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BackgroundAllergen immunotherapy (AIT) is a well-established disease-modifying therapy for allergic rhinitis, yet the fundamental mechanisms underlying its clinical effect remain inadequately understood. Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy was a randomized, double-blind, placebo-controlled trial of individuals allergic to timothy grass who received 2 years of placebo (n = 30), subcutaneous immunotherapy (SCIT) (n = 27), or sublingual immunotherapy (SLIT) (n = 27) and were then followed for 1 additional year.ObjectiveWe used yearly biospecimens from the Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy study to identify molecular mechanisms of response.MethodsWe used longitudinal transcriptomic profiling of nasal brush and PBMC samples after allergen provocation to uncover airway and systemic expression pathways mediating responsiveness to AIT.Trial registrationClinicalTrials.gov Identifier: NCT01335139, EudraCT Number: 2010-023536-16.ResultsSCIT and SLIT demonstrated similar changes in gene module expression over time. In nasal samples, alterations included downregulation of pathways of mucus hypersecretion, leukocyte migration/activation, and endoplasmic reticulum stress (log2 fold changes -0.133 to -0.640, false discovery rates [FDRs] <0.05). We observed upregulation of modules related to epithelial development, junction formation, and lipid metabolism (log2 fold changes 0.104 to 0.393, FDRs <0.05). In PBMCs, modules related to cellular stress response and type 2 cytokine signaling were reduced by immunotherapy (log2 fold changes -0.611 to -0.828, FDRs <0.05). Expression of these modules was also significantly associated with both Total Nasal Symptom Score and peak nasal inspiratory flow, indicating important links between treatment, module expression, and allergen response.ConclusionsOur results identify specific molecular responses of the nasal airway impactin

Background: Randomized controlled trials have demonstrated the efficacy of allergy immunotherapy (AIT) in allergic rhinitis (AR) and the disease-modifying effects of the SQ grass sublingual immunotherapy (SLIT) tablet. Objective: We sought to assess real-world, long-term effectiveness and safety across AIT subgroups: route of administration, therapeutic allergen, persistence to AIT, and SQ grass SLIT tablet. Methods: The primary outcome of AR prescriptions from a retrospective cohort study (REAl-world effeCtiveness in allergy immunoTherapy; 2007-2017) was assessed across prespecified AIT subgroups in subjects with AR with and without AIT prescriptions (controls). Safety was assessed as anaphylaxis for 2 days or less of the first AIT prescription. Subgroup follow-up continued until samples were fewer than 200 subjects. Results: Subcutaneous immunotherapy (SCIT) and SLIT tablets showed similarly greater reductions in AR prescriptions than controls (SCIT vs SLIT tablets: year 3, P = .15; year 5, P = .43). Comparably greater reductions in AR prescriptions were observed for grass- and house dust mite–specific AIT than for controls, but significantly smaller reductions were observed for tree-specific AIT (tree vs house dust mite, and vs grass: years 3 and 5, P < .0001). Persistence to AIT was associated with greater reductions in AR prescriptions versus nonpersistence (persistence vs nonpersistence: year 3, P = .09; year 5, P = .006). SQ grass SLIT tablet showed sustained reductions versus controls for up to 7 years (year 3, P = .002; year 5, P = .03). Rates of anaphylactic shock were low (0.000%-0.092%), with no events for SQ SLIT tablets. Conclusions: These results demonstrate real-world, long-term effectiveness of AIT, complement disease-modifying effects observed in SQ grass SLIT-tablet randomized controlled trials, and highlight the importance of using newer evidence-based AIT products for tree pollen AR.

Introduction: Allergen-specific immunotherapy (IT) is emerging as a viable option for treatment of peanut allergy. Yet, prophylactic IT remains unexplored despite early introduction of peanut in infancy was shown to prevent allergy. There is a need to understand how allergens interact with the immune system depending on the route of administration, and how different dosages of allergen may protect from sensitisation and a clinical active allergy. Here we compared peanut allergen delivery via the oral, sublingual (SL), intragastric (IG) and subcutaneous (SC) routes for the prevention of peanut allergy in Brown Norway (BN) rats. Methods: BN rats were administered PBS or three different doses of peanut protein extract (PPE) via either oral IT (OIT), SLIT, IGIT or SCIT followed by intraperitoneal (IP) injections of PPE to assess the protection from peanut sensitisation. The development of IgE and IgG1 responses to PPE and the major peanut allergens were evaluated by ELISAs. The clinical response to PPE was assessed by an ear swelling test (EST) and proliferation was assessed by stimulating splenocytes with PPE. Results: Low and medium dose OIT (1 and 10 mg) and all doses of SCIT (1, 10, 100 µg) induced sensitisation to PPE, whereas high dose OIT (100 mg), SLIT (10, 100 or 1000 µg) or IGIT (1, 10 and 100 mg) did not. High dose OIT and SLIT as well as high and medium dose IGIT prevented sensitisation from the following IP injections of PPE and suppressed PPE-specific IgE levels in a dose-dependent manner. Hence, administration of peanut protein via different routes confers different risks for sensitisation and protection from peanut allergy development. Overall, the IgE levels toward the individual major peanut allergens followed the PPE-specific IgE levels. Discussion: Collectively, this study showed that the preventive effect of allergen-specific IT is determined by the interplay between the specifi

Background: Randomized controlled trials have demonstrated the efficacy of allergy immunotherapy (AIT) in allergic rhinitis (AR) and the disease-modifying effects of the SQ grass sublingual immunotherapy (SLIT) tablet. Objective: We sought to assess real-world, long-term effectiveness and safety across AIT subgroups: route of administration, therapeutic allergen, persistence to AIT, and SQ grass SLIT tablet. Methods: The primary outcome of AR prescriptions from a retrospective cohort study (REAl-world effeCtiveness in allergy immunoTherapy; 2007-2017) was assessed across prespecified AIT subgroups in subjects with AR with and without AIT prescriptions (controls). Safety was assessed as anaphylaxis for 2 days or less of the first AIT prescription. Subgroup follow-up continued until samples were fewer than 200 subjects. Results: Subcutaneous immunotherapy (SCIT) and SLIT tablets showed similarly greater reductions in AR prescriptions than controls (SCIT vs SLIT tablets: year 3, P = .15; year 5, P = .43). Comparably greater reductions in AR prescriptions were observed for grass- and house dust mite–specific AIT than for controls, but significantly smaller reductions were observed for tree-specific AIT (tree vs house dust mite, and vs grass: years 3 and 5, P < .0001). Persistence to AIT was associated with greater reductions in AR prescriptions versus nonpersistence (persistence vs nonpersistence: year 3, P = .09; year 5, P = .006). SQ grass SLIT tablet showed sustained reductions versus controls for up to 7 years (year 3, P = .002; year 5, P = .03). Rates of anaphylactic shock were low (0.000%-0.092%), with no events for SQ SLIT tablets. Conclusions: These results demonstrate real-world, long-term effectiveness of AIT, complement disease-modifying effects observed in SQ grass SLIT-tablet randomized controlled trials, and highlight the importance of using newer evidence-based AIT products for tree pollen AR.

