稳定期慢性阻塞性肺疾病合并重度肺动脉高压的临床研究

目的探讨稳定期慢性阻塞性肺疾病(COPD)合并重度肺动脉高压的临床特征及意义。方法985例COPD患者,排除其它影响肺血流动力学的因素,脉冲多普勒肺动脉血流频谱分析法测定肺动脉平均压,依据肺动脉压水平将患者分为肺动脉压正常组、轻中度升高组和重度升高组,比较3组患者Borg呼吸困难评分、肺功能检查及动脉血气分析参数。结果稳定期COPD患者重度肺动脉高压的发生率为6.39%(63/985),多为中重度患者;与肺动脉压正常及轻中度升高组患者相比,重度肺动脉高压组患者Borg呼吸困难评分较高,肺泡动脉氧分压差{A-aDO2}增大,第一秒用力呼气容积占预计值的百分比(FEV1%)、一氧化碳弥散量(DLCO)、动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)较低(P<0.05)。结论少数稳定期COPD患者合并重度肺动脉高压,这些患者血管疾病表现突出,需要运用血管扩张剂进行治疗。     

A case of severe pulmonary hypertension associated with COPD treated with epoprostenol

A rare case of chronic obstructive pulmonary disease (COPD) with severe pulmonary hypertension (PH) was found in a 68-year-old man. COPD was diagnosed in his 50s, from which time he received home oxygen therapy. In January 2007, he was admitted due to progression of dyspnea. On admission to our hospital, arterial blood gas analysis showed severe hypoxemia. Moreover, echocardiographic findings demonstrated severe deviation of the interventricular septum toward the left ventricle, with right ventricular dilatation. Cardiac catheterization data demonstrated pulmonary arterial hypertension with a low cardiac output. Because severe PH is uncommon in patients with COPD and there was no apparent etiology of PH other than COPD, we thought this case was predominantly a pulmonary vascular disease such as idiopathic pulmonary arterial hypertension. Though we first treated this patient with bosentan, it was not effective. Therefore, he was treated with continuous infusion of epoprostenol. Epoprostenol administration along with bosentan resulted in decrease of BNP and right ventricular function improvement. We report a case of severe PH due to severe COPD treated with continuous administration of epoprostenol.     

Relationship between arterial blood gases and spirometry in acute exacerbations of chronic obstructive pulmonary disease

Previous studies have established spirometric criteria for arterial blood gas analysis during acute asthmatic attacks. However, only general guidelines have been available regarding the need for blood gas analysis during an acute exacerbation of chronic obstructive pulmonary disease (COPD). We conducted a study to determine the relationship between arterial blood gases and spirometry in 70 emergency department patients during acute exacerbations of COPD. Arterial blood gas analysis and spirometry were performed on arrival at the emergency department. All of the patients with a pCO2 of more than 45 mm Hg had an FEV1 of less than 35% of the predicted normal. We found patients with a pO2 of less than 60 mm Hg who had an FEV1 as high as 54% of the predicted normal. There was no correlation between the FEV1 and pO2. Because spirometry was not reliable for identifying patients with significant hypoxemia, we conclude that arterial blood gas analysis is indicated for patients presenting to the ED with acute exacerbations of COPD. Spirometric criteria that have been used to eliminate the need for arterial blood gases in asthmatic patients cannot be applied safely to patients with COPD.     

Initial Risk Assessment for Pulmonary Hypertension in Patients with COPD

Background  

Pulmonary hypertension (PH) is a comorbidity associated with increased mortality in chronic obstructive pulmonary disease (COPD) patients. It is not known which clinical markers are predictive of PH in COPD. The goal of this study was to develop a clinical tool to identify patients who should be sent for initial screening with echocardiography.     

Relationship between exercise desaturation and pulmonary haemodynamics in COPD patients.

