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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]

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]

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]

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]

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]

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]

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]

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]

Asthma is a heterogeneous disease commonly driven by allergic and/or eosinophilic inflammation, both of which may be present in severe disease. Most approved biologics for severe asthma are indicated for specific phenotypes and target individual downstream type 2 components of the inflammatory cascade. Tezepelumab, a human monoclonal antibody (immunoglobulin G2λ), binds specifically to thymic stromal lymphopoietin (TSLP), an epithelial cytokine that initiates and sustains allergic and eosinophilic inflammation in asthma. By blocking TSLP, tezepelumab has demonstrated efficacy across known asthma phenotypes and acts upstream of all current clinically used biomarkers. In a pooled analysis of the phase 2b PATHWAY (NCT02054130) and phase 3 NAVIGATOR (NCT03347279) studies, compared with placebo, tezepelumab reduced the annualized asthma exacerbation rate over 52 weeks by 62% (95% confidence interval [CI]: 53, 70) in patients with perennial aeroallergen sensitization (allergic asthma); by 71% (95% CI: 62, 78) in patients with a baseline blood eosinophil count ≥300 cells/μL; and by 71% (95% CI: 59, 79) in patients with allergic asthma and a baseline blood eosinophil count ≥300 cells/μL. This review examines the efficacy and mode of action of tezepelumab in patients with allergic asthma, eosinophilic asthma and coexisting allergic and eosinophilic phenotypes. [ABSTRACT FROM AUTHOR]

Objective: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence‐based recommendations for improved patient care. Purpose: The purpose of this clinical practice guideline (CPG) is to identify quality improvement opportunities and provide clinicians trustworthy, evidence‐based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce the risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence‐based quality improvement opportunities judged most important by the guideline development group (GDG). It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. Action Statements: The GDG made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitizations, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre‐ and co‐seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions (LRs) to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The GDG offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta‐blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens. [ABSTRACT FROM AUTHOR]

Objective: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence‐based recommendations for improved patient care. Purpose: The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence‐based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence‐based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. Action Statements: The guideline development group made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The guideline development group made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitization, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre‐ and co‐seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The guideline development group offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta‐blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens. [ABSTRACT FROM AUTHOR]

The plain language summary explains allergen immunotherapy to patients, families, and caregivers. The summary is for patients aged 5 years and older who are experiencing symptoms from inhalant allergies and are considering immunotherapy as a treatment option. It is based on the 2024 "Clinical Practice Guideline: Immunotherapy for Inhalant Allergy." This plain language summary is a companion publication to the full guideline, which provides greater detail for health care providers. Guidelines and their recommendations may not apply to every patient, but they can be used to find best practices and quality improvement opportunities. [ABSTRACT FROM AUTHOR]

Background: Asthma is the most common chronic disease in children with an increasing prevalence. Its development is caused by genetic and environmental factors and allergic sensitization is a known trigger. Dog allergens affect up to 30% of all children and dog dander‐sensitized children show increased expression of cystatin‐1 (CST1) and eotaxin‐3 (CCL26) in nasal epithelium. The aim of our study was to investigate the functional mechanism of CST1 and CCL26 in the alveolar basal epithelial cell line A549. Methods: A549 cells were transfected with individual overexpression vectors for CST1 and CCL26 and RNA sequencing was performed to examine the transcriptomics. edgeR was used to identify differentially expressed genes (= DEG, |log2FC | ≥ 2, FDR < 0.01). The protein expression levels of A549 cells overexpressing CST1 and CCL26 were analyzed using the Target 96 inflammation panel from OLINK (antibody‐mediated proximity extension–based assay; OLINK Proteomics). Differentially expressed proteins were considered with a |log2FC| ≥ 1, p <.05. Results: The overexpression of CST1 resulted in a total of 27 DEG (1 upregulated and 26 downregulated) and the overexpression of CCL26 in a total of 137 DEG (0 upregulated and 137 downregulated). The gene ontology enrichment analysis showed a significant downregulation of type I and III interferon signaling pathway genes as well as interferon‐stimulated genes. At the protein level, overexpression of CST1 induced a significantly increased expression of CCL3, whereas CCL26 overexpression led to increased expression of HGF, and a decrease of CXCL11, CCL20, CCL3 and CXCL10. Conclusion: Our results indicate that an overexpression of CST1 and CCL26 cause a downregulation of interferon related genes and inflammatory proteins. It might cause a higher disease susceptibility, mainly for allergic asthma, as CCL26 is an agonist for CCR‐3‐carrying cells, such as eosinophils and Th2 lymphocytes, mostly active in allergic asthma. [ABSTRACT FROM AUTHOR]

Background: Maintenance doses for allergen immunotherapy (AIT) have been recommended for at least 3 years but little data on long‐term efficacy is available depending on AIT duration. To show sustained efficacy 10 years after completion of treatment with depigmented‐polymerized house dust mite (dpg‐pol HDM) allergen extract in adults with asthma and/or rhinoconjunctivitis. Methods: Patients included in a double‐blind placebo‐controlled AIT study with dpg‐pol HDM allergen extract were reviewed at completion of the perennial treatment and 10‐year follow‐up (10y‐FU). Change in symptom and rescue medication score was the primary objective. Visual analog scale (VAS), asthma control test (ACT), and degree of disease control were the secondary objectives. A comparative analysis between patients who underwent AIT treatment for <3 years and ≥3 years was performed. Results: Data from 31 patients (mean age 38 years) were available at 10y‐FU. All had asthma and 29 had rhinoconjunctivitis at baseline. Twenty‐three patients were treated ≥3 years and 8 for <3 years. Seventeen (55%) patients were asymptomatic at completion of AIT, with significant differences for nasal, conjunctival, and bronchial symptoms (p <.0001) compared with baseline only in those patients treated ≥3 years. Nine (52.9%) patients remained completely asymptomatic at 10y‐FU, all were treated for ≥3 years. Moreover, significant reduction in the number of patients with rhinitis (p =.0117), conjunctivitis (p <.0001), and bronchial (p =.0005) symptoms was observed at 10y‐FU compared with baseline only in the ≥3 years treated. Ten (32.3%) patients did not require any rescue medication at 10y‐FU, all had been treated for ≥3 years. ACT at 10y‐FU showed a good control of asthma (median 23.5; 95% IC[22.0, 25.0]). No significant differences were observed between VAS at end of treatment compared with VAS at 10y‐FU. Conclusions: Sustained clinical efficacy is achieved 10 years after completion of depigmented‐polymerized HDM, however, these findings were observed only if patients are treated for at least 3 years. Key Messages: A minimum of 3 years AIT treatment is required to obtain a sustained long‐term effectiveness.Dpg‐pol HDM is able to remove allergic rhinitis and asthma symptoms completely.Three‐year treatment with dpg‐pol HDM is able to maintain effectiveness 10 years after treatment. [ABSTRACT FROM AUTHOR]

