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PURPOSE: Montelukast is used extensively in children and adolescents for allergic rhinitis and asthma. However, concerns have been raised regarding the increased risk of neuropsychiatric adverse events (NPAEs) associated with montelukast use. Therefore, our case-crossover study was conducted to observe whether there is an increased risk of NPAEs associated with montelukast use in children and adolescents. MATERIALS AND METHODS: A population-based case-crossover study using the customised Health Insurance Review and Assessment (HIRA) dataset was conducted. Paediatric patients aged between 0 and 19 years diagnosed with allergic rhinitis and/or asthma with a history of at least one montelukast prescription between 1 January 2018 and 31 December 2021 were included. Exposure to montelukast was assessed during 3-, 7-, 14-, 28- and 56-day hazard periods prior to each patient's NPAE. Stratified analyses according to age group, gender and season for the risk of NPAEs associated with montelukast use in the previous 7 days and 14 days were performed, respectively. Conditional logistic regression analysis was used to calculate adjusted ORs (aORs) with their corresponding 95% CIs, adjusting for concomitant medications. RESULTS: A total of 161 386 paediatric patients was identified. An increased risk of NPAEs associated with montelukast was found in all time window periods, including 3-day (aOR 1.28, 95% CI 1.24 to 1.32), 7-day (aOR 1.29, 95% CI 1.26 to 1.33), 14-day (aOR 1.34, 95% CI 1.31 to 1.37), 28-day (aOR 1.38, 95% CI 1.36 to 1.41) and 56-day (aOR 1.21, 95% CI 1.19 to 1.22) preceding hazard periods compared with use in the four control periods. CONCLUSION: Children and adolescents with allergic rhinitis and/or asthma should be prescribed montelukast with caution considering clinical benefits.
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Acetatos , Antiasmáticos , Asma , Estudios Cruzados , Ciclopropanos , Quinolinas , Sulfuros , Humanos , Niño , Adolescente , Masculino , Femenino , Preescolar , Acetatos/efectos adversos , Acetatos/uso terapéutico , Quinolinas/efectos adversos , Quinolinas/uso terapéutico , Sulfuros/efectos adversos , Asma/tratamiento farmacológico , Asma/epidemiología , Lactante , Antiasmáticos/efectos adversos , Antiasmáticos/administración & dosificación , Antiasmáticos/uso terapéutico , Rinitis Alérgica/epidemiología , Recién Nacido , Adulto JovenRESUMEN
To document a case of `preliminary` identification of Alternaria sp (a phaeohyphomycotic agent) based on morphology in tissue section in a patient with allergic fungal rhinosinusitis. A 25-year-old male, a known asthmatic in a post Covid -19 state, presented with headache, facial swelling and nasal block with discharge of brownish mucoid material. Debrided material from the right maxillary antrum and middle turbinate showed brownish mucoid material admixed with firm to hard degenerated bony spicules sent in formalin and subjected for histopathological examination. Histopathology showed fragments of tissue, mucoid material, degenerated bony spicules, and blood clots. Amidst ulcerated epithelium and mucoid debris were seen scattered pigmented fungi in a state of `vegetative sporulation` with characteristic brownish multicellular `macroconidia` diagnostic of Alternaria sp. A diagnosis of `Phaeohyphomycosis` possibly due to Alternaria sp was offered. The patient was treated with Amphotericin B. The patient was lost to follow up. Clinical materials such as tissue sections or smears from nasal mucus secretions in cases of allergic fungal rhinosinusitis provide a very good source for `preliminary` identification of species and early institution of therapy while waiting for the fungal culture report.
