Evidence on the association between physical activity (PA) and allergic rhinitis (AR) remains inconsistent. While the prevalence of AR was high in Japan, no epidemiological study regarding this issue has been conducted. This study examined the association between exercise habits including exercise partner and self-reported AR among Japanese young adults. This cross-sectional study included 12,497 university students who underwent annual health checkups. Exercise habits were evaluated using a self-administered questionnaire on frequency (none, 1-2/month, 1-3/week, ≥ 4/week), intensity (none, light, moderate, intense), and exercise partner (no exercise, group, friends, alone). AR was defined as responding "Yes" to the question about self-reported AR. Multivariable logistic regression estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs), controlling for age, sex, body mass index, smoking, and alcohol use. Of 12,497 participants (mean age 20.1 ± 3.1 years; 60.4% men), the prevalence of AR was 20.0% (n = 2,500). Compared with non-exercisers, high-frequency exercise (≥ 4/week) was independently and inversely associated with AR (adjusted OR = 0.83, 95%CI 0.72-0.96; p for trend = 0.008). Inverse associations between intense exercise (adjusted OR = 0.84, 95%CI 0.75-0.95), exercising with groups (adjusted OR = 0.83, 95%CI 0.72-0.94), and AR were also observed. Among Japanese young adults, frequent and intense exercise, particularly in organized settings, was independently and inversely associated with self-reported AR. These findings provide the first large-scale evidence from Japan suggesting an inverse association between habitual exercise and AR.

Although penicillin allergy is frequently reported, the majority of labeled patients do not have confirmed hypersensitivity upon formal evaluation. The PEN-FAST clinical decision rule was developed to identify adults at low risk of true penicillin allergy; however, evidence supporting its performance in children remains limited. To evaluate the diagnostic performance of the PEN-FAST score in a pediatric population with reported penicillin allergy. We performed a retrospective cohort study including children younger than 18 years with a documented penicillin allergy label who underwent allergy evaluation at a tertiary referral center between January 2012 and February 2023. Children with suspected severe cutaneous adverse reactions (SCARs) or insufficient information to calculate the PEN-FAST score were excluded. Diagnostic evaluation included skin testing and/or drug provocation testing (DPT). Diagnostic performance of the PEN-FAST score was assessed by calculating sensitivity, specificity, predictive values, and the area under the receiver operating characteristic curve (AUC). Among 267 children included in the analysis, 19 (7.1%) had confirmed penicillin allergy. Using the original PEN-FAST cutoff of ≥ 3, the AUC was 0.62 (95%CI, 0.51-0.73), with sensitivity of 68.4%, specificity of 55.7%, positive predictive value of 10.6%, and negative predictive value of 95.8%. Exploratory analyses using alternative PEN-FAST score representations showed only minimal differences in discrimination. In this pediatric cohort, the PEN-FAST score demonstrated limited accuracy in distinguishing true penicillin allergy. These findings suggest that the adult-derived decision rule may require further refinement before routine application in children.

The emergence of the SARS-CoV-2 Delta variant necessitated examining hybrid immunity (vaccination- plus-infection) to optimize boosting strategies. We analyzed the kinetics, magnitude, and durability of anti-spike receptor binding domain immunoglobulin G (Anti-sRBD IgG) following Delta infection. This study analyzed the kinetics, magnitude, and long-term durability of anti-spike receptor binding domain immunoglobulin G (Anti-sRBD IgG) levels following Delta variant infection across individuals with diverse vaccination histories. This observational cohort study monitored 161 patients with varying vaccination histories for up to 16 weeks post-infection. Responses were compared against SARS-CoV-2 naïve controls receiving a two-dose inactivated series plus a heterologous booster. Sub-analyses assessed post-infection booster immunogenicity. Prior vaccination significantly enhanced humoral responses. Patients with two prior doses achieved the highest median Anti-sRBD IgG peaks, surpassing vaccine-boosted naïve controls. While unvaccinated individuals exhibited delayed primary responses, hybrid immunity demonstrated superior durability with slower antibody decay than vaccine-only immunity. Crucially, while a post-infection booster effectively primed unvaccinated patients, early boosting in previously vaccinated individuals yielded minimal immunological gain. Prior vaccination significantly enhanced humoral responses. Patients with two prior doses achieved the highest median Anti-sRBD IgG peaks, surpassing vaccine-boosted naïve controls. While unvaccinated individuals exhibited delayed primary responses, hybrid immunity demonstrated superior durability with slower antibody decay than vaccine-only immunity. Crucially, while a post-infection booster effectively primed unvaccinated patients, early boosting in previously vaccinated individuals yielded minimal immunological gain.

