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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]

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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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]

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]

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]

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. Fortytwo 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. [ABSTRACT FROM AUTHOR]

Severe asthma (SA) is still a demanding challenge in clinical practice. Type 2 inflammation is the most common phenotype in children and adolescents with SA. As a result, anti-inflammatory drugs, mainly corticosteroids (CSs), represent the first choice to reduce type 2 inflammation. However, SA patients may require high inhaled and oral CS doses to achieve and maintain asthma control. Some SA patients, despite the highest CS dosages, can even display uncontrolled asthma. Therefore, the biological era constituted a breakthrough in managing this condition. Dupilumab is a monoclonal antibody directed against the IL-4 receptor α-subunit (IL-4Rα), antagonizing against both IL-4 and IL-13, and has been approved for pediatric severe type 2 asthma. This review presents and discusses the most recent published studies on dupilumab in children and adolescents with SA. There is convincing evidence that dupilumab is a safe and effective option in managing SA as it can reduce asthma exacerbations, reduce CS use, and improve lung function, asthma control, and quality of life, also for caregivers. However, a thorough diagnostic pathway is mandatory, mainly concerning phenotyping. In fact, the ideal eligible candidate is a child or adolescent with a type 2 allergic phenotype. [ABSTRACT FROM AUTHOR]

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.

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.

Abstract Background While numerous allergy-related biomarkers and targeted treatment strategies have been developed and employed, there are still signifcant limitations and challenges in the early diagnosis and targeted treatment for allegic diseases. Our study aims to identify circulating proteins causally associated with allergic disease-related traits through Mendelian randomization (MR)-based analytical framework. Methods Large-scale cis-MR was employed to estimate the effects of thousands of plasma proteins on five main allergic diseases. Additional analyses including MR Steiger analyzing and Bayesian colocalisation, were performed to test the robustness of the associations; These findings were further validated utilizing meta-analytical methods in the replication analysis. Both proteome- and transcriptome-wide association studies approach was applied, and then, a protein-protein interaction was conducted to examine the interplay between the identified proteins and the targets of existing medications. Results Eleven plasma proteins were identified with links to atopic asthma (AA), atopic dermatitis (AD), and allergic rhinitis (AR). Subsequently, these proteins were classified into four distinct target groups, with a focus on tier 1 and 2 targets due to their higher potential to become drug targets. MR analysis and extra validation revealed STAT6 and TNFRSF6B to be Tier 1 and IL1RL2 and IL6R to be Tier 2 proteins with the potential for AA treatment. Two Tier 1 proteins, CRAT and TNFRSF6B, and five Tier 2 proteins, ERBB3, IL6R, MMP12, ICAM1, and IL1RL2, were linked to AD, and three Tier 2 proteins, MANF, STAT6, and TNFSF8, to AR. Conclusion Eleven Tier 1 and 2 protein targets that are promising drug target candidates were identified for AA, AD, and AR, which influence the development of allergic diseases and expose new diagnostic and therapeutic targets.

Abstract Background Chelidonium majus is a well-known traditional Chinese medicine, and has been reported of the effect in relieving cough and asthma. However, the mechanism of action is still unknown. Methods Asthmatic SD rats were first sensitized and established through ovalbumin (OVA) motivation. Subsequently, Hematoxylin and eosin (H&E) staining, Masson’s trichrome (Masson) staining, Periodic acid-Schiff (PAS) staining and inflammatory cytokines assay of interleukin (IL)-4, IL-6, IL-17 were implemented to evaluate the protective effects of Chelidonium majus on asthma. Then, the effects of Chelidonium majus and their molecular mechanisms of action on asthma were detected based on the integration of transcriptomics and metabolomics analyses. Results After administration with Chelidonium majus, the histological injuries of inflammation, collagen deposition and mucus secretion in lungs were attenuated and the serum inflammatory cytokines perturbations were also converted. Furthermore, integrated analysis revealed that after Chelidonium majus treatment, 7 different expression genes (DEGs) (Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9) and 9 metabolic biomarkers (ADP, Xanthosine, Hypoxanthine, Inosine, prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a), phosphatidylserine, Creatine and LysoPC (10:0)) were discovered to be connected with the enrichment metabolic pathways, including Purine metabolism, Arachidonic acid metabolism, Arginine and proline metabolism and Glycerophospholipid metabolism. The obtained metabolic biomarkers and DEGs were mainly related to energy metabolism and inflammation, and may be potential therapeutic targets. Conclusion Chelidonium majus relieved OVA-induced asthma in rats by regulating the Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9 genes expression to restore the disorders in energy metabolism and inflammation.

