Efficacy of Adjuvant Sublingual Immunotherapy After Septomeatoplasty.

BACKGROUND: The efficacy of adjuvant sublingual immunotherapy (SLIT) in correcting structural problems in patients with allergic rhinitis (AR) caused by mite who have undergone septomeatoplasty (SMP) has not been studied. METHODS: This non-randomized controlled study recruited patients with AR (caused by mite) and concurrent septal deviation and inferior turbinate hypertrophy, at a tertiary hospital in Taiwan. SMP was performed on all patients as a surgical intervention. The patients were then divided into two groups: the control group, which underwent surgery only, and the experimental group, which received SLIT as an adjuvant treatment. Demographic data and rhinitis control assessment test (RCAT) results were analyzed. RESULTS: A total of 96 patients were enrolled in the study (SMP + SLIT group, n = 52; SMP only group, n = 44). No significant differences were observed in any of the variables between the two groups before and one month after surgery. However, during evaluations at the third and sixth month, the SMP + SLIT group showed significant improvement in the total RCAT scores compared to the SMP only group (28.6 ± 1.56 vs. 24.5 ± 3.66, p < 0.001; 27.1 ± 2.87 vs. 19.9 ± 5.56, p < 0.001). In addition, significantly better control of all RCAT sub-categories was observed in the SMP + SLIT group at the third and sixth month evaluations. CONCLUSIONS: SLIT may serve as an ideal adjuvant therapy after SMP in patients with AR. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3073-3079, 2024.

Immune Cell Alterations and PI3K-PKB Pathway Suppression in Patients with Allergic Rhinitis Undergoing Sublingual Immunotherapy.

INTRODUCTION: Our prior clinical study assessed the efficacy and safety of sublingual immunotherapy (SLIT) with standardized Dermatophagoides farina drops on patients with allergic rhinitis (AR) while analyzing the characteristics of adverse reactions. This study was conducted to evaluate the immune cell composition alterations in AR patients before and after SLIT, and to comprehensively investigate the role and changes of antigen-specific immune cells associated with treatment efficacy. METHODS: A total of 68 AR patients who completed 12 months of SLIT were included in the study. Before the trial's initiation and after 1 year of SLIT, 10 ml of venous blood was collected. Peripheral blood mononuclear cells were isolated using the Ficoll gradient method. The mRNA transcriptome was analyzed using an Affymetrix microarray. The proportions of 22 immune cell types were calculated via the CIBERSORTx platform. Correlations between each immune cell type and SLIT were analyzed. PI3K-PKB pathway dysregulation were analyzed using quantitative PCR and Western blot. Flow cytometry was utilized to assess the percentages of Th1 and Th2 cells. RESULTS: Mono-sensitized AR patients exhibited marked increases in plasma cells, activated memory T cells, regulatory T cells, and activated dendritic cells, while experiencing decreased neutrophils and resting dendritic cells. In poly-sensitized AR patients, the most notable change was an increase in regulatory T cells, coupled with decreased T follicular helper cells, resting dendritic cells, and activated mast cells. These findings indicated that SLIT reshaped immune cell profiles in AR patients, and, notably, the specific changes differed between mono-sensitized and poly-sensitized individuals. Furthermore, SLIT appeared to shift the immune response towards a Th2 decrease profile in both groups. Importantly, suppression of the PI3K-PKB pathway was evidenced as inhibition of PKB phosphorylation and the decrease of glycogen synthase kinase 3 ß (GSKß) and mammalian target of rapamycin (mTOR) expression after SLIT. CONCLUSION: Our study has demonstrated that SLIT treatment led to distinct changes in immune cell profiles between mono-sensitized and poly-sensitized AR patients. Furthermore, SLIT appeared to reduce a Th2 immune response, highlighting its efficacy in AR treatment. Importantly, the study revealed the suppression of the PI3K-PKB pathway, shedding light on the immunological mechanisms underlying SLIT's effectiveness.

Evaluation of the quality of guidelines for sublingual immunotherapy of allergic rhinitis.

