Wiley: Clinical & Experimental Allergy: Table of Contents

Probiotic‐Derived CpG‐DNA Enhances Food Allergy Immunotherapy via TLR9‐Dependent Breg Induction and IL‐10 Epigenetic Activation

Tue, 09 Jun 2026 18:43:12 -0700

Clinical &Experimental Allergy, EarlyView.

Registry‐Based Analysis of Treatment and Retreatment Attacks of Hereditary Angioedema

Sun, 07 Jun 2026 20:25:09 -0700

Clinical &Experimental Allergy, EarlyView.

Asthma Incidence and Risk Factors in Tuberculosis Survivors: A Longitudinal Analysis of National Health Data

Thu, 04 Jun 2026 22:35:18 -0700

Clinical &Experimental Allergy, EarlyView.

A Meta‐Analysis of Anti‐Thyroid Peroxidase Antibody and Omalizumab Response in Chronic Spontaneous Urticaria

Ju Hyun Lee, Min Jung Geum, Do‐Young Kim, Young‐Mi Ah, Yun Mi Yu — Thu, 04 Jun 2026 21:01:51 -0700

Clinical &Experimental Allergy, EarlyView.

Worldwide Impact of Human Development and Inequality on the Prevalence of Asthma, Rhinoconjunctivitis and Eczema. Global Asthma Network's Ecological Study

Thu, 04 Jun 2026 20:51:22 -0700

Global Asthma Network Phase I surveyed children, adolescents, and adults worldwide to assess the prevalence of asthma, rhinoconjunctivitis, and eczema. Human Development Index (HDI) and Gini inequality index (GinI) were important explanatory factors for prevalence variability of these conditions, with hotspots in areas with high HDI and high GinI.

ABSTRACT

Background

Lower-income countries have lower asthma prevalence. However, how differences in human development and inequality can explain changes in the prevalence of asthma and allergic diseases is not known.

Methods

The Global Asthma Network Phase I study reported prevalence of asthma and allergic diseases in children (6–7 years), adolescents (13–14 years), and their parents/guardians in 16, 25 and 17 countries. Gini inequality index (GinI) and human development index (HDI), together with mean annual relative humidity and temperature, and latitude, were used as potential explanatory factors of prevalence differences using meta-regression models, fitted values and heatmaps of prevalence.

Results

GinI and HDI explained some proportion of asthma prevalence variability, which was highest in children (up to ~70% for disease indicators such as current wheeze or symptoms of severe asthma) and lowest in adolescents (~22% for symptoms of severe asthma or asthma ever). Rhinoconjunctivitis prevalence variability was poorly explained by covariates (from ~53% for current rhinoconjunctivitis among children—an exception—to none). Eczema indicators were explained in a range from ~60% in children (current eczema symptoms and symptoms of severe eczema) to ~12% in adolescents (current eczema symptoms). Overall, heatmaps showed areas of higher prevalence in the intersection of high GinI and high HDI values.

Conclusions

HDI and Gini explain part of the worldwide variability in the prevalence of asthma, rhinoconjunctivitis, and eczema. This explanatory power is highest for asthma and lowest for rhinoconjunctivitis. Lower-resourced communities in highly developed countries show the greatest hazard, particularly for asthma.

Comparative Efficacy of Intranasal Corticosteroids and Antihistamines in Enhancing Paediatric Quality of Life in Allergic Rhinoconjunctivitis

Wed, 03 Jun 2026 06:45:51 -0700

Clinical &Experimental Allergy, EarlyView.

Plant‐Based Drinks for Children Aged 1 Year and Over

Aisling Phelan, Claudia Gore, Robert J. Boyle — Mon, 01 Jun 2026 17:31:14 -0700

Clinical &Experimental Allergy, Volume 56, Issue 6, Page 594-596, June 2026.

Issue Information

Mon, 01 Jun 2026 17:31:14 -0700

Clinical &Experimental Allergy, Volume 56, Issue 6, Page 591-593, June 2026.

Correction to “Allergy in Australia”

Mon, 01 Jun 2026 17:31:14 -0700

Boyle, R.J. (2026), Allergy in Australia. Clin Exp Allergy, 56: 309–311. https://doi.org/10.1111/cea.70290.

The article did not acknowledge the collaborative nature of the Australian Government funding awarded to both the National Allergy Centre of Excellence (NACE) and the National Allergy Council (NAC), which is a partnership between the Australasian Society of Clinical Immunology and Allergy (ASCIA) and Allergy & Anaphylaxis Australia.

We apologize for this error.

New Generation of Allergen Immunotherapy Using Virus‐Like Particles: A Comprehensive Review

Alain Jacquet, Antonia Fettelschoss‐Gabriel, Pål Johansen — Mon, 01 Jun 2026 17:31:14 -0700

ABSTRACT

Virus-like particle (VLP)-based allergen immunotherapy (AIT) represents a promising approach to treat allergic diseases by inducing specific IgG responses that suppress IgE-mediated allergic reactions. VLPs, which are non-infectious nanoparticles displaying antigens in repetitive arrays, efficiently activate B cells and antigen-presenting cells, leading to robust polyclonal IgG production. These IgG antibodies can block allergen interactions with IgE receptors on mast cells and basophils, thereby preventing degranulation and allergic symptoms. Additionally, VLPs can stimulate innate immune pathways through Toll-like receptor (TLR) signalling, promoting a Th1-biased immune response that further contributes to the suppression of Th2-driven allergic inflammation. VLP-based allergy vaccines aim to re-educate the immune system, promoting allergen tolerance, stimulating anti-allergen antibody responses, and thereby disrupting pathogenic pathways. Preclinical studies have demonstrated that a few low-dose administrations of VLPs conjugated with allergens can shift the typical Th2-biased allergic response to a non-pathogenic one. Clinical trials have shown that VLP-based allergy vaccines are well-tolerated and can elicit allergen-specific IgG antibodies in humans. However, challenges remain in ensuring consistent quality control of VLP preparations, addressing pre-existing immunity to VLP carriers and validating the efficacy of single-allergen approaches for complex allergens. Future research should focus on optimising VLP formulations, exploring multivalent strategies and conducting large-scale clinical trials to establish the safety and effectiveness of VLP-based AIT.

Perceived Acquired Resistance to Omalizumab in Obese Patients With Chronic Spontaneous Urticaria

Francisco Martins, Ilaria Trave, Sofia Pereira, Margarida Gonçalo — Mon, 01 Jun 2026 17:31:14 -0700

Clinical &Experimental Allergy, Volume 56, Issue 6, Page 671-673, June 2026.

