Immunotherapy with peptide hydrolysates from Lolium perenne (LPP) is an alternative treatment for seasonal allergic rhinitis with or without asthma. The aim of this study was to assess the clinical efficacy and safety of acumulative dose of 170 μg LPP administered subcutaneously over 3 weeks.

In a randomized, double blind, placebo-controlled trial, 554 adults with grass pollen rhinoconjunctivitis were randomized (1:2 ratio) to receive 8 subcutaneous injections of placebo or 170 μg LPP administered in increasing doses in 4 visits over 3 weeks. The primary outcome was the combined symptom and medication score (CSMS) measured over the peak pollen season. Reactivity to conjunctival provocation test (CPT) and quality of life (QOL) were assessed as secondary endpoints.

The mean reduction in CSMS in the LPP vs. placebo group was -15.5% (p=0.041) during the peak period and -17.9% (p= 0.029) over the entire pollen season. LPP treated group had a reduced reactivity to CPT (p<0.001) and, during the pollen season, a lower rhinoconjunctivitis QOL global score (p=0.005) compared to placebo group. Mostly mild and WAO grade 1 early systemic reaction (ESR) were observed ≤ 30 min in 10.5% of LPP-treated patients, whereas 3 patients with a medical history of asthma (<1%) experienced a serious ESR that resolved with rescue medication.

LPP administered over 3 weeks before the grass pollen season significantly reduced seasonal symptoms, was generally safe and well-tolerated.

Serum tryptase (ST) decreases in long-term venom immunotherapy (VIT). A circadian tryptase variation with a small decrease has been found after sting challenge. Both findings have been related to successful VIT.

To assess whether variation (increase or decrease) in ST on the first day of VIT is associated with the likehood of future systemic adverse reactions (SAR) during treatment.

We prospectively studied patients who underwent cluster VIT and continued it for at least 6 months. ST was measured on the first day of VIT, before the first dose (pre-IT tryptase) and after the last dose (post-IT tryptase). Differences between patients’ groups (with and without SAR) were analysed.

One hundred and sixty VIT were administered to 150 patients. The median baseline ST value was 4.3 μg/L. A total of 25 VIT (15.6%) were associated with SAR. In 64% of the 25 patients with SAR, post-IT tryptase value was higher than pre-IT tryptase level; the median increment was 19% in these patients. We found a significant relation between this increase in tryptase level on the first day of VIT and future SAR (risk ratio 7.6). This elevation was independent of the VIT scheduled day and severity of the SAR, as well as of the basal ST value.

A slight increase in tryptase on the first day of VIT is an independent variable strongly related to a high risk of future SAR. This simple biomarker could be helpful to improve patients´ safety.

Although Th2 cells are well known to play important roles in allergic diseases including allergic rhinitis (AR), the factors that induce and sustain the pathogenesis of AR remain unclear. The recent development of sublingual immunotherapy (SLIT) is expected to allow changes to the underlying pathogenesis of AR. However, which Th2 cell subsets are important in house dust mite-induced AR (HDM-AR), the influence of SLIT on the pathogenic Th2 cells, and the association of Th2 cell subsets with SLIT efficacy have not been clarified.

The cytokine production and frequency of HDM-reactive T cell subsets in peripheral blood mononuclear cells (PBMCs) were evaluated using flow cytometry in 89 HDM-AR patients (placebo (n=43) and HDM 300 IR (n=46)) who participated in a placebo-controlled study of SLIT with HDM tablets. All patients provided samples both before treatment as a baseline and at the end of the 52-week study. The PBMCs were stained with CellTrace™ Violet (CTV) before culture with HDM extract, and HDM-reactive T cells were detected as the proliferated cells with diminished CTV.

HDM-reactive IL-5+ IL-13+ CD27- CD161+ CD4+ cells and ST2+ CD45RO+ CD4+ cells were observed in the peripheral blood from each patient with HDM-AR; these cells significantly decreased after SLIT in the group treated with active tablets. HDM-reactive ST2+ CD45RO+ CD4+ cells were significantly lower in active-responders.

