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Allergic asthma is characterized by increased type 2 inflammation, including eosinophils. Subjects with allergic asthma have recurrent symptoms due to their constant exposure to environmental allergens, such as house dust mite (HDM), which can be further exacerbated by respiratory infections like rhinovirus. The immunoproteasome (IP) is a proteolytic machinery that is induced by inflammatory mediators during virus infection, but the role of the IP in airway allergic inflammation during rhinovirus infection remains unknown. Wild-type (WT) and IP knockout (KO) mice were challenged with HDM. At 48 h after the last HDM challenge, mice were infected with rhinovirus 1B (RV-A1B) for 24 h. After HDM and RV-A1B treatment, IP KO (vs. WT) mice had significantly more lung eosinophils and neutrophils, as well as a significantly higher viral load, but less IFN-beta expression, compared to WT mice. A TLR3 agonist polyinosinic-polycytidylic acid (Poly I:C) treatment after RV-A1B infection in HDM-challenged IP KO mice significantly increased IFN-beta expression and reduced viral load, with a minimal effect on the number of inflammatory cells. Our data suggest that immunoproteasome is an important mechanism functioning to prevent excessive inflammation and viral infection in allergen-exposed mice, and that Poly I:C could be therapeutically effective in enhancing the antiviral response and lessening the viral burden in lungs with IP deficiency.

[Display omitted] In the United States, dupilumab is approved for moderate-to-severe eosinophilic or oral corticosteroid–dependent asthma, and omalizumab is approved for managing moderate-to-severe allergic asthma uncontrolled by inhaled corticosteroids. However, limited comparative effectiveness data exist for these biologics due to differing patient characteristics and treatment histories. This study assessed the real-world effectiveness of dupilumab and omalizumab for asthma in patients in the United States. In this retrospective observational study, TriNetX Dataworks electronic medical record data were used to identify patients with asthma age ≥12 years who initiated (index) dupilumab or omalizumab between November 2018 and September 2020 and who had at least 12 months of pre- and post-index clinical information. Inverse probability of treatment weighting was applied to balance potential confounding in treatment groups. Asthma exacerbation rates and systemic corticosteroid (SCS) prescriptions were compared using a doubly robust negative binomial regression model, adjusting for baseline exacerbation/SCS rates and patient characteristics with ≥10% standardized differences after inverse probability of treatment weighting. All inclusion and exclusion criteria were met by 2138 dupilumab patients and 1313 omalizumab patients. After weighting, the majority of baseline characteristics were balanced (standard difference <10%) between the 2 groups. Dupilumab was associated with a 44% lower asthma exacerbation rate (P <.0001) versus omalizumab. Additionally, dupilumab treatment significantly (P <.05) reduced SCS prescriptions by 28% during the follow-up period compared with omalizumab treatment. The US ADVANTAGE real-world study demonstrated a significant reduction in severe asthma exacerbations and SCS prescriptions for patients prescribed dupilumab compared with patients prescribed omalizumab during 12 months of follow-up. [ABSTRACT FROM AUTHOR]

IL-4 and IL-13 play a critical role in allergic asthma pathogenesis via their common receptor IL-4Rα. However, the cell-specific role of IL-4Rα in mixed allergen (MA)-induced allergic asthma has remained unclear. Therefore, we aimed to identify the cell-specific contribution of IL-4Rα signaling in the manifestation of various pathological outcomes in mice with allergic airway disease. We compared MA-induced pathological outcomes between hematopoietic progenitor cell (HPC)- or non–HPC-specific IL-4Rα–deficient chimera, myeloid cell–specific IL-4Rα–deficient (LysMcre+/+IL-4Rαfl/fl), and airway epithelial cell–specific IL-4Rα–deficient (CCSP-Cre+/IL-4Rαfl/fl) mice. Chimeric mice with systemic IL-4Rα sufficiency displayed hallmark features of allergic asthma, including eosinophilic and lymphocytic infiltration, type 2 (T-helper type 2) cytokine/chemokine production, IgE production, and lung pathology. These features were markedly reduced in chimeric mice with systemic IL-4Rα deficiency. Non–HPC-specific IL-4Rα–deficient mice displayed typical inflammatory features of allergic asthma but with markedly reduced mucous cell metaplasia (MCM). Deletion of IL-4Rα signaling on airway epithelial cells, a subpopulation within the non-HPC lineage, resulted in almost complete absence of MCM. In contrast, all features of allergic asthma except for MCM and mucin production were mitigated in HPC-specific IL-4Rα–deficient chimeric mice. Deleting IL-4Rα signaling in myeloid cells, a subpopulation within the HPC lineage, significantly alleviated MA-induced allergic airway inflammatory responses, but, similar to the HPC-specific IL-4Rα–deficient chimeric mice, these mice showed significant MCM and mucin production. Our findings demonstrate that the differential allergen responsiveness seen in mice with HPC-specific and non–HPC-specific IL-4Rα deficiency is predominantly driven by the absence of IL-4Rα in myeloid cells and airway epithelial cells, respectively. Our findings also highlight distinct and mutually exclusive roles of IL-4Rα signaling in mediating pathological outcomes within the myeloid and airway epithelial cell compartments. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions Pulmonary neuroendocrine cells (PNEC) are rare airway epithelial cells that have recently gained attention as potential amplifiers of allergic asthma. However, studying PNEC function in humans has been challenging due to a lack of cell isolation methods, and little is known about human PNEC function in response to asthma‐relevant stimuli. Here we developed and characterized an in vitro human PNEC model and investigated the neuroendocrine response to extracts of the common aeroallergen house dust mite (HDM).PNEC‐enriched cultures were generated from human induced pluripotent stem cells (iPNEC) and primary bronchial epithelial cells (ePNEC). Characterized PNEC cultures were exposed to HDM extract, a volatile chemical odorant (Bergamot oil), or the bacterial membrane component, lipopolysaccharide (LPS), and neuroendocrine gene expression and neuropeptide release determined.Both iPNEC and ePNEC models demonstrated similar baseline neuroendocrine characteristics and a stimuli‐specific modulation of gene expression. Most notably, exposure to HDM but not Bergamot oil or LPS, leads to dose‐dependent induction of the CGRP encoding gene, CALCB, and corresponding release of the neuropeptide. HDM‐induced CALCB expression and CGRP release could be inhibited by a protease‐activated receptor 1 (PAR1) antagonist or protease inhibitors and was mimicked by a PAR1 agonist.We have characterized a novel model of PNEC‐enriched human airway epithelium and utilized this model to demonstrate a previously unrecognized role for human PNEC in mediating a direct neuroendocrine response to aeroallergen exposure. [ABSTRACT FROM AUTHOR]

The assessment of the allergenic potential of chemicals, crucial for ensuring public health safety, faces challenges in accuracy and raises ethical concerns due to reliance on animal testing. This paper presents a novel bioinformatic protocol designed to address the critical challenge of predicting immune responses to chemical sensitizers without the use of animal testing. The core innovation lies in the integration of advanced bioinformatics tools, including the Universal Immune System Simulator (UISS), which models detailed immune system dynamics. By leveraging data from structural predictions and docking simulations, our approach provides a more accurate and ethical method for chemical safety evaluations, especially in distinguishing between skin and respiratory sensitizers. Our approach integrates a comprehensive eight-step process, beginning with the meticulous collection of chemical and protein data from databases like PubChem and the Protein Data Bank. Following data acquisition, structural predictions are performed using cutting-edge tools such as AlphaFold to model proteins whose structures have not been previously elucidated. This structural information is then utilized in subsequent docking simulations, leveraging both ligand–protein and protein–protein interactions to predict how chemical compounds may trigger immune responses. The core novelty of our method lies in the application of UISS—an advanced agent-based modelling system that simulates detailed immune system dynamics. By inputting the results from earlier stages, including docking scores and potential epitope identifications, UISS meticulously forecasts the type and severity of immune responses, distinguishing between Th1-mediated skin and Th2-mediated respiratory allergic reactions. This ability to predict distinct immune pathways is a crucial advance over current methods, which often cannot differentiate between the sensitization mechanisms. To validate the accuracy and robustness of our approach, we applied the protocol to well-known sensitizers: 2,4-dinitrochlorobenzene for skin allergies and trimellitic anhydride for respiratory allergies. The results clearly demonstrate the protocol's ability to differentiate between these distinct immune responses, underscoring its potential for replacing traditional animal-based testing methods. The results not only support the potential of our method to replace animal testing in chemical safety assessments but also highlight its role in enhancing the understanding of chemical-induced immune reactions. Through this innovative integration of computational biology and immunological modelling, our protocol offers a transformative approach to toxicological evaluations, increasing the reliability of safety assessments. [ABSTRACT FROM AUTHOR]

ABSTRACT Previous observational studies focused on the association of tea intake and allergic diseases. However, it is not known whether these associations are causal. We used a bidirectional Mendelian randomization (MR) study to assess the causal relationship of tea intake with the risk of allergic diseases, such as atopic dermatitis (AD), allergic rhinitis (AR), and allergic asthma (AA). Single‐nucleotide polymorphisms (SNPs) which had genetic statistical significance with tea intake were used as instrumental variables (IVs). We employed heritable IVs of tea intake from the UK Biobank, which included 447,485 samples. Sensitivity analyses were further performed using MR Egger and MR‐PRESSO. Inverse variance weighted (IVW) method was used as the main approach. In this MR study, 40 independent SNPs were selected for tea intake. The MR analysis revealed that an increase in genetically predicted tea intake was associated with a lower risk of AD (OR = 0.709, 95% CI = 0.546–0.919, p = 0.009). Furthermore, we observed a causal effect of genetically predicted tea intake on the risk of AA (OR = 0.498, 95% CI = 0.320–0.776, p = 0.002). However, no significant causal relationship was found between genetically predicted tea intake and AR (OR = 1.008, 95% CI = 0.998–1.017, p = 0.115). Our MR analysis suggested that increased tea intake may reduce the risk of AD and AA in European population. This suggests that tea intake is likely a trigger or a prevention strategy for AD and AA. [ABSTRACT FROM AUTHOR]

Purpose of Review: Respiratory allergies are non-communicable diseases caused by the hypersensitivity of the immune system to environmental aeroallergens. The culprits are aero-transported proteins eliciting respiratory symptoms in sensitized/allergic individuals. This review intends to provide a holistic overview on the categorization of aeroallergens into protein families (Part 1) and to exploit the impact of physicochemical properties on inhalant protein allergenicity (Part 2). This first part will focus particularly on aeroallergen organization into families and how this classification fits their physicochemical properties. Recent Findings: Aeroallergen classification into protein families facilitates the identification of common physicochemical properties, thus aiding a better comprehension of known allergens, while predicting the behavior of novel ones. The available online databases gathering important features of aeroallergens are currently scarce. Summary: Information on distinct aeroallergen classification is still lacking, as data is dispersed and often outdated, hampering an efficient evaluation of new aeroallergens. [ABSTRACT FROM AUTHOR]

