Frontiers in allergy最新文献

Chronic spontaneous urticaria (CSU) is a common immune-mediated skin disorder characterized by spontaneous wheals, angioedema, or both, persisting for more than six weeks. Its pathogenesis is multifactorial, involving mast cell and basophil activation, autoimmunity and dysregulation of inflammatory and coagulation pathway. Current treatment guidelines recommended a stepwise algorithm beginning with second-generation H1-antihistamines (sgAH1) at standard doses (which can be increased up to fourfold if needed) before progressing to omalizumab (OMA). Nevertheless, a considerable proportion of patients remain unresponsive, highlighting the need for reliable predictors of treatment response to enable personalized care. This narrative review summarizes the current evidence on demographic, clinical, serological, and cellular biomarkers that may predict outcomes with sgAH1and OMA. Favorable sgAH1 response has been associated with shorter disease duration, low baseline UAS7 scores, and absence of angioedema. In contrast, high disease activity, inducible urticaria, elevated CRP or IL-6 levels, and hematological features such as increased neutrophil-to-lymphocyte ratio, basopenia, eosinopenia, and markers of coagulation activation (e.g., D-dimer, fibrinogen) are linked to resistance. Regarding OMA, predictors of good response include high total IgE levels, elevated basophil FcεRI expression, and reduction in IL-31 and D-dimer during treatment. Poor response correlates with advanced age, high BMI, comorbid autoimmune diseases, low total IgE (<40-50 IU/ml), positivity for ANA or anti-TPO antibodies, and activation markers such as CD203c. Functional test like the autologous serum skin test (ASST), basophil activation test (BAT), and histamine release assays offer additional stratification value. Composite immunological signatures integrating multiple biomarkers hold promise for guiding therapeutic decisions and improving prediction accuracy. Implementing validated markers could enable earlier identification of difficult-to-treat patients, faster disease control and more targeted therapy, advancing precision medicine in CSU.

Continuous exposure to textile dyes can result in potential health risks, such as inflammatory and allergic responses. We investigated immunotoxicity, and epithelial responses induced by Disperse Blue 1, 124, 79.1, and 183 when in co-culture with swine peripheral blood mononuclear cells (PBMCs), intestinal porcine epithelial cells (IPEC), and human epidermal skin scaffolds. PBMC cytokine production (IFN-γ and TNF-α), cell viability, IPEC gene expression profiles (by Nanostring analysis) and histopathology of human epidermis were evaluated. Disperse Blue 124 strongly increased pro-inflammatory cytokines without significant cytotoxicity, suggesting high sensitization potential. Contrarily, Disperse Blue 1 exhibited high cytotoxicity despite moderate cytokine production. Nanostring analysis revealed prominent epithelial inflammation (CCL20 upregulation) and compromised barrier integrity (CLDN-4) with Blue 1 and Blue 124, but not Blue 79.1 and 183. Histopathology further confirmed epidermal damage, with Blue 1 and 124. Therefore, dye-induced effects correlated with chemical structure, molecular weight, hydrophobicity, and functional groups, supporting the hypothesis that structural properties influence toxicity and absorption.

Severe asthma is a chronic respiratory disease characterized by a lack of control with maximal standard therapy or exacerbation upon therapy reduction. Recent advances in the diagnosis and management of severe asthma have improved patient outcomes. An improved mechanistic understanding of asthma has revealed that many cases are driven by type 2 inflammation, which can be targeted with biologic agents including omalizumab (anti-IgE), mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5Rα), dupilumab (anti-IL-4Rα), and tezepelumab (anti-thymic stromal lymphopoietin). Biomarkers, including elevated fractional exhaled nitric oxide, blood eosinophil counts, and serum IgE levels, have been validated for the diagnosis of severe asthma and can be used to help guide disease management. These biologic agents and biomarkers have changed the clinical management of severe asthma, making it possible to pursue the goal of clinical remission. However, despite these advances, a proportion of patients continue to experience uncontrolled severe asthma, which has significant implications for disease management and quality of life. In this review, I briefly examine the current state of biologics and biomarkers in the treatment of uncontrolled severe asthma, and draw on my clinical experience to highlight limitations to optimal management, including persistent treatment heterogeneity. After discussing emerging biomarkers and predictors of disease status and treatment response, I provide my perspective on future approaches and research directions that may enhance clinical treatment and improve patient outcomes.

