Immunotherapy In Asthma Research Articles

Cathepsin B-Activatable Bioactive Peptide Nanocarrier for High-Efficiency Immunotherapy of Asthma.

Asthma, a chronic respiratory disease closely associated with inflammation, presents ongoing treatment challenges. IALLIPF (le-Ala-Leu-Leu-Ile-Pro-Phe) is one of millet prolamins peptides (MPP) which shows anti-oxidant bioactivity by reducing the production of reactive oxygen species (ROS). Tryptophan (Trp, W) is an amino acid that has been demonstrated to possess anti-inflammatory effects. We introduce a novel cathepsin B-activatable bioactive peptides nanocarrier, PEG-IALLIPF-GFLG-W (MPP-Trp), designed for immunotherapy of asthma. MPP-Trp is synthesized, purified, and its characteristics are investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The yield of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) are examined to evaluate anti-inflammatory effects of IALLIPF, Trp and MPP-Trp. The immunomodulatory effects of IALLIPF, Trp and MPP-Trp on Th1/Th2 cell populations and cytokines are investigated by flow cytometry, qRT-PCR and ELISA assays. We explore the therapeutic effect of MPP-Trp in the mouse model of asthma by the analysis of lung histology and ELISA. It is necessary to study the biocompatibility of MPP-Trp by CCK8 assay and histopathologic analysis using hematoxylin and eosin (HE) staining. In asthmatic peripheral blood mononuclear cells (PBMCs), IALLIPF, Trp and MPP-Trp are able to significantly alleviate inflammation by inhibiting the yield of nitric oxide (NO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), especially MPP-Trp. MPP-Trp significantly upregulates Th1 cell levels while notably reducing Th2 cell levels. Furthermore, MPP-Trp effectively elevates the expression and production of interferon-gamma (IFN-γ), an essential cytokine from Th1 cells. Additionally, MPP-Trp markedly diminishes the mRNA expression and levels of key asthma pathogenesis cytokines, such as interleukin-4 (IL-4), interleukin-13 (IL-13), and interleukin-5 (IL-5), in asthma PBMCs. MPP-Trp ameliorates pulmonary pathological alterations and significantly inhibits OVA-induced inflammation in mice with asthma. It has little influence on the cell viability in Asthma-PBMCs treated with various concentrations or durations of MPP-Trp. No pathological changes, including in the heart, liver, spleen, lung, and kidney tissues, are observed in non-sensitized and non-challenged mice treated with MPP-Trp (20 mg/kg). Our research demonstrates that MPP-Trp has immunomodulatory effects on Th1/Th2 cell populations, essential in managing asthma. It considerably alleviates OVA-induced asthma by shifting the immune response towards a Th1-dominant profile, thereby reducing Th2-driven inflammation. Therefore, this novel bioactive peptide nanocarrier, MPP-Trp, holds promise as a candidate for asthma immunotherapy.

Genetic and T2 biomarkers linked to the efficacy of HDM sublingual immunotherapy in asthma

BackgroundHypersensitivity to house dust mite (HDM) allergens is a common cause of allergic asthma symptoms and can be effectively treated with allergy immunotherapy (AIT).ObjectiveTo investigate whether genetic and type 2...

Progressive clinical effects of the combination omalizumab and HDM – allergen immunotherapy in asthma

