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1.
Iran J Allergy Asthma Immunol ; 20(3): 287-293, 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34134450

RESUMO

Asthmatic patients may have aspirin-exacerbated respiratory disease and experience acute dyspnea and nasal symptoms within 3 hours after the ingestion of aspirin. This study aimed to evaluate the effect and outcome of daily low-dose aspirin in the treatment of moderate to severe asthma in patients with concomitant aspirin hypersensitivity and chronic rhinosinusitis with nasal polyposis (CRSwNP). This clinical trial was conducted from February 2014 to February 2015 on 46 adult patients with moderate to severe asthma accompanied by CRSwNP. Patients with a positive aspirin challenge were blindly randomized in three groups receiving placebo/day (A); aspirin 100 mg/day (B); and aspirin 325mg/day (C), respectively. Clinical findings, FEV1 and ACT scores were recorded and compared before, during, and after treatment for 6 months. Of 46 participants at baseline, 30 patients completed this 6-month trial study. The level of asthma control was significant; based on Asthma Control Test (ACT) when comparing the results in groups A and C and also groups B and C, but it was not significant when comparing ACT scores between groups A and B. FEV1 before and after treatment was significant when comparing groups A and B, groups A and C, and groups B and C. To conclude, aspirin desensitization with a daily dose of 325 mg aspirin resulted in the improvement of long-term control of asthma. A daily aspirin dose of 100 mg was not associated with such an increase in ACT score.


Assuntos
Antiasmáticos/administração & dosagem , Aspirina/administração & dosagem , Asma Induzida por Aspirina/tratamento farmacológico , Hipersensibilidade a Drogas , Pulmão/efeitos dos fármacos , Pólipos Nasais/tratamento farmacológico , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Adulto , Antiasmáticos/efeitos adversos , Aspirina/efeitos adversos , Asma Induzida por Aspirina/diagnóstico , Asma Induzida por Aspirina/fisiopatologia , Doença Crônica , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Humanos , Irã (Geográfico) , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/diagnóstico , Pólipos Nasais/fisiopatologia , Rinite/diagnóstico , Rinite/fisiopatologia , Índice de Gravidade de Doença , Sinusite/diagnóstico , Sinusite/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
2.
Ann Allergy Asthma Immunol ; 126(6): 666-673, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33465457

RESUMO

BACKGROUND: Comorbidities are common in asthma and may complicate treatment response. OBJECTIVE: To examine response to omalizumab in patients with moderate-to-severe allergic asthma by asthma-related and allergic comorbidities. METHODS: Patients aged 12 years or more from placebo-controlled 008/009 (n = 1071), EXTRA (n = 848), and INNOVATE (n = 419), and single-armed PROSPERO (n = 801) omalizumab studies were included. Poisson regression/analysis of covariance models were used to estimate adjusted exacerbation rates and forced expiratory volume in 1 second (FEV1) change from baseline after omalizumab initiation for subgroups by number of comorbidities (0, 1 [008/009]; 0, 1, ≥2 [EXTRA and INNOVATE]; 0, 1, 2, ≥3 [PROSPERO]). Self-reported comorbidities included allergic rhinoconjunctivitis, chronic rhinosinusitis, recurrent acute sinusitis, nasal polyps, atopic and contact dermatitis, urticaria, food allergy, anaphylaxis, other allergies, gastroesophageal reflux disease, eosinophilic esophagitis, and eosinophilic granulomatosis with polyangiitis. RESULTS: In the EXTRA and INNOVATE studies, no consistent pattern was observed for placebo-corrected relative rate reduction in normalized asthma exacerbations among omalizumab-treated comorbidity subgroups. In PROSPERO, on-study exacerbation rates in the comorbidity subgroups were similar (0, 0.68; 1, 0.70; 2, 0.77; ≥3, 0.80). FEV1 improvements were observed throughout the study for omalizumab vs placebo for all comorbidity subgroups. There were no consistent differences in FEV1 improvements among comorbidity subgroups in 008/009, EXTRA, or INNOVATE. Similarly, no among-group differences were observed for FEV1 change from baseline at month 12 in PROSPERO (0, 0.05 L; 1, 0.08 L; 2, 0.00 L; ≥3, 0.04 L). The 95% confidence intervals overlapped substantially in all instances. CONCLUSION: In these analyses of placebo-controlled/single-armed studies, on-study exacerbation rates and FEV1 improvements with omalizumab treatment were similar irrespective of comorbidity burden. TRIAL REGISTRATION: ClinicalTrials.gov identifiers are as follows: EXTRA, NCT00314574 (https://clinicaltrials.gov/ct2/show/NCT00314574); INNOVATE, NCT00046748 (https://clinicaltrials.gov/ct2/show/NCT00046748); and PROSPERO, NCT01922037 (https://clinicaltrials.gov/ct2/show/NCT01922037).


