A modified schedule of multiple aeroallergen ultra-rush immunotherapy in perennial allergic rhinitis: safety, efficacy, and T lymphocyte cell population studies.

BACKGROUND: This study assessed whether a modified immunotherapy schedule for allergic rhinitis could be safe and efficient. Ultra-rush immunotherapy (URIT) rapidly desensitizes patients to aeroallergens. OBJECTIVE: We aimed to develop a modified URIT protocol in 3 days to achieve the target dose while observing whether it could improve this situation and decrease the time to achieve the maintenance dose. METHODS: The URIT was exercised in 21 patients with perennial allergic rhinitis. Premeditations were given to the patients 3 days prior to the immunotherapy and during the 3 days injections immunotherapy: pred nisolone, ranitidine, and Airokast/montelukast. Finally, the T cell population frequencies of patients prior to and after immunotherapy, including T helper 1, T helper 2, cytotoxic T lymphocytes, and regulatory T cells, were studied using flow cytometry. During the URIT protocol, 21 patients received 291 injections. RESULT: Six patients (28.6%) showed systemic reactions in our study. All systemic reactions occurred on the third day by the 1:1 dilution of the maintenance dose. These systemic reactions occurred in three patients after 13 injections, and the three remaining patients showed systemic reactions following the last injection. No systemic reaction was observed on the first and second day of the therapy, and the risk of systemic reaction with every injection was about 2%. Among the T cell populations, CD3+ and CD8+ cells decreased significantly. CONCLUSION: The findings emphasized that URIT, alongside premedication with a high dose of antihistamine, helped to achieve the maintenance dose and control clinical manifestations.

Tablet allergen immunotherapy: the anaphylaxis issue.

For the first time 15 years ago, tablet allergen immunotherapy (T-AIT) formulations were approved by regulatory agencies for treating allergic rhinitis caused by grass pollen in adults and children aged >5 years. Extensive evidences existed about effectiveness and safety of AIT. However, the safety profile is particularly compelling in children. Generally, T-AIT causes local reactions, mostly in the oral cavity, that are usually mild-to-moderate and often self-resolving. However, systemic allergic reactions are also observed with T-AIT, anaphylaxis representing the most fearsome adverse event, considering that it occurs in subjects treated for allergic rhinitis. Therefore, we conducted a literature search of patients reporting anaphylaxis because of T-AIT. Nine cases of anaphylactic reactions were reported in literature. Notably, no death was reported using T-AIT. This outcome was very important as it underscored the substantial safety of T-AIT. However, T-AIT deserves careful attention, mainly in the pediatric population. In this regard, after the first report of anaphylactic reaction at the first administration of T-AIT, manufacturers recommended that the first dose should be administered in a medical facility in the presence of staff with experience in managing anaphylaxis and the patient should be observed for at least 30 min. Interestingly, reported anaphylactic reactions were due to grass pollen extracts, with no report concerning other allergen extracts. However, it is relevant to note that anaphylactic reactions because of T-AIT are not reported in recent years.

Current options in the management of tree nut allergy: A systematic review and narrative synthesis.

Tree nut allergy is a lifelong and potentially life-threatening condition. The standard of care is strictly avoiding the culprit nut and treating accidental reactions symptomatically. To evaluate potential therapeutic options for desensitizing patients with IgE-mediated tree nut allergy, we systematically searched three bibliographic databases for studies published until January 2024. We looked for active treatments of IgE-mediated allergy to tree nuts (walnut, hazelnut, pistachio, cashew, almond, pecan, macadamia nut, and brazil nut). We focused on allergen-specific immunotherapy (AIT) using oral (OIT), sublingual (SLIT), epicutaneous (EPIT), or subcutaneous (SCIT) delivery, or other disease-modifying treatments. We found 19 studies that met our criteria: 3 studies investigated sublingual immunotherapy, 5 studied oral immunotherapy to a single tree nut, and 6 used multi-food oral immunotherapy with or without omalizumab. The remaining studies investigated the effectiveness of monoclonal antibodies or IgE-immunoadsorption in multi-food allergic patients, including patients with tree nut allergy. The heterogeneity of the studies prevented pooling and meta-analysis. Oral immunotherapy, single or multi-nut, with or without omalizumab, was the most studied approach and appears effective in conferring protection from accidental exposures. Omalizumab monotherapy is the only approved alternative management for reducing allergic reactions that may occur with accidental exposure.

