Therapy For Allergic Rhinitis Research Articles

Efficacy of Using Photobiomodulation Therapy in Allergic Rhinitis: A Placebo-Controlled Randomized Clinical Trial.

Recent studies have extensively explored new non-invasive and side-effect-free therapeutic strategies for the treatment of allergic rhinitis (AR). Photobiomodulation therapy (PBMT) utilizes photons from the red to infrared spectrum to modulate biological processes, exhibiting anti-inflammatory and regenerative properties. The objective of our study was to evaluate the efficacy of PBMT in patients with AR. This study was a randomized, placebo-controlled, double-blind clinical trial involving 62 patients with AR. Participants underwent PBMT twice weekly, totaling eight sessions over the course of 1 month. The control group consisted of 29 patients who received treatment with a non-light-emitting device, while 33 patients in the laser therapy group received a protocol of 6 J of red and infrared light administered intranasally, along with 1 J of infrared light applied externally to the nose. Objective, psychophysical, and subjective assessments of nasal obstruction and olfactory function were conducted both before and after the treatment. PBMT contributed to significant improvements in various nasal and respiratory parameters. The peak nasal inspiratory flow demonstrated significant improvement (p < 0.001), and the Nasal Obstruction Symptom Evaluation scale indicated notable enhancement in nasal obstruction (p = 0.048). Additionally, the Rhinitis Control Assessment Test reflected significant symptom improvement over the past week (p = 0.035). However, the University of Pennsylvania Smell Identification Test showed no significant change in olfactory function (p = 0.251). Our data suggest that PBMT may serve as a promising therapeutic option for individuals with AR, providing an alternative for those who are unable to tolerate conventional medications. Furthermore, it demonstrates efficacy and safety as a viable treatment alternative.

Pharmacokinetics and Bioequivalence of 2 Products of Fluticasone Propionate Nasal Spray in Healthy Chinese Subjects.

Fluticasone propionate nasal spray is widely regarded as a first-line therapy for allergic rhinitis. To establish bioequivalence between the test and reference products of fluticasone propionate nasal spray, an open-label, randomized, single-dose, and 2-sequence crossover study was conducted on 84 healthy Chinese subjects under fasting conditions to determine the pharmacokinetic bioequivalence of the 2 products. Following a single-dose administration (200µg) of fluticasone propionate nasal spray, pharmacokinetic parameters, including maximum plasma concentration, area under the concentration-time curve from administration to the last measurable concentration, and area under the concentration-time curve from administration to infinity, exhibited similarity between the 2 products, with 90% confidence intervals for the test/reference ratios falling within the bioequivalence range of 80%-125%.

Expert perspectives on the prescription pattern of levocetirizine₊montelukast and fexofenadine₊montelukast for the management of allergic rhinitis in the Indian settings

Background: Studies have shown that oral antihistamines are considered as the gold-standard therapy for allergic rhinitis. However, there is dearth of studies among clinicians, so this study aimed to gather expert opinion on the prescribing pattern of levocetirizine₊montelukast and fexofenadine₊montelukast for managing AR in India. Methods: This cross-sectional study, conducted through a multi-response questionnaire comprising 24 questions, gathered insights from experts across diverse Indian settings. It explored perspectives on clinical observations, experiences, demographic profiles, treatment characteristics in AR, and the utilization of fexofenadine₊montelukast and levocetirizine₊montelukast for AR management in clinical practice. The data were analyzed through descriptive analysis. Results: Majority of clinicians (52%) preferred levocetirizine₊montelukast for AR, with half of them recommending a 2-week course. Additionally, 38% of clinicians noted its effectiveness in addressing all AR symptoms. Most clinicians agreed that levocetirizine and montelukast combination therapy was effective in improving nighttime nasal symptoms (74%) and nasal congestion (69%). Furthermore, majority of clinicians acknowledged that the combination offers both immediate (74%) and long-term (56%) relief from AR symptoms. Approximately 58% of the healthcare providers reported overall improvement across categories with fexofenadine₊montelukast, encompassing daytime nasal symptoms, nighttime nasal symptoms, and daytime eye symptoms. Conclusion: Clinicians recommended the combination of levocetirizine₊montelukast and fexofenadine₊montelukast to manage AR. Levocetirizine₊montelukast combination was preferred by clinicians for its efficacy in alleviating nighttime nasal symptoms and congestion. Fexofenadine₊montelukast combination was also endorsed for overall improvement across various symptoms.