Assuntos
Antialérgicos/uso terapêutico , Antiasmáticos/uso terapêutico , Hipersensibilidade/tratamento farmacológico , Omalizumab/uso terapêutico , Adolescente , Adulto , Idoso , Criança , Comorbidade , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/fisiopatologia , Humanos , Hipersensibilidade/epidemiologia , Hipersensibilidade/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/epidemiologia , Pólipos Nasais/fisiopatologia , Sinusite/tratamento farmacológico , Sinusite/epidemiologia , Sinusite/fisiopatologia , Resultado do Tratamento , Adulto Jovem
4.
Biomed Res Int ; 2020: 1237678, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33274193

RESUMO

BACKGROUND: The abnormal vascular permeability is associated with the formation of chronic rhinosinusitis with nasal polyps (CRSwNP). Previously, our study demonstrated that the nasal lavage fluid- (NLF-) derived exosomes from CRSwNP can promote the vascular permeability of human umbilical vein endothelial cells (HUVECs). miR-22-3p, a specific differentiated miRNA, is reported to regulate microvessels in some diseases. This study is purposed to explore the impact of exosomal miR-22-3p derived from CRSwNP on vascular permeability and identify the underlying targets. METHODS: Exosomes were extracted from NLF of 26 CRSwNP patients and 10 control patients. Quantitative real-time PCR (qRT- PCR) was applied to evaluate the relative level of exosomal miR-22-3p. The impact of exosomal miR-22-3p on HUVECs was assessed by permeability assays in vitro. The potential molecular targets of miR-22-3p were investigated by applying such technologies as dual-luciferase reporter assay and western blot. RESULTS: miR-22-3p was upregulated in NLF-derived exosomes from CRSwNP. Exosomal miR-22-3p derived from CRSwNP enhanced the tubule permeability of HUVECs. Vascular endothelial- (VE-) cadherin (CDH5) was identified as a direct target of miR-22-3p. miR-22-3p regulated the vascular permeability by targeting VE-cadherin in HUVECs. CONCLUSIONS: Exosomal miR-22-3p derived from NLF of CRSwNP plays an important role in regulating vascular permeability by targeting VE-cadherin.


Assuntos
Antígenos CD/metabolismo , Caderinas/metabolismo , Permeabilidade Capilar , Exossomos/genética , MicroRNAs/metabolismo , Pólipos Nasais/complicações , Rinite/complicações , Sinusite/complicações , Adulto , Permeabilidade da Membrana Celular , Doença Crônica , Feminino , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , MicroRNAs/genética , Líquido da Lavagem Nasal , Pólipos Nasais/genética , Pólipos Nasais/fisiopatologia , Rinite/genética , Rinite/fisiopatologia , Sinusite/genética , Sinusite/fisiopatologia
5.
Thorax ; 75(11): 982-993, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33023995

RESUMO

BACKGROUND: Epithelial to mesenchymal transition (EMT) is associated with the pathophysiology of chronic rhinosinusitis with nasal polyp (CRSwNP). Wnt signaling is causative for EMT, whereas the mechanism in CRSwNP is not fully understood. OBJECTIVE: We sought to evaluate the role of Wnt signaling in EMT of CRSwNP using a murine nasal polyp (NP) model and human tissues. METHODS: Inflammatory markers and EMT-related molecules were evaluated in NP models using adenomatosis polyposis coli (Apc)Min/+ mice with activated Wnt signaling and NP models treated with Wnt signaling inhibitor, indocyanine green-001 (ICG-001). EMT markers and Wnt signaling-associated mediators were analysed using human sinonasal tissues from control subjects and CRSwNP patients. RESULTS: ApcMin/+ mice-induced NPs exhibited more frequent polypoid lesions and upregulation of Wnt-related molecules, including nuclear ß-catenin, WNT3A and cyclin D1. Markers of EMT were significantly overexpressed in the ApcMin/+ NP mice (p<0.001 for E-cadherin and α-smooth muscle actin), and interleukin (IL)-17A+ cells and neutrophilic infiltration were increased in ApcMin/+ NP mice (p<0.001). Inhibition of Wnt signaling via ICG-001 resulted in significantly decreased nasal polypoid lesions (p<0.001), EMT-related markers (p=0.019 for E-cadherin and p=0.002 for vimentin) and the mRNA levels of IL-4 (p<0.001) and IL-17A (p=0.004) compared with the positive control group. Finally, nuclear ß-catenin (p=0.042) was significantly increased compared with the control, and the expression levels of Wnt ligands and receptors were upregulated in human NP tissues (p=0.045 for WNT3A and p=0.042 for FZD2), suggesting increased Wnt signaling and EMT in CRSwNP. CONCLUSION: Wnt signaling may contribute to the pathogenesis of NPs through EMT. Therefore, inhibition of Wnt signaling may be a potential therapeutic strategy for patients with CRSwNP.


