Asthma is a common long-term respiratory disease affecting approximately 300 million people worldwide. Approximately half of people with asthma have an important allergic component to their disease, which may provide an opportunity for targeted treatment. Sublingual immunotherapy (SLIT) aims to reduce asthma symptoms by delivering increasing doses of an allergen (e.g. house dust mite, pollen extract) under the tongue to induce immune tolerance. Fifty-two studies were identified and synthesised in the original Cochrane Review in 2015, but questions remained about the safety and efficacy of sublingual immunotherapy for people with asthma.

To assess the efficacy and safety of sublingual immunotherapy compared with placebo or standard care for adults and children with asthma.

Despite continued study in the field, the evidence for important outcomes such as exacerbations and quality of life remains too limited to draw clinically useful conclusions about the efficacy of SLIT for people with asthma. Trials mostly recruited mixed populations with mild and intermittent asthma and/or rhinitis and focused on non-validated symptom and medication scores. The review findings suggest that SLIT may be a safe option for people with well-controlled mild-to-moderate asthma and rhinitis who are likely to be at low risk of serious harm, but the role of SLIT for people with uncontrolled asthma requires further evaluation.

Allergic rhinitis (AR) induced by house dust mites (HDMs) is a highly prevalent but often underdiagnosed and undertreated/untreated chronic disease. It often has a negative impact on sleep, work, leisure activities, and health-related quality of life. Allergen immunotherapy is a proven, safe treatment for respiratory allergies.

To assess the efficacy and safety of a 300 index of reactivity (IR) sublingual tablet formulation of Dermatophagoides pteronyssinus: Dermatophagoides farinae 1:1 extract in adolescents (aged ≥12) and adults with moderate-to-severe HDM-induced AR.

In a Phase III, international, double-blind, placebo-controlled, randomized clinical trial, participants received approximately 12 months of treatment with placebo or the 300°IR tablet. The primary endpoint was the average total combined score (aTCS) during 4 weeks at the end of the treatment period.

1,607 participants were randomized, and 1,476 (including 555 (37.6%) with concomitant mild controlled asthma at inclusion) comprised the full analysis set. Over the primary evaluation period, the least squares mean aTCS in the 300°IR group (3.62) was significantly lower (p<0.0001) than in the placebo group (4.35), with a relative least squares mean difference of -16.9% [95% confidence interval: -24.0%; -9.2%]. All pre-specified secondary endpoints were consistently improved in the 300°IR group, relative to placebo. The 300°IR tablet was generally well tolerated. Treatment-related adverse events (mainly mild or moderate local reactions) were reported for 51.0% of the patients in the 300°IR group and 14.9% in the placebo group.

The 300°IR sublingual HDM tablet is an effective, safe treatment for HDM-induced AR. (NCT02443805, EudraCT 2014-004223-46) CLINICAL IMPLICATIONS: A 300 index of reactivity sublingual tablet formulation of Dermatophagoides pteronyssinus: Dermatophagoides farinae extract is a safe, effective treatment for moderate-to-severe house-dust-mite-induced allergic rhinitis.

In allergology, the intradermal approach is generally used to establish an etiological diagnosis, with limited experience in specific allergen immunotherapy.

To evaluate the efficacy and safety of immunotherapy with an allergen extract of glutaraldehyde-polymerised Phleum pratense, administered intradermally, in patients with rhinoconjunctivitis sensitized to grass pollen.

Multicentre, randomised, double-blind, placebo-controlled clinical trial in patients from 12 to 65 years of age with rhinitis or rhinoconjunctivitis, with or without asthma, due to grass pollen allergy. Patients were divided into three groups and received a total of 6 doses in a weekly interval, of either placebo; 0.03 μg or 0.06 μg of protein per dose of Phleum pratense allergoid. The primary objective was to evaluate the combined symptoms and medication consumption score (CSMS). The secondary objectives were symptoms and medication, tolerance to the conjunctival provocation test, specific IgE and IgG4 antibodies and the safety profile according to the WAO scale.

The dose of 0.06 μg of protein proved to be effective versus the placebo by significantly reducing CSMS and increasing tolerance to the allergenic extract in the conjunctival provocation test, after the first pollen season. This group showed a significant reduction in specific IgE after the second pollen season relative to the baseline. There were no variations in IgG4 levels. Only one grade 2 systemic reaction was recorded.

Intradermal immunotherapy with P. pratense allergoid has been shown to be effective and safe, reducing CSMS, increasing tolerance to the conjunctival provocation test and reducing IgE levels.