ABSTRACT Allergic asthma is the predominant phenotype among asthmatics. Although conventional pharmacotherapy is a central component in the management of asthma, it does not enable control of asthma symptoms in all patients. In recent decades, some uncontrolled asthmatic patients, especially those with allergic asthma, have benefited from biological therapies. However, biologics do not address all the unmet needs left by conventional pharmacotherapy. Furthermore, it is noteworthy that neither conventional pharmacotherapy nor biological therapies have disease‐modifying properties. In this context, allergen immunotherapy (AIT) represents an indispensable component of the therapeutic arsenal against allergic asthma, due to its disease‐modifying immunological effects. In this review article, funded by an AIT manufacturer, we find clinical trials support AIT as the only treatment option able both to improve allergic asthma symptoms and to prevent the onset and worsening of the condition. For patients with severe asthma or other safety concerns, the combination of AIT and biologics offers very promising new treatment modalities for the management of allergic asthma.Trial Registration: clinicaltrials.gov identifier: NCT06027073 [ABSTRACT FROM AUTHOR]

Objective To construct a nomogram prediction model for adverse reactions of mite sublingual immunotherapy (SCIT) in children with allergic asthma, and to evaluate and validate it. Methods Clinical data of children with allergic asthma who were managed by mite SCIT in Department of Pediatrics, the Second Hospital of Tianjin Medical University were retrospectively analyzed. According to the adverse reactions in the initial treatment stage of SCIT, they were divided into adverse reaction group and no adverse reaction group, which together formed the modeling group. Through univariate logistic regression analysis and multivariate logistic regression analysis, independent risk factors were screened out. Then construct the prediction model, draw a nomogram, eventually evaluate and validate the model. Results A total of 350 children were included, including 176 in the adverse reaction group and 174 in the no adverse reaction group. Univariate logistic regression analysis was performed on the baseline data of the children in the modeling group, and the results were as follows. Gender, age, number of asthma exacerbations in the past 1 year, percentage of eosinophils (EOS%), forced expiratory volume in the first second in percent predicted values (FEV1%pred), total IgE (tIgE), dermatophagoides pteronyssinus (Der p) sIgE, dermatophagoides farinae (Der p)sIgE, and the number of other inhaled allergenic species were the risk factors of SCIT-related adverse reactions (all P < 0.1). These were included in the multivariate logistic regression analysis, and the results showed that：age, the number of asthma exacerbations in the past 1 year, tIgE, Der p sIgE, Der f sIgE, and the number of other inhaled allergen species were independent risk factors (all P < 0.05). Based on the results, nomogram was drawn in R language. Model evaluation by receiver operating characteristic curve showed an area under curve of 0.877, a predictive model sensitivity of 73.9%, and a specificity of 90.8%. The predicted probability was consistent with actual probability of occurrence. The model has good prediction performance. Conclusions Age, number of asthma exacerbations in the past 1 year, tIgE, Der p sIgE, Der f sIgE, and the number of other inhaled allergen species were independent risk factors for adverse reactions to mite SCIT in children. The nomogram drawn in this study has good predictive value. [ABSTRACT FROM AUTHOR]

Objective To analyze the characteristics of inhaled allergens in adult patients with allergic asthma in Beijing. Methods Clinical data of adult patients with allergic asthma who tested positive for inhaled allergens admitted to Department of Pulmonary and Critical Care Medicine from January 2021 to December 2023 were collected, and the characteristics of inhaled allergens were analyzed. Results A total of 1 568 patients with allergic asthma who were positive for inhaled allergens were enrolled, with a male-to-female ratio of 0.85 and an average age of (42.84±16.18）years old. The top 5 positive rates for inhaled allergens were house dust mite mix 2 (53.34%), animal dander mix 1 (48.22%), cocklebur (46.59%), mugwort (39.51%), and weed pollen mix 5 (37.19%), respectively. The positive rates of Dermatophagoides farinae, house dust mite, house dust mite mix 2, and Aspergillus fumigatus in male patients were higher than those in female patients (all P < 0.05), while the positive rate of animal dander mix 1 was lower than that in female patients (P = 0.001). The positive rates of cat dander, dog dander, animal dander mix 1, house dust mite mix 2, and common ragweed showed a decreasing trend with age (all P < 0.05). The positive rates of Aspergillus fumigatus and molds and yeasts mix 2 were the lowest among 40-49 years old and 30-39 years old, respectively, and significantly increased after 50 years old (all P < 0.001). The positive rate of cockroach was gradually increased with the age of patients (P = 0.003). Conclusions The proportion of young female patients with allergic asthma positive for inhaled allergens is higher than other counterparts. House dust mite mix 2 positive rate is the highest among all inhaled allergens. The positive rate of certain inhaled allergens varies among different genders and age groups. [ABSTRACT FROM AUTHOR]

Allergic asthma is largely dominated by Th2 lymphocytes. Micropeptides in Th2 cells and asthma remain unmasked. Here, we aimed to demonstrate a micropeptide, T-cell regulatory micropeptide (TREMP), in Th2 cell differentiation in asthma. TREMP translated from lincR-PPP2R5C was validated using Western blotting and mass spectrometry. TREMP knockout mice were generated using CRISPR/Cas9. Coimmunoprecipitation revealed that TREMP targeted pyrroline-5-carboxylate reductase 1 (PYCR1), which was further explored in vitro and in vivo. The levels of TREMP and PYCR1 in Th2 cells from clinical samples were determined by flow cytometry. TREMP, encoded by lincR-PPP2R5C, was in the mitochondrion. The lentivirus encoding TREMP promoted Th2 cell differentiation. In contrast, Th2 differentiation was suppressed in TREMP−/− CD4+ T cells. In the HDM-induced model of allergic airway inflammation, TREMP was increased in pulmonary tissues. Allergic airway inflammation was relieved in TREMP−/− mice treated with HDM. Mechanistically, TREMP interacted with PYCR1, which regulated Th2 differentiation via glycolysis. Glycolysis was decreased in Th2 cells from TREMP−/− mice and PYCR1−/− mice. Similar to TREMP−/− mice, allergic airway inflammation was mitigated in HDM-challenged PYCR1−/− mice. Moreover, we measured TREMP and PYCR1 in asthma patients. And we found that, compared with those in healthy controls, the levels of TREMP and PYCR1 in Th2 cells were significantly increased in asthmatic patients. The micropeptide TREMP encoded by lincR-PPP2R5C promoted Th2 differentiation in allergic airway inflammation by interacting with PYCR1 and enhancing glycolysis. Our findings highlight the importance of neglected micropeptides from noncoding RNAs in allergic diseases. [ABSTRACT FROM AUTHOR]

This study examines the anti‐inflammatory activity of cynaropicrin against lipopolysaccharide (LPS) in vitro and ovalbumin (OVA)‐challenged asthma in mice. Cynaropicrin's antimicrobial effects were tested on Escherichia coli (E. coli) and Streptococcus pyogenes (S. pyogenes) using the disc diffusion technique. Cytotoxicity was assessed with an (3‐(4, 5‐dimethylthiazolyl‐2)‐2, 5‐diphenyltetrazolium bromide) assay. The anti‐inflammatory property was evaluated in LPS‐induced RAW264.7 cells, while OVA‐challenged asthmatic mice were treated with 10 mg/kg of cynaropicrin. Key inflammatory and antioxidant markers were quantified, and lung histology was examined to confirm therapeutic roles. The antimicrobial studies proved that cynaropicrin effectively inhibited the growth of E. coli and S. pyogenes. Cynaropicrin displayed no cytotoxicity on RAW264.7 cells. Furthermore, it significantly inhibited inflammatory cytokine synthesis upon LPS induction. Cynaropicrin treatment decreased the inflammatory cell counts and also suppressed specific allergic markers in OVA‐challenged mice. It also decreased nitric oxide and myeloperoxidase levels and reduced pulmonary edema. Cynaropicrin increased antioxidant levels and decreased proinflammatory cytokines in the asthmatic mice. Lung histological examination confirms the ameliorative potency of cynaropicrin against OVA‐induced asthmatic pulmonary inflammation in mice. Our findings suggest cynaropicrin possesses significant ameliorative potency against allergen‐induced pulmonary inflammation. [ABSTRACT FROM AUTHOR]

Allergic asthma, a type of chronic airway inflammation, is a global health concern because of its increasing incidence and recurrence rates. Camellia sinensis L. yields a variety type of teas, which are also used as medicinal plants in East Asia and are known to have antioxidant, anti-inflammatory, and immune-potentiating properties. Here, we examined the constituents of C. sinensis L. extract (CSE) and evaluated the protective effects of CSE on allergic asthma by elucidating the underlying mechanism. To induce allergic asthma, we injected the sensitization solution (mixture of ovalbumin (OVA) and aluminum hydroxide) into mice intraperitoneally on days 0 and 14. Then, the mice were exposed to 1% OVA by a nebulizer on days 21 to 23, while intragastric administration of CSE (30 and 100 mg/kg) was performed each day on days 18 to 23. We detected five compounds in CSE, including (-)-epigallocatechin, caffeine, (-)-epicatechin, (-)-epigallocatechin gallate, and (-)-epicatechin gallate. Treatment with CSE remarkably decreased the airway hyperresponsiveness, OVA-specific immunoglobulin E level, and inflammatory cell and cytokine levels of mice, with a decrease in inflammatory cell infiltration and mucus production in lung tissue. Treatment with CSE also decreased the phosphorylation of nuclear factor-κB (NF-κB) and the expression of matrix-metalloproteinase (MMP)-9 in asthmatic mice. Our results demonstrated that CSE reduced allergic airway inflammation caused by OVA through inhibition of phosphorylated NF-κB and MMP-9 expression.

