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Aim: To provide paediatricians with a summary of efficacy and safety of SQ sublingual immunotherapy (SLIT) tablets from phase three, randomised, double-blind, placebocontrolled trials in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma. Methods: PubMed searches were conducted and unpublished data were included if necessary. Results: Of the 93 publications, 12 were identified reporting 10 trials. One trial was excluded as paediatric-specific efficacy data were unavailable. The nine eligible trials evaluated grass, house dust mite, ragweed and tree SLIT tablets. Consistent reductions in allergic rhinitis or rhinoconjunctivitis symptoms and medication use were observed with SQ SLIT tablets versus placebo. In a five-year trial, sustained reduction of allergic rhinoconjunctivitis symptoms, asthma symptoms and medication use were observed with SQ grass SLIT tablet versus placebo. The number-needed-to-treat to prevent asthma symptoms and medication use in one additional child during follow-up was lowest in younger children. SQ SLIT tablets were generally well tolerated across trials. Conclusion: Evidence supports use of SQ SLIT tablets in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma. Long-term data demonstrate disease- modifying effects of SQ grass SLIT tablet and suggest the clinical relevance of initiating allergy immunotherapy earlier in the disease course. [ABSTRACT FROM AUTHOR]

Background: Diet restrictions and fear of adverse reactions put a significant burden on the nutrition, growth and life style of children and adults with food allergies. While various disease-modifying options are pursued, there are so far no published clinical data on immunotherapy for crustaceans. The efficacy and safety of desensitization to crustaceans by means of sublingual immunotherapy is assessed for the first time in this study with a view of validating it as a clinical-practice modality. Methods: Charts of a Midwest Allergy-Immunology practice from the period January 2014–June 2023 were reviewed to identify patients with allergy to shrimp treated with sublingual immunotherapy and to retrospectively evaluate their responses to oral challenge. Results: Sixty-six patients were identified who had been treated by sublingual immunotherapy for either systemic or localized reactions to shrimp. Demographics and relevant comorbidities were consistent with those of the atopic population. Sublingual immunotherapy with serially diluted mixtures was initiated at 64–320 ng/dose and was gradually escalated to 0.5 mg/dose three times a day. The sublingual immunotherapy course ranged from 5 to 72 months (average: 51 months), following which, 18 patients underwent shrimp oral challenge. No systemic reactions occurred upon challenge; no patient required epinephrine. Tolerance of target dose equal to or exceeding 42 g shrimp was achieved in 11 patients (61%), seven of whom had originally presented with systemic reactions to crustaceans. Seven patients (38%) developed one or more of the following localized reactions: oral itching, nasal symptoms, localized perioral hives, localized hives at pressure points, nausea, vomiting, abdominal pain upon exposure to a cumulative dose of 39.2–148.2 g of shrimp during the 4 h of the challenge. Five of these patients had originally presented with systemic reactions to crustaceans. Five of the 7 patients who developed localized symptoms during the challenge were subsequently placed on routine exposure to 12–20 g shrimp every other day. Two patients continued sublingual immunotherapy but declined routine exposure to shrimp every other day because they had no intention to incorporate crustaceans to their routine diet. On repeat challenge 6–9 months after original challenge, all five patients who had routine exposure to 12–20 g shrimp every other day tolerated the procedure to target dose without any symptoms. Conclusions: Desensitization to shrimp by sublingual immunotherapy appears to be safe and effective as shown in this study. Whether the immune modification induced by sublingual immunotherapy is permanent resulting in sustained tolerance, or the achieved degree of desensitization depends on regular exposure is not known; therefore, following challenge, regular consumption three-four times per week was recommended. [ABSTRACT FROM AUTHOR]

Background: The symptoms of house dust mite (HDM)‐induced allergic rhinitis (AR) vary with changes in exposure related to the weather or the domestic environment. In allergen immunotherapy (AIT) studies, a certain level of AR disease activity is necessary to demonstrate treatment efficacy; the latter can be underestimated if a substantial proportion of the patient population is weakly symptomatic. Objective: To better estimate the real treatment effect of a HDM sublingual AIT (SLIT) tablet, we analysed the results of natural field studies in detail by applying a tertile approach. Methods: We used data from three randomised, controlled trials (RCT) in a total of 2585 patients with AR treated with the 300 index of reactivity (IR) HDM SLIT‐tablet or placebo. The study centres were grouped into tertiles according to the level of combined symptom and medication scores in patients in the placebo group. In each tertile, the difference between SLIT and placebo was assessed through an analysis of covariance. Results: In the three RCTs, combined scores were found to be similar in the SLIT and placebo groups in the low tertiles. The treatment effect of the 300 IR HDM tablet increased in the medium and high tertiles, with notably significant differences versus placebo in the highest tertile and greater (ranging from −21% to −39%) than in the entire study population (−13% to −20%). The positive relationship between treatment efficacy and the combined score in each tertile was independent of the RCT and the score used. Conclusion and Clinical Relevance: Application of the tertile approach to AIT studies in a field in which many variables interact strongly might provide more accurate and meaningful measurements of efficacy and benefit for patients, better reflecting their real‐life condition. [ABSTRACT FROM AUTHOR]

This article discusses a study on the safety and efficacy of Artemisia annua sublingual immunotherapy (SLIT) in children with seasonal allergic rhinitis (SAR). The study was conducted in Inner Mongolia, China, and included 54 pediatric patients. The results showed that the SLIT group experienced significant improvements in symptom and medication scores compared to the placebo group. Adverse events were reported in both groups but were mild or moderate and did not lead to any withdrawals from the trial. The study suggests that A. annua-SLIT could be an effective and safe treatment option for children with SAR. However, the study had limitations in terms of sample size and duration, and further research is needed to explore the long-term efficacy and larger geographical areas. The authors also mention the potential use of molecular diagnosis for more accurate diagnosis in the future. Overall, the study provides valuable insights into the use of A. annua-SLIT in pediatric populations with SAR. [Extracted from the article]

The article discusses the increasing prevalence of allergic diseases, such as allergic rhinitis and asthma, worldwide. It highlights the role of environmental exposures, including air pollution and climate change, in driving the development of these diseases. The article also presents research on the relationship between outpatient visits for allergic rhinitis, airborne pollen concentration, and meteorological factors. It discusses the impact of air pollutants on the allergenicity of allergens and the importance of improving ambient air quality for the prevention and treatment of allergic diseases. The article further explores various topics related to allergic diseases, including the identification of new allergens, the role of the skin microbiome in atopic dermatitis, and the potential biomarkers for predicting response to allergen immunotherapy. It also mentions the international cooperation and contributions of Chinese researchers in the field of allergies. [Extracted from the article]

This article presents the findings of a 13-year retrospective study on the sensitization profiles of aeroallergens among allergic rhinitis (AR) patients in China. The study included 16,664 patients from three different centers. The most common aeroallergens were house dust mites, cockroaches, mustard plants, and maple trees. Children had a higher sensitization rate than adults, and AR patients with asthma had a higher sensitization rate than AR patients without asthma. The sensitization rates of the aeroallergens changed significantly from 2009 to 2021, with different trends observed in the three centers. The study provides valuable information on prevalent aeroallergens in China and proposes a panel of five aeroallergens for the diagnosis of AR. [Extracted from the article]

