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1.
Front Immunol ; 15: 1406794, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38953030

RESUMO

Introduction: Equine asthma (EA) is a common lower airway disease in horses, but whether its pathogenesis is allergic is ambiguous. Extrinsic stimuli like hay dust induce acute exacerbation of clinical signs and sustained local neutrophilic inflammation in susceptible horses. Aspergillus fumigatus is an EA stimulus, but it is unclear if it merely acts as an IgE-provoking allergen. We aimed to comprehensively analyze immunoglobulin (Ig) isotypes in EA, elucidating their binding to different A. fumigatus antigens, and their quantities systemically in serum and locally in bronchoalveolar lavage fluid (BALF). Methods: Serum and BALF from healthy horses (HE, n = 18) and horses with mild-moderate asthma (MEA, n = 20) or severe asthma (SEA, n = 24) were compared. Ig isotype (IgG1, IgG3/5, IgG4/7, IgG6, IgA, and IgE) binding to nine antigens (A. fumigatus lysate, and recombinant Asp f 1, Asp f 7, Asp f 8, dipeptidyl-peptidase 5, class II aldolase/adducin domain protein, glucoamylase, beta-hexosaminidase, and peptide hydrolase) was compared by enzyme-linked immunosorbent assays. Total Ig isotype contents were determined by bead-based assays. Results: MEA and SEA differed from HE but hardly from each other. Compared to HE, asthmatic horses showed increased anti-A. fumigatus binding of IgG (BALF and serum) and IgA (BALF). Serum and BALF IgE binding and total IgE contents were similar between HE and EA. Single antigens, as well as A. fumigatus lysate, yielded similar Ig binding patterns. Serum and BALF IgG1 binding to all antigens was increased in SEA and to several antigens in MEA. Serum IgG4/7 binding to two antigens was increased in SEA. BALF IgA binding to all antigens was increased in SEA and MEA. Total BALF IgG1 and IgG4/7 contents were increased in SEA, and serum IgG4/7 content was increased in MEA compared to HE. Yet, total isotype contents differentiated EA and HE less clearly than antigen-binding Ig. Discussion: A. fumigatus immunogenicity was confirmed without identification of single dominant antigens here. A. fumigatus provoked elevated BALF IgG1 and IgA binding, and these isotypes appear relevant for neutrophilic EA, which does not support allergy. BALF Ig isotype differentiation beyond IgE is crucial for a comprehensive analysis of immune responses to fungi in EA pathogenesis.


Assuntos
Antígenos de Fungos , Aspergillus fumigatus , Asma , Líquido da Lavagem Broncoalveolar , Doenças dos Cavalos , Imunoglobulina A , Imunoglobulina G , Animais , Cavalos/imunologia , Aspergillus fumigatus/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Asma/imunologia , Asma/microbiologia , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Imunoglobulina A/imunologia , Imunoglobulina A/sangue , Imunoglobulina A/metabolismo , Doenças dos Cavalos/imunologia , Doenças dos Cavalos/microbiologia , Antígenos de Fungos/imunologia , Masculino , Neutrófilos/imunologia , Neutrófilos/metabolismo , Feminino , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Anticorpos Antifúngicos/imunologia , Anticorpos Antifúngicos/sangue
2.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(6): 778-790, 2024 Jun 06.
Artigo em Chinês | MEDLINE | ID: mdl-38955724

RESUMO

Objective: To investigate the effects of subcutaneous immunotherapy (SCIT) on patients' immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers. Methods: A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results: After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT:Z=-2.298, P<0.05; DM-SCIT:Z=-3.411, P<0.001); total ACT score (SM-SCIT:Z=-2.054, P<0.05; DM-SCIT:Z=-2.014, P<0.05) and total medication scores (SM-SCIT:Z=-3.799, P<0.000 1; DM-SCIT:Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group (t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group (P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated (Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions(Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions (Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment (Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment (Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 (r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 (r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion: Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.


