西地那非治疗慢性阻塞性肺疾病相关肺动脉高压的研究进展

肺动脉高压(PH)是慢性阻塞性肺疾病(COPD)的重要并发症,也是COPD患者致死的主要原因之一,故及早控制肺动脉压力,可以改善患者的病程及预后.磷酸二酯酶-5抑制剂西地那非,能够有效地降低肺动脉压力和肺循环血管阻力,提高心输出量和心脏指数,改善心功能,从而用于特发性PH、血栓栓塞性PH、先天性心脏病等引起PH的治疗.但对COPD相关PH的治疗作用仍存在争议,需要大样本的研究资料加以证实.     

慢性阻塞性肺疾病伴肺动脉高压对运动中气体交换的影响

目的:通过比较中重度慢性阻塞性肺疾病相关肺动脉高压(COPD-PH),与慢性阻塞性肺疾病无肺动脉高压(COPD-non PH),在运动中气体交换及运动耐量的差异,旨在为COPD-PH临床诊断、鉴别诊断、评估提供一定参考价值。方法:对54例处于稳定期的中重度慢性阻塞性肺疾病(COPD)患者依据肺动脉收缩压(PASP)分为两组,比较两组间血气分析、常规肺功能(PFT)、心肺运动试验(CPET)。结果:血气分析:COPD-PH的动脉氧分压(Pa O2)明显低于COPD-non PH(P0.01)。PFT:COPD-PH的第一秒用力呼气量(FEV1)、第一秒用力呼气量占预计值的百分比(FEV1%pred)及一氧化碳弥散量(DLco)均低于COPD-non PH(P0.05)。CPET:COPD-PH的峰值功率(Peak Load)、峰值摄氧量(Peak VO2)、峰值公斤摄氧量(Peak VO2/kg)、峰值分钟通气量(Peak VE)、Peak VE%pred及峰值氧脉搏(Peak O2pulse)均明显低于COPD-non PH(P0.01)。COPD-PH的峰值摄氧量占预计值的百分比(Peak VO2%pred)低于COPD-non PH(P0.05)。Pearson相关分析:PASP与DLco、Pa O2、Peak Load、Peak VO2及Peak O2pulse均呈负相关(P0.01)。结论:COPD-PH会导致患者肺换气功能明显受损、运动耐力明显下降,其降低程度与PASP存在相关性。对COPD行CPET,有助于早期发现COPD-PH。     

慢性阻塞性肺疾病与肺动脉高压的研究进展

<正>慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是呼吸系统常见病,患病率居高不下,是致贫致残的重要疾病,是全球第4大死亡原因,至2020年COPD将升至全球死亡原因的第3位,成为世界疾病经济负担的第5位~([1-2])。由于COPD是一种以持续气流受限为特征的肺部疾病,随着疾病的进展,慢性炎症导致肺实质破坏和肺血管的异常而形成肺动脉高压。     

慢性阻塞性肺疾病相关性肺动脉高压研究进展

肺动脉高压是慢性阻塞性肺疾病的一个重要合并症.慢性阻塞性肺疾病相关的肺动脉高压多为轻到中度且进展缓慢,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;肺血管重塑导致管腔变小;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慢性阻塞性肺疾病时的肺动脉高压相关.     