[Recent advances in the practical management of allergic rhinitis.] / Recenti progressi nella gestione pratica della rinite allergica.

Allergic rhinitis (AR) is a widespread disease, and its prevalence is still growing. AR may be associated with other diseases, including conjunctivitis, rhinosinusitis, asthma, food allergy, and atopic dermatitis. Diagnosis is based on history, physical examination, documentation of sensitization, such as the production of allergen-specific IgE, also using molecular diagnostics in selected patients. Treatments is based on education, engagement, allergen avoidance, non-pharmacological and pharmacological remedies, and allergen-specific immunotherapy (Ait). Symptomatic treatments mainly concern intranasal/oral antihistamines and/or nasal corticosteroids. This article also aims to discuss new management strategies for AR patients. The self-management of allergic rhinitis could include new strategies. In this regard, particular interest should be considered to intranasal corticosteroids and antihistamines without medical prescription, probiotics and other natural substances, and new formulations (tablets) of Ait.

Current state and advances in desensitization for peanut allergy in pediatric age.

Peanut allergy affects about 1%-3% of the pediatric population in the world, with an important increase in the last decades. Nowadays, international guidelines recommend the early introduction of peanuts in the infant diet, with poor information about the quantity and the frequency of the intake. Allergen immunotherapy may represent the only therapeutic strategy able to modify the natural history of peanut allergy. In particular, oral immunotherapy showed the most promising results in terms of efficacy, but with significant rates of adverse reactions, mostly gastrointestinal. In 2020, the Food and Drug Administration and the European Medicines Agency approved Palforzia®, an oral drug for patients aged 4-17 years. Several studies are ongoing to improve the tolerability of oral immunotherapy and standardize the desensitization protocols. Sublingual immunotherapy permits to offer much lower doses than oral immunotherapy, but fewer adverse events are shown. Subcutaneous immunotherapy is associated with the greatest systemic adverse effects. Epicutaneous immunotherapy, for which Viaskin® patch was approved, has the highest safety profile. Innovative studies are evaluating the use of biological drugs, such as omalizumab or dupilumab, and probiotics, such as Lactobacillus rhamnosus, in monotherapy or associated with oral immunotherapy. Therapy for peanut allergy is constantly evolving, and new perspectives are ongoing to develop.

The Relationship Between Eosinophilic Esophagitis and Immunotherapy.

Immunotherapy is a treatment approach based on the principle of incremental allergen exposure to achieve desensitization. Recently, oral immunotherapy has been introduced as a treatment of IgE-mediated food allergy. Some patients receiving oral immunotherapy for food allergy may develop eosinophilic esophagitis. Here, we summarize the literature examining this association, its treatment, and outcomes and discuss possible explanations for this clinical phenomenon. We further identify potential associations with aeroallergen sensitivity and other forms of immunotherapy including subcutaneous immunotherapy and sublingual immunotherapy. Finally, we discuss management of immunotherapy-induced eosinophilic esophagitis. Epicutaneous immunotherapy is highlighted as an area of therapeutic investigation.

[Feeling analysis on allergen immunotherapy on Twitter using an unsupervised machine learning model]. / Análisis de sentimientos acerca de la inmunoterapia con alérgenos en Twitter mediante un modelo de aprendizaje automático no supervisado.

OBJECTIVE: Analyze feelings about allergen-specific immunotherapy on Twitter using the VADER model VADER (Valence Aware Dictionary and sEntiment Reasoner) model. METHODS: tweets related to specific allergen immunotherapy were obtained through the Twitter Application Programming Interface (API). The keywords "allergy shot" were used between January 1, 2012, and December 31, 2022. The data was processed by removing URLs, usernames, hashtags, multiple spaces, and duplicate tweets. Subsequently, a sentiment analysis was performed using the VADER model. RESULTS: A total of 34,711 tweets were retrieved, of which 1928 were eliminated. Of the remaining 32,783 tweets, 32.41% expressed a negative sentiment, 31.11% expressed a neutral sentiment, and 36.47% expressed a positive sentiment, with an average polarity of 0.02751 (neutral) over the 11-year period. CONCLUSIONS: The average polarity of tweets about allergen-specific immunotherapy is neutral over the 11 years analyzed. There was an annual increase in the average polarity over the years, with 2017, 2018, and 2022 having positive polarity averages. Additionally, the number of tweets decreased over time.