General practitioner and patient perspectives on intranasal corticosteroids for allergic rhinitis: Treatment duration and obstacles to adherence, findings from a recent survey

Background and objectiveCurrently, there are no guideline recommendations for the duration of intranasal corticosteroid (INCS) treatment for allergic rhinitis (AR). We aimed to catalogue real-world AR-INCS prescription patterns. Materials and methodsThis multicenter, non-interventional, cross-sectional study used online general practitioner (GP) and patient surveys from 4 countries. Eligible GPs had 3–35 years of practical experience, regularly prescribed INCSs for AR treatment, and had managed ≥5 patients with AR per month according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in the previous year. Eligible patients with AR were non-pregnant females or males, aged 18–65 years, previous AR-INCS users (≥12 months), and receiving GP-prescribed AR therapy. Survey participants were from countries with 15–50% AR prevalence and mostly prescription-only INCS use of ≥100 million units annually (Brazil, Mexico, Spain, Thailand). GP surveys and GP-completed patient record forms (PRFs) gathered AR-care and INCS-use data over 10 months; each GP completed patient record forms (PRFs) for 3 patients with AR under their care. The patient survey reflected actual AR-INCS experience, treatment duration, and adherence factors from patient perspectives. The target sample size was 75 GPs, 75 patients, and ≥30 respondents per country. ResultsFrom 900 GP-PRFs, the mean GP-recommended AR-INCS durations reported were 8.4 (Brazil), 8.3 (Mexico), 5.4 (Spain), and 6.4 (Thailand) weeks. From 300 patient surveys, mean reported INCS recommended durations were 6.4 (Brazil), 5.1 (Mexico), 4.0 (Spain), and 4.9 (Thailand) weeks; reported actual use durations were 6.2, 4.8, 3.6, and 6.4 weeks, respectively. The most frequent GP-PRF-reported factors influencing AR-INCS treatment duration were symptom severity (76–85%), symptom recurrence (49–73%), and existing comorbidities (33–57%). The most frequent GP-PRF-reported obstacles to adherence included forgetting to take medication regularly (54–100%), subsiding symptoms (42–91%), and being unable to continue activities (33–51%). Subsiding symptoms (36–53%) and reaching the prescription duration end (20–51%) were most frequent obstacles reported by the patient survey. Patients from all surveyed countries indicated that they visited the GP, a different physician, or a pharmacy for assistance with symptom recurrence; some patients also self-medicated. ConclusionsReal-world AR-INCS prescription durations vary between countries and actual use tends to be shorter than prescribed. Understanding underlying factors may support appropriate AR-INCS use. The study was not powered to statistically compare intercountry differences; hence, comparisons have not been drawn, and the small sample may not reflect a complete picture of clinical practice and patients with AR in each country.

Action-plan and as-needed therapy in allergic rhinitis.

Action-plan is a written set of instructions that helps patient manage their symptoms and respond to worsening of their condition. The action-plan usually includes information on how to recognize, treat, and prevent worsening of symptoms. The plan also helps patient understand when to use their medications, how much to use, and how often to use them as-needed. An action-plan should be developed through a discussion between the patient and the physician, reflecting the patient's severity, preferences, and values and should be regularly updated to reflect changes in the person's condition. In asthma, action-plans and as-needed therapy are already well utilized. Unlike asthma, the importance of an action-plan has been overlooked in allergic rhinitis (AR), but its importance has recently been recognized. AR is a chronic condition that affects people differently, and can cause a range of symptoms, including nasal congestion, runny nose, sneezing, itching, and watery eyes. Therefore, an action-plan and as-needed therapy can help patients manage these symptoms more effectively, reducing the impact on their daily activities and quality of life. Furthermore, it can be tailored to meet the personal needs of each patient, based on the severity of their symptoms, their triggers, and their overall health. Because action-plan can help patients adhere to their treatment regimen by providing clear instructions on when and how to take medication, it can help patients stay on track with their treatment, reducing the likelihood of missed doses and treatment failures. Overall, an action-plan and as-needed therapy are important components of a comprehensive treatment plan for patients with AR. They can help to improve symptom control, prevent complications, and promote adherence to treatment, leading to better outcomes and a higher quality of life.

