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1.
Ter Arkh ; 96(3): 303-308, 2024 Apr 16.
Artigo em Russo | MEDLINE | ID: mdl-38713048

RESUMO

Bronchial asthma and chronic polypous rhinosinusitis are diseases associated with a T2-inflammatory immune response. These nosologies can be combined, creating the preconditions for a more severe course of multimorbidity, requiring the use of genetic engineering biological therapy. Dupilumab is a monoclonal antibody that can specifically bind to the alpha subunit of the interleukin-4 receptor and block the action of interleukins 4 and 13, which play a key role in the development of T2 inflammation. Numerous studies have demonstrated the high effectiveness of this medicament. The use of dupilumab in some cases may be accompanied by an increase in eosinophils in the blood. This article presents scientific base and our own experience in treating patients with dupilumab-associated eosinophilia, in addition we describe an algorithm for examining this group of patients for the purpose of timely diagnosis of diseases such as eosinophilic granulomatosis with polyangiitis, eosinophilic pneumonia, etc. It should be noted that in the most cases eosinophilia during targeted therapy with dupilumab is temporary and does not cause clinical manifestations.


Assuntos
Anticorpos Monoclonais Humanizados , Asma , Eosinofilia , Rinite , Sinusite , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Asma/tratamento farmacológico , Eosinofilia/tratamento farmacológico , Sinusite/tratamento farmacológico , Rinite/tratamento farmacológico , Doença Crônica , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/complicações , Rinossinusite
3.
Laryngorhinootologie ; 103(S 01): S188-S213, 2024 May.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-38697148

RESUMO

The following review article highlights key topics in pediatric rhinology that are currently the focus in research and at conferences as well as in the interdisciplinary discussion between otorhinolaryngologists and pediatricians. In particular, congenital malformations such as choanal atresia or nasal dermoid cysts are discussed, followed by statements on the current procedures for sinogenic orbital complications as well as on the diagnosis and therapy of chronic rhinosinusitis in children. Furthermore, updates on the role of the ENT specialist in the care for children with cystic fibrosis and primary ciliary dyskinesia are provided.


Assuntos
Atresia das Cóanas , Humanos , Criança , Atresia das Cóanas/diagnóstico , Atresia das Cóanas/cirurgia , Rinite/diagnóstico , Rinite/terapia , Sinusite/diagnóstico , Sinusite/terapia , Cisto Dermoide/cirurgia , Cisto Dermoide/diagnóstico , Fibrose Cística/diagnóstico , Fibrose Cística/terapia , Doença Crônica
4.
Front Immunol ; 15: 1356298, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38690264

RESUMO

Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly a type 2 inflammatory disease associated with type 2 (T2) cell responses and epithelial barrier, mucociliary, and olfactory dysfunction. The inflammatory cytokines interleukin (IL)-4, IL-13, and IL-5 are key mediators driving and perpetuating type 2 inflammation. The inflammatory responses driven by these cytokines include the recruitment and activation of eosinophils, basophils, mast cells, goblet cells, M2 macrophages, and B cells. The activation of these immune cells results in a range of pathologic effects including immunoglobulin E production, an increase in the number of smooth muscle cells within the nasal mucosa and a reduction in their contractility, increased deposition of fibrinogen, mucus hyperproduction, and local edema. The cytokine-driven structural changes include nasal polyp formation and nasal epithelial tissue remodeling, which perpetuate barrier dysfunction. Type 2 inflammation may also alter the availability or function of olfactory sensory neurons contributing to loss of sense of smell. Targeting these key cytokine pathways has emerged as an effective approach for the treatment of type 2 inflammatory airway diseases, and a number of biologic agents are now available or in development for CRSwNP. In this review, we provide an overview of the inflammatory pathways involved in CRSwNP and describe how targeting key drivers of type 2 inflammation is an effective therapeutic option for patients.


