寡核苷酸靶向阻断STAT6治疗哮喘的研究进展

支气管哮喘(Asthma,Bronchial asthma,简称哮喘)是一种以嗜酸性粒细胞(EOS)浸润为主,伴多种炎症介质(包括相关细胞因子,趋化因子等)异常表达的气道炎症和气道高反应性疾病.哮喘气道炎症的机制复杂,近年来细胞信号传导途径对哮喘作用的研究越来越受到重视.     

髓过氧化物酶与重症哮喘

支气管哮喘是一个慢性气道炎症性疾病,多种炎症细胞和细胞因子参与发病,与增加的氧化应激有关,在慢性炎症与氧化应激之间的联系已被证实[1]。重症哮喘中性粒细胞和嗜酸性粒细胞均参与了气道炎症,但中性粒细胞在气道炎症中起了决定性作用。重度哮喘患者的诱导痰、支气管肺泡灌洗液BALF)和黏膜组织中存在中性粒细胞增多和浸润[2]。髓过氧     

喘可治注射液的免疫调节作用及临床应用

支气管哮喘是多种细胞和细胞成分参与的气道慢性炎症，由于炎症反复发作及病原体引起的机体免疫功能的紊乱．逐渐演变为一种全身变态反应性疾病。尽管目前全球哮喘防治创议方案推荐糖皮质激素是治疗哮喘最有效的药物，但由于引起哮喘的因素非常复杂涉及的细胞及炎症介质也多种多样．糖皮质激素不可能阻断炎症的所有环节。喘可治注射液是国家二类新药，主要由巴戟天、淫羊藿等组成．具有温阳补肾、止咳平喘的作用，在治疗哮喘上取得较好疗效。下面就其治疗哮喘的药理作用机制作一总结。     

感觉神经系统-肺神经内分泌细胞与支气管哮喘的关系

支气管哮喘（哮喘）是一种严重危害人们生命健康的常见病，不断上升的哮喘患病率和病死率促使我们对其发病机制和治疗进行深入研究。多种因素共同参与的气道慢性炎症被认为是哮喘的本质，其机制复杂，迄今尚不十分清楚。目前神经肽介导的神经源性炎症与哮喘关系受到高度重视。     

近年国外哮喘治疗的观点和方法

一、支气管哮喘现代治疗的观点(一)支气管哮喘的定义支气管哮喘是气道的一种慢性炎症性疾病,其中包括有肥大细胞和嗜酸细胞在内的多种细胞参与反应.这种炎症可引起广泛的可逆性的气道阻塞.阻塞常可自行缓解或经过治疗缓解.同时因此种炎症的存在,使气道对各种刺激的反应增加.     

他汀类药物治疗支气管哮喘的研究进展

支气管哮喘(简称哮喘)是一种由多种细胞和细胞组分别参与的气道慢性炎症性疾病,以气道炎症、气道重构和气道高反应性为主要特征。他汀类药物是临床上常用的调血脂药物,广泛用于心、脑血管疾病的防治。但近年来研究发现,他汀类药物除了降血脂外,还有抗炎症反应、抗氧化应激、免疫调节等作用,对多种疾病的治疗有益,也开始用于治疗哮喘的基础和临床研究,本文就他汀类药物治疗哮喘的研究进展作一综述。1他汀类药物概述     

气流阻塞性疾病及其他肺部疾病

1　老年性哮喘支气管哮喘是由多种细胞,特别是肥大细胞、嗜酸性粒细胞和T淋巴细胞参与的慢性气道炎症,此种炎症可引起反复发作的喘息、气促、胸闷和(或)咳嗽等症状,多在夜间和(或)凌晨发生,常伴有广泛而多变的通气受限,但可部分自然缓解或经治疗缓解。常有气道对多种刺激因子反应性增高。哮喘是一种慢性气道炎症,包括IgE介导、T细胞调控和非IgE介导,T细胞调控的免疫介质释放机制。血管内皮及气道上皮粘附分子释放,使炎症细胞在气道局部的毛细血管聚集、迁徙及活化,上皮细胞释放炎症介质。哮喘的反复发作则是由于T细胞及某些结构细胞(如…     

硫酸镁治疗急性哮喘临床研究近况

现在认识到气道的炎症反应是支气管哮喘的发病基础 [1] ,控制气道的炎症就成了急性哮喘的重要基础治疗[2 ] 。用于急性哮喘的最初治疗药物一般包括 β受体激动剂、抗胆碱能药和皮质激素等。这些药物一般说来对于轻、中度哮喘疗效尚可 ,但是对于严重的哮喘持续状态治疗仍感棘手 ,有时由于严重的不良反应又限制了该类药物的临床应用。在急性哮喘的最初治疗时需要快速扩张支气管 ,而 β受体激动剂此时作用有限 ,氨茶碱也未被证明对成人急性哮喘有益 [3 ]。有鉴于此 ,近年来静注硫酸镁作为一种治疗急性哮喘的选择疗法在临床上的应用日渐增多。1…     

