The Coronavirus disease 2019 (COVID-19) has evolved as a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS-CoV-)2. Allergists and other health care providers (HCPs) in the field of allergies and associated airway diseases are in the front line, taking care of patients potentially infected with SARS-CoV-2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics.

The scientific information on COVID-19 was analyzed by a literature search in Medline, Pubmed, national and international guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library and the Internet.

Based on diagnostic and treatment standards developed by EAACI, on international information regarding COVID-19, on guidelines of the World Health Organization (WHO) and other international organizations as well as on previous experience, a panel of experts including clinicians, psychologists, IT experts and basic scientists along with EAACI and the “Allergic Rhinitis and its Impact on Asthma (ARIA)” inititiative have developed recommendations for the optimal management of allergy clinics during the current COVID-19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies.

This international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients whilst ensuring necessary safety in the current COVID-19 pandemic.

Food allergy is a major health problem affecting 5 to 10% of the population in developed nations, including an estimated 32 million Americans. Despite the large number of patients suffering from food allergies, up until the end of January 2020, no treatment for food allergies had been approved by the U.S. Food and Drug Administration (FDA). The only options were avoidance of food allergen triggers and acute management of allergic reactions. A considerable body of data exists supporting oral immunotherapy (OIT) as a promising, novel treatment option, including that for the now FDA-approved peanut OIT product, Palforzia. However, data for long-term quality of life improvement with OIT varies, depending on the measures used for analysis. Like many therapies, OIT is not without potential harms, and burdens, and the evaluation of patient-specific risk-benefit ratio of food OIT produces challenges for clinicians and patients alike, with many unanswered questions. Food Allergy Research & Education (FARE) organized the Oral Immunotherapy for Food Allergy Summit on November 6, 2019 modeled after the PRACTALL sessions between the European Academy of Allergy and Clinical Immunology (EAACI) and the American Academy of Allergy, Asthma and Immunology (AAAAI) to address these critical issues. Health care providers, patient representatives, researchers, regulators and food allergy advocates came together to discuss OIT and identify areas of common ground as well as gaps in existing research and areas of uncertainty and disagreement. The purpose of this paper is to summarize that discussion and facilitate collaboration among clinicians and patients to help them make better-informed decisions about offering and accepting OIT, respectively, as a therapeutic option.

House dust mite (HDM) sublingual immunotherapy (SLIT) has demonstrated efficacy in clinical trials of patients with asthma. Airway inflammation is a characteristics of respiratory allergy, but its relationship to SLIT remain unclear.

We evaluate the association between clinical outcomes with pulmonary function and biomarkers in before and after HDM SLIT (UMIN-Number 000022390).

One hundred twelve patients with asthma sensitized to HDM were randomized to add-on 6 standardized quality (SQ)-HDM SLIT to pharmacotherapy or pharmacotherapy alone for 48 weeks. At baseline and end of study, biomarkers, blood eosinophils, serum IgE, serum periostin, fractional exhaled nitric oxide (FeNO), and spirometry and clinical symptoms were measured. Association between biomarkers and an increase in FEV1 of 120 ml or greater were analyzed.

SLIT demonstrated a significant reduction of serum periostin (P < 0.001), FeNO (P < 0.01), and increase in HDM specific IgE (P < 0.05), FEV1 (P < 0.001) and improvement of clinical symptom scores, when compared to pharmacotherapy. The change in FEV1 correlated with the changes in serum periostin (r = 0.696, P < 0.001) and the changes in FeNO (r = 0.682, P < 0.001). The independent predictor of improvement in airflow limitation were change in serum periostin (r2 = 0.753, P = 0.013) and FeNO (P = 0.038). Based on cutoff values derived by receiver operating characteristic analysis (periostin 30.9 ng/mL, FeNO 28.0 ppb), patients were distinguished responders from non-responders, but with no predictive value for blood eosinophils or total IgE. The proportion of patients with both high periostin and FeNO levels was significantly higher in responder than in non-responder (P = 0.026).

