Years Of Sublingual Immunotherapy Research Articles

Baseline Severity and Disease Duration Can Predict the Response to Allergen-specific Immunotherapy in Allergic Rhinitis.

Allergen-specific immunotherapy (AIT) has confirmed its efficacy in improving the symptoms of allergic rhinitis. However, no reliable biomarkers have been identified to predict the efficacy of AIT were found. We aimed to find clinical and immunological markers to predict efficacy in children after 2 years of sublingual immunotherapy (SLIT). A total of 285 children diagnosed with allergic rhinitis were recruited. The clinical efficacy was evaluated by comparing endpoint and baseline symptom and medication scores (SMS). Baseline clinical and immunological markers (serum total and specific immunoglobulin [Ig]E) and their correlation with clinical efficacy were analyzed. Of the 285 children recruited, 249 completed the 2-year SLIT program. After 2 years of SLIT, 68.3% of the children showed a significant response. Children in the Remarkable Response Group had the highest baseline SMS and most extended disease duration, followed by the Effective Relief and Unresponsive Group. Correlation analysis demonstrated that SMS improvement was positively correlated with baseline SMS (r=0.67) and disease duration (r=0.35). SMS improvement was not correlated with age, body mass index, total or specific IgE levels, or their ratios. Our results show that baseline SMS and disease duration can predict the efficacy of SLIT. Our study can guide the selection of suitable candidates for SLIT.

Efficacy and immunological changes of sublingual immunotherapy in pediatric allergic rhinitis

BackgroundAllergen-specific immunotherapy, including subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), improves the disease progression of allergic rhinitis (AR). SCIT and SLIT exhibit similar efficacy, but SLIT has less systemic reactions. However, few studies have investigated the underlying mechanisms of SLIT treatment. In this study, we explored the efficacy of SLIT under different treatment durations and immunological changes. MethodsThis retrospective study was conducted from August 2017 to August 2022 in our hospital. A total of 314 children who underwent SLIT were divided into the following groups based on their treatment duration: the 1 year group (6 months–1 year), the 2 years group (1–2 years), and the 3 years group (2–3 years). The treatment efficacy was confirmed using a combined symptom and medication score (SMS). Multiple serum cytokines were measured using Luminex. Various immune cells in PBMCs were determined using flow cytometry. ResultsThe total nasal symptom score (TNSS), rescue medication score (RMS), and SMS of the 3 years group was significantly different from those of the 1 years and 2 years groups. At the end of the 2 years following cessation of SLIT, the following results were observed in the 3 years group: 1) the TNSS, RMS, and SMS had significantly improved, 2) the serum IL-10, TGF-beta, and IL-35 levels had increased significantly, and 3) the percentages of regulatory T cell, regulatory B cell, and follicular regulatory T cell increased significantly. ConclusionOur results suggest that 3 years of SLIT is necessary for long-term effects and continued immunological changes.

Serum Soluble ST2 Correlated with Symptom Severity and Clinical Response of Sublingual Immunotherapy for House Dust Mite-Induced Allergic Rhinitis Patients.

Background Suppressor of tumorigenicity 2 (ST2) is a key biomarker in inflammation and cardiovascular diseases, but limited data is available on its role in allergic rhinitis (AR). Objective The aim of this study is to explore the role of serum soluble ST2 (sST2) in evaluating disease severity and predicting the efficacy of sublingual immunotherapy (SLIT) in house dust mite- (HDM-) induced AR patients. Methods Eighty healthy controls (HC group) and 160 HDM-induced AR patients, including 40 mild patients (MAR group) and 120 moderate-severe patients (MSAR group), were recruited in this study. Serum was collected from all participants and levels of sST2 were determined by ELISA and the relationship between sST2 levels and disease severity was assessed. In the MSAR group, 109 patients received 3 years of SLIT, and the relationship between serum levels of sST2 and efficacy of SLIT was exampled. Results Serum sST2 levels were increased in HDM-induced AR patients compared to the HC group (P < 0.001), and the concentrations were higher in the MSAR group than in the MAR group and HC group (all P < 0.05). Moreover, sST2 levels positively correlated with the total nasal symptom score (TNSS), visual analogue scale (VAS), and specific IgE levels (P < 0.05). Seventy-eight MSAR patients accomplished SLIT, and they were divided into an effective group (n = 40) and an ineffective group (n = 38). The serum sST2 levels in the effective group were lower than those in the ineffective group (P < 0.001). In addition, patients in the effective group levels exhibited significantly lower sST2 levels post-SLIT than pre-SLIT (P < 0.001), but no statistic difference was observed in the ineffective group (P > 0.05). Receiver operating characteristic (ROC) curve showed promising accuracy for predicting clinical efficacy of SLIT in AR patients (area under the curve = 0.839, P < 0.001). Conclusion Serum sST2 is a potential biomarker for assessing disease severity and may serve as a sensitive biomarker for predicting the therapeutic response of SLIT in HDM-induced AR patients.

