Comparison of the Efficacy and Safety of Bilastine 20 mg versus Fexofenadine 180 mg for Treatment of Perennial Allergic Rhinitis: Randomized Controlled Study.

Background: Antihistamines has always remained the mainstay drug treatment for Allergic Rhinitis (AR). Bilastine is a novel, non-sedative antihistamine with a super-selective H1 receptor antagonist property. Both bilastine and fexofenadine are second generation antihistamine drugs commonly used to manage AR and Chronic Urticaria (CU). Autologous Skin Serum Test (ASST) is a practical test for histamine release in CU. These tests have been studied in AR patients with limited data studies. Methods: 114 patients diagnosed with perennial AR were recruited and divided into two groups of 57 each. One group was started Bilastine 20 mg once a day and other group, fexofenadine 180 mg once a day. Total Nasal Symptom Score (TNSS) was calculated at presentation and two weeks of antihistamine therapy. ASST was hypothesized to be the test for AR and performed at the time of presentation and at two weeks follow-up. Intergroup and Intragroup assessment of TNSS, ASST and its variables were done using unpaired and paired t test respectively. Results: Patients showed reduction in symptoms of AR with both antihistamines. A significant improvement of sneezing and rhinorrhoea was seen in Fexofenadine group as compared to Bilastine group. TNSS showed statistically significant improvement in both the groups. ASST had statistically significant reduction in both the groups. Conclusions: Both Bilastine and fexofenadine were found to be effective in reduction of symptoms of allergic rhinitis. Bilastine was found to be more effective in overall as well as sneezing and rhinorrhoea noted two weeks after therapy. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04770-0.

Unveiling a Rare Phenomenon: Sudden Sensorineural Hearing Loss Following Skin Prick Testing.

Introduction: The skin prick test (SPT) is a standard method for diagnosing allergic diseases, while sudden sensorineural hearing loss (SSNHL) remains a perplexing condition often of unknown etiology. We present a unique case of SSNHL emerging shortly after an SPT, suggesting a potential link between allergic reactions and inner ear disorders. Case Report: A 27-year-old male presented with unilateral hearing loss following an SPT for allergic rhinitis. Audiometric findings revealed SSNHL in the affected ear. Treatment with corticosteroids led to a full recovery of hearing function. Conclusion: This case highlights the rare occurrence of SSNHL possibly triggered by a type 1 allergic reaction to an SPT. Prompt corticosteroid therapy proved effective in restoring hearing. Further research is needed to understand the relationship between allergies and SSNHL and explore alternative treatment options.

Prevalence of Migraine Headache among Patients with Allergic Rhinitis in a Tertiary Care Hospital, Puducherry.

Allergic rhinitis is one of the most common and undertreated diseases in the world. In recent times, there has been increased development of non-sinus headaches among patients with allergic rhinitis. Various common endogenous molecules such as nitric oxide, calcitonin gene-related peptide, and histamine have been implicated in the development of migraines, which leads to the development of migraines among allergic rhinitis patients. The study aims to determine the prevalence of migraine among allergic rhinitis patients and to find the association between the various demographic factors and the presence of migraine. This cross-sectional study was conducted in the ENT department of a tertiary care hospital in Puducherry. All patients aged more than 18 years old with the symptoms of allergic rhinitis were included in the study. The study was conducted six months, from July 2023 to December 2023. ARIA classification is used to determine the severity of the allergic rhinitis, and, per International criteria for headache, was used to diagnose migraine. A total of 282 patients with allergic rhinitis participated in the study. The mean age of the patients was found to be 38.89 ± 11.04 years. The prevalence of migraine among allergic rhinitis patients was found to be 69.1%-Economic status (39.4%). About 16.7% of the patients with diabetes were associated with migraine. The study showed a significant association between sex (p-0.006), age (p < 0.001), and socio-economic status (p-0.034) with the presence of migraine. The study also showed a significant association between the severity of allergic rhinitis and the presence of migraine (p-0.034) and the type of migraine (p-0.004). The study concludes that a significant proportion of the patients with allergic rhinitis were associated with migraine. So, clinicians should always screen for the presence of the migraine in all patients with allergic rhinitis to improve the patient's quality of life.

