Results of surveys report that allergists use a wide range of doses for allergy immunotherapy; however, results of randomized, double-blind, placebo controlled studies suggest that the range of the optimum effective dosing is relatively narrow.

To review studies that established effective or less than fully effective doses for allergy immunotherapy.

Studies were reviewed that established effective and ineffective subcutaneous and sublingual immunotherapy doses. Only those studies that expressed dosing in terms of the content of a major allergen in the maintenance doses were included in defining effective and ineffective doses.

Studies were identified that showed effective doses for subcutaneous injection, established in randomized, double-blind, placebo controlled trials, for short ragweed, timothy grass, house-dust mites, cat and dog dander, birch, and Alternaria. For short ragweed, timothy grass, Dermatophagoides pteronyssinus, and cat and dog dander, less effective doses were determined, along with effective doses; the less effective doses were only one-fifth to one-tenth less in allergen content than were the effective doses. Effective doses of cockroach and all fungal extracts except Alternaria have not been established. Information is available on the mean major allergen content of U.S. standardized and a few nonstandardized extracts, which allows the information on effective and ineffective dosing to be used in prescribing subcutaneous allergy immunotherapy. With sublingual allergy immunotherapy, all the approved tablets had multidose studies that determined the optimal dose. For the U.S. liquid extracts, to my knowledge, there are no studies to define effective doses except for ragweed.

Although a wide range of doses are prescribed by U.S. allergists, analysis of available data suggests that effective doses fall within a narrow range and that use of doses one-fifth or one-tenth of the effective doses may sacrifice most or all of the potential efficacy of the treatment.

IgG2 responses are associated with repeated antigen exposure and display highly mutated variable domains. A recent study highlighted a role of IgG2+ memory B cells and allergen-specific IgG2 levels after a 3rd consecutive pre-seasonal sublingual allergen immunotherapy (AIT) with grass pollen tablet. Herein, we aim to explore changes in allergen-specific IgG2 in individuals undergoing house dust mite immunotherapy (HDM-AIT) and explore whether the interrelationship with other humoral responses (i.e. IgG4 and IgE) may discriminate between high and low responders.

Levels of serum D. pteronyssinus- and D. farinae-specific IgG2, IgG4 and IgE antibodies were measured by ELISA or ImmunoCap in a sub-group of individuals enrolled in a randomized, double-blind, placebo controlled, sublingual AIT study evaluating the safety and efficacy of a 300 IR HDM tablet.

After 1-year sublingual AIT, HDM-specific serum IgG2 responses increase mostly in high versus low responders and are distinctive according to the clinical benefit. Higher correlation between HDM specific IgG2, IgE and/or IgG4 responses are seen in subjects benefiting the most from HDM-AIT as indicated by changes in Average Total Combined Scores. More strikingly, statistically significant correlation between HDM-specific IgG2 and IgE responses are only observed in individuals stratified as high responders.

We provide evidence for coordinated serum immune responses upon AIT in HDM-allergic subjects exhibiting high clinical benefit when compared with low responders. Assessing HDM-specific IgE, IgG2 and IgG4 in serum could be used as follow-up combined markers to support decision as to AIT continuation and/or adaptation.

The study was a prospective, double-blind, placebo-controlled trial with patients diagnosed with LAR to HDMs and with concomitant asthma who underwent a 12- month treatment course of SLIT for HDM allergies. Seventeen patients were randomized to SLIT with the use of allergen extracts of D. pteronyssinus and D. farinae (50/50%) in SQ-HDM SLIT tablets and 15 patients were randomized to the placebo group. The total rhinitis score (TRSS), total asthma symptom score (TASS), combined total symptom score (TSS), total medication score (TMS), and FEV1 were analyzed.

In the final analysis, 16 patients who received SLIT and 14 who received placebo who completed the study protocol were included. Significant reductions in TRSS, TASS, TSS, and TMS after 12 months of treatment were observed in patients after SLIT (p < 0.05). A significant increase in the mean FEV1 between baseline and after 12 months of therapy was observed in the study, with p = 0.03 in the study group.

SLIT can improve nasal and bronchial symptoms and reduce symptomatic treatment in patients with LAR and asthma and with hyperresponsiveness to HDMs.

European and US allergists generally do not agree on the approach to subcutaneous allergy immunotherapy in patients with multiple allergies. The North American approach is to treat with a mixture that contains all the allergen extracts to which the patient has evident clinical sensitivity, whereas the European approach is to select for treatment the one or at the most two allergens that are clinically most important for the patient.

