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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]

Background: Allergen immunotherapy (AIT) is the only known causative treatment for Alternaria allergy, but the difficulty in standardizing Alternaria extracts hampers its effectiveness and safety. Summary:Alternaria, a potent airborne allergen, has a high sensitization rate and is known to trigger the onset and exacerbation of respiratory allergies, even inducing fungal food allergy syndrome in some cases. It can trigger a type 2 inflammatory response, leading to an increase in the secretion of type 2 inflammatory cytokines and eosinophils, which are the culprits behind allergic symptoms. Diagnosing Alternaria allergy is a multistep process, involving a careful examination of clinical symptoms, medical history, skin prick tests, serum-specific IgE detection, or provocation tests. Alt a1, the major component of Alternaria, is a vital player in diagnosing Alternaria allergy through component-resolved diagnosis. Interestingly, Alternaria can reduce the protein activity of other allergens like pollen and cat dander when mixed with them. In order to solve the problems of standardization, efficacy and safety of traditional Alternaria AIT, novel AIT methods targeting Alt a1 and innovative vaccines such as epitope, DNA, and mRNA vaccines seem promising in bypassing the standardization issue of Alternaria extracts. But these studies are in early stages, and most researches are still focused on animal models, calling for more evidence to validate their use in humans. Key Messages: This review delves into the various aspects of Alternaria allergy, including characteristics, epidemiology, immune mechanisms, diagnosis, clinical manifestations, and the application and limitations of Alternaria AIT, aiming to provide a foundation for the management of patients with Alternaria allergy. [ABSTRACT FROM AUTHOR]

Hypersensitivity to exogenous or endogenous progesterone presents with a variety of clinical, usually cutaneous, manifestations. The condition can occur at any age during the reproductive years, causes debilitating symptoms and can impact the use of exogenous hormones. Management strategies include symptom control or hormonal manipulation via desensitisation. Strategic testing confirms the diagnosis, while targeted intervention can significantly and positively impact quality of life and further childbearing. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis aimed to evaluate the effectiveness and adverse effects of specific immunotherapy (SIT) in the management of respiratory allergens, including allergic asthma, rhinitis, and related disorders, based on a review of current literature up to November 8, 2022. Methods: We conducted a search of databases, including PubMed, Embase, Cochrane, and Web of Science, to identify relevant randomized controlled trials (RCTs) assessing respiratory allergy-specific immunotherapy. We employed the Consolidated Standards of Reporting Trials (CONSORT) Statement to select RCTs that adhered to rigorous reporting standards. Specifically, we focused on double-blind placebo-controlled (DBPC) trials and open studies involving both adults and children, considering factors such as dosage, inclusion criteria, allergens, and primary outcome measurements. Results: A total of 25 meta-analyses were included in this study. Among them, 14 evaluated sublingual-specific allergen immunotherapy (SLIT), 4 assessed subcutaneous allergen immunotherapy (SCIT), 4 explored both sublingual and subcutaneous immunotherapy, and 3 investigated intralymphatic immunotherapy. The outcomes of these meta-analyses indicated a reduction in medication scores in 20 cases and a decrease in symptom scores in 23 cases. Additionally, six studies reported on changes in IgE levels, seven studies focused on IgG4, four studies examined FEV1 (forced expiratory volume in 1 s), and eight studies reported on symptom and medication scores. Furthermore, 11 studies reported on differences in adverse reactions. Conclusion: The results of our meta-analysis suggest that specific immunotherapy, while associated with some adverse effects, effectively reduces the symptoms of asthma and rhinitis. Therefore, we recommend its use in the treatment of respiratory allergies. [ABSTRACT FROM AUTHOR]

Food allergies are an increasing global problem and societal issue. In addition to the potential for severe allergic reactions from accidental ingestion, food allergies impose a significant burden on the quality of life, nutrition, cost of living, and social activities of both those afflicted and their caregivers. Strict avoidance of allergens and use of emergency medications to treat allergic reactions are the traditional management and treatment strategies; however, significant progress has been made in recent years toward better treatment of food allergies. Many clinical trials on food allergen immunotherapy (oral, epicutaneous, and sublingual) have revealed its efficacy in increasing reaction thresholds and desensitization. These positive results led to the first FDA approval of peanut oral immunotherapy (OIT). However, safer and more effective approaches are required, and adjunct treatments and allergen modifications are being considered. More than 100 facilities in Japan conduct OIT, and numerous studies on it have been reported. Unlike in Europe and the US, stepwise oral food challenges with dietary guidance are conducted separately from the OIT. This review describes the current perspectives on allergen immunotherapy for the treatment of food allergies, focusing on evidence from Japan. [ABSTRACT FROM AUTHOR]

Allergen immunotherapy (AIT), including SCIT and SLIT, is a treatment that involves the administration of allergens to which patients with allergic diseases have been sensitized. HDM-SCIT for asthma is indicated in cases of HDM-sensitized allergic asthma with normal lung function. HDM-SCIT improves asthma symptoms and AHR, and decreases the medication dose. Importantly, AIT can improve other allergic diseases complicated by asthma, such as allergic rhinitis, which can also contribute to the improvement of asthma symptoms. Several studies have suggested that HDM-SLIT also attenuates the risk of asthma exacerbations, and improves lung function in asthma cases with allergic rhinitis. Furthermore, AIT can modify the natural course of allergic diseases, including asthma. For example, the effects of AIT are maintained for at least several years after treatment discontinuation. AIT can prevent the onset of asthma when introduced in allergic rhinitis, and can also inhibit or reduce new allergen sensitizations. Recent data have suggested that AIT may suppress non-targeted allergen-induced immune responses in addition to targeted allergen-induced responses, and suppress infections of the lower respiratory tract by enhancing IFN responses. [ABSTRACT FROM AUTHOR]

Background: Administration of allergen mixtures of many components comprises the most common approach for American allergists regarding the management of polyallergic patients. European allergists, however, are more reluctant to this type of treatment due to the potential drawbacks of mixing extracts. Research design and methods: To assess the efficacy and safety of subcutaneous immunotherapy (SCIT) with polymerized allergen mixtures without dilutional effect in polyallergic patients. This observational, prospective, multicenter study included patients (between 5 and 60 years) with respiratory allergic diseases that had been prescribed with SCIT with mixtures of two pollen or mite extracts. Changes in Symptoms and Medication Score (SMS) and in rhinitis quality of life questionnaire (RQLQ), subjective clinical improvement, treatment satisfaction and tolerability were assessed after the 1-year treatment. Results: A total of 115 patients were included in the assessment. Mean global SMS decreased from 3.5 (SD = 1.1) to 1.6 (SD = 1.2) points, with a mean absolute reduction of 1.6 (SD = 1.3) points in the RQLQ score (p < 0.001, Wilcoxon test). General subjective clinical improvements and a good treatment satisfaction and tolerability were observed. Conclusion: SCIT with polymerized allergen mixtures from either pollen or mite extracts proved to be an effective and safe treatment option for polyallergic patients suffering from allergic respiratory diseases. [ABSTRACT FROM AUTHOR]