Pulmonary hypertension (PH) in patients with chronic obstructive pulmonary disease (COPD) has traditionally been explained as an effect of hypoxaemia. Recently, other mechanisms, such as arterial remodelling caused by inflammation, have been suggested. The aim of this study was to investigate whether exercise-induced PH (EIPH) could occur without concurrent hypoxaemia, and whether exercise-induced hypoxaemia (EIH) was regularly accompanied by increased pulmonary artery pressure or pulmonary vascular resistance index (PVRI). Pulmonary haemodynamics in 17 patients with COPD of varying severity, but with no or mild hypoxaemia at rest, were examined during exercise equivalent to the activities of daily living (ADL) and exhaustion. EIPH occurred in 65% of the patients during ADL exercise. Pulmonary arterial pressure during exercise was negatively correlated with arterial oxygen tension, but EIPH was not invariably accompanied by hypoxaemia. Conversely, EIPH was not found in all patients with EIH. The resting PVRI was negatively correlated with arterial oxygen tension during ADL exercise, but an elevated PVRI without EIH occurred in 35% of the patients. In conclusion, exercise-induced pulmonary hypertension occurred during exercise equivalent to the activities of daily living in chronic obstructive pulmonary disease patients with no or mild hypoxaemia at rest. Although pulmonary artery pressure and arterial oxygen tension were negatively correlated during exercise, a consistent relationship between hypoxaemia and pulmonary hypertension could not be demonstrated. This may indicate that mechanisms other than hypoxaemia contribute significantly in the development of pulmonary hypertension in these patients.     

慢性阻塞性肺疾病合并不成比例肺动脉高压患者血浆D-二聚体水平测定及分析

目的 探讨慢性阻塞性肺疾病(COPD)合并不成比例肺动脉高压患者血液是否呈高凝状态.方法 选择稳定期COPD合并肺动脉高压(PH)患者46例,其中COPD合并不成比例PH患者9例(A组),其余COPD合并PH患者37例(B组),具有可比条件的正常中老年人20例为正常对照组(C组),分别检测三组受检查血浆D-二聚体水平.结果 A组血浆D-二聚体水平显著高于B组(P＜0.05),也显著高于C组(正常对照组)(P＜0.05);B组血浆D-二.聚体水平与C组无明显差异(P＞0.05).COPD合并不成比例PH组患者平均肺动脉压与血浆D-二聚体水平有显著相关性(r=0.86,P＜0.01).结论 COPD合并不成比例PH患者血液呈高凝状态,理论上可行抗凝治疗.     

Tei指数对慢性阻塞性肺病肺动脉高压患者的右心功能评价

目的:应用Tei指数评价慢性阻塞性肺病（chronic obstructive pulmonary disease,COPD）伴肺动脉高压(pulmonary hypertension,PH)患者的右心功能。方法: 临床确诊的慢性阻塞性肺病伴肺动脉高压(COPD+PH)患者68例,另30例正常人作为对照组。根据三尖瓣反流压差,超声估测肺动脉收缩压,并按其分别判定为重度PH组、中度PH组和轻度PH组。超声常规测量参数包括右心室前后径、右心房横径、肺动脉主干内径,并计算右心室Tei指数。结果: 68例COPD+PH患者中,重度PH组22例,中度PH组30例,轻度PH组16例;与对照组相比,重度PH组和中度PH组右心大小、Tei指数均有统计学差异,轻度PH组无明显右心形态改变,Tei指数无统计学差异。结论: 右心室Tei指数可作为COPD伴中重度PH患者右心功能评价的参考指标。     

慢性支气管炎、COPD及肺心病患者BNP、肺功能和血气变化的研究

目的探讨慢性支气管炎(慢支)、COPD、慢性肺源性心脏病(肺心病)患者不同时期BNP(B型钠尿肽)、肺功能、动脉血气的变化。方法慢支、COPD、肺心病患者均空腹抽静脉血检测BNP;另抽动脉血检测血气;并行肺功能检测。三组间对比,并与正常组对照。结果由慢支发展到COPD、肺心病时BNP逐渐升高(P<0.05);慢支、COPD及肺心病各组FEV1/FVC、MMEF逐渐降低(P均<0.05),动脉血氧分压(PaO2)、PH值逐渐降低,二氧化碳分压(PaCO2)逐渐增高(P均<0.05)。BNP与PaO2、PH呈显著负相关(r=-0.69,-0.58,P均<0.01),而与PaCO2呈正相关(r=0.55,P<0.01)。BNP与FEV1/FVC、MMEF均呈显著负相关,P均<0.01)。结论血浆BNP水平与血气分析及肺功能变化关系密切,血浆BNP水平可以作为判断COPD病情严重程度的一个指标。     

Identifying Patients with Group 3 Pulmonary Hypertension Associated with COPD or ILD Using an Administrative Claims Database

Lung - Group 3 pulmonary hypertension (PH) describes a subpopulation of patients with PH due to chronic lung disease and/or hypoxia, with chronic obstructive pulmonary disease (COPD) and...     

