Search Results (88)

The aim of this systematic review was to evaluate the current evidence for the involvement of epithelial-derived extracellular vesicles (EVs) in Immunoglobulin E (IgE)-mediated allergic sensitisation. Original clinical and research studies specifically examining the effect of epithelial-derived EVs in IgE-mediated allergic sensitisation were included. Non-IgE mediated allergies, abstracts and review articles were excluded. A total of 18 publications were identified from three databases (EMBASE, Web of Science and PubMed) that indicate epithelial-derived EVs have the potential to promote tolerance or allergic sensitisation. For example, epithelial-derived EVs have the potential to promote IgE-mediated allergic sensitisation by delivering mRNAs that promote T helper 2 (Th2) polarisation and cytokine secretion, or promote tolerance through the induction of T regulatory (Treg) cells. The results also indicate that the potential role of epithelial-derived EVs in IgE-mediated allergic sensitisation may be dependent on the barrier, with all publications related to intestinal epithelium driving tolerance, but publications on nasal and bronchial/alveolar epithelia gaving mixed effects. No publications were found on cutaneous epithelia. Taken together, the literature suggests that epithelial-derived EVs play a key role in influencing IgE-mediated allergic sensitisation. Further research examining all epithelial barriers, using both robust human in vitro models that give more biologically relevant information, as well as clinical studies, are required to further characterise the role of epithelial-derived EVs in IgE-mediated allergic sensitisation. Full article

Quercetin, a natural flavonoid, present in various vegetables and fruits, has garnered increasing attraction for its potential antiallergic properties. Its broad-spectrum activity depends on its anti-inflammatory, immunomodulatory, and antioxidant effects, which target the critical pathways involved in type 2-driven allergic inflammation. Quercetin inhibits mast cell degranulation, reduces the production of histamine and pro-inflammatory cytokines, and restores homeostasis of the immune system by modulating the Th1/Th2 and Treg/Th17 balances. Additionally, its antioxidant properties help to dampen oxidative stress, a critical factor in the pathophysiology of allergic diseases. In vitro studies have consistently demonstrated quercetin’s ability to suppress allergic reactions. In contrast, in vivo studies, particularly in murine models of allergic rhinitis, have confirmed its efficacy in relieving symptoms (such as nasal itching, sneezing, rhinorrhea, and congestion) and dampening type 2 mucosal inflammation. Preclinical evidence also supports its therapeutic potential in asthma, conjunctivitis, atopic dermatitis, and food allergies. However, human studies are still scarce, as only two clinical trials investigated quercetin as a monotherapy. Both studies reported promising results, including symptom reduction and improved quality of life, though larger, randomized trials are needed to validate these findings. Some other studies have investigated multicomponent products that also contain quercetin. This review aimed to report and discuss the most recent in vitro and in vivo evidence on quercetin’s application in allergic models. It also provides a comprehensive overview of human studies, highlighting its potential as an agent in food supplements to manage patients with allergic diseases. Moreover, this review introduces a new quercetin phospholipids formulation that may represent a keystone in clinical use. The literature search was based on a PubMed consultation considering the most recent (last five years) publications using the keywords “quercetin and allergic disease” and “quercetin and immune system”. Full article

Background: Allergy to Alternaria alternata (Alt a), although often underdiagnosed, is a significant global health issue. In the allergen immunotherapy (AIT) field, novel therapeutic strategies are emerging, particularly with the advent of polymerized allergoids. This study aims to evaluate the efficacy of subcutaneous immunotherapy (SCIT) based on these innovative molecules in children with respiratory allergies, assessing clinical and functional parameters. Methods: We enrolled 42 patients aged between 6 and 16 years, all of whom had allergic rhinitis (AR) and concomitant asthma and all of whom were monosensitized to Alt a. Between December 2020 and December 2021, 17 patients initiated SCIT with Modigoid^® for Alt a1, while 25 patients continued with standard therapy. At the initial visit (T0), all the patients underwent nasal and bronchial evaluation, including exhaled nitric oxide (eFeNO) measurement and spirometry. The Asthma Control Test (ACT) was used to evaluate the control of asthma symptoms. Patients were followed up every 6 months, with a comprehensive re-evaluation at 24 months (T1) replicating the initial assessments. Results: After 24 months of SCIT with the new polymerized molecular allergoid Alt a1 (Modigoid^®), children showed a statistically significant reduction in eFeNO levels, improved FEV1 values, and enhanced ACT scores. Conclusions: SCIT with the new molecular allergoid Alt a1 significantly improves functional parameters (FEV1 and eFeNO) and subjective asthma symptoms (ACT scores) in children with AR and objective asthma signs. This treatment represents an effective preventive strategy that can be used to halt the progression of the classic atopic march from AR to asthma and potentially reverse the atopic march. Full article

