慢性阻塞性肺疾病患者家庭长期氧疗的临床研究

目的：探讨家庭长期氧疗（LTOT）对慢性阻塞性肺疾病（COPD）患者的疗效。方法：将我院同期住院病人随机分为LTOT组（51人）,对照组（52人）。全部病例在缓解期及治疗后每年测定PaO2、PaCO2、FVC、FEV1、HB、HCT的数值及每年住院次数。结果：①氧疗后1、2、3、4、5年与氧疗前比较,低氧血症改善,FEV1明显提高,HB、HCT明显减少;每年住院次数减少;②LTOT组5年生存率62．75％,对照组5年生存率46．15％,差异有显著性（p〈0．05）。结论：合理使用LTOT对COPD患者有良好的治疗作用,可提高患者的5年生存率。     

Emphysema distribution and annual changes in pulmonary function in male patients with chronic obstructive pulmonary disease

Background

The progression of chronic obstructive pulmonary disease (COPD) considerably varies among patients. Those with emphysema identified by quantitative computed tomography (CT) are associated with the rapid progression assessed by forced expiratory volume in one second (FEV₁). However, whether the rate of the decline in lung function is independently affected by the regional distribution or the severity of emphysema in the whole lung is unclear.

Methods

We followed up 131 male patients with COPD for a median of 3.7 years. We measured wall area percent (WA%) in right apical segmental bronchus, total lung volume, percent low attenuation volume (LAV%), and the standard deviation (SD) of LAV% values from CT images of 10 isovolumetric partitions (SD-LAV) as an index of cranial-caudal emphysema heterogeneity. Annual changes in FEV₁ were then determined using a random coefficient model and relative contribution of baseline clinical parameters, pulmonary function, and CT indexes including LAV%, SD-LAV, and WA% to annual changes in FEV₁ were examined.

Results

The mean (SD) annual change in FEV₁ was −44.4 (10.8) mL. Multivariate random coefficient model showed that higher baseline FEV₁, higher LAV%, current smoking, and lower SD-LAV independently contributed to an excessive decline in FEV₁, whereas ratio of residual volume to total lung capacity, ratio of diffusing capacity to alveolar ventilation, and WA% did not, after adjusting for age, height, weight, and ratio of CT-measured total lung volume to physiologically-measured total lung capacity.

Conclusions

A more homogeneous distribution of emphysema contributed to an accelerated decline in FEV₁ independently of baseline pulmonary function, whole-lung emphysema severity, and smoking status. In addition to whole-lung analysis of emphysema, CT assessment of the cranial-caudal distribution of emphysema might be useful for predicting rapid, progressive disease and for developing a targeted strategy with which to prevent disease progression.     

Systemic oxygen extraction during incremental exercise in patients with severe chronic obstructive pulmonary disease

To determine if decreased systemic oxygen (O₂) extraction contributes to the exercise limit in severe chronic obstructive pulmonary disease (COPD), 40 consecutive incremental cycle ergometer exercise tests performed by such patients, from which a “log-log” lactate threshold (LT) was identified, were compared to those of 8 patients with left ventricular failure (LVF) and 10 normal controls. Pulmonary gas exchange and minute ventilation were measured continuously and arterial blood gas tensions, pH, and lactate concentrations were sampled each minute. Cardiac output (Q˙ _c) was measured by first-pass radionuclide ventriculography. The systemic O₂ extraction ratio (O₂ER) was calculated as arterial − mixed venous O₂ content difference (C _aO₂ − C _vO₂)/C _aO₂. Peak exercise O₂ uptake (V˙O_2peak) was markedly reduced in both COPD and LVF [41 (3) and 42 (3)% predicted, respectively], compared to controls [89 (2)% predicted, P < 0.0001 for each]. Similarly, the LT occurred at a low percentage of predicted maximal oxygen consumption in both COPD and LVF [25 (2) and 27 (3)%] compared to normals [46 (3)%, P < 0.0001 for each]. The systemic O₂ER at peak exercise was severely reduced in COPD [0.36 (0.02)] compared to the other groups [P < 0.0001 for each], for whom it was nearly identical [0.58 (0.03) vs 0.63 (0.04), LVF vs control, P > 0.05]. In the COPD group, an early LT correlated with reduced systemic O₂ER at peak exercise (r = 0.64, P < 0.0001), but not with any index of systemic O₂ delivery. These data suggest that lactic acidemia during exercise in patients with severe COPD is better related to abnormal systemic O₂ extraction than to its delivery and contributes to the exercise limit. Accepted: 10 March 1998     

Gait mechanics in patients with chronic obstructive pulmonary disease

Background

Chronic obstructive pulmonary disease (COPD) is characterized by the frequent association of disease outside the lung. The objective of this study was to determine the presence of biomechanical gait abnormalities in COPD patients compared to healthy controls while well rested and without rest.