Objective: To explore factors influencing the acceptance of allergen immunotherapy (AIT) for the treatment of allergic respiratory diseases by pediatric patients and their families. Methods: A total of 406 children (210 males and 196 females) attending the pediatric outpatient clinics and wards of the Renji Hospital, Shanghai Jiao Tong University School of Medicine from June 2020 to April 2022. Those who met the criteria for the AIT treatment, were included in the survey. An online 20-item questionnaire was developed. Data on patient's general characteristics, allergic disease status, family history of allergies, general family information, parental knowledge of allergic diseases, and whether the AIT treatment was recommended by a physician, were collected. The patients were divided into two groups according to their willingness to receive AIT: a reluctant or neutral group (n = 182), and a willing group (n = 224). A univariate analysis of the willingness to undergo AIT was done to detect parameters that significantly differed between the groups, and the identified factors were used as independent variables in the multifactorial logistic regression analysis. Results: The severity of allergic disease, presence of drug allergy, occurrence of severe allergic reactions, mother's education, distance from home to the hospital, parental knowledge of allergic diseases, and whether the doctor recommended AIT were all statistically different between the groups (p < 0.05). Multifactorial logistic regression analysis showed that the degree of allergic rhinitis (AR), or asthma (AS), parental knowledge of allergic diseases, and doctor's recommendation of AIT were the factors that influenced the willingness of pediatric patients to receive AIT. Conclusions: The severity of AR and AS, parental knowledge of allergic diseases, and doctor's recommendation influenced the willingness of pediatric patients to receive AIT. [ABSTRACT FROM AUTHOR]

Tree nut allergy is a lifelong and potentially life‐threatening condition. The standard of care is strictly avoiding the culprit nut and treating accidental reactions symptomatically. To evaluate potential therapeutic options for desensitizing patients with IgE‐mediated tree nut allergy, we systematically searched three bibliographic databases for studies published until January 2024. We looked for active treatments of IgE‐mediated allergy to tree nuts (walnut, hazelnut, pistachio, cashew, almond, pecan, macadamia nut, and brazil nut). We focused on allergen‐specific immunotherapy (AIT) using oral (OIT), sublingual (SLIT), epicutaneous (EPIT), or subcutaneous (SCIT) delivery, or other disease‐modifying treatments. We found 19 studies that met our criteria: 3 studies investigated sublingual immunotherapy, 5 studied oral immunotherapy to a single tree nut, and 6 used multi‐food oral immunotherapy with or without omalizumab. The remaining studies investigated the effectiveness of monoclonal antibodies or IgE‐immunoadsorption in multi‐food allergic patients, including patients with tree nut allergy. The heterogeneity of the studies prevented pooling and meta‐analysis. Oral immunotherapy, single or multi‐nut, with or without omalizumab, was the most studied approach and appears effective in conferring protection from accidental exposures. Omalizumab monotherapy is the only approved alternative management for reducing allergic reactions that may occur with accidental exposure. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is a chronic inflammatory disease of the upper airway, which progresses into allergic asthma (AA) in up to 45% of children. This analysis aimed to investigate clinical and economic benefits of sublingual allergen immunotherapy (SLIT tablets) initiated early in childhood for the treatment of AR by quantifying the long‐term reduction in new cases of AA. Methods: A Markov model was developed to estimate the long‐term effects of SLIT tablets on the risk of developing asthma. Key parameters were primarily based on data from the GRAZAX® Asthma Prevention trial and included the age‐ and treatment‐dependent risk of developing AA as well as annual probabilities of progression/remission in AR severity. Healthcare costs were estimated using data from the REACT study. Results: In a modelled cohort of children with moderate‐to‐severe seasonal AR initiated on SLIT tablets at ages 7 and 12, 24% and 29%, respectively, develop AA during a 20‐year period. In comparison, when initiated at age 5, 19% develop AA. Additionally, initiation of SLIT tablets at age 5 is associated with a total healthcare cost of EUR 20,429 per patient, whereas initiation at ages 7 and 12 is associated with, respectively, EUR 21,050 and EUR 22,379 per patient 20 years after AR diagnosis. Conclusion: Initiation of SLIT tablets in early childhood is associated with a clinically meaningful and permanent reduction in new cases of AA and lower healthcare costs among children with AR. This finding supports the clinical relevance of initiating SLIT tablets early for children with AR to obtain long‐term clinical benefits. [ABSTRACT FROM AUTHOR]

Food allergy is a global public health problem that until recent years lacked any aetiological treatment supported by academy, industry and regulators. Food immunotherapy (AIT) is an evolving treatment option, supported by clinical practice and industry trial data. Recent AIT meta‐analyses have highlighted the difficulty in pooling safety and efficacy data from AIT trials, due to secondary heterogeneity in the study. An EAACI task force (CO‐FAITH) initiated by the Paediatric Section was created to focus on AIT efficacy outcomes for milk, egg and peanut allergy rather than in trial results. A systematic search and a narrative review of AIT controlled clinical trials and large case series was conducted. A total of 63 manuscripts met inclusion criteria, corresponding to 23, 21 and 22 studies of milk, egg and peanut AIT, respectively. The most common AIT efficacy outcome was desensitization, mostly defined as tolerating a maintenance phase dose, or reaching a particular dose upon successful exit oral food challenge (OFC). However, a large degree of heterogeneity was identified regarding the dose quantity defining this outcome. Sustained unresponsiveness and patient‐reported outcomes (e.g. quality of life) were explored less frequently, and to date have been most rigorously described for peanut AIT versus other allergens. Change in allergen threshold assessed by OFC remains the most common efficacy measure, but OFC methods suffer from heterogeneity and methodological disparity. This review has identified multiple heterogeneous outcomes related to measuring the efficacy of AIT. Efforts to better standardize and harmonize which outcomes, and how to measure them must be carried out to help in the clinical development of safe and efficacious food allergy treatments. [ABSTRACT FROM AUTHOR]

Background: There is still great need to develop new strategies to improve the efficacy of allergen immunotherapies with optimal safety standards for patients. A new promising approach is to couple allergoids to mannan. The objective of this phase IIa/IIb study was to identify the optimal dose of mannan‐conjugated birch pollen allergoids for the short‐course treatment of birch pollen–induced allergic rhinoconjunctivitis. Methods: For this prospective, randomized, double‐blind, placebo‐controlled, dose‐finding study, 246 birch pollen–allergic adults received 0.5 mL placebo or 1000, 3000 or 10,000 mTU/mL of mannan‐conjugated birch pollen allergoids at five pre‐seasonal visits. Efficacy was assessed by comparing allergic rhinoconjunctivitis symptoms and use of anti‐allergic medication during the peak of the birch pollen season 2020. Immunologic, tolerability and safety effects were also analysed. Results: The highest dose of mannan‐conjugated birch pollen allergoids reduced the combined symptom and medication score during the peak birch pollen season by a median of 24.7% compared to placebo. The production of Bet v 1 specific IgG4 significantly increased in a dose‐dependent manner (3.6‐ and 4.5‐fold) in the 3000 and 10,000 mTU/mL groups. The Bet v 1 specific IgE/IgG4 ratio was also strongly reduced (up to −70%). No fatalities nor serious adverse events were reported, and no adrenaline was used. In total, four systemic reactions occurred (two grade I and two grade II). Conclusion: All doses of mannan‐conjugated birch pollen allergoids can be considered as safe. Since the application of 10,000 mTU/mL resulted in the highest efficacy, this dose qualifies for further investigation. [ABSTRACT FROM AUTHOR]

