Local Allergic Rhinitis Research Articles

Nasal allergen challenge (NAC): Practical aspects and applications from an EU/US perspective—a Work Group Report of the AAAAI Rhinitis, Rhinosinusitis and Ocular Allergy Committee

Nasal allergen challenge (NAC) is applied in a variety of settings (research centres, specialty clinics and hospitals) as a useful diagnostic and research tool. NAC is indicated for diagnosis of seasonal and perennial allergic rhinitis, local allergic rhinitis, occupational rhinitis, to design the composition of allergen immunotherapy in polysensitized patients and to investigate the physio-pathological mechanisms of nasal diseases. NAC is currently a safe and reproducible technique, although it is time and resource consuming. NAC can be performed by a variety of methods, but the lack of a uniform technique for performing and recording the outcomes, represents a challenge for those considering NAC as a clinical tool in the office. The availability of standardized allergens for NAC is also different in each country. The objective of this workgroup report is to review the current information about NAC, focusing on the practical aspects and application for diagnosis of difficult rhinitis phenotypes (e.g. local allergic rhinitis, occupational rhinitis), taking into account the particular context of practice in the United States and the European Union.

Functional T-cell immunophenotyping in local allergic rhinitis

In allergic rhinitis (AR), T-cell mediated-type 2 immune response plays an important role promoting allergic inflammation. However, its potential role in local allergic rhinitis (LAR) has not been analysed. We investigate the effect of nasal allergen challenge (NAC) with Dermatophagoides pteronyssinus (DP) in peripheral T-cell subpopulations in LAR.

Correlation between the basophil activation test and the severity of rhinitis in local respiratory allergy

Nasal allergen challenge is required to identify local sensitizations in local allergic rhinitis (LAR) and dual allergic rhinitis (DAR, coexistence of LAR to perennial allergens and allergic rhinitis (AR) to seasonal allergens). The basophil activation test (BAT) has been proposed as a time- and resource-saving in vitro alternative diagnostic test in local respiratory allergy.

Establishment of local allergic rhinitis tolerance in mouse model

Objective:To establish a mouse model of local allergic rhinitis tolerance by intranasal infusion of allergen, and study its immunological indexes and characteristics. Methods:The mice were given ovalbumin（OVA） and phosphate buffer solution（PBS） daily, and their allergic symptoms were recorded. OVA-specific antibodies（IgE, IgG1, IgG2a） in serum and cytokine（IL-4, IL-10, IFN-γ） in splenic culture supernatant were detected. The infiltration of eosinophils and goblet cells in nasal mucosa were observed, and the changes in local nasal mucosa genes were analyzed by RNA-seq technique. Results:Mice first showed aggravation of allergic symptoms when stimulated with OVA. The serum OVA-specific antibodies IgE, IgG1, IgG2a and the cytokine（IL-4, IL-10, IFN-γ） Iin splenic culture supernatant were increased, the eosinophils and goblet cells in nasal mucosa were significantly increased. The expression of encoding IL-10, TGF-β gene and eosinophils activation gene in nasal mucosa were up-regulated. As the duration of nasal dripping increased, the allergic symptoms gradually decreased, serum OVA-specific antibodies IgE, IgG1, IgG2a continued to increase. Splenic culture supernatant IL-4 decreased, IL-10 increased, IFN-γ had a downward trend. In nasal mucosa, goblet cells decreased significantly. Genes involved in eosinophils activation were significantly down-regulated. The encoding tolerance genes such as IL-10 and TGF-β genes remained highly expressed. Ten core genes associated with immune tolerance in localized allergic rhinitis were screened, Rps27a, Uba52, Kng2, Gnal, C3, Rtp4, Reep1, Rtp2, Rtp1, Reep5. Conclusion:The mice first develop an allergy and then develop immune tolerance by continuous local drops of the allergen. The generation of immune tolerance may be induced by the continuous action of allergens, which induced systemic and local immune tolerance effects.