Objective : We examined the effects of SLIT with tablets containing JCP antigens on nasal symptoms and sleep disturbance in patients with Japanese cedar pollinosis during pollen dispersal season. Methods : A total of 128 patients with Japanese cedar pollinosis were categorized into four groups : 19 one-year SLIT with tablets group, 16 two-year SLIT with drops group, 19 antihistamine group, and 74 untreated group. The scores of nasal symptoms and sleep disturbance were evaluated based on the Japanese guidelines for allergic rhinitis and the Athens Insomnia Scale. Results : The scores of nasal symptoms and sleep disturbance at the peak cedar pollen period in the two-year SLIT with drop group and the one-year SLIT with tablets group were significantly lower than those in untreated group. Additionally, these scores were significantly lower in the one-year SLIT with tablets group than those in the antihistamine group. Conclusion : It is suggested that SLIT with JCP tablets improved both nasal symptoms and sleep disturbances at peak pollen period in patients with Japanese cedar pollinosis. SLIT with JCP tablets for one year was more effective than SLIT with JCP drops for two years and prophylactic treatment with antihistamines.

Introduction: During COVID-19 pandemic, the massive use of Personal Protective Equipment could provoke severe adverse reactions in latex allergy patients and could negatively affect their quality of life. Methods: Trough a survey the study aimed: (a) to evaluate the incidence of allergic reactions in patients with latex allergy during the SARS-CoV-2 pandemic; (b) to evaluate the protective role of continuous latex sublingual immunotherapy (SLIT) during this period; and (c) to evaluate quality of life of natural rubber latex allergy (NRLA) patients during the pandemic. Results: 67 patients (9 males and 58 females, mean age of 45.9 +/- 11.4 years) suffering from latex allergy were included in the present study. We recorded among our patients 13 cases (34.2%) of urticarial/angioedema (U/A), 9 cases (23.6%) of respiratory symptoms (dyspnoea, shortness of breath and wheezing) and 7 cases (18.4%) of anaphylaxis. In patients who underwent continuous SLIT, we observed less cases of U/A (p < 0.001), respiratory symptoms (p < 0.001), anaphylaxis (p = 0.003), hospitalizations (p = 0.014) and a lower therapy administration. We compared the results of SF-36 questionnaire in patients who underwent continuous and not-continuous SLIT with a significance differences score between these two groups. Conclusions: Our study is the first that investigated the clinical and quality of life effects of COVID-19 pandemic in NRLA patients.

Introducción: la rinitis alérgica (RA) representa un problema de salud a nivel mundial, siendo la enfermedad crónica más frecuente en pediatría. Para tratar de paliar su impacto se emplea la inmunoterapia específica con alérgenos (ITA). Este estudio se centra en el uso de la inmunoterapia sublingual (ITSL) para ácaros del polvo doméstico en niños y adolescentes con RA. Objetivos: evaluar la eficacia y seguridad de la ITSL para ácaros del polvo doméstico en niños y adolescentes con RA, analizar los efectos de la ITSL sobre diferentes parámetros inmunológicos y sobre la prevención de nuevas sensibilizaciones. Material y métodos: se ha realizado una búsqueda bibliográfica exhaustiva en diferentes bases de datos científicas, empleando para ello palabras clave y filtros de búsqueda. Tras aplicar los criterios de inclusión y exclusión, se han seleccionado 11 artículos para llevar a cabo esta revisión sistemática. Resultados: la mayoría de los estudios coinciden en que la ITSL es efectiva, ya que provoca una clara mejoría en los síntomas clínicos y en la calidad de vida, además de inducir un marcado descenso en el uso de medicación de rescate. Por otro lado, se constata como una opción terapéutica segura y bien tolerada debido a que la mayoría de sus efectos adversos fueron locales (prurito lingual, edema bucal o irritación de garganta) de carácter leve-moderado y transitorios. Asimismo, casi la totalidad de los estudios pusieron de manifiesto que la ITSL produce un aumento inicial en los niveles de IgE y un aumento posterior de IgG4, demostrando una modulación del sistema inmune. Conclusiones: la ITSL es un tratamiento eficaz, seguro y bien tolerado pata tratar la RA inducida por ácaros del polvo doméstico en niños y adolescentes. Además, ha demostrado tener un efecto modulador del sistema inmune siendo el único tratamiento capaz de modificar la historia natural de la sensibilización alérgica, Introdución: a rinite alérxica (RA) representa un problema de saúde a nivel mundial, sendo a enfermidade crónica máis frecuente en pediatría. Para tratar de mitigar o seu impacto empregase a inmunoterapia específica con alérxenos (ITA). Este estudo céntrase no uso da inmunoterapia sublingual (SLIT) para os ácaros do po doméstico en nenos e adolescentes con RA. Obxectivos: avaliar a eficacia e seguridade da SLIT para ácaros do po doméstico en nenos e adolescentes con RA, analizar os efectos da SLIT sobre diferentes parámetros inmunolóxicos e sobre a prevención de novas sensibilizacións. Material e métodos: realizouse unha exhaustiva busca bibliográfica en diferentes bases de datos científicas, empregando palabras clave e filtros de busca. Despois de aplicar os criterios de inclusión e exclusión, seleccionáronse 11 artigos para realizar esta revisión sistemática. Resultados: a maioría dos estudos coinciden en que a SLIT é eficaz, xa que provoca unha clara mellora dos síntomas clínicos e da calidade de vida, ademais de inducir unha diminución marcada no uso de medicación de rescate. Por outra banda, confírmase como unha opción terapéutica segura e ben tolerada porque a maioría dos seus efectos adversos foron locais (prurito lingual, edema bucal ou irritación na garganta) de carácter leve-moderado e transitorios. Do mesmo xeito, case todos os estudos demostraron que a SLIT produce un aumento inicial nos niveis de IgE e un aumento posterior en IgG4, demostrando unha modulación do sistema inmune. Conclusións: a SLIT é un tratamento eficaz, seguro e ben tolerado para tratar a AR inducida por ácaros do po doméstico en nenos e adolescentes. Ademais, demostrouse que ten un efecto modulador sobre o sistema inmune, sendo o único tratamento capaz de modificar a historia natural da sensibilización alérxica, Introduction: allergic rhinitis (AR) represents a health problem worldwide, being the most frequent chronic disease in pediatrics. Trying to alleviate its impact specific allergen immunotherapy (ITA) is used. This study focuses on the use of sublingual immunotherapy (SLIT) for house dust mites in children and adolescents with RA. Objective: to evaluate the efficacy and safety of SLIT for house dust mites in children and adolescents with RA, to analyze the effects of SLIT on different immunological parameters and the prevention of new sensitizations. Material and methods: an exhaustive bibliographic search has been carried out in different scientific databases, using keywords and search filters. After applying the inclusion and exclusion criteria, 11 articles were selected to perform this systematic review. Results: most studies agree that SLIT is effective, since it causes a clear improvement in clinical symptoms and quality of life, in addition to inducing a marked decrease in the use of rescue medication. On the other hand, it is confirmed as a safe and well-tolerated therapeutic option because most of its adverse effects were local (tongue itching, mouth edema or throat irritation), mild-moderate, and transitory. Likewise, almost all the studies showed that SLIT produces an initial increase in IgE levels and a subsequent increase in IgG4, thus showing a modulation of the immune system. Conclusions: SLIT is an effective, safe, and well-tolerated treatment for house dust mites-induced RA in children and adolescents. Furthermore, it has been shown to have a modulating effect on the immune system, being the only treatment capable of modifying the natural history of allergic sensitization