嗜酸性粒细胞及其毒性蛋白与哮喘

支气管哮喘是社会上最常见到的慢性气道疾病之一，以气道高反应性和可逆性气道阻塞为主要临床特征，随着对哮喘病理生理的深入研究，气道粘膜炎症在哮喘发病中的作用日益受到重视，目前认为哮喘是在气道已经存在慢性炎症并有部分阻塞的基础上出现间断的急性气道痉挛发作。在其炎症过程中有多种炎性细胞参与，但目前认为大多数细胞最终通过嗜酸性粒细胞（EOS）而产生效应。哮喘的许多病理生理改变与EOS释放的毒性蛋白关系密切。本丈就此进行文献回顾。1嗜酸性粒细胞很久以前就已有人在死于哮喘的病人气道内发现大量EOS，以后在哮喘病人的…     

黄芪甲苷对哮喘模型小鼠气道炎症及IL-22的影响

目的 观察白介素22(IL-22)在哮喘模型中的作用,研究黄芪甲苷(AS-Ⅳ)对哮喘小鼠模型气道炎症及IL-22的调控作用,探讨AS-Ⅳ治疗哮喘的作用机制.方法 32只4周龄BALB/c小鼠随机分为对照组、哮喘组、布地奈德(BUD)组和AS-Ⅳ组4组,用卵清蛋白(OVA)致敏、激发小鼠以制备哮喘模型.小鼠肺组织行HE及AB-PAS染色,进行气道炎症评分,ELISA法检测4组小鼠肺泡灌洗液(BALF)中IL-22的水平,实时荧光定量PCR(RT-PCR)检测小鼠肺组织中IL-22 mRNA的表达水平,流式细胞术检测小鼠脾单细胞悬液中Th22的比例.结果 与对照组相比,哮喘小鼠肺组织炎症评分增加(P<0.05),BALF中IL-22水平增高(P<0.01),肺组织中IL-22 mRNA表达水平升高(P<0.01),脾单细胞悬液中Th22比例增加(P<0.01),差异具有统计学意义.给予BUD及AS-Ⅳ治疗后,小鼠气道炎症评分降低(P<0.05),IL-22 mRNA的表达水平及Th22细胞的比例均较哮喘组降低(P<0.01),差异具有统计学意义.结论 AS-Ⅳ对哮喘气道炎症发挥治疗性作用,这可能与AS-Ⅳ通过抑制Th22细胞分化、抑制IL-22的表达和分泌有关.     

呼出气一氧化氮测定在老年哮喘诊治中的应用研究

目的：探讨呼出气一氧化氮（ FeNO）测定在老年哮喘诊治中的应用价值。方法对我院在2013年3月-2014年2月收治的38例老年支气管哮喘患者进行FeNO检测,并与同期收治的38例非呼吸系统疾病老年患者进行比较。结果治疗前哮喘组FeNO[（59.2±16.8）ppb]显著高于对照组[（18.6±6.1）ppb]（P﹤0.01）;哮喘组FeNO在治疗3 d后[（51.5±13.7）ppb]和出院时[（36.1±9.4）ppb],均较治疗前明显下降（ P﹤0.05或P﹤0.01）,但仍显著高于对照组（ P﹤0.01）。对16例哮喘患者在出院3个月后进行随访,其FeNO为（27.3±8.2）ppb,较出院时明显下降（ P﹤0.01）,但也仍高于对照组（ P﹤0.01）。结论 FeNO在老年哮喘患者中明显增高,FeNO检测对老年哮喘的诊治有很好的指导作用。     

Quantification of airway diameters and 3D airway tree rendering from dynamic hyperpolarized 3He magnetic resonance imaging.

As another step toward extracting quantitative information from hyperpolarized 3He MRI, airway diameters in humans were measured from projection images and multislice images of the lungs. Values obtained were in good agreement with the Weibel lung morphometry model. The measurement of airway caliber can now be achieved without the use of ionizing radiation. Furthermore, it was demonstrated that 3D airway tree renderings could be constructed from the multislice data. Both the measurement of airway diameters and the rendering of 3D airway information hold promise for the clinical assessment of bronchoconstrictive diseases such as asthma and the associated evaluation of treatment effectiveness. Work is being done to address the uncertainties of the manually intensive methods we have developed.     

