Olfaction and Quality of Life in Patients with Eosinophilic CRS Undergoing Endoscopic Sinus Surgery.

Introduction Chronic rhinosinusitis (CRS) is a common inflammatory disease. This high prevalence leads to high direct and indirect public health costs, which include medical visits, laboratory tests and imaging, pharmacotherapy, hospitalizations, and surgical treatment. Furthermore, CRS has a substantial impact on patient quality of life, affecting productivity and being a common cause of absence from work CRS-associated olfactory dysfunction is highly prevalent, the actual effectiveness of surgical intervention remains inconsistent. Although there are studies evaluating the postoperative course of patients with eosinophilic Chronic rhinosinusitis (eCRS) treated with high-volume budesonide irrigation, there is little objective information regarding the impact of this intervention on olfactory status and quality of life. Objective To conduct a pre- and postoperative analysis of olfaction and quality of life in patients with eCRS treated with surgical intervention followed by high-volume budesonide nasal irrigation. Methods Prospective, descriptive, uncontrolled study of patients with eCRS. All patients underwent pre- and postoperative nasal endoscopy, SNOT-22 questionnaire, and the University of Pennsylvania Smell Identification Text (UPSIT), always by the same previously trained examiner. The SNOT-22 questionnaire and the UPSIT were readministered to all patients at 3 months, 6 months, and 1 year postoperatively, and scores compared with those obtained preoperatively. Results Twenty patients were included in the study, 13 males and 7 females, between the ages of 23 and 65; 8 patients had comorbid asthma. Quantitative evaluation using the UPSIT test showed a significant improvement in olfaction 3 months after surgery, which remained 6 months and 1 year after surgery (p = 0.0063). There was no significant association between eosinophil concentrations in polypoid tissue and postoperative SNOT-22 and UPSIT results. Patients with tissue eosinophils >50 had a lower preoperative UPSIT score. As early as 3 months postoperatively, a significant improvement in quality of life was already noticeable, as represented by a decrease in SNOT-22 values, which persisted through the 1-year postoperative follow-up evaluation (p = 0.0005). Quantitative evaluation using the UPSIT test showed a significant improvement in olfaction 3 months after surgery, which remained 6 months and 1 year after surgery (p = 0.0063). Conclusion Surgery effectively controlled eCRS in patients who adhered to high-volume budesonide nasal irrigation postoperatively. There were significant improvements in quality of life and olfaction, which persisted at least up to one year postoperatively.

Effect of Body Weight on Response to Nasal Glucocorticoid Treatment in Allergic Rhinitis.

Allergic rhinitis is among the most common chronic diseases in the world. Obesity can lead to a chronic systemic inflammatory process. In this study, we evaluated the effects of body weight on the response to treatment of allergic rhinitis with nasal corticosteroids. Two groups of patients diagnosed with allergic rhinitis were compared: one composed of obese patients and one composed of normal weight patients. Nasal endoscopy, peak nasal inspiratory flow, quality of life, the VAS, SNOT22, and NOSE-5 questionnaires, and the concentration of nasal cytokines (INF-γ, TNF-ᾳ, IL-4, IL-5, IL-6, and IL-10) through nasal brushing were evaluated before and after treatment with 400 mcg/day nasal beclomethasone. No differences were identified between the groups in nasal endoscopy, peak nasal inspiratory flow, the VAS, SNOT22, and NOSE-5 questionnaires, or in the cytokines INF-γ, TNF-ᾳ, IL-4, IL-5, IL-6, and IL-10 prior to nasal corticosteroid treatment. Both groups showed improvement in the VAS, SNOT-22, and NOSE-5 questionnaires and an increase in peak nasal inspiratory volumes after treatment. In the eutrophic group, there was an increase in INF-γ and IL-5 after treatment. When comparing the variation in cytokines before and after treatment between groups, IL-10 was the cytokine that showed altered behavior dependent on weight. Obesity did not seem to impact nasal symptoms and physiology and presented a similar clinical response to treatment with nasal corticosteroids to normal weight patients. However, obese patients had an impaired anti-inflammatory response during treatment with nasal corticosteroids.