Background: Emerging evidence suggests that nutraceuticals, alongside standard therapy, may benefit children with allergic rhinitis (AR). This study aimed to compare the efficacy of Quertal^® (Neopharmed Gentili S.p.A., Milano, Italy), a nutraceutical supplement based on Perilla frutescens, Quercetin, and vitamin D3, combined antihistamines per os versus antihistamines alone, in improving AR symptoms considering respiratory functional and laboratory biomarkers in pediatric age. Materials and Method: This study included 100 children, 50 in the case group (Quertal^® plus antihistamines) and 50 in the control group (antihistamines alone), with mild/moderate AR sensitized to grass pollens. They underwent assessments of respiratory function (rhinomanometry-AAR, spirometry), inflammation markers (Nasal Nitric Oxide [nFeNO]; exhaled Nitric Oxide [eFeNO]; nasal cytology), and laboratory assays (blood eosinophils, total IgE and specific IgE to Phl p1). Results: After three months of treatment, the case group showed statistically significant improvement in nFeNO and eFeNO values compared to controls (p < 0.001), as well as a reduction in nasal eosinophils (p < 0.001). Conclusions: Adding Quertal^® to standard antihistamine therapy may reduce nasal inflammation and improve AR symptoms in pediatric patients. This combination therapy shows promise as a practical, well-tolerated approach to managing AR and may have broader implications for enhancing long-term outcomes. Full article

Background/Objectives: This systematic review evaluates the efficacy of quail egg-based supplements (QES) as an integrative remedy for treating allergic rhinitis. Methods: A comprehensive search of PubMed, Scopus, EMBASE, Cochrane Library, and Google Scholar was conducted up to January 2025 to address the research question. Results: A total of 294 studies were initially identified, with five clinical reports meeting the inclusion criteria. Participant numbers ranged from 40 to 180 (median: 77), with a balanced gender ratio. Four reports focused on allergic rhinitis, and one investigated nonsymptomatic atopic individuals exposed to volatile allergens. The findings suggest that a combination of QES and zinc significantly improves peak nasal inspiratory flow, mucociliary transport time, and symptoms such as rhinorrhea, nasal congestion, itchy nose and eyes, and sneezing in patients with allergic rhinitis. Additionally, QES may reduce the reliance on standard symptomatic medications. The intervention was generally well tolerated, with side effects being rare, mild, and transient; however, QES should be avoided in patients with egg allergies. Conclusions: The reviewed studies indicate that QES with zinc can serve as an effective integrative approach to alleviating symptoms of allergic rhinitis. Further research is recommended to confirm these findings. Full article

