COPD diagnosis related to different guidelines and spirometry techniques

Background

Several studies have indicated that one of the most potent mediators involved in pulmonary vascular remodeling is vascular endothelial growth factor (VEGF). This study was designed to determine whether airway VEGF level reflects pulmonary vascular remodeling in patients with bronchitis-type of COPD.

Methods

VEGF levels in induced sputum were examined in 23 control subjects (12 non-smokers and 11 ex-smokers) and 29 patients with bronchitis-type of COPD. All bronchitis-type patients performed exercise testing with right heart catheterization.

Results

The mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) after exercise were markedly increased in all bronchitis-type patients. However, both parameters after exercise with breathing of oxygen was significantly lower than in those with breathing of room air. To attenuate the effect of hypoxia-induced pulmonary vasoconstriction during exercise, we used the change in mPAP or PVR during exercise with breathing of oxygen as a parameter of pulmonary vascular remodeling. Change in mPAP was significantly correlated with VEGF level in induced sputum from patients with chronic bronchitis (r = 0.73, p = 0.0001). Moreover, change in PVR was also correlated with VEGF level in those patients (r = 0.57, p = 0.003).

Conclusion

A close correlation between magnitude of pulmonary hypertension with exercise and VEGF level in bronchitis-type patients could be observed. Therefore, these findings suggest the possibility that VEGF level in induced sputum is a non-invasive marker of pulmonary vascular remodeling in patients with bronchitis-type of COPD.     

Vascular endothelial growth factor: an angiogenic factor reflecting airway inflammation in healthy smokers and in patients with bronchitis type of chronic obstructive pulmonary disease?

BackgroundPatients with bronchitis type of chronic obstructive pulmonary disease (COPD) have raised vascular endothelial growth factor (VEGF) levels in induced sputum. This has been associated with the pathogenesis of COPD through apoptotic and oxidative stress mechanisms. Since, chronic airway inflammation is an important pathological feature of COPD mainly initiated by cigarette smoking, aim of this study was to assess smoking as a potential cause of raised airway VEGF levels in bronchitis type COPD and to test the association between VEGF levels in induced sputum and airway inflammation in these patients.Methods14 current smokers with bronchitis type COPD, 17 asymptomatic current smokers with normal spirometry and 16 non-smokers were included in the study. VEGF, IL-8, and TNF-α levels in induced sputum were measured and the correlations between these markers, as well as between VEGF levels and pulmonary function were assessed.ResultsThe median concentrations of VEGF, IL-8, and TNF-α were significantly higher in induced sputum of COPD patients (1,070 pg/ml, 5.6 ng/ml and 50 pg/ml, respectively) compared to nonsmokers (260 pg/ml, 0.73 ng/ml, and 15.4 pg/ml, respectively, p < 0.05) and asymptomatic smokers (421 pg/ml, 1.27 ng/ml, p < 0.05, and 18.6 pg/ml, p > 0.05, respectively). Significant correlations were found between VEGF levels and pack years (r = 0.56, p = 0.046), IL-8 (r = 0.64, p = 0.026) and TNF-α (r = 0.62, p = 0.031) levels both in asymptomatic and COPD smokers (r = 0.66, p = 0.027, r = 0.67, p = 0.023, and r = 0.82, p = 0.002, respectively). No correlation was found between VEGF levels in sputum and pulmonary function parameters.ConclusionVEGF levels are raised in the airways of both asymptomatic and COPD smokers. The close correlation observed between VEGF levels in the airways and markers of airway inflammation in healthy smokers and in smokers with bronchitis type of COPD is suggestive of VEGF as a marker reflecting the inflammatory process that occurs in smoking subjects without alveolar destruction.     

