Peripheral muscle dysfunction in chronic obstructive pulmonary disease

Peripheral muscle dysfunction is a common systemic complication of moderate to severe COPD and may contribute to disability, handicap, and premature mortality. In contrast to the lung impairment, which is largely irreversible, peripheral muscle dysfunction is potentially remediable with exercise training, nutritional intervention, oxygen, and anabolic drugs. Therapeutic success is often incomplete, however, and a better understanding of the mechanisms involved in the development of peripheral muscle dysfunction in COPD is needed to help develop innovative and more effective therapeutic strategies.     

Peripheral muscle dysfunction in chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease (COPD) often develop systemic complications of their disease. Peripheral muscle dysfunction is one such complication and is characterised by atrophy, weakness, and low oxidative capacity. These muscle changes influence exercise tolerance and quality of life independent of the impairment in lung function. In the following article, the evidence for peripheral muscle dysfunction in patients with COPD and the possible clinical implications of this problem will be discussed. Lastly, the available therapeutic options to improve peripheral muscle function in COPD will be reviewed.     

气道炎症与慢性阻塞性肺疾病

慢性阻塞性肺疾病（ＣＯＰＤ）与哮喘均为呼吸系统的常见病和多发病,然而,明确区分或界定ＣＯＰＤ与哮喘则甚为困难。许多ＣＯＰＤ患者其表现虽与哮喘迥然不同,但是某些哮喘患者当其病程发展至晚期时亦常表现为典型的ＣＯＰＤ征象。一般认为,哮喘和ＣＯＰＤ具有各自不...     

Recent findings in chronic obstructive pulmonary disease by using quantitative computed tomography

Chronic obstructive pulmonary disease (COPD) is characterized by an incompletely reversible airflow limitation that results from a combination of airway wall remodeling and emphysematous lung destruction. Forced expiratory volume in 1 s (FEV₁) has been considered the gold standard for diagnosis, classification, and follow-up in patients with COPD, but it has certain limitations and it is still necessary to find other noninvasive modalities to complement FEV₁ to evaluate the effect of therapeutic interventions and the pathogenesis of COPD. Quantitative computed tomography (CT) has partly met this demand. The extent of emphysema and airway dimensions measured using quantitative CT are associated with morphological and functional changes and clinical symptoms in patients with COPD. Phenotyping COPD based on quantitative CT has facilitated interventional and genotypic studies. Recent advances in COPD findings with quantitative CT are discussed in this review.     

下呼吸道细菌定植与慢性阻塞性肺疾病的关系

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)到目前仍为一全球性健康问题.对其病因的探讨具有重要意义.下呼吸道细菌定植所引起的炎症可能是有重要作用.通过应用防污染技术留取支气管分泌物进行定量培养,发现25%～40%的稳定期患者有定植菌的存在,常见者为流感嗜血杆菌属、肺炎链球菌属和卡它莫拉菌.正常呼吸道存在多重防御机制,以抵抗细菌定植,并保持正常下呼吸道处于无菌状态.在COPD、气管内插管等情况下,这种防御机制受到破坏,可导致细菌定植.其中重要的危险因素包括:正常生理的改变、吸烟与气流阻塞程度.COPD患者细菌的慢性定植可导致气道炎症持续存在,造成肺功能的进行性下降,急性加重期无创机械通气治疗的失败.可能的防治方法包括疫苗的应用,以及在口咽部表面及气管导管应用洗必泰等抗菌剂.     