BACKGROUND: Guidelines are intended to facilitate evidence-based clinical decision-making and knowledge translation; however, the quality and rigor of the guidelines are different. This study was conducted to assess the quality of sublingual immunotherapy guidelines for allergic rhinitis, in order to provide a reference for evidence-based clinical treatment and management of sublingual immunotherapy. METHODS: Using both Chinese and English search methods, articles were obtained from PubMed, Cochrane, Web of Science, CNKI, CBM, WanFang Data, VIP, and other databases from the construction of the database to September 2020. The AGREE II instrument was used by two researchers to independently evaluate the quality of the extracted articles, and the consistency of the researchers was evaluated using the inter-group correlation coefficient. RESULTS: Ten articles were included in this study, of which two articles ranked A level, six articles ranked B level, and two articles ranked C level. The six sections of AGREE II included scope and aim, clarity, participant, applicability, rigor, and editorial independence, with standardized scores of 78.06%, 45.83%, 42.81%, 77.50%, 50.42%, and 46.25%, respectively. CONCLUSION: The quality of the current guidelines for sublingual immunotherapy is average. The formulation methodology and reporting standards of these guidelines must be developed. By standardizing the treatment of sublingual immunotherapy properly, it is recommended that guideline makers refer to the AGREE II to formulate high-quality guidelines and promote their wide application.

Extraction, Purification, and Development of Sublingual Film (SLIT Films) Comprising Cockroach Allergen for Treatment of Allergy.

AIM: Allergy associated with cockroaches are mostly from the American cockroach (Periplaneta americana) and German cockroach (Blattella germanica). The effective and safe treatment for cockroach allergy is Sublingual immunotherapy (SLIT). In this study, SLIT Films containing purified allergen extract of Periplaneta americana were prepared by solvent casting and were evaluated for their efficiency in delivery. METHODOLOGY: Cockroach allergen extract was prepared and purified by ultrafiltration and chromatography. The molecular weight of protein content was identified and estimated by SDS- PAGE and ELISA. SLIT films were developed by the Quality by Design (QbD) approach and were evaluated for allergen- excipient compatibility, swelling index, taste, diffusion, in vitro dissolution, local toxicity, and stability analysis. RESULTS: Cockroach allergen protein extracts (cut-off 25-71KDa) were identified by SDS-PAGE and quantified by indirect ELISA and further selected for sublingual film preparation. The indirect ELISA results show a higher optical density (OD) value compared to crude extract. The weight uniformity and thickness of the film were between 13-18 mg and 0.04-0.06 mm. The disintegration time was found to be less than 1 min. The cumulative percentage release was also found to be satisfactory. The local toxicity study indicated no signs of irritation in the buccal mucosa of rabbits. The optimised F3 film had uniform thickness, faster disintegration and drug content within pharmacopeial limits. Ex vivo study revealed better permeability with 90% release of allergen in 7 minutes. The formulation was also stable at room temperature during the study period. CONCLUSION: SLIT Film containing cockroach allergen from Periplaneta americana was successfully developed and evaluated. SLIT films of cockroach allergen could be more beneficial and convenient for emergency use in patients when compared to subcutaneous immunotherapy. SLIT films provide dose accuracy and are a promising alternative for SCIT and SLIT drops and tablets.

Ragweed sublingual immunotherapy (SLIT) tablets in allergic rhinoconjunctivitis: a systematic review and meta-analysis.

PURPOSE: Ragweed allergen causes Allergic rhinoconjunctivitis and sublingual immunotherapy is one of the treatment modalities to desensitize allergic individuals. This systematic review assesses the effectiveness and safety of sublingual immunotherapy for allergic rhinoconjunctivitis caused due to Ragweed. METHODS: The databases search was done through December 2020. English-language randomized controlled trials were included if they compared sublingual immunotherapy with placebo, pharmacotherapy, or other sublingual immunotherapy regimens, and reported clinical outcomes. The strength of the evidence for each comparison and outcome was graded based on the risk of bias, consistency, magnitude of effect, and the directness of the evidence. RESULTS: The searches performed according to the protocol identified 134 abstracts of which 67 were duplicates. A total of 37 full papers were therefore reviewed of which 5 were included for the final study. Participants' ages ranged from 4 to 58 years. The risk of bias was low in most studies. The review suggests that sublingual immunotherapy improves rhinoconjunctivitis symptoms, with 4 of 4 studies reporting efficacy showed improvement in the symptom score of SLIT groups compared to placebo. Local reactions were frequent, but anaphylaxis was not reported in any of the studies. Serious adverse events were very few in all the studies. CONCLUSIONS: The overall evidence showed the effectiveness of sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis with or without asthma, but high-quality studies are still needed to answer questions regarding optimal dosing strategies.