慢性血栓栓塞性肺动脉高压小鼠模型建立初探

目的 探讨建立操作简便、耗资低廉、实用并能更客观模拟临床慢性血栓栓塞性肺动脉高压(chronic thromboembolism pulmonary hypertension,CTEPH)的病理生理过程的小鼠模型.方法 雄性C57BL/6J小鼠56只,随机分为4组,即正常组(n=14)、假手术组(n=11)、模型组(n2=22)和氨甲环酸(tranexamic acid,AMCA)药物组(n=9).皮下注射戊巴比妥钠麻醉模型组和假手术组小鼠,暴露其左侧的颈外静脉,模型组注入自体血栓栓子,栓子则会顺血液循环栓塞肺动脉,从而造成急性肺栓塞.假手术组以生理盐水代替自体血栓栓子注入.AMCA药物组仅腹腔注射药物.正常组小鼠不进行任何处理.首次注栓1、2、3周后重复上述麻醉和注栓实验步骤,左、右颈外静脉交替使用.第6周测量各组小鼠右心室收缩压(right ventricular systolic pressure,RVSP),计算右心室肥大指数(right ventricular hypertrophy index,RVHI),并取肺组织进行后续病理学实验观察.病理组织学检查观察肺表面以及肺内的一系列病理变化,通过HE染色观察肺组织和肺血管结构的变化来判断造模成功与否.结果 与正常组和假手术组相比,模型组小鼠RVSP明显升高[(19.96±0.57) mmHgvs (17.18±1.17) mmHg,(16.73±0.61) mmHg,P＜0.05或P＜0.01)].与正常组、假手术组及AMCA药物组相比,模型组小鼠RVHI明显增加(29.60％±1.69％ vs19.55％±1.16％,19.80％±1.09％,18.07％±o.61％,P值均＜0.001).模型组小鼠肺动脉均有形态学变化,其中以远端细小动脉改变最为突出,主要表现为血管中膜平滑肌层增厚,平滑肌细胞增生,管腔明显缩小,部分管腔近乎闭合;肺中可见肺间质增厚,炎性细胞浸润明显,部分远端肺动脉中发现有大量红细胞聚集,可能是由于继发血栓的形成;栓塞较多部位可见肺泡融合或膨胀不全,肺泡壁充血、水肿.假手术组及AMCA药物组小鼠未见明显血栓栓塞,肺泡结构完整,肺泡及肺泡间隔内未见出血渗出和炎性细胞浸润,与正常组相比无明显改变.结论 用自体血栓栓子反复多次输注可成功诱导小鼠CTEPH形成,用该方法构建模型有一定的科研价值和可行性.     

慢性阻塞性肺疾病及肺动脉高压患者的能量代谢评定

慢性阻塞性肺疾病及肺动脉高压患者的能量代谢评定马国强冀虎岗杜钧刘正大李继平张汉丰将慢性阻塞性肺疾病（ＣＯＰＤ）及并肺动脉高压（ＰＡＨ）患者基础能量消耗实际测值（ＡＢＥＥ）与Ｈａｒｒｉｓ－Ｂｅｎｅｄｉｃｔ公式预计值（ＰＢＥＥ）对照，探讨在该病时基础能量...     

法舒地尔对慢性阻塞性肺疾病相关肺动脉高压患者血浆NT-ProBNP的影响

目的 探讨法舒地尔对慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）相关肺动脉高压患者血浆N端脑钠肽前体（NT-ProBNP）的影响.方法 人选研究对象为上海市浦东新区公利医院呼吸内科病房2012年8月-2014年2月入院的90例COPD急性加重（acute exacerbation COPD,AECOPD）患者,所有患者入院后超声心动图检查肺动脉收缩压（PASP）均＞50 mmHg.90例患者中男51例,女39例,年龄中位数为73.4岁,随机分为2组,一组给予吸氧、抗感染、解痉平喘祛痰等常规治疗（对照组,44例）,另一组在上述常规治疗基础上静脉给予法舒地尔（法舒地尔组,46例）.两组患者入院后测定血浆NT-ProBNP、动脉血气、心脏彩超检查,10d后复查,比较两组间治疗前、治疗后血浆NT-ProBNP、PASP、动脉血pH值、PaO2、PaCO2、氧合指数（PaO2/FiO2）等相关数值的差异,计算两组患者治疗前、治疗后血浆NT-ProBNP与PASP、动脉血pH值、PaO2、PaCO2、PaO2/FiO2的相关系数.结果 治疗前两组患者血浆NT-ProBNP、PASP、动脉血pH值、PaO2、PaCO2、PaO2/FiO2等相关数值的差异均无统计学意义（P均＞ 0.05）;法舒地尔组患者治疗后血浆NT-ProBNP、PASP、PaCO2均明显低于对照组患者治疗后相应指标（P均＜0.05）、动脉血pH值、PaO2、PaO2/FiO2均明显高于对照组患者治疗后相应指标（P均＜0.05）;治疗前、治疗后两组患者血浆NT-ProBNP与PASP、PaCO2均呈正相关性,与动脉血pH值、PaO2及PaO2/FiO2均呈负相关性.结论法舒地尔可以降低COPD相关肺动脉高压患者血浆NT-ProBNP水平,可能与其纠正AECOPD患者缺氧、减轻二氧化碳潴留、降低肺动脉压力有关.     

炎症在慢性阻塞性肺疾病相关肺动脉高压发病机制中的作用的研究进展

慢性阻塞性肺疾病(COPD)是以气道、肺实质、肺血管慢性炎症为主要特征的慢性肺疾病.肺动脉高压是COPD的主要并发症.近年来新的研究表明,COPD相关肺动脉高压的主要发病机制除缺氧外,炎症介质如白介素16、C反应蛋白、肿瘤坏死因子α、内皮素1等及炎症细胞如中性粒细胞、T淋巴细胞、巨噬细胞、肥大细胞等也起重要作用.     

