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Background: The effect of prolonged allergen immunotherapy is still insufficiently known, especially in elderly patients. Objective: The effect after a 3-year course of injected allergen-specific immunotherapy (AIT) for grass pollen allergy in elderly patients with allergic rhinitis was observed. Methods: Thirty-eight elderly patients (mean ± standard deviation, 66.2 ± 2.7 years old) who received preseasonal injected AIT or placebo for grass pollen allergy were monitored for 3 years and compared with a placebo group. The combined symptom medication score (CSMS), serum level of immunoglobulin G4 (IgG4) to phleum pratense 5 (Phl p5) and quality of life were assessed immediately after AIT and 3 years later. Results: After AIT, the CSMS was significantly decreased from 2.15 (range, 1.27-3.00) to 1.13 (range, 0.79-1.36) (p = 0.03) and remained lower (1.41 ± 0.72 versus 2.41 ± 1.11) than that in the placebo group during the 3 years after AIT. Serum-specific IgG4 against increased during the course of AIT and remained at a high level during further observation. Quality of life, based on the Rhinoconjunctivitis Quality of Life Questionnaire, was significantly decreased in the patients who received AIT from 1.51 (95% confidence interval [CI], 1.21-1.84) to 1.01 (95% CI, 0.93-1.87) (p < 0.05) and was decreased to 0.97-1.26 (95% CI, 0.88-1.82) during the 3 years after discontinuation of AIT. Conclusion: A prolonged positive effect after AIT for grass pollen allergy was observed in elderly patients with allergic rhinitis. Further trials are needed to confirm this effect.Clinical trial MC56871/12, www.clinicaltrials.gov.

Introduction : 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. Areas covered : 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. Expert opinion : 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.

Purpose of Review: The impact of new technologies, especially multiplexed molecular allergy diagnostics based on allergen arrays, on the management of complex patients with respiratory allergies has been important., Recent Findings: Currently, the detailed characteristics of the IgE profile of the patient, such as sensitization to genuine or cross-reacting components or the sensitization to potentially harmful allergens, allow an allergist to tailor treatment in the context of precision medicine rules. A number of relevant articles have been published in recent years on this topic, and, in this review, the new added values of allergen array-based diagnostics are reported.

Purpose of Review: In this review, we sought to outline many of the recent evidences about the available clinical trials in which biologic agents [i.e. omalizumab (OMA)] were associated as add-on to allergen-specific immunotherapy (AIT)., Recent Findings: The available literature shows that OMA may be a valuable option as add-on to AIT for respiratory allergy, or food desensitization, especially in the escalation or build-up phases, in which adverse events are more commonly expected. The encouraging data for hymenoptera venom allergy remain limited to case reports, and no structured clinical trial is available., Summary: Over the past decade, studies of OMA used with AIT have shown promising results. Today, big randomized, double-blind, placebo-controlled trials are needed to better select those patients who would benefit from the addition of OMA (or other biologic agents) to AIT, as well as optimal dosing schedules, optimal duration of treatments and, finally, adequate evaluation about pharmacoeconomic aspects.

Background: Large sample sizes are needed for sublingual immunotherapy (SLIT) trials because of inherent data variability secondary to inconsistent allergen exposure. Obtaining large sample sizes for pediatric SLIT trials is challenging, but a Bayesian approach using prior adult data can reduce the necessary sample size., Objective: We sought to describe how a Bayesian framework using prior information from adult trials can be used to improve pediatric SLIT clinical development., Methods: Data were compiled by using a frequentist approach (conventional clinical trial approach independent of prior data) from trials conducted during the clinical development of timothy grass SLIT-tablets., Results: The treatment effect of timothy grass SLIT-tablets was considered similar between pediatric (n = 795) and adult (n = 2299) data pools, with relative total combined symptom plus medication score improvement versus placebo of 21% (95% CI, 11.0% to 30.4%) and 20% (95% CI, 14.6% to 24.4%), respectively. Phleum pratense-specific IgG 4 and IgE-blocking factor increased from baseline in both children and adults treated with timothy grass SLIT-tablets. Given the reasonable assumption in similarity of treatment response between adults and children, a Bayesian approach is described to demonstrate rigorous efficacy criteria for pediatric trials incorporating information from prior adult trials and thereby reduce the sample size., Conclusions: Data support the similarity of efficacy and immunologic changes between children and adults treated with SLIT for allergic rhinoconjunctivitis. Therefore it is appropriate to use data from adult trials to design feasible trials in children, which might reduce unsafe off-label use by promoting more quickly proper labeling of approved products., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: 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., Data Sources: PubMed and Scopus., Study Selections: The most recent and clinically relevant literature was selected and reviewed., Results: 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., Conclusion: This condensed and updated review shows that AIT remains a viable treatment option, especially after the introduction of standardized tablets for some allergens. Food allergy and new administration routes represent a promising expansion., (Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Field clinical trials of pollen allergy are affected by the impossibility of predicting and determining individual allergen exposure because of many factors (eg, pollen season, atmospheric variations, pollutants, and lifestyles). Environmental exposure chambers, delivering a fixed amount of allergen in a controlled environmental setting, can overcome these limitations. Environmental exposure chambers are currently already used in phase 2, 3, and even 4 trials. Unfortunately, few chambers exist in the world, and this makes it difficult to perform large, multicenter clinical trials. The new Global Allergy and Asthma European Network (GA 2 LEN) mobile exposure chamber is a step forward because the mobility of the chamber makes it convenient for patients to participate in clinical testing., Objective: This study was made to validate the reproducibility, sensitivity, and specificity of the results obtained in the new GA 2 LEN chamber., Methods: Seventy-two adult patients (19-61 years old) with allergic rhinitis with or without asthma caused by grass pollen were included in different clinical validation tests. Total symptom scores and total nasal symptom scores were recorded at time zero (0) and every 10 minutes during exposures, along with nasal and respiratory parameters., Results: Exposure tests confirmed the reproducibility between subsequent runs and the sensitivity (P < .00001 vs patients exposed to placebo) and specificity (very low score in nonallergic subjects) in the GA 2 LEN chamber. No adverse reactions were recorded during the tests., Conclusions: The mobility of the GA 2 LEN chamber provides a new, potentially effective, and safe way of generating reliable data in allergy multicenter clinical trials., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Sublingual immunotherapy (SLIT) is increasingly used worldwide, and several products have been recently registered as drugs for respiratory allergy by the European Medicine Agency and the Food and Drug Administration. Concerning inhalant allergens, the safety of SLIT is overall superior to that of subcutaneous immunotherapy in terms of systemic adverse events. No fatality has been ever reported, and episodes of anaphylaxis were described only exceptionally. Looking at the historical and recent trials, most (>90%) adverse events are "local" and confined to the site of administration. For this reason, a specific grading system has been developed by the World Allergy Organization to classify and describe local adverse events. There is an increasing amount of literature concerning oral desensitization for food allergens, referred to as oral immunotherapy. Also, in this case, local side effects are predominant, although systemic adverse events are more frequent than with inhalant allergens. We review herein the description of local side effects due to SLIT, with a special focus on large trials having a declared sample size calculation. The use of the Medical Dictionary for Regulatory Activities nomenclature for adverse events is mentioned in this context, as recommended by regulatory agencies. It is expected that a uniform classification/grading of local adverse events will improve and harmonize the surveillance and reporting on the safety of SLIT., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Allergen-specific immunotherapy (AIT) is considered the only treatment capable of modifying the natural history of allergic respiratory disorders. The possible adverse events related to AIT have, until now, limited its use to mild and controlled asthma. The pre-administration or concomitant treatment of AIT and omalizumab (an anti-IgE humanized antibody), recommended for the treatment of severe allergic asthma, could be useful in reducing the adverse events due to AIT and to allow its use in patients with more severe or uncontrolled asthma. AIT/omalizumab combination has been explored in a few trials on asthma patients and also in other allergic disorders, such as rhinitis, hymenoptera systemic reaction and food allergy with significant results. We are at the beginning a new era where phenotype/endotype-based treatment will be associated with drug mass therapy and/or nonpharmacological phenotype/endotype-driven treatment to optimize disease control and/or to make the use of other treatments safer.