Chronic rhinosinusitis with nasal polyps (CRSwNP), is a prevalent inflammatory airway disease associated with type 2 inflammation. When CRSwNP coexist with asthma, the condition is referred to as global air disease (GAD). People how lives with CRSwNP or GAD often report a high symptom burden, for example persistent nasal obstruction, impaired smell and taste, disturbed sleep, fatigue, and reduced well-being. While these burdens have been quantified through clinical outcomes and patient-reported outcome measures (PROMs), there is limited qualitative research exploring how these peoples experience living with CRSwNP or GAD in their daily lives. The aim of the study was to describe the impact of CRSwNP or GAD on patients' everyday lives before the initiation of biologic treatment.

Methods: A descriptive qualitative interview study was conducted with 13 patients diagnosed with CRSwNP or GAD. Semi-structured interviews were analyzed using qualitative content analyzed as described by Graneheim and Lundman, resulting in the identification of thematic categories reflecting participants' lived experiences.

Results: Five categories were identified: (1) feeling constantly unwell, like having a chronic cold, describing the persistent sense of ill health; (2) loss of senses disrupting everyday life, illustrating how impaired smell and taste influenced both social and practical activities; (3) illness leading to social isolation and emotional distress, highlighting psychological and relational consequences; (4) dependence on prednisolone-choosing between the lesser of two evils, reflecting the balance between temporary relief and side effects; and (5) Longing for a normal life, expressing high expectations of biologic therapy as a potential turning point.

Conclusion: This study showed that patients with CRSwNP or GAD experienced a substantial symptom burden, sensory loss, impaired work ability, and reduced social participation, all of which profoundly affected their daily lives. Many relied on prednisolone for temporary relief despite being aware of its serious side effects. The extensive impact of CRSwNP made participants hopeful that biologic therapy could provide more stable symptom control and help them regain a more "normal" life. CRSwNP or GAD is a multifaceted condition that affects patients' emotional, psychological, and social well-being. These findings highlight the importance of adopting a holistic treatment approach, including consideration of psychosocial support to address the broader consequences of the disease.

[This corrects the article DOI: 10.3389/falgy.2025.1740057.].

Background: Food allergy remains a serious public health concern associated with significantly lowered quality of life and the risk of potentially life-threatening allergic reactions. While oral immunotherapy (OIT) has consistently demonstrated efficacy in the desensitization of multi-food allergic patients, many patients undergoing such treatment are burdened by dose-related side effects that can hinder their compliance and the overall efficacy of OIT. Recent efforts to improve upon OIT have begun to evaluate the concomitant use of biologics such as omalizumab and dupilumab with OIT for their ability to selectively inhibit pathways involved in the underlying pathology of food allergy.

Methods: Herein, we detail the clinical trial design, rationale, and methods for a Phase 2 randomized, double-blind, placebo-controlled, multi-center study evaluating the safety and efficacy of omalizumab and/or dupilumab therapy in combination with participant-specific multi-food (mOIT) in patients aged 4-55 years, with multi-food allergy that includes peanut. In this two-arm superiority trial, participants will be randomized (5:5:1) to (1) omalizumab/placebo-dupilumab with mOIT (n = 50), (2) omalizumab/dupilumab with mOIT (n = 50), or (3) a mechanistic-only arm of placebo-omalizumab/dupilumab with mOIT (n = 10). Double-blind placebo-controlled food challenges (DBPCFCs) will be used to assess desensitization to ≥1,043 mg cumulative protein at Week 32, after which all treatment is to be discontinued. A follow-up assessment of sustained unresponsiveness via DBPCFCs will be conducted at Week 44.

Conclusion: This trial tests the hypothesis that adding dupilumab to omalizumab-facilitated mOIT will increase the likelihood of inducing sustained unresponsiveness and decrease mOIT-related adverse events.

Introduction: House dust mite (HDM) allergens are major triggers of IgE-mediated asthma in tropical regions, yet the role of cockroach allergens and their cross-reactivity with HDM remains unclear. Cross-reactivity among invertebrate allergens is a common challenge in daily practice, especially to define primary sensitizers and reactions of clinical relevance. Multiplexed arrays in molecular allergology constitute a useful tool for better detection and interpretation of cross-reactions.