Background: Acute and chronic sinusitis significantly impact patients’ quality of life. Effective drug delivery to paranasal sinuses is crucial for treating these conditions. However, medications from conventional devices like nasal drops, sprays, and nebulized mists often fail to penetrate the small ostia and reach the sinuses. This study aims to assess the effectiveness of e-vape-generated aerosols entering and filling paranasal sinus cavities, particularly the maxillary sinus. Methods: The aerosol droplets were generated using an electronic vaporizer (e-vape) and were composed solely of vegetable glycerin (VG) and propylene glycol (PG). Patient-specific, transparent nose-sinus models, including one with post-uncinectomy surgery, were used to evaluate the effectiveness of these e-vape-generated VG-PG aerosols in entering the sinuses under unidirectional and bidirectional airflow conditions. Visualizations from various nasal model views and lighting conditions were recorded. Particle size distribution measurements of the e-vape aerosol were conducted using a laser diffraction particle size analyzer. Results: E-vape-generated VG-PG droplets effectively enter paranasal sinuses under specific administration conditions. E-vape aerosol droplet size measurements revealed a mean particle size ranging from 2.895 to 3.359 μm, with a median particle size (D50) averaging 2.963 μm. The speed of aerosol entering the paranasal sinuses is directly proportional to the ostia size; larger ostia result in faster sinus entry. A continuous moderate flow is necessary to gradually fill the paranasal sinus cavities. The aerosol entry into sinuses was observed at 2 L/min and decreased with increasing flow rate. The mechanisms of aerosol entry involve maintaining a positive pressure gradient across the ostial canal, a non-equilibrium transverse pressure distribution, and a two-way flow through the ostium. Gravitational forces and recirculation currents further enhance the deposition of e-vape aerosols. Comparative tests showed that traditional delivery devices exhibited limited penetration into paranasal sinuses. Conclusions: This study demonstrated that e-vape-generated aerosols could serve as a vehicle for delivering active pharmaceutical ingredients (APIs) directly to the paranasal sinuses, improving treatment outcomes. Full article

Allergic diseases triggered by airborne allergens such as allergic rhinitis and conjunctivitis are increasingly prevalent, posing significant challenges for both patients and healthcare systems. Assessing the efficacy of allergen immunotherapy and other anti-allergic treatments requires precise and reproducible methods. Allergen exposure chambers (AECs) have emerged as advanced tools for evaluating clinical outcomes, offering controlled conditions that address many limitations of traditional field-based studies. This review explores the advantages of AECs in allergy management, emphasizing their role in providing standardized allergen exposure for both clinical research and routine assessments. AECs deliver consistent and reproducible data comparable to the nasal allergen challenge and natural allergen exposure, making them a valuable addition to the diagnosis and treatment effectiveness of allergic diseases. Although they are well suited to early-stage clinical trials, further standardization and validation are needed to gain broader acceptance in pivotal phase III studies. Future research should focus on refining AEC protocols and integrating them into regulatory frameworks, ensuring their role in the advancement of therapeutic approaches for allergic diseases. Full article

Mast cells are immune system cells with the most disparate functions, but are also among the least understood. Mast cells are implicated in several known pathological processes, tissue homeostasis, and wound repair. However, they owe their notoriety to allergic diseases, of which they represent the effector cell par excellence. In both allergic and not upper airway pathologies, mast cells play a key role. Exploring the mechanisms through which these cells carry out their physiological and pathological function may help us give a new perspective on existing therapies and identify new ones. A focus will be placed on non-allergic rhinitis, a poorly recognized and often neglected condition with complex management, where the role of the mast cell is crucial in the pathogenetic, clinical, and prognostic aspects. Full article

Nasal polyps (NPs) are usually part of chronic rhinosinusitis with nasal polyposis (CRSwNP). However, the exact etiology of CRSwNP is still unknown. In addition, the suggested etiological causes are infection, allergy, and immunological disorders, among others, such as genetic predisposition. Moreover, it is also suggested that oxygen-free radicals play a vital role in the pathogenesis of nasal polyposis, and inflammatory cells produce free radicals during phagocytosis, which is the primary source of ROS, controlled by the glutathione S-transferase (GST) system. Although, vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, it is closely interwoven with the mobilization of inflammatory cells. This pilot study evaluated the association between genetic variant VEGF-A (rs28357093) and GSTM1/GSTT1 deletion polymorphism in susceptibility to CRSwNP. A case–control study was conducted with 61 individuals diagnosed with CRSwNP and 100 healthy subjects. VEGF-A (rs28357093) and GSTM1/GSTT1 deletion polymorphisms were genotyped by RFLP-PCR and SYBR Green real-time PCR, respectively. Individuals with allergic rhinitis carriers with AC genotype (rs28357093) presented a 4-fold increased risk to CRSwNP (OR = 4.20, 95% CI = 1.31 to 13.50; p = 0.015). This evidence shows that the increased vascular permeability probably causes an inflamed nasal area leading to extensive edema and polyp growth. On the other hand, no association was verified for each genetic variant by inheritance models. Interestingly, the GSTT1 present genotype showed a protective effect on CRSwNP. In conclusion, additional studies that have larger groups in different geographic localizations may be useful to verify and assess the association between genetic variants and CRSwNP. Full article