Early Response of Specific IgE can Predict Satisfaction with Sublingual Immunotherapy.

To investigate predictive parameters at baseline and during the early response to sublingual immunotherapy (SLIT) for house dust mites in allergic rhinitis patients. Retrospective cohort study. Patients were treated with SLIT for at least 3 years and serological tests performed at baseline and at 1-year follow-up to investigate predictive parameters. Satisfaction with SLIT, 4 nasal symptoms, and quality of life were evaluated before and after 3 years of SLIT. Sixty-one patients were enrolled and divided into two groups depending on their satisfaction after 3 years of SLIT: 43 were satisfied (70.5%) and 18 were not (29.5%). Immunological parameters at baseline did not differ significantly between the satisfactory and unsatisfactory groups. However, changes in both Dermatophagoides pteronyssinus (Dp)- and D. farinae (Df)-specific IgEs were significantly higher in the unsatisfactory group than in the satisfactory group during the early response to SLIT (P = .006 and P = .045, respectively). The changes in both Dp- and Df-specific IgE levels during early response may be indicators for favorable long-term treatment outcomes with SLIT. These results suggest that clinicians could measure these immunological parameters 1 year after Dp and Df SLIT to indicate potential responders versus nonresponders. 2b Laryngoscope, 131:467-472, 2021.

House Dust Mite Sublingual Immunotherapy in Children Versus Adults With Allergic Rhinitis.

There are only a few studies in which the clinical efficacy of SLIT has been compared between children and adults. In addition, there is a lack of research on other factors, associated with the treatment, including immunological parameters and quality of life (QOL). To compare the effects of sublingual immunotherapy (SLIT) in adults and children on various factors: clinical efficacy, quality of life (QOL), satisfaction, immunological parameters, and adverse events. Subjects who were sensitized to house dust mites and treated with SLIT for at least 2 years were enrolled. Seventy patients who completed questionnaires measuring nasal symptoms and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores and underwent serologic tests for immunological parameters at initial, 1-year, and 2-year follow-up were selected and divided into two groups based on age: a child group (age 4-12 years, n = 44) and an adult group (age 19-59 years, n = 26). The Total Nasal Symptom Score (TNSS) was significantly decreased after 2 years of SLIT in both the child and adult groups (p < 0.001, both); however, changes in TNSS from baseline did not significantly differ between the two groups (p = 0.365). More patients in adult group were satisfied with SLIT than those in child group (p = 0.050), and changes in RQLQ score from baseline tended to be larger in adult group (p = 0.089). The levels of immunological parameters at baseline were significantly higher in the child group than in the adult group; however, changes in the levels of these parameters were not significantly different. Although more adult patients were satisfied with SLIT, the clinical effects of SLIT on nasal symptoms were comparable between child and adult groups. Despite different immunological values at baseline between the two groups, changing patterns of immunological parameters did not differ.

Comparison of immunologic modification after 2 years of sublingual immunotherapy with house dust mite extract between mono- and poly-sensitized patients

Comparison of immunologic modification after 2 years of sublingual immunotherapy with house dust mite extract between mono- and poly-sensitized patients

30 years of sublingual immunotherapy.

Allergen Immunotherapy (AIT) was introduced in clinical practice on an empirical basis more than 100years ago. Since the first attempts, AIT was administered subcutaneously. Indeed, other routes of administration were proposed and studied, in particular to improve the safety, but only the sublingual route (SLIT) achieved a credibility based on evidence and was then accepted as a viable "alternative" option to the subcutaneous route. SLIT was largely used in clinical trials and clinical practice in this last 30years. Thus, a large amount of data is available, coming from either controlled trials and postmarketing surveillance studies. It is clear that SLIT is overall effective, but it is also clear that the efficacy is not "class-related," as derived from meta-analyses, but restricted to each specific product. The 30-year lasting use of SLIT allowed to clarify many clinical aspects, such as efficacy, safety, use in asthma, regimens of administration, and optimal doses. In parallel, the mechanisms of action of AIT were elucidated, and new indications were proposed (eg food allergy, atopic dermatitis). In addition, the introduction of molecular-based diagnosis, allowed to better refine the prescription of SLIT, based on specific sensitization profiles. The present article will describe the origin and evolution of SLIT for respiratory allergy, taking into account the clinical context that suggested this form of treatment, the recently developed aspects, the future perspectives and unmet needs, This is not, therefore, a systematic review, rather a narrative historical description of the past history, and a look forward to the future opportunities.