Perinatal Exposures Are Related to Atopic Symptom Development in Early Childhood

Mon, 01 Jun 2026 17:31:14 -0700

Clinical &Experimental Allergy, Volume 56, Issue 6, Page 692-694, June 2026.

Prognostic Value of Combining Serum Tryptase and Bone Mineral Density in Predicting Fractures in Systemic Mastocytosis

Mon, 01 Jun 2026 17:31:14 -0700

Clinical &Experimental Allergy, Volume 56, Issue 6, Page 678-680, June 2026.

Binational Association Between Asthma and Life's Essential 8 in South Korea and the United States: A Nationwide Representative Comparative Study

Mon, 01 Jun 2026 17:31:14 -0700

Clinical &Experimental Allergy, Volume 56, Issue 6, Page 695-697, June 2026.

Dual GIPR and GLP‐1R Agonist Tirzepatide Is Associated With Fewer Asthma Exacerbations in Adults With Obesity

Syona Mehta, Syed Fahad Gillani, Rawan Elkomi, Miriam Michael — Mon, 01 Jun 2026 17:31:14 -0700

Clinical &Experimental Allergy, Volume 56, Issue 6, Page 665-667, June 2026.

Body Mass Index Is Not Associated With Cough, Laryngeal Hypersensitivity or Dyspnoea in Patients With Refractory Chronic Cough: A Cross‐Sectional Study

Tina Wilkie, Phoebe Blakey, Anne Vertigan — Mon, 01 Jun 2026 17:31:14 -0700

Clinical &Experimental Allergy, Volume 56, Issue 6, Page 668-670, June 2026.

Variants in Genes Encoding Innate Lymphoid Cells Type 2 Surface Markers Affecting Asthma and Atopy Pathologies

Mon, 01 Jun 2026 17:31:14 -0700

Clinical &Experimental Allergy, Volume 56, Issue 6, Page 681-683, June 2026.

House Dust Mite Sensitisation Effectively Differentiates Atopy From Non‐Atopy in the Tropical Environment of Southeast Asia

Yang Yie Sio, Tan Ching Ong, Yee‐How Say, Kavita Reginald, Fook Tim Chew — Mon, 01 Jun 2026 17:31:14 -0700

Clinical &Experimental Allergy, Volume 56, Issue 6, Page 689-691, June 2026.

Serum Levels and Genetic Variants of CC16: Associations With Asthma and Lung Function Development

Mon, 01 Jun 2026 17:31:14 -0700

Clinical &Experimental Allergy, Volume 56, Issue 6, Page 698-700, June 2026.

Patients With Chronic Urticaria Have Higher Health‐Care Resource Utilisation: A Danish Nationwide Case–Control Study

Mon, 01 Jun 2026 17:31:14 -0700

Clinical &Experimental Allergy, Volume 56, Issue 6, Page 674-677, June 2026.

Effects of Acupuncture as a Therapeutic Intervention Targeting Both Skin and Gastrointestinal Symptoms in Patients With Atopic Dermatitis: A Randomised Controlled Trial

Mon, 01 Jun 2026 17:31:14 -0700

Clinical &Experimental Allergy, Volume 56, Issue 6, Page 684-688, June 2026.

Reframing Mechanistic Inference in Carrageenan‐Induced Epithelial Injury

Man Sun, Dan Zang, Jun Chen — Mon, 01 Jun 2026 17:31:14 -0700

Clinical &Experimental Allergy, Volume 56, Issue 6, Page 701-702, June 2026.

A Walk in the Park: Influence of Natural Co‐Exposure to Grass Pollen and Fungal Spores on Nasal Mycobiome and Cytokine Responses

Mon, 01 Jun 2026 17:31:14 -0700

Volunteers stayed 3 h indoors and followed 1 h outdoors in a flowering meadow. Nasal mycobiome was analysed and aeroallergen content measured in nasal filters. Airborne fungal spores were quantified and fungal isolates were sequenced. Isolated fungal spores were used for stimulation of nasal epithelial cells.

ABSTRACT

Background

During the grass flowering season, fungal spores are abundant in outdoor air. We tested for co-sensitisations to grass pollen and fungal spores, assessed the degree of co-exposure, and studied its impact on the nasal mycobiome and immune responses.

Methods

Fungi-specific IgE-levels were studied in 277 individuals with and without grass pollen sensitisation. In a small cohort (n = 7), exposure to grass pollen and fungal spores was monitored during 5 consecutive indoor and outdoor stays in a flowering meadow and correlated with changes in the nasal mycobiome. Cytokines of nasal epithelial cells were studied under stimulation with recombinant grass pollen allergens, with and without fungal spores derived from outdoor isolates.

Results

IgE-sensitisation against the studied fungi was significantly more frequent among individuals with grass pollen sensitisation than among those without grass pollen sensitisation. Outdoor exposure resulted in changes in the nasal mycobiome, with a transitory enrichment of environmental fungi, for example, Cladosporium species. Most of the fungi cultivated from outdoor air samples belonged to the genera Fusarium, Cladosporium and Penicillium. Apical co-stimulation of nasal epithelial cells with grass pollen allergens and Fusarium, Cladosporium or Penicillium spores led to an increased loss of transepithelial electrical resistance and induction of pro-inflammatory cytokine release compared to mono-stimulation.

Conclusion

Frequent co-exposure to fungal spores and grass pollen may increase the chance of acquiring a co-sensitisation to both allergens. Environmental fungi interact with and transitorily change the local mycobiome. Under co-exposure, fungal spores induce nasal inflammation and foster immune responses to otherwise poorly immunogenic pollen allergens.

Effectiveness and Predictors of House Dust Mite Subcutaneous Immunotherapy in Polysensitised Patients With Allergic Rhinitis: A Multicentre Retrospective Study

Mon, 01 Jun 2026 17:31:14 -0700

Single-allergen dust mite subcutaneous immunotherapy achieved 68.8% perennial symptom response rate in polysensitised allergic rhinitis patients. High mould and dust mite sIgE levels predicted poor allergen immunotherapy response, which indicated allergen-specific sIgE levels may help guide personalised allergen immunotherapy decisions.

ABSTRACT

Background

In China, therapeutic options are limited by the narrow availability of allergen preparations, with house dust mite (HDM) allergen immunotherapy (AIT) as the main choice for most patients. However, polysensitization is highly prevalent, and the benefit of HDM AIT in such patients remains uncertain. The study aims to evaluate the effectiveness of single-allergen HDM AIT on both perennial and coexisting allergen-specific symptoms in polysensitised allergic rhinitis (AR) patients and to explore predictors of treatment response.

