Allergen Immunotherapy For Allergic Rhinitis Research Articles

Allergen-specific immunotherapy for allergic asthma: What’s new?

Allergen-specific immunotherapy for inhalant allergies, using allergen extracts of proven value, is highly effective in selected patients with allergic rhinoconjunctivitis and allergic asthma. Both subcutaneous and sublingual immunotherapy (SLIT) have been shown to modify the underlying cause of the disease, with long-term clinical benefits that persist for years after their discontinuation. Real-world studies have confirmed the long-term efficacy of allergen immunotherapy in allergic rhinitis (AR) and asthma and shown a reduction in the incidence of lower respiratory tract infections. Sublingual house dust mite (HDM) immunotherapy has been suggested to improve innate antiviral immunity—a likely explanation for this finding. Based on robust randomized controlled trials, the Global Initiative for Asthma (GINA) guideline has incorporated the use of SILT for the treatment of adults with HDM-driven asthma and concomitant AR, with sub-optimal control, regardless of the use of low-to-high doses of inhaled corticosteroids, as long as the patient’s forced expiratory volume in 1 second (FEV1) is > 70%.

Single-cell RNA sequencing reveals the landscape of biomarker in allergic rhinitis patient undergoing intracervical lymphatic immunotherapy and related pan-cancer analysis.

Allergic rhinitis (AR) is one of the leading allergic diseases worldwide. Allergen immunotherapy (AIT) induces persistent specific allergen tolerance to achieve remission of the symptoms in AR patients. We creatively conducted the intra-cervical lymphatic immunotherapy (ICLIT) for AR patients. However, the underlying molecular mechanism of immune cell response of AIT in AR remains elusive. To investigate the transcriptome profile in AR patients who underwent ICLIT, we comprehensively investigated the transcriptional changes in B cells from peripheral blood mononuclear cells of AR patient by single-cell RNA sequencing. Immunoglobulins and relative key gene, which influences the B cell differentiation, was demonstrated. The biomarkers' association with different types of tumors was investigated. Naive B cells, germinal center B cells, activated memory B cells, and memory B cells constituted the B cells subsets. The expression of IGHE, IGHGs, IGHA, IGHD, and IGHM from memory B cells was validated. Pseudotime analysis further indicated the dynamic change from the expression of the immunoglobulins in the memory B cells, suggesting that ITGB1 may contribute to the differentiation procedure of memory B cells. The cell-cell communication among these immune cells demonstrated the significantly enhanced CD23, BTLA signaling after ICLIT in AR patient. ITGB1 was upregulated in 13 tumors and downregulated in six others. High ITGB1 expression was linked to poor prognosis in eight types of tumors. ITGB1 expression showed correlations with tumor mutation burden, tissue purity, and microsatellite instability in different types of tumors. ITGB1 was demonstrated as a potential biomarker for AR patients after ICLIT and is significant in identifying immune infiltration in tumor tissue and predicting tumor prognosis.

Future Directions of Allergen Immunotherapy for Allergic Rhinitis: Experts’ Perspective

Allergen immunotherapy (AIT) is broadly used all over the world as the only available disease-modifying treatment option. The aim of this experts' perspective is to address 7 important unmet needs for the further direction of AIT and to provide the readership with the authors' positions on these topics. An international group of experts in the field of AIT have formulated 7 important aspects for the future position of AIT, performed a current literature review, and proposed a consented position on these topics. The aspects discussed and consented by the authors include: (1) alternative routes of allergen application in AIT, (2) potential of recombinant vaccines, (3) the role of allergy diagnosis based on component-resolved diagnosis for AIT composition, (4) the impact of COVID-19 vaccination for further innovations in AIT, (5) potential of combining biologics to AIT, (6) future innovations in high-risk children/adolescents, and (7) the future regulatory position on AIT. Important unmet needs and topics for AIT have been addressed in this expert review. The authors' views and personal position on these 7 aspects have also been elaborated.

Research progress of indications and contraindications of allergen immunotherapy for allergic rhinitis

Research progress of indications and contraindications of allergen immunotherapy for allergic rhinitis

Persistence in allergen immunotherapy: A longitudinal, prescription data-based real-world analysis.

