Allergy, Asthma & Immunology Research最新文献

Purpose: The prevalence of allergic rhinitis (AR) has increased rapidly. However, the AR phenotype in the general population remains poorly explored. In this study, we aimed to determine the distinct features of AR phenotypes according to Allergic Rhinitis and its Impact on Asthma (ARIA) classification in Korean children.

Methods: We enrolled 1,113 children aged 7 years from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA) study. AR was diagnosed by a physician at each scheduled visit, and the AR phenotype was defined according to the ARIA classification. We analyzed the results of skin prick tests and performed cytokine assays using blood samples collected at ages 3 and 7.

Results: The prevalence of AR at age 7 was 48.9%, while that of moderate-to-severe persistent AR phenotype was 4.4%. Cesarean delivery was associated with the mild-intermittent AR phenotype, while prenatal antibiotic use was linked to the moderate-to-severe persistent phenotype. Sensitization to Dermatophagoides pteronyssinus (Der p), Dermatophagoides farinae (Der f), birch, and Japanese hop at age 3 and sensitization to Der p, Der f, birch, oak, and cat at age 7 increased the risk of moderate-to-severe persistent AR phenotype. Upon cytokine analysis, interleukin (IL)-4 tended to be elevated at age 3 in children with moderate-to-severe persistent AR. By age 7, concentrations of IL-5 and IL-17A were significantly higher in children with moderate-to-severe persistent AR phenotype.

Conclusions: These findings suggest that 4.4% of Korean children had a moderate-to-severe persistent AR phenotype, as defined by ARIA. Early sensitization to Der p, Der f, birch, and Japanese hop at age 3 and prenatal antibiotic use are risk factors. Furthermore, this phenotype may involve both T helper 2 and T helper 17-related immune responses, reflecting a potential shift toward more complex or mixed patterns of inflammation.

Purpose: Airway inflammation and remodeling are pivotal in asthma pathogenesis. Interleukin-17D (IL-17D), a recently characterized cytokine within the IL-17 family, is found to be expressed at higher levels in lung tissue; however, its role in asthma remains unclear. This study aims to elucidate the function and mechanisms of IL-17D in asthma, providing new insights for therapeutic strategies.

Methods: We analyzed IL-17D messenger RNA expression levels using datasets from the Gene Expression Omnibus (GEO). Bronchoscopic biopsy tissues and serum samples from asthmatics, along with lung tissues from chronic asthmatic mice, were collected to validate IL-17D expression. Lentivirus-mediated IL-17D knockdown was performed in a chronic asthma mouse model induced by ovalbumin (OVA). Recombinant murine IL-17D protein was intranasally administered to further investigate its impact. In vitro, human bronchial epithelial cells (16HBE) were treated with recombinant human IL-17D or CD93-targeting small interfering RNA to explore signaling mechanisms.

Results: GEO data and experimental findings revealed that IL-17D expression was reduced in the airway epithelia of asthmatics and chronic asthmatic mice. In vivo, knockdown of IL-17D exacerbated peri-airway inflammation and promoted epithelial-mesenchymal transition (EMT) in OVA-induced asthmatic mice. Conversely, recombinant IL-17D protein administration significantly attenuated airway inflammation, extracellular matrix (ECM) deposition, and EMT progression. In vitro, IL-17D mitigated transforming growth factor-β1-induced fibrotic remodeling in 16HBE cells, with CD93 receptor silencing partially reversing these effects.

Conclusions: Our findings suggest that IL-17D could play a protective role in asthmatic airway inflammation and remodeling, partially through the CD93 receptors. These results highlight IL-17D as a potential therapeutic target for asthma management.

Purpose: Allergic rhinitis (AR) is no longer considered an immune dysregulation disorder but rather a neuroimmune disorder regulated by neuronal signals. However, the mechanisms underlying these effects remain unclear. Therefore, we evaluated whether the local nasal mucosa is regulated by neuroimmune signals during nasal allergic reactions.