OBJETIVO: Analizar los sentimientos acerca de la inmunoterapia alérgeno-específica en Twitter mediante el modelo VADER (Valence Aware Dictionary and sEntiment Reasoner). MÉTODOS: Se utilizaron tweets relacionados con la inmunoterapia alérgeno-específica obtenidos a través del API (Application Programming Interface) de Twitter. Se incorporaron las palabras clave "allergy shot" en el período comprendido entre el 1 de enero de 2012 y el 31 de diciembre de 2022. Los datos obtenidos fueron procesados, eliminando las URL, nombres de usuarios, hashtags, espacios múltiples y tweets duplicados. Posteriormente, se realizó un análisis de sentimientos utilizando el modelo VADER. RESULTADOS: Se recolectaron 34,711 tweets, de los que se eliminaron 1928. De los 32,783 tweets restantes, se encontró que el 32.41% de los usuarios expresó un sentimiento negativo, el 31.11% un sentimiento neutral y el 36.47% un sentimiento positivo, con una media de polaridad de 0.02751 (neutral) a lo largo de los 11 años. CONCLUSIONES: La polaridad media de los tweets acerca de la inmunoterapia alérgeno-específica es neutral a lo largo de los 11 años analizados. Existe un aumento anual en la polaridad media positiva a lo largo de los años, sobre todo entre 2017, 2018 y 2022. La cantidad de tweets disminuyó con el tiempo.

[Frequency of sensitization to shrimp with house dust mite immunotherapy with polymerized extracts]. / Frecuencia de sensibilización a camarón con inmunoterapia a ácaros con extractos polimerizados.

OBJECTIVE: To evaluate the risk of IgE sensitization and symptoms to shrimp in a population that has received AIT with polymerized mite extract. METHODS: Patients with allergic rhinitis sensitized to dust mites (Dermatophogides spp) with an indication for mite AIT were included. Those patients who had not yet received AIT or had received less than 6 doses were included as controls and those who had received more than 24 doses of AIT were included as cases. Sensitization to shrimp was assessed by skin prick test with complete shrimp extract and/or shrimp-specific IgE. RESULTS: A total of 68 patients were included; 47 cases and 21 controls. When calculating the odds ratio of sensitization according to time with immunotherapy we observed that there were no differences between the group of cases and controls (OR 0.76 95% CI 0.26 to 2.22 p 0.7 by MacNemar technique). Factors such as consumption or not of shrimp and frequency of consumption do not seem to be related to the outcome. CONCLUSION: In contrast to what was reported with aqueous extracts, we observed that AIT with polymerized extracts is not a risk factor for shrimp sensitization. It is necessary to reproduce these results with a larger sample size to explore other factors.

OBJETIVO: Evaluar el riesgo de sensibilización IgE y síntomas a camarón en una población que ha recibido AIT con extracto polimerizado para ácaros. MÉTODOS: Se incluyeron pacientes con rinitis alérgica sensibilizados a ácaros del polvo (Dermatophogides spp) con indicación de AIT para ácaros. Aquellos pacientes que no habían aún recibido AIT o llevaban menos de seis dosis, fueron incluidos como controles, y aquellos que llevaban más de 24 dosis de AIT, fueron incluidos como casos. Se evaluó la sensibilización a camarón mediante prueba cutánea con extracto completo de camarón y/o IgE específica a camarón. RESULTADOS: En total, 68 pacientes fueron incluidos; 47 casos y 21 controles. Al calcular el odds ratio de la sensibilización de acuerdo al tiempo con la inmunoterapia, observamos que no había diferencias entre el grupo de casos y controles (OR 0,76 95% IC 0,26 a 2,22 p 0,7 por técnica de MacNemar). Factores como el consumo o no de camarón y la frecuencia de consumo, no parecen estar relacionados con el desenlace. CONCLUSIÓN: A diferencia de lo reportado con extractos acuosos, observamos de AIT con extractos polimerizados para no es un factor de riesgo para la sensibilización a camarón. Es necesario reproducir estos resultados con un mayor tamaño de muestra que permita explorar otros factores.