Xiaoqinglong decoction mitigates nasal inflammation and modulates gut microbiota in allergic rhinitis mice.

Allergic rhinitis (AR) is a respiratory immune system disorder characterized by dysregulation of immune responses. Within the context of AR, gut microbiota and its metabolites have been identified as contributors to immune modulation. These microorganisms intricately connect the respiratory and gut immune systems, forming what is commonly referred to as the gut-lung axis. Xiaoqinglong Decoction (XQLD), a traditional Chinese herbal remedy, is widely utilized in traditional Chinese medicine for the clinical treatment of AR. In this study, it is hypothesized that the restoration of symbiotic microbiota balance within the gut-lung axis plays a pivotal role in supporting the superior long-term efficacy of XQLD in AR therapy. Therefore, the primary objective of this research is to investigate the impact of XQLD on the composition and functionality of the gut microbiota in a murine model of AR. An ovalbumin-sensitized mouse model to simulate AR was utilized, the improvement of AR symptoms after medication was investigated, and high-throughput sequencing was employed to analyze the gut microbiota composition. XQLD exhibited substantial therapeutic effects in AR mice, notably characterized by a significant reduction in allergic inflammatory responses, considerable alleviation of nasal symptoms, and the restoration of normal nasal function. Additionally, following XQLD treatment, the disrupted gut microbiota in AR mice displayed a tendency toward restoration, showing significant differences compared to the Western medicine (loratadine) group. This results revealed that XQLD may enhance AR allergic inflammatory responses through the regulation of intestinal microbiota dysbiosis in mice, thus influencing the dynamics of the gut-lung axis. The proposal of this mechanism provides a foundation for future research in this area.

A systematic review of randomised controlled trials on topical nasal steroids.

Intranasal corticosteroids (INCs) are the first line of therapy for chronic sinonasal conditions such as rhinitis and rhinosinusitis. Among these, one of the most frequently used is beclomethasone dipropionate (BDP). Over the years many studies have evaluated the efficacy of BDP as part of therapy for chronic rhinosinusitis (CRS) and allergic rhinitis (AR) along with nasal washes, which seems to be very well tolerated. To analyse the data in the literature regarding the various therapeutic regimens of BDP in different sinonasal disease and their efficacy and tolerability. Using different search engines, the posology, efficacy, and tolerability of BDP were reviewed and a total of 64 full-length articles were examined for eligibility. After applying inclusion and exclusion criteria, 4 articles were reviewed. BDP is among the group of INCs with significant improvement of nasal symptoms and has good efficacy and safety. BDP nasal spray is one of the most frequently prescribed INC for rhinitis and rhinosinusitis. Treatment with BDP resulted in significant and clinically meaningful improvements in nasal symptoms associated with AR and CRS. BDP is well tolerated, and the safety profile is similar to that of placebo in most patients. These results, in conjunction with the significant benefit reported in subjects with CRS and AR, provide convincing evidence of the overall effectiveness of BDP for the treatment of the full spectrum of sinonasal disease.

Pharmacoepidemiological monitoring of allergic rhinitis therapy in children

Pharmacoepidemiological monitoring of allergic rhinitis therapy in children

Montelukast: results and prospects for applications in pediatric practice

The Centers for Disease Control and Prevention reports that more than 4 million children have been diagnosed with asthma. Currently, there is no treatment that could prevent the development of asthma or change its natural course over long-term follow-up. However, the disease can be controlled using treatments used in clinical practice. For persistent asthma in children aged 5 years and younger, low doses of inhaled glucocorticosteroids are recommended, as well as the administration of montelukast, a leukotriene receptor antagonist. In addition, montelukast is prescribed to patients with allergic rhinitis as an alternative to or in combination with oral antihistamines or nasal corticosteroids. Leukotrienes are lipid mediators that play a key role in acute and chronic inflammation and allergic diseases. They exhibit their biological effects by binding to specific G-protein-coupled receptors. Each subtype of the leukotriene receptor has unique functions and expression patterns. Leukotrienes play an important role in various allergic diseases, including bronchial asthma and allergic rhinitis. Montelukast is a cysteinyl leukotriene receptor-1 antagonist widely used to suppress the inflammatory response in asthma and allergic rhinitis. This review briefly summarizes the biology of leukotrienes and their receptors, recent developments in the field of antileukotriene drugs and the prospects for their different therapeutic applications. The role of antileukotriene drugs and key indications for the use of montelukast in the complex therapy of asthma and allergic rhinitis in children have been determined.