Shiyao Zhang,1 Xiuying Zhang,2 Chenghao Wei,1 Lai Zhang,1 Zhaoyang Li1 1Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China; 2The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, 110032, People’s Republic of ChinaCorrespondence: Xiuying Zhang, Email pcxtcm@163.comObjective: To investigate the causal relationship between 91 circulating inflammatory proteins and Various asthma phenotypes by means of Mendelian randomization.Methods: Genome-wide association Studies (GWAS) of 91 inflammatory proteins were pooled from the Olink Target platform with 14,824 participants. Various asthma phenotypes were derived from the FinnGen Biobank. Inverse variance weighting (IVW) was used as the main method for MR Analysis, supplemented by Mr-Egger, Weighted median, Simple mode, and Weighted mode. The MR-Egger intercept term test and Cochran’s Q test were used to test the polymorphism and heterogeneity of IVs, and visual analysis was carried out to draw scatter plots, funnel plots, and leave-out-one plots. The FDR correction was performed due to the possibility of a type 1 error.Results: Genetically predicted IVW results revealed a total of 30 data sets suggesting a potential causal relationship between circulating inflammatory proteins and asthma phenotypes. Among them, 2 results were still strongly positive after FDR correction. The level of CST5 (OR=1.184; 95% CI: 1.075– 1.305; P=0.0001; P-FDR=0.028) is associated with an increased risk of non-allergic asthma. LIF-R (OR=0.723; 95% CI: 0.620– 0.842; P=0.000; P-FDR=0.003) is associated with a reduced risk of asthma in children. There was no pleiotropy or heterogeneity in the remaining 16 results that suggested a potential causal relationship.Conclusion: Increased CST5 levels are associated with an increased risk of non-allergic asthma. LIF-R is associated with a reduced risk of asthma in children.Keywords: mendelian randomization, inflammatory protein, asthma, childhood asthma, allergic asthma, non-allergic asthma, suggestive for eosinophilic asthma, obesity related asthma

Background: Allergic asthma is a chronic and inflammatory disease of the respiratory tract, which is characterized by inflammation, airway obstruction and swelling. Anti-inflammatory compounds can be used to improve the disease severity. Hypericum perforatum (HP)/ St. John’s wort has been used in the treatment of many diseases due to its anti-inflammatory effects. Therefore, this study was performed to investigate the effects of HP on TH1 and TH2 parameters in an animal model of allergic asthma. Methods: Thirty BALB/c mice were sensitized with subcutaneous injection and inhalation of ovalbumin and then administered different doses of HP post-sensitization. Histological analysis of the lungs was performed. The effects of HP on mRNA expression of T-bet and GATA3 (TH1 and TH2 transcription factors, respectively), IFN-γ, IL-4 and IL-10 in the spleen were determined by real-time PCR. The protein levels of IFN-γ, IL-4 and IL-10 cytokines were also determined by ELISA technique in the serum of mice. Results: HP extract (HPE) reduced the clinical severity in asthma-induced mice, and a reduction in the inflammatory cell infiltration in the lung. Furthermore, treatment with HPE inhibited asthma-related mediators as well as increased the anti-inflammatory parameters compared to the control. The study also showed that treatment with HPE significantly increased IFN-γ, IL-10 and T-bet, while decreasing the level of IL-4 and GATA3 in mice treated with HPE. Conclusion: The data indicated that HPE can attenuate allergic asthma autoimmune responses by inhibiting infiltration of immune cell in the lung and TH2-related parameters. It is reasonable to assume that HPE has significant effects in the treatment of allergic asthma.

Objective To construct a nomogram prediction model for adverse reactions of mite subcutaneous immunotherapy（SCIT） in children with allergic asthma， and to evaluate and validate it. Methods Clinical data of children with allergic asthma who were managed by mite SCIT in Department of Pediatrics， the Second Hospital of Tianjin Medical University were retrospectively analyzed. According to the adverse reactions in the initial treatment stage of SCIT， they were divided into adverse reaction group and no adverse reaction group， which together formed the modeling group. Through univariate logistic regression analysis and multivariate logistic regression analysis， independent risk factors were screened out. Then construct the prediction model， draw a nomogram， eventually evaluate and validate the model. Results A total of 350 children were included， including 176 in the adverse reaction group and 174 in the no adverse reaction group. Univariate logistic regression analysis was performed on the baseline data of the children in the modeling group， and the results were as follows. Gender， age， number of asthma exacerbations in the past 1 year， percentage of eosinophils （EOS%）， forced expiratory volume in the first second in percent predicted values（FEV1%pred）， total IgE（tIgE）， dermatophagoides pteronyssinus （Der p） sIgE， dermatophagoides farinae （Der p） sIgE， and the number of other inhaled allergenic species were the risk factors of SCIT-related adverse reactions （all P < 0.1）. These were included in the multivariate logistic regression analysis， and the results showed that： age， the number of asthma exacerbations in the past 1 year ， tIgE， Der p sIgE， Der f sIgE， and the number of other inhaled allergen species were independent risk factors （all P < 0.05）. Based on the results， nomogram was drawn in R language. Model evaluation by receiver operating characteristic curve showed an area under curve of 0.877， a predictive model sensitivity of 73.9%， and a specificity of 90.8%. The predicted probability was consistent with actual probability of occurrence. The model has good prediction performance. Conclusions Age， number of asthma exacerbations in the past 1 year， tIgE， Der p sIgE， Der f sIgE， and the number of other inhaled allergen species were independent risk factors for adverse reactions to mite SCIT in children. The nomogram drawn in this study has good predictive value.

Objective To analyze the characteristics of inhaled allergens in adult patients with allergic asthma in Beijing. Methods Clinical data of adult patients with allergic asthma who tested positive for inhaled allergens admitted to Department of Pulmonary and Critical Care Medicine from January 2021 to December 2023 were collected， and the characteristics of inhaled allergens were analyzed. Results A total of 1 568 patients with allergic asthma who were positive for inhaled allergens were enrolled， with a male-to-female ratio of 0.85 and an average age of （42.84±16.18） years old. The top 5 positive rates for inhaled allergens were house dust mite mix 2 （53.34%）， animal dander mix 1 （48.22%）， cocklebur （46.59%）， mugwort （39.51%）， and weed pollen mix 5 （37.19%）， respectively. The positive rates of Dermatophagoides farinae， house dust mite， house dust mite mix 2， and Aspergillus fumigatus in male patients were higher than those in female patients （all P < 0.05）， while the positive rate of animal dander mix 1 was lower than that in female patients （P = 0.001）. The positive rates of cat dander， dog dander， animal dander mix 1， house dust mite mix 2， and common ragweed showed a decreasing trend with age （all P < 0.05）. The positive rates of Aspergillus fumigatus and molds and yeasts mix 2 were the lowest among 40-49 years old and 30-39 years old， respectively， and significantly increased after 50 years old （all P < 0.001）. The positive rate of cockroach was gradually increased with the age of patients （P = 0.003）. Conclusions The proportion of young female patients with allergic asthma positive for inhaled allergens is higher than other counterparts. House dust mite mix 2 positive rate is the highest among all inhaled allergens. The positive rate of certain inhaled allergens varies among different genders and age groups.

BackgroundDibutyl phthalate (DBP) is one of the most commonly used plasticizers, and has been found to relate to allergic asthma. However, mechanisms behind the phenomenon linking DBP and allergic asthma are still not well comprehended. ObjectiveTo investigate the role of endoplasmic reticulum stress in DBP-exacerbated allergic asthma. MethodsThirty-two male mice were divided into four groups at random, eight mice in each group: control group, allergic asthma model group (ovalbumin, OVA), OVA+40 mg·kg−1 DBP exposure group (OVA+DBP), and OVA+40 mg·kg−1 DBP+50 mg·kg−1 4-phenyl butyric acid (4-PBA) group (OVA+DBP+4-PBA). The control group mice were treated with saline via intraperitoneal injection on day 21, 35, 42, and 49, and atomized saline for 30 min per day from day 54 to 60. The OVA group mice were injected with 0.3 mL OVA sensitizing solution via intraperitoneal injection on day 21, 35, 42, and 49, and atomized with 1% OVA solution from day 54 to 60. The OVA+DBP group was treated in the same way as the OVA group to build an allergic asthma model, and was orally exposed to 40 mg·kg−1 DBP from day 1 to 53, plus atomized with 1% OVA solution from day 54 to 60. In order to verify the role of endoplasmic reticulum stress in DBP-exacerbated allergic asthma, 4-PBA was injected intraperitoneally every 2 d from day 1 to 53 in the OVA+DBP+4-PBA group mice. The pathological changes such as airway remodeling, inflammatory cell infiltration, and airway mucous hyperplasia in lung tissues were observed after hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining. The contents of total immunoglobulin E (T-IgE) and ovalbumin immunoglobulin E (OVA-IgE) levels in serum, and interleukin (IL)-4, IL-5, IL-13, and IL-17A in alveolar lavage fluid (BALF) were detected by Enzyme-Linked ImmunoSorbent Assay(ELISA). The expression levels of endoplasmic reticulum stress-related proteins including inositol-requiring enzyme 1α (IRE1α), protein kinase R-like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6) were detected by immunohistochemistry. ResultsCompared to the control mice, the OVA mice showed significant asthma-like symptoms, including inflammatory cell infiltration, increased inflammatory cytokines, airway remodeling, and mucous hyperplasia. Compared to the OVA group, long-term exposure to DBP aggravated airway pathological changes in the OVA+DBP mice, and increased the serum T-IgE and OVA-IgE levels (P

Background: Allergic asthma is largely dominated by Th2 lymphocytes. Micropeptides in Th2 cells and asthma remain unmasked. Here, we aimed to demonstrate a micropeptide, T-cell regulatory micropeptide (TREMP), in Th2 cell differentiation in asthma. Methods: TREMP translated from lincR-PPP2R5C was validated using Western blotting and mass spectrometry. TREMP knockout mice were generated using CRISPR/Cas9. Coimmunoprecipitation revealed that TREMP targeted pyrroline-5-carboxylate reductase 1 (PYCR1), which was further explored in vitro and in vivo. The levels of TREMP and PYCR1 in Th2 cells from clinical samples were determined by flow cytometry. Results: TREMP, encoded by lincR-PPP2R5C, was in the mitochondrion. The lentivirus encoding TREMP promoted Th2 cell differentiation. In contrast, Th2 differentiation was suppressed in TREMP−/− CD4+ T cells. In the HDM-induced model of allergic airway inflammation, TREMP was increased in pulmonary tissues. Allergic airway inflammation was relieved in TREMP−/− mice treated with HDM. Mechanistically, TREMP interacted with PYCR1, which regulated Th2 differentiation via glycolysis. Glycolysis was decreased in Th2 cells from TREMP−/− mice and PYCR1−/− mice. Similar to TREMP−/− mice, allergic airway inflammation was mitigated in HDM-challenged PYCR1−/− mice. Moreover, we measured TREMP and PYCR1 in asthma patients. And we found that, compared with those in healthy controls, the levels of TREMP and PYCR1 in Th2 cells were significantly increased in asthmatic patients. Conclusions: The micropeptide TREMP encoded by lincR-PPP2R5C promoted Th2 differentiation in allergic airway inflammation by interacting with PYCR1 and enhancing glycolysis. Our findings highlight the importance of neglected micropeptides from noncoding RNAs in allergic diseases.