Methods: We assessed specific IgE levels and skin prick test reactivity to the American cockroach and HDM allergens in cohorts of allergic and asthmatic patients from Cartagena, Colombia, using ImmunoCAP™, skin testing, and multiplex molecular allergology (ALEX2).

Results: Cockroach sensitization was present in 29%-40% of patients but elicited significantly lower IgE responses and smaller skin test wheals compared with HDM. Most cockroach-sensitized individuals were cosensitized to HDM, with limited recognition of cockroach molecular components. Mean specific IgE levels to cockroach were 2.1 kU/L ranging from 0.1 to 25.8 kU/L. The majority of patients had IgE levels in Class 1 (0.35-0.70 kU/L) or Class 2 (0.70-3.5 kU/L). In the ALEX2 array, most cockroach-sensitized patients (by skin tests) did not recognize the Periplaneta americana extract (Per a) or other cockroach allergens in the array, and instead they recognized HDM allergens and the extracts of crustaceans and mollusks. Only one patient recognized the Per a extract, cockroach tropomyosin (Per a 7), and tropomyosins in HDM (Blo t 10, Der p 10), shrimp (Pen m 1), and Anisakis simplex (Ani s 3) together with other allergens in crustaceans and mollusks. Interestingly, IgE reactivity to cross-reactive allergens like arginine kinase, myosin light chain, and sarcoplasmic calcium-binding protein was not detected. Cockroach sensitization was not associated with worsened asthma control or lung function but correlated with higher shrimp-specific IgE in patients reporting shellfish allergy.

Discussion: HDM allergens induce stronger IgE responses than cockroach in this tropical population, indicating HDM as the primary sensitizer. Cockroach sensitization often reflects cross-reactivity and requires careful clinical evaluation to determine its relevance.

Atopic dermatitis (AD) is an inflammatory skin condition associated with chronic itch and inflammation in both humans and animals. While this disease depends upon various immune cell types, the precise role and kinetics of neutrophils remain elusive, particularly in relevant large-animal models. Given a recent report suggesting the involvement of neutrophils in a mouse model, we aimed to characterize the temporal presence and infiltration of these cells in a canine model of house dust mite (HDM)-induced AD. AD was induced in canines via HDM exposure, and skin biopsies were analyzed over a time course (0-96 h) using standard H&E staining and specific immunofluorescent (IF) staining for canine neutrophils. Our results showed general cellular infiltration with the H&E method, while IF further confirmed detectable neutrophil immunoreactivity starting between 24 and 96 h post-challenge in atopic skin. Quantitation demonstrated a significant increase in neutrophil infiltration (cells/mm²) in atopic skin at 48 h following HDM exposure compared to baseline (p = 0.041). Collectively, our data confirms time-dependent infiltration of neutrophils into the skin of the canine AD model following allergen challenge, supporting the hypothesis that this previously overlooked immune cell may play a role in the acute phase of AD pathogenesis and sensitization.

Over the past decade, chronic rhinosinusitis (CRS) management has undergone substantial transformation, shifting from conventional symptom-focused treatments to precision medicine strategies grounded on molecular insights. The introduction of biologic agents has significantly changed the therapeutic landscape for CRS with nasal polyps (CRSwNP), directly addressing key inflammatory pathways and leading to marked reductions in nasal polyp burden, overall disease impact, and corticosteroid use. Concerns regarding long-term effectiveness, financial burden, and accessibility remain unresolved. Advances in the understanding of the mechanisms underlying CRS are paving the way for the development of novel therapeutic strategies, with increasing attention now also being directed toward the phenotype without nasal polyps (CRSsNP), which currently lacks targeted therapies. Despite progress in pharmacologic therapies, surgery remains a fundamental treatment option, with ongoing efforts to standardize surgical approaches and evaluate novel techniques. Optimizing the integration of surgical and medical therapies while expanding access to novel treatments represents a key future goal in CRS care. This review aims to guide researchers and clinicians through the evolving landscape of CRS management, covering the latest evidence on established and emerging therapies, offering practical insights into endotyping, and highlighting important considerations for the management of severe or refractory cases.