Peanut allergy affects about 1%–3% of the pediatric population in the world, with an important increase in the last decades. Nowadays, international guidelines recommend the early introduction of peanuts in the infant diet, with poor information about the quantity and the frequency of the intake. Allergen immunotherapy may represent the only therapeutic strategy able to modify the natural history of peanut allergy. In particular, oral immunotherapy showed the most promising results in terms of efficacy, but with significant rates of adverse reactions, mostly gastrointestinal. In 2020, the Food and Drug Administration and the European Medicines Agency approved Palforzia®, an oral drug for patients aged 4–17 years. Several studies are ongoing to improve the tolerability of oral immunotherapy and standardize the desensitization protocols. Sublingual immunotherapy permits to offer much lower doses than oral immunotherapy, but fewer adverse events are shown. Subcutaneous immunotherapy is associated with the greatest systemic adverse effects. Epicutaneous immunotherapy, for which Viaskin® patch was approved, has the highest safety profile. Innovative studies are evaluating the use of biological drugs, such as omalizumab or dupilumab, and probiotics, such as Lactobacillus rhamnosus, in monotherapy or associated with oral immunotherapy. Therapy for peanut allergy is constantly evolving, and new perspectives are ongoing to develop. [ABSTRACT FROM AUTHOR]

The article discusses the use of artificial intelligence (AI) tools, specifically ChatGPT, in providing statistical advice for scientific research. While AI can be helpful in solving narrow problems, there are concerns about relying too heavily on AI for health advice, as it can lead to misinformation and risks to our health. The article presents a study that analyzed ChatGPT's statistical skills in the field of allergology and found limitations in its ability to provide accurate and reliable answers. The authors emphasize the importance of human oversight and the need for researchers to familiarize themselves with statistical recommendations. They also suggest increasing the use of statistical reviewers by biomedical journal editors to improve the quality of published research. [Extracted from the article]

Background: Local application site reactions are common with sublingual allergy immunotherapy (AIT)‐tablets for the treatment of allergic rhinitis/conjunctivitis (AR/C) and occasionally lead to treatment discontinuation. Because of the lower mast cell density in the vestibular mucosa than the sublingual area, vestibular AIT‐tablet administration may result in fewer adverse events (AEs). This pilot study evaluated the tolerability of the vestibular administration route of AIT‐tablets compared with the sublingual route in adult subjects with AR/C. Methods: Adults (n = 164) aged 18–65 years with AR/C treated with daily birch pollen, grass pollen, ragweed pollen or house dust mite AIT in tablet form were randomized 1:1 to vestibular or sublingual administration for 28 days, followed by 28 days of sublingual administration only. The primary endpoint was the severity (mild, moderate, severe) of local treatment‐related adverse events (TRAEs) during the first 28 days of treatment. Results: During the first 28 days, the percentage of subjects in the vestibular and sublingual groups reporting mild TRAEs were 55.6% versus 50.6%, respectively; moderate TRAEs were 27.2% versus 30.1%; and severe TRAEs were 12.3% versus 6.0% (p =.16). In the vestibular group, 95.1% of the subjects experienced at least one TRAE during the first period versus 81.9% in the sublingual group (p =.01) and discontinuation rates due to AEs were higher (12.3% vs. 3.6%). Conclusion: The frequencies of subjects experiencing severe TRAEs, at least one TRAE, and discontinuations due to AEs at the initiation of AIT‐tablets were numerically higher with vestibular administration than sublingual administration. Sublingual administration should remain the standard of care for subjects treated with AIT‐tablets for AR/C. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In Sweden, allergy immunotherapy (AIT) is available as either subcutaneous immunotherapy (SCIT) injections or sublingual immunotherapy (SLIT) tablets and is used to treat moderate-severe allergic rhinitis (AR). This study sought to determine treatment-related CO2 emissions and travel times in Swedish patients receiving either SCIT or SLIT-tablets. A list of specialized Swedish AR clinics that administer AIT was determined, and respective co-ordinates retrieved. Swedish municipality population data were obtained from a national database. The mean distance from each Swedish municipality to the nearest AR clinic was calculated, adjusted using a detour index, and weighted by estimated patient population size. Transport modality data were obtained from a Swedish urban transport study and CO2 emissions were obtained from Government sources. The mean number of annual SLIT-tablets and SCIT doses required were calculated based on product labels and clinical expert input. The annual number of healthcare professional interactions were layered into the model to estimate changes in mean patient travel time, distance, and travel-related CO2 emissions associated with using SCIT versus SLIT-tablets. Mean annual travel-related CO2 emissions were 410 tonnes (to two significant figures [s.f.]; standard deviation [SD] 90) with SLIT-tablets, versus 1700 tonnes (SD 380) for SCIT, resulting in mean annual savings of approximately 1300 tonnes (SD 290) of CO2 if all AIT patients were to receive SLIT-tablets instead of SCIT, over 380 times greater than 2021 average Swedish CO2 emissions per capita. Approximate mean annual travel times for patients taking SLIT-tablets were 66,500 h (three s.f.; SD 14,400), and 278,000 h (SD 60,200) for SCIT, resulting in mean annual savings of 211,000 h (SD 45,800) if all AIT patients were to receive SLIT-tablets instead of SCIT. Compared with SCIT injections, SLIT-tablets led to substantial reductions in treatment-related CO2 emissions and travel times for Swedish patients. [ABSTRACT FROM AUTHOR]

Background: Canine atopic dermatitis (CAD) is a hereditary pruritic and inflammatory allergic skin disease associated with elevated IgE levels. Although, several treatments for CAD exist, allergen-specific immunotherapy (ASIT) is the only treatment that induces tolerance to pathogenic allergens. Sublingual immunotherapy (SLIT) is effective, convenient, and safe. This case report describes the successful treatment of a dog with atopic dermatitis using SLIT, emphasizing the efficacy and safety of SLIT as a long-term management strategy for CAD. Case: A 3-year-old spayed female Dachshund presented with non-seasonal chronic pruritus and generalized alopecia. The onset of pruritus occurred at 6 months of age, and its severity, measured by the pruritus visual analog scale, score was 5 out of 10. Dermatological examination revealed alopecia and scales on the dorsum and tail, and alopecia, lichenification, and crust on the medial side of the forelimbs. Diagnostic tests confirmed superficial pyoderma and Malassezia dermatitis. Initial treatment included amoxicillin/clavulanate, itraconazole, and a shampoo containing chlorhexidine gluconate and miconazole nitrate. An elimination diet trial was performed using a commercial diet to diagnose canine adverse food reaction (CAFR). However, 11 days after treatment initiation, the microbial and fungal skin infections and pruritus did not improve. Prednisolone was subsequently prescribed to alleviate pruritus and evaluate the response to glucocorticoids. At 24 days after the administration of prednisolone, pruritus reduction and lesion improvement were observed. Thereafter, prednisolone was tapered to 0.5 mg/kg EOD and discontinued 38 days after the initial administration. After prednisolone discontinuation, cytology did not reveal any cocci or Malassezia sp. Therefore, treatment with amoxicillin/clavulanate and itraconazole was discontinued. Two weeks after the discontinuation of prednisolone, pruritus relapsed, and cytology revealed no infection. The dog was initially treated with oclacitinib and planned to be managed with ASIT following an intradermal skin test at 2 weeks later. A provocative challenge was performed after the pruritus, and the lesions were well managed with oclacitinib. Because the clinical signs did not worsen, CAFR was excluded. The Favrot criteria was used to diagnose CAD by ruling out other skin conditions. An intradermal skin test was performed for 27 allergens, and oclacitinib was administered for SLIT, with allergens showing a positive reaction. After the administration of SLIT and oclacitinib, pruritus was well controlled and no recurrence was observed. At 763 days and 1638 days after the commencement of SLIT, oclacitinib and SLIT were discontinued, respectively. Notably, 9 months after discontinuing SLIT, complete remission of CAD was observed. Discussion: ASIT is used in veterinary medicine to treat CAD. A comprehensive clinical study found that SLIT has a success rate of 55%. The oral mucosa's low pro-inflammatory cell counts underscores SLIT's safety. Considering its efficacy and safety, ASIT was initiated with SLIT. ASIT can take > 12 months to improve CAD. Therefore, oclacitinib was prescribed to control pruritus. Complete remission of CAD was confirmed at the time of writing 9 months after SLIT discontinuation. This case indicates that SLIT could be an effective and safe therapeutic option for the long-term management of CAD. [ABSTRACT FROM AUTHOR]