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Alternaria , Alternariosis , COVID-19 , Rinitis Alérgica , Sinusitis , Humanos , Alternaria/aislamiento & purificación , Masculino , Adulto , Sinusitis/microbiología , Sinusitis/patología , COVID-19/complicaciones , Alternariosis/microbiología , Alternariosis/patología , Alternariosis/diagnóstico , Rinitis Alérgica/microbiología , Rinitis Alérgica/patología , Esporas Fúngicas/aislamiento & purificación , Sinusitis Fúngica AlérgicaRESUMEN
BACKGROUND: Consumption of ultra-processed foods [UPFs] may be associated with negative health outcomes. Limited data exist regarding the potential role of UPFs in the occurrence of allergic diseases. The underlying mechanisms underpinning any such associations are also poorly elucidated. METHODS: We performed a systematic review and narrative evidence synthesis of the available literature to assess associations between UPF consumption and pediatric allergy outcomes (n = 26 papers), including data on the association seen with the gut microbiome (n = 16 papers) or immune system (n = 3 papers) structure and function following PRISMA guidelines. RESULTS: Dietary exposure to fructose, carbonated soft drinks, and sugar intake was associated with an increased risk of asthma, allergic rhinitis, and food allergies in children. Commercial baby food intake was associated with childhood food allergy. Childhood intake of fructose, fruit juices, sugar-sweetened beverages, high carbohydrate UPFs, monosodium glutamate, UPFs, and advanced glycated end-products (AGEs) was associated with the occurrence of allergic diseases. Exposure to UPFs and common ingredients in UPFs seem to be associated with increased occurrence of allergic diseases such as asthma, wheezing, food allergies, atopic dermatitis, and allergic rhinitis, in many, but not all studies. CONCLUSION: More preclinical and clinical studies are required to better define the link between UPF consumption and the risk of allergies and asthma. These observational studies ideally require supporting data with clearly defined UPF consumption, validated dietary measures, and mechanistic assessments to definitively link UPFs with the risk of allergies and asthma.
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Hipersensibilidad a los Alimentos , Humanos , Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/etiología , Niño , Comida Rápida/efectos adversos , Microbioma Gastrointestinal/inmunología , Asma/epidemiología , Asma/etiología , Asma/inmunología , Manipulación de Alimentos , Rinitis Alérgica/epidemiología , Rinitis Alérgica/etiología , Preescolar , Comités Consultivos , Alimentos ProcesadosRESUMEN
INTRODUCTION: Traffic-related air and noise pollution are important public health issues. The aim of this study was to estimate their effects on allergic/respiratory outcomes in adult and elderly subjects. MATERIALS AND METHODS: Six hundred and forty-five subjects living in Pisa (Tuscany, Italy) were investigated through a questionnaire on allergic/respiratory symptoms and diseases. Traffic-related air pollution and noise exposures were assessed at residential address by questionnaire, modelled annual mean NO2 concentrations (1 km and 200 m resolution), and noise level over a 24-h period (Lden). Exposure effects were assessed through logistic regression models stratified by age group (18-64 years, ≥65 years), and adjusted for sex, educational level, occupational exposure, and smoking habits. RESULTS: 63.6% of the subjects reported traffic exposure near home. Mean exposure levels were: 28.24 (±3.26 SD) and 27.23 (±3.16 SD) µg/m3 for NO2 at 200 m and 1 km of resolution, respectively; 57.79 dB(A) (±6.12 SD) for Lden. Exposure to vehicular traffic (by questionnaire) and to high noise levels [Lden ≥ 60 dB(A)] were significantly associated with higher odds of allergic rhinitis (OR 2.01, 95%CI 1.09-3.70, and OR 1.99, 95%CI 1.18-3.36, respectively) and borderline with rhino-conjunctivitis (OR 2.20, 95%CI 0.95-5.10, and OR 1.76, 95%CI 0.91-3.42, respectively) only in the elderly. No significant result emerged for NO2. CONCLUSIONS: Our findings highlighted the need to better assess the effect of traffic-related exposure in the elderly, considering the increasing trend in the future global population's ageing.
Global population is ageing.Allergic diseases are globally widespread even on adult population.The susceptibility due to ageing may increase the impact of air pollution on the elderly.Traffic-related air and noise pollution affects allergic status of the elderly.