慢性阻塞性肺疾病合并肺动脉高压的发病机制研究进展

肺动脉高压(pulmonary hypertension,PH)是慢性阻塞性肺疾病(chronic obstructivepulmonary disease,COPD)的一个重要合并症.COPD合并PH是逐渐发生和进展的,最初于运动或睡眠时出现,逐渐发展为休息时即存在PH,运动、睡眠或病情恶化时进一步升高.COPD相关的PH多为轻到中度,但某些COPD患者可表现为"不成比例"的PH.香烟烟雾、炎症产物引起内皮损害,造成内皮功能失调;慢性低氧引起肺血管收缩;肺血管重构导致管腔变小,血管膨胀性降低,阻力增加;重度肺气肿时肺毛细血管的丧失等均与COPD时的PH相关.     

Risk of over-diagnosis of COPD in asymptomatic elderly never-smokers.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has defined stage I chronic obstructive pulmonary disease (COPD) as forced expiratory volume in one second/forced vital capacity (FEV1/FVC)% <70% and a FEV1% predicted of >80%. Stage 2 has been defined as FEV1/FVC <70% and a FEV1% pred of <80%. The authors examined the extent of COPD misdiagnosis using this definition in healthy, never-smoker, asymptomatic adults aged >70 yrs in Bergen, Norway. A respiratory questionnaire was mailed to a random sample of 2,871 persons aged >70 yrs. In a random, well-defined subgroup of 208 never-smoker respondents with no current respiratory disease and significant dyspnoea or heart disease/hypertension complicated with dyspnoea, 71 were able to perform an acceptable spirometry. Approximately 35% of these healthy, elderly never-smokers had an FEV1/FVC% of <70% and would be classified as having at least a stage 1 COPD. This percentage increased with age and in those aged >80 yrs approximately 50% would be classified as having COPD and approximately one-third would have an FEV1 of <80% pred (stage 2 COPD). The estimated 5th percentile of FEV1 was consistently <80% pred. The Global Initiative for Chronic Obstructive Lung Disease criteria will probably lead to a significant degree of over-diagnosis of chronic obstructive pulmonary disease in those aged >70 yrs. The criteria used to define the various stages of chronic obstructive pulmonary disease need to be age-specific.     

Noninvasive prediction of pulmonary hypertension in chronic obstructive pulmonary disease by Doppler echocardiography

Thirty-six patients with chronic obstructive pulmonary disease (COPD) were studied by pulsed Doppler echocardiography. In 32 of the 36 patients, adequate Doppler signals were obtained in the pulmonary arterial trunk and correlated with right cardiac hemodynamics. The studied group included 26 patients with mean pulmonary arterial pressure (MPAP) greater than 20 mm Hg at rest (group A, with pulmonary hypertension) and six patients with MPAP of 20 mm Hg or less (group B, without pulmonary hypertension). A control group (group C) consisted of 12 subjects with normal hemodynamic data and pulmonary function. Analysis of Doppler data included flow velocity curve pattern, presence of a negative presystolic velocity, right ventricular pre-ejection period (RVPEP) and ejection period (RVEP), time between onset and peak of pulmonary velocity (time to peak velocity, TPV) and derived ratios of TPV/RVPEP and TPV/RVEP. In patients with pulmonary hypertension, the Doppler flow velocity curve in the pulmonary trunk showed a rapid acceleration and an early deceleration. The mean value for TPV was 78 +/- 12 msec in group A, 115 +/- 11 msec in group B, and 127 +/- 10 msec in group C. In patients with COPD, significant correlations were observed between TPV and log10 MPAP (r = -0.77; SEE = 0.07) and between TPV and log10 total pulmonary resistances (r = -0.84; SEE = 0.05). Accordingly, pulsed Doppler echocardiography may be a useful tool to predict pulmonary hypertension due to chronic pulmonary disease.     

