慢性阻塞性肺疾病患者痰中性粒细胞弹性蛋白酶和基质金属蛋白酶9的表达及其与气流受限的关系

慢性阻塞性肺疾病（COPD）的发病机制主要为蛋白酶-抗蛋白酶失衡。我们通过痰诱导探讨COPD急性加重期及稳定期患者痰中中性粒细胞弹性蛋白酶（NE）和基质金属蛋白酶9（MMPO）、基质金属蛋白酶抑制物1（TIMP-1）的表达及其与气流受限的关系。     

COPD合并焦虑、抑郁的血清生物标志物研究

目的 寻找COPD患者合并焦虑抑郁可能的生物标记物.分析生物标志物在鉴别COPD患者是否合并焦虑抑郁状态的应用价值,多指标联合检测是否能提高其诊断价值.方法 选取2015年1月1日至8月31日在北京朝阳医院呼吸与危重症医学科门诊就诊以及住院的COPD患者,应用医院焦虑抑郁量表筛选出存在焦虑抑郁状态COPD患者37例作为COPD合并焦虑抑郁组,另选取不合并焦虑抑郁的COPD患者40例作为对照组.检测目前国内外报道过的焦虑抑郁患者及健康对照人群间差异有统计学意义的指标:IL-6、肿瘤坏死因子a(TNF-α)、纤维蛋白原(FIB)和表皮生长因子(EGF),对结果进行统计学分析.结果 COPD合并焦虑抑郁组和对照组间FIB、EGF、IL-6和TNF-α差异有统计学意义(P＜0.05),FIB在COPD合并焦虑抑郁组显著低于对照组,EGF、IL-6和TNF-α在COPD合并焦虑抑郁组显著高于对照组.FIB、TNF-α、IL-6和EGF的ROC曲线下面积(AUC)分别为0.715、0.688、0.681和0.633,单项指标中以FIB的AUC最大,多指标联合应用诊断合并焦虑抑郁的价值优于单项指标.结论 FIB、TNF-α、IL-6和EGF可作为COPD患者合并焦虑抑郁的生物标记物,应用多指标联合检验可提高诊断价值.     

血清生物标志物在AECOPD诊断的研究进展

慢性阻塞性肺疾病可分为稳定期和急性加重期,其特征是慢性气道炎症、肺气肿和不完全可逆的气流受限。其中慢性阻塞性肺疾病急性加重(AECOPD)不仅病因复杂、预后较差,且容易反复发作。早诊断早治疗至关重要。作为评价疾病状况的客观指标,血清生物标志物可以对AECOPD发生、发展及结局提供客观的判断。本文对近年来诊断AECOPD...     

