支气管哮喘小鼠气道反应性无创检测方法的建立

目的 目前国内对支气管哮喘(简称哮喘)小鼠的评价多数仅立足于气道炎性指标,不能完全反映哮喘的病理生理特征.本所率先从国外引进了小动物无创检测和有创检测肺功能仪.无创法检测时小鼠不必麻醉,而且每次可以同时检测多只小鼠,具有较大的优越性,但能否取代有创法尚需更多的数据.本研究旨在建立无创检测小鼠气道高反应性的检测方法,并与有创检测方法进行比较.方法 根据动物模型和气道反应性检测方法不同,动物分为:①无创哮喘组;②无创对照组;③有创哮喘组;④有创对照组.采用卵白蛋白致敏和激发,建立BALB/c小鼠哮喘模型,生理盐水作为对照,分别用无创和有创的方法测定气道反应性.哮喘动物雾化吸入0.2～50 g/L倍增浓度的乙酰甲胆碱(Mch),测定相应浓度下的增强呼气间歇(Penh)值或气道阻力(RL)值等指标.将小鼠吸入Mch后RL或Penh增加2倍的激发浓度以PC100来表示.所有动物都行支气管肺泡灌洗,收集灌洗液,涂片染色后分类计数.结果 无创哮喘组PC100均≤6.25 g/L,对照组PC100均≥12.5 g/L.其Log2(10PC100)值(5.36±0.84)显著低于对照组(7.97±0.82)(P<0.01).无创哮喘组从Mch浓度3.12 g/L开始,其Penh值明显高于对照组.有创哮喘组RL值从Mch浓度0.39 g/L开始就明显高于相应对照组(P<0.05).无创组与有创组的气道反应性相关系数R=0.96(P<0.01).无创哮喘组和有创哮喘组的嗜酸粒细胞分别为(54.00±5.96)%,(55.93±5.92)%,显著高于各自对照组的(0.38±0.52)%,(0.63±0.74)%(P<0.01).结论 本研究表明以Penh为主要测定指标的无创方法,可以成功检测哮喘小鼠气道高反应性.     

支气管哮喘小鼠气道反应性无创检测方法的建立

目的目前国内对支气管哮喘（简称哮喘）小鼠的评价多数仅立足于气道炎性指标,不能完全反映哮喘的病理生理特征。本所率先从国外引进了小动物无创检测和有创检测肺功能仪。无创法检测时小鼠不必麻醉,而且每次可以同时检测多只小鼠,具有较大的优越性,但能否取代有创法尚需更多的数据。本研究旨在建立无创检测小鼠气道高反应性的检测方法,并与有创检测方法进行比较。方法根据动物模型和气道反应性检测方法不同,动物分为：①无创哮喘组;②无创对照组;③有创哮喘组;④有刨对照组。采用卵白蛋白致敏和激发,建立BALB／c小鼠哮喘模型,生理盐水作为对照,分别用无创和有创的方法测定气道反应性。哮喘动物雾化吸入0．2～50g／L倍增浓度的乙酰甲胆碱（Mch）,测定相应浓度下的增强呼气间歇（Penh）值或气道阻力（RL）值等指标。将小鼠吸入Mch后RIJ或Penh增加2倍的激发浓度以PCIoo来表示。所有动物都行支气管肺泡灌洗,收集灌洗液,涂片染色后分类计数。结果无创哮喘组PCIoo均≤6．25g／L,对照组PCIoo均≥12．5g／L。其Log2（10PC100）值（5．36±0．84）显著低于对照组（7．97±0．82）（P〈0．01）。无创哮喘组从Mch浓度3．12g／L开始,其Penh值明显高于对照组。有创哮喘组RIJ值从Mch浓度0．39g／L开始就明显高于相应对照组（P〈0．05）。无创组与有创组的气道反应性相关系数R=0．96（P〈0．01）。无创哮喘组和有创哮喘组的嗜酸粒细胞分别为（54．00±5．96）％,（55．93±5．92）％,显著高于各自对照组的（0．38±0．52）％,（0．63±0．74）％（P〈0．01）。结论本研究表明以Penh为主要测定指标的无创方法,可以成功检测哮喘小鼠气道高反应性。     