Gene polymorphisms of endothelial nitric oxide synthase enzyme associated with pulmonary hypertension in patients with COPD

In this cross-sectional controlled study, we aimed to investigate the role of polymorphisms of the angiotensin-converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS) genes on pulmonary hypertension (PH) in patients with chronic obstructive pulmonary disease (COPD). Forty-two (41 male, 1 female, mean age: 62 +/- 7 years) COPD patients and 40 (all male, mean age: 60 +/- 8 years) healthy controls were included. Respiratory function tests, arterial blood gases, and echocardiographic examinations were performed. ACE and eNOS genotypes were determined using PCR. The ACE and eNOS genotype distribution was not significantly different between COPD patients and controls. On comparing pulmonary artery pressures in different eNOS genotypes, the mean pulmonary artery pressure (Ppa) in patients with the BB genotype was significantly higher than in patients with the nonBB genotypes (41.3 +/- 17.7 mmHg vs. 27.3 +/- 11.2 mmHg, P = 0.02). However, there was no difference in ACE genotype distributions between COPD patients with and without pulmonary hypertension. In stepwise linear regression analysis for predicting pulmonary artery pressure, PaO2 and polymorphism of eNOS gene were found to be independent variables. In conclusion, BB-type polymorphism of the eNOS gene has been associated with PH in addition to hypoxemia. However, ACE gene polymorphism was not found to be associated with PH.     

The 6-min walk distance: change over time and value as a predictor of survival in severe COPD.

The 6-min walk distance (6MWD) is used to evaluate the functional capacity of patients with chronic obstructive pulmonary disease (COPD). The change in 6MWD over time and its correlation with changes in spirometry and survival are unclear. Patients (n=198) with severe COPD and 41 age-matched controls were followed for 2 yrs, and anthropometrics, spirometry, 6MWD and comorbidities were measured. The 6MWD decreased in the COPD group from 238 +/- 107 m to 218 +/- 112 m (-26 +/- 37 m x yr(-1)), and increased in the control group from 532 +/- 82 m to 549 +/- 86 m (12 +/- 25 m x yr(-1)). In both groups, there was a poor correlation with changes in forced expiratory volume in one second (FEV1). Nonsurvivors in the COPD group (42%) had a more pronounced change in the 6MWD (-40 versus -22 m x yr(-1)) but a similar change in FEV1 (118 versus 102 mL x yr(-1)). The 6MWD independently predicted survival, after accounting for age, body mass index, FEV1 and comorbidities. In severe chronic obstructive pulmonary disease, the 6-min walk distance predicts mortality better than other traditional markers of disease severity. Its measurement is useful in the comprehensive evaluation of patients with severe disease.     

Pulmonary Hypertension in a Stable Community-Based COPD Population

Study Objectives  

The etiology and prevalence of pulmonary hypertension (PH) in patients with stable chronic obstructive pulmonary disease (COPD) is uncertain. This study was done to determine the prevalence of PH in stable COPD outpatients and to evaluate the relationship between PH and indices of pulmonary function.     

慢性阻塞性肺疾病合并肺纤维化的肺动脉压力变化及其与肺功能和生活质量关系的研究

目的探究慢性阻塞性肺疾病(COPD)合并肺纤维化患者的肺动脉压力变化及其与肺功能、生活质量的关系。方法 回顾性对比分析天津医科大学总医院2009年7月至2011年3月诊断的20例COPD合并肺纤维化及随机抽取同期30例单纯COPD患者的肺动脉收缩压、肺功能、Medieal Research Council dyspne...     

C-reactive protein levels and clinically important predictive outcomes in stable COPD patients.

The aim of this study was to determine the relationship between C-reactive protein (CRP) levels and factors known to predict outcome in stable chronic obstructive pulmonary disease (COPD) patients. The following were studied in 130 stable COPD patients: spirometry, lung volume, arterial oxygen tension (P(a,O2)), dyspnoea, 6-min walk distance (6MWD), body mass index, fat-free mass index, BODE (body mass index, obstruction, dyspnoea and exercise capacity), health-related quality of life, smoking status, the presence of cardiovascular risk factors or disease, corticosteroid use and number of exacerbations in the previous year. CRP levels were measured in these patients and in 65 controls. Using univariate and multivariate analyses, any possible association with the predictors of outcomes was evaluated. CRP levels were higher in COPD patients than in controls (4.1 versus 1.8 mg.L(-1), respectively). Correlation was found with the following variables: forced expiratory volume in one second (FEV1; -0.23), FEV1 % (-0.20), forced vital capacity (FVC; -0.24), FVC % (-0.24), Global Initiative for Chronic Obstructive Lung Disease stage (0.17), BODE (0.17), inspiratory capacity/total lung capacity (-0.20), P(a,O2) (-0.40) and 6MWD (-0.30). Using multivariate analysis, P(a,O2) and 6MWD manifested the strongest negative association with CRP levels. C-reactive protein levels in stable chronic obstructive pulmonary disease patients are best correlated with arterial oxygen tension and 6-min walk distance. This should be considered when C-reactive protein levels are measured in stable chronic obstructive pulmonary disease patients.     

