House dust mite SCIT reduces asthma risk and significantly improves long-term rhinitis and asthma control-A RWE study.

BACKGROUND: The German Therapy Allergen Ordinance (TAO) triggered an ongoing upheaval in the market for house dust mite (HDM) allergen immunotherapy (AIT) products. Three HDM subcutaneous AIT (SCIT) products hold approval in Germany and therefore will be available after the scheduled completion of the TAO procedure in 2026. In general, data from clinical trials on the long-term effectiveness of HDM AIT are rare. We evaluated real-world data (RWD) in a retrospective, observational cohort study based on a longitudinal claims database including 60% of all German statutory healthcare prescriptions to show the long-term effectiveness of one of these products in daily life. Aim of this analysis was to provide a per product analysis on effectiveness of mite AIT as it is demanded by international guidelines on AIT. METHODS: Subjects between 5 and 70 years receiving their first (index) prescription of SCIT with a native HDM product (SCIT group) between 2009 and 2013 were included. The exactly 3:1 matched control group received prescriptions for only symptomatic AR medication (non-AIT group); the evaluation period for up to 6 years of follow-up ended in February 2017. Study endpoints were the progression of allergic rhinitis (AR) and asthma, asthma occurrence and time to the onset of asthma after at least 2 treatment years. RESULTS: In total, 892 subjects (608 adults and 284 children/adolescents) were included in the SCIT group and 2676 subjects (1824 adults and 852 children/adolescents) in the non-AIT group. During the follow-up period after at least 2 years of SCIT, the number of prescriptions in the SCIT group was reduced by 62.8% (p < .0001) for AR medication and by 42.4% for asthma medication (p = .0003). New-onset asthma risk was significantly reduced in the SCIT vs non-AIT group by 27.0% (p = .0212). The asthma-preventive effect of SCIT occurred 15 months after start of the treatment. In the SCIT group, the time to onset of asthma was prolonged compared to the non-AIT group (p = .0010). CONCLUSION: In this first product based RWD analysis on SCIT with a native HDM product, patients aged 5 to 70 years benefited from AIT in the long term in terms of reduced progression of AR and asthma after at least 2 years of treatment. The effects seemed to last for up to 6 years after treatment termination. A significantly reduced risk of asthma onset was observed, starting after 15 months of treatment.

Developing and validating clinical models to identify candidates for allergic rhinitis pre-exposure prophylaxis.

PURPOSE: Few risk-forecasting models of allergic rhinitis (AR) exist that may aid AR pre-exposure prophylaxis (PrEP) in clinical practice. Therefore, this study aimed to develop and validate an effective clinical model for identifying candidates for AR PrEP using a routine medical questionnaire. METHODS: This study was conducted in 10 Chinese provinces with 13 medical centers (n = 877) between 2019 and 2021. Clinical characteristics and exposure history were collected via face-to-face interviews. Well-trained physicians diagnosed patients with AR based on skin prick test results and clinical performance. The least absolute shrinkage and selection operator model was used to identify potential risk factors for AR, and the logistic regression model was used to construct the risk-forecasting model. Predictive power and model reliability were assessed using area under the receiver operating characteristic curve and calibration curves, respectively. RESULTS: This study diagnosed 625 patients with AR who had positive responses to at least one indoor or outdoor allergen and 460 to at least one outdoor pollen allergen. Two nomograms were established to identify two types of AR with various sensitization patterns. Both models had an area under curve of approximately 0.7 in the development and internal validation datasets. Additionally, our findings found good agreement for the calibration curves of both models. CONCLUSION: Early identification of candidates for AR PrEP using routine medical information may improve the deployment of limited resources and effective health management. Our models showed good performance in predicting AR; therefore, they can serve as potential automatic screening tools to identify AR PrEP candidates.

Meta-analysis: reducing the recurrence rate of allergic rhinitis through oral administration of traditional Chinese medicine.

