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Background: House dust mite (HDM)-induced allergic rhinitis (AR) is a major cause of allergic respiratory disease. The efficacy and safety of the 300 IR HDM sublingual immunotherapy (SLIT) tablet in patients with moderate-to-severe HDM-AR was confirmed in a large, international, phase 3 randomized controlled trials (RCTs). Here, we analyzed the results in the European population. Methods: Data from 91 European centers that participated in the international, double-blind, RCT (EudraCT 2014-004223-46, NCT02443805) with the 300 IR HDM SLIT tablet versus placebo over 12 months were analyzed post hoc. The treatment effect in European adults and adolescents was notably assessed through the European Academy of Allergy and Clinical Immunology (EAACI)-recommended combined symptom and medication score (CSMS0-6, pre-defined endpoint) and the total combined rhinitis score (TCRS0-24, post hoc endpoint, also balanced) during the primary evaluation period (4 weeks at the end of treatment period) using analysis of covariance (ANCOVA). Results: There were 818 patients who comprised the modified full analysis set in Europe. Over the primary period, the differences in CSMS0-6 and TCRS0-24 between the 300 IR and placebo groups were statistically significant (p

In March 2023, the European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual Summit in Brussels with expert panel members of EUFOREA, representatives of the EUFOREA patient advisory board, and the EUFOREA board and management teams. Its aim was to define the research, educational and advocacy initiatives to be developed by EUFOREA over the next 2 years until the 10th anniversary in 2025. EUFOREA is an international non-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic allergic and respiratory diseases via research, education, and advocacy. Based on its medical scientific core competency, EUFOREA offers an evidence-supported platform to introduce innovation and education in healthcare leading to optimal patient care, bridging the gap between latest scientific evidence and daily practice. Aligned with the mission of improving health care, the expert panels of asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS) & European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), allergen immunotherapy (AIT) and paediatrics have proposed and elaborated a variety of activities that correspond to major unmet needs in the allergy and respiratory field. The current report provides a concise overview of the achievements, ambitions, and action plan of EUFOREA for the future, allowing all stakeholders in the allergy and respiratory field to be up-dated and inspired to join forces in Europe and beyond.