Purpose. Determination of the efficacy of sublingual allergen-specific immunotherapy (SLIT) in preschool children with sensitization to allergens of mold Alternaria alternata.Materials and methods. The study involved 447 children aged 4.1 ± 0.9 years (from 3 to 7 years old), with verified diagnoses of allergic bronchial asthma and/or allergic rhinitis. In 58 patients with proven sensitization to Alternaria alternata major allergens, the efficacy of sublingual allergen-specific immunotherapy (SLIT) was assessed, which was carried out for 3 years and evaluated using a visual analogue scale (VAS) and the sIgE level to the major component of Alternaria Alt a1. 27 children (group II) who received exclusively basic therapy were included in the comparison group.Results. During three years, SLIT in patients of the first group showed a significant decrease in the frequency of nasal symptoms: sneezing from 29 (26; 31) mm to 8 (6; 11) mm (P = 0.008), rhinorrhea from 29 (26; 34 ) mm to 5 (4; 6) mm (P = 0.012) mm, itching from 20 (17; 23) mm to 5 (4; 6) (P = 0.002) mm and nasal congestion from 29 (25; 35) mm to 7 (5; 9) mm (P = 0.016) compared with the initial level. Similar dynamics were observed with the nasal symptoms itching of the eyes, redness of the eyes and discharge from the eyes, which significantly decreased from 26 (23; 31) mm to 5 (3; 7) mm (P = 0.007), from 29 (26; 36) mm to 4 (3; 6) mm (P = 0.014) and from 29.5 mm to 5.0 (4; 7) mm (P = 0.003) in comparison with the initial values. Dynamics were also observed in relation to asthma symptoms, namely, the cough and shortness of breath indices reliably decreased from 54 (46; 61) mm to 7 (6; 9) mm (P = 0.013) and from 50 (39; 57) mm to 7 (5; 9) mm (P = 0.011) compared to baseline values. It should be noted that the indicators of VAS in children after the end of the SLIT course were significantly lower than those in children who received basic therapy.Conclusions. The study showed that the use of sublingual immunotherap

Introduction: In the Serbian population allergy to weed pollen is the most common type of pollen-associated allergy, ahead of grass and tree pollens. Besides causing discomfort, allergy to pollen is often associated with rhinitis and asthma. Allergen-specific immunotherapy (ASIT) is the only treatment that can lead to potential long-term immune modification while reducing development of new sensitization and halting disease progression. The aim of the present study is to evaluate the efficacy of sublingual immunotherapy (SLIT) to weeds in the adult patient population using vaccine produced by the local Serbian Torlak Institute for virology, vaccines and serum. Methods: Adult patients with a clinical history of allergic rhinitis with and without asthma were included in the study. IgE-mediated sensitization to grass, tree and weed pollens was confirmed by skin prick testing and/or positive specific IgE. Patients were divided into two groups: patients with allergy to tree and grass pollen and patients with allergy to weeds. All patients received SLIT for three years, either with or without additional symptomatic therapy. Results: Three-year SLIT therapy led to significant improvement in several parameters, including skin-prick reactivity, decrease in specific IgE and use of symptomatic therapy, with mild adverse effects and high patient satisfaction concerning therapy. Conclusion: Three-year SLIT is a safe and efficient treatment option for respiratory allergy to weeds. Further observations in a larger number of patients could provide a better epidemiological evaluation of SLIT, but the positive effects we observed in our study may be considered representative despite the small number of patients.

Introduction: In the Serbian population allergy to weed pollen is the most common type of pollen-associated allergy, ahead of grass and tree pollens. Besides causing discomfort, allergy to pollen is often associated with rhinitis and asthma. Allergen-specific immunotherapy (ASIT) is the only treatment that can lead to potential long-term immune modification while reducing development of new sensitization and halting disease progression. The aim of the present study is to evaluate the efficacy of sublingual immunotherapy (SLIT) to weeds in the adult patient population using vaccine produced by the local Serbian Torlak Institute for virology, vaccines and serum. Methods: Adult patients with a clinical history of allergic rhinitis with and without asthma were included in the study. IgE-mediated sensitization to grass, tree and weed pollens was confirmed by skin prick testing and/or positive specific IgE. Patients were divided into two groups: patients with allergy to tree and grass pollen and patients with allergy to weeds. All patients received SLIT for three years, either with or without additional symptomatic therapy. Results: Three-year SLIT therapy led to significant improvement in several parameters, including skin-prick reactivity, decrease in specific IgE and use of symptomatic therapy, with mild adverse effects and high patient satisfaction concerning therapy. Conclusion: Three-year SLIT is a safe and efficient treatment option for respiratory allergy to weeds. Further observations in a larger number of patients could provide a better epidemiological evaluation of SLIT, but the positive effects we observed in our study may be considered representative despite the small number of patients.

Introduction: In the Serbian population allergy to weed pollen is the most common type of pollen-associated allergy, ahead of grass and tree pollens. Besides causing discomfort, allergy to pollen is often associated with rhinitis and asthma. Allergen-specific immunotherapy (ASIT) is the only treatment that can lead to potential long-term immune modification while reducing development of new sensitization and halting disease progression. The aim of the present study is to evaluate the efficacy of sublingual immunotherapy (SLIT) to weeds in the adult patient population using vaccine produced by the local Serbian Torlak Institute for virology, vaccines and serum. Methods: Adult patients with a clinical history of allergic rhinitis with and without asthma were included in the study. IgE-mediated sensitization to grass, tree and weed pollens was confirmed by skin prick testing and/or positive specific IgE. Patients were divided into two groups: patients with allergy to tree and grass pollen and patients with allergy to weeds. All patients received SLIT for three years, either with or without additional symptomatic therapy. Results: Three-year SLIT therapy led to significant improvement in several parameters, including skin-prick reactivity, decrease in specific IgE and use of symptomatic therapy, with mild adverse effects and high patient satisfaction concerning therapy. Conclusion: Three-year SLIT is a safe and efficient treatment option for respiratory allergy to weeds. Further observations in a larger number of patients could provide a better epidemiological evaluation of SLIT, but the positive effects we observed in our study may be considered representative despite the small number of patients.

