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Frontiers in Immunology 2024Airway allergic disease (AAD) is a class of autoimmune diseases with predominantly Th2-type inflammation, mainly including allergic rhinitis (AR), allergic asthma (AS),...
BACKGROUND
Airway allergic disease (AAD) is a class of autoimmune diseases with predominantly Th2-type inflammation, mainly including allergic rhinitis (AR), allergic asthma (AS), and chronic sinusitis (CRS). There are very complex regulatory mechanisms between immune cells and AAD; however, previous reports found that the functions of the same immune cells in AAD are not identical.
OBJECTIVE
The aim of this study was to explore the causal relationship between different phenotypic immune cells and their association with AAD.
METHOD
Utilizing the publicly available Genome-Wide Association Studies (GWAS) database, this study conducted a bidirectional Mendelian randomization (MR) to assess the causal relationship between immune cells of 731 different immunophenotypes and AAD. The primary assessment methods included inverse variance weighting, weighted median, and MR Egger. Additionally, sensitivity analyses such as MR-PRESSO, leave-one-out, and scatter plots were employed to eliminate the interference of heterogeneity and pleiotropy, ensuring the stability of the causal inference.
RESULT
A total of 38 immune cells with different immunophenotypes were found to be positively and causally associated with AR, of which 26 were protective factors and 12 were risk factors. Positive associations were found between 33 immune cells and AS, of which 14 were protective factors and 19 were risk factors, as well as between 39 immune cells and CRS, of which 22 were protective factors and 17 were risk factors. Finally, the results of all relevant immune cells for the three diseases were taken and intersected, and it was found that CD3 on CD39+-activated Treg (IVW = 0.001, IVW = 0.043, IVW = 0.027) may be the key immune cell that inhibits the development of AAD (OR = 0.940, OR = 0.967, OR = 0.976).
CONCLUSION
This study reveals that different immune phenotypes of immune cells are closely related to AAD at the genetic level, which provides a theoretical basis for future clinical studies.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Phenotype; Asthma; Immunophenotyping; Rhinitis, Allergic; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 38812518
DOI: 10.3389/fimmu.2024.1349470 -
Cureus Apr 2024Allergic rhinitis (AR) and nasal polyps (NP) are common inflammatory disorders of the upper airways that often coexist and significantly impact patients' quality of... (Review)
Review
Allergic rhinitis (AR) and nasal polyps (NP) are common inflammatory disorders of the upper airways that often coexist and significantly impact patients' quality of life. This comprehensive review explores the intricate relationship between AR and NP, elucidating the underlying mechanisms, clinical manifestations, and management strategies. Immunological mechanisms, genetic predispositions, and environmental factors contribute to the development and progression of both conditions. Pharmacological therapies, including intranasal corticosteroids and biologic agents, are cornerstone treatments for managing AR with NP. At the same time, surgical interventions such as functional endoscopic sinus surgery (FESS) may be necessary in refractory cases. Emerging therapies, including immunomodulatory agents and precision medicine approaches, hold promise in improving treatment outcomes. A multidisciplinary approach, personalized treatment plans, and patient education are essential for optimizing clinical practice. Future research should focus on identifying novel therapeutic targets, conducting large-scale clinical trials, exploring precision medicine approaches, and investigating the role of the microbiome. Addressing these research priorities and implementing evidence-based treatment strategies can improve outcomes for patients with AR and NP.
PubMed: 38807811
DOI: 10.7759/cureus.59191 -
Clinical and Translational Allergy Jun 2024It is unclear how each individual asthma symptom is associated with asthma diagnosis or control.
RATIONALE
It is unclear how each individual asthma symptom is associated with asthma diagnosis or control.
OBJECTIVES
To assess the performance of individual asthma symptoms in the identification of patients with asthma and their association with asthma control.
METHODS
In this cross-sectional study, we assessed real-world data using the MASK-air app. We compared the frequency of occurrence of five asthma symptoms (dyspnea, wheezing, chest tightness, fatigue and night symptoms, as assessed by the Control of Allergic Rhinitis and Asthma Test [CARAT] questionnaire) in patients with probable, possible or no current asthma. We calculated the sensitivity, specificity and predictive values of each symptom, and assessed the association between each symptom and asthma control (measured using the e-DASTHMA score). Results were validated in a sample of patients with a physician-established diagnosis of asthma.
MEASUREMENT AND MAIN RESULTS
We included 951 patients (2153 CARAT assessments), with 468 having probable asthma, 166 possible asthma and 317 no evidence of asthma. Wheezing displayed the highest specificity (90.5%) and positive predictive value (90.8%). In patients with probable asthma, dyspnea and chest tightness were more strongly associated with asthma control than other symptoms. Dyspnea was the symptom with the highest sensitivity (76.1%) and the one consistently associated with the control of asthma as assessed by e-DASTHMA. Consistent results were observed when assessing patients with a physician-made diagnosis of asthma.
