Allergic rhinitis, conjunctivitis and asthma are prevalent IgE-mediated respiratory diseases that frequently coexist and impair quality of life. Allergen immunotherapy (AIT) has clinical benefits and potential disease-modifying effects. Until recently, standardised definitions of disease control and remission were lacking in routine clinical practice, particularly for allergic rhinitis and conjunctivitis. This study aimed to propose preliminary definitions of control and remission in patients receiving AIT and to assess expert consensus using the Delphi methodology.

A scientific committee developed a survey based on a literature review and expert input, addressing symptoms, medication use, quality of life, exacerbations and tools for objective and subjective assessment. Forty allergists participated in a two-round Delphi study. Consensus was predefined as ≥ 70% agreement on a 9-point Likert scale.

Consensus was achieved for all items after two rounds. The panel agreed on proposed definitions of disease control and clinical remission for allergic rhinitis, conjunctivitis and asthma in the context of AIT, integrating symptom severity, medication use, validated questionnaires and objective measures.

This study presents preliminary expert-consensus definitions of control and remission in allergic rhinitis, conjunctivitis and asthma in patients undergoing AIT. These definitions should not be interpreted as validated clinical criteria or endpoints. As a preliminary proposal, they aim to provide a structured approach for assessing treatment response in clinical practice by integrating symptom burden, medication use, patient-reported outcomes and objective measures. They should be regarded as an initial conceptual step, and further prospective studies are needed to validate these criteria and confirm their relevance, feasibility and applicability.

Sensitization to birch pollen is a major contributor to allergic rhinitis in Europe, with sensitization rates in many countries from 10% to 20% of the general population. Growing evidence suggests that air pollution enhances the allergenicity of pollen; however, the clinical consequences of this co-exposure remain poorly understood. This study investigated whether air pollution intensifies birch pollen allergenicity and assessed its effects on symptom severity and basophil activation in allergic and non-allergic individuals.

Fifty birch-allergic patients and twenty-five non-atopic controls were examined over two consecutive pollen seasons (2023-2024). Daily nasal, ocular, and asthma symptoms were recorded using a mobile application. Ambient air pollutants (PM2.5, PM10, and O3) and birch pollen concentrations were continuously monitored in Kraków. Basophil activation tests (BAT) were performed using commercial birch pollen extracts, Bet v 1 allergen, and natural pollen collected from highly and less polluted areas. Basophil activation was quantified by CD63 expression using flow cytometry.

Asthmatic symptoms showed significant positive correlations with both birch pollen and PM concentrations (p < 0.05), especially in 2023. Pollen collected from polluted sites induced significantly stronger basophil activation compared with pollen from less polluted areas (p < 0.0001). The magnitude of basophil activation correlated with serum IgE levels to birch and Bet v 1, as well as with clinical symptom scores.

Air pollution enhances the allergenic potency of birch pollen, resulting in heightened basophil activation and more severe allergic symptoms. These findings highlight the importance of integrating air pollution monitoring alongside pollen surveillance when assessing allergic disease burden and evaluating the effectiveness of allergen immunotherapy.

Allergen immunotherapy (AIT) has been acknowledged as the only disease-modifying treatment for respiratory diseases since its introduction in 1911. Although the efficacy and safety have convincingly been established in numerous randomized clinical trials (RCTs), the AIT study results may vary substantially. Several factors that may influence the outcome of RCTs will be addressed. First, the choice of the primary endpoint is essential. Lack of validated endpoints with proven clinical relevance may contribute to the variation in study results. Secondly, heterogeneity of the patient population affects the study outcome, thereby raising the question of whether current selection criteria should be further optimized to capture those patients who will benefit from immunotherapy. Thirdly, variability and particularly low allergen exposure may lead to unsuccessful AIT trials. Fourthly, unsuccessful trials may stem from large placebo effects. Furthermore, discrepancies between Phase II and III studies are asking for cautious interpretation of Phase II studies when planning Phase III studies. Flaws in trial design, inadequate reporting of the clinical trial protocol and data may hamper the interpretation of study results. In addition, this review addresses specific aspects of AIT trial design in children and asthmatic patients. To improve future AIT trials, innovative solutions are urgently needed, including the establishment of an internationally accepted minimal clinically important difference (MCID), the validation of primary endpoints, the integration of field studies and allergen exposure chamber studies, and the publication of negative study results.