Assuntos
Transição Epitelial-Mesenquimal/fisiologia , Pólipos Nasais/fisiopatologia , Rinite/fisiopatologia , Sinusite/fisiopatologia , Via de Sinalização Wnt/fisiologia , Actinas/metabolismo , Proteína da Polipose Adenomatosa do Colo , Animais , Biomarcadores/metabolismo , Caderinas/metabolismo , Ciclina D1/metabolismo , Modelos Animais de Doenças , Humanos , Verde de Indocianina/farmacologia , Camundongos , Pólipos Nasais/tratamento farmacológico , Proteína 1 Relacionada a Twist/metabolismo , Regulação para Cima , beta Catenina/metabolismo
6.
J Breath Res ; 15(1): 016007, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33065563

RESUMO

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory disease highly impacting patient's quality of life, and associated with lower airway inflammation often evolving into asthma. Exhaled nitric oxide (FENO) is a non-invasive tool to assess Type 2 airway inflammation and its extended analysis allows to differentiate between alveolar concentration (CalvNO) and bronchial output (JawNO). It is also possible to assess the sino-nasal production of nitric oxide (nNO). We studied extended nitric oxide production in patients with CRSwNP with or without associated asthma. Consecutive adult patients with CRSwNP, with or without asthma, and 15 healthy controls were enrolled. Exclusion criteria were: smoking, uncontrolled asthma, recent upper or lower airway infections and oral corticosteroid therapy in the 4 weeks preceding clinical evaluation. Patients' demographic and clinical data were collected; patients underwent pulmonary function tests and extended nitric oxide analysis including nasal nNO assessment. A total of 125 subjects were enrolled (15 healthy controls; 69 with CRSwNP and asthma, and 41 with CRSwNP only). FENO, JawNO and CalvNO values were higher, while nNO was lower, in all patients with CRSwNP compared to healthy controls; no difference was found in CalvNO between patients with concomitant asthma and non-asthmatic subjects; in asthmatic patients, FENO and JawNO were significantly higher, while nNO values was lower, compared to patients with CRSwNP only. These results suggest that CRSwNP could be the first manifestation of a more complex systemic inflammatory pathology driven by Type 2 inflammation. An 'inflammatory gradient' hypothesis could describe a pattern of inflammation in CRSwNP patients that starts distally in the alveoli. Finally, our study indirectly reinforces the concept that novel biological drugs could become valid therapeutic options for nasal polyposis.


Assuntos
Asma/complicações , Pólipos Nasais/complicações , Óxido Nítrico/análise , Rinite/complicações , Sinusite/complicações , Adulto , Asma/fisiopatologia , Testes Respiratórios/métodos , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/patologia , Pólipos Nasais/fisiopatologia , Qualidade de Vida , Testes de Função Respiratória , Rinite/patologia , Rinite/fisiopatologia , Sinusite/patologia , Sinusite/fisiopatologia
7.
Otolaryngol Pol ; 74(5): 1-5, 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-33028737

RESUMO

<b>Introduction: </b>The aim of the study was to assess the effect of nasal mucosa irritants on the occurrence of chronic rhinosinusitis without/and with nasal polyps. <br><b>Material and methods:</b> The study involved 100 adult participants, including 39 women and 61 men, aged 21-68, diagnosed and treated at the Department of Otolaryngology, ENT Oncology, Audiology and Phoniatrics at the University Clinical Hospital WAM in Lódz. Based on the otorhinolaryngological and imaging (CT) tests they were divided into two groups: I - 50 patients, including 23 women and 27 men, aged 21-64 - with chronic rhinosinusitis without nasal polyps, II - 50 patients, including 16 women and 34 men, aged 22-68 - with chronic rhinosinusitis with nasal polyps. The control group consisted of 50 people (group III), including 25 women and 25 men, aged 18-30, students of the Faculty of Military Medicine at the Medical University of Lodz. All respondents completed a prepared questionnaire consisting of 17 questions addressed in the form of an anonymous interview among patients treated in the Department of Otolaryngology, ENT Oncology, Audiology and Phoniatrics. <br><b>Results:</b> The conducted surveys indicate the impact of the following factors in pathogenesis of chronic rhinosinusitis without/ with nasal polyps: exogenous factors (viruses, bacteria, fungi, drugs, injuries, toxic substances, environmental pollution), general endogenous factors (allergy, hypersensitivity to acetylsalicylic acid and its derivatives, hormonal disorders, supraesophageal reflux disease, granulation disease, immunity disorders, local endogenous factors. <br><b>Conclusions:</b> In the examined material, patients with chronic rhinosinusitis without/and nasal polyps in most cases are in the age range 51-60 years and over 60 years, they most often live in large cities over 250 thousand inhabitants, suffer from allergic rhinorhinitis in 38.0% in group I and 36.0% in group II, rapid temperature changes and dry air have a negative impact on comfort of breathing. The conducted surveys confirm that the cause of chronic rhinosinusitis with polyps is multifactorial, but a significant factor affecting typical tissue remodeling in this disease is long-term breathing of polluted atmospheric air.