Assuntos
Asma , Dessensibilização Imunológica , Ácidos Graxos Insaturados , Humanos , Animais , Dessensibilização Imunológica/métodos , Asma/terapia , Pyroglyphidae/imunologia , Estudos Longitudinais , Antígenos de Dermatophagoides/imunologia , Alérgenos/imunologia , Criança , Injeções Subcutâneas , Imunoglobulina E/imunologia
3.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(6): 768-777, 2024 Jun 06.
Artigo em Chinês | MEDLINE | ID: mdl-38955723

RESUMO

Objective: To explore the optimal regimen of standardized mite allergen immunotherapy for airway allergic diseases in children, and to observe the clinical efficacy, safety and compliance. Method: Use a retrospective real-world study, clinical data from 156 children aged 5-16 years who received subcutaneous immunotherapy (SCIT) with double mite allergen preparation in the pediatrics department of the Third Affiliated Hospital of Sun Yat sen University from June 2019 to September 2020 were selected for allergic rhinitis (AR) and/or allergic asthma (bronchial asthma, BA), including gender, age, total VAS(visual analogue scale) score and CSMS(combined symptom and medication scores) score at different time points (before treatment, 4-6 months, 1 year, and 2 years after initiation of desensitization), peripheral blood eosinophil counts (EOS), serum total IgE (tIgE), specific IgE (tIgE), and serum IgE (tIgE), specific IgE (sIgE), tIgG4, and incidence of local and systemic adverse reactions. All patients had a consistent regimen during the initial treatment phase (dose-escalation phase), which was performed as directed. Among them, 81 cases (observation group) continued to continue subcutaneous injection of 1 ml of vial No. 3 every 4-6 weeks during the dose maintenance phase, while 75 cases (control group) followed the old traditional regimen during the maintenance phase (i.e., change to a new vial to halve the amount of vial No. 3 by 0.5 ml, and then 0.75 ml after 1-2 weeks, and 1 ml in a further interval of 1-2 weeks). The clinical efficacy, safety and adherence to the treatment were compared between the two groups. Results: A total of 81 cases of 156 children were included in the observation group, of which 58 children with AR, 15 children with BA, and 8 children with AR combined with BA; 75 cases were included in the conventional control group, of which 52 children with AR, 16 children with BA, and 7 children with AR combined with BA. In terms of safety, the difference in the incidence of local and systemic adverse reactions between the two groups was not statistically significant (χ2=1.541 for local adverse reactions in the control group, χ2=0.718 for the observation group; χ2=0.483 for systemic adverse reactions in the control group, χ2=0.179 for the observation group, P value >0.05 for all of these), and there were no grade Ⅱ or higher systemic adverse reactions in any of them. In the control group, there were 15 cases of dropout at 2 years of follow-up, with a dropout rate of 20.0%; in the observation group, there were 7 cases of dropout at 2 years of follow-up, with a dropout rate of 8.6%, and there was a statistically significant difference in the dropout rates of the patients in the two groups (χ2=4.147, P<0.05). Comparison of serological indexes and efficacy (compared with baseline at 3 different time points after treatment, i.e., 4-6 months, 1 year and 2 years after treatment), CSMS scores of the observation group and the conventional control group at 4-6 months, 1 year and 2 years after treatment were significantly decreased compared with the baseline status (t-values of the conventional group were 13.783, 20.086 and 20.384, respectively, all P-values <0.001, and t-values of the observation group were 15.480, 27.087, 28.938, all P-values <0.001), and VAS scores also decreased significantly from baseline status in both groups at 4-6 months, 1 year, and 2 years of treatment (t-values of 14.008, 17.963, and 27.512 in the conventional control group, respectively, with all P-values <0.001, and t-values of 9.436, 13.184, and 22.377 in the observation group, respectively; all P-values <0.001). Intergroup comparisons showed no statistically significant differences in CSMS at baseline status, 4-6 months, 1 year and 2 years (t-values 0.621, 0.473, 1.825, and 0.342, respectively, and P-values 0.536, 0.637, 0.070, and 0.733, respectively), and VAS was no statistically significant difference in comparison between groups at different time points (t-values of 1.663, 0.095, 0.305, 0.951, P-values of 0.099, 0.925, 0.761, 0.343, respectively); suggesting that the treatment regimens of the observation group and the conventional control group were clinically effective, and that the two regimens were comparable in terms of efficacy. The peripheral blood eosinophil counts of the observation group and the conventional control group decreased significantly from the baseline status at 4-6 months, 1 year and 2 years of treatment (t-values of the conventional group were 3.453, 5.469, 6.273, P-values <0.05, and the t-values of the observation group were 2.900, 4.575, 5.988, P-values <0.05, respectively). 4-6 months, 1 year and 2 years compared with the baseline status tIgE showed a trend of increasing and then decreasing (t-value in the conventional group was -5.328, -4.254, -0.690, P-value was 0.000, 0.000, 0.492, respectively, and t-value in the observation group was -6.087, -5.087, -0.324, P-value was 0.000, 0.000, 0.745, respectively). However, the results of intergroup comparisons showed no statistically significant differences in serological indices and efficacy between the two groups in terms of peripheral blood eosinophil counts at baseline status, 4-6 months, 1 year and 2 years (t-values of 0.723, 1.553, 0.766, and 0.234, respectively; P-values of 0.471, 0.122, 0.445, and 0.815, respectively), tIgE (t-values of 0.170, -0.166, -0.449, 0.839, P-values 0.865, 0.868, 0.654, 0.403, respectively), tIgG4 (t-values 1.507, 1.467, -0.337, 0.804, P-values 0.134, 0.145, 0.737, 0.422, respectively). Conclusion: Both immunotherapy regimens for airway allergic diseases with double mite allergen subcutaneous immunotherapy have significant clinical efficacy, low incidence of adverse reactions, and the observation group has better patient compliance than the control group.


