Nasal Inflammation Research Articles

Structural, functional and behavioral impact of allergic rhinitis on olfactory pathway and prefrontal cortex

BackgroundAllergic rhinitis (AR) has been identified as a cause of olfactory dysfunction. Beyond the classic symptoms, AR has been associated with altered sleep patterns, a decline in cognitive performance and higher likelihood of depression and anxiety. The olfactory pathway has been postulated to be a possible link between nasal inflammation and central nervous system (CNS) modifications. Thus, we aimed to investigate the structural, functional and behavioral changes in the olfactory pathway and related areas in an animal model of AR. MethodsAR was induced in adult Wistar rats by ovalbumin sensitization and challenge. Following olfactory and behavioral tests we investigated the synaptic structure of the olfactory bulb (OB), anterior olfactory nuclei (AON), piriform cortex and prefrontal cortex (PFC), by immunofluorescence detection of synaptophysin (Syn) and glutamatergic, GABAergic and dopaminergic neuronal markers. ResultsWe detected a significant decrease in Syn in the glomerular layer (GL) of OB and in the PFC of the AR group. Additionally, the optical density of GAD67 and VGLUT2 was reduced in the OB, AON and PFC, compared to controls. The behavioral tests demonstrated olfactory dysfunction and reduced male aggressiveness in AR rats, but we did not find any difference in the cognition and anxiety-like behavior. ConclusionsWe confirmed olfactory dysfunction in a rat model of AR and we identified modifications in synaptic activity by reduction of Syn optical density in the GL of the OB and in the PFC. This was accompanied by structural changes in glutamatergic and GABAergic activity in essential components of the olfactory pathway and PFC.

Three-dimensional morphologic and molecular atlases of nasal vasculature

Understanding the function of the nasal vasculature in homeostasis and pathogenesis of common nasal diseases is important. Here we describe an extensive network of venous sinusoids (VSs) in mouse and human nasal mucosa. The endothelium of the VSs expressed Prox1 (considered to be a constitutive marker of lymphatic endothelium) and high levels of VCAM-1 and exhibited unusual cell-to-cell junctions. VSs are supported by circular smooth muscle cells (SMCs) and surrounded by immune cells. The nasal mucosa also showed a rich supply of lymphatic vessels with distinctive features, such as the absence of the lymphatic marker LYVE1 and sharp-ended capillaries. In mouse models of allergic rhinitis or acute Coronavirus Disease 2019 (COVID-19) infection, Prox1+ VSs were regressed or compromised. However, in aged mice, the VSs lost the SMC support and were expanded and enlarged. Our findings demonstrate three-dimensional morphological and molecular heterogeneities of the nasal vasculature and offer insights into their associations with nasal inflammation, infection and aging.

Gleditsia sinensis Lam. aqueous extract attenuates nasal inflammation in allergic rhinitis by inhibiting MUC5AC production through suppression of the STAT3/STAT6 pathway

Allergic rhinitis (AR), a chronic respiratory inflammatory disease, is among the most common chronic diseases reported worldwide. Mucus hypersecretion is a critical feature of AR pathogenesis. Although the Gleditsia sinensis extract has several beneficial effects on human health, its effects on allergic inflammation have not yet been investigated. In this study, we examined the effects of G. sinensis aqueous extract (GSAE) on nasal inflammation in an ovalbumin (OVA)-induced AR mouse model. GSAE was administered orally for 1 week and then the clinical nasal symptoms were evaluated. The levels of histamine, OVA-specific immunoglobulin (Ig) E, and interleukin (IL)-13 were measured in the serum using an enzyme-linked immunosorbent assay (ELISA). Inflammatory cells were then counted in the nasal lavage fluid (NALF) and histopathology in the nasal epithelium was evaluated. STAT3/STAT6 phosphorylation was examined in primary human nasal epithelial cells (HNEpCs) using western blot analysis. Oral administration of GSAE to OVA-induced AR mice alleviated nasal clinical symptoms and reduced OVA-specific immunoglobulin E, interleukin (IL)-13, and histamine levels. The accumulation of eosinophils in nasal lavage fluid, nasal mucosa, mast cells, goblet cells, and mucin 5AC (MUC5AC) in the nasal epithelium was also inhibited by GSAE. Treatment with GSAE inhibited the production of MUC5AC in IL-4/IL-13-stimulated primary human nasal epithelial cells through the signal transducer and activator of transcription (STAT)3/STAT6 signaling pathway. These results indicated that GSAE reduces nasal inflammation suggesting that it is a potential treatment option for AR.