Background: In children, indoor allergens play a significant role in the development of asthma. Allergen immunotherapy for the treatment of allergic respiratory diseases has traditionally been administrated by subcutaneous Immunotherapy (SCIT) injections, with certain precautions in administration. Sublingual Immunotherapy (SLIT) could be an alternative to SCIT. Objectives: To evaluate the efficacy, safety and cost of SLIT versus SCIT among asthmatic children. Patients and methods: 46 asthmatic children were divided into two groups. Group 1 received SLIT and group 2 received SCIT with close follow up of the patients every 3 months for 9 months regarding the efficacy and safety of allergen immunotherapy using asthma symptoms score, asthma medication scores and quality of life using a validated questionnaire. A cost-effectiveness analysis was done for both routes at the end of the study. Results: Both routes have nearly equal effects on the course of bronchial asthma. SLIT was the easier route of administration (painless and not needing attendance at the doctor's clinic for each dose). Even though its direct cost was more than SCIT, it eliminates the indirect costs of travel expenses for each dose, stable for a longer time in higher temperatures, with less probability of contamination. Conclusion: Allergen immunotherapy in addition to controller medicines significantly improves both symptoms and medication scores with minimal side effects in atopic asthmatic children with the advantage of SLIT over SCIT in this age group. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) impairs quality of life and affects nearly 40% of the Japanese population. Sublingual immunotherapy (SLIT) is the disease‐modifying treatment for AR, but requires the selection of a biomarker associate with clinical efficacy in patients with AR who are treated with SLIT. The present study sought to examine objective biomarkers used for assessing the clinical efficacy of SLIT. Methods: The authors examined the effects of 1 year of SLIT treatment with house dust mites (HDMs) using peripheral blood mononuclear cells (PBMCs) and serum from patients with AR. The prevalences of follicular regulatory T (Tfr), type 2 follicular helper T (Tfh2), type 2 helper T (Th2), conventional regulatory T (Treg), and type 1 regulatory T (Tr1) cells were examined by flow cytometry. Serum concentrations of HDM‐specific IgA, IgE, and IgG4 antibodies, and HDM‐induced production of interleukin (IL) 5 and IL‐10 from cultured PBMCs were evaluated by enzyme‐linked immunosorbent assay. Results: Following 1 year of SLIT, the prevalences of Tfr, conventional Treg, and Tr1 cells were significantly increased, whereas that of Th2 cells and Tfh2 cells were significantly decreased; the serum concentration of HDM‐specific IgG4 was significantly increased; and HDM‐induced production of IL‐5 from PBMCs was significantly decreased, while that of IL‐10 was significantly increased. The increase in the prevalence of Tfr cells after SLIT correlated positively with the improvement of clinical symptom scores. Conclusion: An increase in Tfr cells may play an important role in SLIT, and may be a useful indicator for the clinical efficacy of SLIT. [ABSTRACT FROM AUTHOR]

Background: Pediatric allergic rhinitis (AR), including cedar pollinosis (CP), is increasing in Japan. We investigated the effects of sublingual immunotherapy (SLIT), which has limited studies of its effectiveness in real‐world settings, on children with CP. Methods: This retrospective cohort study used a claim database in 2018–2021. Children aged ≤15 years with CP records in 2019 were eligible and were followed up through 2021. We included 2962 CP children undergoing SLIT and 547 who were not. The medication score was used to evaluate SLIT effectiveness in the cedar pollen dispersal season each year. Adverse events and the occurrence of allergic diseases were also evaluated. Results: Medication score was higher in the SLIT group during the index period but lower in 2021 compared to the non‐SLIT group (mean ± standard deviation: 5.17 ± 2.39 and 4.74 ± 2.38 in 2019, 3.13 ± 2.30 and 3.55 ± 2.48 in 2021, respectively). The adjusted mean difference between groups from 2019 to 2021 was −0.62 (95% confidence interval: −0.86 to −0.39, p <.0001), and the medication score was reduced in the SLIT group (risk ratio: 1.2: 1.1 to 1.3). The occurrence of adverse events involving abdominal disorders (adjusted odds ratio [aOR]: 0.64: 0.51 to 0.81), asthma exacerbation (aOR: 0.37: 0.24 to 0.57), and allergic diseases involving hay fever unrelated to CP (aOR: 0.60: 0.45 to 0.80) or asthma (aOR: 0.71: 0.58 to 0.86) was lower in the SLIT group. Conclusion: In children with CP, SLIT is effective, well tolerated, and could decrease the occurrence of other allergic diseases. [ABSTRACT FROM AUTHOR]

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

Increasing the efficacy of allergen-specific intranasal immunotherapy (INIT) has recently been the main goal of several studies to establish this route as a safe delivery method through mucosal pathways. In this case, the present study evaluated the potential of INIT using ovalbumin (OVA)- loaded mesenchymal stromal/stem cell (MSC)-derived exosomes (Exo-OVA) in an allergic asthma mouse model. Together with control groups, sensitized Balb/c mice underwent intranasal immunotherapy with Exo-OVA (10 µg OVA per dose) for three consecutive weeks. Serum-specific immunoglobulin E (IgE) levels, transforming growth factor-beta (TGF-ß), interleukin (IL)-4, and interferon-gamma (IFN-γ) production by cultured spleen cells, lung histopathologic analysis, and nasopharyngeal lavage fluid cellular examinations were then conducted. The results showed that INIT using Exo-OVA significantly increased IFN-γ and TGF-ß secretion, while allergen-specific IgE and IL-4 production were dramatically decreased compared to the control group receiving phosphate-buffered saline. In addition, the eosinophil and total cell counts in the nasopharyngeal lavage fluid were reduced, and inflammatory conditions and cell accumulation in lung tissue were ameliorated. In conclusion, the Exo-OVA improved the INIT efficacy compared to free OVA. Therefore, this formulation could be introduced as an effective approach for immunomodulatory purposes with a shorter treatment duration and reduced side effects. [ABSTRACT FROM AUTHOR]

This article discusses the effects of sublingual immunotherapy (SLIT) on patients with Japanese cedar pollinosis, a common allergic disease in Japan. The study found that SLIT reduced clinical symptoms and decreased the avidity of antigen-specific IgE, which is associated with mast cell degranulation and anaphylaxis. The study also examined serum levels of antigen-specific IgE, IgA, IgG1, and IgG4, as well as Tfh cell subsets. The findings suggest that SLIT induces the production of low-affinity IgE and suppresses the production of high-affinity IgE, contributing to the therapeutic efficacy of SLIT. [Extracted from the article]