The prevalence of allergic rhinitis (AR) in children is steadily increasing, and its onset is closely associated with genetic factors, living environment, and exposure to allergens. In recent years, an increasing number of diagnostic methods have been employed to assist in diagnosing AR. In addition to pharmaceutical treatments, personalized approaches such as environmental control and allergen-specific immunotherapy are gradually gaining popularity. In this article, we reviewed recent research on the etiology, diagnostic classification, treatment methods, and health management of AR in children. These insights will benefit the implementation of personalized diagnosis and treatment for children with AR, promoting health management strategies that improve symptoms and quality of life. [ABSTRACT FROM AUTHOR]

The European Academy of Allergy and Clinical Immunology (EAACI) has released updated clinical guidelines for the diagnosis and management of IgE-mediated food allergy. The guidelines provide evidence-based recommendations for clinicians treating patients with suspected food allergies. The guidelines emphasize the importance of a detailed clinical history, including dietary history, in reaching an accurate diagnosis. They also outline various diagnostic tests, such as skin prick tests and specific IgE tests, and recommend oral food challenges when necessary. The guidelines also address management strategies, including dietary advice, treatment plans for allergic reactions, and the potential use of immunomodulatory treatments. [Extracted from the article]

Background Methods Results Conclusions Omalizumab (XOLAIR®)‐assisted multi‐food oral immunotherapy (mOIT) has been shown to safely, effectively, and rapidly desensitize patients with multiple food allergies. In our clinical trial (NCT02626611) on omalizumab‐assisted mOIT, different desensitization outcomes (success or failure of desensitization) were observed following a period of either continued or discontinued mOIT. However, the association between the immunological changes induced by omalizumab‐assisted mOIT and desensitization outcomes has not yet been fully elucidated. In this study, due to the key roles of regulatory T (Treg) cells and the type 2 helper T cell (Th2) pathway in immune tolerance to food allergens, we aimed to characterize their association with the desensitization outcomes of omalizumab‐assisted mOIT.Mass cytometry and multiplex cytokine assays were performed on blood samples obtained from participants with allergies to peanut, cashew, or milk in our phase 2 clinical study (NCT02626611). Comprehensive statistical and bioinformatic analyses were conducted on high‐dimensional cytometry‐based single‐cell data and high‐throughput multiplex cytokine data.Our results demonstrated that the frequency of HLA‐DR+ Treg cells, and the production of Th2 cytokines (IL‐4, IL‐5, IL‐13, and IL‐9) as well as the immunoregulatory cytokine IL‐10 by peripheral blood mononuclear cells (PBMCs) was significantly increased in cultures with allergen compared to cultures with media alone at baseline (Week 0). We also observed increased frequency of allergen responsive HLA‐DR+ Treg cells and enhanced production of IL‐10 by PBMCs in participants who achieved successful desensitization compared to those with failure of desensitization. However, the production of Th2 cytokines by PBMCs did not show significant differences between participants with different desensitization outcomes (success vs. failure of desensitization), despite omalizumab‐assisted mOIT inducing a significant reduction in the production of Th2 cytokines.We demonstrated that the frequency of HLA‐DR+ Treg cells and IL‐10 cytokine production by PBMCs are associated with desensitization outcomes of omalizumab‐assisted mOIT. These findings suggest potential immunological parameters that could be targeted to enhance desensitization success rates. [ABSTRACT FROM AUTHOR]

Summary The prevalence of asthma, rhinitis, and food allergies has increased dramatically over the last few decades. This increase originally started in western countries, but is now also evident in many other regions of the world. Given the fact that the increase is so quick, the noted increase cannot be linked to a genetic effect, and many environmental factors have been identified that are associated with increased or reduced prevalence of allergies, like changing dietary habits, increased urbanization, pollution, exposure to microorganisms and LPS, and the farming environment and raw milk consumption. Although the key role of allergen‐specific IgE in allergies is well known, the role of allergen‐specific IgG and IgA antibodies is less well defined. This review will provide an overview of the functions of allergen‐specific IgE in allergy, the role of allergen‐specific antibodies (IgG (4) and IgA) in allergen immunotherapy (AIT), the possibility to use allergen‐specific antibodies for treatment of ongoing allergies, and the potential role of allergen‐specific antibodies in tolerance induction to allergens in a preventive setting. In the last, more speculative, section we will present novel hypotheses on the potential role of allergen‐specific non‐IgE antibodies in allergies by directing antigen presentation, Th2 development, and innate immune training. [ABSTRACT FROM AUTHOR]

This article discusses the association between cytotoxic effector memory CD8+ T cells and sustained unresponsiveness (SU) after peanut oral immunotherapy (OIT). The study found that a higher frequency of effector memory CD8+ T cells was associated with a higher likelihood of achieving SU. The researchers also identified differentially expressed immune genes and observed that cytolytic molecules such as Granulysin (Gnly) and Granzyme B (GzB) may play a supportive role in the development of SU. However, the study acknowledges the need for further validation using larger cohorts. [Extracted from the article]

Background Objective Materials and Methods Results Conclusion and Clinical Relevance Allergen‐carrying virus‐like particles are effective and safe means of allergen immunotherapy (AIT) in rodent models.To study the development of allergen‐blocking immunoglobulin (Ig)G in dogs injected with Der f 2‐carrying enveloped plant‐based bioparticles (eBPs).Laboratory beagle dogs were injected intradermally (ID) or subcutaneously (SC) with Der f 2‐eBP three times at 2‐week intervals. A basophil mediator release assay was used to compare the reactivity of Der f 2‐eBPs to that of recombinant Der f 2. Allergen‐specific IgG serum levels were determined by immunoblotting and ELISA. The allergen‐blocking potential of postvaccination IgG was assessed by Pet Allergy Xplorer (PAX) macroarray and basophil mediator release inhibition assays.The amount of Der f 2 eBPs needed to induce basophil activation was 1000‐fold higher than that of the soluble natural allergen. In both immunisation groups, eBP injections caused no adverse events and induced Der f 2‐specific IgG, first detected on Day (D)14 and peaking on D41. The co‐incubation of sera with a Der f 2‐IgE‐rich canine serum pool resulted in a mean PAX inhibition of 70% (ID) to 80% (SC) on D41. For both groups, the inhibition of basophil mediator release reached 75% on D28 and D41. The percentage inhibition of PAX and mediator release correlated significantly with Der f 2 IgG levels.Intradermal and subcutaneous injections of Der f 2‐eBPs were safe and increased Der f 2‐specific IgG. The clinical benefit of immunotherapy will be evaluated in future trials enrolling atopic dogs allergic to house dust mites. [ABSTRACT FROM AUTHOR]