Exercised induced asthma in young male asthmatics with symptoms, and in remission

A treadmill exercise test was carried out on 154 male subjects aged 15-25 years who gave a history of mild asthma in childhood, and on 31 similarly aged control subjects. The results were expressed as an exercise lability index, (ELI), based on measurement of FEV. The mean ELI of the control group was 7.6%, range 2.9-12.2% and a positive result in the asthma subjects was an ELI greater than 15%. Seventy five of the asthma subjects were found to have been asymptomatic for a year or more (group 1) and, in 15 of them (20%) the test was positive. The remaining 79 were currently symptomatic, or had been symptomatic within a year (group 2), and in 52 of these (66%), the test was positive. The difference between the two results was significant, p greater than or equal to 0.001. We believe this observation suggests that exercise induced asthma (EIA) cannot be demonstrated in the majority of asthmatics who are in remission.     

Hyperpolarized 3He MRI in asthma measurements of regional ventilation following allergic sensitization and challenge in mice--preliminary results

RATIONALE AND OBJECTIVES: Quantitative regional measurement of physiological parameters of lung may improve both early detection of asthma and its response to treatment by elucidating the characteristics of airway obstruction. Recent emergence of hyperpolarized helium-3 magnetic resonance imaging as a sensitive pulmonary imaging tool has shown great potential in capturing important structural and functional aspects of normal and diseased lungs. The objective of this study was to investigate regional ventilation changes in the mouse lung following allergen sensitization and challenge. MATERIALS AND METHODS: A murine model of allergic airway inflammation was created in mice following allergen challenge using Af and IgE-mediated asthma. The creation of model was verified using pulmonary function test and histology. Regional fractional ventilation was then measured in the animals using hyperpolarized 3He MRI on a pixel-by-pixel basis with a planar resolution of 0.24 mm. The sensitized and healthy animals were then compared statistically to assess the potential sensitivity of this technique in detection of such pulmonary abnormalities. RESULTS: In this work, we have demonstrated for the first time the quantitative measurement of regional ventilation in normal and asthmatic mice. Results of this study show significant changes in regional ventilation in murine model of allergic airway sensitization compared with that in normal control animals. CONCLUSION: Further development of this technique can potentially serve as a quantitative marker to investigate the physiology of allergen-induced airway hyperresponsiveness and to assist in disease treatment and prevention.     

Exercise and the asthmatic

Physical exercise is not hazardous to asthmatics. Some asthmatics may benefit from physical training, and almost all asthmatics can perform any kind of physical exercise. Free running was earlier thought to induce more asthma than swimming, for example; however, when ventilation is identical during running and swimming, the exercise-induced asthma will also be the same. Hyperventilation alone is as good as physical exercise to induce exercise-induced asthma. If the physical exercise provokes an asthmatic attack, this is most often easily reversed by inhaled beta 2-agonists. Pretreatment of exercise-induced asthma is most efficient by inhaled beta 2-agonist; orally dosed beta 2-agonist is not as efficient as inhaled beta 2-agonist in the pretreatment of exercise-induced asthma. Inhaled sodium cromoglycate diminishes exercise-induced asthma, and the effect seems to be better in children than in adults. Inhaled steroids have no immediate effect on exercise-induced asthma, but long term treatment with steroids diminishes exercise-induced asthma. The pathogenesis of exercise-induced asthma remains obscure. If the water content is low in the inhaled air, e.g. in cold air, the changes in ventilatory capacity following exercise. will be greater than when the exercise is performed while inhaling hot air with high humidity. Almost all asthmatics present changes in the ventilatory capacity following exercise. Seasonal changes in exercise-induced asthma are only present in asthmatics with seasonal allergies, e.g. pollen allergy. No diurnal variation is found in exercise-induced asthma. Asthmatics can do any form of physical exercise. Almost all asthmatics can prevent major changes in ventilatory capacity by pretreatment of exercise-induced asthma or be treated for exercise-induced asthma during the physical activity so that they will not suffer from asthma while performing physical exercise. Asthmatics who have been successfully treated for exercise-induced asthma can do physical exercise at the same level as non-asthmatics. Asthmatic children in particular should be encouraged to perform any sport they like, as the physiological and psychological effects may be beneficial to them. It is concluded that almost all asthmatics have exercise-induced asthma, and that physical training may be beneficial. Exercise-induced asthma is best treated and pretreated by inhalation of beta 2-agonists.     

Asthma in elite athletes: pathogenesis, diagnosis, differential diagnoses, and treatment

Elite athletes have a high prevalence of asthma and exercise-induced bronchoconstriction. Although respiratory symptoms can be suggestive of asthma, the diagnosis of asthma in elite athletes cannot be based solely on the presence or absence of symptoms; diagnosis should be based on objective measurements, such as the eucapnic voluntary hyperpnea test or exercise test. When considering that not all respiratory symptoms are due to asthma, other diagnoses should be considered. Certain regulations apply to elite athletes who require asthma medication for asthma. Knowledge of these regulations is essential when treating elite athletes. This article is aimed at physicians who diagnose and treat athletes with respiratory symptoms. It focuses on the pathogenesis of asthma and exercise-induced bronchoconstriction in elite athletes and how the diagnosis can be made. Furthermore, treatment of elite athletes with asthma, anti-doping regulations, and differential diagnoses such as exercise-induced laryngomalacia are discussed.     

