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Background/Purpose: Specific immunotherapy is the only effective etiological treatment for allergic rhinitis, but subcutaneous immunotherapy has a slow onset and poor compliance. Predicting the clinical efficacy of subcutaneous immunotherapy in advance can reduce unnecessary medical costs and resource waste. This study aimed to identify metabolites that could predict the efficacy of subcutaneous immunotherapy on seasonal allergic rhinitis by serum metabolomics. Methods: Patients (n = 43) with Artemisia sieversiana pollen allergic rhinitis were enrolled and treated with subcutaneous immunotherapy for one year. Patients were divided into the ineffective group (n = 10) and effective group (n = 33) according to the therapeutic index. Serum samples were collected before treatment. Metabolomics was determined by liquid chromatography-mass spectrometry combined with gas chromatography-mass spectrometry and analyzed differential compounds and related metabolic pathways. Results: A total of 129 differential metabolites (P

Sijie Jiang,1– 3 Shaobing Xie,1– 3 Ruohao Fan,1– 3 Qingping Tang,4 Hua Zhang,1– 3 Fengjun Wang,1– 3 Shumin Xie,1– 3 Kelei Gao,1– 3 Junyi Zhang,1– 3 Zhihai Xie,1– 3 Weihong Jiang1– 3 1Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 4Department of Rehabilitation, Brain Hospital of Hunan Province, Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Weihong Jiang, Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86-731-8975-3045, Email jiangwh68@126.comPurpose: Subcutaneous immunotherapy (SCIT) is an effective treatment for pediatric allergic rhinitis (AR), but its efficacy fluctuates among individuals. This study aims to identify the profile of serum exosomes derived microRNAs (miRNAs) and evaluate their capacities to early predict SCIT efficacy in pediatric AR.Patients and Methods: High-throughput sequencing was applied to identify the miRNA of serum exosomes in AR children. GO enrichment and KEGG pathway analysis were performed to enrich the biological annotations of target mRNAs of miRNAs. Then we validated differentially expressed miRNAs in two independent cohorts by RT-qPCR. Logistic regression and receiver operating characteristic curve (ROC) were applied to evaluate the abilities of identified miRNAs in predicting the efficacy of SCIT in AR children.Results: A total of 812 miRNAs were detected in the serum exosomes, including 16 upregulated and 14 downregulated. Differentially expressed genes are enriched in the biological process of developmental process and regulation of cellular process, and gathered in pathways such as the signaling pathways regulating pluripotency of stem cells and the Wnt signaling pathway. In the first validation cohort, hsa-miR-4669 (P=0.009) and hsa-miR-4686 (P=0.032) were significantly downregulated in the effective group than the ineffective group, while hsa-miR-3196 (P=0.015) was upregulated. In the second cohort, hsa-miR-4669 level (P< 0.0001) was downregulated in the effective group than the ineffective group. In addition, logistic regression revealed that hsa-miR-4669 level was correlated with the visual analogue scale (r=0.323, P=0.001) and total nasal symptoms score (r=0.269, P =0.007). ROC curve highlighted that hsa-miR-4669 level exhibited a reliable accuracy in predicting SCIT efficacy in pediatric AR (AUC=0.785).Conclusion: Serum exosomes derived miRNA were associated with the efficacy of SCIT. Serum exosomes derived hsa-miR-4669 might serve as a novel biomarker for early predicting the response of SCIT in AR children.Keywords: allergic rhinitis, subcutaneous immunotherapy, miRNA, exosome, children

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]

Background: Subcutaneous immunotherapy (SCIT) is a well-validated and effective disease modification treatment for house dust mites (HDM)-induced allergic rhinitis (AR). Long-term post-treatment comparisons in children and adults treated with SCIT have rarely been published. This study aimed to evaluate the long-term efficacy of HDM-SCIT administered under a cluster schedule in children compared to adults. Methods: This was an open-design, observational, long-term clinical follow-up study on children and adults with perennial AR treated with HDM-SCIT. The follow-up consisted of a three-year treatment duration plus a post-treatment follow-up of over three years. Results: Patients in the pediatric (n = 58) and adult (n = 103) groups completed a post-SCIT follow-up of over three years. The total nasal symptom score (TNSS), combined symptom medication score (CSMS), and rhinoconjunctivitis quality-of-life questionnaire (RQLQ) score decreased significantly at T1 (three-year SCIT completed) and T2 (follow-up completed) in the pediatric and adult groups. In both groups, the improvement rate of TNSS (T0-T1) was moderately correlated with the baseline TNSS (r = 0.681, p < 0.001 and r = 0.477, p < 0.001 for children and adults, respectively). Only in the pediatric group, TNSS was significantly lower at T2 compared with that right after SCIT cessation (T1) (p = 0.030). Conclusions: Children and adults with HDM-induced perennial AR could achieve a sustainable post-treatment efficacy for over three years (up to 13 years) following a three-year SCIT. Patients with relatively severe nasal symptoms at baseline may benefit more from SCIT. Children who have completed an adequate course of SCIT may gain further improvement in nasal symptoms after SCIT cessation. [ABSTRACT FROM AUTHOR]

Background: Given that subcutaneous immunotherapy (SCIT) adherence in the literature is often studied in closely monitored trials, few studies report real‐world SCIT adherence. The purpose of this review is to assess SCIT adherence in real‐world settings. Methods: A literature search of PubMed, Embase, Cochrane Library, Web of Science, and Scopus for real‐world studies examining SCIT adherence was performed. Paired investigators independently reviewed all articles. For this review, "persistence" was defined as continuing therapy and not being lost to follow‐up after initiating SCIT, and "adherence" defined as persistence in accordance with prescribed SCIT dose, dosing schedule, and duration. Article quality was first assessed using a modified Newcastle‐Ottawa scale and then converted to Agency for Healthcare Research and Quality standards (good, fair, and poor). Results: The search yielded 1596 nonduplicate abstracts, from which 17 articles (n = 263,221 patients) met inclusion criteria. Fourteen (82%) studies reported persistence rates, ranging from 16.0% to 93.7%. Seven (41%) studies reported adherence rates, ranging from 15.1% to 99%. Five (29%) studies (n = 416 patients) collected original data on reasons for discontinuing SCIT, of which inconvenience was most cited. All studies were Oxford level of evidence 2b and of good (n = 10) to fair (n = 7) quality. Conclusion: Real‐world SCIT persistence and adherence rates are poor, with the majority of included studies reporting rates <80%; however, they range widely, explained in part by inter‐study differences in measuring and reporting adherence‐related findings. Future studies on SCIT adherence may benefit from following concordant definitions of persistence and adherence in addition to standardized reporting metrics. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is an IgE-mediated inflammatory disease of the upper airway. AR affects the patients' quality of life, is a known risk factor for asthma and a socio-economic burden. Allergen-specific immunotherapy (AIT), comprising sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT), involves administering increasing doses of the causative allergen to induce clinical and immunologic tolerance to the allergens. It is the only currently available treatment for AR that has been proven to induce disease-modifying effects (i.e., long-term remission of allergic symptoms or potential prevention of asthma and new sensitizations). Although AIT is conventionally recommended for patients who are non-responsive to symptom-relieving pharmacotherapy, it is presently recommended as a first-line treatment for patients with moderate to severe AR who prefer a treatment with the potential for long-term remission. In light of the relatively recent implementation of AIT in Malaysia, guidelines on its appropriate indication and application are important to attain optimal outcomes. This consensus statement was developed by an expert group formed by the Malaysian Society of Allergy and Immunology to provide evidence-based recommendations for the practice of AIT in Malaysia. Patient and product selection, choice of AIT, and strategy towards an effective treatment outcome in AIT are presented. [ABSTRACT FROM AUTHOR]

Background: Etiology of allergic rhinitis and asthma is frequently associated with house dust mite sensitization and allergen immunotherapy (AIT) represents the only disease modifying treatment. In a real world setting, clinicians would benefit from biomarkers to monitor or predict response to AIT. Methods: Twenty-four consecutive house dust mite (HDM) mono-sensitized rhinitic patients, treated with subcutaneous immunotherapy (SCIT) as per clinical practice, were enrolled. Multiple in vitro biomarkers such as basophil activation (BAT), IL-10 levels, and molecular allergen-specific IgE were performed during HDM SCIT, to monitor the effects of AIT and then correlated to in vivo scores (VAS, CMSS, RQLQ). Nasal cytology was performed at baseline and after 6 and 12 months of treatment. Finally, the economic impact of SCIT in this cohort of patients was evaluated. Results: Clinical biomarkers confirmed to be useful to monitor AIT efficacy. As for laboratory biomarkers, BAT showed a reduction trend, particularly for D2C1, suggesting that this is a useful parameter in monitoring patients. IL-10 levels tend to remain stable or slightly decrease during treatment. The economic analysis confirmed the favorable impact of immunotherapy. Conclusions: In this cohort of patients, SCIT confirmed its effectiveness in reducing symptoms and drug utilization. Clinical scores confirmed to be valid in monitoring patients and their response. BAT demonstrated to be useful in monitoring more than predicting response. Further studies are needed to better explore the usefulness of these biomarkers in AIT.