Fatal reactions related to subcutaneous allergen immunotherapy are rare: one event in 2.5 million injections has been reported in the USA and none in Europe. The prevalence of very severe systemic reactions (systemic adverse events [SAEs]) is one in 1 million injections. Though the serious events rate is decreasing and the majority of SAEs (∼0.2% per injection) are moderate and reversible, they still represent a major concern. Uncontrolled asthma, long-term therapy with β-blockers and high degree of allergen sensitivity are generally considered risk factors. The relevance of other conditions, like previous local reactions, the use of extracts conjugated with adjuvants and accelerated build-up schedules is controversial, as well as the role of preventative strategies. A careful risk assessment of patients and optimal administration procedures may significantly decrease the risk of SAEs. However, more uniform safety data are required and an accurate safety profile should be provided for every allergen product.

The efficacy of allergen immunotherapy (AIT) is well supported by evidence from trials and meta-analyses. However, its actual performance in daily practice may be diminished by several pitfalls, including inappropriate patient selection, and, especially, the use of allergen extracts of insufficient quality. We performed a survey, the Allergen Immunotherapy Decision Analysis, to evaluate which criteria specialists use to choose products for sublingual immunotherapy (SLIT) in adult patients suffering from allergic respiratory disease. We surveyed a total of 169 Italian allergists randomly chosen from a database belonging to a market research company (Lexis Ricerche, Milan, Italy). The survey was performed between October and November 2012 under the aegis of the European Center for Allergy Research Foundation and consisted of a questionnaire-based electronic survey prepared by a scientific board of 12 AIT experts. The questionnaire comprised two parts, the first of which contained 14 items to be ranked by each participant according to the importance assigned to each when choosing SLIT products. The physicians' rankings assigned major importance to the level of evidence-based validation of efficacy and safety, standardization of the product, efficacy based on personal experience, and defined content(s) of the major allergen(s) in micrograms. The results of this survey show that Italian allergists rank the quality-related characteristics of allergen extracts as highly important when choosing products for AIT. The allergists' preference for high-quality products should be addressed by regulatory agencies and by producers.

The practice of administering sublingual immunotherapy for respiratory allergy is gaining more and more diffusion worldwide as a consequence of the robust demonstration of clinical efficacy and safety provided by recent high-powered and well-designed studies, confirming for individual seasonal allergens the results of previous metanalyses in adult and pediatric populations. Preliminary evidence derives from recent rigorous trials on perennial allergens, like house dust mites, and specifically designed studies addressed the benefits on asthma. Emerging research suggests that SLIT may have a future role in other allergic conditions such as atopic dermatitis, food, latex and venom allergy. Efforts to develop a safer and more effective SLIT for inhalant allergens have led to the development of allergoids, recombinant allergens and formulations with adjuvants and substances targeting antigens to dendritic cells that possess a crucial role in initiating immune responses. The high degree of variation in the evaluation of clinical effects and immunological changes requires further studies to identify the candidate patients to SLIT and biomarkers of short and long term efficacy. Appropriate management strategies are urgently needed to overcome the barriers to SLIT compliance.

Purpose of Review: The aim of this review is to update readers on the growing impact of a molecular approach (CRD) to the diagnosis and treatment of children with respiratory allergies, Recent Findings: A large panel of highly purified natural or recombinant species-specific and cross-reacting allergenic molecules is now available for clinical purposes. Species-specific molecules allow identifying specific sensitization toward a given allergenic source. Cross-reacting molecules allow interpreting polysensitization patterns that cannot be detailed using routine skin prick tests or specific IgE tests based on allergenic extracts. These molecular tools are transforming and improving the interpretation of clinical and laboratory tests used to define patients' IgE-sensitization profile., Summary: The accurate dissection of the IgE repertoire offers new possibilities in the diagnosis, prophylaxis and treatment of pediatric allergic rhinoconjunctivitis and asthma.