Chronic intranasal corticosteroid treatment induces degeneration of olfactory sensory neurons in normal and allergic rhinitis mice.

Nasal eosinophilic inflammation is the therapeutic target for olfactory dysfunction in allergic rhinitis (AR). Intranasal corticosteroids are commonly considered to offer targetable benefit given their immunosuppressive property. However, experimental evidence suggests that continuous corticosteroid exposure may directly cause olfactory damage by disrupting the turnover of olfactory sensory neurons (OSNs). This potentially deleterious effect of corticosteroids calls into question their long-term topical use for treating olfactory loss related to AR. The aim of this study was to assess the impacts of chronic intranasal corticosteroid treatment on olfactory function and OSN population in mice under normal and pathological conditions. BALB/c mice were intranasally treated with fluticasonepropionate (FP, 0.3mg/kg) for up to 8weeks. Additional mice were used to establish an ovalbumin-induced mouse model of AR, followed by nasal challenge with ovalbumin for 8weeks in the presence or absence of intranasal FP treatment. The authors examined olfactory function, OSN existence, neuronal turnover, and nasal inflammation using behavioral test, histological analyses, Western blotting, and enzyme-linked immunosorbent assay. Intranasal treatment with FP for 8weeks (FP-wk8) reduced odor sensitivity in normal mice. This reduction was concomitant with loss of OSNs and the axons projecting to the olfactory bulb, primarily resulting from increased neuronal apoptosis. In FP-wk8 AR mice, intranasal FP treatment attenuated olfactory impairment and eosinophilic inflammation but failed to reconstitute OSN population and axonal projections. These results suggest that chronic intranasal corticosteroid treatment contributes to OSN degeneration that may reduce the therapeutic effectiveness for AR-related olfactory loss.

Allergic rhinitis children with obesity are more vulnerable to air pollution: a cross sectional study

The association between air pollution, allergic rhinitis (AR), and obesity has not been studied. From 2007 to 2011, 52 obese and 152 non-obese children (7–17 years old) with AR were recruited. Pediatric-Rhinoconjunctivitis-Quality-of-Life Questionnaire (PRQLQ) and nasal peak expiratory flow (NPEF) were tested. Association between the scores and rates of the two tests and mean air pollutant concentrations within 7 days before the tests were compared. When exposed to higher concentrations of CO, PM10, and PM2.5, the rates of worse nasal discomfort were 39.4%, 44.4% and 39.3% in obese children; and 18.0%, 21.9% and 19.7% in non-obese children, respectively. Compare to non-obese children, the rates in obese children were higher for CO (odds ratio (OR) 3.54, 95% confidence interval (CI) 1.15 ~ 10.92); PM10 (OR 3.26, 95% CI 1.01 ~ 10.57) and PM2.5 (OR 3.30; 95% CI 1.03 ~ 10.54). In obese children, correlations between higher concentrations of CO, PM10, PM2.5 and higher nasal discomfort (higher PRQLQ); and correlations between higher concentrations of CO, PM10, PM2.5, NMHC (non-methane hydrocarbon) and higher nasal mucosa inflammation (lower NPEF) were noted. Obesity negatively affected AR severity when AR children experienced higher concentrations of CO, PM10, and PM2.5. Increased nasal inflammation induced by air pollutants might be the underlying mechanism.

LINC00632 relates to milder Th1/Th2 imbalance, attenuated nasal symptoms, and better response to therapy in allergic rhinitis patients.