BackgroundSubcutaneous immunotherapy (SCIT) has been proved to be effective and safe in adult asthma. But it is still controversial in children.ObjectTo evaluate the efficacy and safety of SCIT in asthmatic children with allergy to house dust mite.MethodWe searched the databases of Cochrane Library, EMBASE and MEDLINE (from 1 January 1990 to 1 December 2022). Two reviewers independently screened studies, extracted data and critically appraised the risk of bias. We used the Revman 5 to synthesize the effect sizes.ResultsWe finally selected 38 eligible studies including 21 randomized controlled trials to evaluate the efficacy and safety of SCIT and 17 observational studies to assess the safety. The results revealed that short-term asthma symptom scores were declined with a standardized mean difference (SMD) of −1.19 (95% CI: −1.87, −0.50) in 12 researches with high heterogeneity. Short-term asthma medication scores were decreased with SMD −1.04 (95% CI: −1.54, −0.54) in 12 heterogeneous researches. One study showed no significant reduction in combined symptom and medication scores without providing details. No studies we reviewed reported long-term efficacy. SCIT resulted in an obviously increased risk of adverse reactions compared with placebo. For secondary outcomes, SCIT improved life quality and reduced the numbers of annual asthma attacks and allergen-specific airway hyperreactivity, but without significant improvement in pulmonary function, asthma control or hospitalization.ConclusionsSCIT can reduce the short-term symptom scores and medication scores regardless of different treatment duration or mono/polysensitization, but with an increased incidence of local and systemic adverse effects. Further studies on pediatric asthma are needed to evaluate the long-term efficacy, and clarify the effectiveness of SCIT in specific population using mix allergen extracts or with severe asthma. Overall, it is recommended for children with mild-moderate HDM-driven allergic asthma.

Background: The safety of pediatric food oral immunotherapy (Ped-OIT) has been depicted by some as less favorable than subcutaneous immunotherapy (SCIT) owing to the increased number of serious adverse events requiring epinephrine. A review of real-world data comparing Ped-OIT and SCIT safety is necessary to guide shared decision making. Objectives: Our aim was to compare the safety and adverse event profiles of peanut Ped-OIT and SCIT using Canadian real-word literature. Methods: We performed a retrospective review of recent Canadian real-world literature on peanut Ped-OIT and SCIT safety and adverse events. Results: The incidences of systemic reactions requiring epinephrine were 11 in 270 patients (4.07%) and 12 in 41,020 doses (0.029%) in a multicenter study in British Columbia, Alberta, Manitoba, and Nova Scotia studying 270 preschool-age children treated with peanut OIT. Similarly, a multicenter study in South-Western Ontario examining 160 patients between the ages of 1 and 17 years who were treated with peanut OIT showed that the incidences of systemic reactions requiring epinephrine were 5 in 160 patients (3.1%) and 8 in 52,751 doses (0.015%). A single-center retrospective review of 380 patients receiving aeroallergen SCIT showed that the incidences of systemic reactions requiring epinephrine were 28 in 380 patients (7.4%) and 1 in 1047 injection visits (0.095%). These findings are comparable to those of a review of 860 patients in Ontario who received either aeroallergen or venom SCIT, in which the incidence of systemic reaction requiring epinephrine was 10 in 4242 injections (0.24%). Conclusion: Despite differences in the OIT protocols used and age groups studied, recent real-world data suggest that the safety of preschool peanut OIT or peanut OIT using a slower buildup schedule is comparable to that of SCIT.

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

Background: Allergy immunotherapy (AIT), in the form of subcutaneous immunotherapy (SCIT) with alum-precipitated aqueous extracts, SCIT with a modified ragweed pollen allergen tyrosine adsorbate (MRPATA; Pollinex®-R), or a sublingual immunotherapy (SLIT)-tablet are options for the treatment of ragweed pollen allergic rhinoconjunctivitis (ARC) in Canadian children. A cost minimization analysis evaluated the economic implications of the use of the ragweed SLIT-tablet vs SCIT in Canadian children with ragweed ARC. Methods: A cost minimization analysis was conducted comparing the short ragweed SLIT-tablet, 12 Amb a 1-U, preseasonally with preseasonal ragweed SCIT, annual ragweed SCIT, or MRPATA. The analysis was conducted over a time horizon of 3 years from a public payer perspective in Ontario and Quebec. Resources and costs associated with medication and services of healthcare professionals were considered for each treatment. The resource and cost input values for the model were obtained from published literature and validated by Canadian clinical experts in active allergy practice. A discount rate of 1.5% was applied. Several scenario analyses were conducted to determine the impact of many of the key base case assumptions on the outcomes. Results: Over the total 3-year time horizon, the ragweed SLIT-tablet had a potential cost savings of $900.14 in Ontario and $1023.14 in Quebec when compared with preseasonal ragweed SCIT, of $6613.22 in Ontario and $8750.64 in Quebec when compared with annual ragweed SCIT, and $79.62 in Ontario and $429.49 in Quebec when compared with MRPATA. The ragweed SLIT-tablet had higher drug costs compared with the other AIT options, but lower costs for healthcare professional services. The lower costs for healthcare professional services with the ragweed SLIT-tablet were driven by the need for fewer office visits than SCIT. Scenario analysis indicated that costs were most impacted by including societal costs (e.g., costs associated with patient/caregiver travel and time lost). The potential cost savings of the ragweed SLIT-tablet versus SCIT and MRPATA was maintained in most scenarios. Conclusions: In this cost minimization analysis, the ragweed SLIT-tablet provided estimated cost savings from a public payer perspective for the treatment of ragweed ARC in Canadian children compared with SCIT or MRPATA. [ABSTRACT FROM AUTHOR]

Background: The immunological effect of allergen-specific immunotherapy is well documented, but few studies have examined the long-term effects of pollen subcutaneous immunotherapy (SCIT) on health-related quality of life (HRQoL) in children and adolescents. Therefore, the aims of this study were to evaluate the effect of pollen SCIT on HRQoL and to assess the association between HRQoL and symptoms among children and adolescents with allergic rhinoconjunctivitis in a 3-year follow-up. Methods: A prospective cohort study was conducted at a paediatric clinic in Sweden, including 158 children (5–16 years) on SCIT (birch and/or grass). Health-related quality of life, measured with DISABKIDS, symptom scores and allergen-specific IgE and IgG4 antibodies (blood test), were assessed at start, and after 1, 2 and 3 years of treatment. ANOVA and t-test were used to analyse differences over time, between groups and linear mixed model for the association between HRQoL and influencing factors. Results: After 1 year of pollen SCIT, HRQoL improved from 79.5 to 85.1 (p < 0.001), and the improvements were maintained (mean 1 years, 84.8, 3 years 87.2). Symptom scores decreased after 1 year, mean 19.9 to 11.5 (p < 0.001) and were maintained for year two (11.9) and year three (10.3). The proportion of children with severe or very severe symptoms decreased from 35.6% to 4.5% after 1 year of SCIT. Health-related quality of life was associated with symptoms at all measured timepoints (p = 0.001–0.031); higher symptom scores were associated with lower perceived HRQoL. Allergen-specific IgE antibodies decreased, birch from 151.0 to 76.8 kU/L (p < 0.001), and IgG4 antibodies increased, birch from 2.2 to 17.6 g/L (p < 0.001), grass from 0.5 to 14.3 g/L (p < 0.001), during the study period. Conclusion: After 1 year of pollen SCIT, HRQoL improved, and symptoms decreased; these changes were maintained during the study period. The proportion of severe and very severe symptoms significantly decreased. Key message: Treatment with pollen allergen specific-immunotherapy improved health-related quality of life in children. Higher symptom scores were associated with lower perceived health-related quality of life. The proportion of children with severe or very severe symptoms from eyes, Nose and/or lungs had significantly decreased after 1 year of pollen SCIT and was maintained during the treatment years [ABSTRACT FROM AUTHOR]

