CAT、CYBA及NIK基因与慢性阻塞性肺疾病及相关肺动脉高压易感性的关系

目的:探讨细胞色素b-245α多肽(CYBA)、过氧化氢酶(CAT)及核因子κB诱导激酶(NIK)基因单核苷酸多态性与宁夏地区汉族慢性阻塞性肺疾病(COPD)及相关肺动脉高压(PH)发病易感性的关系。方法:取稳定期COPD患者250例(包括COPD相关PH组103例和COPD非PH组147例)及同期健康对照组127例全血,用飞行质谱法检测CYBA基因rs1049255和rs9932581、CAT基因rs1001179和rs7943316及NIK基因rs7222094位点的基因型及等位基因频率。结论:(1)rs1001179位点基因型及等位基因频率分布在健康组和COPD组间差异有统计学显著性(P<0. 05):与C等位基因相比,携带T等位基因的优势比(OR)=0. 21,95%置信区间(CI)为0. 10⁰. 48。(2)rs1049255位点基因型与等位基因频率在COPD相关PH及COPD非PH组间差异有统计学显著性(P<0. 05):与GG基因型相比,携带AA基因型的OR=2. 50,95%CI为1. 15⁵. 46;与G等位基...     

白细胞介素-10 基因启动子多态性与慢性阻塞性肺疾病易感性的关系

目的　探讨中国汉族人白细胞介素 - 10基因启动子单核苷酸多态性及其与慢性阻塞性肺疾病易感性之间的关系。　方法　应用聚合酶链反应 -限制性片段长度多态性分析方法 ,检测 94名健康吸烟者和 88例吸烟慢性阻塞性肺疾病 (chronic obstructive pulmonary disease,COPD)患者白细胞介素 - 10(interleukin- 10 ,IL- 10 )基因启动子 - 10 82 G/ A、- 819C/ T、- 5 92 C/ A单核苷酸多态性位点基因型。　结果共发现 11种启动子基因型 ,以 AA·TT·AA、AA·TC· AC、AA· TC· AA基因型多见 ;通过对 11种启动子基因型进行分析 ,新发现 ATC、ACA两种单倍型 ;健康吸烟者和吸烟 COPD患者 IL- 10基因启动子- 10 82 G/ A、- 5 92 C/ A位点基因型分布频率差异无显著性 ,- 819C/ T多态性位点与中国汉族人 COPD易感性有关 ;中国汉族人 IL- 10基因启动子等位基因频率与日本人相似 ,与白种人之间差异存在显著性。　结论　中国汉族人 COPD易感性与 IL- 10基因启动子 - 819C/ T位点多态性有关 ;中国汉族人 IL- 10基因启动子至少存在 ATA、ACC、GCC、ATC、ACA5种单倍型。     

慢性阻塞性肺疾病发病易感性与单核苷酸多态性相关

目的 探讨慢性阻塞性肺疾病(COPD,慢阻肺)的基因单核苷酸多态性与发病易感性的关系。方法 选择444例慢阻肺患者及434例健康人群作为研究对象,对壳三糖苷酶/几丁质酶1(CHIT1)上的4个位点：rs771576027、rs1402870472、rs61745299和rs527497633以及磷酸二酯酶4D(PDE4D)上的1个位点rs117292391进行Sequenom MassARRAY检测分型,通过数据统计判断单核苷酸多态性(SNP)与慢阻肺发病风险的关系。结果 rs61745299(CHIT1)位点的基因型CG和等位基因C提示慢阻肺的发病风险较高,并且分布频率存在显著性差异(P<0.05);rs117292391(PDE4D)位点的基因型AG和等位基因G同样提示慢阻肺的发病风险较高,并且分布频率存在显著性差异(P<0.05);此外,吸烟也会增加慢阻肺的发病风险。结论 CHIT1的rs61745299位点和PDE4D的rs117292391位点可能成为COPD的潜在生物标志。     