Assuntos
Dessensibilização Imunológica , Humanos , Criança , Dessensibilização Imunológica/métodos , Estudos Retrospectivos , Pré-Escolar , Adolescente , Animais , Imunoglobulina E , Asma/terapia , Alérgenos/imunologia , Masculino , Rinite Alérgica/terapia , Rinite Alérgica/imunologia , Feminino , Ácaros/imunologia , Resultado do Tratamento
4.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(6): 815-822, 2024 Jun 06.
Artigo em Chinês | MEDLINE | ID: mdl-38955728

RESUMO

Objective: To analyze the clinical features and risk factors of chest tightness variant asthma (CTVA) in children, so as to provide basis for the prevention and management of the disease. Methods: A cross-sectional study was conducted to analyze 178 children aged 6-17 years old who were admitted to the Department of Allergy, Capital Institute of Pediatrics Affiliated Children's Hospital from January 2021 to January 2023 due to chest tightness. The age was 8.83(7.50, 11.58) years old, with 89 males (50%) and 89 females (50%). According to the diagnosis of CTVA, 130 cases were divided into CTVA group and 48 non-CTVA cases were divided into control group. Demographic data, personal history, family history, clinical features, auxiliary examination results and other data were collected. The clinical characteristics, allergens, FeNO level and pulmonary function parameters of the two groups were analyzed. Logistic regression analysis was used to explore the risk factors of the disease. Results: The proportion of school-age children (6-11 years old) in CTVA group was higher than that of adolescent children (≥12 years old) [(113/130,86.9%) vs (26/48,54.2%),Z=21.985,P<0.01]. The proportion of CTVA combined with eczema [(74/130,56.9%) vs (19/48,39.6%), χ2=4.225,P<0.05] and rhinitis symptoms [(98/130,75.4%) vs (27/48,56.2%), χ2=6.138,P<0.05] was higher. The positive rates of mold sensitization [(52/130,40.0%) vs (11/48,22.9%), χ2=4.474,P<0.05] and multiple sensitization [(71/130,54.6%) vs (18/48,37.5%), χ2=4.108,P<0.05] in inhaled allergens were significantly higher than those of control group. The proportion of elevated FeNO (>20 ppb) in CTVA children was 20.8% (27/130), which was significantly higher than that in control group 4.2%(2/48)(χ2=7.086,P<0.01). There were no statistical differences in spirometry parameters FEV1 and FVC between CTVA group and control group (P both>0.05). FEV1/FVC, PEF, FEF25, FEF50, FEF75 and MMEF were significantly lower than those in control group (P all<0.05). Logistic regression analysis showed that rhinitis symptoms (OR=2.351, 95%CI 1.105-5.002, P=0.026), multiple sensitizations (OR=2.184, 95%CI 1.046-4.557, P=0.038), tIgE>60 kU/L(OR=3.080, 95%CI 1.239-7.654, P=0.015), FeNO>20 ppb (OR=6.734, 95%CI 1.473-30.796, P=0.014) and small airway dysfunction (OR=3.164, 95%CI 1.089-9.194, P=0.034) were risk factors for chest tightness variant asthma. FeNO combined with FEF50 has the largest area under the curve (Z=2.744, P<0.01) in diagnosing CTVA. Conclusion: CTVA is more common in school-age children than in adolescent children. Rhinitis symptoms, multiple sensitization, tIgE>60 kU/L, FeNO>20 ppb and small airway dysfunction are risk factors for chest tightness variant asthma. FeNO combined with small airway indexes can improve the diagnostic value of CTVA.


