Allergic asthma causes substantial morbidity and constitutes a public health burden, which increases with asthma severity. There is evidence that allergy immunotherapy (AIT) prevents the progression from allergic rhinitis (AR) to asthma. However, evidence is missing on the potential of AIT to prevent progression from milder to more severe asthma.

This population-based cohort study utilized healthcare data (2005 to 2014) from a statutory health insurance in Germany. The severity of asthma was classified according to the treatment steps recommended by the global initiative for asthma (GINA). The effect of AIT on the transition between the GINA steps was analyzed using multivariable Cox regression models adjusted for age and sex.

From the total cohort of 1,739,440 patients, 39,167 individuals aged 14 years or older were classified as having incident asthma during the observation period and were included in the study. From these, 4,111 patients (10.5%) received AIT. AIT exposure was associated with a significantly decreased likelihood of asthma progression from GINA step 1 to GINA step 3 (HR 0.87; 95% CI 0.80-0.95) and GINA step 3 to GINA step 4 (HR 0.66; 95% CI 0.60-0.74). GINA medication for step 2 and step 5 were rarely prescribed.

This observational study in a real-world setting indicates that patients with allergic asthma who receive AIT are less likely to experience progression of asthma severity than asthma patients not receiving AIT.

Only some peanut-allergic subjects undergoing oral immunotherapy (OIT) achieve sustained clinical response. Basophil activation could provide a functional surrogate of efficacy.

We hypothesized that changes in basophil sensitivity and AUC to the immunodominant allergen Ara h 2 correlate with clinical responses to OIT.

Peanut-allergic children, aged 7-13, enrolled in a single-center, open-label peanut OIT trial. Specific immunoglobulins were measured throughout OIT. Peripheral blood from multiple time points was stimulated in vitro with peanut allergens for flow cytometry assessment of the percent CD63hi activated basophils.

Twenty-two of 30 subjects were successfully treated by OIT; post-avoidance, 9 achieved sustained unresponsiveness (SU) and 13 had transient desensitization (TD). Basophil sensitivity, measured by ED50, to Ara h 2 stimulation decreased from baseline in SU (post-OIT p= 0.0041, post-avoidance p=0.0011). At 3 months of OIT, basophil sensitivity in SU decreased from baseline compared to TD (median 18-fold vs. 3-fold, p=0.01) with an ROC of 0.84 and optimal fold-change of 4.9. Basophil AUC, measured by area-under-the-curve, to Ara h 2 was suppressed post-OIT equally in SU and TD (p=0.4). After avoidance, basophil AUC rebounded in TD but not SU (p<0.001). Passively sensitized basophils suppressed with post-avoidance SU serum had lower AUC than TD serum (6.4% vs. 38.9%, p=0.03).

Early decreases in basophil sensitivity to Ara h 2 correlate with SU. Basophil AUC rebounds post-avoidance in TD. Therefore, different aspects of basophil activation may be useful for monitoring of OIT efficacy.

Peanut allergy is a generally persistent, sometimes life-threatening food allergy that is increasing in prevalence in Western countries. There are no FDA-approved therapies for treatment of peanut allergy, and patients must strictly avoid peanut and be prepared to use rescue medication upon symptoms due to unintentional peanut ingestion. However, complete avoidance of peanut is difficult at least in part due to its widespread use as a food ingredient in packaged foods and in restaurant or catered meals. Unexpected allergic reactions to food including peanut are frequent, reportedly occurring in up to half of peanut-allergic patients on a yearly basis, with unpredictable symptoms that can be mild, moderate and severe. With no treatments demonstrating the ability to cure a food allergy, the focus of drugs in development has been on providing a level of protection against accidental exposure reactions by increasing the reaction threshold (i.e., the amount at which an individual experiences an allergic reaction). Caregivers of peanut allergic children have also expressed a desire for a “buffer” against reactions to accidental peanut exposures that will involve minimal risk. Thus, recent studies have aimed to quantitatively model the clinical benefits of increasing a hypothetical individual’s threshold through immunotherapy in the American and European populations. A greater than 95% relative risk reduction was modeled for the risk of accidental allergic reactions due to peanut in packaged foods across food categories for the peanut-allergic individual who achieved an eliciting dose (ED) of 300 mg peanut protein or more after immunotherapy (from initial EDs of 1, 3, 10, 30 or 100mg peanut protein), regardless of the immunotherapy method However, no study to date has investigated the quantitative relative risk reduction of a food-allergic population receiving a specific immunotherapeutic treatment for their allergies.

There has been exciting progress in diagnosis and in the treatment of allergic patients. The objective of this review is to summarize the most relevant contributions in the past 10 years with a special focus on the pediatric population allergic to aeroallergens and provide the most relevant references and practical issues for the decision-making. Current guidelines on allergy diagnosis recommend a thorough clinical history as the first step, followed by allergen extract testing using an in vivo prick test and/or an in vitro specific IgE test. Molecular diagnosis is recommended when previous tests are inconclusive. In practice, the most important factors to decide the AIT treatment are the actual intensity and duration of the patient’s symptoms and the availability of appropriate AIT products for the patient’s sensitization profile at high allergen concentrations and with confirmed efficacy and safety from clinical trials. This document summarizes outstanding references for allergic immunotherapy decision-making and provides summary tables and figures analyzing the most important factors related to the decision for allergen immunotherapy and the safety risks related. The experts concluded that AIT is efficacious and safe for the treatment of allergic patients that is available for the most frequent aeroallergens. What is Known: • The prevalence of allergic asthma and rhinitis in children has increased in recent decades. • The efficacy and safety of allergen immunotherapy has been shown in multiple studies and systematic reviews. What is New: • This document summarizes outstanding references for allergic immunotherapy decision-making and provides summary tables and figures analyzing the most important factors related to the decision for allergen immunotherapy and the safety risks related. Recommendations of expert authors for the decision of the patients more suitable for allergen immunotherapy are included.