Clinic and diagnostics of house dust mite allergy

SummaryHouse dust mite allergens are common triggers for allergic rhinoconjunctivitis and allergic asthma; they can aggravate atopic dermatitis and rarely lead to anaphylactic reactions due to dust mite allergens in food. Typical symptoms are nasal obstruction, sneezing, and irritation, and more often than in pollen allergy, allergic asthma also develops. The symptomatology exists in principle throughout the year with maximum complaints in autumn and winter. Of particular importance are sleep disturbances due to nasal obstruction, which lead to restrictions in the quality of life and performance of affected patients. Sensitization can be proven by skin tests and detection of serum allergen-specific IgE antibodies; proof of allergy is achieved by nasal or conjunctival provocation tests. The diagnosis of local allergic rhinitis can only be made by provocation or by determination of allergen-specific IgE antibodies in nasal secretions. The quality of the allergen extract used is essential for all tests; it must contain the allergens to which a patient is sensitized. The concentration of Der p 23 in house dust mite extracts is particularly critical.

Local Allergic Rhinitis: A Different Rhinitis Endotype? Literature Overview

Chronic rhinitis (CR) is commonly divided into allergic rhinitis (AR) and nonallergic rhinitis (NAR). AR is triggered by the immunoglobulin E (IgE)-mediated response to allergens, whereas NAR is characterized by the absence of allergic sensitization. Previous studies have demonstrated the presence of local IgE in the nasal mucosa of patients suffering from typical allergic rhinitis (AR) symptoms but without a history of atopy and a positive response to a nasal allergen challenge (NAC). This condition was recently defined as local allergic rhinitis (LAR), which is supposed to be a different CR characterized by a type 2 (T2) inflammation response with the release of typical T2 mediators. LAR is defined as a phenotype of AR characterized by a localized nasal allergic response that is negative skin prick testing to allergens in the absence of serum-specific IgE. Diagnosis is based on a positive response to NAC. This review is an update of LAR literature, focusing on the definition of LAR as an independent endotype. LAR, AR, and NAR are characterized by the same clinical symptoms, although there are some differences between these three subtypes. However, the literature data are not yet univocal in defining LAR as an independent endotype.

Nasal eosinophilia as a preliminary discriminative biomarker of non-allergic rhinitis in every day clinical pediatric practice.

Non-allergic rhinitis (NAR) in children, named local allergic rhinitis (LAR) and non-allergic rhinitis with eosinophilia syndrome (NARES), are recently termed entities in childhood characterized by symptoms suggestive of allergic rhinitis in the absence of systemic atopy. Nasal eosinophils (nEo) are the principal cells involved in the allergy inflammation and nasal allergen provocation test is the gold standard method for the diagnosis, albeit with several limitations. The aim of this study was to validate the presence of nEo in combination with the therapeutic response to nasal steroids, as a preliminary discriminator of NAR in real life data. In a prospective cohort study, 128 children (63.3% male, aged 72 ± 42m) with history of NAR were enrolled and followed up for 52 ± 32m. Nasal cytology was performed and nasal steroids trial was recommended initially in all and repeatedly in relapsing cases. Response to therapy was clinically evaluated using 10-VAS. Significant nEo was found in 59.3% of the cases and was related to reported dyspnea episodes. 23.4% had no response to therapy, whereas 51.5% were constantly good responders. Response to therapy was related to nEo and a cutoff point of 20% was defined as the most reliable biological marker with 94% sensitivity and 77% specificity. In children with symptoms of NAR, the presence of nEo > 20% constantly responding to nasal steroid therapy, is a clear indicator of atopy. In an everyday clinical setting, it emerged as an easy, preliminary, cell biomarker suggestive of further investigation such as NAPT, to discriminate LAR from NARES.

