The allergen immunotherapy clinics (AITC) in Spain are very different in terms of structure, organisation, resources and portfolio of services. Therefore, it is essential to unify treatment criteria and define quality standards for the most complex AITCs.

To establish a series of recommendations that will make it possible to guarantee quality and safety in the administration of immunotherapy and to define the quality standards for the most complex AITCs.

This project began with an online survey of 65 allergy departments or units all over Spain conducted in 2013. Next, a two-phase consensus process was carried out. In the first, ten experts defined and agreed on the standards using t

Consensus was reached on minimum safety and quality criteria in the administration of allergen immunotherapy (AIT), and two levels of highly complex AITCs were defined: accredited AITCs (AITCA) and AITCs accredited with excellence (AITCAE). Consensus was also reached on quality standards and accreditation criteria for both levels.

This project is pioneering in terms of its purpose – the definition of quality standards for AITCs – and for the use of structured participation techniques – a combination of the RAND/UCLA and Delphi methods. The results, together with some minimum standards for quality and safety in administering AIT, is a set of quality criteria for AITC accreditation supported by a broad panel of SEAIC experts.

Real-world evidence is sparse on the benefits of allergen immunotherapy [AIT; subcutaneous/sublingual immunotherapy(SCIT/SLIT)], the only diseasemodifying intervention for allergic rhinitis (AR) with long-term efficacy. This real-life study evaluated the effect of 6 AITs (native pollen SLIT/SCIT, 4 allergoid SCITs) versus symptomatic medication use, on AR symptoms and asthma symptoms/onset, in patients with birch pollen-associated AR and/or asthma.

In this retrospective cohort analysis of a German longitudinal prescription database, AIT patients received ≥2 successive seasonal treatment cycles; non-AIT patients had ≥3 AR prescriptions in 3 seasons or previous month. Patients were matched for: index year, age, gender, main indication at index, number of seasonal cycles within treatment period, baseline AR/asthma treatment prescriptions. Multiple-regression analysis compared prescription data in AIT and non-AIT groups as proxy for clinical status/disease progression.

Up to 6 years of follow-up, significantly more AIT (65.4%) vs non-AIT (47.4%) patients were AR medication-free [odds ratio (OR) [95% confidence interval (CI)]: 0.51 [(0.48-0.54); p<0.001] (28.6% covariate-adjusted reduction vs non-AIT; p<0.001), and significantly more AIT (49.1%) vs non-AIT (35.1%) patients were asthma medication-free [OR (95% CI): 0.60 (0.55-0.65); p<0.001] (32% reduction vs non-AIT; p<0.001), or reduced existing asthma medication use (32% covariate-adjusted reduction vs non-AIT; p<0.001). During treatment, new-onset asthma risk was significantly reduced in the AIT vs non-AIT group (OR: 0.83; p=0.001).

Birch pollen AIT demonstrated real-world benefits up to 6 years post-treatment cessation through significantly reduced AR and asthma medication intake, and significantly decreased risk of new-onset asthma medication use on-treatment.

There is limited data on feasibility, efficacy and safety of high-dose oral immunotherapy (OIT) in children highly allergic to peanuts.

In children highly allergic to peanut, we primarily aimed to determine the feasibility of reaching the maximum maintenance dose (MMD) of 5000 mg peanut protein or alternatively, a lower individual maintenance dose (IMD), by OIT up-dosing. Secondarily, we aimed to identify adverse events (AEs), and determine factors associated with reaching a maintenance dose.

The TAKE-AWAY peanut OIT trial enrolled 77 children 5-15 years -old, with a positive oral peanut challenge. Fifty-seven were randomized to OIT with biweekly dose step-up until reaching MMD or IMD, and 20 to observation only. Demographic and biological characteristics, AEs, medication and protocoldeviations were explored for associations with reaching maintenance dose.

All children had anaphylaxis defined by objective symptoms in minimum two organ systems during baseline challenge. The MMD was reached by 21.1%, while 54.4% reached an IMD of median (minimum, maximum) 2700 (250, 4000) mg peanut protein, whereas 24.5% discontinued OIT. During up-dosing, 19.4% experienced anaphylaxis. Not reaching the MMD was caused by distaste for peanuts (66.7%), unacceptable AEs (26.7%) and social reasons (6.7%). Increased peanut s-IgG₄/s-IgE ratio (OR (95% CI)) 1.02 (1.00, 1.04) was associated with reaching MMD.

