Immunotherapy For Allergic Asthma Research Articles

Biomarkers for house dust mite subcutaneous immunotherapy in allergic asthma

BackgroundAllergen immunotherapy (AIT) has demonstrated clinical efficacy in patients with allergic asthma. However, there is little information on biomarkers to evaluate the effect of house dust mite (HDM) subcutaneous immunotherapy (SCIT) on allergic asthma. ObjectiveTo evaluate the association between clinical outcomes with pulmonary function and biomarkers in before and after HDM SCIT. Methods139 patients with asthma sensitized to HDM were recruited, 75 subjects received SCIT as an add-on therapy to drug treatment, and 64 subjects received drug treatment alone. Spirometry, fractional exhaled nitric oxide (FeNO), blood eosinophil counts, total IgE (TIgE), serum specific IgE for HDM, and frequency of exacerbations (ACT scores) were measured at baseline, 6 months, and 12 months. The relationship between biomarkers and pulmonary function improvement was investigated. ResultsSCIT demonstrated a significant reduction in FeNO, serum IL-25 and ACT scores at 6 months and significantly improved airflow limitation at 12 months compared to pharmacotherapy. The changes in FEV1 were dramatically correlated with changes in blood eosinophils ( r =-0.35, P=0.002), FeNO ( r =-0.57, P＜0.0001), serum IL-25 ( r =-0.68, P＜0.0001) and ACT scores( r =0.562, P＜0.0001). The multivariate regression analysis revealed that the changes in serum IL-25 concentration and FeNO were independently associated with an increase in FEV1 (r2 = 0.514, P < 0.05, respectively) in patients with allergic asthma treated with HDM SCIT. ConclusionsAdding HDM SCIT to pharmacotherapy reduced serum IL-25 and FeNO and improved pulmonary function in allergic asthma. Serum IL-25 and FeNO may be useful biomarkers for predicting HDM SCIT in allergic asthma, even in the absence of significant improvement in airflow limitation.

Allergen immunotherapy for allergicasthma.

Remission is the goal of modern asthma treatment. Allergen immunotherapy (AIT) is an essential component in the armamentarium of personalized asthma therapy. Subcutaneous AIT (SCIT) or sublingual AIT (SLIT) offer the possibility to prevent asthma in patients with allergic rhinitis (reduction of the risk of developing asthma) and the possibility to achieve remission in patients with allergic asthma. Accordingly, AIT should always be considered in patients with asthma and a documented, clinically relevant allergy. However, precise phenotyping of the patient is an essential prerequisite for a success of AIT in asthma.

Allergen immunotherapy in allergic asthma

Allergen immunotherapy (AIT) is a specific treatment consisting of repeated administration of allergens with the aim of inducing immunological tolerance. It comprises two subtypes: subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). According to multiple studies, AIT improves the clinical symptoms, reduces airway hyperresponsiveness, improves asthma control and reduces the need for inhaled corticosteroids (ICS). In addition, this therapy is able to suppress sensitization to new allergens, and if given to patients with allergic rhinitis may even prevent the development of asthma. The effects caused by AIT may be visible for at least several years, even after the therapy has ended (Nakagome et al., 2021).

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.

Standardization of clinical outcomes used in allergen immunotherapy in allergic asthma: An EAACI position paper.

In allergic asthma patients, one of the more common phenotypes might benefit from allergen immunotherapy (AIT) as add-on intervention to pharmacological treatment. AIT is a treatment with disease-modifying modalities, the evidence for efficacy is based on controlled clinical trials following standardized endpoint measures. However, so far there is a lack of a consensus for asthma endpoints in AIT trials. The aim of a task force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) is evaluating several outcome measures for AIT in allergic asthma. The following domains of outcome measures in asthmatic patients have been evaluated for this position paper (PP): (i) exacerbation rate, (ii) lung function, (iii) ICS withdrawal, (iv) symptoms and rescue medication use, (v) questionnaires (PROMS), (vi) bronchial/nasal provocation, (vii) allergen exposure chambers (AEC) and (viii) biomarkers. Exacerbation rate can be used as a reliable objective primary outcome; however, there is limited evidence due to different definitions of exacerbation. The time after ICS withdrawal to first exacerbation is considered a primary outcome measure. Besides, the advantages and disadvantages and clinical implications of further domains of asthma endpoints in AIT trials are elaborated in this PP. This EAACI-PP aims to highlight important aspects of current asthma measures by critically evaluating their applicability for controlled trials 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.