Methods: We identified genes that were differentially expressed between patients with AR and healthy controls using GSE46171 gene chip data. Expression levels of neuromedin U (NMU), NMU receptor 1 (NMUR1), and group 2 innate lymphoid cells (ILC2s) in the nasal mucosa were determined the impacts of NMU on patients with AR were assessed. An AR animal model was established to observe the effects of local NMU intervention on local and systemic ILC2s in the nasal cavity.

Results: We identified 1,137 differentially expressed genes and focused on the neuropeptide NMU. NMU was widely distributed in the lamina propria of the nasal mucosa of patients with AR. NMUR1 was expressed at high levels in the lamina propria, basal layer, and glandular epithelium. Local ILC2 expression in the nasal mucosa of the AR group was elevated and positively correlated with NMU and NMUR1 expression. Using the AR model, we found that NMU significantly enhanced both local and systemic inflammatory responses in ovalbumin-sensitized mice and promoted activation of ILC2s to release additional type 2 inflammatory cytokines. However, this effect was blocked by an extracellular signal-regulated kinase (ERK) pathway inhibitor, indicating that NMU activates ILC2s via the ERK pathway, contributing to AR pathogenesis.

Conclusions: During nasal allergic reactions, local NMU increases significantly in the nasal cavity, activating ILC2s via the ERK pathway to release type 2 cytokines, thereby participating in or exacerbating the onset of AR. These findings lay the groundwork for exploration of diverse factors that contribute to AR and suggest new approaches to prevention and treatment.

Rhinoviruses (RVs) are the most frequent viral causes of respiratory infections worldwide and contribute substantially to a spectrum of respiratory diseases, including wheezing, asthma, and lower respiratory tract illnesses throughout the lifespan. Despite their substantial disease burden, vaccine development for RVs has been hindered for decades due to extensive serotypic diversity and limited cross-reactive immune responses. However, recent progress in structural virology, immune profiling, and antigen discovery─particularly through peptide array mapping and the identification of conserved neutralizing epitopes─has revived interest in the design of RV vaccines. Novel strategies targeting conserved B cell capsid domains, conserved T cell epitopes, and high-valent vaccine formulations have shown promise in preclinical models. This review summarizes the current understanding of RV infection epidemiology, risk stratification for early vaccine prioritization, and evolving vaccine development strategies, while highlighting critical gaps and the growing scientific momentum toward clinical translation. With continued innovation, RV vaccination may become a viable strategy to mitigate the longstanding and pervasive global health burden of RV infection.

Purpose: We aimed to investigate the prevalence of atopic dermatitis (AD) and its associated risk factors in Korean children in 2022, and to compare to our findings with previous results to identify changes or trends over time.

Methods: A nationwide, cross-sectional study of randomly selected schoolchildren aged 6-7, 9-10, and 12-13 years, respectively, was completed. Information was obtained through the International Study of Asthma and Allergies in Childhood questionnaire, and comparisons between the current and prior surveys performed in 1995, 2000, and 2010 were conducted using a trend test.

Results: In the 2022 survey, the prevalence of "itchy eczema, ever" was 18.3% in 6- to 7-year-olds, 21.6% in 9- to 10-year-olds, and 18.8% in 12- to 13-year-olds. The prevalence of "AD diagnosis, ever" in 6- to 7-year-olds rose from 20.9% in 1995 to 35.4% in 2010, then dropped to 13.6% in 2022 (P < 0.001), while in 12- to 13-year-olds, it increased from 7.1% in 1995 to 23.7% in 2010, then declined to 17.5% in 2022 (P < 0.001). In 6- to 7-year-olds, the prevalence of "AD only" and "AD and asthma" decreased between 1995 and 2022 (all P < 0.001). In 12- to 13-year-olds, the prevalence of "AD only," "AD and rhinitis," and "AD and asthma and rhinitis" all increased during the same period (all P < 0.001).