Recent society guidelines continue to recommend these differing practices of treating the polyallergic patient and reviews of prescribing practices indicate these divergent recommendations are followed in Europe and the USA.

The objections by European allergists to the practice by US allergists are that multiallergen immunotherapy leads to dilution of allergens to less than effective doses, that proteases in some extracts can degrade allergens in other extracts, that there is a problem of safety and inability to determine which component extract caused a systemic reaction, and finally that there is alack of convincing studies demonstrating efficacy of multiallergen mixtures. Each of these contentions is addressed.

Caregiver values and preferences with regard to oral immunotherapy (OIT) for treatment of food allergies are not widely reported. Understanding caregiver perspectives is integral to establishing shared decision-making in the treatment of food allergy.

We aimed to understand caregiver opinions that may influence caregivers in their decisions about OIT through social media.

We searched a popular parenting web site for posts related to OIT from December 2008 to September 2019. We applied a Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework to review posts for inclusion, performed thematic content analysis to determine common themes, and calculated frequencies for each theme and subtheme. Posts and comments were included if they contained discussions about OIT for immunoglobulin E-mediated food allergy and were excluded if they were duplicates, comments from an original post from the original user, or comments on a nonrelevant original post.

Of 1300 posts and comments retrieved, 174 were included (13%). Most were excluded because they did not directly address OIT for food allergy. Relevant posts could fall into multiple themes and were categorized under three main themes: attitudes (n = 128, "I am scared to do OIT but scared not to!"), logistics (n = 168, "We will be doing this once LO [little one] is a little older"), and questions (n = 32, "How does it work?")

Caregivers communicate with each other through social media, expressing attitudes, logistics, and questions about OIT. Understanding these lay perspectives may help guide clinicians in counseling and engage caregivers in decision-making.

During the past years, there has been a global outbreak of allergic diseases, presenting a considerable medical and socioeconomical burden. A large fraction of allergic diseases is characterized by a type 2 immune response involving Th2 cells, type 2 innate lymphoid cells, eosinophils, mast cells, and M2 macrophages. Biomarkers are valuable parameters for precision medicine as they provide information on the disease endotypes, clusters, precision diagnoses, identification of therapeutic targets, and monitoring of treatment efficacies. The availability of powerful omics technologies, together with integrated data analysis and network based approaches can help the identification of clinically useful biomarkers. These biomarkers need to be accurately quantified using robust and reproducible methods, such as reliable and pointof-care systems. Ideally, samples should be collected using quick, cost-efficient and noninvasive methods. In recent years, a plethora of research has been directed toward finding novel biomarkers of allergic diseases. Promising biomarkers of type 2 allergic diseases include sputum eosinophils, serum periostin and exhaled nitric oxide. Several other biomarkers, such as pro-inflammatory mediators, miRNAs, eicosanoid molecules, epithelial barrier integrity, and microbiota changes are useful for diagnosis and monitoring of allergic diseases and can be quantified in serum, body fluids and exhaled air. Herein, we review recent studies on biomarkers for the diagnosis and treatment of asthma, chronic urticaria, atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, food allergies, anaphylaxis, drug hypersensitivity and allergen immunotherapy. In addition, we discuss COVID-19 and allergic diseases within the perspective of biomarkers and recommendations on the management of allergic and asthmatic patients during the COVID-19 pandemic.

Immunoglobulin E (IgE)-mediated food allergy is a real public health problem worldwide. The prevalence of food allergy is particularly high in children. Patients with food allergy experience high morbidity with a change in quality of life due to the risk of severe anaphylaxis. Current treatment options are poor. Allergen avoidance is widely recommended but exposes patients to accidental ingestion. Oral immunotherapy is also used in patients with food allergies to the most common allergens. Oral immunotherapy consists of a daily administration of small, gradually increasing amounts of allergens to induce desensitisation. This procedure aims at inducing immune tolerance to the ingested food allergens. However, some patients experience adverse reactions and discontinue oral immunotherapy.Given that IgE plays a crucial role in food allergy and anti-IgE are effective in allergic asthma, the use of anti-IgE therapeutic monoclonal antibodies (mAbs) such as omalizumab has been assessed in food allergy patients. The use of omalizumab as a monotherapy in food allergy has not been extensively studied but looks promising. There is more published evidence regarding the effect of omalizumab and oral immunotherapy in food allergy. Given the promising results of oral immunotherapy regarding sustained tolerance in clinical trials and the potential capacity of omalizumab to reduce symptoms in case of accidental exposure, a strategy combining oral immunotherapy with omalizumab pre-treatment has been suggested as a safer option in patients with severe food allergy compared to isolated therapy. Omalizumab seems useful in ensuring safer administration of oral immunotherapy with the oral immunotherapy maintenance dose being reached more rapidly. Quality-of-life improvement is greater with oral immunotherapy + omalizumab compared to oral immunotherapy alone. Moreover, sustained unresponsiveness is achieved more frequently with omalizumab. Considering that precision medicine and personalised therapy are major goals for allergic diseases, predictive biomarkers are crucial inorder to identify food allergy patients more likely to benefit from anti IgE therapies.