Long intergenic noncoding RNA 00632 (LINC00632) regulates nasal inflammation and CD4+ T cell differentiation into T helper (Th) 2 cells in allergic rhinitis (AR). This study aimed to explore the relationship between LINC00632 and Th1/Th2 balance, and the clinical value of LINC00632 in AR patients. In total, 120 AR patients, 20 non-atopic obstructive snoring patients as disease controls (DCs), and 20 healthy controls (HCs) were recruited. Their LINC00632 expressions in peripheral blood mononuclear cells were detected by RT-qPCR. LINC00632 expression was declined in AR patients compared with DCs and HCs (both P ˂ 0.001). Moreover, LINC00632 could distinguish AR patients from DCs with an area under curve (AUC) of 0.795 (95% confidence interval [CI]: 0.701-0.889), and from HCs with an AUC of 0.895 (95%CI: 0.831-0.960). LINC00632 was positively related to Th1 cells (P = 0.037) and Th1/Th2 axis (P ˂ 0.001) in AR patients. In addition, LINC00632 was inversely associated with Th2 cells (P ˂ 0.001) and interleukin (IL)-4 (P = 0.010) in AR patients. Besides, LINC00632 was negatively related to rhinorrhea score (P = 0.019), itching score (P = 0.008), sneezing score (P = 0.004), and total nasal symptom score (TNSS) (P ˂ 0.001), but no correlation between LINC00632 and congestion score was observed (P = 0.093). During treatment, LINC00632 was elevated, while TNSS score was reduced (both P ˂ 0.001). Furthermore, LINC00632 increment was associated with the reduction of TNSS score during the therapy (P = 0.005). LINC00632 relates to milder Th1/Th2 imbalance, attenuated nasal symptoms, and better response during 4-week therapy in AR patients.

Changes in percentage of GATA3+ regulatory T cells and their pathogenic roles in allergic rhinitis

To investigate the changes in percentage of GATA3+ regulatory T (Treg) cells in patients with allergic rhinitis (AR) and mouse models. The nasal mucosa specimens were obtained from 6 AR patients and 6 control patients for detection of nasal mucosal inflammation. Peripheral blood mononuclear cells (PBMC) were collected from 12 AP patients and 12 control patients to determine the percentages of Treg cells and GATA3+ Treg cells. In a C57BL/6 mouse model of AR, the AR symptom score, peripheral blood OVA-sIgE level, and nasal mucosal inflammation were assessed, and the spleen of mice was collected for detecting the percentages of Treg cells and GATA3+ Treg cells and the expressions of Th2 cytokines. Compared with the control patients, AR patients showed significantly increased eosinophil infiltration and goblet cell proliferation in the nasal mucosa (P < 0.01) and decreased percentages of Treg cells and GATA3+ Treg cells (P < 0.05). The mouse models of AR also had more obvious allergic symptoms, significantly increased OVA-sIgE level in peripheral blood, eosinophil infiltration and goblet cell hyperplasia (P < 0.01), markedly lowered percentages of Treg cells and GATA3+ Treg cells in the spleen (P < 0.01), and increased expressions of IL-4, IL-6 and IL-10 (P < 0.05). The percentage of GATA3+ Treg cells is decreased in AR patients and mouse models. GATA3+ Treg cells possibly participate in Th2 cell immune response, both of which are involved in the occurrence and progression of AR, suggesting the potential of GATA3+ Treg cells as a new therapeutic target for AR.

Peripheric and central smell regions in patients with chronic rhinosinusitis with nasal polyps: An MRI evaluation

Abstract OBJECTIVE. We evaluated the effect of olfactory deficiency caused by sinonasal polyposis using a magnetic resonance imaging (MRI) evaluation. MATERIAL AND METHODS. In this retrospective study, 33 adult patients with bilateral chronic rhinosinusitis with nasal polyps (CRSwNP) (Group 1) and 30 healthy subjects without nasal polyps (Control, Group 2) were included. On coronal T2 weighted SPIR images of the MRI, the olfactory bulb (OB) volume and the olfactory sulcus (OS) depth were measured; the same action was performed on the axial T1 weighted images, for the corpus amygdala and insular gyrus areas. RESULTS. OB volume, insular gyrus and corpus amygdala areas of the CRSwNP group were significantly lower than those in the control group (p&lt;0.05). In the CRSwNP group, there were positive correlations between OB volumes, OS depths, and insular gyrus areas and corpus amygdala areas bilaterally (p&lt;0.05). In females, bilateral insular gyrus areas decreased compared to the males (p&lt;0.05). When polyp duration got longer, the right corpus amygdala area decreased (p&lt;0.05). In older patients with a CRSwNP, the left corpus amygdala area decreased (p&lt;0.05). CONCLUSION. OB volume was found to be smaller in the CRSwNP group. We think that the OB volume has decreased primarily due to decreased transfer of odor particles (sensory input) related to nasal obstruction and inflammation in the presence of nasal polyps. After OB volume shrinkage, the insular gyrus and corpus amygdala areas shrink due to the decreased data transfer to the central odor system. In patients with nasal polyps, olfactory functions may improve after endoscopic sinus surgery.

