噻托溴铵联合奥达特罗治疗慢性阻塞性肺疾病患者的疗效及对免疫功能的影响

目的:探讨噻托溴铵联合奥达特罗治疗慢性阻塞性肺疾病(COPD)患者的疗效及对免疫功能的影响。方法:选取我院于2018年10月到2019年10月期间接收的108例COPD患者,按照随机数字表法将患者分为噻托溴铵组(n=36,噻托溴铵治疗)、奥达特罗组(n=36,奥达特罗治疗)、联合组(n=36,噻托溴铵联合奥达特罗治疗),比较三组患者疗效、肺功能、免疫功能及不良反应。结果:联合组治疗3个月后的临床总有效率、肺活量(FVC)、第1秒用力呼气容积(FEV1)、FEV1/FVC、CD3+、CD4+、免疫球蛋白G(Ig G)、免疫球蛋白M(Ig M)均高于奥达特罗组、噻托溴铵组(P0.05)。奥达特罗组、噻托溴铵组治疗3个月后的的临床总有效率、FVC、FEV1、FEV1/FVC、CD3+、CD4+、Ig G、Ig M比较差异无统计学意义(P0.05)。三组治疗期间不良反应发生率整体比较差异无统计学意义(P0.05)。结论:噻托溴铵联合奥达特罗治疗COPD患者,疗效显著,可有效改善免疫功能及肺功能,且不增加不良反应发生率。     

噻托溴铵治疗老年稳定期COPD 临床观察

目的:探讨噻托溴铵吸入剂对老年吸烟稳定期慢性阻塞性肺疾病(COPD)的临床疗效。方法:入选稳定期COPD老年患者92例,随机分为2组各46例,观察组予噻托溴铵吸入剂18微克每日一次,对照组予缓释茶碱0.1克每12小时口服,两组均按需使用沙丁胺醇气雾剂,随访2月,比较两组治疗前后的肺功能与生活质量改善情况。结果:观察组治疗后St George评分明显下降(P<0.01),显著低于对照组(P<0.01),FEV1/FVC、FEV1/Pred、FEV1均较治疗前明显升高(P<0.01),而对照组治疗前后无显著差异(P>0.05)。结论:吸入噻托溴铵能显著改善老年吸烟COPD稳定期患者的肺功能与生活质量。     

噻托溴铵联合布地奈德福莫特罗治疗重度慢性阻塞性肺疾病稳定期效果与安全性

目的探讨噻托溴铵联合布地奈德福莫特罗治疗重度慢性阻塞性肺疾病稳定期的效果与安全性。方法选取2015年4月~2017年4月在我院治疗的60例重度慢性阻塞性肺疾病患者作为研究对象,按随机数字法分成对照组和观察组,两组患者均进行常规治疗,观察组患者在常规治疗基础上配合布地奈德福莫特罗联合噻托溴铵吸入,对照组患者在常规治疗的基础上配合布地奈德福莫特罗治疗,比较两组患者的治疗效果。结果治疗后,观察组患者6 MWT、呼吸困难改善情况均明显优于对照组,差异有显著统计学意义(P0.05);观察组患者的用力肺活量(FVC)、第1秒用力呼气容积(FEV1)、FEV1/FVC均较对照组明显升高,动脉血气指标明显优于对照组,差异均有统计学意义(P0.05)。结论噻托溴铵联合布地奈德福莫特罗治疗重度慢性阻塞性肺疾病患者的效果显著,可有效改善患者肺功能以及动脉血气情况。     