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 3years 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. 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 3years until the cessation of treatment. Patients, who were still on treatment after 3years were deemed to be censored. Kaplan-Meier curves of persistence were generated and compared by log-rank tests. The number of patients included in the three allergen categories was 38,717GP, 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 12months. The equivalent figures for dSCIT were 52.0%-64.1% and for oSCIT 38.3%-50.3%. Persistence in AIT in AR was low in this retrospective prescription-based database and was clearly linked to patient age and application route.

Real-life evidence in allergen immunotherapy: Moving forward with mHealth apps.

The efficacy and safety of allergen immunotherapy (AIT) in allergic rhinitis has been classically assessed using randomized controlled trials (RCTs). However, RCTs may have limitations in their external validity, and their evidence may be complemented with that from real-world studies. We aimed to review the mHealth apps that can be used for retrieving real-world data on AIT in allergic rhinitis. We applied an automatic tool to identify the mHealth apps (available in the Google Play and Apple App stores) that can be used to assess patients under AIT for allergic rhinitis. Apps meeting the inclusion criteria were reviewed, and the corresponding scientific evidence was assessed. We identified five apps with scientific publications in the context of allergic rhinitis: AirRater, AllergyMonitor, MASK-air, Husteblume, and Pollen App. Of those, only MASK-air and AllergyMonitor assessed AIT in patients with allergic rhinitis. MASK-air has enabled the comparison of reported symptoms among patients treated vs. not-treated with AIT. MASK-air has also allowed for the development of combined symptom-medication scores that can be used as endpoints for AIT trials. AllergyMonitor has identified that mobile technology can improve adherence to AIT and is set to support the prescription of AIT for patients with allergic rhinitis by a more precise identification of the pollen season. Mobile health tools allow for the collection of large volumes of real-world data and can be useful for generating hypotheses on AIT. However, such hypotheses require confirmation by epidemiological studies and RCTs.

Present status and future prospects of allergen immunotherapy in allergic rhinitis of China

过敏原特异性免疫治疗（allergenimmunotherapy，AIT）是在明确患者过敏原的前提下，让患者反复接触过敏原提取物，逐渐增加浓度和剂量，直至达到目标维持剂量，使患者对过敏原产生耐受，是目前唯一有望根治变应性鼻炎的对因治疗方法。近二十余年，国内学者在AIT临床实践和研究领域均取得较大进展。本文对我国变应性鼻炎的AIT现状进行了全面概述，并展望了我国AIT的发展方向。.

Diverse immune mechanisms of allergen immunotherapy for allergic rhinitis with and without asthma

Allergen immunotherapy (AIT) is an effective treatment for allergic rhinitis, inducing long-term clinical tolerance to the sensitizing allergen. Clinical tolerance induction can be achieved when AIT is administered for at least 3 years. AIT is associated with the modulation of innate and adaptive immune systems. This comprises inhibition of IgE-dependent activation of mast cells and basophils in the local target organ, suppression of TH2 cells, immune deviation toward TH1 cells, induction of T and B regulatory cells, and production of allergen-neutralizing antibodies. However, recent developments in their underpinning mechanisms have revealed that AIT, administered subcutaneously or sublingually, induces immune regulation through novel cell targets and molecular mechanisms. This comprehensive review discusses how immune tolerance driven by subcutaneous immunotherapy and sublingual immunotherapy is associated with the induction of a novel regulatory subset of innate lymphoid cells and suppression of proinflammatory TH2, allergen-specific TH2 (TH2A), and T follicular helper cells. Moreover, they are associated with exhaustion of TH2A cells and differential expression of nasal and systemic IgA antibodies. Uncovering the underpinning mechanisms of a successful AIT and immune tolerance induction will allow the development of targeted therapeutics for allergic rhinitis with and without asthma.