Methods

We performed a multicenter retrospective cohort study including 81 patients with AR who were polysensitised to HDM and at least one other inhalant allergen (e.g., pollens, mould or animal dander). All participants received HDM subcutaneous immunotherapy (SCIT) for 12 to 36 months. Baseline characteristics, including serum allergen-specific IgE (sIgE) levels and comorbidities, were collected. Symptom severity was assessed using the Visual Analog Scale (VAS), and treatment response was defined as a ≥ 30% reduction in VAS scores from baseline. Statistical comparisons between responders and non-responders were conducted using Fisher's exact test for categorical variables and Mann–Whitney U tests for continuous data. Firth logistic regression was used to identify predictors of treatment response.

Results

The overall response rate for perennial symptoms was 68.8%, and varied in patients with co-existing allergies: 72.7% for moulds, 70.0% for animal dander, 65.5% for tree pollen, 70.2% for weed pollens. Allergen-specific symptom response rates varied across allergens: 68.2% for moulds, 30.0% for animal dander, 56.7% for tree pollens, 74.5% for weed pollens. Higher sIgE levels to HDM and mould were significantly associated with lower response rates in patients co-sensitised to both. A predictive model incorporating both sIgEs showed good specificity.

Conclusion

Single-allergen HDM AIT is effective in many polysensitised AR patients; however, its efficacy varies by coexisting allergen type and sIgE level. Patients co-sensitised to mould with high HDM and mould sIgE appeared to have poorer outcomes. These preliminary findings require confirmation in larger prospective studies to guide tailored AIT strategies.

Identifying an At‐Risk Asthma Phenotype: Allergy and Recurrent Infections Predict Severe Disease

Mon, 01 Jun 2026 17:31:14 -0700

Allergic asthma and recurrent antibiotic-treated infections synergistically accelerate progression to severe asthma, underscoring the need for early, targeted preventive strategies.

ABSTRACT

Background

Asthma severity is influenced by complex immunologic and environmental factors. While allergic asthma is linked to increased susceptibility to respiratory infections, the combined role of allergy and antibiotic-treated infections in progression to severe asthma has not been fully evaluated.

Objective

To evaluate whether allergic asthma and recurrent respiratory infections (RRI) requiring antibiotics are associated with increased risk of developing severe asthma.

Methods

We conducted a registry-based cohort study using Swedish national registry data. Adults with mild-to-moderate asthma were identified in 2014 (baseline) based on prescription records and absence of severe disease indicators. During a two-year exposure window (2015–2016), RRI was defined as ≥ 2 antibiotic prescriptions for lower respiratory tract infections. The outcome was development of severe asthma during 2017–2019, based on ERS/ATS treatment criteria. Allergic asthma was defined by ≥ 2 prescriptions for anti-allergic medications at baseline.

Results

Among 113,393 patients, 24,692 (21.8%) had allergic asthma. RRI occurred more frequently in allergic versus non-allergic asthma (7.5% vs. 5.9%, p < 0.001). A total of 869 patients (0.77%) developed severe asthma. Incidence was higher in those with RRI and highest among patients with both allergic asthma and RRI (2.0%), corresponding to a relative risk of 3.47 (95% CI: 2.49–4.83) versus patients with neither exposure. Results were consistent after adjustment for age, sex and comorbidities.

Conclusion

Allergic asthma and antibiotic-treated respiratory infections were independent and additive predictors of severe asthma progression. These findings support a clinically actionable risk profile and may inform targeted preventive strategies in asthma management.

Prognostic Significance of Eosinophil Extracellular Traps in Chronic Rhinosinusitis and Innovative Nanosheets‐Based Clearance Therapy

Mon, 01 Jun 2026 17:31:14 -0700

EETs area emerges as a superior prognostic biomarker in ECRSwNP. EETs drive disease persistence via epithelial barrier disruption and immune dysregulation. TLPG_A nanosheets effectively scavenge EETs and attenuate type 2 inflammation. EETs, eosinophil extracellular traps; FESS, functional endoscopic sinus surgery; PBMCs, peripheral blood mononuclear cells.

ABSTRACT

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) can be classified into Eosinophilic CRSwNP (ECRSwNP) and non-Eosinophilic CRSwNP (nECRSwNP) based on eosinophilic infiltration in nasal polyps. However, no consensus criteria exist for eosinophilic infiltration in nasal polyps, including different cutoffs for eosinophil (EOS) counts or different EOS proportions among inflammatory cells.

Methods

Inferior turbinate (IT) tissues from controls (n = 27) and nasal polyp (NP) tissues from ECRSwNPs (n = 50) were collected. ECRSwNPs (n = 38) underwent 2-year post-FESS follow-up. Clinical assessments (SNOT-22, Lund-Mackay, Lund-Kennedy scores), eosinophil indicators (polyp/blood EOS counts, EETs area), and Th2 cytokines pre/post-FESS were recorded for correlation analysis and prognostic model building. Subsequently, functional nanosheets TLPG_A targeting EETs were synthesized and tested for EETs clearance in human EOS, epithelial cell models, and NP models.

Results

Our findings demonstrated positive correlations between EETs area and ECRSwNP severity, including Lund-Mackay CT scores (r = 0.72, p < 0.001), Lund-Kennedy Endoscopic score (r = 0.57, p < 0.001), IL-4 (r = 0.50, p < 0.001), IL-5 (r = 0.50, p < 0.001), IL-13 (r = 0.39, p < 0.01), and Periostin (r = 0.34, p < 0.05). And we first demonstrated that increased preoperative EETs area predicts both impaired mucosal recovery and elevated nasal polyp uncontrolled risk within 2 years post-FESS. Furthermore, we developed novel nanosheets TLPG_A and demonstrated that TLPG_A effectively scavenges EETs and alleviates the type 2 inflammatory cascade in human nasal polyp tissues and epithelial cell model.

Conclusion

These findings highlight the potential of EETs and EOS morphology in assessing preoperative ECRSwNP severity and predicting postoperative prognosis. Moreover, this also supports TLPG_A as a promising therapeutic approach for managing ECRSwNP with high EETs levels.

Managing Renewed Food Avoidance Following an Allergic Reaction for Patients With Avoidant/Restrictive Food Intake Disorder

Kaitlin B. Proctor, Tanya Auguste‐Jones, William G. Sharp, Brian P. Vickery — Mon, 01 Jun 2026 17:31:14 -0700

Clinical &Experimental Allergy, Volume 56, Issue 6, Page 613-616, June 2026.