Assuntos
Irritantes/efeitos adversos , Pólipos Nasais/fisiopatologia , Rinite/fisiopatologia , Sinusite/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/efeitos dos fármacos , Mucosa Nasal/efeitos dos fármacos , Polônia , Índice de Gravidade de Doença , Adulto Jovem
8.
Clin Exp Allergy ; 50(12): 1362-1371, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32986902

RESUMO

BACKGROUND: There is clinical evidence for impaired lung function in chronic rhinosinusitis with nasal polyps (CRSwNP) patients, which may be due to a high incidence of asthma comorbidity. The lung function characteristics of non-asthmatic CRSwNP patients are not known. Small airway dysfunction (SAD) is involved in the pathogenesis of asthma. However, whether SAD is detected in non-asthmatic patients with CRSwNPs remains unclear. OBJECTIVE: This study analysed the lung function of non-asthmatic patients with CRSwNPs and evaluated its clinical relevance in CRSwNPs. METHODS: The clinical data for 191 consecutive CRSwNP patients (73 asthmatic and 118 non-asthmatic) and 30 control subjects were prospectively collected. The patients were followed up for at least 3 years (mean [standard deviation], 42.47 ± 8.38 months). Serum and tissue total IgE levels were measured in 95 and 93 patients, respectively. Tissue eosinophil counts were documented in 63 patients. RESULTS: Non-asthmatic CRSwNP patients had decreased forced expiratory flow at 75% of the FVC (FEF75 ) and FEF50 compared to the control subjects, and this difference was related to the severity of CRSwNP. The risk factors for impaired lung function in asthmatic and non-asthmatic patients were duration of asthma and smoking. A multivariate logistic analysis showed that decreased FEF50 was associated with the recurrence of non-asthmatic CRSwNPs. The lung function of CRSwNP patients negatively correlated with the degree of type-2 inflammation, which was defined by the levels of Eos and IgE in polyp tissues and blood. The SAD of non-asthmatic CRSwNP patients was related to serum IgE levels. CONCLUSIONS AND CLINICAL RELEVANCE: This study provides evidence that non-asthmatic CRSwNP patients may have SAD, which correlated with the severity and recurrence of CRSwNP. The decreased lung function of patients with CRSwNP was related to the degree of type-2 inflammation.


Assuntos
Pulmão/fisiopatologia , Pólipos Nasais/complicações , Rinite/etiologia , Sinusite/etiologia , Adulto , Idoso , Asma/imunologia , Asma/fisiopatologia , Doença Crônica , Feminino , Humanos , Pulmão/imunologia , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/diagnóstico , Pólipos Nasais/imunologia , Pólipos Nasais/fisiopatologia , Prognóstico , Estudos Retrospectivos , Rinite/diagnóstico , Rinite/imunologia , Rinite/fisiopatologia , Índice de Gravidade de Doença , Sinusite/diagnóstico , Sinusite/imunologia , Sinusite/fisiopatologia , Fatores de Tempo
9.
Am J Med Sci ; 360(2): 137-145, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32423746