Immunologic modification in mono- and poly-sensitized patients after sublingual immunotherapy.

To compare immunologic modification and treatment outcomes after 2 years of sublingual immunotherapy (SLIT) with house dust mite extracts (HDM) between monosensitized and polysensitized patients with allergic rhinitis. Retrospective cohort study. Among the patients who were prospectively enrolled in the SLIT cohort study, patients with allergic rhinitis who were sensitized to HDM and treated with SLIT for at least 2 years were studied. All participants underwent serologic tests at baseline and after SLIT to evaluate changes in immunologic parameters. The total nasal symptom score (TNSS) was measured before and after SLIT, and effective and less effective responder groups were categorized depending on whether patients had a TNSS reduction of 50%, as compared with baseline. The increase in Dermatophagoides pteronyssinus and Dermatophagoides farinae specific immunoglobulin G4 levels was significantly higher in monosensitized patients than in polysensitized patients (P = .020 and P = .005, respectively). The TNSS significantly improved after SLIT in both the monosensitized and polysensitized groups (P < .001 in both groups). However, the difference in the changes in TNSS from baseline was not significant between the two groups (P = .374). This study demonstrated different immunologic modifications after SLIT between monosensitized and polysensitized patients. However, patients in the polysensitized group who were treated with single-allergen SLIT experienced clinical improvement in TNSS that was comparable with that in the monosensitized group despite demonstrating different immunologic changes. 2b Laryngoscope, 129:E170-E177, 2019.

Effect of 2 Years of Treatment With Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at 3 Years Among Patients With Moderate to Severe Seasonal Allergic Rhinitis

Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment. To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up. A randomized double-blind, placebo-controlled, 3-parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015. Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation). Total nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy. Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score for the sublingual immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5.48) at 3 years, and for the placebo group, the score was 6.06 (95% CI, 5.23 to 6.88) at pretreatment and 4.81 (95% CI, 3.97 to 5.65) at 3 years. The between-group difference (adjusted for baseline) was -0.18 (95% CI, -1.25 to 0.90; [P = .75]). Among patients with moderate to severe seasonal allergic rhinitis, 2 years of sublingual grass pollen immunotherapy was not significantly different from placebo in improving the nasal response to allergen challenge at 3-year follow-up. clinicaltrials.gov Identifier: NCT01335139; EudraCT Number: 2010-023536-16.

Evaluation of a sublingual immunotherapy solution in olive-induced respiratory allergy in Jordan: a retrospective observational study.

BackgroundOlive pollen is an important cause of respiratory allergy in the Middle East. In this study, the clinical characteristics of adults and children with confirmed allergic rhinitis (AR; with or without asthma) in Jordan were described, and the use of sublingual immunotherapy (SLIT) in a real-life clinical setting was assessed.MethodsThis retrospective observational study evaluated the clinical features of olive-induced allergy and the use of an SLIT solution of standardized extracts toward Ole e 1 given in a pre- and coseasonal scheme with a daily dose of 300 index of reactivity for two consecutive seasons. Inclusion criteria were as follows: ≥5 years of age, AR, proven olive sensitization, and at least 2 years follow-up after SLIT initiation. The following data were recorded at SLIT initiation: clinical characteristics, rhinitis and asthma symptom scores, and concomitant symptomatic medications. During follow-up and at the end of each season, the following data were recorded: symptom progression/scores, any changes to symptomatic medications, and treatment compliance. The secondary objective was to determine any effect on quality of life, use of concomitant AR medications, and treatment compliance.ResultsEighty-six patients with seasonal AR were included in this analysis (52.3% with coexisting asthma). Between the initiation of treatment and the end of second pollen season, symptoms of AR and asthma were decreased by 79.5% and 41.7%, respectively, with an improvement in quality of life score in 71.5% of the patients (P<0.0001 for all). Physicians reported that after 2 years of SLIT, there was an improvement in the symptoms of both AR (95.2%) and asthma (93.3%), with 98.8% of the patients showing good treatment compliance. A reduction in symptomatic medications was also found. SLIT was well tolerated with no systemic reactions being reported.ConclusionIn children and adults with olive-associated respiratory allergy in Jordan, the use of a pre- and coseasonal SLIT with a 300 index of reactivity daily dose is effective in reducing the clinical burden of AR and asthma with no tolerability issues.