Re: Markedly Increased Diamine Oxidase During Acute Anaphylaxis Is Associated With an Underlying Clonal Mast Cell Disorder

Maajid Mohi Ud Din Malik — Mon, 01 Jun 2026 02:34:48 -0700

Clinical &Experimental Allergy, EarlyView.

Allergenicity of Eight Soy Products: Allergy to Soy Milk Is Most Frequent and Most Severe

Mon, 01 Jun 2026 01:12:56 -0700

Clinical &Experimental Allergy, EarlyView.

Comment on ‘Prenatal Air Pollution Exposure During Late Pregnancy Associates With Food Sensitization at 18 Months’

Yushu You, Dongfang Zhong — Mon, 01 Jun 2026 01:10:34 -0700

Clinical &Experimental Allergy, EarlyView.

Radiation‐Induced Skin Toxicity Risk in Breast Cancer Patients With Atopic or Allergic Conditions

Mon, 01 Jun 2026 01:04:05 -0700

Clinical &Experimental Allergy, EarlyView.

Phase Ib/II Study of Preliminary Efficacy, Safety and Pharmacodynamics of MG‐K10, a Humanised Monoclonal Antibody Targeting IL‐4Rα, in Adult Chinese Patients With Asthma

Fri, 29 May 2026 03:33:03 -0700

This study evaluated the efficacy and safety of long-acting MG-K10 (anti-IL-4Rα mAb) via two dosing regimens versus placebo in Chinese adults with moderate-to-severe asthma. MG-K10 effectively inhibited type-2 inflammation, significantly improved lung function, reduced exacerbation risk and key biomarkers, with comparable efficacy between Q2W and Q4W administration.

ABSTRACT

Background

MG-K10 is a long-acting, humanised monoclonal antibody against interleukin-4 receptor alpha (IL-4Rα), which inhibits IL-4 and IL-13-mediated signalling to reduce type 2 inflammation in asthma.

Objective

This Phase Ib/II study aimed to evaluate the preliminary efficacy, safety and pharmacodynamic characteristics of MG-K10 in Chinese patients with asthma.

Methods

This study included an initial phase Ib to evaluate safety and tolerability, followed by a phase II study in which eligible patients with moderate-to-severe asthma were randomised 1:1:1 to receive MG-K10 300 mg every 2 weeks (Q2W), MG-K10 300 mg every 4 weeks (Q4W), or a matched placebo (2 mL) Q2W subcutaneously for 24 weeks. The primary endpoint was the absolute change from baseline in the prebronchodilator forced expiratory volume in 1 s (FEV₁) at week 12. Secondary efficacy endpoints, including asthma control, the rate of severe exacerbations and safety, were assessed. This trial is registered with ClinicalTrials.gov (NCT05382910).

Results

A total of 64, 60 and 63 patients were randomised to the MG-K10 Q2W, MG-K10 Q4W and placebo groups respectively. At week 12, the least squares mean improvements in prebronchodilator FEV₁ were significantly greater in both MG-K10 groups than in the placebo group [Q2W vs. placebo: 0.35 L (95% CI, 0.208–0.490), Q4W vs. placebo: 0.30 L (95% CI, 0.156 to 0.441), both p < 0.0001]. Greater FEV₁ improvements were observed in patients with baseline blood eosinophils ≥ 0.3 × 10⁹/L. The incidence of adverse events was similar across groups [MG-K10 300 mg, Q2W (79.7%), MG-K10 300 mg Q4W (85.0%) and placebo groups (79.4%)]. MG-K10 was safe and well-tolerated, and consistent with the known safety signals.

Conclusions

MG-K10 was superior to placebo in improving lung function, enhancing asthma control and reducing severe exacerbations in patients with asthma. The once-every-4-week regimen offers extended dosing intervals that may enhance medication adherence.

A Real‐World Controlled Multicentre Study Evaluating the Association Between Benralizumab Therapy and Major Outcomes in Severe Asthma

Wed, 27 May 2026 02:06:34 -0700

Among patients with severe eosinophilic asthma, benralizumab was associated with greater improvements in asthma outcomes—such as improved asthma control, quality of life and remission rates—compared to biologic-naïve patients.

ABSTRACT

Background

Real-world data on benralizumab in patients with severe eosinophilic asthma–while controlling for confounding factors–is currently lacking.

Aim

This real-world controlled multicentre study evaluated asthma outcomes in patients who received benralizumab compared with a severe asthma cohort who did not receive biologic therapy.

Methods

Two years of data from patients with severe eosinophilic asthma in the Australian Benralizumab Registry (ABenRa) and the Australasian Severe Asthma Registry (ASAR) were included in the analysis. Asthma control questionnaire-5 (ACQ-5) scores, asthma-related quality of life (AQLQ) scores, maintenance oral corticosteroid (OCS) dose, annualised exacerbation rate and clinical remission (ACQ-5 ≤ 1, with no asthma attacks or OCS use for 12 months, assessed at the 24-month follow-up) rates were compared between the groups after adjusting for baseline imbalances.

Results

A total of 211 participants from ABenRa (64.5% female; mean age 57.4 ± 14.5 years) and 250 from ASAR (63.1% female; mean age 53.7 ± 14.8 years) were included. ACQ and AQLQ improved significantly in both groups. Participants in the ABenRa showed greater improvements in ACQ at 12- (β = −0.5, p = 0.002) and 24-months (β = −0.5, p = 0.003), as well as in AQLQ at 12- (β = 0.6, p < 0.001) and 24-months (β = 0.4, p = 0.019), compared with the ASAR group, with no difference in maintenance OCS dose or annualised exacerbation rates between groups. At 12- and 24-months, approximately 60% of participants in the ABenRa achieved controlled or partially controlled asthma as per the GINA guidelines. Notably, clinical benefit was evident within 14 days of initiating treatment. A higher proportion of participants in the ABenRa achieved clinical remission (30.9% vs. 20.4%; OR 2.1 (95% CI 1.1, 4.1), p = 0.037).

Conclusion

Benralizumab was associated with significant improvement in asthma outcomes in patients with severe eosinophilic asthma. This benefit persisted when compared with patients who had severe eosinophilic asthma but did not receive any biologic therapy.

MAternal Dietary changEs (MADE) Study Protocol: A Mixed‐Methods Study of Breastfeeding Mothers in England

Tue, 26 May 2026 06:39:52 -0700

Clinical &Experimental Allergy, EarlyView.

Comment on ‘Effects of Acupuncture as a Therapeutic Intervention Targeting Both Skin and Gastrointestinal Symptoms in Patients With Atopic Dermatitis: A Randomised Controlled Trial’

Yintao Zhang, Yue Wen, Jingxing Li, Jiachun Xu, Zhen Zhou — Tue, 26 May 2026 00:55:51 -0700

Clinical &Experimental Allergy, EarlyView.

