Journal of Asthma and Allergy最新文献

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.

Background: The prevalence of hypersensitivity reactions to different allergens varies according to the population studied and is subject to environmental and lifestyle factors. Early and delayed hypersensitivity are diagnosed with skin prick test and patch test.

Objective: This study aimed to identify the common environmental and chemical allergens sensitizing Yemeni allergic patients.

Subjects and methods: A retrospective study was conducted using registries of patients who attended Elaj Medical Center in Sana'a city, Yemen, from January 1^st to December 31^st 2023. The collected data included sex, age, and the clinical laboratory test results of the skin prick test and the patch test.

Results: The skin prick test was performed on sixty-five patients compared to twenty-two who were tested with a patch test. Most of the positive participants were male, aged between 18 and 40 years. The most frequent environmental allergens causing immediate hypersensitivity were Dermatophagoides farinae and Dermatophagoides pteronyssinus mites (64.6% and 69.2%, respectively), Aspergillus (47.7%), cat dander and dog dander (43.1% and 35.4%, respectively). Dermatophagoides farinae mites mostly sensitized females with an odds ratio of 3.43 (95% CI, 1.13-10.42, p=0.05). The most common chemical allergens that caused delayed hypersensitization were paraphenylenediamine (45.5%), potassium bichromate (45.5%), cobalt sulfate (36.4%), thiuram mix (27.3%), Vaseline (27.3%), and nickel sulfate (27.3%). Polysensitization was more frequent. The age of patients was directly proportional to the number of allergens responsible for immediate hypersensitivity (r-0.298, p=0.016).

Conclusion: Yemeni patients exhibited high sensitization to aeroallergens and chemical allergens. Females showed a higher propensity for polysensitization. The pattern of sensitization to environmental and chemical allergens in Yemen differs somewhat from neighboring Arab and Asian countries. Further multi-center studies are needed to support and establish a standard country-specific allergens panel for testing.

Purpose: Asthma is a heterogeneous disease with phenotypic variations potentially influenced by dietary factors. This cross-sectional study aimed to estimate the prevalence of current allergic asthma (AA), characterize its phenotypic variants, and examine dietary associations with asthma manifestations among young Chinese adults in Singapore.

Patients and methods: We assessed 10,544 young Chinese participants (mean age 22.3 ± 5.5 years; male: female = 0.74) using a standardized, investigator-administered questionnaire adapted from the International Study of Asthma and Allergies in Childhood. Current AA was defined as a history of doctor diagnosis with symptoms in the past 12 months and having allergic sensitization to common house dust mites. Dietary intake across 16 food groups was assessed using a semi-quantitative food frequency questionnaire. Multivariable logistic regression, adjusted for sociodemographic and lifestyle factors, examined dietary associations with AA outcomes.

Results: The prevalence of current AA was 5.24%. Among those with current AA, 67.0% (370/552) had mild, 21.7% (120/552) moderate, and 11.2% (62/552) severe asthma. Asthma was well-controlled in 60.7% (319/552), partly controlled in 39.3% (217/552), and poorly controlled in 2.9% (16/552). Common phenotypes included cough-variant (57.6%), wheezy variant (55.1%), and exercise-induced asthma (31.5%), with overlapping symptoms. Frequent intake (most or all days) of pulses (Adjusted odds ratio [AOR]: 0.65; 95% confidence intervals [CI]: 0.47-0.89; p < 0.001), probiotic drinks (AOR: 0.69; 95% CI: 0.50-0.94; p < 0.001), fruits (AOR: 0.47; 95% CI: 0.31-0.71; p = 0.001), and vegetables (AOR: 0.58; 95% CI: 0.35-0.99; p = 0.003) was associated with protective odds of current AA. Pulses were also associated with reduced odds of exacerbated and wheezy AA, while occasional (once or twice per week) intake of probiotic drinks was associated with reduced odds of cough-variant and wheezy AA.

Conclusion: While certain plant-based foods and probiotic drinks were associated with reduced odds of AA and its phenotypes, these findings should be interpreted with caution given the cross-sectional design. Longitudinal or interventional studies are needed to clarify causality and underlying mechanisms.

Background: Pediatric atopic dermatitis (AD), a common chronic relapsing inflammatory skin disorder, often co-occurs with iron deficiency. However, the causal relationship and mechanisms linking iron homeostasis to AD pathogenesis remain unclear. This study investigates etiopathogenetic role of iron deficiency in childhood AD by analyzing molecular pathways and clinical impacts on disease progression.

Methods: We have enrolled 298 pediatric AD patients based on the Hanifin and Rajka criteria to evaluate the relationship between peripheral iron and the severity of AD, as well as the levels of serum iron, ferritin, and transferrin in children with AD. The percentages of Th2 cells and IL-10-producing CD24⁺CD38⁺CD19⁺ regulatory B (Breg) cells were quantified by flow cytometry. RNA-sequencing and bioinformatic analysis were performed to explore the iron deficiency-sensitive genes in CD19⁺ B cells treated with Ciclopiroxolamine (CPX). The differentially expressed genes, including T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and IL10, were further confirmed by RT-qPCR. 5-mC level was determined to evaluate the effect of iron deficiency on DNA methylation. TIGIT was inhibited in CD19⁺ B cells using a blocking antibody to assess its regulatory role in Breg cells.

Results: Children with severe AD have lower levels of iron ions in peripheral blood compared with the mild patients (P<0.0001). Children with AD exhibited decreased serum levels of iron (P<0.01), ferritin (P< 0.01), and transferrin (P<0.05), along with an elevated percentage of Th2 cells (P<0.01) and reduced CD24⁺CD38⁺CD19⁺ Breg cells (P<0.01). CPX-mediated iron chelation suppressed IL-10-producing Breg cells (P<0.01) by inducing DNA methylation (P<0.05) and downregulating TIGIT (P<0.001), while promoting the expansion of IL-4-producing Th2 cells (P<0.05).

Conclusion: Iron deficiency contributes to Th2 cell expansion in pediatric AD via DNA methylation and TIGIT suppression in IL-10-producing Breg cells.

Background: Hereditary angioedema (HAE) is typically autosomal dominant, though recessive cases exist. It is characterized by recurrent episodes of swelling affecting the subcutaneous tissues, oropharyngeal mucosa, and gastrointestinal tract. This report describes a misdiagnosed case with a novel "SERPING1" variant.

Case presentation: A 22-year-old Chinese male presented with recurrent acute abdominal pain since March 2018, initially misdiagnosed as gastroenteritis or intestinal obstruction at multiple hospitals. During current hospitalization, detailed history revealed non-pitting eyelid edema in July 2019 that progressed to facial edema within 24 hours after a cold. Over the subsequent three years, he experienced recurrent subcutaneous edema involving face and extremities, typically resolving spontaneously within one week. Family history showed his father had similar self-limiting episodes of abdominal pain and edema between ages 20-30, with no recurrence after age 40. Physical examination demonstrated upper abdominal tenderness without rebound pain. Low C4 levels prompted C1INH testing and genetic analysis, confirming HAE due to C1INH deficiency type 1 (HAE-C1INH-Type1) with a novel SERPING1 variant. Since initiating lanadelumab (300mg biweekly) on April 26, 2023, the patient has completed 11 injections and remains in good condition.

Conclusion: HAE is a rare disease that is often misdiagnosed. Complement C4 remains a critical screening biomarker for patients with HAE. In addition, we reported a novel frameshift variant in the coding region of the SERPING1 gene, and the specificity of the position offers a unique point of interest in the discussion of the disease's causative locus.