The efficacy of an allergen-specific IgG cocktail to treat cat allergy suggests that allergen-specific IgG may be a major protective mechanism elicited by allergen immunotherapy. Extending these findings, we tested a Bet v 1–specific antibody cocktail in birch-allergic subjects. This was a phase 1, randomized, double-blind, study with 2 parts. Part A administered ascending doses of the Bet v 1–specific antibody cocktail REGN5713/14/15 (150-900 mg) in 32 healthy adults. Part B administered a single subcutaneous 900-mg dose or placebo in 64 birch-allergic subjects. Total nasal symptom score response to titrated birch extract nasal allergen challenge and skin prick test (SPT) with birch and alder allergen were assessed at screening and days 8, 29, 57, and 113 (SPT only); basophil activation tests (n = 26) were conducted. Single-dose REGN5713/14/15 significantly reduced total nasal symptom score following birch nasal allergen challenge relative to baseline. Differences in total nasal symptom score areas under the curve (0-1 hour) for subjects treated with REGN5713/14/15 versus those given placebo (day 8: −1.17, P =.001; day 29: −1.18, P =.001; day 57: −0.85, P =.024) and titration SPT with birch difference in area under the curve of mean wheal diameters for subjects treated with REGN5713/14/15 versus placebo (all P <.001) were sustained for ≥2 months; similar results were observed with alder SPT. REGN5713/14/15 was well tolerated. Basophil responsiveness to birch-related allergens was significantly decreased in subjects treated with REGN5713/14/15 versus those given placebo on days 8, 57, and 113 (all P <.01). Single-dose REGN5713/14/15 was well tolerated and provided a rapid (1 week) and durable (2 months) reduction in allergic symptoms after birch allergen nasal allergen challenge, potentially offering a new paradigm for the treatment of birch allergy symptoms. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary: Background: In humans, both basophils and dendritic cells (DCs) express the high‐affinity IgE receptor (FcεRI). Objective: To gain more insight into the relation between serum IgE levels and FcεRI expression and IgE binding by DCs and basophils in house dust mite (HDM) allergy and during subcutaneous immunotherapy (SCIT). Methods: We measured FcεRI, IgE and HDM allergen on DCs (conventional type 2 DCs, cDC2s; plasmacytoid dendritic cells, pDCs) and basophils by flow cytometry in 22 non‐allergic vs 52 allergic subjects and upon HDM SCIT in 28 allergic subjects. IgE levels were measured in serum. Results: Serum IgE correlated differentially with FcεRI expression and IgE binding depending on cell type and allergic status. In non‐allergic subjects, FcεRI/IgE surface densities increased with serum IgE to a significantly stronger degree on basophils compared to cDC2s. By contrast, in allergic subjects FcεRI/IgE surface densities increased with serum IgE to a slightly stronger degree on cDC2s compared to basophils. In addition, the data set suggests sequential loading of IgE onto FcεRI expressed by these cells (basophils>cDC2s>pDCs). Finally, HDM SCIT induced a temporary increase in serum IgE, which was paralleled by a peak in FcεRI and IgE on DCs, but not on basophils. Conclusions & Clinical Relevance: This study provides a comprehensive insight into the relation between serum IgE and FcεRI/IgE on basophils and DC subsets. The novel finding that HDM SCIT induces a temporary increase in FcεRI expression on DCs, but not on basophils, can be an incentive for future research on the potential tolerogenic role of IgE/FcεRI signalling in DCs in the setting of allergen immunotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Nasal allergen challenge (NAC) is an important tool to diagnose allergic rhinitis. In daily clinical routine, experimentally, or when measuring therapeutic success clinically, nasal allergen challenge is fundamental. It is further one of the key diagnostic tools when initiating specific allergen immunotherapy. So far, national recommendations offered guidance on its execution; however, international divergence left many questions unanswered. These differences in the literature caused EAACI to initiate a task force to answer unmet needs and find a consensus in executing nasal allergen challenge. On the basis of a systematic review containing nasal allergen challenges of the past years, task force members reviewed evidence, discussed open issues, and studied variations of several subjective and objective assessment parameters to propose a standardized way of a nasal allergen challenge procedure in clinical practice. Besides an update on indications, contraindications, and preparations for the test procedure, main recommendations are a bilaterally challenge with standardized allergens, with a spray device offering 0.1 mL per nostril. A systematic catalogue for positivity criteria is given for the variety of established subjective and objective assessment methods as well as a schedule for the challenge procedure. The task force recommends a unified protocol for NAC for daily clinical practice, aiming at eliminating the previous difficulty of comparing NAC results due to unmet needs. [ABSTRACT FROM AUTHOR]

Allergen immunotherapy (AIT) is an effective treatment strategy for allergic diseases and has been used for more than 100 years. In recent years, however, the expectations on concepts, conduct, statistical evaluation, and reporting have developed significantly. Products have undergone dose-response and confirmative studies in adults and children to provide evidence for the optimal dosage, safety, and efficacy of AIT vaccines using subcutaneous and sublingual delivery pathways in large patient cohorts, ensuring solid conclusions to be drawn from them for the advantage of patients and societies alike. Those standards should be followed today, and products answering to them should be preferred over others lacking optimization and proof of efficacy and safety. Molecular and cellular mechanisms of AIT include early mast cell and basophil desensitization effects, regulation of T- and B-cell responses, regulation of IgE and IgG 4 production, and inhibition of responses from eosinophils, mast cells, and basophils in the affected tissues. There were many developments to improve vaccination strategies, demonstration of new molecules involved in molecular mechanisms, and demonstration of new biomarkers for AIT during the last few years. The combination of probiotics, vitamins, and biological agents with AIT is highlighting current advances. Development of allergoids and recombinant and hypoallergenic vaccines to skew the immune response from IgE to IgG 4 and regulation of dendritic cell, mast cell, basophil, innate lymphoid cell, T-cell, and B-cell responses to allergens are also discussed in detail. [ABSTRACT FROM AUTHOR]