Nasal polyposis is defined as a Th2-driven chronic inflammation of the nose and sinus with polyps visible in the nasal fossae. It is a prevalent disease with a significant impact on health-related quality of life (HRQL). Allergies, allergic rhinitis, asthma, and aspirin intolerance are frequently associated. The management is individual. The first line of treatment is long-term treatment with intranasal corticosteroids. Oral corticosteroids should be used with caution. When the medical treatment fails, the patient is eligible for sinus surgery, which usually consists of a complete sphenoethmoidectomy. In the case of symptomatic recurrence after both medical and surgical treatment, biologics are currently a very promising treatment effective on all respiratory tracts. Dupilumab is considered in the literature to be the molecule of choice. However, besides the international guidelines published by EPOS and Euforea, the molecule prescribed depends also on its availability in each country and the criteria edited by the health authorities to receive reimbursement. Traditional medical treatment remains necessary as a complement to biologics. At the moment, there is no consensus on when the medical treatment can be stopped. Full article

Allergic rhinitis (AR) is a series of allergic reactions to allergens in the nasal mucosa and is one of the most common allergic diseases that affect both children and adults. Shi-Bi-Lin (SBL) is the modified formula of Cang Er Zi San (CEZS), a traditional Chinese herbal formula used for treating AR. Our study aims to elucidate the anti-inflammatory effects and mechanisms of SBL in house dust mite-induced AR by regulating gut microflora metabolism. In vivo studies showed that nasal allergies and the infiltration of inflammatory cells in the nasal epithelium were significantly suppressed by SBL. Moreover, SBL restored the impaired nasal epithelial barrier function with an increased tight junction protein expression and reduced the endothelial nitric oxide synthase (eNOS). Interestingly, SBL significantly reconstituted the abundance and composition of gut microbiota in AR mice; it increased the relative abundance of potentially beneficial genera and decreased the relative abundance of harmful genera. SBL also restored immune-related metabolisms, which were significantly increased and correlated with suppressing inflammatory cytokines. Furthermore, a network analysis and molecular docking indicated IL-6 was a possible target drug candidate for the SBL treatment. SBL dramatically reduced the IL-6 level in the nasal lavage fluid (NALF), suppressing the IL-6 downstream Erk1/2 and AKT/PI3K signaling pathways. In conclusion, our study integrates 16S rRNA sequencing, microflora metabolism, and network pharmacology to explain the immune mechanism of SBL in alleviating HDM-induced allergic rhinitis. Full article

Conventional immunization methods such as intramuscular injections lack effective mucosal protection against pathogens that enter through the mucosal surfaces. Moreover, conventional therapy often leads to adverse events and compromised immunity, followed by complicated outcomes, leading to the need to switch to other options. Thus, a need to develop safe and effective treatment with long-term beneficial outcomes to reduce the risk of relapse is mandatory. Mucosal vaccines administered across mucosal surfaces, such as the respiratory or intestinal mucosa, to prompt robust localized and systemic immune responses to prevent the public from acquiring pathogenic diseases. Mucosal immunity contains a unique immune cell milieu that selectively identify pathogens and limits the transmission and progression of mucosal diseases, such as allergic dermatitis and inflammatory bowel disease (IBD). It also offers protection from localized infection at the site of entry, enables the clearance of pathogens on mucosal surfaces, and leads to the induction of long-term immunity with the ability to shape regulatory responses. Regulatory T (Treg) cells have been a promising strategy to suppress mucosal diseases. To find advances in mucosal treatment, we investigated the therapeutic effects of intranasal pep27 mutant immunization. Nasal immunization protects mucosal surfaces, but nasal antigen presentation appears to entail the need for an adjuvant to stimulate immunogenicity. Here, a novel method is developed to induce Tregs via intranasal immunization without an adjuvant to potentially overcome allergic diseases and gut and lung inflammation using lung–gut axis communication in animal models. The implementation of the pep27 mutant for these therapies should be preceded by studies on Treg resilience through clinical translational studies on dietary changes. Full article