Efficacy of 300 IR house dust mite immunotherapy as a function of disease activity: Tertile analysis in clinical trials.

BACKGROUND: The symptoms of house dust mite (HDM)-induced allergic rhinitis (AR) vary with changes in exposure related to the weather or the domestic environment. In allergen immunotherapy (AIT) studies, a certain level of AR disease activity is necessary to demonstrate treatment efficacy; the latter can be underestimated if a substantial proportion of the patient population is weakly symptomatic. OBJECTIVE: To better estimate the real treatment effect of a HDM sublingual AIT (SLIT) tablet, we analysed the results of natural field studies in detail by applying a tertile approach. METHODS: We used data from three randomised, controlled trials (RCT) in a total of 2585 patients with AR treated with the 300 index of reactivity (IR) HDM SLIT-tablet or placebo. The study centres were grouped into tertiles according to the level of combined symptom and medication scores in patients in the placebo group. In each tertile, the difference between SLIT and placebo was assessed through an analysis of covariance. RESULTS: In the three RCTs, combined scores were found to be similar in the SLIT and placebo groups in the low tertiles. The treatment effect of the 300 IR HDM tablet increased in the medium and high tertiles, with notably significant differences versus placebo in the highest tertile and greater (ranging from -21% to -39%) than in the entire study population (-13% to -20%). The positive relationship between treatment efficacy and the combined score in each tertile was independent of the RCT and the score used. CONCLUSION AND CLINICAL RELEVANCE: Application of the tertile approach to AIT studies in a field in which many variables interact strongly might provide more accurate and meaningful measurements of efficacy and benefit for patients, better reflecting their real-life condition.

Transcriptomic changes associated with oral immunotherapy for food allergy.

This review summarizes recent advances in characterizing the transcriptional pathways associated with outcomes following Oral Immunotherapy. Recent technological advances including single-cell sequencing are transforming the ways in which the transcriptional landscape is understood. The application of these technologies is still in its infancy in food allergy but here we summarize current understanding of gene expression changes following oral immunotherapy for food allergy and specific signatures underpinning the different clinical outcomes of desensitization and remission (sustained unresponsiveness). T helper 2A cells have been identified as a cell type which correlates with disease activity and is modified by treatment. Molecular features at study entry may differentiate individuals who achieve more positive outcomes during OIT. Recent findings point to T cell anergy and Type 1 interferon pathways as potential mechanisms supporting redirection of the allergen-specific immune response away from allergy towards remission. Despite these developments in our understanding of immune mechanisms following OIT, there are still significant gaps. Additional studies examining immune signatures associated with long term and well-defined clinical outcomes are required to gain a more complete understanding of the pathways leading to remission of allergy, in order to optimize treatments and gain improved outcomes for patients.

Role of biologics in severe food allergy.

PURPOSE OF REVIEW: This review examine the dynamic landscape of food allergy treatment within the context of emerging biologics. Our purpose is to comprehensively evaluate the potential benefits, challenges, and transformative impact associated with the utilization of biologics in comparison to conventional therapeutic modalities. RECENT FINDINGS: This document synthesizes recent scientific investigations to various biologics, such as omalizumab, ligelizumab, dupilumab, and tezepelumab, providing a nuanced understanding of their roles in oral immunotherapy, rapid desensitization, and overall food allergy management. Recent studies and clinical trials highlight the impact of anti-IgE treatment on food allergies, revealing critical findings such as dose-related efficacy, facilitation of rapid desensitization in peanut allergies, and the sustained positive outcomes observed in individuals with multifood allergies. SUMMARY: The use of biologics presents a groundbreaking approach in the treatment of food allergies. The multifaceted action of these agents, along with their potential to overcome the challenges associated with traditional therapies, marks a significant advancement. Despite the persisting challenges of economic constraints and the need for further safety studies, biologics offer a promising avenue for improving the quality of life for individuals with food allergies. Ongoing research and collaborative efforts are imperative to fully realize the transformative potential inherent in these emerging therapeutic frontiers.

