抽象
本研究的目的是确定的发病率和风险因素的慢性阻塞性肺病(COPD)的加重静脉血栓栓塞(VTE)。
慢性阻塞性肺病患者住院与一个恶化被包括连续。记录入院时的症状、体征、临床、血液学和流行病学参数。所有患者均接受了计算机断层血管造影和超声检查,以确定是否存在深静脉血栓和肺栓塞(PE)。计算威尔斯和日内瓦分数。随访1年以确定死亡率。
深静脉血栓形成和PE在14两18例患者分别进行检测。The prevalence of VTE was three times higher in patients with an exacerbation of unknown origin than in patients with an exacerbation of known origin (p = 0.016). Of patients with VTE, 20 (95%) had high D-dimer levels. The negative predictive value of D-dimer testing was 0.98. Although the moderate- and high-risk categories of both the Wells and Geneva methods covered all PE patients, the Wells method identified 49% less potential patients for PE investigation. Mortality at 1 yr was higher (61.9%与(31.8%)静脉血栓栓塞患者(p = 0.013)。
VTE与恶化住院COPD患者一个共同的问题,从而导致长期的高死亡率。d二聚体水平,并且将孔的标准可以被用来确定这些患者是否被评估一种对血栓栓塞事件。
慢性阻塞性肺疾病(COPD)是死亡率和发病率全世界的主要原因之一1。一旦因住院任何原因的慢性阻塞性肺病加重,患者的5-10%,尽管竭尽全力死亡2。间COPD恶化的触发因素,肺栓塞(PE)的作用尚未清楚确定。在以前的研究中,只有发作的原因不明,住院患者被纳入3.- - - - - -7。然而,除了具有很强的共同的危险因素,比如是非常老人和不动,被排除的患者群体(含因支气管炎感染,肺炎和心衰加重)确实是在肺血栓栓塞的发展的风险增加。相反,高度相关的实体,在COPD急性加重深静脉血栓(DVT)的发生,评估只有在一些关于PE的研究5- - - - - -7。有一项研究解决深静脉血栓形成的COPD急性加重存在作为一个单独的问题8。
方法论的变化和参与者在前人的研究数量有限,未允许调查人员得出确定的结论为如何处理加剧COPD患者在静脉血栓栓塞(VTE)的角度去约会。因此,本研究旨在探索与加重住院的所有COPD患者VTE的频率。除了这一点,目的是确定其死亡率和相关因素的影响。
患者和方法
本研究在伊诺努大学医院(马拉蒂亚,土耳其)的肺部门进行。这家医院作为最大的地区医院,并与该地区加剧广大的COPD患者在本单位住院治疗。由于COPD急性加重肺部药物或急救医学科的门诊住院的所有病人均连续参加到前瞻性的方式本研究。根据社会保障制度,患者在该地区约70%可以直接向大学医院无需任何转诊。该研究方案经图尔古特·厄扎尔研究中心(马拉蒂亚,土耳其)的马拉蒂亚市地区伦理委员会,并从所有参与者获得知情同意书。COPD的诊断为取决于患者特征,如病史(以往的诊断,住院,门诊就诊次数和病人及相关报表),可用的官方医疗记录(肺功能测试结果,胸片及血气组合水平)和药物利用。根据一个或多个以下指示中的存在下进行住院的测定:严重症状加重;紫绀和外周性水肿的新发;混乱; lethargy; coma; use of accessory muscles for ventilation; significant comorbid conditions; failure to respond to initial treatment; judgment that treatment at home would be insufficient; acidosis; persistent or worsening hypoxaemia and/or severe or worsening hypercapnia and new-onset arrhythmias. Patients with exacerbation due to pneumothorax or iatrogenic reasons were excluded.