Atopic asthma in childhood with the tendency to persist into adult life is an important issue in pediatrics. Allergen-specific immunotherapy (SIT) is the only curative treatment option for these children, being directed to the causes of the disease. The Th2 phenotype is a predominant immunological pattern in atopic asthma and SIT leads to apoptosis/anergy of T cells and induces immune-regulatory responses and immune deviation towards Th1. Many factors can affect the safety and efficacy of SIT, such as pattern of sensitization, allergy vaccine (allergen extracts, adjuvants and conjugated molecules), route of administration (subcutaneous or sublingual) and different treatment schedules. Overall, asthma symptoms and medication scores usually decrease following a SIT course and the most common observed side effects are restricted to local swelling, erythema and pruritus. Compared with conventional pharmacotherapy, SIT may be more cost effective, providing a benefit after discontinuation and a steroid-sparing effect. In addition, it can prevent new sensitizations in monosensitized asthmatic children. Microbial supplements such as probiotics, immunomodulatory substances like anti-IgE/leukotrienes, antibodies and newer allergen preparations such as recombinant forms have been tested to improve the efficacy and safety of SIT with inconclusive results. In conclusion, SIT provides an appropriate solution for childhood asthma that should be employed more often in clinical practice. Further studies are awaited to improve current knowledge regarding the mechanisms behind SIT and determine the most appropriate materials and schedule of immunotherapy for children with asthma.

Immunotherapy was introduced 100 years ago and still is the only treatment that modifies the course of allergic diseases. The success of its use depends on correct indications, use of standardized extracts and monitoring the therapeutic response., (© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.)

Purpose of Review: To evaluate the relevance of results obtained using allergen microarray technique for the description of the IgE repertoire in allergic patients., Recent Findings: Allergen microarray was introduced at the beginning of the last decade. Since then, an increasing number of allergens have been identified, correspondingly increasing the accuracy of the description of immunoglobulin (Ig)E repertoire. In the last 2 years, a large number of articles were published that accurately described not only the general features of this technique, but also the use of allergen microarray in specific situations., Summary: The recent availability of highly purified or recombinant allergen components has deeply modified the laboratory approach to allergy diagnosis that, now, it cannot be limited to the detection of IgE specific to extractive allergens. Indeed, these contain both specific components (i.e. molecules strictly associated to that allergen source) and pan-allergen or cross-reacting allergens (i.e. molecules that are present in different similar allergen sources or that are present in highly homologous structures in different species). Newer techniques such as recombinant allergen testing and allergen microarray allow a more detailed evaluation of IgE responses. Future research is needed to more clearly define their role in clinical practice.

Purpose of Review: To update and assess the quality of the evidence concerning the efficacy of allergen immunotherapy for atopic eczema. Desensitization for eczema as a clinical manifestation of food allergy was not a target of this review., Recent Findings: In the past 5 years, from the last comprehensive systematic review of Bussmann et al., four controlled trials have been published on this topic, two using injection and two sublingual immunotherapy. The active treatment was compared with placebo, pharmacotherapy or different schedules of immunotherapy. The studies variably involved adults and children and showed an improvement of atopic dermatitis severity. Severe eczema seems less responsive to hyposensitization, and a minimal treatment duration of 9-12 months appears necessary., Summary: The efficacy of immunotherapy in patients with atopic eczema has been poorly investigated in the past 5 years. The available trials have small dimension and some methodological shortcomings, in addition to incomplete reporting. Clinical and methodological interstudy heterogeneity is apparent. Only one study adopted a placebo control. The evidence of efficacy has not critically changed from previous systematic observations. No long-term studies have been conducted to determine the disease-modifying potential of specific immunotherapy in the context of the 'allergy march'.

Background: It is well known that allergy evolves at clinical level from the birth to adulthood, and this has been clearly demonstrated also at a level of sensitization. However, little information is available on the evolution of the IgE repertoire directed to single allergenic components. In this cross-sectional, observational study, the evolution of the IgE repertoire was analysed at component level., Methods: Serum samples from 901 allergic patients, stratified in 6 groups according to age, were analysed by ImmunoCAP ISAC, a microarray chip that allows to identify the presence of specific IgE towards 103 different allergen components. Total IgE were also evaluated., Results: The behaviour of total IgE according to age strictly paralleled that of the sum of specific IgE directed to molecular components. As expected, food-related components (in particular those of milk and egg) were the most frequently recognized in the earliest ages, whereas specific IgE to plant allergens appeared invariably later. Nonetheless, IgE specific to mite components was the most represented in all age classes. Of note, specific IgE against cross-reacting allergens was virtually absent in the first years and tended to appear only after the age of 6., Conclusion: Despite this was not a study performed on a cohort of patients followed up from birth to adolescence, the molecular patterns of allergen recognition resulted modified according to age. These findings may support, at molecular level, the clinical features of the allergic march., (© 2012 John Wiley & Sons A/S.)

Purpose of Review: The aim of this review is to describe the relationships between allergy and infectious diseases, with specific attention on bacterial infection. According to the most recent literature, bacteria could be considered also as one of the major causes of asthma exacerbations that we need to further explore., Recent Findings: The availability of novel methods to detect large panels of pathogens, including viruses and bacteria specific for the upper respiratory tract, together with the capacity of evaluating how basophils are activated, has changed the point of view of the mechanisms related to asthma exacerbations. The recent finding that basophils are activated in the presence of suboptimal doses of allergens and bacteria has been recently described and may explain the clinical behavior of allergy exacerbation. Indeed the activation of basophils induces the secretion of mediators, which, at bronchial level, may cause bronchospasm that leads to an asthma exacerbation in patients with infection. The contrary is also true., Summary: Although the explanations for these facts are numerous, at present, bacteria seem to play a relevant role in the worsening of asthma in infected patients.