Mechanism of Kruppel-Like Factor 4 in Pyroptosis of Nasal Mucosal Epithelial Cells in Mice With Allergic Rhinitis.

Allergic rhinitis (AR) is a chronic nasal inflammation, characterized by nasal epithelial dysfunction. Gene therapy targeting transcription factors is a promising strategy for quenching allergic inflammation, including AR. This study sought to probe the mechanism of Kruppel-like factor 4 (KLF4) in pyroptosis of nasal mucosal epithelial cells (NEpCs) in AR mice and provide targets for AR treatment. AR mouse models were established using sensitization with ovalbumin, followed by injection with short hairpin RNA KLF4 (sh-KLF4). AR symptoms were assessed by the times of sneezing and nose rubbing, hematoxylin-eosin, and periodic acid-Schiff staining. Levels of KLF4, nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3), cleaved caspase-1, and N-terminal domain (GSDMD-N) in nasal mucosal tissues were determined by Western blot assay, and levels of interleukin (IL)-1β and IL-18 in nasal lavage fluid were determined by enzyme-linked immunosorbent assay. The binding of KLF4 to the NLRP3 promoter was verified using chromatin immunoprecipitation and dual-luciferase assays. The functional rescue experiment was performed with oe-NLRP3 and sh-KLF4 in AR mice. KLF4 was upregulated in nasal mucosal tissues of AR mice. KLF4 inhibition reduced the times of sneezing and nose rubbing, inflammatory cell infiltration, and goblet cell hyperplasia in nasal mucosal tissues, and levels of NLRP3, cleaved caspase-1, GSDMD-N, IL-1β, and IL-18. KLF4 was enriched on the NLRP3 promoter and improved NLRP3 expression. NLRP3 overexpression reversed the inhibition of sh-KLF4 on pyroptosis of NEpCs in AR mice. KLF4 bound to the NLRP3 promoter and promoted pyroptosis of NEpCs in AR mice via activating NLRP3.

The Role of Nasal Cytology and Serum Atopic Biomarkers in Paediatric Rhinitis.

A Nasal Provocation Test allows the differentiation of allergic and non-allergic rhinitis, but it is difficult and expensive. Therefore, nasal cytology is taking hold as an alternative. We carried out a cross-sectional study, including 29 patients with persistent rhinitis according to ARIA definition and negative skin prick tests. Nasal symptoms were scored from 0 to 5 using a visual analogue scale, and patients underwent blood tests to investigate blood cell count (particularly eosinophilia and basophilia), to analyze serum total and specific IgE and eosinophil cationic protein (ECP), and to perform nasal cytology. We performed a univariate logistical analysis to evaluate the association between total serum IgE, serum eosinophilia, basophils, and ECP and the presence of eosinophils in the nasal mucosa, and a multivariate logistic model in order to weight the single variable on the presence of eosinophils to level of the nasal mucosa. A statistically significant association between serum total IgE levels and the severity of nasal eosinophilic inflammation was found (confidence interval C.I. 1.08-4.65, odds ratio OR 2.24, p value 0.03). For this reason, we imagine a therapeutic trial with nasal steroids and oral antihistamines in patients with suspected LAR and increased total IgE levels, reserving nasal cytology and NPT to non-responders to the first-line therapy.