Epinephrine autoinjectors (EAIs) are used for the treatment of severe allergic reactions in a community setting; however, their utility is limited by low prescription fulfillment rates, failure to carry, and failure to use due to fear of needles. Given that delayed administration of epinephrine is associated with increased morbidity/mortality, there has been a growing interest in developing needle-free, easy-to-use delivery devices. neffy (epinephrine nasal spray) consists of three Food and Drug Administration (FDA)-approved components: epinephrine, Intravail A3 (absorption enhancer), and a Unit Dose Spray (UDS). neffy’s development pathway was established in conjunction with the FDA and the European Medicines Agency and included multiple clinical trials to evaluate pharmacokinetic and pharmacodynamic responses under a variety of conditions, such as self-administration and allergic and infectious rhinitis, as well as an animal anaphylaxis model of severe hypotension, where neffy demonstrated a pharmacokinetic profile that is within the range of approved injection products and a pharmacodynamic response that is as good or better than injections. The increased pulse rate (PR) and blood pressure (BP) observed even one minute following the administration of neffy confirm the activation of α and β adrenergic receptors, which are the key components of epinephrine’s mechanism of action. The results suggest that neffy will provide a safe and effective needle-free option for the treatment of severe allergic reactions, including anaphylaxis. Full article

This narrative review study investigates the correlations between obesity, allergies, and sleep-disordered breathing in pediatric populations. Searches for pertinent articles were conducted on the Medline PubMed Advanced Search Builder, Scopus, and Web of Science databases from unlimited to April 2024. Sleep-disordered breathing causes repeated upper airway obstructions, leading to apneas and restless sleep. Childhood obesity, which affects around 20% of children, is often associated with sleep-disordered breathing and allergies such as asthma and allergic rhinitis. It is distinguished between diet-induced obesity (resulting from excess of diet and physical inactivity) and genetic obesity (such as is seen in Down syndrome and Prader–Willi syndrome). In children with diet-induced obesity, chronic inflammation linked to weight can worsen allergies and increase the risk and severity of asthma and rhinitis. Furthermore, the nasal congestion typical of rhinitis can contribute to upper respiratory tract obstruction and obstructive sleep apnea. A vicious circle is created between asthma and sleep-disordered breathing: uncontrolled asthma and sleep-disordered breathing can worsen each other. In children with genetic obesity, despite alterations in the immune system, fewer allergies are observed compared to the broader population. The causes of this reduced allergenicity are unclear but probably involve genetic, immunological, and environmental factors. Additional research is necessary to elucidate the underlying mechanisms. The present narrative review study emphasizes the importance of jointly evaluating and managing allergies, obesity, and obstructive sleep apnea in children considering their close interconnection. Full article

Background: Aspergillus can cause fungal rhinosinusitis (FRS). We aimed to identify risk factors for sinonasal Aspergillus disease. Methods: Patients with a positive sinonasal mycological culture for Aspergillus species diagnosed in our hospital located in a continental climate were included in the 9-year retrospective study. Results: Of the 86 patients, 3 had invasive FRS (IFRS), 51 had fungal ball (FB) disease, and 32 had chronic rhinosinusitis with fungus (CFRS). In the IFRS group, all patients had a malignancy and were immunocompromised. Allergies, allergic rhinitis, asthma, nasal polyps, and the use of inhaled and nasal steroids were more common in the CFRS group, and IgE levels were greater than those in the FB and IRFS groups (p < 0.05). Conclusion: FB disease is a relatively symptom-free single-sinus disease among elderly individuals, and IFRS is dominant among immunocompromised patients. We discovered a third patient group, predominantly with nasal polyps, atopy, asthma, and elevated blood IgE and eosinophils, that did not fulfill the allergic FRS (AFRS) criteria. It is possible that a less fulminant category of underdiagnosed AFRS exists in cold climates. Treatment with local debridement is usually sufficient for FRS, apart from IFRS, and relapses are not common in cold climates. Full article