Peanut allergy is the the most common cause of life-threatening food-induced anaphylaxis. There is currently no effective long-term treatment. There is a pressing need for definitive treatments that improve the quality of life and prevent fatalities. Allergen oral immunotherapy (OIT) is a promising approach, which is effective at inducing desensitisation; however, OIT has a limited ability to induce sustained unresponsiveness (SU). We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut OIT (Probiotic Peanut Oral ImmunoTherapy (PPOIT)) is highly effective at inducing SU, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. Here we describe the protocol for a Phase IIb multicentre, double-blind, randomised, controlled trial (PPOIT-003) with dual primary objectives to evaluate the effectiveness of PPOIT at inducing SU (assessed at 8 weeks after treatment cessation) compared with placebo treatment and peanut OIT alone, in children with peanut allergy.

200 children 1 to 10 years of age with current peanut allergy confirmed by failed double-blind placebo-controlled food challenge (DBPCFC) at study screening will be recruited from three tertiary paediatric hospitals in Australia. There are three intervention arms-PPOIT, peanut OIT alone or placebo. Interventions are administered once daily for 18 months. The dual primary outcomes are: (1) the proportion of children who attain 8-week SU in the PPOIT group versus placebo group and (2) the proportion of children who attain 8-week SU in the PPOIT group versus OIT group.

This study has been approved by the Human Research Ethics Committees at the Royal Children’s Hospital (HREC 35246) and the Child and Adolescent Health Service (RGS 2543). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences.

Allergic rhinitis (AR) is a common inflammatory condition of the nasal mucosa affecting approximately 20% of the population worldwide. Current therapies include intranasal antihistamines, corticosteroids, subcutaneous and sublingual immunotherapy (SLIT). This review and meta-analysis assesses the efficacy of SLIT in the management of grass pollen-induced AR in adults.

Ovid EMBASE, Ovid EBM Reviews, Cochrane Central Register of Controlled Trials, Ovid MedLine and PubMed were searched using the following terms: ‘sublingual immunotherapy’, ‘SLIT’, ‘rhinitis’, ‘allergic rhinitis’, ‘rhinosinusitis’ and ‘rhino-conjunctivitis’. All included studies were double-blind, placebo-controlled and randomised trials. Primary outcome was symptom score and secondary outcome included quality of life and safety profile. Meta-analysis of symptom improvement was carried out.

Six studies were identified with 979 subjects randomly allocated to SLIT and 992 to a placebo control. All studies reported an improvement in symptoms with SLIT, with five reaching statistical significance (p <0.05). Four studies reported statistically significant improvement in quality of life (p <0.05). Oral pruritus was the most common adverse event reported. The overall risk of bias was high in 50% of the studies.

SLIT was a safe and effective treatment for grass pollen-induced AR in adults and therefore consideration should be given to its use for moderate-to-severe disease in the UK wide population.

A good compliance often attributes to good efficacy and safety of sublingual immunotherapy (SLIT). However, few studies have been conducted on the safety of SLIT treatment in children. We aimed to confirm the pretreatment parameters to predict the safety in children who underwent SLIT. 601 children with allergic rhinitis (AR) treated with SLIT were enrolled in this study. Baseline clinical information and laboratory parameters were collected. The clinical response and adverse events (AEs) were recorded and evaluated. A multivariate logistic regression model was established to confirm the predictors for AEs. The AEs were reported in 75 children (13.8%). The serum-specific IgE (s-IgE) level was significantly correlated with the occurrence of AEs by multivariate logistic regression analysis. Our receiver operating characteristic (ROC) analysis of the serum s-IgE levels >21.6 IU/mL had the best sensitivity (83.7%) and specificity (76.7%) to predict safety. The serum s-IgE level was significantly correlated with safety of SLIT in children, which may be helpful for patient selection before SLIT.

The introduction of personalized medicine (PM) has been a milestone in the history of medical therapy, because it has revolutionized the previous approach of treating the disease with that of treating the patient. It is known today that diseases can occur in different genetic variants, making specific treatments of proven efficacy necessary for a given endotype. Allergic diseases are particularly suitable for PM, because they meet the therapeutic success requirements, including a known molecular mechanism of the disease, a diagnostic tool for such disease, and a treatment blocking the mechanism. The stakes of PM in allergic patients are molecular diagnostics, to detect specific IgE to single allergen molecules and to distinguish the causative molecules from those merely cross-reactive, pursuit of patient’s treatable traits addressing genetic, phenotypic and psychosocial features, and omics, such as proteomics, epi-genomics, metabolomics and breathomics, to forecast patient’s responsiveness to therapies, to detect biomarker and mediators, and verify the disease control. This new approach has already improved the precision of allergy diagnosis and is likely to significantly increase, through the higher performance achieved with the personalized treatment, the effectiveness of allergen immunotherapy by enhancing its already known and unique characteristics of treatment that acts on the causes.