Recent Advances in Allergic Rhinitis: A Narrative Review.

Allergic rhinitis (AR) is a prevalent chronic respiratory condition characterized by nasal inflammation, sneezing, congestion, and itching, significantly impacting quality of life. Over recent years, considerable advancements have been made in understanding the pathophysiology, diagnosis, and management of AR. This narrative review aims to synthesize these recent developments, providing a comprehensive overview of key areas. Emerging insights into AR pathophysiology have elucidated the complex interplay between genetic predisposition, environmental factors, and immune system dysregulation. Notably, the role of the epithelial barrier and the microbiome in AR pathogenesis has garnered increasing attention, offering potential targets for novel therapies. Advances in diagnostic technologies, such as component-resolved diagnostics and molecular allergology, have enhanced the precision of allergy identification, enabling more personalized treatment approaches. In terms of management, significant progress has been made in pharmacological and non-pharmacological treatments. Novel biologics targeting specific pathways involved in AR, including monoclonal antibodies against immunoglobulin (Ig)E and interleukin (IL)-4/13, have shown promise in reducing symptoms in refractory cases. Additionally, there has been a resurgence in interest in non-pharmacological strategies, including allergen avoidance, immunotherapy, and complementary therapies, which offer holistic options for patient care. The integration of digital health tools and mobile applications in AR management has further empowered patients, allowing for real-time symptom tracking and personalized treatment adjustments. Recent guidelines emphasize a multidisciplinary approach to AR management, promoting integrated care models that involve collaboration between allergists, primary care providers, and other specialists. These guidelines also highlight the importance of patient-centered care, advocating for shared decision-making and tailored treatment plans based on individual patient profiles. In conclusion, the landscape of allergic rhinitis management is rapidly evolving, with ongoing research and innovation paving the way for improved outcomes. This review underscores the importance of staying abreast of these advances to optimize the care and quality of life for individuals affected by allergic rhinitis.

Roles of noncoding RNA in allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is one of the most common respiratory noninfectious diseases and chronic inflammatory diseases, the incidence of which has been increasing in recent years. The main pathological characteristics of AR are repeated inflammation, airway hyperreactivity, mucus hypersecretion, and reversible airway obstruction due to inflammatory cell response. AR occurrence is associated with various factors, including those of genetic and environmental origins. Noncoding RNAs (ncRNAs) are a group of RNA molecules that cannot be converted into polypeptides. The three main categories of ncRNAs include microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs). NcRNAs play a crucial role in controlling gene expression and contribute to the development of numerous human diseases. METHODS: Articles are selected based on Pubmed's literature review and the author's personal knowledge. The largest and highest quality studies were included. The search selection is not standardized. Several recent studies have indicated the relationship of ncRNAs with the development of respiratory allergic diseases. NcRNAs, including miRNAs, lncRNAs, and circRNAs, are important gene expression regulatory factors. We review the expression and function of ncRNAs in AR, their role as disease biomarkers, and their prospective applicability in future research and clinically. We also discuss interactions between ncRNAs and their influence on AR comprehensively, these interactions are essential for determining the underlying pathological mechanisms further and discovering new drug therapeutic targets. RESULTS: NcRNAs can be used as biomarkers for early AR diagnosis, disease surveillance and prognosis assessment. Various categories of ncRNAs play distinct yet interconnected roles and actively contribute to intricate gene regulatory networks. They are also therapeutic targets and biomarkers in other allergic diseases. CONCLUSION: This article demonstrates ncRNAs have a wide range of applications in AR treatment. The database covers three key areas: miRNAs, lncRNAs, and circRNAs. Additionally, potential avenues for future research to facilitate the practical application of ncRNAs as therapeutic targets and biomarkers will be explore. With further research and technological development, ncRNAs may provide additional innovative, effective solutions for AR treatment.