Autonomous Breakdown of the Allergen Tolerance in the Nose: A Hypothesis

The prevalence of conventional and new pathogenic types of allergies is increasing. For the last few years, new atopic disorders – local allergic rhinitis (LAR), local allergic asthma, “dual” allergic rhinitis, and local allergic conjunctivitis – have been described. In particular, LAR was identified a decade ago, whereas its immunopathogenesis is still unclear. Nevertheless, the network of immune cells and neurons determining the maintenance or breakdown of allergen tolerance has partially been studied. Therefore, this field of research is currently at the cutting edge. However, there is still not any definitive answer as to why local disorders take place. Specifically, the nasal cavity is characterized by the following prevalent neuro molecules: acetylcholine, norepinephrine, substance P, neuromedin U, vasoactive intestinal peptide, and calcitonin-gene-related peptide; some of which are pro-immunogenic and a slightly smaller part is protolerogenic. In the spotlight, the hypothesis of an autonomous breakdown of tolerance to allergens in LAR is presented. The article describes immune tolerance as the antipode of the active immune response, which does not lead to producing effector cells and molecules, and vice versa is based on active immunosuppressive processes. In addition, this article focuses on the mechanisms of the maintenance and breakdown of allergen tolerance, a form of immune tolerance, at the nasal level and throughout the body, and the essential role of various cells and molecules, including neuro molecules, in the pathogenesis of LAR.

The Role of Allergen-Specific Immunotherapy in ENT Diseases: A Systematic Review.

Previous studies have demonstrated that both subcutaneous (SCIT) and sublingual specific immunotherapy (SLIT) are effective in treating allergic rhinitis (AR). Further studies have evaluated the efficacy of allergen-specific immunotherapy (AIT) on different ear, nose, and throat (ENT) manifestations, in which allergy might have an etiopathogenetic role, such as local allergic rhinitis (LAR), rhinosinusitis (RS), otitis media (OM), and adenotonsillar (AT) disease. Nevertheless, the management of allergy in ENT diseases is still debated. To the best of our knowledge, this is the first systematic review assessing the efficacy of AIT in ENT diseases aside from AR. Literature data confirmed that AIT might be an effective therapeutic option in LAR, although its effect is restricted to studies with short-term follow-up. Furthermore, previous research demonstrated that AIT may improve symptoms and surgical outcomes of chronic rhinosinusitis when used as an adjunctive treatment. Few studies supported the hypothesis that AIT may exert positive therapeutic effects on recurrent upper airway infections as adenotonsillar disease. Finally, some clinical observations suggested that AIT may add some benefits in the management of otitis media with effusion (OME). The results of this systematic review allow us to conclude that the efficacy of AIT in ENT disorders has been only slightly investigated and additional studies are needed.

Sequential class switch recombination to IgE and allergen-induced accumulation of IgE+ plasmablasts occur in the nasal mucosa of local allergic rhinitis patients.

The involvement of allergen-specific (s)IgE in local allergic rhinitis (LAR) has been debated. Here, we investigate the effect of nasal allergen challenge with Dermatophagoides pteronyssinus (NAC-DP) in mucosal and peripheral B-cell subpopulations in LAR patients. Nine LAR, 5 allergic rhinitis (AR), and 5 non-atopic healthy control (HC) individuals were subjected to a 3-day NAC-DP protocol, and nasal biopsies and blood samples were collected before and after provocation. Nasal biopsies were used for immunohistochemistry and gene expression studies, whereas the frequency of lymphocyte subsets and basophil activation test (BAT) were analyzed in blood samples by flow cytometry. sIgG was measured in sera. NAC-DP induced an increase in IgE+ CD38+ plasmablasts in the nasal mucosa of LAR patients, but not in AR or HC individuals. Markers of sequential recombination to IgE (εCSR) (from IgG) were observed in 33% of LAR, 20% of AR, and 0% of HC subjects. NAC-DP increased the proportion of peripheral CD19+ CD20+ CD38+ plasmablasts in AR and LAR patients, but not in HC. Expression of the mucosal homing receptor CXCR3 in peripheral CD19+ CD20+ CD38+ plasmablasts from LAR, AR, and HC individuals was 7%, 5%, and 0.5%, respectively. In vitro DP stimulation increased proliferating CD19+ CD20+ CD38+ plasmablasts in LAR and AR patients, but not in HC. Serum DP-sIgG was higher in LAR and AR patients as compared to HC. BAT was positive in 33%, 100%, and 0% of LAR, AR, and HC subjects, respectively. These results suggest that allergen exposure induces the sequential εCSR of IgG+ CD19+ CD20+ CD38+ plasmablasts in the nasal mucosa of LAR patients.