住院治疗后,至少两名临床医生进行了详细的初步临床评估,包括PE风险分层的计算。这些临床医生对VTE调查结果不知情。所有患者都接受了详细的体检和病史询问。记录流行病学资料、加重期和静止期患者的特征。立即对呼吸室内空气时静息动脉血气体水平和详细的生化和血液学参数进行分析,包括d -二聚体水平。肺动脉栓塞的含量< 0.5μg·毫升−1被认为在正常范围内(STA Liatest D-Di;诊断Stago, Inc., Parsippany, NJ, USA)。常规胸片和肺活量测量。对于每个患者,慢性阻塞性肺病严重程度的分类是根据全球慢性阻塞性肺病倡议(Global Initiative For Chronic Obstructive Lung Disease, GOLD)标准进行的,该标准依赖于稳定状态肺量测量、长期耗氧量和既往慢性呼吸功能不全诊断的存在1。接着,将患者分为两个亚组:1)患者具有已知病因的恶化住院;和住院病因不明的急性发作2)患者。根据感染的迹象(增加的痰和/或脓痰,发热,寒战,咽痛,胸部X光片对肺炎明显上呼吸道感染和固结的存在下),客观发现心脏衰竭,曝光存在下进行病原学判定到关于不遵守药物或氧处理,安排肺康复和营养状况明显的问题和病人的家庭护理的忽视吸入刺激性颗粒或有毒气体,病人声明。根据上述数据,将患者使用Wells和日内瓦标准为在低,中和PE的高风险分类,如其他地方所详细描述9,10。
All patients underwent dynamic computed tomography (CT) scanning (CT angiography) to reveal thrombus formation in the lower extremities and emboli in the lungs (spiral CT; Philips Secura; Philips, Best, The Netherlands) within 24 h following hospitalisation. CT scans of the thorax were performed during breath-holding, with injection of 130 mL nonionic contrast material (iopromide; Ultravist-300; Schering, Baar, Switzerland) for patients with a body mass index of ≤30 kg·m−2,功率注射器为3ml·s−1and using a slice thickness of 3 mm, tube voltage of 120 kV and tube current of 240 mA. The injection volume of the contrast material was increased to 150 mL for patients with a body mass index of >30 kg·m−2,and tube voltage to 140 kV. The reconstruction interval was 2 mm. PE was diagnosed if the contrast material outlined an intraluminal defect, or if the vessel was totally occluded by low-attenuation material. For detection of DVT, starting from the subdiaphragmatic level to the popliteal level, all veins were scanned 180 s after contrast material injection for CT pulmonary angiography, with a slice thickness of 5 mm and slice interval of 5 cm. The diagnostic criteria for DVT on CT venography were the presence of an intraluminal filling defect in an opacified vein, or a localised non-opacified venous segment on at least two consecutive axial CT images if the vein distal and proximal to the non-opacified segment was opacified. Doppler ultrasonography (ATL-HDI 3500; ATL, Seattle, WA, USA) was also utilised as a standard method in the identification of thrombi in the lower extremities. From the common femoral vein to the popliteal vein of both lower extremities were examined using the venous compression technique with ultrasonography. Noncompressibility of the veins was considered to indicate DVT.
心脏功能的心电图记录和超声心动图检查(ATL-HD 5000; ATL)进一步评估,以揭示PE的直接和间接征象,如肺动脉栓塞的直接观察,左室间隔膨隆,右心室运动功能减退超声心动图和窦性心动过速,心房纤维性颤动,T波异常,一个S1Q3T3图案,右心室应变和右束支传导阻滞,并在ECG轴右偏。The evaluation sequence of the study population is described in the flow chart (fig. 1⇓)。
![图1 -](http://www.qdcxjkg.com/content/erj/35/6/1243/F1.medium.gif)
流程图示出了研究人群的评估序列。PA:后前位;COPD:慢性阻塞性肺病;CT:计算机断层扫描。
在独立组率的比较,卡方测试使用。组装置使用非配对t检验进行比较。接收器工作特性进行(ROC)分析,以确定d二聚体水平的灵敏度和特异性。阳性预测值(阳性预测值)和阴性预测值(净现值)分别计算不同d二聚体阈值。ROC分析也用于区域的曲线(的AUC),用于PE的临床概率标准(Wells和日内瓦的标准)下的计算。为了确定VTE对1年死亡率的影响,一个Cox比例风险模型运行。在addition to the presence or absence of VTE, the model included widely accepted classical parameters (age, sex, smoke load, serum albumin level, forced expiratory volume in 1 s, arterial oxygen and carbon dioxide tension, body mass index and systolic pulmonary arterial pressure). The survival of the patients with and without a thromboembolic event was analysed using the Kaplan–Meier method. A p-value of <0.05 was considered significant.