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.     

慢性阻塞性肺疾病并肺动脉高压的实验动物模型研究现状

借助实验动物模型研究慢性阻塞性肺疾病(COPD)并肺动脉高压形成的机制,一直是COPD研究工作中的一大热点。用于反映COPD并肺动脉高压形成的动物模型有多种,其中低氧性肺动脉高压动物模型最为常用。导致COPD并肺动脉高压形成的因素很多,在疾病发展的过程中各种细胞生长因子、炎症因子和炎症细胞同时存在,相互影响。低氧、炎症因素和基因多态性均被纳入不同模型中进行研究。用单一因素诱发的肺动脉高压模型很难复制出人类COPD并肺动脉高压的病理、生理改变。     

吸烟与血管内皮损伤

越来越多的体内和体外研究表明 ,吸烟会损伤血管内皮 ,发生冠心病的危险性增加。至于香烟引起内皮损伤的具体成分以及机制尚未阐明     

Cigarette smoking and the risk of endometrial cancer: a meta-analysis

Objective

Epidemiologic findings are inconsistent concerning the association of endometrial cancer risk with cigarette smoking. We conducted a meta-analysis of epidemiologic studies to examine this relation.

Methods

A systematic literature search up to June of 2007 was performed in MEDLINE and EMBASE. Study-specific risk estimates were pooled using a random-effects model.

Results

Ten prospective and 24 case-control studies were included in the analysis of the effect of ever smoking. Ever smoking was statistically significantly associated with a reduced risk of endometrial cancer among prospective studies (relative risk 0.81; 95% confidence interval [CI], 0.74-0.88) and case-control studies (odds ratio 0.72; 95% CI, 0.66-0.79). The inverse association was significant among current and former smokers. Six prospective and 6 case-control studies were included in the quantitative analysis. We noted that an increase in smoking of 20 cigarettes per day was statistically significantly associated with 16% and 27% reduced risks of endometrial cancer in prospective and case-control studies, respectively. We also found that cigarette smoking was significantly associated with a decreased risk of endometrial cancer among postmenopausal women (relative risk 0.71; 95% CI, 0.65-0.78) but not among premenopausal women. In addition, the risk reduction seemed to be stronger among hormone replacement therapy users than nonusers.

Conclusion

Cigarette smoking was found to be significantly associated with a reduced risk of endometrial cancer, especially among postmenopausal women.     

Cigarette smoking and cognitive impairment: A 10-year cohort study in Taiwan

The relationship between cigarette smoking and cognitive impairment is not a simple one. Some studies have demonstrated that cigarette smoking is a risk factor for cognitive impairment in the elderly, whereas other studies have shown cigarette smoking to be protective against dementia. This study aims to explore the relationship between cigarette smoking and cognitive impairment in elderly persons without dementia, during a 10-year period. Data were derived from a population-based cohort study of 1436 elderly Taiwanese. Cognitive function was measured by the SPMSQ both in 1993 and in 2003. A total of 1436 participants free of cognitive impairment at baseline (SPMSQ ≥ 6 in 1993) were included in these analyses. Subsequently, participants were divided into three groups: never, past, and current smokers. The effect of cigarette smoking on cognitive function was assessed using logistic regression. In the logistic regression model adjusted for age, education, hypertension, diabetes, heart disease, and stroke at baseline, persons who had quit smoking (Odds ratio = OR = 0.31; 95% CI = 0.18-0.53; p < 0.001) and those who continued to smoke (OR = 0.37; 95% CI = 0.20-0.70; p < 0.001) were about one-third as likely to develop cognitive impairment as were those who never smoked. However, no dose-response relationship was observed between pack-years and cognitive impairment. Past and current smokers were less likely to develop cognitive impairment during a 10-year follow-up than were those who had never smoked. The present study suggests that smoking may be protective for cognitive function.     

Cigarette smoking and alcohol drinking and esophageal cancer risk in Taiwanese women

AIM:To investigate the etiology of esophageal cancer among Taiwanese women.METHODS:This is a multi-center,hospital-based,case-control study.Case patients consisted of women who were newly diagnosed and pathology-proven to have esophageal squamous cell carcinoma(ESCC) from three large medical centers(one from Northern and two from Southern Taiwan,respectively)between August 2000 and December 2008.Each ESCC patient was matched with 4 healthy women based on age(within 3 years)and hospital of origin,from the De...     