The influence of local allergic rhinitis on asthma and the efficacy of allergen immunotherapy

局部变应性鼻炎容易被误诊或漏诊，患者的鼻部症状可在数年内进展至中-重度，显著影响其生活质量，并可进一步发展为哮喘。当患者出现变应性鼻炎症状但过敏原特异性免疫球蛋白E检测结果为阴性时，应将局部变应性鼻炎作为鉴别诊断之一。目前局部变应性鼻炎的诊断依赖于鼻黏膜过敏原激发试验。参照变应性鼻炎的治疗策略，其治疗应包括避免接触过敏原、药物治疗和过敏原特异性免疫治疗，其中过敏原特异性免疫治疗可改善局部变应性鼻炎患者的生活质量，提高其对过敏原的耐受性。.

Local allergic rhinitis in children: A systematic review.

Local allergic rhinitis (LAR) is a well-defined and reported phenotype in adults, but data is scarce for children and adolescents, and it is probably an undiagnosed and highly underestimated condition in childhood. The objectives of this systematic review were to identify original observational studies published on LAR in children and adolescents and to describe the prevalence and characteristics of this phenotype in the pediatric age group. A systematic search was performed in PubMed and EMBASE databases. The search was limited to publications on humans, written in English, published between January 1, 2000 and September 20, 2021. Participants had to be under 18 years old and with a diagnosis of LAR confirmed by nasal allergen provocation test (NAPT). Ten articles were identified. Despite the wide variability of protocols, prevalence rates ranged from 3.7 to 83.3% among children previously diagnosed as having nonallergic rhinitis, being markedly lower in Eastern countries (3.7-16.6%) when compared to Western countries (22.3-83.3%). To date, no relevant clinical characteristics capable of differentiating LAR patients from other childhood rhinitis phenotypes have been identified. LAR is an allergic rhinitis phenotype also found in children. Population and regional differences and differences in NAPT protocols may explain the heterogeneity in LAR prevalence rates observed in different parts of the world. In addition to clarifying this large discrepancy, longitudinal studies are also needed to assess the clinical characteristics of the LAR phenotype in the pediatric age group, and its stability into adulthood must be confirmed.

Characteristics of allergen profile, sensitization patterns and Allergic Rhinitis in SouthEast Asia.

To highlight the characteristics of allergic rhinitis, local allergic rhinitis (LAR), and importance of allergens in Southeast Asian countries. The Asia-Pacific region is very diverse with disparities in the epidemiological data between countries as well as in the unmet needs. The prevalence of allergic rhinitis has markedly increased in the past decades, with a high variation between countries, ranging from 4.5--80.3%. In terms of LAR, the reported prevalence in Southeast Asia is similar to that of other Asian countries (3.7-24.9%) but lower than that in western countries. House dust mites, cockroach, pollens, and molds are major allergens that are known triggers for of allergic rhinitis in this region, whereas the association with helminth infection requires further investigation. There are gaps and high variation between countries in Southeast Asia regarding the prevalence of allergic rhinitis and LAR. Further studies are needed to fully elucidate the association between allergens and allergic rhinitis in Southeast Asia.

Sustained benefit of a 3-year cycle of subcutaneous house dust mite immunotherapy in local allergic rhinitis individuals

Subcutaneous allergen immunotherapy (SCIT) decreases allergic and local allergic rhinitis (AR and LAR, respectively) symptoms. In AR patients also induces a sustained effect lasting several years after therapy withdrawal. Whether SCIT has a comparable long-lasting effect in LAR is currently unknown. We evaluated the long-term evolution of LAR patients with a 3-year SCIT treatment with Dermatopagoidespteronyssinus (DP) (DP-SCIT), as compared to AR subjects.

Diagnosis and Treatment of Local Allergic Rhinitis.