Background/purpose: Specific immunotherapy is the only effective etiological treatment for allergic rhinitis, but subcutaneous immunotherapy has a slow onset and poor compliance. Predicting the clinical efficacy of subcutaneous immunotherapy in advance can reduce unnecessary medical costs and resource waste. This study aimed to identify metabolites that could predict the efficacy of subcutaneous immunotherapy on seasonal allergic rhinitis by serum metabolomics.Methods: Patients (n = 43) with Artemisia sieversiana pollen allergic rhinitis were enrolled and treated with subcutaneous immunotherapy for one year. Patients were divided into the ineffective group (n = 10) and effective group (n = 33) according to the therapeutic index. Serum samples were collected before treatment. Metabolomics was determined by liquid chromatography-mass spectrometry combined with gas chromatography-mass spectrometry and analyzed differential compounds and related metabolic pathways.Results: A total of 129 differential metabolites (P < 0.05) were identified and 4 metabolic pathways, namely taurine and hypotaurine metabolism, pentose and glucuronate interconversions, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism, were involved.Conclusion: Some metabolites, such as hypotaurine, taurine, and l-alanine, have the potential to become predictive biomarkers for effective subcutaneous immunotherapy. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is an important public health issue worldwide due to its increasing prevalence and impact on quality of life, school performance, and work productivity. Subcutaneous immunotherapy (SCIT) is used to treat AR and involves repeated injections of allergen extracts. SCIT is used for cases of severe AR with symptoms that are not adequately controlled by medication, when the side effects of medication limit treatment options, or where the aim is to cure rather than symptomatically treat. Although SCIT is effective, it is not necessarily curative. Furthermore, there is also a low but present risk of systemic allergic reactions, with systemic side effects occurring in less than 0–1% of treated patients. Sublingual immunotherapy (SLIT) has emerged as an effective and safe alternative to SCIT. SCIT and SLIT are the only immunotherapies currently available for AR. In addition to sublingual administration as an alternative to SCIT, other routes of antigen administration have been attempted with the goal of increasing safety while maintaining efficacy. This review discusses the efficacies of SCIT and SLIT, their mechanisms, the utility of intralymphatic immunotherapy (ILIT) as an alternative route of antigen administration, and the potential for immunotherapy using other routes of antigen administration.

Introduction Understanding sensitization patterns helps clinicians tailor care more effectively. Most clinical studies with positive results used single allergens, but many patients are sensitized to multiple allergens. Aim This study was planned to assess the correlation between different allergen sensitization patterns (the presence of sensitization to some but not other allergens) and clinical effectiveness of subcutaneous allergen-specific immunotherapy. Patients and methods This ex post facto study was conducted on patients with already diagnosed allergic disorders, who were attending our allergy and immunotherapy clinic and receiving subcutaneous allergen-specific immunotherapy. Data collected include patient’s demographic data, diagnosis of allergic disorders, and sensitization pattern duration of subcutaneous immunotherapy. The outcome of subcutaneous allergen-specific immunotherapy was assessed based on symptom score, medication score, and overall clinical outcome. Results A total of 100 patients were included. The frequencies of allergens, to which the patients were sensitized, were pollen (1 and 2) (63%), mold (61%), mite (59%), hay dust (41%), and chicken feather (23%). There were no significant association between sensitization patterns and the preimmunotherapy symptom and medication. Apart from cotton pollen, all other allergens were not associated with improvement in symptom score, and apart from chicken feather and dog sensitization all other allergens were not associated with improvement in medication score. Conclusion Allergen sensitization pattern could affect clinical outcome of subcutaneous allergen-specific immunotherapy in polysensitized patients. Cotton pollen sensitization is associated with less improvement in symptoms score. Chicken feather sensitization is associated with significant improvement in medication score in contrast to dog hair sensitization. The number of allergens in each patient is not significantly associated with the clinical outcome of subcutaneous immunotherapy.

Objective: To analyze various risk factors including causes that may lead to adverse reactions, especially systemic adverse reactions（SRs）, before and after mite allergen subcutaneous immunotherapy (SCIT), so as to provide real-world reference data for further improving the safety of mite allergen SCIT. Methods: The local adverse reactions（LRs）and SRs of 230 patients with allergic rhinitis and/or asthma who received SCIT in Weifang people's hospital were analyzed retrospectively. The data of patient characteristics, drug factors and environmental elements of adverse reactions were collected and statistically analyzed. Results: There were 28 cases (12.2%) of SRs in 230 patients. All the patients received a total of 7515 injections and 37 SRs (0.49%) were observed. 32.4% (12/37) of SRs could identify their external and subjective triggers. SRs patients had higher 2-year SCIT compliance than no-SRs patients (p = 0.026). The prevalence of SRs in SCIT patients with atopic dermatitis or simple allergic asthma are no statistical significance (P = 0.111). Conclusion: the incidence of SRs in this study is within an ideal range. Through professional patient education and pre injection risk factor assessment, Compliance is still well-controlled and guaranteed although SRs occurred.

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

IntroductionAllergen immunotherapy (AIT) is considered to be the only treatment that may change the natural process of allergic diseases. Subcutaneous immunotherapy (SCIT) is a type of allergen immunotherapy that is commonly used in clinical practice. However, SCIT has inconsistent effects on individuals, and it is yet unclear what factors affect therapeutic efficacy. In recent years, vitamin D levels have been speculated as a potential factor influencing SCIT efficacy.ObjectiveTo investigate the effect of serum vitamin D level on the SCIT efficacy in children with allergic rhinitis and/or asthma caused by dust mite allergy.MethodsAccording to the panel consensus, children with asthma and/or allergic rhinitis who received SCIT were divided into the vitamin D deficiency group (20 ng/ml). Serum 1–25(OH) D3, blood eosinophil, total IgE, dermatophagoides pteronyssinus (Dp), and dermatophagoides farina (Df) specific IgE (sIgE) were detected, and questionnaires of symptom and medication scores were collected before and after one year of treatment.ResultsAfter one year of SCIT treatment, the symptom and medication score significantly decreased (P 0.05). Our study found a statistical difference in Dp sIgE level between the vitamin D deficiency and the sufficiency groups (P = 0.024), and vitamin D levels become lower with children's growth (Y = −0.8981*X + 34.26, P = 0.0025).ConclusionsNo difference was found between the efficacy of one-year SCIT and serum vitamin D levels based on symptom and medication scores. Nevertheless, higher vitamin D levels may be associated with a decreased indicator of Dp allergy.

Asthma represents one of the biggest global health concerns with increasing prevalence and influence on global health. Several distinct asthma phenotypes have been identified with one of the most common, earliest recognized, and described being the allergic asthma phenotype, in which allergens trigger asthma through mechanisms involving allergen-specific immunoglobulin E (IgE). Allergen-specific immunotherapy (AIT), in the forms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), has been used for many decades as a tool for reducing IgE-mediated sensitization and controlling symptoms of allergic disease, most commonly for allergic rhinitis, and it remains the only currently available disease modifying therapy in atopic patients. AIT has been studied for use in mild to moderate allergic asthma. While the data are often inconsistent, and utilize a multitude of different methods, antigens, and outcome measures, in general, AIT may have several beneficial effects on asthma disease control, quality of life, and requirement for medication. These benefits are notable when immunotherapy is used as an adjunct to pharmacologic treatment in carefully selected and monitored patients with mild to moderate persistent asthma. Patients with severe asthma are excluded from these trials. Importantly, patients with asthma, and in particular severe asthma, may have a higher rate of systemic adverse reactions to SCIT, including anaphylaxis; however, these events are overall rare. Future research in the area is needed to definitively assess the benefit of SCIT and SLIT for patients with asthma, comparing outcomes with different methods, addressing the role of AIT in severe asthma, significance of multiallergen AIT in allergic asthma, and safety concerns in asthma. [ABSTRACT FROM AUTHOR]