RESUMO

BACKGROUND: At present, the effect of operation intervention on pulmonary function is not clear in patients with allergic rhinitis and chronic rhinosinusitis with nasal polyps (AR&CRSwNP). This study was conducted to investigate the effect of vidian neurectomy on pulmonary function and airway hyperresponsiveness (AHR) in patients with AR&CRSwNP. METHODS: The incidences of AHR, bronchial asthma (BA) and pulmonary function impairment in 112 patients with AR&CRSwNP were investigated. Subsequently, we evaluated the outcome of vidian neurectomy and its effect on pulmonary function and AHR. Furthermore, we explored the correlation between postoperative level of eosinophilic cationic protein (ECP) and the changes of pulmonary function indices or dose of methacholine. RESULTS: In this study, the incidences of pulmonary function impairment, bronchial asthma, and AHR in patients with AR&CRSwNP were 61.61%, 69.64%, and 66.96%, respectively. Particularly, vidian neurectomy effectively alleviated nasal symptoms, improved pulmonary function, and reduced AHR in AR&CRSwNP patients. Furthermore, the postoperative level of ECP, IgE, Interleukin-4 and Interleukin-IL-5 was dramatically decreased, and there was an obvious inverse correlation between ECP level and pulmonary function index or dose of methacholine. CONCLUSIONS: Vidian neurectomy is effective in alleviating nasal symptoms, improving pulmonary function, and reducing the risk of AHR of patients with AR&CRSwNP by decreasing the level of ECP.


Assuntos
Denervação/métodos , Gânglio Geniculado/cirurgia , Pólipos Nasais/cirurgia , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Rinite Alérgica/cirurgia , Sinusite/cirurgia , Adulto , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/fisiopatologia , Testes de Provocação Brônquica , Doença Crônica , Proteína Catiônica de Eosinófilo/imunologia , Feminino , Volume Expiratório Forçado , Humanos , Imunoglobulina E/imunologia , Interleucina-4/imunologia , Interleucina-5/imunologia , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/imunologia , Pólipos Nasais/fisiopatologia , Complicações Pós-Operatórias/epidemiologia , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/fisiopatologia , Rinite Alérgica/imunologia , Rinite Alérgica/fisiopatologia , Sinusite/imunologia , Sinusite/fisiopatologia , Resultado do Tratamento , Capacidade Vital
10.
Auris Nasus Larynx ; 47(5): 807-813, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32139285

RESUMO

OBJECTIVE: Nucleophosmin (NPM1) has been suggested to be involved in the pathophysiologic mechanism of inflammatory disorders. We measured the expression level of NPM1 in nasal polyp (NP) tissues of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). We also assessed the correlation between NPM1 expression and other parameters such as eosinophilic infiltration, inflammatory cytokines, and clinical indicators such as Lund-Mackay computed tomography (CT) score. METHODS: Thirty patients with CRSwNP were included. We performed pre-operative CT scan to determine Lund-Mackay CT scores. During endoscopic sinus surgery, we harvested NP tissues from patients with CRSwNP. We performed Sirius red staining to evaluate eosinophilia and conducted immunohistochemical staining for NPM1 and real-time PCR for cytokines including interleukin (IL)-5, IL-17A, and IL-32. RESULTS: The mRNA expression of NPM1 was significantly up-regulated in eosinophilic NP tissues (RQ 0.58 ± 0.06), compared to non-eosinophilic NP tissues (RQ 0.38 ± 0.08, p < 0.05). In the epithelium of NP tissue, a significant positive correlation was observed between eosinophilic infiltration and NPM1 expression. The expression of NPM1 was significantly correlated with that of IL-5 (r = 0.6229, p = 0.0004), IL-17A (r = 0.5971, p = 0.001), and IL-32 (r = -0.5985, p = 0.0068). There was no significant correlation between the mRNA expression of NPM1 and the Lund-Mackay CT score (Spearman r = -0.2563, p = 0.1879). CONCLUSION: Expression of NPM1 was significantly increased in eosinophilic NP tissues from patients with CRSwNP. We observed an association between NPM1 expression and various pro-inflammatory cytokines such as IL-5, IL-17, and IL-32 and eosinophilic infiltration, which is thought to contribute to the pathophysiology of NP.


Assuntos
Pólipos Nasais/metabolismo , Proteínas Nucleares/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adulto , Doença Crônica , Citocinas/metabolismo , Eosinofilia/complicações , Eosinofilia/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Pólipos Nasais/fisiopatologia , Proteínas Nucleares/genética , Nucleofosmina , RNA Mensageiro/metabolismo , Rinite/complicações , Rinite/fisiopatologia , Sinusite/complicações , Sinusite/fisiopatologia , Tomografia Computadorizada por Raios X
11.
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
12.
Int Forum Allergy Rhinol ; 10(1): 7-14, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31899859