Alveolar macrophages (alvMs) play an important role for maintenance of lung function by constant removal of cellular debris in the alveolar space. They further contribute to defense against microbial or viral infections and limit tissue damage during acute lung injury. alvMs arise from embryonic progenitor cells, seed the alveoli before birth, and have life‐long self‐renewing capacity. However, recruited monocytes may also help to restore the alvM population after depletion caused by toxins or influenza virus infection. At present, the population dynamics and cellular plasticity of alvMs during allergic lung inflammation is poorly defined. To address this point, we used a mouse model of Aspergillus fumigatus‐induced allergic lung inflammation and observed that Th2‐derived IL‐4 and IL‐13 caused almost complete disappearance of alvMs. This effect required STAT6 expression in alvMs and also occurred in various other settings of type 2 immunity‐mediated lung inflammation or administration of IL‐4 complexes to the lung. In addition, Th2 cells promoted conversion of alvMs to alternatively activated macrophages and multinucleated giant cells. Given the well‐established role of alvMs for maintenance of lung function, this process may have implications for resolution of inflammation and tissue homeostasis in allergic asthma. [ABSTRACT FROM AUTHOR]

Atopy has been long used as the screening method for airway allergy. Nevertheless, aeroallergens can trigger respiratory symptoms not only in atopic patients (atopic respiratory allergy, ARA), but also in non‐atopic subjects (local respiratory allergy, LRA). Moreover, ARA and LRA can coexist in the same patient, and this clinical scenario has been called dual respiratory allergy (DRA). When the clinical history cannot determine the relevance of sensitizations in ARA patients, nasal, conjunctival or bronchial allergen challenges (NAC, CAC, and BAC, respectively) should be conducted. Moreover, these tests are required to identify patients with LRA and DRA. The clarification of the allergic triggers of airway diseases has a profound impact on the management strategies the patients can be offered. Importantly, allergen immunotherapy (AIT) remains as the only disease‐modifying intervention for ARA. Recent data indicate that AIT might have a similar effect on LRA patients. Nevertheless, AIT success relies largely on the correct phenotyping of allergic individuals, and NAC, CAC, and BAC are very helpful tools in this regard. In this review, we will summarize the main indications and methodology of CAC, NAC, and BAC. Importantly, the clinical implementation of these tests might translate into precision medicine approaches and better health outcomes for patients with airway allergy. [ABSTRACT FROM AUTHOR]

There is limited data on the use of benralizumab in patients with severe asthma, who have allergic bronchopulmonary aspergillosis (ABPA). We report the case of a 65‐year‐old woman with combined severe eosinophilic and allergic asthma, who presented with refractory respiratory symptoms, hypereosinophilia and high immunoglobulin E (IgE) level. The patient had consistently poor Asthma Control Test (ACT) scores, despite a maximum dose of inhalation therapy. Upon further investigations, she was diagnosed with concomitant ABPA. The patient was started on oral prednisolone and itraconazole, but her symptoms persisted. She was then started on subcutaneous omalizumab, but switched to benralizumab after developing a severe allergic reaction. The patient experienced rapid clinical improvements after the first dose of subcutaneous benralizumab. Benralizumab demonstrated a significant role in reducing the exacerbation rate and oral corticosteroid use in this patient, as well as improving lung function, asthma control, and quality of life measures. [ABSTRACT FROM AUTHOR]

Macrophage migration inhibitory factor (MIF) is present in high amounts in the BALF and serum of asthmatic patients, contributing to the pathogenesis of experimental asthma induced by OVA in mice. Whether MIF contributes to the physiopathology on a more complex and relevant asthma model has not been characterized. Mif‐deficient (Mif−/−) or WT mice treated with anti‐MIF antibody were challenged multiple times using house dust mite (HDM) extract by the intranasal route. HDM‐challenged Mif−/− mice presented decreased airway hyperresponsiveness, lung infiltration of eosinophils, mucus hypersecretion, and subepithelial fibrosis compared to HDM‐challenged WT mice. Amounts of IL‐4, IL‐5, and IL‐13 were decreased in the lungs of Mif−/− mice upon HDM challenges, but the increase of CCL11 was preserved, compared to HDM‐challenged WT mice. We also observed increased numbers of group 2 innate lymphoid cells and Th2 cells in the BALF and mediastinal LNs (mLN)‐induced challenged by HDM of WT mice, but not in HDM‐challenged Mif−/− mice. Anti‐MIF treatment abrogated the airway infiltration of eosinophils, mucus hypersecretion, and subepithelial fibrosis in the lungs of HDM‐challenged mice. In conclusion, MIF ablation prevents the pathologic hallmarks of asthma in HDM‐challenged mice, reinforcing the promising target of MIF for asthma therapy. [ABSTRACT FROM AUTHOR]

The present study aims to evaluate the efficacy of an anti‐immunoglobulin E monoclonal antibody (omalizumab) in the treatment of allergic asthma (AS). A total of 34 patients with moderate‐to‐severe bronchial asthma admitted to the Respiratory Department of Tianjin First Central Hospital between September 2019 and September 2021 were enrolled in this study. The patients were treated with omalizumab in addition to conventional inhaled corticosteroids + long‐acting β2 agonist treatment. The therapeutic effects before and after the addition of omalizumab were compared. The lung function indicators (ratio of the forced expiratory volume [FEV] in the first second to the forced vital capacity, FEV in the first second, forced expiratory flow [FEF] at 50% of vital capacity, FEF at 75% of vital capacity, and maximum mid‐expiratory flow), fractionated exhaled nitric oxide values, asthma control test scores, rhinoconjunctivitis quality of life questionnaire scores, and urticaria control test scores were significantly different after 4 months of the regular administration of omalizumab (p < 0.05) compared with before administration. The use of omalizumab had a significant efficacy in the treatment of patients with AS, and the effects were obvious in the subgroups of patients with a combination of AS and atopic dermatitis, chronic urticaria, and allergic rhinitis. These results indicate that the treatment is worthy of clinical promotion. [ABSTRACT FROM AUTHOR]

