【摘要翻译】 胸腺基质淋巴生成素( TSLP) 触发树突状细胞介导的Th2 型炎症反应。一个位于TSLP 基因启动子区域的rs3806933 位点的单核苷酸多态性能产生转录因子激活蛋白( AP) -1 的结合位点。这种变异增强了AP-1 结合到调控元件的能力, 并增强聚肌苷酸胞苷酸刺激人类正常支气管上皮细胞时TSLP 启动子-报告子反应活性。我们研究了这种包括rs3806933 位点的多态性是否影响支气管哮喘的易感性和临床表型。我们选择了三个具有代表性的单核苷酸多态位点进行TSLP 基因相关性研究, 对象为两个独立的人群( 其中一个为693 例儿童特应性哮喘患者和838 例对照者, 另一个为641 例成年哮喘患者和376 名对照者) 。我们进一步检测了糖皮质激素和长效β2 受体激动剂( 沙美特罗) 对聚肌苷酸胞苷酸刺激的人类正常支气管上皮细胞TSLP 基因表达的影响。我们发现启动子多态性位点rs3806933、rs2289276 与儿童特应性哮喘和成人哮喘的易感性均显著相关。功能单核苷酸多态性位点rs3806933 与哮喘相关( Meta 分析, P = 0. 000056; 比值比, 1. 29; 95% 可信区间, 1. 14 ～1. 47) 。Rs2289278 的基因型和肺功能相关。并且, 糖皮质激素和沙美特罗可协同性地抑制聚肌苷酸胞苷酸刺激导致人类正常支气管上皮细胞TSLP mRNA 及蛋白的上调表达。TSLP 多态性变异与支气管哮喘和肺功能显著相关。因此, TSLP可能作为联合治疗的分子靶点。【述评】 越来越多的研究表明哮喘是一种环境和遗传因素相互作用的疾病。本研究不但发现TSLP 启动子多态rs3806933、rs2289276 与儿童特应性哮喘和成人哮喘的易感性均显著相关, 并研究了其导致哮喘炎症反应可能与该多态性位点产生激活蛋白( AP) -1 的转录因子的结合位点。这种变异增强了AP-1 结合到调控元件从而导致基因表达异常。同时, 作者还发现临床常用的哮喘治疗药物ICS 与LABA 的联合制剂可调节TSLP 表达。这些数据表明TSLP在哮喘发病中起重要作用, 并进一步阐明ICS 与LABA 联合治疗的分子机制。该研究不但从分子遗传和分子生物学的角度阐明TSLP多态性在哮喘发病中的分子机制, 并从分子药理层面进一步证实目前常用哮喘治疗方案的合理性, 研究较为深入。
ObjectiveTo investigate the fatigue of asthma patients, and to analyze its influencing factors, and provide a reference for clinical intervention.MethodsThe convenience sampling method was adopted to select asthma patients who were in clinic of the First Affiliated Hospital of Guangxi Medical University from November 2018 to March 2019. The patients’ lung function were measured. And questionnaires were conducted, including general data questionnaire, Chinese version of Checklist Individual Strength-Fatigue, Asthma Control Test, Chinese version of Self-rating Depression Scale. Relevant data were collected for multiple stepwise linear regression analysis.ResultsFinally, 120 patients were enrolled. The results of multiple stepwise linear regression analysis showed that age, education level, place of residence, time period of frequent asthma symptoms, degree of small airway obstruction, Asthma Control Test score and degree of depression were the influencing factors of fatigue in asthma patients (P≤0.05). Multivariate linear stepwise regression analysis showed that degree of small airway obstruction, degree of depression and time period of frequent asthma symptoms were the main influencing factors of fatigue in asthma patients, which could explain 51.8% of the variance of fatigue (ΔR2=0.518).ConclusionsThe incidence of fatigue in asthma patients is at a relatively high level. Medical staff should pay attention to the symptoms of fatigue in asthma patients. For asthma patients, it is recommended to strengthen standardized diagnosis and treatment, reduce the onset of symptoms at night and eliminate small airway obstruction. Psychological intervention methods are needed to improve patients’ depression, reduce fatigue symptoms, and improve quality of life.