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Exposición a Riesgos Ambientales , Humanos , Persona de Mediana Edad , Masculino , Femenino , Anciano , Italia/epidemiología , Adulto , Adolescente , Exposición a Riesgos Ambientales/efectos adversos , Adulto Joven , Contaminación del Aire/efectos adversos , Contaminación por Tráfico Vehicular/efectos adversos , Encuestas y Cuestionarios , Emisiones de Vehículos , Ruido/efectos adversos , Rinitis Alérgica/epidemiología , Rinitis Alérgica/etiología , Hipersensibilidad/epidemiología , Hipersensibilidad/etiología , Modelos Logísticos , Dióxido de Nitrógeno/efectos adversos , Dióxido de Nitrógeno/análisis , Contaminantes Atmosféricos/efectos adversos , Ruido del Transporte/efectos adversosRESUMEN
BACKGROUND: Sleep-disordered breathing (SDB) and allergic rhinitis (AR) are common problems that can lead to worsening quality of life (QOL) in children with these conditions. There is scarce evidence on the QOL of children with SDB outside of the hospital setting with inconsistent evidence on the association of AR and QOL concerning the SDB in children. Thus, the primary objective of this study is to determine the QOL concerning the SDB of elementary school students by using OSA-18. We also aim to provide the relationship of allergic rhinitis to the QOL. METHODS: A cross-sectional study was conducted on all elementary school students, aged 6-12 years, from 10 elementary schools. The QOL of all participants was evaluated by the Thai version of the caregiver-administered OSA-18 questionnaire. The simple and multiple linear regression models were used to determine the effect of allergic rhinitis on the OSA-18 total scores. RESULTS: A total of 3,053 children were included in the final analysis, 50.1% male. At least a moderate impact on QOL from SDB was observed in 9.4% of the population. Children with AR had significantly higher mean total OSA- 18 scores than the children without AR (47.5 ± 15.0 VS 38.5 ± 13.1, p < 0.001). After the adjustment for age, gender, body mass index, household income, and history of asthma, the point estimate of the adjusted beta regression coefficient on the OSA-18 total score in children with AR was 7.82 (95% CI: 6.00-9.65, p < 0.001). Significant associations were observed between AR and all domains except for emotional distress. CONCLUSIONS: A substantial number of elementary school children had at least a moderate impact on the QOL from SDB, especially those with AR. Thus, effective screening of SDB in children with AR should be done to improve the QOL of these children.
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Calidad de Vida , Rinitis Alérgica , Síndromes de la Apnea del Sueño , Estudiantes , Humanos , Masculino , Femenino , Niño , Tailandia/epidemiología , Rinitis Alérgica/epidemiología , Síndromes de la Apnea del Sueño/epidemiología , Síndromes de la Apnea del Sueño/psicología , Estudios Transversales , Encuestas y Cuestionarios , Estudiantes/psicología , Instituciones AcadémicasRESUMEN
Phthalates are ubiquitous in diverse environments and have been linked to a myriad of detrimental health outcomes. However, the association between phthalate exposure and allergic rhinitis (AR) remains unclear. To address this knowledge gap, we conducted a systematic review and meta-analysis to comprehensively evaluate the relationship between phthalate exposure and childhood AR risk. We searched the Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica Database, and PubMed to collect relevant studies and estimated pooled odds ratios (OR) and 95% confidence intervals (CI) for risk estimation. Ultimately, 18 articles, including seven cross-sectional, seven case-control, and four prospective cohort studies, were selected for our systematic review and meta-analysis. Our pooled data revealed a significant association between di-2-ethylhexyl phthalate (DEHP) exposure in children's urine and AR risk (OR = 1.188; 95% CI = 1.016-1.389). Additionally, prenatal exposure to combined phthalates and their metabolites in maternal urine was significantly associated with the risk of childhood AR (OR = 1.041; 95% CI = 1.003-1.081), although specific types of phthalates and their metabolites were not significant. Furthermore, we examined environmental phthalate exposure in household dust and found no significant association with AR risk (OR = 1.021; 95% CI = 0.980-1.065). Our findings underscore the potential hazardous effects of phthalates on childhood AR and offer valuable insights into its pathogenesis and prevention.
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Exposición a Riesgos Ambientales , Ácidos Ftálicos , Rinitis Alérgica , Humanos , Rinitis Alérgica/epidemiología , Ácidos Ftálicos/efectos adversos , Ácidos Ftálicos/orina , Niño , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Riesgo , Exposición Materna/efectos adversos , PreescolarRESUMEN
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.