The research progress of mechanism of allergen immunotherapy in allergic rhinitis

Allergic rhinitis（AR） is a chronic non-infectious nasal mucosal disease mediated by IgE. It can be divided into seasonal and perennial according to the types of allergens.At present, there are many treatments for AR, among which allergen immunotherapy（AIT） is the only treatment option that can change the natural process of AR.AIT can improve innate immune response by reducing local hypertrophy, eosinophils, basophils and type 2 innate lymphocytes, and affect various T cells, B cells and many cytokines to regulate adaptive immunity. The mechanism of AIT on immune response is complex.In this review, the mechanism of immunotherapy on the innate and adaptive immunity of AR patients is highlighted, hoping to further understand the immunotherapy pathway of AR, and provide more theoretical basis for immunotherapy of AR.

Efficacy of mite allergen immunotherapy in allergic rhinitis and the immune synergistic effect on cross-allergens.

Aim: To compare the efficacy of single- and double-species mite allergen immunotherapy. Materials and methods: An open, pseudo-randomized, controlled study was conducted (n=125 allergic rhinitis patients). The primary end point involved the visual analogue scale. Secondary end points included a basophil activation test and serum specific IgE and IgG4 assays. Results: Visual analogue scale analysis indicated considerable reductions in both groups. Both treatments improved quality of life and induced sIgG4 antibody production. Basophil activation and serum IgE inhibition were not evident in either treatment. Neither treatment displayed an early stage immune synergistic effect on cross-allergens. Conclusions: Both treatments were effective against allergic rhinitis, and statistical differences were not observed. Future studies may require long-term, large-scale research.

Quality of life of patients undergoing specific allergen immunotherapy in allergic rhinitis

Although allergic diseases have been known since antiquity, both their understanding and systematics came later. The World Allergy Organization (WAO) defines the phenomenon of atopy as a predisposition of a person or family to the uncontrolled synthesis and release of IgE antibodies. Allergic rhinitis (AR) is one of the most important clinical diseases of rhinitis (NN, rhinitis). AR significantly reduces the quality of life, tends to increase, and its consequences may be life-threatening diseases. The aim of the study is to determine the quality of life of patients who underwent specific allergen immunotherapy in allergic rhinitis. The study was conducted at the Center for Specialist Allergology in Lublin between October 2018 - February 2019. The study covered a group of 157 patients. The diagnostic method used was a questionnaire. The first research tool was own questionnaire consisting of 31 questions. The second tool was the standardized questionnaire, the Polish version of the SF-36 Quality of Life Questionnaire. Studies have shown statistically significant changes in the symptoms of before and after immunotherapy, which means improving the quality of life and reducing the severity of symptoms and problems of respondents after therapy. The respondents were not in the best of health (50%). Over 50% of respondents said that the immunotherapy process significantly reduced personal / family expenses for treatment associated with allergic rhinitis. The conducted process of specific allergen immunotherapy improved the quality of life of respondents by increasing awareness of the quality of life through the prism of health change in relation to the general indicator in the area of mental problems by reducing their nuisance value more than in the area of somatic symptoms.

Rhinitis 2020: A practice parameter update

This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance on diagnosis, assessment, selection of monotherapy and combination pharmacologic options, and allergen immunotherapy for AR. Newer information about local AR is reviewed. Cough is emphasized as a common symptom in both AR and NAR. Food allergy testing is not recommended in the routine evaluation of rhinitis. Intranasal corticosteroids (INCS) remain the preferred monotherapy for persistent AR, but additional studies support the additive benefit of combination treatment with INCS and intranasal antihistamines in both AR and NAR. Either intranasal antihistamines or INCS may be offered as first-line monotherapy for NAR. Montelukast should only be used for AR if there has been an inadequate response or intolerance to alternative therapies. Depot parenteral corticosteroids are not recommended for treatment of AR due to potential risks. While intranasal decongestants generally should be limited to short-term use to prevent rebound congestion, in limited circumstances, patients receiving regimens that include an INCS may be offered, in addition, an intranasal decongestant for up to 4 weeks. Neither acupuncture nor herbal products have adequate studies to support their use for AR. Oral decongestants should be avoided during the first trimester of pregnancy. Recommendations for use of subcutaneous and sublingual tabletallergen immunotherapy in AR are provided. Algorithms based on a combination of evidence and expert opinion are provided to guide in the selection of pharmacologic options for intermittent and persistent AR and NAR.