This paper reports a Phase 1, randomised, placebo-controlled, dose-escalation trial (NCT06037148) with DM-101PX that contains a recombinant hypoallergenic Bet v 1 variant formulated with thermosensitive hydrogel. The objectives of the study included assessment of treatment-related adverse events and the number of participants reaching the maximum dose. In addition, Bet v 1-specific immunoglobulins were analysed to explore the immunological effects of treatment. The trial was funded by Desentum Oy.

The study included three cohorts differing in starting and maximum dose. Per cohort, subjects were randomised (4:1) to receive 10 weekly subcutaneous injections with DM-101PX or placebo. Main inclusion criteria comprised adult subjects with a birch pollen allergy for ≥ 2 years, positive skin prick test, birch pollen-IgE ≥ 0.7 kU/L and symptoms upon exposure to birch pollen. The randomisation schedule was generated using software. During the trial, the investigator, clinic staff, participants and sponsor remained blinded to the treatment groups. The primary endpoint was the occurrence of treatment emergent adverse events and adverse events of special interest.

In each cohort, 10 subjects were randomised and all were used for analysis of safety data. Treatment-related adverse events were reported by 22/24 (91.7%) DM-101PX treated subjects and by 5/6 (83.3%) placebo-treated subjects, which were only of mild or moderate intensity. The DM-101PX and placebo-treated subjects had mainly local injection site reactions, 138/153 (90.2%) and 22/24 (91.2%), respectively. Fifteen systemic allergic reactions were reported by 5/24 (20.8%) DM-101PX-treated subjects, and 2 systemic allergic reactions were reported by 1/6 (16.7%) placebo-treated subject, all of which were of Grade 1. 21/24 (88%) of subjects reached the maximum dose. Treatment with DM-101PX induced pronounced levels of Bet v 1-specific IgG4 and post-treatment sera effectively blocked basophil activation.

This small study demonstrated that DM-101PX was generally well tolerated and induced a strong and functional immune response.

Platelet-activating factor (PAF), a key mediator of anaphylaxis, is inactivated by PAF-acetylhydrolase (PAF-AH). PAF-AH circulates complexed to low-density lipoprotein (LDL). Lipid-lowering medications interfere with PAF inactivation by lowering the concentration of LDL-PAF-AH complex, but their effect on anaphylaxis severity is unknown.

To determine whether lipid-lowering medication use alters anaphylaxis severity. We hypothesized that lipid-lowering medication use would increase the risk of severe anaphylaxis.

Retrospective chart review of patients from Canada, US, and Germany, assessed between 2010-2023 for multisystem reactions to insect stings. Logistic regression examined the association between lipid-lowering medication use and anaphylaxis severity (mild-moderate vs severe). Multivariable analyses adjusted for age, sex, beta-blocker, ACE inhibitor, respiratory disorders, and mastocytosis/hereditary alpha tryptasemia (HaT).

Among the total 778 patients, 111 (14%) were taking lipid-lowering medications. Lipid-lowering medication use was associated with increased odds of severe anaphylaxis in multivariable analysis (aOR 2.0; 95% CI 1.3-3.1; p = 0.0036). The association remained significant among 518 patients with Hymenoptera allergy confirmed by skin and/or serum tests (aOR 2.0; 95% CI 1.2-3.5; p = 0.012). In a sensitivity analysis substituting baseline tryptase for mastocytosis/HaT among patients with available measurements (n = 197), the association was directionally consistent but not statistically significant (aOR 1.9; 95% CI 0.9-3.8; p = 0.092).

Lipid-lowering medication use was associated with increased anaphylaxis severity in the primary analysis and confirmed-allergy cohort. Patients receiving lipid-lowering medications may be at higher risk for severe reactions, and clinicians should consider risk mitigation strategies, including venom immunotherapy (e.g., modified build-up protocols, extended treatment duration), ready access to self-administered epinephrine, and multidisciplinary care.