Efferocytosis can resolve airway inflammation and enhance airway tolerance in allergic asthma. While previous work has reported that progranulin (PGRN) regulated macrophage efferocytosis, but it is unclear whether PGRN‐mediated efferocytosis is associated with asthma. Here, we found that in an ovalbumin (OVA)‐induced allergic asthma model, the airway inflammation was suppressed and the apoptosis in lung tissues was ameliorated in PGRN‐deficient mice. In contrast, PGRN knockdown in human bronchial epithelial cells increased apoptosis in vitro. Furthermore, PGRN‐deficient macrophages had significantly stronger efferocytosis ability than wild type (WT) macrophages both in vitro and in vivo. PGRN‐deficient peritoneal macrophages (PMs) exhibited increased expression of genes associated with efferocytosis including milk fat globule‐epidermal growth factor 8 (MFG‐E8), peroxisome proliferator‐activated receptor gamma (PPAR‐γ) and sirtuin1 (SIRT1) and increased capacity to produce the anti‐inflammatory mediator interleukin (IL)‐10 during efferocytosis. GW9662, the inhibitor of PPAR‐γ, abolished increased efferocytosis and MFG‐E8 expression in PGRN‐deficient PMs suggesting that PGRN deficiency enhanced MFG‐E8‐mediated efferocytosis through PPAR‐γ. Correspondingly, efferocytosis genes were increased in the lungs of OVA‐induced PGRN‐deficient mice. GW9662 treatment reduced MFG‐E8 expression but did not significantly affect airway inflammation. Our results demonstrated that PGRN deficiency enhanced efferocytosis via the PPAR‐γ/MFG‐E8 pathway and this may be one of the reasons PGRN deficiency results in inhibition of airway inflammation in allergic asthma. [ABSTRACT FROM AUTHOR]

Introduction: Allergic asthmatics with both an early (EAR) and a late allergic reaction (LAR) following allergen exposure are termed 'dual responders' (DR), while 'single responders' (SR) only have an EAR. Mechanisms that differentiate DR from SR are largely unknown, particularly regarding the role and phenotypes of neutrophils. Therefore, we aimed to study neutrophils in DR and SR asthmatics. Methods: Thirty‐four allergic asthmatics underwent an inhaled allergen challenge, samples were collected before and up to 24 h post‐challenge. Cell differentials were counted from bronchial lavage, alveolar lavage and blood; and tissue neutrophils were quantified in immune‐stained bronchial biopsies. Lavage neutrophil nuclei lobe segmentation was used to classify active (1–4 lobes) from suppressive neutrophils (≥5 lobes). Levels of transmigration markers: soluble (s)CD62L and interleukin‐1Ra, and activity markers: neutrophil elastase (NE), DNA‐histone complex and dsDNA were measured in lavage fluid and plasma. Results: Compared with SR at baseline, DR had more neutrophils in their bronchial airways at baseline, both in the lavage (p =.0031) and biopsies (p =.026) and elevated bronchial neutrophils correlated with less antitransmigratory IL‐1Ra levels (r = −0.64). DR airways had less suppressive neutrophils and more 3‐lobed (active) neutrophils (p =.029) that correlated with more bronchial lavage histone (p =.020) and more plasma NE (p =.0016). Post‐challenge, DR released neutrophil extracellular trap factors in the blood earlier and had less pro‐transmigratory sCD62L during the late phase (p =.0076) than in SR. Conclusion: DR have a more active airway neutrophil phenotype at baseline and a distinct neutrophil response to allergen challenge that may contribute to the development of an LAR. Therefore, neutrophil activity should be considered during targeted diagnosis and bio‐therapeutic development for DR. [ABSTRACT FROM AUTHOR]

Basophils are crucial in regulating allergic reactions via immediate secretion of multiple mediators upon IgE‐induced degranulation. IL‐3 regulates the development and activation of human basophils while epithelial cytokine thymic stromal lymphopoietin (TSLP) is another key regulator for murine basophils. Despite association of increased TSLP with exaggerated basophil responses in oesophageal biopsies, the effects of TSLP in regulating human basophil degranulation and activation are under debate. In this study, we aimed to examine whether human basophils responded to TSLP by co‐expression of TSLP receptors, TSLPR and IL‐7Rα (CD127), upon in vitro activation and in sputum of allergic asthmatic patients. Flow cytometric analysis of fresh basophils from healthy controls revealed no detectable TSLPR and CD127. Further flow cytometric analysis of basophils from healthy controls in vitro stimulated by multiple established basophil modulators for 24 hours showed induction of TSLPR but not CD127 by IL‐3 (10 ng/ml), anti‐IgE (10 μg/ml) and C5a (50 ng/ml). One‐hour stimulation of basophils from allergic asthmatic patients and healthy controls by TSLP (50 ng/ml) with or without IL‐3 (10 ng/ml) and anti‐IgE (10 μg/ml) had no effect on induction of CD63+ degranulated basophils. Similarly, TSLP (50 ng/ml) with or without IL‐3 (10 ng/ml) and anti‐IgE (10 μg/ml) did not induce IL‐4 and IL‐13 production by basophils from healthy controls. Further ex vivo analysis revealed that sputum basophils from allergic asthmatic patients did not express CD127. We conclude that human basophils from healthy controls and allergic asthmatic patients do not respond to TSLP as lacking CD127. [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCTs) are the gold‐standard for benefit–risk assessments during drug approval processes. Real‐word data (RWD) and the resulting real‐world evidence (RWE) are becoming increasingly important for assessing the effectiveness of drug products after marketing authorization showing how RCT results are transferred into real life care. The effectiveness of allergen immunotherapy (AIT) has been assessed in several RWE studies based on large prescription databases. We performed a literature search for retrospective cohort assessments of prescription databases in Europe to provide an overview on the methodology, long‐term effectiveness outcomes, and adherence to AIT. Thirteen respective publications were selected. AIT was more effective in reducing the progression of allergic rhinitis (AR) compared to a non‐AIT control group receiving only symptomatic treatment for AR for up to 6 years. The development and progression of asthma were hampered for most endpoints in patients treated with most preparations compared to the non‐AIT group, receiving only anti‐asthmatic medication. The results for "time to onset" of asthma were inconsistent. Adherence to AIT decreased during the recommended 3‐year treatment period, however, in most studies higher adherence to subcutaneous than to sublingual AIT was shown. The analysis of long‐term effectiveness outcomes of the RWE studies based on prescription databases confirms the long‐term efficacy of AIT demonstrated in RCTs. Progression of rhinitis and asthma symptoms as well as delayed onset of asthma triggered by different allergens, real life adherence to the treatment shows differences in particular application routes. [ABSTRACT FROM AUTHOR]

