Background Tonsils are strategically located in the gateway of both alimentary and respiratory tracts representing the first contact point of food and aeroallergens with the immune system. ...Tonsillectomy removes only the palatine tonsils and sometimes adenoids. Lingual tonsil is anatomically big and remains lifelong intact. Objective The aim of this study was to demonstrate cellular and molecular mechanisms of oral tolerance induction to food and aeroallergens in human tonsils. Methods Tonsil allergen-specific FOXP3+ regulatory T (Treg) cells, plasmacytoid dendritic cells (pDCs), and myeloid dendritic cells were characterized by flow cytometry and suppressive assays. Intracellular staining, 3 H-thymidine incorporation, and carboxy-fluorescein succinimidyl ester dilution experiments were performed. Tonsil biopsies were analyzed by confocal microscopy. Results CD4+ FOXP3+ Treg cells and pDCs constitute important T- and dendritic cell–compartments in palatine and lingual tonsils. Tonsil pDCs have the ability to generate functional CD4+ CD25+ CD127− FOXP3+ Treg cells with suppressive property from naive T cells. CD4+ FOXP3+ Treg cells proliferate and colocalize with pDCs in vivo in T-cell areas of lingual and palatine tonsils. Tonsil T cells did not proliferate to common food and aeroallergens. Depletion of FOXP3+ Treg cells enables the allergen-induced proliferation of tonsil T cells, indicating an active role of Treg cells in allergen-specific T-cell unresponsiveness. High numbers of major birch pollen allergen, Bet v 1–specific CD4+ FOXP3+ Treg cells, are identified in human tonsils compared with peripheral blood. A positive correlation between the percentages of FOXP3+ Treg cells and pDCs is observed in tonsils from nonatopic individuals. Conclusion Functional allergen-specific Treg cells are identified both in lingual and in palatine tonsils.
The history of saline nasal irrigation (SNI) is indeed a long one, beginning from the ancient Ayurvedic practices and gaining a foothold in the west at the beginning of the 20th century. Today, there ...is a growing number of papers covering the effects of SNI, from in vitro studies to randomized clinical trials and literature overviews. Based on the recommendations of most of the European and American professional associations, seawater, alone or in combination with other preparations, has its place in the treatment of numerous conditions of the upper respiratory tract (URT), primarily chronic (rhino)sinusitis, allergic rhinitis, acute URT infections and postoperative recovery. Additionally, taking into account its multiple mechanisms of action and mounting evidence from recent studies, locally applied seawater preparations may have an important role in the prevention of viral and bacterial infections of the URT. In this review we discuss results published in the past years focusing on seawater preparations and their use in clinical and everyday conditions, since such products provide the benefits of additional ions vs. saline, have an excellent safety profile and are recommended by most professional associations in the field of otorhinolaryngology.
Nasal polyps recur in approximately one-third of patients after surgical treatment. It would be beneficial to be able to predict the patients in whom we might expect recurrence and to predict the ...clinical outcome after surgery. The study included 30 patients operated for nasal polyps. Removed polyps were analyzed by immunohistochemical analysis for IL-5, IgE, vascular endothelial growth factor and eosinophilic infiltration. These parameters together with preoperative CT score were used as independent variables, and subjective score improvement after 2 years was used as a dependent variable in multiple linear regression analysis. Furthermore, the patients were divided into two groups: low and high polyp tissue immunoreactivity. The Chi-squared test was used to determine whether polyp immunoreactivity influences polyp recurrence and subjective score. Preoperative CT score had a slightly positive correlation with subjective score after 2 years. High eosinophil infiltration significantly predicted a higher risk for polyp recurrence. High IL-5 positivity was related to greater risk for polyp recurrence than low IL-5 reactivity but not significantly. IgE and VEGF reactivity in polyp specimens did not have any effect on polyp recurrence. High eosinophilic infiltration in polyps can predict worse outcome after surgical treatment of chronic rhinosinusitis with nasal polyposis. IgE and VEGF do not have prognostic significance to polyp recurrence after surgery. The preoperative extent of disease measured by CT score had a slightly positive correlation with worse outcome after surgery.
