Journal of Asthma and Allergy最新文献

Allergic rhinitis (AR) is a prevalent chronic inflammatory allergic disease, characterized by paroxysmal nasal congestion, itching, sneezing, and rhinorrhea, which affects mental health in severe cases. Western medical treatments primarily rely on glucocorticoids and antihistamines, which, while providing symptomatic relief, are associated with varying degrees of side effects and fail to ensure long-term efficacy. The pathogenesis of AR is intricately related to immune system dysregulation, and the treatment of AR has not yet been fully clarified. Natural products, having co-evolved with humans over millennia, boast structural diversity and rich biological activity, and they can precisely interact with intracellular targets such as enzymes, receptors, and ion channels, positioning them as a vital resource for therapeutic interventions. Notably, validated natural products often contain multiple active constituents, which confer broader therapeutic effects compared to single-component compounds. These constituents also exhibit lower acute toxicity than synthetic drugs, ensuring superior long-term. The synergistic interactions among their components endow them with dual potential for both prevention and treatment. Natural products modulate AR pathogenesis through various signaling pathways, addressing key etiological factors such as immune dysregulation, inflammatory responses, as well as oxidative stress. These developments will drive research and application of natural products in AR management, unlocking their untapped potential. This review systematically examines the mechanisms by which natural products regulate AR pathogenesis through signaling pathways, drawing on both animal studies and laboratory research, though clinical data are still relatively limited. By elucidating their specific mechanisms of action, this work not only provides novel insights for developing effective, long-term AR management drugs but also offers scientific guidance for experimental research and clinical application in AR therapeutics.

Purpose: The COVID-19 pandemic altered patterns of indoor allergen exposure. However, longitudinal dynamics of sensitization kinetics across allergens remain poorly characterized. This study delineated allergen-specific sensitization dynamics during 2019-2022, contrasting responses to dust mites and cat dander.

Patients and methods: The retrospective cohort study of 43,314 children (0-17 years) in Shenzhen, China, analyzed specific IgE (sIgE) reactivity. Adjusted odds ratios (aORs) were calculated using logistic regression (adjusted for age/sex; 2019 baseline) and E-values assessed unmeasured confounding.

Results: Dust mite sensitization increased significantly in 2020 (Dermatophagoides pteronyssinusfarinae aOR = 1.291.42, 95% CI: 1.16-1.441.29-1.57, both P <0.001), declined in 2021, and partially rebounded in 2022. Conversely, cat dander sensitization exhibited a delayed peak, rising significantly only by 2022 (aOR = 1.83, 95% CI: 1.30-2.65, P <0.001, E-value = 3.07). German cockroach sensitization decreased by 35% in 2022 (aOR = 0.65, 95% CI: 0.54-0.78, P <0.001, E-value = 2.26). Adolescents (6-17 years) showed heightened cat dander sensitization (2022: aOR = 2.05, P =0.001, E-value = 3.52), while males had steeper cockroach declines (2022: aOR = 0.61, P <0.001). Food sensitization remained stable except wheat (aOR = 0.80, P =0.005).

Conclusion: We identify distinct allergen-specific dynamics. Dust mites acted as early-response allergens linked to confinement intensity, while cat dander emerged as delayed-response allergens likely driven by cumulative behavioral and exposure changes. Targeted environmental interventions (eg, pest control) significantly reduced cockroach sensitization. These findings advocate for allergen-tailored, time-resolved prevention strategies during public health crises, with priority protection for adolescents.

Clinical trial registration: National Medical Research Registration Information System/MR-44-24-056093.

Purpose: The objective of this work was to describe the disease characteristics and evolution over time among severe asthma patients in Spain, with and without biologic treatment, based on the interim analysis of the BREATHE study.

Methods: The BREATHE study is a multicentre, observational, longitudinal cohort study conducted in Spain, involving patients aged ≥12 years with severe asthma, who were treated with high doses of ICS + LABA for at least 6 months prior to inclusion. This interim analysis was carried out with the information from the baseline and retrospective visits (at 6 and 12 months prior to index date) collected on June 29, 2023, including sociodemographic, clinical characteristics, lung function, symptoms, laboratory assessments, and treatment regimens.