Three-Year Follow-up Results of Sublingual Immunotherapy in Patients With Allergic Rhinitis Sensitized to House Dust Mites.

PurposeThis study investigated the long-term efficacy, safety, and compliance associated with sublingual immunotherapy (SLIT) in Korean patients with allergic rhinitis sensitized to house dust mites.MethodsThis is a retrospective cohort study. A total of 164 patients who were sensitized to Dermatophagoides pteronyssinus and Dermatophagoides farinae and who received SLIT were enrolled between November 2007 and January 2010. Each patient was followed up using a diary card, on which a symptom score, rescue medication score, and adverse events (AEs) were recorded.ResultsAll allergic rhinitis symptoms improved after 3 years of SLIT (P<0.05), and the rescue medication score decreased with time (P<0.05). The incidence of AEs associated with SLIT was 31% (51 of 164 patients) during the first month of therapy, and there were no severe AEs. The dropout rate was 19.5% (32 of 164 patients) during the first month, 34% (56 of 164 patients) after 6 months, and 41% (68 of 164 patients) after 1 year of SLIT. The 3-year compliance rate was approximately 40% (65 of 164 patients). The most common causes of dropout during the first month of SLIT were high cost and inconvenience. The improvement in allergic symptoms was the most common cause of dropout after 6 months.ConclusionsAllergic symptoms significantly decreased after 1 year of SLIT treatment, and this effect was sustained after 2 or 3 years of treatment. By increasing compliance through patient education, the 3-year use of SLIT for house dust mite allergies may be effective in the management of allergic rhinitis.

Immunological mechanisms of sublingual allergen-specific immunotherapy

Within the last 100 years of allergen-specific immunotherapy, many clinical and scientific efforts have been made to establish alternative noninvasive allergen application strategies. Thus, intra-oral allergen delivery to the sublingual mucosa has been proven to be safe and effective. As a consequence, to date, sublingual immunotherapy (SLIT) is widely accepted by most allergists as an alternative to conventional subcutaneous immunotherapy. Although immunological mechanisms remain to be elucidated in detail, several studies in mice and humans within recent years provided deeper insights into local as well as systemic immunological features in response to SLIT. First of all, it was shown that the target organ, the oral mucosa, harbours a sophisticated immunological network as an important prerequisite for SLIT, which contains among other cells, local antigen-presenting cells (APC), such as dendritic cells (DCs), with a constitutive disposition to enforce tolerogenic mechanisms. Further on, basic research on local DCs within the oral mucosa gave rise to possible alternative strategies to deliver the allergens to other mucosal regions than sublingual tissue, such as the vestibulum oris. Moreover, characterization of oral DCs led to the identification of target structures for both allergens as well as adjuvants, which could be applied during SLIT. Altogether, SLIT came a long way since its very beginning in the last century and some, but not all questions about SLIT could be answered so far. However, recent research efforts as well as clinical approaches paved the way for another exciting 100 years of SLIT.

Efficacy of Long-term Sublingual Immunotherapy as an Adjunct to Pharmacotherapy in House Dust Mite-Allergic Children With Asthma