Objectives: The aims of presenting study were trying to expose the course of SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus) in patients with allergic rhinitis (AR), to compare the prevalence of SARS-CoV-2 infection, hospitalization and pneumonia rates in patients with AR receiving allergen immunotherapy (AIT) and patients did not receiving AIT (non-receivers) and to define possible risk factors for SARS-CoV-2 positivity in patients with AR. Methods: A total of 419 patients with AR who were being followed-up in a tertiary allergy clinic between June 1, 2020 and December 31, 2020, were selected for the study. Results: Seventy-nine (18.9%) patients became infected with the SARS-CoV-2 [32 (19.6%) patients in AR patients with AIT and 47 (18.4%) patients in non-receivers] and the rate of pneumonia was 2.4% [12.7% of SARS-CoV-2 (+) patients]. There was no significant difference was determined between the AR patients with AIT and the non-receivers in regard of the rate of SARS-CoV-2 infection, pneumonia and hospitalization (p = 0.864, p = 0.055 and p = 0.075; respectively). There was a significant difference between the groups in terms of gender, duration of disease, sensitivity to allergens (atopy) and serum IgE levels (p = 0.009, p = 0.001, p = 0.001 and p = 0.001; respectively). The accompanying comorbidities, eosinophil cout, AIT and duration of AIT were not found to be associated with an increased risk SARS-CoV-2 PCR positivity. However, female gender was shown to be associated with an decreased risk for SARS-CoV-2 PCR positivity (OR, 0.571; 95% confidence interval, 0.330-0.987; p = 0.045) Conclusions: The course of SARS-CoV-2 is similar in patients with AR who underwent AIT and patients with AR who did not undergo AIT, and AIT does not seem to increase the risk for SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) and allergic rhinitis (AR) usually represent the latest manifestations of the atopic march, sharing a common type 2 inflammation response. A relevant prevalence of AR in EoE cohorts has been widely confirmed. An increasing literature assessed the involvement of aeroantigens in EoE pathogenesis, focusing foremost on the seasonality of new diagnoses, symptoms, and response to therapy. Unfortunately, no diriment direction has been achieved, probably due to the retrospective design of the studies so far available, which chose surrogate markers of EoE activity (mostly the date of new diagnosis) which may be affected by geographical, logistic and personal factors, probably not dependent by the disease itself. EoE exacerbations reported in the context of the pollen levels (preferably pollen counts) may represent a more reliable marker. AR might promote the onset and the re-exacerbation of EoE through mechanisms that are both local (ie, massive exposure to airborne antigens mediated by post-nasal drip) and systemic (type 2 inflammation). Furthermore, AR may facilitate EoE onset by predisposing to pollen food allergic syndrome (PFAS), and EoE patients with PFAS reported higher rate of AR, thus suggesting a bond among these 3 conditions whose causative relationship have still to be ascertained. In addition, because of its shifting activity from Th2 to Th1 inflammation, several case reports focused on the effect of allergen immunotherapy (AIT) employed to treat AR in EoE patients. Also in this instance, no certainties could be guaranteed, although sublingual immunotherapy (SLIT) is more frequently reported to exacerbate EoE, while SCIT is mostly described as a remission adjuvant. The real life experience reported from our allergy service appears to confirm such hypothesis. Finally, a watchful eye should be reserved to monoclonal antibodies as a potential future option for concomitant EoE and AR. In light of all this, an attentive evaluation of allergic history of EoE patients should be relevant. Future perspectives should be addressed on prospective studies targeted to shed light on causative relations among airborne antigens, AR and EoE, and to viable comprehensive treatments., Competing Interests: ER, FN, CL, GP and GS declare no conflict of interest. GWC has received research grants and lecture or advisory board fees from A. Menarini, Allergy – Therapeutics, AstraZeneca-MedImmune, Boehringer Ingelheim, Chiesi, Faes, Genentech, Guidotti-Malesci, GlaxoSmithKline, HAL Allergy, Novartis, Sanofi-Aventis, Sanofi-Genzyme/Regeneron, Stallergenes-Greer, Thermo Fisher, Valeas, and Vifor Pharma in the last 3 years., (© 2024 The Authors.)

Objective: To evaluate the impact of smoking statuses on disease severity and subcutaneous immunotherapy (SCIT) efficacy in allergic rhinitis (AR)., Study Design: Open observational cohort study., Setting: Tertiary referral center., Methods: Five hundred and five AR patients undergoing dust mite allergen SCIT were categorized into never smokers, former smokers, and current smokers. AR severity was assessed using widely employed questionnaires. The changes in questionnaire scores pre- and post-SCIT were evaluated for SCIT efficacy. The differences in disease severity and SCIT efficacy were compared for different smoking statuses among AR patients., Results: Compared to never smokers, former and current smokers exhibited higher proportion of male, alcohol, and asthma (P < .05). Current smokers had a greater prevalence of allergic conjunctivitis than former smokers (P < .05). Before SCIT, AR severity was similar across 3 groups, even after adjusting for confounders (P > .05). Current smokers reported lower SCIT efficacy in the first year (P < .05). By the third year, 3 groups showed comparable long-term efficacy (P > .05). However, current smokers experienced a significant decrease in benefits 2 years post-SCIT (P < .05) and lower improvement rates at the end of the 3-years SCIT period and 2 years following SCIT (P < .05)., Conclusion: AR patients across different smoking statuses demonstrated similar baseline disease severity and long-time SCIT efficacy. Active smoking was associated with increased asthma risk, delayed early SCIT efficacy perception, reduced improvement over 3 years, and diminished benefits 2 years after SCIT. Prompt smoking cessation is crucial to mitigate these effects., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: The use of allergen immunotherapy is one of the definitive treatments for allergic diseases due to the cellular and molecular changes developed in the immune system response. The aim of this study was to assess the efficacy of subcutaneous immunotherapy in patients with allergic diseases presenting to the allergy clinic of Persian Gulf Hospital in Bushehr, Iran. Materials and Methods: Patients with respiratory allergic diseases were enrolled in this observational study. The patients who had a positive skin prick test underwent immunotherapy for one year and were randomly included in this study. To evaluate the efficacy of immunotherapy, two questionnaires were completed for all the patients before and one year after the start of immunotherapy, including the Total Nasal Symptom Score (TNSS) and Asthma Control Test (ACT). Results: A total of 878 patients (53.6% male and 46.4% female) entered the study, including 45.8% who had allergic rhinitis, 25.5% with asthma and 28.5% with both diseases. The mean TNSS was examined for 258 patients before and after immunotherapy and was 13.64 and 5.83 (P

Jonathan Corren,1 Sarbjit S Saini,2 Remi Gagnon,3 Mark H Moss,4 Gordon Sussman,5 Joshua Jacobs,6 Elizabeth Laws,7 Elinore S Chung,8 Tatiana Constant,8 Yiping Sun,8 Jennifer Maloney,8 Jennifer D Hamilton,8 Marcella Ruddy,8 Claire Q Wang,8 Meagan P O’Brien8 1Departments of Medicine and Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; 2Department of Internal Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA; 3Clinique Spécialisée en Allergie de la Capitale, Québec, QC, Canada; 4Departments of Medicine and Pediatrics, Division of Allergy, Pulmonary and Critical Care, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; 5Department of Medicine, University of Toronto, Toronto, ON, Canada; 6Allergy and Asthma Clinical Research, Inc, Walnut Creek, CA, USA; 7Sanofi, Bridgewater, NJ, USA; 8Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USACorrespondence: Meagan P O’BrienRegeneron Pharmaceuticals, Inc, 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USATel +1 914 826-5271Email meagan.obrien@regeneron.comJonathan CorrenDepartments of Medicine and Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Ave, Los Angeles, CA, 90095, USATel +1 310 312-5050, ext 250Email jcorren@ucla.eduBackground: Subcutaneous immunotherapy (SCIT) has been proven as an effective therapy against some allergens for seasonal allergic rhinitis (SAR) patients unresponsive to intranasal corticosteroids and/or antihistamines but carries risk of systemic allergic reactions. Dupilumab blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation in multiple diseases.Objective: To evaluate the efficacy and safety of SCIT+dupilumab vs SCIT alone.Methods: This phase 2a, multicenter, double-blind, placebo-controlled parallel-group study conducted in 103 adults with grass pollen-induced SAR (NCT03558997) randomized patients 1:1:1:1 to SCIT, dupilumab (300 mg every 2 weeks), SCIT+dupilumab, or placebo. SCIT was administered using an 8-week cluster protocol followed by 8 weeks of maintenance injections. Primary endpoint was change from pre-treatment baseline in area under the curve (AUC) in total nasal symptom score (TNSS) 0– 1 h following nasal allergen challenge (NAC) with timothy grass extract at Week 17.Results: Although 16 weeks of treatment with SCIT+dupilumab did not significantly improve TNSS AUC (0– 1 h) following NAC at Week 17 vs SCIT (least squares mean − 56.76% vs − 52.03%), a higher proportion of SCIT+dupilumab-treated patients (61.5%) achieved SCIT maintenance dose vs SCIT (46.2%). A lower proportion of SCIT+dupilumab-treated patients (7.7%) required epinephrine rescue treatment vs SCIT (19.2%). There were significantly fewer withdrawals in the SCIT+dupilumab group than in the SCIT group (n = 2 [7.7%] vs n = 8 [30.8%]; P = 0.0216); the majority of SCIT group withdrawals were due to SCIT-related intolerability, compared with no discontinuations from the SCIT+dupilumab group.Conclusion: In SAR patients, 16 weeks of SCIT+dupilumab may improve SCIT tolerability but did not incrementally reduce post-allergen challenge nasal symptoms compared with SCIT alone.Clinical Study Number: NCT03558997.Keywords: dupilumab, seasonal allergic rhinitis, subcutaneous immunotherapy, nasal allergen responses

