Frontiers in allergy最新文献

Background: Type 2-low asthma is a severe, steroid-resistant phenotype characterized by neutrophilic inflammation and limited treatment options. PTX3, an acute-phase protein involved in innate immunity, has been linked to inflammatory diseases; but its role in type 2-low asthma remains unclear.

Methods: A chronic HDM + c-di-GMP murine model was used to mimic type 2-low asthma. PTX3^-/- and WT mice were assessed for inflammation, cytokine profiles, antibody responses, and lung function. AHR was measured using FlexiVent. BALF inflammatory cells were analyzed by cytospin and flow cytometry. Cytokines were quantified using mesoscale assay, and serum immunoglobulins by ELISA.

Results: In mice, the type 2-low model exhibited increased systemic and airway PTX3 levels. PTX3^-/- mice exposed to the type 2-low protocol developed significantly greater airway inflammation, with higher total BALF cell counts and a 2-fold increase in neutrophils, but no change in eosinophils. PTX3 deficiency led to increased total and HDM-specific IgE levels. BALF cytokine analysis revealed elevated IL-17A in PTX3^-/- mice, while IL-4, IL-5, and IL-13 remained unchanged. PTX3^-/- mice also exhibited significantly higher AHR parameters.

Conclusions: PTX3 absence enhances neutrophilic inflammation, IL-17A production, IgE responses, and AHR, highlighting PTX3 as a potential biomarker and therapeutic target in type 2- low asthma.

Allergic diseases persist as a significant global health concern, profoundly diminishing the quality of life for millions of people across the globe. Allergic diseases exert a growing economic toll worldwide, with prevalence rates rising sharply - now affecting between 10% and 30% of the global population. This upward trend underscores the urgent need for more effective prevention, diagnosis, and management strategies. Rapid urbanization and shifting environmental conditions - particularly those driven by global warming - are increasingly recognized as key contributors to the rising prevalence of allergic diseases worldwide. We examine the current challenges in addressing these complex disorders, from diagnostic limitations to the heterogeneity of clinical presentations. We explore the role of statistical computational tools in predicting allergenicity, offering new avenues for precision medicine in this evolving field.

Allergic inflammation arises from a dysregulated immune response in which immunoglobulin E (IgE) plays a central pathogenic role. By binding to its high-affinity FcεRI on mast cells and basophils, IgE orchestrates the rapid activation and mediator release that underlies immediate hypersensitivity reactions. Compelling experimental evidence indicates that the pathogenic role of IgE extends well beyond of the mere effector cells degranulation, contributing also to shape antigen presentation, to regulate the function of dendritic cells, and to endorse an immune environment that favours type 2 inflammation. Within this complex network, regulatory T cells (Tregs) serve as a critical counterbalance, maintaining tolerance to environmental allergens and restraining excessive type 2 inflammatory responses. Individuals with allergic diseases often display quantitative and/or functional alterations within the Tregs compartment, including signs of phenotypic plasticity shifted toward pro-allergic states. These observations raise important questions about how IgE-mediated signalling pathways might directly or indirectly impair proper Tregs development or stability. In this context, anti-IgE therapies such as omalizumab have shown that, beyond reducing free IgE levels and downregulating FcεRI expression, they may also promote the expansion or restoration of Tregs, which might well contribute to the reestablishment of immune tolerance. Deciphering the interplay among IgE, Tregs, and anti-IgE agents can help to pave the way towards the development of innovative disease-modifying strategies for allergic diseases and other inflammatory immune-mediated diseases.

Introduction: Allergic Rhinitis (AR) is an IgE- mediated inflammatory disease of the nasal mucosa. While the diagnosis mainly relies on a typical clinical history and physical examination, the evaluation of eosinophils in nasal smears is considered a direct marker of inflammation and can play a role in the diagnosis and monitoring of treatment response. The aim of this study was to evaluate the levels of nasal eosinophils among patients with AR, and to correlate these levels with disease severity and frequency.