噻托溴铵联合布地奈德福莫特罗对慢性阻塞性肺疾病的疗效及对TGF-β、TIMP-1、IL-6水平的影响

目的:探讨噻托溴铵联合布地奈德福莫特罗治疗慢性阻塞性肺疾病(COPD)患者的临床疗效及对转化生长因子-β(TGF-β)、基质金属蛋白酶抑制因子-1(TIMP-1)及白细胞介素-6(IL-6)水平的影响。方法:选取我院于2016年1月至2016年12月期间收治的80例稳定期的COPD患者,按乱数表法分为对照组和观察组,两组均为40例。两组患者均进行常规治疗和布地奈德福莫特罗吸入治疗,观察组在此基础上加用噻托溴铵吸入剂。连续治疗12周后对两组患者的临床疗效、肺功能、血气指标、细胞因子水平进行评价。结果:观察组患者总有效率高于对照组(P0.05)。治疗后,观察组肺功能指标用力肺活量(FVC)、一秒用力呼气容积(FEV1)、第一秒用力呼气容积占用力肺活量比值(FEV1/FVC)、动脉血氧分压(PaO_2)和动脉血二氧化碳分压(PaCO_2)改善程度均优于对照组(P0.05)。治疗后观察组患者血清中IL-6、TIMP-1及TGF-β水平均低于对照组(P0.05)。结论:噻托溴铵与布地奈德福莫特罗的联合治疗稳定期的COPD患者疗效显著,并且能够有效改善患者肺功能和血气指标,降低血清TGF-β、TIMP-1及IL-6水平,值得临床推广使用。     

沙美特罗联合噻托溴铵对慢性阻塞性肺疾病患者血清MMP-2, MMP-9及IL-8水平的影响

目的:探讨沙美特罗联合噻托溴铵对慢性阻塞性肺疾病患者血清炎症因子水平及肺功能的影响。方法:选择2014年5月-2016年5月我院收治的慢性阻塞性肺病患者83例作为研究对象,根据治疗方法不同,将所选患者分为研究组(45例)和对照组(38例)。研究组患者采用沙美特罗联合噻托溴铵吸入治疗,对照组患者采用沙美特罗治疗。观察并比较两组患者治疗前后血清MMP-2,MMP-9及IL-8水平及肺功能指标的变化情况。结果:治疗前两组患者血清MMP-2,MMP-9及IL-8水平比较,差异无统计学意义(P0.05);治疗后两组患者血清MMP-2,MMP-9及IL-8水平均低于治疗前,且研究组低于对照组,差异均具有统计学意义(P0.05)。与治疗前比较,两组患者治疗后FEV1/FVC,FEV1及MVV均升高,差异具有统计学意义(P0.05);与对照组比较,研究组患者治疗后FEV1/FVC,FEV1及MVV较高,差异具有统计学意义(P0.05)。结论:沙美特罗联合噻托溴铵治疗慢性阻塞性肺疾病的临床效果显著,不仅能够降低患者血清炎症因子水平,还可改善患者肺功能,值得临床推广应用。     

噻托溴铵联合沙美特罗治疗慢性阻塞性肺疾病的临床效果

目的:探讨噻托溴铵联合沙美特罗治疗慢性阻塞性肺疾病的临床效果。方法:选取我院2008年8月~2016年8月期间收治的68例慢性阻塞性肺疾病患者,由电脑随机均分为两组,每组34例,其中对照组给予沙美特罗进行治疗,而观察组在此基础上施加噻托溴铵治疗。对比观察两组患者治疗前后肺功能指标的变化、运动能力、生活质量、预后及不良事件发生率。结果:治疗前,两组患者的肺功能各项指标、6分钟步行距离(6MWD)和圣乔治呼吸问卷(SGRQ)评分均无明显差异(P0.05)。治疗后均较治疗前有明显改善,且观察组同期改善程度均显著高于对照组(P0.05)。观察组在治疗后12个月内发生急性加重的例数明显少于对照组(P0.05),且不良事件发生率明显低于对照组(P0.05)。结论:联合使用噻托溴铵与沙美特罗治疗慢性阻塞性肺疾病,可更好地改善患者的肺功能、运动能力及生活质量,且急性加重率和不良事件发生率更低,值得进一步推广与应用。     