OBJECTIVE: A systematic review and meta-analysis were carried out to investigate the medical evidence of oral Chinese herbal medicine in reducing the recurrence of allergic rhinitis (AR). MATERIALS AND METHODS: Through computer retrieval of PubMed, ScienceDirect, WOS, and other databases, relevant randomized controlled literature was obtained based on the inclusion criteria and retrieval strategies. The retrieval time was set from January 1, 2013, to December 31, 2022. The bias of the literature was evaluated using the bias evaluation module in Cochrane Manual Version 5.1.0, and the meta-analysis was conducted using RevMan software to verify the effectiveness of oral administration of traditional Chinese medicine (TCM) and its impact on reducing the recurrence rate. RESULTS: The meta-analysis included 7 articles. In the meta-analysis of all articles, the effective treatment rate of oral administration of TCM reached 97.09%. Additionally, when comparing the recurrence rate of AR between patients taking Chinese medicine orally and other treatment groups, the recurrence rate of patients taking Chinese medicine orally was only 24.46%, which was significantly lower (p<0.05). Furthermore, the quality of life of patients taking Chinese medicine orally after treatment was significantly higher than that of patients in the control group (C), indicating the good safety of oral Chinese medicine. CONCLUSIONS: Oral administration of TCM has demonstrated an effective reduction in the recurrence rate of AR, offering patients a good prognosis. This finding holds significant value for the clinical diagnosis and treatment of AR.

[Role of allergen immunotherapy in the prevention of allergic asthma].

The prevalence of allergic asthma is still increasing, which affects the quality of life of patients, threatens their lives, and brings enormous social and economic burden. Allergen immunotherapy (AIT) is the only treatment that can alter the progression of the "Atopic March". It has been widely used in the treatment of allergic rhinitis and conjunctivitis, and its role and effect in the treatment of allergic asthma have been gradually recognized. A few studies have shown that AIT may have a preventive effect on the development and progression of allergic asthma. In this article, the definition of tertiary prevention of allergic asthma is described, and the respective role of AIT in primary, secondary and tertiary prevention of allergic asthma is summarized and analyzed. The aim of this article is to provide evidence for the prevention and control of allergic asthma.

Research Progress on the Mechanism of Acupuncture in the Prevention and Treatment of Allergic Rhinitis.

Objective: To research the mechanism of acupuncture and moxibustion in treating and preventing allergic rhinitis. Methods: We searched PubMed; Google Scholar; Semantic Scholar; Academic Keys; Citation; Dimensions; EuroPub; Index (A & HCI); Compendex; Conference Proceedings Citation; and Science Citation Index. We reviewed the mechanism of acupuncture and moxibustion in the prevention and treatment of allergic rhinitis from the perspectives of Th1/Th2 balance regulation, IgE level reduction, lowering of inflammatory cell infiltration in the nasal mucosa, regulation of nasal neuropeptide (substance P) level, inhibition of Toll-like receptors, and NFκB protein expression. Results: Acupuncture can play a therapeutic role in AR. Combining different aspects such as the influence on Th1 and Th2 subsets of cells, regulation of Th1/Th2 balance, reduction of IgE level, reduction of inflammatory cell infiltration in the nasal mucosa, regulation of nasal neuropeptide (substance P) level, inhibition of Toll-like receptor, and NFκB protein expression, the mechanism of action of acupuncture for AR can be elucidated more comprehensively. Conclusion: Acupuncture and moxibustion can be used to treat allergic rhinitis in several ways.

[Environment control and healthy education are the most important methods for prevention and treatment of allergic rhinitis].

The almost all guidelines of allergic rhinitis (AR) diagnosis and treatment in the world agree the strategy of "combination of prevention and treatment, four in one". There are more descriptions about anti-allergic medications and allergen immunotherapy (AIT), but less contents of environmental control and health education. It is necessary to emphasize again that clinicians must attach great importance to environmental control and strengthen health education in order to realize the three-level prevention of AR and reduce its harm.

