背景: 在容易暴露于大量微生物的环境( 如传统的农场) 中成长的儿童, 不易患儿童哮喘和特应性体质。在既往的研究中, 微生物暴露的标志物与这些疾病呈负相关关系。方法: 在两项横断面研究中, 我们比较了居住于农场的儿童与参照组儿童哮喘和特应性体质的患病率以及微生物暴露的多样性。在一项PARSIFAL研究[ 变态反应的预防-与农业及特别信仰( Anthroposophic) 生活方式相关的儿童致敏作用的危险因素] 中, 研究者采用单链构型多态性( SSCP) 分析筛查了床垫灰尘样本的细菌DNA, 以检测出培养技术无法检测到的环境细菌。在另一项GABRIELA 研究[ 鉴定欧共体中哮喘的遗传和环境原因的多学科研究( GABRIEL) 高级研究] 中, 研究者采用培养技术对儿童房间落尘样本的细菌和真菌的分类进行了评估。结果: 在这两项研究中, 居住于农场的儿童哮喘与特应性体质的患病率较低, 并且他们比对照组儿童暴露于更多种类的环境微生物中。相反, 微生物暴露的多样性与哮喘发生危险呈负相关[ PARSIFAL 研究的比值比为0. 62; 95% 可信区间( CI) 为0. 44 ～0. 89; GABRIELA 研究的比值比为0. 86; 95% CI 为0. 75 ～0. 99] 。此外, 存在某种更为局限的暴露也与哮喘发生危险呈负相关; 这包括暴露于真菌中曲菌属中的某些物种( 经校正的比值比为0. 37; 95% CI 为0. 18 ～0. 76) , 以及暴露于多种细菌物种, 包括单核细胞增生李斯特菌、芽孢杆菌属物种、棒杆菌属物种和其他细菌( 经校正的比值比为0. 57,95% CI 为0. 38 ～0. 86) 。结论: 居住于农场的儿童比参照组儿童有更大范围的微生物暴露, 这种暴露解释了哮喘与成长在农场之间呈负相关关系的本质部分。【述评】哮喘发病机制的卫生学说认为在儿童时期接触大量的抗原能减少成年后哮喘的发病率, 主要机制是在人体免疫系统发育的过程中接触抗原可诱导免疫耐受, 此学说主要基于流行病学调查得出的结论。本研究采用分子生物学的方法研究儿童时期微生物暴露对哮喘发病率的影响, 结果证实微生物暴露的程度与哮喘发病呈负相关, 进一步证实了哮喘发病的卫生学说, 同时表明环境因素在哮喘发病中具有重要意义, 并提示儿童在发育过程中尽量接触多种抗原对减少成人过敏性疾病具有一定意义。
ObjectiveTo investigate the medical knowledge and treatment compliance of parents of asthma children in Gaoming District, Foshan City. MethodOne hundred consecutive parents of asthma children who sought pediatric service in Gaoming People's Hospital from January to December in 2012 were surveyed by the use of Knowledge-Belief-Behavior Questionnaire developed by Capital Research Center of Pediatrics. ResultsNinety-five of the one hundred questionnaires provided useful data for analysis. Among these parents, 63.18% understood the nature of asthma being hyperactive inflammatory disease of the airways; 78.91% believed it to be controllable by regular treatment; only 21.05% of asthma children under parental guidance received inhaled corticosteroids on a regular basis; 14.74% considered their children fit for physical exercises when stabilized; 22.10% chose inhaled β2 agonists as "relievers" during attacks; 61.05% were concerned about the side effects on growth of inhaled corticosteroids and 48.42% discontinued its use against physician's instruction; 82.11% of asthma children had not been evaluated by Asthma Control Questionnaire. ConclusionsParents of asthma children in Gaoming District, Foshan City have weak links in the understanding of this condition. Though most believe it to be controllable under regular treatment, the overall compliance is unsatisfactory. Therefore, knowledge of asthma should be propagated at various public fronts in order to better improve the treatment compliance and consequently the disease control, of asthma children.
Objective To explore the inducing factors, the serum total immunoglobulin E (IgE) and specific IgE of bronchial asthma in Mianyang children, for better control of childhood asthma. Methods A total of 1 288 cases of asthma who were hospitalized in pediatric respiratory ward or asthma clinic from March 2013 to February 2016 were enrolled in the study. All cases complied with the diagnostic criteria for acute episode of childhood bronchial asthma revised in 2008 by the National Children’s Asthma Cooperative Group. The causes of asthma attack were asked by doctors, and the patient’s serum total IgE and specific IgE was tested. Results Respiratory tract infections were the most common cause (1 057 cases, 82.1%), which was followed by weather changes and exposure to cold air (694 cases, 53.9%), and then food (304, 23.6%). The risk of asthma induced by respiratory infections was highest in <2-year old group (358 cases, 97.5%), and lowest in 10-14-year old group (42 cases, 33.3%), with a decreasing trend with age (χ2trend=239.865, P<0.001). Food was also an important inducing factor, and seafood was the most frequent (121 cases, 39.8%). Total serum IgE was positive in 868 cases (67.4%). The positive rate in <2-year old group (52.6%) was the lowest, and the positive rate in 10-14-year old group (89.7%) was the highest, with an increasing trend with age (χ2trend=88.055, P<0.001). Serum specific IgE was positive in 733 cases (56.9%). The positive rate in <2-year old group (37.1%) was the lowest, and the positive rate in 10-14-year old group (92.6%) was the highest, with an increasing trend with age (χ2trend=150.361, P<0.001). The progressive rate of dust mites in inhalation and dietary allergens was highest (668 cases, 51.8%), which was followed by house dust (431 cases, 33.4%). Conclusions The most common inducing factor for bronchial asthma in Mianyang children is respiratory tract infection, followed by the weather changes and cold air exposure, and then food. Detection of serum total IgE and specific IgE is more valuable in elderly children with bronchial asthma.