Introduction: Tape‐strips, a minimally invasive method validated for the evaluation of several skin diseases, may help identify asthma‐specific biomarkers in the skin of children with allergic asthma. Methods: Skin tape‐strips were obtained and analyzed with RNA‐Seq from children with moderate allergic asthma (MAA) (n = 11, mean age 7.00; SD = 1.67), severe allergic asthma (SAA) (n = 9, mean age 9.11; SD = 2.37), and healthy controls (HCs) (n = 12, mean age 7.36; SD = 2.03). Differentially expressed genes (DEGs) were identified by fold change ≥2 with a false discovery rate <0.05. Transcriptomic biomarkers were analyzed for their accuracy in distinguishing asthma from HCs, their relationships with asthma‐related outcomes (exacerbation rate, lung function‐FEV1, IOS‐R5‐20, and lung inflammation‐FeNO), and their links to skin (barrier and immune response) and lung (remodeling, metabolism, aging) pathogenetic pathways. Results: RNA‐Seq captured 1113 in MAA and 2117 DEGs in SAA. Epidermal transcriptomic biomarkers for terminal differentiation (FLG/filaggrin), cell adhesion (CDH19, JAM2), lipid biosynthesis/metabolism (ACOT2, LOXL2) were significantly downregulated. Gene set variation analysis revealed enrichment of Th1/IFNγ pathways (p <.01). MAA and SAA shared downregulation of G‐protein‐coupled receptor (OR4A16, TAS1R3), upregulation of TGF‐β/ErbB signaling‐related (ACVR1B, EGFR, ID1/2), and upregulation of mitochondrial‐related (HIGD2A, VDAC3, NDUFB9) genes. Skin transcriptomic biomarkers correlated with the annualized exacerbation rate and with lung function parameters. A two‐gene classifier (TSSC4‐FAM212B) was able to differentiate asthma from HCs with 100% accuracy. Conclusion: Tape‐strips detected epithelial barrier and asthma‐associated signatures in normal‐appearing skin from children with allergic asthma and may serve as an alternative to invasive approaches for evaluating asthma endotypes. [ABSTRACT FROM AUTHOR]

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. Rises in the epithelial barrier permeability of airways alter tissue homeostasis and allow the penetration of allergens and other external agents. Different factors contribute to barrier impairment, such as eosinophilic infiltration and allergen protease action—eosinophilic cationic proteins' effects and allergens' proteolytic activity both contribute significantly to epithelial damage. In the airways, allergen proteases degrade the epithelial junctional proteins, allowing allergen penetration and its uptake by dendritic cells. This increase in allergen–immune system interaction induces the release of alarmins and the activation of type 2 inflammatory pathways, causing or worsening the main symptoms at the skin, bowel, and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic protease-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance, and progression. Moreover, we will explore potential clinical and radiological biomarkers of airway remodeling in allergic asthma patients. [ABSTRACT FROM AUTHOR]

Background: Poor asthma control may adversely affect mental health. Our study investigates the correlation between inadequate asthma control, exhaled nitric oxide (FENO) levels, and anxiety and depression among pediatric asthma patients with COVID‐19. Methods: This prospective case–control study enrolled 520 asthmatic children (8–15 years), including 336 patients diagnosed with COVID‐19 after rapid antigen testing at home and 184 age‐matched asthmatic patients without COVID‐19 infection. FENO and spirometry were performed 1 month after COVID‐19 infection. Scores for Child Anxiety‐Related Disorders (SCARED) and depression screen derived from Patient Health Questionnaire‐9 (PHQ‐9) to assess their mental health status. Childhood asthma control test (C‐ACT), FENO levels, and spirometry were correlated with the SCARED and PHQ‐9 questionnaires. Results: SCARED subscales, including generalized anxiety disorder, social anxiety disorder, school avoidance, and depression scores from PHQ‐9, exhibited a significant increase in asthmatic patients diagnosed with COVID‐19 (p <.05). Among asthmatic children with SARS‐CoV‐2 infection, the poor asthma control group exhibited the highest SCARED and PHQ‐9 measurements (p <.01). Multiple linear regression analysis indicated that reduced C‐ACT scores and elevated FENO levels in asthmatic children with COVID‐19 were significant risk factors for both anxiety and depression scores (p <.05). Lower C‐ACT scales were associated with high scores of SCARED (r = −0.471) and PHQ‐9 (r = −0.329) in asthmatic children (p <.001). Conclusions: The current study emphasizes the need for healthcare professionals to closely monitor asthma control in asthmatic children to prevent heightened risks of depression and anxiety during the ongoing COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Background: For decades, studies have demonstrated the anti‐inflammatory potential of proteins secreted by helminths in allergies and asthma. Previous studies have demonstrated the immunomodulatory capabilities of Succinate Coenzyme A ligase beta‐like protein (SUCLA‐β) derived from Trichinella spiralis, a crucial excretory product of this parasite. Objective: To explore the therapeutic potential of SUCLA‐β in alleviating and controlling ovalbumin (OVA)‐induced allergic asthma, as well as its influence on host immune modulation. Methods: In this research, we utilized the rTs‐SUCLA‐β protein derived from T. spiralis to investigate its potential in mitigating airway inflammation in a murine model of asthma induced by OVA sensitization/stimulation, both pre‐ and post‐challenge. The treatment's efficacy was assessed by quantifying the extent of inflammation in the lungs. Results: Treatment with rTs‐SUCLA‐β demonstrated efficacy in ameliorating OVA‐induced airway inflammation, as evidenced by a reduction in eosinophil infiltration, levels of OVA‐specific Immunoglobulin E, interferon‐γ, interleukin (IL)‐9, and IL‐17A, along with an elevation in IL‐10. The equilibrium between Th17 and Treg cells plays a pivotal role in modulating the abundance of inflammatory cells within the organism, thereby ameliorating inflammation and alleviating symptoms associated with allergic asthma. Conclusions and Clinical Relevance: Our data revealed that T. spiralis‐derived Ts‐SUCLA‐β protein may inhibit the allergic airway inflammation by regulating host immune responses. [ABSTRACT FROM AUTHOR]