[Background]: In the first 2 years of grass tablet sublingual immunotherapy treatment, we have previously demonstrated a progressive development of a regulatory T‐cell response, which was preceded by an early decrease in the frequency of both IL‐4+ cells and sIgE levels. A progressive increase in sIgG4 levels and FAB blockage were also found., [Methods]: By monitoring immunological kinetics during 3 years of active treatment + 2 years of follow‐up, we aimed to identify key immunological parameters that could explain sustained clinical benefit of grass tablet sublingual immunotherapy., [Results]: Thirty patients completed the 5‐year clinical trial protocol. Although individual responses were heterogeneous, reduction in both sIgE and circulating IL‐4+ cells compared to the initial 1‐ to 4‐month peak was maintained throughout the 3‐year treatment period and for 2 years after discontinuation. Meanwhile, after a 2‐year increase in sIgG4, the levels were stabilized during the third year and decreased post‐therapy. FAB inhibition remained significantly inhibited throughout the study compared to preimmunotherapy in 83% of patients. A sustained regulatory T‐cell response, after IT cessation, occurs in two‐thirds of the patients. There was a statistical association between this regulatory response, the maintenance of lower eosinophil counts during grass pollen seasons, and sIgE titers lower than before immunotherapy treatment, and the latter were significantly associated with clinical response., [Conclusion]: Our results suggest that the immunological mechanisms underlying the sustained response after 2 years of cessation of immunotherapy (3‐year treatment period) are linked to the acquisition and maintenance of a regulatory T‐cell response.

It is expected that probiotics may act synergistically to improve the clinical efficacy of sublingual immunotherapy (SLIT). The aim of this study was to investigate the role of probiotics in enhancing efficacy of sublingual immunotherapy in childhood allergic asthma. This was a randomized single blind clinical trial conducted on 6-17 year-old asthmatic children sensitive to house dust mite allergens. Subjects were allocated to Group A receiving SLIT, Group B receiving probiotics and SLIT, Group C receiving probiotics only. Clinical parameters (FEV1 reversibility, medication score, and symptom score) and immunological parameters (total IgE, eosinophil count, IFN-γ, IL-2, IL-4, IL5, IL10, and TGF-b were evaluated in week 0 until 14. Statistical analysis revealed that the difference of clinical parameters (FEV1 reversibility, medication score, and symptom score) between groups were not significant. The difference of the immunological parameters of total IgE, IFN-γ, IL-2, IL-4, IL5, IL10, and TGF-íŸ were also not significant. Eosinophil count decreased in subjects who received combination SLIT with probiotics. In conclusion, probiotics enhanced the efficacy of sublingual immunotherapy in childhood allergic asthma by decreasing the eosinophil count.

Background: Sublingual immunotherapy (SLIT) is effective, tolerable, and convenient for many allergic patients. Still, real-world evidence is scarce and the aim of this study is to assess the patient reported outcome of treatment with SLIT against grass pollen allergy in a consecutive patient population. Methods: Patients (n = 329) who were confirmed to be allergic to timothy grass and had been prescribed SLIT were consecutively enrolled in the study and completed a questionnaire online or in hard copy. Results: 207 (62.9%) patients responded to the questionnaire. The female/male ratio was 105/102 with a mean age of 39 ± 11 years (range 19-70 years). 113 (55%) patients reported they had completed the full 3-year treatment period, 49 (24%) were still on treatment, and 45 (22%) had discontinued treatment prematurely. Respondents who had completed the full treatment period reported that their allergy symptoms in the most recent grass pollen season had improved to a larger extent than subjects still on treatment or discontinuing the treatment prematurely. Improvement of asthma was twice as common among patients who completed compared to discontinued treatment (42 vs. 20%). Younger age (37 ± 12 vs. 41 ± 11 years, p < 0.001) and a higher prevalence of reported oral and/or gastrointestinal side effects (49 vs. 24%, p = 0.02) characterised the group that terminated SLIT. Forgetfulness was the most commonly reported specific reason. Conclusion: Treatment perseverance resulted in improved patient reported outcome. Forgetfulness was the most frequently reported reason for discontinuing SLIT treatment against grass pollen allergy.

Background: Sublingual immunotherapy (SLIT) is effective, tolerable, and convenient for many allergic patients. Still, real-world evidence is scarce and the aim of this study is to assess the patient reported outcome of treatment with SLIT against grass pollen allergy in a consecutive patient population. Methods: Patients (n = 329) who were confirmed to be allergic to timothy grass and had been prescribed SLIT were consecutively enrolled in the study and completed a questionnaire online or in hard copy. Results: 207 (62.9%) patients responded to the questionnaire. The female/male ratio was 105/102 with a mean age of 39 ± 11 years (range 19-70 years). 113 (55%) patients reported they had completed the full 3-year treatment period, 49 (24%) were still on treatment, and 45 (22%) had discontinued treatment prematurely. Respondents who had completed the full treatment period reported that their allergy symptoms in the most recent grass pollen season had improved to a larger extent than subjects still on treatment or discontinuing the treatment prematurely. Improvement of asthma was twice as common among patients who completed compared to discontinued treatment (42 vs. 20%). Younger age (37 ± 12 vs. 41 ± 11 years, p < 0.001) and a higher prevalence of reported oral and/or gastrointestinal side effects (49 vs. 24%, p = 0.02) characterised the group that terminated SLIT. Forgetfulness was the most commonly reported specific reason. Conclusion: Treatment perseverance resulted in improved patient reported outcome. Forgetfulness was the most frequently reported reason for discontinuing SLIT treatment against grass pollen allergy.

Background: Sublingual immunotherapy (SLIT) is effective, tolerable, and convenient for many allergic patients. Still, real-world evidence is scarce and the aim of this study is to assess the patient reported outcome of treatment with SLIT against grass pollen allergy in a consecutive patient population. Methods: Patients (n = 329) who were confirmed to be allergic to timothy grass and had been prescribed SLIT were consecutively enrolled in the study and completed a questionnaire online or in hard copy. Results: 207 (62.9%) patients responded to the questionnaire. The female/male ratio was 105/102 with a mean age of 39 ± 11 years (range 19-70 years). 113 (55%) patients reported they had completed the full 3-year treatment period, 49 (24%) were still on treatment, and 45 (22%) had discontinued treatment prematurely. Respondents who had completed the full treatment period reported that their allergy symptoms in the most recent grass pollen season had improved to a larger extent than subjects still on treatment or discontinuing the treatment prematurely. Improvement of asthma was twice as common among patients who completed compared to discontinued treatment (42 vs. 20%). Younger age (37 ± 12 vs. 41 ± 11 years, p < 0.001) and a higher prevalence of reported oral and/or gastrointestinal side effects (49 vs. 24%, p = 0.02) characterised the group that terminated SLIT. Forgetfulness was the most commonly reported specific reason. Conclusion: Treatment perseverance resulted in improved patient reported outcome. Forgetfulness was the most frequently reported reason for discontinuing SLIT treatment against grass pollen allergy.