Objective The combination of allergen immunotherapy (AIT) and omalizumab is used to treat patients at risk of anaphylaxis. There is currently a very little evidence that this combination increases the effectiveness of AIT in patients with inhalant allergies. The study aimed to evaluate the effectiveness of HDM-SCIT therapy (injection immunotherapy for house dust mites) in combination with omalizumab in treating HDM-induced asthma. Methods This study was a placebo-controlled, randomized, multicenter trial including 82 patients with HDM-driven mild to moderate asthma. Omalizumab alone (A), HDM SCIT + omalizumab (B), SCIT alone (C), or placebo (D) for 24 months were applied. All patients received asthma treatment in accordance with GINA recommendations. The treatment efficacy was defined by a reduction in the daily dose of inhaled steroids (ICS) and a reduction in the number of asthma exacerbations (AX). Results After 24 months of therapy, a statistically significant reduction in the daily doses of ICS in groups A and B was observed (p = 0.021 and p = 0.008). Daily ICS reduction was considerably more significant in group B (p = 0.01). During 24 months of observation, the AX was significantly reduced in all study groups, with the greatest significant difference observed between groups A and B and groups C and D (placebo) as follows: 0.42 patient/per year vs. 0.39 vs. 0.84 vs. 0.91 (p = 0.023). Conclusion The combination of HDM SCIT and omalizumab is significantly and progressively reducing ICS use and AX in a 24-month study. The combination is significantly more effective than the single treatments or placebo.

Allergic Asthma Immunotherapy and Nursing Care

Allergic Asthma Immunotherapy and Nursing Care

Predicting the therapeutic efficacy of AIT for asthma using clinical characteristics, serum allergen detection metrics, and machine learning techniques

Bronchial asthma is a prevalent non-communicable disease among children. The study collected clinical data from 390 children aged 4–17 years with asthma, with or without rhinitis, who received allergen immunotherapy (AIT). Combining these data, this paper proposed a predictive framework for the efficacy of mite subcutaneous immunotherapy in asthma based on machine learning techniques. Introducing the dispersed foraging strategy into the Salp Swarm Algorithm (SSA), a new improved algorithm named DFSSA is proposed. This algorithm effectively alleviates the imbalance between search speed and traversal caused by the fixed partitioning pattern in traditional SSA. Utilizing the fusion of boosting algorithm and kernel extreme learning machine, an AIT performance prediction model was established. To further investigate the effectiveness of the DFSSA-KELM model, this study conducted an auxiliary diagnostic experiment using the immunotherapy predictive medical data collected by the hospital. The findings indicate that selected indicators, such as blood basophil count, sIgE/tIgE (Der p) and sIgE/tIgE (Der f), play a crucial role in predicting treatment outcome. The classification results showed an accuracy of 87.18% and a sensitivity of 93.55%, indicating that the prediction model is an effective and accurate intelligent tool for evaluating the efficacy of AIT.

A review of allergen immunotherapy in asthma.

Asthma is one of the most common chronic diseases worldwide. Besides symptomatic treatments, allergen immunotherapy (AIT) is a possible add-on treatment for asthmatic patients. In case of an immunologically proven allergen-driven mechanism of asthma, AIT represents the only etiologic treatment for allergic symptoms. AIT has proven both its efficacy and effectiveness in reducing asthma symptoms and asthma medications. It is still debated whether its prescription in severe asthmatic patients is allowed and safe. As for uncontrolled asthma, such a condition should be considered temporary, and AIT may be started as asthma becomes at least partially controlled after treatment adjustment. Finally, randomized trials and real-life studies in recent years have proven that AIT could be administered as a preventive strategy to reduce the risk of developing asthma in patients suffering from allergic rhinitis. More studies are needed to provide more precise indications on the role in clinical practice of AIT in asthmatic patients. Nevertheless, present data are already strong enough to highlight its role as a therapeutic option for allergic asthma and as a preventive strategy to stop or at least decelerate the allergic march.

Immunotherapy for Asthma.

