Allergy to house dust mites (HDM) is a perennial respiratory disease that affect more than half a billion people worldwide. Dermatophagoides pteronyssinus and D. farinae, two HDM species, are major sources of indoor allergens triggering allergic inflammation. Although symptomatic drugs are widely used to block the allergic reaction, allergen immunotherapy is the only curative treatment of IgE-mediated type I respiratory allergies. In this article, we review recent advances in various routes of allergen immunotherapy. We particularly focus on subcutaneous (SCIT) and sublingual (SLIT) immunotherapy, used as a reference therapy since they have transformed allergic treatments by improving symptoms (asthma and rhinitis) as well as the quality of life of patients. We also highlight recent data in more exploratory routes (i.e., oral, intralymphatic, epicutaneous and intradermal) and discuss respective advantages of various route, as well as their foreseen modes of action. Finally, we provide an update on biomarkers as well as on the relevance of the molecular profiling of allergic individuals related to treatment efficacy or asthma prediction.

Studies are limited on the efficacy of peanut sublingual immunotherapy (SLIT). The durability of desensitization after SLIT has not been well described.

To evaluate the efficacy and safety of 4 mg peanut SLIT and persistence of desensitization after SLIT discontinuation.

Challenge proven peanut-allergic 1-11 year old children were treated with open-label 4 mg peanut SLIT for 48 months. Desensitization after peanut SLIT was assessed by 5000 mg double-blind, placebo-controlled food challenge (DBPCFC). A novel randomly assigned avoidance period between 1-17 weeks was followed by a DBPCFC. Skin prick testing (SPT), immunoglobulins, basophil activation testing (BAT), TH1, TH2, and IL-10 cytokines were measured longitudinally. Safety was assessed through patient-reported home diaries.

Fifty-four participants were enrolled and 47 (87%) completed peanut SLIT and the 48- month DBPCFC per protocol. Mean successfully consumed dose (SCD) during DBPCFC increased from 48 mg to 2723 mg peanut protein after SLIT (p800 mg) and 36% full desensitization (SCD = 5000 mg). Modeled median time to loss of clinically significant desensitization was 22 weeks. Peanut SPT; peanut-specific IgE, IgG4, IgG4/IgE ratio; and peanut-stimulated BAT, IL-4, IL-5, IL-13, IFNgamma, and IL-10 changed significantly compared to baseline with changes seen as early as 6 months. Median rate of reaction per dose was 0.5% with transient oropharyngeal itching most common and no dosing symptoms requiring epinephrine.

In this open-label, prospective study, peanut SLIT was safe and induced clinically significant desensitization in the majority of children lasting more than 17 weeks after discontinuation of therapy.

The reduction of pharmacological treatment after allergen immunotherapy (AIT) for house dust mites (HDMs) has been little studied in children.

To evaluate the reduction of pharmacological treatment comparing children that receive HDM immunotherapy (AIT group) versus only pharmacotherapy.

A historic cohort of children with rhinitis or asthma was assessed. The main outcome was the frequency of complete drug discontinuation.

100% drug reduction was higher for rhinitis (4-year cumulative incidence: 30 vs 10.7%) and asthma (24.1 vs 10.5%) in the AIT group (n = 987) than in the pharmacotherapy group (n = 2012).

Immunotherapy is associated with a significant reduction of pharmacotherapy in children. This is a marker of clinical control and could be associated with positive economic impact.

Oral immunotherapy (OIT) is now recognized as an alternative active treatment to strict food avoidance in certain patients with IgE-mediated food allergy. Studies have confirmed the efficacy of OIT to desensitize children with allergy to cow's milk, eggs, and peanuts. The benefits, risks, and constraints of OIT are becoming increasingly well understood. However, there is no consensual criteria to select patients to whom OIT could be proposed, and many issues remain to address including the definitions of desensitization and long-term efficacy, the as sessment of patient's experience in real life, the optimization of buildup and maintenance protocols, and the utility of multiple food OIT. The recent authorization by medical agency concerning the first medicine for peanut OIT is a step forward towards higher standardization in the practice of OIT. This article summarizes in comprehensive narrative format data on efficacy, tolerance, impact on quality of life and adverse effects of OIT and discuss elements to consider in clinical practice before starting OIT.

Racial and ethnic differences exist in the severity of various atopic diseases including allergic rhinitis (AR). Patients of under represented races and ethnicities may be subjected to disparate subcutaneous allergen immunotherapy (SCIT) prescription practices.

To explore the racial and ethnic disparities in the use of SCIT among patients with AR.

In this retrospective matched cohort study, we used the TriNetX US Collaborative Network, a multicenter electronic health record-based database to identify patients with AR 18 years and older. Patients were grouped according to their racial and ethnic identification. Study groups were matched for baseline demographics, atopic comorbidities, heart diseases and utilization of β blockers, and angiotensin-converting enzyme inhibitors. The proportion of patients of under-represented racial and ethnic groups started on SCIT was contrasted to the non-Hispanic White cohort.

We identified 1,038,000 patients with AR; the mean age (±standard deviation) at the index was 49.7 (±16.1) years, and 64.6% were female. Ethnicity information was available from 87.3% of patients, and the majority (92.3%) were non-Hispanic. Over a 3-year observation period, fewer Black patients (relative risk [RR], 0.40; 95% confidence interval [CI], 0.33-0.48) and Hispanic patients (RR, 0.80; 95% CI, 0.64-0.99) were started on SCIT compared with non-Hispanic White patients. The proportions of Asian patients who were initiated on SCIT tended to be lower when compared with non-Hispanic White patients (RR, 0.69; 95% CI, 0.47-1.009).