Background: The hygiene hypothesis suggests that early life exposure to helminth infections can reduce hypersensitivity in the immune system. Objective: The present study aims to evaluate the effects of Toxocara cati (T. cati) somatic products on allergic airway inflammation. Methods: Between 2018 and 2020, T. cati adult worms were collected from stray cats in Mashhad, Iran (31 out of 186 cats), and their somatic extract was collected. Thirty BALB/c mice were equally divided into three groups, including the OVA group (sensitized and challenged with ovalbumin), the somatic administered group (received somatic extract along with ovalbumin sensitization), and the PBS group (sensitized and challenged with phosphate buffer saline). Bronchoalveolar lavage (BAL) fluid was collected to assess the number of cells, and lung homogenates were prepared for cytokine analysis. Histopathological analysis of the lungs was performed, and inflammatory cells and mucus were detected. Cytokine levels (IL‐4, IL‐5, IL‐10) were measured using enzyme‐linked immunosorbent assay (ELISA), and ovalbumin‐specific immunoglobulin E (IgE) levels were determined using a capture ELISA. Results: The somatic group significantly decreased regarding the lung pathological changes, including peribronchiolitis, perivasculitis, and eosinophil influx, compared to the group treated with ovalbumin alone. These changes were accompanied by a decrease in proinflammatory cytokines IL‐4 and IL‐5 and an increase in the anti‐inflammatory cytokine IL‐10, indicating a shift toward a more balanced immune response. The number of inflammatory cells in the BAL fluid was also significantly reduced in the somatic group, indicating a decrease in inflammation. Conclusion: These preclinical findings suggest that in experimental models, T. cati somatic extract exhibits promising potential as a therapeutic agent for mitigating allergic airway inflammation. Its observed effects on immune response modulation and reduction of inflammatory cell infiltration warrant further investigation in clinical studies to assess its efficacy and safety in human patients. Highlights: Allergic asthma is linked to Th2 cell responses, while corticosteroid side effects discourage patients.The hygiene hypothesis suggests helminth infections could reduce immune hypersensitivity.The administration of Toxocara cati somatic extract significantly decreased lung pathological changes associated with allergic airway inflammation, including peribronchiolitis, perivasculitis, and eosinophil influx.This reduction was accompanied by a shift in cytokine levels, with decreases in proinflammatory cytokines IL‐4 and IL‐5 and an increase in the anti‐inflammatory cytokine IL‐10, suggesting a rebalancing of the immune response.The somatic extract treatment significantly reduced inflammatory cell infiltration in the bronchoalveolar lavage fluid, indicating a decrease in overall inflammation within the airways. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma. Methods In a prospective randomized controlled study, 98 children with dust mite-induced allergic asthma were randomly divided into a control group (n=49) and an SCIT group (n=49). The control group received inhaled corticosteroid treatment, while the SCIT group additionally received a standardized three-year SCIT regimen. The two groups were compared based on peripheral blood eosinophil percentage, visual analogue score (VAS), total medication score, Asthma Control Test/Childhood Asthma Control Test scores, fractional exhaled nitric oxide (FeNO), and lung function before treatment, and at 6 months, 1 year, 2 years, and 3 years after treatment. Adverse reactions were recorded post-injection to evaluate the safety of SCIT. Results Compared with pre-treatment levels, the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils, VAS, total medication score, and FeNO, while lung function significantly improved, and asthma control levels were better 3 years after treatment (P<0.05). Compared with the control group, the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment (P<0.05). A total of 2 744 injections were administered, resulting in 157 cases (5.72%) of local adverse reactions and 4 cases (0.15%) of systemic adverse reactions, with no severe systemic adverse events. Conclusions SCIT is an effective and safe treatment for allergic asthma in children. [ABSTRACT FROM AUTHOR]