Methods

Patients with COPD (N = 17) and aged-matched, healthy controls (N = 21) walked at their self-selected pace down a 10-meter walkway while biomechanical gait variables were collected. A one-minute rest was given between each of the five collected trials to prevent tiredness (REST condition). Patients with COPD then walked at a self-selected pace on a treadmill until the onset of self-reported breathlessness or leg tiredness. Subjects immediately underwent gait analysis with no rest between each of the five collected trials (NO REST condition). Statistical models with and without covariates age, gender, and smoking history were used.

Results

After adjusting for covariates, COPD patients demonstrated more ankle power absorption in mid-stance (P = 0.006) than controls during both conditions. Both groups during NO REST demonstrated increased gait speed (P = 0.04), stride length (P = 0.03), and peak hip flexion (P = 0.04) with decreased plantarflexion moment (P = 0.04) and increased knee power absorption (P = 0.04) as compared to REST. A significant interaction revealed that peak ankle dorsiflexion moment was maintained from REST to NO REST for COPD but increased for controls (P < 0.01). Stratifying by disease severity did not alter these findings, except that step width decreased in NO REST as compared to REST (P = 0.01). Standardized effect sizes of significant effects varied from 0.5 to 0.98.

Conclusions

Patients with COPD appear to demonstrate biomechanical gait changes at the ankle as compared to healthy controls. This was seen not only in increased peak ankle power absorption during no rest but was also demonstrated by a lack of increase in peak ankle dorsiflexion moment from the REST to the NO REST condition as compared to the healthy controls. Furthermore, a wider step width has been associated with fall risk and this could account for the increased incidence of falls in patients with COPD.     

beta-Adrenoceptor-mediated thermogenesis and lipolysis in patients with chronic obstructive pulmonary disease

The present study investigated whether development or maintenance of a relatively increased fat mass in normal-weight patients with chronic obstructive pulmonary disease (COPD), despite periods of weight loss, may be related to impaired beta-adrenoceptor-mediated responses in lipid utilization and thermogenesis. Nine COPD patients and nine healthy controls (body mass index: 23.0 +/- 1.3 vs. 23.8 +/- 0.6 kg/m2, not significant; fat mass: 19.0 +/- 2.1 vs. 11.9 +/- 1.5 kg, P < 0.01) received consecutive 30-min infusions of 6, 12, and 24 ng x kg fat free mass(-1) x min(-1) isoproterenol. During beta-adrenergic stimulation, nonesterified fatty acid levels increased significantly less in COPD patients (P < 0.001). Respiratory exchange ratio decreased similarly in both groups, indicating a similar change in the rate of lipid to carbohydrate oxidation. Energy expenditure increased similarly in both groups during beta-adrenergic stimulation. However, because plasma isoproterenol concentrations were significantly higher in COPD patients, thermogenesis related to isoproterenol concentration was significantly reduced in this group (P < 0.05). In conclusion, beta-adrenoceptor-mediated lipolysis and thermogenesis are impaired in COPD patients. This may play a role in the development or maintenance of their relatively increased fat mass.     

Long term transtracheal oxygen delivery through microcatheter in patients with hypoxaemia due to chronic obstructive airways disease.

Transtracheal administration of oxygen is a new technique for long term treatment. Twenty patients with hypoxaemia due to chronic obstructive airways disease were studied while receiving oxygen through a microcatheter inserted percutaneously into the trachea. By bypassing most of the dead space and avoiding oxygen wastage at the face this method of delivery reduced oxygen requirements by roughly half compared with delivery through nasal cannulas, thus reducing costs and facilitating portable treatment. Twelve of these patients continued to use the system for up to 13 months in preference to using nasal cannulas. Two important complications were a staphylococcal infection and a fractured catheter. Transtracheal oxygen reduced breathlessness and helped patients with routine daily activities. Transtracheal administration of oxygen is a practical method of treatment which may have an important role in rehabilitating patients with chronic lung disease.     