An Observational Study to Determine the Real-Life Effectiveness of MP-AzeFlu® in Austrian Patients with Persistent Allergic Rhinitis.

Many patients with allergic rhinitis (AR) have moderate-to-severe persistent AR. Meda Pharma's AzeFlu (MP-AzeFlu®) is an intranasal AR treatment comprising a novel formulation of azelastine hydrochloride and fluticasone propionate in a single device. This prospective observational study of 214 adults and adolescents in Austria with moderate-to-severe persistent AR assessed the effectiveness of MP-AzeFlu (one spray/nostril twice daily; daily doses: azelastine hydrochloride 548μg; and fluticasone propionate 200μg) for AR control in clinical practice using the visual analog scale. Symptom severity was reported on days 0, 1, 3, 7, 14, 21, 28, 35, and 42. Patient demographics, AR phenotype, allergen sensitization, symptomatology, AR treatments in the previous year, and the reason for the MP-AzeFlu prescription were recorded. MP-AzeFlu treatment was associated with a rapid and statistically significant reduction in the visual analog scale score from baseline to each timepoint measured, including day 1 (all p < 0.0001). Mean (standard deviation) visual analog scale score was 53.5mm (26.3) at baseline, 25.3mm (21.0) on day 28, and 19.6mm (17.4) on day 42, a mean overall reduction from baseline of 41.4 (23.9) mm for completers. Results were consistent irrespective of patient age, gender, severity, or traditional AR phenotype. Prior to MP-AzeFlu prescription, congestion was considered the most bothersome symptom. The majority of patients reported using at least two AR therapies in the past year, including oral antihistamines, intranasal corticosteroids, and intranasal antihistamines. Many patients in Austria live with uncontrolled persistent AR despite treatment. MP-AzeFlu provides effective and rapid control of persistent AR in a real-world Austrian setting.

The effectiveness of pollen allergen immunotherapy on allergic rhinitis over 18 years: A national cohort study in Denmark.

Because long-term effectiveness of pollen allergen immune therapy (AIT) for allergic rhinitis (AR) is not well-described, we studied effectiveness over 18 years in Denmark. A register-based cohort study using data on filled prescriptions, 1995-2016, Denmark. In a cohort of 1.1 million intranasal corticosteroid inhaler users (proxy for AR), we matched users treated with grass, birch or mugwort AIT 1:2 with non-treated users on baseline year and 24 characteristics in the 3 years prior to baseline. The primary outcome was the odds ratio (OR) of using anti-allergic nasal inhaler during the pollen season in the treated versus non-treated group by years since baseline. Among 7760 AR patients treated with pollen AIT, the OR of using nasal inhaler 0-5 years after baseline was reduced when compared with 15,520 non-treated AR individuals (0-2 years, OR 0.84 (0.81-0.88); 3-5 years, OR 0.88 (0.84-0.92)), but was close to unity or higher thereafter (6-9 years, OR 1.03 (0.97-1.08); 10-18 years, OR 1.18 (1.11-1.26)). In post hoc analyses, results were more consistent for those who already had 3 of 3 baseline years of use, and in patients using nasal inhaler in the latest pollen season (0-2 years, OR 0.76 (0.72-0.79); 3-5 years OR 0.86 (0.81-0.93); 6-9 years, OR 0.94 (0.87-1.02); 10-18 years, OR 0.94 (0.86-1.04)) as opposed to no such use. Patients treated with pollen AIT in routine care to a higher degree stopped using anti-allergic nasal inhaler 0-5 years after starting the standard 3 years of therapy, and not beyond 5 years. Post hoc analyses suggested effectiveness was more consistent among patients with persistent AR.