BackgroundCritical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR).MethodsUsing previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus.ResultsThe ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR.ConclusionThis critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.

Introduction: sublingual immunotherapy makes its way into allergological practice and numerous studies confirm its effectiveness and safety. Objective: to characterize the results with the use of Valergen sublingual vaccines in asthmatic patients of Cabaiguan municipality. Method: a descriptive-prospective investigation was conducted from January 2013 to December 2016 in patients diagnosed with intermittent bronchial asthma, persistent, slow and moderate. The universe was constituted by 467 patients. The sample was of 44 patients, of all ages and sexes, who met these conditions, were seen in consultation during the studied period and evaluated each patient after three years of treatment with immunotherapy. The data were obtained from the clinical records and the vaccination record of the allergy department. Results: female patients between 5-14 years (34.1%),and Dermatophagoide pteronyssinus was the mite with the highest sensitivity and use (45.4%), after 3 years of treatment, patients with a better control of their symptoms (72.7%), there were no adverse events (79.5%) in the patients, those presented were classified as local and mild systemic (20.5%). Conclusions: sublingual immunotherapy for bronchial asthma proved to be safe and clinically favorable in the patients., Introdução: a imunoterapia sublingual faz parte da prática alergológica, e numerosos estudos confirmam sua eficácia e segurança. Objetivo: caracterizar os resultados com o uso de vacinas sublinguais de Valergen, em pacientes asmáticos, do município de Cabaiguán. Método: inquérito descritivo-prospectivo foi realizado no período de janeiro de 2013 a dezembro de 2016 em pacientes com diagnóstico de asma brônquica intermitente, persistente leve e moderada. O universo foi constituído por 467 pacientes. A amostra foi de 44 pacientes, de todas as idades e sexos que preencheram essas condições, foram atendidos em consulta durante todo o período do estudo e avaliaram cada paciente após três anos de tratamento com imunoterapia. Os dados foram obtidos a partir dos registros clínicos e do registro de vacinação do departamento de alergia. Resultados: predominaram pacientes do sexo feminino, entre 5-14 anos (34,1%), Dermatophagoide pteronyssinus foi o ácaro com maior sensibilidade e utilização (45,4%), após 3 anos de tratamento, pacientes com melhor controle de seus sintomas (72,7%), não houve eventos adversos (79,5%) nos pacientes, aqueles apresentados foram classificados como sistêmicos locais e / ou leves (20,5%). Conclusões: a imunoterapia sublingual para asma brônquica mostrou-se segura e clinicamente favorável nos pacientes estudados., Introducción: la inmunoterapia sublingual se abre paso en la práctica alergológica, numerosos estudios avalan su eficacia y seguridad. Objetivo: caracterizar los resultados con el uso de las vacunas Valergen vía sublingual, en pacientes asmáticos, del municipio Cabaiguán. Método: se realizó una investigación descriptiva-prospectiva, de enero del 2013 a diciembre del 2016 en pacientes con diagnóstico de asma bronquial intermitente, persistente leve y moderado. El universo quedó constituido por 467 pacientes. La muestra fue de 44 pacientes, de todas las edades y sexos que reunían esas condiciones, fueron atendidos en consulta durante todo el periodo de estudio y evaluado cada paciente al cumplir tres años de tratamiento con inmunoterapia. Los datos fueron obtenidos de las historias clínicas y del registro de vacunación del departamento de alergia. Resultados: predominaron los pacientes del sexo femenino, entre 5-14 años (34,1 %), el Dermatofagoide pteronyssinus fue el ácaro de mayor sensibilidad y utilización (45,4 %), a los 3 años de tratamiento predominaron los pacientes con un mejor control de sus síntomas (72,7 %), no se presentaron eventos adversos (79,5 %) en los pacientes, los presentados fueron clasificados como locales y/o sistémicos leves (20,5 %). Conclusiones: la inmunoterapia sublingual para el asma bronquial demostró ser segura y clínicamente favorable en los pacientes estudiados.

Background: Sublingual immunotherapy (SLIT) is effective, tolerable, and convenient for many allergic patients. Still, real-world evidence is scarce and the aim of this study is to assess the patient reported outcome of treatment with SLIT against grass pollen allergy in a consecutive patient population. Methods: Patients (n = 329) who were confirmed to be allergic to timothy grass and had been prescribed SLIT were consecutively enrolled in the study and completed a questionnaire online or in hard copy. Results: 207 (62.9%) patients responded to the questionnaire. The female/male ratio was 105/102 with a mean age of 39 ± 11 years (range 19-70 years). 113 (55%) patients reported they had completed the full 3-year treatment period, 49 (24%) were still on treatment, and 45 (22%) had discontinued treatment prematurely. Respondents who had completed the full treatment period reported that their allergy symptoms in the most recent grass pollen season had improved to a larger extent than subjects still on treatment or discontinuing the treatment prematurely. Improvement of asthma was twice as common among patients who completed compared to discontinued treatment (42 vs. 20%). Younger age (37 ± 12 vs. 41 ± 11 years, p < 0.001) and a higher prevalence of reported oral and/or gastrointestinal side effects (49 vs. 24%, p = 0.02) characterised the group that terminated SLIT. Forgetfulness was the most commonly reported specific reason. Conclusion: Treatment perseverance resulted in improved patient reported outcome. Forgetfulness was the most frequently reported reason for discontinuing SLIT treatment against grass pollen allergy.

Background: Sublingual immunotherapy (SLIT) is effective, tolerable, and convenient for many allergic patients. Still, real-world evidence is scarce and the aim of this study is to assess the patient reported outcome of treatment with SLIT against grass pollen allergy in a consecutive patient population. Methods: Patients (n = 329) who were confirmed to be allergic to timothy grass and had been prescribed SLIT were consecutively enrolled in the study and completed a questionnaire online or in hard copy. Results: 207 (62.9%) patients responded to the questionnaire. The female/male ratio was 105/102 with a mean age of 39 ± 11 years (range 19-70 years). 113 (55%) patients reported they had completed the full 3-year treatment period, 49 (24%) were still on treatment, and 45 (22%) had discontinued treatment prematurely. Respondents who had completed the full treatment period reported that their allergy symptoms in the most recent grass pollen season had improved to a larger extent than subjects still on treatment or discontinuing the treatment prematurely. Improvement of asthma was twice as common among patients who completed compared to discontinued treatment (42 vs. 20%). Younger age (37 ± 12 vs. 41 ± 11 years, p < 0.001) and a higher prevalence of reported oral and/or gastrointestinal side effects (49 vs. 24%, p = 0.02) characterised the group that terminated SLIT. Forgetfulness was the most commonly reported specific reason. Conclusion: Treatment perseverance resulted in improved patient reported outcome. Forgetfulness was the most frequently reported reason for discontinuing SLIT treatment against grass pollen allergy.