Ozdemir C, Yazi D, Gocmen I, et al. Pediatr Allergy Immunol. 2007;18(6):508–515 PURPOSE OF THE STUDY. To evaluate the effect of 3 years of dust mite sublingual immunotherapy (SLIT) on clinical and laboratory outcome measurements. STUDY POPULATION. This was a prospective study of 90 children aged 4 to 16 years who were followed for 4 years from the time of enrollment. Inclusion criteria were mild-to-moderate persistent asthma requiring an inhaled steroid, monosensitization to dust mite, and no previous history of immunotherapy. METHODS. Participants were randomly assigned to treatment for 3 years with dust mite SLIT plus standard pharmacotherapy or pharmacotherapy alone. The prescribed SLIT solution consisted of 50% Dermatophagoides pteronyssinus and 50% Dermatophagoides farinae. Doses were increased gradually to a maintenance dose, which was taken 2 times per week. All participants were initially started on 800 μg/day of inhaled budesonide. Follow-up visits were performed every 2 to 3 months, at which times the inhaled corticosteroid (ICS) dose was decreased until either it was discontinued or the minimum dose allowing for control of symptoms was reached. Pulmonary-function testing was performed at each visit. Skin-prick testing to 15 aeroallergens and a serum total immunoglobulin E measurement were performed annually. RESULTS. A total of 90 children were randomly assigned: 62 to SLIT plus pharmacotherapy and 28 to pharmacotherapy alone. There were 19 drop-outs (31%) in the SLIT group after 3 years compared with 5 (18%) in the pharmacotherapy group. The number of months per year in which the children required ICS, as well as mean dose per day of budesonide, was significantly lower in the SLIT group compared with pharmacotherapy group during all 3 years. By the end of the 3 years, 52.4% in the SLIT group versus 9.1% in the pharmacotherapy group were able to successfully discontinue ICSs for at least 6 months. Both forced expiratory volume in 1 second and forced expiratory flow, midexpiratory phase, were significantly increased from baseline in the SLIT group after 3 years, whereas the pharmacotherapy controls showed no change. Total immunoglobulin E levels were significantly decreased only in the SLIT group after 3 years. Finally, there were no serious adverse reactions during the study. CONCLUSIONS. Three years of SLIT as an adjunct to pharmacotherapy in house dust mite–allergic children with asthma resulted in a reduction of the necessity for ICS usage along with improvement in lung functions. REVIEWER COMMENTS. This study adds to the body of work defining SLIT as a modality that is capable of providing clear but modest benefit in the treatment of allergic airway disease. The primary focus was on evaluating the steroid-sparing effect of SLIT. Unfortunately, symptom scores and rescue-medication usage were not reported. There was a 31% drop-out rate after 3 years among the SLIT group, compared with 18% among the pharmacotherapy group. So, although there may be some compliance advantage in SLIT over injection immunotherapy, there are clearly still some adherence challenges. This study demonstrates that the addition of SLIT to standard pharmacotherapy can provide a significant decreases in ICS usage and modest increases in lung function over the course of 3 years of treatment.

Efficacy of long‐term sublingual immunotherapy as an adjunct to pharmacotherapy in house dust mite‐allergic children with asthma

Although sublingual immunotherapy (SLIT) is accepted to be a viable alternative of specific-allergen immunotherapy, the efficacy of long-term SLIT in asthmatic children is not well established. The efficacy of 3 yr of SLIT in addition to pharmacotherapy was compared with pharmacotherapy alone in a prospective, open, parallel-group, controlled study. Children with asthma aged 4-16 yr, sensitive to house dust mite (HDM) were followed up for a run-in period of 1 yr and then grouped as those who would receive SLIT + pharmacotherapy (n = 62) or pharmacotherapy alone (n = 28). All patients were evaluated based on symptom-medication scores and lung function tests every 3 months, as well as skin-prick test and serum total immunoglobulin E (IgE) levels annually for 3 yr. Children in the SLIT + pharmacotherapy group demonstrated significantly lower mean daily dose and annual duration of inhaled corticosteroid (ICS) usage when compared with controls. At the end of the 3 yr, within-group comparisons revealed statistically significant decreases in the dose and duration of ICS only in the SLIT group. Furthermore, 52.4% of subjects in the SLIT + pharmacotherapy group were able to discontinue ICS treatment for at least 6 months, which was only 9.1% for the pharmacotherapy group. Three years of SLIT as an adjunct to pharmacotherapy resulted in reduction of both the duration and dose of ICSs and successful discontinuation of ICSs along with improvement in lung functions in HDM-allergic children with asthma.

Long‐Term Efficacy of Sublingual Immunotherapy in Patients With Perennial Rhinitis

Sublingual immunotherapy has a documented clinical efficacy, but only a few long-term studies have been performed in people with perennial rhinitis. The purpose of this study was to evaluate the long-term efficacy of sublingual immunotherapy. One hundred thirty-seven patients with allergies to house dust mites were treated with sublingual house dust-mite-specific immunotherapy for 2 or 3 years and were also observed for 3 years after discontinuation of the treatment. The patients were divided into 2 groups: group A (67 patients) received active treatment for 2 years and then 1 year for placebo, and group B (70 patients) received active treatment for 3 years. The success of the treatment was evaluated with the symptom score, skin prick test results, and the nasal allergen challenge score. According to our study results, we found a greater improvement in the 3 years of sublingual immunotherapy compared with the 2 years of sublingual immunotherapy when we looked at the comparative results of the total 6 years. We suggest 3 years of sublingual immunotherapy for patients with perennial allergic rhinitis who require immunotherapy and do not accept the subcutaneous route of allergen administration.