Background: The airways and the upper digestive tract have a common embryonic origin. In sensitized subjects they can respond to allergens with an immediate reaction (asthma, rhinitis, or oral allergy syndrome [OAS])., Objective: To investigate the possible functional connection between respiratory and upper digestive tract by means of specific oral allergen challenges., Methods: Patients sensitized to birch and apple were subdivided into group A (n = 12; asthma + rhinitis caused by birch and OAS caused by apple); group B (n = 10; OAS caused by apple without asthma/rhinitis); group C (n = 8; asthma and rhinitis caused by birch without OAS). Healthy subjects represented the control group D (n = 6). Oral provocation test with apple was performed out of the pollen season. Visual analog scale for eye, nose, and mouth symptoms, spirometry, nasal eosinophil count, and exhaled nitric oxide were assessed before and 6 hours after challenge., Results: No change occurred in nasal and ocular symptoms before versus after challenge in all groups. On the contrary, in groups A and B the oral scores significantly increased after challenge (P < .001), whereas no change was seen in groups C and D. Exhaled nitric oxide and nasal eosinophils showed no change before versus after challenge in all groups. Nitric oxide was higher before and after challenge in groups A and C vs groups B and D. No change was seen in either forced vital capacity or forced expiratory volume in 1 second., Conclusion: In the case of birch-apple syndrome, eating apple does not functionally or clinically affect the respiratory tract., (Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the performances of an allergen microarray in multi-sensitized allergic patients with respiratory symptoms., Design and Methods: 321 patients and 92 controls were included in this study. Specific serum IgE were assayed using ImmunoCAP ISAC, a microarray containing 103 components derived from 47 allergens and results were compared with extract-based ImmunoCAP Allergens sIgE to 15 common airborne allergens., Results: The reproducibility of ISAC was good. The Positive Percent Agreement (PPA) varied between 75% and 100% for sIgE levels above 1 kUA/l. For samples with sIgE levels below 0.1 kUA/l, the Negative Percent Agreement (NPA) ranged between 90% and 100%. Notably, 58% of respiratory allergy patients had IgE to food-specific proteins and 52% resulted sensitized to cross-reactive pan-allergens., Conclusion: ImmunoCAP ISAC detects allergen sensitization at component level and adds important information by defining both cross and co-sensitization to a large variety of allergen molecules., (Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Allergic ocular symptoms, although frequently trivialised, are common and represent an important comorbidity of allergic rhinitis. Sublingual Immunotherapy (SLIT) is an effective and well-tolerated treatment for allergic rhinitis, but its effects on symptoms of ocular allergy have not been well established., Objectives: To evaluate the efficacy of SLIT compared with placebo for reductions in ocular symptoms, topical ocular medication requirements and conjunctival immediate allergen sensitivity., Search Strategy: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 1), MEDLINE (January 1950 to January 2011), EMBASE (January 1980 to January 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2011), Web of Science (January 1970 to January 2011), Biosis Previews, (January 1979 to January 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (January 2011), ClinicalTrials.gov (www.clinicaltrials.gov) (January 2011), the Australian New Zealand Clinical Trials Registry (ANZCTR) (www.actr.org.au) (July 2010), SCOPUS (November 2008) and the UK Clinical Trials Gateway (January 2010). There were no language or date restrictions in the search for trials. All electronic databases except for SCOPUS, the UK Clinical Trials Gateway and ANZCTR were last searched on 19 January 2011., Selection Criteria: Randomised controlled trials (RCTs), double-masked and placebo controlled, which evaluated the efficacy of SLIT in patients with symptoms of allergic rhinoconjunctivitis (ARC) or allergic conjunctivitis (AC)., Data Collection and Analysis: The primary outcome was the total ocular symptom scores. Secondary endpoints included individual ocular symptom scores (such as itchy eyes, red eyes, watery eyes, swollen eyes), ocular medication scores (eye drops) and conjunctival immediate allergen sensitivity (CIAS). Data were analysed and reported as standardised mean differences (SMDs) using Review Manager software., Main Results: Forty-two trials (n = 3958 total participants; n= 2011 SLIT and n = 1947 placebo) had available data to evaluate the efficacy of SLIT on AC and were included in the meta-analyses. Heterogeneity among studies (I(2) statistic) was around 50% or below for all endpoints. Sublingual immunotherapy induced a significant reduction in both total ocular symptom scores (SMD -0.41; 95% confidence interval (CI) -0.53 to -0.28; P < 0.00001; I(2) = 59%) and individual ocular symptom scores for red eyes (SMD -0.33; 95% CI -0.45 to -0.22; P < 0.00001; I(2) = 27%), itchy eyes (SMD -0.31; 95% CI -0.42 to -0.20; P < 0.00001; I(2) = 46%) and watery eyes (SMD -0.23; 95% CI -0.34 to -0.11; P < 0.0001; I(2) = 42%) compared to placebo. Those participants having active treatment showed an increase in the threshold dose for the conjunctival allergen provocation test (SMD 0.35; 95% CI 0.00 to 0.69; P = 0.05; I(2) = 43%). No significant reduction was observed in ocular eye drops use (SMD -0.10; 95% CI -0.22 to 0.03; P = 0.13; I(2) = 34%)., Authors' Conclusions: Overall, SLIT is moderately effective in reducing total and individual ocular symptom scores in participants with ARC and AC. There were however some concerns about the overall quality of the evidence-base, this relating to inadequate descriptions of allocation concealment in some studies, statistical heterogeneity and the possibility of publication bias. There is a need for further large rigorously designed studies that study long-term effectiveness after discontinuation of treatment and establish the cost-effectiveness of SLIT.

Subcutaneous immunotherapy (SCIT) is effective and safe when properly prescribed and administered. However, a certain risk of severe side effects exists, even when the reaction is managed correctly. These potential adverse effects stimulated the search for new administration routes (nasal, bronchial, oral, sublingual), which were expected to be safer. Not all of these alternative routes provided an improved benefit-safety profile compared with SCIT. The sublingual route (SLIT) seemed to be a good candidate for the clinical practice because of its satisfactory safety profile and is now considered an acceptable alternative to SCIT in adults and children., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose of Review: Sublingual immunotherapy (SLIT) has progressively gained credibility. Randomized double-blind placebo-controlled trials, meta-analyses and mechanistic studies have accumulated rapidly in the last years. We will review herein a brief history of SLIT, its indications and the safety aspects and will discuss the main unmet needs and the points to be developed in the field., Recent Findings: During the last year, new information on SLIT has become available, mainly from the so-called big trials, and some important aspects have been partially clarified. In addition, the possible indications to SLIT began to be expanded., Summary: The dose dependency of the efficacy of SLIT and the optimal maintenance dose have been identified at least for grass allergens. The safety is well demonstrated in both adults and children.

