Journal of Asthma and Allergy最新文献

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare multi-organ autoimmune disease characterized by eosinophilic infiltration of peripheral blood and tissues, and necrotizing granulomatous inflammation of small and medium-sized blood vessels. In the prodromal stage of EGPA, patients may present with features of refractory asthma, with the involvement of other organs occurring later when the diagnosis of EGPA is made. The difficulty of early diagnosis makes treatment difficult.

Methods: We retrospectively describe patients (N=13) who attended the asthma clinic at the First Affiliated Hospital of Guangzhou Medical University between 2008 and 2024. The disease course was categorized into three stages: asthma, lung-limited or lung-dominant EGPA (L-EGPA), and systemic EGPA (S-EGPA). Patients with severe eosinophilic asthma served as controls. We evaluated baseline demographic, as well as organ involvement, complication, laboratory findings, lung function, high-resolution computed tomography (HRCT), and treatment across different disease stages. A case-crossover design and Bayesian conditional logistic regression were employed to evaluate the impact of medication use on disease progression.

Results: We identified a group of EGPA patients who exhibited consistent disease progression to transit from asthma to L-EGPA, and eventually to S-EGPA. These stages exhibit distinct clinical and imaging features, with significantly elevated eosinophilic inflammatory markers in induced sputum or blood being a hallmark of L-EGPA. This distinction may aid in differentiating refractory asthma from L-EGPA.

Conclusion: In conclusion, the L-EGPA phase may represent a distinct stage in EGPA development that is often challenging to distinguish from refractory asthma. Characterizing this phase and identifying specific biomarkers could facilitate earlier diagnosis and treatment, potentially improving patient outcomes-a hypothesis that warrants further validation.

Purpose: To evaluate the Achieving Clinical Audits with Electronic Records (ACAER) program in supporting primary care providers in quality improvement initiatives across asthma and COPD.

Patients and methods: This observational cohort study included individuals aged ≥12 years with documented diagnosis of asthma or COPD, receiving asthma or COPD therapy, at high risk of exacerbation and hospitalization. Data were derived from the intervention, linked patient questionnaires completed as part of practice evaluation and quality improvement, and routine primary care electronic medical records (EMR) within the Optimum Patient Care Research Database Australia (OPCRDA). Changes in exacerbation rates and maintenance treatment were evaluated.

Results: 7512 asthma and 6526 COPD patients were evaluated with EMR collection. A subset of 1327 asthma patients and 629 COPD patients were classified as active and high-risk. Patient questionnaires and evaluation reports were sent out between 29 October 2019 and 21 September 2021, the intervention period. For those at risk during the entire study period (2018-2023; N=1276), 48.4% and 59.3% of patients in the high-risk asthma and COPD populations, respectively, had maintenance therapy change in the first year post-intervention. Exacerbation rates fell after the intervention period in the high-risk asthma (74.8 to 32.4 per 1000 per month) and COPD (122.9 to 91.2 per 1000 per month) populations. High-risk asthma patients had increasing rates of exacerbations in the 2 years prior to the intervention period (linear trend: 2.79 exacerbations per 1000 per month [1.34, 4.24]; p=0.001), which declined and remained stable after the intervention (p=0.87; up to 2023). Exacerbation rates for high-risk COPD patients were stable pre-intervention (p=0.29). Post-intervention rates initially declined and then showed a marginal non-statistically significant increase (p=0.28).

Conclusion: Our findings support the potential for the ACAER asthma and COPD program to drive treatment change and improve long-term outcomes in high-risk patients in primary care settings.

Background: Viral-induced wheezing, a common respiratory issue in children, is characterized by wheezing triggered by viral infections. This study aims to evaluate parental knowledge, perceptions, and practices regarding viral-induced wheezing in Jordan.

Methods: A cross-sectional survey was conducted with 510 parents, recruited from schools and online platforms.

Results: The study found that 32.1% of parents had good knowledge about viral-induced wheezing, and 73.5% were aware that it could resolve in children over time. Parents of children with asthma, allergic rhinitis, or atopy were more informed about viral-induced wheezing. Regression analysis showed a significant association between children's recurrent upper respiratory tract infections and parental knowledge. During wheezing episodes, the majority of parents (91.8%) administered medications, and 80.1% used herbal remedies.

Conclusion: Parents of children with frequent upper respiratory tract infections exhibited greater knowledge related to wheezing management. Enhancing parental education may contribute to improved symptom recognition and management. These findings underscore the need for targeted educational initiatives and future longitudinal studies to explore the long-term impact of parental knowledge on respiratory outcomes.

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.