Environment control and healthy education are the most important methods for prevention and treatment of allergic rhinitis / 中华预防医学杂志

The almost all guidelines of allergic rhinitis (AR) diagnosis and treatment in the world agree the strategy of "combination of prevention and treatment, four in one". There are more descriptions about anti-allergic medications and allergen immunotherapy (AIT), but less contents of environmental control and health education. It is necessary to emphasize again that clinicians must attach great importance to environmental control and strengthen health education in order to realize the three-level prevention of AR and reduce its harm.

A Novel Strategy for the Treatment of Allergic Rhinitis: Regulating Treg/Th17 and Th1/Th2 Balance In Vivo by Vitamin D.

Objective: This prospective study is aimed at observing the number of nasal itching and sneezing in rats from the macroscopic level and examine the pathological changes of nasal mucosa, Th1 and Th2-related cytokines, and Treg/Th17 by vitamin D3 administration from the microscopic level, in order to explore the role of vitamin D in allergic rhinitis and to provide theoretical guidance for prevention and treatment. Results: There were significant differences in nasal itching and sneezing between the administration groups and the positive groups. Meanwhile, the level of Th1 and Treg in the administration groups increased, while the level of Th2 and Th17 decreased, indicating that the balance of Th1/Th2 was corrected. Our study revealed that vitamin D3 has preventive and therapeutic effects on allergic rhinitis, which provides theoretical guidance for practical application.

Does allergen immunotherapy for allergic rhinitis prevent asthma?

Asthma and allergic rhinitis (AR) have overlapping clinical and pathologic features, sustained by an underlying T helper 2 bias, resulting in airway inflammation that extends from the nose to the lung. Children who are monosensitized often develop polysensitization over time, and they are at high risk of developing asthma. The effect of allergen immunotherapy (AIT) is allergen specific, resulting in symptom improvement and reduction in medication requirement. It is the only known treatment that alters the natural history of allergic disease and induces long-term remission. A bystander or allergen-nonspecific effect of AIT has also been proposed-that AIT to 1 allergen might reduce the risk of development of sensitization to other allergens. Furthermore, several observational studies and clinical trials, in seasonal (pollen) and perennial (house dust mite) AR, have investigated a protective effect of AIT to prevent asthma. The overall evidence favors an asthma preventive effect of AIT in AR to grass and birch tree pollen. Fewer studies have investigated the use of AIT in children with perennial AR due to house dust mite allergy to prevent asthma, and the results are less convincing. The use of AIT to reduce the risk of progression to asthma, in children with AR, potentially has high impact, and it will make AIT more attractive and cost-effective. However, most studies have been of small sample size or of poor design, using different allergens and AIT methodology, making it challenging to draw firm conclusions. There is a need to do adequately powered studies with optimal design and assess cost-effectiveness of this strategy.

Pneumococcal Δpep27 Immunization Attenuates TLRs and NLRP3 Expression and Relieves Murine Ovalbumin-Induced Allergic Rhinitis.

Allergic rhinitis (AR), one of the most common inflammatory diseases, is caused by immunoglobulin E (IgE)-mediated reactions against inhaled allergens. AR involves mucosal inflammation driven by type 2 helper T (Th2) cells. Previously, it was shown that the Streptococcus pneumoniae pep27 mutant (Δpep27) could prevent and treat allergic asthma by reducing Th2 responses. However, the underlying mechanism of Δpep27 immunization in AR remains undetermined. Here, we investigated the role of Δpep27 immunization in the development and progression of AR and elucidated potential mechanisms. In an ovalbumin (OVA)-induced AR mice model, Δpep27 alleviated allergic symptoms (frequency of sneezing and rubbing) and reduced TLR2 and TLR4 expression, Th2 cytokines, and eosinophil infiltration in the nasal mucosa. Mechanistically, Δpep27 reduced the activation of the NLRP3 inflammasome in the nasal mucosa by down-regulating the Toll-like receptor signaling pathway. In conclusion, Δpep27 seems to alleviate TLR signaling and NLRP3 inflammasome activation to subsequently prevent AR.