A Review of Shared Decision-Making, Published Protocols, and Post-desensitization Strategies in Oral Immunotherapy (OIT).

PURPOSE OF REVIEW: The aim of this review is to highlight key published oral immunotherapy (OIT) protocols and post-desensitization strategies for the major food allergens and to cover important concepts to consider when evaluating OIT for food-allergic patients. Shared decision-making should help identify patient and family values which will help influence the type of evidence-based protocol and maintenance strategy to use. RECENT FINDINGS: With food OIT emerging as a treatment option, there is a pressing need for patients, physicians, and other providers to have a nuanced understanding of the management choices available to them. There are now randomized controlled trials (RCT) of OIT for peanut, egg, milk, and wheat, and reports of cohorts of patients who have undergone OIT for tree nuts and sesame clinically. The current published protocols contain significant diversity in terms of starting dose, build-up schedule, maintenance dose, and even the product used for desensitization. Emerging data can help direct the long-term maintenance strategy for patients on OIT. Based on patient and family values elicited through the shared decision-making process, an OIT protocol may be selected that balances the level of desensitization, potential side effects, frequency of clinic visits, and potential to induce sustained unresponsiveness, among other factors. Once maintenance dosing is reached, most patients will need to maintain regular exposure to the food allergen to remain desensitized. The option to transition to commercial food products with equivalent amounts of food protein as the OIT maintenance dose would simplify the dosing process and perhaps improve palatability as well. Less frequent or decreased OIT dosing can provide practical benefits but may affect the level of desensitization and safety for some patients.

Blood Transcriptomics Identifies Multiple Gene Expression Pathways Associated with the Clinical Efficacy of Hymenoptera Venom Immunotherapy.

Allergen-specific venom immunotherapy (VIT) is a well-established therapy for Hymenoptera venom allergy (HVA). However, the precise mechanism underlying its clinical effect remains uncertain. Our study aimed to identify the molecular mechanisms associated with VIT efficiency. We prospectively included 19 patients with HVA undergoing VIT (sampled before the beginning of VIT, after reaching the maintenance dose, one year after finishing VIT, and after a sting challenge) and 9 healthy controls. RNA sequencing of whole blood was performed on an Illumina sequencing platform. Longitudinal transcriptomic profiling revealed the importance of the inhibition of the NFκB pathway and the downregulation of DUX4 transcripts for the early protection and induction of tolerance after finishing VIT. Furthermore, successful treatment was associated with inhibiting Th2, Th17, and macrophage alternative signalling pathways in synergy with the inhibition of the PPAR pathway and further silencing of the Th2 response. The immune system became activated when reaching the maintenance dose and was suppressed after finishing VIT. Finally, successful VIT restores the immune system's balance to a state similar to that of healthy individuals. Our results underline the important role of the inhibition of four pathways in the clinical effect of VIT: Th2, Th17, NFκB, and macrophage signalling. Two biomarkers specific for successful VIT, regardless of the time of sampling, were C4BPA and RPS10-NUDT3 and should be further tested as potential biomarkers.

House dust mite SCIT reduces asthma risk and significantly improves long-term rhinitis and asthma control-A RWE study.