Allergen-reactive ST2+ CD45RO+ CD4+ cells or those combined with IL-5+ IL-13+ CD27- CD161+ CD4+ cells may be useful as markers indicating the successful treatment of SLIT. These cells may play a crucial role in the pathogenesis of AR as pathogenic memory Th2 cells.

Treatment options for allergic asthma include allergen avoidance, pharmacotherapy, and allergen immunotherapy.

Summarize and update current evidence for the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in pediatric allergic asthma.

PubMed, Embase, Cochrane Central Register of Controlled Trials (January 1, 2005, through May 8, 2017), ClinicalTrials.gov, and the US Food and Drug Administration Adverse Event Reporting System. We reevaluated trials from our 2013 systematic review.

We included studies with children ≤18 years of age in which researchers reported on pre-specified outcomes and had an intervention arm receiving aeroallergen SCIT or SLIT. Only randomized controlled trials (RCTs) were included for efficacy. RCTs and non-RCTs were included for safety outcomes.

Two reviewers extracted data. We included 40 studies (17 SCIT trials, 11 SLIT trials, 8 non-RCTs for SCIT safety, and 4 non-RCTs for SLIT safety).

We found moderate-strength evidence that SCIT reduces long-term asthma medication use. We found low-strength evidence that SCIT improves asthma-related quality of life and forced expiratory volume in 1 second. There was also low-strength evidence that SLIT improves medication use and forced expiratory volume in 1 second. There was insufficient evidence on asthma symptoms and health care use.

There were no trials in which researchers evaluated asthma symptoms using a validated tool. Study characteristics and outcomes were reported heterogeneously.

In children with allergic asthma, SCIT may reduce long-term asthma medication use. Local and systemic allergic reactions are common, but anaphylaxis is reported rarely.

Specific immunotherapy is the only causal treatment in respiratory allergy. Due to high treatment cost and possible severe side effects subcutaneous immunotherapy (SCIT) is not indicated in all patients. Nevertheless, reported treatment rates seem to be low. This study aims to analyze the effects of increasing treatment rates of SCIT in respiratory allergy in terms of costs and quality-adjusted life years (QALYs).

A state-transition Markov model simulates the course of disease of patients with allergic rhinitis, allergic asthma and both diseases over 10 years including a symptom-free state and death. Treatment comprises symptomatic pharmacotherapy alone or combined with SCIT. The model compares two strategies of increased and status quo treatment rates. Transition probabilities are based on routine data. Costs are calculated from the societal perspective applying German unit costs to literature-derived resource consumption. QALYs are determined by translating the mean change in non-preference-based quality of life scores to a change in utility. Key parameters are subjected to deterministic sensitivity analyses.

Increasing treatment rates is a cost-effective strategy with an incremental cost-effectiveness ratio (ICER) of 3484€/QALY compared to the status quo. The most influential parameters are SCIT discontinuation rates, treatment effects on the transition probabilities and cost of SCIT. Across all parameter variations, the best case leads to dominance of increased treatment rates while the worst case ICER is 34,315€/QALY. Excluding indirect cost leads to a twofold increase in the ICER.

Measures to increase SCIT initiation rates should be implemented and also address improving adherence.

To evaluate the impact of allergic rhinitis (AR) on the development of asthma and to update readers on recent literature suggesting that early treatment of allergic subjects with immunotherapy may prevent asthma onset.

AR is frequently associated with asthma, leading to the concept that these two conditions are different aspects of the same disease. There is increasing evidence that AR precedes the onset of asthmatic symptoms and current treatment strategies are beneficial in symptom control with no impact prevention. There is limited knowledge about the risk factors responsible for the progression of AR to asthma, though recent data supports the notion that it is possible to prevent asthma onset by allergen immunotherapy. Despite significant advances in specific immunotherapy (SIT) therapy strengthening its efficacy in AR and possible prevention of progression to asthma, the adoption of this therapeutic strategy is still restricted in comparison to therapies directed towards treatment of AR symptoms. Unlike corticosteroids and other symptomatic therapies, the benefit of SIT treatment in allergic individuals has been shown to prevent the development of allergic conditions. Hence, large well-conducted randomized clinical trials with long-term efficacy of SIT are required to confirm or refute the concept that SIT may abrogate the progression of AR to asthma in patients.