Introduction Understanding sensitization patterns helps clinicians tailor care more effectively. Most clinical studies with positive results used single allergens, but many patients are sensitized to multiple allergens. Aim This study was planned to assess the correlation between different allergen sensitization patterns (the presence of sensitization to some but not other allergens) and clinical effectiveness of subcutaneous allergen-specific immunotherapy. Patients and methods This ex post facto study was conducted on patients with already diagnosed allergic disorders, who were attending our allergy and immunotherapy clinic and receiving subcutaneous allergen-specific immunotherapy. Data collected include patient's demographic data, diagnosis of allergic disorders, and sensitization pattern duration of subcutaneous immunotherapy. The outcome of subcutaneous allergen-specific immunotherapy was assessed based on symptom score, medication score, and overall clinical outcome. Results A total of 100 patients were included. The frequencies of allergens, to which the patients were sensitized, were pollen (1 and 2) (63%), mold (61%), mite (59%), hay dust (41%), and chicken feather (23%). There were no significant association between sensitization patterns and the preimmunotherapy symptom and medication. Apart from cotton pollen, all other allergens were not associated with improvement in symptom score, and apart from chicken feather and dog sensitization all other allergens were not associated with improvement in medication score. Conclusion Allergen sensitization pattern could affect clinical outcome of subcutaneous allergen-specific immunotherapy in polysensitized patients. Cotton pollen sensitization is associated with less improvement in symptoms score. Chicken feather sensitization is associated with significant improvement in medication score in contrast to dog hair sensitization. The number of allergens in each patient is not significantly associated with the clinical outcome of subcutaneous immunotherapy. [ABSTRACT FROM AUTHOR]

This study aims to evaluate safety issues of house dust mite subcutaneous immunotherapy (SCIT) among allergic rhinitis (AR) children. A retrospective cohort study was done between 2015 and 2020 to investigate the side effects of SCIT among AR children caused by a house dust mite allergy. Among 1098 patients who received house dust mite subcutaneous immunotherapy injections, 284 patients (25.87%) had side effects (SE). SE were found to be 699 times higher or in 2.27% of the 30,744 subcutaneous immunotherapy injections. A total of 17.9% of the patients had local SE during SCIT administration. Systemic side effects occurred in 8.38% of children receiving SCIT and in 0.53% of the total population who received SCIT injections. Only 2/92 (2.18%) of patients suffered an allergic reaction within 30 minutes of injection and these patients responded well to antiallergic medication. Severe anaphylaxis occurred in 0.091% of the 1098 patients in the SCIT group and in 0.0033% of the 30,774 SCIT injections. Systemic SE after SCIT occurred in 8.38% of patients receiving SCIT or 0.53% of the total number of SCIT injections. Anaphylactic episodes occurred in 16 patients (1.46%) and 15 patients (1.37%) who had first and second episodes. One severe attack was found and it was resolved with adrenaline. This study demonstrates that in pediatric patients with AR who received HDM SCIT for 18 months with high adherence, some experienced significant local SE and systemic SE caused by SCIT, but this did not interfere with the course of AR treatment or the effectiveness of SCIT. [ABSTRACT FROM AUTHOR]

Patients with moderate to severe allergic rhinitis may benefit from subcutaneous immunotherapy (SCIT), despite the risk of systemic allergic reaction. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin‐4 and interleukin‐13, key drivers of the type 2 inflammation seen in allergic rhinitis, thereby inhibiting their signaling. In the LIBERTY Grass AID trial (NCT03558997), 16 weeks of treatment with 300 mg of dupilumab every 2 weeks plus timothy grass (TG) SCIT did not reduce TG allergen challenge nasal symptom scores compared with SCIT only but did improve tolerability of SCIT up‐titration in patients with a history of grass pollen–induced seasonal allergic rhinitis. Here, we present the pharmacokinetics of functional serum dupilumab and concentration‐response relationships in 52 patients enrolled in this trial. Functional dupilumab concentrations and concentrations of TG‐specific IgE and IgG4 were assessed in blood samples collected from dupilumab‐only and SCIT + dupilumab–treated groups. Mean functional dupilumab concentrations were similar in both groups and reached a steady state of ≈70–80 mg/L at week 5. One week after the end of treatment, TG‐specific IgG4 concentrations were increased in the SCIT + dupilumab group, but not in the dupilumab‐only group, over the range of dupilumab concentrations evaluated, whereas no changes were seen for TG‐specific IgE concentrations. This study demonstrates that SCIT does not alter functional concentrations of serum dupilumab, and the impact of SCIT on TG‐specific immunoglobulins is not affected by functional dupilumab concentrations over the range studied, indicating that maximum response was achieved in all patients. [ABSTRACT FROM AUTHOR]

Abstract Background Subcutaneous immunotherapy (SCIT) is an effective treatment for allergic rhinoconjunctivitis. However, adverse events, including life-threatening systemic reactions, may occur. The purpose of this project is to identify risk factors for systemic reactions to SCIT and to provide practice-based solutions using a quality improvement (QI) framework. Methods A QI initiative was performed in a hospital-based, Canadian Allergy clinic administering SCIT in a 12-month period. Results A total of 4242 injections of SCIT were performed over a period of 12 months. Of these, 10 injections resulted in a systemic reaction requiring epinephrine administration (i.e., an incidence of 1 in 424 injections, or 0.24%). Eight patients had at least one documented risk factor for a systemic reaction, and six had multiple risk factors. Major risk factors included seasonal exacerbation of allergic rhinitis, uncontrolled asthma, and an error in route of administration. All reactions occurred with the highest allergen extract concentration. Conclusion This QI initiative highlights the need for improved patient and health care practitioner education and pre-administration screening. We suggest several considerations for SCIT administration: provide patients with written information on safety; screen patients before injections, including a review of treatment plan adherence and asthma control; adjust dosing to slow down buildup of the most concentrated immunotherapy extract, particularly in high risk patients; and apply additional safety measures in patients with multiple risk factors.

Purpose: To elucidate the usefulness of Japanese cedar pollen (JCP)-specific antigen-specific immunoglobulin (IgG) 4 as a biomarker for predicting the efficacy of sublingual immunotherapy for cedar pollen-induced allergic rhinitis. Methods: We divided a total of 105 cases with Japanese cedar pollinosis into three groups: “SLIT Successful,” SLIT Unsatisfactory,” and “SCIT” groups. The SLIT group patients were treated with JCP Droplet (Torii Pharmaceutical Co. Ltd., Tokyo, Japan) for one year from 2015 and were divided into two groups, the SLIT Successful group or the SLIT Unsatisfactory group. The SLIT Successful group (n = 16) were subjects treated by SLIT only, who were able to experience control of their naso-ocular symptoms without the need for antiallergic rescue agents during the peak season of atmospheric pollen. The SLIT Unsatisfactory group (n = 76) comprised subjects treated with SLIT only, who did not respond successfully, and were administered with rescue agents to control their naso-ocular symptoms. The SCIT group had been treated with standardized JCP extract (Torii Pharmaceutical Co., Ltd., Tokyo, Japan) for three years from 2012, and were also able to experience control of their symptoms during the peak pollen season without the need for antiallergic rescue agents. We determined the serum level of JCP-specific immunoglobulin E (IgE), IgG, and IgG4 used in the 3gAllergy-specific IgE assay (3gAllergy). The serum levels of periostin and SCCA2 were measured using established ELISA procedures (clones SS18A and SS17B; Shino-Test, Japan) following the manufacturer’s instructions. We then made ROC curves for each group and assessed which index was best able to predict the efficacy of sublingual immunotherapy. Results: Serum JCP-specific IgE was significantly lower in the SCIT group than in the SLIT Successful group and the SLIT Unsatisfactory group (p < 0.05). Serum JCP-specific IgG was significantly higher in the SCIT group and the SLIT Successful group than in the SLIT Unsatisfactory group (p < 0.05). Serum JCP-specific IgG4 was also significantly higher in the SCIT group and the SLIT Successful group than in the SLIT Unsatisfactory group (p < 0.05). There was no significant difference among serum levels of periostin in the SCIT group, the SLIT Successful group, or the SLIT Unsatisfactory group. There was also no significant difference in SCCA2 among the three groups. In terms of ROC curves, a serum JCP-specific IgG4 value greater than 989.5 UA/mL showed the best sensitivity (93.3%) and specificity (94.7%) (p < 0.05) among other parameters. Conclusions: The serum JCP-specific IgG4 level is significantly correlated with the clinical efficacy of SLIT. Serum JCP-specific IgG4 cutoff levels greater than 989.5 UA/mL were correlated with an effective clinical response to SLIT, with a sensitivity of 93.3% and a specificity of 94.7%.