Introduction: The only etiological and decisive therapy, able to influence the natural history of latex allergy is the specific desensitization. Aim: To verify the clinical efficacy and immunological changes determined by latex sublingual immunotherapy in allergic patients who underwent this treatment for at least 3 years. Material and methods: We enrolled 76 patients (16 males and 60 females, mean age 34 years old) with evidence of a natural rubber latex allergy. To assess the effectiveness of the immunotherapy we performed a latex skin prick test, specific IgE and IgG4 and challenge tests before and after at least 3 years of desensitization. Results: We observed a reduction in the mean diameter of the wheal area at the skin prick test and a decrease in latex specific IgE while no significant changes of latex IgG4 values were found. Moreover a reduction of symptoms and scores at the provocation tests were remarked. Conclusions: Although the primary prevention (which still remains the gold standard treatment for patients suffering from the latex allergy) sublingual immunotherapy can be offered with efficacy in addition to symptomatic treatment to selected patients.

[Scope] Food‐specific immunotherapy (SIT) is a promising treatment for lipid transfer protein (LTP)‐syndrome. We propose a novel sublingual‐SIT (SLIT) that combines a Pru p 3 T‐cell peptide and an oligodeoxyribonucleotide (ODN) with CpG motifs (ODN‐CpG) as adjuvants to induce a specific Th1/Treg response., [Methods and results] LTP‐peach allergic mice were treated sublingually with a combination of a CpG sequence and mono‐ or tetravalent systems including a Pru p 3 peptide, D1(Prup3) or D4(Prup3). Mice were challenged intraperitoneally with Pru p 3 one or three weeks after SLIT and tolerance was assessed. Mice treated with D1(Prup3)+CpG were protected from anaphylaxis after Pru p 3 challenge. They showed no change in body temperature, lower levels of Pru p 3‐specific IgE and IgG1 antibodies and higher levels of sIgG2a compared to the untreated group. They had fewer IgE and IgG1 secreting cells and more sIgG2a secreting cells. Moreover, a significantly lower number of Pru p 3‐specific CD4+T cells and a higher number of Treg cells were found, alongside a Th1 cytokine pattern. These changes were maintained for three weeks after stopping treatment., [Conclusion] D1Prup3+CpG represents a promising SIT for food allergy. It is easily synthesized and induces protection from anaphylaxis to Pru p 3 that is maintained for at least three weeks.

Background: To inform the development of the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines on Allergen Immunotherapy (AIT) for allergic asthma, we assessed the evidence on the effectiveness, cost-effectiveness and safety of AIT. Methods: We performed a systematic review, which involved searching nine databases. Studies were screened against predefined eligibility criteria and critically appraised using established instruments. Data were synthesized using random-effects meta-analyses. Results: 98 studies satisfied the inclusion criteria. Short-term symptom scores were reduced with a standardized mean difference (SMD) of −1.11 (95% CI −1.66, −0.56). This was robust to a prespecified sensitivity analyses, but there was evidence suggestive of publication bias. Short-term medication scores were reduced SMD −1.21 (95% CI −1.87, −0.54), again with evidence of potential publication bias. There was no reduction in short-term combined medication and symptom scores SMD 0.17 (95% CI −0.23, 0.58), but one study showed a beneficial long-term effect. For secondary outcomes, subcutaneous immunotherapy (SCIT) improved quality of life and decreased allergen-specific airway hyperreactivity (AHR), but this was not the case for sublingual immunotherapy (SLIT). There were no consistent effects on asthma control, exacerbations, lung function, and nonspecific AHR. AIT resulted in a modest increased risk of adverse events (AEs). Although relatively uncommon, systemic AEs were more frequent with SCIT; however no fatalities were reported. The limited evidence on cost-effectiveness was mainly available for sublingual immunotherapy (SLIT) and this suggested that SLIT is likely to be cost-effective. Conclusions: AIT can achieve substantial reductions in short-term symptom and medication scores in allergic asthma. It was however associated with a modest increased risk of systemic and local AEs. More data are needed in relation to secondary outcomes, longer-term effectiv

Immunotherapy by sublingual administration of allergens provides high patient compliance and has emerged as an alternative to subcutaneous immunotherapy for the - treatment of IgE-associated allergic diseases. However, sublingual immunotherapy (SLIT) can cause adverse events. Development of allergen delivery systems enabling more efficient delivery and hence lower allergen load might reduce the adverse events. In the present study, we have investigated neutral and cationic liposomes as delivery systems of ovalbumin (OVA), as a model allergen, in an OVA-induced allergic airway inflammation model. We investigated the liposome carriers' ability to improve tolerance induction of antigens compared to the - corresponding dose of free OVA. Mice were treated sublingually over 2 weeks with free or liposome encapsulated OVA followed by intraperitoneal injections and intranasal challenge. Mice sublingually treated with OVA-liposomes showed a significant reduction of airway eosinophilia and splenocyte proliferation in comparison to free OVA. A similar nonsignificant pattern was seen for OVA-specific IgE antibodies. In addition, reduced levels of interferon-gamma and interleukin-5 were observed in spleen cell culture supernatants from OVA-liposome-treated mice compared to the sham-treated group. In conclusion, in vivo efficacy data showed that prophylactic SLIT with OVA-liposomes is significantly more effective in preventing allergic inflammation than the corresponding dose of free OVA.

Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Sante). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing.

Sublingual allergen immunotherapy (SLIT) is considered to be safer and more convenient than subcutaneus immunotherapy. SLIT trials with house dust mites involving patients with allergic rhinitis (AR) and asthma reported discordant results. The aim of the study was to investigate the clinical efficacy and safety of SLIT with Dermatophagoides pteronyssinus (D.pt) extract produced in Serbia and patient's satisfaction through open-label trial. Adult patients with allergic rhinitis were randomized into two groups: one received drugs and SLIT, while other received only drugs. Symptom score (SS), medication score (MS) and cumulative score (CS), skin prick tests (SPT) and serum level of D. pt specific IgE were assessed. One year after, the patients were re-evaluated. In total, 61 patients were enrolled in the study, but 52 of them were analyzed at the end of the year. CS (29.3%, p lt 0.001) and MS (54.3%, p lt 0.05) reduced significantly in the SLIT group. There was a significant improvement of MS and CS in the SLIT compared to control group (p lt 0.001 and p lt 0.05 respectively). There was no significant improvement of SS as well as specific slgE. Patients in the SLIT group were more satisfied with treatment (p lt 0.001). The incidence of mild adverse reaction was 38.4%. Specific lgG was not done. One year SLIT with D. pt extract was clinically efficient treatment in AR patients.