[Research progress of memory T cells in the pathogenesis of allergic rhinitis].

Allergic rhinitis（AR） is a non-infectious chronic inflammatory disease of the nasal mucosa mainly mediated by immunoglobulin E（IgE） in atopic individuals after exposure to allergens. T cells are the core cell population. In recent years, studies have shown that memory T cells play an important role in the development of allergic rhinitis. This article reviews the pathogenesis of memory T cells in allergic rhinitis, in order to further improve the pathogenesis of allergic rhinitis and provide theoretical basis and reference for subsequent clinical drug treatment.

Allergic rhinitis management: a survey on Italian primary care pediatricians.

Summary: Background. Allergic rhinitis (AR) is a widespread condition. The Italian Society of Pediatric Allergology and Immunology (SIAIP) promoted an initiative to update the knowledge on AR in children and adolescents. The present survey directly addressed primary care pediatricians, thus reflecting the real-world management of AR in children and adolescents. The aim was to investigate common practice in managing AR children. Methods. A panel of experts drafted a series of questions concerning the practical management of children with AR in clinical practice. The questionnaire was administered to a large sample of primary care pediatricians (864). Results. 864 primary care pediatricians participated to the survey. Each pediatrician on average follows 94 children with AR; globally 81,231 children. More than 70% of participants follow ARIA guidelines. Accordingly, 42% of children have mild AR and 58% moderate/severe. Asthma, conjunctivitis and adenoid hypertrophy are the most common comorbidity. Most pediatricians autonomously follow their patients. The intensity of treatment (use of medication) is directly proportional to the symptom severity.  Intranasal corticosteroids are the most common medication used followed by oral antihistamines and nasal lavages (with hypertonic or isotonic solution). Up to 20% of participants prescribe the fixed association topical corticosteroids plus antihistamine. Conclusions. The present survey demonstrated that Italian primary care pediatricians accomplish ARIA guidelines and adapt treatment on the basis of the intensity of symptoms. Corticosteroids and antihistamines are the most common prescribed medications. Nasal lavages are also popular.

The Protective Effects and Mechanisms of Essential oil from Chimonanthus nitens Oliv. Leaves in Allergic Rhinitis Based on the NF-κB and T-bet/GATA-3 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Preliminary studies showed that Shanlameiye granules are derived from Chimonanthus nitens Oliv. Leaves ameliorate inflammatory responses in mice with Allergic Rhinitis (AR). The essential oil from Chimonanthus nitens Oliv. Leaves (CLO) have been identified as the key active substances in these granules. However, whether CLO constitutes the primary mechanism for the mitigation of AR-related inflammation by these granules has not yet been investigated. AIM OF THE STUDY: This experiment was to validate the effects and mechanism of CLO on inflammatory responses in RAW264.7 cells and AR rat model. MATERIALS AND METHODS: An inflammatory model was induced in RAW264.7 cells by Lipopolysaccharide (LPS) & Interferon-gamma (IFN-γ) stimulation. AR rat model was established using both systemic and local challenges with Ovalbumin (OVA). RESULTS: In cell experiments, CLO obviously decreased the secretion of cytokines and inhibited the the NF-κB signaling pathway activation. In animal experiments, CLO decreased the number of eosinophils in the blood and lowered the levels of cytokines in nasal lavage fluid (NALF). Additionally, CLO inhibited the expression of STAT6, GATA-3, and p-p65, while increasing the expression of STAT4 and T-bet in the nasal mucosa. CONCLUSION: In AR rat model, CLO may play an anti-inflammatory role in AR rat model by regulating NF-κB and T-bet/GATA-3 signaling pathways.