目的:探讨妊娠合并哮喘的临床表现及治疗方法。方法:对32 例妊娠合并支气管哮喘患者的临床资料进行回顾性分析。结果:经过适当的治疗,32例支气管哮喘合并妊娠患者症状缓解,随访至产后1 个月,婴儿和母亲均正常。结论:支气管哮喘合并妊娠时,妊娠早期可选用对胎儿无影响的药物如头孢菌素类抗生素、β2 受体激动剂、糖皮质激素(吸入布地奈德,强的松口服,短期甲强龙静滴),妊娠中晚期还可选用茶碱类药物及全身使用糖皮质激素等药物。
ObjectiveTo systematically review the association between ADAM33 (a disintegrin and metalloproteinase domain33) T2 (rs2280090), S2 (rs528557), and V4 (rs2787094) polymorphisms and asthma in Chinese Han population. MethodsWe electronically searched databases including PubMed, Web of Science, CNKI, WanFang Data and VIP from inception to December 2014, to collect case-control studies about the association between ADAM33 polymorphisms and asthma in Chinese Han population. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using Stata 12.1 software. ResultsA total of 8 case-control studies including 1651 asthma patients and 1639 controls were included. The results of meta-analysis showed that: ADAM33 T2 polymorphism was associated with decreased risk of asthma (AA+AG vs. GG: OR=0.316, 95%CI 0.151 to 0.659, P=0.002), and the S2 polymorphism was associated with increased risk of asthma (GG+GC vs. CC: OR=1.271, 95%CI 1.023 to 1.578, P=0.030). However, no significant association was found between asthma risk and V4 polymorphism (GG+GC vs. CC: OR=1.561, 95%CI 0.638 to 3.823, P=0.330). Subgroup analysis by age indicated that the T2 polymorphism was associated with decreased risk of asthma in both adults and children, the S2 polymorphism was only associated with increased risk of asthma in adults, however, no significant association was found between asthma and the ADAM33 V4 polymorphism in both adults and children subgroups. ConclusionCurrent evidence shows that the ADAM33 T2 and S2 polymorphisms are associated with risk of asthma in Chinese Han population. Due to the limited quantity and quality of the studies, the above conclusion still need to be verified by further more high-quality studies.
ObjectiveTo evaluate the prevalence of obstructive sleep apnea hypopnea syndrome (OSAHS) in patients with asthma, and explore the association of OSAHS with asthma. MethodsPatients who were diagnosed as asthma between March 2014 and February 2015 were recruited in the study. They were categorized into an OSAHS group and a non-OSAHS group according to the Berlin questionnaire. The data of clinical characteristics and pulmonary function test were collected. Logistic regression analysis was performed to evaluate the factors associated with the incidence of OSAHS in asthma. ResultsA total of 64 patients with asthma were enrolled and 36 patients were complicated with OSAHS. The body mass index (BMI), allergic rhinitis history, inspiratory capacity, maximal mid-expiratory flow and provoking dose which make FEV1 reduce 20% were significantly different between two groups (all P < 0.05). Multivariate logistic regression analysis revealed that the increased BMI was an independent risk factor of OSAHS in patients with asthma. ConclusionThe occurrence of OSAHS with asthma is very high, and BMI may be an important associated risk factor.