Objective: Allergic asthma (AA) is a chronic airway inflammatory disease characterized by airway hyper-responsiveness (AHR). Pudilan anti-inflammatory oral liquid (PDL), along with its main medicinal material, Taraxaci Herba (Taraxacum mongolicum Hand.-Mazz, TH), has been widely used to treat upper respiratory tract infections. Research has shown that the major ingredient of TH, the organic acid component (OAC), possesses favorable AA activity. However, the attenuated effects of PDL and OAC from TH (TH-OAC) on AA and their possible mechanisms remain poorly understood. This study analyzed the attenuating effects of PDL and TH-OAC on AA and the underlying mechanisms. Methods: Young BALB/c mice were sensitized and stimulated to develop asthma using ovalbumin. Histological examinations were performed by hematoxylin and eosin staining. Western blotting, immunohistochemistry, and protein expression detection of toll-like receptor 2 (TLR2), TLR4, and orosomucoid 1-like protein 3 (ORMDL3) were performed to detect the presence of inflammatory components in the lung tissue. The messenger RNA (mRNA) expression levels were determined using quantitative real-time polymerase chain reaction. Results: Results showed that PDL and TH-OAC alleviated augmented AHR and typical asthmatic pathological changes, including inflammatory infiltration and thickening of the alveolar wall. They also significantly reduced the levels of the immunoglobulin E, IL-4, IL-5, IL-6, tumor necrosis factor-α, and Nitric oxide (NO) in lung tissues of mice. Protein and mRNA expression levels of TLR2, TLR4, and ORMDL3 were downregulated following treatment with PDL and TH-OAC. Conclusions: PDL and TH-OAC can reduce asthma-induced inflammatory damage to the bronchi. These results provide a theoretical basis for the treatment of asthma in clinical settings.

Désirée Larenas-Linnemann,1 Blanca María Morfín-Maciel,2 Victor Gonzalez-Uribe,3 Claudia Ivonne Gallego-Corella,4 Germán Agustín Rico-Solís,5 Luiana Hernández-Velázquez,6 Daniel García-Imperial,7 Chrystopherson Gengyny Caballero-Lopez,8 Ondina Marlene Garibay-Vargas,9 José Luis Gálvez-Romero,10 Daniela García Fajardo,11 Joel Barroso-Santos,12 Herberth de Jesús Pérez-Áviles,13 Jorge Agustín Luna-Pech,14 Cecilia Yvonne García-Cobas,15 Kareli Guadalupe Coronado-Hernández,16 Margarita Ortega-Cisneros,17 Carlos Humberto González-Gutiérrez,18 Daniela Rivero-Yeverino,8 Elsy Maureen Navarrete-Rodríguez,19 Leticia Lezama-Vázquez,20 Karen Lilian Rivera-Alvarado,21 Georgina Guadalupe Ochoa-López,22 Sara Elizabeth Covarrubias-Ramírez,23 Claudia Patricia Reyes-Galindo,24 Beatriz Bayardo-Gutiérrez,25 María del Carmen Calderón-Ezquerro26 1Centro de Excelencia en Asma y Alergia Larenas, Hospital Médica Sur, Mexico City, DF, Mexico; 2Private practice, Mexico City, DF, Mexico; 3AlergiaMx, Mexico City, DF, Mexico; 4Centro de Alergia y Asma de Tijuana, Tijuana, BCN, Mexico; 5Hospital Regional Valentín Gómez Farías, Department of Allergy and Clinical Immunology, Colima, COL, Mexico; 6IMSS Hospital General de Zona Número 8, Ensenada, BCN, Mexico; 7Private Practice, Querétaro, QRO, Mexico; 8Hospital Universitario de Puebla, Benemérita Universidad Autónoma de Puebla, Puebla, PUE, Mexico; 9Private practice, Uruapan, MICH, Mexico; 10Jefatura de investigación, Hospital Regional ISSSTE, Puebla, PUE, Mexico; 11Private Practice, San Luis Potosí, SLP, Mexico; 12Private practice, Pachuca, HGO, Mexico; 13Private Practice, Mérida, YUC, Mexico; 14Departamento de Disciplinas Filosófico, Metodológico e Instrumentales, CUCS, Universidad de Guadalajara, JAL, Mexico; 15Alergia e Inmunología, HGR 46, Instituto Mexicano del Seguro Social, Guadalajara, JAL, Mexico; 16Centro Médico Nacional del Occidente Pediatrics, Guadalajara, JAL, Mexico; 17Centro Médico Nacional de Occidente UMAE Hospital de Especialidades, Department of clinical immunology and allergy, Guadalajara, JAL, Mexico; 18HGZ &num; 1 IMSS, Zacatecas, ZAC, Mexico; 19Hospital Infantil de México ‘Federico Gómez’, Mexico City, DF, Mexico; 20Private practice, Tuxtla-Gutiérrez, CHIS, Mexico; 21IMSS UMAE 14, Veracruz, VER, Mexico; 22Private practice, Ciudad Juárez, CHIH, Mexico; 23Plebitos, Especialidades Pediátricas, Mazatlán, SIN, Mexico; 24ISSSTE, Ciudad Victoria, TAMPS, Mexico; 25Centro Médico Nacional de Occidente UMAE Hospital de Especialidades, Departamento de Inmunología Clínica y Alergia, Hospital Regional ISSSTE, Puebla, PUE, Mexico; 26Instituto de Ciencias de la Atmósfera y Cambio Climático, Universidad Autónoma de México, Mexico City, DF, MexicoCorrespondence: Désirée Larenas-Linnemann, Centro de Excelencia en Asma y Alergia Larenas, Hospital Médica Sur, Torre 2 cons. 602, Puente de Piedra 150, Col. Toriello Guerra, Del. Tlalpan, Ciudad de México, 14050, Mexico, Tel +52-55-5171-2248 ; +5606-6222 Ext.4372 ; +52-55-8509-5950, Email marlar1@prodigy.net.mxIntroduction: Aeroallergen exposure has an intra- and extra-domiciliary component and varies according to climatological zones. Mexico is a large country with a great variety of climates. A previous study (2009) evaluated skin prick test results (SPT) in different regions. In this study, we compare previous sensitization patterns from 14y ago with current ones and compare them between different climatological zones.Methods: Mexican allergists were asked to share their last 100 SPT results in patients with respiratory allergy. Clinics were grouped in (semi)humid vs (semi)dry zones. Results were analyzed nationwide and compared to the 2009 results, calculating odds ratio (OR) and 95% confidence intervals (95% CIs), with p < 0.05 as cut-off. Similarly, we compared (semi)humid versus dry zones.Results: We collected 2915 SPT results from 28 clinics (19 cities). Dermatophagoides was the most frequently sensitizing allergen. There was a significant increase in SPT positivity from 2009 to 2023 in both in- and outdoor aeroallergens (OR 1.26– 2.65, 95% CI from 1.06– 1.50 to 1.99– 3.52). Comparing dry-humid zones, sensitization to pollen from Oleaceae, Fagaceae (p < 0.0001 all) and most weeds is more frequent in humid zones, as are Dermatophagoides and cockroach (both p < 0.0001). Eucalyptus, mesquite, and all grass pollen sensitizations predominate in dry zones (p < 0.05– 0.0001). There are no differences in sensitization to cat or dog between zones.Conclusion: We found a general increase in SPT sensitization over the past fourteen years, suggesting that this is probably not only due to climate change. The different sensitization profile throughout the country was mainly related to humidity. Repeating epidemiologic SPT studies over the years could help tracking changes in allergen sensitization over time.Keywords: allergy, diagnosis, skin prick testing, aeroallergen, climate change, pollen allergy, allergic rhinitis, allergic asthma

Background and objectives: Allergic asthma is an inflammatory respiratory system disease. Capparis spinosa L. has been traditionally used to treat inflammatory diseases. Our goal was to examine the anti-inflammatory activity of C. spinosa extract on a mouse model of allergic asthma. Methods: Capparis spinosa fruits were extracted with methanol 80% by maceration method. Forty-two Balb/c mice were divided into six groups of seven. The healthy control group received normal saline and the other five groups were treated with ovalbumin to induce asthma. Subsequently, one group received dexamethasone, three groups were treated with C. spinosa extract (185, 370 and 740 mg/kg/day) for 7 days and the sixth group remained untreated as the positive control. The number of eosinophils and neutrophils and the levels of interleukins -4, -5, and -13 were measured in bronchoalveolar lavage fluid (BALF) of all mice. Histopathological changes in the lung tissues of all animals were also analyzed. Results: The number of eosinophils and neutrophils and the levels of interleukins -4, -5, and -13 in BALFs significantly decreased in C. spinosa extract-treated mice compared with the positive control. Capparis spinosa extract inhibited goblet cell hyperplasia and mucus hypersecretion in lung tissues. Inflammation in the peribronchial and perivascular spaces was non-significantly ameliorated in extract-treated mice. The results of C. spinosa extract-treated mice were comparable with dexamethasone-administered animals. Conclusions: This study is the first report of anti-inflammatory and antiasthmatic properties of C. spinosa extract by modulating eosinophilic trafficking and type 2 inflammatory responses.

Panax species include Panax ginseng Meyer, Panax quinquefolium L., Panax notoginseng, Panax japonicum, Panax trifolium, and Panax pseudoginseng, which contain bioactive components (BCs) such as ginsenosides and polysaccharides. Recently, growing evidence has revealed the pharmacological effects of Panax species and their BCs on allergic airway diseases (AADs), including allergic asthma (AA) and allergic rhinitis (AR). AADs are characterized by damaged epithelium, sustained acquired immune responses with enforced Th2 responses, allergen-specific IgE production, and enhanced production of histamine and leukotrienes by activated mast cells and basophils. In this review, we summarize how Panax species and their BCs modulate acquired immune responses involving interactions between dendritic cells and T cells, reduce the pro-inflammatory responses of epithelial cells, and reduce allergenic responses from basophils and mast cells in vitro. In addition, we highlight the current understanding of the alleviative effects of Panax species and their BCs against AA and AR in vivo. Moreover, we discuss the unmet needs of research and considerations for the treatment of patients to provide basic scientific knowledge for the treatment of AADs using Panax species and their BCs.