Sublingual allergen immunotherapy (SLIT) is considered to be safer and more convenient than subcutaneus immunotherapy. SLIT trials with house dust mites involving patients with allergic rhinitis (AR) and asthma reported discordant results. The aim of the study was to investigate the clinical efficacy and safety of SLIT with Dermatophagoides pteronyssinus (D.pt) extract produced in Serbia and patient's satisfaction through open-label trial. Adult patients with allergic rhinitis were randomized into two groups: one received drugs and SLIT, while other received only drugs. Symptom score (SS), medication score (MS) and cumulative score (CS), skin prick tests (SPT) and serum level of D. pt specific IgE were assessed. One year after, the patients were re-evaluated. In total, 61 patients were enrolled in the study, but 52 of them were analyzed at the end of the year. CS (29.3%, p lt 0.001) and MS (54.3%, p lt 0.05) reduced significantly in the SLIT group. There was a significant improvement of MS and CS in the SLIT compared to control group (p lt 0.001 and p lt 0.05 respectively). There was no significant improvement of SS as well as specific slgE. Patients in the SLIT group were more satisfied with treatment (p lt 0.001). The incidence of mild adverse reaction was 38.4%. Specific lgG was not done. One year SLIT with D. pt extract was clinically efficient treatment in AR patients.

BACKGROUND: The SQ HDM SLIT-tablet (ALK) has been developed for treatment of house dust mite (HDM)-induced respiratory allergic disease.OBJECTIVE: This trial investigated the efficacy and safety of the SQ HDM SLIT-tablet in adults with moderate-to-severe HDM-induced allergic rhinitis (AR).METHODS: The trial was a randomized, double-blind, placebo-controlled phase III trial conducted in 12 European countries including 992 adults with moderate-to-severe HDM-induced AR despite treatment with pharmacotherapy. Subjects were randomized 1:1:1 to 1 year of daily treatment with placebo, 6 SQ-HDM, or 12 SQ-HDM. The primary end point was the total combined rhinitis score (ie, the sum of rhinitis symptom and medication scores) during the efficacy assessment period (approximately the last 8 weeks of the treatment period). Key secondary end points were rhinitis symptoms, medication scores, quality of life, and the combined rhinoconjunctivitis score.RESULTS: Analysis of the primary end point (observed data) demonstrated absolute reductions in total combined rhinitis score of 1.18 (P = .002) and 1.22 (P = .001) compared with placebo for 6 SQ-HDM and 12 SQ-HDM, respectively. The statistically significant treatment effect was evident from 14 weeks of treatment onward. For all key secondary end points, efficacy was confirmed for 12 SQ-HDM, with statistically significant reductions of rhinitis symptoms and medication scores, improved quality of life, and a reduced combined rhinoconjunctivitis score in the efficacy assessment period compared with placebo. The treatment was well tolerated.CONCLUSION: The trial confirmed the efficacy and favorable safety profile of both 6 SQ-HDM and 12 SQ-HDM in adults with HDM-induced AR. The treatment effect was present from 14 weeks of treatment onward.

Guidelines and systematic review report that allergen immunotherapy (AIT) is, in general, effective in the treatment of allergic rhinitis. However, experts suggest not generalising the results of different clinical studies: for example, it would not be advisable to translate the results found in an adult population to a paediatric population or the results on the efficacy of AIT against a specific allergen to the AIT against a different allergen. Moreover, according to Evidence Based Medicine (EBM), clinical decisions are individualised and should derive from the "integration of best research evidence with clinical expertise and patient values". Taking into account the high specificity of the AIT and EBM principles, we tried to answer the question on how advisable it is to prescribe the AIT for the management of grass allergic rhinitis in children. To do this, we revised the scientific literature in order to solve a specific case scenario.

One of the most common reasons people seek primary care and emergency care is to reduce the symptoms of allergies, such as hay fever. To meet this high demand, several recent FDA-approved methods for treating seasonal and perennial allergies have been developed, including sublingual immunotherapy tablets. Furthermore, no longer must a patient endure allergy shots; this can now be delivered sublingually. Although this method has been shown to have high safety and efficacy, very few clinicians actually utilize this form of therapy. The purpose of this paper is describe the use of sublingual immunotherapy among Nurse Practitioners (NPs) and discuss barriers that may prevent its use. Nurse Practitioners working in primary care settings were surveyed regarding their use of sublingual immunotherapy. Although many nurse practitioners treat patients with allergic disease, not one participant reported using sublingual immunotherapy. This discussion outlines some of the reasons NPs are not currently utilizing this method of allergy treatment and the findings are compared with the extant literature. This paper culminates in an evidence-based algorithm to outline best practices for utilizing sublingual immunotherapy to reduce allergy symptoms.

We have prepared this document, "Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update", according to the evidence-based criteria, revising and updating chapters of the originally published paper, "Sublingual Immunotherapy: World Allergy Organization Position Paper 2009", available at. Namely, these comprise: "Mechanisms of sublingual immunotherapy;" "Clinical efficacy of sublingual immunotherapy" - reporting all the data of all controlled trials published after 2009; "Safety of sublingual immunotherapy" - with the recently published Grading System for adverse reactions; "Impact of sublingual immunotherapy on the natural history of respiratory allergy" - with the relevant evidences published since 2009; "Efficacy of SLIT in children" - with detailed analysis of all the studies; "Definition of SLIT patient selection" - reporting the criteria for eligibility to sublingual immunotherapy; "The future of immunotherapy in the community care setting"; "Methodology of clinical trials according to the current scientific and regulatory standards"; and "Guideline development: from evidence-based medicine to patients' views" - including the evolution of the methods to make clinical recommendations. Additionally, we have added new chapters to cover a few emerging crucial topics: "Practical aspects of schedules and dosages and counseling for adherence" - which is crucial in clinical practice for all treatments; "Perspectives and new approaches" - including recombinant allergens, adjuvants, modified allergens, and the concept of validity of the single products. Furthermore, "Raising public awareness about sublingual immunotherapy", as a need for our patients, and strategies to increase awareness of allergen immunotherapy (AIT) among patients, the medical community, all healthcare stakeholders, and public opinion, are also reported in detail.

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.

Allergic rhinitis is one of the most prevalent chronic diseases in Europe. Besides nose symptoms such as sneezing and a blocked nose, patients also suffer from general complaints like fatigue, sleeping problems and difficulty concentrating. Allergic rhinitis can have a serious impact on the daily life of children, because it interferes with their social activities, hobbies and schoolwork. Allergen avoidance and symptomatic treatment will only result in short-term relief. Allergen-specific immu

Cytokines can be functionally active across species barriers. Bovine IL-10 has an amino acid sequence identity with human IL-10 of 76.8%. Therefore, the aim of this study was to evaluate whether bovine IL-10 has immunomodulatory activities on human monocytes and dendritic cells. Peripheral blood monocytes were isolated from healthy donors, and used directly or allowed to differentiate to dendritic cells under the influence of IL-4 and GM-CSF. Recombinant bovine IL-10 inhibited TLR induced activation of monocytes, and dose-dependently inhibited LPS-induced activation of monocyte-derived DCs comparable to human IL-10. By using blocking antibodies to either bovine IL-10 or the human IL-10 receptor it was demonstrated that inhibition of monocyte activation by bovine IL-10 was dependent on binding of bovine IL-10 to the human IL-10R. These data demonstrate that bovine IL-10 potently inhibits the activation of human myeloid cells in response to TLR activation. Bovine IL-10 present in dairy products may thus potentially contribute to the prevention of necrotizing enterocolitis and allergy, enhance mucosal tolerance induction and decrease intestinal inflammation and may therefore be applicable in infant foods and in immunomodulatory diets.