Characteristics and Risk Factors of Dupilumab‐Associated Head and Neck Dermatitis in Patients With Atopic Dermatitis

Zifan Li, Ruoxi Yu, Hongxiang Chen, Ying Lin — Tue, 26 May 2026 00:43:47 -0700

Clinical &Experimental Allergy, EarlyView.

Correlation and Agreement Between Parent‐Report and Self‐Report Food Allergy Quality of Life Questionnaires After Oral Immunotherapy

Mon, 25 May 2026 19:23:40 -0700

Clinical &Experimental Allergy, EarlyView.

Bronchial Fibroblasts Respond to IL‐4 Challenge With Cytokine Secretion: Role in Allergic Airway Inflammation

Mon, 25 May 2026 19:00:02 -0700

Clinical &Experimental Allergy, EarlyView.

Impact of Biologics on Oscillometry Defined Small Airway Dysfunction in Uncontrolled Asthma

Robert Greig, Philipp Suter, Rory Chan, Brian Lipworth — Sun, 24 May 2026 19:00:42 -0700

Forced oscillometry technique defined small airways dysfunction as a treatable trait in asthma. Monoclonal antibodies can improve small airways dysfunction, but their effects vary by mechanism of action.

ABSTRACT

Small airways dysfunction (SAD) is a recognised treatable trait within severe asthma, associated with worse symptom control and increased exacerbations. It can be measured using forced oscillometry technique (FOT). FOT is an effective and effort-independent method of measuring peripheral lung resistance and compliance. Type 2 inflammation can affect the small airways via eosinophilic inflammation, mucus plugging and smooth muscle inflammation. These are all potential targets of monoclonal antibody therapy. Clinical trials have shown that mepolizumab, dupilumab and tezepelumab all effect both significant and clinically meaningful improvements in oscillometry-defined SAD; however, benralizumab does not. Furthermore, in indirect matched head-to-head comparisons, dupilumab exerts greater improvements compared to either benralizumab or tezepelumab. Future research should consider oscillometry-defined SAD being incorporated as a key clinical outcome in phase 2 studies as new monoclonal antibodies are developed, such as bispecifics, especially both dual upstream (IL33/TSLP) or downstream blockade (IL4/5/13).

Population‐Scale Plasma Proteomics Reveals Systemic Inflammatory Signatures Associated With Chronic Rhinosinusitis

Dachan Kim, Hyung‐Ju Cho, Chang‐Hoon Kim, Min‐Seok Rha — Thu, 21 May 2026 23:55:52 -0700

Clinical &Experimental Allergy, EarlyView.

National and Individual‐Level Economic Burden of Local Corticosteroid Use and Concomitant Use of Multiple Local Corticosteroid Formulations—A Nationwide Cohort Study

Thu, 21 May 2026 20:39:08 -0700

Clinical &Experimental Allergy, EarlyView.

How Does the Immune System Choose? Rethinking Food Allergy Through the Lens of Immune Pathway Selection in a Changing World

Sowmya Arudi Nagarajan, Neeraj Gupta — Thu, 21 May 2026 02:31:51 -0700

Clinical &Experimental Allergy, EarlyView.

Real‐World Use of Topical Treatments for Atopic Eczema in Children and Young People: Systematic Review

Wed, 20 May 2026 07:18:52 -0700

Clinical &Experimental Allergy, EarlyView.

Lack of Patient and Public Involvement Reporting in Allergy Prevention Trials: The Example of Complementary Feeding

Wed, 20 May 2026 07:09:06 -0700

Clinical &Experimental Allergy, EarlyView.

Endotype Classification of Nonsteroidal Anti‐Inflammatory Drug‐Exacerbated Respiratory Disease According to Chronic Rhinosinusitis Comorbidity

Tue, 19 May 2026 03:35:58 -0700

Clinical &Experimental Allergy, EarlyView.

Asthma and Multimorbidity Amongst Ethnic Minority Groups in High Income Countries

Fri, 15 May 2026 00:11:46 -0700

There is a tight intersection between asthma, deprivation, ethnicity, multimorbidity and poor clinical outcomes. An integrated, holistic and culturally tailored approach is needed to improve clinical outcomes amongst ethnic minority groups with asthma and multimorbidity.

ABSTRACT

Asthma is one of the commonest noncommunicable diseases worldwide. Poor clinical outcomes have been reported in asthma amongst ethnic minority groups (EMGs) and reasons are likely to be multifactorial. There is a suggestion that underlying disease may behave differently amongst EMGs, alongside other factors including deprivation, cultural, religious, social, literacy, patient beliefs, healthcare access, treatment adherence, alongside greater burden of multimorbidity. Multimorbidity (presence of ≥ 2 long-term health conditions) in asthma is increasingly known to contribute to greater asthma burden, with differences in multimorbidity burden and patterns seen across ethnicities with a tight association with deprivation. Earlier onset of multimorbidity with relatively reduced survival has been reported amongst EMG patients, particularly those from a deprived background compared to White patients. Data regarding asthma, multimorbidity and ethnicity are scant, but emerging data suggest that multimorbidity is heterogenous, and that ethnic background is associated with variations in asthma outcomes and multimorbidity phenotypes. What is currently lacking is population-based research with a joined-up interrogation of primary care and secondary care databases to determine the prevalence and patterns of T2 and non T2 multimorbidity in asthma amongst EMGs, and analysis of patterns of associations and link to socio-demographic variables and clinical outcomes. Deeper insight into views of EMG patients and their carers regarding lived experiences of asthma and multimorbidity management, as well as those of healthcare professionals is needed, to allow development of culturally tailored resources. These studies are likely to shape a holistic culturally tailored multidimensional and an equitable approach to management of asthma with multimorbidity amongst EMGs.

Clinical Implications of Incidental Arg r 1 Sensitization Identified by Multiplex Allergy Testing

Wed, 13 May 2026 18:44:47 -0700

Clinical &Experimental Allergy, EarlyView.

Serum Eosinophil‐Derived Neurotoxin (EDN) as a Biomarker for Treatment Response in Atopic Dermatitis

J. I. Olydam, S. Sengkerij, S. Veenbergen, D. J. Hijnen — Tue, 12 May 2026 17:29:16 -0700

Clinical &Experimental Allergy, EarlyView.

Prenatal Air Pollution Exposure During Late Pregnancy Associates With Food Sensitization at 18 Months

Tue, 12 May 2026 04:41:26 -0700

Clinical &Experimental Allergy, EarlyView.