Background: Inflammasomes are large protein complexes that assemble in the cytosol in response to danger such as tissue damage or infection. Following activation, inflammasomes trigger cell death and the release of biologically active forms of pro‐inflammatory cytokines interleukin (IL)‐1β and IL‐18. NOD‐like receptor family pyrin domain containing 6 (NLRP6) inflammasome is required for IL‐18 secretion by intestinal epithelial cells, macrophages, and T cells, contributing to homeostasis and self‐defense against pathogenic microbes. However, the involvement of NLRP6 in type 2 lung inflammation remains elusive. Methods: Wild‐type (WT) and Nlrp6−/− mice were used. Birch pollen extract (BPE)‐induced allergic lung inflammation, eosinophil recruitment, Th2‐related cytokine and chemokine production, airway hyperresponsiveness, and lung histopathology, Th2 cell differentiation, GATA3, and Th2 cytokines expression, were determined. Nippostrongylus brasiliensis (Nb) infection, worm count in intestine, type 2 innate lymphoid cell (ILC2), and Th2 cells in lungs were evaluated. Results: We demonstrate in Nlrp6−/− mice that a mixed Th2/Th17 immune responses prevailed following birch pollen challenge with increased eosinophils, ILC2, Th2, and Th17 cell induction and reduced IL‐18 production. Nippostrongylus brasiliensis infected Nlrp6−/− mice featured enhanced early expulsion of the parasite due to enhanced type 2 immune responses compared to WT hosts. In vitro, NLRP6 repressed Th2 polarization, as shown by increased Th2 cytokines and higher expression of the transcription factor GATA3 in the absence of NLRP6. Exogenous IL‐18 administration partially reduced the enhanced airways inflammation in Nlrp6−/− mice. Conclusions: In summary, our data identify NLRP6 as a negative regulator of type 2 immune responses. [ABSTRACT FROM AUTHOR]

Background: Obesity has often been associated with severe allergic asthma (AA). Here, we analyzed the frequency of different circulating CD4+T‐cell subsets from lean, overweight and obese AA patients. Methods: Mononuclear cells from peripheral blood were obtained from 60 AA patients and the frequency of different CD4+T‐cell subsets and type 1 regulatory B cells (Br1) was determined by cytometry. The effect of obese‐related leptin dose on cytokine production and Treg cell function in AA‐derived CD4+ T cell cultures was evaluated by ELISA and 3H thymidine uptake, respectively. Leptin levels were quantified in the plasma by ELISA. According to the BMI, patients were stratified as lean, overweight and obese. Results: AA severity, mainly among obese patients, was associated with an expansion of hybrid Th2/Th17 and Th17‐like cells rather than classic Th2‐like cells. On the other hand, the frequencies of Th1‐like, Br1 cells and regulatory CD4+ T‐cell subsets were lower in patients with severe AA. While percentages of the hybrid Th2/Th17 phenotype and Th17‐like cells positively correlated with leptin levels, the frequencies of regulatory CD4+ T‐cell subsets and Br1 cells negatively correlated with this adipokine. Interestingly, the obesity‐related leptin dose not only elevated Th2 and Th17 cytokine levels, but also directly reduced the Treg function in CD4+ T cell cultures from lean AA patients. Conclusion: In summary, our results indicated that obesity might increase AA severity by favoring the expansion of Th17‐like and Th2/Th17 cells and decreasing regulatory CD4+T cell subsets, being adverse effects probably mediated by leptin overproduction. [ABSTRACT FROM AUTHOR]

Allergic asthma (AA) is a common asthma phenotype, and its diagnosis requires both the demonstration of IgE‐sensitization to aeroallergens and the causative role of this sensitization as a major driver of asthma symptoms. Therefore, a bronchial allergen challenge (BAC) would be occasionally required to identify AA patients among atopic asthmatics. Nevertheless, BAC is usually considered a research tool only, with existing protocols being tailored to mild asthmatics and research needs (eg long washout period for inhaled corticosteroids). Consequently, existing BAC protocols are not designed to be performed in moderate‐to‐severe asthmatics or in clinical practice. The correct diagnosis of AA might help select patients for immunomodulatory therapies. Allergen sublingual immunotherapy is now registered and recommended for controlled or partially controlled patients with house dust mite‐driven AA and with FEV1 ≥ 70%. Allergen avoidance is costly and difficult to implement for the management of AA, so the proper selection of patients is also beneficial. In this position paper, the EAACI Task Force proposes a methodology for clinical BAC that would need to be validated in future studies. The clinical implementation of BAC could ultimately translate into a better phenotyping of asthmatics in real life, and into a more accurate selection of patients for long‐term and costly management pathways. [ABSTRACT FROM AUTHOR]

Progressive loss of effector functions, especially IFN‐γ secreting capability, in effector memory CD8+ T (CD8+ TEM) cells plays a crucial role in asthma worsening. However, the mechanisms of CD8+ TEM cell dysfunction remain elusive. Here, we report that S100A4 drives CD8+ TEM cell dysfunction, impairing their protective memory response and promoting asthma worsening in an ovalbumin (OVA)‐induced asthmatic murine model. We find that CD8+ TEM cells contain two subsets based on S100A4 expression. S100A4+ subsets exhibit dysfunctional effector phenotypes with increased proliferative capability, whereas S100A4− subsets retain effector function but are more inclined to apoptosis, giving rise to a dysfunctional CD8+ TEM cell pool. Mechanistically, S100A4 upregulation of mitochondrial metabolism results in a decrease of acetyl‐CoA levels, which impair the transcription of effector genes, especially ifn‐γ, facilitating cell survival, tolerance, and memory potential. Our findings thus reveal general insights into how S100A4+ CD8+ TEM cells reprogram into dysfunctional and less protective phenotypes to aggravate asthma. [ABSTRACT FROM AUTHOR]

Introduction: Although clinical trials have shown the efficacy and safety of allergen‐specific immunotherapy (AIT) in the treatment of allergic asthma, there is a need for real‐life studies. We aimed to assess the effectiveness and safety of a microcrystalline tyrosine‐adjuvanted Dermatophagoides pteronyssinus allergoid (Acarovac Plus®) in patients with house dust mite (HDM)‐induced allergic asthma in a real‐life study. Methods: A subanalysis of a multicenter, prospective, observational, real‐life study. Patients with rhinitis and allergic asthma caused by HDMs were assessed before AIT with Acarovac Plus® and at 6 and 12 months after this treatment. Assessment parameters were percentage of days with asthma symptoms, percentage of days on asthma medication, classification of asthma according to Spanish guidelines for the management of asthma, asthma‐related quality of life (quality of life in adults with asthma questionnaire [QLAAQ]), perception of symptoms (visual analog scale [VAS]), and treatment satisfaction (treatment satisfaction questionnaire for medication [TSQM]). Safety was assessed by the number and severity of adverse reactions. Results: This subanalysis included 55 patients. Treatment with Acarovac Plus® showed significant differences in the analyzed variables when the baseline visit was compared with the 12‐month visit: reduction of the mean (SD) percentage of days with asthma symptoms (23.9 [9.2] vs. 5.1 [12.8]; p =.002), of the mean [SD] percentage of days on asthma medication (67.6 [42.9] vs. 45.1 [46.8]; p =.002), and of the percentage of patients with persistent asthma (78.2% vs. 38.9%; p =.009). Acarovac Plus® significantly improved asthma‐related quality of life, as shown by a decrease of 1.39 points in QLAAQ score at 12 months (p <.001), and in the subjective perception of symptoms on the VAS (−3.50, p <.0001). Patients showed high treatment satisfaction according to the TSQM, and it was well tolerated. No serious adverse events were reported. Conclusions: Acarovac Plus® was effective and safe for the treatment of patients with HDM‐induced allergic asthma in a real‐life study. [ABSTRACT FROM AUTHOR]