Recently, clonidine has been increasingly utilized for the treatment of tic disorders in children rather than for hypertension in adults. The transdermal patch is a common route of administration. Allergic contact dermatitis caused by clonidine transdermal patch was reported in adults with hypertension but never in children with tic disorder. We report on the first pediatric case developed allergic contact dermatitis within one to two weeks after using clonidine transdermal patch. Patch test with clonidine and Chinese baseline series including adhesive components (ethyl acrylate, methyl methacrylate, and 2-hydroxyethyl methacrylate) from the adhesive layer of the transdermal patch were performed. We report the first pediatric case with allergic contact dermatitis due to clonidine transdermal patch confirmed by patch test. She presented with pruritic erythema, blistering, and rupture at the patch site, matching its size and shape. Patch test with clonidine hydrochloride elicited positive reactions (++ to +++), while tests for specific components from the adhesive layer, including ethyl acrylate, methyl methacrylate, and 2-hydroxyethyl methacrylate, were negative, thereby identifying clonidine as the primary allergen. This case highlights that although clonidine itself has weak sensitizing potential, the transdermal therapeutic system may increase the risk of clonidine-induced sensitization and make it become a potential trigger for allergic contact dermatitis in clonidine transdermal patch users.

Asthma is a heterogeneous disease influenced by genetic and environmental factors. Type 2 (T2)-high asthma has been extensively studied; however, the pathophysiological mechanisms of T2-low asthma remain unclear. The present study aimed to determine the clinical indices contributing to asthma exacerbation and identify the phenotypes of T2-low asthma. We used data from the NHOM Asthma Study (N = 1925), a nationwide asthma cohort study conducted in Japan. T2-low asthma was defined by eosinophils < 150/μL and fractional exhaled nitric oxide levels < 25 ppb. The clinical indices associated with asthma exacerbation were identified using univariate and multivariate analyses. Hierarchical cluster analysis was performed to classify the phenotypes of T2-low asthma. Multivariate analysis revealed that younger age and comorbid allergic diseases contributed to the exacerbation of T2-low asthma. Four phenotypes were identified: Cluster 1 (n = 19, 7.8%, smoking-related T2-low asthma with preserved pulmonary function), Cluster 2 (n = 18, 7.4%, smoking-related T2-low asthma with low pulmonary function), Cluster 3 (n = 99, 40.7%, elderly, female-dominant, late-onset T2-low asthma), and Cluster 4 (n = 107, 44.0%, younger, female-dominant, comorbid with allergic disease T2-low asthma). Clusters 2 and 4 were prone to asthma exacerbation, indicating distinct allergen sensitization. These findings indicate that antigen-specific IgE profiles may reflect the phenotypic heterogeneity of T2-low asthma and could serve as potential biomarkers for identifying subgroups at increased risk of exacerbations.

Allergic asthma in children significantly impacts quality of life, and immunotherapy, including subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), has emerged as an effective treatment. However, their comparative immunological mechanisms remain unclear. This study aimed to compare the effects of SCIT and SLIT on immune response in children with allergic asthma and to explore their underlying immunological mechanisms. A total of 86 children aged 5-12 years with allergic asthma who visited Hangzhou Children's Hospital were prospectively enrolled and randomly assigned to three groups: inhaled corticosteroids (ICS) group (n = 30), SCIT group (n = 30), and SLIT group (n = 26). Clinical and immunological parameters-including Childhood Asthma Control Test (C-ACT) scores, forced expiratory volume in the first second percentage (FEV1%), Th17, Treg cells, and serum levels of IL-17, IL-9, IL-10-were assessed before treatment and after one year. After treatment, all three groups showed significant improvements in C-ACT scores and FEV1% compared to baseline (all p < 0.05). The SCIT and SLIT groups demonstrated greater improvements than the ICS group (all p < 0.05), with no significant differences between the SCIT and SLIT groups (p > 0.05). In terms of immune markers, significant differences were observed in all parameters before and after treatment in the SCIT and SLIT groups (all p < 0.05), while Treg levels in the ICS group remained unchanged (p > 0.05). No statistically significant differences in immune markers were found among the three groups post-treatment (all p >0.05). Both SCIT and SLIT, when combined with ICS, offer superior efficacy compared to ICS monotherapy. The comparable immunological changes observed in SCIT and SLIT suggest a shared mechanism of immune tolerance, potentially mediated through Treg cell induction.

Dermatophagoides pteronyssinus and D. farinae are major indoor allergens. Raw materials derived from these house dust mites (HDMs) are used to produce allergen extracts. The stability of these materials is influenced by storage form and conditions, which can affect protein integrity. To compare storage formats and conditions for maintaining physicochemical stability of HDM raw materials. Pure mite bodies (PMBs), prepared in fresh frozen and lyophilized forms, were stored at -80°C, -20°C, and 25°C. Over a 12-month period, samples were assessed for total protein and major allergens (Der p 1 and Der f 1) using ELISA. Protein integrity was analyzed by SDS-PAGE. Accelerated stability testing at 25°C for up to 14 days was also performed. Storage at -80°C best preserved total protein and Group 1 allergen content over 12 months. At -20°C, moderate declines were observed, with D. farinae showing greater reductions than D. pteronyssinus. Lyophilized samples were generally more stable than fresh-frozen ones at -20C°. Accelerated testing at 25°C caused marked losses over 14 days. Ultra-low temperature storage (-80°C) remains optimal for preserving physicochemical stability of HDM raw materials. Lyophilization with -20°C storage is a promising, context-dependent option; however, in the absence of residual-moisture and immunological data, these findings should be interpreted as preliminary and limited to raw-material handling.