RESUMO

BACKGROUND: Olfactory dysfunction (OD) in chronic rhinosinusitis (CRS) is common. It is likely that numerous factors such as sex, race, age, allergies, asthma, smoking, and other comorbidities play a role in CRS-related OD. In order to determine which aspects of OD are due solely to CRS and which are associated with other confounders, control populations are needed to allow appropriate risk assessments. METHODS: Prospective, multi-institutional enrollment of patients with CRS and control subjects without CRS was performed. Demographic information, comorbidities, and olfactory testing (Sniffin' Sticks) of threshold (T), discrimination (D), and identification (I) scores (TDI) was collected. RESULTS: A total of 224 patients with CRS and 164 control subjects were enrolled. Olfaction was worse in CRS patients compared to controls (mean ± standard deviation (SD) TDI = 22.4 ± 9.5 vs 28.8 ± 7.0, respectively, p < 0.001). Only 27% of CRS patients were normosmic compared to 49% of controls (p < 0.001). When stratifying by nasal polyp (NP) status, CRSwNP patients had significant impairments in TDI, T, D, and I compared to controls with mean differences of 11.2, 3.3, 3.5, and 4.4 points, respectively (all p < 0.001). In contrast, CRSsNP patients only had impaired T when compared to controls with a mean difference of 2.2 points (p < 0.001). Multivariate modeling of TDI scoring showed that OD was driven by polyps, asthma, diabetes, and age. CRSsNP was not independently associated with worse TDI scores. CONCLUSION: OD in CRS patients is multifactorial. Independent drivers appear to be polyp status, asthma, diabetes, and age. OD in patients with CRSsNP is similar to controls with the exception of impaired thresholds.


Assuntos
Transtornos do Olfato/etiologia , Rinite/complicações , Sinusite/complicações , Adulto , Idoso , Estudos de Casos e Controles , Doença Crônica , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Pólipos Nasais/epidemiologia , Pólipos Nasais/fisiopatologia , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/fisiopatologia , Estudos Prospectivos , Rinite/epidemiologia , Rinite/fisiopatologia , Fatores de Risco , Sinusite/epidemiologia , Sinusite/fisiopatologia
13.
J Voice ; 34(4): 650.e1-650.e6, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30853310

RESUMO

OBJECTIVE: Functional Endoscopic Sinus Surgery (FESS) is the surgery of choice for nasal polyposis and chronic rhinosinusitis. The aim of our study is to assess the influence of this surgery in the acoustic parameters of voice, and their implications in the systems of identification or verification of the speaker through the speech. MATERIAL AND METHODS: A prospective study was performed between January 2017 and June 2017 including two groups of patients: those undergoing FESS, and a control group. Demographic data and GRBAS assessment were statistically analyzed. In addition, a recording of patients' voices was made with a subsequent acoustic analysis and automatic identification of the speaker through machine learning systems, establishing the equal error rate. Samples were taken before surgery, 2 weeks after surgery and 3 months later. RESULTS: After FESS, a significant difference was observed in Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS). Besides, acoustic analysis showed a significance decrease in fundamental frequency (F0), when compared with the control group. For the automatic identification of the speaker through computer systems, we found that the equal error rate is higher in the FESS group. CONCLUSIONS: Results suggest that FESS produce a decrease of F0 and changes in the vocal tract that derive in an increase in the error of recognition of the speaker in FESS patients.


Assuntos
Acústica , Endoscopia , Pólipos Nasais/cirurgia , Rinite/cirurgia , Sinusite/cirurgia , Medida da Produção da Fala , Interface para o Reconhecimento da Fala , Prega Vocal/fisiopatologia , Qualidade da Voz , Adulto , Doença Crônica , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/fisiopatologia , Reconhecimento Automatizado de Padrão , Estudos Prospectivos , Rinite/fisiopatologia , Sinusite/fisiopatologia , Espectrografia do Som , Fatores de Tempo , Resultado do Tratamento
14.
Int Forum Allergy Rhinol ; 10(3): 343-355, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31856395

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common causes of olfactory loss, but the pathophysiology underlying olfactory dysfunction in CRS has not been fully elucidated. Previous studies found correlations between olfactory cleft (OC) inflammatory cytokines/chemokines and olfaction in CRS. The purpose of this study was to evaluate the relationship between OC mucus inflammatory proteins and olfaction in a multi-institutional cohort. METHODS: Adults with CRS were prospectively recruited. Demographics, comorbidities, olfactory assessment (Sniffin' Sticks), computed tomography (CT), and OC mucus for protein analysis were collected. Statistical analysis was performed to determine associations between olfactory function, OC mucus protein concentrations, and CT opacification. RESULTS: Sixty-two patients were enrolled in the study, with an average age of 48.2 (standard deviation, 16.2) years, and 56.5% were female and 59.7% were classified as CRS with nasal polyps (CRSwNP). Ten of 26 OC mucus proteins were significantly correlated with threshold, discrimination, and identification (TDI) scores and OC opacification. Subgroup analysis by polyp status revealed that, within the CRSwNP group, C-C motif ligand 2 (CCL2), interleukin-5 (IL-5), IL-6, IL-13, IL-10, IL-9, tumor necrosis factor-α (TNF-α), CCL5, and CCL11 were significantly correlated with olfaction. For CRS without nasal polyps (CRSsNP), only C-X-C ligand 5 (CXCL5) showed a correlation. In CRSwNP, IL-6, IL-10, vascular endothelial growth factor-A, and immunoglobulin E (IgE) correlated with OC opacification, whereas, in CRSsNP, only CXCL5 showed a correlation. OC mucus proteins and Lund-Mackay score correlated only in the CRSsNP group (CXCL5, IL-5, IL-13, IgE). CONCLUSION: Several OC mucus proteins have been found to correlate with olfactory function and OC opacification. The profile of OC mucus proteins differs between CRSsNP and CRSwNP subgroups, suggesting different mechanisms between groups, but further study is required.


