慢阻肺与微量元素

从慢阻肺疾病的临床观察与动物实验，通过分子生物学、组织形态学以及超微结构的变化进行探讨，观测到治疗前后毛发中微量元素的分布、合成和转化。及其维持机体健康的物质基础作用。     

Exhaled breath condensate: Determination of non-volatile compounds and their potential for clinical diagnosis and monitoring. A review

Exhaled breath condensate is a promising, non-invasive, diagnostic sample obtained by condensation of exhaled breath. Starting from a historical perspective of early attempts of breath testing towards the contemporary state-of-the-art breath analysis, this review article focuses mainly on the progress in determination of non-volatile compounds in exhaled breath condensate. The mechanisms by which the aerosols/droplets of non-volatile compounds are formed in the airways are discussed with methodological consequences for sampling. Dilution of respiratory droplets is a major problem for correct clinical interpretation of the measured data and there is an urgent need for standardization of EBC. This applies also for collection instrumentation and therefore various commercial and in-house built devices are described and compared with regard to their design, function and collection parameters. The analytical techniques and methods for determination of non-volatile compounds as potential markers of oxidative stress and lung inflammation are scrutinized with an emphasis on method suitability, sensitivity and appropriateness. The relevance of clinical findings for each group of possible non-volatile markers of selected pulmonary diseases and methodological recommendations with emphasis on interdisciplinary collaboration that is essential for future development into a fully validated clinical diagnostic tool are given.     

Ultrafast gas chromatography coupled to electronic nose to identify volatile biomarkers in exhaled breath from chronic obstructive pulmonary disease patients: A pilot study

An analytical method to identify volatile organic compounds (VOCs) in the exhaled breath from patients with a diagnosis of chronic obstructive pulmonary disease (COPD) using a ultrafast gas chromatography system equipped with an electronic nose detector (FGC eNose) has been developed. A prospective study was performed in 23 COPD patients and 33 healthy volunteers; exhalation breathing tests were performed with Tedlar bags. Each sample was analyzed by FCG eNose and the identification of VOCs was based on the Kovats index. Raw data were reduced by principal component analysis (PCA) and canonical discriminant analysis [canonical analysis of principal coordinates (CAP)]. The FCG eNose technology was able to identify 17 VOCs that distinguish COPD patients from healthy volunteers. At all stages of PCA and CAP the discrimination between groups was obvious. Chemical prints were correctly classified up to 82.2%, and were matched with 78.9% of the VOCs detected in the exhaled breath samples. Receiver operating characteristic curve analysis indicated the sensitivity and specificity to be 96% and 91%, respectively. This pilot study demonstrates that FGC eNose is a useful tool to identify VOCs as biomarkers in exhaled breath from COPD patients. Further studies should be performed to enhance the clinical relevance of this quick and ease methodology for COPD diagnosis.     

大螺距低剂量肺部CT技术在COPD患者中的应用价值

选择2014年1月~2018年12月本院呼吸内科住院部收治的拟实施肺部CT扫描的270例慢性阻塞性肺疾病(COPD)患者作为研究对象,根据不同螺距和辐射剂量,将患者分为大螺距低剂量组、小螺距低剂量组和大螺距常规剂量组,探讨大螺距低剂量肺部CT技术在COPD患者中的应用价值。结果显示,大螺距低剂量组肺实质CT均值标准差和伪影发生率比小螺距低剂量组明显降低,而SNR、CNR和图像质量评分较之明显增高(P<0.05)。大螺距低剂量组扫描时间明显短于另两组(P<0.05),CTDIvol、DLP和ED明显低于大螺距常规剂量组(P<0.05)。大螺距低剂量肺部CT技术在COPD患者中的应用价值满意,可明显提高图像质量和降低辐射剂量。     

细菌溶解产物对预防 COPD急性发作的临床价值--基于多项随机对照试验的荟萃分析

目的评价细菌溶解产物减少慢性阻塞性肺疾病（COPD）的急性发作及其应用的临床价值。方法检索Cochrane、MEDLINE、EMBASE、CNKI、CBM，纳入细菌溶解产物用于预防COPD急性发作的随机对照研究。评价对照试验的方法学，提取试验的相关指标，对临床数据进行荟萃分析。结果纳入16个研究，共1746例稳定期COPD患者，结果显示细菌溶解产物相较于安慰剂组，可明显减少患者的年平均急性感染次数[SMD=-0.93，95%CI （-1.26~-0.60），P＜0.01]，急性感染的持续时间[SMD=-1.38,95%CI （-1.6~-1.11），P＜0.01]，平均住院时间[SMD=-9.01，95%CI （-10.24~-7.78），P＜0.01]，抗生素应用时间[SMD=-1.07，95%CI （-1.32~-0.82），P＜0.01]，提高患者的 T淋巴细胞水平[SMD=1.38，95%CI （0.64~2.13），P＜0.01]、IgG [SMD=1.46，95%CI （1.18~1.59），P=0.02]、IgM [SMD=0.26，95%CI （0.18~0.41），P=0.01]及6min步行距离[SMD=58.7，95%CI （33.5~84.1），P＜0.01]。然而，细菌溶解产物对肺功能指标并无影响。结论细菌溶解产物对COPD的急性发作的临床价值在于减少感染次数，其对COPD的肺功能并无改善。     