支气管哮喘和慢性阻塞性肺疾病患者诱导痰中基质金属蛋白酶及其抑制剂与气道炎症及气流受限

目的探讨支气管哮喘（简称哮喘）和慢性阻塞性肺疾病（COPD）患者诱导痰中基质金属蛋白酶9（MMP-9）和基质金属蛋白酶抑制剂1（TIMP-1）的水平及其与炎性细胞数、肺功能的关系。方法分别选择14例缓解期哮喘患者（哮喘组）、12例稳定期COPD患者（COPD组）和10名健康对照者（健康对照组）进行肺功能测定和用诱导痰检查方法对痰炎性细胞进行分类计数，并用酶联免疫吸附试验（ELISA）法测定诱导痰上清液中自细胞介素4（IL-4）、MMP-9和TIMP-1浓度。结果哮喘组患者诱导痰中嗜酸粒细胞、中性粒细胞分别为0．181±0．067、0．30±0．07，健康对照组为0．007±0．005、0．26±0．06，COPD组为0．042±0．017、0．50±0．10，3组细胞间比较差异有统计学意义（F值分别为4．32、4．13，P均〈0．05）。哮喘组、COPD组、健康对照组间诱导痰中IL-4浓度分别为（19±7）×10^-3／L、（14±6）×10^-3g／L、（11±4）×10^-3g／L，3组诱导痰中IL-4浓度比较差异无统计学意义（F=1．56，P均〉0．05），且分别与嗜酸粒细胞、中性粒细胞和第一秒用力呼气容积占预计值百分比（FEV1占预计值％）无相关（r分别为0．33、0．11、0．19、0．25、0．39、0．40、0．21、0．35、0．17，P均〉0．05）。哮喘组和COPD组诱导痰中MMP-9、TIMP-1浓度分别为（15．9±6．0）g／L、（13．4±5．1）g／L、（19．8±8．5）g／L、（16．7±7．6）g／L，健康对照组分别为（1．8±1．1）g／L、（1．3±0．9）g／L，两组MMP-9、TIMP-1浓度比较差异有统计学意义（F值分别为2．99、4．22，P均〈0．05）。哮喘组MMP-9浓度与嗜酸粒细胞呈正相关（r=0．71，P〈0．05）；COPD组MMP-9浓度与中性粒细胞呈正相关（r=0．59，P〈0．05），但与FEV。占预计值％和第一秒用力呼气容秽用力肺活量（FEV1／FVC）无相关（r分别为0．22、0．16、0．25、0．30，P均〉0．05）。哮喘组和COPD组TIMP．1浓度均与嗜酸粒细胞和中性粒细胞无相关（r分别为0．27、0．31、0．20、0．35，P均〉0．05），但与FEV。占预计值％呈负相关（r分别为-0．58、-0．62，P均〈0．05）。哮喘组和COPD组诱导痰中MMP-9／TIMP-1比值分别为0．8±0．7、0．8±0．6，两组比较差异无统计学意义（F=1．78，P〉0．05），但与健康对照组（1．5±0．6）比较差异有统计学意义（F=3．70，P〈0．05），且与FEV1占预计值％呈正相关（r分别为0．56、0．61，P均〈0．05）。结论哮喘组和COPD组患者诱导痰中MMP-9／TIMP-1比值的失衡与气道炎症和气流受限有关，这种失衡在哮喘和COPD细胞外基质的重塑和气流受限的发病机制中发挥重要作用。     

基质金属蛋白酶-9及其抑制剂在COPD合并肺间质纤维化大鼠中的作用

目的 观察基质金属蛋白酶-9(MMP-9)及组织型蛋白酶抑制剂-1(TIMP-1)在慢阻肺继发肺间质纤维化(PIFCOPD)大鼠肺组织中的变化,评价其与PIF-COPD的病理变化及发病机制的相关性.方法 雄性大鼠24只,随机分为正常对照组(1组),21天(2组)和42天(3组)模型组.以烟熏联合气管内滴注脂多糖建立PIF-COPD模型.免疫组化法检测肺组织中MMP-9及TIMP-1水平.结果 MMP-9和TIMP-1在1组有少量表达;在2和3组MMP-9为0.1970±0.0017和0.2414 ±0.0017;TIMP-1为0.1265 ±0.0018和0.2171 ±0.0023(与l组相比P＜0.05)水平逐渐增高且与肺间质纤维化的严重程度成正相关.结论 MMP-9及TIMP-1的水平与PIF-COPD的发病机制及病程有关.     