Background: Grass pollen is a worldwide cause of respiratory allergy. Identifying the causative species is essential, for example for choosing the appropriate immunotherapy, because not all grass allergens are totally cross-reacting, and the pollen calendars provide only a gross estimate. Phenologic analyses allow identification of the pollen release for each individual grass., Objectives: To assess, using phenologic analyses, the true flowering periods of grasses and to compare the data with the standard pollen calendar., Methods: Phenologic analyses were performed of the following grasses: black grass, sweet vernal grass, common wild oat, barren brome, cocksfoot, tall fescue, Yorkshire fog, ryegrass, Timothy grass, bulbous meadow-grass, Kentucky bluegrass, and Bermuda grass. Sampling was performed every 10 days, starting in April 2009, at 50 stations distributed across Italy. The flowering phase was assessed using a stereomicroscopy-based method for the detection of spreading stamens. The official pollen calendar was used for comparison., Results: Relevant differences were found between grass pollen count and effective flowering of the grass species. Only some species contributed to the pollen peak, and a relevant pollen load for other species was also present out of the peak. Important Pooideae, such as Timothy grass, were not present during the pollen peak in northern and central Italy, and the same occurred with Bermuda grass., Conclusions: The various species of grasses release their pollen grains at different times during the pollen season, and this information is missing with pollen calendars. This may have a relevant effect on the choice of an appropriate immunotherapy., (Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy of allergen specific immunotherapy in the treatment of allergic asthma and rhinitis as derived by the available meta-analyses., Data Sources: Electronic databases were searched up to April 30, 2008, for meta-analyses of randomized, placebo-controlled trials assessing specific immunotherapy in respiratory allergy. We looked for studies that evaluated effects on symptom scores and use of rescue medication., Study Selection: If 2 or more reviews evaluated the same subject, we selected the study with the larger number of patients. We evaluated the quality of individual meta-analyses by following the recommendations of the Cochrane Collaboration and the QUOROM (Quality of Reporting of Meta-analyses) statement., Results: Seven of 13 meta-analyses met the inclusion criteria: 5 evaluating sublingual immunotherapy and 2 evaluating subcutaneous immunotherapy. All 7 meta-analyses reported a reduction in symptom and medication scores, although 1 sublingual immunotherapy meta-analysis did not find a significant size effect, probably because of the inclusion criteria. Heterogeneity was significant in all 7 included reviews, and standardized mean differences using the random-effects model were adopted., Conclusions: According to evidence-based criteria, specific immunotherapy can be recommended for the treatment of respiratory allergy because of its efficacy in reducing asthma and rhinitis symptoms. Also, future methodological approaches that consider safety and costs should corroborate this positive evaluation.

Background: Recent studies have documented the efficacy and safety of sublingual immunotherapy (SLIT) in patients with rhinitis, but the value of this treatment in those with asthma is still debated. We evaluated the efficacy of SLIT in the treatment of allergic asthma in children by a metaanalysis of randomized, double-blind, and placebo-controlled (DBPC) clinical trials., Methods: Electronic databases were searched up to May 31, 2006, for randomized DBPC trials assessing SLIT in pediatric cases of asthma. Effects on primary outcomes (ie, symptom scores and concomitant use of rescue medication) were calculated with standardized mean differences (SMDs) using the random-effects model. We performed the metaanalysis using a statistical software package (RevMan, 4.2.8; The Cochrane Collaboration; Oxford, UK), and we followed the recommendations of the Cochrane Collaboration and the Quality of Reporting of Metaanalyses guidelines., Results: Seventy-three articles were identified and reviewed. Nine studies, all published after 1990, fulfilled the selection criteria. A total of 441 patients had a final assessment and were included in the analysis. Two hundred thirty-two patients received SLIT, and 209 patients received placebo. The results of the present analysis demonstrated a relevant heterogeneity due to widely differing scoring systems. Overall, there was a significant reduction in both symptoms (SMD - 1.14; 95% confidence interval [CI], - 2.10 to - 0.18; p = 0.02) and medication use (SMD, - 1.63; 95% CI, - 2.83 to - 0.44; p = 0.007) following SLIT., Conclusion: SLIT with standardized extracts reduces both symptom scores and rescue medication use in children with allergic asthma compared with placebo.

Sublingual immunotherapy (SLIT) was proposed for clinical practice about 20 years ago with the main aim of improving the safety and of avoiding the side effects. More than 30 randomized controlled trials have been published so far, in addition to several post marketing surveys. Thus, the literature provides a solid documentation of the safety profile of this treatment. Concerning the randomized controlled trials, the more frequently reported side effect of SLIT is the oral itching or swelling, followed by gastrointestinal complaints. These side effects are invariantly described as mild and easily managed by temporarily adjusting the dose. Systemic relevant adverse events (asthma, urticaria, angioedema) occur sporadically, with their rate not being different from the placebo groups. Moreover, the safety profile seems not to differ in adults and children. More interestingly, the post marketing surveys consistently showed that the occurrence of all side effects is less than 20% of patients and less than 1 per 1,000 doses, thus being quite insignificant compared to subcutaneous immunotherapy. The most recent surveys showed that the rate of adverse events does not increase in children below the age of 5 years, being traditionally considered as a prudential limit for injection IT. Finally, it seems that the occurrence of some adverse events, at variance with injection route, does not depend strictly on the dose of allergen administered.

Purpose of Review: Sublingual immunotherapy is currently accepted as a viable therapeutic option, and is widely used in many European countries. In the past 2 years, new data concerning clinical, immunological and practical aspects of sublingual immunotherapy have been published, and many critical points have been addressed., Recent Findings: In addition to the new data on clinical efficacy, the most recent studies have shown that, similar to the injection route, sublingual immunotherapy can also prevent the onset of new sensitizations and the onset of asthma. Moreover, several postmarketing surveys have confirmed the satisfactory safety profile, even in very young children, and compliance has been measured. The good safety profile has also suggested the possibility of using sublingual immunotherapy without the updosing phase. Finally, the mechanisms of action have been systematically investigated and the biodistribution of sublingual allergens has been further clarified., Summary: More new data on sublingual immunotherapy are rapidly appearing in the international literature. These data consistently confirm the value of this treatment and show that sublingual immunotherapy is a viable and useful form of immunotherapy.