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Vesículas Extracelulares , Células Th2 , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/inmunología , Humanos , Células Th2/inmunología , Células Th2/metabolismo , Animales , Asma/inmunología , Asma/metabolismo , Asma/terapia , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/patología , Sinusitis/inmunología , Sinusitis/metabolismo , Sinusitis/patología , Sinusitis/terapia , Rinitis Alérgica/inmunología , Rinitis Alérgica/metabolismo , Rinitis Alérgica/terapia , Pólipos Nasales/inmunología , Pólipos Nasales/terapia , Pólipos Nasales/metabolismo , Pólipos Nasales/patología , Rinitis/inmunología , Rinitis/terapia , Rinitis/metabolismo , Rinitis/patologíaRESUMEN
Background: Allergen-specific immunotherapy, a unique inducer of tolerance, may result in T cell exhaution. Aims: To investigate how the duration of house dust mite (HDM) subcutaneous immunotherapy (SCIT) affects the expression of major immune checkpoint (ICP) molecules on the surface of CD4+ T-helper and regulatory T (Treg) cells. Study Design: Cross-sectional study. Methods: We enrolled 28 children with HDM-induced allergic rhinitis (AR) and six controls. The study participants were divided into six groups: one group each of patients in their first, second, and third years of HDM-SCIT; one group each comprising those in the first year following HDM-SCIT and those on pharmacotherapy; and the control group. The expression of ICPs on CD4+ T and Treg cells was determined using flow cytometry, and plasma levels of soluble ICPs were estimated by ELISA. Results: Our results revealed a significant increase in the expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and lymphocyte activation gene 3 (LAG-3) on CD4+ T cells during the second and third years of SCIT, respectively. Additionally, a strong correlation was observed between the expression of CTLA-4 and T cell immunoglobulin and mucin domain containing molecule-3 in CD4+ T cells. Furthermore, we observed a significant correlation between the expressions of programmed cell death protein-1, CTLA-4, T cell Immunoreceptor with Immunoglobulin and Immunoreceptor Tyrosine-Based Inhibitory Motif domain, and LAG-3 on both CD4+ T and Treg cells. A robust correlation was observed between the plasma levels of soluble ICPs. Conclusion: HDM-SCIT induces CD4+ T cell exhaution, which may contribute to tolerance induction in children with AR.
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Linfocitos T CD4-Positivos , Pyroglyphidae , Rinitis Alérgica , Linfocitos T Reguladores , Humanos , Niño , Animales , Rinitis Alérgica/terapia , Rinitis Alérgica/inmunología , Rinitis Alérgica/sangre , Masculino , Estudios Transversales , Femenino , Pyroglyphidae/inmunología , Linfocitos T Reguladores/inmunología , Linfocitos T CD4-Positivos/inmunología , Antígeno CTLA-4/análisis , Desensibilización Inmunológica/métodos , AdolescenteRESUMEN
Allergic rhinitis (AR) is a chronic, non-infectious inflammatory condition of the nasal mucosa mediated by IgE. There is a need for the development of novel medications to treat this ailment. Isoorientin is a naturally occurring flavonoid that possesses antioxidant, anti--inflammatory, and various other advantageous characteristics. However, its potential effects on AR remain unclear. This study evaluates the therapeutic effects of isoorientin on ovalbumin (OVA)-induced allergic rhinitis (AR) in mice and explores the underlying mechanism. Our study revealed that isoorientin administration effectively decreased the frequency of nose rubbing and sneezing in AR mice. The groups treated with isoorientin showed a significant decrease in serum levels of IgE and histamine, with reductions of 40% and 30%, respectively. Isoorientin ameliorated inflammation of the nasal mucosa and restored the Th1/Th2 balance. In addition, isoorientin inhibited the activation of the NF-κB pathway in nasal tissues. In summary, Isoorientin alleviates OVA-stimulated AR in mice by restoring Th1/Th2 balance and blocking the NF-κB pathway. Thus, isoorientin exhibits promise as a natural therapeutic agent for allergic rhinitis.