In recent years, there has been a global increase in the prevalence of allergic diseases, including allergic rhinitis, chronic rhinosinusitis, allergic asthma, atopic dermatitis, allergic conjunctivitis, and food allergies. Since the pathogenic mechanisms of these allergic diseases are not yet fully understood, targeted and effective therapies are lacking. The NLRP3 inflammasome, a multiprotein complex implicated in various inflammatory diseases, can be activated by diverse stimuli. It assembles into NLRP3 inflammasome complexes through conformational changes, initiating the proteolytic cleavage of dormant procaspase-1 into active caspase-1 and promoting the maturation of inflammatory cytokines, including IL-1β and IL-18. Dysfunction of the NLRP3 inflammasome may serve as a key driver of inflammatory diseases, leading to pyroptosis and amplifying the local inflammatory response. As preliminarily demonstrated, specific NLRP3 inflammatory vesicle inhibitors play refectory roles in animal models of allergic diseases, and it is believed that specific NLRP3 inflammasome inhibitors may be potential therapeutic agents for allergic diseases. This review highlights the progress of research on the NLRP3 inflammasome in allergic diseases, explores its contribution to different types of allergic diseases, and identifies promising clinical targets for intervention. [ABSTRACT FROM AUTHOR]

\nIntroduction: Baicalin is a flavonoid chemical extracted and purified from the traditional Chinese medicine named Scutellaria baicalensis Georgi, which possesses broad pharmacological properties. Our work aimed to explore the protective role of baicalin in allergic asthma and its potential mechanisms on regulating type 2 immune response. Methods: Mice were injected intraperitoneally with ovalbumin (OVA) twice, further challenged with OVA aerosol for continuous 5 days. For baicalin group, mice were pre-administrated with baicalin. After the final challenge, the immune cells in bronchoalveolar lavage fluid (BALF) and blood were examined. The cytokines were evaluated by ELISA. Histological inspections were examined by hematoxylin and eosin staining and Periodic Acid-Schiff staining. Thymic stromal lymphopoietin (TSLP) expression in lungs were detected using immunohistochemistry and Western blotting. Results: The eosinophils infiltrating in BALF were reduced remarkably in baicalin-treated asthmatic mice. Baicalin decreased OVA-induced inflammatory cytokines and total serum immunoglobulin E secretion significantly. Moreover, baicalin alleviated the asthmatic pathological changes and substantially suppressed TSLP expression in the lung tissues. Conclusion: Our study indicates that baicalin attenuates OVA-induced allergic asthma in mice effectively by suppressing type 2 immune responses, which might provide a novel insight into the anti-asthmatic activity of baicalin. Baicalin is a flavonoid chemical extracted and purified from Scutellaria baicalensis Georgi, which possesses broad pharmacological properties. Our work objected to explore the protective effect of baicalin on allergic asthma and the possible mechanisms on regulating type 2 immune response. Mice were stimulated with OVA and administrated with baicalin. We found that eosinophils infiltrate in BALF were reduced remarkably in baicalin-treated asthmatic mice. Baicalin decreased OVA-induced inflammatory cytokines and serum immunoglobulin E secretion significantly. Moreover, baicalin alleviated the asthmatic pathological changes and substantially suppressed TSLP expression in the lung tissues. Our study indicates that baicalin attenuates OVA-induced allergic asthma in mice effectively by suppressing type 2 immune responses, which may provide a new mechanistic insight into the anti-asthmatic activity of baicalin. [ABSTRACT FROM AUTHOR]

Rationale: In asthma, sputum group 2 innate lymphoid cells (ILC2s) are activated within 7 hours after allergen challenge. Neuroimmune interactions mediate rapid host responses at mucosal interfaces. In murine models of asthma, lung ILC2s colocalize to sensory neuronal termini expressing the neuropeptide neuromedin U (NMU), which stimulates type 2 (T2) cytokine secretion by ILC2s, with additive effects to alarmins in vitro. Objectives: To investigate the effect of the NMU/NMUR1 (NMU receptor 1) axis on early activation of ILC2s in asthma. Methods: Subjects with mild asthma (n = 8) were enrolled in a diluent-controlled allergen inhalation challenge study. Sputum ILC2 expression of NMUR1 and T2 cytokines was enumerated by flow cytometry, and airway NMU levels were assessed by ELISA. This was compared with samples from subjects with moderate to severe asthma (n = 9). Flow sort–purified and ex vivo–expanded ILC2s were used for functional assays and transcriptomic analyses. Measurements and Main Results: Significant increases in sputum ILC2s expressing NMUR1 were detected 7 hours after allergen versus diluent challenge whereby the majority of NMUR1+ ILC2s expressed IL-5/IL-13. Sputum NMUR1+ ILC2 counts were significantly greater in mild versus moderate to severe asthma, and NMUR1+ ILC2s correlated inversely with the dose of inhaled corticosteroid in the latter group. Coculturing with alarmins upregulated NMUR1 in ILC2s, which was attenuated by dexamethasone. NMU-stimulated T2 cytokine expression by ILC2s, maximal at 6 hours, was abrogated by dexamethasone or specific signaling inhibitors for mitogen-activated protein kinase 1/2 and phosphoinositol 3-kinase but not the IL-33 signaling moiety MyD88 in vitro. Conclusions: The NMU/NMUR1 axis stimulates rapid effects on ILC2s and may be an important early activator of these cells in eosinophilic inflammatory responses in asthma. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionsThis study aimed to explore the effects of Parkin (Prkn) knockout in a juvenile mouse model of asthma.Prkn knockout (KO) and wild type (WT) mice were utilized to establish a juvenile mouse asthma model. The asthma model involved exposure to hyperoxia/ovalbumin (OVA), encompassing hyperoxia from postnatal day 1 (P1) to P7, sensitization on P21 and P28, and challenge from P36 to P42. Room air/phosphate-buffered saline (PBS) served as the control condition. Following airway resistance measurement, bronchoalveolar lavage fluid (BALF) was collected for cellular analysis, and lung tissues were subjected to histological examination and oxidative stress assessment. Serum levels of ovalbumin-specific immunoglobulin E (IgE), total IgE, interleukin-4 (IL-4), IL-5, and IL-13 were quantified using enzyme-linked immunosorbent assay (ELISA).WT mice exposed to hyperoxia/OVA showed decreased body weight and increased airway resistance compared to those exposed to control condition. Conversely, KO mice exhibited increased body weight under asthma conditions. KO mice with asthma had reduced total cell counts, along with lower levels of lymphocytes, eosinophils, and neutrophils, compared to WT asthma mice. Histological assessment showed attenuated inflammation and reduced collagen deposition in KO mice relative to WT mice, with lower serum levels of inflammatory markers and improved lung oxidative stress profiles. No significant differences were observed between KO and WT mice under room air/PBS conditions.Parkin knockout in juvenile mice mitigates asthma-related alterations in airway resistance, histopathological changes, inflammation status, and oxidative stress. These findings highlight a protective role of Parkin deficiency against asthma-associated pathologies. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionsThis study aimed to compare the clinical characteristics and treatment outcomes of allergic patients (AP) and non-allergic patients (NAP) with severe eosinophilic asthma (SEA) treated with anti-IL5/IL5R biologic agents (mepolizumab, benralizumab, or reslizumab) over one year. Sub-analyses assessed treatment response variations between AP and NAP based on the biological used and compared outcomes among AP with and without fungal allergy.Observational retrospective analysis. Clinical characteristics, laboratory findings, pulmonary function tests, Asthma Control Test (ACT) scores, oral corticosteroid (OCS) usage, and exacerbation frequency were assessed at the initiation of biological treatment and after one year.Sixty-five patients with SEA were included, 41 AP and 24 NAP. 55.4% were treated with mepolizumab, 33.8% with benralizumab, and 10.8% with reslizumab. Before anti-IL5/5R treatment, AP had worse baseline outcomes but there were no differences in pulmonary function. Mean annual exacerbation rate and percentage of patients requiring OCS and dose of prednisone were higher in AP than NAP. AP had significantly higher total IgE values. After one year of treatment, more AP discontinued OCS than NAP (p = 0.025). Both experienced a significant reduction in exacerbation frequency (p = 0.001) and improved respiratory function. 70.7% of AP and 60% of NAP improved ACT ≥3 points. There was no significant difference between AP and NAP using mepolizumab (p = 0.145) or benralizumab (p = 0.174) in reducing OCS.Anti-IL5/IL5R reduced the need for OCS and improved asthma control, regardless of allergic status. Fungal allergy led to lower ACT scores and higher exacerbations than other allergens; both groups improved with anti-IL5/ILR. [ABSTRACT FROM AUTHOR]

Allergic asthma is a chronic inflammatory disease characterized by airway inflammation and hyper-responsiveness. Silymarin is a natural compound recognized for its potential anti-inflammatory properties in various conditions, including asthma. In this study, we investigated the anti-inflammatory effects of silymarin on a mouse model of allergic asthma. Thirty-five mice were categorized into five groups (n = 7 per group). The normal control group received phosphate-buffered saline (PBS), while the remaining four groups were induced with allergic asthma using ovalbumin (OVA). One sensitized group was treated with PBS (Asthma/Baseline), another received beclomethasone, and two groups were administered silymarin (25 mg/kg and 50 mg/kg) intraperitoneally. Subsequently, we quantified the changes in inflammatory cell influx in bronchoalveolar lavage fluid (BALF) and the levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) in BALF and blood. Histopathological alterations of leukocytes were examined in the lung tissues of all animals. The results showed that silymarin reduced inflammatory cells, including eosinophils and lymphocytes, in the BALF. Additionally, the silymarin-treated groups exhibited decreased IL-4 levels and increased IFN-γ levels in the blood, surpassing the effects of beclomethasone. Furthermore, histopathological analysis demonstrated a significant decrease in leukocyte infiltration following silymarin treatment. Our findings demonstrate the anti-inflammatory effects of silymarin in allergic asthma, likely through the modulation of inflammatory cells. [ABSTRACT FROM AUTHOR]

Allergic asthma is a complex heterogeneous disease of respiratory system. It has extensive variability at the genetic level, and has a variety of opportunities to change genetic diversity. More and more studies have shown that targeting Wnt/β-catenin signaling pathway can affect the occurrence and development of allergic asthma, but its specific immune mechanism is not clear. In this paper, we mainly introduce Wnt/β-catenin signal and its role and function in allergic asthma provide a new target for drug inter‑ vention in the treatment of allergic asthma [ABSTRACT FROM AUTHOR]