Comparison between upper and lower airway microbiome profiles in chronic rhinosinusitis patients.

BACKGROUND: Dysregulation of the airway microbiota is thought to contribute to airway inflammation in both chronic rhinosinusitis (CRS) and asthma. However, the relationship between the upper and lower airway microbiome remains unclear. METHODS: Sinus and lung brushes were collected from 29 CRS participants undergoing sinus surgery. DNA was extracted and submitted for 16s rRNA microbiome sequencing. Alpha and beta diversity metrics, taxonomic composition, and differences between individual taxa were compared for paired sinus and bronchial samples. RESULTS: Twenty-three out of 29 participants had sufficient samples for analysis. The mean (standard deviation) age was 51.59 (14.57) years, and 10 (44%) patients were female. Twelve (52%) patients had comorbid asthma. Sinus brushes had significantly higher alpha diversity indexes (Shannon and Faith) compared to bronchial brushes (p < 0.001). Beta diversity metrics were significantly different between the sinus and bronchial samples. Principal coordinate analysis showed no clustering of paired nasal and bronchial samples. Sinus brushes had significantly more Lawsonella, Corynebacterium, and Staphylococcus compared to bronchia brushes, while the latter were enriched in Tropheryma and Sphingomonas, among others (false discovery rate [FDR]-adjusted p < 0.01). Finally, CRS patients with comorbid asthma had significantly higher Pseudomonas and Peptoniphilus in sinus brushes and lower Prevotella in bronchial brushes when compared to non-asthmatics (FDR-adjusted p < 0.01). CONCLUSION: The sinus and bronchial bacterial microbiomes differ in important ways. Our study suggests that migration of bacteria from the sinus into the lower airways is unlikely in patients with CRS.

Differential Angiogenic Induction Impacts Nasal Polyp Tissue Growth.

In chronic rhinosinusitis with nasal polyps, inflammatory edema drives tissue remodeling favoring anomalous growth of the nasal mucosa, but a proangiogenic contribution of nasal polyp in support of tissue growth is still controversial. The chorioallantoic membrane of chicken embryo model was employed to address the potentiality of nasal tissue fragments to modulate angiogenesis. Fifty-seven fertilized eggs were implanted with polyp or healthy nasal mucosa tissue or were kept as non-implanted controls. The embryos' size, length, and development stage, and chorioallantoic membrane vasculature morphology were evaluated after 48 h. Quantitative computer vision techniques applied to digital chorioallantoic membrane images automatically calculated the branching index as the ratio between the areas of the convex polygon surrounding the vascular tree and the vessels' area. Ethics approval and consent to participate: the study was approved by the Human Research Ethics Committee of the Federal University of São Paulo (CAAE number: 80763117.1.0000.5505) and by the Animal Research Ethics Committee of University of São Paulo (nº CEUA 602-2019). Mucosal, but not polyp tissue implants, hampered embryo development and induced underdeveloped chorioallantoic membranes with anastomosed, interrupted, and regressive vessels. Vessels' areas and branching indexes were higher among the chorioallantoic membranes with polyp implants and controls than among those with healthy mucosa implants. Nasal polyp presents differential angiogenic induction that impacts tissue growth.

Impact of Chronic Rhinosinusitis with Nasal Polyposis on IL-12 and IL-8.

Introduction: The pathophysiology of Chronic Rhinosinusitis is coordinated by distinct inflammatory reactions in different individuals. Inflammatory environments with a predominance of Th2 lymphocytes tend also to be rich in eosinophils. These environments are common during the formation of nasal polyps associated with aspirin intolerance, which is also marked by an increase in inflammatory mediators, especially IL-4, IL-5, and IL-13. Despite the significance of these inflammatory mediators, the relevance of IL-12 subunits' presence within eosinophilic nasal polyps, however, has been less studied. The current study aims to evaluate the presence of IL-12 subunits, IL-12p40 and IL-12p70, in eosinophilic nasal polyps and their correlations with IL-8 presence. Materials and Methods: We compared the concentrations of IL-8, IL12p40, and IL12p70 among samples of eosinophilic nasal polypoid tissue, eosinophilic nasal polypoid tissue associated with aspirin intolerance, and healthy nasal mucosa, using an indirect immunoassay (ELISA) kit. Results: When compared to healthy nasal mucosa, there was a lower concentration of IL-8 in Chronic Rhinosinusitis with Nasal Polyp (CRSwNP) tissue. Aspirin Intolerant polypoid tissue also presented a lower concentration of IL-12 subunits compared to healthy nasal mucosa. There was no significant correlation between IL-8 and IL-12 in the eosinophilic polypoid conditions. Conclusion: In CRSwNP, there is a reduction in IL-8 and IL-12 subunits compared to control, with a lack of correlation between IL-12 and IL-8. The lack of correlation can be justified by a type two inflammatory storm environment.