Objective To screen the key genes in childhood therapy-resistant asthma by bioinformatic method, and to verify its expression and diagnostic value in peripheral blood of children with therapy-resistant asthma. Methods The transcriptome dataset GSE27011 of peripheral blood mononuclear cells from healthy children (healthy control group), mild asthma (MA) children (MA group) and severe asthma (SA) children (SA group) was downloaded from the Gene Expression Omnibus of the National Center for Biotechnology Information of the United States. Key genes were obtained by using R software for gene differential expression analysis, weighted gene co-expression network analysis (WGCNA) and clinical phenotypic correlation analysis. The differential expression levels of key genes were verified in children with asthma and immune cell transcriptome datasets. Seventy-eight children with asthma and 30 healthy children who were diagnosed in the Department of Pediatrics of Tangshan People’s Hospital between September 2020 and September 2021 were selected and divided into control group, MA group and SA group. Peripheral blood samples from children with asthma and healthy children who underwent physical examination were collected to detect the expression levels of key genes and inflammatory factors interleukin (IL)-4 and IL-17 in peripheral blood of children. Receiver operating characteristic curve was used to evaluate the sensitivity, specificity and accuracy of key genes in predicting childhood therapy-resistant asthma. Results The key gene GNA15 was obtained by bioinformatic analysis. Analysis of asthma validation dataset showed that GNA15 was up-regulated in asthma groups, and was specifically expressed in eosinophils. Clinical results showed that the expression levels of IL-4, IL-17 and GNA15 among the three groups were significantly different (P<0.05). The expression levels of IL-4 and IL-17 in the MA group and the SA group were higher than those in the control group (P<0.05). Compared with the control group and the MA group, the expression level of GNA15 in the SA group was up-regulated (P<0.05). Neither the difference in the expression level of IL-4 or IL-17 between the MA group and the SA group, nor the difference in the expression level of GNA15 between the control group and the MA group was statistically significant (P>0.05). The specificity, sensitivity and accuracy of GNA15 in predicting SA were 92.90%, 80.00% and 86.10%, respectively. Conclusion GNA15 has a significant clinical value in predicting the childhood therapy-resistant asthma, and may become a potential diagnostic marker for predicting the severity of asthma in children.
Objective To analyze the causal relationship between gut microbiota and childhood asthma based on Mendelian randomization (MR). Methods The human gut microbiota dataset was downloaded from the MiBioGen database, and 196 known bacterial groups (9 phyla, 16 classes, 20 orders, 32 families, and 119 genera) were retained as exposure factors. Single nucleotide polymorphisms (SNPs) that were strongly correlated with exposure factors and independent of each other were selected as effective instrumental variables. A childhood asthma dataset with 3 025 patients and 135 449 controls was downloaded from the genome-wide association studies database as the outcome variable. Two-sample MR analysis was performed using inverse variance weighted, weighted median, MR-Egger, weighted model and simple model methods, respectively. The causal association between gut microbiota and childhood asthma was evaluated by odds ratio (OR). Sensitivity analysis was performed by leave-one-out method. Horizontal pleiotropy was tested by MR-Egger intercept test and MR-PRESSO global test, and Cochran’s Q test was used for heterogeneity. Results A total of 15 out of 196 gut microbiota groups were found to have a causal association (P<0.05) with the risk of childhood asthma, with a total of 181 SNPs included in the analysis. Inverse variance weighted analysis showed that Mollicutes [OR=1.42, 95% confidence interval (CI) (1.10, 1.83), P=0.007], Escherichia-Shigella [OR=1.39, 95%CI (1.02, 1.90), P=0.036], Oxalobacter [OR=1.30, 95%CI (1.10, 1.54), P=0.002], Ruminococcaceae UCG-009 [OR=1.34, 95%CI (1.09, 1.64), P=0.006] and Tenericutes [OR=1.42, 95%CI (1.10, 1.83), P=0.007] were significantly positively correlated with childhood asthma. Actinobacteria [OR=0.76, 95%CI (0.58, 0.99), P=0.042], Bifidobacteriaceae [OR=0.76, 95%CI (0.58, 0.98), P=0.035], Eubacterium nodatum group [OR=0.81, 95%CI (0.70, 0.94), P=0.007], Bifidobacterales [OR=0.76, 95%CI (0.58, 0.98), P=0.035] and Actinobacteria [OR=0.74, 95%CI (0.56, 0.99), P=0.040] were negatively correlated with childhood asthma. In addition, the results of leave-one-out sensitivity analysis were stable, MR-Egger intercept test and MR-PRESSO global test showed no horizontal pleiotropy, and Cochran’s Q test showed no heterogeneity. Conclusions There is a causal relationship between gut microbiota and childhood asthma. Mollicutes, Escherichia-Shigella, Oxalobacter, Ruminococcaceae UCG-009 and Tenericutes may increase the risk of childhood asthma. Actinobacteria, Bifidobacteriaceae, Eubacterium nodatum group, Bifidobacterales and Actinobacteria can reduce the risk of childhood asthma.