Modern approaches to rational combination pharmacotherapy of allergic rhinitis

Allergic rhinitis (AR) can significantly reduce the quality of life of patients leading to increased fatigue, mood changes, cognitive impairment, and depression. In clinical practice, insufficient effectiveness of initial AR monotherapy is often noted, and a significant proportion of patients referring for medical care have moderate-severe AR. In this regard, the issues of optimization of combined pharmacological treatment of AR are becoming more and more urgent. This paper provides analysis of the opportunities of combined pharmacotherapy within the framework of current management strategy of AR. Based on the results of some studies and known pharmacological properties of medications it is being discussed the advantages of combined use of intranasal corticosteroids and leukotriene receptor antagonists, in particular mometasone furoate and montelukast, in the therapy of AR, including such comorbidities as bronchial asthma, chronic polyposis rhinosinusitis and pharyngeal tonsil hyperplasia. Some aspects of combination therapy with montelukast and second-generation systemic antihistamines as an alternative approach in case of inability to take intranasal corticosteroids, including the reasonability of using a fixed combination of montelukast and levocetirizine, are analyzed from the perspective of rational pharmacotherapy. The problem of interchangeability of brand-name and generic drugs for the treatment of AR is discussed, considering the almost complete absence of studies of their therapeutic equivalence.

Biomarkers in allergen immunotherapy: Focus on eosinophilic inflammation.

Asthma and allergic rhinitis (AR) are 2 of the most common chronic inflammatory disorders and they appear to be on the rise. Current pharmacotherapy effectively controls symptoms but does not alter the underlying pathophysiology. Allergen immunotherapy (AIT) is an evidence-based therapy for asthma and AR and has been recognized as the only therapeutic method that actually modifies the allergic disease process. There is a lack of objective markers that accurately and reliably reflect the therapeutic benefits of AIT. A biomarker indicating patients that would benefit most from AIT would be invaluable. Eosinophilic inflammation is a cardinal feature of many allergic diseases. Biomarkers that accurately reflect this inflammation are needed to better diagnose, treat, and monitor patients with allergic disorders. This review examines the current literature regarding AIT's effects on eosinophilic inflammation and biomarkers that may be used to determine the extent of these effects.

Quality of life of children with allergic rinitis and ways of correction

Introduction. Allergic rhinitis is a common disorder that significantly impairs the children’s quality of life. The problem is particularly pertinent in relation to the paediatric population living in areas with advanced manufacturing industries, where well-known trigger factors, being added by increased concentration of pollutants in the atmospheric air, further complicate the selection of an effective course of treatment.Aim. To determine the effectiveness of a course of treatment with an antihistamine medicine Cetirizine based on the assessment of quality-of-life criteria for children with intermittent allergic rhinitis (IAR) in the Chelyabinsk region.Materials and methods. A prospective study of 147 children with respiratory allergic diseases living in the Chelyabinsk region was conducted. The quality of life of children who received a course of treatment with the antihistamine medicine was assessed using the Paediatric Quality-of-Life inventory (PedsQL) that consisted of combined Likert scales (school life, social, physical functioning, etc.), clinical symptoms were assessed using a developed visual analogue scale.Results and discussion. The assessment findings confirmed that the use of Cetirizine in the complex therapy of intermittent allergic rhinitis and associated comorbid conditions made it possible to significantly improve the clinical symptoms and quality of life of children over the entire treatment period.The most striking positive response in the form of decreased nasal obstruction was seen during the prescribed treatment in patients of Groups 1 and 2. Thus, the filling VAS ratings for children with mild to moderate IAR showed that only 10 (20%) patients in Group 1 experienced mild nasal breathing difficulty. Patients with severe IAR reported a decrease in nasal obstruction only by the end of two-month treatment.Conclusion. Cetirizine demonstrated a good effect of blocking H1-histamine receptors, high bioavailability, good tolerability and safety in the treatment of allergic rhinitis in children with comorbid conditions.

Impact of the Allergic Therapeutic Adherence in Children with Allergic Rhinitis and ADHD: A Pilot Study.