结果
Patients who gave informed consent (n = 138) were included in the study. Seven patients were excluded due to technical problems with their angiographic and ultrasonographic scans (n = 4) and contrast allergy (n = 3), and 131 patients completed the study. The mean age of the participants was 67.1±10.1 yrs; 27 (20.6%) were female and 34 (26%) were nonsmokers. The admission characteristics of the patients are shown in table 1⇓。
在21(16%; 95%CI 9.7-22.3%)患者,VTE(DVT和/或PE)进行检测。虽然PE 18中检测到(13.7%; 95%CI 7.8-19.6%)患者,DVT在14被检测(10.6%; 95%CI 5.3-15.9%)。CT造影和多普勒ultrasosonography分别揭示了在下肢DVT在10个11例。DVT在11(61.1%)PE患者中检测到。由于这两种技术用于检测DVT的功效相似,它们彼此间的互补的作用被认为是分别27.2和40%。Table 2⇓显示的PE病例的本地化。的四种情况亚段PE三是由读者(观察员协议0.75)同意。虽然一个DVT病变双边发现,六个,七病变左右分别片面。
共计60例(45.8%)患者被评估为COPD病因不明加重,71例(54.2%)患者被评估为COPD病因已知加重。表3描述了已知病因恶化的触发因素⇓。VTE在15被检测(25%; 95%CI 14-36%)和6个(8.5%; 95%CI 2-15%)患者分别未知的恶化和已知的病因,住院治疗。The distribution of the patients according to unknown and known aetiology was significant (p = 0.016).
稳定状态后支气管扩张spirograms可以在116例谁完成了研究获得。The classification of COPD severity according to GOLD guidelines is described in table 4⇓。VTE在一个,八和12 GOLD阶段II,III和IV的患者分别检测。VTE的这些基团之间的分配是不显着的(P> 0.05)。
Except for female sex, chest pain, syncope and hypotension, no significant relationship could be established between epidemiological, haematological, biochemical and arterial blood gas, and spirometric parameters and the occurrence of VTE (table 1⇑)。虽然VTE在女性患者中的患病率为29.6%,但在男性患者中的患病率为12.5% (p = 0.041)。在传统的心电图中,仅有房颤与PE相关(p = 0.006)。超声心动图检查发现5例PE患者右心室运动功能减退及室间隔左偏(27.7%),为急性右心衰的指标(p = 0.0001)(表1)⇑)。All of these patients were subsequently evaluated as having massive (n = 3) and submassive (n = 2) PE according to their clinical and radiological findings.
均值d二聚体水平在VTE组显著更高(5.2±4.5与1.2±1.8μg·毫升−1;p < 0.001)。除了一个病人,肺动脉栓塞水平升高(> 0.5μg·毫升−1)。在这个截断水平上,敏感性、特异性、PPV和NPV分别为0.95、0.37、0.22和0.98。d -二聚体水平的敏感性、特异性、PPV和NPV分析没有显示出更好的d -二聚体截止水平。
根据Wells标准,低风险判定的患者中无一例(n = 71),中风险判定的患者中有20.7% (n = 53),高风险判定的患者中均有PE (n = 7)(表5)⇓)。在a similar manner, Geneva risk determination yielded PE in none (n = 14) of the low-risk patients, 11.7% (n = 111) of the moderate-risk patients and 83.3% (n = 6) of the high-risk patients. Using ROC curves, the value of these two methods in the diagnosis of PE were compared. As a test probability criteria, the AUC was significantly higher for the Wells method (0.882 (95% CI 0.819–0.945)与0.663(95%CI 0.532-0.794)为日内瓦方法;p = 0.018).