诱导痰黏蛋白5AC对支气管哮喘和慢性阻塞性肺疾病的鉴别价值

摘要 目的：对支气管哮喘（BA）患者和慢性阻塞性肺疾病（COPD）患者诱导痰黏蛋白5AC（MUC5AC）、炎症细胞和炎症因子水平进行比较以及相关性分析,评估MUC5AC鉴别BA和COPD的价值。方法：选取2018年9月至2019年9月来海南医学院第一附属医院就诊的BA稳定期患者（BA组）60例,同期COPD稳定期（COPD组）患者60例。诱导痰法采样并处理痰液,检测诱导痰MUC5AC、炎症细胞中性粒细胞（Neu）、巨噬细胞（Mac）、嗜酸性粒细胞（Eos）、淋巴细胞（Lym）、炎症因子血管内皮生长因子（VEGF）、细胞间黏附分子-1（ICAM-1）、白介素13（IL-13）和白介素17（IL-17）水平,通过Pearson相关分析对MUC5AC水平与Neu、Mac、Eos、Lym、VEGF、ICAM-1、IL-13、IL-17的关系进行分析。此外,采用受试者工作特征(ROC)曲线分析MUC5AC、炎症细胞及炎症因子鉴别诊断BA及COPD的效能。结果：COPD组诱导痰MUC5AC水平高于BA组,差异有统计学意义（P＜0.05）;COPD组诱导痰Mac和Eos水平均低于BA组,COPD组诱导痰Neu水平高于BA组,差异均有统计学意义（P＜0.05）;COPD组诱导痰VEGF、ICAM-1、IL-13和IL-17水平均低于BA组,差异均有统计学意义（P＜0.05）;Pearson相关分析结果显示,诱导痰MUC5AC与炎症细胞Mac、Eos和炎症因子VEGF、ICAM-1、IL-13和IL-17呈负相关（P＜0.05）,与炎症细胞Neu呈正相关（P＜0.05）。经ROC曲线分析可得：诱导痰MUC5AC鉴别BA和COPD的曲线下面积、灵敏度、特异度以及约登指数均高于炎症细胞Neu、Mac、Eos以及炎症因子VEGF、ICAM-1、IL-13、IL-17。结论：COPD患者诱导痰MUC5AC水平高于BA患者,MUC5AC与炎症细胞和炎症因子有关,MUC5AC的检测有助于鉴别BA或COPD,其有望作为临床BA或COPD的监测指标和治疗靶点。     

Levels of angiopoietins 1 and 2 in induced sputum supernatant in patients with COPD

Pathological features of chronic obstructive pulmonary disease (COPD) include lung vascular remodeling and angiogenesis. Angiopoietin-1 (Ang-1), is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor. We determined the levels of angiopoietins in sputum supernatants of patients with COPD and investigated their possible association with mediators and cells involved in the inflammatory and remodeling process. Fifty-nine patients with COPD, 25 healthy smokers and 20 healthy non-smokers were studied. All subjects underwent lung function tests, sputum induction for cell count identification and Ang-1, Ang-2, VEGF, TGF-β1, MMP-2, LTB4, IL-8, albumin measurement in sputum supernatants. Airway vascular permeability (AVP) index was also assessed. Ang-2 levels were significantly higher in patients with COPD compared to healthy smokers and healthy non-smokers [median, interquartile ranges pg/ml, 267 (147-367) vs. 112 (67-171) and 98 (95-107), respectively; p<0.001]. Regression analysis showed a significant association between Ang-2 levels and AVP index, VEGF, IL-8 and MMP-2 levels in COPD, the strongest being with VEGF. Our results indicate that induced sputum Ang-2 levels are higher in COPD compared to healthy smokers and healthy non-smokers. Moreover, Ang-2 is associated with AVP, IL-8, MMP-2, and VEGF, indicating a possible role for Ang-2 in the pathogenesis of the disease.     

Serum vascular endothelial growth factor and its receptor level in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a disorder which encompasses not only morphological changes in parenchyma, central and peripheral airways but also in structural and functional changes of pulmonary vessels. The role of angiogenic factors leading to abnormal pulmonary vessel remodeling remains unclear. We have investigated a cytokine vascular endothelial growth factor (VEGF) known to be involved in angiogenesis, and its soluble receptors (sVEGF R1, sVEGF R2) in the serum of 20 patients with mild COPD and 10 patients with very severe COPD, using sensitive enzyme-linked immunoassays. The control group consisted of 10 healthy volunteers. We found that the concentration of VEGF in the serum of patients with mild COPD was significantly higher (665.31 +/- 102.20 pg/mL) in comparison to the control group (318.94 +/- 51.40 pg/mL; p < 0.05), and there was a strong negative correlation with FEV1 (r = -0.859; p < 0.001). Additionally, the level of sVEGF R1 in the serum of patients with very severe COPD was also significantly higher (96.60 +/- 26.85 pg/mL) than in the control (36.01 +/- 3.29 pg/mL; p < 0.05) and a positive correlation between the serum level of sVEGF R1 and FEV1 was found (r = 0.748; p < 0.01). Moreover, we observed an insignificant increase of sVEGF R2 in the serum of patients with mild COPD and those with very severe COPD. These results suggest that VEGF and sVEGF R1 receptor are involved in the development of abnormal pulmonary vascular remodelling in patients with COPD.     