Objective: To detect the expression of Toll-like receptor 7 (TLR7) in blood neutrophils of patients with allergic rhinitis (AR), allergic asthma (AA) and allergic rhinitis combined with allergic asthma (ARA) before and after allergen challenge. Methods: A total of 44 AR, 36 AA, 19 ARA patients and 19 healthy control (HC) were recruited, the extracts of Artemisia siever⁃ siana wild allergen (ASWE), house dust mite allergen (HDME) and Platanus pollen allergen (PPAE) were used to challenge peripheral blood of HC as well as the patients, the expression of TLR7 in neutrophils was detected by flow cytometry. Results: In a resting state, compared with HC, upregulated expression of TLR7 in neutrophils in patients with airway allergy: the percentage of TLR7+ neutrophils in AR, AA, ARA patients increased 6 times, 3.18 times and 6.15 times, respectively, and the mean fluorescence intensity (MFI) of TLR7 expression in neutrophil in ARA was enhanced by 24%. The results of allergen challenge tests showed that the expression of neutrophils TLR7 did not change in HC subjects after the allergen challenge, whereas the expression of TLR7 in neutrophils of patients with airway allergy was upregulated after the allergens challenge. After HDME and PPAE challenge, the percentage of TLR7+neutrophils in peripheral of AR patients increased by 8.40% and 33.03%, respectively, and the MFI of TLR7 enhanced by 29.62% and 35.72%, respectively. After ASWE and PPAE challenge. The percentage of TLR7+ neutrophils in peripheral of AA patients increased by 59.18% and 1.06 times, respectively, and the MFI of TLR7 enhanced by 68.93% and 47.33%, respectively. However, after HDME stimulation only enhanced the MFI of neutrophil TLR7 in AA patients by 66.14%; after HDME challenge, the percentage of TLR7 and MFI in peripheral blood neutrophils of patients with ARA increased by 21.05% and 35.61%, respectively, while after PPAE challenge, the percentage of TLR7+ cells in patients with ARA increased by 20.07%. Conclusion: The expression of TLR7 n blood neutrophils is increased in patients with allergic airway diseases after allergen stimulation, suggesting that allergens may be involved in the occurrence and development of allergic airway diseases by inducing TLR7 expression changes in neutrophils. [ABSTRACT FROM AUTHOR]

Asthma is a chronic lung disease with persistent airway inflammation, bronchial hyper-reactivity, mucus overproduction, and airway remodeling. Antagonizing T2 responses by triggering the immune system with microbial components such as Toll-like receptors (TLRs) has been suggested as a therapeutic concept for allergic asthma. The aim of this study was to evaluate the effect of a TLR2/6 agonist, FSL-1 (Pam2CGDPKHPKSF), administered by intranasal instillation after an allergic airway reaction was established in the ovalbumin (OVA) mouse model and to analyze the role of natural killer (NK) cells in this effect. We showed that FSL-1 decreased established OVA-induced airway hyper-responsiveness and eosinophilic inflammation but did not reduce the T2 or T17 response. FSL-1 increased the recruitment and activation of NK cells in the lung parenchyma and modified the repartition of NK cell subsets in lung compartments. Finally, the transfer or depletion of NK cells did not modify airway hyper-responsiveness and eosinophilia after OVA and/or FSL-1 treatment. Thus, the administration of FSL-1 reduces airway hyper-responsiveness and bronchoalveolar lavage eosinophilia. However, despite modifications of their functions following OVA sensitization, NK cells play no role in OVA-induced asthma and its inhibition by FSL-1. Therefore, the significance of NK cell functions and localization in the airways remains to be unraveled in asthma. [ABSTRACT FROM AUTHOR]

The mechanisms underlying severe allergic asthma are complex and unknown, meaning it is a challenge to provide the most appropriate treatment. This study aimed to identify novel biomarkers for stratifying allergic asthmatic patients according to severity, and to uncover the biological mechanisms that lead to the development of the severe uncontrolled phenotype. By using miRNA PCR panels, we analyzed the expression of 752 miRNAs in serum samples from control subjects (n = 15) and mild (n = 11) and severe uncontrolled (n = 10) allergic asthmatic patients. We identified 40 differentially expressed miRNAs between severe uncontrolled and mild allergic asthmatic patients. Functional enrichment analysis revealed signatures related to inflammation, angiogenesis, lipid metabolism and mRNA regulation. A random forest classifier trained with DE miRNAs achieved a high accuracy of 97% for severe uncontrolled patient stratification. Validation of the identified biomarkers was performed on a subset of allergic asthmatic patients from the CAMP cohort at Brigham and Women's Hospital, Harvard Medical School. Four of these miRNAs (hsa-miR-99b-5p, hsa-miR-451a, hsa-miR-326 and hsa-miR-505-3p) were validated, pointing towards their potential as biomarkers for stratifying allergic asthmatic patients by severity and providing insights into severe uncontrolled asthma molecular pathways. [ABSTRACT FROM AUTHOR]

Obesity is a known risk factor for asthma development, progression, and exacerbation. Nevertheless, the underlying pathophysiological mechanisms explaining how obesity contributes to the development and progression of asthma have yet to be established. Here, we review human studies examining the associations between asthma and obesity, focusing on the literature from the past 10 years. Overall, current evidence suggests that while both asthma and obesity are complex diseases with significant heterogeneity, they both share various features of chronic inflammation. Furthermore, the interactions between asthma and obesity likely involve allergen-specific T helper type 2 (type 2) immune responses, as well as diverse non-type 2 inflammatory pathways. However, despite considerable progress, studies to date have not definitively elucidated the mechanisms that account for the observed association. A large-scale population-based study combined with translational immunological research, including targeted asthma therapies and pharmacological weight loss therapies, may be required to properly dissect the details of obesity-related asthma pathophysiology. [ABSTRACT FROM AUTHOR]

Atopic diseases, including atopic dermatitis (AD) and allergic asthma (AA), are characterized by complex immune responses involving various T cells subsets and their cytokine profiles. It is assumed that single nucleotide polymorphisms (SNPs) in the Vitamin D receptor (VDR) gene and the Vitamin D-binding protein (GC) gene are related to the action of Vitamin D and, consequently, play a role in regulating the immune response. However, there is not enough data to unequivocally support the hypothesis about the relationship between T cells profile and VDR or GC SNPs. Two hundred sixty-six subjects (aged > 18 years) were involved in the study: 100 patients with mild or moderate AD, 85 patients with mild or moderate AA, and 81 healthy individuals. Blood cell counts were determined by standard methods. Flow cytometric analysis was used to evaluate CD4+ T-helper (Th) cell subtypes: Th2, Th1, Th17, and T regulatory (Treg) cells in peripheral blood. Measurements of cytokines, total immunoglobulin E (IgE), and Vitamin D levels in serum were evaluated by ELISA. Significantly higher levels of Th1, Th2, and Th17 cells, along with lower levels of Tregs, were found in patients with atopic diseases compared to healthy individuals. Additionally, higher serum levels of interleukin (IL) 5, IL-17A, and transforming growth factor-β1 (TGF-β1), as well as lower levels of IL-10, were observed in patients with atopic diseases than in control. The study established associations between VDR SNPs and immune profiles: the AA genotype of rs731236 was associated with increased Th2 and Th17 cells and a higher Th1/Th2 ratio; the GG genotype of rs731236 was linked to decreased serum IL-10 and TGF-β1 levels; and the TT genotype of rs11168293 was associated with increased IL-10 levels. Additionally, the GG genotype of GC gene SNP rs4588 was associated with reduced Th2 and Th17 lymphocytes, while the TT genotype of rs4588 was linked to decreased IL-10 levels. Furthermore, the CC genotype of rs7041 was associated with higher levels of Th2, Th17, IL-10, and IL-35, as well as reduced levels of TGF-β1, while the GG genotype of rs3733359 was associated with reduced IL-10 levels. In conclusion, our study demonstrates that the Vitamin D receptor gene single nucleotide polymorphisms rs731236 and rs11168293, along with polymorphisms in the Vitamin D-binding protein gene (rs4588, rs7041, rs3733359), are significantly associated with variations in T cell profiles in atopy. These variations may play a crucial role in promoting inflammation and provide insight into the genetic factors contributing to the pathogenesis of atopy. [ABSTRACT FROM AUTHOR]

Introduction: Atopic diseases have been steadily increasing over the past decades and effective disease-modifying treatment options are urgently needed. These studies introduce a novel synthetic Toll-like receptor 4 (TLR4) agonist, INI-2004, with remarkable efficacy as a therapeutic intranasal treatment for seasonal allergic rhinitis. Methods: Using a murine airway allergic sensitization model, the impact of INI-2004 on allergic responses was assessed. Results: One or two intranasal doses of INI-2004 significantly reduced airway resistance, eosinophil influx, and Th2 cytokine production - providing strong evidence of allergic desensitization. Further investigations revealed that a liposomal formulation of INI-2004 exhibited better safety and efficacy profiles compared to aqueous formulations. Importantly, the liposomal formulation demonstrated a 1000-fold increase in the maximum tolerated intravenous dose in pigs. Pre-clinical GLP toxicology studies in rats and pigs confirmed the safety of liposomal INI-2004, supporting its selection for human clinical trials. Discussion: These findings lay the groundwork for the ongoing clinical evaluation of INI-2004 in allergic rhinitis as a stand-alone therapy for individuals poly-sensitized to multiple seasonal allergens. The study underscores the significance of innovative immunotherapy approaches in reshaping the landscape of allergic rhinitis management. [ABSTRACT FROM AUTHOR]

