The relationships among the levels of oxidative and antioxidative parameters,FEV1 and prolidase activity in COPD

Introduction: Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by poorly reversible airflow limitations associated with an abnormal inflammatory response of the lung.

Methods: We investigated whether prolidase levels in serum, total antioxidant status, total oxidative status (TOS), and the oxidative stress index (OSI) were associated with the etiopathogenesis of COPD, and whether there is a relationship between prolidase activity and oxidative parameters and carotid artery intima-media thickness (CIMT) in patients with COPD. This study included 91 patients with COPD and 15 control cases. Routine haematological and biochemical parameters were determined in all patients. All subjects were fully informed about the study and provided consent.

Results: The mean age of the patients with COPD was 61.3?±?10.5 years and that of the control group was 56.2?±?12.1 years. The control group had a significantly higher plasma prolidase level than that in the COPD group. TOS and OSI levels in the control group were significantly lower than those in the COPD group. However, no significant differences were found in TALs or CIMT levels between the COPD and control groups. A negative correlation was detected between prolidase activity and age; however, no significant difference in age was observed between the two groups.

Conclusion: These results indicate that prolidase activity decreases in patients with COPD.     

腹部手术伴COPD病人围手术期处理体会（附35例临床报告）

目的：探讨伴有COPD病人行腹部手术时的危险性、手术耐受力评估以及围手术期的处理。方法：主要分析35例COPD病人行上腹部手术的临床资料。结果：35例病人中术后有发生肺部感染、腹部创口破裂等并发症,无一例发生呼衰,术后均治愈出院。结论：COPD病人手术有一定危险性,主要在术后,但术前与术中应进行适当的准备与处理,能降低术后并发症发生。不能过分强调其危险性而丧失手术时机。     

Combination bronchodilator therapy in the management of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact. Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations. The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events. Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy. GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β₂-agonists (LABAs), such as formoterol and salmeterol. Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present. Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components. This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease.     

Inhibition of phosphodiesterase 4 modulates cytokine induction from toll like receptor activated,but not rhinovirus infected,primary human airway smooth muscle

Background

Virus-induced exacerbations of Chronic Obstructive Pulmonary Disease (COPD) are a significant health burden and occur even in those receiving the best current therapies. Rhinovirus (RV) infections are responsible for half of all COPD exacerbations. The mechanism by which exacerbations occur remains undefined, however it is likely to be due to virus-induced inflammation. Given that phophodiesterase 4 (PDE₄) inhibitors have an anti-inflammatory effect in patients with COPD they present a potential therapy prior to, and during, these exacerbations.

Methods

In the present study we investigated whether the PDE₄ inhibitor piclamilast (10^-6 M) could alter RV or viral mimetic (5 μg/mL of imiquimod or poly I:C) induced inflammation and RV replication in primary human airway smooth muscle cells (ASMC) and bronchial epithelial cells (HBEC). The mediators IL-6, IL-8, prostaglandin E₂ and cAMP production were assayed by ELISA and RV replication was assayed by viral titration.

Results

We found that in ASMCs the TLR3 agonist poly I:C induced IL-8 release was reduced while induced IL-6 release by the TLR7/8 agonist imiquimod was further increased by the presence of piclamilast. However, in RV infected ASMCs, virus replication and induced mediator release were unaltered by piclamilast, as was also found in HBECs. The novel findings of this study reveal that although PDE inhibitors may not influence RV-induced cytokine production in ASMCs and replication in either ASMCs or HBECs, they have the capacity to be anti-inflammatory during TLR activation by modulating the induction of these chemotactic cytokines.

Conclusion

By extrapolating our in vitro findings to exacerbations of COPD in vivo this suggests that PDE₄ inhibitors may have beneficial anti-inflammatory properties when patients are infected with bacteria or viruses other than RV.     

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。     

氨溴索对慢性阻塞性肺疾病急性加重期患者血清炎症因子的影响

目的:系统评价氨溴索注射液对慢性阻塞性肺疾病急性加重期(AECOPD)的临床疗效及对患者血清炎症因子CRP及TNF-α的影响。方法:①按照诊断标准共纳入60例患者,按入院或就诊的先后顺序随机分成氨溴索治疗组和对照组,每组30例患者;另设30名COPD稳定期患者作为稳定期对照组。②治疗前后抽取静脉血,待测CRP及TNF-α水平;③对照组患者仅给予抗菌药物及解痉平喘药物等常规治疗;治疗组患者给予常规治疗外,还给予盐酸氨溴索注射液30mg,每天分2次静滴,10天为1疗程;④治疗1疗程后观察临床疗效及血清炎症因子水平的变化。结果:①两组患者在性别,年龄,病程,病情,合并疾病的分布等基线资料上无显著性差异,P>0.05;②AECOPD患者机体炎症因子水平较COPD稳定期患者显著升高,P<0.01;氨溴索治疗组无论在临床疗效抑或降低血清炎症因子水平方面均要优于对照组,P<0.05。结论:盐酸氨溴索注射液辅助治疗可显著降低AECOPD患者血清炎症因子水平,提高临床疗效。     

