Clinical trials (CTs) have shown that allergen immunotherapy (AIT) is effective for local allergic rhinitis (LAR) while treatment is ongoing. However, its long-term effects remain unknown. This study investigates the long-term clinical and preventive effect of AIT in responder LAR patients.

LAR patients obtaining a clinical benefit from 1-year CT of subcutaneous AIT were enrolled in this 10-year follow-up study (AIT cohort). All completed a full 3-year AIT course and were followed for additional 7 years. A matched group of LAR patients who did not receive AIT (non-AIT cohort) was followed over the same period. Primary outcomes included nasal-ocular symptom scores (visual analogue scale, VAS), reliever medication use and medication-free days (MFD). Secondary outcomes were asthma incidence, asthma control (asthma control test, ACT), lung function (FEV1), quality of life (QoL), emergency visits, new sensitizations detected by nasal allergen challenge (NAC), and the analysis of the minimal clinically important difference (MCID). Assessments were conducted at baseline and at years 1, 3, 5, 7, and 10.

Sixty-six patients were included (AIT n = 32; non-AIT n = 34). The AIT cohort showed a sustained reduction in nasal-ocular symptoms from year 1 (p < 0.001) and significantly more MFD from year 3 (p < 0.001). Asthma developed in 40.7% of non-AIT vs. 8.0% of AIT patients (p = 0.021). New sensitizations occurred in 38.2% of non-AIT and 6.3% of AIT patients (p = 0.002). FEV1 improved in the AIT cohort and declined in non-AIT (p < 0.001). QoL and emergency visits also favored AIT.

AIT induces a sustained clinical improvement and prevents the onset of asthma and local sensitizations in responder LAR patients.

The double-blind placebo-controlled oral food challenge (DBPCFC) has been the "gold standard" for diagnosing IgE-mediated food allergy for the past 50 years. Despite tremendous strides in our understanding of basic mechanisms and clinical features of food allergy, we remain dependent on refinements of old technologies, i.e., skin tests and serum IgE measurements, to complement clinical history in making an accurate diagnosis of food allergies. However, recent technical advances in two effector cell assays, i.e., the basophil and mast cell activation tests, may soon bring these diagnostic biomarkers to the clinic. In addition, new advances in antibody assays, T-cell assays, transcriptomics, and metabolomics in conjunction with machine learning and artificial intelligence may soon enable us to diagnose food allergy and accurately monitor immunotherapeutic outcomes without the need for an oral food challenge.

Routine allergy diagnostic assessment relies on the patient's medical history, skin testing, and the detection of specific IgE (sIgE) in the serum. In addition, molecular allergy diagnostics and the basophil activation test (BAT) can be used; however, these additional tests are costly and sometimes time-consuming. Therefore, our objective was to identify the test with the highest sensitivity, determine the most effective combination of tests to enhance sensitivity, and develop a simple IgE ratio to distinguish between bee and vespid venom allergy in cases of double positivity.

We retrospectively analyzed data from 190 bee venom-allergic and 809 vespid venom-allergic patients, along with 61 non-allergic subjects. Sensitivity and specificity were assessed for sIgE (ImmunoCAP), the intradermal test (IDT), and the BAT.

Applying a lower cut-off of 0.1 kU/L in patients with total IgE < 30 kU/L (while keeping the standard cut-off of 0.35 kU/L otherwise) increased sensitivity for sIgE to bee venom from 85.7% to 94.6% and for vespid venom from 92.2% to 97.0%. The highest sensitivity (100%) was achieved by combining this sIgE dual cut-off approach with the intradermal test for bee venom allergy, while sensitivity for vespid venom allergy reached 98.5%. A vespid/bee ratio ≥ 2.68 indicated vespid venom allergy with 59.3% sensitivity, while a bee/vespid ratio ≥ 5.33 identified bee venom allergy with 50.6% sensitivity, both with 100% specificity.

Conventional tests, such as sIgE determination or intradermal testing, are usually sufficient. Combining both increases sensitivity, while additional tests provide no further benefit. Double-positive findings may often be clarified using a simple sIgE ratio, though sensitivity remains limited.

Previously, we reported the success of egg oral immunotherapy (OIT) in liberating most participants from dietary restrictions. The diminishing symptoms and declining inflammation were accompanied by differential expression of genes in peripheral blood mononuclear cells (PBMCs) of 50 egg-allergic children following 8 months of OIT.

Here, we explore the impact of OIT on long non-coding RNA (lncRNA) expression and its downstream effects on allergen-specific immune response with the help of PBMC transcriptome, co-expression gene module identification, pathway enrichment analyses and in vitro stimulation in both PBMC and THP1 cells.

We observed 17 lncRNAs which correlated positively with genes involved in IL-13, IL-4, and IL-10 signaling pathways. The same set of lncRNAs correlated negatively with genes playing a role in neutrophil degranulation, phagosome formation, and pyroptosis signaling. The expression of one of the most important lncRNAs, LOC644727, was found to align with CXCL8 expression in egg extract-stimulated PBMCs and LPS-stimulated THP1-derived macrophages.