Gene expression profiling of nasal inflammation induced by diesel particles using an in vivo system

Korean diesel particulate matter 20 (KDP20) is a pollutant comprising a complex mixture of carbon and chemical irritants. Although particulate matter and nasal inflammation are strongly associated, the underlying molecular mechanism based on systematic transcriptome analysis remains unknown. In this study, genome-wide gene expression profiles of mouse nasal tissues were determined following exposure to KDP20 for 5 and 10 days and compared with those of the control (n = 4/group). We identified 758 significant differentially expressed genes (DEGs) and classified them as 5-day-specific, 10-day-specific, and common among groups based on their expression patterns. The terms “regulation of alpha-beta T cell differentiation,” “macrophage differentiation,” and “cell adhesion mediated by integrin” were significantly enriched in each group. Receiver operating characteristic analysis revealed six genes as potential predictive biomarkers. The differential expression of these six genes was validated using quantitative RT-PCR (n = 3/group). Furthermore, a possible mechanism for nasal inflammation was suggested through the binding analysis between metal ions and genes. The genes identified in this study may play important roles in regulating the mechanism of nasal inflammation induced by diesel particles, especially immune cell regulation, and may function as markers for diesel particle-induced nasal inflammation.

Loss of SENP3 mediated the formation of nasal polyps in nasal mucosal inflammation by increasing alternative activated macrophage.

Small ubiquitin-like modifier (SUMO)-specific protease (SENP)3 is a protease molecule that responds to reactive oxygen species (ROS) with high sensitivity. However, the role of ROS and SENP3 in the formation of nasal polyps (NPs) remains unclear. This study aimed to explore how SENP3 influenced the outcome of chronic rhinosinusitis (CRS) by altering macrophage function, that is, the formation of NPs. The alternative activation of macrophage (M2) was detected with CD68+ CD206+ in humans and CD206+ in mice. The nasal mucosa of patients with CRS was tested using flow cytometry (CD68, CD80, and CD206) and triple-color immunofluorescence staining (CD68, CD206, and SENP3). The bone marrow-derived macrophages from SENP3 knockout and control mice were stimulated with interleukin (IL)-4 and IL-13 to analyze alternative macrophage polarization in vitro. An animal model of allergic rhinitis was constructed using SENP3 knockout mice. CD206 was detected by immunofluorescence staining. The thickening of eosinophil-infiltrated mucosa was detected by Luna staining. The number of CD68+ CD206+ M2 increased in the nasal mucosa of patients with CRS with NP (CRSwNP) compared with patients with CRS without NP (CRSsNP), but with no significant difference between the groups. SENP3 knockout increased the polarization of F4/80+ CD206+ M2. Meanwhile, the number of CD206+ M2 significantly increased in the allergic rhinitis model constructed using SENP3 knockout mice and controls, with a more obvious proliferation of the nasal mucosa. Downregulation of SENP3 promotes the formation of nasal polyps mediated by increasing alternative activated macrophage in nasal mucosal inflammation.

BMP-2 and IL-1β as Markers of Nasal Mucosa Inflammation in Rhinosinusitis with Nasal Polyps.

Rhinosinusitis with nasal polyps is characterized by chronic inflammation and hyperplasia of the nasal mucosa. The key mechanism for polyp formation is the expression of molecules that regulate proliferation and inflammation. We studied immunolocalization of bone morphogenetic protein-2 (BMP-2) and IL-1β in the nasal mucosa in patients aged 35-70 years (n=70, mean age 57.4±1.52 years). The typology of polyps was determined depending on the distribution of inflammatory cells, subepithelial edema, the presence of fibrosis and cysts. The immunolocalization of BMP-2 and IL-1β had the same pattern in edematous, fibrous, and eosinophilic (allergic) polyps. Goblet and connective tissue cells, microvessels and terminal sections of the glands were positively stained. BMP-2+ and IL-1β+ cells predominated in polyps of the eosinophilic type. BMP-2/IL-1β can be considered as a specific marker of inflammatory remodeling of the nasal mucosa in refractory rhinosinusitis with nasal polyps.