支气管哮喘小鼠气道反应性无创检测方法的建立

目的目前国内对支气管哮喘(简称哮喘)小鼠的评价多数仅立足于气道炎性指标,不能完全反映哮喘的病理生理特征。本所率先从国外引进了小动物无创检测和有创检测肺功能仪。无创法检测时小鼠不必麻醉,而且每次可以同时检测多只小鼠,具有较大的优越性,但能否取代有创法尚需更多的数据。本研究旨在建立无创检测小鼠气道高反应性的检测方法,并与有创检测方法进行比较。方法根据动物模型和气道反应性检测方法不同,动物分为:①无创哮喘组;②无创对照组;③有创哮喘组;④有创对照组。采用卵白蛋白(OVA)致敏和激发,建立BALB/c小鼠哮喘模型,生理盐水作为对照,分别用无创和有创的方法测定气道反应性。哮喘动物雾化吸入0.2～50mg/ml倍增浓度的乙酰甲胆碱(Mch),测定相应浓度下的增强呼气间歇(Penh)值或气道阻力(RL)值等指标。将小鼠吸入Mch后RL或Penh增加2倍的激发浓度以PC100来表示。所有动物都行支气管肺泡灌洗,收集灌洗液,涂片染色后分类计数。结果无创哮喘组PC100均≤6.25mg/ml,对照组PC100均≥12.5mg/ml。其Log2(10PC100)值(5.36±0.84)显著低于对照组(7.97±0.82)(P<0.01)。无创哮喘组从Mch浓度3.12mg/ml开始,其Penh值明显高于对照组。有创哮喘组RL值从Mch浓度0.39mg/ml开始就明显高于相应对照组(P<0.05)。无创组与有创组的气道反应性相关系数R=0.96(P<0.01)。无创哮喘组和有创哮喘组的EOS(%)分别为(54.00±5.96)%,(55.93±5.92)%,显著高于各自对照组的(0.38±0.52)%,(0.63±0.74)%(P<0.01)。结论本研究表明以Penh为主要测定指标的无创方法,可以成功检测哮喘小鼠气道高反应性。     

气道变应性炎症与支气管哮喘

本文概述了气道变应性炎症和支气管哮喘的气道通气障碍、气道高反应性和迟发性哮喘反应之间的密切关系,据此并提出了哮喘发病机理和治疗的新概念。     

支气管哮喘气道炎症的非侵入性检测方法进展

目前公认的诊断和判断支气管哮喘（简称哮喘）疗效指标是临床症状及肺功能测定,但随着对哮喘发病机制和病理生理学的深入了解,需要有能够更直接的气道炎症的指标反映哮喘临床病情改变及预后。而非侵入性方法检测气道炎症已经成为目前研究的焦点,因为直接的气道炎症指标能够更确切指导哮喘抗炎治疗。     

气道炎症介质受体和支气管哮喘

气道内肥大细胞释放的炎症介质,是引起支气管哮喘病理生理改变的主要因素。这些炎症介质通过激活气道靶细胞表面的特异性受体,引起细胞反应而导致发病。开发特异性介质拮抗剂对于哮喘的临床治疗可能具有重要意义。     

支气管哮喘与气道炎症和支气管高反应性

现已普遍认为支气管哮喘是一种气道炎症（ＡＩ）疾病，支气管高反应性（ＢＨＲ）是其重要特征。本探讨了哮喘与ＡＩ和ＢＨＲ的关系，进而阐述哮喘的可能发病机制。     

Clinical features and airway inflammation in mild asthma versus asymptomatic airway hyperresponsiveness