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.

Decrease in CD38+ TH2A cell frequencies following immunotherapy with house dust mite tablet correlates with humoral responses.

BACKGROUND: In line with evidence for a role of pathogenic TH2A in seasonal allergies, we previously showed that individuals suffering from food allergy exhibited a decrease in circulating TH2A cells following multi-food immunotherapy. Herein, we aim to confirm the decline of TH2A cells in individuals undergoing house dust mite immunotherapy (HDM-AIT) and extend our observation to a new subset of CD38 expressing activated TH2A cells. METHODS: The frequencies of TH2A and CD38+ TH2A cells were analysed by flow cytometry in blood cells from 182 Japanese HDM-allergic individuals included in a 1-year clinical trial assessing the efficacy of HDM tablets. Interrelationship between these cellular responses and humoral mite-specific IgE and IgG4 levels was further explored. RESULTS: A decrease in TH2A cells was observed in both active and placebo groups. Interestingly, CD38+ TH2A cell frequencies significantly decreased only in active groups. In younger individuals (16-30 years), both TH2A and CD38+ TH2A cells were significantly reduced in active groups but not in the placebo group. Significant inverse correlations were observed in the course of HDM-AIT between changes in TH2A or CD38+ TH2A frequencies and IgG4 antibody levels. CONCLUSIONS: We confirm the value of monitoring TH2A cell frequencies in allergic individuals and extend this observation to perennial allergy to HDM. We highlight the interest of CD38 to better identify the subset of TH2A cell down-regulated by AIT. Finally, correlated cellular and humoral responses observed in immunoreactive individuals stress that coordinated pathways occur in the adaptive responses during AIT.

Bet v 1 contiguous overlapping peptides anchored to virosomes with TLR4 agonist enhance immunotherapy efficacy in mice.

BACKGROUND: Whereas sublingual allergen immunotherapy (AIT) is routinely performed without any adjuvant or delivery system, there is a strong scientific rationale to better target the allergen(s) to oral dendritic cells known to support regulatory immune responses by using appropriate presentation platforms. OBJECTIVE: To identify a safe presentation platform able to enhance allergen-specific tolerance induction. METHODS: Virosomes with membrane-integrated contiguous overlapping peptides (COPs) of Bet v 1 and TLR4 or TLR2/TLR7 agonists were assessed for induction of Bet v 1-specific IgG1, IgG2a and IgE antibodies, hypersensitivity reactions and body temperature drop following subcutaneous injection in naive CD-1 mice. The most promising candidate, Bet v 1 COPs anchored to virosomes with membrane-incorporated TLR4 agonist (Vir.A-Bet v 1 COPs), was further evaluated by the sublingual route in a therapeutic setting in BALB/c mice with birch pollen-induced allergic asthma. Airway hyperresponsiveness, pro-inflammatory cells in bronchoalveolar lavages and polarization of Th cells in the lungs and spleen were then assessed. RESULTS: Both types of adjuvanted virosomes coupled to Bet v 1 COPs triggered a boosted Th1 immunity. Given a more favourable safety profile, Vir.A-Bet v 1 COPs were further evaluated and shown to able to fully reverse asthma symptoms and lung inflammation in a sublingual therapeutic model of birch pollen allergy. CONCLUSIONS AND CLINICAL RELEVANCE: We report herein for the first time on the capacity of a novel and safe presentation platform, that is virosomes with membrane-integrated TLR4 agonist, to improve dramatically sublingual AIT efficacy in a murine model due to its intrinsic dual properties of targeting and stimulating to further promote anti-allergic immune responses. As such, our study paves the ground for further clinical development of this allergen presentation platform for patients suffering from respiratory allergies.