[Clinical efficacy of intranasal acupuncture combined with Tiaoshen acupuncture in the treatment of moderate-to-severe persistent allergic rhinitis]. / é¼»å† é’ˆåˆºè”åˆè°ƒç¥žé’ˆæ²»ç–—ä¸­é‡åº¦æŒç»­æ€§å˜åº”æ€§é¼»ç‚Žçš„ä¸´åºŠç–—æ•ˆ.

OBJECTIVES: To observe the therapeutic effect of intranasal acupuncture combined with Tiaoshen (spirit-regulation) acupuncture for patients with moderate-to-severe persistent allergic rhinitis (AR), and to explore its mechanism of anti-inflammation. METHODS: 135 patients with persistent AR were randomly divided into western medicine group, intranasal acupuncture group, and combination group, with 45 cases in each group. The western medicine group was treated with budesonide nasal spray, 1 press (32 µg/press) in each nostril, once a day. Patients in the intranasal acupuncture group were treated with intranasal acupuncture at the Neiyingxiang (EX-HN9) and Biqiu (nasal hillock) for 20 min. Patients in the combination group were treated with intranasal acupuncture combined with spirit-regulation acupuncture at Baihui (GV20), Sishencong (EX-HN1), Daling (PC7), Shenmen (HT7), Yintang (GV24+), Shenting (GV24), Anmian, and Yingxiang (LI20) for 20 min. Each group was treated once daily for 2 weeks. Total nasal symptom score (TNSS), total non-nasal symptom score (TNNSS), rhinoconjunctivitis quality of life questionnaire (RQLQ), self-assessment scale of anxiety (SAS), and self-assessment scale of depression (SDS) were observed before and after treatment respectively. Serum total immunoglobulin E (IgE), substance P (SP), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP) levels were detected before and after treatment using ELISA. The number of eosinophil (EOS) in peripheral venous blood was detected using a blood analyzer. The clincial efficacy of the 3 groups was evaluated. RESULTS: Compared with those before treatment, TNSS, TNNSS, RQLQ, SAS, SDS scores, EOS number and serum IgE, SP and VIP contents were decreased (P<0.05), and serum NPY content was increased (P<0.05) after treatment in the 3 groups. After treatment, the observation indexes in the intranasal acupuncture group were significantly improved (P<0.05) than those in the western medication group. The observation indexes of the combination group were better (P<0.05) than those of the other 2 groups. The total effective rate of the combination group (40/45, 88.89%) was higher (P<0.05) than that of the intranasal acupuncture group (35/45, 77.78%) and higher (P<0.05) than that of the western medication group (33/45, 73.33%). CONCLUSIONS: Intranasal acupuncture combined with spirit-regulation acupuncture can improve the nasal clinical symptoms and accompanying symptoms of AR patients, reduce EOS and IgE, as well as regulate the secretion of neuropeptide and relieve the negative emotions of anxiety and depression.

Research progress in OX40/OX40L in allergic diseases.

OX40/OX40L are costimulatory molecules in the tumor necrosis factor superfamily. Numerous studies have shown that OX40/OX40L are involved in immune regulation, especially in the proliferation and differentiation of T cells and the generation of memory T cells, which play important roles in allergic diseases. In recent years, the use of OX40/OX40L as therapeutic targets for treating T-cell-mediated diseases has attracted the interest of scholars. This paper reviews the role of OX40/OX40L in allergic diseases and the progress in clinical treatments targeting this signaling pathway.

[Therapeutic effect of vitamin D supplementation in mexican patients with allergic rhinitis]. / Efecto de la suplementación con vitamina D en pacientes mexicanos con rinitis alérgica.