Upper Airway Mucociliary Clearance is Impaired in Dyspneic COVID-19 Patients.

Covid-19 is transmitted mainly by respiratory droplets and as the upper airway mucosa is the first innate immune barrier, it is crucial to understand the effects of SARS-CoV-2 on this system. In the current study, we aimed to evaluate the nasal mucociliary clearance in patients with SARS-CoV-2 infection and their symptom development. Observational cross-sectional study. The nasal mucociliary clearance (NMC) time was evaluated by the saccharin test and the results were compared between patients with SARS-CoV-2 infection (group 1) and controls (group 2, asymptomatic patients with a negative polymerase chain reaction test). We also compared the NMC time for each specific symptom suffered by participants in group 1 with the NMC time of the control group as well as with the patients in group 1 who were asymptomatic. There was a significant increase in NMC time in group 1 with dyspnea when compared to the control group (p = 0.032) and also when compared to patients who were infected were not dyspneic (p = 0.04). There were no differences in the clearance times when considering other symptoms. COVID-19 patients with dyspnea present with altered nasal mucociliary clearance.

Three-dimensional cell culture for the study of nasal polyps

Abstract Objectives: Three-dimensional (3D) cell cultures have many applications such as stem cell biology research, new drug discovery, cancer, and Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). This disease is characterized by a significant impact on quality of life and productivity. The diversity of factors that act in the progression of CRSwNP point to the creation of a cell culture model that allows the integration of different cell types with extracellular matrix. This work aimed to create a cell culture model in 3 dimensions (spheroids) for the study of Nasal Polyposis. Methods: Nasal polyp tissue from patients diagnosed with CRSwNP was mechanically dissociated using tweezers and a scalpel and the solution containing cells and small aggregates of nasal polyps was transferred to a Petri dish containing 5 mL of culture medium at the concentration of 106 cells/mL. Results: The spheroids were cultivated for 20 days, fixed and analyzed using confocal microscopy. In a 3D culture environment, the spheroids were formed both by clustering cells and from small tissue fragments. In the cultures analyzed, the ciliary beat was present from the dissociation of the cells up to 20 days in culture. Conclusion: Our findings also point to these characteristics showing the environment generated in our study, the cells remained differentiated for a longer time and with ciliary beating. Thus, this work shows that nasal polyp-derived cells can be maintained in a 3D environment, enabling better strategies for understanding CRSwNP in situations similar to those found in vivo. Level of evidence: Laboratory studies.

New Nasopharyngeal Flap for Posterior Skull-base Reconstruction: The Upper-Tongue Flap

Abstract Introduction Reconstructions of clival resection are still challenging, and additional reconstructive methods may be necessary to achieve full coverage of the skull-base defect in patients with middle- and lower-clivus disease. Objective To describe a new nasopharyngeal flap for the middle and lower clivus. Methods Using nasal endoscopy in a cadaver dissection, we demonstrated a new nasopharygeal flap to cover the lower and middle clival resection. Results We described a new nasopharyngeal flap capable of covering the lower and middle portion of the clivus. Discussion The new nasopharyngeal flap, called the upper-tongue flap, is particularly adequate as an alternative for the reconstruction of middle and lower clivus defects, and it is better used in association with a nasalseptal flap in cases in which the nasalseptal flap alone does not provide enough mucosal coverage. Conclusion The new nasopharyngeal flap can be used in the reconstruction of clival resection.