Objective: To evaluate the efficacy of sublingual immunotherapy (SLIT) in the treatment of allergic rhinitis in children., Data Sources: A comprehensive search of the EMBASE, MEDLINE, LILACS, and CINAHL databases from January 1966 to February 10, 2006, was performed., Study Selection: Randomized, double-blind, placebo-controlled trials of SLIT in the treatment of allergic rhinitis in patients 18 years or younger were selected. Outcomes measured were symptom scores and rescue medication use. Analysis was performed with standardized mean differences (SMDs) and a random-effects model., Results: Seventy articles were identified and reviewed. Ten studies, published between 1990 and 2004, fulfilled the selection criteria. Five hundred seventy-seven patients were initially included in the studies. Of these patients, 484 (245 SLIT and 239 placebo) had a final clinical evaluation and could be evaluated. A relevant heterogeneity due to widely differing scoring systems was found. Overall, there was a significant reduction in both symptoms (SMD, 0.56, 95% confidence interval, 1.01-0.10; P = .02) and medication use (SMD, 0.76; 95% confidence interval, 1.46-0.06; P = .03) after immunotherapy. The subanalyses performed for treatment duration and type of allergen showed that SLIT for more than 18 months and with pollen extracts was effective compared with SLIT courses shorter than 18 months and with mites., Conclusion: The results of this meta-analysis showed that,compared with placebo, SLIT with standardized extracts is effective in pediatric patients with allergic rhinitis.

Background: Due to optimal safety of sublingual immunotherapy (SLIT), it was suggested that a slow up-dosing phase maybe not necessary, and therefore the treatment will be more patient-friendly, avoiding dosing mistakes., Patients: Twenty adult patients suffering allergic rhinitis due to Parietaria, were enrolled. Half of them received the traditional schedule and the other half immediately started with 200 STU., Results: No difference was observed between the traditional up-dosing treatment schedule and no-up-dosing treatment schedule in terms of side effects, even mild local side effects, even mild local side effects was greater with traditional regimen.

Allergen specific immunotherapy, together with drugs and allergen avoidance, is a cornerstone in the management of respiratory allergy. The non-injection or local routes were developed with the main goal of improving the safety and minimizing the risk of those side effects, which can accompany the injection route. The pure oral route and the bronchial route showed, in the clinical trials, only a marginal efficacy with not negligible side effects. Therefore, these routes are no longer recommended for clinical use. The nasal route proved effective and safe, but its efficacy is strictly limited to the nose. Moreover, the practical problems with administration have made the use of nasal immunotherapy progressively declining. The efficacy of the sublingual route is confirmed by numerous controlled trials, and a meta analysis (in allergic rhinitis). The safety profile, as derived from clinical trials and post marketing surveillance studies, is satisfactory, with mild gastrointestinal complaints being the more frequent side effect reported. Recent studies have also demonstrated that SLIT has a long-lasting effect and a preventive effect on the onset of new skin sensitizations, and interesting data on adherence and mechanisms of action have become recently available. Based on these experimental data, SLIT is now officially accepted as a viable alternative to the subcutaneous route in adults and children. Several points still need to be elucidated, including: mechanisms of action, optimal dosages, and indications in pediatric patients.

It is widely acknowledged that avoidance of allergens such as those derived from foods, drugs, latex and stinging insects results in a complete disappearance of symptoms. By contrast, although it has been clearly shown that allergens are an important risk factor for the development of respiratory symptoms and that several avoidance measures reduce allergen levels, whether this gives clinical improvement in symptoms is debatable. Many reasons could be invoked to justify this evident discrepancy. Apart from the intrinsic methodological aspects (e.g. single or combined interventions measure, population studied, severity of respiratory symptoms, outcomes, evaluated parameters, etc.), it is important to outline that a successful approach requires that the avoided allergen is the only and real factor responsible for symptoms, the patient's education and the use of a comprehensive protocol to reduce allergen exposure. Other important factors include the involvement of the patient, the relevance of other allergens/non-specific agents, and exposure to sensitizing agents also outside patient's home. It is likely that the clinical phase of allergic airway disease and the degree of bronchial (and also nasal) remodelling, in each individual, represent relevant factors for the clinical outcome of allergen avoidance procedures. Since the management of respiratory allergy is a complex strategy (including drugs, allergen avoidance, immunological and educational interventions), it is difficult in real life to distinguish the efficacy of a single intervention in comparison to the others. A combined strategy is likely to produce better clinical results.

Background: Presently, sublingual immunotherapy is widely used as an alternative to the injection route for respiratory allergy, but its pharmacokinetics in humans is poorly known, and data are available only for Par j 1 allergen. We aimed at assessing the biodistribution of iodine-123-radiolabelled Der p 2 in allergic volunteers., Methods: Purified Der p 2 and its monomeric allergoid were radiolabelled with iodine-123 and administered sublingually to 7 allergic volunteers. The subjects were allowed to swallow 6 min after administration. Dynamic (up to 10 min) and static scintigraphic images (30 min, 1, 2, 3 and 20 h) were recorded, and blood samples were obtained at different time points to measure the plasma radioactivity and to assess the presence of circulating radiolabelled species by gel chromatography., Results: The local pharmacokinetics did not differ between allergen and allergoid. Plasma radioactivity began to increase only after swallowing and peaked at 1-2 h. Both the allergen and the allergoid persisted in the mouth for several hours, and traces could be detectable up to 20 h. At radioactivity plasma peak, gel chromatography showed that a fraction of the allergoid, but not the allergen, was absorbed as an intact molecule., Conclusions: These results indicate that the pharmacokinetics of sublingual administration is independent of the allergen used and characterized by the long persistence in the mouth. The contribution of enteric absorption of the allergoid in the mechanism of action of sublingual immunotherapy remains to be defined., (Copyright (c) 2005 S. Karger AG, Basel.)