Summary: Despite the near ubiquitous presence of Ig‐based antibodies in vertebrates, IgE is unique to mammals. How and why it emerged remains mysterious. IgE expression is greatly constrained compared to other IgH isotypes. While other IgH isotypes are relatively abundant, soluble IgE has a truncated half‐life, and IgE plasma cells are mostly short‐lived. Despite its rarity, IgE is consequential and can trigger life‐threatening anaphylaxis. IgE production reflects a dynamic steady state with IgG memory B cells feeding short‐lived IgE production. Emerging evidence suggests that IgE may also potentially be produced in longer‐lived plasma cells as well, perhaps as an aberrancy stemming from its evolutionary roots from an antibody isotype that likely functioned more like IgG. As a late derivative of an ancient systemic antibody system, the benefits of IgE in mammals likely stems from the antibody system's adaptive recognition and response capability. However, the tendency for massive, systemic, and long‐lived production, common to IgH isotypes like IgG, were likely not a good fit for IgE. The evolutionary derivation of IgE from an antibody system that for millions of years was good at antigen de‐sensitization to now functioning as a highly specialized antigen‐sensitization function required heavy restrictions on antibody production—insufficiency of which may contribute to allergic disease. [ABSTRACT FROM AUTHOR]

Compared with oral or injection administration, percutaneous immunotherapy presents a promising treatment modality for food allergies, providing low invasiveness and safety. This study investigated the efficacy of percutaneous immunotherapy using hen egg lysozyme (HEL)-loaded PLGA-PEG-PLGA nanoparticles (NPs), as an antigen model protein derived from egg white, compared with that of HEL-loaded chitosan hydroxypropyltrimonium chloride (CS)-modified PLGA NPs used in previous research. The intradermal retention of HEL in excised mouse skin was measured using Franz cells, which revealed a 2.1-fold higher retention with PLGA-PEG-PLGA NPs than that with CS-modified PLGA NPs. Observation of skin penetration pathways using fluorescein-4-isothiocyanate (FITC)-labeled HEL demonstrated successful delivery of HEL deep into the hair follicles with PLGA-PEG-PLGA NPs. These findings suggest that after NPs delivery into the skin, PEG prevents protein adhesion and NPs aggregation, facilitating stable delivery deep into the skin. Subsequently, in vivo percutaneous administration experiments in mice, with concurrent iontophoresis, demonstrated a significant increase in serum IgG1 antibody production with PLGA-PEG-PLGA NPs compared with that with CS-PLGA NPs after eight weeks of administration. Furthermore, serum IgE production in each NP administration group significantly decreased compared with that by subcutaneous administration of HEL solution. These results suggest that the combination of PLGA-PEG-PLGA NPs and iontophoresis is an effective percutaneous immunotherapy for food allergies. [ABSTRACT FROM AUTHOR]

Background: Allergen-specific immunotherapy, a unique inducer of tolerance, may result in T cell exhaution. Aims: To investigate how the duration of house dust mite (HDM) subcutaneous immunotherapy (SCIT) affects the expression of major immune checkpoint (ICP) molecules on the surface of CD4+ T-helper and regulatory T (Treg) cells. Study Design: Cross-sectional study. Methods: We enrolled 28 children with HDM-induced allergic rhinitis (AR) and six controls. The study participants were divided into six groups: one group each of patients in their first, second, and third years of HDM-SCIT; one group each comprising those in the first year following HDM-SCIT and those on pharmacotherapy; and the control group. The expression of ICPs on CD4+ T and Treg cells was determined using flow cytometry, and plasma levels of soluble ICPs were estimated by ELISA. Results: Our results revealed a significant increase in the expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and lymphocyte activation gene 3 (LAG-3) on CD4+ T cells during the second and third years of SCIT, respectively. Additionally, a strong correlation was observed between the expression of CTLA-4 and T cell immunoglobulin and mucin domain containing molecule-3 in CD4+ T cells. Furthermore, we observed a significant correlation between the expressions of programmed cell death protein-1, CTLA-4, T cell Immunoreceptor with Immunoglobulin and Immunoreceptor Tyrosine-Based Inhibitory Motif domain, and LAG-3 on both CD4+ T and Treg cells. A robust correlation was observed between the plasma levels of soluble ICPs. Conclusion: HDM-SCIT induces CD4+ T cell exhaution, which may contribute to tolerance induction in children with AR. [ABSTRACT FROM AUTHOR]

Background: Severe atopic dermatitis (AD) is a complex disease requiring systemic treatment. This study aimed to assess the effectiveness of combined therapy consisting of dupilumab and sublingual dust mite allergen immunotherapy (SLIT-HDM) in patients with severe AD and HDM allergies. Methods: Patients diagnosed with severe AD were included in this randomised, placebo-controlled, double-blind 12-month trial; they received SLIT for HDMs and/or dupilumab for 12 months and were compared with patients on cyclosporine. The primary outcomes for the treatment arms were changes in the Eczema Area and Severity Index (EASI), body surface area (%BSA), and Investigator Global Assessment (IsGA) over 12 months. The secondary outcomes were the proportion of patients who achieved IsGA success and reduced medication scores. Results: Significant improvements were observed in all analysed groups after 12 months of therapy based on the EASI, %BSA, and IsGA. However, the most substantial changes were observed in the groups treated with dupilumab or a combination of SLIT-HDM and dupilumab. Additionally, the proportion of patients who achieved an IsGA reduction was significantly greater in the group receiving combination therapy than in the other groups (9/14 [64% of the group receiving SLIT-HDM] vs. 11/14 [73% of the group receiving dupilumab] vs. 15/17 [88% of the group receiving dupilumab and SLIT-HDM] vs. 7/13 [53% of the group receiving cyclosporine]) (p < 0.05). Conclusions: In patients with severe AD and HDM allergies, combination treatment with dupilumab and allergen immunotherapy for HDMs may increase the therapeutic benefit over treatment with these methods separately. [ABSTRACT FROM AUTHOR]

In human leukocyte antigen (HLA)-mismatched allogeneic stem cell transplantation settings, donor-specific anti-HLA antibodies (DSAs) can independently lead to graft failure, including both primary graft rejection and primary poor graft function. Although several strategies, such as plasma exchange, intravenous immunoglobulin, rituximab, and bortezomib, have been used for DSA desensitization, the effectiveness of desensitization and transplantation outcomes in some patients remain unsatisfactory. In this review, we summarized recent research on the prevalence of anti-HLA antibodies and the underlying mechanism of DSAs in the pathogenesis of graft failure. We mainly focused on desensitization strategies for DSAs, especially novel methods that are being investigated in the preclinical stage and those with promising outcomes after preliminary clinical application. [ABSTRACT FROM AUTHOR]

This document provides concise and factually accurate information on the primary care management of allergic rhinitis (AR) in children. It highlights the importance of recognizing the signs of AR in children and provides strategies for diagnosis and management, including allergen avoidance, pharmacotherapy, and specific immunotherapy. The document discusses various pharmacological treatments and practical strategies to reduce exposure to common allergens. It emphasizes the importance of proper administration techniques and highlights the safety and effectiveness of intranasal corticosteroids in children. The document also mentions cost considerations and the availability of subsidized medications in Singapore. Overall, it provides valuable information for library patrons conducting research on the management of AR in children. [Extracted from the article]