Histamine and cysteinyl leukotrienes (CysLTs) are potent inflammatory mediators in allergic rhinitis (AR). Studies involving other combinations of antihistaminics (Levocetirizine) and highly selective leukotriene receptor antagonist (LTA) (Montelukast) combination have shown additive benefits and are widely prescribed for AR. Evaluate the efficacy and safety of Bilastine 20 mg and Montelukast 10 mg fixed-dose combination (FDC) therapy in patients with AR. A randomized, double-blind, comparative, parallel, phase III study was conducted to evaluate efficacy and safety of Bilastine 20 mg and Montelukast 10 mg FDC at 16 tertiary care otolaryngology centres in India. Adult patients with AR for one year with IgE antibody positive and 12-h NSS score >36 in 3 days were randomized to receive either Bilastine 20 mg and Montelukast 10 mg or Montelukast 10 mg & Levocetirizine 5 mg tablets for 4 weeks. The change in total symptom score (nasal symptom scores (NSS) & non-nasal symptom scores (NNSS)) from baseline to week 4 was assessed as primary endpoint. Secondary endpoints included changes in TSS, NSS, NNSS, individual symptom scores (ISS), Rhinoconjunctivitis Quality of Life (RQLQ), discomfort due to rhinitis (VAS), and clinical global impression (CGI) scores. The change in mean TSS from baseline to week 4 in Test group (16.6 units) was comparable to reference group (17 units) (p= 0.8876). The difference in change in mean NSS, NNSS and ISS from baseline to day 7, 14, 28 were comparable. RQLQ improved from baseline to Day 28. Significant improvements were observed in discomfort due to AR measured by VAS and CGI scores from baseline to day 14 and 28. The safety and tolerability of patients were comparable between the groups. All adverse events (AEs) were mild to moderate in severity. No patient discontinued due to AEs. The FDC of Bilastine 20 mg and Montelukast 10 mg was efficacious and well tolerated in Indian patients with AR. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy of sublingual immunotherapy (SLIT) in children with mite allergic rhinitis (AR) and to determine the time to efficacy. Methods Sixty-four children with mite AR were recruited and treated with sublingual corresponding dust mite drops once daily according to the treatment schedule, along with symptomatic medication as needed. The patients were divided into the ≤6 years old group and the ＞6 years old group according to school age. The TNSS, TMS and VAS scores were compared before, half a year, and one year after SLIT treatment between the two groups and within the groups. Results Compared with pre-treatment, TNSS, TMS and VAS scores were significantly reduced in 64 AR children after half a year of SLIT treatment, and scores further reduced after one year of treatment (P＜ 0.05). There were no significant differences in TNSS, TMS and VAS scores before treatment, half a year and one year after treatment between the ≤6 years old group and the ＞6 years old group (P＞0.05). All scores were significantly lower after half a year of treatment than those before treatment in the two groups, and scores were further reduced after one year treatment (P＜0.05). Conclusion Children with AR have shown good clinical results after SLIT, and should be initiated as early as possible to reduce the occurrence of long-term complications. [ABSTRACT FROM AUTHOR]

Objective: This study investigates the efficacy and safety of sublingual immunotherapy (SLIT) with A. annua allergens in patients with seasonal allergic rhinoconjunctivitis over two pollen seasons. Methods: Seventy patients with moderate-severe seasonal allergic rhinoconjunctivitis were divided evenly into the SLIT and control groups. The SLIT last from 3 months before the summer-autumn pollen season in 2021 till the end of the summer-autumn pollen season in 2022. The daily individual symptom score, total rhinoconjunctivitis symptom score (dTRSS), total medication score (dTMS), combined score of medication and rhinoconjunctivitis symptom (dCSMRS), visual analog scale (VAS) score, and adverse events (AEs) were evaluated. Results: The average pollen concentration in 2022 was twice that previous two-year during the pollen season. Fifty-six patients completed treatments (SLIT group: 29, control group: 27). Compared with baseline, the individual symptoms, dTRSS, dTMS, dCSMRS, and VAS scores of SLIT group declined in 2021. After 16 months of SLIT, all efficacy indexes in 2022 were still lower than baseline and equivalent to those in 2021. In control group, the efficacy indexes in 2022 were higher than that in 2020 and 2021. The efficacy indexes of SLIT group were lower than those of control group in 2021 and 2022. SLIT is effective for both mono- and poly-sensitized patients. AEs incidence in SLIT group was 82.7% without severe AEs. Conclusions: The A. annua-SLIT can obtain efficacy and safety over two pollen seasons for patients with moderate-severe seasonal allergic rhinoconjunctivitis. [ABSTRACT FROM AUTHOR]

This article discusses a study conducted in Japan to examine compliance rates and factors associated with high compliance for sublingual allergen immunotherapy (SLIT) in children and parents. SLIT is a treatment for allergic rhinitis (AR) that requires long-term compliance to be effective. The study found that compliance rates decreased over time, with younger children being more compliant than adolescents. Factors associated with high compliance included the type of treatment, age category, sex, treatment history for AR, comorbid allergic diseases, family members undergoing SLIT, medical facility types, and month of initial treatment. The study provides insights that can be used to improve compliance with SLIT among children and parents. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

We aimed to compare the effectiveness and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) with standardized house dust mite (HDM) extract for allergic rhinitis. Participants with allergic rhinitis selected their treatment between HDM SCIT or HDM SLIT, according to their wishes. We prospectively followed symptoms of allergic rhinitis using the allergic rhinitis symptom medication score (ARSMS), along with adverse reactions, during the dose escalation and maintenance phases for two years. We compared the outcomes between propensity score-matched groups to adjust the confounding factors. After propensity score matching, 88 patients in the HDM SCIT (n = 44) and HDM SLIT groups (n = 44) remained for analysis. The HDM SCIT group showed significantly earlier effectiveness than the HDM SLIT group (median time to decrease in ARSMS [≥2 points]: 5.5 vs. 18.0 months, p < 0.001). The incidence of systemic reactions was not significantly different between the two groups in the dose escalation phase (68.2% vs. 56.8%, p = 0.379). In the maintenance phase, the incidence of systemic reactions was higher in the HDM SCIT group than in the HDM SLIT group (18.2% vs. 0%, p < 0.006). All 44 patients in the HDM SCIT group completed two years of treatment, while nine patients in the HDM SLIT group discontinued treatment. The HDM SCIT group showed an earlier onset of therapeutic effect and a lower discontinuation rate than the HDM SLIT group, although more severe systemic reactions were observed during the maintenance phase. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: A modified grass allergen subcutaneous immunotherapy (SCIT) product with MicroCrystalline Tyrosine and monophosphoryl lipid‐A as an adjuvant system (Grass MATA MPL [PQ Grass]) is being developed as short‐course treatment of grass‐pollen allergic rhinitis (SAR) and/or rhinoconjunctivitis. We sought to evaluate the combined symptom and medication score (CSMS) of the optimized cumulative dose of 27,600 standardized units (SU) PQ Grass in a field setting prior to embarking on a pivotal Phase III trial. Methods: In this exploratory, randomized, double‐blind, placebo‐controlled trial subjects were enrolled across 14 sites (Germany and the United States of America). Six pre‐seasonal subcutaneous injections of PQ Grass (using conventional or extended regimens) or placebo were administered to 119 subjects (aged 18–65 years) with moderate‐to‐severe SAR with or without asthma that was well‐controlled. The primary efficacy endpoint was CSMS during peak grass pollen season (GPS). Secondary endpoints included Rhinoconjunctivitis Quality of Life Questionnaire standardized (RQLQ‐S) and allergen‐specific IgG4 response. Results: The mean CSMS compared to placebo was 33.1% (p =.0325) and 39.5% (p =.0112) for the conventional and extended regimens, respectively. An increase in IgG4 was shown for both regimens (p <.01) as well as an improvement in total RQLQ‐S for the extended regimen (mean change −0.72, p =.02). Both regimens were well‐tolerated. Conclusions: This trial demonstrated a clinically relevant and statistically significant efficacy response to PQ Grass. Unprecedented effect sizes were reached for grass allergy of up to ≈40% compared to placebo for CSMS after only six PQ Grass injections. Both PQ Grass regimens were considered equally safe and well‐tolerated. Based on enhanced efficacy profile extended regime will be progressed to the pivotal Phase III trial. [ABSTRACT FROM AUTHOR]