EFFICACY AND SAFETY OF SUBLINGUAL IMMUNOTHERAPY IN ALLERGIC ASTHMA AMONG CHILDREN AND ADOLESCENTS INTERVENTIONAL STUDY

Background: bronchial asthma is a chronic inflam­matory disorder with bronchial hyper-responsiveness. Environmental exposure in sensitized individuals is a major inducer of Allergy-associated asthma in children and adults, sublingual immunotherapy (SLIT) leads to improvement in their pulmonary functions and asthma control. Objectives: To Evaluate the Efficacy and Safety of Sublingual Immunotherapy in Allergic Asthma among Children and Adolescents. Methods: A 12 months prospective, open, low Interventional, Randomized, Controlled, single-site Study (Egyptian company for production of vaccines, sera and drugs VACSERA, allergy, and immunology clinic) was conducted between March 29, 2016, and December 27, 2018. Four groups including 62 allergic asthmatics patients both children (n = 30), and adults (n = 32), evaluating SLIT for a single-allergen (i.e. house dust mite) for 12 months, Adults received either SLIT with the pharmacotherapy (n = 17), or pharmacotherapy alone (n = 15).Children received either SLIT with the pharmacotherapy (n = 14), or pharmacotherapy alone (n = 16). Physiological parameters (Spirometry), Asthma control Questionnaires, A complete blood picture including peripheral blood Eosinophilic count, and the environmental preventive therapy were done to all patients. Results: After 1-year treatment of patients treated with SLIT and pharmacotherapy, were compared with those who received pharmacotherapy alone. There was a significant improvement in asthma control score, a significant increase in actual FEV1, FVC in SLIT with the pharmacotherapy groups in adults and children when compared with pharmacotherapy alone. There was a significant decrease in the eosinophilic count when compared with patients treated with the pharmacotherapy alone. There is a significant difference between children and adults regarding the occurrence of adverse effects in the form of Local reaction not requiring treatment (mouth, throat, and skin; irritation/swelling/pain) reported in SLIT with the pharmacotherapy groups. Conclusion: patients treated with SLIT demonstrated clinical improvement compared with those who received pharmacotherapy in adult asthmatics and children sensitized to HDM.

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.

Association between biomarkers and house dust mite sublingual immunotherapy in allergic asthma.

House dust mite (HDM) sublingual immunotherapy (SLIT) has demonstrated efficacy in clinical trials of patients with asthma. Airway inflammation is a characteristic of respiratory allergy, but its relationship to SLIT remains unclear. We evaluate the association between clinical outcomes with pulmonary function and biomarkers in before and after HDM SLIT (UMIN Number 000022390). One hundred twelve patients with asthma sensitized to HDM were randomized to add-on 6 standardized quality (SQ)-HDM SLIT to pharmacotherapy or pharmacotherapy alone for 48weeks. At baseline and end of study, biomarkers, blood eosinophils, serum IgE, serum periostin, fractional exhaled nitric oxide (FeNO), and spirometry and clinical symptoms were measured. Association between biomarkers and an increase in FEV1 of 120mL or greater were analysed. Sublingual immunotherapy (SLIT) demonstrated a significant reduction of serum periostin (P<.001), FeNO (P<.01), and increase in HDM-specific IgE (P<.05), FEV1 (P<.001) and improvement of clinical symptom scores, when compared to pharmacotherapy. The change in FEV1 correlated with the changes in serum periostin (r=.696, P<.001) and the changes in FeNO (r=.682, P<.001). The independent predictor of improvement in airflow limitation was changed in serum periostin (r2 =.753, P=.013) and FeNO (P=.038). Based on cut-off values derived by receiver operating characteristic analysis (periostin 30.9ng/mL, FeNO 28.0ppb), patients were distinguished responders from non-responders, but with no predictive value for blood eosinophils or total IgE. The proportion of patients with both high periostin and FeNO levels was significantly higher in responder than in non-responder (P=.026). Adding HDM SLIT to pharmacotherapy resulted in reduced serum periostin and FeNO, and improved pulmonary function. Serum periostin and FeNO may be useful biomarkers for prediction of SLIT.

