慢性阻塞性肺疾病加重风险与血纤维蛋白原、C 反应蛋白和白细胞的关系

近年来,慢性阻塞性肺疾病（COPD）的系统性炎症标记物成为热点,临床需要有更多的客观指标来评估 COPD,为其诊治提供更多的帮助。有研究表明,血纤维蛋白原（Fib）、C 反应蛋白（CRP）和白细胞计数（WBC）等均可作为炎症介质用以评估COPD 病情［1］,但其与 COPD 高风险急性加重的关系,尚待进一步探讨。     

慢性阻塞性肺疾病的肺部炎症与全身炎症

慢性阻塞性肺疾病(COPD)是以不完全可逆性气流受限为特征的炎症性疾病,与肺部对香烟烟雾等有害气体或有害颗粒的异常炎症反应有关,同时也存在慢性的全身炎症反应和全身性不良影响,共同影响气流受限的程度和进展。COPD患者体内多种生物标志物明显升高,相关生物标志物的研究,将有助于探索新的干预切入点以及COPD病情评估和治疗反应性监测。     

慢性阻塞性肺疾病患者纤维蛋白原水平与血气分析的相关性

慢性阻塞性肺疾病(COPD)急性加重期患者存在系统性炎症并处于高凝状态,疾病进展与全身循环中炎性蛋白增加、血液高凝状态有关,纤维蛋白原(FIB)是反映系统性炎症的有效标志物.本研究旨在探讨COPD患者血浆FIB与血气分析的相关性. 1对象与方法 1.1 研究对象 2010年3月至2011年6月我院呼吸科住院的COPD患者63例,男49例,女14例,平均年龄(65±4)岁,诊断均符合《慢性阻塞性肺疾病诊治指南》[1],同时排除COPD外的呼吸系统疾病.同时期体检中心健康体检者73例设为对照组:男性53例,女性20例,年龄50～ 83岁,平均年龄(65±3)岁,均符合健康者标准.各组年龄、性别差异无统计学意义,具有可比性.     

冠心病患者血浆D-二聚体和纤维蛋白原含量的变化及其临床意义

D—二聚体(DD)是交联纤维蛋白的降解产物，即反映体内的纤溶活性，又反映凝血活动。纤维蛋白原(Fg)是一种急性时相蛋白，参与凝血过程，是血栓的主要成份，因此DD和Fg被认为是冠心病发生发展的危险因素之一。我们检测了126例冠心病(CHD)患者DD和Fg含量，并与正常对照组进行对比分析，旨在探讨其临床意义。     

静脉血栓栓塞症与脂蛋白(a)、纤维蛋白原浓度的关系

静脉血栓栓塞症(VTE)是一种严重的、潜在致死性疾病,包括肺血栓栓塞症和深静脉血栓形成。这一疾病在我国的发病率有逐年增高趋势,目前临床上仍缺乏有效的手段来早期评估血栓和栓塞的风险及预后。我们通过对静脉血栓栓塞症病人的血清脂蛋白(a)[Lp(a)]水平和纤维蛋白原[Fg]浓度的检测,以探讨Lp(a)和Fg这一危重疾病的关系。临床资料1.对象:选择2002~2005年急性肺血栓栓塞住院病人32例,男20例,女12例,年龄30~82岁,平均年龄60岁±12岁,设为肺血栓栓塞症组。所有病人经肺螺旋CT或MRI确诊。另选同期经下肢血管超声明确诊断的深静脉血栓形成病…     

COPD患者D-二聚体和纤维蛋白原检测的临床价值

目的 探讨COPD患者血浆D-二聚体和纤维蛋白原检测的临床意义.方法 分别检测122例按病情严重程度分期、分度的COPD患者和30例健康对照组血浆D-二聚体和纤维蛋白原含量,分析比较各组间血浆D-二聚体和纤维蛋白原含量的差异.结果 COPD患者血浆D-二聚体和纤维蛋白原含量明显高于健康对照组(P＜0.05),且急性加重期明显高于稳定期(P＜0.05).在75例急性加重期COPD患者中,轻、中、重、极重度患者其血浆D-二聚体和纤维蛋白原含量间相互比较(P＜0.05).结论 COPD患者存在血液高凝状态,且随着病情的加重而加重,对其监测和预防性使用抗凝、溶栓剂是非常必要的.     