Clinical course of asthma in 4 cases of coronavirus disease 2019 infection

Clinical course of asthma in 4 cases of coronavirus disease 2019 infection

A Precision Medicine Approach to Rhinitis Evaluation and Management.

Purpose of ReviewPrecision medicine (PM) represents a new paradigm in disease diagnosis, prevention, and treatment. The PM approach focuses on the characterization of different phenotypes and pathogenic pathways in order to allow the selection of specific biomarkers that will be useful in disease management. Rhinitis is a highly prevalent and heterogeneous disease, both in terms of underlying endotypes and clinical presentations. Therefore, to apply the PM principles to the various rhinitis subtypes rise as a meaningful strategy to improve evaluation and treatment.Recent FindingsThe technology of recombinant allergens has allowed molecular characterization of IgE reactivity of specific individual components of allergenic extracts. Recently published and ongoing clinical trials based on component resolved diagnosis (CRD) bring more precision to allergen immunotherapy for allergic rhinitis. Monoclonal antibodies against various cytokines involved in inflammatory allergic and nonallergic rhinitis endotypes show promissory results.SummaryBetter understanding of pathogenic pathways together with an accurate phenotype classification of patients presented with rhinitis symptoms contributes to point out clinical usefulness of biomarkers and other diagnostic tools, which leads to more accurate environmental control measures, personalized pharmacologic options, and new biological therapy developments.

Illustrative Case Series and Narrative Review of Therapeutic Failure of Immunotherapy for Allergic Rhinitis.

This is a series of 4 cases (3 therapeutic failure and 1 early relapse) in adult patients treated with allergen immunotherapy (AIT) for allergic rhinitis (AR) in our immunotherapy clinic, which treats 110 new patients per year. AIT includes both subcutaneous and sublingual routes. The current national/international AIT recommendations and the literature have been searched to identify guidance for the optimal management of therapeutic failure of AIT in AR. There is scant information available to support clinicians when treatment failure and/or intolerable side effects occur. The importance is highlighted for developing the guidance and evidence base for the benefit of this patient subgroup. The potential strategies that clinicians have proposed are discussed in this article, though it is acknowledged that these are mostly not evidence-based.

Asthma in adults: Principles of treatment.

The goals of treatment are prevention of fatalities, hospitalizations, and emergency department visits, along with achieving good long-term control of asthma, with reduction of symptoms, maintenance of normal activity level, prevention of exacerbations and accelerated loss of pulmonary function (forced expiratory volume in the first second of expiration [FEV1]), and avoidance of harm from therapies. Treatment is often initiated based on the severity of symptoms, physical examination findings, and, for some patients, the FEV1 or peak expiratory flow rates. Comorbidities such as gastroesophageal reflux disease and laryngopharyngeal reflux, rhinitis or rhinosinusitis, sleep apnea, recurrent infections, smoking, and substance abuse should be addressed. Two treatment modalities are indicated only for individuals with allergic asthma: allergen-specific immunotherapy (commonly known as allergy shots), and biologic therapies that target type-2 (T2) inflammation. Allergen immunotherapy is effective in decreasing symptoms and medication use in select patients with mild-to-moderate allergic asthma. In addition, patients who receive allergen immunotherapy for allergic rhinitis may have a decreased risk of developing asthma. Omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab are monoclonal antibodies that target T2 inflammation and are indicated for either moderate-to-severe or severe asthma. These have been well studied to improve asthma symptoms and have specific characteristics unique to each individual medication. A focus on adherence can be considered in choosing therapy because it is not clear which biologic to choose in T2 high asthma at this time.

Prospects of Allergen Immunotherapy for Allergic Rhinitis

Prospects of Allergen Immunotherapy for Allergic Rhinitis

Chinese Guideline on allergen immunotherapy for allergic rhinitis.