Allergen bioavailability underpins the efficacy and safety of SLIT tablets. Three product-related factors are likely to influence this: tablet potency, formulation and sublingual holding time.

Tablet formulation determines the rate and extent of solubilized allergen release. Using validated in vitro dissolution assays, the two licensed grass pollen SLIT tablets are shown to release ≥85% of their total allergenic activity within several minutes. Sublingual holding time affects the contact duration between solubilized allergens and sublingual tissue. Maximal uptake of allergens by sublingual tissue requires ~5 minutes, with little uptake occurring within the first minute. A higher potency tablet with longer sublingual holding time would provide higher bioavailability, while faster rates of allergen release in vitro are unlikely to translate to a greater increase in bioavailability. Differences in dissolution times cannot serve as a surrogate of in vivo bioavailability, and are not related to differences in efficacy at the marketed tablet dosages. Rapid in vitro dissolution is likely not a key requirement for inducing a potent immune response.

In vitro dissolution cannot predict the clinical efficacy of SLIT tablets but could be important in immune tolerance and safety. In addition, a discontinuous administration regimen may have benefits for adherence and cost without compromising efficacy.

Although allergen immunotherapy (AIT) for fungi has been performed for many years, evidence clearly demonstrating its clinical benefit are still lacking. Here, we reviewed the available studies assessing efficacy and safety of AIT for molds.

Studies on AIT for fungi were performed only for the two predominating mold species in the external environment, namely Cladosporium and Alternaria. There is no evidence for other mold species. Recent finding in the literature are lacking; the 2 most recent studies on AIT for molds were published in 2011. Overall, 13 studies were identified (the first was published in 1986), but only nine of these compared AIT to placebo. The studies are small (median study sample size, 27 patients) and of low quality, owing to several defects leading to moderate-to-high risk of bias. Symptoms improvement and medication use reduction, which are the main outcome measures of the studies, were inconsistently demonstrated. There are some concerns about safety with Cladosporium extracts, whereas vaccines with Alternaria extracts seem to be safe and well tolerated.

Low strength evidence suggests that mold AIT is efficacious for the treatment of respiratory allergies. High-quality studies with an adequate sample size are needed.

For patients with peanut allergy, there are currently no methods to predict who will develop sustained unresponsiveness (SU) after oral immunotherapy (OIT).

Assess IgE binding to peanut (PN), Ara h 2 and to specific linear epitopes of Ara h 2 as predictors of the important clinical parameters: eliciting dose threshold and attainment of SU following OIT.

Samples and clinical data were collected from children undergoing OIT. PN- and Ara h 2-sIgE were quantified by ImmunoCap® . IgE binding to linear peptides of Ara h 2 and Ara h 6 was measured with peptide microarrays.

Lower values of PN-sIgE correlated with eliciting dose (P = 0.001) and with a higher likelihood of achieving SU (P < 0.0001) but these relationships were lost at higher values for PN-sIgE (≥ 14 kIU for eliciting dose and ≥ 35 kIU/L for SU). In subjects with PN-sIgE ≥ 14kIU/L, binding of IgE to epitopes 5 & 6 of Ara h 2 was associated with a lower eliciting dose at baseline challenge (P < 0.001; Pc < 0.02). In subjects with PN-sIgE ≥ 35kIU/L, a combined model of IgE binding to epitopes 1, 5 and 6 with PN-sIgE was highly predictive of attainment of SU (AUC of 0.86; P = 0.0067).

In young patients with peanut allergy, measurement of PN-sIgE and IgE binding to specific linear epitopes of Ara h 2 in baseline samples may allow stratification of patients regarding sensitivity to challenge and outcome of OIT.

Cluster schedule of allergen-specific immunotherapy (AIT) is a cost-effective choice for allergic rhinitis (AR) patients, but its safety has been questioned due to the greater dosages required at each treatment compared with conventional immunotherapy. It remains a question that whether cluster schedule leads to a higher risk of side effects.

This study was designed to update the evidence and investigate whether cluster schedule leads to a higher risk of local adverse reactions (LARs) and systemic adverse reactions (SARs) than cluster schedule does.

We searched the Cochrane Central Register of Controlled Trials, EMBASE and Medline thoroughly and included studies comparing cluster and conventional schedules. A meta-analysis of 5 outcomes related to adverse events was performed after bias and heterogeneity assessments. And as a result of language limitations, we considered only articles in Chinese and English.

5 observational studies and 6 interventional studies were included in the meta-analysis. There were no differences between cluster and conventional schedules when analyzing SARs by the number of patients, delayed SARs, grade 2 SARs and LARs. Analyses of SARs by injection, grade 1 SARs and LARs by injection in observational studies showed that cluster schedule had a lower risk of adverse events than did conventional schedule.

Our data suggest that cluster schedule is as safe as or even safer than conventional schedule for AR patients with or without asthma (AS).

Allergic rhinitis is a common disorder that regularly occurs in children and adolescents. The disease is associated with other allergic diseases, such as asthma, and it carries a heavy burden, with effects on sleep, school performance, and quality of life. Classic symptoms include sneezing, rhinorrhea, nasal obstruction, and nasal itching. When the eyes are involved, the term allergic rhinoconjunctivitis is used. Triggers may include airborne pollens, molds, dust mites, and animals. Skin or blood allergy testing can be a useful diagnostic modality that may guide therapy. Immunotherapy can prevent the development of further allergic sensitizations as well as subsequent asthma.