Assuntos
Interleucina-13 , Interleucina-4 , Pólipos Nasais , Rinite , Sinusite , Humanos , Sinusite/imunologia , Sinusite/metabolismo , Pólipos Nasais/imunologia , Pólipos Nasais/metabolismo , Rinite/imunologia , Rinite/metabolismo , Doença Crônica , Interleucina-13/metabolismo , Interleucina-13/imunologia , Interleucina-4/metabolismo , Interleucina-4/imunologia , Transdução de Sinais , Inflamação/imunologia , Inflamação/metabolismo , Animais , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Rinossinusite
6.
Ophthalmic Plast Reconstr Surg ; 40(3): e84-e86, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38738720

RESUMO

A 47-year-old Japanese woman presented with a 1-year history of right-sided epiphora. On initial consultation, the patient had a high right tear meniscus height. CT images revealed bilateral soft tissue opacification in the nasal cavity and maxillary, frontal, and ethmoid sinuses. The lesion in the right nasal cavity and maxillary sinus involved the right lacrimal sac and nasolacrimal duct. Blood test results showed elevated eosinophil count. Endoscopic sinus surgery and excisional biopsy of the nasolacrimal duct were performed. Histopathological examinations of the excised right nasolacrimal duct and nasal polyps from the nasal cavity and maxillary sinus showed high levels of eosinophilic inflammatory infiltrates. The definite diagnosis of eosinophilic chronic rhinosinusitis was made, based on clinical, radiological, and histopathological findings. At 1.5-year follow-up, tear meniscus height was normal, the lacrimal drainage system remained patent, and the rhinosinusitis did not recur.


Assuntos
Eosinofilia , Obstrução dos Ductos Lacrimais , Ducto Nasolacrimal , Rinite , Sinusite , Tomografia Computadorizada por Raios X , Humanos , Feminino , Pessoa de Meia-Idade , Sinusite/diagnóstico , Sinusite/complicações , Doença Crônica , Rinite/diagnóstico , Rinite/complicações , Ducto Nasolacrimal/patologia , Ducto Nasolacrimal/diagnóstico por imagem , Obstrução dos Ductos Lacrimais/diagnóstico , Obstrução dos Ductos Lacrimais/etiologia , Eosinofilia/diagnóstico , Eosinofilia/complicações , Endoscopia , Rinossinusite
7.
Acta Otorhinolaryngol Ital ; 44(2): 100-112, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38651552

RESUMO

The goal of this meta-analysis was to study nasal nitric oxide (nNO) measurements in allergic rhinitis (AR) and non-allergic rhinitis (non-AR). The protocol was registered with PROSPERO (no: CRD4202124828). Electronic databases from PubMed, Google Scholar, Scopus, Web of Science, and Cochrane were all thoroughly searched and studies were chosen based on the qualifying requirements. The quality of the studies was evaluated by Joanna Briggs Institute evaluation tools, and publication bias using funnel plots. The meta-analysis included 18 studies, whereas the systematic review included 20 studies, totaling 3097 participants (1581 AR, 458 non-AR, and 1058 healthy/control). Patients with AR had significantly greater nNO levels than the control group, although this did not change significantly before or after treatment. AR patients had significantly greater nNO levels than non-AR patients, but there was no significant difference between non-AR patients and healthy controls. Nineteen of the studies were of high quality and the remaining one was of moderate quality. nNO measurement has a promising role in the management of AR and non-AR patients, but more investigations are needed to document clinical benefits.


Assuntos
Óxido Nítrico , Rinite Alérgica , Rinite , Humanos , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Rinite Alérgica/diagnóstico
8.
Int J Mol Sci ; 25(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38674045

RESUMO

Chronic rhinosinusitis (CRS) is a highly prevalent disease and up to 83% of CRS patients suffer from olfactory dysfunction (OD). Because OD is specifically seen in those CRS patients that present with a type 2 eosinophilic inflammation, it is believed that type 2 inflammatory mediators at the level of the olfactory epithelium are involved in the development of this olfactory loss. However, due to the difficulties in obtaining tissue from the olfactory epithelium, little is known about the true mechanisms of inflammatory OD. Thanks to the COVID-19 pandemic, interest in olfaction has been growing rapidly and several studies have been focusing on disease mechanisms of OD in inflammatory conditions. In this paper, we summarize the most recent data exploring the pathophysiological mechanisms underlying OD in CRS. We also review what is known about the potential capacity of olfactory recovery of the currently available treatments in those patients.