The Economic Value of Reducing Asthma Mortality in 64 Countries, 2000–2022, With Projections up to 2040: A Global Modelling Study

Tue, 12 May 2026 04:37:34 -0700

Clinical &Experimental Allergy, EarlyView.

Variants at 8p21.3 Mediate BMP1 Expression, Contributing to Higher Atopic Dermatitis Risk

Fri, 08 May 2026 18:58:48 -0700

Clinical &Experimental Allergy, EarlyView.

Fixed Very‐Low‐Dose Oral Immunotherapy in Infants and Toddlers With Low‐Threshold Egg, Milk or Wheat Allergy: A Prospective Cohort Study

Thu, 07 May 2026 05:45:53 -0700

Clinical &Experimental Allergy, EarlyView.

When a Positive IgE Test Is Not an Allergy: Distinguishing Sensitisation, Cross‐Reactivity and Irritant Responses in Clinical Practice

Neeraj Gupta, Sowmya Arudi Nagarajan — Wed, 06 May 2026 23:36:35 -0700

Clinical &Experimental Allergy, EarlyView.

Circulating 1‐Methylnicotinamide Predicts Dupilumab Response in Adult Asthma: A Prediction Model

Wed, 06 May 2026 17:05:10 -0700

Clinical &Experimental Allergy, EarlyView.

Comparison of Allergic Rhinitis Treatments on Utilities and Quality of Life: A MASK‐air Study

Wed, 06 May 2026 01:28:43 -0700

This mHealth study has shown that fixed combinations of intranasal antihistamines and corticosteroids were associated with higher quality of life than oral antihistamines and intranasal antihistamines. Both intranasal corticosteroids and oral antihistamines were associated with higher quality of life than intranasal antihistamines.

ABSTRACT

Background

Allergic rhinitis displays a relevant impact on quality of life. Medications used in the treatment of rhinitis have been assessed on their impact on rhinoconjunctivitis-related quality of life, but not on generic health-related quality of life metrics, such as utilities or EQ-5D visual analogue scale (VAS) levels. This study aimed to compare different medication classes and individual medications on utilities and EQ-5D VAS levels using data from a mobile app.

Methods

We conducted an observational study using direct patient data from the MASK-air mobile application, collected between May 2015 and December 2024. We compared rhinitis medication classes and individual medications on health utilities (computed from the EQ-5D-5L questionnaire) and the EQ-5D VAS. To account for confounding, we employed inverse probability treatment weighting based on propensity scores, adjusting for demographics, baseline symptom control, and asthma status.

Results

The study analysed 69,973 observations with EQ-5D VAS data and 842 observations with utility data. At the medication class level, fixed combinations of intranasal antihistamines and corticosteroids were associated with improvements in EQ-5D VAS (mean difference = 1.900; 95% CI = 1.316–2.484) and utilities (mean difference = 0.022; 95% CI = −0.015 to 0.059) compared with oral antihistamines (OAH). Intranasal antihistamines were associated with lower EQ-5D VAS and utility scores than other intranasal treatments. For individual medications, mometasone was associated with a lower EQ-5D VAS than budesonide and fluticasone furoate, while fexofenadine and levocetirizine tended to be associated with lower VAS values than other OAH.

Conclusion

Fixed combinations of intranasal antihistamines and corticosteroids were associated with better quality-of-life than oral antihistamines and intranasal antihistamines. These findings could support future cost-effectiveness analyses.

The Gap Between Prescription and Practice: Adrenaline Autoinjector Carriage in an Australian Cohort

Sat, 02 May 2026 00:25:54 -0700

Clinical &Experimental Allergy, EarlyView.

Aeroallergen Sensitization Phenotypes and Multimorbidity in Allergic Rhinitis and Asthma: A Large Urban Cluster Analysis

Fri, 01 May 2026 02:30:00 -0700

Clinical &Experimental Allergy, EarlyView.

Sustained Clinical Improvement in Birch Pollen Allergy After Two Pre‐Seasonal Short Courses of Allergen‐Specific Immunotherapy: A Long‐Term Open‐Label Extension Study

Thu, 30 Apr 2026 00:00:00 -0700

3 years follow-up study to a DBPC dose-finding trial investigating subcutaneous immunotherapy with T502 in birch-pollen induced allergic rhinoconjunctivitis. 154 birch-pollen allergic adults received short-course treatment of 10,000 mTU/mL of T502 for 2 years and were observed during the next season without treatment. The treatment with mannan-conjugated birch pollen polymerised allergoid resulted in a sustained reduction of CSMS, also in the group having received only two pre-seasonal courses of treatment. CSMS, combined symptom and medication score; DBPC, Double-blind, placebo-controlled trial; mTU/mL: Mannan therapeutic units per millilitre.

ABSTRACT

Background

Mannan-conjugated allergoids represent an effective option for treating allergic diseases. This study evaluated the clinical impact of the mannan-conjugated, polymerised birch pollen allergoid EP-088_T502 in patients with birch pollen-induced allergic rhinoconjunctivitis over 3 years.

Methods

Following up to a double-blind, placebo-controlled dose-finding study, in this open, long-term extension study, 154 birch pollen-allergic patients were enrolled in Germany. Patients were treated with a cumulative dose of 48,000 mTU EP-088_T502 administered subcutaneously over five pre-seasonal visits in each of the two treatment years (2021, 2022) with a subsequent follow-up year in 2023. The primary efficacy endpoint was the combined symptom and medication score (CSMS) during the peak birch pollen season, which was compared with the CSMS of the placebo group during the peak pollen season of 2020. Safety, tolerability, and immunogenicity were also analysed.

Results

Compared to the placebo group of the preceding study, median CSMS during the peak birch pollen seasons showed reductions of 47.5% in 2021 (p < 0.001), 51.8% in 2022 (p < 0.001), and 36.5% in 2023 (p < 0.001). Median daily symptom scores were reduced by 40.7% in 2021 (p < 0.001), 40.7% in 2022 (p < 0.001), and 25.6% in 2023 (p < 0.010). Median daily medication scores reached 0.07 in 2021 and 0.04 in 2022 (p < 0.001) and were reduced by 65.9% in 2023 (p < 0.003). Immunological responses showed a 4.82-fold increase in Bet v1 sIgG4 (p = 0.001) and a marked decrease (−65.5%, p = 0.001) in the sIgE/sIgG4 ratio after the first treatment phase. EP-088_T502 demonstrated good safety and tolerability, with only six mild to moderate systemic allergic reactions (Grade I/II). No epinephrine was used.