Adjuvanting Allergen Extracts for Sublingual Immunotherapy: Calcitriol Downregulates CXCL8 Production in Primary Sublingual Epithelial Cells.

Application of allergens onto the sublingual epithelium is used to desensitize allergic individuals, a treatment known as sublingual immunotherapy. However, the response of sublingual epithelial cells to house dust mite allergen and potential tolerance-promoting adjuvants such as Toll-like receptor (TLR) ligands and calcitriol has not been investigated. In order to study this, primary sublingual epithelial cells were isolated from dogs and cultured in vitro. After 24-h incubation with a Dermatophagoides farinae extract, a Dermatophagoides pteronyssinus extract, TLR2 ligands (FSL-1, heat-killed Listeria monocytogenes, Pam3CSK4), a TLR3 ligand (poly I:C), a TLR4 ligand [lipopolysaccharide (LPS)], and calcitriol (1,25-dihydroxyvitamin D3), viability of the cells was analyzed using an MTT test, and their secretion of interleukin 6 (IL-6), IL-10, CXCL8, and transforming growth factor ß1 (TGF-ß1) was measured by enzyme-linked immunosorbent assay. Additionally, to evaluate its potential effect as an adjuvant, sublingual epithelial cells were incubated with calcitriol in combination with a D. farinae extract followed by measurement of CXCL8 secretion. Furthermore, the effect of D. farinae and calcitriol on the transcriptome was assessed by RNA sequencing. The viability of the sublingual epithelial cells was significantly decreased by poly I:C, but not by the other stimuli. CXCL8 secretion was significantly increased by D. farinae extract and all TLR ligands apart from LPS. Calcitriol significantly decreased CXCL8 secretion, and coadministration with D. farinae extract reduced CXCL8 concentrations to levels seen in unstimulated sublingual epithelial cells. Although detectable, TGF-ß1 secretion could not be modulated by any of the stimuli. Interleukin 6 and IL-10 could not be detected at the protein or at the mRNA level. It can be concluded that a D. farinae extract and TLR ligands augment the secretion of the proinflammatory chemokine CXCL8, which might interfere with sublingual desensitization. On the other hand, CXCL8 secretion was reduced by coapplication of calcitriol and a D. farinae extract. Calcitriol therefore seems to be a suitable candidate to be used as adjuvant during sublingual immunotherapy.

Comparative analysis of sublingual immunotherapy medicines for adherence and clinical outcomes.

OBJECTIVE: Sublingual immunotherapy (SLIT) has been considered as an effective and safe alternative to the subcutaneous route. However, different modalities and administration methods may lead to significant changes in their adherence and clinical outcomes. The purpose of this study was to compare the adherence, efficacy, and side effects of SLIT medicines: SLITone®, Lais®, and Staloral®. SUBJECTS AND METHODS: Eighty-two patients suffering from AR symptoms and sensitized only to house dust mite allergens were included. The patients were treated with SLITone®, Lais®, or Staloral®. Treatment outcomes related to efficacy, dropout rate, and adverse events were evaluated. The visual analogue scale (VAS) including sneezing, rhinorrhea, nasal obstruction, and itching was scored from 0 (normal) to 10 (severe), before and after SLIT. Dropout rate was defined as the number of patients who discontinue SLIT of oneself compared to the number of patients who receive SLIT. RESULTS: All of the nasal symptoms and total symptom scores were significantly decreased in SLITone®, Lais®, and Staloral®. Furthermore, there were significant difference in the improvement of rhinorrhea and TNSS between SLITone® and Staloral® group (p = 0.011 and p = 0.001, respectively). Four patients out of 26 in SLITone® group, 4 patients out of 30 in Lais® group, and 11 patients out of 26 in Staloral® group have stopped SLIT of themselves. The dropout rate was significantly higher in the Staloral® group than other two groups (p = 0.024). Only one patient complained adverse reaction such as swelling of mouth floor in the Staloral® group. CONCLUSION: Although all three SLIT medicines are effective in improving AR symptoms, the adherence to SLIT assessed in accordance with dropout rate was the lowest in the Staloral®.