Two clusters, CD4 c6 and CD4 c30, were expanded in AA vs HC (Figure 1D,E,S1G,H). Keywords: allergic asthma; clinical disease parameters; CyTOF; pediatric; T-cell subpopulations EN allergic asthma clinical disease parameters CyTOF pediatric T-cell subpopulations 313 316 4 12/31/21 20220101 NES 220101 ACKNOWLEDGMENTS This work was generously supported by the Else Kröner-Fresenius-Stiftung (Research group: "Functional, therapy-aimed clustering of T-cell sub-phenotypes across plasticity"). Thus, eTregs (eTreg c2 and eTreg c10) and naïve/resting Tregs (CD4 c30) are involved in two different pathological features of AA, in the eosinophilia and in part in the lung function, respectively. [Extracted from the article]

Background: Rhinoviruses are the predominant cause of respiratory viral infections and are strongly associated with asthma exacerbations. While humoral immunity plays an important role during virus infections, cellular aspects of this response are less well understood. Here, we investigated the antiviral response of circulating B cells upon experimental rhinovirus infection in healthy individuals and asthma patients. Methods: We purified B cells from experimentally infected healthy individuals and patients with asthma and subjected them to total RNA‐sequencing. Rhinovirus‐derived RNA was measured in isolated B cells using a highly sensitive PCR. B cells were stimulated with rhinovirus in vitro to further study gene expression, expression of antiviral proteins and B‐cell differentiation in response rhinovirus stimulation. Protein expression of pro‐inflammatory cytokines in response to rhinovirus was assessed using a proximity extension assay. Results: B cells isolated from experimentally infected subjects exhibited an antiviral gene profile linked to IFN‐alpha, carried viral RNA in vivo and were transiently infected by rhinovirus in vitro. B cells rapidly differentiated into plasmablasts upon rhinovirus stimulation. While B cells lacked expression of interferons in response to rhinovirus exposure, co‐stimulation with rhinovirus and IFN‐alpha upregulated pro‐inflammatory cytokine expression suggesting a potential new function of B cells during virus infections. Asthma patients showed extensive upregulation and dysregulation of antiviral gene expression. Conclusion: These findings add to the understanding of systemic effects of rhinovirus infections on B‐cell responses in the periphery, show potential dysregulation in patients with asthma and might also have implications during infection with other respiratory viruses. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous immunotherapy (SCIT) is an effective, safe, preventative treatment for allergic asthma; however, potential biomarkers for monitoring SCIT have rarely been reported. Objective: Metabolomics was utilized for the discovery of new biomarkers and analyzing disease pathophysiology of allergic asthma, and it was also applied to determine the metabolomic profiles of serum samples from children with asthma undergoing SCIT and identify potential biomarkers for allergic asthma and its therapeutic monitoring. Methods: Untargeted metabolomics using ultra‐high‐performance liquid chromatography‐quadrupole‐time‐of‐flight mass spectrometry was performed on 15 asthmatic and 15 healthy pediatric sera to profile carboxylic acids. Statistical analysis combined with pathway enrichment analysis was applied to identify potential biomarkers. Then, targeted metabolomics was performed to study longitudinal changes of eicosanoid profiles on sera from 20 participants with asthma who received SCIT at baseline, 6 months, one, two, and three years (ChiCTR‐DDT‐13003728). Results: Metabolomic analysis revealed that levels of eicosanoids, particularly 12(S)‐hydroxyeicosatetraenoic acid (HETE; AUC = 0.94, p <.0001) and 15(S)‐HETE (AUC = 0.89, p =.0028), metabolized from arachidonic acid by lipoxygenase and glutathione peroxidase enzymes, were significantly higher in asthma group than in healthy individuals. Furthermore, levels of these important metabolites increased in the first year of SCIT treatment and then decreased from years one to three, being significantly lower after three years of treatment than baseline levels. Conclusion: 12(S)‐ and 15(S)‐HETEs are potential biomarkers to participate in the pathogenesis and treatment of allergic asthma. Moreover, these metabolites may be a new target for biological indicators to monitor the therapeutic effect of SCIT, particularly in the setting of allergic asthma. [ABSTRACT FROM AUTHOR]