Pollen-food allergy syndrome (PFAS) is an immunoglobulin E (IgE)-mediated allergic reaction caused when patients with pollen allergy ingest food having cross-reactivity with pollen. To date, no effective treatment method for this has been established. Here we report the case of a patient with PFAS who experienced lip edema, causing difficulties in treatment. This report describes the case of a 12-year-old boy with perennial allergic rhinitis since the age of 8 years. After ingesting fresh fruits and raw vegetables at the age of 11 years, he started to experience lip edema repeatedly. Thus, the patient was referred to our department. Based on the results of serum antigen-specific IgE, prick-to-prick, and allergen component tests, he was diagnosed with PFAS. He has been instructed to avoid causative food. Furthermore, the treatment using an antihistamine and antileukotriene receptor antagonist was initiated for pollen allergy. Sublingual immunotherapy (SLIT) for Japanese cedar pollen was initiated because the patient experienced severe nasal allergy symptoms during the dispersal season of this pollen. These treatments alleviated the nasal symptoms; however, the lip edema persisted. Omalizumab administration improved the lip edema. The combination of SLIT and omalizumab may be an effective treatment option for patients with PFAS. [ABSTRACT FROM AUTHOR]

To investigate the tolerability and safety of two sublingual tree pollen extracts approved in 2018, a non-interventional study (NIS) was performed. This NIS was an 8-month observational study conducted at 84 sites throughout Germany. Study participants received either a sublingual liquid allergen extract of birch pollen (SBPE) or a liquid allergen extract consisting of a mixture of birch, hazel, and alder tree pollen (STPE). Data from 432 patients were analyzed for the occurrence of adverse events and patient compliance. At least one local reaction occurred in 69 (22.2%) patients, whereas systemic reactions were only observed in 27 (6.3%) patients. STPE-treated patients developed systemic reactions more frequently than SBPE-treated patients (SBPE: 9 (4.3%) vs. STPE: 18 (8.0%)). Only one patient developed a systemic grade III reaction. Severe systemic grade IV reactions were not observed. A total of 348 (98.6%) of the patients who completed all visits were satisfied or very satisfied with the sublingual immunotherapy (SLIT), and 322 (71%) patients completed all visits. Both investigated products were well tolerated by the patients and demonstrated a good safety profile. AEs were observed less frequently than in the preceding clinical phase III trial, and no new safety concerns were identified. [ABSTRACT FROM AUTHOR]

Background/aim: Cupressus sempervirens is a tree native to the Mediterranean region. We aimed to investigate the frequency of sensitization/allergy to Cupressus arizonica pollen, which is not native to Anatolia. Materials and methods: Patients aged 5-18 years who underwent respiratory allergy screening in Türkiye's largest referral center over a 1-year period were reviewed retrospectively for a diagnostic study of Cupressus allergy. Results: Of 246 patients, 207 (67.6% male) with a median age of 11.7 (IQR 9.2-15) years were found to be aeroallergen-sensitive and C. arizonica (32%) was the second most common sensitivity after grass pollen (83.6%). In the C. arizonica-sensitive subgroup, only 3% (2/67) were monosensitive, and grass (77.6%), cat (38.8%), and weeds (38.8%) were the most common co-sensitivities. Cup a 1 specific IgE (sIgE) was measured in 26 patients with C. arizonica sensitivity and all were found to be positive. A nasal allergen challenge (NAC) was performed for 44 of 67 patients with C. arizonica sensitivity, and 13 of 44 patients had a positive outcome (NAC+) at the highest two extract concentrations. The Cupressus wheal sizes and Cup a 1 sIgE levels of the NAC+ subgroup were higher than those of the NAC-subgroup but reached significance only for wheal size [6 (5-7.5) vs. 4.5 (4-6), p=0.004]. The NAC+ subgroup reported more frequent nasal discharge, congestion, and eye symptoms than the NAC-subgroup during the relevant pollen season. Conclusion: C. arizonica sensitivity has increased in the East Mediterranean region, similarly to North Mediterranean data, and this is associated with the presence of allergy both clinically and in laboratory findings. C. arizonica should be included in the aeroallergen screening panels of children from the East Mediterranean. [ABSTRACT FROM AUTHOR]

Objective: To observe the efficacy of Montelukast combined with sublingual immunotherapy (SLIT) in the treatment of children with obstructive sleep apnea hypopnea syndrome (OSAHS) complicated with allergic rhinitis (AR). Methods: This is a prospective study. A total of 102 children with OSAHS complicated with allergic rhinitis admitted to Hunan Children’s Hospital from April 2020 to April 2021 were selected and randomly divided into two groups: sublingual group and two-drug combination group. Children in the sublingual group were treated with standardized dust mite drops Nos. 1-4 for SLIT, while those in the two-drug combination group were treated with Montelukast on top of the sublingual group. Statistical analysis and comparison were made between the two groups of children in terms of Sleep apnea hypopnea index (AHI), Hypoxic saturation (Lsao2), interleukin-4, Il-4), interleukin-17 (IL-17), OSA-18 Snoring Symptom Scale for Children (OSA-18), allergic rhinitis symptom scale (TNSS), efficacy, occurrence of adverse reactions, etc. Results: After treatment, the AHI index of the two-drug combination group was significantly decreased, and the Lsao2 index was significantly increased compared with the sublingual group (P<0.05). Compared with the sublingual group, the levels of IL-4 and IL-17 in the two-drug combination group were significantly decreased (P<0.05), the OSA-18 score and TNSS score were significantly lower (P<0.05). Moreover, compared with the sublingual group, the efficacy of the two-drug combination group was significantly increased (P<0.05), the incidence of adverse reactions was significantly lower (P<0.05). Conclusion: Montelukast combined with sublingual immunotherapy offers many advantages, such as effectively controlling nasal allergy symptoms in children with OSAHS complicated with allergic rhinitis and improving OSAHS symptoms. [ABSTRACT FROM AUTHOR]

MJ reports personal fees from ALK-Abello, personal fees from Allergopharma, personal fees from Stallergenes, personal fees from Anergis, personal fees from Allergy Therapeutics, personal fees from Leti, personal fees from HAL, during the conduct of the study; personal fees from GSK, personal fees from Novartis, personal fees from Teva, personal fees from Takeda, personal fees from Chiesi, outside the submitted work. JS reports grants and personal fees from SANOFI, personal fees from GSK, personal fees from NOVARTIS, personal fees from ASTRA ZENECA, personal fees from MUNDIPHARMA, personal fees from FAES FARMA, outside the submitted work. LC reports personal fees from Thermofisher, personal fees from Sanofi, personal fees from Astra Zeneca, personal fees from Novartis, outside the submitted work. PK reports personal fees from Adamed, personal fees from Berlin Chemie Menarini, personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Celon Pharma, personal fees from Polpharma, personal fees from Teva, personal fees from Novartis, personal fees from Glenmark, personal fees from Zentiva, outside the submitted work. [Extracted from the article]