Chronic rhinitis and rhinosinusitis (CR and CRS) can lead to impairment of the health-related quality of life (HRQL) with higher psychological perceived distress, resulting in disease worsening and ...poor treatment outcomes. W aimed to evaluate the potential association between disease severity and HRQL impairment with the perceived acute psychological distress in newly diagnosed CR/CRS patients. This single-center cross-sectional study included otherwise healthy consecutive adults with newly diagnosed CR/CRS (European position paper on rhinosinusitis and nasal polyp criteria and International Consensus Statement on Allergy and Rhinology - Allergic Rhinitis criteria or non-allergic rhinitis), who were evaluated for CR/CRS symptom severity and HRQL (Sino Nasal Outcome Test 22 SNOT-22, visual analog scale VAS) and acute perceived distress (Perceived Stress Scale PSS). Principal component analysis (SNOT-22 items, VAS) identified 6 components as CR/CRS severity indicators, i.e,, poor sleep, wakes-up tired, nasopharynx, obstruction, torment and rhinorrhea, which were evaluated for association with PSS score. Of the 63 included patients (20 men, age median 38, range 19-75 years), 27 suffered from CR and 36 from CRS. Upon adjustment for age and sex, higher total SNOT-22 (geometric means ratio GMR=1.04, 95% CI 1.01-1.06), higher "torment" (GMR=1.13, 1.04-1.24), higher "poor sleep" (GMR=1.11, 1.02-1.21) and higher "wakes-up tired" (GMR=1.11, 1.01-1.21) scores were each associated with a higher PSS score, overall and consistently in CR and CRS patients. In conclusion, more severe CR/CRS is associated with greater perceived psychological distress already at earlier stages of the disease. Paying attention to patient level of distress and anxiety over time may enable better understanding of the connection between exacerbations, symptom severity and psychological burden of the disease.
This EAACI Task Force document aims at providing the readers with a comprehensive and complete overview of the currently available tools for diagnosis of nasal and sino‐nasal disease. We have tried ...to logically order the different important issues related to history taking, clinical examination and additional investigative tools for evaluation of the severity of sinonasal disease into a consensus document. A panel of European experts in the field of Rhinology has contributed to this consensus document on Diagnostic Tools in Rhinology.
Objective
Сhronic rhinosinusitis with nasal polyps (CRSwNPs) is a distinct entity within the chronic rhinosinusitis group of diseases, which are chronic upper airway diseases with several pheno- and ...endotypes. Oxidative stress plays an important role in the pathogenesis of CRSwNPs. The aim was to assess the association between expression of the aryl hydrocarbon receptor (AhR) and 4-hydroxynonenal (4-HNE) in patients with CRSwNPs.
Methods
The study included 26 patients who underwent endoscopic sinus surgery: Fourteen patients with CRSwNPs, and 12 controls with healthy sinus mucosa. Expression of AhR and 4-HNE was assessed in tissue samples using immunohistochemistry. The level of 4-HNE in serum samples was measured using the ELISA assay. Total oxidative capacity (TOC) was assessed by measuring the peroxidase activity.
Results
Higher levels of 4-HNE expression were observed in tissues (3, range 1–3 vs. 0, range 0–0 p<0.001) and serum (27.7±11.5 vs 9.8±7.7 pmol/mg, p < 0.001) samples of CRSwNPs patients, as compared to healthy controls. Higher expression of AhR was found in inflammatory cells (plasma cells, lymphocytes, eosinopholes) of CRSwNPs patients, compared to controls (3, range 1–3 vs. 2, range 1–2, p = 0.001). There were no differences in TOC across groups (0.0285±0.0207 vs 0.02, 978±0.0197 µM H2O2 eq., p = 0.848). Patients with bronchial asthma (57%) had abundant eosinophil in tissue samples. Patients with recalcitrant CRSwNPs had higher 4-HNE serum levels, compared to non-recalcitrant cases (27.3 vs 24.2 pmol/mg, p = 0.339).
Conclusion
Patients suffering from CRSwNPs have oxidative stress–mediated overexpression of AhR, which is linked to a chronic inflammatory response in the paranasal sinus tissues.
Chronic stress exposure carries greater risk of onset of atopic respiratory disorders such as rhinitis and asthma. The interaction between depression, anxiety, and severity of chronic rhinosinusitis ...(CRS) has been suggested. We aimed to access the relationship between psychological stress, severity of CRS, and atopy. Sixty-three consecutive patients referred with CRS were asked to score the severity of rhinosinusitis symptoms on a visual analog scale and to fill in questionnaires on the disease-specific quality of life and perceived stress-22-item Sino-Nasal Outcome Test (SNOT-22) and measure of perceived stress (MPS) scale, respectively. Inclusion criteria for the study were a reliable allergy evaluation and a recent computerized tomography (CT) scan of the sinuses. Patients with nasal polyps (NPs), asthma, and previous surgery were excluded. The study group consisted of 14 allergic and 18 nonallergic patients with CRS without NPs (CRSsNPs). Correlation between MPS and SNOT-22 scores in the study group was highly significant (Pearson r = 0.61; p = 0.001). Patients with higher stress scores had significantly stronger postnasal discharge, thick discharge, cough, disturbed sleep, fatigue, and sadness. Postnasal drip was significantly stronger in patients with allergy. The correlation between SNOT-22 and CT scores was insignificant. The correlation between MPS and SNOT-22 scores suggests an interaction between severity of CRS and chronic stress, but not with the extent of the disease on CT in CRSsNPs. Chronic psychological stress might be one of the factors that modifies the disease severity and may lead to uncontrolled disease in CRS patients.