CONCLUSIONS
Wheezing and chest tightness were the asthma symptoms with the highest specificity for asthma diagnosis, while dyspnea displayed the highest sensitivity and strongest association with asthma control.
PubMed: 38804596
DOI: 10.1002/clt2.12358 -
Cureus Apr 2024Ayurveda, an ancient Indian system of medicine, encapsulates comprehensive principles and formulations for disease prevention and treatment. A herbo-mineral Ayurvedic...
BACKGROUND
Ayurveda, an ancient Indian system of medicine, encapsulates comprehensive principles and formulations for disease prevention and treatment. A herbo-mineral Ayurvedic formulation, IMMBO, comprising and 18 herbs has shown promising results in treating allergic rhinitis in clinical studies.
OBJECTIVE
This discussed series of experimental studies were conducted to explore the immuno-modulatory potential of IMMBO.
METHODOLOGY
A series of experimental studies were carried out in immunosuppressed rats to explore the immune-modulatory effects of IMMBO.
RESULTS
IMMBO was effective in reinstating neutrophil activation, stimulating cellular and humoral immunity, and counteracting immunosuppression at the molecular level. The modulation of key signalling molecules, including tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-1 beta (IL-1β), extracellular signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K), and nuclear factor-kappa B (NF-κb), showcased the formulation's multifaceted impact. Additionally, its ability to block histamine release suggests potential in controlling allergic states, positioning it as a promising therapeutic candidate for immune-related disorders. However, the precise mode of action remains elusive, warranting further in-depth pharmacological studies.
CONCLUSION
This research substantiates the ancient Ayurvedic wisdom using modern scientific parameters, endorsing IMMBO's potential as an immune-modulatory agent.
PubMed: 38800281
DOI: 10.7759/cureus.58913 -
Refractory and Recurrent Skin Manifestations in an Adult With Selective Immunoglobulin M Deficiency.Cureus Apr 2024Selective immunoglobulin M (IgM) deficiency (sIgMD) is a rare immunodeficiency disorder characterized by decreased serum levels of IgM. Symptoms of sIgMD include...
Selective immunoglobulin M (IgM) deficiency (sIgMD) is a rare immunodeficiency disorder characterized by decreased serum levels of IgM. Symptoms of sIgMD include repeated infections and allergic manifestations such as asthma and allergic rhinitis. The etiology and pathology of sIgMD remain largely unknown. Moreover, no genetic cause of sIgMD and associated symptoms has been established. Herein, we describe a 47-year-old female with sIgMD who presented with repeated fevers of unknown cause since childhood. She was referred to our department because of recently developed severe dermatitis without a history of atopic dermatitis or asthma. In addition to histological evaluation by skin biopsy, immunological parameters were investigated in her peripheral blood, and the cellular immunity profile was determined by flow cytometry. The patient with refractory skin manifestations was found to have sIgMD with normal surface levels of IgM in the B cells. Along with recurrence and exacerbation in dermatitis, she showed an increase in peripheral blood eosinophils and serum IgE levels, suggesting an underlying allergic mechanism. The present case strongly indicates the importance of measuring serum IgM levels when seeing patients with recurring fever and intractable skin manifestations.
PubMed: 38800270
DOI: 10.7759/cureus.59015 -
MedRxiv : the Preprint Server For... May 2024Development of new therapies in melanoma has increased survival, and as a result more patients are living to develop brain metastasis (BrM). Identifying patients at...
IMPORTANCE
Development of new therapies in melanoma has increased survival, and as a result more patients are living to develop brain metastasis (BrM). Identifying patients at increased risk of BrM is therefore of significant public health importance.
OBJECTIVE
To determine whether history of atopy is associated with improved survival or reduced incidence of BrM in cutaneous melanoma.
DESIGN
A retrospective cohort study conducted from June 2022 to March 2024.
SETTING
Population-based in states with Surveillance, Epidemiology and End Results (SEER) supported cancer registries.
PARTICIPANTS
Individuals (≥65 years) diagnosed with cutaneous melanoma between January 1, 2008 and December 31, 2017 that are participants in traditional Medicare.
EXPOSURES
Individuals were compared that had history of atopy (allergic rhinitis, atopic dermatitis, asthma, and/or allergic/atopic conjunctivitis) diagnosed prior to melanoma diagnosis, ascertained using ICD-9 or ICD-10 codes in Medicare claims.
MAIN OUTCOMES AND MEASURES
Primary endpoints were diagnosis with a BrM or death during the follow-up period. Associations between atopy and endpoints were assessed using cox proportional hazards models to estimate hazard ratios (HR) and p-values.
