【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 explore the application of pulmonary ventilation and perfusion imaging (V/P SPECT/CT) in quantitative evaluation of ventilation and perfusion function and its potential value in guiding local treatment of lung in patients with asthma.MethodsA total of 20 patients with asthma were included in this study. All patients underwent V/P SPECT/CT and pulmonary function test, and symptoms were assessed by the ACT questionnaire. Patients were graded for degree of airway obstruction according to V/ P SPECT/CT image visual scoring criteria. The comprehensive lung function (%) of the patients was quantitatively evaluated by combining the ventilation and perfusion defect of each lung segment in V/P imaging. The correlation between the degree of airway obstruction, comprehensive lung function, pulmonary function test and ACT score was analyzed.ResultsV/P SPECT/CT imaging can be used to grade the degree of airway obstruction in asthma patients (0-3 grade). Airway obstruction grading by V/P SPECT/CT visual score was associated with predictive forced expiratory volume in one second (FEV1%pred) of patients (r=–0.74, P<0.001). V/P SPECT/CT can also comprehensively evaluate ventilation and perfusion function in patients with asthma, and comprehensive lung function measured by this method was also correlated with FEV1%pred (r=0.629, P=0.003). V/P SPECT/CT can be used to quantitatively analyze the percentage of ventilation and perfusion function in each lung lobe. Compared with V/P SPECT/CT results, the CT volume overestimates the contribution in the upper lobes, and underestimates the lower lobes contribution to overall function.ConclusionsV/P SPECT/CT can be used as a new method to directly reflect the degree of airway obstruction in patients with asthma. Moreover, it can comprehensively and quantitatively evaluate the ventilation and perfusion function of asthma patients. V/P SPECT/CT can also be used to evaluate lobe function in patients with asthma, helping to identify the heterogeneity of changes in pulmonary function in patients with asthma, and has potential value for future treatment targeting specific areas of the lung.
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.
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.
ObjectiveTo survey the current asthma impact on quality of life and related factors in China. MethodsTwo thousand and thirty-four asthmatic patients, from bronchial asthma prevalence epidemiology survey in the population over 14 years old in 8 areas of China from 2009 to 2013, were enrolled. The data about medical resource use, control status and quality of life were collected by detailed questionnaire and analysed using the Epidata database and SAS 9.2 software. ResultsOut of the 2034 asthma patients, 1213 patients (59.6%) reported that their activities including entertainment, learning, fertility and employment were limited due to asthma. In the four aspects of entertainment, education, family and employment, 688 patients (33.8%) had one limited activity in one aspect, 165 patients (8.19%) had most of activities limited in one aspect, 246 patients (12.1%) had limited activities in two or three aspects, 114 patients (5.6%) had limited activities in all aspects. One hundred and eighty-one patients (8.9%) needed help in daily life, such as cooking, shopping, doing housework. Seventy-one patients (3.5%) even needed help in eating, personal hygiene, toilet, and their daily activities were remarkably restricted. Eighty-one patients (4.0%) had motive of suicide. Aging, comorbidity, and medication use were the most important factors. ConclusionAsthma has a significant negative effects on the life and emotion of patients, and proper control of comorbidity and regular treatment of asthma are effective ways to improve the life and emotional state of patients with asthma.
Objection To investigate the changes of insulin and insulin receptor in asthma patients.Methods Forty asthma patients were allocated into two groups：20 newly diagnosed treatment–naiuml;ve mild-moderate asthma patients，20 mild-moderate persistent asthma patients treated with inhaled corticosteroid. 20 healthy volunteers were enrolled as normal control.Blood samples were obtained from 40 asthma patients and 20 healthy volunteers.Total and differential leukocyte counts,blood glucose concentration and serum insulin concentration were measured.The level of lymphocyte insulin receptor in peripheral blood were assayed by flow cytomertry.Pulmonary function were performed at the same time.Results The numbers of eosinophil in the two asthma groups were significantly higher than those in the normal control group [(4.04±2.57)% and (4.24±2.34)% vs (0.90±1.38)%，Plt;0.05)，the levels of insulin and insulin receptor in the treatment-naiuml;ve group were significantly higher than those in the control group [insulin：(13.00±5.20)mIU/L vs (10.08±3.79)mIU/L，Plt;0.05；insulin receptor：(2.59±3.11)% vs (0.99±0.62)%，Plt;0.05).Conclusion Insulin secretion and insulin receptor expression in asthma patients are increased in the presence of inflammation.
