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Frontiers in Neurology 2023The prevalence rate of allergic rhinitis (AR) is high worldwide. The inhalation of allergens induces AR, which is an immunoglobulin E-mediated and type 2... (Review)
Review
The prevalence rate of allergic rhinitis (AR) is high worldwide. The inhalation of allergens induces AR, which is an immunoglobulin E-mediated and type 2 inflammation-driven disease. Recently, the role of neuroimmune communication in AR pathogenesis has piqued the interest of the scientific community. Various neuropeptides, such as substance P (SP), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), nerve growth factor (NGF), and neuromedin U (NMU), released via "axon reflexes" or "central sensitization" exert regulatory effects on immune cells to elicit "neurogenic inflammation," which contributes to nasal hyperresponsiveness (NHR) in AR. Additionally, neuropeptides can be produced in immune cells. The frequent colocalization of immune and neuronal cells at certain anatomical regions promotes the establishment of neuroimmune cell units, such as nerve-mast cells, nerve-type 2 innate lymphoid cells (ILC2s), nerve-eosinophils and nerve-basophils units. Receptors expressed both on immune cells and neurons, such as TRPV1, TRPA1, and Mas-related G protein-coupled receptor X2 (MRGPRX2) mediate AR pathogenesis. This review focused on elucidating the mechanisms underlying neuroimmune communication in AR.
PubMed: 38178883
DOI: 10.3389/fneur.2023.1282130 -
Biomedicine & Pharmacotherapy =... Aug 2023Combined allergic rhinitis and asthma syndrome (CARAS) causes chronic respiratory inflammation in allergic individuals. Long-term exposure to particulate matter 2.5...
Bergapten ameliorates combined allergic rhinitis and asthma syndrome after PM2.5 exposure by balancing Treg/Th17 expression and suppressing STAT3 and MAPK activation in a mouse model.
Combined allergic rhinitis and asthma syndrome (CARAS) causes chronic respiratory inflammation in allergic individuals. Long-term exposure to particulate matter 2.5 (PM2.5; particles 2.5 µm or less in diameter) can aggravate respiratory damage. Bergapten (5-methoxysporalen) is a furocoumarin mostly found in bergamot essential oil and has significant antioxidant, anticancer, and anti-inflammatory activity. This study created a model in which CARAS was exacerbated by PM2.5 exposure, in BALB/c mice and explored the potential of bergapten as a therapeutic agent. The bergapten medication increased ovalbumin (OVA)-specific immunoglobulin (Ig) G2a level in serum and decreased OVA-specific IgE and IgG1 expression. Clinical nasal symptoms diminished significantly, with weakened inflammatory reaction in both the nasal mucosa and lungs. Furthermore, bergapten controlled the T helper (Th)1 to Th2 ratio by increasing cytokines associated with Th1-like interleukin (IL)-12 and interferon gamma and decreasing the Th2 cytokines IL-4, IL-5, and IL-13. Factors closely related to the balance between regulatory T cells and Th17 (such as IL-10, IL-17, Forkhead box protein P3, and retinoic-related orphan receptor gamma) were also regulated. Notably, pro-inflammatory cytokines IL-6, IL-1β, and tumor necrosis factor-alpha were reduced by bergapten, which suppressed the activation of both the signal transducer and activator of transcription 3 signaling pathway and the mitogen-activated protein kinase signaling pathway. Therefore, bergapten might have potential as a therapeutic agent for CARAS.
Topics: Mice; Animals; 5-Methoxypsoralen; STAT3 Transcription Factor; T-Lymphocytes, Regulatory; Rhinitis, Allergic; Asthma; Inflammation; Cytokines; Particulate Matter; Ovalbumin; Mice, Inbred BALB C; Disease Models, Animal
PubMed: 37267637
DOI: 10.1016/j.biopha.2023.114959 -
Brazilian Journal of Otorhinolaryngology 2023Oral H antihistamines are the first-line treatment for patients with allergic rhinitis, while it is uncertain which kind and dosage of the antihistamines are more... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Oral H antihistamines are the first-line treatment for patients with allergic rhinitis, while it is uncertain which kind and dosage of the antihistamines are more effective in improving symptoms of patients.
OBJECTIVE
To evaluate the efficacy of different oral H antihistamine treatments on patients with allergic rhinitis by performing a network meta-analysis.