Introduction: There is a need to evaluate the safety and efficacy of intralymphatic immunotherapy (ILIT) for inducing tolerance in patients with allergic rhinitis. Methods: Thirty‐seven patients with seasonal allergic symptoms to birch and grass pollen and skin prick test >3 mm and/or IgE to birch and timothy >0.35 kU/L were randomized to either ILIT, with three doses of 0.1 mL of birch pollen and 5‐grass pollen allergen extracts on aluminium hydroxide (10,000 SQ‐U/ml; ALK‐Abelló) or placebo using ultrasound‐guided intralymphatic injections at monthly intervals. Daily combined symptom medical score and rhinoconjunctivitis total symptom score were recorded during the peak pollen seasons the year before and after treatment. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were recorded annually starting 2 years after treatment. Circulating proportions of T helper cell subsets and allergen‐induced cytokine and chemokine production were analysed using flow cytometry and ELISA. Results: There were no differences between the groups related to daily combined symptom medical score the year before and after treatment. Two years after ILIT (after unblinding), the actively treated group reported significantly fewer symptoms, lower medication use and improved quality of life than did the placebo group. After the pollen seasons the year after ILIT, T regulatory cell frequencies and grass‐induced IFN‐γ levels increased only in the actively treated group. Conclusion: In this randomized controlled trial, ILIT with birch and grass pollen extract was safe and accompanied by immunological changes. Further studies are required to confirm or refute the efficacy of the treatment. [ABSTRACT FROM AUTHOR]

Background. Allergen-specific immunotherapy (AIT) is the only disease-modifying therapy for allergic conditions, resulting in a long-lasting tolerance beyond the duration of the treatment. Due to the strong relationship between the effectiveness, its optimal duration (at least three years) and the observation of the correct administration protocol, appropriate adherence to the plan of treatment represents a critical factor for the therapeutical success of AIT. Methods. Analysis of studies about the rate of adherence in subcutaneous and sublingual immunotherapy, which are the main routes of administration of AIT. Results. There are different causes leading to a premature interruption of the therapy or to it being incorrectly carried out; the most reported include erroneous expectations of the effectiveness and the adverse effects, economic issues, inconvenience and unrelated clinical conditions. Conclusions. An attentive analysis of the main causes of dropouts may be useful to improve the management of these patients and to develop new strategies for a personalized approach. These strategies should be dynamic, involving attentive communication between the physician and the patient about all the possible criticalities, especially in the initial phase of the therapy, and facilitating, as much as possible, access to healthcare providers over the course of the maintenance phase, including by exploiting technological tools. [ABSTRACT FROM AUTHOR]

Coordinated IgG2 and IgE responses as a marker of allergen immunotherapy efficacy. Such coordinated specific IgG2 and IgE responses were not observed in low responders, but were observed in high responders, for both the I Der f i - ( I p i < .01; Figure 1B,C) and the I Der p- i specific responses ( I p i < .05; Figure 2B,C). Allergen immunotherapy (AIT) is the only approach recognized as an etiologic treatment of allergy with long-lasting effects.[1] Numerous studies have shown that AIT is accompanied by changes in cellular (e.g., ILC2, Th2A, B and Treg, Tfh) and humoral (e.g., IgE, IgG4, and IgA) parameters.[2] However, no biomarkers have been established to date that either predict or associate with the outcome of AIT.[3] Recent studies focusing on IgG2 antibodies showed an increase in grass pollen or house dust mite (HDM) allergen-specific IgG2 in the course of AIT with sublingual tablets.[[4]] Particularly, coordinated IgG2 and IgE responses have been observed after 1 year of AIT in European allergic individuals, but only in those exhibiting high clinical benefit (high responders), when compared to low responders.[5] The present study aimed to confirm those results with a cohort of HDM-allergic Japanese individuals, and to assess HDM specific-IgG2 responses as early as 4 months after AIT initiation. [Extracted from the article]

Allergen immunotherapy (AIT) is a treatment in which clinically corresponding allergens are administered to patients with allergic diseases, either by subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT), or by oral immunotherapy (OIT) in the case of food allergy. Since etiological allergens are administered to patients, AIT is presumed to modify mainly allergen-specific immune responses. In bronchial asthma, AIT with house dust mites (HDM) alleviates clinical symptoms, suppresses airway hyperresponsiveness, and reduces medication doses of HDM-sensitive asthmatics. Moreover, AIT can suppress the symptoms of other allergic diseases associated with asthma including allergic rhinitis. However, AIT sometimes reduces allergic symptoms not induced by the responsible allergens, such as non-targeted allergens, in clinical settings. Furthermore, AIT can suppress the spread of sensitization to new allergens that are not targeted allergens by AIT, suggesting the suppression of allergic immune responses in an allergen-nonspecific manner. In this review, the nonspecific suppression of allergic immune responses by AIT is discussed. AIT has been reported to increase regulatory T cells that produce IL-10, transforming growth factor-β, and IL-35, IL-10-producing regulatory B cells, and IL-10-producing innate lymphoid cells. These cells can suppress type-2 mediated immune responses mainly through the production of anti-inflammatory cytokines or a cell–cell contact mechanism, which may be involved in the nonspecific suppression of allergic immune responses by AIT. [ABSTRACT FROM AUTHOR]

Canine atopic dermatitis and feline atopic skin syndrome are common presentations in small animal practice. Numerous drugs are used for symptomatic therapy. The only definitive treatment based on the cause of the disease is allergen immunotherapy. Classical allergen immunotherapy (AIT) consists of subcutaneous injections of an extract containing offending allergens, with increasing doses and allergen concentrations at short intervals during the induction phase of several weeks to months followed by a maintenance phase, where a fixed dose is typically given at longer intervals. Dose and interval are tailored to the individual patient. Newer types of AIT include rush immunotherapy, where the induction phase is abbreviated, intralymphatic immunotherapy, and oromucosal or sublingual immunotherapy. AIT aims at inducing a regulatory T-cell response and subsequently downregulating the exaggerated immune response to offending allergens leading to clinical signs. This article reviews the published knowledge about allergen immunotherapy in dogs and cats for small animal practitioners. [ABSTRACT FROM AUTHOR]

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

Introduction: Allergic rhinitis (AR) is a widespread disease with increasing prevalence in developed countries. The only treatment that tackles the underlying causes is allergen immunotherapy (AIT). This treatment is performed through two application routes, the subcutaneous immunotherapy (SCIT) or the sublingual immunotherapy (SLIT). However, persistence during the long course of treatment over 3 years is key for the efficacy of this treatment option. The impaired adherence significantly impacts public health resources. The aim of this study was to assess the persistence of AIT for both application routes. Methods: IQVIATM LRx was used to identify patients starting AIT between 2009 and 2018 with grass pollen (GP), early flowering tree pollen (EFTP) and house dust mite (HDM) allergens. Patients were classified within each allergen category by AIT groups (subcutaneous depigmented polymerised allergen AIT [dSCIT], other subcutaneous AIT [oSCIT] and SLIT) and age (5‐11 years, 12‐17 years, 18+ years). Furthermore, they were followed up for up to 3 years until the cessation of treatment. Patients, who were still on treatment after 3 years were deemed to be censored. Kaplan‐Meier curves of persistence were generated and compared by log‐rank tests. Results: The number of patients included in the three allergen categories was 38,717 GP, 23,183 EFTP, and 41,728 HDM AIT. In all allergen categories and for any product group, patient persistence decreased with increasing age class with the difference between 5‐11 years and 12‐17 years greater than between the latter and 18+ years. The percentage of patients completing the first year of AIT was low, particularly for SLIT where 22.2%–27.1% of patients remained persistent after 12 months. The equivalent figures for dSCIT were 52.0%–64.1% and for oSCIT 38.3%–50.3%. Conclusion: Persistence in AIT in AR was low in this retrospective prescription‐based database and was clearly linked to patient age and application route. [ABSTRACT FROM AUTHOR]