纤维蛋白(原)、纤维蛋白(原)降解产物及其基序拮抗剂与动脉粥样硬化

动脉粥样硬化是缺血性脑血管病最主要的病理学基础。作为动脉粥样硬化的独立危险因素,纤维蛋白(原)及其降解产物参与了动脉粥样硬化的形成和发展过程。文章综述了纤维蛋白(原)及其降解产物与动脉粥样硬化的关系,并对纤维蛋白(原)某些特定基序拮抗剂在治疗动脉粥样硬化和缺血性脑血管病方面的开发和应用前景做了介绍。     

老年心肌梗死的早期预警指标

<正>老年心肌梗死症状不典型,临床上容易漏诊,严重威胁着老年人群的健康与生命,如何早期识别急性心肌梗死的发生已成为大家广泛关注的焦点。急性心肌梗死(AMI)是在冠状动脉病变的基础上,发生冠状动脉血流供应急剧减少或中断导致相应心肌严重而持久的急性缺血。其病理基础是冠状动脉粥样硬化,同时在疾病发展过程中存在着凝血和纤溶系统失调。D-二聚体(D-D)是交联纤维蛋白特异性降解产物,当体内有活     

血液CPR、IL-6和纤维蛋白原动态检测与不稳定型心绞痛患者预后的关系

不稳定型性心绞痛（UAP）是急性冠脉综合症（ACS）的一种。冠状动脉粥样硬化（AS）是ACS的病理生理基础，炎症贯穿于AS病变发生、发展和恶化的全过程。炎症细胞大量激活、炎症介质释放及水平的增加、粥样斑块破裂、血栓形成等因素共同参与ACS的发生和发展。心血管疾病标志物种类繁多，C-反应蛋白（CPR）、白细胞介素6（IL-6）和纤维蛋白原（Fib）检测在ACS患者中应用的报道较多，     

慢性阻塞性肺疾病与凝血-纤溶功能异常

慢性阻塞性肺疾病（COPD）是以气道、肺实质和肺血管的慢性炎症为特征。因肺内通气血流比例失调致慢性缺氧，可继发红细胞增多和血黏滞度增高，引起血流高黏、高聚、高凝及微血栓形成。COPD急性加重期凝血-纤溶功能异常进一步恶化，对病情进展的影响已经为临床高度关注。研究同时发现COPD与静脉血栓栓塞症（VTE）关系密切，其合并深静脉血栓（DVT）甚至肺血栓栓塞症（PTE）已成为重要的医疗保健问题。     

慢性阻塞性肺疾病全身炎症表型的特点

COPD是一种异质性疾病,有或者没有肺外表现,且疾病进展、治疗效果及预后不尽相同,仅仅用FEV,来描述其异质性是远远不够的,需要一个能在临床上更加符合疾病发展及预后评估的标准。于是便引出了COPD表型的概念,通过COPD患者临床表现、加重频率、疾病进展、治疗的有效性及预后等研究,将疾病分成几个亚型,每个亚型均有各自特征,根据这些特征来采取针对性或个性化治疗,使诊疗更具有效性。炎症在COPD疾病发生和发展中有着重要的作用,c0PD的全身炎症表型已被列为一个单独的亚型,而其在COPD诊断、治疗及预后评估中的价值仍有待更进一步研究。     

Helicobacter pylori seroprevalence in patients with chronic obstructive pulmonary disease and its relation to pulmonary function tests