肺心通对慢性肺源性心脏病模型大鼠肺动脉高压、血流动力学及肺血管重构的影响

摘要 目的：研究肺心通对慢性肺源性心脏病（CPHD）大鼠的治疗效果,并探讨其治疗对慢性肺源性心脏病大鼠肺动脉高压、血流动力学以及肺血管重构的影响。方法：30只Wistar大鼠被随机均分为正常对照组（Normal control）、模型组（Model）和肺心通组（Feixintong）。模型组和肺心通组大鼠腹腔注射野百合碱建立CPHD模型,肺心通组CPHD大鼠通过灌胃给药肺心通进行治疗3周。治疗3周后,测量三组大鼠0.3秒呼出量（FEV0.3）、呼出肺功能量（FVC）、肺动脉压、左室射血分数（Left ventricular ejection fraction,LVEF）、左心室舒张末期内径（Left ventricular end diastolic diameter ,LVEDD）、室间隔厚度 （Ventricular septal thickness,IVST）和左室后壁厚度（Left ventricular posterior wall thickness,LVPWT）、肺动脉收缩压（pulmonary artery systolic pressure,PASP）、血氧分压（Partial pressure of blood oxygen,PO₂）、肺动脉平均压（mean pulmonary artery pressure,mPAP）以及舒张压（pulmonary artery diastolic pressure,PADP）以及肺血管重构相关指标。结果：与模型组大鼠相比,肺心通组大鼠活动量、饮食饮水量以及体重均显著增高,呼吸和舌色等症状均改善。肺心通治疗3周后,CPHD大鼠肺功能指标FEV0.3、FVC和FEV0.3/FVC均显著升高（P<0.05）,心脏功能结构指标LVEF、LVEDD、IVST和LVPWT均显著升高（P<0.05）,血流动力学指标PASP、PADP和mPAP均显著降低（P<0.05）,以及肺血管重构指标MA、WT和WA均显著降低（P<0.05）,而肺血管重构指标NMA却显著升高（P<0.05）。结论：肺心通对慢性肺源性心脏大鼠具有较好的治疗效果,可显著降低慢性肺源性心脏大鼠肺动脉高压,改善其血流动力学变化并有助于重构肺血管。     

Exercise Physiology and Pulmonary Hemodynamic Abnormality in PH Patients with Exercise Induced Venous-To-Systemic Shunt

Objectives

To identify the pulmonary hypertension (PH) patients who develop an exercise induced venous-to-systemic shunt (EIS) by performing the cardiopulmonary exercise test (CPET), analyse the changes of CPET measurements during exercise and compare the exercise physiology and resting pulmonary hemodynamics between shunt-PH and no-shunt-PH patients.

Methods

Retrospectively, resting pulmonary function test (PFT), right heart catheterization (RHC), and CPET for clinical evaluation of 104 PH patients were studied.

Results

Considering all 104 PH patients by three investigators, 37 were early EIS+, 61 were EIS-, 3 were late EIS+, and 3 others were placed in the discordant group. PeakVO₂, AT and OUES were all reduced in the shunt-PH patients compared with the no-shunt-PH subjects, whereas VE/VCO₂ slope and the lowest VE/VCO₂ increased. Besides, the changes and the response characteristics of the key CPET parameters at the beginning of exercise in the shunt group were notably different from those of the no shunt one. At cardiac catheterization, the shunt patients had significantly increased mean pulmonary artery pressure (mPAP), mean right atrial pressure (mRAP) and pulmonary vascular resistance (PVR), reduced cardiac output (CO) and cardiac index (CI) compared with the no shunt ones (P<0.05). Resting CO was significantly correlated with exercise parameters of AT (r = 0.527, P<0.001), OUES (r = 0.410, P<0.001) and Peak VO₂ (r = 0.405, P<0.001). PVR was significantly, but weakly, correlated with the above mentioned CPET parameters.

In Conclusions

CPET may allow a non-invasive method for detecting an EIS and assessing the severity of the disease in PH patients.     

