543

RESUMO

AIMS: In chronic rhinosinusitis with nasal polyps (CRSwNP), tools based on objective evidence, such as histopathology, are needed to assist clinical decision-making. The main aim of this exploratory investigation was to determine whether structured histopathology could be used to classify CRSwNP in homogeneous histological clusters. METHODS AND RESULTS: A cohort of 135 CRSwNP patients was assessed, on the basis of clinicopathological features: allergic fungal rhinosinusitis (17 patients); non-steroidal anti-inflammatory drug-exacerbated respiratory disease (19 patients); intrinsic asthma (18 patients); extrinsic asthma (21 patients); allergy (21 patients); histologically eosinophilic (22 patients); and histologically non-eosinophilic (17 patients). For structured histopathology, we considered: the degree of inflammation; eosinophil count; eosinophil aggregates; neutrophil infiltration; goblet cell hyperplasia; basement membrane thickening; fibrosis; hyperplastic/papillary changes; squamous metaplasia; mucosal ulceration; and subepithelial oedema. Cluster analysis identified four distinct sets of cases. On discriminant analysis, the global error rate was 1.48%, and the stratified error rates were 4.34%, 0%, 0%, and 0% for clusters 1, 2, 3 and 4, respectively. Cluster 1 was characterised by infrequent fibrosis (<4.5% of cases). Cluster 2 mainly featured neutrophil infiltration in 100% of cases, hyperplastic/papillary changes in 70% of cases, and fibrosis in 65% of cases. Cluster 3 showed fibrosis in 100% of cases. Cluster 4 showed hyperplastic/papillary changes in 100% of cases, and fibrosis in 92% of cases. CONCLUSIONS: This study shows that cluster analysis can identify different histotypes among CRSwNP patients. The next step will be to investigate, in a larger series, the clinical (e.g. prognostic) implications of identifying such homogeneous clusters of patients with CRSwNP on the basis of their structured histopathology.


Assuntos
Fibrose/classificação , Inflamação/classificação , Pólipos Nasais/classificação , Rinite/classificação , Sinusite/classificação , Doença Crônica , Análise por Conglomerados , Estudos de Coortes , Eosinófilos/patologia , Fibrose/patologia , Fibrose/cirurgia , Humanos , Inflamação/patologia , Inflamação/cirurgia , Pólipos Nasais/patologia , Pólipos Nasais/cirurgia , Estudos Retrospectivos , Rinite/patologia , Rinite/cirurgia , Sinusite/patologia , Sinusite/cirurgia
20.
Orbit ; 39(1): 53-60, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30821588

RESUMO

This case report deals with two patients with lacrimal sac swellings. Case 1 presented with bilateral sac swelling and Case 2 with a unilateral presentation. Dacrocystorhinostomy (DCR) followed by biopsies of both sacs in Case 1 revealed inflammatory polyps of the sac mucosa, identical in appearance to typical nasal allergic inflammatory polyps. The biopsies were accompanied by typical allergic mucin, featuring tiered mucin layers between which were numerous eosinophils, accompanied by Charcot-Leyden crystals. The histology of the dacryocystectomy specimen for Case 2 showed identical histopathological changes with the additional feature of prominent numbers of Immunoglobulin G (IgG)4-positive plasma cells in the stroma of the lacrimal sac inflammatory polyps. These features extend the sites affected by allergic inflammatory polyps and allergic mucin and possible pathogenesis is discussed.


Assuntos
Dacriocistorinostomia/métodos , Aparelho Lacrimal/patologia , Micoses/diagnóstico por imagem , Pólipos Nasais/cirurgia , Ducto Nasolacrimal/patologia , Idoso , Biópsia por Agulha , Seguimentos , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/fisiopatologia , Imuno-Histoquímica , Aparelho Lacrimal/diagnóstico por imagem , Aparelho Lacrimal/cirurgia , Masculino , Pessoa de Meia-Idade , Mucinas/metabolismo , Micoses/tratamento farmacológico , Micoses/patologia , Pólipos Nasais/diagnóstico por imagem , Pólipos Nasais/patologia , Ducto Nasolacrimal/diagnóstico por imagem , Ducto Nasolacrimal/cirurgia , Amostragem , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
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