Precision medicine ( PM) is increasingly recognized as the way forward for optimizing patient care. Introduced in the field of oncology, it is now considered of major interest in other medical domains like allergy and chronic airway diseases, which face an urgent need to improve the level of disease control, enhance patient satisfaction and increase effectiveness of preventive interventions. The combination of personalized care, prediction of treatment success, prevention of disease and patient participation in the elaboration of the treatment plan is expected to substantially improve the therapeutic approach for individuals suffering from chronic disabling conditions. Given the emerging data on the impact of patient stratification on treatment outcomes, European and American regulatory bodies support the principles of PM and its potential advantage over current treatment strategies. The aim of the current document was to propose a consensus on the position and gradual implementation of the principles of PM within existing adult treatment algorithms for allergic rhinitis ( AR) and chronic rhinosinusitis ( CRS). At the time of diagnosis, prediction of success of the initiated treatment and patient participation in the decision of the treatment plan can be implemented. The second-level approach ideally involves strategies to prevent progression of disease, in addition to prediction of success of therapy, and patient participation in the long-term therapeutic strategy. Endotype-driven treatment is part of a personalized approach and should be positioned at the tertiary level of care, given the efforts needed for its implementation and the high cost of molecular diagnosis and biological treatment. [ABSTRACT FROM AUTHOR]

The article focuses on a pilot randomized clinical trial. on probiotics-impregnated bedding covers for house dust mite allergic rhinitis (AR). AR affects up to one-third of the adult population and causes illness and disability world-wide. Main symptoms include sneezing, rhinorrhea and nasal obstruction.

This report has been prepared by the European Academy of Allergy and Clinical Immunology Task Force on Allergic Rhinitis (AR) comorbidities. The aim of this multidisciplinary European consensus document is to highlight the role of multimorbidities in the definition, classification, mechanisms, recommendations for diagnosis and treatment of AR and to define the needs in this neglected area by a literature review. AR is a systemic allergic disease and is generally associated with numerous multi-morbid disorders, including asthma, eczema, food allergies, eosinophilic oesophagitis (EoE), conjunctivitis, chronic middle ear effusions, rhinosinusitis, adenoid hypertrophy, olfaction disorders, obstructive sleep apnea, disordered sleep and consequent behavioural and educational effects. This report provides up-todate usable information to: (1) improve the knowledge and skills of allergists, so as to ultimately improve the overall quality of patient care; (2) to increase interest in this area and (3) to present a unique contribution to the field of upper inflammatory disease. [ABSTRACT FROM AUTHOR]

The last year has seen great progress in the understanding of upper airway disease and in its management. For allergic rhinitis, authors focused on the prediction of and effect on the natural course of disease. New evidence was published for the disease-modifying effect of allergen immunotherapy in terms of avoidance of new sensitizations and prevention of asthma in either randomized or real-life studies. Specifically, for patients with house dust mite allergies, which are often underestimated and difficult to diagnose, the efficacy of SQ house dust mite sublingual immunotherapy tablets has been demonstrated in patients with allergic rhinitis and asthma. For the first time, allergen immunotherapy significantly reduced asthma exacerbations. In patients with chronic rhinosinusitis, a novel endotyping approach purely based on T helper cell biomarkers has been developed and has shown clinical relevance through associations with asthma comorbidity and recurrence after surgery. Severe nasal polyposis with high risk for asthma comorbidity and disease recurrence is characterized by type 2 inflammatory patterns, including IgE antibodies to staphylococcal superantigens; several studies using biologic agents have targeted exactly this spectrum of mediators. This goes in parallel with new knowledge on even more type 2 mediators derived from epithelial cells, which will expand the number of possible candidates for innovative intervention. [ABSTRACT FROM AUTHOR]