Assuntos
Asma , Humanos , Criança , Masculino , Feminino , Fatores de Risco , Asma/epidemiologia , Estudos Transversais , Adolescente , Alérgenos , Testes de Função Respiratória , Modelos Logísticos
5.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(6): 869-874, 2024 Jun 06.
Artigo em Chinês | MEDLINE | ID: mdl-38955735

RESUMO

Objective: To explore the incidence and influencing factors of wheezing among children and adolescents aged 3-18 years in 11 cities in China from 2022 to 2023. Methods: From October 2022 to August 2023, 11 cities including Xishuangbanna in Yunnan Province, Suqian in Jiangsu Province, Chifeng and Hohhot in Inner Mongolia, Tangshan in Hebei Province, Changzhi in Shanxi Province, Yinchuan in Ningxia Province, Lanzhou and Dingxi in Gansu Province, Linyi in Shandong Province, and Tonghua in Jilin Province were selected as research sites to recruit kindergarten children and primary and secondary school adolescents in local urban areas. A total of 21 959 children and adolescents were included in this study. Demographic information, wheezing data (whether wheezing has occurred in the past and whether wheezing attacks have occurred in the past one year), personal history, family history and other information were collected through questionnaires. The multivariate logistic regression model was used to analyze the influencing factors of wheezing attacks in the past one year. Results: The mean age of 21 959 children and adolescents was (12.09±3.65) years old, and 52.3% (11 480) were boys. The incidence of wheezing history was 3.7% (816 cases), and the incidence of wheezing attacks in the past year was 2.5% (556 cases). The multivariate logistic regression model analysis results showed that compared with older age, girls, full-term natural delivery, no allergic rhinitis, no family history of allergic diseases, no passive smoking, partial diet, natural conception and childbirth, the children aged 3-18 years with young age, male, partial diet, passive smoking, family history of allergic diseases, allergic rhinitis, cesarean section, premature birth, and assisted reproduction had a higher risk of wheezing [OR (95%CI): 0.86(0.84-0.88), 1.27(1.07-1.51), 2.31(1.95-2.75), 2.09(1.76-2.47), 3.5(2.80-4.37), 4.05(3.39-4.83), 1.20(1.02-1.43), 2.26(1.66-3.09), and 1.67(1.01-2.78)]. Conclusion: From 2022 to 2023, the incidence of wheezing among children aged 3-18 years in China is not significantly higher than before, and childhood wheezing may be related to factors such as children's age, gender, dietary habits, family and personal history of allergic diseases, passive smoking, and perinatal period.


Assuntos
Sons Respiratórios , Humanos , China/epidemiologia , Adolescente , Criança , Masculino , Feminino , Pré-Escolar , Asma/epidemiologia , Fatores de Risco , Incidência , Inquéritos e Questionários , Modelos Logísticos
6.
Artigo em Chinês | MEDLINE | ID: mdl-38965849

RESUMO

Objective: To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis. Methods: The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software. Results: Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP. Conclusion: The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.


Assuntos
Pólipos Nasais , Fenótipo , Sinusite , Humanos , Pólipos Nasais/complicações , Masculino , Feminino , Sinusite/complicações , Pessoa de Meia-Idade , Adulto , Doença Crônica , Adolescente , Idoso , Análise por Conglomerados , Adulto Jovem , Criança , Idoso de 80 Anos ou mais , Eosinófilos , Rinite/complicações , Imunoglobulina E/sangue , Asma/complicações , Neutrófilos/metabolismo , Rinossinusite
7.
Pediatr Allergy Immunol ; 35(7): e14187, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38967090

RESUMO

BACKGROUND: The immunological mechanisms behind the clinical association between asthma and obesity in adolescence are not fully understood. This study aimed to find new plasma protein biomarkers associated specifically with coincident asthma and obesity in adolescents. METHODS: This was a cross-sectional study in children and adolescents 10-19 years old (N = 390). Relative plasma concentrations of 113 protein biomarkers related to inflammation and immune response were determined by proximity extension assay (Target 96; Olink, Uppsala, Sweden). Differences in protein concentrations between healthy controls (n = 84), subjects with asthma (n = 138), subjects with obesity (n = 107), and subjects with both asthma and obesity (AO; n = 58) were analyzed by ANCOVA, adjusting for age and sex, and in a separate model adjusting also for the sum of specific IgE antibody concentrations to a mix of food allergens (fx5) and aeroallergens (Phadiatop). Proteins elevated in the AO group but not in the obesity or asthma groups were considered specifically elevated in asthma and obesity. RESULTS: Five proteins were elevated specifically in the AO group compared to controls (here sorted from largest to smallest effect of asthma and obesity combined): CCL8, IL-33, IL-17C, FGF-23, and CLEC7A. The effects of adjusting also for specific IgE were small but IL-33, IL-17C, and FGF-23 were no longer statistically significant. CONCLUSION: We identified several new potential plasma biomarkers specifically elevated in coincident asthma and obesity in adolescents. Four of the proteins, CCL8, IL-33, IL-17C, and CLEC7A, have previously been associated with viral mucosal host defense and Th17 cell differentiation.