OBJETIVES: To evaluate the impact of cholecalciferol (D3) supplementation using clinical and paraclinical variables in patients with RA and vitamin D insufficiency and deficiency. METHODS: A randomized, double-blind, placebo-controlled study included patients from 5 to 40 years with a diagnosis of RA and vitamin D insufficiency and deficiency. They were supplemented for 8 weeks with 4000 or 5000 IU, depending on age. Total nasal symptoms score (TNSS) was measured monthly and 25(OH)D3 levels at baseline and at the end of the study. RESULTS: A total of 31 patients were included, with a mean age of 18.19 years. In the active group, there was a significant improvement in symptomatology with respect to the TNSS score and an increase in serum vitamin D levels (p < 0.01). There were no adverse reactions with cholecalciferol or placebo. CONCLUSIONS: Supplementing patients with vitamin D3, at the evaluated dose, together with conventional treatent for allergic rhinitis results in symptoms and quality of life improvement in patients with this disease.

OBJETIVOS: Evaluar el impacto de la suplementación con colecalciferol (D3) mediante variables clínicas y paraclínicas en pacientes con RA e insuficiencia y deficiencia de vitamina D. MÉTODOS: Estudio aleatorio, doble ciego, placebo controlado, en el que se incluyeron pacientes de 5 a 40 años, con diagnóstico de RA e insuficiencia y deficiencia de vitamina D. Fueron suplementados con 4000 o 5000 UI, dependiendo de la edad, durante 8 semanas. Mensualmente se midió la puntuación total síntomas nasales (TNSS) y las concentraciones de 25(OH)D3 al inicio y al final del estudio. RESULTADOS: Se incluyeron 31 pacientes, con una edad promedio de 18.19 años. En el grupo activo existió una mejoría significativa en la sintomatología respecto a la puntación de TNSS y un incremento en los niveles séricos de vitamina D (p < 0.01). No se presentaron reacciones adversas con la ingesta de colecalciferol o placebo. CONCLUSIONES: Suplementar a los pacientes con vitamina D3, a la dosis evaluada, junto con el tratamiento convencional para la rinitis alergica resulta en una mejoría sintomática y en la calidad de vida de los pacientes con esta enfermedad.

New insights into allergic rhinitis treatment: MSC nanovesicles targeting dendritic cells.

Allergic rhinitis (AR) is a condition with limited treatment options. This study investigates the potential use of mesenchymal stem cell (MSC) nanovesicles as a novel therapy for AR. Specifically, the study explores the underlying mechanisms of MSC nanovesicle therapy by targeting dendritic cells (DCs). The researchers fabricated DC-targeted P-D2-EVs nanovesicles and characterized their properties. Transcriptomic sequencing and single-cell sequencing analyses were performed to study the impact of P-D2-EVs on AR mice, identifying core genes involved in the treatment. In vitro cell experiments were conducted to validate the effects of P-D2-EVs on DC metabolism, Th2 differentiation, and ILC2 activation. The results showed that P-D2-EVs efficiently targeted DCs. Transcriptomic sequencing analysis revealed differential expression of 948 genes in nasal tissue DCs of mice treated with P-D2-EVs. Single-cell sequencing further revealed that P-D2-EVs had inhibitory effects on DC activation, Th2 differentiation, and ILC2 activation, with Fut1 identified as the core gene. Validation experiments demonstrated that P-D2-EVs improved IL10 metabolism in DCs by downregulating Fut1 expression, thereby suppressing Th2 differentiation and ILC2 activation. Animal experiments confirmed the inhibitory effects of P-D2-EVs and their ability to ameliorate AR symptoms in mice. The study suggests that P-D2-EVs reshape DC metabolism and suppress Th2 differentiation and ILC2 activation through the inhibition of the Fut1/ICAM1/P38 MAPK signaling pathway, providing a potential therapeutic approach for AR.

Sex-Specific and Long-Term Trends of Asthma, Allergic Rhinitis, and Atopic Dermatitis in South Korea, 2007-2022: A Nationwide Representative Study.