Allergic rhinitis (AR) is the most common chronic allergic disease in children. Several studies have shown an association between attention deficit hyperactivity disorder (ADHD) and allergies, especially AR. Patients with ADHD usually have poor therapeutic adherence, and untreated AR symptoms may worsen the quality of life of patients. The aim of our study was to analyse therapeutic adherence in patients with ADHD and AR and estimate the impact of the adherence on ADHD symptoms. Total Nasal Symptoms Score (TNSS), Paediatric or Adolescent Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ 6-12 years; ARQLQ 13-17 years), Swanson, Nolan, and Pelham version IV scale (SNAP-IV), and Medication Assessment Questionnaire (MGL MAQ) were recorded. In the AR-ADHD group, a positive correlation between TNSS and SNAP-IV subscales was found: worse AR symptoms were related to a negative effect on ADHD scores. AR-ADHD patients with better ADHD therapeutic adherence showed higher AR symptoms and higher oppositional defiant disorder scores in the SNAP-IV questionnaire. Our results suggest that better adherence to AR therapy (oral antihistamines and/or intranasal corticosteroids, INCS) is associated with a reduction in inattention symptoms in children with ADHD. This data could prove to be fundamental for the psychic outcome of these patients.

Exploring the latest understanding on the role of immune mediators, genetic and environmental factors in pathogenesis of allergic rhinitis: a systematic review.

Despite well-defined clinical phenotypes of chronic rhinitis, the underlying in-depth pathophysiological mechanism, particularly with reference to the involvement of immune mediators, genetic, and environmental factors, are still not fully understood. Therefore, our aim was to give updated information on the pathogenesis of allergic rhinitis (AR), with an emphasis on the role of cytokines in adults aged 18 years and above. Additionally, we investigated the impact of genetic and environmental factors in the pathogenesis of AR. A search in various databases identified 1,178 records, and 18 studies were ultimately selected from January 2018 to April 2023. The total sample size in our studies was 4,317, with 2,186 in the experimental and 2,131 in control groups, respectively. The mean age was 33.4 years, with 43% were male, while 57% were female. According to the selected studies, various factors, including immune mediators, particularly cytokines, genetic, and environmental factors, were identified in the development of AR. The selected studies presented findings on different factors and sub-factors in the pathogenesis of AR, making it a challenge for us to compare their results. However, based on our findings, researchers can link our identified factors to potential therapies for AR.

Mesenchymal stem cell derived extracellular vesicles loaded thermosensitive chitosan-based hydrogel alleviates allergic rhinitis in mouse model

Allergic rhinitis (AR) has gained an increasing prevalence over the years, a more effective and safe treatment strategy need to be carried out. Mesenchymal stem cell derived extracellular vesicles (MSC-EVs) show great therapeutic potential for AR, however, their low bioavailability through currently available delivery methods inhibits the process of clinical application. In the present study, an injectable thermosensitive chitosan based hydrogel was developed as an intranasal delivery platform for bone marrow-derived MSC-EVs (BMSC-EVs) and BMSC-EVs were proved to be effective in treating AR animal models for the first time. Our results showed that the BMSC-EVs loaded thermosensitive chitosan based hydrogel (BMSC-EVs@CHI hydrogel) could be prepared easily by ion-crosslinking and its gelation properties were suitable for intranasal administration. In vitro studies demonstrated that the BMSC-EVs@CHI hydrogel could achieve sustained release of BMSC-EVs mainly by degradation control and preserve the therapeutic functions of BMSC-EVs. An in vivo experiment revealed that the BMSC-EVs@CHI hydrogel could enhance the efficacy of BMSC-EVs for AR alleviation. This study provides a suitable delivery platform for BMSC-EVs-based AR therapy.

Current situation of allergological health care at German hospitals.

Allergic medical care in Germany is organized on an interdisciplinary basis. An overview of the current care situation is necessary to manage and improve interdisciplinary cooperation. Between January and February 2022, questionnaires were sent online and by mail to chief physicians of inpatient clinical departments to which most allergological diseases are assigned (dermatology, otorhinolaryngology [ENT], pulmonology, pediatrics, environmental/occupational medicine, gastroenterology; n = 899). The response rate was 52.1%. Allergology departments of dermatology, ENT and pulmonology were predominantly located in metropolitan areas (>100,000 inhabitants), whereas responses of pediatric departments were mostly from smaller towns. 76.8% of the respondents reported existing interdisciplinary treatment plans with other specialties. Pediatric and pulmonology clinics stated disproportionately few interdisciplinary treatment concepts with dermatology and ENT clinics, especially in smaller cities with <100,000 inhabitants. Diagnosis and therapy of allergic rhinitis were performed in particular by the departments of ENT, asthma mainly by the pulmonology departments. Care of other allergological diseases was most frequently reported by chief physicians of dermatology and pediatrics. In metropolitan areas, participating departments provide allergology care in a cooperative manner. A large spectrum of care is covered in cooperation with dermatological clinics. In more rural areas, cooperation is rarer; here, mainly pediatric departments provide allergological care, which may explain the more limited range of services compared to metropolitan areas.