CRP、纤维蛋白原及白细胞计数水平在COPD临床诊断中的作用

为了研究C-反应蛋白(CRP)、纤维蛋白原(FIB)及白细胞计数(WBC)与慢性阻塞性肺疾病急性(COPD)的相关性及用于诊断慢性阻塞性肺疾病的临床意义,本研究将2015年8月至2017年2月在本院呼吸与危重症医学科住院治疗的60例慢性阻塞性肺疾病急性加重期患者作为AECOPD组,并选择同期住院的60例慢性阻塞性肺疾病稳定期患者设为SCOPD组,60例健康人员作为健康对照组,用受试者工作特征曲线(receiver operator characteristic curve,ROC curve)分析血清CRP、FIB、WBC水平及诊断COPD疾病的临床价值。研究结果表明,AECOPD组及SCOPD组血清CRP、FIB及WBC水平均明显高于健康对照组(tCRP=7.14,tFIB=2.72,tWBC=9.82),AECOPD组血清CRP、FIB及WBC水平(tCRP=37.29,tFIB=5.28,tWBC=14.36)也明显高于SCOPD组(tCRP=14.45,tFIB=4.71,tWBC=12.77),差异均有统计学意义(均p<0.05)。同时,在SCOPD者中,CRP水平与FIB和WBC呈正相关(γ=0.687,0.512,均p<0.05),FIB和WBC也呈正相关(γ=0.445,0.512,p<0.05);在AECOPD组中,CRP水平与FIB和WBC呈正相关(γ=0.733,0.587,均p<0.05),FIB和WBC也具有相关性(γ=0.676,p<0.05)。本研究初步结论认为,CRP、FIB、WBC水平与COPD患者的病情严重程度存在明显相关性,联合CRP、FIB、WBC因子检测有助于鉴别COPD恶化程度,并可作为COPD疾病的监测指标。     

Moraxella catarrhalis induces CEACAM3‐Syk‐CARD9‐dependent activation of human granulocytes

The human restricted pathogen Moraxella catarrhalis is an important causal agent for exacerbations in chronic obstructive lung disease in adults. In such patients, increased numbers of granulocytes are present in the airways, which correlate with bacteria‐induced exacerbations and severity of the disease. Our study investigated whether the interaction of M. catarrhalis with the human granulocyte‐specific carcinoembryonic antigen‐related cell adhesion molecule (CEACAM)‐3 is linked to NF‐κB activation, resulting in chemokine production. Granulocytes from healthy donors and NB4 cells were infected with M. catarrhalis in the presence of different inhibitors, blocking antibodies and siRNA. The supernatants were analysed by enzyme‐linked immunosorbent assay for chemokines. NF‐κB activation was determined using a luciferase reporter gene assay and chromatin‐immunoprecipitation. We found evidence that the specific engagement of CEACAM3 by M. catarrhalis ubiquitous surface protein A1 (UspA1) results in the activation of pro‐inflammatory events, such as degranulation of neutrophils, ROS production and chemokine secretion. The interaction of UspA1 with CEACAM3 induced the activation of the NF‐κB pathway via Syk and the CARD9 pathway and was dependent on the phosphorylation of the CEACAM3 ITAM‐like motif. These findings suggest that the CEACAM3 signalling in neutrophils is able to specifically modulate airway inflammation caused by infection with M. catarrhalis.     

Chemical modification-mediated optimisation of bronchodilatory activity of mepenzolate,a muscarinic receptor antagonist with anti-inflammatory activity

The treatment for patients with chronic obstructive pulmonary disease (COPD) usually involves a combination of anti-inflammatory and bronchodilatory drugs. We recently found that mepenzolate bromide (1) and its derivative, 3-(2-hydroxy-2, 2-diphenylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (5), have both anti-inflammatory and bronchodilatory activities. We chemically modified 5 with a view to obtain derivatives with both anti-inflammatory and longer-lasting bronchodilatory activities. Among the synthesized compounds, (R)-(–)-12 ((R)-3-(2-hydroxy-2,2-diphenylacetoxy)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octane bromide) showed the highest affinity in vitro for the human muscarinic M3 receptor (hM₃R). Compared to 1 and 5, (R)-(–)-12 exhibited longer-lasting bronchodilatory activity and equivalent anti-inflammatory effect in mice. The long-term intratracheal administration of (R)-(–)-12 suppressed porcine pancreatic elastase-induced pulmonary emphysema in mice, whereas the same procedure with a long-acting muscarinic antagonist used clinically (tiotropium bromide) did not. These results suggest that (R)-(–)-12 might be therapeutically beneficial for use with COPD patients given the improved effects seen against both inflammatory pulmonary emphysema and airflow limitation in this animal model.