疏血通对慢性阻塞性肺疾病合并肺动脉高压患者凝血状态及血清NO、NOS水平的影响

目的 观察疏血通治疗慢性阻塞性肺疾病(COPD)合并肺动脉高压(PAH)的疗效及对患者凝血状态及血清NO、NOS水平的影响.方法 将80例COPD合并PAH患者随机分为对照组和观察组,每组40例.对照组给予常规综合治疗,观察组在对照组基础上加用疏血通注射液治疗.分别于治疗前后检测患者血清一氧化氮(N0)、一氧化氮合成酶(NOS)、内皮素-1(ET-1)、抵抗素水平及血红蛋白(HB)、全血高切、低切黏度,比较两组治疗前后肺动脉收缩压、血气指标、肺功能指标及症状、体征改善情况.结果 治疗前,观察组与对照组各项测定指标差异均无统计学意义;治疗后,观察组较对照组血清NOS、NO水平明显升高(P＜0.05),ET、抵抗素水平明显降低(P＜0.05);全血高切黏度、全血低切黏度及HB水平明显降低(P＜0.05);肺动脉收缩压明显降低(P＜0.05),血气指标(PaO2、PaCO2、SaO2)、肺功能指标(FEV1、FEV1/FVC)及咳嗽、喘息、紫绀等症状、体征评分明显改善(P＜0.05).结论 疏血通辅助治疗COPD合并PAH,可通过调节血清NO、ET-1平衡,降低血清抵抗素水平,改善血管内皮功能,缓解血液高凝状态,降低肺动脉压,从而明显改善患者血气指标、肺功能指标及临床症状、体征.     

老年慢性阻塞性肺疾病患者血浆N-端脑钠肽前体与肺动脉高压的关系

目的:探讨老年慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者中血浆N-端脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)与肺动脉高压的关系.方法:将99例老年COPD患者,根据心脏彩超分为单纯...     

低氧性肺动脉高压和慢性支气管炎、肺气肿并肺动脉高压动物模型的异同

目的 比较低氧性肺动脉高压与慢性支气管炎、肺气肿并肺动脉高压动物模型的异同,为研究慢性阻塞性肺疾病中肺动脉高压形成机制提供良好的实验模型.方法 24只雄性SD大鼠随机纳入10%低氧组(A组)、慢性支气管炎、肺气肿并肺动脉高压组(B组)及正常对照组(C组),8只/组.吸入10%氧2周制作A组,气管内注入脂多糖和每天烟熏混合刺激加18%低氧制作B组模型.各组测定血气分析、肺血流动力学并对肺泡灌洗液行白细胞计数、分类.肺组织HE染色或三联染色后观测气道炎症和肺血管重构的病理形态学改变.结果 (1)与C组比较,A、B组右心室收缩压、平均肺动脉压、右心室与左心室+室间隔重量比升高,腺泡内肌化型动脉增多、管壁增厚(P＜0.05).(2)BALF分析A组白细胞总数与C组差异无显著性(P＞0.05);B组白细胞总数及中性粒细胞增多(P＜0.05).(3) A组气道炎症以上皮细胞变性坏死、黏液杯状细胞增生为主,炎细胞浸润不明显.B组气道炎症符合慢性支气管炎、肺气肿改变,管壁呈现以淋巴细胞为主的多种炎细胞浸润.结论 B组同时体现了慢性气道炎症、肺气肿改变和肺血管重构的特征,更适合用于慢性阻塞性肺疾病中肺动脉高压形成机制的研究.     

慢性阻塞性肺疾病患者夜间低氧血症与血小板活化

目的 探讨慢性阻塞性肺疾病（COPD）患者夜间低氧血症的发生情况及血小板活化与肺动脉高压的相关性。方法 55例稳定期COPD患者分为非呼吸衰竭组（A组,40例）及呼吸衰竭组（B组,15例）;对照组（C组,15例）为急性肺炎治愈患者。进行睡眠时监测,用彩色多普勒估测肺动脉压,流式细胞仪测定血小板活化分子CD61、CD42b和CD49b。结果COPD患者夜间睡眠时出现低氧或低氧血症加重,伴夜间低氧血症患者的血小板活化增强。结论 推测低氧所致血小板活化增强在肺动脉高压的形成过程中起重要作用。     