Some patients with chronic rhinitis have a positive nasal allergen provocation test (NAPT) without systemic IgE sensitization by skin prick tests or serum allergen-specific IgE (sIgE). This novel concept is called local allergic rhinitis (LAR) and affects children and adults worldwide, but is underdiagnosed. LAR is not just the initial state of allergic rhinitis (AR), it is a unique form of chronic rhinitis that is neither classical AR nor non-AR. Many of the features of AR and LAR are similar, such as a positive NAPT, positive type 2 inflammatory markers, including the nasal discharge of sIgE, and a high incidence of asthma. A differential diagnosis of LAR needs to be considered in patients with symptoms suggestive of AR in the absence of systemic atopy, regardless of age. The diagnostic method for LAR relies on positive responses to single or multiple allergens in NAPT, the sensitivity, specificity, and reproducibility of which are high. The basophil activation test and measurement of IgE in nasal secretions also contribute to the diagnosis of LAR. Treatment for LAR is similar to that for AR and is supported by the efficacy and safety of allergen exposure avoidance, drug therapy, and allergen immunotherapy. This review discusses current knowledge on LAR.

Synaptic transmission molecules and their role in the pathogenesis of allergic rhinitis

Immune cells and molecules, as well as synaptic transmission molecules play a regulatory role in the communication pathways of the entire body when it is necessary to engage all body resources in the fight against infections or tumor cells wherever they appear. In potential allergy, the neuroimmune network controls allergen tolerance maintenance at both local and systemic levels.The review focuses on different neurotransmitters and our understanding of a balance and imbalance between the immune system and the nervous system in allergic inflammation, including allergic rhinitis. However, the pathogenesis of the two endotypes of rhinitis (conventional allergic rhinitis and local allergic rhinitis) and the impact of the neuroimmune network on it remain unresolved.

The aspects of local allergic rhinitis in Polish children and adolescents.

Local allergic rhinitis (LAR) is one of the endotypes of rhinitis which occurs commonly in different age groups. To present the occurrence and characteristics of LAR in Polish children and adolescents. In the study protocol, three hundred sixty-one patients aged 5-17 with chronic rhinitis were included from 8 centres in Poland. Medical history and diagnostic procedures were performed with aeroallergens: skin prick tests, allergen-specific serum IgE and nasal provocation tests. In addition to LAR, allergic rhinitis (AR), dual allergic rhinitis (DUAL) and non-allergic rhinitis (NAR) were explored and compared. LAR was confirmed in 21% of patients, systemic allergic rhinitis (SAR) in 43.9%, DUAL in 9.4% and NAR in 33.9% of patients. Based on nasal provocation test (NPT), allergy to HDM prevailed in the LAR group (68%), grass in the SAR group (58%), and grass and HDM in the DUAL group (32% and 64%). Girls were prevalent in the LAR group, and severe rhinitis and asthma were more common than other endotypes (p < 0.05). LAR is a common disease in children and adolescents and is often associated with severe rhinitis and frequently coexists with asthma.

Local allergic rhinitis in pediatric population

Local allergic rhinitis in pediatric population

Nasal lavage fluid sIgE levels in differential diagnostics of allergic rhinitis.

Differential diagnosis plays a key role in diagnosing specific types of allergic rhinitis. The method involving allergen-specific immunoglobulin E (sIgE) detection in nasal lavage fluid, which has continually been the object of standardization efforts, is characterized by high specificity/sensitivity and plays a special role in diagnosing local allergic rhinitis. This article is a systematic review of the literature on the methodology, standardization, and use of sIgE detection in nasal lavage fluid in patients undergoing diagnostic tests for allergic rhinitis.

Diagnostic markers of local allergic rhinitis

Local allergic rhinitis is a new atopic disease recognized in modern allergy and rhinology. Its clinical symptoms are currently well described and compared with conventional allergic rhinitis, however, diagnostic and therapeutic protocols, including antigen-specific immunotherapy (ASIT), should be specified. Therefore, local allergic rhinitis often remains underdiagnosed and by mistake is referred to non-allergic rhinitis. Yet, the pathogenesis and mechanisms of allergen tolerance breakdown in this endotype of allergic rhinitis remain understudied. Researchers continue to study the network of tolerogenic cells and biomolecules, such as regulatory T cells, tolerogenic dendritic cells, interleukin (IL)-10, IL-35, transforming growth factor-β (TGF-b), vegetative innervation of the nose, and neurotransmitters. The review focuses on diagnostic markers of local allergic rhinitis.