Impact of allergen immunotherapy in allergic asthma.

Although traditional pharmacological approaches improve outcomes in disease management for allergic asthma, these fail to modify the underlying immune responses. Allergen immunotherapy remains the only etiological therapy for the treatment of respiratory allergies for which clinical efficacy has been demonstrated through several well-controlled studies. In this review, we examine evidence from the past 5 years regarding the impact of allergen immunotherapy on allergic asthma to inform practitioners and stimulate further discussion and research.

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

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

Specific allergen immunotherapy for the treatment of allergic asthma: a review of current evidence.

Asthma is frequently associated with atopy, characterized by the production of specific immunoglobulin E in response to environmental allergens. Currently, two types of allergen immunotherapy (AIT) are used in clinical practice: subcutaneous and sublingual immunotherapy, both accepted as key components of the therapeutic repertoire for allergic rhinitis and conjunctivitis. However, their role in asthma remains controversial. The present document is aimed at providing the clinicians with a review of the evidence on the use of AIT in asthma, focusing on the most relevant aspects of its mechanism of action, its efficacy, and existing data on safety, tolerability, and cost-effectivity, both in pediatric and adult populations. A systematic search of MEDLINE, Cochrane, and Clinical Trials databases from 2000 to April of 2016 was carried out by a panel of experts from the Spanish Allergy and Clinical Immunology Scientific Society. Relevant studies prior to the year 2000 included in ulterior systematic reviews were also considered. More than 4000 articles were identified during the search and 241 were selected to retrieve available evidence on AIT, which was graded according to the Oxford classification. All the group members reviewed the resulting text until the final version reached the consensual agreement. A summary of recommendations on the more relevant topics are proposed. The role of AIT as a valuable therapeutic strategy for prevention of exacerbation and progressive decline in lung function is highlighted. Future research should include specific tools for asthma evaluation when assessing AIT effectiveness in asthmatic patients.

Subcutaneous and Sublingual Immunotherapy in Allergic Asthma in Children.

This review presents up-to-date understanding of immunotherapy in the treatment of children with allergic asthma. The principal types of allergen immunotherapy (AIT) are subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). Both of them are indicated for patients with allergic rhinitis and/or asthma, who have evidence of clinically relevant allergen-specific IgE, and significant symptoms despite reasonable avoidance measures and/or maximal medical therapy. Studies have shown a significant decrease in asthma symptom scores and in the use of rescue medication, and a preventive effect on asthma onset. Although the safety profile of SLIT appears to be better than SCIT, the results of some studies and meta-analyses suggest that the efficacy of SCIT is better and that SCIT has an earlier onset than SLIT in children with allergic asthma. Severe, not controlled asthma, and medical error were the most frequent causes of SCIT-induced adverse events.

Clinical and immunological effect of subcutaneous immunotherapy in allergic asthma

BackgroundAllergen immunotherapy is a potentially curative treatment approach in allergic diseases, subcutaneous immunotherapy is therapeutic option in treatment of allergic asthma. Aim of the studyIn the present study, subcutaneous immunotherapy (SCIT) using multiple allergen was administered to allergic asthmatic patients without allergic rhinitis or mixed allergy aiming to evaluate its efficacy, safety and evaluate the changes in the immune response. Patients and methodsThe study included 56 patients with allergic asthma alone, all patients received SCIT according to the results of skin prick test over a period of 1year, initial clinical evaluation including the presence of exacerbation and need of inhalers treatment, pulmonary function tests were performed also total immunoglobulin E(IgE), immunoglobulin A(IgA) and leukotriene C4(LTC4) were measured and repeated after 1year of initiation of the course of SCIT. ResultsThere were highly significant clinical improvement as regard exacerbation presence, need for inhalers and improvement of the forced expiratory volume in the first second FEV1 also there were highly significant decrease in total IgE, LTC4 and highly significant increase of IgA, after one year of SCIT. ConclusionSCIT is a safe treatment strategy that significantly reduce exacerbation and medication requirement in allergic asthma without mixed allergy also improve immunological response.

Clinical contraindications to allergen immunotherapy: an EAACI position paper.