解整合素－金属蛋白酶33与慢性阻塞性肺疾病关系的研究现状

慢性阻塞性肺疾病(COPD)是不完全可逆、气流受限为特征的疾病,目前理论认为该病与个体因素及遗传因素相关,气道结构改变为该病主要病理表现。近几年,解整合素原金属蛋白酶33(A distintegrin and metal oproteinase 33)被发现是ADAMs中的成员,ADAM33基因多态性和气道的结构改变有关,可以引起COPD的发病。本文就遗传和ADAM33基因与COPD发病的关系进行综述。     

肺表面活性物质相关蛋白A基因多态性与新疆蒙古族慢性阻塞性 肺疾病患者的发病

背景：目前慢性阻塞性肺疾病的遗传易感性机制未完全阐明。肺表面活性物质相关蛋白A可能在其易感性机制中发挥重要作用,且可能有种族差异。 目的：探讨肺表面活性物质相关蛋白A基因位点aa62、aa219多态性与新疆蒙古族慢性阻塞性肺疾病易感性的关系。 方法：采用病例-对照研究设计,纳入新疆蒙古族吸烟慢性阻塞性肺疾病患者119例(病例组)和吸烟健康体检者116例(对照组)为研究对象。采用Taqman探针标记荧光定量PCR法检测肺表面活性物质相关蛋白A基因的aa62(CCA/CCG,rs1136451)和aa219(CGG/TGG,rs4253527)位点的单核苷酸多态性,获得各基因型和等位基因的分布情况。 结果与结论：在aa62位点,两组的基因型频率(AA,AG、GG)及等位基因频率(A、G)比较差异均有显著性意义 (χ²=7.164,P=0.028;χ²=2.239,P=0.019);且基因型频率在肺功能Ⅱ级与Ⅲ级慢性阻塞性肺疾病患者间差异有显著性意义(χ²=8.721,P=0.013)。在aa219位点,两组基因型频率(CC,CT)及等位基因频率(C、T)比较差异均无显著性意义(χ²=0.367,P=0.545;χ²=0.332,P=0.565)。提示肺表面活性物质相关蛋白A基因aa62位点多态性可能与新疆蒙古族吸烟慢性阻塞性肺疾病的易感性相关。     

胸腺五肽辅助治疗慢性阻塞性肺病的疗效观察

目的观察胸腺五肽辅助治疗慢性阻塞性肺病(COPD)的疗效。方法将78例COPD患者随机分为2组,对照组给予常规治疗,治疗组加用胸腺五肽,观察比较2组患者症状体征缓解时间、平均住院时间以及3个月内再入院率。结果治疗组症状体征缓解时间、平均住院时间均较对照组显著缩短(P<0.05),治疗组3个月内再入院率较对照组显著降低(P<0.05)。结论胸腺五肽可增强COPD患者的免疫功能,缩短平均住院时间,降低再发风险,提高患者生活质量。     

Left heart function in chronic obstructive lung disease

Summary In patients with varying degrees of chronic obstructive pulmonary disease (COPD), simultaneous measurements of central hemodynamics and left ventricular radionuclide ventriculograms at rest and during exercise were made. In 21 of these patients, satisfactory echocardiograms could be performed. In seven of the patients, arterial blood pressure at rest was increased. Decreased compliance of the left ventricle was thought to be present in patients with COPD and additional arterial hypertension. The left ventricular ejection fraction (LVEF) at rest was in the high normal range in all patients. During exercise, no further increase was observed. This pattern of LVEF response seems to be typical in patients with COPD. Because the highest values were observed in the more severe COPD and right ventricular hypertrophy, it is unlikely that an impairment of left ventricular function is caused by COPD. In five of 27 patients, an abnormal decrease of LVEF and regional hypokinesis occurred during exercise, thus suggesting additional coronary heart disease. The fact that at least 30% of the patients with COPD suffered from arterial hypertension and 20% of the patients exhibited unexpected ischemia detected by regional hypokinesis in RNV during exercise, but not in the ECG, may be of practical relevance. Coronary angiography was not indicated because most of these patients were over 65 and the factor limiting the working capacity was ventilatory impairment and not angina pectoris, in all patients. For this reason, a diagnostic uncertainty remains with regard to additional coronary heart disease in the older patients with advanced chronic obstructive pulmonary disease.Lung Function Parameters VC (1) inspiratory vital capacity - FEV1 (1) forced exspiratory volume in 1 sec - Raw (cmH20/l/s) airways resistance - RV/TLC (%) residual volume/total lung capacity - paO₂ (mm Hg) O₂ partial pressure Hemodynamic Parameters CI (1/min/sqm) cardiac index - SVI (ml/sqm) stroke volume index - PAP (mm Hg) pulmonary artery mean pressure - PwP (mm Hg) pulmonary capillary wedge pressure - RRs (mm Hg) systolic arterial pressure - RRd (mm Hg) diastolic arterial pressure (at the time of catheterization) - RR(WHO) (mm Hg) mean values measured at different days (at least 3 values). Parameters Derived from Combined Radionuclide Ventriculography and Central Hemodynamics LVEF (%) left ventricular ejection fraction - LVESVI (ml/sqm) left ventricular endsystolic volume index - P/V (mm Hg/ml/sqm) peak systolic pressure/endsystolic volume index - PFR (1/sec) peak filling rate: endsystolic volume/sec Echocardiographic Parameters RV d wth (mm) right ventricular enddiastolic wall thickness - LV d wth (mm) left ventricular enddiastolic wall thickness In honor to Prof. W.E. Adam's 60th birthday     