Assuntos
Asma , Biomarcadores , Proteínas Sanguíneas , Diferenciação Celular , Células Th17 , Humanos , Asma/imunologia , Asma/sangue , Asma/diagnóstico , Adolescente , Feminino , Masculino , Células Th17/imunologia , Criança , Estudos Transversais , Biomarcadores/sangue , Adulto Jovem , Obesidade/imunologia , Obesidade/sangue , Imunoglobulina E/sangue
11.
Artigo em Chinês | MEDLINE | ID: mdl-38973033

RESUMO

Objective:Neosensitizations may be occur during the allergen specific immunotherapy(AIT) due to the differences between allergen vaccine's content and a patient's molecular sensitization profile. This study investigates whether AIT with HDM extract changes the sensitization profile, whether de novo sensitization occurs, and the clinical importance of the neosensitization. Methods:Fifty-three patients with HDM allergic rhinitis ,with/without asthma, patients were received one year HDM subcutaneous AIT . Fourteen patients were recruited as control group and received only necessary medications. Serum samples were collected at baseline, 6thmoths and 12thof AIT, respectively. Serum samples were tested specific IgE against Der p, Der p 1/2/3 and Der f, Der f 1/2/3, as well as IgG4 against Der p, Der p 1/2 and Der f, Der f 1/2. VAS were collected at the time-points as well. Results:In AIT group, Der p, Der p 1/3, and Der f 1/3 specific IgE levels were significantly higher after one-year treatment, especially for Der p 3. There were 69.2%(18/26) patients whose Der p 3 specific IgE below 0.35 kU/L at baseline but became positive(>0.35 kU/L) after treatment, that is, neosensitization occurred. All tested allergen specific IgG4 level significantly increased after one year AIT treatment and the VAS declined dramatically. However, for patients with neosensitization and without neosensitization, there were no significantly changes concerning to IgG4 level and VAS. Conclusion:Patients undergoing AIT might have a risk of neosensitization to the allergen components in the vaccines. However, the clinical importance of the neosensitization remains unclear and warrants further studies.


Assuntos
Alérgenos , Antígenos de Dermatophagoides , Dessensibilização Imunológica , Imunoglobulina E , Pyroglyphidae , Humanos , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Dessensibilização Imunológica/métodos , Animais , Pyroglyphidae/imunologia , Alérgenos/imunologia , Antígenos de Dermatophagoides/imunologia , Masculino , Feminino , Adulto , Rinite Alérgica/imunologia , Rinite Alérgica/terapia , Asma/imunologia , Asma/terapia , Cisteína Endopeptidases/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia
12.
Allergol Immunopathol (Madr) ; 52(4): 68-72, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38970267

RESUMO

INTRODUCTION AND OBJECTIVES: Both asthma prevalence and the percentage of cesarean sections have increased in parallel in recent years. Research studies suggest an increased risk of developing atopic diseases and asthma after cesarean section birth compared to vaginal delivery. The main objective of this study is to analyze the risk of asthma admission after cesarean section birth compared to vaginal delivery in the pediatric population. POPULATION AND METHODS: Retrospective observational analytical case-control study from 1993 to 2020. The cases include all admitted patients to our health area hospital, for patients aged 7 to 16 diagnosed with asthma. For each case, a control without a diagnosis of asthma is selected with the same age, and that has also caused an episode of admission. RESULTS: A total of 290 admission episodes with a diagnosis of asthma were obtained, caused by 155 patients. Out of these, 145 cases with documented delivery types were selected. For cases, 155 controls were selected. The historical proportion of cesarean sections in the asthmatic group is 18.6%, compared to 14.2% in the non-asthmatic group. There is a statistically non-significant difference of 4.4% more cesarean sections in the asthmatic group compared to the control group. DISCUSSION: We have not demonstrated a statistically significant association between being born by cesarean section and an increased risk of asthma admission. Based on this finding, we cannot conclude that there is an association between being born by cesarean section and a higher risk of suffering from asthma, unlike what has been postulated in other research studies.