Assuntos
COVID-19 , Transtornos do Olfato , Rinite , Sinusite , Humanos , Sinusite/complicações , Sinusite/metabolismo , Sinusite/patologia , Rinite/complicações , Transtornos do Olfato/etiologia , Transtornos do Olfato/fisiopatologia , COVID-19/complicações , Doença Crônica , Mucosa Olfatória/metabolismo , Mucosa Olfatória/patologia , SARS-CoV-2 , Olfato/fisiologia , Rinossinusite
9.
JAMA ; 331(18): 1586-1587, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38630502

RESUMO

A 41-year-old with type 1 diabetes had generalized weakness, muffled voice, and slurred speech. Neck computed tomography showed soft-tissue gas in the nasopharynx and prevertebral fascia; examination of sinus mucosal samples identified numerous broad, nonseptate right-angled hyphae and fruiting bodies. What is the diagnosis and what would you do next?


Assuntos
Diabetes Mellitus Tipo 1 , Rinite , Sinusite , Humanos , Diabetes Mellitus Tipo 1/complicações , Sinusite/complicações , Rinite/complicações , Doença Aguda , Masculino , Adulto , Feminino , Rinossinusite
10.
Med Mycol ; 62(4)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38578660

RESUMO

Aspergillus flavus is a commonly encountered pathogen responsible for fungal rhinosinusitis (FRS) in arid regions. The species is known to produce aflatoxins, posing a significant risk to human health. This study aimed to investigate the aflatoxin profiles of A. flavus isolates causing FRS in Sudan. A total of 93 clinical and 34 environmental A. flavus isolates were studied. Aflatoxin profiles were evaluated by phenotypic (thin-layer and high-performance chromatography) and genotypic methods at various temperatures and substrates. Gene expression of aflD and aflR was also analyzed. A total of 42/93 (45%) isolates were positive for aflatoxin B1 and AFB2 by HPLC. When the incubation temperature changed from 28°C to 36°C, the number of positive isolates decreased to 41% (38/93). Genetic analysis revealed that 85% (79/93) of clinical isolates possessed all seven aflatoxin biosynthesis-associated genes, while 27% (14/51) of non-producing isolates lacked specific genes (aflD/aflR/aflS). Mutations were observed in aflS and aflR genes across both aflatoxin-producers and non-producers. Gene expression of aflD and aflR showed the highest expression between the 4th and 6th days of incubation on the Sabouraud medium and on the 9th day of incubation on the RPMI (Roswell Park Memorial Institute) medium. Aspergillus flavus clinical isolates demonstrated aflatoxigenic capabilities, influenced by incubation temperature and substrate. Dynamic aflD and aflR gene expression patterns over time enriched our understanding of aflatoxin production regulation. The overall findings underscored the health risks of Sudanese patients infected by this species, emphasizing the importance of monitoring aflatoxin exposure.


Aspergillus flavus, mainly causing fungal rhinosinusitis in Sudan, poses health risks due to aflatoxin production. This study revealed diverse levels of aflatoxin and gene expression of clinical isolates by pheno- and genotypic methods, emphasizing the need for vigilant monitoring in the region.


Assuntos
Aflatoxinas , Aspergillus flavus , Sinusite , Aspergillus flavus/genética , Aspergillus flavus/isolamento & purificação , Aspergillus flavus/classificação , Sudão , Humanos , Sinusite/microbiologia , Aspergilose/microbiologia , Temperatura , Rinite/microbiologia , Genótipo , Proteínas Fúngicas/genética , Rinossinusite
11.
Int J Pediatr Otorhinolaryngol ; 179: 111936, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38583371