BACKGROUND: The German Therapy Allergen Ordinance (TAO) triggered an ongoing upheaval in the market for house dust mite (HDM) allergen immunotherapy (AIT) products. Three HDM subcutaneous AIT (SCIT) products hold approval in Germany and therefore will be available after the scheduled completion of the TAO procedure in 2026. In general, data from clinical trials on the long-term effectiveness of HDM AIT are rare. We evaluated real-world data (RWD) in a retrospective, observational cohort study based on a longitudinal claims database including 60% of all German statutory healthcare prescriptions to show the long-term effectiveness of one of these products in daily life. Aim of this analysis was to provide a per product analysis on effectiveness of mite AIT as it is demanded by international guidelines on AIT. METHODS: Subjects between 5 and 70 years receiving their first (index) prescription of SCIT with a native HDM product (SCIT group) between 2009 and 2013 were included. The exactly 3:1 matched control group received prescriptions for only symptomatic AR medication (non-AIT group); the evaluation period for up to 6 years of follow-up ended in February 2017. Study endpoints were the progression of allergic rhinitis (AR) and asthma, asthma occurrence and time to the onset of asthma after at least 2 treatment years. RESULTS: In total, 892 subjects (608 adults and 284 children/adolescents) were included in the SCIT group and 2676 subjects (1824 adults and 852 children/adolescents) in the non-AIT group. During the follow-up period after at least 2 years of SCIT, the number of prescriptions in the SCIT group was reduced by 62.8% (p < .0001) for AR medication and by 42.4% for asthma medication (p = .0003). New-onset asthma risk was significantly reduced in the SCIT vs non-AIT group by 27.0% (p = .0212). The asthma-preventive effect of SCIT occurred 15 months after start of the treatment. In the SCIT group, the time to onset of asthma was prolonged compared to the non-AIT group (p = .0010). CONCLUSION: In this first product based RWD analysis on SCIT with a native HDM product, patients aged 5 to 70 years benefited from AIT in the long term in terms of reduced progression of AR and asthma after at least 2 years of treatment. The effects seemed to last for up to 6 years after treatment termination. A significantly reduced risk of asthma onset was observed, starting after 15 months of treatment.

New biologics for food allergy.

PURPOSE OF REVIEW: This review aims to explore role of emerging biologics, including ligelizumab, UB-221, dupilumab, and antialarmins, in food allergy management. With a focus on recent developments, we evaluate their promise in mitigating adverse events during oral immunotherapy (OIT), reducing allergic reactions, and addressing the limitations of current therapeutic options. RECENT FINDINGS: Antiimmunoglobulin E mAbs, exemplified by omalizumab, demonstrate efficacy in desensitization and safety improvement during multiallergen OIT. Next-generation antibodies like ligelizumab and UB-221 exhibit enhanced potency and unique mechanisms, holding promise for food allergy treatment. Dupilumab, targeting IL-4 receptor alpha, presents potential benefits in decreasing allergen-specific IgE and modifying the atopic march. Exploration of antialarmins, specifically anti-IL-33 (etokimab) and anti-TSLP (tezepelumab), reveals encouraging results, with etokimab showing early success in peanut allergy trials. SUMMARY: Biologics hold promising potential for food allergy treatment. Tailoring therapeutic approaches based on shared decision-making becomes pivotal. While omalizumab remains a significant option, next-generation anti-IgE antibodies and agents targeting alarmins exhibit unique strengths. Dupilumab, despite limited success as monotherapy, shows promise as an adjunct for OIT. Careful consideration of treatment goals, patient preferences, and the evolving landscape of biologics will shape future clinical practice, offering allergists an expanded toolbox for personalized food allergy management.

Baseline Severity and Disease Duration Can Predict the Response to Allergen-specific Immunotherapy in Allergic Rhinitis.

Allergen-specific immunotherapy (AIT) has confirmed its efficacy in improving the symptoms of allergic rhinitis. However, no reliable biomarkers have been identified to predict the efficacy of AIT were found. We aimed to find clinical and immunological markers to predict efficacy in children after 2 years of sublingual immunotherapy (SLIT). A total of 285 children diagnosed with allergic rhinitis were recruited. The clinical efficacy was evaluated by comparing endpoint and baseline symptom and medication scores (SMS). Baseline clinical and immunological markers (serum total and specific immunoglobulin [Ig]E) and their correlation with clinical efficacy were analyzed. Of the 285 children recruited, 249 completed the 2-year SLIT program. After 2 years of SLIT, 68.3% of the children showed a significant response. Children in the Remarkable Response Group had the highest baseline SMS and most extended disease duration, followed by the Effective Relief and Unresponsive Group. Correlation analysis demonstrated that SMS improvement was positively correlated with baseline SMS (r=0.67) and disease duration (r=0.35). SMS improvement was not correlated with age, body mass index, total or specific IgE levels, or their ratios. Our results show that baseline SMS and disease duration can predict the efficacy of SLIT. Our study can guide the selection of suitable candidates for SLIT.