Prediction of exacerbation onset in chronic obstructive pulmonary disease patients

The objective of this study was to develop an algorithm for prediction of exacerbation onset in Chronic Obstructive Pulmonary Disease (COPD) patients based on continuous self-monitoring of physiological parameters from telehome-care monitoring. 151 physiological parameters of COPD patients were monitored on a daily/weekly basis for up to 2 years. Data were segmented in 30-day periods leading up to an exacerbation (exacerbation episode) and starting from a 14-day recovery period post-exacerbation (control episode) and tested in 6 intervals to predict exacerbation onset using k-nearest neighbour (k?=?1, 3, 5). A classifier with sensitivity of 73%, specificity of 74%, positive predictive value of 69%, negative predictive value of 78% and an accuracy of 74% was achieved using data intervals consisting of 5 days. Intelligent processing of physiological recordings have potential for predicting exacerbation onset.     

外周血Th17细胞对慢性阻塞性肺疾病症状严重程度及预后的评估价值

 目的: 观察Th17细胞水平与慢性阻塞性肺疾病(COPD)患者症状严重程度及预后因素的相关性,以期探讨Th17细胞水平在判断COPD临床预后方面的可能价值。方法: 选取2013年5月～2014年12月我院就诊的110例COPD患者为研究对象,40例健康体检者为对照组。根据COPD全球倡议(GOLD)将COPD患者分为A组(低危、症状轻)、B组(低危、症状重)、C组(高危、症状轻)及D组(高危、症状重),给予吸入性糖皮质激素/长效β₂受体激动剂或吸入性糖皮质激素/长效β₂受体激动剂+长效胆碱能药物治疗,收集患者治疗前及治疗3个月后相关临床资料,包括外周血Th17细胞比例、细胞因子(IL-17和IL-6)、慢性阻塞性肺疾病评估测试(CAT)评分、年龄、体重指数、肺功能指标及诊断前12个月COPD急性加重(AECOPD)次数,分析Th17细胞水平与其它临床特征间的相关性。结果: COPD患者外周血Th17细胞、IL-17及IL-6水平显著高于对照组(P < 0.05)。随着COPD症状严重程度的增加,B、D组COPD患者外周血Th17细胞、细胞因子(IL-17和IL-6)水平及CAT评分显著高于A、C组患者(P < 0.05)。单变量相关分析发现,治疗前B、D组外周血Th17细胞水平与CAT评分呈正相关(P < 0.05),而与FEV₁ 、FEV₁%Pred、FVC及FVC%Pred呈负相关(P < 0.05);A、C组外周血Th17细胞水平与CAT评分、FEV₁、FEV₁%Pred、FVC及FVC%Pred无明显相关性。治疗后外周血Th17细胞水平与CAT评分呈正相关(P < 0.05),而与FEV₁、FEV₁%Pred、FVC及FVC%Pred呈负相关(P<0.05)。结论: 外周血Th17细胞水平与COPD患者IL-17、IL-6、CAT评分及肺功能指标有较好的相关性,具有评估COPD患者症状严重程度及预后的潜在临床价值。     