Objective: To explore significance of eosinophil and eosinophil/lymphocyte ratio （ELR） in predicting allergic asthma in children in different seasons. Methods: Retrospective analysis of children with asthma who visited pediatric respiratory department outpatient clinic and ward of Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2021 to December 2021, whose allergen specific IgE （sIgE） and peripheral blood cell analysis were complete. sIgE≥0.35 kUA/L were included in allergic asthma group, sIgE<0.35 kUA/L and total allergen IgE<60 kUA/L were included in non-allergic asthma group. General data and changes in peripheral blood cells of two groups were analyzed. Results: There were 1 378 qualified subjeats, including 999（ 72.5%） in allergic asthma group and 379 （27.5%） in non-allergic asthma group. Number of visits in allergic asthma group varied seasonally, with the most in autumn. Peripheral blood lymphocyte count （LYMPH）, eosinophil count （EOS） and ELR were all higher in children with allergic asthma than in children with non-allergic asthma （P<0.05）, and platelet/lymphocyte ratio （PLR） was lower than that in children with non-allergic asthma （P<0.05）. Peripheral blood LYMPH, PLT, EOS and ELR of children with allergic asthma differed between four seasons, which were higher than those of non-allergic asthma in each season in EOS and ELR, LYMPH was significantly higher than that of children with non-allergic asthma in autumn, and PLT was significantly lower than that of children with non-allergic asthma in spring （P<0.05）. EOS predicted AUC of spring, summer, autumn and winter were 0.79, 0.77, 0.71 and 0.64 in children with allergic asthma, and ELR predicted AUC were 0.72, 0.48, 0.73 and 0.68 in children with allergic asthma. Conclusion: Allergic asthma in children is seasonally variable and peaks in autumn. EOS and ELR in peripheral blood cells in children with allergic asthma are higher than in children with non-allergic asthma in each season of year, LYMPH is significantly higher than children with nonallergic asthma in the fall, and PLT is lower than in children with non-allergic asthma in spring, suggesting that allergic asthma type Ⅱ inflammation persists, and EOS and ELR have predictive value for children's allergic asthma. [ABSTRACT FROM AUTHOR]

Simple Summary: Oxidative stress generates harmful oxygen radicals that activate biomolecules in the lungs of asthmatics. The effects of these mediators are not directly targeted by first-line therapeutics. Using a clinically relevant murine model of allergic asthma, this study reveals that immuno-pharmacological neutralization of oxidized phospholipids in the lung can ameliorate inflammation and asthma symptoms. This suggests that specifically targeting mediators generated by oxidative stress could offer new therapeutic options for asthma to complement conventional therapies. Oxidative stress is associated with asthma pathobiology. We reported that oxidized phosphatidylcholines (OxPCs) are mediators of oxidative stress and accumulate in the lung in response to allergen challenge. The current study begins to unravel mechanisms for OxPC accumulation in the lung, providing the first insights about how OxPCs underpin allergic airway pathophysiology, and pre-clinical testing of selective neutralization of OxPCs in a murine model of allergic asthma. We hypothesized that intranasal delivery of E06, a natural IgM antibody that neutralizes the biological activity of OxPCs, can ameliorate allergen-induced airway inflammation and airway hyperresponsiveness. Adult BALB/c mice were intranasally (i.n.) challenged with house dust mite (HDM) (25 μg/mouse, 2 weeks). Some animals also received E06 monoclonal antibody (mAb) (10 µg) i.n. 1 hr before each HDM challenge. HDM challenge reduced mRNA for anti-oxidant genes (SOD1, SOD2, HO-1, and NFE2L2) in the lung by several orders of magnitude (p < 0.05). Concomitantly, total immune cell number in bronchoalveolar lavage fluid (BALF) increased significantly (p < 0.001). E06 mAb treatment prevented allergen-induced BALF immune cell number by 43% (p < 0.01). This included a significant blockade of eosinophils (by 48%, p < 0.001), neutrophils (by 80%, p < 0.001), macrophages (by 80%, p < 0.05), and CD4 (by 30%, p < 0.05) and CD8 (by 42%, p < 0.01) lymphocytes. E06 effects correlated with a significant reduction in TNF (by 64%, p < 0.001) and IL-1β (by 75%, p < 0.05) and a trend to diminish accumulation of other cytokines (e.g., IL-4, -10, and -33, and IFN-γ). E06 mAb treatment also inhibited HDM exposure-induced increases in total respiratory resistance and small airway resistance by 24% and 26%, respectively. In conclusion, prophylactic treatment with an OxPC-neutralizing antibody significantly limits allergen-induced airway inflammation and airway hyperresponsiveness, suggesting that OxPCs are important mediators of oxidative stress-associated allergic lung pathophysiology. [ABSTRACT FROM AUTHOR]

Background Cognitive impairments are linked to poor treatment response and disease control in allergic asthma. However, there are no studies exploring attention-related functional brain alterations in allergic asthma. Here, we explore attention deficit and its association with clinical characteristics and common neuropsychiatric disorders in patients with allergic asthma. Methods We recruited 38 participants, equally distributed into healthy and asthma groups. Behavioral, neurophysiological, and lung function assessment tools were used in this study. Results Our behavioral data show that allergic asthma induces attention impairment. Additionally, the event-related potentials (ERP) analysis reveals that this attention deficit is associated with a disruption in cognitive processing capability in frontal brain areas. These behavioral and neurophysiological abnormalities were strongly correlated with disease severity and neuropsychiatric comorbidities of asthmatic patients. Conclusion Together, here we propose that disrupted neurophysiological responses in frontal brain areas might lead to attention impairments in patients with allergic asthma. These findings could help characterizing the neuro-pathophysiology of cognitive disorders in allergic asthma, possibly opening the way for development of novel treatment strategies. [ABSTRACT FROM AUTHOR]

Background: We aim to investigate the effect of YiQi GuBen formula (YQGB) on airway inflammation and airway remodeling in the ovalbumin (OVA)-induced asthma model to further explore the potential mechanisms of YQGB in treating allergic asthma. Methods: Mice were divided into five groups randomly (n = 10): the control group, OVA group, OVA + Dex (0.1 mg/kg) group, OVA + low-dose (1.1 g/kg) YQGB group, and OVA + high-dose (2.2 g/kg) YQGB group. Inflammatory cell count and IgE were detected in bronchoalveolar lavage fluid (BALF). Lung tissue histopathology was observed by using H&E, PAS, Masson, and immunohistochemistry staining. qRT-PCR and western blot were applied to analyze key genes and proteins associated with TLR4 and NF-κB signaling pathways. Results: In OVA-induced asthma mice, YQGB decreased eosinophils and IgE in BALF. YQGB alleviated the OVA-induced inflammatory infiltration and declined IL-4, IL-5, IL-13, Eotaxin, ECP, GM-CSF, LTC4, and LTD4. YQGB attenuated the OVA-induced goblet cell metaplasia and mucus hypersecretion. YQGB mitigated the OVA-induced subepithelial fibrosis and lowered TGF-β1, E-Cadherin, Vimentin, and Fibronectin. YQGB ameliorated the OVA-induced airway smooth muscle thickening and lessened α-SMA and PDGF levels. YQGB reduced the expression of TLR4, MyD88, TRAF6, IκBα, and p65 mRNAs, and IκBα and p-p65 protein levels were also reduced. Conclusion: YQGB exhibits the anti-asthma effect by reducing airway inflammation and airway remodeling through suppressing TLR4/NF-κB signaling pathway, and is worth promoting clinically. [ABSTRACT FROM AUTHOR]

Background: The impact of allergic rhinoconjunctivitis on the early (EAR) and late asthmatic response (LAR) has yet to be assessed during optimal allergen exposure conditions. Objective: We aimed to assess predictive factors of the EAR and LAR and to evaluate the relation between rhinitis, conjunctivitis and asthma induced by cat allergen exposure in an environmental exposure chamber (EEC). Methods: Data from two cohort studies involving asthmatic patients with cat allergy who performed a cat allergen exposure challenge in ALYATEC EEC were analysed. Spirometry, visual analogue scale (VAS) for asthma, VAS for rhinitis, Total Nasal Symptoms Score, Total Ocular Symptoms Score (TOSS), Rhinoconjunctivitis Total Symptoms Score and Abelson score were used to assess asthma, rhinitis and conjunctivitis during and after exposure. Results: An EAR occurred in 65.1% of patients, 32.1% of whom had a LAR. The diameter of the prick test to cat allergens and non‐specific bronchial hypersensitivity level were independent risk factors for EAR (p <.05). No independent risk factors for LAR were identified. Rhinoconjunctivitis severity during exposure correlated with the asthma VAS during EAR and LAR (p <.05). Allergen exposure time needed to trigger an EAR correlated with the Abelson score during exposure (p <.05). The asthma VAS and TOSS during exposure correlated with faster LAR occurrence (p <.05). Conclusion: Prick test size and non‐specific bronchial hypersensitivity level were confirmed as independent predictive factors of EAR during allergen exposure in an EEC. This study demonstrated the relation between the severity of rhinitis, conjunctivitis and asthma induced by allergen exposure for both EAR and LAR. [ABSTRACT FROM AUTHOR]

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Purpose This study sought to investigate the causal effects of circulating C-reactive protein (CRP) level on risk of asthma and its subtypes by two-sample Mendelian randomization (MR) analysis. Methods We utilized single nucleotide polymorphisms (SNPs) associated with both CRP and outcomes of asthma, allergic asthma, and obesity-related asthma as genetic variables via a genome-wide summary association study (GWAS). MR analysis mainly based on the inverse variance weighted (IVW) method was performed to infer the causal relationship between exposure and outcomes. Cochran's Q test and MR-Egger regression analysis were performed to determine respectively the heterogeneity and pleiotropy among instrumental variables (IVs), and leave-one-out analysis was conducted to determine the stability of the MR results. Results In our study, 42 SNPs were identified as IVs for MR analyses. According to the primary inference results by IVW methods, circulating CRP was demonstrated to be significantly associated with risk of asthma [odds ratio (OR): 1.046; 95% confidence interval (95% CI): 1.004–1.090; P  = .030] and obesity-related asthma (OR: 1.072; 95% CI: 1.009–1.138; P  = 0.025), whereas no distinct causality with allergic asthma was found (OR: 1.051; 95% CI: 0.994–1.112; P  = .081). Sensitivity analyses indicated that there was no horizontal pleiotropy among IVs, and the MR results were proved to be robust by leave-one-out sensitivity analysis, despite the presence of heterogeneity. Conclusion The present study suggested that higher CRP might genetically predict an increased risk of developing asthma and obesity-related asthma, without causality with allergic asthma. Key message What is already known on this topic C-reactive protein (CRP) plays a critical role in asthma development and is usually elevated in asthmatic patients. However, the causal association between CRP and asthma remains unknown. What this study adds This Mendelian randomization study demonstrated that circulating CRP causally increased the risk of asthma, especially obesity-related asthma. How this study might affect research, practice, or policy The findings of our study carry the implication for clinicians that controlling circulating CRP levels might be a promising strategy for reducing the risk of asthma and obesity-related asthma. [ABSTRACT FROM AUTHOR]

In recent years, there has been abundant research concerning human microbiome and its impact on the host's health. Studies have shown that not only the commensal bacteria itself, but also postbiotics, understood as inanimate microorganisms, possibly with the presence of their components, may themselves have an effect on various elements of human physiology. In this review, we take a closer look at the specific ways in which postbiotics can alter immune response in allergic asthma, which is one of the most prevalent allergic diseases in today's world and a serious subject of concern. Through altering patients' immune response, not only to allergens but also to pathogens, postbiotics could have a significant role in lowering the number of asthma exacerbations. We suggest that more profound research should be undertaken in order to launch postbiotics into clinical standards of asthma treatment, given the greatly promising findings in terms of their immunomodulating potential. [ABSTRACT FROM AUTHOR]