Diagnosis of invasive fungal disease in hospitalized patients with chronic obstructive pulmonary disease

Background

The role of culture-independent techniques (galactomannan, (1-3)-β-d-glucan) in the early diagnosis of invasive fungal diseases (IFD) is well assessed in hematological patients, but there are no clear conclusions in patients with chronic obstructive pulmonary disease (COPD).

Relation of pressure and flow of pulmonary circulation in patients with chronic obstructive pulmonary disease

A series of 31 patients with various degrees of chronic obstructive pulmonary disease underwent right heart catheterization using flow-directed thermodilution catheters. Both rest and supine exercise values were obtained. The patients were divided into two groups on the basis of their reduction in forced expiratory volume in 1 s (FEV1). In patients with FEV1 values of greater than or equal to 1,300 ml (group 1), the arterial oxygen partial pressure (PaO2) did not significantly change with exercise, while in patients with FEV1 of less than or equal to 1,200 ml (group 2) PaO2 significantly (p less than 0.05) fell in response to exercise. In group 2, a significant increase of total pulmonary resistance (TPR) with exercise was found (p less than 0.01). Pulmonary vascular resistance (PVR) remained unchanged in both subgroups. It is suggested that the value of PVR for subgroup 2 is artificially low because an important variable, namely pulmonary artery wedge pressure, is influenced by alveolar pressure in patients with an uneven distribution of perfusion and ventilation at pulmonary venous pressures lower than alveolar pressure. The steeper slope of the pressure-flow relationship in these patients is probably due to an increased vascular tone caused by chronic hypoxia at rest and further fall of PaO2 and rise of arterial CO2 partial pressure in response to exercise.     

慢性阻塞性肺疾病患者继发肺部真菌感染的临床分析

目的探讨慢性阻塞性肺疾病(COPD)患者继发肺部真菌感染的临床特点。方法回顾性分析2008年1月到2010年12月安徽医科大学第一附属医院收治的COPD继发肺部真菌感染患者病例,并对其耐药情况进行比较。结果本组199例COPD患者检出白色念珠菌137例(68.84%),光滑念珠菌32例(16.08%),热带念珠菌17例(8.54%),克柔念珠菌9例(4.52%),毛霉菌3例(1.51%),清酒假丝酵母菌1例(0.50%);白色念珠菌检出率有下降趋势,热带念珠菌有上升趋势;196例真菌对伏立康唑、氟康唑、两性霉素B、伊曲康唑、氟胞嘧啶的耐药率分别为3.6%、5.1%、1.0%、8.7%和0;2008年至2010年白色念珠菌和光滑念珠菌耐药率变化差异无统计学意义。结论 COPD患者继发肺部真菌感染病原菌仍以白色念珠菌为主,其次为光滑念珠菌和热带念珠菌;白色念珠菌和光滑念珠菌耐药率无明显改变。     

Evaluation of epithelial mesenchymal transition in patients with chronic obstructive pulmonary disease

Background

The reticular basement membrane (Rbm) in smokers and especially smokers with COPD is fragmented with "clefts" containing cells staining for the collagenase matrix-metalloproteinase-9 (MMP-9) and fibroblast protein, S100A4. These cells are also present in the basal epithelium. Such changes are likely hallmarks of epithelial mesenchymal transition (EMT). We aimed to confirm the epithelial origin of these Rbm cells, and to exclude potential confounding by infiltrating inflammatory cells.

Methods

Endobronchial biopsy sections from 17 COPD current smokers, with documented Rbm splitting and cellularity were stained for neutrophil elastase (neutrophil marker), CD68 (macrophage/mature fibroblasts), CD4+/CD8+ T lymphocytes, CD19 (B-cells), CD11c (dendritic cells/inflammatory cells), and S100 (Langerhans cells). The number of cells in the Rbm and epithelium staining for these "inflammatory" cell markers were then compared to numbers staining for S100A4, "a documented EMT epitope". Slides were double stained for S100A4 and cytokeratin(s).