INTRODUCTION: Although sex differences in allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), and asthma are considered important, a limited number of studies during the COVID-19 pandemic investigated this aspect. Therefore, this study aimed to analyze sex-specific and long-term trends and risk factors for allergic diseases before and during the pandemic. METHODS: This study utilized data from the Korea National Health and Nutrition Examination Survey, 2007-2022, including 92,135 participants aged 19 years and older. This study used weighted multivariate regression analysis to examine the estimates of related factors and assessed weighted odds ratios or ß-coefficients for these factors across multiple categories. RESULTS: During the study period (2007-2022), the prevalence of AR was more common in females than in males. Particularly in 2022, the prevalence among females was 19.3% (95% confidence interval, 17.3-21.3), while among males, it was 15.6% (13.8-17.4). The prevalence of AD and asthma showed a slight disparity between males and females. Before and during the pandemic, the prevalence of AD and AR showed a continuous increase (AD: from 2.8% [2.5-3.2] in 2007-2009 to 4.7% [3.9-5.4] in 2022; AR: from 11.7% [11.1-12.4] in 2007-2009 to 17.4% [16.0-18.9] in 2022), while asthma maintained a relatively stable trend. Moreover, this study identified several sex-specific factors that seem to be associated with a higher prevalence of allergic diseases in females, such as high household income, smoking, and being overweight or obese. CONCLUSIONS: Throughout all the periods examined, females consistently exhibited a higher prevalence of AR compared to males. Moreover, the risk factors for males and females varied depending on the disease, with females generally facing a greater number of risk factors. Consequently, this study highlights the necessity for sex-specific health interventions and further research to comprehend the complex influence of socioeconomic factors and lifestyle choices on the prevalence and risk of AD, AR, and asthma.

High volume nasal irrigations with steroids for chronic rhinosinusitis and allergic rhinitis.

PURPOSE: The primary aim of this systematic review is to assess the efficacy, safety, and cost-effectiveness of high-volume steroid nasal irrigation (SNI) for treating chronic rhinosinusitis (CRS) and allergic rhinitis (AR). METHODS: A systematic review of literature from 2012 to 2024 was conducted using PubMed to identify relevant studies. The search focused on terms related to AR, CRS, and steroid nasal irrigation. Studies were screened for relevance and duplicates removed, resulting in 20 studies being included in the final analysis. These studies were categorized based on their focus on efficacy, safety, or both, and underwent a risk of bias assessment using Cochrane and ROBINS-I tools. RESULTS: Of the 20 studies included, 13 examined the effectiveness of high-volume nasal steroid irrigations, 4 investigated safety, and 3 covered both. High-volume irrigations demonstrated superior efficacy in symptom improvement for CRS and AR compared to nasal sprays, particularly post-surgery. Budesonide was the most commonly used steroid. Safety evaluations indicated no significant hypothalamic-pituitary-adrenal axis suppression or increases in intraocular pressure, although minor adverse events were reported. CONCLUSION: High-volume steroid nasal irrigations are more effective than standard nasal sprays for CRS and AR, particularly post-surgery, without significant safety concerns. However, no studies on cost-effectiveness were found, suggesting a need for further research in this area.

Increased circulating LOX-1+ neutrophils activate T cells and demonstrate a pro-inflammatory role in allergic rhinitis.

Background: Low-density neutrophils are heterogeneous immune cells with immunosuppressive (such as polymorphonuclear myeloid-derived suppressor cells [PMN-MDSC]) or pro-inflammatory (such as low-density granulocytes [LDG]) properties that have been well described in multiple cancers and immune diseases. However, its role in allergic rhinitis (AR) is still unclear. Methods: In the present study, we defined low-density neutrophils as CD14-CD11B+CD15+LOX-1+ (LOX-1+ neutrophils), and their levels in the peripheral blood (PB) were evaluated and compared between patients with AR and healthy donors using flow cytometric analysis. LOX-1 expression on polymorphonuclear neutrophils was identified. Carboxyfluorescein succinimidyl ester (CFSE)-stained CD3+ T cells were cultured alone or with LOX-1+ neutrophils, T cell proliferation was assessed using flow cytometry, and pro-inflammatory cytokines in the supernatants were detected using enzyme-linked immunosorbent assay (ELISA). Clinicopathological analyses were performed to gain a thorough understanding of LOX-1+ neutrophils. Results: We determined that LOX-1+ neutrophils were significantly increased in the PB of patients with AR, and LOX-1 expression in neutrophils from patients with AR was elevated. Interestingly, LOX-1+ neutrophils derived from patients with AR, unlike PMN-MDSC, promoted T cell proliferation and pro-inflammatory cytokine production. Moreover, clinicopathological analysis revealed that there was no any relation between circulating LOX-1+ neutrophil levels and the levels of IgE, age and sex. Conclusion: These findings indicate that elevated circulating LOX-1+ neutrophils play a pro-inflammatory role in AR.