Asthma represents one of the biggest global health concerns with increasing prevalence and influence on global health. Several distinct asthma phenotypes have been identified with one of the most common, earliest recognized, and described being the allergic asthma phenotype, in which allergens trigger asthma through mechanisms involving allergen-specific immunoglobulin E (IgE). Allergen-specific immunotherapy (AIT), in the forms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), has been used for many decades as a tool for reducing IgE-mediated sensitization and controlling symptoms of allergic disease, most commonly for allergic rhinitis, and it remains the only currently available disease modifying therapy in atopic patients. AIT has been studied for use in mild to moderate allergic asthma. While the data are often inconsistent, and utilize a multitude of different methods, antigens, and outcome measures, in general, AIT may have several beneficial effects on asthma disease control, quality of life, and requirement for medication. These benefits are notable when immunotherapy is used as an adjunct to pharmacologic treatment in carefully selected and monitored patients with mild to moderate persistent asthma. Patients with severe asthma are excluded from these trials. Importantly, patients with asthma, and in particular severe asthma, may have a higher rate of systemic adverse reactions to SCIT, including anaphylaxis; however, these events are overall rare. Future research in the area is needed to definitively assess the benefit of SCIT and SLIT for patients with asthma, comparing outcomes with different methods, addressing the role of AIT in severe asthma, significance of multiallergen AIT in allergic asthma, and safety concerns in asthma.

GITRL on dendritic cells aggravates house dust mite-induced airway inflammation and airway hyperresponsiveness by modulating CD4+ T cell differentiation

BackgroundGlucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) plays an important role in tumors, autoimmunity and inflammation. However, GITRL is not known to modulate the pathogenesis of allergic asthma. In this study, we investigated whether regulating GITRL expressed on dendritic cells (DCs) can prevent asthma and to elucidate its mechanism of action.MethodsIn vivo, the role of GITRL in modulating house dust mite (HDM)-induced asthma was assessed in adeno-associated virus (AAV)-shGITRL mice. In vitro, the role of GITRL expression by DCs was evaluated in LV-shGITRL bone marrow dendritic cells (BMDCs) under HDM stimulation. And the direct effect of GITRL was observed by stimulating splenocytes with GITRL protein. The effect of regulating GITRL on CD4+ T cell differentiation was detected. Further, GITRL mRNA in the peripheral blood of asthmatic children was tested.ResultsGITRL was significantly increased in HDM-challenged mice. In GITRL knockdown mice, allergen-induced airway inflammation, serum total IgE levels and airway hyperresponsiveness (AHR) were reduced. In vitro, GITRL expression on BMDCs was increased after HDM stimulation. Further, knocking down GITRL on DCs partially restored the balance of Th1/Th2 and Th17/Treg cells. Moreover, GITRL stimulation in vitro inhibited Treg cell differentiation and promoted Th2 and Th17 cell differentiation. Similarly, GITRL mRNA expression was increased in the peripheral blood from asthmatic children.ConclusionsThis study identified a novel role for GITRL expressed by DCs as a positive regulator of CD4+ T cells responses in asthma, which implicates that GITRL inhibitors may be a potential immunotherapy for asthma.

Safety, Efficacy, and Preventive Role of Subcutaneous and Sublingual Allergen Immunotherapy for the Treatment of Pediatric Asthma.

Allergen-specific immunotherapy is currently the only treatment with the potential to modify and prevent progression of allergic asthma in children. In clinical practice, it is available in two forms: subcutaneous immunotherapy and sublingual immunotherapy. Trials and meta-analyses showed both the safety and the short- and long-term benefits of allergen-specific immunotherapy in asthmatic children. However, its use and role in asthma remains controversial, since studies are largely heterogeneous. This is mainly due to the lack of consensus on the optimal primary outcome to be considered for clinical trials evaluating the efficacy of allergen-specific immunotherapy in asthma. Therefore, well-conducted researchis needed using standardized and validated tools to evaluate key outcomes in asthmatic children.

Advances in allergen immunotherapy for asthma.