Background Methods Results Conclusion Registries can yield important insights on allergen immunotherapy (AIT) outcomes in daily clinical practice. However, systematic recordings of adverse events (AE) due to AIT in real‐life are lacking.The Allergen Immunotherapy Adverse Events Registry (ADER) is a prospective, multicenter registry on real‐life AIT safety. Data on adults (>18 years old) with respiratory allergies receiving AIT with mites, pollens, epithelia, and/or molds were retrieved and analyzed from ADER. The frequency, characteristics and risk factors of AE were investigated. The MedDRA terminology was used to record AE.A total of 1545 individuals with a mean age of 33 ± 10 years receiving 1815 AIT courses (n = 1060 sublingual (SLIT); n = 755 subcutaneous (SCIT)) in centers from eight countries were included. Patients had allergic rhinitis (65%) or, asthma only (3.7%) or rhinitis with asthma (31.2%). Grass was the most frequent specific sensitizer (60.7%), followed by mites (45.5%), birch pollen (20.6%), epithelia (16.1%), and molds (8%). There were 296 AE recorded in 115 patients (7.4%). A higher frequency of AE occurred during up‐dosing (59%) compared to maintenance. Severe reactions were rare (0.2%), all in the context of SCIT. After 6 weeks of maintenance only one moderate AE was recorded. The most frequently reported symptoms were from the respiratory system and the skin. Having asthma, doing SCIT, AIT with mugwort, cat, or birch were associated with higher risk for AE while the use of allergoids induced lower risk.In real life clinical practice, AIT‐associated AE occur in a minority of patients, while severe reactions are rare. The presence of asthma and use of SCIT are risk factors, while the use of modified allergens lowers the risk. [ABSTRACT FROM AUTHOR]

This article discusses a study that compares two different definitions of pollen seasons based on 10 years of data from two central European cities. The study found that pollen seasons can vary significantly between countries and regions due to factors such as climate, vegetation, and pollution. The European Academy of Allergy and Clinical Immunology (EAACI) has published a definition for pollen seasons that correlates with allergic rhinitis symptoms. The study compared the EAACI definition with a percentage analysis method and found some differences in defining the start and end of pollen seasons. The study emphasizes the importance of accurately defining pollen seasons for planning allergy treatments and clinical trials. The document provides acknowledgments, funding information, conflict of interest statements, and author contributions related to the study. The study was supported by the European Academy of Allergy and Clinical Immunology, and the data supporting the findings are available upon request. [Extracted from the article]

Objective: Rapid drug desensitization (RDD) is a safe and effective method of inducing temporary tolerance and gradually increasing the dose over a few hours to a few days, thereby preventing severe hypersensitivity reactions. Despite the limited number of pediatric desensitization studies in the literature, it is important to explore this area further to provide better treatment options for patients. This study will determine the safety and efficacy of desensitization and present management strategies for breakthrough reactions in pediatric patients with immediate hypersensitivity reactions (HSR). Materials and Methods: This retrospective study enrolled 14 pediatric patients with drug HSRs who underwent drug desensitization between January 2020 and January 2024. The desensitization protocols used were developed by Castells and consisted of a 12-step protocol with 3 parenteral preparations with increasing concentrations. The standard protocol included premedication with antihistamine (pheniramine) and methylprednisolone (1 mg/kg) 30 minutes before the infusion. Results: The study involved 14 patients. A total of 64 desensitizations were carried out for 16 different drugs. Only 13% resulted in mild to severe reactions. Overall, almost 92% of all desensitizations were successful. Additionally, it is important to highlight that all breakthrough reactions (BRs) occurred with monoclonal antibodies. Mild BRs during RDD were associated with more severe reactions during the next RDDs. No BRs were seen during RDD in patients with mild initial reactions. Conclusion: It is important to note that desensitization is not an extreme method, and that pediatric age is not a contraindication. Desensitization is a safe and successful method for children, with a positive impact on survival and overall prognosis. [ABSTRACT FROM AUTHOR]

Anaphylaxis typically occurs due to immunological mechanisms involving IgE, IgG, or complement-mediated responses, but nonimmunological mechanisms can also contribute to the development of anaphylaxis by triggering mast cell and basophil degranulation. In cases where alternative treatment options are unavailable, or when the use of a specific drug is essential, a desensitization protocol should be considered. In this context, we present a successful oral desensitization protocol in a pediatric patient who experienced anaphylaxis after taking acetazolamide orally. [ABSTRACT FROM AUTHOR]

Introduction: Allergen immunotherapy is the only modifying treatment of the natural course of respiratory allergic diseases; however, the lack of evidence leads to little inconclusive results. Real life studies are on the rise and are becoming a valuable tool to confirm and complement findings from clinical trials. The objective of this study was to evaluate the effectiveness and safety of a depigmented-polymerized undiluted subcutaneous extract of grass and olive pollen, under routine clinical practice conditions. Methods: This was an observational, retrospective, longitudinal, single-center study on the use of a 2-pollen (grass mix and Olea europaea) undiluted subcutaneous extract over at least 3 consecutive years. Data were collected from 76 patients (n = 44 female; median age: 12.5 years old) diagnosed with allergic rhinoconjunctivitis with/without allergic asthma due to sensitization to both grasses and O. europaea. Primary and secondary effectiveness endpoints were symptom severity, concomitant medication, and immunological profile before and after completing the immunotherapy. A 2-year follow-up of patients’ symptoms and medication history after completing the subcutaneous immunotherapy (SCIT) was performed. Results: There was a significant improvement of symptoms and medication consumption after 3 years of SCIT treatment, and a significant decrease in specific IgE levels for grasses and O. europaea was observed after finishing the treatment. Conclusion: Three years treatment of allergic patients using an undiluted mixture of two allergen extracts was shown to be safe and effective for rhinitis and asthma, with efficacy maintained for at least 2 years after finishing SCIT. These results reinforce the importance of real life clinical data in addition to those from clinical trials, helping to individualize allergic treatments. [ABSTRACT FROM AUTHOR]

Food allergies can pose significant risks and profoundly impactthe quality oflife of children and their families, making them a major public health concern.Allergen avoidance has been the traditional mainstay of treatment; however, recent research has focused on various approaches to food allergen immunotherapy. This review summarizes the recent advancements in oral, sublingual, and epicutaneous immunotherapies, highlighting their respective advantages and disadvantages. The ultimate goal of food allergen immunotherapy is to maximize efficacy while minimizing risks, leading to the exploration of strategies such as lowdose immunotherapy and the use of biologics. When selecting candidates for immunotherapy among patients with food allergies, factors such as allergen characteristics, the likelihood of natural resolution, age, symptom severity, and impact on quality of life require consideration, and an individualized approach should be adopted to determine the most suitable treatment method. [ABSTRACT FROM AUTHOR]

Local allergic rhinitis (LAR) represents a medical provocation for allergists and otorhinolaryngologists. LAR is considered to be a subtype of allergic rhinitis (AR) that affects a great percentage of patients who were, for decades, diagnosed as having chronic non-allergic rhinitis. The clinical picture is represented by rhinorrhea, sneezing, and nasal itching correlated with specific pollen season or dust, mold, or pet interior exposure. Usual assessment of AR (skin prick testing and serum IgE assessment) produces negative results. Specialized centers in allergology and ENT around the globe use a nasal allergen challenge, assessment of local IgE, basophil activation test (BAT), and nasal cytology in the diagnostic approach to the disease, taking into account their current limitations. The impact of LAR on quality-of-life indicators is the same as in AR. Treatment for LAR is similar to that for AR and is the same as for AR: allergen exposure avoidance, drug therapy, and allergen immunotherapy. This scoping review gathers the current up-to-date open access evidence available on PubMed on the subject of LAR. [ABSTRACT FROM AUTHOR]