Mannan-conjugated allergoids represent an effective option for treating allergic diseases. This study evaluated the clinical impact of the mannan-conjugated, polymerised birch pollen allergoid EP-088_T502 in patients with birch pollen-induced allergic rhinoconjunctivitis over 3 years.

Following up to a double-blind, placebo-controlled dose-finding study, in this open, long-term extension study, 154 birch pollen-allergic patients were enrolled in Germany. Patients were treated with a cumulative dose of 48,000 mTU EP-088_T502 administered subcutaneously over five pre-seasonal visits in each of the two treatment years (2021, 2022) with a subsequent follow-up year in 2023. The primary efficacy endpoint was the combined symptom and medication score (CSMS) during the peak birch pollen season, which was compared with the CSMS of the placebo group during the peak pollen season of 2020. Safety, tolerability, and immunogenicity were also analysed.

Compared to the placebo group of the preceding study, median CSMS during the peak birch pollen seasons showed reductions of 47.5% in 2021 (p < 0.001), 51.8% in 2022 (p < 0.001), and 36.5% in 2023 (p < 0.001). Median daily symptom scores were reduced by 40.7% in 2021 (p < 0.001), 40.7% in 2022 (p < 0.001), and 25.6% in 2023 (p < 0.010). Median daily medication scores reached 0.07 in 2021 and 0.04 in 2022 (p < 0.001) and were reduced by 65.9% in 2023 (p < 0.003). Immunological responses showed a 4.82-fold increase in Bet v1 sIgG4 (p = 0.001) and a marked decrease (-65.5%, p = 0.001) in the sIgE/sIgG4 ratio after the first treatment phase. EP-088_T502 demonstrated good safety and tolerability, with only six mild to moderate systemic allergic reactions (Grade I/II). No epinephrine was used.

In this open-label study, two consecutive years of pre-seasonal short-course allergen immunotherapy (AIT) with EP-088_T502 markedly reduced symptoms and medication need in patients with birch pollen-induced rhinoconjunctivitis. Persistent therapeutic effects observed during the follow-up year, although limited by attrition of the study population, suggest sustained clinical improvement and indicate the potential disease-modifying impact of this treatment regimen.

Hymenoptera venom allergy (HVA) is a potentially life-threatening condition and the second most common cause of severe allergic reactions in children after food allergy. The risk of recurrence of systemic reaction is approximately 32% in untreated children; therefore, these patients need to undergo diagnostic tests and, if indicated, venom immunotherapy (VIT). However real-life data on VIT in children remain limited.

We conducted an observational study in a cohort of children and adolescents (n = 40) with HVA and treated with VIT in an Italian tertiary allergy center between 1999 and 2023. Data included demographic features, index reaction, pre-existing risk factors, timeline of VIT, adverse reactions to VIT, re-sting outcomes and serological exams were analyzed.

The cohort was predominantly male (87.5%). Adverse reactions to VIT were infrequent, occurred mainly as local reactions, and showed low rates per injection. Among patients who completed ≥3 or ≥5 years of VIT, no severe systemic reactions were observed during treatment and epinephrine was never required. Re-stings during VIT were common, occurring up to 75.0%, mainly during the maintenance phase. Reactions were mild and limited to cutaneous symptoms. Among patients re-stung after completion of VIT (9/27 patients, 33%), no systemic reactions were observed and no epinephrine was required. Venom-specific IgE levels significantly decreased after completion of VIT (p = .004).

The EAACI guidelines provide general recommendations for children, but many are based on limited pediatric evidence. This study provides additional data about the favorable safety profile and efficacy of VIT in children and adolescents with HVA.

Sublingual immunotherapy (SLIT) has been shown to be effective in controlling the symptoms of allergic rhinitis and asthma, but few studies have assessed its long-term preventive effects on lower-airway inflammation and asthma onset.

We sought to evaluate prospectively the long-term effects of SLIT on lower-airway function in patients with allergic rhinitis caused by house dust mites (HDM).