Cardiovascular autonomic neuropathy in chronic obstructive pulmonary disease

BACKGROUND: While autonomic neuropathy has been reported in chronically hypoxaemic patients of chronic obstructive pulmonary disease (COPD), whether it also occurs in patients with milder disease and in those without chronic hypoxaemia has not been explored. METHODOLOGY: Lung function measurements including spirometry and transfer factor for carbon monoxide, mean pulmonary artery pressure estimation by color-doppler echocardiography and arterial blood gas analysis were carried out in 56 patients with COPD and 11 age-matched controls. Autonomic function was assessed by tests of cardiovascular reflexes and expressed as valsalva ratio, 30:15 ratio, IE difference and the blood pressure response to postural change. RESULTS: Among patients, majority of the test responses were in the abnormal or borderline range compared to more than 90% of test responses in the normal or borderline range among normals. Almost 50% of patients had definite neuropathy as compared to none in normals. Although, the autonomic neuropathy tended to be observed more often in patients with moderate and severe COPD, it was also found in a fair proportion of patients with mild COPD. Similarly, while it was more prevalent in patients with hypoxaemia, it was also found to occur in those without hypoxaemia. The responses to tests of autonomic function had weak relationships with FEV1% predicted and PaO2. CONCLUSIONS: Cardiovascular autonomic neuropathy is common in COPD and is found even in early stages of the disease.     

Predominant emphysema phenotype in chronic obstructive pulmonary.

Patients with fixed airflow limitation are grouped under the heading of chronic obstructive pulmonary disease (COPD). The authors investigated whether COPD patients have distinct functional, radiological and sputum cells characteristics depending on the presence or absence of emphysema. Twenty-four COPD outpatients, 12 with and 12 without emphysema on high-resolution computed tomography scan of the chest, were examined. Patients underwent chest radiography, pulmonary function tests and sputum induction and analysis. Subjects with documented emphysema had lower forced expiratory volume in one second (FEV1), FEV1/forced vital capacity ratio, and lower carbon monoxide diffusion constant (K(CO)), compared with subjects without emphysema. Chest radiograph score of emphysema was higher, chest radiograph score of chronic bronchitis was lower, and the number of sputum lymphocytes was increased in patients with emphysema, who also showed a negative correlation between K(CO) and pack-yrs. Chronic obstructive pulmonary disease patients with emphysema, documented by high-resolution computed tomography scan, have a different disease phenotype compared with patients without emphysema. Identification of chronic obstructive pulmonary disease-related phenotypes may improve understanding of the natural history and treatment of the disease.     

Echocardiographic Screening for Pulmonary Hypertension in Stable COPD Out-Patients and NT-proBNP as a Rule-Out Test

Abstract

Pulmonary hypertension (PH) worsens the prognosis in chronic obstructive pulmonary disease (COPD). The diagnosis of PH is established by right heart catheterisation (RHC), while echocardiography can be used for screening. We aimed to asses the outcome of echocardiographic screening for PH in a group of stable COPD out-patients, and to evaluate NT-proBNP as a first line screening tool. Criteria for PH on echocardiography were a tricuspid regurgitation pressure gradient > 40 mmHg, a tricuspid annular plane systolic excursion < 1.8 cm or right ventricular dilatation. Positively screened patients were asked to undergo RHC. Results (Mean ± SEM): 16 of 117 patients (14%) had PH on echocardiography. They had a higher mortality (hazard ratio for death: 2.7 ± 1.3, p = 0.037) and lower six minute walk test (224 ± 33 vs. 339 ± 15, p = 0.006). NT-proBNP below 95 ng/l excluded PH on echocardiography with a negative predictive value of 100 (95% CI: 89–100%). RHC was obtained in six patients screened positive. In three of these, PH was not confirmed. Conclusions: Signs of PH on echocardiography as defined here was found in 14% and had prognostic significance in COPD. A value of NT-proBNP less than 95 ng/l may be used to exclude signs of PH.