Longitudinal study of airway dimensions in chronic obstructive pulmonary disease using computed tomography

Background and objective:   Chest CT has been widely used for the evaluation of structural changes in lung parenchyma and airways in cross-sectional studies. There has been no report on the annual changes in airway dimensions as assessed by CT in COPD patients. The objective of this study was to investigate the annual changes in airway dimensions and lung attenuation using CT in patients with COPD and to evaluate the correlations among annual changes in CT measurements and pulmonary function.
Methods:   Eighty-three men with COPD had completed five annual assessments of CT scans and pulmonary function tests over 4 years. Airway dimensions of the basal segment bronchi and lung attenuation on CT images were analysed in 38 subjects in whom the same airway could be measured at least three times, including at entry and at the end of the study.
Results:   Mean annual decline in FEV₁ was 21 mL/year. Annual changes in the percentage of low attenuation areas were not significantly correlated with decline in FEV₁. On the other hand, annual changes in the percentage of wall area (WA%/year) were significantly inversely correlated with annual changes in FEV₁ ( r  = −0.363, P  = 0.025), whereas WA%/year did not differ among severity stages at entry and did not correlate with baseline FEV₁.
Conclusions:   The results showing that annual changes in airway thickening correlated with annual decline in air flow limitation suggests the importance of treatment of airway inflammation in COPD. CT is a useful tool for quantitative estimation not only of emphysema but also of airway lesions in longitudinal studies.     

Peripheral arterial disease: an underestimated aetiology of exercise intolerance in chronic obstructive pulmonary disease patients.

OBJECTIVE: To assess the prevalence of peripheral arterial disease and its implications for exercise limitation in chronic obstructive pulmonary disease (COPD) patients. METHOD: One hundred and fifty-one moderate-to-severe COPD patients (forced expiratory volume in 1 s: 37+/-6 SD% predicted) and 73 healthy age-matched control individuals (divided into 31 smokers and 42 nonsmokers) participated in this study. All COPD patients were either exsmokers or current smokers and their tobacco-smoking history was similar to that of healthy smokers. To evaluate the existence of arterial disease, lower limb perfusion pressure impairment was assessed using the ankle brachial index, whereas arterial stiffness was assessed by the pulse wave velocity (PWV). The definition of peripheral arterial disease required an ankle brachial index value of 0.90 or less, whereas the PWV increment was considered to be a direct witness of arterial stiffness increase. A 6-min walk test was performed to assess physical exercise capacity. RESULTS: Prevalence of peripheral arterial disease was higher in COPD patients than in healthy participants (81+/-3 SD; 49+/-5 SD and 9+/-2 SD%, respectively, in COPD, healthy smokers and nonsmokers). PWV mean values were significantly higher in COPD patients compared with healthy smokers and nonsmokers (10.3+/-2.1 SD m/s; 9.2+/-1.3 SD m/s and 8.7+/-2.2 SD m/s, respectively). The distance covered during the 6-min-walk test was associated positively with the degree of peripheral arterial disease (r=0.78; P=0.05) and negatively with the PWV values (r=-0.74; P=0.05). Not only tobacco-smoking history but also COPD severity was shown to influence these associations. CONCLUSION: The effect of peripheral arterial disease on exercise intolerance in COPD seems to be considerable. Therefore, COPD patients participating in a pulmonary rehabilitation programme should profit from a systematic search for arterial disease. Arterial dysfunction has to be taken into account in the multidisciplinary treatment of these patients.     

慢性阻塞性肺疾病下呼吸道细菌定植

慢性阻塞性肺疾病（COPD）反复发作是导致疾病进行性发展的重要因素之一。许多学者认为感染是引起COPD急性发作的一个重要原因,并且发现部分COPD患者在稳定期存在下呼吸道细菌定植,这一现象为什么会产生？主要的定植菌是什么？它在COPD的发病过程中起到一个什么作用？存在下呼吸道细菌定植的患者是否需要使用抗生素抗感染治疗？目前均无定论,本文就此作一综述。     