Material and methods: This was a descriptive cross-sectional study conducted at a tertiary referral hospital in Kenya from November 2022 to January 2023. Patients were diagnosed with AR using the Score for Allergic Rhinitis (SFAR) questionnaire. A Total Nasal Symptom Score (TNSS) questionnaire was administered to evaluate for nasal symptoms and assign severity scores. The patients were categorized according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines into either intermittent or persistent allergic rhinitis groups, and further sub-classified into mild, or moderate-to-severe AR. Nasal smears were collected to quantify eosinophil counts.

Results: The study included 73 patients comprising 35 (47.9%) males and 38 (52.1%) females. The median age of the participants was 19 years (Interquartile Range 9-38), with an age range of 5-84 years. Most patients presented with intermittent symptoms (58.9%) and moderate-to-severe disease (61.6%). Pathological levels of eosinophils were found in 15 patients (20.5%). However, there was no statistically significant correlation between the level of nasal eosinophilia and either disease severity (p = 0.23) or symptom frequency (p = 0.80).

Conclusion: In this study, nasal eosinophils counts did not correlate with the severity or frequency of AR as defined by the ARIA classification. These findings suggest that while the presence of nasal eosinophilia is useful for confirming the underlying type 2 inflammation in AR, it should not be used as a standalone biomarker to determine disease severity or guide management.

Background: Oral immunotherapy (OIT) has emerged as a promising food allergy treatment with significant evidence of increased efficacy in preschool-aged children. However, current OIT protocols are generally burdensome and focus on single food allergies, while many children have multiple food allergies. A feasibility-oriented approach that minimizes the impact of therapy while allowing both single and multiple food allergy treatment is important to enhance accessibility for routine clinical practice. This study assesses the safety of a feasibility-oriented OIT protocol in preschool-aged children with single and multiple food allergies.

Methods: This single-center prospective intervention study included children aged 9-24 months with proven food allergy (sensitization and a positive oral food challenge (OFC)). After a short dose escalation phase, children received one year of low-dose (300 mg protein/day) OIT, followed by an exit OFC four weeks after stopping therapy. Children with multiple food allergies received OIT for up to four allergens. Each allergen treatment is referred to as an OIT trajectory. Allergic dosing reactions (ADR) were recorded and classified using Sampson's severity score (grades I-V).

Results: Between May 2019 and Oct 2022, 124 children (median age 17 months, IQR 11-20 months) started OIT for 189 food allergies. Peanut (n = 52), cashew nut (n = 46) and egg (n = 38) allergies were the most common. The median number of hospital-based dose escalations per patient was three (IQR 2-5). ADR occurred in 89 children and 117 OIT trajectories, most frequently during dose escalation (48.1%). Most reactions (95.3%) were mild (Sampson I-II) and resolved spontaneously (55.6%) or with antihistamines (29.9%). Ten reactions were severe (Sampson III-IV), of which one required epinephrine. Ten trajectories were discontinued due to side effects.

Conclusions: Our novel feasibility-oriented OIT protocol appears safe for various allergens and multifood OIT in preschool-aged children. Side effects were common but typically mild. However, they may lead to therapy discontinuation.

Clinical trial registration: https://www.onderzoekmetmensen.nl/en/trial/49735, identifier NL7663.

Calcium-binding proteins, particularly those in the EF-hand family, are found ubiquitously in nature, primarily for calcium transport and storage in the body. In this review, we discuss allergens in the parvalbumin, polcalcin, sarcoplasmic calcium-binding protein, and troponin C families, as well as additional allergens. Allergens from these protein families display a wide range of IgE reactivity and cross-reactivity. They are implicated in both inhaled and food allergies, and, due to their common presence, they are difficult to avoid.

Background: The increase in polyallergy highlights allergen-specific immunotherapy (AIT) as a crucial therapeutic option for these patients. It is the only etiological treatment capable of modifying the natural course of allergic diseases. Its use, particularly with mixtures from different allergenic sources, varies across regions. In Spain, geographic and environmental diversity leads to complex, heterogeneous sensitization patterns not fully addressed by international guidelines, reinforcing the need for context-specific recommendations integrating current evidence and real clinical practice.