Conclusions: The prevalence of AD decreased in Korean children aged 6-7 years and increased in those aged 12-13 years, respectively, between 1995 and 2022, with a concomitant rise in allergic comorbidities among adolescents, suggesting age-dependent trends influenced by diverse AD phenotypes.

Atopic dermatitis (AD) is a prevalent chronic inflammatory disease that significantly burdens individuals and healthcare systems worldwide. The incidence of AD has risen sharply in both developed and emerging economies, necessitating an understanding of its complex etiological factors, including environmental influences and lifestyle changes. Generally, 2 primary preventive strategies for AD have been implemented so far: (1) the "Inside Out" approach that which involves allergen elimination, probiotic supplementation, fish oil supplementation, and vitamin D supplementation aim to regulate the immune system in pregnancy and early childhood and (2) the "Outside In" approach that focuses on improving skin barrier function through emollient use and environmental changes. Although current evidence suggests the potential benefits from these interventions, randomized controlled trials have revealed inconsistencies in their efficacy. It is imperative not only to explore the minute research gaps in existing studies, but also to develop novel interventional studies that consider individual and regional differences based on the epithelial barrier hypothesis, the biodiversity hypothesis, and the 'old friends' hypothesis evolved from the hygiene hypothesis. Ultimately, reversing the rising trend of AD prevalence will most likely require a multifaceted approach that integrates new scientific evidence and promote comprehensive lifestyle changes.

Purpose: Atopic dermatitis (AD) is a chronic condition characterized not only by skin lesions but also by significant patient burden, impacting mental health and quality of life. The Atopic Dermatitis Control Tool (ADCT) is recommended as an assessment tool for evaluating the long-term management of AD. However, there is a scarcity of studies comparing the utility of ADCT in real-world clinical practice to that of the other existing AD evaluation tools. This study aimed to investigate long-term changes in the ADCT and examine its correlations with the other evaluation tools in AD patients undergoing dupilumab treatment.

Methods: A retrospective study was conducted on 89 outpatients with AD who received treatment with dupilumab between April 2020 and March 2023. Patients underwent assessments using the ADCT and other evaluation tools before treatment initiation and at 1, 2, and 3 years following treatment commencement.

Results: Of the 89 patients, with a mean age of 28.7 years (range: 12 to 65 years), 68 (76.4%) were male. All 89 patients were followed for 1 year, 44 for 2 years, and 17 for 3 years. The mean total ADCT score decreased at year 1 (58.2% reduction, P < 0.001), with this reduction continuing at years 2 and 3 (73.8% and 75.3% reduction, respectively, P < 0.001). Furthermore, the distribution of patients achieving an Eczema Area and Severity Index (EASI) 90 and those with an ADCT < 7 during the dupilumab treatment period appeared almost identical. Moreover, this study established significant correlations between the ADCT score and the following parameters: EASI, body surface area, Dermatology Life Quality Index, Pruritus Numeric Rating Scale, and Patient-Oriented Eczema Measure.

Conclusions: Our findings indicate that the ADCT can serve as a reliable tool for assessing long-term control of AD in real-world settings.

Purpose: Clinical remission (CR), an emerging treatment goal in asthma, was assessed by a post hoc analysis of a phase 3 study of mepolizumab in severe asthma with an eosinophilic phenotype (SA-EP).

Methods: Asthmatic patients aged ≥ 12 years, with a blood eosinophil count of ≥ 150 cells/µL at screening (or ≥ 300 cells/µL in the previous year), receiving fluticasone propionate ≥ 500 µg/day or equivalent plus ≥ 1 controller medication, and experiencing ≥ 2 exacerbations in the previous year were randomised to receive add-on mepolizumab or placebo every 4 weeks for 52 weeks. CR was assessed using both 3- and 4-component definitions (at 1 year, no maintenance oral corticosteroids, no clinically significant exacerbations, and asthma control questionnaire-5 [ACQ-5] score ≤ 1.5 for both, plus change from baseline in pre-bronchodilator forced expiratory volume in 1 second ≥ 0 mL for 4-component definition).