Assuntos
Transtornos do Olfato/metabolismo , Mucosa Olfatória/metabolismo , Rinite/fisiopatologia , Sinusite/fisiopatologia , Adulto , Doença Crônica , Citocinas/metabolismo , Feminino , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/metabolismo , Pólipos Nasais/patologia , Pólipos Nasais/fisiopatologia , Transtornos do Olfato/patologia , Transtornos do Olfato/fisiopatologia , Mucosa Olfatória/patologia , Rinite/metabolismo , Rinite/patologia , Sinusite/metabolismo , Sinusite/patologia , Olfato
15.
Auris Nasus Larynx ; 47(1): 98-104, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31272842

RESUMO

OBJECTIVE: Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a disease that features a mechanical dysfunction involving chronic inflammation and altered tissue remodeling. In this study, we aim to evaluate the fibroblast morphology and its cellular traction force in primary fibroblasts cell cultures obtained from both healthy individuals (n=7) and patients with CRSwNP (n=8). METHODS: Using a Traction-force Microscopy we analyzed parameters of Force/Tension in fibroblasts cultures in both experimental groups. RESULTS: The analysis of the Projected Area of Cell revealed that fibroblasts derived from nasal mucosa of healthy individuals have an area on average 39.24% larger than the fibroblasts obtained from the nasal polyp tissue. We also observed that the parameters directly related to the force of the cell, Max Cumulative Force and Net Contractile Moment, presented a high Force/Tension per unit of area in the fibroblasts derived from the healthy nasal mucosa (on average 41% and 52.54% higher than the fibroblasts of the nasal polyp respectively). CONCLUSION: Our results demonstrate a cellular mechanism that may be associated with the mechanical dysfunction found in the Nasal Polyp tissue. The weak traction force of nasal polyp-derived fibroblast may, in lower dimensions, impact on the remodeling of nasal mucosa in CRSwNP.


Assuntos
Fenômenos Biomecânicos , Fibroblastos/ultraestrutura , Pólipos Nasais/ultraestrutura , Pseudópodes/ultraestrutura , Estudos de Casos e Controles , Doença Crônica , Feminino , Fibroblastos/patologia , Fibroblastos/fisiologia , Humanos , Masculino , Microscopia de Força Atômica , Microscopia de Contraste de Fase , Pessoa de Meia-Idade , Pólipos Nasais/patologia , Pólipos Nasais/fisiopatologia , Cultura Primária de Células , Pseudópodes/patologia , Rinite/patologia , Sinusite/patologia
16.
Eur Rev Med Pharmacol Sci ; 23(18): 8124-8129, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31599440

RESUMO

OBJECTIVE: Samter's triad is the combination of asthma, aspirin sensitization, and nasal polyposis. Few data are available on the use of omalizumab in this disease. The study aimed to describe the impact of omalizumab on clinical and functional parameters and the quality of life of a series of patients with Samter's triad. Moreover, we aimed to provide a review of the literature on this topic. PATIENTS AND METHODS: We retrospectively described four patients with Samter's triad undergoing omalizumab therapy. Clinical, functional, and immunological data of these patients were collected at baseline and follow-up. RESULTS: Reduction of asthma exacerbations and salbutamol rescue therapy were observed in all patients after anti-IgE treatment together with an improvement in the quality of life. A significant improvement in FEV1, FVC, and FEF25-75 was observed. No major side-effects were observed. A total of 14 studies regarding omalizumab in aspirin-exacerbated respiratory diseases were included in the review, comprising 78 patients. All studies reported a good efficacy in improving asthma control; restoration of aspirin tolerance was repeatedly reported. CONCLUSIONS: The results of our case series and review of the literature suggest that omalizumab effectively improves asthma control, lung function tests, and quality of life in patients with Samter's triad.