基质金属蛋白酶在大鼠慢性阻塞性肺疾病模型气道细胞外基质重塑中的作用

目的 研究基质金属蛋白酶（MMPs)及其组织抑制剂（TIMP－1）在大鼠慢性阻塞性肺疾病（COPD）模型气道和肺组织中的表达及其在细胞外基质重塑中的作用。方法 采用熏香烟加气管注内毒素法,建立大鼠COPD模型,观察其气道重塑的病理改变、肺功能及血气变化;用生化法测定支气管肺组织羟脯氨酸含量;用免疫组化法观察MMP－9、MMP－2及TIMP－1的蛋白定位及表达;用逆转录－聚合酶链反应法测定MMP－9、MMP－2及TIMP－1mRNA表达;用SDS－PAGE明胶酶谱学测定支气管肺组织MMPs酶活性。结果 用熏香烟加气管注内毒素法建立的大鼠COPD模型,其病理形态学改变、肺功能及血气变化均与人类COPD的改变相似。COPD模型组支气管肺组织羟脯胺酸含理、支气管黏膜下成纤维细胞、淋巴细胞数和肺泡巨噬细胞数及以I型胶原为主的细胞外基质含量显著高于健康对照组（P值均＜0.001)。COPD模型组MMP－9、MMP－2及TIMP－1在气道上皮、成纤维细胞、肺泡巨噬细胞、血管内皮细胞及部分肺泡壁细胞表达均明显增强,支气管肺组织MMP－9、MMP－2及TIMP－1 mRNA表达亦显著增强,72000MMP－2及92000 MMP-9酶活性亦显著增高。结论 MMPs表达增强提示细胞外基质降解增加,支气管肺结构破坏增加。TIMP－1在抑制MMPs活性的同时,促进成纤维细胞增生及胶原等合成增多,是导致细胞外基质修复和重塑的重要机制之一。     

慢性阻塞性肺疾病评估相关生物标志物研究进展

气流受限是COPD的主要疾病特征,其主要发生机制与吸入有毒气体或颗粒(通常是烟雾)引起的复杂的病理改变有关,包括大、小气道的炎症和肺实质破坏.慢性阻塞性肺疾病急性加重期(acute exacerbation chronic obstructive pulmonary disease,AECOPD)是造成老年人死亡的重要原因之一,早诊断、早治疗是及早阻止疾病发展、改善预后的关键.生物标志物在协助该病的病因、评估、预后及治疗方面起重要作用.评估COPD严重程度在临床工作中显得十分重要,本文综述了与COPD严重程度相关生物标志物的研究现状.     

硫化氢作为慢性阻塞性肺疾病生物标志物的研究进展

慢性阻塞性肺疾病(COPD)已经成为一个严重的公共卫生问题,以高患病率、高病死率、高致残率及低知晓率为特点。由于其不可逆性,早期预防成为关键。近年来研究发现硫化氢与COPD的发生和预后密切相关,可能作为COPD早期诊断和预后预测生物标志物。本文综述了硫化氢在COPD中的作用和适宜检测方法,探讨了硫化氢作为COPD生物标...     

健康教育在COPD稳定期治疗中的作用

目的研究健康教育对慢性阻塞性肺疾病(COPD)稳定期患者治疗效果的影响及作用。方法选择25例COPD稳定期患者,测定其肺功能(FEV1%pred)、6分钟步行试验(6MWT)、慢性阻塞性肺病评估测试(CAT),进行健康教育,要求患者每月定期随访,6个月后重复测定上述指标。结果经过系统的健康教育后,25例COPD稳定期患者吸入制剂、康复运动依从性显著提高(P<0.01),肺功能(FEV1%pred)改善不明显(P>0.05),但6MWT、CAT评分显著改善(P<0.05,P<0.01)。6MWT、CAT评分与肺功能指标具有高度相关性(P<0.01)。结论对COPD稳定期患者进行健康教育管理,可以提高患者对疾病的认识,增加治疗信心,提高长期治疗的依从性,从而有望达到改善肺功能、减少急性发作次数,降低病死率。     

关注慢性阻塞性肺疾病诊治指南的发表

1995年 ,欧美等国相继制定了“慢性阻塞性肺疾病 (ＣＯＰＤ)诊治指南”以规范ＣＯＰＤ的诊断和治疗 ,加强对ＣＯＰＤ的研究工作。 1 997年中华医学会呼吸病学分会制定了我国的“慢性阻塞性肺疾病(ＣＯＰＤ)诊治规范 (草案 )”。近年 ,美国国立心肺血管研究所和世界卫生组织组织多国有关专家制定了“慢性阻塞性肺疾病防治全球创议 (ＧＯＬＤ)”(我刊于2 0 0 1年第 7期刊登了“慢性阻塞性肺疾病全球创议简介”) ,就ＣＯＰＤ的定义、机制、诊断及治疗进行了全面阐述。参照ＧＯＬＤ的有关内容 ,在广泛汲取我国呼吸病学专家意见的基础上 ,中华医…     

Symptom burden in stable COPD patients with moderate or severe airflow limitation

Objectives

To describe a multidimensional symptom profile in patients with stable chronic obstructive pulmonary disease (COPD) and determine whether symptom experience differed between patients with moderate or severe airflow limitations.