Our results highlight the involvement of lncRNA in the regulation of gene expression during OIT. LOC644727 may serve as a potential marker for inflammatory responses and it may offer a therapeutic target for future desensitization protocols.

OIT-induced gastrointestinal eosinophilic reactions (OITIGER) is comprised of abdominal pain/vomiting unrelated to the timing of dose administration, typically associated with increased absolute eosinophil counts (AEC). Previously described risk factors during milk OIT included higher baseline AEC, higher OIT starting dose (SD) and faster dose increase. The effect of a revised milk OIT protocol (lower SD and slower dose escalations), on the rate and severity of OITIGER, was examined.

Milk OIT patients treated with a revised protocol between 2017 and 2021 (n = 269) were compared to a milk cohort from 2010 to 2015 (n = 604) who were treated with the previous protocol. OITIGER rate, severity, and treatment outcomes were compared.

Patients in the revised protocol were slightly older (p 600/μL was a risk factor [OR 2.16 (CI 1.30–3.60), p = 0.003] for OITIGER, while the revised protocol was protective for severe OITIGER [OR 0.30 (CI 0.10–0.89), p = 0.031]. Older age was associated with less OITIGER [OR 0.92 (CI 0.85–0.99), p = 0.018] and borderline less severe OITIGER [OR 0.85 (CI 0.72–1.00), p = 0.050]. A lower fold increase in AEC was observed in OITIGER patients in the revised protocol (2.25 [1.63–3.45] vs. 1.79 [1.34–2.11], p = 0.009).

A revised protocol was associated with reduced AEC increase, and ameliorated the severity of OITIGER during OIT.

Peanut oral immunotherapy (pOIT) is a recognized treatment for patients with peanut allergy, though not all patients who undergo this therapy achieve desensitization or remission.

To determine whether missed doses or dosing-reactions predict clinical outcomes with pOIT.

Data from the IMPACT trial, a randomized, double-blind, placebo-controlled trial of pOIT in children aged 1 to 4 years with peanut allergy, was analyzed to determine whether treatment-emergent variables influence desensitization (ability to consume 5000 mg of peanut protein without reaction during a blinded oral food challenge after 134 weeks of pOIT) and remission (six months after discontinuation of pOIT). Logistic regression models, controlling for age and Ara h2-specific IgE, were performed to assess the relationship between dosing reactions, missed doses, and outcomes.

Consecutive missed doses during build-up significantly correlated with reduced likelihood of desensitization (p = 0.03, OR 0.69 (0.49, 0.96)), whereas consecutive missed doses during maintenance did not (p = 0.10, OR 0.79 (0.59, 1.05)). Furthermore, the total individual missed doses did not significantly correlate with desensitization or remission in either phase of pOIT. Conversely, dosing-reactions during maintenance did significantly correlate with reduced likelihood of desensitization (p = 0.01, OR 0.71 (0.54, 0.93)), while dosing-reactions during build-up did not significantly correlate with desensitization (p = 0.57, OR 0.95 (0.79, 1.14)). Fewer than 10% of missed doses were attributed to dosing reactions.

Missed doses during therapy and dosing-reactions during maintenance associated with poorer pOIT outcomes. Clinicians should support adherence during build-up and consider dose adjustments for patients having dosing-reactions during maintenance therapy.

Allergic rhinitis (AR) is a prevalent condition significantly impacting children's health globally. Allergen immunotherapy (AIT), via sublingual (SLIT) or subcutaneous (SCIT) routes, offers disease modification, but direct pediatric comparisons are limited. This systematic review evaluates the relative efficacy and safety of SLIT versus SCIT in children with AR based on randomized clinical trial (RCT) evidence.

A systematic literature search (PubMed, Embase, Cochrane Library, Scopus; July 2024) identified RCTs comparing SLIT vs SCIT, or either vs control, in children (≤18 years) with AR. Data on study design, participants, interventions, outcomes (symptom/medication scores, safety, adherence, immunological markers), were extracted. Methodological quality was assessed using the Cochrane Risk of Bias tool version 2 (RoB-2). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed.

Seven RCTs met inclusion criteria. Both SLIT and SCIT effectively reduced AR symptoms and medication use versus controls. Comparative efficacy was nuanced: several studies found comparable reductions in symptom/medication scores, while others suggested potential SCIT advantages for specific outcomes (asthma symptoms, Total Rhinitis Symptom Score from baseline). SLIT consistently showed a more favorable safety profile (mainly local reactions), whereas SCIT carried a higher risk of systemic reactions. Limited data suggested potential SLIT benefits in asthma prevention. Adherence data from included RCTs were sparse.

Both SLIT and SCIT are effective for pediatric AR. SLIT offers comparable efficacy for many outcomes with better safety/convenience, while SCIT may have advantages for certain outcomes but requires clinic administration. Treatment choice requires individualization based on efficacy, safety, adherence potential, and patient/family factors. Further high-quality, long-term comparative trials are needed.

Egg allergy is a common IgE-mediated food allergy in children. Oral immunotherapy (OIT) reduces allergic reactions via gradual allergen exposure. Although high maintenance doses (1-6 g egg protein) are often used, they carry higher risks of adverse reactions. Evidence on the safety and effectiveness of lower-dose egg OIT (E-OIT) remains limited.