Assuntos
Asma , Cesárea , Humanos , Cesárea/estatística & dados numéricos , Cesárea/efeitos adversos , Asma/epidemiologia , Feminino , Estudos Retrospectivos , Criança , Estudos de Casos e Controles , Adolescente , Gravidez , Masculino , Fatores de Risco , Prevalência , Risco
13.
Allergol Immunopathol (Madr) ; 52(4): 91-96, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38970271

RESUMO

Asthma is a widely prevalent chronic disease that brings great suffering to patients and may result in death if it turns severe. Jolkinolide B (JB) is one diterpenoid component separated from the dried roots of Euphorbia fischeriana Steud (Euphorbiaceae), and has anti--inflammatory, antioxidative, and antitumor properties. However, the detailed regulatory role and associated regulatory mechanism in the progression of asthma remain elusive. In this work, it was demonstrated that the extensive infiltration of bronchial inflammatory cells and the thickening of airway wall were observed in ovalbumin (OVA)-induced mice, but these impacts were reversed by JB (10 mg/kg) treatment, indicating that JB relieved the provocative symptoms in OVA-induced asthma mice. In addition, JB can control OVA-triggered lung function and pulmonary resistance. Moreover, JB attenuated OVA-evoked inflammation by lowering the levels of interleukin (IL)-4, IL-5, and IL-13. Besides, the activated nuclear factor kappa B (NF-κB) and transforming growth factor-beta-mothers against decapentaplegic homolog 3 (TGFß/smad3) pathways in OVA-induced mice are rescued by JB treatment. In conclusion, it was disclosed that JB reduced allergic airway inflammation and airway remodeling in asthmatic mice by modulating the NF-κB and TGFß/smad3 pathways. This work could offer new opinions on JB for lessening progression of asthma.


Assuntos
Remodelação das Vias Aéreas , Asma , Modelos Animais de Doenças , Diterpenos , Camundongos Endogâmicos BALB C , NF-kappa B , Ovalbumina , Animais , Asma/tratamento farmacológico , Asma/imunologia , Remodelação das Vias Aéreas/efeitos dos fármacos , Camundongos , Diterpenos/farmacologia , Diterpenos/administração & dosagem , Diterpenos/uso terapêutico , Ovalbumina/imunologia , NF-kappa B/metabolismo , Feminino , Fator de Crescimento Transformador beta/metabolismo , Citocinas/metabolismo , Proteína Smad3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Humanos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antiasmáticos/farmacologia , Antiasmáticos/uso terapêutico , Euphorbia/química
14.
Cell Mol Life Sci ; 81(1): 287, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970705

RESUMO

Lung type 2 pneumocytes (T2Ps) and alveolar macrophages (AMs) play crucial roles in the synthesis, recycling and catabolism of surfactant material, a lipid/protein fluid essential for respiratory function. The liver X receptors (LXR), LXRα and LXRß, are transcription factors important for lipid metabolism and inflammation. While LXR activation exerts anti-inflammatory actions in lung injury caused by lipopolysaccharide (LPS) and other inflammatory stimuli, the full extent of the endogenous LXR transcriptional activity in pulmonary homeostasis is incompletely understood. Here, using mice lacking LXRα and LXRß as experimental models, we describe how the loss of LXRs causes pulmonary lipidosis, pulmonary congestion, fibrosis and chronic inflammation due to defective de novo synthesis and recycling of surfactant material by T2Ps and defective phagocytosis and degradation of excess surfactant by AMs. LXR-deficient T2Ps display aberrant lamellar bodies and decreased expression of genes encoding for surfactant proteins and enzymes involved in cholesterol, fatty acids, and phospholipid metabolism. Moreover, LXR-deficient lungs accumulate foamy AMs with aberrant expression of cholesterol and phospholipid metabolism genes. Using a house dust mite aeroallergen-induced mouse model of asthma, we show that LXR-deficient mice exhibit a more pronounced airway reactivity to a methacholine challenge and greater pulmonary infiltration, indicating an altered physiology of LXR-deficient lungs. Moreover, pretreatment with LXR agonists ameliorated the airway reactivity in WT mice sensitized to house dust mite extracts, confirming that LXR plays an important role in lung physiology and suggesting that agonist pharmacology could be used to treat inflammatory lung diseases.