Adding HDM SLIT to pharmacotherapy resulted in reduced serum periostin and FeNO, and improved pulmonary function. Serum periostin and FeNO may be useful biomarkers for prediction of SLIT.

While desensitization and sustained unresponsiveness (SU) have been shown with egg oral immunotherapy (OIT), the benefits of baked egg (BE) therapy for egg allergy have not been well studied.

To evaluate the safety and efficacy of BE ingestion compared to egg OIT in participants allergic to unbaked egg but tolerant to BE tolerant but unbaked egg reactive children ages 3-16 years were randomized to 2 years of treatment with either BE or egg OIT.

Double-blind, placebo-controlled food challenges (DBPCFC) were conducted after 1 and 2 years of treatment to assess for desensitization, and after 2 years of treatment followed by 8-10 weeks off of treatment to assess for SU. Mechanistic studies were conducted to assess for immune modulation. A cohort of BE reactive participants underwent egg OIT and identical DBPCFCs as a comparator group.

Fifty participants (median age 7.3 years) were randomized and initiated treatment. SU was achieved in 3 of 27 (11.1%) BE participants versus 10 of 23 (43.5%) egg-OIT participants (p=0.009). In the BE reactive comparator group, 7 of 39 (17.9%) participants achieved SU. More BE tolerant participants withdrew from BE versus egg OIT (29.6% versus 13%). Dosing symptom frequency in BE tolerant participants was similar with BE and egg OIT, but more frequent in BE reactive participants. Egg white-specific IgE, skin testing and basophil activation decreased similarly after BE and egg OIT.

Among children allergic to unbaked egg but tolerant to BE, those treated with egg OIT were significantly more likely to achieve SU compared to children ingesting BE.

Concerning development of medicinal products, children belong to a so-called “special population” for which additional legislation applies: Regulation (EC) No 1901/2006 on medicinal products for paediatric use sets up a system of requirements, rewards and incentives to ensure that medicinal products are researched, developed and authorized to meet the therapeutic needs of children. Allergen Immunotherapy (AIT) is believed to contain a strong potential for immunomodulatory effects inducing sustained clinical efficacy after cessation of treatment (disease modifying effect) and thereby may prevent the progression of the atopic march towards asthma manifestation. However, to this day only few data on long-term effects in general exist and even fewer in children. These are predominantly data from open studies, which are strongly influenced in their validity by the known placebo effect of AIT. Furthermore, there are no studies allowing for the conclusion that efficacy in adults are mirrored by a similar efficacy in children and thus, up to now, it is not possible to extrapolate data from adults to children. The Paediatric Committee (PDCO)-European Medicines Agency’s (EMA) scientific committee responsible for activities on medicines for children-initiated a Multi-Stakeholder Meeting on AIT for Children held at the Paul-Ehrlich-Institut in Langen, Germany, to provide a platform for discussion and exchange of thoughts to this topic between allergy experts from academia, regulators and AIT-manufacturers. The consented meeting minutes, conclusions and participants are presented.

Epicutaneous immunotherapy (EPIT) for peanut allergy is a potential novel immunotherapy that utilizes the unique cutaneous immunologic properties to induce desensitization. A randomized, double-blind, placebo-controlled Phase 3 trial (PEPITES) in peanut-allergic children 4-11 years demonstrated an epicutaneous patch (DBV712) with 250 micrograms peanut protein was statistically superior to placebo in inducing desensitization following 12 months of daily treatment.

To investigate what baseline and in-study factors influenced response to DBV712 250 micrograms, with a focus on patch adhesion, by posthoc analysis of PEPITES data.

A posthoc multivariate model built with log-transformed Month 12 eliciting dose (ED) as the dependent variable was used to assess the influence of baseline characteristics and patch adhesion. Baseline characteristics and treatment response were also evaluated by stratifying subjects into decile subgroups by patch detachment rates over the 12-month study.