Objective To investigate the effects of a mixed bacterial lysate (OM-85 BV) on lung function and serum IgE in asthmatic mice under acute attack, and to explore the therapeutic effect of OM-85 BV on acute attack and the application value of OM-85 BV in non-acute attack. Methods A total of 30 SPF Kunming mice aged 4 to 6 weeks were randomly divided into 3 groups, namely a blank control group (Group A), an asthma model group (Group B), and an OM-85 BV intervention group (Group C). The mice in groups B and C were sensitized by intraperitoneal injection of ovalbumin on day 1, 8 and 15, respectively. From day 22, the asthma model was stimulated by inhalation of 5% ovalbumin every day for 30 min for 5 consecutive days. The mice in group C were treated with OM-85 BV dissolved in normal saline from day 1, and each mouse was gavaged continuously for 10 days. The intraperitoneal injection, intragastric administration and aerosol inhalation reagent of mice in group A were all replaced by normal saline, while the intragastric administration of mice in group B was replaced by normal saline. One hour after the last stimulation, the mice were anesthetized, their lung function was measured, blood was collected from the eyeballs and then they were sacrificed, and the blood was centrifuged and the serum was separated and stored. Hematoxylin and eosin staining was used for pathological examination. Serum IgE was determined by enzyme-linked immunosorbent assay. Results Compared with group A, forced vital capacity in 0.15 second (FEV0.15), FEV0.15/forced vital capacity (FVC) and peak expiratory flow (PEF) of mice in group B were significantly decreased. The lung function of group C was improved compared with group B. In group B, the pathological manifestations were dysplasia and collapse of bronchial epithelium, infiltration of inflammatory cells, mainly lymphocytes and eosinophils, a small amount of mucus and shed epithelial cells in the tracheal lumen, and significant thickening of airway wall. The asthma mouse model was well established. The pathological manifestations of airway in group C were less severe than those in group B, the thickness of airway wall was reduced, and the inflammatory cells were also significantly reduced. The serum IgE concentration in groups B and C increased, and the IgE level in group C decreased significantly compared with group B. The differences were statistically significant (all P<0.05). Conclusions Exogenous administration of OM-85 BV in asthmatic mice can effectively reduce the concentration of serum IgE, alleviate airway inflammation, reduce eosinophil infiltration, and improve the pulmonary function performance of asthmatic mice during acute attack, showing that FEV0.15/FVC, FEV0.15 and PEF indicators are significantly improved. OM-85 BV can alleviate the symptoms of bronchial asthma in the acute attack of mice, improve the physiological function of the lung during the acute attack, inhibit airway inflammation, and have certain application value in the stable asthma control.
小气道病变曾经是全球呼吸界研究的热点，许多肺功能测定方法和指标被用于小气道功能的诊断，其后热度骤减，最近又引起一些学者的重视。
Objective To explore the clinical features and diagnostic procedure of atypical asthma characteristic of chest pain.Methods The patients with unexplained chest pain were screened by lung function test and bronchial provocation test.The diagnosis of asthma was established by therapeutic test and exclusive procedure.The clinical manifestations were analyzed.Results In 56 cases of unexplained chest pain 20 cases were diagnosed as asthma.While all patients referred to clinic with chest pain as chief complaint，a majority of patients (11 cases，85%) showed obscure chest tightness，breath shortness and cough..Some cases reported the same trigger factors as asthma.Chest pain was relieved in all cases after regular antiasthma treatments.Conclusions Chest pain could be a specific presentation of asthma which may be misdiagnosed as other diseases.Bronchial provocation tests and antiasthma therapy should be considered to screen and diagnose this atypical asthma.
ObjectiveTo explore whether education and management of medical care integration can improve asthma control. MethodsA prospective, 12-month, cohort study was undertaken in a real-world setting based on Australasian severe asthma network (ASAN). A total of 516 patients with stable asthma were consecutively recruited, who received education and management of medical care integration, and step-wise anti-asthma regimens determined by physicians’ standard practice. Furthermore, inhaled corticosteroid (ICS) adherence, lung function, asthma symptom control and exacerbation were assessed at 1, 3, 6, and 12 months. ResultsAt the end of 12 months, ICS adherence (47.7% vs. 81.5%, P<0.05), lung function, and asthma symptoms were assessed by asthma control text (ACT) [20 (16, 23) vs. 23 (21, 24), P<0.05], which were significantly improved in comparison to the status at baseline, and 86.0% of patients achieved total/well-controlled level of asthma. The exacerbation (14.2% vs. 36.2%, P<0.01) and hospitalizations (8.5% vs. 15.3%, P<0.01) because of asthma for the following year significantly decreased compared with those in the past year. The multivariate regression analysis indicated that poor ICS adherence (RR=1.52, 95%CI 1.02 to 2.25, P=0.039), depression symptoms (RR=1.19, 95%CI 1.05 to 1.34, P=0.007), and exacerbation during the past year (RR=2.81, 95%CI 1.49 to 5.27, P=0.001) were associated with an increased risk of future exacerbation. ConclusionIn a real-world setting, most of asthmatics achieve total/well-controlled asthma by education and management of medical care integration including shared decision-making between physicians and patients and step-wise anti-asthma regimens. ICS adherence and depression symptoms independently predict asthma exacerbations, and strengthening education and management of medical care integration, esp. psychological nursing, would improve asthma control levels.