Background

Patients with severe airflow limitation experience numerous symptoms, but little is known regarding patients with moderate airflow limitation.

Methods

A multidimensional symptom profile (Memorial Symptom Assessment Scale) was assessed in 42 outpatients with moderate and 49 with severe airflow limitations.

Results

The mean number of symptoms in the total sample was 7.9 (±4.3) with no difference between patients with moderate and severe airflow limitations. The most prevalent symptoms with the highest MSAS symptom burden scores were shortness of breath, dry mouth, cough, sleep problems, and lack of energy in both groups.

Conclusions

Patients with moderate or severe airflow limitations experience multiple symptoms with high severity and distress. An assessment of their multidimensional symptom profile might contribute to better symptom management.     

稳定期慢性阻塞性肺疾病患者潮气呼吸肺功能测定的临床意义

目的探讨潮气流速-容积曲线(TBFV)测定对了解稳定期慢性阻塞性肺疾病(COPD)患者的气流阻塞程度的临床意义。方法2002-062004-06对上海交通大学附属第一人民医院的61例中重度COPD患者(COPD组)以及健康体检者68名(正常对照组),进行坐位常规肺通气功能和TBFV测定,其中26例COPD患者在吸入沙丁胺醇干粉剂后重复上述测定。结果COPD患者在TBFV测定中VPTEF/VTE、TPTEF/TE均明显低于18%[分别为(12·8±2·7)%和(11·6±2·4)%],明显低于正常对照组的(25·0±3·1)%和(29·5±3·7)%(均P<0·05),而PTEF和PTIF却无明显变化(P>0·05)。26例COPD患者在吸入沙丁胺醇后重复TBFV测定显示,不仅VPTEF/VTE、TPTEF/TE出现显著增高,TEF50/PTEF和TEF25/PTEF分别增至(47·3±13·9)%和(36·9±12·4)%,接近正常对照组(均P<0·05)。结论通过测定TBFV可了解稳定期中重度COPD患者的肺功能状况,且可用于评价支气管舒张剂的治疗效应,由于无须患者特别配合,TBFV测定易于推广。     

Association between airflow limitation and prognosis in patients with chronic pulmonary aspergillosis

BackgroundPrevious studies have shown that reduced levels of lung function, characterized by forced expiratory volume in 1 second (FEV₁), are associated with higher respiratory events and mortality in general population and some chronic lung diseases. Chronic pulmonary aspergillosis (CPA) is a destructive, fatal lung disease caused by Aspergillus infection in non-immunocompromised patients with suboptimal pulmonary function. However, there is limited information on the status and features of CPA according to FEV₁.MethodsWe performed a retrospective observational study to investigate the FEV₁ and airflow limitation in patients with CPA between March 2017 and February 2019 at a tertiary hospital in South Korea.ResultsOf the 144 CPA patients, 104 underwent spirometry, demonstrating median forced vital capacity (FVC) and FEV₁ of 2.35 L (68%) and 1.43 L (62%), respectively. Among them, 56 patients had airflow limitation on PFT, with median FVC, and FEV₁ of 2.47 L (73%) and 1.11 L (47%), respectively. Low body mass index (BMI) (20.1 vs. 22.1 kg/m²; P=0.011), breathlessness (60% vs. 20%; P=0.002), and bilateral pulmonary lesions (33.3% vs. 4%; P=0.006) were more common in patients with moderate to very severe airflow limitation than in those with normal to mild airflow limitation.ConclusionsModerate to very severe airflow limitation was observed in 43.3% of patients with CPA. Additionally, low BMI, breathlessness, and bilateral pulmonary lesions contributing to poor prognosis were more common in patients with moderate to very severe airflow limitation than in those with normal to mild airflow limitation. Our findings suggest that airflow limitation can be associated with the prognosis of CPA. Further investigations are needed to demonstrate the clinical significance of this association.     