Mast cell activation is initiated by two signalling pathways: immunoglobulin E (IgE)‐dependent and IgE‐independent pathway. It is reported that the IgE‐independent type or pseudo‐allergy pathway gets activated by G‐protein‐dependent activation of the mast cell. Recently, adiponectin (APN) receptors, AdipoR1, and AdipoR2 have been identified as G‐protein‐coupled receptors (GPCRs). Interestingly, APN replenishment is reported to activate the Nrf2/HO‐1 signalling axis. However, no study has been performed interlinking the role of APN and the Nrf2/HO‐1 signalling axis in pseudo‐allergic reaction. In the present study, we evaluated the anti‐pseudo‐allergic effects of β‐caryophyllene, an FDA‐approved food additive, in activating AdipoR1/AdipoR2 and Nrf2/HO‐1 axis signalling pathway. Compound 48/80 (C48/80)‐induced systemic and cutaneous anaphylaxis‐like shock in BALB/c mice was performed to assess the efficacy of β‐caryophyllene (BCP). To assess the effect of BCP in anaphylactic hypotension, mean arterial pressure was measured in Wistar rats. Inhibitory properties of BCP in mast cell degranulation were estimated in rat peritoneal mast cells (RPMCs). ELISA was performed to estimate interleukin (IL)‐6, tumour necrosis factor (TNF), IL‐1β, IgE, ovalbumin (OVA)‐IgE and APN and western blotting for protein expression of Nrf2/HO‐1 and AdipoR1‐AdipoR2. BCP dose‐dependently inhibited systemic and cutaneous anaphylaxis‐like shock induced by C48/80. BCP dose‐dependently inhibited the mast cell degranulation followed by inhibition of histamine release. Also BCP dose‐dependently activated the Nrf2/HO‐1 and AdipoR1‐AdipoR2 signalling axis pathway. Moreover, BCP reversed the drop in blood pressure when the haemodynamic parameters were accessed. Our findings suggest that BCP is a potent AdipoR1/AdipoR2‐Nrf2/HO‐1 axis pathway agonist that may suppress the IgE‐independent pathway towards allergic response to secretagogues. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a raw material of polycarbonate and epoxy resin. It is used for various household electrical appliances, electronic equipment, office automation equipment, medical equipment, mobile phones, paints for automobiles, internal surface coating of cans, and adhesives for civil engineering and construction. BPA is a well‐known endocrine‐disrupting chemical, and it was reported that BPA has an adverse effect on the nervous and immune systems. However, BPA‐induced memory impairment and changes in neuroimmune biomarkers in the allergic asthmatic subject are not known yet. We aim to investigate the dietary exposure effect of BPA on brain function and biomarkers using allergic an asthmatic mouse model. Five‐week‐old male C3H/HeJSlc mice were fed two doses of BPA [0.901, 9.01 μg/kg/day] contained chow diet from 5 to 11 weeks old and ovalbumin (OVA) was given by intratracheal instillation every 2 weeks. Memory function was determined by a novel object recognition test. Genes related to memory and immune markers in the hippocampus were investigated with the real‐time polymerase chain reaction (RT‐PCR) method. In this study, impaired novel object recognition occurred in BPA‐exposed mice in the presence of an allergen. Moreover, upregulation of expression level of neuroimmune biomarkers such as N‐methyl‐D‐aspartate receptor, tumor necrosis factor‐α, ionized calcium‐binding adapter molecule‐1, cyclooxygenase‐2, and heme oxygenase‐1 in the hippocampus was observed in BPA‐exposed allergic asthmatic mice. These findings show that BPA exposure can induce neuroinflammation and which triggers impairment of memory function in mice with allergic asthma. Our study indicated that dietary exposure to BPA may affect higher brain functions by modulating neuroimmune biomarkers in allergic asthmatic subjects. Dietary BPA exposure affects neuroimmune biomarkers. Dietary BPA exposure impaired memory in allergic asthmatic mice. Neuroimmune activation was observed in BPA in the presence of allergen. [ABSTRACT FROM AUTHOR]

Keywords: Allergic asthma; circadian rhythms; lung Inflammation; microRNA/miRNA EN Allergic asthma circadian rhythms lung Inflammation microRNA/miRNA 1 4 4 08/28/21 20210801 NES 210801 Asthma is a chronic inflammatory lung disease that shows a time-of-day effect (increased airway inflammation and altered lung function) on the severity of the disease.1 Recent studies support the functional role of miRNAs in the molecular pathophysiology of asthma phenotypes/endotypes2,3 through the post-transcriptional gene regulation of key signaling pathways and cellular processes in human airways, immune cells in asthmatics, and in mouse model of allergic asthma.4-6 However, whether a rhythmic change in expression of miRNAs is responsible for the time-of-day effects observed during asthma and its exacerbations are not known. These data clearly indicate that miRNA expression changes in lung tissues in a time-dependent manner and that HDM exposure significantly affects the DE miRNAs at ZT12 versus ZT0. Lung miRNA profiles show a time-of-day response in house dust mite-induced allergic asthma in mice. [Extracted from the article]

Objective: This study analysed whether the persistence of both reversible airway obstruction (RAO) and elevated BE counts was associated to reduced asthma control and accelerated lung function decline in treated severe asthmatics. Methods: About 202 severe asthmatics were studied after 12–120 months of step‐5 treatment associated to anti‐IgE therapy. Following treatments, reversibility tests, after inhaling 400 mcg of Salbutamol, were performed. FEV1 > 12% or ≤12% changes differentiated RAO+ from RAO− subjects. Blood eosinophil (BE) counts after treatment were considered. Results: Pre‐/post‐treatment bronchodilator FEV1% and ACT were lower (61% [50–71], 74.4% [62.5–83.7] and 20[18–22]), whereas BE were higher (380 cells/µl [170–590]) in RAO+ compared to RAO− subjects (77% [64–88], p = 0.0001, 81.8% [66.1–94.3], p = 0.0001, 21[18–23], p = 0.045 and 230 cells/µl [80–360], p = 0.003). A negative relationship between SABA‐induced FEV1% changes and pre‐bronchodilator FEV1% (β = −0.551%; p = 0.0001) and ACT (β = −0.059; p = 0.038) was found. Conversely, post‐treatment BE levels were positively related (β = 145.565 cells/µl; p = 0.003) to FEV1 > 12% increases. A rising trend of pre‐/post‐bronchodilator FEV1% in time was observed in RAO− subjects with BE < 300 cells/µl. Conversely, we highlighted significant declining tendencies of pre/post‐bronchodilator FEV1% in RAO+ patients with BE > 300 cells/µl reaching lower values after more than 36 months of step‐5 treatment (59.6% [39.9–72.1] vs 74[66.5–89.2] of RAO+ individuals with BE < 300 cells/µl [p = 0.026] and 81.6% [66.1–91.8] of RAO‐subjects with BE > 300 cells/µl [p = 0.009]). Conclusion: Persistent SABA‐induced FEV1 > 12%, especially when associated to BE > 300 cells/ml, may be a marker of accelerated lung function decline in severe asthmatics despite maximal step‐5 treatment. The highest bronchodilation associated to the lowest BE levels should be the main goal of asthma treatment to prevent such decline. [ABSTRACT FROM AUTHOR]

Allergic airway disorders such as asthma and allergic rhinitis are mainly caused by inhaled allergen‐induced improper activation and responses of immune and non‐immune cells. One important response is the production of IL‐27 by macrophages and dendritic cells (DCs) during the early stage of airway allergies. IL‐27 exerts powerful modulatory influences on the cells of innate immunity [eg neutrophils, eosinophils, mast cells, monocytes, macrophages, dendritic cells (DCs), innate lymphoid cells (ILCs), natural killer (NK) cells and NKT cells)] and adaptive immunity (eg Th1, Th2, Th9, Th17, regulatory T, CD8+ cytotoxic T and B cells). The IL‐27‐mediated signalling pathways may be modulated to attenuate asthma and allergic rhinitis. In this review, a comprehensive discussion concerning the roles carried out by IL‐27 in asthma and allergic rhinitis was provided, while evidences are presented favouring the use of IL‐27 in the treatment of airway allergies. [ABSTRACT FROM AUTHOR]

Biologic agents, monoclonal antibodies that target highly-specific molecular pathways of inflammation, are becoming integrated into care pathways for multiple disorders that are relevant in otolaryngology and allergy. These conditions share common inflammatory mechanisms of so-called Type 2 inflammation with dysregulation of immunoglobulin E production and eosinophil and mast cell degranulation leading to tissue damage. Biologic agents are now available for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, eosinophilic granulomatosis with polyangiitis (EGPA), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). This paper summarizes the diagnosis and management of these conditions and critically reviews the clinical trial data that has led to regulatory approval of biologic agents for these conditions. [ABSTRACT FROM AUTHOR]