Specific immunotherapy represents the only potentially curative treatment for allergic asthma. Allergens can be administered subcutaneously (SCIT) or sublingually (SLIT). The aim of the current study was to evaluate and compare the efficacy of SCIT and SLIT for the treatment of allergic asthma in children. Our study included 69 children with allergic asthma who underwent immunotherapy for house dust mites or pollen for at least 3 consecutive years. After 3 years of SCIT and SLIT, the median number of asthma exacerbations in the last three months decreased from 2 to 0 (p < 0.01) and from 1 to 0 (p < 0.01), respectively. When comparing the efficacy of SCIT and SLIT, our study revealed a significantly better efficacy of SCIT only in terms of increasing lung function. The median increase in forced expiratory volume in one second (FEV1) after 3 years was 8% with SCIT and −1% with SLIT (p < 0.01). Daily controller therapy could be withdrawn or reduced in 9 out of 16 (56.3%) children who received it before SCIT (p < 0.01) and in 19 of 29 (65.6%) children who received it before SLIT (p < 0.01), but the difference in efficacy was not significant (p = 0.88). Both SCIT and SLIT are effective treatments for allergic asthma in children. [ABSTRACT FROM AUTHOR]

Introduction: It was intended to research the level changes and clinical significance of interleukin (IL)-10, transforming growth factor β1 (TGF-β1), and CD4+CD25 cytokines in paediatric allergic rhinitis (AR) accompanied with allergic asthma (AA). Material and methods: Eighty children of AA with AR receiving immunotherapy indications were included as the experimental group (EG), while another 40 healthy children in the same period were selected as the control group (CG). IL-10, TGF-β1, and CD4+CD25 levels in cells of the two groups before and after treatment were compared and analysed. Results: The serum TGF-β1 level was determined as 1,045.7 ±44.7 pg/ml in the EG at admission, remarkably higher than that in the CG (p < 0.05). The IL-10 level was 21.4 ±2.8 pg/ml; CD4+CD25 cells accounted for 9.2 ±2.4%, CD4+CD25high cells accounted for 0.6 ±0.3%. These were all greatly lower than those in the CG (p < 0.05). At discharge, the serum TGF-β1 level in the EG was 903.7 ±29.4 pg/ml, which was still memorably higher than that in the CG (p < 0.05). The IL-10 level changed to 32.8 ±3.7 pg/ml; the percentage of CD4+CD25 was 11.3 ±1.8, respectively, among CD4+T cells. These were also notably lower than those in the CG at discharge (p < 0.05). Conclusions: IL-10, TGF-β1, and CD4+CD25 level changes in cells might be of reference value as therapeutic indicators for clinical treatment or evaluation of paediatric AR with AA. [ABSTRACT FROM AUTHOR]

Background: While numerous allergy-related biomarkers and targeted treatment strategies have been developed and employed, there are still signifcant limitations and challenges in the early diagnosis and targeted treatment for allegic diseases. Our study aims to identify circulating proteins causally associated with allergic disease-related traits through Mendelian randomization (MR)-based analytical framework. Methods: Large-scale cis-MR was employed to estimate the effects of thousands of plasma proteins on five main allergic diseases. Additional analyses including MR Steiger analyzing and Bayesian colocalisation, were performed to test the robustness of the associations; These findings were further validated utilizing meta-analytical methods in the replication analysis. Both proteome- and transcriptome-wide association studies approach was applied, and then, a protein-protein interaction was conducted to examine the interplay between the identified proteins and the targets of existing medications. Results: Eleven plasma proteins were identified with links to atopic asthma (AA), atopic dermatitis (AD), and allergic rhinitis (AR). Subsequently, these proteins were classified into four distinct target groups, with a focus on tier 1 and 2 targets due to their higher potential to become drug targets. MR analysis and extra validation revealed STAT6 and TNFRSF6B to be Tier 1 and IL1RL2 and IL6R to be Tier 2 proteins with the potential for AA treatment. Two Tier 1 proteins, CRAT and TNFRSF6B, and five Tier 2 proteins, ERBB3, IL6R, MMP12, ICAM1, and IL1RL2, were linked to AD, and three Tier 2 proteins, MANF, STAT6, and TNFSF8, to AR. Conclusion: Eleven Tier 1 and 2 protein targets that are promising drug target candidates were identified for AA, AD, and AR, which influence the development of allergic diseases and expose new diagnostic and therapeutic targets. [ABSTRACT FROM AUTHOR]