Modern health care requires a proactive and individualized response to diseases, combining precision diagnosis and personalized treatment. Accordingly, the approach to patients with allergic diseases encompasses novel developments in the area of personalized medicine, disease phenotyping and endotyping, and the development and application of reliable biomarkers. A detailed clinical history and physical examination followed by the detection of IgE immunoreactivity against specific allergens still represents the state of the art. However, nowadays, further emphasis focuses on the optimization of diagnostic and therapeutic standards and a large number of studies have been investigating the biomarkers of allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, food allergy, urticaria and anaphylaxis. Various biomarkers have been developed by omics technologies, some of which lead to a better classification of distinct phenotypes or endotypes. The introduction of biologicals to clinical practice increases the need for biomarkers for patient selection, prediction of outcomes and monitoring, to allow for an adequate choice of the duration of these costly and long-lasting therapies. Escalating healthcare costs together with questions about the efficacy of the current management of allergic diseases require further development of a biomarker-driven approach. Here, we review biomarkers in diagnosis and treatment of asthma, atopic dermatitis, allergic rhinitis, viral infections, chronic rhinosinusitis, food allergy, drug hypersensitivity and allergen immunotherapy with a special emphasis on specific IgE, the microbiome and the epithelial barrier. In addition, EAACI guidelines on biologicals are discussed within the perspective of biomarkers.

Asthma is one of the most common childhood chronic diseases worldwide. Subcutaneous immunotherapy (SCIT) is commonly used in the treatment of house dust mite (HDM)‑related asthma in children. However, the therapeutic mechanism of SCIT in asthma remains unclear. The present study aimed to investigate the molecular biomarkers associated with HDM‑related asthma in asthmatic children prior and subsequent to SCIT treatment compared with those in healthy children via proteomic analysis. The study included a control group (30 healthy children), ‑Treatment group (30 children with HDM‑related allergic asthma) and +Treatment group (30 children with HDM‑related allergic asthma treated with SCIT). An isobaric labeling with relative and absolute quantification‑based method was used to analyze serum proteome changes to detect differentially expressed proteins, while functional enrichment and protein‑protein interaction network analysis were used to select candidate biomarkers. A total of 72 differentially expressed proteins were detected in the ‑Treatment, +Treatment and control groups. A total of 33 and 57 differentially expressed proteins were observed in the ‑Treatment vs. control and +Treatment vs. control groups, respectively. Through bioinformatics analysis, 5 candidate proteins [keratin 1 (KRT1), apolipoprotein B (APOB), fibronectin 1, antithrombin III (SERPINC1) and α‑1‑antitrypsin (SERPINA1)] were selected for validation by western blotting; among them, 4 proteins (KRT1, APOB, SERPINC1 and SERPINA1) showed robust reproducibility in asthma and control samples. This study illustrated the changes in proteome regulation following SCIT treatment for asthma. The 4 identified proteins may serve as potential biomarkers prior and subsequent to SCIT treatment, and help elucidate the molecular regulation mechanisms of SCIT to treat HDM‑related asthma.

Allergen-specific immunotherapy (AIT) is the mainstay treatment for the cure of allergic disorders, with depicted efficacy and safety by several trials and meta-analysis. AIT impressively contributes to the management of allergic rhinitis, asthma and venom allergies. Food allergy is a new arena for AIT with promising results, especially via novel administration routes. Cell subsets with regulatory capacities are induced during AIT. IL-10 and transforming growth factor (TGF)-β are the main suppressor cytokines, in addition to surface molecules such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1) within the micro milieu. Modified T- and B-cell responses and antibody isotypes, increased activity thresholds for eosinophils, basophils and mast cells and consequent limitation of inflammatory cascades altogether induce and maintain a state of sustained allergen-specific unresponsiveness. Established tolerance is reflected into the clinical perspectives as improvement of allergy symptoms together with reduced medication requirements and evolved disease severity. Long treatment durations, costs, reduced patient compliance and risk of severe, even life-threatening adverse reactions during treatment stand as major limiting factors for AIT. By development of purified non-allergenic, highly-immunogenic modified allergen extracts, and combinational usage of them with novel adjuvant molecules via new routes may shorten treatment durations and possibly reduce these drawbacks. AIT is the best model for custom-tailored therapy of allergic disorders. Better characterization of disease endotypes, definition of specific biomarkers for diagnosis and therapy follow-up, as well as precision medicine approaches may further contribute to success of AIT in management of allergic disorders.