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Modelos Animales de Enfermedad , Inmunoglobulina E , Luteolina , Ratones Endogámicos BALB C , FN-kappa B , Mucosa Nasal , Ovalbúmina , Rinitis Alérgica , Balance Th1 - Th2 , Animales , Luteolina/farmacología , Ovalbúmina/inmunología , Ratones , Rinitis Alérgica/inmunología , Rinitis Alérgica/tratamiento farmacológico , Balance Th1 - Th2/efectos de los fármacos , Mucosa Nasal/inmunología , Mucosa Nasal/efectos de los fármacos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , FN-kappa B/metabolismo , Células Th2/inmunología , Femenino , Humanos , Alérgenos/inmunología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Células TH1/inmunología , Células TH1/efectos de los fármacos , Histamina/metabolismo , Histamina/sangreRESUMEN
OBJECTIVES: This thesis aims to provide patients with a preventive and therapeutic basis by analyzing IgE level influencing factors of common allergens for Allergic Rhinitis (AR). METHOD: Multiple linear regression analysis is made upon questionnaires among 749 cases of AR patients that are divided into 5 age-based groups. Perform serum-specific IgE content testing on patients. RESULTS: Cockroach being an allergen, AR patients' IgE Level is influenced by allergic history, home-raised plants and animals. For AR patients with mugwort as an allergen, allergy and asthma history could increase IgE level, respectively, ß = 4.291 and ß = 4.364. If the allergen turns out to be peanut, allergic history would increase the IgE level (ß = 0.171), however, the level would be lower in female patients compared with male patients (ß = -0.078). For patients with egg as an allergen, allergic history, home-raised plants and animals (pets) would all affect the IgE level, respectively, ß = 0.182, ß = 0.118 and ß = -0.101. CONCLUSIONS: IgE level varies according to allergic history, home-raised plants & animals, gender, furniture renewal, asthma, and ages for patients with different allergens including cockroach, mold, mugwort, peanut, egg and crab. For each kind of allergen, the IgE levels react differently to different influencing factors, thus requiring a thorough analysis of each AR patient's allergen and allergenic factors.
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Alérgenos , Inmunoglobulina E , Rinitis Alérgica , Humanos , Femenino , Inmunoglobulina E/sangre , Masculino , Alérgenos/inmunología , China/epidemiología , Adulto , Niño , Adolescente , Adulto Joven , Rinitis Alérgica/inmunología , Rinitis Alérgica/sangre , Animales , Persona de Mediana Edad , Preescolar , Factores Sexuales , Factores de Edad , Encuestas y Cuestionarios , AncianoRESUMEN
Allergic rhinitis ï¼ARï¼ is a nasal hypersensitivity disease that is influenced by environmental factors, genetic factors, and various inflammatory factors. The role and mechanisms of ozone, as a component of air pollution, in the pathogenesis of AR are not yet fully understood. This article provides a review of the impact of ozone on the epidemiology and pathology of AR, as well as its possible mechanisms, to provide new insights into the prevention and treatment of AR.
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Ozono , Rinitis Alérgica , Humanos , Ozono/efectos adversos , Rinitis Alérgica/etiología , Rinitis Alérgica/epidemiología , Contaminación del Aire/efectos adversos , Contaminantes Atmosféricos/efectos adversosRESUMEN
Allergic rhinitis (AR) can significantly reduce the quality of life of patients leading to increased fatigue, mood changes, cognitive impairment, and depression. In clinical practice, insufficient effectiveness of initial AR monotherapy is often noted, and a significant proportion of patients referring for medical care have moderate-severe AR. In this regard, the issues of optimization of combined pharmacological treatment of AR are becoming more and more urgent. This paper provides analysis of the opportunities of combined pharmacotherapy within the framework of current management strategy of AR. Based on the results of some studies and known pharmacological properties of medications it is being discussed the advantages of combined use of intranasal corticosteroids and leukotriene receptor antagonists, in particular mometasone furoate and montelukast, in the therapy of AR, including such comorbidities as bronchial asthma, chronic polyposis rhinosinusitis and pharyngeal tonsil hyperplasia. Some aspects of combination therapy with montelukast and second-generation systemic antihistamines as an alternative approach in case of inability to take intranasal corticosteroids, including the reasonability of using a fixed combination of montelukast and levocetirizine, are analyzed from the perspective of rational pharmacotherapy. The problem of interchangeability of brand-name and generic drugs for the treatment of AR is discussed, considering the almost complete absence of studies of their therapeutic equivalence.