New Nasopharyngeal Flap for Posterior Skull-base Reconstruction: The Upper-Tongue Flap.

Introduction Reconstructions of clival resection are still challenging, and additional reconstructive methods may be necessary to achieve full coverage of the skull-base defect in patients with middle- and lower-clivus disease. Objective To describe a new nasopharyngeal flap for the middle and lower clivus. Methods Using nasal endoscopy in a cadaver dissection, we demonstrated a new nasopharygeal flap to cover the lower and middle clival resection. Results We described a new nasopharyngeal flap capable of covering the lower and middle portion of the clivus. Discussion The new nasopharyngeal flap, called the upper-tongue flap, is particularly adequate as an alternative for the reconstruction of middle and lower clivus defects, and it is better used in association with a nasalseptal flap in cases in which the nasalseptal flap alone does not provide enough mucosal coverage. Conclusion The new nasopharyngeal flap can be used in the reconstruction of clival resection.

CD133, a Progenitor Cell Marker, is Reduced in Nasal Polyposis and Showed Significant Correlations with TGF-β1 and IL-8

Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.

Impact of SARS-CoV-2 on saliva: TNF-⍺, IL-6, IL-10, lactoferrin, lysozyme, IgG, IgA, and IgM.

OBJECTIVES: Understanding the role of certain salivary components, such as TNF-⍺, IL-6, IL-10, lactoferrin, lysozyme, IgG, IgA, and IgM, in airway defense during the ongoing SARS-CoV-2 pandemic is essential. The salivary immune barrier of patients with COVID-19 may play a role in their prognosis. The present study aims to evaluate the impact of SARS-CoV-2 on saliva composition. METHODS: A longitudinal study was carried out with male and female firefighters aged 24-48 years. The study sample (n = 34) was divided into 3 groups: asymptomatic volunteers with a negative polymerase chain reaction (PCR) test for SARS-CoV-2 (group 1, Control, n = 21); patients with symptoms of COVID-19 of less than 7 days' duration and a diagnosis of SARS-CoV-2 infection by PCR (group 2, COVID-19, n = 13); and recovered patients from group 2 who were free of COVID-19 symptoms for at least 2 months (group 3, post-COVID-19 recovery, n = 13). All groups underwent real-time PCR to detect the presence of SARS-CoV-2, as well as analysis of the salivary concentrations of TNF-⍺, IL-6, IL-10, lactoferrin, lysozyme, IgG, IgA, and IgM by the ELISA method. RESULTS: Lactoferrin concentrations were significantly decreased in the infected group (COVID-19) when compared to those not infected by SARS-CoV-2 (control) (p = 0.032). IgA concentrations were decreased in the COVID-19 and post-COVID-19 groups compared to the control group (p = 0.005 and p = 0.016, respectively). Comparison of the COVID-19 and post-COVID-19 groups also revealed an increase in IgM concentrations during acute SARS-CoV-2 infection (p = 0.010). CONCLUSION: SARS-CoV-2 alters the composition of the salivary immune barrier.

CD133, a Progenitor Cell Marker, is Reduced in Nasal Polyposis and Showed Significant Correlations with TGF-ß1 and IL-8.

Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor ß1 (TGF-ß1). Methods A total of 74 subjects were divided in the following groups: control group ( n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group ( n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group ( n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-ß1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-ß1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-ß1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.

The Effects in the Upper Airway of Heat and Exposure to Combustion Byproducts of Burning Materials on Larynx of Firefighters.

INTRODUCTION: High exposure to heat and combustion byproducts is associated with health problems and an increased risk of cancer. OBJECTIVE: To study the effects of heat and smoke derived from burning on the upper airway of firefighters. METHODS: Thirteen firefighters underwent a 4-week training program in Compartment Fire Behavior Training simulators while working with live fire, heat, and smoke from pallets and oriented-strand board sheet burns. The firefighters were evaluated before exposure and at the end of the first and fourth weeks of training. The larynx was assessed by the Voice Handicap Index GRBASI scale, laryngoscopy, and peak expiratory flow. RESULTS: There was no change in Voice Handicap Index and GRBASI (only one in three speech therapists judged tension as worse by one point). Laryngoscopy showed alterations in one-third of the firefighters, with the most frequent being increased viscous mucus. Peak expiratory flow decreased significantly from 685 to 552 and 550 L/min in the first and fourth weeks, respectively. CONCLUSIONS: Although participants were protected from gases and smoke during the exercises, which proved to be very effective, the airway was slightly impacted by heat and combustion-derived byproducts.