RESUMO

BACKGROUND: Studies in adult chronic rhinosinusitis (CRS) showed poor correlation between patient reported outcome measures (PROMs) and objective findings. Our goal is to study the correlation between the sinus and nasal quality of life (SN-5) and the 22-items sinonasal outcome test (SNOT-22) surveys with endoscopy findings in children with chronic adenoiditis (CA) and CRS. METHODS: Cross-sectional study of all pediatric patients (age 2-18) presenting for CA or CRS was performed. Patients and caregivers were asked to fill the SN-5 and SNOT-22 questionnaires at initial and follow up visits. Demographics and comorbidities were collected. Objective findings included endoscopy Modified Lund-Kennedy (MLK) scores and adenoid tissue size. RESULTS: 124 children were included, with mean age of 9.9 years (SD = 4.8) and 46.8% female. 36.3% had allergic rhinitis, 23.4% had asthma, and 4% had obstructive sleep apnea. Moderate correlation was found between the rhinologic domain of SNOT-22 and MLK scores (r = 0.36, p = 0.001) and between SN5 scores and adenoid size in all patients (r = 0.39, p < 0.001). SNOT-22 scores showed moderate correlation with adenoid size (r = 0.42, p < 0.001) more specifically in CA patients (r = 0.54, p < 0.001). The correlation of SN5 and MLK scores were higher in children with allergic rhinitis or asthma. The correlation between SN5 and adenoid size was lower in children with allergic rhinitis or asthma. CONCLUSION: There is discrepancy between the subjective measures and the objective findings in children with CA or CRS. The physical exam findings may not reflect the effect of CRS on the quality of life of children.


Assuntos
Asma , Rinite Alérgica , Rinite , Rinossinusite , Sinusite , Adulto , Humanos , Feminino , Criança , Pré-Escolar , Adolescente , Masculino , Estudos Transversais , Qualidade de Vida , Rinite/complicações , Rinite/diagnóstico , Sinusite/complicações , Sinusite/diagnóstico , Medidas de Resultados Relatados pelo Paciente , Endoscopia , Doença Crônica
12.
Artigo em Chinês | MEDLINE | ID: mdl-38563171

RESUMO

Objective:To evaluate the expression of eosinophil cationic protein and myeloperoxidase in nasal secretions in different types of rhinitis, and to explore their values in the differential diagnosis of different types of rhinitis. Methods:Six hundred and eighty-four subjects were selected, including 62 subjects in the acute rhinitis group, 378 subjects in the allergic rhinitis group, 94 subjects in the vasomotor rhinitis group, 70 subjects in the eosinophilic non-allergic rhinitis group, and 80 subjects in the control group. Nasal secretion samples were collected from the five groups, and the percentages of inflammatory cells were counted by Rachel's staining, and the expression of ECP/MPO was detected by colloidal gold assay. The correlation between the clinical diagnosis, the inflammatory cells in the nasal secretions and the expression of ECP/MPO was analyzed. Results:Nasal cytological smears showed that compared with the control group, the percentage of eosinophils in the AR and NARES groups were significantly higher (P<0.05), while the percentage of neutrophils was not different (P>0.05); the percentage of neutrophils was significantly higher in the acute rhinitis group compared with the control group (P<0.05), while the percentage of eosinophils was not statistically different (P>0.05); in vasomotor rhinitis group, the eosinophils and neutrophils were not statistically different compared with the control group(P> 0.05). The colloidal gold results showed that there were differences in the expression of ECP/MPO in different types of rhinitis, among which 49 cases (79.0%) in the acute rhinitis group expressed ECP+/MPO+; 267 cases (70.6%) in the AR group and 56 cases (75.7%) in the NARES group expressed ECP+/MPO-; 80 cases (85.1%) in the vasomotor rhinitis group and 69 cases (86.3%) in the control group expressed ECP-/MPO-. Conclusion:The differences in ECP and MPO expression between different types of rhinitis have certain reference value for the differential diagnosis of different types of rhinitis and the selection of treatment programs.