Conclusion

In this open-label study, two consecutive years of pre-seasonal short-course allergen immunotherapy (AIT) with EP-088_T502 markedly reduced symptoms and medication need in patients with birch pollen-induced rhinoconjunctivitis. Persistent therapeutic effects observed during the follow-up year, although limited by attrition of the study population, suggest sustained clinical improvement and indicate the potential disease-modifying impact of this treatment regimen.

Gender‐Dependent Differences in Serum Osteopontin Levels in Chronic Spontaneous Urticaria: A Link to Disease Activity in Females

Mon, 27 Apr 2026 20:10:36 -0700

Clinical &Experimental Allergy, EarlyView.

Evaluating Basophil Histamine Content as a Biomarker for Omalizumab Responsiveness in Chronic Spontaneous Urticaria

Sun, 26 Apr 2026 21:25:12 -0700

Clinical &Experimental Allergy, EarlyView.

Unraveling the Natural History of Atopic Dermatitis: Prospective Disease Trajectories and Longitudinal IgE Sensitization from Birth to Adolescence

Sun, 26 Apr 2026 21:19:55 -0700

Clinical &Experimental Allergy, EarlyView.

Berotralstat and Health‐Related Quality of Life in Hereditary Angioedema: Pooled Analysis of the APeX‐2 and APeX‐J Trials

Sun, 26 Apr 2026 00:00:00 -0700

Pooled analysis of the phase 3 APeX-2 and APeX-J trials evaluated the impact of berotralstat 150 mg on health-related quality of life in patients with hereditary angioedema using the Angioedema Quality of Life (AE-QoL) questionnaire. Berotralstat significantly improved AE-QoL total and domain scores for daily functioning and fears/shame versus placebo through Week 24. Improvements in the berotralstat group were sustained through Week 96.

ABSTRACT

Background

In the phase 3 APeX-2 and APeX-J trials, improvements in health-related quality of life (HRQoL) were reported for berotralstat, the only oral, once-daily, long-term prophylaxis for hereditary angioedema (HAE). We conducted a post hoc trial analysis to evaluate the impact of berotralstat on HRQoL versus placebo through 24 weeks, and the long-term effects of treatment up to 96 weeks, using pooled APeX-2 and APeX-J patient data.

Methods

Patients receiving berotralstat 150 mg or placebo using the Angioedema QoL (AE-QoL) questionnaire; total and domain scores were analysed. Changes from baseline through Week 24 were compared using mixed models for repeated measures (MMRM) to estimate least squares mean differences (LSMDs) with 95% confidence intervals (CI) and nominal p-values. After Week 24, in the absence of a placebo comparator, long-term changes from baseline were evaluated using within-subject effect sizes (Cohen's d) through Week 96 in patients receiving berotralstat. Clinical meaningful improvements in AE-QoL total and domain scores were assessed by minimal clinically important difference (6-point reduction in AE-QoL total score) and distributional criterion methods, respectively. The manufacturer of berotralstat (BioCryst Pharmaceuticals) funded this study.

Results

Overall, 47 and 45 patients received berotralstat and placebo, respectively. At Week 24, berotralstat showed significantly greater improvement in AE-QoL total (LSMD: −7.4; 95% CI: −14.3, −0.6; p < 0.05), functioning domain (LSMD: −10.9; 95% CI: −19.6, −2.3; p = 0.013) and fears/shame domain (LSMD: −8.7; 95% CI: −17.2, −0.2; p = 0.046) scores compared with placebo. Among patients receiving berotralstat, consistent sustained improvements were observed across all AE-QoL domains up to Week 96. Analyses of meaningful improvement in total score and domains showed an increase over time in the proportion of patients achieving meaningful change.

Conclusion

Berotralstat significantly improved HRQoL versus placebo through 24 weeks and showed long-term beneficial effects through 96 weeks.

Incidence of New Asthma and Asthma Exacerbation Pre‐ and Post‐COVID‐19 Pandemic in the United States

Tue, 21 Apr 2026 22:55:55 -0700

Clinical &Experimental Allergy, EarlyView.

Institutional Trends in Penicillin Allergy: A New Era of Active Penicillin Allergy Delabeling

Tue, 21 Apr 2026 22:23:49 -0700

Clinical &Experimental Allergy, EarlyView.

Racial Differences in Patterns of Long‐Term Conditions Among Adults With Asthma

Tue, 21 Apr 2026 22:21:05 -0700

Clinical &Experimental Allergy, EarlyView.

Respiratory Viral Infections and the Tonsillar Transcriptome: An Exploratory Study

Mon, 20 Apr 2026 20:30:18 -0700

Clinical &Experimental Allergy, EarlyView.

T Cell O‐GlcNAcylation Increases in Patients With Allergic Rhinitis After the Natural Pollen Season

Mon, 20 Apr 2026 20:25:05 -0700

Clinical &Experimental Allergy, EarlyView.

Circulating Piwi‐Interacting RNAs Associate With Childhood Asthma ICS Response With Vitamin D Effect Modification

Mon, 20 Apr 2026 20:20:08 -0700

Circulating piRNAs correlate with inhaled corticosteroid (ICS) response in childhood asthma, modified by vitamin D status. piR-36241 predicts ICS responsiveness specifically in vitamin D–insufficient children (AUROC = 0.84). Mechanistically, piR-36241 targets immune pathways and shows differential expression in asthmatic bronchial cells, supporting its biomarker potential and biological relevance.

ABSTRACT

Background

Piwi-interacting RNAs (piRNAs) have been linked to type 2-high asthma phenotypes. Although vitamin D modulates inhaled corticosteroid (ICS) response via microRNAs, its potential role through piRNAs remains unknown.

Methods

Baseline plasma piRNA expression was profiled by small RNA sequencing in 492 participants from the Childhood Asthma Management Program (CAMP), with 187 children randomised to the ICS arm. Serum vitamin D levels were classified as insufficient (≤ 30 ng/mL) or sufficient (> 30 ng/mL). Linear regression was used to assess associations between piRNA expression and changes in prebronchodilator percent predicted forced expiratory volume in 1 s (FEV₁%) over 4 years, including interaction analyses with vitamin D status. Replication was performed in 375 ICS-treated participants from the Genetics of Asthma in Costa Rica Study (GACRS).

Results

Fourteen piRNAs were significantly associated with FEV₁% changes among vitamin D–insufficient children, six showing significant interactions with vitamin D status (p < 0.05). Four piRNAs were replicated in GACRS, with piR-36241 also confirmed in interaction analyses. Predicted targets of piR-36241 were enriched in immune- and respiratory-related pathways. piR-36241 demonstrated strong predictive performance for ICS response in vitamin D–insufficient children (AUROC = 0.84) and was detected in bronchial epithelial cells, where it was differentially expressed in asthma.