METHODS
The search was executed in PubMed, Embase, OVID, the Cochrane Library and ClinicalTrials.gov for relevant studies. The network meta-analysis was performed by using Stata 16.0, and the outcome measures of the analysis were symptom score reductions of patients. Relative risks with 95% Confidence Intervals were used in the network meta-analysis to compare the clinical effect of treatments involved, and Surface Under the Cumulative Ranking Curves (SUCRAs) were also calculated to rank the treatments' efficacy.
RESULTS
18 eligible randomized controlled studies, involving a total of 9419 participants, were included in this meta-analysis. All the antihistamine treatments outperformed placebo in total symptom score reduction and each individual symptom score reduction. According to the results of SUCRA, rupatadine 20 mg and rupatadine 10 mg were ranked relatively high in reductions of total symptom score (SUCRA: 99.7%, 76.3%), nasal congestion score (SUCRA: 96.4%, 76.4%), rhinorrhea score (SUCRA: 96.6%, 74.6%) and ocular symptom score (SUCRA: 97.2%, 88.8%); rupatadine 20 mg and levocetirizine 5 mg were ranked relatively high in reductions of nasal itching score (SUCRA: 84.8%, 83.4%) and sneezing score (SUCRA: 87.3%, 95.4%); loratadine 10 mg was ranked the lowest in each symptom score reduction besides placebo.
CONCLUSION
This study suggests that rupatadine is the most effective in alleviating symptoms of patients with allergic rhinitis among different oral H antihistamine treatments involved, and rupatadine 20 mg performs better than rupatadine 10 mg. While loratadine 10 mg has inferior efficacy for patients to the other antihistamine treatments.
Topics: Humans; Loratadine; Network Meta-Analysis; Randomized Controlled Trials as Topic; Histamine H1 Antagonists; Histamine Antagonists; Rhinitis, Allergic; Treatment Outcome
PubMed: 37271114
DOI: 10.1016/j.bjorl.2023.03.009 -
Frontiers in Allergy 2024Rhinitis arises from either allergic or non-allergic inflammation of the nasal mucosa, characterized by the infiltration of inflammatory cells into the tissue and nasal... (Review)
Review
Rhinitis arises from either allergic or non-allergic inflammation of the nasal mucosa, characterized by the infiltration of inflammatory cells into the tissue and nasal secretions, along with structural alterations in the nasal mucosa. The pathways through which air pollution affects rhinitis may diverge from those affecting asthma. This article aims to review the effects of diverse air pollutants on the nose, the correlation of climate change and pollution, and how they aggravate the symptoms of patients with rhinitis.
PubMed: 38863567
DOI: 10.3389/falgy.2024.1387525 -
International Journal of Molecular... Sep 2023Allergic diseases, such as food allergies, asthma, and allergic rhinitis, continue to present a significant challenge for a broad cross-section of the population,...
Allergic diseases, such as food allergies, asthma, and allergic rhinitis, continue to present a significant challenge for a broad cross-section of the population, despite recent advancements in their treatment and prevention [...].
Topics: Humans; Prevalence; Rhinitis, Allergic; Asthma; Food Hypersensitivity
PubMed: 37762615
DOI: 10.3390/ijms241814312 -
Scientific Reports Aug 2023The concept of "one-airway-one-disease", coined over 20 years ago, may be an over-simplification of the links between allergic diseases. Genomic studies suggest that...
The concept of "one-airway-one-disease", coined over 20 years ago, may be an over-simplification of the links between allergic diseases. Genomic studies suggest that rhinitis alone and rhinitis with asthma are operated by distinct pathways. In this MeDALL (Mechanisms of the Development of Allergy) study, we leveraged the information of the human interactome to distinguish the molecular mechanisms associated with two phenotypes of allergic rhinitis: rhinitis alone and rhinitis in multimorbidity with asthma. We observed significant differences in the topology of the interactomes and in the pathways associated to each phenotype. In rhinitis alone, identified pathways included cell cycle, cytokine signalling, developmental biology, immune system, metabolism of proteins and signal transduction. In rhinitis and asthma multimorbidity, most pathways were related to signal transduction. The remaining few were related to cytokine signalling, immune system or developmental biology. Toll-like receptors and IL-17-mediated signalling were identified in rhinitis alone, while IL-33 was identified in rhinitis in multimorbidity. On the other hand, few pathways were associated with both phenotypes, most being associated with signal transduction pathways including estrogen-stimulated signalling. The only immune system pathway was FceRI-mediated MAPK activation. In conclusion, our findings suggest that rhinitis alone and rhinitis and asthma multimorbidity should be considered as two distinct diseases.