Assuntos
Rinite Vasomotora , Rinite , Humanos , Eosinófilos/metabolismo , Coloide de Ouro/metabolismo , Mucosa Nasal/metabolismo , Peroxidase/metabolismo , Rinite/diagnóstico , Rinite/metabolismo , Rinite Vasomotora/metabolismo
13.
Rev Alerg Mex ; 71(1): 77, 2024 Feb 01.
Artigo em Espanhol | MEDLINE | ID: mdl-38683094

RESUMO

OBJECTIVE: To present the baseline clinical and demographic characteristics of CRSwNP patients over the age of 18 enrolled in a Patient Support Program (PSP) prior to biologic treatment. METHODS: Descriptive, cross-sectional study performed in a Colombian CRSwNP asthma PSP sponsored by Sanofi from Aug-2021 to Jul-2022. Data was collected from CRSwNP patients, prior to the start of Dupilumab treatment, who consented to the use of their data. The following information was reported: Age, reporting city, treating medical specialty, comorbidities, and persistence of treatment. RESULTS: 339 patients were included, 171 (50,4%) were women and 168 (49,6%) were men. The mean age at Dupilumab treatment initiation was 52,4 years. 62,8% began treatment during adulthood (26-59y), while 34.1% started at elderly (+60y) and 3.1% were young adults (18-25y). Most cases (29,7%) were included in Bogotá, followed by Antioquia (19%), Valle del Cauca (7,3%) and the remaining 44% nationwide. Comorbidities were present in 67,1% of the patients, with diagnosis of allergic rhinitis, atopic dermatitis, asthma, and other non-type 2 inflammatory diseases. Nasal surgical history was present in 89,6% of the patients, most of them with one to three previous surgeries. Continuous treatment was observed in 70,3% of patients for 6 to 12 months, in 21,3% for more than 12 months and in 8,4% for less than six months. The most frequently treating medical specialty was otorhinolaryngology (79,6%), followed by allergology (16%) and other medical professionals (4,4%). CONCLUSIONS: There is concordance with the literature on a higher presentation of the disease in women than in men. There is a large proportion of patients with nasal surgical history and type 2 inflammatory comorbidities by the moment of biologic treatment initiation. The care and identification of CRSwNP colombian patients is mainly provided by otorhinolaryngologists, followed by allergologists.


OBJETIVO: Presentar las características clínicas y demográficas iniciales de los pacientes con RSCcPN, mayores de 18 años, inscritos en un Programa de Soporte al Paciente (PSP), antes del inicio de tratamiento biológico. MÉTODOS: Estudio descriptivo y transversal realizado en un PSP para RSCcPN en Colombia, entre agosto de 2021 y julio de 2022, patrocinado por Sanofi. Los datos se recopilaron de pacientes con RSCcPN, antes de comenzar el tratamiento con Dupilumab, quienes dieron su consentimiento para el uso de sus datos. Se reportó la siguiente información: edad, ciudad de origen, especialidad médica tratante, comorbilidades y persistencia del tratamiento. RESULTADOS: Se incluyeron 339 pacientes, 171 mujeres (50,4%), y 168 hombres (49,6%). La edad promedio al inicio del tratamiento con Dupilumab, fue de 52,4 años. El 62,8% inició tratamiento durante la edad adulta (entre 26 y 59 años), mientras que el 34,1% comenzó en la vejez (+60 años), y el 3,1% entre los 18 y 25 años. La mayoría de los casos (29,7%) se incluyeron en Bogotá, seguidos por Antioquia (19%), Valle del Cauca (7,3%) y el 44% restante en todo el país. Las comorbilidades estuvieron presentes en el 67,1% de los pacientes, con diagnóstico de rinitis alérgica, dermatitis atópica, asma y otras enfermedades no inflamatorias tipo 2. El 89,6% de los pacientes tenía antecedentes de cirugía nasal, la mayoría de ellos con entre una y tres cirugías previas. Se observó tratamiento continuo en el 70,3% de los pacientes durante 6 y 12 meses, en el 21,3%, durante más de 12 meses, y en el 8,4% durante menos de 6 meses. La especialidad médica que trató a los pacientes con más frecuencia fue la otorrinolaringología (79,6%), seguida por la alergología (16%) y otros profesionales médicos (4,4%). CONCLUSIONES: Existe concordancia con la literatura con una mayor presentación de la enfermedad en mujeres que en hombres. Hay una gran proporción de pacientes con antecedentes de cirugía nasal y comorbilidades inflamatorias tipo 2, al inicio del tratamiento biológico. La atención e identificación de los pacientes colombianos con RSCcPN es proporcionada principalmente por otorrinolaringólogos, seguidos por alergólogos.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Humanos , Masculino , Colômbia/epidemiologia , Feminino , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Sinusite/epidemiologia , Pólipos Nasais/epidemiologia , Pólipos Nasais/complicações , Doença Crônica , Adulto Jovem , Rinite/epidemiologia , Adolescente , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Estudos de Coortes , Comorbidade , Rinossinusite
14.
Acta Otorhinolaryngol Ital ; 44(2): 71-75, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38651550