Abstract Introduction Humulus pollen is an important cause of allergic asthma in East Asia. There have been some murine models for Humulus pollen allergy established by intraperitoneal (IP) sensitization and nasal drip stimulation, but they were not comprehensive enough. Here, we used atomized inhalation for challenge and compared the subcutaneous (SC) and IP sensitization routes to determine the optimal method to establish a model of asthma induced by Humulus pollen. Subsequently, we tried to develop a rapid subcutaneous immunotherapy (SCIT) model for Humulus allergy. Methods BALB/c Mice were sensitized through the SC or IP route, with respective reference to previously established sensitization methods and allergen dosing, and challenged with nebulized Humulus pollen extract to induce asthma. To compare the two sensitization methods, airway hyperresponsiveness (AHR), inflammatory cell infiltration, allergen‐specific serum immunoglobulin (Ig)E (sIgE) levels, cytokine levels, and lung histopathology were assessed. The effects of SCIT (once every other day for 16 days) on airway inflammation, AHR, sIgE, and allergen‐specific serum IgG2a (sIgG2a) levels were evaluated by using the model established in this study. Results Although mice sensitized by the SC or IP routes both showed AHR and airway inflammation, the SC route elicited significantly higher levels of sIgE, eosinophil inflammation, and T helper type 2 cytokines, compared with the IP route. SCIT in the treatment group significantly reduced the titers of sIgE, enhanced the titers of sIgG2a, and effectively alleviated pulmonary inflammation and AHR, compared with the vehicle group. Conclusions The SC route can be used to establish a murine model of Humulus pollen allergy that recapitulates the characteristics of clinical allergic asthma. Short‐term SCIT can significantly improve symptoms and pathophysiology in asthmatic mice.

BackgroundC-X-C motif ligand 13 (CXCL13) and B cell-activating factor (BAFF) are proven to be involved in inflammatory diseases, but their role in allergic rhinitis (AR) remains unclear. The aim of this study was to investigate the role of serum CXCL13 and BAFF in AR and their clinical values as objective biomarkers to predict the efficacy of subcutaneous immunotherapy (SCIT).MethodsWe prospectively recruited 90 children with AR treated with SCIT and collected their serum specimens before SCIT. One-year follow-up was conducted for all patients, and they were categorized into effective and ineffective groups based on efficacy. The serum concentrations of CXCL13 and BAFF were detected and compared between the two groups. A validation cohort of 52 responders and 26 non-responders were further assessed for both cytokines and serum CXCL13 and BAFF levels were assayed by enzyme-linked immunosorbent assay (ELISA).ResultsEighty children completed the follow-up schedule, and 56 children were categorized into the effective group and 24 children into the ineffective group. The serum levels of CXCL13 in the effective group were clearly higher than those in the ineffective group (P < 0.05). Receiver operating characteristic (ROC) curves revealed the potential values of CXCL13 as a biomarker in predicting the response of SCIT. Further, in the validation cohort, ELISA results demonstrated that serum CXCL13 levels were increased in responders than non-responders (P < 0.05). ROC curves showed good accuracy of serum CXCL13 in predicting the efficacy of SCIT.ConclusionOur discovery–validation study demonstrated that circulating CXCL13 might serve as a novel biomarker to predict the outcome of SCIT in childhood AR. The findings indicated that CXCL13 was involved in the pathological mechanisms of AR and made help to the fundamental therapeutic mechanism of SCIT.

Abstract Background Allergen immunotherapy (AIT) is the only causal therapy for IgE-mediated allergy. There is less evidence about the safety and efficacy of AIT especially subcutaneous immunotherapy (SCIT) in children under 5 years old. We aimed to investigate the side effects and associated risk factors of house dust mite (HDM) SCIT in preschool children with respiratory allergic diseases. Methods The preschool children who had HDM-related allergic rhinitis with/without asthma were enrolled and undergone standardized HDM SCIT in our department from June 2013 to December 2019. Local reactions (LRs) and systemic reactions (SRs) were recorded and categorized according to World Allergy Organization recommendations. Demographic data and other therapeutic-related parameters were also recorded to investigate potential risk factors for these side effects. Results A total of 91 children (60 boys, 65.93%; 31 girls, 34.07%; mean age 4.13 years old) were included in the study. Among the 91 patients, 3109 SCIT injections were recorded, 62/91 (68.13%) experienced 186 immediate LRs, 4 /91(4.40%) experienced 6 delayed LRs, 11/91 (12.09%) children experienced 44 immediate SRs, 21/44 (47.73%) were grade 1 SRs, 21/44 (47.73%) were grade 2, 2/44 (4.55%) were grade 3, no grade 4 or 5 SRs occurred. Furthermore, 1/91 (1.10%) experienced 1 delayed SRs, manifested by urticaria 2 days later after allergen injection. 9/91 (9.89%) experienced 2 or more times SRs. Multivariable logistic regression analysis showed BMI (OR 1.506; 95%CI 1.091 to 2.079; p 0.05). Conclusions HDM subcutaneous immunotherapy is considered to be safe in preschool children with respiratory allergic diseases. Higher BMI and HDM sIgE level in children are risk factors for developing LRs. The incidence of SRs and the rate of severe SRs are low in preschool children.

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Background: Subcutaneous immunotherapy (SCIT) has been used for treating local allergic rhinitis (LAR) patients. However, the clinical efficacy and safety were still questioned. Objective: This study was designed to estimate the efficacy and safety of SCIT for treating LAR patients through meta-analysis. Methods: We systemically searched MEDLINE, Cochrane Library, and Embase publications. Randomized, double-blind, clinical trials for the efficacy and safety of Allergen Immunotherapy (AIT) for LAR were included. A meta-analysis of 4 clinical endpoints (combined symptom and medication scores [CSMS], symptom scores [SS], medication scores [MS] and rhinoconjunctivitis quality of life questionnaire [RQLQ]) and adverse events (AEs)) was performed after bias and heterogeneity assessments. The immunologic response results were summarized. Results: Four RCTs with 134 patients were included. Four studies for analyzing primary outcomes (CSMS, SS, MS) and AEs, three for RQLQ results. The results indicated an important significant difference between SCIT and placebo groups, list as follows: CSMS (SMD = −2.42, 95% CI: −3.60 to −1.25, P <.0001), SS (SMD = −2.08, 95% CI −3.68 to −0.48, P =.01), MS (SMD = −1.43, 95% CI: −2.65 to −0.21, P = 0.02), RQLQ (SMD = −0.70, 95% CI −1.29 to −0.12, P =.02), Local AEs (RR = 4.13, 95% CI 1.08 to 15.77, P =.04). For immunologic response, significantly increased serum sIgG4 levels and improvements of allergen tolerance was observed after SCIT. Conclusions: Our meta-analysis suggests that SCIT has a significant effect on improving symptoms and reducing medicine consumption for LAR patients. Larger and multicenter clinical trials are needed to clarify the safety and long-term efficacy. [ABSTRACT FROM AUTHOR]

Allergen immunotherapy is effective for the treatment of allergic rhinitis, allergic asthma, and Hymenoptera venom allergy. In view of potential side effects, cost, and the necessary patient commitment, an important question is whether allergen immunotherapy provides persistent clinical benefits after treatment discontinuation. Here, we appraise the existing evidence for long-term effects of both subcutaneous and sublingual immunotherapy in terms of clinical efficacy, immune mechanisms, prevention of asthma development, and prevention of new allergen sensitizations. Evidence from large, randomized, double-blind, placebo-controlled clinical trials that include a follow-up phase after treatment cessation demonstrate long-term efficacy. The data strongly support recommendations in international guidelines that both sublingual and subcutaneous immunotherapy should be continued for a minimum of 3 years to achieve disease modification and long-term tolerance. Grass pollen immunotherapy for seasonal rhinitis may inhibit the onset of asthma symptoms and requirements for asthma medication. Whether early intervention in infancy with mite sublingual immunotherapy may prevent asthma remains to be tested. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT) better improves patient outcomes and quality of life for adults with allergic rhinitis or rhinoconjunctivitis (AR/C) with or without mild to moderate asthma. Methods: Systematic review methodology was based on the Cochrane Collaboration handbook and Preferred Reporting Items for Systematic Reviews and Meta‐analyses. Four databases (PubMed, Cochrane Library, EMBASE, and Web of Science) were queried from inception to July 30, 2020. Two independent reviewers screened potentially relevant studies and assessed risk of bias. Outcomes of interest were symptom score (SS), medication score (MS), combined symptom medication score (CSMS), and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Meta‐analyses with an adjusted indirect comparison were conducted in RevMan 5.4.1. Results: Seven SCIT versus SLIT randomized controlled trials (RCTs) demonstrated no significant differences for any outcomes, but insufficient data precluded direct meta‐analysis. For the adjusted indirect comparison, 46 RCTs over 39 studies were included for SCIT versus placebo (n = 13) and SLIT versus placebo (n = 33). Statistically significant results favoring SCIT were found for SS (standardized mean difference [SMD] = 0.40; 95% confidence interval [CI] = 0.31–0.49), MS (SMD = 0.26; 95% CI = 0.14–0.39), CSMS (SMD = 0.42; 95% CI = 0.17–0.67), and RQLQ (MD = 0.24; 95% CI = 0.04–0.44). Statistically significant results favoring SLIT were found for SS (SMD = 0.42; 95% CI = 0.32–0.53), MS (SMD = 0.40; 95% CI = 0.28–0.53), CSMS (SMD = 0.37; 95% CI = 0.29–0.45), and RQLQ (MD = 0.32; 95% CI = 0.20–0.43). No significant differences were found between SCIT and SLIT for SS (SMD = −0.02; 95% CI = −0.15 to 0.11), MS (SMD = −0.14; 95% CI = −0.31 to 0.03), CSMS (SMD = 0.05; 95% CI = −0.21 to 0.31), or RQLQ (MD = −0.08; 95% CI = −0.31 to 0.15). Conclusion: SCIT and SLIT are comparably effective treatments for adults with AR/C. More RCTs analyzing SCIT versus SLIT are needed to directly compare the two. Laryngoscope, 132:499–508, 2022 [ABSTRACT FROM AUTHOR]

