Allergic rhinoconjunctivitis is a public health problem. Allergen Immunotherapy is an effective and safe treatment, that modifies the natural course of allergic disease and induces long-term tolerance.

To correlate basophil and antibody biomarkers of subcutaneous immunotherapy to clinical outcomes and cellular changes in target tissue.

To correlate basophil and antibody biomarkers of subcutaneous immunotherapy to clinical outcomes and cellular changes in target tissue.

Subcutaneous immunotherapy led to a 447-fold decrease in basophil sensitivity during the first treatment year. This remained 100-fold lower than baseline during the 3 year-treatment period and 10-fold lower during the follow-up year (n = 18, P = .03). Decrease in basophil sensitivity after three weeks of treatment predicted long-term improvement in seasonal combined symptom and medication scores (ῥ=-0.69, P = .0027) during three years of treatment. AUC of IgE-blocking factor correlated to nasal allergen challenge (ῥ = 0.63, P = .0012) and SPT (ῥ = 0.45, P = .03). Plasma cell numbers in the nasal mucosa increased during treatment (P = .02).

Decrease in basophil sensitivity after three weeks of subcutaneous allergen immunotherapy predicted the clinical outcome of this treatment.

Randomized controlled trials (RCTs) show that allergen immunotherapy (AIT) has proven long-term efficacy in patients with allergic rhinitis (AR). However, RCTs have limited generalizability and there is growing recognition that real-world evidence (RWE) is necessary to provide complementary data to those of RCTs, and corroborate their findings. Until recently, data from the real-world setting investigating the benefits of AIT for the treatment of patients with grass and birch pollen-associated AR were sparse, but new retrospective claims database studies from France and Germany have confirmed the sustained benefits of grass and birch pollen AIT in terms of significantly reduced progression of AR and asthma, and a significantly decreased risk of new-onset asthma.

Here, we review the value of RWE used alongside data from traditional RCTs, and its potential strengths and limitations, and summarize the findings of the recent RWE studies investigating the benefits of AIT for the management of patients with grass and birch pollen-associated AR.

There is growing recognition of the necessity and value of RWE as a complement to data acquired in RCTs, to better understand the effects of AIT treatments in a broader, more representative patient population, and to help guide clinical decision-making.

Children who avoid cow’s milk (CM) because of food allergy may show disturbed growth. Calcium insufficiency, in particular, was reported among those who completely avoided dairy products. We retrospectively examined whether oral immunotherapy (OIT) affected the stature of patients who had completely avoided CM owing to their severe CM allergy.

The CM-OIT group included subjects who had completely avoided milk their entire lives and were administered OIT between 2009 and 2013. The complete milk avoidance (CM-Avoid) group included subjects who were diagnosed with a CM allergy using oral food challenges between 2013 and 2014 who subsequently avoided CM completely. By examining clinical records and questionnaires, we investigated patient height changes over time. We calculated age- and sex-stratified height standard deviation scores (HtSDS) and analyzed changes in HtSDS retrospectively. The observation period was 1-2 years. To exclude pubertal growth spurts, we set the age criteria as less than 11 years in boys and less than 9 years in girls.

We recruited 29 patients (19 boys) for the CM-OIT group and 20 (9 boys) for the CM-Avoid group. The patients’ median ages at the start of the observation period were 7.5 years (6.1-9.6) for boys and 6.8 years (5.8-7.8) for girls in the CM-OIT group, and 5.4 years (5.0-7.5) for boys and 5.7 years (5.0-7.1) for girls in the CM-Avoid group. The initial HtSDS in the CM-OIT group was -0.31 (median) and increased to -0.22 (median) after OIT (p = 0.016). In contrast, there was no significant change in HtSDS for the CM-Avoid group.

Physical growth of pediatric patients with severe CM allergies, who have avoided CM completely, could be improved by OIT for CM allergy.

Japanese cedar pollinosis (JCP) is a common affliction caused by an allergic reaction to cedar pollen and is considered a disease of national importance in Japan. Antigen-specific immunotherapy (AIT) is the only available curative treatment for JCP. However, low compliance and persistence have been reported among patients subcutaneously or sublingually administered AIT comprising a conventional antigen derived from a pollen extract. To address these issues, many research studies have focused on developing a safer, simpler, and more effective AIT for JCP. Here, we review the novel antigens that have been developed for JCP AIT, discuss their different administration routes, and present the effects of anti-allergy treatment. Then, we describe a new form of AIT called transcutaneous immunotherapy (TCIT) and its solid-in-oil (S/O) nanodispersion formulation, which is a promising antigen delivery system. Finally, we discuss the applications of S/O nanodispersions for JCP TCIT. In this context, we predict that TCIT delivery by using a S/O nanodispersion loaded with novel antigens may offer an easier, safer, and more effective treatment option for JCP patients.

Ragweed pollen sensitivity is a common cause of allergic rhinitis (AR) worldwide. AR symptoms include itchy and runny eyes, sneezing, blocked nose, impaired sleep and social and emotional problems, which can have a significant impact on quality of life.

The objective of this analysis was to estimate utilities for two pooled standardised quality (SQ) ragweed sublingual immunotherapy (SLIT) tablet trials by applying a previously developed mapping algorithm. This study validated the algorithm and extended its application to ragweed seasonal allergy trials. The mapping algorithm relates disease-specific quality-of-life scores to preference-based utilities that may be used to calculate quality-adjusted life-years (QALYs) in cost-effectiveness studies.