RESUMO

Introduction: Intranasal corticosteroids (INCs) are the first line of therapy for chronic sinonasal conditions such as rhinitis and rhinosinusitis. Among these, one of the most frequently used is beclomethasone dipropionate (BDP). Over the years many studies have evaluated the efficacy of BDP as part of therapy for chronic rhinosinusitis (CRS) and allergic rhinitis (AR) along with nasal washes, which seems to be very well tolerated. Objective: To analyse the data in the literature regarding the various therapeutic regimens of BDP in different sinonasal disease and their efficacy and tolerability. Materials and methods: Using different search engines, the posology, efficacy, and tolerability of BDP were reviewed and a total of 64 full-length articles were examined for eligibility. After applying inclusion and exclusion criteria, 4 articles were reviewed. Results: BDP is among the group of INCs with significant improvement of nasal symptoms and has good efficacy and safety. Conclusions: BDP nasal spray is one of the most frequently prescribed INC for rhinitis and rhinosinusitis. Treatment with BDP resulted in significant and clinically meaningful improvements in nasal symptoms associated with AR and CRS. BDP is well tolerated, and the safety profile is similar to that of placebo in most patients. These results, in conjunction with the significant benefit reported in subjects with CRS and AR, provide convincing evidence of the overall effectiveness of BDP for the treatment of the full spectrum of sinonasal disease.


Assuntos
Administração Intranasal , Beclometasona , Ensaios Clínicos Controlados Aleatórios como Assunto , Rinite , Sinusite , Humanos , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Beclometasona/administração & dosagem , Beclometasona/uso terapêutico , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Doença Crônica
15.
BMJ Case Rep ; 17(4)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684354

RESUMO

Varicella is the manifestation of primary infection with the varicella-zoster virus, mainly affecting preschool and school-aged children. The children suffer from a generalised, vesicular rash and fever. Despite the infection's typically non-threatening course, a variety of severe complications have been described.The authors present the case of a female infant suffering from varicella and developing preseptal cellulitis with a frontal abscess while being treated with intravenous antibiotics. Otorhinolaryngology consultation was sought since the clinical image was highly suggestive for sinusitis complications, namely orbital cellulitis and frontal bone osteomyelitis (Pott's puffy tumour). However, the child was below the age of frontal sinus development and there was no other apparent sign of sinonasal involvement. Ultrasonography revealed a mid-frontal collection without signs of abscess formation preseptally or postseptally, leading to the diagnosis of cutaneous superinfection of varicella lesions. The frontal abscess was drained, and the child fully recovered under antibiotic treatment.


Assuntos
Abscesso , Antibacterianos , Varicela , Humanos , Feminino , Lactente , Varicela/complicações , Varicela/diagnóstico , Diagnóstico Diferencial , Antibacterianos/uso terapêutico , Abscesso/diagnóstico , Abscesso/diagnóstico por imagem , Abscesso/tratamento farmacológico , Sinusite/tratamento farmacológico , Sinusite/diagnóstico , Sinusite/complicações , Rinite/diagnóstico , Rinite/tratamento farmacológico , Doença Aguda , Rinossinusite
16.
Sci Rep ; 14(1): 9722, 2024 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678138