RATIONALE: We still do not know why some subjects with airway hyperresponsiveness (AHR) experience no respiratory symptoms. OBJECTIVES: Our aim was to compare pulmonary function, perception of bronchoconstriction, and airway inflammation in atopic subjects with mild recently diagnosed (<5 years, n=30) or longer-standing (5 years or more, n=30) symptomatic asthma in comparison with atopic subjects with asymptomatic AHR (n=27). METHODS: All subjects had measurements of expiratory flows, PC(20) methacholine, perception of breathlessness and induced sputum cell differential, eosinophil cationic protein and alpha(2)-macroglobulin levels. RESULTS: Compared with the other groups, PC(20) was significantly lower in longer-standing asthma and perception score for breathlessness at 20% fall in FEV(1) was lower in asymptomatic subjects. Markers of airway inflammation were similar in all groups. There were no significant correlations between sputum eosinophils, alpha(2)-macroglobulin and/or eosinophil cationic protein levels and FEV(1), FVC or PC(20) in either group. CONCLUSION: Subjects with mild asthma or asymptomatic AHR are similar in regard to induced sputum markers of airway inflammation. Although perception of bronchoconstriction was slightly lower in asymptomatic subjects, additional factors are probably involved to explain why they report no respiratory symptoms. Further studies are needed to determine why these last are asymptomatic.     

Clinical use of noninvasive measurements of airway inflammation in steroid reduction in children

The use of noninvasive methods of monitoring airway inflammation, such as exhaled nitric oxide (eNO) and induced sputum, has been shown to improve asthma monitoring and optimize treatment in adult patients with asthma. There is a lack of comparable data in children. Forty children with stable asthma eligible for inhaled steroid reduction were reviewed every 8 weeks, and their inhaled steroid dose halved if clinically indicated. eNO, sputum induction combined with bronchial hyperreactivity testing, and exhaled breath condensate collection were performed at each visit to predict success or failure of reduction of inhaled steroids. Thirty of 40 (75%) children tolerated at least one dose reduction, 12 of 40 (30%) were successfully weaned off, and in total, 15 of 40 (38%) children experienced loss of asthma control. Treatment reduction was successful in all children who had no eosinophils in induced sputum before the attempted reduction. Using multiple logistic regression, increased eNO (odds ratio, 6.3; confidence interval, 3.75-10.58) and percentage of sputum eosinophils (odds ratio, 1.38; confidence interval, 1.06-1.81) were significant predictors of failed reduction. These findings suggest that monitoring airway inflammation may be useful in optimizing treatment in children with asthma.     

Pharmacology of airway inflammation in asthma

Chronic desquamative eosinophilic bronchitis is a characteristic pathologic feature of asthma which may even antedate the onset of symptoms. The pharmacology of asthmatic inflammation has been relatively poorly studied and most of the current data available have been inferred indirectly from studies of bronchial hyperresponsiveness and late-phase responses. Apart from mast cells, the effects of drugs used in the treatment of asthma on other airway inflammatory cells such as eosinophils, alveolar macrophages, etc. have not been extensively studied. The pharmacology of asthmatic inflammation should comprise the study of various aspects of this inflammatory response such as airway microvascular leakage, mediator release, and cell chemotaxis. Ultimately the pharmacologic modulation of the pathologic features of the asthmatic airway by the chronic use of antiasthma drugs, coupled with clinical responses, need to be investigated using bronchial biopsies and broncholveolar lavage in asthmatic patients.     

支气管哮喘气道炎症可能机制的探讨

目的探讨支气管哮喘（简称哮喘）患者气道炎症特征及其可能机制,并进一步观察吸入糖皮质激素治疗对气道炎性细胞分类计数、炎症介质等的影响。方法分别选择轻度（轻度组）、中度（中度组）和重度（重度组）持续哮喘患者15例、14例和19例,正常对照组15名,分别行哮喘症状控制评分、肺功能测定、诱导痰炎性细胞分类计数、调节激活正常T细胞表达和分泌细胞因子（RANTES）、嗜酸粒细胞阳离子蛋白（ECP）、白介素8（IL～8）及髓过氧化物酶（MPO）浓度检测,然后规范吸入糖皮质激素治疗4周,随访复查上述指标。结果诱导痰中性粒细胞百分比、IL-8及MPO重度组明显升高,分别为（62．40±22．05）％、594．53±85．11、39．25±10．67与轻度组[（47．23±15．12）％、183．63±120．98、12．47±4．15]、中度组[（46．13±19．23）％、352．76±71．72、22．93±7．353、正常对照组[（31．44±13．31）％、103．26±36．33、10．22±4．13]比较差异均有统计学意义（P〈O．01）;RANTES、嗜酸粒细胞百分比（EOS％）和ECP浓度在各哮喘组间比较差异无统计学意义（P〉0．05）。EOS％与RANTES、ECP水平呈正相关（r=0．557,P〈0．05;r=0．852,P〈0．01）;中性粒细胞百分比与IL-8、MPO水平呈正相关（r=0．732,P〈0．05;r=0．806,P〈0．05）;经糖皮质激素治疗后,对轻、中、重度哮喘患者合并进行分析表明,治疗后症状评分由（9．8±5．4）分下降至（4．0±3．5）分和肺功能指标第1秒用力呼气容积占预计值百分比由（62．2±23．3）％升高至（75．9±17．5）％显著改善,差异有统计学意义（P〈0．01）。在接受糖皮质激素治疗后,RANTES、EOSO和ECP水平均显著降低。另外MPO水平也显著降低（P〈0．01）;但治疗后在重度组仍显著高于轻、中度组（P〈0．01）。但IL-8、中性粒细胞百分比治疗后?     