Cigarette price, affordability and smoking prevalence in the European Union

Aims To describe current and recent changes in cigarette affordability across the current 27 European Union (EU) Member States, and to assess the impact of these changes on smoking prevalence in countries that were EU members in 2004 (old Member States) compared to countries that have joined since 2004 (new Member States). Design Investigation of cigarette affordability using the minutes of labour measure, and comparisons of changes in affordability, tax and smoking prevalence in old and new EU Member States. Participants Current 27 EU Member States. Settings European Union. Measurements Cigarette prices, overall tax yield and incidence, hourly wages and smoking prevalence in the EU were obtained from published sources, and the affordability of the EU Most Popular Price Category (MPPC) cigarettes estimated as the number of minutes of labour required to earn the price of 20 cigarettes in the years 2003, 2006 and 2009. Findings The mean [standard deviation (SD)] number of minutes of labour required to purchase 20 MPPC cigarettes in EU Member States in 2009 was 31.3 (SD 10.7), but ranged fourfold across the EU, and was significantly higher in new than old Member States. The number of minutes of labour measure increased more, although not significantly so, between 2003 and 2009 in new [mean (SD) 12.1 (10.9)] than in old [6.7 (4.0)] Member States, largely because of proportionately higher increases in taxation. However, there was no correlation between change in affordability and change in smoking prevalence in recent years. Conclusions Cigarette affordability varies substantially and cigarettes are generally becoming less affordable in European Union Member States. However, these reductions in affordability do not appear to have impacted substantially on smoking prevalence in recent years.     

Cigarette smoking among Chinese PLWHA: An exploration of changes in smoking after being tested HIV positive

Prevention and cessation of Tobacco use among persons living with HIV/AIDS (PLWHA) represents a significant challenge for HIV/AIDS patient care in China and across the globe. Awareness of HIV-positive status may alter the likelihood for PLWHA smokers to change their smoking habit. In this study, we tested the risk enhancement and risk reduction hypotheses by assessing changes in cigarette smoking behavior among PLWHA after they received the positive results of their HIV tests. Cross-sectional survey data collected from a random sample of 2973 PLWHA in care in Guangxi, China were analyzed. Changes in cigarette smoking after receiving the HIV-positive test results, as well as the current levels of cigarette smoking were measured. Among the total participants, 1529 (51.7%) were self-identified as cigarette smokers, of whom 436 (28.9%) reduced smoking and 286 (19.0%) quit after receiving their HIV-positive test results. Among the quitters, 210 (73.9%) remained abstinent for a median duration of two years. There were also 124 (8.2%) who increased cigarette smoking. Older age, female gender, more education, and receiving antiretroviral therapy were associated with quitting. In conclusion, our study findings support the risk reduction and risk enhancement hypotheses. A large proportion of smoking PLWHA reduced or quit smoking, while a small proportion increased smoking. Findings of this study suggest that the timing when a person receives his or her HIV-positive test result may be an ideal opportunity for care providers to deliver tobacco cessation interventions. Longitudinal studies are indicated to verify the findings of this study and to support smoking cessation intervention among PLWHA in the future.     

吸入盐酸氨溴索对烟雾暴露大鼠COPD的防治效应研究

目的观察盐酸氨溴索(AMB)注射液对吸烟引致大鼠慢性阻塞性肺疾病(COPD)的干预效果。方法2006年3月至8月,在哈尔滨医科大学第一临床医学院呼吸内科应用单纯吸烟法引致大鼠COPD模型,雾化吸入AMB进行干预。对各组进行支气管肺泡灌洗液(BALF)细胞计数;测定BALF中基质金属蛋白酶-9(MMP-9)、白细胞介素-8(IL-8)及肿瘤坏死因子-α(TNF-α)的质量浓度;定量分析肺平均内衬间隔(MLI)、平均肺泡数(MAN)、肺泡腔面积与总面积比(PAA)、肺内弹力纤维的相对面积。结果COPD组BALF中MMP-9、IL-8及TNF-α与BALF中白细胞总数、中性粒细胞百分比、中性粒细胞绝对计数均呈正相关;COPD组大鼠肺内弹力纤维受到严重破坏,MLI、PAA高于对照组,MAN和弹力纤维的相对面积低于对照组,BALF中MMP-9、IL-8及TNF-α的质量浓度均明显高于对照组;AMB组BALF中IL-8、TNF-α、MLI、PAA及MAN均介于其他2组之间,而弹力纤维的相对面积、MMP-9质量浓度与COPD组差异无显著性意义。结论单纯吸烟可导致大鼠COPD,气道和肺泡内的MMP-9、IL-8和TNF-α均可能参与了弹力纤维的破坏和COPD的形成过程。AMB在一定程度上可抑制COPD大鼠气道及肺泡内的IL-8和TNF-α释放。     