Clinical indications for allergen immunotherapy (AIT) in respiratory and Hymenoptera venom allergy are well established; however, clinical contraindications to AIT are not always well documented. There are some discrepancies when classifying clinical contraindications for different forms of AIT as 'absolute' or 'relative'. EAACI Task Force on 'Contraindications to AIT' was created to evaluate and review current literature on clinical contraindications, and to update recommendations for both sublingual and subcutaneous AIT for respiratory and venom immunotherapy. An extensive review of the literature was performed on the use of AIT in asthma, autoimmune disorders, malignant neoplasias, cardiovascular diseases, acquired immunodeficiencies and other chronic diseases (including mental disorders), in patients treated with β-blockers, ACE inhibitors or monoamine oxidase inhibitors, in children under 5years of age, during pregnancy and in patients with poor compliance. Each topic was addressed by the following three questions: (1) Are there any negative effects of AIT on this concomitant condition/disease? (2) Are more frequent or more severe AIT-related side-effects expected? and (3) Is AIT expected to be less efficacious? The evidence, for the evaluation of these clinical conditions as contraindications, was limited, and most of the conclusions were based on case reports. Based on an extended literature research, recommendations for each medical condition assessed are provided. The final decision on the administration of AIT should be based on individual evaluation of any medical condition and a risk/benefit assessment for each patient.

House Dust Mite Allergy and Associated Allergen-Specific Immunotherapy in Allergic Asthma

Allergic asthma, an important subtype of asthma endotypes, is characterized by allergen-specific and Th2 cellmediated airway inflammation. Except for pharmacologic treatment, Allergen-specific immunotherapy (ASIT) has also been considered as a potential therapy for allergic asthma. House dust mite (HDM) is a common airborne allergen among patients with allergic asthma. This review is focused on the relationship between HDM allergy and allergic asthma, underlying mechanism of ASIT, and current evidence of HDM-specific immunotherapy for allergic asthma. It was demonstrated that HDM allergy is a risk factor associated with disease development of allergic asthma. The induction of immune tolerance by regulatory T cells was proved to play a pivotal role in the immunological mechanisms of ASIT. Experimental studies in murine models of allergic asthma reveal that HDM-specific immunotherapy has not only therapeutic efficacy but also preventive potential for disease development. The clinical trials also demonstrated the efficacy of HDM-specific immunotherapy in reducing asthma symptoms and medication use. Today, the clinical application of ASIT in allergic asthma has limitation when considering the extent of benefit and systemic adverse reactions. Although sublingual immunotherapy with HDM extract was demonstrated to have better safety profile when comparing with subcutaneous immunotherapy. To make HDM-specific immunotherapy more practicable in clinical application, further advances in the development of immunotherapy and clinical trials are needed.

The Effect of Immunotherapy in Allergic Respiratory Diseases: Reappraisal of Current Knowledge

Allergic rhino-conjunctivitis and asthma are induced by sensitization to one or more allergens in susceptible individuals. Specific immunotherapy (SIT) is indicated in allergic diseases, because it modulates the immune response inducing peripheral T-cell tolerance and activation of regulatory T-cells. On this basis, SIT is considered the only therapeutic approach that can modify the natural history of the allergic diseases. The development of engineered-allergen has contributed to reduce the allergenicity thus preventing the risk of side effects. The monomeric allergoids, with structural conformation and molecular size that facilitate the mucosal absorption, carry a lower risk for side effects compared to the administration of native allergens, maintaining the immunological stimulation. The efficacy of SIT, administered percutaneously (SCIT) or sublingual (SLIT), has been largely demonstrated in rhino-conjunctivitis; moreover, clinical trials have also demonstrated the efficacy of immunotherapy in allergic asthma. A therapeutic effect on asthma control has been shown in asthmatic subjects allergic to house dust mites, parietaria or grass pollen. An important and intriguing aspect of immunotherapy, not shared with the standard pharmacological treatments, is the long-lasting effect after discontinuation. In this respect, several SLIT studies in adults and children have clearly shown that the beneficial effects are maintained for up to 6 years after discontinuation of immunotherapy. The current review describes the main indications for SIT, and discusses its efficacy and safety in allergic rhino-conjunctivitis and asthma.