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Administración Intranasal , Quimioterapia Combinada , Antagonistas de Leucotrieno , Rinitis Alérgica , Humanos , Rinitis Alérgica/tratamiento farmacológico , Antagonistas de Leucotrieno/administración & dosificación , Antagonistas de Leucotrieno/uso terapéutico , Antialérgicos/administración & dosificación , Antagonistas de los Receptores Histamínicos/administración & dosificación , Corticoesteroides/administración & dosificación , Resultado del Tratamiento , Ciclopropanos/administración & dosificación , Ciclopropanos/uso terapéutico , Quinolinas/administración & dosificación , Quinolinas/uso terapéutico , Sulfuros/administración & dosificación , Acetatos/uso terapéutico , Acetatos/administración & dosificaciónRESUMEN
OBJECTIVES: Previous studies have revealed a correlation between eosinophils and allergic rhinitis, but the causal relationship has not been fully confirmed. This study aims to evaluate the causal link between blood eosinophils and allergic rhinitis using the Mendelian randomization (MR) method. METHODS: Summary data from the Genome-Wide Association Study Catalog (GWAS) for eosinophil count (exposure variable) and allergic rhinitis (outcome variable) were collected. GWAS data for the exposure variable were obtained from the IEU Open GWAS Project developed by the Integrative Epidemiology Unit at the University of Bristol, while data for the outcome variable were sourced from the FinnGen Biobank (Finland) database. The causal relationship between eosinophils and allergic rhinitis was analyzed using the two-sample MR method with inverse variance weighted (IVW) analysis. Sensitivity analyses were conducted using the weighted median method, MR-Egger regression, leave-one-out analysis, and funnel plots. RESULTS: An increase in blood eosinophil count showed a potential causal relationship with an increased risk of allergic rhinitis (OR=1.187, 95% CI 1.051 to 1.341, P=0.006). This finding was consistent across the weighted median method and MR-Egger regression. Leave-one-out analysis indicated that no single nucleotide polymorphism significantly influenced the causal inference. CONCLUSIONS: There is a causal association between increased eosinophil count and a higher risk or worsening of allergic rhinitis.
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Eosinófilos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Rinitis Alérgica , Humanos , Rinitis Alérgica/genética , Rinitis Alérgica/etiología , Recuento de Leucocitos , Factores de RiesgoRESUMEN
BACKGROUND: The etiology of allergic rhinitis (AR) is not fully understood. Studies have shown that the maturation of children's immune systems is closely related to microecology. However, few studies have focused simultaneously on changes in respiratory and gut microbiota in AR and their correlation between microecological changes and Th1/Th2/Treg. OBJECTIVE: The aim is to investigate the pathogenesis of AR based on respiratory microecology, gut microecology, and Th1/Th2/Treg levels by applying microbiome techniques and correlation analysis. METHODS: Standardized OVA-induced AR mice were established. Serum OVA-sIgE, IL-4, IFN-γ, IL-10 were measured by ELISA, Tregs in lymph nodes were determined by flow cytometry, and the histological characteristics of nasal tissues were evaluated by Hematoxylin & Eosin (H&E). Nasal symptoms were observed to determine the reliability of the AR mouse model. Nasal lavage fluid (NALF) and fecal samples were collected after the last OVA challenge. The composition of respiratory microbiota in NALF and gut microbial in feces samples via 16S rRNA gene sequencing between the two groups, further explored the relationship between microbiota and Th1/Th2/Treg levels. RESULTS: In the AR group, the incidence of nose rubbing and sneezing in each mouse was significantly increased compared with the control group (all P < 0.001) and the inflammatory cell infiltration of NALF shows a significant increase in eosinophilic and neutrophilic infiltrates upon the AR group; H&E showed that the nasal mucosa of AR mice infiltration of massive eosinophils cells and neutrophils cells. OVA-sIgE and IL-4 in the AR group were increased (P < 0.01, P < 0.05) and IFN-γ, IL-10 were significantly decreased (P < 0.01, P < 0.05). Tregs showed a downward trend in the AR group, but there was no statistical difference. Compared with the control group, the respiratory microbiota of AR mice did not change significantly, while the gut microbiota changed significantly. In gut microbiota, compared to the control group, Shannon index in the AR group revealed a significant decrease at the genus level (P < 0.01), and Simpson index was significantly increased at all levels (all P < 0.05). PCoA also showed significant differences in beta diversity between the two groups (all P < 0.05). Compared to the control group, Deferribacteres at phylum level, Roseburia, Ruminiclostridium, Anaerotruncus at genus level were significantly decreased in the AR group (all P < 0.05). Spearman's rank correlation showed that OVA-sIgE was positively correlated with Bacteroidetes, Muribaculaceae and Erysipelotrichaceae (all P < 0.05); IL-4 was significantly negatively correlated with Epsilonbacteraeota and Deferribacteres (all P < 0.05). Treg was significantly positively correlated with Patescibacteria, Lachnospiraceae, and Saccharimonadaceae in gut microecology. CONCLUSION: Our results showed that the respiratory microbiota of AR mice was not significantly altered, but the gut microbiota varied significantly and there was a correlation between gut microbiota and Th1/Th2/Treg.