We performed a post hoc analysis of a previously published prospective, open-label study involving patients with allergic rhinitis who were monosensitized to mites and followed for 15 years. All participants had bronchial hyperreactivity and were originally assigned to 4 groups receiving either pharmacological therapy alone or SLIT for 3, 4, or 5 years (SLIT 3, SLIT 4, and SLIT 5). Skin sensitization, methacholine reactivity, and respiratory function were evaluated annually during the winter months.

Seventy-eight patients were enrolled, and 59 completed the study. Over 15 years of observation, new sensitizations occurred in all participants in the control group but in fewer than one-quarter of patients who received SLIT for 3, 4, or 5 years (21%, 12%, and 11%, respectively). Among patients with rhinitis treated only with intranasal corticosteroids and systemic antihistamines, the development of asthma, defined as a decline in FEV to below 80% of the predicted value, was observed in 58% (7 of 12). In contrast, progression to asthma was significantly less frequent among patients with rhinitis treated with SLIT, regardless of treatment duration: 1 of 14 patients in the SLIT 3 group (7%), 1 of 16 in the SLIT 4 group (6%), and 1 of 17 in the SLIT 5 group (6%).

In the long term, SLIT provided a significant clinical benefit in HDM-induced allergic rhinitis by reducing both the allergic march and asthma onset and by limiting the decline in lung function, as measured by FEV1.

In a large randomized controlled trial (NCT02443805) in moderate-to-severe house dust mite (HDM) allergic rhinitis (AR) patients with/without controlled asthma, the 300IR HDM sublingual immunotherapy (SLIT) tablet confirmed its efficacy in reducing symptoms and rescue medication (RM) use. This post hoc analysis aimed at assessing the potential steroid sparing effect of this tablet.

Participants receiving 300IR HDM SLIT-tablet or placebo for 12 months could use antihistamines (AH1), corticosteroids (CS - intranasal ∼ (INCS), or oral (OCS)) in a stepwise manner for subjective intolerable nasal/ocular symptoms. The proportions of patients and days with RM intake (overall and by drug class) were assessed over time and compared between groups (Chi-squared or Wilcoxon rank-sum tests). An odds that is, ratio of probability of using CS/probability of not using CS was calculated. Mean weekly CS doses were analyzed by ANCOVA.

Of 1262 evaluable patients, ∼60% used at least one CS at baseline: 300IR = 373 and placebo = 396. During treatment, the proportions of patients using RM, oral AH1, and CS and of days with RM use decreased in both groups, systematically in favor of 300IR (p < 0.05 at end-of-treatment). Odds results indicated SLIT-patients were more likely not to use CS, whereas placebo-patients were more likely to use CS (p < 0.05 at end-of-treatment). After 12 months, 54% SLIT patients were able to discontinue CS completely versus 42% placebo-patients (p = 0.0007). Those who were still using CS were taking fewer and lower doses than placebo-patients.

In moderate to severe HDM-AR patients, the 300IR HDM SLIT-tablet showed a steroid sparing effect.

Lipid transfer protein (LTP) allergy is a clinically relevant phenotype of IgE-mediated food allergy, particularly prevalent in Mediterranean populations and frequently associated with systemic and cofactor-dependent reactions. Therapeutic options remain limited, and the role of allergen immunotherapy is not well established.

To provide an updated systematic review of the efficacy and safety of Pru p 3-based immunotherapy in LTP-mediated food allergy.

A systematic literature search was conducted to identify studies published up to March 2026 evaluating sublingual (SLIT) or oral immunotherapy (OIT) in patients with LTP allergy. Eligible studies were analyzed qualitatively with respect to clinical outcomes, immunological parameters, and safety.

Fifteen studies were included, the majority observational and conducted in Mediterranean countries. Available data suggest that SLIT and, less frequently, OIT may increase the threshold of clinical reactivity to peach and, in some patients, improve tolerance to other LTP-containing foods. These effects are accompanied by changes in Pru p 3-specific IgE and IgG4 levels. However, substantial heterogeneity in study design, outcome assessment, and immunotherapy protocols, as well as the limited number of controlled trials, restrict the strength of the evidence.

Pru p 3-based immunotherapy appears promising for selected patients with LTP allergy; however, the overall certainty of evidence remains low. Well-designed randomized controlled trials with standardized outcome measures are needed to define its role in clinical practice.