无创正压通气治疗COPD 合并肺源性心脏病的疗效及对血浆C反应蛋白和脑钠素水平的影响

目的 探讨无创正压通气对慢性阻塞性肺疾病（COPD）合并肺源性心脏病的疗效和对患者血浆C 反应蛋白（CRP）和脑钠素（BNP）水平的影响。方法 将2012 年1 月到2014 年1月收治的120 例COPD 急性加重期合并肺源性心脏病患者随机分为观察组（60 例）和对照组（60 例）,对照组给予常规治疗,观察组在此基础上给予无创正压通气治疗。治疗前和治疗3d 后分别进行动脉血气分析,比较患者血pH 值、PaO2、PaCO2和动脉血氧饱和度（SaO2）在治疗前后的改变,并监测治疗前后血浆CRP和BNP 水平的改变。结果 治疗3d 后,两组患者的pH 值、PaO2、SaO2均较治疗前明显升高,PaCO2较治疗前明显降低,而观察组患者治疗后的动态血气分析指标的改善情况明显优于对照组,均有统计学差异（均P＜0.05）。两组患者的血浆CRP 和BNP 水平均较治疗前明显降低,而观察组患者治疗后的血浆CRP 和BNP 水平明显低于对照组,均有统计学差异（均P＜0.05）。结论 无创正压通气治疗COPD 合并肺源性心脏病,能够有效改善血气指标,提高SaO2和PaO2,同时降低血浆CRP 和BNP 的水平,值得在临床推广应用。     

A Highly Convergent Synthesis of 2‐Phenyl Quinoline as Dual Antagonists for NK2 and NK3 Receptors

A novel and highly convergent synthesis leading to 2‐phenyl‐quinolines has been developed. As demonstrated in the preparation of 6‐fluoro‐3‐(3‐oxo‐piperazin‐1‐ylmethyl)‐2‐phenyl‐quinoline‐4‐carboxylic acid [(S)‐1‐cyclohexyl‐ethyl]‐amide (8), the method provides fascile access to this class of analogues via the common intermediate 7.     

Methodological Fallacies in the Determination of Serum/Plasma Glutathione Limit Its Translational Potential in Chronic Obstructive Pulmonary Disease

This study aimed to review and critically appraise the current methodological issues undermining the suitability of the measurement of serum/plasma glutathione, both in the total and reduced form, as a measure of systemic oxidative stress in chronic obstructive pulmonary disease (COPD). Fourteen relevant articles published between 2001 and 2020, in 2003 subjects, 1111 COPD patients, and 892 controls, were reviewed. Nine studies, in 902 COPD patients and 660 controls, measured glutathione (GSH) in the reduced form (rGSH), while the remaining five, in 209 COPD patients and 232 controls, measured total GSH (tGSH). In the control group, tGSH ranged between 5.7 and 7.5 µmol/L, whilst in COPD patients, it ranged between 4.5 and 7.4 µmol/L. The mean tGSH was 6.6 ± 0.9 µmol/L in controls and 5.9 ± 1.4 µmol/L in patients. The concentrations of rGSH in the control group showed a wide range, between 0.47 and 415 µmol/L, and a mean value of 71.9 ± 143.1 µmol/L. Similarly, the concentrations of rGSH in COPD patients ranged between 0.49 and 279 µmol/L, with a mean value of 49.9 ± 95.9 µmol/L. Pooled tGSH concentrations were not significantly different between patients and controls (standard mean difference (SMD) = −1.92, 95% CI −1582 to 0.0219; p = 0.057). Depending on whether the mean concentrations of rGSH in controls were within the accepted normal range of 0.5–5.0 µmol/L, pooled rGSH concentrations showed either a significant (SMD = −3.8, 95% CI −2.266 to −0.709; p < 0.0001) or nonsignificant (SMD = −0.712, 95% CI −0.627 to 0.293; p = 0.48) difference. These results illustrate the existing and largely unaddressed methodological issues in the interpretation of the serum/plasma concentrations of tGSH and rGSH in COPD.     

超极化Xenon 对慢阻肺的可视化加权成像

超极化气体3He 或者¹²⁹Xe 扩散加权成像已经被证明了能够有效检测慢性阻塞性肺部疾病(COPD)中肺部微结构的改变．相比于³He,¹²⁹Xe 更便宜而且更容易获得,但是¹²⁹Xe 成像中较低的信噪比致使¹²⁹Xe 的肺部表面扩散系数(ADC)的测量面临着许多困难．在该研究中,为了得到更高的图像信噪比,作者对气球模型,健康大鼠和COPD大鼠进行了单个b 值(14 cm2/s)的扩散加权超极化¹²⁹Xe 磁共振成像(MRI)．所有的COPD模型大鼠是通过烟熏和注射内毒素(LPS)进行诱导得到的．在7 T 磁共振成像仪上面获得了大鼠肺实质的超极化¹²⁹Xe ADC 值分布图．COPD 大鼠肺实质的¹²⁹Xe ADC 值是0.044 22±0.002 9 和0.042 34±0.002 3 cm2/s (Δ = 0.8/1.2 ms),远大于健康大鼠肺实质的¹²⁹Xe ADC 值0.037 7±0.002 3 和0.036 7±0.001 3 cm2/s．而且COPD 大鼠肺实质相关的¹²⁹Xe ADC 直方图也表现出了一定的展宽．这些结果说明了COPD 大鼠肺泡空腔的增大能够通过129Xe 在肺里面的ADC 增长和相关直方图的拓宽反应出来,从而证明了单个b 值的扩散加权MRI 方法可以有效地对COPD 大鼠进行检测．