Randomized controlled trials have demonstrated responses to clinical parameters, but a significant proportion of allergy patients in real-life settings would have been excluded from such studies. Therefore, real-world research is needed, and there is a growing body of information on allergen immunotherapy's long-term effectiveness and safety. Real-world evidence can be a valuable instrument to better understand the patient's journey and the effectiveness and safety of therapies. For this purpose, a registry will be used for the first time in Italy to evaluate the impact of allergen immunotherapy on several outcomes, including quality of life and disease-related effects in the pediatric and adult allergic population with a socio-economic assessment and respect to real-world health. [ABSTRACT FROM AUTHOR]

Background: Osimertinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine‐kinase inhibitor (TKI) and an available therapy for patients with non‐small cell lung cancer (NSCLC) that have an EGFR or T790M mutation. It has become the preferred TKI in this patient group as it is superior to first‐generation TKIs; however, osimertinib may be discontinued due to various toxicities or reactions. Aim: We report two instances of successful osimertinib desensitisation in a 70‐year‐old woman requiring treatment for NSCLC following two hypersensitivity reactions presenting as angioedema and urticaria. Clinical details: Osimertinib desensitisation started at 5 mg/day and was gradually increased to 80 mg/day over a period of 30 days. Outcomes: The patient continued osimertinib 80 mg daily for over a year until treatment was withheld for 4 weeks due to thrombocytopenia and diverticulitis. She restarted osimertinib, completing a second desensitisation to a reduced dose of 40 mg daily without serious adverse effect. The patient continues reduced‐dose osimertinib with stable disease. Conclusion: This case report proposes an osimertinib desensitisation strategy useful for select patients experiencing osimertinib‐induced hypersensitivity reactions. It also demonstrates that if there is prolonged disruption to treatment, a second desensitisation can be completed successfully in the same patient so effective treatment in NSCLC may be continued. [ABSTRACT FROM AUTHOR]

This article explores the differences in mast cell activation between anaphylaxis and desensitization in human peanut allergy. The study used human mast cells and sera from peanut-allergic individuals to investigate the functional differences in mast cell activation after anaphylaxis and desensitization. The findings suggest that desensitization reduces the overall activation and release of interleukin 8 (IL-8) compared to anaphylaxis. The study also found that refractoriness, or temporary antigen-specific resistance, occurs independently of the initial activation modality. Further research is needed to understand the immune response to allergen-specific immunotherapy in vivo. [Extracted from the article]

Background: Intralymphatic immunotherapy (ILIT) represents a promising novel approach treating allergic diseases. However, no standardized procedures or recommendations have been established or reported, despite the recognized fact that treatment efficacy relies on the ability to inject the allergen intranodally. Objective: We aim to provide a critical appraisal of ILIT as a method of allergen immunotherapy and to deliver practical recommendations for accurate ILIT. Methods: One hundred and seventy‐three ILIT injections were performed in 28 (47%) women and 32 (53%) men with median age of 29 years (21–59). The injections were ultrasound‐guided and recorded for retrospective analysis with respect to injection location, needle visibility, medication release, and patient characteristics. Results: The results show that the correct positioning of the needle within the lymph node (LN) was most critical. If the whole length of the needle bevel was not inserted into the LN, substance backflush into the interstitium was observed. Selecting a more superficial LN and inserting the needle at a smaller angle towards the LN significantly improved needle visibility in the ultrasound. Longitudinal results showed that continuous practice significantly correlated with improved needle visibility and more accurate ILIT injections. Conclusion: Based on our results and practical experience, we propose several recommendations for LN selection and the correct handling of ultrasound probe and needle. We are confident that ILIT standardization and training will be important as to meet the goals of good safety and efficacy of ILIT. [ABSTRACT FROM AUTHOR]

In rhinitis and asthma, several mHealth apps have been developed but only a few have been validated. However, these apps have a high potential for improving person‐centred care (PCC), especially in allergen immunotherapy (AIT). They can provide support in AIT initiation by selecting the appropriate patient and allergen shared decision‐making. They can also help in (i) the evaluation of (early) efficacy, (ii) early and late stopping rules and (iii) the evaluation of (carried‐over) efficacy after cessation of the treatment course. Future perspectives have been formulated in the first report of a joint task force (TF)—Allergic Rhinitis and Its Impact on Asthma (ARIA) and the European Academy of Allergy and Clinical Immunology (EAACI)—on digital biomarkers. The TF on AIT now aims to (i) outline the potential of the clinical applications of mHealth solutions, (ii) express their current limitations, (iii) make proposals regarding further developments for both clinical practice and scientific purpose and (iv) suggest which of the tools might best comply with the purpose of digitally‐enabled PCC in AIT. [ABSTRACT FROM AUTHOR]

The efficacy and safety of preventive allergen immunotherapy (pAIT) in children are currently under investigation. Here, we provide an overview of pAIT with respiratory allergens concerning the prevention of new sensitizations, allergic disease onset and progression as well as further immunomodulatory effects. Three databases were searched for clinical pAIT studies in children. Selected publications were reviewed for preventive outcomes according to prevention level (primary, secondary, and tertiary), allergen type, administration route, dose, and treatment duration. The primary prevention approach appears safe but showed no allergen‐specific effect on new sensitizations. Secondary prevention seems feasible and may induce regulatory T cell‐mediated immunotolerance. The number of studies at these prevention levels is limited. Tertiary prevention with grass and/or tree pollen‐based pAIT has shown efficacy in preventing disease progression from allergic rhinitis/conjunctivitis to asthma. Data on tertiary pAIT with house dust mites and other allergen types are inconclusive. Subcutaneous and sublingual routes appear similarly effective, but head‐to‐head comparative paediatric studies are scarce. Additionally, there are fewer placebo‐controlled studies. Nevertheless, immunomodulatory outcomes of pAIT are encouraging. Currently, limited but favourably suggestive evidence is available for preventing respiratory allergic diseases in children by pAIT. Primary and secondary prevention have potential and warrant further investigation through well‐designed studies. [ABSTRACT FROM AUTHOR]