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a slowly progressive condition characterized by poorly reversible airflow limitation that is associated with an abnormal inflammatory response of the lung. It has been shown that there is a seroepidemiological association of Helicobacter pylori (Hp) infection with many inflammatory conditions. OBJECTIVE: In this study, we aimed to investigate seroprevalence in Hp patients with COPD and to determine whether there is an association between Hp infection and COPD. METHODS: Forty-nine voluntary patients with COPD and 50 healthy control subjects of similar age and sex were included in the study. Hp-specific IgG was measured with a commercially available kit from venous blood samples. RESULTS: Serum levels of Hp-specific IgG and Hp IgG seropositivity were significantly higher in the patients with COPD than in the control subjects (p < 0.001 and p = 0.006, respectively). In addition, when the patients with COPD were grouped according to Hp IgG seropositivity, forced expiratory volume in 1 s (FEV(1)) values were lower in the seropositive patients compared to seronegative patients, and Hp serum IgG levels were correlated with FEV(1) values, which indicate the severity of COPD, in the COPD group (r = -0.306, p = 0.032). CONCLUSION: The results suggest that there is an association between Hp infection and COPD, and Hp IgG levels are correlated with the severity of COPD.     

Leptin as local inflammatory marker in COPD

INTRODUCTION: Chronic inflammation of the lung is a characteristic finding in chronic obstructive pulmonary disease (COPD). Leptin is a pleiotropic cytokine thought to play a role in host response to inflammation. As recent studies have shown that leptin receptors are present in the lung, this study aimed to determine if leptin is detectable in induced sputum of COPD patients and if there is a relationship between leptin and other inflammatory markers in sputum. METHODS: Sputum was induced in 14 male patients with moderate COPD (FEV1: 56 (15) % pred.). Leptin, total tumour necrosis factor (TNF)-alpha, and C-reactive protein (CRP) were analyzed in induced sputum supernatant by ELISA. Leptin was also determined in EDTA plasma. RESULTS: Leptin was detectable in induced sputum of 10 COPD patients. A significant relationship was found between sputum leptin and CRP (r = 0.943, P < 0.001) and total TNF-alpha (r = 0.690, P < 0.01). Plasma leptin and sputum leptin were inversely correlated (r = -0.643, P < 0.01). CONCLUSION: The present study demonstrated that leptin is detectable in induced sputum of patients with moderate COPD and is related to other inflammatory markers. The observed correlations between leptin and inflammatory markers in sputum may indicate that leptin is involved in the local inflammatory response in COPD.     

Airway inflammation in severe chronic obstructive pulmonary disease: relationship with lung function and radiologic emphysema

The lung pathology of severe chronic obstructive pulmonary disease (COPD) has been poorly investigated. We examined surgical specimens obtained from patients with severe (forced expiratory volume in 1 second [FEV(1)] = 29 +/- 3% predicted, n = 9) or mild/no airflow limitation (FEV(1) = 86 +/- 5% predicted, n = 9) and similar smoking history. With histochemical and immunohistochemical methods we quantified the structural changes and the inflammatory cells in small airways and in muscular pulmonary arteries. As compared with smokers with mild/no COPD, smokers with severe COPD had an increased number of leukocytes in the small airways, which showed a positive correlation with the radiologic score of emphysema and with the value of residual volume, and a negative correlation with the values of FEV(1) and carbon monoxide diffusing capacity. The inflammatory process was characterized by an increase in CD8(+) and CD4(+) T-lymphocytes in the airway wall and by an increase in macrophages in the airway epithelium. When all smokers were considered together, the smoking history was correlated with both the airway wall and smooth muscle thickness, suggesting that smoking itself may play a role in the development of structural changes. No structural and cellular differences were observed in pulmonary arteries between smokers with severe COPD and smokers with mild/no COPD. In conclusion, in the small airways of smokers with severe COPD, there is an increased number of leukocytes, which is correlated with reduced expiratory flow, lung hyperinflation, carbon monoxide diffusion impairment, and radiologic emphysema, suggesting a role for this inflammatory response in the clinical progression of the disease.     

Airway mucosal inflammation in COPD is similar in smokers and ex-smokers: a pooled analysis.