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Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Ovalbúmina , ARN Ribosómico 16S , Sistema Respiratorio , Rinitis Alérgica , Linfocitos T Reguladores , Células TH1 , Células Th2 , Animales , Ratones , Microbioma Gastrointestinal/inmunología , Linfocitos T Reguladores/inmunología , Células Th2/inmunología , Rinitis Alérgica/inmunología , Rinitis Alérgica/microbiología , Células TH1/inmunología , Ovalbúmina/inmunología , ARN Ribosómico 16S/genética , Sistema Respiratorio/microbiología , Sistema Respiratorio/inmunología , Femenino , Ratones Endogámicos BALB C , Citocinas/metabolismo , Interleucina-10/genética , Inmunoglobulina E/sangre , Heces/microbiología , Líquido del Lavado Nasal/inmunología , Líquido del Lavado Nasal/microbiología , Interferón gamma/genética , Interleucina-4RESUMEN
Several studies reveal that allergic rhinitis (AR) is a significant risk factor of systemic lupus erythematosus (SLE). However, studies investigating the common pathogenesis linking AR and SLE are lacking. Our study aims to search for the shared biomarkers and mechanisms that may provide new therapeutic targets for preventing AR from developing SLE. GSE50223 for AR and GSE103760 for SLE were downloaded from the Gene Expression Omnibus (GEO) database to screen differentially expressed genes (DEGs). The Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to explore the functions of shared DEGs. Hub genes were screened by cytoHubba (a plugin of Cytoscape) and validated in another two datasets. Gene set enrichment analysis (GSEA) and single-sample Gene set enrichment analysis (ssGSEA) algorithm were applied to understand the functions of hub gene. ENTPD1 was validated as a hub gene between AR and SLE. GSEA results revealed that ENTPD1 was associated with KRAS_SIGNALING_UP pathway in AR and related to HYPOXIA, TGF_BETA_SIGNALING and TNFA_SIGNALING_VIA_NFKB pathways in SLE. The expression of ENTPD1 was positively correlated with activated CD8 T cell in both diseases. Thus, ENTPD1 may be a novel therapeutic target for preventing AR from developing SLE.
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Biomarcadores , Lupus Eritematoso Sistémico , Rinitis Alérgica , Humanos , Lupus Eritematoso Sistémico/genética , Rinitis Alérgica/genética , Ontología de Genes , Perfilación de la Expresión Génica , Bases de Datos Genéticas , Transducción de Señal , Redes Reguladoras de Genes , Biología Computacional/métodosRESUMEN
Objective: To explore the causal relationship between asthma, allergic rhinitis (AR), and chronic sinusitis (CRS), using two sample Mendelian randomization (MR) analysis, thereby providing foundational evidences for the pathogenesis and treatment of CRS. Methods: The genetic variations in AR and asthma were used as instrumental variables, with genetic data from the Integrated Epidemiology Unit (IEU) Open database. A total of 14 283 asthma and 18 934 AR cases were included, with 98 300 and 64 595 corresponding normal control cases, respectively. For CRS, there were 3 236 CRSwNP and 8 524 CRSsNP, respectively, with 167 849 and 167 849 corresponding normal control cases, respectively. The genetic data were analyzed using the inverse variance weighting method (IVW), MR Egger method, weighted median method, and Cochran's Q-test. Results: The IVW analysis showed that asthma increased the risk of both CRSwNP (OR=482.8, 95%CI: 57.18-4 077.78, P<0.001) and CRSsNP (OR=25.73, 95%CI: 9.79-67.56, P<0.001); AR significantly increased the risk of CRSsNP (OR=5.40, 95%CI: 1.68-17.26, P=0.004), but not CRSwNP (OR=7.38, 95%CI: 0.80-67.73, P=0.077). Conversely, neither CRSwNP nor CRSsNP increased the risk of asthma or AR. Conclusion: According to Mendelian genetic laws, asthma is a risk factor for CRSwNP and CRSsNP, while AR is a risk factor for CRSsNP.