Evaluation of efficacy of 0.1% of chlorine dioxide mouthwash against oral malodor – A pilot study

BACKGROUND: Oral malodor, also known as halitosis or bad breath can be defined as an offensive odor that emerges from the oral cavity and can be easily detected by others. The etiology of halitosis is multifactorial and can include several intra- and extraoral factors such as gingivitis, periodontitis, chronic sinusitis, nasal inflammation, diabetes mellitus, lung carcinoma, liver insufficiency, cirrhosis, uremia, trimethylaminuria, and postnasal drip. Chlorine dioxide associated with chlorite anion results in the oxidative consumption of amino acids such as cysteine and methionine, which are precursors of volatile sulfur compounds (VSC). Thus, it can reduce the concentrations of VSCs which help in the reduction of oral malodor. Due to the lesser availability of literature to prove the effectiveness of this chlorine dioxide formula, this study is conducted to evaluate the inhibiting effect of commercially available chlorine dioxide-containing mouthwash – FRESHCLOR to combat oral malodor in patients.MATERIALS AND METHODS: The study was conducted among the patients reporting at the outpatient department of periodontics who visited with the chief complaint of bad breath and bleeding gums at KAHER'S VK Institute of Dental Sciences, Belagavi. Patients were selected according to inclusion criteria and divided into test and control groups. Post scaling Freshclor mouthwash was distributed to all test group participants. The organoleptic ratings for halitosis, gingival index (given by Loe H and Silness J, 1963), and plaque index (given by Loe H and Silness J, 1964) were recorded at baseline and 2 weeks for the group.RESULTS: There was a statistically significant reduction in halitosis with a reduction of gingival and plaque indices at 2 weeks from baseline in the test group.CONCLUSION: With the results, it can be concluded that chlorine dioxide-containing mouthwash – freshclor is effective in reducing halitosis.

The natural history of childhood-onset nonallergic rhinitis; a long-term follow-up study.

Non-allergic rhinitis (NAR) is characterized by symptoms of nasal inflammation without allergic sensitization. The long-term outcome of NAR in children is poorly defined. To determine the natural history of childhood-onset NAR and the development of allergic rhinitis (AR) in these children. NAR patients who were followed for more than 10 years were evaluated at 3-5 years (E2) and 9-12 years (E3) after the first evaluation (E1). Nasal symptoms, disease severity, comorbidities, medication used, and aeroallergen sensitization were assessed. Eighty-two NAR patients (58.5% male) completed all 3 evaluations. The age at onset was 2.0 (range 2.0-4.0) years. The follow-up period was 13.6 (range 12.3-14.3) years. At E2, 37.8% of patients developed AR. At E3, the patients were classified into four groups based on results of skin prick tests in E2 and E3 (group I: NAR→NAR→NAR, 39.0%, group II: NAR→NAR→AR, 23.2%, group III: NAR→AR→NAR, 12.2% and group IV: NAR→AR→AR, 25.6%). The most common aeroallergen sensitization was house dust mite. The family history of atopy, asthma and allergic rhinitis were higher in group III and IV than other groups (p < 0.05). The atopic dermatitis, obstructive sleep apnea and adenotonsillar hypertrophy at E1 and E2 were predominantly found in group IV (p < 0.05). At E2, group III and IV patients had higher proportion of exposure to house dust, animal dander and smoking compared to other groups (p < 0.05). The overall remission rate was 14.6%. Children with NAR should be reevaluated periodically to determine aeroallergen sensitization for the appropriate diagnosis and management.

ASSESSMENT OF NASAL IRRIGATION WITH XYLITOL IN THE POSTOPERATIVE ENDOSCOPIC SURGERIES OF PARANASAL SINUSES

Chronic rhinosinusitis is a condition of nasal inflammation that requires multifactorial treatment, including surgery, with indication of nasal irrigation to reduce nasal symptoms. Xylitol can be associated with nasal irrigation due to its therapeutic effect. Our study aims to assess the relationship between the effects of nasal irrigation with saline solution compared to xylitol through clinical questionnaires (visual analogue scale, NOSE and SNOT-22). Fifty-two patients, divided into two groups (26 in the “Xylitol” group and 26 in the “Saline” group) answered validated questionnaires in Portuguese about their nasal symptoms (nasal obstruction, runny nose, need to blow out sneezes, among others), and general symptoms, before and after endoscopic endonasal surgery, after a period of 30 days of nasal irrigation. The “Xylitol” group showed significant improvement in pain symptoms and nasal symptoms after surgery and irrigation using a xylitol solution. The “Saline” group also showed improvement in symptoms, but to a lesser extent. Our study suggests that xylitol solutions can be used in the postoperative period of endoscopic endonasal surgery, as it leads to a greater reduction in nasal symptoms without incurring higher costs to patients.