Topics: Humans; Rhinitis; Asthma; Rhinitis, Allergic; Multimorbidity; Cytokines
PubMed: 37573373
DOI: 10.1038/s41598-023-39987-6 -
Nature Communications Aug 2023Allergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e., the...
Allergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e., the microorganisms and their genes within the gastrointestinal tract. Maturation of the infant immune system and gut microbiota occur in parallel; thus, the conformation of the microbiome may determine if tolerant immune programming arises within the infant. Here we show, using deeply phenotyped participants in the CHILD birth cohort (n = 1115), that there are early-life influences and microbiome features which are uniformly associated with four distinct allergic diagnoses at 5 years: atopic dermatitis (AD, n = 367), asthma (As, n = 165), food allergy (FA, n = 136), and allergic rhinitis (AR, n = 187). In a subset with shotgun metagenomic and metabolomic profiling (n = 589), we discover that impaired 1-year microbiota maturation may be universal to pediatric allergies (AD p = 0.000014; As p = 0.0073; FA p = 0.00083; and AR p = 0.0021). Extending this, we find a core set of functional and metabolic imbalances characterized by compromised mucous integrity, elevated oxidative activity, decreased secondary fermentation, and elevated trace amines, to be a significant mediator between microbiota maturation at age 1 year and allergic diagnoses at age 5 years (β = -2.28; p = 0.0020). Microbiota maturation thus provides a focal point to identify deviations from normative development to predict and prevent allergic disease.
Topics: Infant; Humans; Child; Gastrointestinal Microbiome; Hypersensitivity; Microbiota; Asthma; Dermatitis, Atopic
PubMed: 37644001
DOI: 10.1038/s41467-023-40336-4 -
Autoimmunity Dec 2023Allergic rhinitis (AR) is a common inflammation that affects many people globally. Quercetin has anti-allergic biological activity in AR. Here, we aimed to explore the...
Allergic rhinitis (AR) is a common inflammation that affects many people globally. Quercetin has anti-allergic biological activity in AR. Here, we aimed to explore the effects of quercetin on type 1 helper T (Th1)/Th2 and regulatory T cells (Treg)/Th17 balance. We established an ovalbumin (OVA)-induced mouse model and orally administered 20, 35, and 50 mg/kg/day quercetin. The nasal symptoms of mice were observed. The immunoglobulin levels, Treg/Th17-related factors, and pro-inflammatory factors were examined by ELISA. The differentiated inflammation cells were visualized using the diff-quick staining assay. The nasal histopathology was evaluated using H&E, periodic acid Schiff (PAS), and Giemsa staining assay. The results showed that quercetin attenuated OVA-induced rubbing and sneezing. Quercetin reduced IgE, IgG1, histamine, and increased IgG2 in serum. The number of differentiated inflammation cells and goblet cells in tissues that elevated by OVA was reduced by quercetin. Moreover, OVA increased the Treg cell percentage, the levels of IL-17, TGF-β, IL-6, TNF-α, and decreased Th17 cell percentage, IL-10 and FOXP3 levels, while quercetin abrogated their levels induced by OVA. Additionally, quercetin inactivated the NF-κB pathway. Taken together, quercetin attenuated AR symptoms by balancing the Th1/Th2, Treg/Th17 ratios, and inactivating the NF-κB pathway. The results suggested that quercetin may use for AR treatment.
Topics: Animals; Mice; T-Lymphocytes, Regulatory; Quercetin; Th2 Cells; Nasal Mucosa; NF-kappa B; Th17 Cells; Rhinitis, Allergic; Inflammation; Immunoglobulin G; Disease Models, Animal; Mice, Inbred BALB C; Cytokines
PubMed: 36938614
DOI: 10.1080/08916934.2023.2189133 -
PLoS Pathogens Sep 2023The worldwide prevalence of asthma and allergic disorders (allergic rhinitis, atopic dermatitis, food allergy) has been steadily rising in recent decades. It is now... (Review)
Review
The worldwide prevalence of asthma and allergic disorders (allergic rhinitis, atopic dermatitis, food allergy) has been steadily rising in recent decades. It is now estimated that up to 20% of the global population is afflicted by an allergic disease, with increasing incidence rates in both high- and low-income countries. The World Allergy Organization estimates that the total economic burden of asthma and allergic rhinitis alone is approximately $21 billion per year. While allergic stimuli are a complex and heterogenous class of inputs including parasites, pollens, food antigens, drugs, and metals, it has become clear that fungi are major drivers of allergic disease, with estimates that fungal sensitization occurs in 20-30% of atopic individuals and up to 80% of asthma patients. Fungi are eukaryotic microorganisms that can be found throughout the world in high abundance in both indoor and outdoor environments. Understanding how and why fungi act as triggers of allergic type 2 inflammation will be crucial for combating this important health problem. In recent years, there have been significant advances in our understanding of fungi-induced type 2 immunity, however there is still much we don't understand, including why fungi have a tendency to induce allergic reactions in the first place. Here, we will discuss how fungi trigger type 2 immune responses and posit why this response has been evolutionarily selected for induction during fungal encounter.