腹式呼吸训练法对COPD伴Ⅱ型呼吸衰竭患者肺通气状态、血气指标及运动耐力的影响

摘要 目的：探讨腹式呼吸训练法对慢性阻塞性肺疾病（COPD）伴Ⅱ型呼吸衰竭患者肺通气状态、血气指标及运动耐力的影响。方法：选择我院2020年07月2022年12月期间收治的100例COPD伴Ⅱ型呼吸衰竭患者,根据随机数字表法将患者分为对照组[常规治疗基础上接受双水平气道正压（BIPAP）辅助通气,n=50]和研究组（对照组的基础上接受腹式呼吸训练法干预,n=50）。对比两组临床相关指标、肺通气状态、血气指标及运动耐力指标。结果：研究组的喘憋消失时间、体温恢复正常时间、住院时间、肺部啰音消失时间短于对照组（P<0.05）。两组干预1周后第1秒呼气的最大容积（FEV₁）、最大自主分钟通气量（MVV）、用力肺活量（FVC）均升高,且研究组高于对照组（P<0.05）。两组干预1周后氧分压（PaO2₂）、血氧饱和度（SpO₂）均升高,且研究组高于对照组;二氧化碳分压（PaCO₂）下降,且研究组低于对照组（P<0.05）。两组干预1周后6 min步行距离（6MWT）升高,且研究组高于对照组（P<0.05）。结论：腹式呼吸训练法有助于改善COPD伴Ⅱ型呼吸衰竭患者的临床症状,调节肺通气状态、血气指标,提高运动耐力。     

Level of Fatty Acid Binding Protein 5 (FABP5) Is Increased in Sputum of Allergic Asthmatics and Links to Airway Remodeling and Inflammation

BackgroundThe inflammatory processes in the upper and lower airways in allergic rhinitis and asthma are similar. Induced sputum and nasal lavage fluid provide a non-invasive way to examine proteins involved in airway inflammation in these conditions.ObjectivesWe conducted proteomic analyses of sputum and nasal lavage fluid samples to reveal differences in protein abundances and compositions between the asthma and rhinitis patients and to investigate potential underlying mechanisms.MethodsInduced sputum and nasal lavage fluid samples were collected from 172 subjects with 1) allergic rhinitis, 2) asthma combined with allergic rhinitis, 3) nonallergic rhinitis and 4) healthy controls. Proteome changes in 21 sputum samples were analysed with two-dimensional difference gel electrophoresis (2D-DIGE), and the found differentially regulated proteins identified with mass spectrometry. Immunological validation of identified proteins in the sputum and nasal lavage fluid samples was performed with Western blot and ELISA.ResultsAltogether 31 different proteins were identified in the sputum proteome analysis, most of these were found also in the nasal lavage fluid. Fatty acid binding protein 5 (FABP5) was up-regulated in the sputum of asthmatics. Immunological validation in the whole study population confirmed the higher abundance levels of FABP5 in asthmatic subjects in both the sputum and nasal lavage fluid samples. In addition, the vascular endothelial growth factor (VEGF) level was increased in the nasal lavage fluid of asthmatics and there were positive correlations between FABP5 and VEGF levels (r=0.660, p<0.001) and concentrations of FABP5 and cysteinyl leukotriene (CysLT) (r=0.535, p<0.001) in the nasal lavage fluid.ConclusionsFABP5 may contribute to the airway remodeling and inflammation in asthma by fine-tuning the levels of CysLTs, which induce VEGF production.     

八段锦联合肺功能康复训练对慢性阻塞性肺病稳定期患者肺功能、运动耐力及生活质量的影响

摘要 目的：观察肺功能康复训练联合八段锦对慢性阻塞性肺病（COPD）稳定期患者运动耐力、肺功能及生活质量的影响。方法：选取80例COPD稳定期患者,纳入病例时间：2018年1月~2020年7月,采用随机数字表法分为观察组（肺功能康复训练联合八段锦,40例）、对照组（肺功能康复训练,40例）,干预6个月。对比两组干预前、干预6个月后的肺功能[用力肺活量（FVC）、1秒用力呼气容积（FEV₁）]、运动耐力[6 min步行距离（6MWD）]及生活质量[世界卫生组织生存质量量表简表（WHOQOL-BREF）评分]、症状评分[改良英国医学研究学会呼吸困难量表（mMRC）评分、慢阻肺综合评估测试（CAT）评分]。结果：两组干预6个月后FVC、6MWD、FEV₁均较干预前升高,且观察组高于对照组（P<0.05）。两组干预6个月后WHOQOL-BREF各维度评分较干预前升高,且观察组高于对照组（P<0.05）。干预6个月后, 两组mMRC评分、CAT评分较干预前下降,且观察组低于对照组（P<0.05）。结论：肺功能康复训练联合八段锦干预COPD稳定期患者,可缓解其临床症状,提高肺部适应性,进而改善患者运动耐力及生活质量。     