RESULTS
A total of 29,956 cutaneous melanoma cases were identified (median age 76, 60% male and 97% non-Hispanic White). Overall, 7.1% developed BrM during follow up. Among the 35% that had history of atopy, the most common condition was atopic dermatitis (19%). After adjustment for demographic and prognostic factors, atopy was associated with a 16% decrease in death (HR=0.84 [95%CI:0.80-0.87], p<0.001). Among those with non-metastatic disease at time of diagnosis, atopy conferred a 15% decrease in cumulative incidence BrM (HR=0.85 [95%CI: 0.76-0.94], p=0.006), with a 25% decrease associated with atopic dermatitis (HR=0.75 [95%CI:0.65-0.86], p<0.001). Among those with metastatic disease at diagnosis (any metastatic site), only those who received immune checkpoint inhibitors had a survival benefit associated with atopy (HR=0.31, [95%CI:0.15-0.64], p=0.001 vs HR=1.41, [95%CI:0.87-2.27], p=0.165).
CONCLUSIONS AND RELEVANCE
Atopy, particularly atopic dermatitis, was significantly associated with improved survival and decreased incidence of BrM. The improved survival associated with these conditions in the context of immunotherapy suggests that these conditions in the elderly may identify those with more robust immune function that may be more responsive to treatment.
PubMed: 38798534
DOI: 10.1101/2024.05.15.24307061 -
Journal of Asthma and Allergy 2024Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa. However, few studies focus on the distributional characteristics of allergens in AR...
BACKGROUND
Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa. However, few studies focus on the distributional characteristics of allergens in AR patients in Southern Fujian Province, China.
METHODS
A skin prick test (SPT) was performed and eight common allergens including ( (), weeds, animal dander, molds, cockroaches, and mangoes were chosen.
RESULTS
The positive reactions rate to the allergens was 65.79% in 6689 patients in Southern Fujian Province. Positive reactions to and had a negative association with age, whereas positive reactions to cockroach and weed had a positive association with age. A linear trend analysis demonstrated a significant positive relationship between positive reactions to various allergens from 2016 to 2019. Positive reactions to and were both correlated with the season. Positive reactions to , cockroach and weed were related to disease duration and positive reactions to cockroach were correlated with city residence. Multivariate analysis revealed that male positive reactions gradually decreased with age (≤ 60), in contrast to female (≤ 60) positive reactions. Statistical difference was observed between the genders with regard to AR incidence from 2016 to 2019. The positive rate of skin tests was highest in summer in men, whereas in women it was lowest in summer. The gender composition ratios of positive cases in Xiamen, Zhangzhou, and Quanzhou cities differed significantly. The proportion of patients with positive reactions to the allergens in the three cities decreased with age. The highest proportions of patients with positive reactions all occurred during summer in the three cities. Furthermore, there were statistically significant differences in the age composition ratios across the seasons.
CONCLUSION
This study analyzed the distributional characteristics of AR allergens in Southern Fujian Province, China. These findings will inform specific immunotherapy for AR patients.
PubMed: 38798279
DOI: 10.2147/JAA.S453914 -
Environmental Research Sep 2024Recent studies have related high pollen concentrations to increased cardiovascular morbidity and mortality, yet very little research concerns pre-clinical cardiovascular...
BACKGROUND
Recent studies have related high pollen concentrations to increased cardiovascular morbidity and mortality, yet very little research concerns pre-clinical cardiovascular health, including effects on blood pressure (BP). The EPOCHAL panel study investigated the exposure-response relationship between ambient pollen exposure and systolic and diastolic BP in adults.
METHODS
BP was measured in 302 adults with and in 94 without pollen allergy during the pollen season, on approximately 16 days per person (6253 observations). Average individually-relevant pollen exposure in the 96 h prior to each BP measurement was calculated by summing up the averages of all ambient pollen concentrations to which the individual was found to be sensitized in a skin prick test, and which originated from seven highly allergenic pollen types (hazel, alder, birch, ash, grasses, mugwort and ragweed). Generalized additive mixed models were used to study the association between mean individually-relevant pollen exposure in the last 96 h and BP, adjusting for individual and environmental time-varying covariates. Effect modification by pollen allergy status, sex and BMI was evaluated.
RESULTS
Positive non-linear associations between individually-relevant pollen exposure and both systolic and diastolic BP were found in the allergic but not in the non-allergic group. BP increased sharply for exposures from zero to 60/80 pollen/m (diastolic/systolic BP), followed by a tempered further increase at higher concentrations. Increases of 2.00 mmHg [95% confidence interval (CI): 0.80-3.19] in systolic and 1.51 mmHg [95% CI: 0.58-2.45] in diastolic BP were associated with 96-h average pollen exposure of 400 pollen/m, compared to no exposure. Obesity and female sex were associated with larger BP increases.