Assuntos
Homeostase , Receptores X do Fígado , Macrófagos Alveolares , Pneumonia , Surfactantes Pulmonares , Transdução de Sinais , Animais , Receptores X do Fígado/metabolismo , Receptores X do Fígado/genética , Surfactantes Pulmonares/metabolismo , Camundongos , Pneumonia/metabolismo , Pneumonia/patologia , Macrófagos Alveolares/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pulmão/metabolismo , Pulmão/patologia , Células Epiteliais Alveolares/metabolismo , Asma/metabolismo , Asma/patologia , Asma/genética , Colesterol/metabolismo , Metabolismo dos Lipídeos , Fagocitose
17.
BMC Infect Dis ; 24(1): 667, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38961350

RESUMO

BACKGROUND: The available evidence presented inconsistencies and inconclusive findings regarding the associations between co-existing asthma and mortality among COVID-19 patients. The objective of the current study is to investigate the relationship between asthma and severe outcomes after SARS-CoV-2 Omicron infection in an infection-naïve population. METHODS: A retrospective cohort study using propensity score matching was conducted. The COVID-19 patients requiring hospitalisation in Hong Kong from January 1, 2022, to November 13, 2022, an Omicron-predominated period, were identified. Severe clinical outcomes were defined as ICU admission and inpatient death after the first positive PCR results as well as a composite outcome of both. RESULTS: Of the 74,396 hospitalised COVID-19 patients admitted, 1,290 asthma patients and 18,641 non-asthma patients were included in the matched cohort. The rates of death and the composite outcome were 15·3% and 17·2%, respectively, among the non-asthma patients,12·2% and 13·6%, respectively, among the asthma patients, with adjusted hazard ratios equal to 0·775 (95% CI: 0·660-0·909) and 0·770 (95% CI: 0·662-0·895), respectively. The negative association was more apparent in the elderly and female groups. Asthma remained a factor that lowered the risk of disease severity even though the patients were not fully vaccinated with at least two doses. CONCLUSIONS: We used real-world data to demonstrate that asthma was not a risk factor for COVID-19 severity of the infections of Omicron variant, even though the patients were not fully vaccinated.


Assuntos
Asma , COVID-19 , Hospitalização , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , COVID-19/epidemiologia , COVID-19/mortalidade , COVID-19/complicações , Feminino , Masculino , Estudos Retrospectivos , Asma/epidemiologia , Asma/complicações , Pessoa de Meia-Idade , Hong Kong/epidemiologia , Idoso , Adulto , Hospitalização/estatística & dados numéricos , Pontuação de Propensão , Fatores de Risco
18.
J Transl Med ; 22(1): 615, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961500

RESUMO

OBJECTIVE: To explore the correlation between asthma risk and genetic variants affecting the expression or function of lipid-lowering drug targets. METHODS: We conducted Mendelian randomization (MR) analyses using variants in several genes associated with lipid-lowering medication targets: HMGCR (statin target), PCSK9 (alirocumab target), NPC1L1 (ezetimibe target), APOB (mipomersen target), ANGPTL3 (evinacumab target), PPARA (fenofibrate target), and APOC3 (volanesorsen target), as well as LDLR and LPL. Our objective was to investigate the relationship between lipid-lowering drugs and asthma through MR. Finally, we assessed the efficacy and stability of the MR analysis using the MR Egger and inverse variance weighted (IVW) methods. RESULTS: The elevated triglyceride (TG) levels associated with the APOC3, and LPL targets were found to increase asthma risk. Conversely, higher LDL-C levels driven by LDLR were found to decrease asthma risk. Additionally, LDL-C levels (driven by APOB, NPC1L1 and HMGCR targets) and TG levels (driven by the LPL target) were associated with improved lung function (FEV1/FVC). LDL-C levels driven by PCSK9 were associated with decreased lung function (FEV1/FVC). CONCLUSION: In conclusion, our findings suggest a likely causal relationship between asthma and lipid-lowering drugs. Moreover, there is compelling evidence indicating that lipid-lowering therapies could play a crucial role in the future management of asthma.