A mapping algorithm based on a grass pollen allergy immunotherapy trial, GT-08 (EudraCT no. 2004-000083-27) was applied to pooled data from two ragweed pollen immunotherapy trials, P05233 (EudraCT 2008-003863-38) and P05234 (EudraCT 2008-003864-20) to generate EuroQoL 5-Dimensions, 3-Levels (EQ-5D-3L) utilities from Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) data.

The mean utility difference between the SQ ragweed SLIT tablet and placebo was 0.025 [95% confidence interval (CI) 0.011-0.038]. The SQ ragweed SLIT tablet showed an incremental quality-adjusted life-days (QALDs) benefit of 1.900 (95% CI 0.835-2.916) over 75 days.

Application of a previously developed mapping function allowed for the calculation of QALDs associated with the SQ ragweed SLIT tablet. The results showed a QALD benefit of the SQ ragweed SLIT tablet in P05233 and P05234 trials in the treatment of ragweed pollen-induced AR.

In 2004, it was estimated that one fatal anaphylactic reaction (FR) occurred in every 2.4 million subcutaneous immunotherapy (SCIT) injection visits. Uncontrolled asthma was the most commonly cited factor that contributed to FRs. Results of the annual American College of Allergy, Asthma, and Immunology/American Academy of Allergy, Asthma and Immunology sponsored survey conducted among practicing allergists suggest that one nonfatal systemic reactions (SR) occurred in 0.15% of injection visits and in 0.7% of patients who were treated. Analysis of recent data indicated that FRs are 3.75-fold less frequent. Life-threatening grade 4 anaphylactic reactions are estimated to occur in 0.005% of patients who receive SCIT (or 1/160,000 injection visits). Analysis of data from annual surveys identified the following possible risk factors for SRs: a history of SRs to SCIT, the administration of injections in patients with uncontrolled asthma, use of accelerated buildup regimens, and never adjusting doses during the height of the allergy season. Delayed-onset SRs beginning >30 minutes after injections represented 15% of all SRs in clinics with 30-minute observation periods. The safety profile of sublingual immunotherapy is favorable, with no FRs yet identified for sublingual tablet or liquid formulations. Risk management should focus mainly on patients with uncontrolled asthma by withholding injections in such patients, with recent worsening in asthma symptoms and lung function (e.g., peak expiratory flow rate). Because nearly all FRs and SRs occur within 30 minutes of injections, a 30-minute observation period is recommended. Routinely prescribing epinephrine for all patients did not prevent severe SRs, likely due to poor adherence when SRs occurred. Also, no local or systemic infections were identified in 2.3 million patients attending 24.5 million injection visits, which allayed concerns over infections associated with compounding of allergen extracts by practicing allergists.

A new understanding of factors leading to the development of asthma has pointed to potential primary, secondary, and tertiary prevention strategies. Some, such as genetic makeup, are not yet modifiable. Interventions targeting other factors such as maternal intake of vitamin D or environmental control can be used to decrease the risk of asthma development (primary prevention). The benefits of a diversified microbiome could be considered when recommending allergen avoidance and pet ownership. In addition to reducing symptoms, allergen immunotherapy is also worth considering for prevention of new sensitivities (secondary prevention) in addition to the development of asthma. Ongoing studies involving the use of bacterial vaccines and biologics may provide additional strategies for primary prevention of asthma and for reducing symptoms once it has developed (tertiary prevention). As the relative benefits of these strategies are defined, they should have an increasingly important place in the prevention and management of asthma.

Atopic dermatitis (AD) is one of the most common inflammatory skin conditions, affecting 15% to 30% of children and 2% to 10% of adults. Population-based studies suggest that having AD is associated with subsequent development of other atopic diseases, in what is known as the “atopic march.” We will provide an overview of studies that investigate primary prevention strategies for the first 2 diseases in the march, namely, AD and food allergies (FA). These strategies include emollients, breastfeeding, microbial exposures, probiotics, vitamin D and UV light, water hardness, and immunotherapy. Some studies, including randomized controlled trials on emollients and microbial supplementation, have found encouraging results; however, the evidence remains limited and contradictory. With regard to breastfeeding, microbial and lifestyle exposures, vitamin D and UV light, water hardness, and immunotherapy, the lack of randomized controlled trials makes it difficult to draw definitive conclusions. Current American Academy of Pediatrics guidelines support the idea that breastfeeding for 3 to 4 months can decrease AD incidence in children less than 2 years old. Recommendations regarding a direct relationship between breastfeeding on FA, however, cannot be made because of insufficient data. Regarding microbial supplementation, most guidelines do not recommend probiotics or prebiotics for the purpose of preventing allergic diseases because of limited evidence. Before definitive conclusions can be made regarding these interventions, more well-designed, longitudinal, and randomized controlled trials, particularly in at-risk populations, are required.

A food allergy is an immunoglobulin E (IgE)-mediated hypersensitive reaction to food, which consists in the appearance of allergic symptoms; it can vary from common urticaria to even fatal anaphylaxis. The prevalence of food allergies has been increasing in the past twenty years and it represents a major public health problem in industrialized countries. The mechanism that leads to food allergies is the lack of immunologic and clinical tolerance to food allergens. The diagnosis of IgE-mediated food allergies is based on the combined use of a detailed medical history, in-vivo, and in-vitro research of specific IgE, the elimination diet, and the double-blind placebo-controlled food challenge. The only currently available treatment for allergies is the strict elimination diet. This type of attitude, which we could define as “passive”, does not overcome the risk of accidental reactions due to involuntary intake of the culprit food. For food allergy management, an “active” approach is urgently needed, such as specific allergen immunotherapy, which is currently under development and only used for research purposes. This article aims to give an updated review of IgE-mediated food allergies in pediatric populations in terms of epidemiology, pathogenesis, prevention, diagnosis, and management.