Effects of Caryota mitis profilin-loaded PLGA nanoparticles in a murine model of allergic asthma

BackgroundPollen allergy is the most common allergic disease. However, tropical pollens, such as those of Palmae, have seldom been investigated compared with the specific immunotherapy studies done on hyperallergenic birch, olive, and ragweed pollens. Although poly(lactic-co-glycolic acid) (PLGA) has been extensively applied as a biodegradable polymer in medical devices, it has rarely been utilized as a vaccine adjuvant to prevent and treat allergic disease. In this study, we investigated the immunotherapeutic effects of recombinant Caryota mitis profilin (rCmP)-loaded PLGA nanoparticles and the underlying mechanisms involved.MethodsA mouse model of allergenic asthma was established for specific immunotherapy using rCmP-loaded PLGA nanoparticles as the adjuvant. The model was evaluated by determining airway hyperresponsiveness and levels of serum-specific antibodies (IgE, IgG, and IgG2a) and cytokines, and observing histologic sections of lung tissue.ResultsThe rCmP-loaded PLGA nanoparticles effectively inhibited generation of specific IgE and secretion of the Th2 cytokine interleukin-4, facilitated generation of specific IgG2a and secretion of the Th1 cytokine interferon-gamma, converted the Th2 response to Th1, and evidently alleviated allergic symptoms.ConclusionPLGA functions more appropriately as a specific immunotherapy adjuvant for allergen vaccines than does conventional Al(OH)3 due to its superior efficacy, longer potency, and markedly fewer side effects. The rCmP-loaded PLGA nanoparticles developed herein offer a promising avenue for specific immunotherapy in allergic asthma.

Delphi project in bronchial asthma. Two stages

From the paediatric point of view, we have undertaken two Delphi studies into bronchial asthma. The first is related to the consensus known as the consensus document of the five associations. The second is more recent and has been undertaken with GEMA (the Spanish Guidelines on the Management of Asthma). The aim of this paper is to carry out a descriptive study comparing the 2 Delphi processes and to objectively assess if in some way behaviour over the past two years has changed as far as expert opinion is concerned. In the consensus document those points giving rise to most controversy were the treatment of children under three years of age and treatment with immunotherapy in allergic asthma. It is also necessary to highlight how important it was at that particular point in time to define the phenotypes of wheezing and the predictive index of asthma in children of less than 3 years of age. Of the 52 questions in the questionnaire, in 13.6% the panel of experts reached no consensus in their positions. Following GEMA the Delphi methodology, 56 questions were asked in the first round of the questionnaire, and consensus was reached in 87.5%. As regards the paediatric part relating to diagnosis and treatment in children, agreement was reached on all the questions in the first round. Agreement was reached in 8.92% questions in the second round. Clinical guidelines and consensus documents can modify behaviour towards an illness, both in the diagnosis and treatment.

Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma

Although specific immunotherapy is a valuable treatment option for patients with allergic asthma, the potential for systemic allergic reactions has limited its use, especially for patients with symptomatic disease. To evaluate omalizumab's effect on the tolerability of specific immunotherapy in patients with symptomatic persistent asthma not adequately controlled with inhaled corticosteroids. This multicenter, double-blind, parallel-group study randomized patients to treatment with omalizumab or placebo, after which they received specific immunotherapy to at least 1 of 3 perennial aeroallergens (cat, dog, and house dust mite) according to a 4-week, 18-injection cluster regimen, followed by 7 weeks of maintenance therapy. The primary efficacy variable, a systemic allergic reaction after immunotherapy, was analyzed by using the Cochrane-Mantel-Haenszel test. A total of 248 randomized patients (126 omalizumab, 122 placebo) received at least 1 dose of immunotherapy and were evaluated for efficacy. Patients receiving omalizumab experienced significantly fewer systemic allergic reactions to immunotherapy than those receiving placebo (17/126 [13.5%] vs 32/122 [26.2%]; P = .017; 95% CI, 2.91% to 22.56%) and had fewer respiratory-related (grade 3) systemic allergic reactions (6 vs 24, respectively). Grade 4 reactions were reported in 2 patients in each group. More omalizumab patients were able to reach the target maintenance immunotherapy dose (110 [87.3%] vs 88 [72.1%], respectively; P = .004). Use of omalizumab in patients whose asthma was symptomatic despite use of inhaled corticosteroids was associated with fewer systemic allergic reactions to specific immunotherapy and enabled more patients to achieve the target immunotherapy maintenance dose.