Nasal route of administration offers a unique opportunity of brain targeted drug delivery via olfactory and trigeminal pathway, providing effective CNS concentrations at lower doses and lower risk ...for adverse reactions compared to systemic drug administration. Therefore, it has been recently proposed as a route of choice for glucocorticoids to control neuroinflammation processes in patients with severe Covid-19. However, appropriate delivery systems tailored to enhance their efficacy yet need to emerge. In this work we present the development of sprayable brain targeting powder delivery platform of dexamethasone sodium phosphate (DSP). DSP-loaded microspheres, optimised employing Quality-by-Design approach, were blended with soluble inert carriers (mannitol or lactose monohydrate). Powder blends were characterized in terms of homogeneity, flow properties, sprayability, in vitro biocompatibility, permeability and mucoadhesion. Nasal deposition studies were performed using 3D printed nasal cavity model. Mannitol provided better powder blend flow properties compared to lactose. Microspheres blended with mannitol retained or enlarged their mucoadhesive properties and enhanced DSP permeability across epithelial model barrier. DSP dose fraction deposited in the olfactory region reached 17.0% revealing the potential of developed powder platform for targeted olfactory delivery. The observed impact of nasal cavity asymmetry highlighted the importance of individual approach when aiming olfactory region.
Chronic rhinosinusitis (CRS) is a widespread disease with various symptoms. It is defined as an inflammation of the nasal mucosa and paranasal sinuses lasting for 12 weeks, with symptoms of nasal ...obstruction and/or congestion and facial pain and/or pressure as well as decreased sense of smell. Despite the widespread prevalence of the disease, the diagnosis and treatment of CRS are still not adequately developed, so many patients remain misdiagnosed. This study involved 150 patients who, according to EPOS guidelines, met the diagnosis of CRS without nasal polyposis. Each patient underwent a computerized tomography (CT) scan of the paranasal sinuses, which was evaluated according to the Lund-Mackay scoring system. Furthermore, patients completed a visual analog scale (VAS) score questionnaire which examined the severity of their symptoms. The aim of this study was to find an association between the degree of mucositis and the clinical symptoms reported by the patient. Our results showed a low positive correlation between nasal secretion and Lund-Mackay score for the bilateral ostiomeatal complex (OMC). Furthermore, a low positive correlation was found between the severity of reduced sense of smell and severity of anterior ethmoid and sphenoid sinusitis. The results demonstrated a low negative correlation between the severity of facial pain or pressure and the severity of inflammation of the anterior ethmoid and sphenoid sinus. The results of statistical testing did not show statistical differences in severity of subjective symptoms for almost all of the observed symptoms in persons with unilateral inflammation and persons without unilateral inflammation, except for cough. People who did not have unilateral inflammation had a more pronounced cough compared with people who had unilateral inflammation. However, these correlations were very mild and not clinically significant, so we cannot say that the distribution of sinusitis significantly affects the occurrence of characteristic symptoms in chronic rhinosinusitis.
Donepezil nasal delivery strategies are being continuously investigated for advancing therapy in Alzheimer's disease. The aim of this study was to develop a chitosan-based, donepezil-loaded ...thermogelling formulation tailored to meet all the requirements for efficient nose-to-brain delivery. A statistical design of the experiments was implemented for the optimisation of the formulation and/or administration parameters, with regard to formulation viscosity, gelling and spray properties, as well as its targeted nasal deposition within the 3D-printed nasal cavity model. The optimised formulation was further characterised in terms of stability, in vitro release, in vitro biocompatibility and permeability (using Calu-3 cells), ex vivo mucoadhesion (using porcine nasal mucosa), and in vivo irritability (using slug mucosal irritation assay). The applied research design resulted in the development of a sprayable donepezil delivery platform characterised by instant gelation at 34 °C and olfactory deposition reaching a remarkably high 71.8% of the applied dose. The optimised formulation showed prolonged drug release (
about 90 min), mucoadhesive behaviour, and reversible permeation enhancement, with a 20-fold increase in adhesion and a 1.5-fold increase in the apparent permeability coefficient in relation to the corresponding donepezil solution. The slug mucosal irritation assay demonstrated an acceptable irritability profile, indicating its potential for safe nasal delivery. It can be concluded that the developed thermogelling formulation showed great promise as an efficient donepezil brain-targeted delivery system. Furthermore, the formulation is worth investigating in vivo for final feasibility confirmation.
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