Effect of incremental exercise on airway and systemic inflammation in patients with COPD

Airway and systemic inflammation are features of chronic obstructive pulmonary disease (COPD), and there is growing interest in clarifying the inflammatory processes. Strenuous exercise induces an intensified systemic inflammatory response in patients with COPD, but no study has investigated the airway inflammatory and anti-inflammatory responses to exercise. Twenty steroid-na?ve, ex-smokers with diagnosed COPD (forced expired volume in 1 s = 66 ± 12%) underwent baseline collection of venous blood and induced sputum followed by an incremental exercise test to symptom limitation 48 h later. Additional venous blood samples were collected following exercise at 0, 2, and 24 h, while induced sputum was collected 2 and 24 h after exercise. Sputum and blood samples were analyzed for differential cell count, CD4(+) and CD8(+) T lymphocytes (serum only), interleukin (IL)-6, IL-8, IL-10, chemokine (C-C motif) ligand 5 (CCL5), and high sensitivity C-reactive protein (serum only). There was an increase in the number of sputum eosinophils (cells/gram, P = 0.012) and a reduction in sputum IL-6 (P = 0.01) 24 h postexercise. Sputum IL-8 and CCL5 were also persistently decreased after exercise (P = 0.0098 and P = 0.0012, respectively), but sputum IL-10 did not change. There was a decrease in serum eosinophils 2 h after exercise (P = 0.0014) and a reduction in serum CCL5 immediately following and 2 h postexercise (P < 0.0001). Both serum eosinophils and CCL5 returned to baseline levels within 24 h. An acute bout of exercise resulted in a significant increase in the number of sputum eosinophils, which may be mediated by serum CCL5. However, there was also a reduction in sputum proinflammatory cytokines, suggesting some anti-inflammatory effect of exercise in the lungs of steroid-na?ve patients with COPD.     

Dynamic differences in dietary polyunsaturated fatty acid metabolism in sputum of COPD patients and controls

IntroductionDisturbances in onset and resolution of inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood. Dietary polyunsaturated fatty acids (PUFAs) can be converted into lipid mediators here collectively named oxylipins. These include classical eicosanoids, but also pro-resolving mediators. A balanced production of pro-inflammatory and pro-resolving oxylipins is of importance for adequate inflammatory responses and subsequent return to homeostasis.ObjectivesHere we investigated if PUFA metabolism is disturbed in COPD patients.MethodsFree PUFA and oxylipin levels were measured in induced sputum samples from the Bergen COPD cohort and COPD exacerbation study using liquid chromatography-mass spectrometry. Additionally, effects of whole cigarette smoke on PUFA metabolism in air-liquid interface cultures of primary bronchial epithelial cells were assessed.ResultsSignificantly lower levels of free alpha-linolenic acid, linoleic acid and eicosapentaenoic acid (EPA) were detected in sputum from stable COPD patients compared to controls. During acute exacerbation (AE), levels of free arachidonic acid and docosapentaenoic acid were higher than in stable COPD patients. Furthermore, levels of omega-3 EPA- and docosahexaenoic acid-derived oxylipins were lower in sputum from stable COPD patients compared to controls. Cyclooxygenase-2-converted mediators were mostly increased during AE. In vitro studies additionally showed that cigarette smoke exposure may also directly contribute to altered epithelial PUFA metabolism, and indirectly by causing airway epithelial remodelling.ConclusionsOur findings show significant differences in PUFA metabolism in COPD patients compared to controls, further changed during AE. Airway epithelial remodelling may contribute to these changes. These findings provide new insight in impaired inflammatory resolution in COPD.     