Background: Sublingual immunotherapy (SLIT) has been proved effective in allergic rhinitis, but there are few studies assessing its effects on inflammation and on the lower airways., Objective: We sought to evaluate at the same time the effects of SLIT on rhinitis symptoms, nasal inflammation, and lower airways function in patients with birch pollinosis., Methods: Adult patients with rhinitis and asthma monosensitized to birch were evaluated during a run-in pollen season and then randomized to receive openly either drugs alone or drugs plus SLIT and reevaluated in the subsequent 4 pollen seasons. Rhinitis symptoms and consumption of bronchodilators were assessed by means of diary card. A nasal smear for eosinophil count was carried out in and out of pollen seasons, and pulmonary function tests with methacholine challenge were performed at each season., Results: Of 79 enrolled patients, 27 dropped out, with a significantly higher rate of dropouts in the control group. There was a decrease in symptoms and bronchodilator use in the SLIT group versus the control group, becoming significant at the second and third pollen seasons, respectively ( P < .01 at all times). Nasal eosinophils decreased significantly in the active group, starting from the third pollen season ( P < .01). In the SLIT group a significant increase in FEV 1 , specific airways conductance, and maximal expiratory flow at 25% of forced vital capacity was seen starting from the second year and was associated with an increase in the methacholine threshold dose ( P < .01). The differences were significant also at the intragroup comparison over time., Conclusion: SLIT achieved a significant clinical benefit in birch pollinosis, reduced the eosinophil infiltration in nasal mucosa, and significantly improved pulmonary function during the pollen seasons.

Background: In our previous in vitro model, allergen incubation of passively sensitized human airways reduced the response to salbutamol. However, whether cytokines play a role in this model is still unknown., Objective: To investigate interleukin 1beta and tumor necrosis factor a expression in allergen-challenged human airways., Methods: Nonasthmatic airways (n = 13) were passively sensitized by overnight atopic serum incubation and then challenged with allergen for 1 hour (n = 9). After repeated washouts, airways were immersed in physiologic salt solution for 6 hours and finally in formaldehyde for immunohistochemical studies. The effect of co-incubation in anti-interleukin 1beta and anti-tumor necrosis factor a specific neutralizing antibodies on salbutamol response was also studied (n = 4)., Results: No differences were found among control, sensitized, and challenged rings in the number of inflammatory cells. The percentage of basement membrane covered by epithelium was similar in the different conditions. There was a higher percentage of degranulating to total mast cells in allergen-challenged rings than in sensitized rings (P < .001). A significant correlation was observed between allergen-induced contraction and mast cell degranulation (r = 0.88; P < .001). The sensitization procedure was validated by paired allergen-induced contractions. No expression of the 2 cytokines was detectable up to 6 hours after allergen challenge, and specific neutralizing antibodies did not attenuate the impaired response to salbutamol in allergen-challenged rings., Conclusion: These data suggest that in our in vitro model of allergic inflammation, beta2 pathway dysfunction can occur without cytokine involvement, thus supporting previous results that suggest a role for leukotrienes.

Allergen-specific immunotherapy is a well-established treatment for respiratory allergy. It is usually administered subcutaneously, and with this route several severe adverse events and fatalities have been described. Therefore, in the last 15 years, novel routes of administration (local routes) were developed. Sublingual and local nasal immunotherapy are now considered as viable alternatives to the injection route, mainly due to their optimal safety. The use of nasal immunotherapy is at present declining. On the other hand, sublingual immunotherapy was investigated in twenty-two randomized controlled trials and two postmarketing surveys: its safety profile turned out to be satisfactory in both adults and children, gastrointestinal complaints being the most frequently reported side effects. These side effects were always mild and could be treated with proper dose adjusting. At variance with injection immunotherapy, no severe systemic adverse event has ever been described. Its safety is also supported by pharmacokinetics and immunological data. Experimental data on the safety of sublingual and nasal immunotherapy will be reviewed.

Background: There is considerable interest in improving the scoring methods for evaluating the efficacy of allergen immunotherapy (AIT) and to show if this is associated with clinically meaningful results from the patient's perspective. We aimed to assess the efficacy and clinical relevance of a 300 index of reactivity (IR) 5‐grass pollen sublingual immunotherapy (SLIT) tablet in children, adolescents and adults with moderate to severe grass‐induced allergic rhinoconjunctivitis (ARC) with or without controlled asthma using the combined symptom and medication score CSMS0‐36. Methods: The data of the European population that participated in 3 Phase III, international, randomized double‐blind placebo‐controlled clinical trials were analyzed post hoc. Results: A total of 864 patients randomized to 300 IR 5‐grass tablet or placebo were analyzed. Over the primary evaluation period, the difference in CSMS0‐36 between the 300 IR and placebo groups was statistically significant (point estimates: −2.51, CI95% [−3.88; −1.14], p < 0.0001 in clinical trial1; −2.31, CI95% [−3.39; −1.23], p < 0.0001 in CT2; and −2.31, CI95% [−3.58; −1.03], p = 0.0004 in CT3). The relative differences between the 300 IR 5‐grass tablet and placebo were −29.7%, −33.8%, and −26.3%, respectively. The results based on CSMS0‐36 were consistent with those obtained with the primary endpoints of the trials and support the consideration of the 2‐point threshold of the CSMS0‐36 for clinical relevance of AIT. Conclusion: Post hoc analysis of 3 CTs with the 300 IR 5‐grass SLIT tablet confirmed its significant and clinically relevant effect in the European population with grass pollen‐induced ARC with or without controlled asthma. [ABSTRACT FROM AUTHOR]