多索茶碱与噻托溴铵粉联合治疗对慢阻肺患者肺功能影响的临床观察

目的：探讨多索茶碱与噻托溴铵粉联合治疗慢阻肺对肺功能的影响。方法：选取2009年7月至2012年11月在我院进行治疗慢阻肺患者114例,随机分为观察组和对照组,观察组采用多索茶碱与噻托溴铵粉联合治疗,对照组给予多索茶碱单独治疗,比较疗效。结果：观察组有效率为96.49%,对照组有效率为70.18%;治疗后,观察组与对照组的社会活动、日常生活、焦虑、抑郁评分以及总分、FEV1、FVC、FEV1/FVC水平差异显著（P〈0.05）。结论：多索茶碱与噻托溴铵粉联合治疗慢阻肺,可显著改善患者肺功能,提高治疗疗效,提高患者生活质量,值得临床运用。     

CTLA-4 gene polymorphisms and susceptibility to chronic obstructive pulmonary disease

Objective: The aim of this study was to investigate whether four single nucleotide polymorphisms (SNPs) in CTLA-4 gene are associated with chronic obstructive pulmonary disease (COPD) in a Chinese population. Methods: Samples were collected from a Chinese population and analyzed for the association of SNPs in CTLA-4 gene with COPD in a case-control study. Four SNPs (rs231775, rs3087243, rs231725, rs5742909) in CTLA-4 gene were chosen and genotyped. The results were then analyzed using statistical methods. Results: We found that none of these four SNPs (rs231775, rs3087243, rs231725, rs5742909) in CTLA-4 gene were associated with the disease. Conclusion: Our data suggested that there was no significant association between these four SNPs in CTLA-4 gene and COPD susceptibility in a Chinese population.     

慢性阻塞性肺疾病的全身效应

 慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease,COPD）是一种常见病、多发病,其典型表现为气流受限和气道重塑,导致肺的结构与功能的改变。由于COPD的患者多种炎症介质的激活使患者处于系统性炎症状态,使得COPD不仅仅是呼吸系统的疾病,同时还包含许多肺外表现,即全身效应。常见的全身性表现包括：骨骼肌萎缩、恶液质、骨质疏松;而慢性炎症使COPD的患者缺血性心脏病、肺动脉高压、糖尿病等疾病的患病率大大增加。     

慢性阻塞性肺疾病小鼠模型制备方法的比较研究

目的:采用香烟烟雾(cigarette smoke,CS)暴露、肺炎克雷伯杆菌(Klebsiella pneumoniae,KP)感染、聚肌胞苷酸(polyinosinic-polycytidylic acid,Poly I:C)滴鼻、CS暴露联合KP感染和CS暴露联合Poly I:C滴鼻5种方法,建立并比较慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)小鼠模型。方法:将288只雄性BALB/c小鼠随机分为正常组(normal组)、CS组、KP组、CS+KP组、Poly I:C组及CS+Poly I:C组,每组48只。第1～8周造模,分别于第4、8、16和24周末取材。观察小鼠肺组织平均肺泡数(mean alveolar number,MAN)、肺泡平均截距(mean linear intercept,MLI)、肺功能呼气峰流速(peak expiratory flow,PEF)和50%潮气量呼气流量(50%tidal volume expiratory flow,EF50)的变化,检测肺组织中肿瘤坏死因子α(tumor nec...     

Severe chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) exacts a heavy toll on society, yet its prevention, diagnosis and treatment receives inadequate attention from both the medical community and from society at large. Guidelines released in 2001 from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) are aimed at redressing this inequity. In this review, we integrate information from the GOLD guidelines with recent updates on the prevention, treatment and management as related specifically to the most severe form of this disease. In order to help distinguish COPD from other disorders that may mimic or confound its treatment, we place particular emphasis on the definition, underlying pathophysiology and diagnosis of COPD. In addition, we discuss future directions in pharmacotherapy.