In the United States, differences in SCIT prescription exist between Black and Hispanic patients relative to White patients. Barriers to treatment should be explored and mitigated.

Asthma poses a significant threat to public health, with an estimated burden of over 334 million people worldwide. Available treatments are often inadequate. We developed a thermo-sensitive hydrogel vaccine containing allergen and FK506 that induced immune tolerance via intranasal administration to treat experimental allergic asthma. The hydrogel delivery system was formulated based on Poloxamer 407 (P407), Carbopol 974P NF, and Polyoxyl 15 hydroxystearate (Kolliphor HS15, HS15). It flowed freely at room temperature and rapidly formed a hydrogel in the nasal cavity once the temperature rose over 33 °C. Ovalbumin and FK506 were slowly released from the hydrogel form and their mucosal residence time was significantly prolonged compared to the liquid formulation. In both an OVA-induced asthma model and an HDM-induced asthma model, the vaccines formulated in hydrogel gave lower levels of eosinophilic inflammation, and airway remodeling. The reduction of lung function was ameliorated, and Foxp3-expressing CD4 + Treg cells were significantly higher. The frequency of Foxp3 + Tregs in lung-draining lymph nodes (dLNs) was correlated with the amelioration. Depletion of Foxp3 + Treg cells abolished the beneficial effects of the allergen/FK506 hydrogel vaccinations. Thus, the allergen/FK506 hydrogel formulation has the potential to be a delivery system for therapeutic allergy vaccines to induce immune tolerance.

While efficacy, safety, and quality of life measures associated with peanut oral immunotherapy (OIT) have been studied, the relationship between peanut OIT and clinical anxiety has not yet been assessed. The latter is important to help providers and families have an improved shared medical decision discussion around the benefits of initiating OIT.

We aimed to investigate the relationship between undergoing OIT and anxiety in patients with peanut allergy.

In this prospective cross-sectional cohort study, using validated and age appropriate anxiety scales administered with electronic survey questionnaires, we used generalized linear regressions to compare anxiety between patients undergoing OIT and similar patients with peanut allergy but not on OIT (controls).

In the younger cohort ( 7 years, n=125), there was a higher prevalence of anxiety but no clinically meaningful difference between anxiety scores of patients on OIT and controls. In the older cohort, patients with asthma were more likely to have higher mean anxiety scores (p=0.04), as were female patients compared to male patients (p=0.004).

No disponible. Carta al editor.

Like in many fields of medicine, the concept of precision dosing has re emerged in routine practice in allergology. Only one retrospective study on French physicians' practice has addressed this topic so far and generated preliminary data supporting dose adaptation, mainly based on experience, patient profile understanding and response to treatment. Both intrinsic and extrinsic factors shape the individual immune system response to allergen immunotherapy (AIT). Herein, we focus on key immune cells (i.e., dendritic cells, innate lymphoid cells, B and T cells, basophils and mast cells) involved in allergic disease and its resolution to further understand the effect of AIT on the phenotype, frequency or polarization of these cells. We strive to discriminate differences in immune responses between responders and non-responders to AIT, and discuss the eligibility of a non/low-responder subset for dose adaptation. A differential behavior in immune cells is clearly observed in responders, highlighting the importance of conducting clinical trials with large cohorts of well-characterized subjects to decipher the immune mechanism of AIT. We conclude that there is a need for designing new clinical and mechanistic studies to support the scientific rationale of dose adaptation in the interest of patients who do not properly respond to AIT.

Safer and more effective cow milk (CM)-oral immunotherapy that does not induce allergic reactions has not yet been standardised. We sought to explore the efficacy and feasibility of a combination of heat-killed Lactiplantibacillus plantarum YIT 0132 (LP0132) and oral immunotherapy for treating IgE-mediated cow milk allergy (CMA). We conducted a 24-week, double-blind, randomised (1:1), two-arm, parallel-group, placebo-controlled, phase 2 trial of LP0132 intervention for treating IgE-mediated CMA in children aged 1-18 years (n=60) from January 29, 2018 to July 12, 2019 in Tokyo, Japan. Participants were randomly assigned to the LP0132 group receiving citrus juice fermented with LP0132 or to the control group receiving citrus juice without. Both groups received low-dose slow oral immunotherapy with CM. The primary outcome was improved tolerance to CM, proven by the CM challenge test at 24 weeks. Secondary outcomes were changes in serum biomarkers of serum-specific β-lactoglobulin-IgE (sIgE) and β-lactoglobulin-IgG4 (sIgG4). Exploratory outcomes included changes in serum cytokine levels and gut microbiota composition. A total of 61 participants were included. Finally, 31 children were assigned to the LP0132 group and 30 to the control group, respectively. After the intervention, 41.4 and 37.9% of the participants in the LP0132 and control groups, respectively, showed improved tolerance to CM. In serum biomarkers after the intervention, the sIgG4 level was significantly higher, and interleukin (IL)-5 and IL-9 were significantly lower, in the LP0132 group than in the control group. In the gut microbiome, the α-diversity and Lachnospiraceae increased significantly in the LP0132 group, and Lachnospiraceae after the intervention was significantly higher in the LP0132 group than in the control group. In conclusion, low-dose oral immunotherapy with modulating gut microbiota might be a safer and more effective approach for treating cow's milk allergy.