Assuntos
Asma , Hipolipemiantes , Análise da Randomização Mendeliana , Humanos , Asma/genética , Asma/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Hipolipemiantes/farmacologia , Pró-Proteína Convertase 9/genética , Estudos de Associação Genética , Pulmão/efeitos dos fármacos , Pulmão/patologia , Lipase Lipoproteica/genética , Triglicerídeos/sangue , Receptores de LDL/genética , Hidroximetilglutaril-CoA Redutases/genética , Proteína 3 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina/genética , Apolipoproteína C-III/genética , Apolipoproteínas B/genética , Testes de Função Respiratória , LDL-Colesterol/sangue , Proteínas de Membrana Transportadoras , PPAR alfa
19.
FASEB J ; 38(13): e23756, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38949649

RESUMO

Asthma is a chronic pulmonary disease with the worldwide prevalence. The structural alterations of airway walls, termed as "airway remodeling", are documented as the core contributor to the airway dysfunction during chronic asthma. Forkhead box transcription factor FOXK2 is a critical regulator of glycolysis, a metabolic reprogramming pathway linked to pulmonary fibrosis. However, the role of FOXK2 in asthma waits further explored. In this study, the chronic asthmatic mice were induced via ovalbumin (OVA) sensitization and repetitive OVA challenge. FOXK2 was upregulated in the lungs of OVA mice and downregulated after adenovirus-mediated FOXK2 silencing. The lung inflammation, peribronchial collagen deposition, and glycolysis in OVA mice were obviously attenuated after FOXK2 knockdown. Besides, the expressions of FOXK2 and SIRT2 in human bronchial epithelial cells (BEAS-2B) were increasingly upregulated upon TGF-ß1 stimulation and downregulated after FOXK2 knockdown. Moreover, the functional loss of FOXK2 remarkably suppressed TGF-ß1-induced epithelial-mesenchymal transition (EMT) and glycolysis in BEAS-2B cells, as manifested by the altered expressions of EMT markers and glycolysis enzymes. The glycolysis inhibitor 2-deoxy-d-glucose (2-DG) inhibited the EMT in TGF-ß1-induced cells, making glycolysis a driver of EMT. The binding of FOXK2 to SIRT2 was validated, and SIRT2 overexpression blocked the FOXK2 knockdown-mediated inhibition of EMT and glycolysis in TGF-ß1-treated cells, which suggests that FOXK2 regulates EMT and glycolysis in TGF-ß1-treated cells in a SIRT2-dependnet manner. Collectively, this study highlights the protective effect of FOXK2 knockdown on airway remodeling during chronic asthma.


Assuntos
Remodelação das Vias Aéreas , Asma , Fatores de Transcrição Forkhead , Glicólise , Sirtuína 2 , Asma/metabolismo , Asma/patologia , Animais , Sirtuína 2/metabolismo , Sirtuína 2/genética , Camundongos , Remodelação das Vias Aéreas/fisiologia , Humanos , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Transição Epitelial-Mesenquimal , Camundongos Endogâmicos BALB C , Feminino , Fator de Crescimento Transformador beta1/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Linhagem Celular
20.
NPJ Prim Care Respir Med ; 34(1): 18, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951547

RESUMO

Every year, there are ~100,000 hospital admissions for asthma in the UK, many of which are potentially preventable. Evidence suggests that carefully conceptualised and implemented audit and feedback (A&F) cycles have the potential to improve clinical outcomes for those with chronic conditions. We wanted to investigate the technical feasibility of developing a near-real time asthma dashboard to support A&F interventions for asthma management in primary care. We extracted cross-sectional data on asthma from 756 participating GP practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) database in England comprising 7.6 million registered people. Summary indicators for a GP practice were compared to all participating RCGP RSC practices using practice-level data, for the week 6-12th-Mar-2023. A weekly, automated asthma dashboard with features that can support electronic-A&F cycles that compared key asthma indicators for a GP practice to RCGP RSC could be created ( https://tinyurl.com/3ydtrt85 ): 12-weeks-incidence 0.4% vs 0.4%, annual prevalence 6.1% vs 6.7%, inhaled relievers to preventer 1.2 vs 1.1, self-management plan given 83.4% vs 60.8%, annual reviews 36.8% vs 57.3%, prednisolone prescriptions 2.0% vs 3.2%, influenza vaccination 56.6% vs 55.5%, pneumococcal vaccination ever (aged ≥65 years) 90.2% vs 84.1% and current smokers 14.9% vs 14.8%. Across the RCGP RSC, the rate of hospitalisations was 0.024%; comparative data had to be suppressed for the study practice because of small numbers. We have successfully created an automated near real-time asthma dashboard that can be used to support A&F initiatives to improve asthma care and outcomes in primary care.


Assuntos
Asma , Melhoria de Qualidade , Humanos , Asma/terapia , Asma/epidemiologia , Inglaterra/epidemiologia , Estudos Transversais , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Atenção Primária à Saúde/estatística & dados numéricos , Idoso , Adolescente , Adulto Jovem , Criança , Medicina Geral
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