Allergen immunotherapy (AIT) is a well-known disease-modifying intervention for allergic diseases. Its benefit in allergic asthma, ranging from prevention to facilitating asthma control, is yet to be clarified. In 2017, following several well-designed randomised controlled trials (RCTs) with house-dust mites (HDM) sublingual (SLIT) tablets in asthma, global initiative for asthma (GINA) guidelines highlighted the need to treat the allergic component of asthma. In 2019, the European Academy of Allergy and Clinical Immunology published the first comprehensive guidelines for HDM AIT in allergic asthma, formulating separate recommendations for subcutaneous, SLIT drops, and SLIT tablets. Significant steps were undertaken in understanding the mechanisms of allergic asthma, facilitating the stratified approach for selecting responders and in translating the immune-modulation effect in achieving long-term control of the chronic inflammation in asthma. Currently existing guidelines recommend AIT as a therapeutic option in controlled or partially controlled HDM allergic asthma. Limited data are available for pollen, molds and pets, as well as for the severe allergic asthma population. The challenge for the future research will be to clarify the subendotypes of allergic asthma responding to AIT, the mechanisms facilitating its' preventive and disease-modifying effect, the optimal duration of the treatment, and route of administration.

Asthma immunotherapy and treatment approaches with mesenchymal stem cells.

Asthma is a chronic inflammatory disease of the airways where exaggerated T helper 2 immune responses and inflammatory mediators play a role. Current asthma treatment options can effectively suppress symptoms and control the inflammatory process; however, cannot modulate the dysregulated immune response. Allergen-specific immunotherapy is one of the effective treatments capable of disease modification. Injecting allergens under the skin in allergen-specific immunotherapy can reduce asthma and improve the sensitivity of the lungs, however, has a risk of severe reactions. Mesenchymal stem cells have immunoregulatory activity with their soluble mediators and contact dependent manner. In this review, we focus on the current treatment strategies with mesenchymal stem cells in asthma as a new therapeutic tool and compare those with immunotherapy.

Subcutaneous allergen immunotherapy for asthma: A randomized, double-blind, placebo-controlled study with a standardized Blomia tropicalis vaccine

BackgroundSensitization to Blomia tropicalis (Bt) is very frequent in the tropics, and particularly in Cuba, being a significant cause of allergic asthma. Allergen immunotherapy (AIT) with Bt can be a therapeutic option, however, placebo-controlled clinical trials have not been reported. ObjectiveTo assess the therapeutic effect and safety of AIT for asthma using a standardized allergen vaccine of B. tropicalis by subcutaneous route, in allergic asthmatic patients exposed and sensitized to this mite species. MethodsA double-blind, placebo-controlled Phase II trial was conducted in 35 adults (18 with treatment and 17 with placebo), with mild to moderate asthma, predominantly sensitized to Bt. AIT was administered subcutaneously in increasing doses from 4 to 6000 Biological Units using a locally manufactured standardized extract (BIOCEN, Cuba). Patient assessment was performed using symptom-medication score (SMS), peak expiratory flow and skin reactivity relative to Histamine as measured by skin prick test (SPT). ResultsThe 12-month treatment achieved a significant (p < 0.001) decrease of SMS. Symptom score showed only 41% (CI: 26–61) of placebo values, whereas medication was 34.5% (22.4%–63.3%). Treatment was regarded clinically effective in 67% of patients (OR 32; 95%CI: 17 to 102). The effect size on symptoms and medication was higher than has been reported with equivalent allergen dosages of D. pteronyssinus and D. siboney in Cuban asthmatic patients. Skin reactivity to Bt was also significantly reduced (p = 0.0001), increasing 148-fold the allergen threshold to elicit a positive skin test. This desensitization effect was specific to Bt and did not modify the reactivity to Dermatophagoides. The change of specific skin reactivity was significantly (p < 0.05) correlated to clinical improvement. All adverse events were local with a frequency of 2.4% of injections. ConclusionsSubcutaneous AIT with Blomia tropicalis was effective and safe in asthmatic adults exposed and sensitized to this mite species in a tropical environment. Trial registrationCuban Public Registry of Clinical Trials: RPCEC00000026 (WHO International Clinical Trial Registry Platform ICTRP).