[Efficacy, safety and compliance of immunotherapy in the treatment of allergic rhinitis: a Meta-analysis].

Objective: By use of Meta analysis to compare efficacy, safety and compliance of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) on allergic rhinitis (AR). Methods: Cochrane Library, Pubmed, Embase, CNKI Database, Wan Fang and Chinese Sci-tech Journal Database (from established time to May of 2018) were searched for trials about the AR treated by SCIT and SLIT. The relevant literatures were screened, and the randomized controlled studies were chosen. Nasal symptom scores, visual analogue scale (VAS) scores, adverse reactions and compliance were used as the outcome indicators, and the methodological quality of the literatures was evaluated strictly. The extracted data were analyzed by RevMan 5.3 and Stata 14 software. Results: A total of 20 randomized controlled studies were included, the overall quality of which was relatively high. No publication bias was found. There was no significant difference in nasal symptom scores, VAS scores and compliance between SCIT and SLIT (SMD value was 0.03, 0.14, respectively, RR=1.12; 95%CI value was -0.17-0.23, -0.03-0.31, 0.92-1.35, respectively, all P>0.05); SLIT group resulted in lower overall incidence of adverse reactions than that of SCIT group (RR=1.79, 95%CI: 1.42-2.26, P<0.05). Conclusion: Both SCIT and SLIT have similar eppecacy and compliance for treatment of AR, while adverse reactions are more frequently observed in SCIT.

Efficacy of Sublingual Administration of Dermatophagoides Farinae Drops for Treatment of Pediatric Allergic Rhinitis Accompanied by Adenoid Hypertrophy and Improvement of Immune Function.

BACKGROUND The aim of this study was to determine the efficacy of sublingual administration of Dermatophagoides farinae drops for the treatment of allergic rhinitis (AR) accompanied by adenoid hypertrophy and the effect on immune function in children. MATERIAL AND METHODS Eosinophil counts in peripheral blood before and after treatment were determined; serum levels of immunoglobulin E (IgE), total IgE (T-IgE), immunoglobulin G4 (IgG4), interleukin-2 (IL-2), and interleukin-6 (IL-6) before and after treatment were detected by enzyme-linked immunosorbent assay. RESULTS The total effective rate in the study group was significantly higher than that in the control group (P<0.05). In both the study and control groups, symptom scores, medication scores, eosinophil counts in the peripheral blood, and serum levels of IgE, T-IgE, and IL-6 were significantly lower than those before treatment (P<0.05), while the serum levels of IgG4 and IL-2 were significantly higher than those before treatment (P<0.05). After treatment, symptom scores, medication scores, eosinophil counts in the peripheral blood, and serum levels of IgE, T-IgE, and IL-6 in the study group were significantly lower than those in the control group (P<0.05), while the serum levels of IgG4 and IL-2 were significantly higher in the study group than those in the control group (P<0.05). CONCLUSIONS Sublingual administration of D. farinae drops improved the clinical symptoms of pediatric AR caused by Dermatophagoides mites and improved the immune functions in children.

Role of leptin in allergic rhinitis during sublingual immunotherapy.

OBJECTIVE: Increasing evidence suggests that leptin is upregulated during allergic reactions in the airway and related to the severity of disease in allergic rhinitis (AR). In this study, we aimed to investigate the expression of leptin during sublingual immunotherapy (SLIT) in AR patients. METHODS: Forty AR patients without obesity were recruited in this study. Twenty patients received house dust mite (HDM) allergen extract for SLIT and twenty patients received placebo randomly. Protein expression of leptin in serum and nasal lavage was tested by enzyme-linked immuno sorbent assay (ELISA) 1 and 2 years after SLIT treatment, respectively. Peripheral blood mononuclear cells (PBMCs) and human nasal epithelial cell were prepared and stimulated by recombinant leptin after 24 months' SLIT treatment and the induction of Th2 cytokines (IL-4/IL-5/IL-13) were detected by ELISA. RESULTS: SLIT treatment decreased the expression of leptin protein in serum and nasal lavage significantly compared with placebo group 1 and 2 years after SLIT treatment. Nasal leptin level was correlated to decreased Th2 response (IL-4/IL-5/IL-13) and enhanced Treg (IL-10/TGF-beat) response after 2 years' SLIT. We also found that SLIT decreased the ability of leptin in promoting Th2 cytokines expression by PBMCs and human nasal epithelial cell after 2 years' SLIT treatment. CONCLUSION: Changes of leptin expression in serum and nasal lavage may be correlated with Th2/Treg regulation during SLIT. Our results suggested that leptin served as an important biomarker during SLIT.