CONCLUSIONS
The finding that short-term pollen concentration is associated with increased systolic and diastolic BP in persons with pollen allergy strengthens the evidence that pollen may cause systemic health effects and trigger cardiovascular events.
Topics: Humans; Pollen; Male; Female; Adult; Blood Pressure; Middle Aged; Environmental Exposure; Young Adult; Rhinitis, Allergic, Seasonal; Allergens; Air Pollutants
PubMed: 38797464
DOI: 10.1016/j.envres.2024.119224 -
Scientific Reports May 2024Allergic rhinitis is a prevalent inflammatory condition that impacts individuals of all age groups. Despite reports indicating the potential of berberine in alleviating...
Allergic rhinitis is a prevalent inflammatory condition that impacts individuals of all age groups. Despite reports indicating the potential of berberine in alleviating allergic rhinitis symptoms, the specific molecular mechanisms and therapeutic targets of berberine remain unclear. This research aims to explore the pharmacological mechanism of berberine in the treatment of allergic rhinitis through bioinformatic analyses and experimental validation. The research utilized public databases to identify potential targets of berberine. Furthermore, differentially expressed genes (DEGs) related to allergic rhinitis were pinpointed from the GSE52804 dataset. Through bioinformatics techniques, the primary targets were discovered and key KEGG and GO-BP pathways were established. To confirm the therapeutic mechanisms of berberine on allergic rhinitis, an OVA-induced allergic rhinitis model was developed using guinea pigs. We identified 32 key genes responsible for the effectiveness of berberine in treating allergic rhinitis. In addition, five central genes (Alb, Il6, Tlr4, Ptas2, and Il1b) were pinpointed. Further examination using KEGG and GO-BP pathways revealed that the main targets were primarily involved in pathways such as NF-kappa B, IL-17, TNF, and inflammatory response. Molecular docking analysis demonstrated that berberine exhibited strong affinity towards these five key targets. Furthermore, the expression levels of IL-6, TLR4, PTGS2, and IL-1β were significantly upregulated in the model group but downregulated following berberine treatment. This research has revealed the mechanism through which berberine combats allergic rhinitis and has identified its potential to regulate pathways linked to inflammation. These discoveries provide valuable insights for the development of novel medications for the treatment of allergic rhinitis.
Topics: Berberine; Rhinitis, Allergic; Animals; Molecular Docking Simulation; Guinea Pigs; Computational Biology; Disease Models, Animal; Gene Expression Profiling; Humans; Male; Ovalbumin
PubMed: 38796469
DOI: 10.1038/s41598-024-60871-4 -
Life (Basel, Switzerland) Apr 2024Allergic rhinitis (AR) is a systemic allergic disease that has a considerable impact on patients' quality of life. Current treatments include antihistamines and nasal...
Allergic rhinitis (AR) is a systemic allergic disease that has a considerable impact on patients' quality of life. Current treatments include antihistamines and nasal steroids; however, their long-term use often causes undesirable side effects. In this context, traditional Asian medicine (TAM), with its multi-compound, multi-target herbal medicines (medicinal plants), offers a promising alternative. However, the complexity of these multi-compound traits poses challenges in understanding the overall mechanisms and efficacy of herbal medicines. Here, we demonstrate the efficacy and underlying mechanisms of these multi-compound herbal medicines specifically used for AR at a systemic level. We utilized a modified term frequency-inverse document frequency method to select AR-specific herbs and constructed an herb-compound-target network using reliable databases and computational methods, such as the Quantitative Estimate of Drug-likeness for compound filtering, STITCH database for compound-target interaction prediction (with a high confidence score threshold of 0.7), and DisGeNET and CTD databases for disease-gene association analysis. Through this network, we conducted AR-related targets and pathway analyses, as well as clustering analysis based on target-level information of the herbs. Gene ontology enrichment analysis was conducted using a protein-protein interaction network. Our research identified 14 AR-specific herbs and analyzed whether AR-specific herbs are highly related to previously known AR-related genes and pathways. AR-specific herbs were found to target several genes related to inflammation and AR pathogenesis, such as PTGS2, HRH1, and TBXA2R. Pathway analysis revealed that AR-specific herbs were associated with multiple AR-related pathways, including cytokine signaling, immune response, and allergic inflammation. Additionally, clustering analysis based on target similarity identified three distinct subgroups of AR-specific herbs, corroborated by a protein-protein interaction network. Group 1 herbs were associated with the regulation of inflammatory responses to antigenic stimuli, while Group 2 herbs were related to the detection of chemical stimuli involved in the sensory perception of bitter taste. Group 3 herbs were distinctly associated with antigen processing and presentation and NIK/NF-kappa B signaling. This study decodes the principles of TAM herbal configurations for AR using a network pharmacological approach, providing a holistic understanding of drug effects beyond specific pathways.
PubMed: 38792575
DOI: 10.3390/life14050553