Multivariate analysis identified higher baseline ED and lower baseline peanut-specific IgE as the variables most predictive of higher Month 12 ED, followed by mean daily patch application duration, baseline SCORing Atopic Dermatitis(SCORAD) score, and age. By decile stratification, no association between patch detachment and treatment response was identified for 80% of DBV712-treated subjects. All DBV712-treated subjects, including those with the highest patch detachment rates, demonstrated treatment benefit measured by fold-changes in geometric mean ED.

We identified subject baseline characteristics of higher baseline ED and lower baseline peanut-specific IgE as most predictive of higher Month 12 ED. For the majority of treated subjects, patch detachment did not impact treatment response. A minority of subjects, highly sensitive to peanut at baseline, had lower prespecified responder rates and higher patch detachment rates, yet still benefited from treatment based upon fold-changes in ED.

Post hoc analyses presented herein evaluate eliciting dose changes after epicutaneous immunotherapy treatment in clinical trials in a more insightful way than a binomial endpoint approach allows.

Asthma is a chronic inflammatory disease of the airways where exaggerated T helper 2 immune responses and inflammatory mediators play a role. Current asthma treatment options can effectively suppress symptoms and control the inflammatory process; however, cannot modulate the dysregulated immune response. Allergen-specific immunotherapy is one of the effective treatments capable of disease modification. Injecting allergens under the skin in allergen-specific immunotherapy can reduce asthma and improve the sensitivity of the lungs, however, has a risk of severe reactions. Mesenchymal stem cells have immunoregulatory activity with their soluble mediators and contact dependent manner. In this review, we focus on the current treatment strategies with mesenchymal stem cells in asthma as a new therapeutic tool and compare those with immunotherapy.

Oral immunotherapy (OIT) has been reported to be effective but associated with a risk of severe symptoms. Thus, an OIT method with decreased risk is required.

We aimed to evaluate the efficacy and safety of low- and high-dose OIT regimens in children with severe milk allergy.

Overall, 33 participants (median age, 9 years; median final dose of the milk oral food challenge [OFC], 2 mL) were included. The participants were randomly assigned to groups that received either a low (20 mL; n = 19) or high (100 mL; n = 14) maintenance target dose of OIT. The dose was gradually increased to the target dose in the rush escalation phase and was then maintained daily at home. The primary endpoint was the final OFC dose at 6 months of OIT. Adverse events during OIT were evaluated.

The final OFC dose after OIT was significantly higher than that before OIT in both groups (low-dose, p = 0.000; high-dose, p = 0.006), but there was no significant difference in the final OFC dose between the 2 groups (p = 0.767). In the maintenance phase, the high-dose group had significantly more severe symptoms than did the low-dose group (0.5%, 11/2,355 total intake events vs. 0.1%, 4/3,230 total intake events; p = 0.018).

An equally increased dose effect was observed for maintenance OIT doses of 20 and 100 mL in children with severe milk allergy. The risk of severe symptoms in the maintenance phase was lower in the low-dose group. A low-dose OIT regimen is recommended for severe milk allergy.

Food allergy is a common condition which can have a significant impact on the quality of life of affected individuals and their caregivers. Recent years have witnessed an increased effort to identify new treatments for food allergy. Here we review the need to identify core outcomes for measurement in clinical trials of food allergy treatments.

We reviewed literature regarding core outcome set development, the important role that these play in prioritising patient-relevant outcomes and the potential for core outcomes to accelerate the path to product marketing by allowing prompt and reliable evidence synthesis following trial publication.

We reviewed recent clinical trials of food allergy treatments in order to understand which outcomes have previously been measured; and reviewed available core outcome set initiatives for other allergic conditions in order to understand which other outcomes might be explored in future trials.

Clinical trials of food allergy treatments have largely focussed on outcomes which are relevant to investigators and to commercial investors, especially threshold of reactivity and immunological changes. Future trials should consider addressing patient important outcomes and should report the experiences of both adult and child participants and their caregivers.

There is a pressing need for core outcome set development for food allergy treatment trials.