Background: Asthma is heterogeneous disease with different phenotypes, endotypes and severities. Definition of these subgroups requires the identification of biomarkers in biological samples, and serum proteomics is a useful and minimally invasive method for this purpose. Therefore, the aim of this study was to detect serum proteins whose abundance is distinctively associated with different asthma phenotypes (allergic vs nonallergic) or severities. Methods: For each group of donors (32 healthy controls, 43 allergic rhinitis patients and 192 asthmatics with different phenotypes and severities), we generated two pools of sera that were analysed by a shotgun MS approach based on combinatorial peptide ligand libraries and iTRAQ‐LC‐MS/MS. Results: MS analyses identified 18 proteins with a differential abundance. Functional/network study of these proteins identified key processes for asthma pathogenesis, such as complement activation, extracellular matrix organization, platelet activation and degranulation, or post‐translational protein phosphorylation. Furthermore, our results highlighted an enrichment of the "Regulation of Insulin‐like Growth Factor (IGF) transport and uptake by Insulin‐like Growth Factor Binding Proteins (IGFBPs)" route in allergic asthma and the lectin pathway of complement activation in nonallergic asthma. Thus, several proteins (eg IGFALS, HSPG2, FCN2 or MASP1) displayed a differential abundance between the different groups of donors. Particularly, our results revealed IGFALS as a useful biomarker for moderate‐severe allergic asthma. Conclusion: Our data suggest a set of serum biomarkers, especially IGFALS, capable of differentiating allergic from nonallergic asthma. These proteins reveal different pathophysiological mechanisms and may be useful in the future for diagnosis, prognosis or targeted therapy purposes. [ABSTRACT FROM AUTHOR]

Background and Purpose: Epidemiological and experimental studies suggest that microbial exposure in early childhood is linked with reduced risk to suffer asthma. Thus microbial components with immunoregulatory capabilities might serve as a preventive strategy for allergic asthma. Recently, it was identified that Streptococcus pneumoniae aminopeptidase N (PepN) could suppress T cell effector function. We sought to investigate the effect of PepN on murine allergic asthma and elucidate the underlying mechanism. Experimental Approach The effects of intranasal administration of PepN during or before sensitization were examined in ovalbumin (OVA)‐induced murine allergic asthma. The roles of CD11b+ dendritic cells in PepN treated OVA‐induced allergic asthma were evaluated by flow cytometry, cytokines detection and adoptive transfer. Moreover, the numbers of lung type 2 innate lymphoid cells (ILC2s) were also detected. Key Results: Administration of PepN during or before sensitization attenuated type‐2 airway inflammation (eosinophilia, mucus hypersecretion, Th2 cytokines production and IgE production) in allergic asthma mice. PepN reduced lung accumulation of CD11b+ dendritic cells, which was accompanied by diminished dendritic cell‐attracting chemokine CCL20 production as well as CCL17 and CCL22, which are Th2‐cell chemokines predominantly produced by CD11b+ dendritic cells. Adoptive transfer of BM‐derived CD11b+ dendritic cells abolished the inhibitory effect of PepN on OVA‐induced type‐2 airway inflammation. The numbers of lung ILC2s were decreased in asthmatic mice receiving PepN. Conclusion and Implications: PepN alleviated type‐2 inflammation in OVA‐induced allergic asthma mice, which was mediated by regulation of lung CD11b+ dendritic cells. Our study provides a novel strategy for the prevention of allergic asthma. [ABSTRACT FROM AUTHOR]

Tris(2‐butoxyethyl) phosphate (TBEP) is a major organophosphorus flame retardant and has been widely increasing as a substitute for brominated flame retardants. TBEP may have adverse effects on human health; however, its impact on immune and allergic responses remains largely uncharacterized. In this study, the effects of low‐dose TBEP comparable with the level of actual human exposure to that of human tolerable daily intake on allergic asthmatic mice were explored. Five‐week‐old C3H/HeJSlc male mice consumed a diet containing approximately 0.02, 0.2 or 2 μg/kg/day TBEP and were intratracheally administrated ovalbumin (OVA) (1 μg/mouse every 2 weeks from 5 to 11 weeks of age). Exposure to 2 μg/kg/day TBEP with OVA tended to enhance allergic pulmonary inflammation and significantly elevated mRNA levels of interleukin‐5, eotaxin‐1 and estrogen receptor alpha (ERα) compared with OVA alone. In mediastinal lymph nodes (MLNs), TBEP (0.2 or 2 μg/kg/day) with OVA significantly increased in total cell number and promoted conventional dendritic cell activation than OVA alone; MLN cell proliferation by OVA restimulation was also enhanced in these groups. In the bone marrow (BM), TBEP (0.02 or 0.2 μg/kg/day) with OVA resulted in a net decrease in total cell number and fraction of CCR2+Gr‐1+ cells; the fraction of Gr‐1+ cells increased. In conclusion, oral exposure to low‐dose TBEP levels equivalent to tolerable daily intake may exacerbate allergic pulmonary inflammation by promoting a skewed T‐helper 2 cell response, upregulation of ERα and dysregulation of both MLN and BM microenvironments. We investigated the effects of oral exposure to low‐dose tris(2‐butoxyethyl) phosphate (TBEP) on allergic asthma mice. TBEP slightly enhanced allergic pulmonary inflammation via increase in the mRNA levels of interleukin‐5, eotaxin‐1 and estrogen receptor alpha. In mediastinal lymph nodes, TBEP + ovalbumin significantly increased total cell number and promoted conventional dendritic cell activation and allergen‐restimulated cell proliferation. Furthermore, there was slight dysregulation in the bone marrow microenvironments. Oral exposure to low‐dose TBEP levels equivalent to tolerable daily intake may exacerbate allergic responses. [ABSTRACT FROM AUTHOR]

Keywords: allergic asthma; biomarker; inhaled corticosteroid; MRGPRX2; prognosis EN allergic asthma biomarker inhaled corticosteroid MRGPRX2 prognosis 959 962 4 04/23/20 20200401 NES 200401 To the Editor, Allergic asthma, the most common phenotype of asthma, is clinically defined by the presence of allergic sensitization and a correlation between asthma symptoms and allergen exposure.[[1]] Although several biomarkers for allergic asthma have been proposed, their role in reflecting treatment efficacy is controversial.[[3]] Mas-related G protein-coupled receptor-X2 (MRGPRX2), expressed in mast cells, is an endogenous receptor associated with IgE-independent activation of mast cells. Serum MRGPRX2 levels in allergic asthma patients according to (B) required ICS dose, and (C) asthma control status according to ICS response. Additionally, high levels of MRGPRX2 were significantly associated with allergic asthma requiring moderate-to-high ICS doses and those with good responses (well-controlled) to ICS for the 12-month follow-up period (especially those with MRGPRX2 value >= 100 ng/mL). [Extracted from the article]