Asunto(s)
Asma , Análisis de la Aleatorización Mendeliana , Rinitis Alérgica , Sinusitis , Humanos , Asma/genética , Asma/etiología , Asma/epidemiología , Sinusitis/genética , Sinusitis/etiología , Rinitis Alérgica/epidemiología , Rinitis Alérgica/genética , Enfermedad Crónica , Factores de RiesgoRESUMEN
Allergic rhinitis (AR) is a chronic, non-infectious condition affecting the nasal mucosa, primarily mediated mainly by IgE. Recent studies reveal that AR is intricately associated not only with type 2 immunity but also with neuroimmunity. Nociceptive neurons, a subset of primary sensory neurons, are pivotal in detecting external nociceptive stimuli and modulating immune responses. This review examines nociceptive neuron receptors and elucidates how neuropeptides released by these neurons impact the immune system. Additionally, we summarize the role of immune cells and inflammatory mediators on nociceptive neurons. A comprehensive understanding of the dynamic interplay between nociceptive neurons and the immune system augments our understanding of the neuroimmune mechanisms underlying AR, thereby opening novel avenues for AR treatment modalities.
Asunto(s)
Nociceptores , Rinitis Alérgica , Humanos , Nociceptores/metabolismo , Nociceptores/inmunología , Rinitis Alérgica/inmunología , Rinitis Alérgica/metabolismo , Animales , Mucosa Nasal/inmunología , Mucosa Nasal/metabolismo , Mucosa Nasal/inervación , Neuroinmunomodulación , Neuropéptidos/metabolismo , Neuropéptidos/inmunologíaRESUMEN
There is growing evidence that neurogenic inflammation contributes to the pathophysiology of upper airway diseases, with nasal hyperreactivity (NHR) being a key symptom. The rare neuroendocrine cells (NECs) in the epithelium have been linked to the pathophysiology of bronchial and intestinal hyperreactivity, however their presence in the nasal mucosa and their potential role in NHR remains unclear. Therefore, we studied the presence of NECs in the nasal epithelium of controls, allergic rhinitis patients and chronic rhinosinusitis with nasal polyps patients, and their link to NHR. The expression of typical NECs markers, CHGA, ASCL1 and CGRP, were evaluated on gene and protein level in human samples using real-time quantitative PCR (RT-qPCR), western blot, immunohistochemistry fluorescence staining, RNA scope assay, flow cytometry and single cell RNA-sequencing. Furthermore, the change in peak nasal inspiratory flow after cold dry air provocation and visual analogue scale scores were used to evaluate NHR or disease severity, respectively. Limited gene expression of the NECs markers CHGA and ASCL1 was measured in patients with upper airway diseases and controls. Gene expression of these markers did not correlate with NHR severity nor disease severity. In vitro, CHGA and ASCL1 expression was also evaluated in primary nasal epithelial cell cultures from patients with upper airway disease and controls using RT-qPCR and western blot. Both on gene and protein level only limited CHGA and ASCL1 expression was found. Additionally, NECs were studied in nasal biopsies of patients with upper airway diseases and controls using immunohistochemistry fluorescence staining, RNA scope and flow cytometry. Unlike in ileum samples, CHGA could not be detected in nasal biopsies of patients with upper airway diseases and control subjects. Lastly, single cell RNA-sequencing of upper airway tissue could not identify a NEC cluster. In summary, in contrast to the bronchi and gut, there is only limited evidence for the presence of NECs in the nasal mucosa, and without correlation with NHR, thereby questioning the relevance of NECs in upper airway pathology.