Asthma in Elite Athletes: Pathogenesis,Diagnosis, Differential Diagnoses,and Treatment

Abstract

Elite athletes have a high prevalence of asthma and exercise-induced bronchoconstriction. Although respiratory symptoms can be suggestive of asthma, the diagnosis of asthma in elite athletes cannot be based solely on the presence or absence of symptoms; diagnosis should be based on objective measurements, such as the eucapnic voluntary hyperpnea test or exercise test. When considering that not all respiratory symptoms are due to asthma, other diagnoses should be considered. Certain regulations apply to elite athletes who require asthma medication for asthma. Knowledge of these regulations is essential when treating elite athletes. This article is aimed at physicians who diagnose and treat athletes with respiratory symptoms. It focuses on the pathogenesis of asthma and exercise-induced bronchoconstriction in elite athletes and how the diagnosis can be made. Furthermore, treatment of elite athletes with asthma, anti-doping regulations, and differential diagnoses such as exercise-induced laryngomalacia are discussed.     

Bronchial walls in the radiological diagnosis of asthma

Although bronchial wall thickening is known to occur in asthma, its radiological visibility and significance are matters of dispute. The present study shows that thickening can be detected in the plain chest radiographs of patients with severe asthma, but it cannot be reliably detected in patients with mild asthma. Measurements of bronchi made on lung tomograms showed that the lumen-wall ratio more clearly separated the asthma and normal groups than did observation of bronchial wall thickness alone.     

肺表面活性蛋白A在皮质类固醇调节哮喘小鼠树突细胞共刺激分子表达中的作用

目的 研究皮质类固醇激素调节小鼠哮喘模型树突细胞表面共刺激分子表达的机制，以及肺表面活性蛋白A（SP-A）在其调节中的作用。方法 BALB/c小鼠30只，分为3组：哮喘组，采用卵蛋白（OVA）致敏和激发；对照组，以生理盐水代替OVA；治疗组，每次OVA激发后10min，腹腔注射地塞米松01mg。用免疫组化法检测SP-A在肺内的表达情况。采用Leica DM Snk软件进行图像采集，并用Qwin软件计算小气道内棕色区域面积，取平均值，进行统计分析。分离培养脾脏树突细胞，用流式细胞仪（FACS）检测树突细胞表面共刺激分子CD80的表达变化。结果 哮喘组肺组织表现为嗜酸性细胞及淋巴细胞浸润为主的炎症变化，治疗组和对照组无此变化。哮喘组的SP-A表达明显低于对照组和治疗组（P〈0．01），CD80的表达率明显高于治疗组（P〈0.01）；哮喘组小气道内SP-A表达与树突细胞CD80阳性率呈负相关（r=-0．907，P〈0．01）。结论 皮质类固醇对小鼠哮喘模型的肺表面活性蛋白有明显的保护作用，可通过激发肺表面活性蛋白抑制树突细胞表面共刺激分子CD80的表达。     

Application of adjusted subpixel method (ASM) in HRCT measurements of the bronchi in bronchial asthma patients and healthy individuals

Background

Recently, we described a model system which included corrections of high-resolution computed tomography (HRCT) bronchial measurements based on the adjusted subpixel method (ASM).

Objective

To verify the clinical application of ASM by comparing bronchial measurements obtained by means of the traditional eye-driven method, subpixel method alone and ASM in a group comprised of bronchial asthma patients and healthy individuals.

Methods

The study included 30 bronchial asthma patients and the control group comprised of 20 volunteers with no symptoms of asthma. The lowest internal and external diameters of the bronchial cross-sections (ID and ED) and their derivative parameters were determined in HRCT scans using: (1) traditional eye-driven method, (2) subpixel technique, and (3) ASM.

Results

In the case of the eye-driven method, lower ID values along with lower bronchial lumen area and its percentage ratio to total bronchial area were basic parameters that differed between asthma patients and healthy controls. In the case of the subpixel method and ASM, both groups were not significantly different in terms of ID. Significant differences were observed in values of ED and total bronchial area with both parameters being significantly higher in asthma patients. Compared to ASM, the eye-driven method overstated the values of ID and ED by about 30% and 10% respectively, while understating bronchial wall thickness by about 18%.

Conclusions

Results obtained in this study suggest that the traditional eye-driven method of HRCT-based measurement of bronchial tree components probably overstates the degree of bronchial patency in asthma patients.