住院时间是显著更长患者VTE(13.4±5.0与9。0±5.6 days; p = 0.001). Of the patients, 51% had one or more comorbid conditions, such as cardiac disorders of extrapulmonary origin, malignancies, hypertension, diabetes mellitus, cerebrovascular accidents and connective tissue disorders. Of the patients, 11 (8.4%) died during index hospitalisation; five of these were in the group with VTE (p = 0.016). PE was present in all of these patients, two of the emboli being massive and sub-massive. All of the patients were followed-up for 1 yr, and the mortality rate was significantly higher in patients with VTE (61.9与31.8%;p = 0.013)(图2⇓)。The Cox's regression model revealed that the presence of VTE was the only parameter that had a significant influence on 1-yr mortality (p = 0.022) (table 6⇓)。
![图2 -](http://www.qdcxjkg.com/content/erj/35/6/1243/F2.medium.gif)
Kaplan-Meier曲线显示了患有(-)和不患有(-)静脉血栓栓塞的慢性阻塞性肺疾病患者的死亡率。p = 0.013。
讨论
本结果表明,VTE由于恶化的复杂化或触发因素是目前在住院COPD患者的16%。虽然VTE的患病率被证明是在未知病因的COPD恶化越高,VTE患病患者中发现与已知病因的恶化是也相当可观。For the first time, it was demonstrated that life expectancy is remarkably low in exacerbating patients with VTE at 1 yr.
在慢性阻塞性肺病患者中,PE可能加重症状,甚至导致部分患者死亡,而从任何临床基础上都不可能将PE与其他导致病情加重的原因区分开来。尽管有这一被广泛接受的经典知识,PE的流行和作用在COPD加重中还没有被精确地确定。关于这一问题的有限数量的研究发现了不同的患病率,范围在0-29%之间3.- - - - - -8。在尸检,这个速度提高到了50%11,12。这种变异的主要原因似乎与研究人群的选择有关。在最近的一项荟萃分析中,慢性阻塞性肺病(COPD)加重期PE的总体患病率被定义为20%,患者的加重原因不明13。DVT在COPD加重患者中是一个更不常被提及的问题,据报道其在COPD加重患者中的患病率为1.6-12.7%5- - - - - -8。然而,显而易见的是,PE和DVT有共同的基本因素和机制。
本研究还纳入了已知病因的患者,这些患者的VTE患病率为8.4%。虽然这一比率在病因不明的患者中低于25%,但似乎足以表明,这些患者不应被直接排除在今后处理同一问题的研究之外。在已知的恶化原因中,下呼吸道感染和心力衰竭通常被认为是最常见的。有趣的是,目前所有关于静脉血栓栓塞的指南都建议将此类患者评估为静脉血栓栓塞发展的高风险人群。认为COPD患者应该被排除在这个名单之外是不合理的。目前还没有足够的数据,但更好的方法可能是将任何来源的病情加重视为COPD患者VTE发展的危险因素,在评估时应特别考虑VTE。
在terestingly, the multiple parameters analysed to predict patients with VTE did not reveal any significant result, except for female sex, chest pain, syncope, hypotension and atrial fibrillation on ECG and right heart failure on echocardiography (table 1⇑)。Since there were a limited number of female patients in the present study group (n = 28), appropriate subgroup analysis to explain the relationship between the occurrence of VTE and female sex could not be undertaken. Unless the same relationship is shown in larger groups, it would seem to be a better approach to consider it coincidental rather than cause-related. Amongst the many symptoms and signs on admission (dyspnoea, cough, sputum, haemoptysis, wheezing, cyanosis and fever), chest pain, syncope and hypotension are not unexpected candidates for having some correlation with a thromboembolic event. However, ECG findings are not in concordance with classical knowledge for patients with PE. Apart from atrial fibrillation, none of the other PE indicators on ECG reached a significant level in the present patients. Since ECG findings in PE and COPD exacerbation are somewhat similar, ECG findings related to right ventricular strain in patients with an exacerbation might not be easy to differentiate from those in PE. Increased right ventricular strain arising from exacerbation itself probably mimicked the expected PE findings on ECG to reach a level of statistical significance in the present patients.