Bronchial biopsy specimens from chronic obstructive pulmonary disease (COPD) patients demonstrate increased numbers of CD8+ T-lymphocytes, macrophages and, in some studies, neutrophils and eosinophils. Smoking cessation affects the rate of forced expiratory volume in one second (FEV(1)) decline in COPD, but the effect on inflammation is uncertain. Bronchial biopsy inflammatory cell counts were compared in current and ex-smokers with COPD. A pooled analysis of subepithelial inflammatory cell count data from three bronchial biopsy studies that included COPD patients who were either current or ex-smokers was performed. Cell count data from 101 subjects, 65 current smokers and 36 ex-smokers, were analysed for the following cell types: CD4+ and CD8+ T-lymphocytes, CD68+ (monocytes/macrophages), neutrophil elastase+ (neutrophils), EG2+ (eosinophils), mast cell tryptase+ and cells mRNA-positive for tumour necrosis factor-alpha. Current smokers and ex-smokers were similar in terms of lung function, as measured by FEV(1) (% predicted), forced vital capacity (FVC) and FEV(1)/FVC. The results demonstrate that there were no significant differences between smokers and ex-smokers in the numbers of any of the inflammatory cell types or markers analysed. It is concluded that, in established chronic obstructive pulmonary disease, the bronchial mucosal inflammatory cell infiltrate is similar in ex-smokers and those that continue to smoke.     

Chronic obstructive pulmonary disease: linking outcomes and pathobiology of disease modification

Recent guidelines define chronic obstructive pulmonary disease (COPD) as a preventable and treatable disease characterized by airflow limitation and systemic consequences. Airflow limitation in COPD worsens over years as assessed by the forced expiratory volume in one second (FEV(1)). Regardless, while it is likely that cardiovascular and other systemic components also worsen as COPD progresses, there are no accepted or validated outcomes to measure such pathophysiologic changes as they relate to COPD disease progression. It is clear that health status in COPD is more closely related to levels of patients' physical functional capacity than it is to changes in FEV(1). Furthermore, the relative contributions of pathoanatomic changes such as small airways fibrosis and pulmonary emphysema to declining airflow remain unknown. These features may even progress at different rates in the same individuals. Although stopping smoking is the only intervention shown to alter the relentless progression of COPD, the resultant slowing of FEV(1) decline takes several years to evince and requires at least 1,000 subjects to demonstrate annual therapeutic benefits of as little as 20 ml. The FEV(1) cannot distinguish between peribronchiolar fibrosis and emphysema and it is feasible that, as techniques are developed and validated, lung imaging methodologies may become important and sensitive outcomes measures of time- and age-dependent lung structural changes in COPD. The development of biomarkers of lung damage, pulmonary inflammation, and systemic disease will be essential to our further understanding of the natural history of COPD and the discovery of new, effective treatments for its progression.     

Airway epithelial inflammatory responses and clinical parameters in COPD.

This study examined inflammatory responses from primary cultured human bronchial epithelial cells in chronic obstructive pulmonary disease (COPD) and the clinical factors modulating them. Epithelial cells from bronchoscopic biopsies from 14 patients with COPD ((mean +/- SD) age 74.6 +/- 5.7 yrs, forced expiratory volume in one second (FEV1) 1.21 +/- 0.36 L, FEV1 %, predicted 51.1 +/- 15.8%, 51.5 +/- 24.0 pack-yrs of smoking, inhaled steroid dosage 1237.5 +/- 671.0 microg x day(-1), Medical Research Council (MRC) dyspnoea score 3.18 +/- 1.33) and eight current/exsmokers with normal pulmonary function (age 60.4 +/- 13.5 yrs, FEV1 2.66 +/- 1.27 L, FEV1 % pred 89.6 +/- 17.7%, 49 +/- 44 pack-yrs of smoking, MRC dyspnoea score 1 +/- 0) were grown in primary culture and exposed to 50 ng x mL(-1) tumour necrosis factor-alpha. Stimulated COPD cells produced significantly more interleukin (IL)-6 at 24 and 48 h, and IL-8 at 6 and 24 h than unstimulated COPD cells. This response was not seen in cells from current/exsmokers. IL-6 and IL-8 production was lower in COPD patients taking inhaled steroids. Following an inflammatory stimulus, bronchial epithelial cells in chronic obstructive pulmonary disease show a significant cytokine response not seen in smokers with normal pulmonary function and this may be modified by inhaled steroid therapy.     

The 6-min walking distance: long-term follow up in patients with COPD.