Background: Sublingual immunotherapy (SLIT) adherence in the literature is often evaluated in closely monitored trials that may impact patient behavior; real‐world SLIT adherence is relatively unknown. This systematic review intends to assess SLIT adherence in studies that reflect real‐world settings. Methods: A literature search of PubMed, Embase, Cochrane, Web of Science, and Scopus for real‐world studies examining SLIT adherence was performed. Monitored clinical trials were excluded. Paired investigators independently reviewed all articles. For this review, "persistence" was defined as continuing therapy and not being lost to follow‐up and "adherence" as persistence in accordance with prescribed SLIT dose, dosing schedule, and duration. Article quality was assessed using a modified Newcastle–Ottawa scale and then converted to AHRQ standards (good, fair, and poor). Results: The search yielded 1596 nonduplicate abstracts, from which 32 articles (n = 63,683 patients) met criteria. Twenty‐six (81%) studies reported persistence rates ranging from 7.0% to 88.7%, and 18 (56%) reported adherence rates ranging from 9.6% to 97.0%. Twenty‐one (66%) studies surveyed reasons for discontinuing SLIT. All studies were Oxford level of evidence 2b and of good (n = 12) to fair (n = 20) quality. Conclusion: Reported rates of real‐world SLIT persistence and adherence varied widely by study methodology (e.g., follow‐up duration, objective vs. subjective assessment). Studies with longer follow‐up generally reported lower rates; 3‐year persistence ranged from 7% to 59.0% and 3‐year adherence from 9.6% to 49.0%. Future studies of SLIT adherence would benefit from following concordant definitions of persistence/adherence and standardized reporting metrics. [ABSTRACT FROM AUTHOR]

The article reviews the efficacy of sublingual immunotherapy (SLIT) tablets, composed of standardized allergen extracts, for treatment of grass pollen-induced allergic rhinitis (AR). It summaries studies which compared the effects of five-grass pollen tablet and a one-grass pollen tablet, examined the role of temperate grass pollen in seasonal AR, and evaluated the efficacy of SLIT versus placebo. It also outlines nursing care considerations when administering Grastek or Oralair SLIT tablets.

The pathophysiology of Parkinson's disease (PD) tremor remains incompletely understood and there is a lack of clinical trials specifically addressing its pharmacological treatment. Levodopa is the most efficacious drug for most patients and should be used as primary approach to control troublesome tremor. While the efficacy of oral dopamine agonists on PD tremor has been demonstrated in controlled trials, there is no evidence of greater antitremor efficacy compared to levodopa. The magnitude of the antitremor effect of anticholinergics is generally lower than that of levodopa. Due to their adverse effects, anticholinergics have a limited role in selected young and cognitively intact patients. Propranolol may improve resting and action tremor and may be considered as an adjunct in patients with insufficient tremor response to levodopa and this also applies to clozapine, despite its unfavorable adverse effect profile. Treating motor fluctuations with MAO-B and COMT inhibitors, dopamine agonists, amantadine, or on-demand treatments such as subcutaneous or sublingual apomorphine and inhaled levodopa as well as with continuous infusions of levodopa or apomorphine will improve off period tremor episodes. For patients with drug-refractory PD tremor despite levodopa optimization deep brain stimulation and focused ultrasound are first-line considerations. Surgery can also be highly effective for the treatment medication-refractory tremor in selected patients without motor fluctuations. The present review highlights the clinical essentials of parkinsonian tremor, critically examines available trial data on the effects of medication and surgical approaches and provides guidance for the choice of treatments to control PD tremor in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Sublingual immunotherapy is currently promoted by various companies, with administration schedules variable in the different products even though almost all are standardized immunologically. So, this study was planned to examine the efficacy of simple nondaily dosing of sublingual immunotherapy instead of the widely used daily schedule. Materials and Methods: Fifty-two patients with allergic rhinitis and bronchial asthma were enrolled. Sublingual immunotherapy (manufactured at the allergen immunotherapy preparation unit at Mansoura University) was given in suitable bottles with a dropper mechanism that permits comfortable dosing under the tongue. The physician recommended that the patient put the drops under his/her tongue and leave the drops beneath the tongue for 2 minutes before swallowing. This was repeated every 3 days, with the drop number and concentration gradually rising. Results: After 2 months of follow-up, 65.8% responded partially to the symptom score and 26.3% responded completely to the medication score. There was a significant decline in the symptom and medication scores from the baseline scores (p<0.0001). After 4 months of follow-up, 95.8% responded partially to symptom scores and no one has not responded; 54.2% responded completely to medication scores; and 81% of studied patients had no side effects. However, the most frequent side effect was a sore throat. Conclusion: Our nondaily schedule of sublingual immunotherapy is tolerable, safe, and effective in patients with allergic rhinitis and bronchial asthma. [ABSTRACT FROM AUTHOR]

Allergic Rhinitis is one of the most common allergic disease and characterized by sneezing, rhinorrhea, nasal congestion and nasopharyngeal itching. The initial management includes pharmacological treatment and the patients who are refractory to pharmacological treatment are then reffered for immunotherapy. SLIT has been widely used for treatment of allergic rhinitis and has proven its clinical efficacy. The objective of the present study was to assess the clinical effects, safety and tolerability of sublingual immunotherapy (SLIT) among the patients suffering from allergic rhinitis. The study was conducted from Aug 2018 to April 2021 and 40 patients with convincing history, positive skin prick test to one or more allergen extracts were recruited. SLIT was conducted with antigens (mix), namely dust mites, tree pollens, grass pollens and weed pollens in patients of allergic rhinitis for 1 year. There was significant improvement in quality of life and symptoms severity(Nasal and Non-Nasal) from base line to end of 1 year. SLIT lowers the total IgE, absolute eosinophilic count and medication requirement. Sublingual Immunotherapy for specific allergens decreases clinical symptoms in patients with allergic rhinitis and sensitivity to multiple allergen. [ABSTRACT FROM AUTHOR]

Background: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation fromthe full document. Methods: ICAR-Allergic Rhinitis 2023 employed established evidence-based reviewwith recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensuswas performed for each topic. The final document was then collated and includes the results of this work. Results: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment. [ABSTRACT FROM AUTHOR]

The most frequent PROMs in allergen immunotherapy trials include total nasal symptom score (TNSS), total ocular symptom score (TOSS), total symptom score (TSS) and visual analogue scales (VASs). The TOSS was less well correlated with RQLQ and VAS-RS.[5] Although ocular symptoms are bothersome and affect RQLQ, RQLQ may not be optimal at reflecting ocular symptoms. Patient-reported outcome measures in birch pollen allergic patients treated with sublingual immunotherapy reflect real life. [Extracted from the article]

Objective Data on preoperative immunotherapy combined with chemotherapy in potentially resectable lung squamous cell carcinoma (LUSC) remain scarce. This study was designed to investigate the safety and efficacy of preoperative immunotherapy and chemotherapy for stage IIIA-IIIB LUSC. Methods This study consecutively enrolled stage IIIA-IIIB LUSC who received preoperative immunotherapy combined with chemotherapy between January 2019 and July 2021. Patients received two to four cycles of immunotherapy combined with platinum-based doublet chemotherapy (platinum + paclitaxel) before surgery. Patients were assessed radiographically every one to two cycles until surgery. Postoperative pathological evaluation was also performed. Follow-up was performed until at least 3 months after surgery. Results Sixty-five patients with stage IIIA-IIIB LUSC were enrolled. The objective response rate was 78.46% (51/65), and no patients had progressive disease. Fifty-seven patients underwent surgery, and 55 patients achieved R0 resection. There were no perioperative deaths. The rate of pathological complete response (pCR) was 31.58% (18/57) and major pathological response was 68.42% (39/57). The incidence of grade 3 and 4 adverse reactions was 21.21 and 1.54%, respectively. Conclusion Perioperative immunotherapy combined with chemotherapy followed by surgical resection for male patients with stage IIIA-IIIB LUSC was effective with a tolerable toxicity profile. [ABSTRACT FROM AUTHOR]