[Research progress on intralymphatic immunotherapy].

Intralymphatic immunotherapy (ILIT) is an effective and safe causative treatment for allergic diseases. Compared with conventional specific immunotherapy such as subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), ILIT could significantly reduce treatment duration. This article will review the results of previous researches focusing on ILIT.

Inmunoterapia con extractos industriales de ácaros domésticos en niños menores de 5 años de edad con rinitis y asma / Immunotherapy with industrial extracts of house mites in children under 5 years old with rhinitis and asthma

La inmunoterapia sublingual (ITSL), se emplea en niños por la seguridad que ofrece, aunque existen algunas discordancias en cuanto a la edad de aplicación. Con el objetivo de profundizar en esta vía de tratamiento, se realizó un estudio en el universo de niños de 6 meses hasta 5 años cumplidos, en el área de salud Previsora Camagüey, Cuba. La muestra se estableció en aquellos que tenían antecedentes personales y familiares de atopia con rinitis y asma. El grupo de estudio, los atendidos en el servicio de Alergología con prueba de punción cutánea positiva a Dermatophagoides pteronyssinus (Dp), Dermatophagoides siboney (Ds) y Blomia tropicalis (Bt) e ITSL a los mencionados ácaros. El grupo control, los no atendidos por Alergología. En ambos grupos se registró la asistencia a urgencias, ingresos hospitalarios, consumo de medicamentos, cuestionarios RQLQm y AQLQm de Juniper, al inicio del estudio y a los 15 años de seguimiento. La positividad de la prueba fue mayor en rinitis alérgica, tanto en los menores de 2 años como en los de 2 a 5 años. No se encontraron diferencias estadísticamente significativas entre estos dos grupos de edad. Predominaron los sensibilizados a Dp+Ds+Bt, con porcentajes superiores al 50 por ciento. La asistencia a servicios de urgencias e ingresos hospitalarios, en el grupo de estudio fue menor que en el control, así como el consumo de medicamentos, y la puntuación de calidad de vida fue superior en el grupo de estudio. Los niños menores de 5 años con ITSL tienen menor probabilidad de consumir medicamentos, asistir a urgencias e ingresar a hospitales y su calidad de vida es superior a los controles(AU)

Sublingual immunotherapy (SLIT) is used in children for its safety, although there are some disagreements regarding the age of application. In order to study this treatment in depth, a study was conducted in children from 6 months to 5 years old in the health area of Previsora Camagüey, Cuba. The sample was taken in the children population with rhinitis, asthma and personal and family history of atopy. The study group, those treated in the Allergology service with positive skin prick test (SPT) to mites: Dermatophagoides pteronyssinus (Dp), Dermatophagoides siboney (Ds) and Blomia tropicalis (Bt) and SLIT to these mites. Children not treated by the Allergology service were the control group. In both groups, emergency attendance, hospital admissions, drug consumption were recorded, as well as the RQLQm and Juniper AQLQm questionnaires, at the beginning of the study and after 15 years of follow-up. The positive SPT were higher in allergic rhinitis, both children under 2 years and 2 to 5 years old. No statistical significance was found between these age groups. Allergic sensitivity was mainly found to Dp+Ds+Bt, with percentages higher than 50 percent. The attendance to emergency services and hospital admissions in the study group was lower than in the control, as well as the drug consumption. The quality of life score was higher in the study group. Children under 5 years old with SLIT are less likely to consume medications, to attend the emergency room and hospitalization, and their quality of life is superior to controls(AU)

Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation.