Three-dimensional cell culture for the study of nasal polyps.

OBJECTIVES: Three-dimensional (3D) cell cultures have many applications such as stem cell biology research, new drug discovery, cancer, and Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). This disease is characterized by a significant impact on quality of life and productivity. The diversity of factors that act in the progression of CRSwNP point to the creation of a cell culture model that allows the integration of different cell types with extracellular matrix. This work aimed to create a cell culture model in 3 dimensions (spheroids) for the study of Nasal Polyposis. METHODS: Nasal polyp tissue from patients diagnosed with CRSwNP was mechanically dissociated using tweezers and a scalpel and the solution containing cells and small aggregates of nasal polyps was transferred to a Petri dish containing 5 mL of culture medium at the concentration of 106 cells/mL. RESULTS: The spheroids were cultivated for 20 days, fixed and analyzed using confocal microscopy. In a 3D culture environment, the spheroids were formed both by clustering cells and from small tissue fragments. In the cultures analyzed, the ciliary beat was present from the dissociation of the cells up to 20 days in culture. CONCLUSION: Our findings also point to these characteristics showing the environment generated in our study, the cells remained differentiated for a longer time and with ciliary beating. Thus, this work shows that nasal polyp-derived cells can be maintained in a 3D environment, enabling better strategies for understanding CRSwNP in situations similar to those found in vivo. LEVEL OF EVIDENCE: Laboratory studies.

Effect of topical corticosteroids on nasal patency after acute positive airway pressure exposure / Efeito dos corticosteroides tópicos na patência nasal após exposição aguda à pressão positiva nas vias aéreas

Abstract Introduction Nasal congestion and obstruction are reported in the majority of continuous positive airway pressure users and are frequently cited as reasons for noncompliance. Baseline inflammation due to allergic rhinitis could increase or exacerbate the inflammatory effect of high airflow in the nasal cavity as the result of continuous positive airway pressure and lead to greater continuous positive airway pressure intolerance. In this setting, intranasal steroids would be expected to counteract the nasal inflammation caused by allergic rhinitis and/or continuous positive airway pressure. Objective The aim of the present study is to evaluate the effects of topical corticosteroid use on nasal patency after acute exposure to positive pressure. Methods Ten individuals with allergic rhinitis were exposed to 1 h of continuous airway pressure (15 cm H2O) in the nasal cavity, delivered by a continuous positive airway pressure device. Visual analog scale, nasal obstruction symptom evaluation scale, acoustic rhinometry and peak nasal inspiratory flow were performed before and after the intervention. After 4 weeks topical nasal steroid (budesonide) application, positive pressure exposure was repeated as well as the first assessments. Results Patients reported a statistically significant improvement both on the visual analog (p = 0.013) and obstruction symptom evaluation scales (p < 0.01). Furthermore, objective measurements were improved as well, with increased nasal cavity volume on acoustic rhinometry (p = 0.02) and increased peak nasal inspiratory flow (p = 0.012), after corticosteroid treatment. Conclusion In patients with allergic rhinitis, intranasal corticosteroid therapy improved objective and subjective parameters of nasal patency after acute exposure of the nasal cavity to positive pressure.