Several microRNAs (miRs) have been described as potential biomarkers in liquid biopsies and in the context of allergic asthma, while therapeutic effects on the airway expression of miRs remain elusive. In this study, we investigated epigenetic miR-associated mechanisms in the sputum of grass pollen-allergic patients with and without allergen-specific immunotherapy (AIT).

Induced sputum samples of healthy controls (HC), AIT-treated and -untreated grass pollen-allergic rhinitis patients with (AA) and without asthma (AR) were profiled using miR microarray and whole-transcriptome microarray analysis of the same samples. miR targets were predicted in silico and used to identify inverse regulation. Local PGE2 levels were measured using ELISA.

Two hundred and fifty-nine miRs were upregulated in the sputum of AA patients compared with HC, while only one was downregulated. The inverse picture was observed in induced sputum of AIT-treated patients: while 21 miRs were downregulated only 4 miRs were upregulated in asthmatics upon AIT. Of these 4 miRs, miR-3935 stood out, as its predicted target PTGER3, the prostaglandin EP3 receptor, was downregulated in treated AA patients compared with untreated. The levels of its ligand PGE2 in the sputum supernatants of these samples were increased in allergic patients, especially asthmatics, and downregulated after AIT. Finally, local PGE2 levels correlated with ILC2 frequencies, secreted sputum IL-13 levels, inflammatory cell load, sputum eosinophils and symptom burden.

While profiling the sputum of allergic patients for novel miR expression patterns, we uncovered an association between miR-3935 and its predicted target gene, the prostaglandin E3 receptor, which might mediate AIT effects through suppression of the PGE2 -PTGER3 axis.

Oral immunotherapy (OIT) has emerged to build sustained unresponsiveness or tolerance in patients with egg allergy. However, it is important to increase compliance and ensure safety because OIT requires an extended period of time and has a risk of side effects like anaphylaxis. We aimed to show the feasibility and safety of OIT during the build-up phase using a home-based, up-dosing method in children with egg allergy. Sixteen patients aged 4 to 12 years with egg allergy were enrolled. Patients increased the dose of boiled egg white (EW) by 5% per day at home and 25% per month at the hospital, with a target dose of 40 g of boiled EW (4.0 g of EW proteins). A historical control group (n = 16) was matched for age, sex, and clinical characteristics for comparisons with the OIT group. Oral food challenge (OFC) tests were performed after completing the build-up phase. In the OIT group, 93.8% (15/16) of patients achieved desensitization, with only 1 patient discontinuing OIT before the maintenance phase due to repeated allergic reactions. Mild allergic reactions and anaphylaxis occurred in 12 (75.0%) and 2 patients (12.5%), respectively. However, there were no significant adverse reactions such as serious anxiety or life-threatening events that required discontinuation of treatment. On the contrary, only 1 patient (6.3%) in the control group passed an OFC of 40 g of boiled EW during the same period (P < 0.001). Our results suggest that home based up-dosing protocols using boiled eggs may be safe and feasible for the build-up phase of OIT in children with egg allergy.

In this review, we outline and reflect on the important differences between allergen-specific immunotherapy for inhalant allergies (i.e., aeroallergens) and venom-specific immunotherapy (VIT), with a special focus on Venomil® Bee and Wasp. Venomil® is provided as a freeze dried extract and a diluent to prepare a solution for injection for the treatment of patients with IgE-mediated allergies to bee and/or wasp venom and for evaluating the degree of sensitivity in a skin test. While the materials that make up the product have not changed, the suppliers of raw materials have changed over the years. Here, we consolidate relevant historical safety and efficacy studies that used products from shared manufacture supply profiles, i.e., products from Bayer or Hollister–Stier. We also consider the characterization and standardization of venom marker allergens, providing insights into manufacturing controls that have produced stable and consistent quality profiles over many years. Quality differences between products and their impacts on treatment outcomes have been a current topic of discussion and further research. Finally, we review the considerations surrounding the choice of depot adjuvant most suitable to augmenting VIT.