Characteristics of outpatients with COPD in daily practice: The E4 Spanish project

The objective of this 1-week cross-sectional survey was to assess the clinical features of outpatients with chronic obstructive pulmonary disease (COPD). A one-page questionnaire was used to collect demographic data, smoking status, and COPD-related variables. Ten or 20 consecutive patients were selected from Primary care or specialised setting during a week. Pulmonary function (FEV1) was measured using an electronic device (Piko-1). The study sample comprised 11,973 COPD patients (83% men) with a mean (sd) age of 67 (10.7) years. Thirty-five percent of patients were current smokers and smoked a mean of 17.4 (9.9) cigarettes daily. COPD severity according to GOLD stages was mild in 20% of patients, moderate in 38%, severe in 30%, and very severe in 12%. A higher percentage of men showed severe (33%) or very severe (14%) disease compared to women (16% and 6%, respectively) (P<0.005). Forty-two percent of patients had severe functional impairment and 35% continued smoking. Moreover, 11% of patients with very severe COPD smoked more than 20 cigarettes a day. The mean frequency of visits in the previous year was every 4.6 (4.1) months, with cough as the main reason for consultation. The most commonly used drugs were long-acting beta2-agonists (78%) and inhaled steroids (77%). Inhaled steroids were used by 84% of patients with very severe, 82% with severe disease, 73% with moderate disease, and 69% with mild disease (chi2 for trend, P<0.0001). This survey carried out in a real life setting shows that 42% of the patients who completed the questionnaire had severe COPD, 35% of them continued smoking, and 69% of patients with mild COPD used inhaled steroids.     

Analysis of the structure of the muscular pulmonary arteries in patients with pulmonary hypertension and COPD: National Institutes of Health Nocturnal Oxygen Therapy Trial

We examined the cardiovascular function as well as the structure of the muscular pulmonary arteries in patients who had died while enrolled in the National Institutes of Health nocturnal oxygen therapy trial (NOTT). The cardiovascular function of the patients classified into groups based on the severity of the pulmonary hypertension was examined, and we compared the morphologic data in these groups to those obtained from age-matched controls who died with no evidence of cardiovascular disease. The groups with severe pulmonary hypertension had markedly increased pulmonary vascular resistance but similar cardiac index to the group with only mild hypertension. In the structural analyses, we found definite alterations in arterial structure from the control population: the patients who had pulmonary hypertension had markedly increased percentages of intima and media. These differences were most pronounced in the medium and larger muscular arteries. The degree of pulmonary hypertension did not appear to alter vascular structure consistently, although there was a trend towards an increase in muscle media in the smaller vessels. When the patients were classified into a group who responded to oxygen administration by a decrease in Ppa, and an age- and Ppa-matched group who did not respond, there were no differences in vascular structure between these groups, although both groups had greater percentages of intima and media compared to the control group. We conclude that, in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD), there are structural alterations of the muscular pulmonary arteries, but these do not correlate with either the severity of the pulmonary hypertension or the ability of the pulmonary vasculature to respond to oxygen administration. Offprint requests to: J. L. Wright     

慢性阻塞性肺疾病患者NT-proBNP的表达与患者肺功能、血气指标的关系

目的 探讨COPD患者血浆N端B型脑钠肽前体(NT-proBNP)的表达,以及与患者肺功能和血气指标的关系.方法 选取2014年1月至2015年12月在我院治疗的COPD患者68例,根据GOLD指南将患者分为A组(n=21)、B组(n=24)、C组(n=23),同时选取25名健康者作为对照组,检测各组血浆NT-proBNP、肺功能和血气指标.结果 各组NT-proBNP、FEV1％pred、FEV2/FVC、PaO2、PaCO2比较差异有统计学意义(F=20.834、22.153、34.238、15.637、18.526,P＜0.05);A、B、C3组NT-proBNP水平明显高于对照组,其中C组NT-proBNP水平最高(271.31±37.54)ng/L;A、B、C3组肺功能指标FEV1％ pred和FEV1/FVC均明显低于对照组(F=7.831、8.103,8.933、7.606,9.012、8.105,P＜0.05);B、C2组PaO2明显低于对照组(F=7.714、9.015,P＜0.05);A、B、C3组PaCO2明显高于对照组(F=10.011、9.391、8.944,P＜0.05);血浆NT-proBNP与FEV1％ pred、FEV1/FVC、PaO2呈负相关(r=-0.553、-0.383、-0.577,P＜0.05),与PaCO2呈正相关(r=0.480,P＜0.05).结论 血浆NT-proBNP水平有助于判断COPD患者疾病严重程度,且与患者肺功能下降及动脉血气分析恶化密切有关.     