Resumo Introdução Congestão e obstrução nasais são relatadas na maioria dos usuários de pressão positiva contínua nas vias aéreas e são frequentemente mencionadas como razões para a falta de aderência. A inflamação basal devida à rinite alérgica pode aumentar ou agravar o efeito inflamatório do alto fluxo de ar na cavidade nasal como resultado da pressão positiva contínua nas vias aéreas e aumentar a intolerância à mesma. Nesse cenário, espera-se que os esteróides intranasais neutralizem a inflamação nasal causada pela rinite alérgica e/ou pela pressão positiva contínua nas vias aéreas. Objetivo Avaliar os efeitos do uso tópico de corticosteroides na patência nasal após exposição aguda à pressão positiva. Métodos Dez indivíduos com rinite alérgica foram expostos a uma hora de pressão contínua nas vias aéreas (15 cm H2O) na cavidade nasal, fornecida por um dispositivo de pressão positiva contínua nas vias aéreas. A escala visual analógica, a escala Nasal Obstruction Symptom Evaluation, rinometria acústica e pico de fluxo inspiratório nasal foram aplicados antes e após a intervenção. Após 4 semanas de aplicação tópica de esteroide nasal (budesonida), a exposição positiva à pressão foi repetida, bem como as primeiras avaliações. Resultados Os pacientes relataram uma melhoria estatisticamente significante tanto na escala visual analógica (p = 0,013) quanto na escala Nasal Obstruction Symptom Evaluation (p < 0,01). Além disso, as medidas objetivas também foram melhoradas, com aumento do volume da cavidade nasal na rinometria acústica (p = 0,02) e aumento do pico de fluxo inspiratório nasal (p = 0,012), após o tratamento com corticosteroide. Conclusão Em pacientes com rinite alérgica, a terapia com corticosteroide intranasal melhorou os parâmetros objetivos e subjetivos da patência nasal após exposição aguda da cavidade nasal à pressão positiva.

Prospective evaluation of clarithromycin in recurrent chronic rhinosinusitis with nasal polyps / Avaliação prospectiva da claritromicina na rinossinusite crônica com polipose nasossinusal recorrente

Abstract Introduction The antiinflammatory effects of macrolides, especially clarithromycin, have been described in patients with chronic rhinosinusitis without polyps and also other chronic inflammatory airway diseases. There is no consensus in the literature regarding the effectiveness of clarithromycin in patients with chronic rhinosinusitis with sinonasal polyposis and the national literature does not report any prospective studies on the efficacy of clarithromycin in chronic rhinosinusitis in our population. Objective To evaluate the effect of clarithromycin in the adjunctive treatment of recurrent chronic rhinosinusitis with sinonasal polyposis refractory to clinical and surgical treatment. Methods Open prospective study with 52 patients with chronic rhinosinusitis and recurrent sinonasal polyposis. All subjects received nasal lavage with 20 mL 0.9% SS and fluticasone nasal spray, 200 mcg / day, 12/12 h for 12 weeks; and clarithromycin 250 mg 8/8 h for 2 weeks and, thereafter, 12/12 h for 10 weeks. The patients were assessed by SNOT 20, NOSE and Lund-Kennedy scales before, immediately after treatment and 12 weeks after treatment. The patients were also evaluated before treatment with paranasal cavity computed tomography (Lund-Mackay) and serum IgG, IgM, IgA, IgE and eosinophil levels. The outcomes evaluated were: SNOT-20, NOSE and Lund-Kennedy. Results Most patients were women, aged 47 (15) years (median / interquartile range), and 61.5% (32/52) had asthma. All patients completed the follow-up after 12 weeks and 42.3% (22/52) after 24 weeks. Treatment resulted in a quantitative decrease in the SNOT-20 [2.3 (1.6) vs. 1.4 (1.6); Δ = −0.9 (1.1); p < 0.01]; NOSE [65 (64) vs. 20 (63); Δ = −28 (38), p < 0.01] and Lund-Kennedy [11 (05) vs. 07 (05); Δ = −2 (05); p < 0.01] scores. SNOT-20 showed a qualitative improvement (>0.8) in 54% (28/52, p < 0.04) of patients, a group that showed lower IgE level [108 (147) vs. 289 (355), p < 0.01]. The group of patients who completed follow-up 12 weeks after the end of treatment (n = 22) showed no worsening of outcomes. Conclusion Long-term adjuvant use of low-dose clarithromycin for chronic rhinosinusitis patients with recurrent sinonasal polyposis refractory to clinical and surgical treatment has resulted in improved quality of life and nasal endoscopy findings, especially in patients with normal IgE levels. This improvement persisted in the patient group evaluated 12 weeks after the end of the treatment.