Results: At week 52, 41.6% (62/149) of mepolizumab-treated patients and 21.2% (32/151) of placebo-treated patients met the 4-component definition (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.59-4.41; P < 0.001), with a difference of 20.4% (95% CI, 9.1%-31.2%), and 54.4% (81/149) of mepolizumab-treated patients and 32.5% (49/151) of placebo-treated patients met the 3-component definition (OR, 2.48; 95% CI, 1.55-3.96; P < 0.001), with a difference of 21.9% (95% CI, 10.5%-32.7%). Baseline characteristics potentially associated with CR in the mepolizumab group were lower ACQ-5 score and lower St George's Respiratory Questionnaire scores.

Conclusions: A higher proportion of Chinese SA-EP patients treated with mepolizumab achieved CR compared to those receiving placebo. Certain baseline characteristics are potentially predictive of CR.

Trial registration: ClinicalTrials.gov Identifier: NCT03562195.

Purpose: Recent attention has been directed toward understanding how exposure to green areas in residential urban environments can impact asthma morbidity. Limited and inconsistent results have explored the link between exposure to greenness and asthma, highlighting the need for further research in this area. We analyzed airborne fungal microbiomes from urban forests and urban centers to better understand how airborne microorganisms affect asthma and allergic inflammatory responses.

Methods: Fungi were isolated from air samples collected from 25 urban forests and 4 urban centers in Seoul Metropolitan City, and the diversity of fungal microbiomes was analyzed. The number of asthma episodes in each district in Seoul Metropolitan City was examined using data from the National Health Insurance. Allergic inflammatory responses of fungi from the urban forests and urban centers were measured using human mast cells (HMC-1) and an experimental asthma animal model.

Results: Fungal microbiome diversity in urban forests was significantly higher than in urban centers. A significant inverse correlation was observed between the number of urban forests per each district and asthma episodes among residents. Allergic inflammation in the activated HMC-1 cells and lungs of the asthma animal model was significantly suppressed by the fungal strains isolated from the urban forest samples compared to those from the urban centers.

Conclusions: Fungal microbiome diversity, particularly from the urban forests, plays a role in reducing asthma morbidity and can modulate allergic inflammation. Residential proximity to urban forests was positively associated with current asthma, potentially indicating a role in reducing allergic inflammation through the diversity of the fungal microbial flora. These findings support the increasing public recognition of urban forest as an essential component of health-supportive environments.

Purpose: Severe asthma with fungal sensitization (SAFS) is associated with life-threatening exacerbation and severe airflow limitation. We aimed to investigate the prevalence of fungal sensitization in asthma and clinical characteristics of SAFS.

Methods: This study analyzed data from the Cohort for Reality and Evolution of Adult Asthma in Korea and the Korean Severe Asthma Registry cohorts. Study subjects were classified based on fungal sensitization and asthma severity. Clinical characteristics of patients with severe asthma were compared according to fungal sensitization status.

Results: The rate of skin test positivity to fungi was 14.1% and 7.1% in severe asthma (n = 270) and non-severe asthma (n = 2,605). Patients with SAFS were diagnosed with asthma earlier than those with severe asthma without fungal sensitization (SANFS) (P = 0.019), and had a lower body mass index compared to the SANFS group (P = 0.044). Factional exhaled nitric oxide levels and sputum eosinophilia/neutrophilia showed significant differences between the SAFS and SANFS groups (all P < 0.05). Patients with SAFS were more frequently treated with biologics (36.8% vs. 24.6%, P = 0.116) than those with SANFS. Multivariate analysis revealed that early diagnosed asthma was significantly associated with SAFS.

Conclusions: The prevalence of fungal sensitization in severe asthma is approximately twice as high as in non-severe asthma. Early diagnosed asthma may be a risk factor for SAFS, and patients with SAFS face a greater burden of additional treatment compared to those with SANFS. SAFS has a distinct airway inflammation profile that differentiates it from SANFS.