Objective: This study aims to explore the effect of YiQi GuBen capsule on improving mitochondrial dysfunction in an animal model of asthma.Methods: The mice (n = 8) were divided into four groups including control (NC), ovalbumin (OVA), dexamethasone (OVA + DEX), and YiQi GuBen (OVA + YQGB) groups. Firstly, we established an OVA-induced mouse asthma model except for the NC group, which then were treated with dexamethasone and YiQi GuBen capsule. Subsequently, HE staining and Masson staining were used for pathological analysis of mice lung tissues. Next, we used transmission electron microscopy (TEM) to observe the effect of the Yiqi Guben capsule on the ultrastructure of mitochondria. Flow cytometry was used to analyze the ROS level, membrane potential, and the number of mitochondria in lung tissue. Moreover, we analyzed the copy number of mitochondrial DNA (mtDNA) and the expression levels of activator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial transcription factor A (TFAM).Results: The results of the pathological analysis showed that after treatment with the YiQi GuBen capsule, the lung tissue damage was significantly reduced. In addition, we observed that the ultrastructural damage of mitochondria was improved. Flow cytometry proved that after treatment with the YiQi GuBen capsule, the level of ROS in the mitochondria was effectively reduced, while the mitochondrial membrane potential decreased and the number increased significantly. Moreover, we found that the copy number of mtDNA was significantly increased and the expression levels of PGC-1α and TFAM were significantly upgraded.Conclusion: This study suggests YiQi GuBen capsule can effectively improve mitochondrial dysfunction in the OVA-induced mouse model. [ABSTRACT FROM AUTHOR]

Allergic asthma (AA) is closely associated with the polarization of T helper (Th)2 and Th17 cells. Interleukin (IL)-18 acts as an inducer of Th2 and Th17 cell responses. However, expressions of IL-18 and IL-18 receptor alpha (IL-18Rα) in blood Th2 and Th17 cells of patients with AA remain unclear. We therefore investigated their expressions in Th2 and Th17 cells using flow cytometric analysis, quantitative real-time PCR (qPCR), and murine AA model. We observed increased proportions of Th2, Th17, IL-18+, IL-18+ Th2, and IL-18+ Th17 cells in blood CD4+ T cells of patients with AA. Additionally, house dust mite seemed to upregulate further IL-18 expression in Th2 and Th17, and upregulate IL-18Rα expression in CD4+ T, Th2, and Th17 cells of AA patients. It was also found that the plasma levels of IL-4, IL-17A, and IL-18 in AA patients were elevated, and they were correlated between each other. In ovalbumin (OVA)-induced asthma mouse (AM), we observed that the percentages of blood CD4+ T, Th2, and Th17 cells were increased. Moreover, OVA-induced AM expressed higher level of IL-18Rα in blood Th2 cells, which was downregulated by IL-18. Increased IL-18Rα expression was also observed in blood Th2 cells of OVA-induced FcεRIα−/− mice. Collectively, our findings suggest the involvement of Th2 cells in AA by expressing excessive IL-18 and IL-18Rα in response to allergen, and that IL-18 and IL-18Rα expressing Th2 cells are likely to be the potential targets for AA therapy. Collectively, our findings suggest the involvement of Th2 cells in allergic asthma (AA) by expressing excessive IL-18 and IL-18Rα in response to allergen, and that IL-18 and IL-18Rα expressing Th2 cells are likely to be the potential targets for AA therapy. This summary graph shows allergen-induced IL-18 and IL-18Rα expressions in blood CD4, Th2, and Th17 cells of AA. Graphical Abstract [ABSTRACT FROM AUTHOR]

Background: House dust mite (HDM) sensitisation can contribute to the development of allergic rhinoconjunctivitis (AR) or allergic asthma (AA). As treatment, allergen immunotherapy (AIT) is a promising approach, since it aims building immunotolerance against allergens, therewith establishing long‐term efficacy. The evaluation of AIT has been investigated in many randomised controlled trials, whereas few real‐world evidence studies are available. Methods: We used data from the longitudinal prescription data base IQVIA™ LRx. Data on initial AIT prescriptions against HDM from January 2009 to December 2013 was analysed regarding treatment (subcutaneous AIT with either depigmented polymerised allergen extract [dSCIT] or other allergens [oSCIT], or sublingual immunotherapy [SLIT]) and treatment duration. Treatment groups were compared with a control group of AR patients not receiving AIT. Data on symptomatic medication was collected until February 2017 and progression of AR and AA was compared. Results: Data of 7260 patients with AIT prescriptions and of 21,780 control patients was analysed. AIT was associated with a significant decrease of AR medication intake compared with control (dSCIT: −34.0%, p < 0.0001; oSCIT: −25.7%, p < 0.0001; SLIT: −37.7%, p = 0.0026). In asthmatics, SCIT was associated with a significant decrease of asthma medication compared with control (dSCIT: −45.2%, p < 0.0001; oSCIT: −32.9%, p < 0.0001). Further, a significantly reduced likelihood for onset of asthma medication was demonstrated in patients treated with SCIT compared with controls (dSCIT OR: 0.759, p = 0.0476; oSCIT OR: 0.815, p = 0.0339). Conclusion: Real‐world data analyses indicate that AIT, particularly given via a subcutaneous route, reduces the need of medication against AR and AA and might delay the onset of asthma medication in patients with AR. [ABSTRACT FROM AUTHOR]

Background An increasing body of observational studies has indicated a potential link between allergic diseases, namely atopic dermatitis (AD), allergic rhinitis (AR), allergic asthma (AA), and psoriasis (PSO) as well as psoriatic arthritis (PSA). However, the presence and causal direction of this association remain uncertain. Methods We conducted two-sample Mendelian randomization (TSMR) analyses utilizing summary statistics derived from genome-wide association studies (GWAS) consortia. The summary statistics were obtained from a substantial participant cohort, consisting of 116,000 individuals (21,000 AD cases and 95,000 controls), 462,933 individuals (26,107 AR cases and 436,826 controls), and 140,308 individuals (4859 AA cases and 135,449 controls). The summary statistics for PSO (9267 cases and 360,471 controls) and PSA (3186 cases and 240,862 controls) were sourced from the FinnGen database. The primary analytical approach employed inverse variance weighting (IVW) as the main method within TSMR. We validated our findings through a series of sensitivity analyses. Furthermore, we performed reverse TSMR analyses to evaluate the potential presence of reverse causality. Results Our investigation revealed a potential protective effect of AD against both PSO (OR = 0.922, 95% CI = 0.863–0.984, p = 0.015)and PSA(OR = 0.915, 95% CI = 0.843–0.993, p = 0.033). Moreover, employing inverse MR analysis, we obtained compelling evidence supporting the protective role of PSO in preventing AD (OR = 0.891, 95% CI = 0.829–0.958, p = 0.002), as well as AR (OR = 0.998, 95% CI = 0.996–0.999, p = 0.008), these associations remained statistically significant even after Bonferroni correction was applied to account for multiple comparisons. Furthermore, our findings did not reveal any substantial causal relationship between AA and either PSO or PSA. Conclusion Our study provides compelling evidence that PSO significantly confers protection against both AD and AR, while AD is likely to act as a protective factor for both PSO and PSA. Despite previous studies suggesting an association between allergic diseases and the incidence of PSO and PSA, our findings do not support this claim. To obtain more accurate and reliable conclusions regarding the causal mechanisms involved, larger sample sizes in randomized controlled trials or MR studies are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Demethylzeylasteral (T-96), a new extract of Tripterygium wilfordii Hook F, exerted immunomodulatory properties in autoimmune diseases, but its effect on airway inflammatory diseases remains unclear. Our study aims to explore the protective effect and underlying mechanism of T-96 in allergic asthma. Methods: The OVA-induced asthmatic mice were administered by gavage with T-96 (0.1 mg/10 g, 0.3 mg/10 g, or 0.6 mg/10 g) 1 h before each challenge. The airway hyperresponsiveness was assessed, pathological changes were evaluated by HE and PAS staining, and expressions of Th2 cytokines were determined by PCR and ELISA. The activation of MAPK/ERK and NF-κB pathway was assessed by western blot. Results: T-96 significantly relieved airway hyperresponsiveness in asthmatic mice, evidenced by reduced airway resistance (Raw) and increased lung compliance dynamic compliance (Cdyn). Also, enhanced inflammatory infiltration and mucus hypersecretion were ameliorated in lungs of asthmatic mice following increasing doses of T-96 treatment, accompanied by decreased eosinophils in bronchoalveolar lavage fluid (BALF), IgE and OVA-specific IgE levels in serum, and downregulated IL-5 and IL-13 expressions in BALF and lung tissues as well. Notably, phosphorylation levels of p38 MAPK, ERK, and p65 NF-κB were obviously increased in asthmatic mice compared with the control group, which were then abrogated upon T-96 treatment. Conclusion: This study first revealed that T-96 alleviated allergic airway inflammation and airway hyperresponsiveness via inhibiting MAPK/ERK and NF-κB pathway. Thus, T-96 could potentially act as a new anti-inflammatory agent in allergic asthma. [ABSTRACT FROM AUTHOR]

Objective: The prevalence of allergic diseases is increasing worldwide. Phototherapy has been identified as a potential risk factor associated with childhood allergic diseases, including allergic asthma, allergic rhinitis (AR), and atopic dermatitis (AD). In this study, our aim is to assess the relationship between phototherapy and these common childhood allergic diseases. Material and Methods: We analyzed 621 children between the ages of 3-17, including a patient group of 371 who received phototherapy during the neonatal period and a control group of 250 who did not receive phototherapy. The International Study of Asthma and Allergy in Childhood (ISAAC) survey was administered to all cases. For participants with allergic diseases, plasma eosinophil and total immunoglobulin (Ig) E levels were analyzed, and a skin prick test was conducted. Results: There was no statistically significant association between the patient and control groups in terms of the diagnosis of wheeze/asthma, AR, AD, and phototherapy treatment. The percentage of eosinophilia was significantly higher in the patient group (p=0.01). Cesarean section was more frequent in the control group (p<0.05). Conclusion: According to our study, there was no significant relationship between phototherapy treatment and the incidence of childhood asthma, AR, and AD. [ABSTRACT FROM AUTHOR]