RESUMO

Chronic rhinosinusitis with nasal polyp (CRSwNP) is a highly prevalent disorder characterized by persistent nasal and sinus mucosa inflammation. Despite significant morbidity and decreased quality of life, there are limited effective treatment options for such a disease. Therefore, identifying causal genes and dysregulated pathways paves the way for novel therapeutic interventions. In the current study, a three-way interaction approach was used to detect dynamic co-expression interactions involved in CRSwNP. In this approach, the internal evolution of the co-expression relation between a pair of genes (X, Y) was captured under a change in the expression profile of a third gene (Z), named the switch gene. Subsequently, the biological relevancy of the statistically significant triplets was confirmed using both gene set enrichment analysis and gene regulatory network reconstruction. Finally, the importance of identified switch genes was confirmed using a random forest model. The results suggested four dysregulated pathways in CRSwNP, including "positive regulation of intracellular signal transduction", "arachidonic acid metabolic process", "spermatogenesis" and "negative regulation of cellular protein metabolic process". Additionally, the S100a9 as a switch gene together with the gene pair {Cd14, Tpd52l1} form a biologically relevant triplet. More specifically, we suggested that S100a9 might act as a potential upstream modulator in toll-like receptor 4 transduction pathway in the major CRSwNP pathologies.


Assuntos
Calgranulina B , Pólipos Nasais , Rinite , Transdução de Sinais , Sinusite , Receptor 4 Toll-Like , Pólipos Nasais/metabolismo , Pólipos Nasais/genética , Humanos , Sinusite/metabolismo , Sinusite/genética , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Rinite/metabolismo , Rinite/genética , Doença Crônica , Calgranulina B/genética , Calgranulina B/metabolismo , Redes Reguladoras de Genes , Regulação da Expressão Gênica , Perfilação da Expressão Gênica , Rinossinusite
17.
Front Immunol ; 15: 1285598, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38680486

RESUMO

Significant advancements have been achieved in understanding the roles of different immune cells, as well as cytokines and chemokines, in the pathogenesis of eosinophilic airway conditions. This review examines the pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex immune dysregulation, with major contributions from type 2 inflammation and dysfunctional airway epithelium. The presence of eosinophils and the role of T-cell subsets, particularly an imbalance between Treg and Th17 cells, are crucial to the disease's pathogenesis. The review also investigates the pathogenesis of eosinophilic asthma, a unique asthma subtype. It is characterized by inflammation and high eosinophil levels, with eosinophils playing a pivotal role in triggering type 2 inflammation. The immune response involves Th2 cells, eosinophils, and IgE, among others, all activated by genetic and environmental factors. The intricate interplay among these elements, chemokines, and innate lymphoid cells results in airway inflammation and hyper-responsiveness, contributing to the pathogenesis of eosinophilic asthma. Another scope of this review is the pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (EGPA); a complex inflammatory disease that commonly affects the respiratory tract and small to medium-sized blood vessels. It is characterized by elevated eosinophil levels in blood and tissues. The pathogenesis involves the activation of adaptive immune responses by antigens leading to T and B cell activation and eosinophil stimulation, which causes tissue and vessel damage. On the other hand, Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitive response that occurs when the airways become colonized by aspergillus fungus, with the pathogenesis involving activation of Th2 immune responses, production of IgE antibodies, and eosinophilic action leading to bronchial inflammation and subsequent lung damage. This analysis scrutinizes how an imbalanced immune system contributes to these eosinophilic diseases. The understanding derived from this assessment can steer researchers toward designing new potential therapeutic targets for efficient control of these disorders.


Assuntos
Asma , Eosinófilos , Humanos , Eosinófilos/imunologia , Asma/imunologia , Asma/patologia , Pólipos Nasais/imunologia , Pólipos Nasais/patologia , Sinusite/imunologia , Sinusite/patologia , Animais , Inflamação/imunologia , Inflamação/patologia , Células Th2/imunologia , Rinite/imunologia , Rinite/patologia , Citocinas/metabolismo , Citocinas/imunologia , Doença Crônica
18.
Artigo em Chinês | MEDLINE | ID: mdl-38563173