Background The majority of grass pollen-sensitized rhinitis patients develops allergic symptoms when exposed to the causal allergen and shows a positive nasal allergen provocation test ( NAPT). Chronic rhinosinusitis with nasal polyposis ( CRSw NP) patients, also characterized by eosinophilic inflammation and local IgE production, can suffer from comorbid inhalant allergy, but may show a different response to allergens. Objective We aimed to explore the allergic response to grass pollen allergens by NAPT in grass pollen-sensitized CRSw NP patients. Methods Twelve grass pollen-sensitized CRSw NP patients underwent NAPT with grass pollen and were compared with 12 grass pollen allergic rhinitis patients, 12 control patients and 12 CRSw NP patients without grass pollen sensitization. A positive NAPT was based on change in nasal airflow and symptoms. Further, VAS scores of different symptoms were noted before and after NAPT. Biomarkers such as total IgE, grass pollen-specific IgE and tryptase were measured in serum and nasal secretions. Results NAPT was positive in 6 of 12 of the grass pollen-sensitized CRSw NP patients, and another four patients developed allergic symptoms not fulfilling the criteria of positivity. In contrast, all patients with allergic rhinitis developed a positive provocation test, whereas in the control group one of the patients and in the non-sensitized CRSw NP group two of the patients developed a positive provocation test. Conclusion and clinical relevance These results show that allergen exposure induces an attenuated clinical response in patients with CRSw NP and sensitization to grass pollen as compared with grass pollen allergic rhinitis patients. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis with nasal polyps ( NP) and allergic rhinitis ( AR) is characterized by local Th2 inflammation and up-regulation of IgE; however, IgE in NP is 'polyclonal' and allergen specific, whereas IgE in AR is 'oligoclonal' and allergen specific. Germinal center ( GC) reactions occur in AR, while only the formation of GC-like structures in NP is described. The aim of this study was to investigate the involvement of local IgE production, class switch recombination, and receptor revision in NP. Methods We compared the levels of local IgE, germline gene transcripts, and mature Ig mRNA expression, recombination activating gene (RAG1 and RAG2), key markers of Th2 inflammation, and GC reactions in NP tissue vs AR and control tissue. Nasal mucosa was immunostained for the co-expression of RAG1 and RAG2 in B cells, plasma cells, and T cells, using dual or triple immunofluorescence (IF). Results In NP, local IgE level and key markers of local class switching are increased compared with AR and normal controls (NC). In NP, switch circle transcripts reveal ongoing local class switch recombination to IgE. Up to 30% of B cells, plasma cells, and T cells in nasal polyps re-express both RAG1 and RAG2, required for receptor revision. RAG1 and RAG2 mRNA concentrations are increased in NP and correlated with the magnitude of inflammation and the presence of S. aureus enterotoxin (superantigen)-specific IgE in the nasal polyp mucosa. Conclusion Our results provide the first evidence of local receptor revision and class switching to IgE, and B-cell differentiation into IgE-secreting plasma cells in NP. [ABSTRACT FROM AUTHOR]

State-of-the-art documents like ARIA and EPOS provide clinicians with evidence-based treatment algorithms for allergic rhinitis ( AR) and chronic rhinosinusitis ( CRS), respectively. The currently available medications can alleviate symptoms associated with AR and RS. In real life, a significant percentage of patients with AR and CRS continue to experience bothersome symptoms despite adequate treatment. This group with so-called severe chronic upper airway disease ( SCUAD) represents a therapeutic challenge. The concept of control of disease has only recently been introduced in the field of AR and CRS. In case of poor control of symptoms despite guideline-directed pharmacotherapy, one needs to consider the presence of SCUAD but also treatment-related, diagnosis-related and/or patient-related factors. Treatment-related issues of uncontrolled upper airway disease are linked with the correct choice of treatment and route of administration, symptom-oriented treatment and the evaluation of the need for immunotherapy in allergic patients. The diagnosis of AR and CRS should be reconsidered in case of uncontrolled disease, excluding concomitant anatomic nasal deformities, global airway dysfunction and systemic diseases. Patient-related issues responsible for the lack of control in chronic upper airway inflammation are often but not always linked with adherence to the prescribed medication and education. This review is an initiative taken by the ENT section of the EAACI in conjunction with ARIA and EPOS experts who felt the need to provide a comprehensive overview of the current state of the art of control in upper airway inflammation and stressing the unmet needs in this domain. [ABSTRACT FROM AUTHOR]