Background: Local allergic rhinitis (LAR) is defined by chronic nasal symptoms, absence of atopy, positive nasal allergen challenge (NAC) and a good response to subcutaneous allergen immunotherapy (SCIT). We sought to investigate SCIT capacity to induce local and systemic blocking antibodies in LAR patients. Methods: A RDBPC study of grass SCIT was performed, with participants receiving either SCIT (Group A; n = 10) or placebo (Group B; n = 14) in the first 6 months. Both groups subsequently received SCIT for 12 months at Year 2. Nasal and serum antibodies (IgG4, IgA1 and IgA2) and their inhibitory capacity were measured at multiple timepoints. Results: The allergen concentration tolerated increased significantly at 6 months (Group A; p =.047) and 24 months (Group B; p =.049) compared with baseline and persisted until the end of the study. Induction of serum sIgA1 to Phl p was seen in Groups A and B, albeit the former being induced earlier (1.71‐fold, p =.027). A significant induction in sIgG4 to Phl p 1 and 5 was observed in serum of Group A (p =.047 and p =.0039) and sIgA2 to Phl p in Group B (p =.032 and p =.0098) at 18 and 24 months, respectively. Both local and systemic blocking antibodies can inhibit allergen–IgE complexes binding to CD23 on B cells, and this correlated with level of allergen tolerated intra‐nasally in Group A (serum; 휌 = −.47, p =.0006, nasal; 휌 = −.38, p =.0294). Conclusions: Grass pollen SCIT induced functional systemic blocking antibodies that correlate with the concentration of allergen tolerated following NAC, highlighting their potential as a biomarker of SCIT in LAR. [ABSTRACT FROM AUTHOR]

Certain chemotherapy agents have an increased potential to cause allergic reactions. These reactions can vary in severity from mild to severe, and a change in treatment may be suggested for the patient to avoid the causative agent going forward. This can lead to suboptimal treatment and a change from first-line therapy to a second-line therapy. In certain scenarios, drug desensitization may be considered to allow for continued administration of a standard-of-care chemotherapy agent to cure or palliate a patient's cancer. [ABSTRACT FROM AUTHOR]

Hypersensitivity reactions to anticancer drugs include treatment‐limiting toxicity. Standard drug desensitisation offers temporary tolerance and hence requires repetition. We used omalizumab, an anti‐immunoglobulin E antibody, to overcome immediate and delayed hypersensitivity reactions to various anticancer drugs. Seven of the eight patients in the current study successfully resumed the desired anticancer drug regimen without standard desensitisation. No safety issues from omalizumab were observed. [ABSTRACT FROM AUTHOR]

Background: Studying the sensitisation profiles of patients with allergies allows for a deeper understanding of the disease which may facilitate the selection of the best‐personalised allergen immunotherapy. This observational, cross‐sectional, multicentre study aimed to demonstrate the heterogeneity of the German population with allergies by analysing specific immunoglobulin E (sIgE) patterns towards aeroallergens and exploring the relationship between sensitisation and clinical symptoms. Methods: In total, 500 patients with allergies from different regions of Germany were recruited based on their case histories, clinical allergic symptoms and skin prick test data for aeroallergens. Serum samples were analysed using ImmunoCAP assays to determine sIgE levels for 33 allergenic sources and 43 molecular allergens. Results: Most patients (81%) were polysensitised. Betula verrucosa pollen was the most common cause of sensitisation (59%), followed by Phleum pratense (58%) and Dermatophagoides pteronyssinus (44%). The highest prevalence rates of molecular allergens were observed for Bet v 1 (84%) from birch pollen, Phl p 1 from grass pollen (82%), Der p 2 (69%) from mites and Fel d 1 (69%) from cat. Polysensitisation was significantly associated with the presence of asthma and the severity of rhinitis symptoms. Conclusions: Our findings show a high rate of polysensitisation and emphasise the importance of molecular diagnosis for more precise and comprehensive insights into sensitisation patterns and their association with clinical symptoms. These data may help improve personalised diagnosis and immunotherapy adapted to the needs of individual patients in the region. [ABSTRACT FROM AUTHOR]

Asthma poses significant challenges in pediatric care, particularly in resource-limited settings. The Global Initiative for Asthma (GINA) 2024 guidelines represents a crucial step forward in addressing these challenges. This review critically evaluates the guidelines, focusing on their implementation and impact in developing countries like India. There have been certain key updates including a revised diagnostic flow chart and emphasis on alternative tools like peak flow meters. Challenges related to bronchodilator reversibility and interpreting FEV1/FVC are also explored. The article further addresses the implications of bronchial provocation testing in pediatric asthma. Detailed insights into cough-variant asthma highlight its rising recognition and management strategies. The GINA 2024 guidelines reflect updated criteria for commencing a particular step of therapy, aiming to optimize management and outcomes in pediatric asthma care. The guidelines have updated the role of allergen immunotherapy in pediatric asthma based on emerging evidence of efficacy and safety. Overall, the GINA2024 guidelines offer a realistic approach to pediatric asthma care, with a potential for broader applications pending further research and adaptation. [ABSTRACT FROM AUTHOR]

Objective: Subcutaneous Immunotherapy (SCIT) is the long-lasting causal treatment of allergic rhinitis (AR). How to enhance the adherence of patients to maximize the benefit of allergen immunotherapy (AIT) plays a crucial role in the management of AIT. This study aims to leverage novel machine learning models to precisely predict the risk of non-adherence of AR patients and related local symptom scores in 3 years SCIT. Methods: The research develops and analyzes two models, sequential latentvariable model (SLVM) of Stochastic Latent Actor-Critic (SLAC) and Long Short-Term Memory (LSTM). SLVM is a probabilistic model that captures the dynamics of patient adherence, while LSTM is a type of recurrent neural network designed to handle time-series data by maintaining long-term dependencies. These models were evaluated based on scoring and adherence prediction capabilities. Results: Excluding the biased samples at the first time step, the predictive adherence accuracy of the SLAC models is from 60% to 72%, and for LSTM models, it is 66%-84%, varying according to the time steps. The range of Root Mean Square Error (RMSE) for SLAC models is between 0.93 and 2.22, while for LSTM models it is between 1.09 and 1.77. Notably, these RMSEs are significantly lower than the random prediction error of 4.55. Conclusion: We creatively apply sequential models in the long-term management of SCIT with promising accuracy in the prediction of SCIT nonadherence in AR patients. While LSTM outperforms SLAC in adherence prediction, SLAC excels in score prediction for patients undergoing SCIT for AR. The state-action-based SLAC adds flexibility, presenting a novel and effective approach for managing long-term AIT. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Antigen‐specific memory B cells play a key role in the induction of desensitization and remission to food allergens in oral immunotherapy and in the development of natural tolerance (NT). Here, we characterized milk allergen Bos d 9‐specific B cells in oral allergen‐specific immunotherapy (OIT) and in children spontaneously outgrowing cow's milk allergy (CMA) due to NT.Samples from children with CMA who received oral OIT (before, during, and after), children who naturally outgrew CMA (NT), and healthy individuals were received from Stanford biobank. Bos d 9‐specific B cells were isolated by flow cytometry and RNA‐sequencing was performed. Protein profile of Bos d 9‐specific B cells was analyzed by proximity extension assay.Increased frequencies of circulating milk allergen Bos d 9‐specific B cells were observed after OIT and NT. Milk‐desensitized subjects showed the partial acquisition of phenotypic features of remission, suggesting that desensitization is an earlier stage of remission. Within these most significantly expressed genes, IL10RA and TGFB3 were highly expressed in desensitized OIT patients. In both the remission and desensitized groups, B cell activation‐, Breg cells‐, BCR‐signaling‐, and differentiation‐related genes were upregulated. In NT, pathways associated with innate immunity characteristics, development of marginal zone B cells, and a more established suppressor function of B cells prevail that may play a role in long‐term tolerance. The analyses of immunoglobulin heavy chain genes in specific B cells demonstrated that IgG2 in desensitization, IgG1, IgA1, IgA2, IgG4, and IgD in remission, and IgD in NT were predominating. Secreted proteins from allergen‐specific B cells revealed higher levels of regulatory cytokines, IL‐10, and TGF‐β after OIT and NT.Allergen‐specific B cells are essential elements in regulating food allergy towards remission in OIT‐received and naturally resolved individuals. [ABSTRACT FROM AUTHOR]