Tryptophan metabolite-regulated Treg responses contribute to attenuation of airway inflammation during specific immunotherapy in a mouse asthma model

ABSTRACT In allergen-specific immunotherapy for asthma, antigens attached to dendritic cells increase the tryptophan metabolism in these cells and alter the Th17/Treg balance in the airways. Tryptophan metabolism has long been suggested to be relevant in the pathophysiology of allergic disorders, including asthma. Our study investigated whether tryptophan metabolites are responsible for the changes in Th17/Treg balance and decreases in airway hyperreactivity and inflammation seen during allergen-specific immunotherapy in an asthma model. Ovalbumin was injected intraperitoneally into mice to establish an asthma model, and then high dose ovalbumin allergen-specific immunotherapy was administered to induce immune tolerance. Airway hyperreactivity and serum ovalbumin-specific immunoglobulin E were measured to assess whether the animal model was successfully established. We then examined the influence of inhibition of tryptophan metabolism and the addition of tryptophan metabolites on allergen-specific immunotherapy-induced changes in the Th17/Treg balance and decreases in airway inflammation and inflammatory cytokines. Production of tryptophan metabolites was partly responsible for the allergen-specific immunotherapy-induced increase in Tregs, decrease in airway inflammation, and decrease in inflammatory cytokines. Ovalbumin-specific immunoglobulin E and airway hyperreactivity were not affected. In the context of asthma, an increase in tryptophan metabolites is one of the mechanisms by which allergen-specific immunotherapy achieves immune tolerance.

Green propolis increases myeloid suppressor cells and CD4+Foxp3+ cells and reduces Th2 inflammation in the lungs after allergen exposure

Ethnopharmacological relevancePropolis is a natural product produced by honeybees used as a medicine at least to 300 BC. In the last decades, several studies showed biological and pharmacological properties of propolis, witch scientifically explains the empirical use for centuries. The anti-inflammatory activity of propolis with the purpose to reduce Th2 inflammation has been evaluated in allergic asthma. However, it remains to be determined how propolis negatively regulates the immune response after allergen re-exposure. Aim of the studyWe hypothesized that the anti-inflammatory activity of propolis is dependent on the induction of myeloid derived suppressor cells (MDSC) and regulatory T cells. Materials and methodsTo assess this hypothesis, we used an ovalbumin-induced asthma model to evaluate the effect of EPP-AF® dry extract from Brazilian green propolis. ResultsPropolis treatment decreased pulmonary inflammation and mucus production as well as eosinophils and IL-5 in the broncoalveolar lavage. Propolis enhanced also in vitro differentiation and in vivo frequency of lung MDSC and CD4+Foxp3+ regulatory T cells. ConclusionsTogether these results confirm the immunomodulatory potential of propolis during sensitization and challenge with allergen. In addition, the collecting findings show, for the first time, that propolis increases the frequency of MDSC and CD4+Foxp3+ regulatory T cells in the lungs, and suggest that it could be use as target for development of new immunotherapy or adjuvant immunotherapy for asthma.

Allergen Immunotherapy for asthma in a public healthcare setting: The Cuban experience

Allergen Immunotherapy for asthma in a public healthcare setting: The Cuban experience

Safety of subcutaneous allergen immunotherapy in children: A retrospective review and bird eye to literature.

Toprak-Kanık E, Yılmaz Ö, Yangın-Ergon E, Türkeli A, Yüksel H. Safety of subcutaneous allergen immunotherapy in children: A retrospective review and bird eye to literature. Turk J Pediatr 2018; 60: 684-690. Subcutaneous allergen immunotherapy (SCIT) has been shown to improve clinical course in children with asthma and allergic rhinitis (AR). Systemic and local side-effects may be seen during its administration. The purpose of this study was to evaluate risk factors associated with systemic and local side-effects in children receiving SCIT. We performed a retrospective chart review in the children who received allergen subcutaneous immunotherapy for asthma and/or allergen rhinitis. Demographic data, diagnosis, skin prick test results, presence of additional allergic diseases, the seasonal variation of adverse events in the first and third years of SCIT were recorded. A total of 508 eligible patients were included in the study. Mean age of the children was 10.9±3.2 years, and 65.4% were male. Asthma was present in 21.9% of the children, AR in 44.7%, 33.5% of them had both asthma and AR. According to the skin prick test results, sensitivity to more than one allergen was present in 45.1%, while the most common single-allergen sensitivities were to grass pollen and dermatophagoids (32.5% and 14.4%, respectively). Ratio of systemic and local side-effects was 4.7% and 9.3%, respectively. Local side-effects were more common than systemic reaction. SCIT is a safe treatment modality while using the appropriate dose and with the administration of dose-escalation protocol.