Resumo Introdução Os efeitos anti-inflamatórios dos macrolídeos são reconhecidos, principalmente da claritromicina para os pacientes com rinossinusite crônica sem pólipos e outras doenças inflamatórias crônicas das vias aéreas em outras populações. Não existe consenso na literatura quanto a sua prescrição para os pacientes de rinossinusite crônica com polipose nasossinusal e a literatura nacional não dispõe de estudos prospectivos sobre a eficácia da claritromicina na rinossinusite crônica em nossa população. Objetivo Avaliar o efeito da claritromicina no tratamento adjuvante da rinossinusite crônica recorrente com polipose nasossinusal refratária ao tratamento clínico e cirúrgico. Método Estudo prospectivo aberto, com 52 pacientes, portadores de rinossinusite crônica com polipose nasossinusal recorrente. Todos os indivíduos receberam lavagem nasal com SF 0,9% 20 mL e fluticasona spray nasal, 200 mcg/dia, 12/12 horas por 12 semanas; e claritromicina 250 mg, de 8/8 horas, por 2 semanas e posteriormente 12/12 horas, por 10 semanas. Os pacientes foram avaliados através do SNOT 20, do NOSE e Lund-Kennedy antes, pós-tratamento imediato e 12 semanas após o tratamento. Os pacientes também foram avaliados antes do tratamento por tomografia computadorizada das cavidades paranasais (Lund-Mackay) e dosagem sérica de IgG, IgM, IgA, IgE e eosinófilos. Os desfechos avaliados foram: SNOT-20, NOSE e Lund-Kennedy. Resultados A maioria dos pacientes era mulher, idade de 47 (15) anos (mediana/intervalo interquartílico) e 61,5% (32/52) portadores de asma. Todos os pacientes completaram o seguimento após 12 semanas e 42,3% (22/52) após 24 semanas. O tratamento resultou em uma diminuição quantitativa do SNOT-20 [2,3 (1,6) vs. 1,4 (1,6); Δ = -0,9 (1,1); p< 0,01]; do NOSE [65 (64) vs. 20 (63); Δ = -28 (38), p< 0,01] e do Lund-Kennedy [11 (05) vs. 07 (05); Δ = -2 (05); p< 0,01]. O SNOT-20 mostrou uma melhoria qualitativa (> 0,8) em 54% (28/52, p< 0,04) dos pacientes, grupo que evidenciou menor nível de IgE [108 (147) vs. 289 (355), p< 0,01]. O grupo de pacientes que completou o seguimento 12 semanas após o término do tratamento (n = 22) não mostrou uma pioria dos desfechos. Conclusão O uso prolongado adjuvante da claritromicina em baixas doses para pacientes com rinossinusite crônica com polipose nasossinusal recorrente refratária ao tratamento clínico e cirúrgico resultou em melhoria na qualidade de vida e endoscopia nasal, principalmente em pacientes com níveis de IgE normal. Essa melhoria se sustentou no grupo de pacientes avaliado 12 semanas após o término do tratamento.

BMP-7, MMP-9, and TGF-ß tissue remodeling proteins and their correlations with interleukins 6 and 10 in chronic rhinosinusitis.

INTRODUCTION: Chronic rhinosinusitis without nasal polyposis (CRSsNP) and Chronic rhinosinusitis with nasal polyposis (CRSwNP) present distinct tissue remodeling processes. The proteins involved in the process of tissue remodeling have their production and activity related to the inflammatory environment they are. This study aimed to evaluate the protein expression of BMP-7, MMP-9, TGF-ß in chronic sinusitis with and without nasal polyposis and their relations with IL-6 and IL-10. METHODS: Cross-sectional observational study with 86 participants was divided into three groups: patients with CRSwNP (n = 34), patients with CRSsNP (n = 26), and a control group (CG) without inflammatory disease of the nasal mucosa (n = 26). The primary outcomes were the concentrations of BMP-7, MMP-9, TGF-ß, IL-6, and IL-10. Secondary outcomes were the correlations of these markers. RESULTS: The TGF-ß dosage was elevated in the CRSsNP group and reduced in the CSwNP group. The dosage of IL-6 was higher in the CSwNP group, and the IL-10 dosage lower in the groups with sinusitis, and IL-10 was positively correlated with BMP-7 in all groups. There was a negative correlation between IL-6 and IL-10 in all groups observed. The correlation between MMP-9 and interleukins was lost in the CRSsNP group. There was a positive correlation between TGF-ß and IL-6 in the CG, and negative in the CRSsNP group. CONCLUSION: An inflammation shown in rhinosinusitis with an increase in IL-6 and decrease in IL-10 when compared with the control group; only TGF-ß was altered in the tissue remodeling process when compared with BMP-7 and MMP-9 in rhinosinusitis. There is a loss of correlation between tissue remodeling proteins and interleukins studied in CRSsNP.