Allergen immunotherapy for long-term tolerance and prevention.

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.

Implementation of the MASK-Air® App for Rhinitis and Asthma in Older Adults: MASK@Puglia Pilot Study.

INTRODUCTION: MASK-air® is an app whose aim is to reduce the global burden of allergic rhinitis and asthma. A transfer of innovative practices was performed to disseminate and implement MASK-air® in European regions. The aim of the study was to examine the implementation of the MASK-air® app in older adults of the Puglia TWINNING in order to investigate (i) the rate of acceptance in this population, (ii) the reasons for refusal and (iii) the evaluation of the app after its use. METHODS: All consecutive geriatric patients aged between 65 and 90 years were included by the outpatient clinic of the Bari Geriatric Immunoallergology Unit. After a 1-h training session, older adults used the app for 6 months. A 6-item questionnaire was developed by our unit to evaluate the impact of the app on the management of the disease and its treatment. RESULTS: Among the 174 recruited patients, 102 accepted to use the app (mean age, SD: 72.4 ± 4.6 years), 6 were lost to follow-up, and 63 had a low education level. The reasons given not to use the app included lack of interest (11%), lack of access to a smartphone or tablet (53%), low computer literacy (28%), and distrust (8%). At follow-up, the overall satisfaction was high (89%), the patient considered MASK-air® "advantageous" (95%), compliance to treatment was improved (81%), and the rate of loss to follow-up had decreased to 6%. CONCLUSION: Older adults with a low level of education can use the MASK-air® app after a short training session.

The mucosal immune system of the upper respiratory tract and recent progress in mucosal vaccines.

The mucosal immune system prevents microorganism invasion through mucosal surfaces and consists of inductive and effector sites. Nasopharynx-associated lymphoid tissue (NALT) functions as an inductive site, inducing mucosal immune responses in the upper respiratory tract. It follows that intranasal vaccines may prevent upper respiratory infections. To induce and enhance the immune response by administering inactivated antigens intranasally, mucosal adjuvants have been developed, including mutant cholera toxin and cationic cholesteryl pullulan nanogel, which do not accumulate in the central nervous system. Moreover, multivalent pneumococcal polysaccharide conjugate vaccines are used to prevent invasive pneumococcal infections and otitis media, although they only provide moderate protection against acute otitis media because non-vaccine serotypes of Streptococcus pneumoniae and Haemophilus influenzae also cause this infection. To address this problem, pneumococcal surface protein A of S. pneumoniae and P6 of H. influenzae are used as broad-spectrum vaccine antigens. Alternatively, phosphorylcholine (PC) is present in the cell walls of both gram-positive and gram-negative bacteria and induces immune responses through antigenic activity. The significant effects of PC as a mucosal vaccine have been demonstrated through intranasal and sublingual immunization in mice. Furthermore, intranasal administration of PC reverses increases in IgE levels and prevents allergic rhinitis. After immunization with pneumococcal polysaccharide conjugate vaccine, intranasal immunization with PC boosts immune responses to vaccine strains and to PC itself. Thus, PC may be useful as a mucosal vaccine to prevent upper respiratory infections and allergic rhinitis, and it could be used as a booster to the currently used pneumococcal vaccine as it protects against non-vaccine strains.

Prolonged breastfeeding and protective effects against the development of allergic rhinitis: a systematic review and meta-analysis.

BACKGROUND: There is insufficient evidence to confirm the protective effects of prolonged breastfeeding against the development of allergic rhinitis (AR). METHODOLOGY: A systematic review and meta-analysis was performed to assess the associations between prolonged breastfeeding and AR symptoms later in life. Comparisons were conducted between breastfeeding durations less than 6 months and 6 months or more and between less than 12 months and 12 months or more. Exclusive breastfeeding and nonexclusive breastfeeding were analysed separately. Outcomes were risks of AR development later in life. RESULTS: Twenty-three observational studies (161,611 children, age 2-18 years, 51.50% male) were included. Two studies (9%) were with high quality. Both exclusive and nonexclusive prolonged breastfeeding (6 months or more) decreased the risk of AR. The long-term (12 months or more) nonexclusive breastfeeding lowered the likelihood of AR compared to the 12 months or fewer. The long-term exclusive breastfeeding did not show the same protective effect; however, this result was restricted to only one study. CONCLUSIONS: Exclusive breastfeeding and nonexclusive breastfeeding for 6 months or more may have protective effects against the development of AR up to 18 years of age. The findings should be interpreted with caution given the limitation of low-quality observational studies.