Allergic asthma and allergic rhinitis/conjunctivitis are characterized by a TH2-dominated immune response associated with increased serum IgE levels in response to inhaled allergens. Because IgE is a key player in the induction and maintenance of allergic inflammation, it represents a prime target for therapeutic intervention. However, our understanding of IgE biology remains fragmentary. This article puts together our current knowledge on IgE in allergic airway diseases with a special focus on the identity of IgE-secreting cells (“who”), their location (“where”), and the circumstances in which they are induced (“when”). We further consider the therapeutic implications of the insights gained. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus may modify airway disease by inducing local formation of polyclonal IgE antibodies (abs), the role of which is unknown. Methods: Nasal mucosal tissue and serum was obtained from 12 allergic rhinitis (AR) and 14 nasal polyp (NP) subjects. Skin prick tests were performed, and total and specific IgE abs to inhalant allergens and enterotoxin B were determined in serum and tissue. Tissue fragments were stimulated with anti-IgE, enterotoxin B, or grass and house dust mite allergens in different concentrations for 30 min. RBL SX38 cells were sensitized with NP homogenates containing IgE and stimulated with grass pollen extracts. Results: In AR patients, degranulation of tissue mast cells upon allergen exposure and presence of specific IgE to inhalant allergens corresponded in almost all cases. Total IgE concentrations in serum and mucosal tissue homogenates highly correlated. In contrast, in NP patients, reactivity of tissue mast cells upon allergen exposure and presence of specific IgE to inhalant allergens or Staphylococcus aureus enterotoxin B corresponded for tissue, but not for serum. Total IgE was significantly higher in tissue compared to serum and failed to show correlation. Tissue IgE to grass pollen was functional to degranulate RBL cells. Conclusion: We here demonstrate that mucosal IgE abs in NP tissue are functional and able to activate mast cells; specific IgE abs in NP tissue can be found independently of their presence in serum. We postulate that superantigen-induced polyclonal IgE in airway disease contributes to chronic inflammation by continuously activating mast cells. [ABSTRACT FROM AUTHOR]

Background The role of bacterial enterotoxins like Staphylococcus aureus enterotoxin B (SEB) in allergic asthma remains unknown. We used a mouse model of airway allergy to study the effects of nasal or bronchial contact with SEB on bronchial allergic inflammation. Methods The features of allergic asthma were induced in ovalbumin (OVA)-sensitized mice (days 1–13) by repeated exposures to nebulized OVA (days 33–37). Nasal or bronchial application of SEB was performed on three occasions (days 33–35–37), and the effects on bronchial inflammation, IgE titres and expression levels of mRNA for T helper type 2 cytokines and other inflammatory mediators were evaluated. Results Both nasal and bronchial SEB enhanced the allergen-induced bronchial inflammation, as reflected by more eosinophilic inflammation in the airway lumen and in bronchial tissue. Aggravation of experimental asthma correlated with higher expression of mRNA for IL-5, IL-4, IFN-γ, IL-12 p40, eotaxin-1 and TGF-β in bronchi. In addition, nasal SEB elevated concentrations of IL-4, IL-5 and IFN-γ in serum and bronchial SEB increased titres of OVA-specific and total IgE in serum. Conclusion Our data illustrate the potential of both nasal as well as bronchial SEB to aggravate several features of allergic asthma in a mouse model. [ABSTRACT FROM AUTHOR]