ObjectiveTo investigate the effect of ADAM33 gene silencing in VSMCs on the proliferation and lumen formation of airway vascular endothelial cells (VECs) in a co-culture system and the possible regulatory mechanism. MethodsThe Human aortic smooth muscle cells (HASMCs) and human pulmonary microvascular endothelial cells (HPMECs) were used to construct a cell co-culture system. ADAM33 gene expression was silenced by lentivirus transfection technique, and the subjects were divided into endothelial cell blank group, co-culture group, co-culture +shRNA negative control group, and co-culture + ADAM33-SHRNA group. The expressions of sADAM33, VEGFA,VEGER2, ang-1 and ang-2 in co-culture system were detected by ELISA. The proliferation and lumen formation of HPMECs were observed by CCK-8 and Transwell experiments. The protein expression of Tie2, PI3K, Akt, and mTOR key molecules in Tie2/PI3K/Akt/mTOR signaling pathway and the phosphorylation levels of AKT and mTOR were detected by Western-blotting method. Results① Compared with the co-culture group (0.851±0.036) and the co-culture + shRNA negative control group (0.828±0.047), the OD value of the co-culture + ADAM33shRNA group (0.699±0.038) was significantly decreased (P<0.05). ② Compared with the co-culture group (159.169±15.740) and the co-culture +shRNA negative control group (157.357±21.612), the tube length of the co-culture +ADAM33shRNA group (120.812±2.791) was also significantly decreased (P<0.05). ③ After ADAM33 gene expression of HASMCs was silted in co-culture system, the expression levels of VEGFA, VEGFR2, ang-1 and ang-2 were significantly decreased (P<0.05), while the expression levels of Tie2, PI3K, P-Akt and P-mtor were decreased (P<0.05). ConclusionsSilencing the expression of the ADAM33 gene could reduce the release of sADAM33 from the membrane of the airway VSMCs, regulate the proliferation and lumen formation of airway VECs by reducing the expression of VEGF/VEGFR and inhibiting the activities of the Tie2/PI3K/Akt/mTOR signaling pathways,and then participate in airway vascular remodeling in asthma.
ObjectiveTo analyze the relationship between medication compliance of patients with uncontrolled asthma and lung function,airway inflammation level, asthma control level and quality of life so as to obtain important references for improving patient compliance and asthma control level in the future. MethodsQuestionnaires were performed in asthma patients who did not achieve asthma control and had poor compliance in 32 third-class hospitals in 28 provinces of China mainland. All patients were tested for lung function and airway inflammation levels. So the relevant data of asthma compliance was investigated and analyzed. ResultsA total of 923 patients were investigated and the questionnaire recovery rate was 100%. Two hundred and forty-three (26.33%) answered cognitive related questions about asthma completely correctly. Treatment compliance in asthma patients was positively correlated with lung function and significantly negatively correlated with exhaled nitric oxide. Better treatment compliance in asthma has higher level of asthma control and quality of life. Poor compliance in asthma patients will lead to decreased lung function and elevated levels of airway inflammation, resulting in decreased asthma control and quality of life. ConclusionAsthma treatment compliance is related to lung function, airway inflammation, asthma control level and quality of life.
Objective To determine the diagnostic value of fractional exhaled nitric ( FeNO)measurement in diagnosis of bronchial asthma. Methods The patients with unkown-cause respiratory symptoms including wheezing, cough, and breathlessness were enrolled from August to September in 2008.FeNO was measured by nitric oxide analyzer ( NIOX; Aerocrine AB; Solna, Sweden) . Bronchial challenge test ( BCT) or bronchodilator test was defined as golden standard for asthma diagnosis. The value of FeNO was assessed and the optimal operating point of FeNO testing was determined by the means of the receiver operating characteristic ( ROC) curves. Results A total of 101 patients were enrolled, in which 48 cases were diagnosed as asthma by positive yield in BCT ( in 38 cases) or bronchodilator test ( in 10 cases) . The severity of airway hyperresponsiveness ( AHR) judged by BCT was mild in 15 cases, moderate in 15 cases and severe in 8 cases. The levels of FeNO of asthma group were higher than those of non-asthma group [ ( 68. 19 ±43. 00) ppb vs ( 19. 52 ±10. 60) ppb, P lt; 0. 05] . A linear correlation of FeNO with lnPD20 FEV1 was revealed in the cases with AHR. Area under ROC curve was 0. 9. The optimal diagnostic cutoff point was 36. 5 ppb which was capable of differentiating asthma and non-asthma with sensitivity of 92. 7% ,specificity of 83. 3% , positive predictive value of 79. 17% , negative predictive value of 94. 34% and accuracy of 87. 13% . Conclusion FeNO test may be helpful in the diagnosis of asthma with high sensitivity and specificity.