Montelukast Has no Impact on the Systemic Production of TGFß-1 in Patients with Nasal Polyposis Associated with Aspirin Intolerance.

Introduction Nasal polyposis is a disease characterized by a mechanical dysfunction of the nasal mucosa, closely related to the unique makeup of its extracellular matrix, which develops as the result of an anomalous tissue remodeling process. Transforming growth factor beta 1 (TGF-ß1) is reduced not only in the nasal polypoid tissue, but also in the plasma of aspirin-intolerant patients. These patients exhibit an imbalance in the production of eicosanoids characterized by an increase in leukotrienes. Thus, it is important that the relationship between the production of leukotrienes and TGF-ß1 be assessed. Objective To evaluate the effects of the cysteinyl leukotriene (CysLT) receptor antagonist montelukast on the systemic production of TGF-ß1 in patients with nasal polyposis, with or without concomitant aspirin intolerance. Methods The sample comprised 48 individuals with diagnosis of nasal polyposis and 15 healthy controls for comparison of the baseline TGF-ß1 levels in the peripheral blood and after treatment with CysLT receptor antagonist montelukast in the nasal-polyposis group. Results There was no difference in the change in TGF-ß1 levels after the treatment with montelukast in the subgroup of patients with polyposis and asthma ( p = 0.82) and in the subgroup with polyposis, asthma, and aspirin intolerance ( p = 0.51). Conclusion we found no impact of the therapy with a leukotriene receptor blocker on the production of TGF-ß1, making the antileukotriene therapy a highly questionable choice for the treatment of nasal polyposis, particularly from the standpoint of seeking to modify the remodeling process in this disease.

Montelukast Has no Impact on the Systemic Production of TGFβ-1 in Patients with Nasal Polyposis Associated with Aspirin Intolerance

Abstract Introduction Nasal polyposis is a disease characterized by a mechanical dysfunction of the nasal mucosa, closely related to the unique makeup of its extracellular matrix, which develops as the result of an anomalous tissue remodeling process. Transforming growth factor beta 1 (TGF-β1) is reduced not only in the nasal polypoid tissue, but also in the plasma of aspirin-intolerant patients. These patients exhibit an imbalance in the production of eicosanoids characterized by an increase in leukotrienes. Thus, it is important that the relationship between the production of leukotrienes and TGF-β1 be assessed. Objective To evaluate the effects of the cysteinyl leukotriene (CysLT) receptor antagonist montelukast on the systemic production of TGF-β1 in patients with nasal polyposis, with or without concomitant aspirin intolerance. Methods The sample comprised 48 individuals with diagnosis of nasal polyposis and 15 healthy controls for comparison of the baseline TGF-β1 levels in the peripheral blood and after treatment with CysLT receptor antagonist montelukast in the nasal-polyposis group. Results There was no difference in the change in TGF-β1 levels after the treatment with montelukast in the subgroup of patients with polyposis and asthma (p = 0.82) and in the subgroup with polyposis, asthma, and aspirin intolerance (p = 0.51). Conclusion we found no impact of the therapy with a leukotriene receptor blocker on the production of TGF-β1, making the antileukotriene therapy a highly questionable choice for the treatment of nasal polyposis, particularly from the standpoint of seeking to modify the remodeling process in this disease.