Results: The interim analysis of the BREATHE study included 344 patients, with 325 meeting all criteria for analysis. The study found that 50.8% of patients had partially or poorly controlled asthma according to the ACT score, with a higher percentage of well-controlled asthma in patients undergoing biological therapy (52.5%) compared to those without (45.0%). Despite biological treatment, patients continued to experience exacerbations, and the most common treatments at the index date were ICS/LABA, biological therapy, and antileukotrienes.

Conclusion: The interim analysis of the BREATHE study reveals that severe asthma patients in Spain, predominantly female and around 50 years old, continue to experience exacerbations despite biological therapy, with nearly half having poorly controlled asthma. The study highlights the need to reassess treatment strategies for patients with high biomarker levels and frequent exacerbations.

Purpose: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent upper respiratory disease with eosinophilic infiltration. Epithelial-to-mesenchymal transition (EMT) has been considered an important pathological mechanism of CRSwNP. The Wnt signaling pathway is a well-established promoter of EMT, while Protein Phosphatase 2A (PP2A) exerts dual regulatory effects on Wnt pathway. However, the contribution of PP2A to CRSwNP has not been reported. This research aimed to explore the possible mechanisms by which PP2A modulates EMT in CRSwNP.

Patients and methods: About 56 patients with CRSwNP and 20 control subjects were enrolled in this study. We collected nasal polyps (NPs) and inferior turbinate tissues; the expression of PP2A, EMT markers, and Wnt signaling-related mediators in tissues were analyzed by Western blotting, immunohistochemistry, and quantitative RT-PCR. Primary cells isolated from NPs were cultured with PP2A inhibitor LB-100. The rhWNT3A-induced EMT cell model using BEAS-2B cell line was established in vitro and treated with either LB-100 or the PP2A agonist DT-061. Murine NP model was developed in vivo and treated with LB-100. The expression changes of EMT markers and Wnt signaling mediators were detected using Western blotting, immunofluorescence staining, and hematoxylin-eosin staining to estimate the effect of PP2A in the pathogenesis of CRSwNP.

Results: Compared to controls, NPs exhibited increased PP2A expression and activity, activation of Wnt signaling, and evidence of EMT. These changes were more pronounced in eosinophilic NPs. PP2A inhibition alleviated, whereas PP2A activation promoted, EMT in epithelial cells by regulating Wnt pathway. PP2A inhibition could also suppress the formation of NPs and alleviate eosinophilic inflammation in the murine NP models.

Conclusion: PP2A promotes EMT through the activation of Wnt/β-catenin signaling pathway, leading to epithelial barrier dysfunction in NPs. PP2A exerts a positive regulatory effect on the modulation of Wnt signaling in CRSwNP. Targeting PP2A might represent a viable therapeutic option for treating CRSwNP.

Purpose: This study explores the role of miR-206 and KLF4 in neutrophilic asthma, focusing on their interaction and the molecular mechanisms by which miR-206 regulates Th17 cell-mediated immune-inflammatory responses through KLF4.

Methods: RT-qPCR and flow cytometry assessed miR-206, KLF4 mRNA, and Th17 cell levels in asthma patients and healthy controls. CD4+ T cells were transfected to overexpress or inhibit miR-206, and KLF4, IL-17, and Th17 cell ratios were analyzed using RT-qPCR, ELISA, and flow cytometry. Correlation analysis evaluated relationships between miR-206, KLF4, and Th17 cells.

Results: Severe asthma patients showed reduced miR-206 and elevated KLF4 mRNA levels, with increased Th17 cells and IL-17. miR-206 downregulated KLF4, negatively correlating with KLF4, Th17 cells, and IL-17. KLF4 positively correlated with Th17 cells and IL-17. miR-206 suppressed Th17 differentiation and IL-17 production by modulating KLF4.

Conclusion: miR-206 is downregulated in acute asthma and targets KLF4, inhibiting Th17 cell differentiation and IL-17 production. These findings highlight miR-206 as a potential therapeutic target for asthma through its anti-inflammatory effects mediated by KLF4 and Th17 regulation.