We sought to determine whether a low dose of 300 mg E-OIT is safe and effective for desensitization.

Twenty-two participants were recruited from the Montreal Children's Hospital; 20 were randomized to an immediate-treatment group or an observation group (egg avoidance for 1 year before OIT). Cumulative tolerated dose (CTD), Gal d 1- and Gal d 2-specific IgE (sIgE) and -specific IgG4 (sIgG4), and skin prick test responses were measured at baseline, postescalation, and maintenance. Adverse events were recorded throughout the study.

At baseline, CTD did not differ between groups (treatment: median, 14.1 mg; observation: 20.1 mg; P= 1). After 1 year of egg avoidance, CTD in the observation group remained low (32.3 mg; P= .06). Following E-OIT, the treatment group showed a significant increase in CTD to 2000 mg at postescalation (P= .004) and 6000 mg at the exit double-blind, placebo-controlled food challenge (P= .009). The observation group, after crossover, reached 1000 mg postescalation (P= .02) and 5000 mg at exit (P= .04). Adverse reactions occurred in 15.6% of 5971 doses, mostly mild. Skin prick test wheal diameters decreased significantly (P< .001); s-IgE levels declined whereas s-IgG4 levels increased (P< .001), and sIgG4/sIgE ratios improved. No significant clinical or immunologic changes occurred during the observation period.

Targeting a low maintenance dose of 300 mg E-OIT produces significant clinical and immunologic changes in individuals with egg allergy while maintaining low risk of adverse reactions.

This study aimed to evaluate the accuracy of prick tests for Der p1, Der p2, and Der p23 in estimating specific IgE sensitization to these components in children with rhinitis. A retrospective cohort study was conducted in 125 children with rhinitis who had a positive prick test to Dermatophagoides pteronyssinus. We compared the number of children sensitized by prick test to Der p1, Der p2, and Der p23 with those sensitized by specific IgE (ImmunoCAP) for each component. We used Student's t-test and chi-squared tests for the analysis. We also evaluated the accuracy of the molecular prick tests for estimating specific IgE to the components using ROC curves. The percentage of children sensitized by the prick test differed from those sensitized by specific IgE for Der p1 and Der p2. For Der p1, the percentages were 62.4% vs. 78.9% (p = 0.03). For Der p2, the rates were 41.4% vs. 72.7% (p < 0.001). For Der p23, the difference was not significant (64.2% vs. 68.2%, p = NS). Positive prick tests showed high accuracy for estimating specific IgE sensitization to Der p1 (AUC: 0.88, PPV: 93.7%, p < 0.001), Der p2 (AUC: 0.78, PPV: 100%, p < 0.001), and Der p23 (AUC: 0.86, PPV: 92.3%, p < 0.001). Conclusions:Prick tests are highly accurate for estimating specific IgE sensitization to Der p1, Der p2, and Der p23. When positive, they could guide specific immunotherapy in children without the need for additional laboratory tests. What is known:• IgE Der p components are highly useful for diagnostic and prognostic evaluation. They also guide the indication for immunotherapy in children with rhinitis, with or without allergic asthma, sensitized to D. pteronyssinus. What is new:• This study is the first to describe the profile of allergic sensitization to Der p components using a prick test in children with rhinitis sensitized to D. pteronyssinus. Additionally, we describe for the first time the high predictive value of having positive IgE to Der p components in children with rhinitis who show positive prick test results for Der p components.

"Treatable traits" (TT) have been proposed as a new paradigm for asthma but never applied to anaphylaxis. Hymenoptera venom-induced anaphylaxis (HVA) is one of the leading causes of anaphylaxis worldwide.

Our aim was to propose TT to HVA based on evidence-based data.

Historic-prospective study, based on the Hymenoptera venom-induced allergy and hypersensitivity database (VAHD) fed regularly by allergists at the Montpellier University hospital. Patients were classified as having "mild anaphylaxis" (MA), "moderate-severe anaphylaxis" (MSA) or "non-anaphylaxis" (NA), following Ring and Messmer severity score, and characteristics have been evaluated for each group. The potential risk factors have been classified as modifiable/controllable (MCRF) and non-modifiable (NRF), and treatable traits have been proposed from a preventive perspective.

From 602 patients, 54.2% were men, mean age was 42.3, 218 patients (36.2%) developed MA, 159 (26.4%) MSA and 213 (35.4%) NA. Age, atopic and cardiovascular diseases were identified as significant NRF. Symptoms appeared within 5 minutes (p<0.01), and less than 1 hour in MSA. Skin tests and in vitro ves v5 (p<0.0355) were significant and sensitive tools for the diagnosis. Occupational exposure (30%) along with the use of adrenaline, and Venom Immunotherapy (VIT) were considered MCRF.

Our results brought the evidence to TT through HVA data and tailored adapted preventive strategies to all severity degrees of HVA. This manuscript based on real-life data is a wake-up call for actions. Step forward implementation of actions among specialists and the general population should be put in place to reduce the morbi-mortality induced by HVA.