Topics: Humans; Inflammation; Rhinitis, Allergic; Asthma; Eukaryota
PubMed: 37703276
DOI: 10.1371/journal.ppat.1011623 -
JAMA Dermatology Jan 2024Biologics used for plaque psoriasis have been reported to be associated with an atopic dermatitis (AD) phenotype, or paradoxical eczema, in some patients. The risk...
IMPORTANCE
Biologics used for plaque psoriasis have been reported to be associated with an atopic dermatitis (AD) phenotype, or paradoxical eczema, in some patients. The risk factors for this are unknown.
OBJECTIVE
To explore risk of paradoxical eczema by biologic class and identify factors associated with paradoxical eczema.
DESIGN, SETTING, AND PARTICIPANTS
This prospective cohort study used data from the British Association of Dermatologists Biologics and Immunomodulators Register for adults treated with biologics for plaque psoriasis who were seen at multicenter dermatology clinics in the UK and Ireland. Included participants were registered and had 1 or more follow-up visits between September 2007 and December 2022.
EXPOSURES
Duration of exposure to tumor necrosis factor (TNF) inhibitors, interleukin (IL) 17 inhibitors, IL-12/23 inhibitors, or IL-23 inhibitors until paradoxical eczema onset, treatment discontinuation, last follow-up, or death.
MAIN OUTCOMES AND MEASURES
Incidence rates of paradoxical eczema, paradoxical eczema risk by biologic class, and the association of demographic and clinical variables with risk of paradoxical eczema were assessed using propensity score-weighted Cox proportional hazards regression models.
RESULTS
Of 56 553 drug exposures considered, 24 997 from 13 699 participants were included. The 24 997 included exposures (median age, 46 years [IQR, 36-55 years]; 57% male) accrued a total exposure time of 81 441 patient-years. A total of 273 exposures (1%) were associated with paradoxical eczema. The adjusted incidence rates were 1.22 per 100 000 person-years for IL-17 inhibitors, 0.94 per 100 000 person-years for TNF inhibitors, 0.80 per 100 000 person-years for IL-12/23 inhibitors, and 0.56 per 100 000 person-years for IL-23 inhibitors. Compared with TNF inhibitors, IL-23 inhibitors were associated with a lower risk of paradoxical eczema (hazard ratio [HR], 0.39; 95% CI, 0.19-0.81), and there was no association of IL-17 inhibitors (HR, 1.03; 95% CI, 0.74-1.42) or IL-12/23 inhibitors (HR, 0.87; 95% CI, 0.66-1.16) with risk of paradoxical eczema. Increasing age (HR, 1.02 per year; 95% CI, 1.01-1.03) and history of AD (HR, 12.40; 95% CI, 6.97-22.06) or hay fever (HR, 3.78; 95% CI, 1.49-9.53) were associated with higher risk of paradoxical eczema. There was a lower risk in males (HR, 0.60; 95% CI, 0.45-0.78).
CONCLUSIONS AND RELEVANCE
In this study, in biologic-treated patients with psoriasis, paradoxical eczema risk was lowest in patients receiving IL-23 inhibitors. Increasing age, female sex, and history of AD or hay fever were associated with higher risk of paradoxical eczema. The overall incidence of paradoxical eczema was low. Further study is needed to replicate these findings.
Topics: Adult; Female; Humans; Male; Middle Aged; Biological Factors; Biological Products; Dermatitis, Atopic; Eczema; Interleukin-12; Interleukin-17; Interleukin-23; Prospective Studies; Psoriasis; Rhinitis, Allergic, Seasonal; Tumor Necrosis Factor Inhibitors
PubMed: 38055239
DOI: 10.1001/jamadermatol.2023.4846