Anti-Allergic and Anti-Inflammatory Effects of Lidocaine-Derived Organic Compounds in a House Dust Mite-Induced Allergic Rhinitis Mouse Model.

Allergic rhinitis (AR) is a common chronic disease that significantly impacts the quality of life. Lidocaine is known to have anti-inflammatory and immunomodulatory effects. This study evaluated the effect of lidocaine analogs in a Dermatophagoides pteronyssinus (DP)-induced AR mouse model. An AR model was developed using BALB/c mice via intraperitoneal sensitization with DP and intranasal challenge with DP. One hour before stimulation with DP, lidocaine analogs, EI137 and EI341 (at a dose of 0.5 or 5 ug/g), were administered intranasally. Nasal symptoms and serum total IgE, interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels were evaluated. Reverse-transcription polymerase chain reaction was used to determine IL-4, IL-10, and IFN-γ, as well as the expression of their mRNA transcription factors in the sinonasal mucosa. Histologic changes were evaluated using hematoxylin and eosin and periodic acid-Schiff staining. The DP-induced AR mouse model had increased serum levels of total IgE and cytokines. EI137 and EI341 significantly suppressed the levels of total IgE, IL-4, and TNF-α. Intranasal instillation of EI137 and EI341 significantly inhibited IL-4, IL-10, and IFN-γ mRNA expression, as well as inflammatory cells and mucus-producing goblet cells. Lidocaine analogs also suppressed DP-stimulated IL-4, IFN-γ, and IFN-γ production by splenocytes. Intranasal instillation of EI137 and EI341 exhibited anti-allergic and anti-inflammatory effects, influenced by Th1 and Th2 inflammatory cytokines. These lidocaine analogs suppressed DP-induced sinonasal mucosal inflammation, inflammatory cell infiltration, and mucus hypersecretion.

Differential regulation of viral entry-associated genes modulated by inflammatory cytokines in the nasal epithelium.

This study aimed to investigate the impact of different types of nasal inflammation on the regulation of entry-associated genes of respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus 229E (HCoV-229E), and influenza virus, in the nasal epithelium. Subjects were classified into three groups: control, eosinophilic chronic rhinosinusitis (ECRS), and noneosinophilic CRS (NECRS) groups. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), alanyl aminopeptidase (ANPEP), dipeptidyl peptidase 4 (DPP4), and beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1), and beta-galactoside alpha-2,3-sialyltransferase 4 (ST3GAL4) were selected as key entry-associated genes for SARS-CoV-2, HCoV-229E, MERS-CoV, and influenza, respectively, and were evaluated. Brushing samples obtained from each group and human nasal epithelial cells cultured using an air-liquid interface system were treated for 7 days with typical inflammatory cytokines and analyzed using real-time polymerase chain reaction. Western blot analysis and confocal microscopy were performed. The entry-associated genes showed distinct regulation patterns in response to each interleukin-4 (IL-4), interleukin-13 (IL-13), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Specifically, ACE2 significantly decreased in type 2 cytokines (IL-4 and IL-13), while TMPRSS2 significantly decreased in type 1 cytokines (TNF-α and IFN-γ). ANPEP significantly decreased in both types of cytokines. Remarkably, DPP4 significantly increased in type 2 cytokines and decreased in type 1 cytokines. Moreover, ST6GAL1 and ST3GAL4 significantly increased in type 2 cytokines and decreased in type 1 cytokines, particularly IFN-γ. These findings were supported by western blot analysis and confocal imaging results, especially for ACE2 and DPP4. The findings regarding differential regulation suggest that patients with ECRS, primarily mediated by type 2 inflammation, may have lower susceptibility to SARS-CoV-2 and HCoV-229E infections but higher susceptibility to MERS-CoV and influenza infections.