Effects of nasal inflammation on the olfactory bulb.

Sinonasal diseases, such as rhinosinusitis, affect up to 12% of individuals each year which constitutes these diseases as some of the most common medical conditions in the world. Exposure to environmental pathogens and toxicants via the nasal cavity can result in a severe inflammatory state commonly observed in these conditions. It is well understood that the epithelial and neuronal cells lining the olfactory mucosa, including olfactory sensory neurons (OSNs), are significantly damaged in these diseases. Prolonged inflammation of the nasal cavity may also lead to hyposmia or anosmia. Although various environmental agents induce inflammation in different ways via distinct cellular and molecular interactions, nasal inflammation has similar consequences on the structure and homeostatic function of the olfactory bulb (OB) which is the first relay center for olfactory information in the brain. Atrophy of the OB occurs via thinning of the superficial OB layers including the olfactory nerve layer, glomerular layer, and superficial external plexiform layer. Intrabulbar circuits of the OB which include connectivity between OB projection neurons, OSNs, and interneurons become significantly dysregulated in which synaptic pruning and dendritic retraction take place. Furthermore, glial cells and other immune cells become hyperactivated and induce a state of inflammation in the OB which results in upregulated cytokine production. Moreover, many of these features of nasal inflammation are present in the case of SARS-CoV-2 infection. This review summarizes the impact of nasal inflammation on the morphological and physiological features of the rodent OB.

Pharyngeal Inflammation on Positron Emission Tomography/Magnetic Resonance Imaging Before and After Obstructive Sleep Apnea Treatment.

Rationale: There is upper airway inflammation in patients with obstructive sleep apnea (OSA), which reduces with continuous positive airway pressure (CPAP) therapy. Objectives: Validate the use of positron emission tomography (PET)/magnetic resonance imaging (MRI) to quantify metabolic activity within the pharyngeal mucosa of patients with OSA against nasal lavage proteomics and assess the impact of CPAP therapy. Methods: Adults with OSA underwent [18F]-Fluoro-2-deoxy-D-glucose PET/MRI of the neck before and 3 months after initiating CPAP. Nasal lavage samples were collected. Inflammatory protein expression from samples was analyzed using the Olink platform. Upper airway imaging segmentation was performed. Target-to-background ratio (TBRmax) was calculated from target pharyngeal maximum standard uptake values (SUV) and personalized background mean SUV. Most-diseased segment TBRmax was identified per participant at locations with the highest PET avidity. Correlation analysis was performed between baseline TBRmax and nasal lavage proteomics. TBRmax was compared before and after CPAP using linear mixed-effect models. Results: Among 38 participants, the baseline mean age was 46.3 years (standard deviation [SD], 12.5), 21% were female, the mean body mass index was 30.9 kg/m2 (SD, 4.6), and the mean respiratory disturbance index measured by peripheral arterial tonometry was 31 events/h (SD, 16.4). There was a significant positive correlation between pharyngeal mucosa most-diseased segment TBRmax and nasal lavage proteomic inflammation (r = 0.41 [P < 0.001, false discovery rate = 0.002]). Primary analysis revealed a reduction in the most-diseased segment TBRmax after a median of 2.91 months of CPAP therapy (-0.86 [standard error (SE) ± 0.30; P = 0.007]). Stratified analysis by smoking status revealed a significantly decreased most-diseased segment TBRmax after CPAP therapy among never-smokers but not among ever-smokers (-1.01 [SE ± 0.39; P = 0.015] vs. -0.64 [SE ± 0.49; P = 0.201]). Conclusions: CPAP therapy reduces metabolic activity measured by PET/MRI within the upper airway of adults with OSA. Furthermore, PET/MRI measures of upper airway metabolic activity correlate with a noninvasive marker of inflammation (i.e., nasal lavage inflammatory protein expression).

Early Negativization of SARS-CoV-2 Infection by Nasal Spray of Seawater plus Additives: The RENAISSANCE Open-Label Controlled Clinical Trial.