Background: Although T cell immunoglobulin and mucin domain-4 (TIM-4) is involved in immune regulation, the function of TIM-4 in allergic responses is not understood. We investigated the effects of anti-TIM-4 monoclonal antibody (mAb) in a murine model of allergic airway inflammation.

Methods: Anti-mouse TIM-4 mAb was administered to various allergic airway inflammatory model mice. A soluble form of TIM-4 (sTIM-4) was detected by newly developed a sandwich Enzyme-Linked Immunosorbent Assay (ELISA) and immunoblotting using anti-mouse or human TIM-4 mAbs. Bone marrow-derived mast cells (BMMCs) were generated from C57BL/6 and CD300b-deficient mice to determine the contribution of sTIM-4 to mast cell activation. The concentrations of serum sTIM-4 in patients with asthma in 124 adult patients were quantified using ELISA.

Results: Accumulation of eosinophils and production of T helper type 2 (Th2) cytokines in the lung were significantly reduced in anti-TIM-4-treated mice. High amounts of sTIM-4 through proteolytic cleavage were detected in bronchoalveolar lavage fluid and sera from allergic airway inflammatory mice. sTIM-4 induced proinflammatory cytokine production in mast cells by interacting with CD300b. We also detected human sTIM-4 on TIM-4 transfected cells, which induced interleukin-6 (IL-6) production in a human mast cell line. Moreover, serum sTIM-4 levels were associated with asthma severity in patients with asthma.

Conclusion: TIM-4 contributes significantly to the effector phase of allergic airway inflammation. TIM-4 may serve as a therapeutic target and sTIM-4 may have the potential to be used as surrogate marker in asthma.

Purpose: Evidence on the link between parental smoking and allergic conjunctivitis (AC) is limited, particularly in Chinese children. This study aimed to examine the association between parental smoking and the risk of AC in children.

Patients and methods: The cross-sectional study was conducted in the ophthalmology department at Tianjin Children's Hospital from 2021 to 2022. We used logistic regression to explore the association between parental smoking and AC. The stability of the results was ensured using subgroup analysis and propensity score matching (PSM).

Results: A total of 4249 participants met the inclusion criteria and were analyzed. After adjusting for all covariates, parental smoking was significantly associated with AC. The adjusted odds ratio was 1.17 (1.03-1.34). Significant interactions were observed for mode of delivery and multiple pregnancies, in relation to the prediction of AC (P < 0.05). Further exploratory subgroup analyses in children with myopia, hyperopia, and astigmatism revealed no significant interactions (all P values for interaction were > 0.05). After adjusting for potential confounders using PSM, the results remained stable.

Conclusion: This cross-sectional study showed that influence of inappropriate parental smoking on the risk of incident AC. Parental smoking was associated with increased risk of AC in children. Reducing parental smoking may help lower this risk. These findings underscore the importance of public health interventions to reduce children's exposure to secondhand smoke.

Introduction: To assess the relationship between body mass index (BMI) and BMI z-scores with lung function parameters in children with asthma, aiming to provide scientific evidence for individualized treatment and management strategies.

Methods: We enrolled 328 children with asthma during acute exacerbation. The BMI and BMI z-scores were analyzed in relation to lung function parameters, including maximum vital capacity (VCmax), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak expiratory flow (PEF), maximal mid-expiratory flow rate (MMEF), and instantaneous flows at 25%, 50%, and 75% of maximal expiratory flow (MEF25, MEF50, MEF75). Both linear regression and piecewise regression models were used to identify linear associations and potential threshold effects.

Results: BMI showed significant positive linear correlations with VCmax, FVC, FEV1, MEF50, MEF75, and MMEF, while BMI z-scores demonstrated positive linear associations with VCmax, FVC, FEV1, MEF25, MEF50, and MMEF. After adjusting for age, sex, immunoglobulin E (IgE), eosinophil count (EOS), fractional exhaled nitric oxide (FeNO), and asthma severity, both BMI and BMI z-scores remained positively associated with VCmax, FVC, and FEV1. Piecewise regression analysis revealed significant threshold effects in the relationships between BMI z-scores and VCmax, FVC, FEV1, PEF, MEF25, MEF50, MEF75, and MMEF. Below a z-score of ~2.3-3.9, BMI z-score was positively associated with pulmonary function. Above this threshold, the association reversed; for instance, FEV1 decreased by 9.7% (β = -9.69, 95% CI: -18.93 to -0.46) and PEF decreased by 12.2% (β = -12.17, 95% CI: -21.12 to -3.22) for every unit increase in BMI z-score beyond 3.945.