Functions and Clinical Applications of Extracellular Vesicles in TH2 Cell-Mediated Airway Inflammatory Diseases: A Review.

Type 2 airway inflammation (T2AI), driven by type 2 innate lymphoid and CD4+ T helper 2 cells, leads to various diseases and conditions, such as chronic rhinosinusitis with nasal polyps, allergic rhinitis, and asthma. Emerging evidence suggests the involvement of extracellular vesicles (EVs) in these diseases. In this review, we describe the immunological T2AI pathogenic mechanisms, outline EV characteristics, and highlight their applications in the diagnosis and treatment of T2AI. An extensive literature search was conducted using appropriate strategies to identify relevant articles from various online databases. EVs in various biological samples showed disease-specific characteristics for chronic rhinosinusitis with nasal polyps, allergic rhinitis, and asthma, with some demonstrating therapeutic effects against these conditions. However, most studies have been limited to in vitro and animal models, highlighting the need for further clinical research on the diagnostic and therapeutic applications of EVs.

The function and mechanism of Human nasal mucosa-derived mesenchymal stem cells in allergic rhinitis in mice.

PURPOSE: To investigate the immunomodulatory effects and potential mechanisms of human nasal mucosa-derived mesenchymal stem cells(hNMSCs) on mouse allergic rhinitis, and to compare them with human umbilical cord-derived mesenchymal stem cells (hUCMSCs). METHOD: hNMSCs and hUCMSCs were isolated and cultured for identification from human nasal mucosa and umbilical cord tissues. A co-culture system of LPS-stimulated RAW264.7 cells/mouse peritoneal macrophages and MSCs was employed.Changes in inflammatory factors in RAW264.7 cells and the culture medium as well as the expression of NF-κB signaling pathway in RAW264.7 cells were detected. Forty-eight BALB/c mice were randomly divided into control, OVA, hNMSCs, and hUCMSCs groups. An allergic rhinitis (AR) model was established through ovalbumin (OVA) stimulation and treated with hNMSCs and hUCMSCs. Subsequent assessments included related symptoms, biological changes, and the expression of the NF-κB signaling pathway in the nasal mucosa of mice. RESULTS: MSCs can be successfully isolated from human nasal mucosa. Both hNMSCs and hUCMSCs interventions significantly reverseed the inflammation induced by LPS and suppressed the upregulation of the NF-κB signaling pathway in RAW264.7 cells. Treatment with hNMSCs and hUCMSCs alleviated mouse allergic symptoms, reduced levels of total IgE, OVA-specific IgE and IgG1 in mouse serum, TH2-type cytokines and chemokines in mouse nasal mucosa, and TH2-type cytokines in mouse spleen culture medium, while also inhibiting the expression of the NF-κB signaling pathway in the nasal mucosa of mice. moreover, the hNMSCs group showed a more significant reduction in OVA-specific IgG1 in serum and IL-4 expression levels in mouse spleen culture medium compared to the hUCMSCs group. CONCLUSION: Our findings suggest that hNMSCs can ameliorate allergic rhinitis in mice, with a certain advantage in anti-inflammatory effects compared to hUCMSCs. The NF-κB pathway is likely involved in the anti-inflammatory regulation process by hNMSCs.Therefore, hNMSCs might represent a novel therapeutic approach for allergic rhinitis.