Background: This study investigated patients' preference for allergy immunotherapy (AIT) administered as either sublingual immunotherapy‐tablets versus monthly or weekly subcutaneous immunotherapy (SCIT) from a Spanish patient perspective. Methods: A discrete choice experiment (DCE) consisting of two blocks with eight choice sets in each was constructed to elicit the preferences for AIT. Three attributes were included in the DCE for the mode of administration, including the frequency of administration, the risk of systemic reactions and the co‐payment. Adults and caregivers of children with moderate to severe allergic rhinitis (AR) were included if they were not currently receiving or had not previously received AIT. Results: In total, 587 adults and 613 caregivers started the survey. Of those, 579 adults and 611 caregivers completed the survey and were included in the study. Both adults and caregivers had a significant preference for tablets compared with both monthly and weekly injections (p ≤ 0.0001). Furthermore, the respondents showed a significant preference for reducing the risk of systemic reactions. Subgroup analyses showed that caregivers of polyallergic children and female caregivers were significantly less price sensitive when choosing their preferred treatment. Conclusion: Our study demonstrated that both adults with AR and caregivers of children with AR prefer daily SLIT‐tablets to SCIT with either a weekly or monthly dose schedule. [ABSTRACT FROM AUTHOR]

The role of an allergist in recognizing the pollen-food allergy syndrome (PFAS) and lipid transfer protein syndrome (LTPS) is essential. LTPS differs from PFAS by having a different family of panallergens and clinical characteristics. Both are complex syndromes posing diagnostic and therapeutic challenges. Many cross-reactive allergen components are involved, such as plant panallergens profilins, PR-10 proteins (Bet v 1 homologous), and lipid transfer proteins (LTP). PFAS results from cross-reactivity between pollen-specific immunoglobulin E (IgE) and homologous proteins found in fruits and vegetables. In most cases, grass pollen is responsible for profilin hypersensitivity. But, tree and weed pollen may also act as primary sensitizers, depending on geographical differences. Nonspecific LTP (nsLTP) is ubiquitous in terrestrial plants and can induce systemic allergic severe reactions. Peach (Pru P 3) is the primary sensitizer for LTP-driven allergy, and its clinical relevance is considered the prototypic marker for LTPS. nsLTPs have been identified as a major allergen in tree and weed plants. A second critical point is the diagnosis of LTPS associated with cofactors such as exercise, alcohol, antacids, and NSAIDS, that can promote severe reactions. Skin Prick Test (SPT) with Peach extracts that have been highly enriched for Pru p 3 with very low content of other allergens for LTPS, is suggestive of LTPS. For PFAS, positive SPT with profilin-enriched date palm pollen and watermelon extract shows sensitivity and specificity that is very close to that of the recombinant grass pollen profilin. The present review address differences between the PFAS from LTP syndrome with particular attention to the clinical impact on cross-reactivity or cross-sensitization to pollens.

Abstract Background Subcutaneous immunotherapy (SCIT) is the standard approach for treating patients with sensitizations to aeroallergens. However, immunotherapy can trigger severe systemic reactions if delivered inappropriately or to high risk patients. We sought to characterize and quantify SCIT systemic reactions requiring epinephrine administration during a 6-year period in a Canadian setting following the recommendations for components and dosages published in the 2010 Canadian Society of Allergy and Clinical Immunology (CSACI) Immunotherapy Manual. Methods A single centre retrospective chart review was performed for all patients with systemic reactions to subcutaneous immunotherapy requiring intramuscular epinephrine injection between January 2011 and October 2017. Each systemic reaction requiring epinephrine was reviewed for baseline patient characteristics, details of the reaction, and reaction severity. Research ethics approval was obtained through McMaster University. Results 28 of 380 patients experienced a systemic reaction requiring epinephrine administration, with an incidence rate of 1 per 1,047 injection visits (0.095%). 26 of the 28 reactions occurred within the mandatory 30-minute observation period post allergen immunotherapy. Of the 28 patients that experienced a systemic reaction to SCIT, 11 patients had asthma and 5 patients had a history of possible food allergy. All of the systemic reactions occurred during injections from vial number 4, and five patients reacted to their first shot of a re-ordered extract. 10 of the 28 patients required more than one intramuscular injection of epinephrine, and 20 of 28 patients were transferred to the hospital by ambulance. Conclusions This is the first Canadian study to review patients with systemic reactions to subcutaneous immunotherapy. Several best practice methods were employed throughout the study to optimize subcutaneous delivery of immunotherapy extract, and our recorded per injection incidence rate for systemic reactions was comparable or below the rate published in similar studies. The recommendations in the CSACI Immunotherapy Manual provide an approach to standardizing prescriptions for SCIT to maximize immunotherapy efficacy and reduce the risk of systemic reactions, though similar studies in larger multicenter settings are needed to confirm these observations. These observations provide important objective information to clinicians about the potential risks for systemic reactions in patients considering SCIT.

Background: Subcutaneous immunotherapy (SCIT) is an effective treatment for children with allergic rhinitis (AR), but its efficacy fluctuates among patients. There are no reliable candidate biomarkers for monitoring and predicting the response to SCIT. The present study aims to identify novel biomarkers for early predicting the efficacy of SCIT in pediatric AR patients based on multiple cytokine profiling. Methods: We prospectively recruited 72 children with house dust mite (HDM)-induced AR who were assigned to receive SCIT. The serum samples were collected and multiple cytokine profiling was conducted by Luminex assay at baseline. All patients were followed-up for 1 year and then categorized into effective and ineffective group based on their efficacy, and levels of 48 selected cytokines were tested and compared between the two groups. The potential cytokines were further validated by enzyme-linked immunosorbent assay (ELISA) in a cohort with 54 responders and 26 non-responders. Results: Sixty-nine of 72 children completed one-year follow-up schedule with 46 included in effective group and 23 in ineffective group. The results of multiple cytokine profiling showed that 15 cytokines (eotaxin, G-CSF, GM-CSF, IFN-γ, IL-12(p40), IL-13, IL-15, IL-16, IL-4, MIF, MIP-1α, RANTES, SCF, SDF-1α and VEGF) were dysregulated between effective and ineffective group (all P < 0.05). Unadjusted and adjusted multivariate analysis models highlighted that serum eotaxin, IFN-γ, IL-4 and MIF levels closely associated with the efficacy of SCIT in pediatric HDM-induced AR patients. In addition, receiver operating characteristic (ROC) curves revealed potential values of these four biomarkers in predicting the response to SCIT. Further ELISA validation results in the cohort of 80 pediatric patients demonstrated that serum eotaxin and IL-4 levels were elevated in responders while IFN-γ levels decreased in responders (all P < 0.05). ROC curves demonstrated that serum IL-4 exhibited more reliable accuracy in predicting SCIT efficacy than eotaxin and IFN-γ. Conclusion: Our discover–validation study suggested that cytokines including IL-4, eotaxin and IFN- γ may serve as robust biomarkers for early predicting response of SCIT in children with HDM-induced AR. These results strengthen the evidence that cytokines were associated with the response of SCIT and contributed to understand its underlying therapeutic mechanisms. [ABSTRACT FROM AUTHOR]

Objective: Allergic rhinitis and allergic asthma are the most common chronic diseases in children. Allergen immunotherapy has also been shown to improve symptoms and medication scores in patients with allergic rhinitis and/or asthma. In our study, it was aimed to evaluate the patients who have completed allergen immunotherapy in terms of clinical improvement and new allergic sensitizations in the skin prick test. Materials and Methods: Patients who received allergen immunotherapy between 1999 and 2018 were included in the study. Age, sex, diagnosis, medications, sensitizations in the first skin test, immunoglobulin E level, eosinophil count, allergen immunotherapy content and duration, and time after the end of immunotherapy were recorded from patient files. It was asked from the patients to compare their clinical findings before and after allergen immunotherapy as the same, better, or worse. Skin prick tests were performed with inhalant allergens in all patients. Results: A total of 154 patients were included in the study, 68 of whom were subcutaneous and 86 were sublingual immunotherapy. Age, sex, disease severity, immunoglobulin E levels, and eosinophil counts of patients were similar in the subcutaneous and sublingual immunotherapy groups. In the subcutaneous immunotherapy group, self-reported clinical improvement for allergic rhinitis and asthma were 53.3% and 60.4%, respectively. In the sublingual immunotherapy group, self-reported clinical improvement for allergic rhinitis and asthma were 61.9% and 61.6%, respectively. New sensitization in the subcutaneous immunotherapy group was 12.1% and it was 3.5% in the sublingual immunotherapy group. Conclusion: More than half of our patients who received immunotherapy reported clinical improvement according to self-report. In the subcutaneous immunotherapy group, new sensitizations were higher than the sublingual immunotherapy group, but it was thought that longer follow-up time in the subcutaneous immunotherapy group may have also contributed to this result. [ABSTRACT FROM AUTHOR]