布地格福与布地奈德福莫特罗粉对COPD缓解期患者肺功能、运动耐力的影响对比

摘要 目的：探讨布地格福与布地奈德福莫特罗粉对慢性阻塞性肺疾病（COPD）缓解期患者肺功能、运动耐力的影响。方法：选取2020年1月至2022年12月本院收治的300例COPD缓解期患者,将其随机分为A组（n=150）和B组（n=150）,A组予以布地格福吸入治疗,B组予以布地奈德莫特罗粉吸入治疗。连续治疗3个月后,比较两组疗效及用药安全性;比较两组肺功能、血气水平、运动耐力和生活质量、炎症指标变化。结果：连续治疗3个月后,A组治疗总有效率为96.00 %,高于对照组的90.00 %（P＜0.05）;治疗后两组第1 s用力呼气容积（FEV₁）、FEV₁/用力肺活量、FEV₁占预计值百分数、血氧分压、6 min步行距离较治疗前均有提升,且A组高于B组（P＜0.05）;治疗后两组残气容积/肺总量、二氧化碳分压、白细胞介素-17、基质金属蛋白酶-9、圣乔治呼吸问卷评分较治疗前均有降低,且A组低于B组（P＜0.05）;治疗期间两组均未发生严重的不良反应（P＞0.05）。结论：相较于布地奈德福莫特罗,布地格福对COPD缓解期的治疗效果更佳,能有效减低气道炎症损伤,改善其肺功能及血气水平,提升患者运动耐力及生活质量。     

Multi analyte profiling and variability of inflammatory markers in blood and induced sputum in patients with stable COPD

Background

We analyzed serial concentrations of multiple inflammatory mediators from serum and induced sputum obtained from patients with stable COPD and controls. The objective was to determine which proteins could be used as reliable biomarkers to assess COPD disease state and severity.

Methods

Forty-two subjects; 21 with stable COPD and 21 controls, were studied every 2 weeks over a 6-week period. Serum and induced sputum were obtained at each of 3 visits and concentrations of 19 serum and 22 sputum proteins were serially assessed using multiplex immunoassays. We used linear mixed effects models to test the distribution of proteins for an association with COPD and disease severity. Measures of within- and between-subject coefficients of variation were calculated for each of the proteins to assess reliability of measurement.

Results

There was significant variability in concentrations of all inflammatory proteins over time, and variability was greater for sputum proteins (median intra-subject coefficient of variation 0.58) compared to proteins measured in serum (median intra-subject coefficient of variation 0.32, P = 0.03). Of 19 serum proteins and 22 sputum proteins tested, only serum CRP, myeloperoxidase and VEGF and sputum IL-6, IL-8, TIMP-1, and VEGF showed acceptable intra and inter-patient reliability and were significantly associated with COPD, the severity of lung function impairment, and dyspnea.

Conclusions

Levels of many serum and sputum biomarkers cannot be reliably ascertained based on single measurements. Multiple measurements over time can give a more reliable and precise estimate of the inflammatory burden in clinically stable COPD patients.     

结缔组织生长因子在慢性阻塞性肺疾病血管重建中表达研究

目的:探讨结缔组织生长因子(CTGF)在慢性阻塞性肺疾病(COPD)血管重建中的表达及意义。方法:将30例有吸烟史的男性鳞癌需要手术的患者按其肺功能结果分成二组,对照组:(肺功能正常组);COPD稳定期组:(肺功能异常组),每组15例,标本来自于癌旁的肺组织,肺血管重塑的形态学观察行HE和MASSON三色染色,行免疫组化来观察CTGF蛋白、PCNA蛋白在肺血管平滑肌中的表达。结果:(1)COPD组肺动脉管壁面积/管总面积(WA%)、管壁的胶原厚度、肺动脉平滑肌中CTGF蛋白及PCNA蛋白的表达与对照组相比差异有统计学意义。(2)CTGF与管壁面积/管总面积(WA%)、管壁的胶原厚度及血管平滑肌中PCNA表达呈正相关(,r值分别为0.81、0.68、0.86,P<0.05)。吸烟指数与管壁面积/管总面积及PCNA的表达呈正相关(r=0.73,0.99,P<0.01)。结论:单纯吸烟者即有血管重建,吸烟伴COPD者血管重建更加严重,CTGF在COPD患者肺血管中的表达较对照组高,可能参与了COPD血管重建过程。     