支气管哮喘气道炎症可能机制的探讨

目的 探讨支气管哮喘(简称哮喘)患者气道炎症特征及其可能机制,并进一步观察吸入糖皮质激素治疗对气道炎性细胞分类计数、炎症介质等的影响.方法 分别选择轻度(轻度组)、中度(中度组)和重度(重度组)持续哮喘患者15例、14例和19例,正常对照组15名,分别行哮喘症状控制评分、肺功能测定、诱导痰炎性细胞分类计数、调节激活正常T细胞表达和分泌细胞因子(RANTES)、嗜酸粒细胞阳离子蛋白(ECP)、白介素8(IL-8)及髓过氧化物酶(MPO)浓度检测,然后规范吸人糖皮质激素治疗4周,随访复查上述指标.结果 诱导痰NEU%、IL-8及MPO重度组明显升高,分别为(62.40±22.05)%、594.53±85.11、39.25±10.67与轻度组[(47.23±15.12)%、183.63±120.98、12.47±4.15]、中度组[(46.13±19.23)%、352.76±71.72、22.93±7.35]、正常对照组[(31.44±13.31)%、103.26±36.33、10.22±4.13]比较差异均有统计学意义(P＜0.01);RANTES、嗜酸粒细胞百分比(EOS%)和ECP浓度在各哮喘组间比较差异无统计学意义(P＞0.05).EOS%与RANTES、ECP水平呈正相关(r=0.557,P＜0.05;r=0.852,P＜0.01);NEU%与IL-8、MPO水平呈正相关(r=0.732,P＜0.05;r=0.806,P＜0.05);经糖皮质激素治疗后,对轻、中、重度哮喘患者合并进行分析表明,治疗后症状评分由(9.8±5.4)分下降至(4.0±3.5)分和肺功能指标第一秒用力呼气容积占预计值百分比由(62.2±23.3)%升高至(75.9±17.5)%显著改善,差异有统计学意义(P＜0.01).在接受糖皮质激素治疗后,RANTES、EOS%和ECP水平均显著降低.另外MPO水平也显著降低(P＜0.01);但治疗后在重度组仍显著高于轻、中度组(P＜0.01).但IL-8、NEU%治疗后无明显降低(P＞0.05),而且治疗后IL-8、NEU%在重度组仍显著高于轻、中度组(P＜0.01).结论 中性粒细胞增多是重度哮喘的气道炎症特征之一,EOS与病情严重程度无关.EOS哮喘的发生可能与RANTES的趋化、EOS的活化、ECP的释放有关,激素可以抑制EOS气道炎症.而中性粒细胞哮喘的发生可能与IL-8的趋化、NEU的活化、MPO的释放有关.     

Measurement of airway inflammation in asthma.

Chronic airway inflammation is considered responsible for symptoms and disorders of airway function associated with asthma. This process is the target of anti-inflammatory therapy, so a number of standardized, noninvasive techniques have been developed to assess it. More recent approaches include the measurement of exhaled gases and nonvolatile substances in breath condensate. Results from studies using a wide variety of inflammatory markers have shown group differences between patients with asthma and healthy control subjects, but evidence for the diagnostic use of these markers in individual patients is scarce. Similarly, despite many studies demonstrating some correlation between markers of airway inflammation and a measure of disease control, none has yet convincingly shown a place for the use of these markers in an individual with corticosteroid-treated asthma. However, application of these markers continues to further our understanding of the disease process and provides the potential for more appropriate, customized therapy.     