气道微生态在慢性阻塞性肺疾病中的研究进展

慢性阻塞性肺疾病（COPD）是一种慢性气道炎症性疾病,其特征为慢性呼吸道症状（呼吸困难、咳嗽、咳痰、急性加重）。感染是COPD恶化以及肺功能下降的主要原因,呼吸道微生态以及其所带来的免疫调节功能在其中发挥重要作用。新一代基因测序技术使得更清楚地了解呼吸道微生态组成及其与呼吸系统疾病相关性,不仅揭示了健康人群肺部拥有丰富的微生物群落,而且与健康人群相比,COPD患者的气道微生态结构和各菌群的相对丰度均发生了改变。本文对气道微生态在COPD中的研究进展作一综述。     

Airflow limitation and airway dimensions in chronic obstructive pulmonary disease

RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation caused by emphysema and/or airway narrowing. Computed tomography has been widely used to assess emphysema severity, but less attention has been paid to the assessment of airway disease using computed tomography. OBJECTIVES: To obtain longitudinal images and accurately analyze short axis images of airways with an inner diameter>or=2 mm located anywhere in the lung with new software for measuring airway dimensions using curved multiplanar reconstruction. METHODS: In 52 patients with clinically stable COPD (stage I, 14; stage II, 22; stage III, 14; stage IV, 2), we used the software to analyze the relationship of the airflow limitation index (FEV1, % predicted) with the airway dimensions from the third to the sixth generations of the apical bronchus (B1) of the right upper lobe and the anterior basal bronchus (B8) of the right lower lobe. MEASUREMENTS AND MAIN RESULTS: Airway luminal area (Ai) and wall area percent (WA%) were significantly correlated with FEV1 (% predicted). More importantly, the correlation coefficients (r) improved as the airways became smaller in size from the third (segmental) to sixth generations in both bronchi (Ai: r=0.26, 0.37, 0.58, and 0.64 for B1; r=0.60, 0.65, 0.63, and 0.73 for B8). CONCLUSIONS: We are the first to use three-dimensional computed tomography to demonstrate that airflow limitation in COPD is more closely related to the dimensions of the distal (small) airways than proximal (large) airways.     

慢性阻塞性肺疾病与气道微生物群关系的研究现状

慢性阻塞性肺疾病(COPD)已成为高患病率、高病死率的全球疾病负担之一。在传统的支气管舒张剂、糖皮质激素、抗生素等治疗措施之外,新的防治措施和治疗靶点亟待开发。近年来随着基因测序技术的发展,关于COPD气道微生物群的研究已取得较多进展。本文将从COPD气道微生物群的群谱特征及其与COPD的相关性,气道微生物群影响COP...     

Use of an ultrathin bronchoscope in the assessment of central airway obstruction

STUDY OBJECTIVE: To assess the utility of an ultrathin bronchoscope (UB) in the assessment of central airway obstruction (CAO). DESIGN: Prospective evaluation SETTING: Tygerberg Hospital, a tertiary teaching hospital. PATIENTS: Consecutive patients referred to the Lung Unit with CAO. INTERVENTIONS: Fiberoptic bronchoscopy (FOB) was performed with a prototype UB (Olympus BF XP40; Olympus Europe; Hamburg, Germany; outer diameter, 2.8 mm; working channel, 1.2 mm). The UB was used whenever a standard bronchoscope (SB) could not pass the obstruction or could not be tolerated by the patient. MEASUREMENTS AND RESULTS: Data relating to indication and performance of FOB, patient demographics, utility in establishing a diagnosis, and planning definitive management were documented. Twenty-four patients (17 men; mean age, 46 years) were studied. Twelve patients (50%) had malignant CAO, 8 patients (33%) had benign tracheal stenosis, 3 patients (12.5%) had stent occlusion, and 1 patient (4%) had bilateral vocal cord paralysis. In 42% of patients, an initial attempt at passing the obstruction with an SB had failed. Vocal cords or trachea were involved in 62% of patients. The mean luminal occlusion was 84% of the total airway lumen (range, 50 to 100%). One complication (desaturation) led to early termination of FOB. In all but three patients with complete obstruction, the UB was able to pass the CAO and allowed assessment of the obstruction and the distal airways (87%). CONCLUSION: UB-FOB was useful and safe in the assessment of patients with CAO from both benign and malignant disease. It aided in establishing a diagnosis and/or planning of definitive management in all patients examined.     