Although 75.5% of children with peanut anaphylaxis reached a maintenance dose of 0.25 – 5 g, only 21.1% reached the MMD. Distaste for peanuts and AEs, including high risk of anaphylaxis, limited feasibility of reaching MMD.

This randomised, double-blind trial was conducted to determine the optimal dose for clinical efficacy of the SQ tree SLIT-tablet. An environmental exposure chamber (EEC) was used to reduce variability of allergen exposure and allow investigation of symptom reduction towards different species from the birch homologous group in separate EEC sessions.

Eligible subjects (N=219) were randomised to receive treatment with placebo or the SQ tree SLIT-tablet (2, 7, or 12 DU) for 24 weeks. EEC pollen challenges were conducted outside the birch pollen season and included 4 birch and 2 oak EEC sessions. The primary efficacy endpoint was the average allergic rhinoconjunctivitis (ARC) total symptom score (TSS) after 24 weeks of treatment.

There was a statistically significantly lower TSS during the 24-week birch EEC session for 7 DU and 12 DU compared to placebo with relative differences of 24% (p=0.03) and 25% (p=0.02). For the 24-week oak EEC session, there was a statistically significant difference for 12 DU (24%, p=0.03). IgE and IgG4 measurements supported these findings and demonstrated cross-reactivity to all other species within the birch homologous group. Treatment was welltolerated with the most frequently reported adverse reactions being local reactions in the oral cavity of mild-to-moderate severity.

This trial demonstrates that the SQ tree SLIT-tablet reduce ARC symptoms triggered by birch or oak pollen. The optimal dose for further development was 12 DU. Clinical and immunological findings suggest that the tablet may be used to treat allergies to all species within the birch homologous group

Although Th2 cells are well known to play important roles in allergic diseases including allergic rhinitis (AR), the factorsthat 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.

This review paper aims to provide an overview of recent developments in the field of allergic and non-allergic rhinitis, as well allergen immunotherapy. Recent advances in phenotyping and endotyping various forms of rhinitis has brought us one step closer towards tailoring treatment more appropriately for a given patient. Updates on local allergic rhinitis is also covered. Allergen immunotherapy (AIT) is an area of significant interest, with multiple original papers and recent position papers and guidelines published. Evidence related to the application of AIT in seasonal and perennial allergic rhinitis (AR), local allergic rhinitis, as well as novel and expanded applications is discussed in the publication.

Component resolved diagnosis (CRD) allows to precisely identify the sensitization to specific molecules of a given allergenicsource, resulting in an important improvement in clinical management, particularly of polysensitized subjects. This will end in the correct prescription of allergen immunotherapy (AIT) for respiratory allergy and in adequate avoidance diets or prescription of self-injectable adrenaline in food allergy.

The aim of this multicenter, real life study is to evaluate the percentage change of the diagnostic-therapeutic choice in polysensitized patients with respiratory allergy and in patients with food allergy, after using CRD compared to a first level diagnosis, along with an economic analysis of the patient’s overall management according to the two different approaches.

An overall number of 462 polysensitized patients, as suggested by skin prick tests (SPT), and with clinical symptoms related to a respiratory (275 pts) or food (187 pts) allergy, were recruited. All patients underwent CRD for specific IgE against food or inhalant recombinant molecules, which were chosen according to medical history and positivity to SPT. The first diagnostic-therapeutic hypothesis, based only on medical history and SPT, was recorded for each patient while the final diagnostic-therapeutic choice was based on the results from CRD. The rate of change of the diagnostic-therapeutic choice from the first hypothesis to the final choice was statistically evaluated. The economic impact of CRD on the overall management of the allergic patients was analyzed to evaluate whether the increase in the diagnostic costs would be compensated and eventually exceeded by savings coming from the improved diagnostic-therapeutic appropriateness.

An approximate 50% change (k index 0.54) in the prescription of AIT for respiratory allergy as well as a change in the prescription of self-injectable adrenaline (k index 0.56) was measured; an overall saving of financial resources along with a higher diagnostic-therapeutic appropriateness was also detected.

There is moderate agreement concerning prescription of AIT and self-injectable adrenaline before and after performing CRD: this highlights the usefulness of CRD, at least in polysensitized patients, in indicating the risk assessment and therefore the correct therapy of respiratory and food allergy, which results in a cost-saving approach.

Increasing evidence suggests that leptin is upregulated during allergic reactions in the airway and related to the severity of disease in allergic rhinitis (AR). In this study, we aimed to investigate the expression of leptin during sublingual immunotherapy (SLIT) in AR patients.