Assuntos
Antiasmáticos/uso terapêutico , Asma Induzida por Aspirina/tratamento farmacológico , Pólipos Nasais/tratamento farmacológico , Omalizumab/uso terapêutico , Adulto , Idoso , Asma/tratamento farmacológico , Asma/fisiopatologia , Asma Induzida por Aspirina/fisiopatologia , Intervalo Livre de Doença , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/fisiopatologia , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Fluxo Máximo Médio Expiratório , Pessoa de Meia-Idade , Pólipos Nasais/fisiopatologia , Hipersensibilidade Respiratória/tratamento farmacológico , Hipersensibilidade Respiratória/fisiopatologia , Teste de Desfecho Sinonasal , Terapêutica , Capacidade Vital
17.
Curr Allergy Asthma Rep ; 19(10): 46, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31486905

RESUMO

PURPOSE OF REVIEW: Chronic rhinosinusitis and nasal polyps (CRSwNP) is a common condition that significantly affects patients' life. This work aims to provide an up-to-date overview of CRSwNP in older adults, focusing on its aging-related clinical presentations, pathophysiology, and comorbidity associations including asthma. RECENT FINDINGS: Recent large population-based studies using nasal endoscopy have shown that CRSwNP is a mostly late-onset disease. Age-related changes in physiologic functions, including nasal epithelial barrier dysfunction, may underlie the incidence and different clinical presentations of CRSwNP in older adults. However, there is still a paucity of evidence on the effect of aging on phenotypes and endotypes of CRSwNP. Meanwhile, late-onset asthma is a major comorbid condition in patients with CRSwNP; they frequently present with type 2 inflammatory signatures that are refractory to conventional treatments when they are comorbid. However, as they are more commonly non-atopic, causative factors other than classical atopic sensitization, such as Staphylococcus aureus specific IgE sensitization, are suggested to drive the type 2 inflammation. There are additional comorbidity associations in older patients with CRSwNP, including those with chronic otitis media and head and neck malignancy. Age is a major determinant for the incidence and clinical presentations of CRSwNP. Given the heterogeneity in phenotypes and endotypes, longitudinal investigations are warranted to elucidate the effects of aging on CRSwNP.


Assuntos
Pólipos Nasais/etiologia , Rinite/epidemiologia , Sinusite/epidemiologia , Idoso , Doença Crônica , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/fisiopatologia , Rinite/fisiopatologia , Sinusite/fisiopatologia
18.
Eur Arch Otorhinolaryngol ; 276(12): 3359-3366, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31270597

RESUMO

PURPOSE: Anticipating the possibility of olfactory recovery after functional endoscopic surgery (FES) in nasal polyposis (NP) is difficult. The main objective of this study was to assess the predictive factors of recovering the sense of smell after radical bilateral ethmoidectomy. Secondary objectives were to identify other predictors of olfactory recovery. METHODS: Open prospective study was conducted at the Nantes University Hospital including all patients with NP operated on in the Ear, Nose, and Throat Department between January 2011 and September 2017. These patients underwent functional endoscopic surgery (radical ethmoidectomy) after medical treatment failure. Olfaction was quantified prospectively and systematically during the preoperative consultation using a visual analog scale. Multivariate analysis evaluated the presence of predictive factors of postoperative olfactory recovery. RESULTS: One hundred nineteen patients were included in the study. Overall, olfaction was partially improved after surgery. For patients who presented greater than 50% recovery of olfaction after systemic corticosteroid therapy before surgery, we observed a predictive better rate of olfactory recovery after surgery (p < 0.001). Age over 65 years, a history of sinonasal surgery, associated asthma, and bacterial colonization were not associated with less postoperative olfactory recovery. CONCLUSION: This study identified an objective factor that may influence olfactory recovery after FES using a therapeutic trial for olfactory recovery after oral corticosteroid treatment taken before surgery.


Assuntos
Corticosteroides/uso terapêutico , Endoscopia/métodos , Seio Etmoidal/cirurgia , Pólipos Nasais/cirurgia , Transtornos do Olfato/fisiopatologia , Olfato/efeitos dos fármacos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Pólipos Nasais/fisiopatologia , Transtornos do Olfato/etiologia , Transtornos do Olfato/terapia , Procedimentos Cirúrgicos Otorrinolaringológicos/efeitos adversos , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Medição da Dor , Período Pós-Operatório , Estudos Prospectivos , Recuperação de Função Fisiológica , Olfato/fisiologia , Resultado do Tratamento , Escala Visual Analógica
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