BACKGROUND: In sublingual immunotherapy (SLIT), the immune system is addressed by solubilized allergen that interacts with immunocompetent cells of the oral mucosa, the efficiency of which is governed by 2 main factors of SLIT allergen bioavailability: the allergen concentration and the mucosal contact time. Recently, 3 house dust mite (HDM) SLIT tablets were developed that differ with regard to allergen content, nominal strength (maintenance doses: 6 SQ-HDM/10,000 Japanese Allergen Units [JAU], 12 SQ-HDM/ 20,000 JAU, and 300 IR/57,000 JAU), and formulation (freeze-dried/compressed). Here, the importance of the SLIT tablet formulation for HDM major allergen bioavailability is examined. METHODS: The HDM major allergen content, tablet disintegration times, and allergen release kinetics were determined. Dissolution kinetics (allergen concentration vs. time) of Der f 1, Der p 1, and Der 2 were measured. Area under the curve (AUC) was used as a surrogate parameter for allergen bioavailability. RESULTS: The release of HDM major allergens from the freeze-dried tablets was complete after 30 s, while only partial release was achieved with the compressed tablets, even after prolonged dissolution. At 1 min, i.e., the recommended sublingual holding time for the freeze-dried tablets, the allergen bioavailability (AUC) of the compressed 300 IR/57,000 JAU tablet was 4.7-fold (Der f 1), 10.8-fold (Der p 1), and 23.6-fold (Der 2) lower than that of the freeze-dried 12 SQ-HDM/20,000 JAU tablet and similar to (Der f 1) and 5.3-fold (Der p 1) and 12.5-fold (Der 2) lower than that of the freeze-dried 6 SQ-HDM/10,000 JAU tablet. CONCLUSIONS: SLIT tablet allergen bioavailability depends highly on the tablet formulation. Only the fast-dissolving freeze-dried tablets provide maximal delivery of soluble allergens and achieve allergen concentrations that reflect the nominal tablet strengths within the recommended sublingual holding time.

Prolonged effect of allergen sublingual immunotherapy for house dust mites in elderly patients.

BACKGROUND: The prolonged effect of allergen immunotherapy is unknown, especially in older patients. OBJECTIVE: To analyze the 3-year effect of sublingual allergen-specific immunotherapy (SLIT) to house dust mites in elderly patients with allergic rhinitis. METHODS: Forty-seven elderly patients (65.78 ± 4.89 years old) underwent SLIT to house dust mites and were monitored for 3 years and compared with a placebo group. SLIT was performed with the use of oral Staloral 300 SR Der p and Der f 50/50% extract (Stallergens Greer, London, United Kingdom) or placebo. Symptoms and medication score, represented by the average adjusted symptom score (AAdSS), serum level of immunoglobulin (Ig) G4 to Dermatophagoides pteronyssinus, Dermatophagoides farinae, Der p 1, and Der p 2, and quality of life, were assessed immediately after SLIT and 3 years later. RESULTS: The AAdSS was significantly decreased after SLIT, and the level remained low during the 3 years after SLIT compared with placebo. Serum-specific IgG4 against D pteronyssinus, D farinae, Der p 1, and Der p 2 increased during the SLIT trial in the study group. For the 3 years of observation after SLIT, there were no significant changes of specific IgG4 levels against the analyzed allergens compared with results just after SLIT. Quality of life based on the Rhinoconjunctivitis Quality of Life Questionnaire score was significantly decreased in patients who received SLIT, from 1.48 (95% confidence interval 1.33-1.79) to 0.98 (95% confidence interval 0.67-1.07; P < .05) compared with 0.94 (95% confidence interval 0.55-1.04) 3 years after SLIT. CONCLUSION: The prolonged positive effect after SLIT to house dust mites was observed in elderly patients with allergic rhinitis. Further trials are needed to confirm this effect. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01605760.

Immunotherapy for food allergy.