Results

In the basal epithelium significantly more cells stained for S100A4 compared to infiltrating macrophages, fibroblasts or immune cells: median, 26 (21.3 - 37.3) versus 0 (0 - 9.6) per mm, p < 0.003. Markedly more S100A4 staining cells were also observed in the Rbm compared to infiltrating macrophages, neutrophils, fibroblasts or immune cells or any sub-type: 58 (37.3 - 92.6) versus 0 (0 - 4.8) cells/mm Rbm, p < 0.003. Cells in the basal epithelium 26 (21.3 - 37.3) per mm) and Rbm (5.9 (2.3 - 13.8) per mm) frequently double stained for both cytokeratin and S100A4.

Conclusions

These data provide additional support for active EMT in COPD airways.     

Combination bronchodilator therapy in the management of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact. Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations. The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events. Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy. GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β₂-agonists (LABAs), such as formoterol and salmeterol. Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present. Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components. This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease.     

MAPK signaling in the quadriceps of patients with chronic obstructive pulmonary disease

Muscle atrophy in chronic obstructive pulmonary disease (COPD) is associated with reduced exercise tolerance, muscle strength, and survival. The molecular mechanisms leading to muscle atrophy in COPD remain elusive. The mitogen-activated protein kinases (MAPKs) such as p38 MAPK and ERK 1/2 can increase levels of MAFbx/Atrogin and MuRF1, which are specifically involved in muscle protein degradation and atrophy. Our aim was to investigate the level of activation of p38 MAPK, ERK 1/2, and JNK in the quadriceps of patients with COPD. A biopsy of the quadriceps was obtained in 18 patients with COPD as well as in 9 healthy controls. We evaluated the phosphorylated as well as total protein levels of p38 MAPK, ERK 1/2, and JNK as well as MAFbx/Atrogin and MuRF1 in these muscle samples. The corresponding mRNA expression was also assessed by RT-PCR. Ratios of phosphorylated to total level of p38 MAPK (P = 0.02) and ERK 1/2 (P = 0.01) were significantly elevated in patients with COPD compared with controls. Moreover, protein levels of MAFbx/Atrogin showed a tendency to be greater in patients with COPD (P = 0.08). mRNA expression of p38 MAPK (P = 0.03), ERK 1/2 (P = 0.02), and MAFbx/Atrogin (P = 0.04) were significantly elevated in patients with COPD. In addition, phosphorylated-to-total p38 MAPK ratio (Pearson's r = -0.45; P < 0.05) and phosphorylated-to-total ERK 1/2 ratio (Pearson's r = -0.47; P < 0.05) were negatively associated with the mid-thigh muscle cross-sectional area. These data support the hypothesis that the MAPKs might play a role in the development of muscle atrophy in COPD.     

慢性阻塞性肺疾病患者肠道微生物组成及基因功能分析

探讨慢性阻塞性肺疾病（COPD）患者肠道微生物组成、丰度及差异基因功能变化。

收集我院呼吸科10例确诊COPD患者（COPD组）和10例对照受试者（对照组）粪便样品进行宏基因组高通量测序分析。

PCA分析组间比较发现2组研究对象粪便样品微生物群落差异大,具有可比性。物种组成分析显示：对照组粪便样品中高度富集的菌科主要包括毛螺菌科、理研菌科、韦荣球菌科、优杆菌科、臭杆菌科、氨基酸球菌科、乳杆菌科等,属层面富集的主要包括罗斯菌属、胃瘤球菌属、小杆菌属、真杆菌属、拟杆菌属、粪球菌属、双歧杆菌属等;COPD组粪便样品富集菌群主要包括紫单胞菌科、Selenomonadaceae、巨单胞菌属和韦荣球菌属。物种多样性分析与对照组相比,COPD组多样性更低,差异有统计学意义（W = 87,P = 0.0039）。物种相关性网络图分析显示与其他门类菌群相比,拟杆菌门、厚壁菌门、变形菌门与其他物种的关联性最强（size = 52.07、18.87、14.01）。组间差异基因进行GO功能显著性富集分析,差异基因均富集在如细胞学过程、刺激应答、生物学黏附及调节、代谢过程及信号通路等。KEGG功能显著性富集分析显示差异基因主要富集途径包括代谢途径、次生代谢物合成、淀粉和蔗糖的合成、抗生素的合成等。

COPD患者肠道内存在菌群及基因功能失调。