Eosinophilic asthma is a severe phenotype in pediatrics, often refractory to conventional therapy. Biologic agents targeting Type 2 inflammatory pathway are increasingly used in children and adolescents. To evaluate the efficacy and safety of omalizumab, mepolizumab, benralizumab, and dupilumab in pediatric eosinophilic asthma. We systematically searched eight databases to March 31, 2025 (PROSPERO: CRD420251017602). Eligible studies were randomized controlled or controlled observational trials in patients 1≤8 years. Outcomes included lung function, asthma control, quality of life (QoL), and adverse events (AEs). Twenty-two studies (n = 2,468) were included. Biologics significantly improved predicted FEV1 (SMD = 0.97, 95%CI: 0.38-1.57), asthma control also improved (SMD = 2.84, 95%CI: 1.40-4.28), as did quality of life (SMD = 1.72, 95%CI: 0.39-3.05). Overall AEs were more frequent (OR 1.48, 95%CI 1.22-1.81), but serious AEs were rare and not increased. Evidence was strongest for omalizumab; data for other biologics remain limited. Biologic therapies are associated with improvements in clinical outcomes in children and adolescents with eosinophilic asthma, with an increased incidence of predominantly mild adverse events. However, the current evidence is largely driven by studies of omalizumab, and data for other biologics remain limited in pediatric populations. Further long-term and comparative studies are warranted to better define the efficacy and safety profiles of individual biologic agents.

Accurate diagnosis of IgE-mediated allergic diseases is crucial for effective management. This study compared the diagnostic performance of two multiplex allergy assays-AllergyChip and ALEX2-by measuring IgE reactivity to 31 inhalant allergens in serum from 90 participants. To compare the diagnostic performance of AllergyChip with ALEX2 as reference method for specific IgE detection. Agreement between the assays was evaluated by calculating overall (OPA), positive (PPA), and negative percentage agreement (NPA). Cohen's kappa measured agreement beyond chance. ROC analysis evaluated AllergyChip's ability to discriminate between positive and negative sIgE results. Spearman's correlation assessed concordance between sIgE classes, and Bland-Altman analysis evaluated quantitative agreement. AllergyChip showed substantial agreement with ALEX2 (OPA 88%, Cohen's kappa 0.792). ROC analysis showed excellent discrimination (AUC 0.891). Spearman's correlation (Rs 0.792) indicated strong agreement. However, AllergyChip had PPA below 70% for nine allergens, notably 0% for Phl p 12 and 30% for Bet v 2. AllergyChip performs well in detecting IgE to inhalant allergens and may be a viable alternative assay. However, its lower sensitivity for certain allergens suggests it should complement, rather than replace, ALEX2, particularly in cost-sensitive settings. Further studies are needed to confirm these findings and improve accuracy in multiplex allergy diagnostics.

Extrachromosomal circular DNA (eccDNA) has transitioned from genomic curiosity to a pivotal regulator at the intersection of genomics and immunology. This review synthesizes recent advances in eccDNA biology, elucidating its integral roles in both innate and adaptive immunity and its pathogenic contributions to autoimmune diseases. eccDNA arises from diverse genomic events, including DNA damage repair, replication stress, and chromothripsis. In innate immunity, it functions as a potent damage-associated molecular pattern (DAMP), activating cytosolic sensors like cGAS-STING and AIM2 to drive type I interferon and pro-inflammatory cytokine responses. In the adaptive immune system, eccDNA is not merely a byproduct of processes such as V(D)J recombination (e.g., TRECs, KRECs); it also acts as an active modulator regulating immune gene expression via enhancer-like activity, influencing antigen presentation, and shaping T and B cell development. Critically, aberrant eccDNA accumulation is implicated in the pathogenesis of autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis. Here, plasma eccDNA levels not only correlate with clinical disease activity indices but also track with therapeutic response, positioning eccDNA as a powerful non-invasive biomarker. Targeting eccDNA biogenesis or its sensing pathways thus represents a promising therapeutic frontier for restoring immune homeostasis. Future research integrating single-cell omics and longitudinal profiling is poised to dissect cell-specific functions and unlock the full clinical potential of eccDNA. Collectively, these findings establish eccDNA as both a functional regulator and a diagnostic tool, offering novel insights into the fundamental interplay between genomic integrity and immune function.