Conclusion: A nonlinear relationship exists between BMI z-scores and lung function parameters in children with asthma. Weight-guided interventions may enhance lung function and asthma control.

Purpose: This study aims to explore the potential role of Nrf2 as a biomarker in asthma and its associations with hypoxia, oxidative stress, and ferroptosis-related indicators in a cross-sectional study.

Patients and methods: This study involved the collection of peripheral blood samples from participants to isolate serum and peripheral blood mononuclear cells (PBMCs). Enzyme-linked immunosorbent assay (ELISA) and other assay kits was performed to quantify the levels of Nrf2, HIF-1α, SOD, and MDA in PBMCs, alongside the activities of SOD and GSH-Px, and serum concentrations of IL-4 and IL-13. Quantitative Real-time PCR (qRT-PCR) was used to assess the expression levels of GPX4, NCOA4, SCL7A11, and HMGB1 in PBMCs. Clinical data were collected and analyzed statistically. Receiver operating characteristic (ROC) curve analysis was employed to assess the diagnostic performance of these indicators.

Results: Compared with the control group, asthma patients showed significantly lower levels of Nrf2 and SOD in PBMCs, as well as reduced expression of GPX4, SCL7A11, and NCOA4 (P < 0.05). In contrast, levels of HIF-1α and MDA, as well as the expression of HMGB1, were significantly elevated in the asthma group (P < 0.05). Correlation analysis indicated that Nrf2, HIF-1α, and MDA levels in PBMCs were associated with certain clinical indicators in asthma patients. ROC curve analysis further demonstrated that these indicators exhibited a certain diagnostic performance for asthma and severe asthma. Additionally, in asthma patients, Nrf2 expression in PBMCs was negatively correlated with HIF-1α levels and eosinophil counts, but positively correlated with SOD and GPX4 levels.

Conclusion: The interplay between hypoxia, oxidative stress, and ferroptosis may be involved in asthma pathogenesis. Based on the findings, Nrf2 may have potential as a biomarker for asthma. However, given the study's limitations, further research is needed to confirm these associations and fully understand the role of Nrf2 in asthma diagnosis and progression.

Purpose: Evaluating productivity loss and healthcare costs among working-aged individuals with asthma is critical for comprehending the economic burden and guiding healthcare policy decisions. An optimized care of asthma could result in substantial societal benefits by improving workforce participation and reducing healthcare resource use. Recent data on the impact of both asthma severity and exacerbation frequency on overall costs are scarce.

Patients and methods: In this retrospective study from Finland, 89,606 working aged patients with asthma were followed from national registers for four years from 2017 to 2020 with the objective to assess the impact of asthma severity and exacerbation frequency on the overall costs arising from direct healthcare resource utilization (visits and drug purchases) and productivity loss (long term sick leaves and disability pensions) with gamma regression models.

Results: Severe asthma, noted in 10% of patients, increased healthcare resource utilization and productivity loss costs by 30% and frequent exacerbations, noted in 13% of patients, by 25%, independently of each other and of age, sex and Charlson comorbidity index. The annual overall cost per patient was € 14,359 for severe asthma with frequent exacerbations, followed by €11,802 in those with non-severe asthma and frequent exacerbations. Most costs were related to productivity losses (60%) compared to direct healthcare costs (40%). The prevalence of asthma increased from 2.7% to 3.0% over the four-year period, an increase was also observed in the subgroup of those with severe asthma.

Conclusion: A substantial disease burden associated with frequent exacerbations in both patients with asthma and severe asthma leads to increased productivity loss and direct healthcare costs. The estimated the total annual cost of working-aged patients with asthma was €715 million in Finland, with 25% of additional costs associated with frequent exacerbations, indicating the potential savings that could be achievable through improved disease control.