Clinical and Experimental Allergy最新文献

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.

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.

The AllergoOncology field brings together the study of allergic and cancer immune responses, having evolved from early epidemiological studies that reported inverse associations between allergies, IgE and cancer risk. Insights from studying allergic inflammation are revealing previously unappreciated immune mechanisms that confer protective effects against cancer, and evasion pathways that facilitate tumour progression. AllergoOncology sheds light on cancers with poor prognosis, including glioma, where evidence has pointed to allergic triggers that may influence glioma biology through rewiring immune surveillance. Allergic signals point to new biomarkers that may identify groups at higher risk of developing cancer, aid patient stratification and help monitor treatment and clinical outcomes. Allergic mediators such as histamine and IgE levels are emerging biomarkers that can inform cancer risk and lead to clinical interventions that improve outcomes. Emerging cancer immunotherapies, such as tumour antigen-specific IgEs, an evolving therapy class, are and will continue to be inspired by understanding allergic immune response mechanisms. Assays, including the Basophil Activation Test developed for monitoring and managing allergic reactions, are translated to the oncology clinic to evaluate hypersensitivity to anti-cancer therapeutics. Allergy research brings fundamental benefits for oncology through understanding and harnessing allergic and cancer-associated mechanisms in AllergoOncology for patient benefit.

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.