Conclusions

Circulating piRNAs are associated with ICS response in childhood asthma, with vitamin D acting as an effect modifier, which may serve as non-invasive biomarkers for ICS responsiveness, particularly in vitamin D–insufficient patients.

Trial Registration

ClinicalTrials.gov Identifier: NCT00000575 and NCT00021840

Residential Greenness and Incident Chronic Rhinosinusitis After SARS‐CoV‐2 Infection in South Korea: A Nationwide Cohort Study

Sun, 19 Apr 2026 18:54:49 -0700

Clinical &Experimental Allergy, EarlyView.

Low‐Dose, Slow‐Escalation Home‐Based and Sustainable Oral Immunotherapy for Walnut and Cashew Allergy: A Retrospective Case Series

Sun, 19 Apr 2026 18:48:34 -0700

Clinical &Experimental Allergy, EarlyView.

Active Paediatric Food‐Allergy Interventions Pursue Distinct Clinical Goals: A Brief, Goal‐Directed Synthesis

Ping Wei, Fenghui Yu, Yijun Liu, Sichu Yu, Wei Kou — Fri, 17 Apr 2026 22:35:08 -0700

Clinical &Experimental Allergy, EarlyView.

Dupilumab in Chronic Rhinosinusitis With Nasal Polyps Patients: Impact on Tissue Eosinophilic Inflammation and Eosinophil Subphenotypes

Fri, 17 Apr 2026 22:24:48 -0700

Clinical &Experimental Allergy, EarlyView.

Association Between Domestic Mold Detection and Clinical Outcomes in House Dust Mite Allergic Patients

Fri, 17 Apr 2026 22:19:01 -0700

Clinical &Experimental Allergy, EarlyView.

Building Tolerance Remotely: Telemedicine Support for Egg Ladder Completion in IgE‐Mediated Egg Allergy

Mayah Cousens, Aoife Gallagher, Caoimhe Cronin, Sadhbh Hurley, Juan Trujillo — Thu, 16 Apr 2026 18:32:17 -0700

Clinical &Experimental Allergy, EarlyView.

The Clinical Value of Measuring Nasal Nitric Oxide in Addition to Exhaled Nitric Oxide in Asthma Associated With Eosinophilic Chronic Rhinosinusitis

Thu, 16 Apr 2026 03:13:30 -0700

Clinical &Experimental Allergy, EarlyView.

Patterns of Mouse Allergen–Specific IgE and IgG4 in Contemporary Animal Research Environments

Thu, 16 Apr 2026 02:54:28 -0700

Clinical &Experimental Allergy, EarlyView.

Functional Endoscopic Sinus Surgery in Adults With CRSwNP Treated With Mepolizumab: Airway Physiology Outcomes From a Randomised Controlled Trial

Mon, 13 Apr 2026 00:00:00 -0700

Clinical &Experimental Allergy, EarlyView.

Association Between Asthma and Chronic Bone Diseases: A Cross‐Sectional Analysis From the Longitudinal Ageing Study in India (LASI) Data

Arundhati Garud, Saibal Moitra, Subhabrata Moitra — Thu, 09 Apr 2026 17:04:40 -0700

Clinical &Experimental Allergy, EarlyView.

Novel CD8+ Regulatory T Cells Attenuate Eosinophilic Infiltration in a Murine Allergic Asthma Model

Jia‐Ning Fan, Tien‐Hsuan Chen, Bor‐Luen Chiang — Wed, 08 Apr 2026 18:30:29 -0700

Clinical &Experimental Allergy, EarlyView.

Association of Penicillin Allergy Label With Post‐COVID‐19 Condition and Subsequent Clinical Outcomes: A Population‐Based Cohort Study

Ubonphan Chaichana, Kenneth K. C. Man, Chengsheng Ju, Yogini H. Jani, Li Wei — Mon, 06 Apr 2026 19:45:44 -0700

Clinical &Experimental Allergy, EarlyView.

Effects of Common Food Additives Kappa‐, Iota‐ and Lambda‐Carrageenans on Intestinal Epithelial Cell Activation and Barrier Disruption

Mon, 06 Apr 2026 00:00:00 -0700

Carrageenans, widely used food additives, disrupted intestinal epithelial integrity in a gut-on-a-chip model. All types (κ-, ɩ-, λ-) induced cytotoxicity, inflammation and tight junction (TJ) disruption, triggering TNF-mediated immune responses. λ-Carrageenan had the most severe effects, supporting the Epithelial Barrier Theory linking food additives to chronic inflammatory diseases.

ABSTRACT

Background

The epithelial barrier theory has been proposed to link the onset of many chronic inflammatory diseases to the damaged epithelial barrier induced by numerous environmental factors, including food emulsifiers. This study aimed to investigate the effects of food emulsifiers kappa-, iota- and lambda-carrageenan on intestinal epithelial barrier integrity and the underlying mechanisms.

Methods

The cytotoxicity and apoptosis of carrageenans were determined using Hoechst/propidium iodide staining and FITC annexin V/propidium iodide staining, respectively. The gut-on-a-chip was established and transepithelial electrical resistance measurement, paracellular flux assay, immunofluorescence staining of tight junction proteins, RNA-sequencing and targeted proteomics were performed.

Results

Kappa-, iota- and lambda-carrageenans induced dose-dependent cytotoxicity, with lambda-carrageenan showing a more severe cytotoxic effect in relatively lower doses. All three carrageenans elicited a dose- and time-dependent decrease of gut epithelial barrier strength, a significant increase in the paracellular flux and irregular and heterogeneous staining of occludin and ZO-1 compared to the untreated group, suggesting the disruption of the intestinal epithelial barrier integrity. Transcriptomics data revealed that iota- and lambda-carrageenan induced more severe pro-inflammatory responses, which were associated with the upregulation of genes involved in TNF signalling, IL-17 signalling cellular response to chemokines, cholesterol metabolism and NF-kappa B signalling pathways. Targeted proteomics data from exposed gut-on-a-chips indicated an upregulation of inflammation- and immune response-related proteins for all three carrageenans.

Conclusions

The present study provides direct evidence for the detrimental effects of kappa-, iota- and lambda-carrageenans on gut epithelial cell activation and barrier integrity. The underlying mechanism of epithelial barrier disruption was largely attributed to the activation of innate immune responses by carrageenans, resulting in a pro-inflammatory response.