Immunotherapy is the only treatment for allergy that has the potential to alter the natural course of the disease. Sublingual immunotherapy for grass pollen-induced rhinoconjunctivitis has been developed to make immunotherapy available to a broader group of allergic patients. Here, a safe dose range and the safety during daily sublingual administration were investigated for a new tablet-based sublingual immunotherapy for grass pollen allergy. Simultaneously, immunological changes were monitored. A randomized, double-blind, placebo-controlled phase I trial was undertaken, with stepwise dose-escalation during the dose-finding period, and afterwards with daily dosing 8 weeks prior to and 15 weeks during the grass pollen season (2500, 25 000, or 75 000 standardized quality tablet [SQ-T] units, or placebo). Fifty-two participants with grass pollen-induced rhinoconjunctivitis and a positive skin prick test and specific IgE to Phleum pratense entered the trial. During the daily-dose treatment periods, 67% of the participants reported adverse events. The most frequent were itching in the mouth, eyes, or throat, and rhinitis, and most were mild and resolved within 1 day. Two participants withdrew due to adverse events (sting and blisters in the mouth and itching in the mouth). Time- and dose-dependent increases of P pratense-specific IgG, IgA, IgE, and IgE-competing components were found in serum during the first 8 weeks of daily dosing, indicating that the treatment had a significant allergen-specific effect on the immune system. In conclusion, the grass allergen tablet, administered in a dose of 75 000 SQ-T once daily, was well tolerated and displayed systemic immunogenicity.

Immunotherapy is the only treatment for allergy that has the potential to alter the natural course of the disease. Sublingual immunotherapy for grass pollen-induced rhinoconjunctivitis has been developed to make immunotherapy available to a broader group of allergic patients. Here, a safe dose range and the safety during daily sublingual administration were investigated for a new tablet-based sublingual immunotherapy for grass pollen allergy. Simultaneously, immunological changes were monitored. A randomized, double-blind, placebo-controlled phase I trial was undertaken, with stepwise dose-escalation during the dose-finding period, and afterwards with daily dosing 8 weeks prior to and 15 weeks during the grass pollen season (2500, 25 000, or 75 000 standardized quality tablet [SQ-T] units, or placebo). Fifty-two participants with grass pollen-induced rhinoconjunctivitis and a positive skin prick test and specific IgE to Phleum pratense entered the trial. During the daily-dose treatment periods, 67% of the participants reported adverse events. The most frequent were itching in the mouth, eyes, or throat, and rhinitis, and most were mild and resolved within 1 day. Two participants withdrew due to adverse events (sting and blisters in the mouth and itching in the mouth). Time- and dose-dependent increases of P pratense-specific IgG, IgA, IgE, and IgE-competing components were found in serum during the first 8 weeks of daily dosing, indicating that the treatment had a significant allergen-specific effect on the immune system. In conclusion, the grass allergen tablet, administered in a dose of 75 000 SQ-T once daily, was well tolerated and displayed systemic immunogenicity.

Immunotherapy is the only treatment for allergy that has the potential to alter the natural course of the disease. Sublingual immunotherapy for grass pollen-induced rhinoconjunctivitis has been developed to make immunotherapy available to a broader group of allergic patients. Here, a safe dose range and the safety during daily sublingual administration were investigated for a new tablet-based sublingual immunotherapy for grass pollen allergy. Simultaneously, immunological changes were monitored. A randomized, double-blind, placebo-controlled phase I trial was undertaken, with stepwise dose-escalation during the dose-finding period, and afterwards with daily dosing 8 weeks prior to and 15 weeks during the grass pollen season (2500, 25 000, or 75 000 standardized quality tablet [SQ-T] units, or placebo). Fifty-two participants with grass pollen-induced rhinoconjunctivitis and a positive skin prick test and specific IgE to Phleum pratense entered the trial. During the daily-dose treatment periods, 67% of the participants reported adverse events. The most frequent were itching in the mouth, eyes, or throat, and rhinitis, and most were mild and resolved within 1 day. Two participants withdrew due to adverse events (sting and blisters in the mouth and itching in the mouth). Time- and dose-dependent increases of P pratense-specific IgG, IgA, IgE, and IgE-competing components were found in serum during the first 8 weeks of daily dosing, indicating that the treatment had a significant allergen-specific effect on the immune system. In conclusion, the grass allergen tablet, administered in a dose of 75 000 SQ-T once daily, was well tolerated and displayed systemic immunogenicity.

AIMS: To evaluate the clinical efficacy of sublingual immunotherapy (SLIT) in respiratory allergy in children. METHODS: A systematic literature review was conducted. The search was focused on all the double blind (and double dummy if necessary) studies. Search strategy: Medline, Embase, Cochrane Controlled Trial Register, Abstract of Cochrane Airways Group, hand search, and archives of some SLIT producers. All the selected studies were assessed and evaluated for quality in a standardised independent way. RESULTS: Eight randomised, double blind, placebo controlled studies on SLIT were selected. Five studies were run with house dust mite (HDM), one with olive pollen, one with wall pellitory (Parietaria) pollen, and one with grass pollen. A quantitative evaluation of the studies was not possible because the outcomes and the results of single studies were presented according to different criteria. Therefore only qualitative analysis was performed. No clinically relevant results were shown, independently from statistical significance, in the use of SLIT for respiratory allergies due to seasonal allergens (olive, wall pellitory, and grass pollens) and, on the whole, for rhinoconjunctivitis due to HDM in children. For mild to moderate persistent asthma due to HDM, statistically significant and low to moderate relevant clinical effects were observed. CONCLUSIONS: SLIT can be currently considered to have low to moderate clinical efficacy in children of at least 4 years of age, monosensitised to HDM, and suffering from mild to moderate persistent asthma. This benefit seems to be adjunctive with respect to the environmental preventive measures against HDM.

"Sublingual immunotherapy (SLIT) represents a safer, more comfortable and more convenient allergen immunotherapy than its subcutaneous counterpart. There is an increasing body of evidence showing that SLIT for house dust mites (HDM), grass, ragweed and/or tree pollen improves allergic symptoms and asthma control. 1 It is unclear whether SLIT consistently reduces the occurrence of asthma attacks. [...]"