Background: The success of subcutaneous immunotherapy (SCIT) mostly depends on regular injections. Our aim was to investigate adherence to SCIT with aeroallergens during the COVID‐19 pandemic and demonstrate clinical consequences of treatment disruptions in real life. Methods: Visual analogue scale for quality of life (VAS‐QoL), VAS for symptom scores (VAS‐symptom), medication scores (MSs), and total symptom scores (TSS‐6) were recorded during the pandemic in 327 adult allergic rhinitis and/or asthmatic patients receiving maintenance SCIT, and these scores were compared with the pre‐pandemic data. Patients were grouped according to SCIT administration intervals; no delay (Group 1), <2 months (Group 2), and ≥2‐month intervals (Group 3). Results: A total of 104 (31.8%) patients (Group 3) were considered as nonadherent which was mostly related to receiving SCIT with HDMs and using public transportation for reaching the hospital. Median MS, VAS‐symptom, and TSS‐6 scores of Group 3 patients during the pandemic were higher than the pre‐pandemic scores (p = 0.005, p < 0.001, p < 0.001, respectively), whereas median VAS‐QoL scores of Group 3 during the pandemic were lower than the pre‐pandemic scores (p < 0.001). Median TSS‐6 and VAS‐symptom scores were the highest in Group 3 compared with other groups (p < 0.001 for each comparison). Median VAS‐QoL scores were the lowest in Group 3 compared with Group 1 and Group 2 (p < 0.001, p = 0.043, respectively). Conclusion: When precautions in allergy clinics are carefully applied, adherence to SCIT can be high during a pandemic. Patients must be encouraged to regularly adhere to SCIT injections since delays in SCIT administration can deteriorate clinical symptoms. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous immunotherapy (SCIT) is an effective, safe, preventative treatment for allergic asthma; however, potential biomarkers for monitoring SCIT have rarely been reported. Objective: Metabolomics was utilized for the discovery of new biomarkers and analyzing disease pathophysiology of allergic asthma, and it was also applied to determine the metabolomic profiles of serum samples from children with asthma undergoing SCIT and identify potential biomarkers for allergic asthma and its therapeutic monitoring. Methods: Untargeted metabolomics using ultra‐high‐performance liquid chromatography‐quadrupole‐time‐of‐flight mass spectrometry was performed on 15 asthmatic and 15 healthy pediatric sera to profile carboxylic acids. Statistical analysis combined with pathway enrichment analysis was applied to identify potential biomarkers. Then, targeted metabolomics was performed to study longitudinal changes of eicosanoid profiles on sera from 20 participants with asthma who received SCIT at baseline, 6 months, one, two, and three years (ChiCTR‐DDT‐13003728). Results: Metabolomic analysis revealed that levels of eicosanoids, particularly 12(S)‐hydroxyeicosatetraenoic acid (HETE; AUC = 0.94, p <.0001) and 15(S)‐HETE (AUC = 0.89, p =.0028), metabolized from arachidonic acid by lipoxygenase and glutathione peroxidase enzymes, were significantly higher in asthma group than in healthy individuals. Furthermore, levels of these important metabolites increased in the first year of SCIT treatment and then decreased from years one to three, being significantly lower after three years of treatment than baseline levels. Conclusion: 12(S)‐ and 15(S)‐HETEs are potential biomarkers to participate in the pathogenesis and treatment of allergic asthma. Moreover, these metabolites may be a new target for biological indicators to monitor the therapeutic effect of SCIT, particularly in the setting of allergic asthma. [ABSTRACT FROM AUTHOR]

Background: People with allergic rhinitis (AR) who are not controlled on conventional therapy can be treated using allergy immunotherapy (AIT) administered as tablets, injections or drops. In the US, the use of sublingual immunotherapy as tablets (SLIT-tablets) is limited in comparison to subcutaneous immunotherapy (SCIT). Objective: This study investigated patients' preference for SLIT-tablets vs monthly or weekly SCIT from a US patient perspective. Methods: We carried out a discrete choice experiment (DCE) consisting of two blocks with eight choice sets. Adults and caregivers of children with moderate-to-severe AR were included if they had not previously or were not currently receiving AIT. Three attributes were included in the design: the mode and frequency of administration, the risk of systemic reactions and the co-payment. Results: A total of 724 adults with AR and 665 caregivers of children with AR were included in the study. Both adults and caregivers had a significant preference for SLIT-tablets compared with both weekly and monthly injections and for less risk of anaphylactic shock. Caregivers were more risk-averse than adults when choosing their treatment, and the younger the child, the more risk-averse the caregiver. The preference for SLIT-tablets was found for both monoallergic and polyallergic adults and caregivers of monoallergic and polyallergic children. Respondents not wanting AIT for free were more risk-averse than those indicating that they wanted AIT for free. Conclusion: Our findings suggest that SLIT-tablets is the preferred route of administration for AIT among adults and caregivers of children with AR. [ABSTRACT FROM AUTHOR]

Purpose: The efficacy of subcutaneous immunotherapy (SCIT) for allergic rhinitis (AR) have been proven but application is still limited by concerns about the safety. The aims of this study were to investigate the incidence of adverse reactions and to ascertain possible risk factors in patients treated with SCIT in central China. Methods: This study retrospectively analyzed the application of SCIT from 2016 to 2018, in 236 patients with AR. After each injection, allergen dosage and details about local reactions (LRs)/systemic reactions (SRs) were recorded. Results: Totaling 236 patients received 5844 injections. The rates of LR were 3.0% per injection and 34.7% per patient, while the rates of SR were 0.48% per injection and 10.6% per patient. 86.9 percent LRs were small. Most SRs were grade 1 (16/57.1%), followed by grade 2 (8/28.6%), grade 3 (4/14.3%). No fatal SRs was recorded. Children, high sensitization and absence of premedication were identified as risk factors for LRs. Recurrent LRs increased the risk of SRs. Premedication could reduce the number and severity of LRs, but not SRs. Dual therapy with antihistamine and montelukast did not provide additional benefit when compared with antihistamine alone. Conclusion: The incidence of SRs was low while LRs were common in SCIT. Children may be prone to develop LRs, while pretreatments could reduce the number and severity of LRs. Recurrent LRs was a risk factor for SRs. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the time use and both direct and indirect costs associated with subcutaneous immunotherapy (SCIT) for adults with allergic rhinitis (AR) and caregivers of children with AR in the US. We conducted a survey to assess the retrospective time use and direct costs of SCIT. The populations surveyed included adults and caregivers of children (aged 5–17) with symptomatic AR of moderate or higher severity who are currently receiving or have previously started allergy immunotherapy (AIT). The retrospectively collected, self-reported time consumption and direct costs per clinic visit when receiving SCIT were assessed as well as the productivity loss associated with SCIT. Data were analyzed using univariate descriptive statistics. The study included 106 adults with AR and 191 caregivers of children with AR. We found that the median time spent per visit to the clinic was 50 min for both groups, including travel time and time at the clinic. The direct costs related to each visit included parking fees, road tolls and other costs. Adults spent $10 on parking, $9 on tolls and $10 on other costs. Finally, a median of 4 h of work was missed for both the adult patients and the adults accompanying a child. We found that SCIT is associated with substantial direct patient costs and productivity loss for both adults with AR and caregivers of children with AR. [ABSTRACT FROM AUTHOR]

Abstract Background and Objective Nasal symptoms were reduced following allergen‐specific sublingual immunotherapy (SLIT) for allergic rhinitis. The mechanisms underlying the effectiveness of SLIT for Japanese cedar pollinosis are poorly understood. We studied changes in the numbers of metachromatic cells, eosinophils, and neutrophils following SLIT for Japanese cedar pollinosis. Methods Nasal swabs were taken in the preseason (n = 32) and in pollinosis season (n = 49) from subjects given sublingual drop immunotherapy for an average duration of 1.5 years. The numbers of metachromatic cells (mast cells and basophils), eosinophils and neutrophils were determined and compared with those from untreated subjects in preseason (n = 65) and in season (n = 54). Results SLIT subjects had a significantly reduced frequency of moderate to most severe symptoms in comparison to untreated subjects in preseason (P