心肺康复训练联合冬病夏治穴位贴敷对慢性阻塞性肺疾病稳定期患者肺功能、免疫功能和生活质量的影响

摘要 目的：探讨冬病夏治穴位贴敷联合心肺康复训练对慢性阻塞性肺疾病（COPD）稳定期患者免疫功能、肺功能和生活质量的影响。方法：将2021年3月至2022年3月湖北民族大学附属民大医院接收的80例COPD稳定期患者纳为研究对象。按照随机数字表法分为研究组（n=40,接受心肺康复训练联合冬病夏治穴位贴敷）和对照组（n=40,接受心肺康复训练）。对比两组6 min步行试验（6MWT）、COPD急性加重住院次数、住院时间、肺功能、免疫功能和生活质量。结果：研究组治疗后6MWT长于对照组（P<0.05）,研究组的COPD急性加重住院次数少于对照组,住院时间短于对照组（P<0.05）。研究组治疗后咳嗽、睡眠、咳痰、情绪、运动耐力、胸闷、精力和日常运动评分低于对照组（P<0.05）。研究组治疗后CD4⁺、CD4⁺/CD8⁺、免疫球蛋白（Ig）A、IgG、IgM高于对照组,CD8⁺低于对照组（P<0.05）。研究组治疗后用力肺活量（FVC）、呼气峰值流速（PEF）、第1秒用力呼气容积（FEV₁）高于对照组（P<0.05）。结论：冬病夏治穴位贴敷联合心肺康复训练治疗COPD稳定期患者,可有效提高患者的免疫功能和肺功能,提高患者的生活质量。     

Systemic and Pulmonary Vascular Remodelling in Chronic Obstructive Pulmonary Disease

BackgroundChronic Obstructive Pulmonary Disease (COPD) is associated with subclinical systemic atherosclerosis and pulmonary vascular remodelling characterized by intimal hyperplasia and luminal narrowing. We aimed to determine differences in the intimal thickening of systemic and pulmonary arteries in COPD subjects and smokers. Secondary aims include comparisons with a non-smokers group; determining the clinical variables associated with systemic and pulmonary intimal thickening, and the correlations between systemic and pulmonary remodelling changes.MethodsAll consecutive subjects undergoing lung resection were included and divided into 3 groups: 1) COPD, 2) smokers, and 3) non-smokers. Sections of the 5th intercostal artery and muscular pulmonary arteries were measured by histo-morphometry. Four parameters of intimal thickening were evaluated: 1) percentage of intimal area (%IA), 2) percentage of luminal narrowing, 3) intimal thickness index, and 4) intima-to-media ratio.ResultsIn the adjusted analysis, the systemic arteries of COPD subjects showed greater intimal thickening (%IA) than those of smokers (15.6±1.5% vs. 14.2±1.6%, p = 0.038). In the pulmonary arteries, significant differences were observed for %IA between the 2 groups (37.3±2.2% vs. 29.3±2.3%, p = 0.016). Among clinical factors, metabolic syndrome, gender and COPD status were associated with the systemic intimal thickening, while only COPD status was associated with pulmonary intimal thickening. A correlation between the %IA of the systemic and pulmonary arteries was observed (Spearman’s rho = 0.46, p = 0.008).ConclusionsGreater intimal thickening in systemic and pulmonary arteries is observed in COPD patients than in smokers. There is a correlation between systemic and pulmonary vascular remodelling in the overall population.     

Effect of chemokine receptor CXCR4 on hypoxia-induced pulmonary hypertension and vascular remodeling in rats

Background

CXCR4 is the receptor for chemokine CXCL12 and reportedly plays an important role in systemic vascular repair and remodeling, but the role of CXCR4 in development of pulmonary hypertension and vascular remodeling has not been fully understood.

Methods

In this study we investigated the role of CXCR4 in the development of pulmonary hypertension and vascular remodeling by using a CXCR4 inhibitor AMD3100 and by electroporation of CXCR4 shRNA into bone marrow cells and then transplantation of the bone marrow cells into rats.

Results

We found that the CXCR4 inhibitor significantly decreased chronic hypoxia-induced pulmonary hypertension and vascular remodeling in rats and, most importantly, we found that the rats that were transplanted with the bone marrow cells electroporated with CXCR4 shRNA had significantly lower mean pulmonary pressure (mPAP), ratio of right ventricular weight to left ventricular plus septal weight (RV/(LV+S)) and wall thickness of pulmonary artery induced by chronic hypoxia as compared with control rats.