Forty AR patients without obesity were recruited in this study. Twenty patients received house dust mite (HDM) allergen extract for SLIT and twenty patients received placebo randomly. Protein expression of leptin in serum and nasal lavage was tested by enzyme-linked immuno sorbent assay (ELISA) 1 and 2 years after SLIT treatment, respectively. Peripheral blood mononuclear cells (PBMCs) and human nasal epithelial cell were prepared and stimulated by recombinant leptin after 24 months’ SLIT treatment and the induction of Th2 cytokines (IL-4/IL-5/IL-13) were detected by ELISA.

SLIT treatment decreased the expression of leptin protein in serum and nasal lavage significantly compared with placebo group 1 and 2 years after SLIT treatment. Nasal leptin level was correlated to decreased Th2 response (IL-4/IL-5/IL-13) and enhanced Treg (IL-10/TGF-beat) response after 2 years’ SLIT. We also found that SLIT decreased the ability of leptin in promoting Th2 cytokines expression by PBMCs and human nasal epithelial cell after 2 years’ SLIT treatment.

Changes of leptin expression in serum and nasal lavage may be correlated with Th2/Treg regulation during SLIT. Our results suggested that leptin served as an important biomarker during SLIT.

Allergic rhinitis affects around one quarter of the Western European population. Prophylactic allergen immunotherapy may be useful to reduce the risk of acute symptomatic attacks (hayfever). A five-grass pollen extract sublingual immunotherapy (5GPE-SLIT) has been developed for the treatment of allergic rhinitis to grass pollen. The objective of this study was to describe real-world treatment patterns with 5GPE-SLIT in France with respect to the prescribing information.

This prospective cohort study was conducted by 90 community and hospital allergists. Adults and children (> 5 years old) starting a first treatment with 5GPE-SLIT prior to the 2015 pollen season were eligible. Data was collected at the inclusion visit and at the end of the pollen season. The primary outcome variable was compatibility of 5GPE-SLIT prescription with the prescribing information. This was determined with respect to four variables: (1) interval between 5GPE-SLIT initiation and onset of the pollen season ≥ 3 months, (2) age of patient ≥ 5 years, (3) intermittent symptoms or mild symptom severity (4) confirmatory diagnostic test. At study end, symptoms reported during the pollen season and any modifications to treatment or adverse events were documented.

280 adults and 203 children were enrolled. The prescribing information was respected for 82.5% of adults and 86.7% of children. A skin test was performed for all patients. 5GPE-SLIT was started 3-5 months before the pollen season for 85.3%. Treatment was discontinued before the start of the pollen season in 11.0% of patients overall, generally because of an adverse event (78.8% of discontinuations). The mean duration of treatment was 5.2 months in adults and 5.6 months in children. At the end of follow-up, symptoms during the pollen season were intermittent for 75.0% of adults and 85.7% of children, and severity was mild for 61.8 and 66.0% respectively. During 5GPE-SLIT, the following symptoms reported during the previous year were not reported again in > 50% of patients: nasal congestion, rhinorrhoea, repeated sneezing, conjunctivitis and nasal pruritus.

5GPE-SLIT use was generally consistent with prescribing recommendations and was associated with an improvement of AR severity, with resolution of the principal AR symptoms in around half the patients treated.

The analysis of epigenetic modifications in allergic diseases has recently attracted substantial interest because epigenetic modifications can mediate the effects of the environment on the development of or protection from allergic diseases. Furthermore, recent research has provided evidence for an altered epigenomic landscape in disease-relevant cell populations. Although still in the early phase, epigenetic modifications, particularly DNA methylation and microRNAs, might have potential for assisting in the stratification of patients for treatment and complement or replace in the future biochemical or clinical tests. The first epigenetic biomarkers correlating with the successful outcome of immunotherapy have been reported, and with personalized treatment options being rolled out, epigenetic modifications might well play a role in monitoring or even predicting the response to tailored therapy. However, further studies in larger cohorts with well-defined phenotypes in specific cell populations need to be performed before their implementation. Furthermore, the epigenome provides an interesting target for therapeutic intervention, with microRNA mimics, inhibitors, and antisense oligonucleotides being evaluated in clinical trials in patients with other diseases. Selection or engineering of populations of extracellular vesicles and epigenetic editing represent novel tools for modulation of the cellular phenotype and responses, although further technological improvements are required. Moreover, interactions between the host epigenome and the microbiome are increasingly recognized, and interventions of the microbiome could contribute to modulation of the epigenome with a potential effect on the overall goal of prevention of allergic diseases.