Nasal and blood transcriptomic pathways underpinning the clinical response to grass pollen immunotherapy

Allergen immunotherapy (AIT) is a well-established disease-modifying therapy for allergic rhinitis, yet the fundamental mechanisms underlying its clinical effect remain inadequately understood. Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy was a randomized, double-blind, placebo-controlled trial of individuals allergic to timothy grass who received 2 years of placebo (n= 30), subcutaneous immunotherapy (SCIT) (n= 27), or sublingual immunotherapy (SLIT) (n= 27) and were then followed for 1 additional year. We used yearly biospecimens from the Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy study to identify molecular mechanisms of response. We used longitudinal transcriptomic profiling of nasal brush and PBMC samples after allergen provocation to uncover airway and systemic expression pathways mediating responsiveness to AIT. ClinicalTrials.gov Identifier: NCT01335139, EudraCT Number: 2010-023536-16. SCIT and SLIT demonstrated similar changes in gene module expression over time. In nasal samples, alterations included downregulation of pathways of mucus hypersecretion, leukocyte migration/activation, and endoplasmic reticulum stress (log2 fold changes -0.133 to -0.640, false discovery rates [FDRs] <0.05). We observed upregulation of modules related to epithelial development, junction formation, and lipid metabolism (log2 fold changes 0.104 to 0.393, FDRs <0.05). In PBMCs, modules related to cellular stress response and type 2 cytokine signaling were reduced by immunotherapy (log2 fold changes -0.611 to -0.828, FDRs <0.05). Expression of these modules was also significantly associated with both Total Nasal Symptom Score and peak nasal inspiratory flow, indicating important links between treatment, module expression, and allergen response. Our results identify specific molecular responses of the nasal airway impacting barrier function, leukocyte migration activation, and mucus secretion that are affected by both SCIT and SLIT, offering potential targets to guide novel strategies for AIT.

Effects of 101BHG-D01, a novel M receptor antagonism, on allergic rhinitis in animal models and its mechanism

Allergic rhinitis (AR) is a nasal mucosal disease with sneezing and nasal itching as the main symptoms. Although AR treatment continues to improve, there remains a lack of effective drugs. There are still controversies regarding whether anticholinergic drugs can effectively and safely relieve the symptoms of AR and reduce inflammation in the nasal mucosa. Here, we synthesized 101BHG-D01, which is a novel anticholinergic drug that mainly targets the M3 receptor and may reduce the adverse effects of other anticholinergic drugs on the heart. We evaluated the effects of 101BHG-D01 on AR and investigated the potential molecular mechanism of anticholinergic therapy for AR. We found that 101BHG-D01 effectively alleviated AR symptoms, reduced the infiltration of inflammatory cells and attenuated the expression of inflammatory factors (IL-4, IL-5, IL-13, etc.) in various AR animal models. In addition, 101BHG-D01 reduced the activation of mast cells and the release of histamine from rat peritoneal mesothelial cells (RPMCs) challenged by IgE. Moreover, 101BHG-D01 reduced the expression of MUC5AC in IL-13-challenged rat nasal epithelial cells (RNECs) and human nasal epithelial cells (HNEpCs). Furthermore, IL-13 stimulation significantly increased JAK1 and STAT6 phosphorylation, which was suppressed by 101BHG-D01. We demonstrated that 101BHG-D01 reduced mucus secretion and inflammatory cell infiltration in the nasal mucosa, which may occur through a reduction in activation of the JAK1-STAT6 signaling pathway, indicating that 101BHG-D01 is a potent and safe anticholinergic therapy for AR.