Evaluating the Protective Properties of a Xyloglucan-Based Nasal Spray in a Mouse Model of Allergic Rhinitis.

A breached nasal epithelial barrier plays an important role in driving allergic rhinitis (AR). Corticosteroids remain the standard of care (SoC) but come with side effects, thus alternative safe and effective treatments able to avoid inflammation and restore barrier integrity are needed. The aim of the present study is to evaluate the barrier-forming capacity of a xyloglucan-based nasal spray (XG) and compare its efficacy to several SoC treatments (corticosteroid spray, oral mast-cell stabilizer and oral antihistamine) in reducing allergic responses in addition to its effect when concomitantly administered with an antihistamine. An ovalbumin (OVA)-induced mouse AR model was used. XG shows a significant efficacy in reducing histological damage in AR mice; improves nasal rubbing and histamine-induced hyper-responsiveness. Total and OVA-specific IgE as well as pro-inflammatory cytokines are significantly reduced compared to OVA challenged-mice, with im-proved efficacy when used as an add-on treatment. However, XG reduces mucous secreting cells (PAS-positive) and mucin mRNA expression similar to the corticosteroid-treated mice. XG-spray maintains tight junction protein expression (ZO-1) and conversely decreases HDAC1 significantly; the latter being highly expressed in AR patients. Moreover, the concomitant treatment showed in all of the endpoints a similar efficacy to the corticosteroids. This innovative approach may represent a novel therapeutic strategy for nasal respiratory diseases like AR, reducing undesirable side effects and improving the quality of life in patients.

The Protective Role of Cirsilineol against Ovalbumin-Induced Allergic Rhinitis in Mice by Suppression of Inflammation and Oxidative Stress.

Allergic rhinitis (AR) is a common type of inflammatory disease with symptoms including rhinorrhea, fatigue, sneezing, and disturbed sleep. AR affects nearly 40% of peoples worldwide with the increased numbers of new cases. In this work, the study was conducted to disclose the anti-inflammatory and antiallergic properties of cirsilineol against the ovalbumin (OVA)-sensitized AR in mice. AR was provoked in BALB/c mice through the OVA challenge 30 days along with 10 and 20 mg/kg of cirsilineol treatment. The nasal symptoms, i.e., rubbing and sneezing was monitored after the final OVA challenge. The status of OVA-specific IgE, PGD2, and LTC4 was investigated using assay kits. The status of pro-inflammatory markers also examined using assay kits. The levels of oxidative markers, SOD activity, and pro-inflammatory markers in the spleen mononuclear cells (SMEs) were studied by using respective assay kits. The mRNA expression of TXNIP was assessed using RT-PCR study. The 10 and 20 mg/kg of cirsilineol treatment effectively decreased the sneezing and nasal rubbings in OVA-provoked mice. Cirsilineol also decreased the IgE, PGD2, and LTC4 status in the AR animals. The status of pro-inflammatory markers, i.e., IL-4, IL-5, IL-6, IL-33 and TNF-α was found to be decreased in the cirsilineol administered AR mice. Cirsilineol effectively reduced the ROS and MDA and improved SOD in the OVA-challenged SMCs. The mRNA expression of TXNIP was appreciably suppressed by the cirsilineol treatment. Altogether, these findings proved the beneficial actions of cirsilineol against the OVA-triggered AR in mice. The additional studies on the cirsilineol could lead to the development of new drug for AR management.