Background: COVID-19 is an asymptomatic condition in 40% of cases, and most symptomatic patients present with mild/moderate disease not requiring hospitalization or intensive care, especially during the Omicron wave, when the hospitalization rate was estimated to be 0.3%. The main port of entry for SARS-CoV-2 in the human body is the nasal cavity and the upper respiratory tract is affected since the early stages of the infection. Nasal irrigation or aerosol by isotonic or hypertonic saline solution is a traditional therapeutic approach for respiratory or nasal inflammation, also featured by prophylactic properties against upper respiratory infections. Methods: We conducted a prospective open-label controlled study to assess the superiority of an already existing medication (Tonimer Lab Panthexyl 800)-a sterile hypertonic solution containing seawater, xylitol, panthenol and lactic acid-to reduce the viral shedding time in patients affected by asymptomatic or mild COVID-19. COVID-19 patients (N = 108) were split into two groups: a treatment arm (50 participants receiving standard of care plus nasal spray 3 times/day with Tonimer Lab Panthexyl 800) and a control arm (58 participants receiving standard of care but nasal spray with Tonimer Lab Panthexyl 800). The two groups, both testing initially positive for SARS-CoV-2 at real-time PCR (RT-PCR) on nasal swab, were followed up over time to assess the daily number of positive swab tests turning negative (study endpoint). Treatment effectiveness at various time lags since the first positive RT-PCR swab test was measured by rate of events in the experimental arm (EER) and in the control arm (CER), absolute risk increase (ARI) = (EER - CER), and number needed to treat (NNT) = (1/ARI). To investigate the endpoint, we used logistic and Cox regression models, expressing the result as odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (95%CI), respectively. The symptoms recorded with a modified COVID-Q questionnaire at both diagnosis and first negative antigenic swab test were compared in each group (treated versus controls) by exact symmetry test. Results: During the first five days of treatment, COVID-19 patients treated with Tonimer Lab Panthexyl 800 were more likely to become negative two days before controls. According to NNT, four subjects had to be treated for five days to achieve the study endpoint in one individual. The negativization rate in patients treated with Tonimer Lab Panthexyl 800 was significantly higher than patients' treated with standard of care alone (OR = 7.39, 95%CI: 1.83-29.8; HR = 6.12, 95%CI: 1.76-21.32). There was no evidence of side effects. Conclusions: Nasal spray with Tonimer Lab Panthexyl 800 was effective against SARS-CoV-2, stopping viral shedding in the treatment arm two days before the control group. This treatment should be continued for at least five days after the first positive swab test for SARS-CoV-2.

A safety investigation into topical effects of naproxen sodium on nasal epithelial cells and potential toxicity in local application

ObjectivesWe examined how topically-applied naproxen sodium affects human nasal epitheliocytes in culture. MethodsSamples of healthy human primary nasal epithelium (NE) harvested during septoplasty from volunteers without rhinosinusitis were incubated in cell culture. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays may be utilised when assessing cellular damage (toxicity), as evidenced by DNA fragmentation, nuclear condensation, alteration in the outer plasma membrane and cytoskeletal alteration. This was the method used in the study. Cultured epitheliocytes were incubated with naproxen sodium for 24 h at 37 °C. The MTT assay was then performed and the cells' morphology was examined by confocal microscopy. Additionally, cellular proliferation was assessed by the artificial scratch method followed by light microscopy. ResultsThe results indicated that naproxen sodium does not cause any cytotoxic effects upon nasal epithelial cells when applied topically. There was no evidence indicating cytotoxicity on the nasal epitheliocytes in culture for the 24 h period over which the drug was applied. In particular, there was no alteration in cellular morphology, damage to the intracellular organelles structure or the cytoskeleton secondary to naproxen sodium. Furthermore, cellular proliferation occurred normally in these conditions, as on scratch test. ConclusionTopical naproxen sodium may be used on nasal epithelial cells without inducing toxicity. This agent is therefore suitable, given its known anti-inflammatory effects, for use in patients suffering from diseases involving nasal and paranasal sinusal inflammation, including rhinosinusitis (both chronic and acute) and nasal polyposis which should be investigated. In the future, topical medication forms for nasal usage should be developed.