Applicability of evidence from previous systematic reviews on immunotherapy in current practice of childhood asthma treatment: a GRADE (Grading of Recommendations Assessment, Development and Evaluation) systematic review

ObjectiveBecause most children with asthma now use inhaled corticosteroids (ICS), the added benefit of immunotherapy in asthmatic children needs to be examined. We re-assessed the effectiveness of subcutaneous (SCIT) and...

Economic consequences in real life of allergen immunotherapy in asthma, rhinitis and dermatitis

Allergen immunotherapy has proved effective in the treatment of various allergies, but whether the clinical benefits outweigh the economic costs has been little evaluated. To explore the economic consequences of immunotherapy in asthma, rhinitis and dermatitis. Descriptive study. Patients with at least 18 months' follow-up were selected, whose medical history allowed evaluation of drugs received, manner of use, check-ups, treatment changes, reasons for these, and so on. Patients were classified according to whether they received drug treatment + immunotherapy (active group) or drug therapy alone (control group). 1848 patients were included: 648 in the active group and 1200 in the control. Immunotherapy increased the cost of treatment during the first few months, but after 9 to 12 months drug treatment decreased significantly compared to the control group. In patients with asthma or various diseases, immunotherapy reduced costs of treatment (p < 0.05). The active group saw fewer relapses at 18 months (p < 0.05). Allergen immunotherapy allows the sustained reduction in drug treatment, with medium-term financial savings for the patient and the health system.

Safety of sublingual immunotherapy for asthma with standardized house dust mite vaccines in a tropical setting: Results of a nation-wide pharmacovigilance study

Background Pharmacovigilance studies are helpful to follow the use of allergen immunotherapy in clinical practice. Industrially manufactured allergen vaccines (VALERGEN) of three mite species (including the tropical species Dermatophagoides siboney and Blomia tropicalis) have been recently introduced country-wide in Cuba for asthma treatment. To assess the safety and efficacy of allergen immunotherapy by injection or sublingual routes, using VALERGEN vaccines in the routine clinical practice.

Cockroach allergy and allergen-specific immunotherapy in asthma: potential and pitfalls.

To provide a summary and discussion of cockroach allergy and clinical trials of cockroach allergen immunotherapy. Cockroach allergen exposure among sensitized children is increasingly recognized as a key factor contributing to asthma morbidity. Recent trials suggest that cockroach immunotherapy holds promise as a treatment strategy with studies demonstrating immunomodulatory and clinical effects. However, a few obstacles need to be overcome to realize the full potential of this treatment modality as cockroach-allergic patients often exhibit complex sensitization patterns to multiple cockroach-associated proteins, and an immunodominant allergen has not been identified. These factors have made it difficult to produce standardized cockroach allergen extracts that are potent and provide the broad allergen profiles needed for optimal treatment. There have been important advances in the identification and cloning of cockroach allergens, and several strategies are being developed to provide therapeutic cockroach allergen products with enhanced clinical efficacy. Allergen immunotherapy has the capability of modulating the immune response to cockroach allergen and has potential as a valuable treatment modality. Further studies of the clinical efficacy, along with the development of improved therapeutic products, are needed to advance our knowledge and realize the full potential of this promising therapy.