Conclusions

The hypothesis that CXCR4 is critical in hypoxic pulmonary hypertension in rats has been demonstrated. The present study not only has shown an inhibitory effect caused by systemic inhibition of CXCR4 activity on pulmonary hypertension, but more importantly also has revealed that specific inhibition of the CXCR4 in bone marrow cells can reduce pulmonary hypertension and vascular remodeling via decreasing bone marrow derived cell recruitment to the lung in hypoxia. This study suggests a novel therapeutic approach for pulmonary hypertension by inhibiting bone marrow derived cell recruitment.     

Right atrial pressure affects the interaction between lung mechanics and right ventricular function in spontaneously breathing COPD patients

Introduction

It is generally known that positive pressure ventilation is associated with impaired venous return and decreased right ventricular output, in particular in patients with a low right atrial pressure and relative hypovolaemia. Altered lung mechanics have been suggested to impair right ventricular output in COPD, but this relation has never been firmly established in spontaneously breathing patients at rest or during exercise, nor has it been determined whether these cardiopulmonary interactions are influenced by right atrial pressure.

Methods

Twenty-one patients with COPD underwent simultaneous measurements of intrathoracic, right atrial and pulmonary artery pressures during spontaneous breathing at rest and during exercise. Intrathoracic pressure and right atrial pressure were used to calculate right atrial filling pressure. Dynamic changes in pulmonary artery pulse pressure during expiration were examined to evaluate changes in right ventricular output.

Results

Pulmonary artery pulse pressure decreased up to 40% during expiration reflecting a decrease in stroke volume. The decline in pulse pressure was most prominent in patients with a low right atrial filling pressure. During exercise, a similar decline in pulmonary artery pressure was observed. This could be explained by similar increases in intrathoracic pressure and right atrial pressure during exercise, resulting in an unchanged right atrial filling pressure.

Conclusions

We show that in spontaneously breathing COPD patients the pulmonary artery pulse pressure decreases during expiration and that the magnitude of the decline in pulmonary artery pulse pressure is not just a function of intrathoracic pressure, but also depends on right atrial pressure.     

Association between pulmonary function and peak oxygen uptake in elderly: the Generation 100 study

Chronic obstructive lung disease (COPD) is a common cause of death in industrialized countries often induced by exposure to tobacco smoke. A substantial number of patients with COPD also suffer from pulmonary hypertension that may be caused by hypoxia or other hypoxia-independent stimuli - inducing pulmonary vascular remodeling. The Ca2+ binding protein, S100A4 is known to play a role in non-COPD-driven vascular remodeling of intrapulmonary arteries. Therefore, we have investigated the potential involvement of S100A4 in COPD induced vascular remodeling. Lung tissue was obtained from explanted lungs of five COPD patients and five non-transplanted donor lungs. Additionally, mice lungs of a tobacco-smoke-induced lung emphysema model (exposure for 3 and 8 month) and controls were investigated. Real-time RT-PCR analysis of S100A4 and RAGE mRNA was performed from laser-microdissected intrapulmonary arteries. S100A4 immunohistochemistry was semi-quantitatively evaluated. Mobility shift assay and siRNA knock-down were used to prove hypoxia responsive elements (HRE) and HIF binding within the S100A4 promoter. Laser-microdissection in combination with real-time PCR analysis revealed higher expression of S100A4 mRNA in intrapulmonary arteries of COPD patients compared to donors. These findings were mirrored by semi-quantitative analysis of S100A4 immunostaining. Analogous to human lungs, in mice with tobacco-smoke-induced emphysema an up-regulation of S100A4 mRNA and protein was observed in intrapulmonary arteries. Putative HREs could be identified in the promoter region of the human S100A4 gene and their functionality was confirmed by mobility shift assay. Knock-down of HIF1/2 by siRNA attenuated hypoxia-dependent increase in S100A4 mRNA levels in human primary pulmonary artery smooth muscle cells. Interestingly, RAGE mRNA expression was enhanced in pulmonary arteries of tobacco-smoke exposed mice but not in pulmonary arteries of COPD patients. As enhanced S100A4 expression was observed in remodeled intrapulmonary arteries of COPD patients, targeting S100A4 could serve as potential therapeutic option for prevention of vascular remodeling in COPD patients.