RESUMO

Objective:After selecting NCF2 based on bioinformatics, clinical experiments were conducted to verify the expression of NCF2 in chronic rhinosinusitis with nasal polyps to study its correlation. Methods:The differentially expressed genes(DEGs) between CRSwNP and non-CRS patients were explored using the CRS-related dataset from the gene expression omnibus GEO database. The weighted gene co-expression network(WGCNA) was used for cluster analysis. The expression and cell distribution of NCF2 in the tissues were determined by single gene enrichment analysis(GSEA), immune inflammatory infiltration analysis, and principal component(PCA) analysis. The expression degree of NCF2 in the tissues of the subjects was determined by immunohistochemistry, and the percentage of EOS in the peripheral blood of the subjects was detected and the correlation was analyzed. EOS in the tissues of the subjects were counted under a microscope and compared. Results:①The Venn diagram was obtained by crossing the module with the highest correlation between DEGs and WGCNA to determine the core gene NCF2. ②GSEA analysis showed that NCF2 was significantly related to the immunological processes such as allogeneic rejection and asthma. ③The area under the ROC curve was 1, indicating that NCF2 had diagnostic value for CRSwNP. ④NCF2 was highly expressed in nasal polyps, mainly distributed in monocytes and eosinophils. ⑤HE staining showed that the number of EOS in ECRSwNP tissues and the percentage of eosinophils in peripheral blood were higher than those in nonECRSwNP and control groups. ⑥The immunohistochemistry results showed that NCF2 was significantly expressed in the nasal polyps of ECRSwNP patients, which was higher than that in the nasal mucosa of nonECRSwNP group and control group. ⑦The expression of NCF2 in tissues was positively correlated with EOS count in ECRSwNP group and EOS expression in peripheral blood. Conclusion:The expression of NCF2 is increased in eosinophilic chronic rhinosinusitis with nasal polyps, and it is significantly correlated with the expression of eosinophils in peripheral blood and tissues, suggesting that NCF2 may be used as a basis for the intrinsic classification of ECRSwNP and a reference index for clinical diagnosis and treatment.


Assuntos
Pólipos Nasais , Rinite , Rinossinusite , Sinusite , Humanos , Pólipos Nasais/metabolismo , Rinite/cirurgia , Correlação de Dados , Sinusite/cirurgia , Eosinófilos/metabolismo , Doença Crônica , NADPH Oxidases
20.
Biochem Biophys Res Commun ; 714: 149967, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38669752

RESUMO

Butyrate and other Short-chain fatty acids (SCFAs) are microbial metabolites from Bacteroides and Clostridium species that may suppress type 2 inflammation. However, the mechanisms of SCFAs in the nasal sinuses are not fully understood. We aimed to clarify the in vitro and in vivo roles of SCFAs in eosinophilic chronic rhinosinusitis (ECRS) pathophysiology. We investigated whether SCFAs induced changes in type 2 cytokines, IgE, and apoptosis and the roles of GPR41, GPR43, and histone deacetylase. Analysis of the control subjects demonstrated that butyrate of SCFAs effectively inhibited type 2 cytokine production in PBMCs, ILC2s, and CD4+ T cells and IgE production in CD19+ B cells. In annexin V analysis, butyrate also induced late apoptosis of PBMCs. The butyrate-induced inhibition of type 2 cytokines appeared involved in histone deacetylase inhibition but not in GPR41 or GPR43. In an analysis of ECRS in humans, butyrate inhibited type 2 cytokine production in PBMCs and nasal polyp-derived cells. The butyrate concentration in nasal lavage fluid was significantly decreased in ECRS patients compared to controls and non-ECRS patients. Our findings confirm that butyrate can inhibit type 2 inflammation and may be a potential therapeutic target for ECRS.


Assuntos
Butiratos , Citocinas , Receptores de Superfície Celular , Receptores Acoplados a Proteínas G , Rinite , Sinusite , Humanos , Sinusite/tratamento farmacológico , Sinusite/metabolismo , Sinusite/imunologia , Sinusite/patologia , Butiratos/farmacologia , Doença Crônica , Rinite/tratamento farmacológico , Rinite/metabolismo , Rinite/imunologia , Rinite/patologia , Citocinas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Masculino , Adulto , Apoptose/efeitos dos fármacos , Feminino , Pessoa de Meia-Idade , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Imunoglobulina E/imunologia , Eosinofilia/tratamento farmacológico , Eosinofilia/metabolismo , Eosinofilia/patologia , Eosinofilia/imunologia , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/metabolismo , Pólipos Nasais/patologia , Pólipos Nasais/imunologia , Células Cultivadas , Rinossinusite
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