Monitoring cigarette smoking prevalence in Britain in a timely fashion

Background Available estimates of cigarette smoking prevalence from the General Household Survey (GHS), the source of official smoking data in Britain, can be over a year out of date. With a number of policy initiatives being undertaken at national level, it would be useful to be able to track changes in a more timely manner. Aims and design We compared prevalence estimates from the Omnibus Survey, a monthly survey conducted by the Office for National Statistics, with those from the General Household Survey in order to examine whether they may provide a complementary and more timely source of cigarette smoking prevalence data. Findings The age and socio‐economic structure of the samples from the Omnibus and GHS surveys was very similar. When data from monthly Omnibus Surveys for the year 2000 were combined, prevalence estimates were within 1% point of those from the GHS for 2000, and overall sample sizes were also similar. The Omnibus data show a significant linear decline in prevalence between 1999 and 2002 of about 0.4% per year. This coincides with the introduction of a national strategy for reducing smoking prevalence. Conclusions The Omnibus Survey can be a useful additional tool for assessing changes in smoking prevalence.     

Correlates of regular cigarette smoking in a population-based sample of Australian twins

AIMS: To investigate the role of measured risk factors and the influence of genetic and environmental factors on regular cigarette smoking. Design Members of monozygotic and dizygotic, including unlike-sex twin pairs (n = 6257) from a young adult cohort from the Australian Twin Registry. METHODS: Cox proportional hazards models were used to determine whether putative risk factors were significantly associated with regular cigarette smoking. Risk factors were classified into four tiers: tier 1 (parental history, including parental education, alcoholism and cigarette smoking), tier 2 (early home and family influences), tier 3 (early life events, e.g. trauma) and tier 4 (psychiatric symptoms/disorders with onset prior to 14 years), after controlling for gender, zygosity and their interactions. Genetic models were fitted to examine the heritability of smoking behavior before and after controlling for significant covariates from the four tiers. FINDINGS: Parental history of cigarette smoking and alcoholism, parental closeness and home environment, as well as incidence of childhood sexual abuse or other trauma, a history of early onset panic attacks and conduct problems were associated with regular cigarette smoking. Important age interactions were found, particularly for family background risk factors. Regular cigarette smoking was moderately heritable, even after accounting for significant covariates. CONCLUSIONS: Several measured risk factors are associated with regular smoking. While some of the genetic influences on regular smoking may be shared with these risk factors, a significant proportion of the genetic vulnerability to regular smoking is phenotype-specific.     

Biglycan expression in current cigarette smokers: A possible link between active smoking and atherogenesis

Objective: Cigarette smokers present early signs of vascular damage and systemic inflammation. Biglycan (BGN), an ubiquitous component of extracellular matrix orchestrating several physiological functions, has recently been indicated as a major source of low-density lipoprotein retention in the normal arterial intima-media layer. We evaluated whether BGN-mRNA expression was enhanced in peripheral monocytes of smokers with no additional cardiovascular risk factors (CVRFs), and if it was associated with altered carotid arterial stiffness (AS) or intima media thickness (cIMT). We also evaluated plasma markers of systemic and vascular inflammation, and correlation with BGN-mRNA. Methods: Two-hundred-fifty-one young smokers were enrolled, with no additional CVRFs, and 60 controls. Plasma lipids, fibrinogen, C-reactive protein (CRP), interleukin-6 (IL-6), AS and cIMT were assessed. A smoke exposure index (SEIx) was calculated. Results: Fibrinogen, CRP, AS indices, cIMT, and BGN-mRNA were higher in smokers compared to controls; HDL-C levels were lower, no difference was detected in IL-6 levels. After stratification of smokers in quartiles based on SEIx values, smokers in the highest quartiles presented highest fibrinogen, CRP, AS, cIMT, BGN, and also IL-6 values, and lowest HDL-C. Conclusion: BGN-mRNA was enhanced in young smokers, compared to controls, and appears associated to a proatherogenic profile, characterized by increased fibrinogen, CRP, and IL-6, lower HDL-C, altered AS and cIMT values, particularly in those with higher SEIx: the more cigarettes smoked over years, the more marked the alterations. Although we cannot state whether BGN have a direct causal role in inducing, maintaining and developing vascular damage, including intima-media wall thickening and arterial stiffening, our data could suggest that it may represent a link between proatherogenic status induced by cigarette smoking, and the development and progression of vascular damage.