Nonrandomized studies (NRS) on allergen immunotherapy (AIT) particularly lend themselves to evaluate outcomes that are insufficiently addressed in randomized controlled studies (RCTs). However, NRS are prone to several sources of bias, which limit their validity. We aimed at comparing AIT effects between RCTs and NRS and evaluate the reasons for discrepancies in study results. In this analysis, we compared NRS on AIT (including subcutaneous and sublingual immunotherapy, SCIT and SLIT, respectively) with SLIT and SCIT RCTs from published meta‐analyses, assessing the Risk of Bias (RoB) for each study and the certainty of evidence from NRS and RCTs using the GRADE approach. We found: (1) very serious RoB in the 7 NRS included in the meta‐analysis showing a large difference between AIT and controls (standardized mean difference [SMD] for symptom score [SS], −1.77; 95% CI, −2.30, −1.24; p <.001; I2 = 95%) with very low certainty evidence; (2) serious RoB in the 13 SCIT‐RCTs reporting a moderate‐to‐high difference between SCIT and controls (SMD for SS, −0.81; 95% CI, −1.12, −0.49; p <.001; I2 = 88%) with moderate certainty evidence; (3) low RoB in the 13 SLIT‐RCTs reporting a small benefit (SMD for SS, −0.28; 95% CI, −0.37, −0.19; p <.001; I2 = 54.2%) with high certainty evidence. Similar results were reported for medication score. Our evidence is sufficient to conclude that the magnitude of effect estimates of NRS and RCTs directly correlate with the degree of RoB and inversely with the overall evidence certainty. NRS, which are more affected than RCTs by bias resulting in low certainty evidence, showed the largest effect size. Sound NRS are needed to complement RCTs. [ABSTRACT FROM AUTHOR]

Allergen-immunotherapy (AIT) is an efficacious and disease-modifying treatment option for IgE-mediated diseases. Among these allergic rhinitis, insect venom allergy, food allergy, and allergic asthma are the most common candidates for AIT. AIT gives rise to clinical immunotolerance which may last for years after the treatment cessation. Mechanisms of AIT include suppression of allergic inflammation in target tissues and stimulation of the production of blocking antibodies, especially IgG4 and IgA. These mechanisms are followed by a reduction of underlying allergen-specific Th2 cell-driven responses to the allergens. Tolerance induction takes place through the desensitization of effector cells and stimulation of regulatory T cells that show their effects by mechanisms involving cell-cell cross-talk, but also other mechanisms, e.g., by the production of immunomodulatory cytokines such as, e.g., IL-10 and TGF-beta. From a personalized medical perspective, there is a need for clinical biomarkers of value in selecting responders and optimizing patient care during AIT. Also, a deeper understanding of underlying mechanistic processes will improve AIT's future outcomes. In this paper, the current knowledge of mechanisms in AIT is reviewed with a special focus on biomarkers of this therapy. [ABSTRACT FROM AUTHOR]

Background: Molecular antibody reactivity profiles have not yet been studied in depth in patients treated by sublingual house dust mite (HDM) tablet immunotherapy. Humoral immune responses to a large panel of HDM mite allergens were studied using allergen microarray technology in a subset of clinically defined high and low responder patients from a double‐blind placebo‐controlled allergen‐specific immunotherapy (AIT) trial using sublingual 300 IR HDM tablets. Methods: Serum levels of IgE, IgG and IgG4 to 13 Dermatophagoides pteronyssinus molecules were measured at baseline and after 1‐year AIT, using allergen microarrays in 100 subjects exhibiting high or low clinical benefit. Results: Der p 1, Der p 2 and Der p 23 were the most frequently recognized allergens in the study population. Patients with HDM‐related asthma had significantly higher allergen‐specific IgE levels to Der p 1 and Der p 23. No significant difference in the distribution of allergen sensitization pattern was observed between high and low responders. An increase in serum allergen‐specific IgG and IgG4 occurred upon AIT, in particular to allergens Der p 1, Der p 2 and Der p 23 (p < 0.0001). Conclusions: We confirm for our study population that Der p 1‐ and Der p 23‐specific IgE levels are associated with asthma. IgE reactivity profiles were not predicitive of sublingual AIT outcomes, with 300 IR tablets as efficacious in pauci‐ and multi‐sensitized subjects. Our study is the first to demonstrate the induction of IgG and IgG4 specific for the HDM allergens Der p 1, Der p 2 and Der p 23 by sublingual AIT. [ABSTRACT FROM AUTHOR]

Local allergic rhinitis (LAR) is a clinical rhinitis phenotype characterized by the presence of nasal symptoms of AR in nonatopic patients with a negative skin prick test and undetectable specific IgE (sIgE) in serum against inhalant allergens but with a positive nasal allergen provocation test. This study evaluated the effectiveness of a 12-month course of sublingual immunotherapy (SLIT) for house dust mite (HDM) allergies in adult patients with confirmed LAR and concomitant asthma. The study was a prospective, double-blind, placebo-controlled trial with patients diagnosed with LAR to HDMs and with concomitant asthma who underwent a 12-month treatment course of SLIT for HDM allergies. Seventeen patients were randomized to SLIT with the use of allergen extracts of D. pteronyssinus and D. farinae (50/50%) in SQ-HDM SLIT tablets and 15 patients were randomized to the placebo group. The total rhinitis score (TRSS), total asthma symptom score (TASS), combined total symptom score (TSS), total medication score (TMS), and FEV1 were analyzed. Results: In the final analysis, 16 patients who received SLIT and 14 who received placebo who completed the study protocol were included. Significant reductions in TRSS, TASS, TSS, and TMS after 12 months of treatment were observed in patients after SLIT (p < 0.05). A significant increase in the mean FEV1 between baseline and after 12 months of therapy was observed in the study, with p = 0.03 in the study group. Conclusion: SLIT can improve nasal and bronchial symptoms and reduce symptomatic treatment in patients with LAR and asthma and with hyperresponsiveness to HDMs. [ABSTRACT FROM AUTHOR]

Allergic diseases are particularly suitable for personalized medicine, because they meet the needs for therapeutic success, which include a known molecular mechanism of the disease, a diagnostic tool for that disease and a treatment that blocks this mechanism. A range of tools is available for personalized allergy diagnosis, including molecular diagnostics, treatable traits and omics (i.e., proteomics, epigenomics, metabolomics, transcriptomics and breathomics), to predict patient response to therapies, detect biomarkers and mediators and assess disease control status. Such tools enhance allergen immunotherapy. Higher diagnostic accuracy results in a significant increase (based on a greater performance achieved with personalized treatment) in efficacy, further increasing the known and unique characteristics of a treatment designed to work on allergy causes. [ABSTRACT FROM AUTHOR]