The present document is based on a consensus reached by a panel of experts from Chinese Society of Allergy (CSA) and Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G). Allergen immunotherapy (AIT), has increasingly been used as a treatment for allergic rhinitis (AR) globally, as it has been shown to provide a long-term effect in improving nasal and ocular symptoms, reducing medication need, and improving quality of life. AIT is currently the only curative intervention that can potentially modify the immune system in individuals suffering from AR and prevent the development of new sensitization and the progression of disease from AR to asthma. Although the use of AIT is becoming more acceptable in China, to date no AR immunotherapy guideline from China is available for use by the international community. This document has thus been produced and covers the main aspects of AIT undertaken in China; including selection of patients for AIT, the allergen extracts available on the Chinese market, schedules and doses of allergen employed in different routes of AIT, assessment of effect and safety, patients' administration and follow-up, and management of adverse reactions. The Chinese guideline for AR immunotherapy will thus serve as a reference point by doctors, healthcare professionals and organizations involved in the AIT of AR in China. Moreover, this guideline will serve as a source of information for the international community on AIT treatment strategies employed in China.

Health economic analysis of allergen immunotherapy for the management of allergic rhinitis, asthma, food allergy and venom allergy: A systematic overview.

The European Academy of Allergy and Clinical Immunology (EAACI) is developing guidelines for allergen immunotherapy (AIT) for the management of allergic rhinitis, allergic asthma, IgE-mediated food allergy and venom allergy. To inform the development of clinical recommendations, we undertook systematic reviews to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT for these conditions. This study focusses on synthesizing data and gaps in the evidence on the cost-effectiveness of AIT for these conditions. We produced summaries of evidence in each domain, and then, synthesized findings on health economic data identified from four recent systematic reviews on allergic rhinitis, asthma, food allergy and venom allergy, respectively. The quality of these studies was independently assessed using the Critical Appraisal Skills Programme tool for health economic evaluations. Twenty-three studies satisfied our inclusion criteria. Of these, 19 studies investigated the cost-effectiveness of AIT in allergic rhinitis, of which seven were based on data from randomized controlled trials with economic evaluations conducted from a health system perspective. This body of evidence suggested that sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) would be considered cost-effective using the (English) National Institute for Health and Clinical Excellence (NICE) cost-effectiveness threshold of £20 000/quality-adjusted life year (QALY). However, the quality of the studies and the general lack of attention to characterizing uncertainty and handling missing data should be taken into account when interpreting these results. For asthma, there were three eligible studies, all of which had significant methodological limitations; these suggested that SLIT, when used in patients with both asthma and allergic rhinitis, may be cost-effective with an incremental cost-effectiveness ratio (ICER) of £10 726 per QALY. We found one economic modelling study for venom allergy which, despite being based largely on expert opinion and plausible assumptions, suggested that AIT for bee and wasp venom allergy is only likely to be cost-effective for very high-risk groups who may be exposed to multiple exposures to venom/year (eg bee keepers). We found no eligible studies investigating the cost-effectiveness of AIT for food allergy. Overall, the evidence to support the cost-effectiveness of AIT is limited and of low methodological quality, but suggests that AIT may be cost-effective for people with allergic rhinitis with or without asthma and in high-risk subgroups for venom allergy. We were unable to draw any conclusions on the cost-effectiveness of AIT for food allergy.

Update on Allergen Immunotherapy for Allergic Rhinitis: Drops, Tablets, or Shots?

Allergen immunotherapy (AIT) is the only disease-modifying treatment available for allergic rhinitis (AR). Dosing considerations, efficacy, and safety of subcutaneous (SCIT), sublingual (SLIT), and intralymphatic (ILIT) immunotherapy are discussed. Patients with AR who cannot tolerate or do not wish to continue indefinite pharmacotherapy may be candidates for AIT. SCIT is the gold standard formulation but requires repeat injections over several years and may place the patient at risk for systemic allergic reactions such as anaphylaxis. SLIT has been developed as an alternative formulation by which the patient can avoid multiple injections and physician visits as it is dosed at home. SLIT has been proven to be very safe but still requires prolonged treatment, and efficacy compared to SCIT has been questioned. ILIT is currently being developed with the goal of shortening length of treatment while maintaining the efficacy and safety of SCIT and SLIT. SCIT and SLIT are current options for patients wishing to undergo AIT. Further studies are required to determine if ILIT may become an effective option for patients who do not wish to undergo long-term treatments.