血嗜酸粒细胞作为糖皮质激素治疗慢性阻塞性肺疾病疗效的生物标志物研究

有研究证实部分 COPD急性加重期痰液嗜酸粒细胞(eosinophils,EOS)增加,对此类患者应用糖皮质激素治疗,能促进肺功能恢复、缩短病程并降低治疗失败率。然而,在日常临床实践中,诱导痰项目存在技术要求高、检测有效性低、部分患者不能耐受等情况。所以,探讨血 EOS和痰 EOS之间的相关性,选择血 EOS计数作为一种标志物,评估 COPD患者的激素治疗反应,可能更实用。本文就这些方面作一综述。     

Statin Therapy is Associated with Decreased Pulmonary Vascular Pressures in Severe COPD

Background: Pulmonary hypertension (PH) in COPD carries a poor prognosis. Statin therapy has been associated with numerous beneficial clinical effects in COPD, including a possible improvement in PH. We examined the association between statin use and pulmonary hemodynamics in a well-characterized cohort of patients undergoing evaluation for lung transplantation. Methods: We conducted a cross-sectional analysis of 112 subjects evaluated for lung transplant with a diagnosis of COPD. Clinical characteristics, pulmonary function, cardiac catheterization findings and medical comorbidities were compared between statins users and non-users. Results: Thirty-four (30%) subjects were receiving statin therapy. Statin users were older and had an increased prevalence of systemic hypertension and coronary artery disease (CAD). Mean pulmonary arterial pressure (mPAP) in the statin group was lower [26 ± 7 vs 29 ± 7 mmHg, p = 0.02], as was pulmonary artery wedge pressure (PAWP) [12 ± 5 vs. 15 ± 6 mmHg, p = 0.02]. Pulmonary vascular resistance did not differ between the groups. In multiple regression analysis, statin use was associated with a 4.2 mmHg (95% CI: 2 to 6.4, p = <0.001) lower PAWP and a 2.6 mmHg (95% CI: 0.3 to 4.9, p = 0.03) reduction in mPAP independent of PAWP. Conclusions: In patients with severe COPD, statin use is associated with significantly lower PAWP and mPAP. These finding should be evaluated prospectively.     

214例老年人肺弥散功能测定分析

目的探讨健康老年人和老年ＣＯＰＤ患者肺弥散功能差异和临床应用价值。方法用美国６２００ＡｕｔｏｂｏｘＤＬ型体积描记仪分别测定９７例健康老年人和１１７例ＣＯＰＤ患者的肺弥散功能。结果慢支组与健康组比较肺一氧化碳弥散量（ＤＬＣＯ）差异非常显著（Ｐ＜０．０１）。轻、中、重度肺气肿组与健康组比较ＤＬＣＯ、弥散量／肺泡容积比值（ＤＬＣＯ／ＶＡ）、转送系数（Ｋｃｏ）、弥散时间常数（ＣＯＴ．Ｃ．）相差非常显著（Ｐ＜０．０１）。结论老年人患有慢性呼吸道病变时，肺弥散功能测定是一项较为敏感的指标，常在其他肺功能检查出现异常之前就已有变化。     

慢性阻塞性肺疾病的肺康复进展

肺康复目前被认为是COPD综合治疗方案中不可或缺的一部分,但对于严重的COPD患者,肺康复的效果似乎还不太明确,一些新的方法被应用以增加肺康复的效果.这篇综述将目前肺康复领域的一些新措施总结如下.