Background: Polymerized allergoids conjugated with mannan represent a novel approach of allergen immunotherapy targeting dendritic cells. In this study, we aimed to determine the optimal dose of mannan-allergoid conjugates derived from grass pollen (Phleum pratense and Dactylis glomerata) administered via either the subcutaneous or sublingual route. Methods: A randomized, double-blind, placebo-controlled trial with a doubledummy design was conducted, involving 162 participants across 12 centers in Spain. Subjects were randomly allocated to one of nine different treatment groups, each receiving either placebo or active treatment at doses of 500, 1,000, 3,000, or 5,000 mTU/mL over four months. Each participant received five subcutaneous (SC) doses of 0.5 mL each, every 30 days, and a daily sublingual (SL) dose of 0.2 mL. Participants who received active treatment through SC, received placebo through SL. Participants who received active treatment through SL, received placebo SC. One Group, as control, received bot SC and SL placebo. The primary efficacy outcome was the improvement in titrated nasal provocation tests (NPT) at the end of the study compared to baseline. Secondary outcomes included specific antibody (IgG4, IgE) and cellular (IL-10 producing and regulatory T cell) responses. All adverse events and side reactions were recorded and assessed. Results: Post-treatment, the active groups showed improvements in NPT ranging from 33% to 53%, with the highest doses showing the greatest improvements regardless of the administration route. In comparison, the placebo group showed a 12% improvement. Significant differences over placebo were observed at doses of 3,000 mTU/mL (p=0.049 for SL, p=0.015 for SC) and 5,000 mTU/mL (p=0.011 for SL, p=0.015 for SC). A dose-dependent increase in IgG4 was observed following SC administration, and an increase in IL-10 producing cells for both routes of administration. No serious systemic or local adverse reactions were recorded, and no adrenaline was required. Conclusion: Grass pollen immunotherapy with mannan-allergoid conjugates was found to be safe and efficacious in achieving the primary outcome, whether administered via the subcutaneous or sublingual routes, at doses of 3,000 and 5,000 mTU/mL. [ABSTRACT FROM AUTHOR]

Potential kidney transplant patients with HLA-specific antibodies have reduced access to transplantation. Their harmful effects are mediated by the Fc portion of IgG, including activation of the complement system and Fc receptor-initiated cytotoxic processes by circulating leucocytes. Avoiding antibody incompatibility is the conventional approach, but for some patients this can mean extended waiting times, or even no chance of a transplant if there are no alternative, compatible donors. For these cases, pretransplant antibody removal may provide access to transplantation. Plasmapheresis is currently used to achieve this, with acceptable outcome results, but the process can take days to reduce the antibody levels to a safe level, so has limited use for deceased donors. There is now an alternative, in the form of an IgG-digesting enzyme, Imlifidase, which can be administered for in vivo IgG inactivation. Imlifidase cleaves human IgG, separating the antigen-binding part, F(ab')2 from Fc. Typically, within six hours of dosing, most, if not all, of the circulating IgG has been inactivated, allowing safe transplantation from a previously incompatible donor. For deceased donor transplantation, where minimizing cold ischaemia is critical, this six-hour delay before implantation should be manageable, with the compatibility testing processes adjusted to accommodate the treatment. This agent has been used successfully in phase 2 clinical trials, with good short to medium term outcomes. While a donation rate that matches demand may be one essential answer to providing universal access to kidney transplantation, this is currently unrealistic. IgG inactivation, using Imlifidase, is, however, a realistic and proven alternative. [ABSTRACT FROM AUTHOR]

Introduction: Procarbazine is an oral chemotherapeutic agent used in the treatment of brain malignancies and is associated with hypersensitivity reactions. In case of grade 4 reactions, rechallenge should be avoided, and the agent should be replaced, unless the treatment is curative, in which case the application of a desensitization protocol should be considered. We present a successful case of desensitization in procarbazine anaphylaxis. Case report: A 53-year-old male patient was diagnosed with recurrent anaplastic oligodendroglioblastoma. The patient received three cycles of procarbazine, lomustine, and vincristine chemotherapy for malignancy recurrence. In the fourth cycle, on the 12th day of procarbazine treatment, the patient developed anaphylaxis. Procarbazine was given together with premedication as part of the 12-step desensitization process, and the fourth cycle was successfully completed. Management and outcome: Procarbazine hypersensitivity reactions are observed less frequently than reactions to other chemotherapeutics. We presented a case of procarbazine-associated severe anaphylaxis that was able to continue procarbazine chemotherapy with successful desensitization. This case is important in terms of confirming the procarbazine desensitization protocol. Discussion: In literature there is only one protocol developed was successfully applied in one patient with procarbazine anaphylaxis. In the current case, we took this protocol into consideration in the management of our patient. Following the use of this protocol, the patient was able to continue procarbazine chemotherapy successfully. Procarbazine anaphylaxis is rare, and more cases are needed to be reported to confirm the desensitization protocol and when to continue procarbazine treatment. [ABSTRACT FROM AUTHOR]

Background: Hypersensitivity reactions to anticancer chemotherapy and monoclonal antibodies may lead to discontinuation of first-line treatment options. Identification of these reactions can provide specific diagnosis and treatment by rapid drug desensitizations. Objective: To determine the hypersensitivity reactions involved in anticancer chemotherapy and monoclonal antibodies, and the safety and efficacy of rapid drug desensitization. Methods: We conducted an observational study of hypersensitivity reaction presented after the administration of anticancer chemotherapy and monoclonal antibodies in Mexico. We documented the symptoms of initial reaction and their severity, and the results of skin tests. We also report our experience of the administration of 12-step (mild-moderate reactions) and 16-step (severe reactions) desensitization protocols in these patients. Results: Overall, 93 patients received 336 rapid drug desensitization; 105 to taxanes, 115 to platinum drugs, 101 to monoclonal antibodies, and 15 other anticancer chemotherapy. Hypersensitivity reaction to taxanes occurred in the first or second administration, platinum drugs after the sixth cycle, and rituximab in the first cycle. The most common symptom in carboplatin was urticaria, paclitaxel back pain, oxaliplatin and docetaxel dyspnea, and in the monoclonal antibodies cardiovascular symptoms. Skin tests were positive in 75% of the carboplatin group, and only 16.7% in docetaxel. There was a rapid drug desensitization success rate of 99.4% and 85.7% did not present any related hypersensitivity reaction. Conclusion: The diagnosis of hypersensitivity reaction to anticancer chemotherapy and monoclonal antibodies offers a panorama in the management of oncological diseases. Our standardized desensitization protocol is safe and effective and can be reproduced in other centers to treat patients who need to maintain first-line treatment. [ABSTRACT FROM AUTHOR]