Allergies to dogs and cats affect 10%-20% of the population worldwide and is a growing public health concern as these rates increase. Given the prevalence of detectable dog and cat allergens even in households without pets, there is a critical need to accurately diagnose and treat patients to reduce morbidity and mortality from exposure. The ability to diagnose cat sensitization is good, in contrast to dogs. Component resolved diagnostics of sensitization to individual allergenic proteins will dramatically improve diagnosis. This review focuses on the current state of knowledge regarding allergies to dogs and cats, recent advances, therapies such as subcutaneous immunotherapy, and discusses important areas to improve diagnosis and therapy.

Allergen-specific immunotherapy (AIT) in its subcutaneous and sublingual forms is currently a well-established and experimentally supported treatment for respiratory allergy and hymenoptera venom allergy. There have been advances in its use linked strictly to the advancement in the knowledge of the molecular mechanisms of allergy, the production of well-characterized extracts, and diagnostic techniques. The use of AIT in asthma and the application of new approaches are expanding. We briefly review the advances and concerns in the use of AIT.

PubMed and Scopus.

The most recent and clinically relevant literature was selected and reviewed.

The introduction of high-quality products supported by large dose-finding trials has yielded better defined indications, contraindications, and modalities of use. Some specific products in tablet form have recently been approved in the United States. Sublingual immunotherapy has been found to be effective in asthma, which until recently had been a matter of debate. Another promising therapy is oral and sublingual desensitization for food allergy, for which encouraging results have recently been reported. In the near future, other options will be available, including new routes of administration (intralymphatic and epicutaneous), allergoids, engineered allergens, and peptides. The use of component-resolved diagnosis techniques will further refine and target AIT prescriptions.

Allergen immunotherapy (AIT) is the only disease-modifying treatment approved for allergic rhinitis and allergic asthma and represents a suitable therapeutic option, especially in childhood, to modify the progression of respiratory allergic diseases. Starting from the previous "generic class effect" evaluation, as testified by the numerous meta analyses, AIT is now considered a product-specific pathogenic-oriented treatment.

AIT was empirically proposed more than one century ago in the subcutaneous form (SCIT), but the IgE-mediated mechanism of allergy was elucidated only after 50 years of clinical use of the treatment. The sublingual administration (SLIT) was developed during the 1980 ties, to achieve an improvement in safety and convenience. While SCIT is approved in the United States for the treatment of asthmatic patients with more than 12 years, so far few trials evaluated the clinical efficacy and safety of SLIT in children with allergic asthma, although the indications and some aspects remain unclear. Certainly, due to compliance problems, the age below 3 years may be reasonably considered a practical contraindication.

Given that some specific AIT products are effective and approved as drugs (AIFA, EMA, FDA), the use in children is still debated. Some aspects still need robust confirm: (a) the safety of AIT in asthma; (b) the optimal regimen of administration; (c) the role of AIT as preventative treatment for asthma development.

The prevalence of food allergy is increasing. More children are being diagnosed with food allergies, and it is taking longer to outgrow them, among those who develop tolerance. The aim of this review is to draw the profile of the persistent food allergic, so that prevention strategies can be developed and active treatment set up.

Many determinants are involved in food allergy prognosis: ethnicity and sex, type of food, innate immune system, eliciting dose, sensitization status and other biomarkers determination, gut microbiome composition, and the presence of comorbidities. Once identified, a persistent food allergy could be conveyed to active treatments, such as oral immunotherapy or the use of biologics, always taking into account their experimental nature.

A better understanding of prognostic factors and phenotypes of food allergy is crucial in decision-making when it comes to food allergy prevention and management. A good classification of the allergic patient allows to determine the degree of exclusion diets and the timing of the reintroduction of avoided food when possible. In the cases of persistent and severe food allergy, many promising interventions are emerging which could improve prognosis and quality of care.