PURPOSE OF REVIEW: The current review discusses strategies for administering specific immunotherapy (SIT) for the treatment of food allergy. It focuses on three delivery routes for food allergens, immunomodulatory adjuvants and allergen modifications. RECENT FINDINGS: Interest in SIT for food allergy has been increasing significantly. Sublingual immunotherapy is effective for desensitization with a very favorable adverse event profile. Epicutaneous immunotherapy is also effective, most notably in younger children, with a high rate of local reactions. Oral immunotherapy demonstrates high efficacy, but with a higher risk of gastrointestinal and systemic adverse events. The need for long-term application to sustain desensitization is currently unclear. Immunomodulatory adjuvants may be added to enhance or diminish the immunogenicity of proteins, whereas genetic modifications of food allergens are designed to limit the risk of adverse reactions and address the issues of standardization and supply. SUMMARY: SIT for food allergy is reaching the point where it may soon be used routinely in clinical practice. Current research focuses on new delivery routes and methods to enhance the effectiveness of the therapy while minimizing the risk of adverse reactions. Future efforts are underway to determine the optimal dose for each delivery method and the length of maintenance dosing required to retain the protective effect.

[Efficacy and safety of specific sublingual immunotherapy in children with allergic asthma and rhinitis].

Objective:To evaluate the efficacy and safety of specific sublingual immunotherapy (SLIT) with Dermatophagoides farina drops in different courses with allergic asthma and allergic rhinitis.Method:This study retrospectively analyzed the efficacy of SLIT in 158 children with allergic asthma and rhinitis which induced by house dust mites. The children were treated with Dermatophagoides farina drops; clinical observation and follow-up study were conducted. According to the treatment duration, children were divided into 4 groups (1-year, 2-year, 3-year, and 4-year). Symptom scores and medication scores were recorded at each visit. Asthma symptom scores (day and night), the rhinitis symptom scoresand medication scores were evaluated in 4 groups before and after SLIT. The adverse events during the treatment were collected.Result:There were significant differences in asthma symptom scores (day, night), asthma medication scores, rhinitis symptom scores, rhinitis medication scores among children who accepted 1-year, 2-year, 3-year and 4-year SLI treatment as compared with baseline (P< 0.01). As compared with 1-year, 2-year, 3-year groups, the asthma medication scores of 4-year group had obviously decrease (P< 0.05). Rhinitis medication score of SLIT3 years group was significantly lower than 2 years group (P< 0.05). Asthma symptom scores in the day, asthma symptom scores at night, rhinitis symptom scores of four groups children had no statistically significant difference (P>0.05).Conclusion:Different courses of sublingual immunotherapy with Dermatophagoides farina drops had significant effects; the 4-year course of treatment showed the best effect.

[Long-term clinical effect and safety observation of sublingual dermatophagoides farinae drop in preschool and school-age children with allergic rhinitis].

Objective:To evaluate the efficacy of specific sublingual immunotherapy (SLIT) with Dermatophagoides farinae drops on preschool and school age children with allergic rhinitis.Method:Fifty preschool children (≤6 year), and 52 school age children (> 6 year), who suffered from dust mite induced allergic rhinitis, were randomly divided into subingual immunotherapy (SLIT) + drug group and drug group. SLIT + drug group was treated with a standardized subingual immunotherapy drops of Dermatophagoides farinae and combined with symptomatic therapy, drug group was treated with mometasone furoate nasal spray and dseloratdine tablets as symptomatic treatment. These children were followed up for 2 years with one visit in every 3 months. Symptom scores and medication scores were record at each visit. Comprehensive evaluation of symptom, medication, and patients' degree of satisfaction were used.Result:Two years after SLIT finished, symptom scores (SLIT + drug group: 1.13±1.05; drug group: 4.68±3.09), medication scores (SLIT + drug group: 0.07±0.04; drug group: 0.36±0.25) of SLIT+drug group were significantly lower than those in drug group respectively, all P< 0.01. The subjective assessment of patient' symptom, medication, and treatment satisfaction in SLIT+drug group was significantly lower than those in drug group. Subjective assessment symptoms, medication, and treatment satisfaction in preschool group was the same as in school age group. After SLIT ended for 2 years, subjective assessment and treatment satisfaction in the school age group was better than those in preschool group in medication score.Conclusion:SLIT demonstrated clinical improvement in children of different ages during 2 years treatment. the symptom scores, medication scores and subjective satisfaction in school age group are better than those in preschool group.