The 6-min walking distance (6MWD) test is used in clinical practice and research into patients with chronic obstructive pulmonary disease (COPD). However, little is known about natural long-term change in this parameter. The 6MWD was measured at baseline and then annually for 5 yrs in 294 patients with COPD and its annual rate of decline was determined. Forced expiratory volume in one second (FEV1) was also measured and the relationship between changes in both markers was explored. At baseline, the median 6MWD was 380 m (range 160-600 m). It declined by 19% (16 m.yr(-1)) over the 5 yrs compared with baseline in patients with American Thoracic Society/European Respiratory Society stage III COPD (FEV1 30-50% predicted) and by 26% (15 m.yr(-1)) in patients with stage IV COPD (FEV1 <30% pred). Over the 5-yr follow-up, the proportion of patients with a minimal clinically significant decline of 54 m increased with the severity of the disease. It was 24% in stage II, 45% in stage III, and 63% in stage IV disease. In contrast, the rate of decline of FEV1 was greater in patients with milder airflow obstruction and lesser in patients with lower absolute FEV1 values. In conclusion, the 6-min walking distance test provides increasingly useful information as the severity of chronic obstructive pulmonary disease increases.     

Evolution of changes in carbon monoxide transfer factor in men with chronic obstructive pulmonary disease

Progression of chronic obstructive pulmonary disease (COPD) has been studied predominantly by following change in forced expiratory volume in 1s (FEV1) which reflects both primary airway disease and associated alveolar disease. Carbon monoxide transfer (Tlco) (the product of the transfer coefficient Kco and alveolar volume Va) is the only simple, widely available test of alveolar function, but few studies have followed long-term changes in an individual. Seventeen middle-aged men with moderate chronic airflow obstruction (mean FEV1 56% of predicted values) were observed with yearly measurements of FEV1, Tlco and Kco over a mean of 18.9 yr. At the end of follow-up FEV1 had fallen to 29% of predicted values. Va, measured by single breath dilution, fell in each man. Kco at recruitment ranged from 41% to 110% predicted and remained >75% predicted in eight men at the end of follow-up supporting a phenotype of COPD with predominant airway disease and little emphysema. Fall in FEV1 was faster (2.03% predicted FEV1/yr) in seven men with low initial Kco<75% pred. than in men with initial Kco>75% pred. (1.14% predicted FEV1/yr, P=0.006). Repeated measurements of CO transfer in an individual should increase the present poor knowledge of the contribution of alveolar disease to the progression of chronic airflow obstruction.     

Dissociation of lung function and airway inflammation in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is defined by progressive, irreversible airflow limitation and an inflammatory response of the lungs, usually to cigarette smoke. However, COPD is a heterogeneous disease in terms of clinical, physiologic, and pathologic presentation. We aimed to evaluate whether airflow limitation, airway responsiveness, and airway inflammation are separate entities underlying the pathophysiology of COPD by using factor analysis. A total of 114 patients (99 males/15 females, age 62 +/- 8 years, 42 pack-years smoking, no inhaled or oral steroids > 6 months) with irreversible airflow limitation (postbronchodilator FEV(1) 63 +/- 9% predicted, FEV(1)/inspiratory vital capacity [IVC] 48 +/- 9%) and symptoms of chronic bronchitis or dyspnea were studied in a cross-sectional design. Postbronchodilator FEV(1) and FEV(1)/IVC, reversibility to inhaled beta(2)-agonists, diffusing capacity, provocative concentration of methacholine required to produce a 20% drop in FEV(1), total serum IgE, exhaled nitric oxide, and induced sputum cell counts (% eosinophils, % neutrophils) were collected. Factor analysis yielded 4 separate factors that accounted for 63.6% of the total variance. Factor 1 was comprised of FEV(1), FEV(1)/IVC, and residual volume/total lung capacity. Factor 2 included reversibility, IgE, provocative concentration of methacholine required to produce a 20% drop in FEV(1,) and diffusing capacity. Factor 3 contained exhaled nitric oxide and factor 4 included sputum % neutrophils and % eosinophils. We conclude that airflow limitation, airway inflammation, and features commonly associated with asthma are separate and largely independent factors in the pathophysiology of COPD.