Objective: To establish general recommendations for managing polyallergic patients undergoing AIT with mixtures of different allergenic sources in Spain.

Methodology: Eight regional meetings with 61 experts were held across Spain using the Workmat® methodology: evidence-based exercises designed to facilitate discussion and consistent data collection.

Results: Experts agreed that polymerized allergen extract mixtures offer several advantages over AIT with simultaneous use of individual allergen extracts, as they allow multiple sensitizations to be treated in a single application, simplifying the treatment without compromising safety or efficacy while also saving time and costs and improving treatment adherence. Furthermore, the use of polymerized allergen extracts has improved efficacy and safety in AIT. It is essential to perform an individualized evaluation, according to the type of extract, the mixture, and the patient's comorbidities.

Conclusion: The increasing prevalence of polyallergy has emerged as a growing challenge in routine clinical practice. In this context, AIT using polymerized allergen extract mixtures, at optimal doses, tailored to individual sensitization profiles represent a practical and effective approach for managing polyallergy in the Spanish clinical setting.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) comorbid with asthma (CRSwA) represents a severe "unified airway" phenotype, yet the metabolic mechanisms linking upper and lower airway inflammation remain unclear. This study aimed to identify shared metabolic signatures connecting local pathology with systemic circulation by comparing the metabolic profiles of nasal polyp tissue and serum.

Methods: We performed an integrated analysis using non-targeted metabolomics and transcriptomics on paired nasal polyp tissue and serum samples from 22 CRSwA patients and 40 non-asthmatic CRSwNP patients to identify differential metabolites and explore their association with the immune microenvironment.

Results: CRSwA patients exhibited distinct metabolic signatures dominated by lipids and their derivatives in both tissue and serum. An analysis of the metabolome shared between compartments revealed a weak but significant positive correlation in metabolic fold changes, suggesting a subtle systemic link to the local inflammation. This shared metabolic profile was strongly associated with a local Th2-polarized immune microenvironment. This shared profile was strongly associated with a local Th2-polarized immune microenvironment, where key metabolites (e.g., Resolvin D2, Lipoxin A4) correlated significantly with the abundance of M2 macrophages and eosinophils. Furthermore, a logistic regression model based on serum metabolites effectively distinguished CRSwA from non-asthmatic CRSwNP (AUC = 0.8322).

Conclusion: Our study reveals a highly conserved "metabolic-immune axis" that connects local tissue inflammation with systemic circulation, positioning metabolic dysregulation as a central hub in the unified airway disease model for CRSwA. These findings offer new perspectives for developing serum-based diagnostic markers and metabolically-targeted therapies for this challenging clinical condition.

Background: Since 2022, several biologics are indicated and reimbursed for Belgian patients with severe uncontrolled CRSwNP despite previous endoscopic sinus surgery (ESS). Data on the impact of biologics on the number of patients undergoing revision ESS are lacking.

Methods: We analyzed the trend in numbers and percentages of patients with severe uncontrolled CRSwNP being offered primary ESS, revision ESS or biologics according to both academic- and reimbursement criteria at a tertiary care Rhinology center (University Hospitals Leuven) in Belgium, from 2019 until 2023.

Results: A total of 641 patients with severe uncontrolled CRSwNP had been offered primary/revision ESS or biologics in the past 5 years. In contrast to the overall increase in annual numbers of CRSwNP patients treated for uncontrolled CRSwNP from 2019 (n = 128) until 2023 (n = 160) by ESS or biologics, the absolute number of patients undergoing revision surgery is reduced by the advent of biologics since 2022. Patient numbers undergoing revision ESS were 66 and 59 in 2019 and 2020 respectively, and 48 in 2023. Moreover, the percentage of patients undergoing revision surgery dropped from 52% and 56% in 2019 and 2020, respectively to 34% and 30% in 2022 and 2023, respectively. The percentage of primary ESS procedures remained stable.

Conclusion: The advent of biologics reduced the number and percentage of severe uncontrolled CRSwNP patients undergoing revision ESS, in contrast to number and percentage of primary ESS.