气道高反应性在COPD和哮喘的比较

目的 探讨慢性阻塞性肺疾病(chronic obstructive pulmonary diseases,COPD)和支气管哮喘(简称哮喘)患者在组胺支气管激发试验中气道高反应性(airway hyperresponsiveness,AHR)的不同.方法 将我院2008～2010年间诊断为COPD和哮喘的并经随访一年处于稳定期的患者共80例,其中COPD组39例,哮喘组41例,均行支气管组胺激发试验,观察FEF25％～75％/FVC(肺活量为25％～75％时最大呼气流量与用力肺活量的比值)在两组患者的变化.结果 COPD组FEF25％～75％和FEF25％～75 ％/FVC均明显低于哮喘组(P值均＜0.01);以激发试验阳性的两组患者为对象分别进行简单相关分析,在COPD组和哮喘组中FEF25％～75％/FVC与Log10DRS呈负相关(r分别为-0.510和-0.466,P＜0.05),与PD20FEV1呈正相关(r分别为0.518和0.487,P＜0.05),说明相对于肺容积而言,气道容积越小,气道收缩性越强,反应性越高.随后在以气道收缩性指标Log10DRS为因变量,以年龄、体表面积、FEV1％及FEF25％～75 ％/FVC为自变量进行线性回归分析,在COPD组FEV1％对Log10DRS较FEF25％～75％/FVC影响大(P＜0.05),而哮喘组不存在这情况.结论 在COPD中AHR患者并不少见,其发生机制与哮喘是不同的.     

气道高反应性在COPD和哮喘的比较

目的探讨慢性阻塞性肺疾病(chronic obstructive pulmonary diseases,COPD)和支气管哮喘(简称哮喘)患者在组胺支气管激发试验中气道高反应性(airwayhyperresponsiveness,AHR)的不同。方法将我院2008～2010年间诊断为COPD和哮喘的并经随访一年处于稳定期的患者共80例,其中COPD组39例,哮喘组41例,均行支气管组胺激发试验,观察FEF25%～75%/FVC(肺活量为25%～75%时最大呼气流量与用力肺活量的比值)在两组患者的变化。结果 COPD组FEF25%～75%和FEF25%～75%/FVC均明显低于哮喘组(P值均<0.01);以激发试验阳性的两组患者为对象分别进行简单相关分析,在COPD组和哮喘组中FEF25%～75%/FVC与Log10DRS呈负相关(r分别为-0.510和-0.466,P<0.05),与PD20FEV1呈正相关(r分别为0.518和0.487,P<0.05),说明相对于肺容积而言,气道容积越小,气道收缩性越强,反应性越高。随后在以气道收缩性指标Log10DRS为因变量,以年龄、体表面积、FEV1%及FEF25%～75%/FVC为自变量进行线性回归分析,在COPD组FEV1%对Log10DRS较FEF25%～75%/FVC影响大(P<0.05),而哮喘组不存在这情况。结论在COPD中AHR患者并不少见,其发生机制与哮喘是不同的。     

Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations

RATIONALE: Severe exacerbations of chronic obstructive pulmonary disease (COPD) are major causes of health care costs mostly related to hospitalization. The role of infections in COPD exacerbations is controversial. OBJECTIVES: We investigated whether COPD exacerbations requiring hospitalization are associated with viral and/or bacterial infection and evaluated relationships among infection, exacerbation severity, assessed by reduction of FEV1, and specific patterns of airway inflammation. METHODS: We examined 64 patients with COPD when hospitalized for exacerbations, and when in stable convalescence. We measured lung function, blood gases, and exhaled nitric oxide, and examined sputum for inflammation and for viral and bacterial infection. RESULTS: Exacerbations were associated with impaired lung function (p < 0.01) and increased sputum neutrophilia (p < 0.001). Viral and/or bacterial infection was detected in 78% of exacerbations: viruses in 48.4% (6.2% when stable, p < 0.001) and bacteria in 54.7% (37.5% when stable, p = 0.08). Patients with infectious exacerbations (29.7% bacterial, 23.4% viral, 25% viral/bacterial coinfection) had longer hospitalizations (p < 0.02) and greater impairment of several measures of lung function (all p < 0.05) than those with noninfectious exacerbations. Patients with exacerbations with coinfection had more marked lung function impairment (p < 0.02) and longer hospitalizations (p = 0.001). Sputum neutrophils were increased in all exacerbations (p < 0.001) and were related to their severity (p < 0.001), independently of the association with viral or bacterial infections; sputum eosinophils were increased during (p < 0.001) virus-associated exacerbations. CONCLUSIONS: Respiratory infections are associated with the majority of COPD exacerbations and their severity, especially those with viral/bacterial coinfection. Airway neutrophilia is related to exacerbation severity regardless of viral and/or bacterial infections. Eosinophilia is a good predictor of viral exacerbations.     

慢性阻塞性肺疾病气道炎症在肺动脉重构中的作用

慢性阻塞性肺疾病(COPD)的慢性气道炎症是COPD的重要病理基础,它不仅在气道结构重构中起关键作用,而且在肺动脉重构亦有重要作用,甚至在无低氧血症时已引起肺动脉功能和结构的改变,以平滑肌增殖和细胞外基质在肺动脉内层沉积为特征,伴有肺动脉最大舒张性及最大收缩性降低,肺动脉外膜出现以CD8 T细胞浸润为主的炎症反应,在此期间肺组织中慢性炎症过程引起的肺动脉内皮功能障碍、转移生长因子过度表达、成纤维细胞生长因子及血管内皮生长因子及其受体的改变在肺血管结构重构中起作用。     

稳定期慢性阻塞性肺疾病气道炎症的研究

目的 研究稳定期慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)气道炎症和肺功能、下气道细菌定植(lower airway bacterial colonization,LABC)的关系.方法 随机入选45例稳定期COPD门诊患者和28名健康志愿者,行肺功能、血常规和胸片检查.采用痰诱导方法 留取深部合格痰液,COPD患者的痰液行细菌定量培养,两组研究对象的痰液均行细胞因子检测.结果 稳定期COPD组痰液中白介素8(IL-8)、肿瘤坏死因子α(TNF-α)、IL-10、IL-19明显高于对照组(P＜0.05).第1秒用力呼气容积占预计值百分比(FEV1%pred)＜50%组痰液中IL-8、TNF-α、IL-19明显高于FEV1%pred≥50%组(P＜0.05),而IL-10在两组间比较差异无统计学意义.在本实验中LABC量≥107CFU/ml者占总人数的33.33%,主要的下气道定植菌为卡他莫拉菌、副流感嗜血杆菌、肺炎链球菌、流感嗜血杆菌等.LABC量≥107 CFU/ml组痰液中IL-8、TNF-α、IL-19明显高于LABC＜107 CFU/ml组(P＜0.05),而IL-10在两组间比较差异无统计学意义.相关性分析显示,IL-19与IL-10呈负相关,相关系数r=-0.548(P＜0.05),IL-19与IL-8、TNF-α呈正相关,相关系数分别为r=0.702(P＜0.05)、r=0.708(P＜0.05).FEV1%pred＜50%组细菌定植量明显高于FEV1%pred≥50%组(P＜0.05).FEV1%pred＜50%预计值组的吸烟指数明显高于FEV1%pred≥50%组(P＜0.05).结论 稳定期COPD患者存在气道炎症,既与LABC有关,又与吸烟有关,这种与LABC和吸烟相关的气道炎症可能是导致COPD患者肺功能进行性下降的原因.