Clinical efficacy and safety of preseasonal sublingual immunotherapy with grass pollen carbamylated allergoid in rhinitic patients. A double-blind, placebo-controlled study

Background The aim of this study was to confirm the clinical efficacy and safety of a preseasonal sublingual immunotherapy (SLIT) in a group of allergic patients with seasonal rhinoconjunctivitis with or without mild intermittent or mild persistent asthma. The immunotherapy was administered through the oral mucosa with a monomeric carbamylated allergoid (allergoid SLIT) for grass pollens. A secondary endpoint was to evaluate the effect of the allergoid SLIT on nasal reactivity. Methods and results A single-center, randomized, double-blind, placebo-controlled study was performed.Patients were selected and randomly allocatedto two groups: one group received active treatment (allergoid SLIT) for 2 years and the otherreceived placebo. Both groups received the necessary drug treatment throughout the trial. Thirty-three outpatients (20 men and 13 women, mean age: 30 years; range: 19-43) attending our center were enrolled in the study. Symptoms and medications were scored on diary cards during the pollen season. An allergen nasal challenge was performed at baseline and after 2 years of SLIT to evaluate nasal reactivity. Because the clinical scores were non-normally distributed, the Mann-Whitney and the Chi-square tests for intergroup comparisons and the Wilcoxon test for intragroup comparisons were used. The results were evaluated after 1 and 2 years of treatment. Between the first and second years of treatment, no changes in the scores for the placebo group were found, while for the active vaccine group significant decreases were found in rhinorrhea (p < 0.03), sneezing (p < 0.03), and conjunctivitis (p < 0.02). Symptom scores after nasal challenge decreased (p < 0.03) after 2 years’ treatment. Nasal steroid use significantly decreased in the active treatment group during May and June in both the years of treatment (p < 0.02). Only two mild local adverse events were reported in the active group and none was reported in the placebo group. Conclusions The results of this study show thatthe allergoid SLIT is safe and effective in decreasing symptom scores and drug use in rhinitic patients allergic to grass pollen.

Lack of Detectable Alterations in Immune Responses during Sublingual Immunotherapy in Children with Seasonal Allergic Rhinoconjunctivitis to Grass Pollen

Background: Recent work indicates that subcutaneous specific immunotherapy induces specific T-cell anergy, a shift in the TH1/TH2 ratio, and antibody production in favor of IgG4. There are few data on sublingual immunotherapy (SLIT), especially in children. Methods: We assessed the proliferation of peripheral blood mononuclear cells (³H-thymidine incorporation) and secretion of interleukin (IL)-4, interferon (IFN)γ and IL-5 (ELISA) after in vitro stimulation with allergen or phytohemagglutinin (PHA) in 29 children with allergic rhinoconjunctivitis receiving SLIT with grass pollen before, and after 1 and 2 years of treatment in a multicenter placebo-controlled study on the efficacy of the treatment. Further, non-specific intracellular production of IL-4, IL-13, IFNγ, IL-2, IL-10 and IL-5 (FACS) and serum total and specific IgE and IgG4 (ELISA) were analyzed. Results: Proliferation and IL-4 and IL-5 secretion after stimulation with allergen or PHA did not differ between the groups. In addition, we observed no effect of SLIT on intracellular cytokine production. IFNγ secretion after allergen coculture was comparable between the groups. Following PHA stimulation, IFNγ secretion was significantly higher in the SLIT group after 1 year, and a trend was observable already before and after 2 years of treatment, probably due to the inhomogeneity in the groups despite randomization (for age and asthma). No significant changes were observed for sIgE/sIgG4 ratios over time either in or between the groups. Conclusion: During 2 years of SLIT in children with a positive effect on rescue medication use, we observed no significant effects on in vitro T-cell immune responses or immunoglobulins. So far, pediatric studies demonstrating stable effects of SLIT on such reactions are missing, probably due to limited effects of SLIT on systemic immunologic reactions.