Background: House dust mite (HDM) sensitisation can contribute to the development of allergic rhinoconjunctivitis (AR) or allergic asthma (AA). As treatment, allergen immunotherapy (AIT) is a promising approach, since it aims building immunotolerance against allergens, therewith establishing long‐term efficacy. The evaluation of AIT has been investigated in many randomised controlled trials, whereas few real‐world evidence studies are available. Methods: We used data from the longitudinal prescription data base IQVIA™ LRx. Data on initial AIT prescriptions against HDM from January 2009 to December 2013 was analysed regarding treatment (subcutaneous AIT with either depigmented polymerised allergen extract [dSCIT] or other allergens [oSCIT], or sublingual immunotherapy [SLIT]) and treatment duration. Treatment groups were compared with a control group of AR patients not receiving AIT. Data on symptomatic medication was collected until February 2017 and progression of AR and AA was compared. Results: Data of 7260 patients with AIT prescriptions and of 21,780 control patients was analysed. AIT was associated with a significant decrease of AR medication intake compared with control (dSCIT: −34.0%, p < 0.0001; oSCIT: −25.7%, p < 0.0001; SLIT: −37.7%, p = 0.0026). In asthmatics, SCIT was associated with a significant decrease of asthma medication compared with control (dSCIT: −45.2%, p < 0.0001; oSCIT: −32.9%, p < 0.0001). Further, a significantly reduced likelihood for onset of asthma medication was demonstrated in patients treated with SCIT compared with controls (dSCIT OR: 0.759, p = 0.0476; oSCIT OR: 0.815, p = 0.0339). Conclusion: Real‐world data analyses indicate that AIT, particularly given via a subcutaneous route, reduces the need of medication against AR and AA and might delay the onset of asthma medication in patients with AR. [ABSTRACT FROM AUTHOR]

Background: The SQ tree sublingual immunotherapy (SLIT)‐tablet is authorised for treatment of allergic rhinoconjunctivitis with or without asthma in trees of the birch homologous group in 21 European countries. The primary objective of this study was to explore the safety in real‐life. Methods: In a prospective, non‐interventional post‐authorisation safety study (EUPAS31470), adverse events (AEs) and adverse drug reactions (ADRs) at first administration and follow‐up visits, symptoms, medication use, and pollen food syndrome were recorded by physicians in 6 European countries during the first 4–6 months of treatment. Results: ADRs with the SQ tree SLIT‐tablet were reported in 57.7% of 1069 total patients (median age 36.0 years, 53.7% female) during the entire observation period (severity, mild‐to‐moderate: 70.1%, severe: 4.7%, serious: 0.7%) and in 45.9% after first administration. ADRs were not increased with pollen exposure at first administration. With coadministration of the SQ tree and grass SLIT‐tablet AEs were reported in 73.8% of patients and in 52.8% with the SQ tree SLIT‐tablet alone. Nasal and eye symptoms improved in 86.9% and 80.9% of patients and use of symptomatic medication in 76.0%. PFS with symptoms was reported in 43.0% of patients at baseline and in 4.3% at the individual last visit. Conclusions: The results of this non‐interventional safety study with the SQ tree SLIT‐tablet confirm the safety profile from placebo‐controlled clinical trials and support effectiveness in real‐life according to the published efficacy data. Safety was not impaired by pollen exposure at first administration or co‐administration with other SLIT‐tablets. [ABSTRACT FROM AUTHOR]

This article discusses the development of a potential immunotherapy treatment for peanut allergy. The researchers conjugated peanut extract with galactomannan, a higher molecular weight saccharide, to reduce the allergenicity of the extract. They found that the conjugated extract, known as PE-GM, showed reduced reactivity with IgE antibodies and basophil activation in patients with peanut allergy. In a mouse model, PE-GM also demonstrated a lower anaphylactic response compared to untreated mice. These findings suggest that PE-GM could be a safer and more effective treatment option for peanut allergy. [Extracted from the article]

Background: Sublingual immunotherapy (SLIT) for perennial allergic rhinitis (AR) has not been extensively studied in preschoolers. We investigated the efficacy and safety of house dust mite (HDM) SLIT‐tablet for children aged 1–4 years. Methods: Children aged 1–4 years with AR were divided into SLIT (n = 22) and control (n = 12) groups based on their guardians' preferences. The SLIT group received a daily dose of 10,000 JAU of HDM SLIT‐tablet for 12 months, whereas the control group received symptomatic treatment only. Results: The baseline median age was 41 and 34 months in the SLIT and control groups, respectively, and the median AR symptom score was 4 for both groups. Compared with baseline, the AR symptom score had decreased significantly in the SLIT group after 12 months (score: 3, p =.002), whereas it tended to increase in the control group (score: 6, p =.08). Adverse reactions to SLIT were mild and occurred in eight patients (36%). In the SLIT group, Dermatophagoides (D.) farinae‐specific IgE (sIgE) levels increased during the first 6 months and decreased to baseline levels at 12 months. In the control group, D. farinae‐sIgE levels had increased significantly at 12 months compared to baseline (p =.01). D. farinae‐specific IgG4 and HDM IgE‐blocking factor levels were significantly increased at 12 months compared to baseline in the SLIT group only (p <.001). A lower wheezing frequency was seen in the SLIT group (0.3%) compared to the control group (0.7%). Conclusion: This pilot study demonstrated the efficacy, safety, and immunomodulatory effects of HDM SLIT‐tablet in preschoolers with AR. [ABSTRACT FROM AUTHOR]

Background: The fluctuation in concentrations of airborne allergens frequently presents a challenge to assessing the efficacy of allergen immunotherapy (AIT) in 'field' studies. Allergen exposure chambers (AECs) are specialized medical installations developed to expose individuals to allergens at defined and consistent concentrations under a controlled environment. The aim of the study was to validate the provocation test with timothy grass pollen as well as to assess its safety in the AEC in patients with allergic rhinitis. Methods: In the ALLEC® AEC, varying concentrations of timothy grass pollen were dispersed. Allergic symptoms were measured by total nasal symptom score (TNSS), acoustic rhinometry, peak nasal inspiratory flow (PNIF) and nasal discharge volume. Lung function, assessed through peak expiratory flow rate (PEFR) and forced expiratory volume in the first second (FEV1), was used to evaluate safety. Results: The consistency of the test was proved by the stability of environmental conditions, including temperature, humidity and CO2 levels, as well as constant concentrations of grass pollen at predetermined levels ranging from 1000 to 10,000 particles per cubic meter (p/m3). Allergic individuals developed symptoms at concentrations of 3000 p/m3 and above, across all measured endpoints. Lung function was not affected throughout all the challenges. The reproducibility of symptoms was confirmed throughout the tests. The concentration of 8000 p/m3 together with a challenge duration of 120 min was found to be optimal. Conclusion: The study demonstrates that the ALLEC® grass pollen exposure chamber provides a reliable and safe method for inducing repeatable symptoms in patients with allergic rhinitis. This approach can be effectively applied for allergy diagnostics and clinical endpoint determination during AIT. [ABSTRACT FROM AUTHOR]