Mechanism of TCONS_00147848 regulating apoptosis of nasal mucosa cells and alleviating allergic rhinitis through FOSL2-mediated JAK/STAT3 signaling pathway.

This study was conducted to explore the roles and related mechanisms of lncRNA-TCONS_00147848 (TCONS_00147848) in nasal mucosa cell apoptosis and allergic rhinitis (AR). AR mice were sensitized with ovalbumin (OVA), with the TCONS_00147848 interference lentiviral vector (TCONS_00147848 shRNA) and FOSL2 overexpressing lentiviral vectors (pCDH-FOSL2) constructed respectively. NC shRNA, TCONS_00147848 shRNA and TCONS_00147848 shRNA + pCDH-FOSL2 were transfected into AR mice and mice with TNF-α induced nasal mucosa cells. The allergic reaction symptoms were evaluated by scoring. And in this study, we used Hematoxylin-Eosin (HE) staining and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) to detect the histological changes of nasal mucosa and apoptosis of nasal mucosa epithelial cells in mice, cell counting kit-8 (CCK-8) assay, Transwell and annexin V/PI to detect proliferation, migration and apoptosis of nasal mucosa cells of mice, respectively, enzyme-linked immunosorbent assay (ELISA) to detect the expression of inflammatory factors, qRT-PCR to detect TCONS_00147848 expression, Western blot assay to detect the expressions of FOSL2, JAK-2, STAT3, p-STAT3, BAX and BCL-2, RNA-binding protein immunoprecipitation (RIP) assay, RNA pull down assay and Co-immunoprecipitation (CoIP) assay to identify TCONS_00147848 targeting FOSL2. All these findings above reveal that knocking down TCONS_00147848 can reduce the allergic reaction symptom score of AR mice and the inflammatory reaction. The expression of IgE, IL-4, IL-5, IL-10, IL-9, IFN-γ and TNF-α in serum decreased. The expression of FOSL2, JAK-2, p-STAT3 and BAX in nasal mucosa and nasal mucosa cells of mice decreased as well, but BCL-2 expression increased. In addition, koncking down TCONS_00147848 can also inhibit the apoptosis of TNF-α induced nasal mucosa cells in mice and promote cell proliferation and migration. However, FOSL2 overexpression neutralized the effect of TCONS_00147848 shRNA. In nasal mucosa cells of mice, TCONS_00147848 can target FOSL2, interacting with STAT3. Inhibition of TCONS_00147848 can regulate JAK/STAT3 signaling pathway and reduce inflammatory response in AR mice.

Yiqi Jiemin decoction alleviates allergic rhinitis in a guinea pig model by suppressing inflammation, restoring Th1/Th2 balance, and improving cellular metabolism.

We investigated the mechanisms underlying the therapeutic effects of Yiqi Jiemin decoction (YJD), a traditional Chinese medicine (TCM), in the ovalbumin (OVA)-induced allergic rhinitis (AR) model in guinea pigs. YJD significantly decreased infiltration of mast cells and eosinophils into the nasal mucosa of AR model guinea pigs. YJD also increased expression of TGF-ß in the nasal mucosa, restored the balance of Th1/Th2 immune cell responses, and decreased serum levels of various pro-inflammatory mediators, including histamine (HA), neuropeptide Y (NPY), acetylcholine (ACH), norepinephrine and immunoglobulin E (IgE). Metabolic analyses using liquid chromatography coupled with high-resolution mass spectrometry revealed that YJD improved cellular metabolism in AR model guinea pigs and increased serum levels of glycocholic acid while decreasing levels 1-palmitoyl lysophosphatidic acid. RNA-sequencing analysis identified BPIFB2 as a potential diagnostic biomarker and therapeutic target for AR. Functional enrichment analyses showed that YJD significantly inhibited cytokine secretion pathways in AR model guinea pigs. These findings demonstrate that YJD protects against OVA-induced AR in guinea pigs by suppressing inflammation in the nasal mucosa, restoring Th1/Th2 balance, and improving cellular metabolism.