Background: The prevalence and severity of asthma, particularly the most common (atopic) form of the disease, increase amongst females but not males after puberty, and asthma activity also changes throughout the menstrual cycle and during pregnancy. The contribution of female sex hormones to asthma pathogenesis is incompletely understood. Objective: To obtain insight into the role of oestrogen (E2) in experimental atopic asthma, and guide future research on sex‐related variations in atopic asthma susceptibility/intensity in humans. Methods: We utilized an experimental model comprising rat strains expressing dichotomous Th2‐high vs Th2‐low immunophenotypes exemplified by eosinophilia, mirroring differences between human atopics/non‐atopics. We compared the efficiency of Th2‐associated immunoinflammatory mechanisms, which differed markedly between the two strains, and between sexes in the Th2‐high strain, and determined the effects of E2 administration on these differences. Results: Unique to the Th2‐high strain, eosinophil: neutrophil ratios in the airways at baseline and following sensitization/aeroallergen challenge were logfold higher in females relative to males, and this was reflected by higher baseline blood eosinophil numbers in females. Pretreatment of Th2‐high males with E2 abrogated this sex difference by selectively boosting Th2‐associated genes in the airways and eosinophilia, but was without corresponding effect in the Th2‐low strain. In contrast, parallel E2 effects on myeloid and lymphoid cell populations were relatively modest. Conclusions and Clinical Relevance: E2 acts to amplify the eosinophilic component of pre‐existing Th2‐high immunophenotype, possibly acting at the level of the common eosinophil/neutrophil precursor in bone marrow to preferentially drive eosinophil differentiation. Constitutive granulocyte profiles in which the balance between eosinophils and neutrophils is skewed towards eosinophils have been identified in independent cohort studies as markers of asthma risk, and these findings suggest that more detailed studies on the role of E2 in this context, and in relation to asthma pathogenesis in post‐pubertal females in particular, appear warranted. [ABSTRACT FROM AUTHOR]

We evaluated the effects of L-PBM using a 610 nm LED in an ovalbumin (OVA)-induced mouse model of allergic asthma and compared them with those of dexamethasone (DEX), a corticosteroid typically used to treat asthma. GLO:1X5/01jan20:all13929-fig-0001.jpg PHOTO (COLOR): Inhibitory effect of L-PBM on ovalbumin (OVA)-induced airway inflammation. To examine the effects of L-PBM on airway inflammation induced by OVA exposure, total and differential cells in the bronchoalveolar lavage fluid (BALF) of mice were determined. Noteworthy, contrary to L-PBM, DEX did not change the collagen deposition and airway smooth muscle thickness increased by OVA. [Extracted from the article]

Airway inflammation, allergic asthma, Notch4 receptor, Th2 cell, Treg cell They discovered that the deletion of Notch4 in Treg cells in mice suppressed ovalbumin-specific IgE production along with lung tissueTh2 and Th17 cell responses. Keywords: airway inflammation; allergic asthma; Notch4 receptor; Th2 cell; Treg cell EN airway inflammation allergic asthma Notch4 receptor Th2 cell Treg cell 3852 3854 3 12/01/21 20211201 NES 211201 Abbreviations AMs alveolar macrophages GDF15 cytokine growth and differentiation factor 15 IL interleukin IL-4R interleukin-4 receptor IL-6R interleukin-6 receptor ILC2s type 2 innate lymphoid cells Th T helper Treg cells regulatory T cells UFPs pollutant ultrafine particles Asthma is a chronic inflammatory disease of the airways that causes bronchial hyperreactivity, mucus overproduction, airway remodeling, and narrowing. [Extracted from the article]

The seventh "Future of the Allergists and Specific Immunotherapy (FASIT)" workshop held in 2019 provided a platform for global experts from academia, allergy clinics, regulatory authorities and industry to review current developments in the field of allergen immunotherapy (AIT). Key domains of the meeting included the following: (a) Biomarkers for AIT and allergic asthma; (b) visions for the future of AIT; (c) progress and data for AIT in asthma and the updates of GINA and EAACI Asthma Guidelines (separated for house dust mite SCIT, SLIT tablets and SLIT drops; patient populations) including a review of clinically relevant endpoints in AIT studies in asthma; (d) regulatory prerequisites such as the "Therapy Allergen Ordinance" in Germany; (e) optimization of trial design in AIT clinical research; (f) challenges planning and conducting phase III (field) studies and the future role of Allergen Exposure Chambers (AEC) in AIT product development from the regulatory point of view. We report a summary of panel discussions of all six domains and highlight unmet needs and possible solutions for the future. [ABSTRACT FROM AUTHOR]

Helminths and their products can shape immune responses by modulating immune cells, which are dysfunctional in inflammatory diseases such as asthma. We previously identified SJMHE1, a small molecule peptide from the HSP60 protein of Schistosoma japonicum. SJMHE1 can inhibit delayed‐type hypersensitivity and collagen‐induced arthritis in mice. In the present study, we evaluated this peptide's potential intervention effect and mechanism on ovalbumin‐induced asthma in mice. SJMHE1 treatment suppressed airway inflammation in allergic mice, decreased the infiltrating inflammatory cells in the lungs and bronchoalveolar lavage fluid, modulated the production of pro‐inflammatory and anti‐inflammatory cytokines in the splenocytes and lungs of allergic mice, reduced the percentage of Th2 cells and increased the proportion of Th1 and regulatory T cells (Tregs). At the same time, Foxp3 and T‐bet expression increased, and GATA3 and RORγt decreased in the lungs of allergic mice. We proved that SJMHE1 can interrupt the development of asthma by diminishing airway inflammation in mice. The down‐regulation of Th2 response and the up‐regulation of Th1 and Tregs response may contribute to the protection induced by SJMHE1 in allergic mice. SJMHE1 can serve as a novel therapy for asthma and other allergic or inflammatory diseases. [ABSTRACT FROM AUTHOR]

The direct effect of MSCs on CD4 SP + sp T cells was defined by using purified CD4 SP + sp T cells (Figure S2). To test the effect of pcMSCs on low-reactive T cells above commented, we obtained low-reactive T cells by reducing the plating density of PBMCs from healthy subjects. Allergic asthma, autoimmune disease, children, mesenchymal stem cells, T cells. [Extracted from the article]