Formoterol attenuates neutrophilic airway inflammation in asthma

STUDY OBJECTIVES: Airway neutrophil levels are increased in patients with severe asthma and during asthma exacerbations. Long-acting beta2-agonists (LABAs), such as formoterol, reduce the number of asthma exacerbations. While beta2-agonists may affect neutrophil function in vitro, it is uncertain whether they have effects on neutrophilic inflammation in asthmatic patients in vivo. DESIGN: In a double-blind randomized crossover study, we evaluated the effects of 4 weeks of treatment with formoterol (Turbuhaler), 24 microg bid, compared to placebo on sputum neutrophil numbers and interleukin (IL)-8 levels in asthmatic patients. Therapy with budesonide (administered via Turbuhaler), 400 microg bid for 4 weeks, was added at the end as a "gold standard" antiinflammatory effect comparison. PATIENTS: We studied 15 steroid-na?ve nonsmoking patients who ranged from 19 to 51 years of age and had mild persistent asthma. RESULTS: Formoterol therapy significantly reduced sputum IL-8 levels and neutrophil numbers compared to placebo. There was a significant correlation between the reduction in sputum IL-8 levels and the number of neutrophils, indicating that formoterol may attenuate neutrophilic airway inflammation by inhibiting IL-8 production. CONCLUSIONS: Our data suggest that the LABA formoterol reduces neutrophilic airway inflammation in patients with mild asthma and that this might be beneficial in preventing asthma exacerbations.     

Pharmacology of airway inflammation in asthma and COPD

The current asthma therapies are not cures and symptoms return soon after treatment is stopped even after long term treatment. Although inhaled glucocorticoids are highly effective in controlling airway inflammation in asthma, they are ineffective in the small group of patients with glucocorticoid-dependent and -resistant asthma. With very few exceptions, COPD is caused by tobacco smoking, and smoking cessation is the only truly effective treatment of COPD available. Current pharmacological treatment of COPD is unsatisfactory, as it does not significantly influence the severity of the disease or its natural course. Glucocorticoids are scarcely effective in COPD patients without concomitant asthma. Bronchodilators improves symptoms and quality of life, in COPD patients, but, with the exception of tiotropium, they do not significantly influence the natural course of the disease. Theophylline is the only drug which has been demonstrated to have a significant effect on airway inflammation in patients with COPD. Here we review the pharmacology of currently used antiinflammatory therapies for asthma and COPD and their proposed mechanisms of action. Recent understanding of disease mechanisms in severe steroid-dependent and -resistant asthma and in COPD, has lead to the development of novel compounds, which are in various stages of clinical development. We review the current status of some of these new potential drugs.     

Clinical assessment of asthma severity partially corresponds to sputum eosinophilic airway inflammation

In the aim to evaluate the relationship between sputum eosinophil percentages and eosinophil cationic protein (ECP) concentrations, as markers of airway inflammation, and different Levels of asthma severity, we examined 223 patients consecutively observed in our asthma clinic. Diagnosis of asthma was made according to internationally accepted criteria. Asthma severity was evaluated according to frequency of symptoms, FEV1, peak expiratory flow variability and level of asthma treatment needed to control asthma. Spontaneous or induced sputum was collected. Adequate sputum samples were obtained in 68 untreated subjects and in 117 subjects regularly treated with ICS. A control group of 14 normal subjects was also examined. In untreated subjects, mild intermittent asthmatics showed a lower sputum eosinophil percentage in comparison with other groups of asthma severity, while no difference in ECP levels was detected. In treated subjects, severe asthmatics showed higher levels of sputum eosinophils and ECP in comparison with other groups of asthma severity. Mild persistent and moderate persistent patients did not differ for sputum eosinophils or ECP in both untreated and treated subjects. Controls were significantly different from all groups of untreated and treated asthmatics. In conclusion, the assessment of asthma severity according to clinical and functional findings only partially corresponds to the severity of eosinophilic airway inflammation as assessed by induced sputum analysis.