Background: This paper reports a study on the concentrations of the pro-inflammatory cytokines IL-18 and IL-1β in nasal secretions of allergic rhinitis patients in relation to ECP and nasal symptoms. Methods: We measured IL-18 and IL-1β concentrations using ELISA, and eosinophilic cationic protein (ECP) using the CAP system, in nasal secretions of 15 seasonal allergic rhinitis (SAR) patients at six visits throughout the pollen season. Pollen exposure, nasal and ocular symptoms were monitored daily. Furthermore, we measured IL-18, IL-1β and ECP concentrations in nasal secretions of 19 controls and 20 symptomatic persistent allergic rhinitis (PAR) patients with house dust mite allergy. Results: In SAR, the increase of IL-18, IL-1β and ECP paralleled the pollen flight with a time delay. IL-18 and IL-1β significantly increased during the pollen season compared to baseline, and differently from ECP, remained elevated until 4 weeks after the season. In PAR, the concentrations of IL-18 and ECP, but not IL-1β, were significantly higher compared to controls, with IL-18 concentrations also being significantly higher than in SAR. Conclusion: This is the first study to demonstrate the up-regulation of IL-18 in nasal secretions in allergic rhinitis. The persistence of elevated IL-18 concentrations until after the season and the high concentrations in PAR compared to SAR suggests its role in persistent allergic inflammation. [ABSTRACT FROM AUTHOR]

Allergic rhinitis induced by house dust mites (HDMs) is a highly prevalent but often underdiagnosed and undertreated/untreated chronic disease. It often has a negative impact on sleep, work, leisure activities, and health-related quality of life. Allergen immunotherapy is a proven, safe treatment for respiratory allergies. We sought to assess the efficacy and safety of a 300 index of reactivity (IR) sublingual tablet formulation of Dermatophagoides pteronyssinus : Dermatophagoides farinae 1:1 extract in adolescents (aged ≥12) and adults with moderate to severe HDM-induced allergic rhinitis. In a phase III, international, double-blind, placebo-controlled, randomized clinical trial, participants received approximately 12 months of treatment with placebo or the 300 IR tablet. The primary end point was the average total combined score during 4 weeks at the end of the treatment period. A total of 1607 participants were randomized, and 1476 (including 555 [37.6%] with concomitant mild controlled asthma at inclusion) comprised the full analysis set. Over the primary evaluation period, the least squares mean average total combined score in the 300 IR group (3.62) was significantly lower (P <.0001) than in the placebo group (4.35), with a relative least squares mean difference of −16.9% (95% CI, −24.0% to −9.2%). All prespecified secondary end points were consistently improved in the 300 IR group, relative to placebo. The 300 IR tablet was generally well tolerated. Treatment-related adverse events (mainly mild or moderate local reactions) were reported for 51.0% of the patients in the 300 IR group and 14.9% in the placebo group. The 300 IR sublingual HDM tablet is an effective, safe treatment for HDM-induced allergic rhinitis. [ABSTRACT FROM AUTHOR]

Abstract Allergic rhinitis (AR) affects 23–30% of the European population with equal prevalence reported in Belgium. Despite guidelines on the correct use of effective treatment, up to 40% of AR patients remain uncontrolled. Allergen immunotherapy (AIT) has been shown to improve the level of control up to 84% of patients being controlled by AIT. Recently, new guidelines for AIT have been published, supporting the clinical evidence for effectiveness of various subcutaneous and sublingual products for AIT in patients who are allergic to airborne allergens. AIT in AR patients not only reduces nasal and/or ocular symptoms but also induces tolerance and has preventive potential. Adoption of AIT into daily clinical practice in Belgium and other European countries is hampered primarily by reimbursement issues of each of the single products but also by several patient- and physician-related factors. Patients need to be better informed about the effectiveness of AIT and the different routes of administration of AIT. Physicians dealing with AR patients should inform patients on tolerance-inducing effects of AIT and are in the need of a harmonized and practical guide that supports them in selecting eligible patients for AIT, in choosing evidence-based AIT products and in following treatment protocols with proven efficacy. Therefore, a stepwise and holistic approach is needed for better adoption of AIT in the real-life setting in Belgium.