PE is a common disorder, and a quarter of patients with PE die within 1 yr14。虽然在任何专门设计的临床试验尚未确定,预计死亡率应该是COPD患者高。Nevertheless, a highly selective subgroup analysis of COPD patients (n = 45) in the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study revealed a mortality rate of 53.3% in 1 yr15。这个比率是两倍于那些既普通PIOPED PE患者和COPD患者无PE。根据这些调查结果一致,本研究还发现,无论是在医院和1年死亡率在COPD患者的静脉血栓栓塞是显著较高。Additionally, the Cox's regression model yielded the fact that the presence of VTE was the only parameter that had a significant relationship with mortality within 1 yr following hospitalisation (p = 0.022) (table 6⇑)。慢性阻塞性肺病住院且病情加重的患者VTE亚组的1年死亡率是前者的两倍(31.8)与61。9%) (fig. 2⇑)。除了死亡率增加外,静脉血栓栓塞患者的住院时间也延长了4-5天(p = 0.001)。毫无疑问,静脉血栓栓塞患者住院时间的延长对医院护理的总成本产生了相当大的影响。
首次使用Wells和Geneva标准预测COPD患者的PE并进行比较。中等和高概率情况下(n = 60), Wells准则的敏感性和PPV均高于Geneva准则(n = 117)(表5)⇑)。虽然在COPD患者的PE 39%达到了井高概率标准(100%PPV)的PE其余患者被诊断为韦尔斯中等概率标准(22%PPV)。相反地,日内瓦高概率标准可以由所有患者的33%用PE(83%PPV)满足。虽然中等概率标准还覆盖的患者使用该方法PE的其余部分,PPV仅为12%。在蒙雷亚尔的研究等。16,日内瓦方法的高概率类别只覆盖11%的COPD患者的用PE。然而,结果的直接比较可能不是由于研究和患者群体之间的差异之间的主要方法的变化是适当的。迄今为止,PE估计模型(日内瓦和比萨型号)已经被用在一个非常有限的研究解决COPD患者病情加重号6,16。韦尔斯方法得到的高概率的类别的患者在本研究中优异的PPV;如此强劲的预测值并没有在以前的研究描述。这可能是由于这样的事实,包括在井方法的参数更适合于PE的COPD患者的评估。然而,对于患者落入在韦尔斯方法本先驱研究的高概率的类别数量有限,我们认为,在确认本结果进一步前瞻性研究,绘制关于该问题的明确结论之前需要。
低d -二聚体水平仍然是排除VTE的唯一最有用的血液学参数。目前的研究结果只是简单地指出,其他疑似VTE人群的一般规则也完全适用于COPD加重患者。也就是说,如果d -二聚体水平在正常范围内,VTE的评估只能在特殊情况下进行。此外,综合考虑Wells标准(中度和高概率)和高d -二聚体水平进一步减少了COPD潜在PE患者总评估数的20%(从60例减少到47例)。以同样的方式,日内瓦的组合标准(中等和高概率)肺动脉栓塞高水平可能潜在PE患者的数量减少28%(从117年到84年的病人)这也表明,即使与肺动脉栓塞程度高,日内瓦的辨别力PE几乎一半的标准井标准。因此,Wells标准似乎是探索COPD患者PE的一个更好的工具。
总之,本研究结果表明,VTE是在COPD患者的常见病理与恶化住院。此外,在第一时间,住院和长期死亡率被发现在分化具有VTE的基础上,COPD患者是显著较高。由于本病的症状,体征及实验室和流行病学数据是慢性阻塞性肺病患者和无VTE类似,它可能不容易排除VTE的鉴别诊断。我们认为,与任何来源的恶化住院的所有COPD患者应血栓栓塞事件进行评估,除非血清d二聚体水平和威尔斯标准表明并非如此。
感兴趣的语句
无声明。
- 收到2009年7月29日。
- 接受2009年10月12日。
- ©人队