噻托溴铵粉吸入剂治疗稳定期中重度COPD 患者的临床疗效观察

目的:研究噻托溴铵粉吸入剂治疗稳定期中重度COPD患者的临床疗效.方法:选择稳定期中重度COPD患者60例,在患者知情同意的情况下随机均分为对照组(30例)与观察组(30例),对照组患者施行常规药物治疗措施,观察组患者在常规药物治疗措施基础上加用噻托溴铵粉吸入剂治疗,比较两组患者治疗10周后肺功能指标、血气分析指标、呼吸困难评分、生活质量评分及不良反应例数.结果:治疗10周后,两组患者肺功能指标、血气分析指标、呼吸困难评分和生活质量评分比较,差异均具有统计学意义(P＜0.05),观察组优于对照组;发生不良反应例数比较,差异无统计学意义(P＞0.05).结论:在稳定期中重度COPD患者临床治疗过程中,应加用噻托溴铵粉吸入剂治疗,可显著提高临床疗效,且不增加不良反应.     

加味麻杏石甘汤联合噻托溴铵对慢性阻塞性肺疾病急性加重期患者肺功能、血气指标及炎症因子的影响

目的:探讨加味麻杏石甘汤联合噻托溴铵对慢性阻塞性肺疾病急性加重期(AECOPD)患者肺功能、血气指标及炎症因子的影响。方法:选取2018年2月-2019年11月我院收治的97例AECOPD患者,按随机数字表法将其分为对照组(n=48,噻托溴铵治疗)、研究组(n=49,加味麻杏石甘汤联合噻托溴铵治疗),比较两组患者疗效、中医证候积分、肺功能、血气指标、炎症因子及不良反应。结果:治疗14 d后研究组临床总有效率较对照组高(P<0.05)。两组不良反应发生率比较无差异(P>0.05)。两组治疗14 d后中医证候积分均下降,且研究组低于对照组(P<0.05)。两组治疗14 d后第1秒用力呼气容积(FEV1)、用力肺活量(FVC)、FEV1/FVC均较治疗前升高,且研究组高于对照组(P<0.05)。两组治疗14 d后动脉血氧分压(PO2)升高,且研究组高于对照组(P<0.05),二氧化碳分压(PCO2)下降,且研究组低于对照组(P<0.05)。两组治疗14 d后血清白细胞介素-8(IL-8)、C反应蛋白(CRP)水平均下降,且研究组低于对照组(P<0.05)。结论:加味麻杏石甘汤联合噻托溴铵治疗AECOPD患者,疗效显著,可有效改善患者临床症状、肺功能、血气指标及炎症因子,且安全可靠。     

吸入噻托溴铵治疗慢性阻塞性肺疾病的疗效研究

目的：观察噻托溴铵粉吸入剂治疗稳定期慢性阻塞性肺疾病的有效性及安全性。方法：对2010年1月一2010年12月在本院就诊的60例稳定期COPD患者随机分成两组,对照组接受口服茶碱缓释片治疗,治疗组接受噻托溴铵粉吸入剂治疗。结果：治疗组与对照组治疗后28天FEV1改善率相互比较,差异有统计学意义（P〈0．05）;治疗组与对照组治疗后（d28）以及随访期（疗后第3个月、第6个月）圣·乔治呼吸疾病问卷调查比较,总评分差异均有统计学意义（P〈0．05）;治疗组与对照组治疗后（d28）的6MwT,差异有统计学意义（P〈0．05）;两组患者随访期AECOPD发病次数,有统计学差异（P〈0．05）;两组患者的不良反应相互比较,无统计学意义（P〉0．05）。结论：噻托溴铵粉吸入剂治疗慢性阻塞性肺疾病（COPD）疗效确切和可靠,值得临床推广。     

噻托溴铵辅助治疗呼吸窘迫综合征对血清NO与VEGF水平的影响研究

摘要 目的：探讨与研究噻托溴铵辅助治疗呼吸窘迫综合征对血清一氧化氮(Nitric oxide,NO)与血管内皮生长因子(vascular endothelial growth factor,VEGF)水平的影响。方法：2016年9月到2020年9月选择在本院进行急诊的呼吸窘迫综合征患者84例,根据随机数字表法把患者分为噻托溴铵组与对照组各42例。对照组给予鼻塞式持续气道正压通气治疗,噻托溴铵组在对照组治疗的基础上给予噻托溴铵治疗,两组都治疗观察2 w,检测血清NO与VEGF表达变化情况。结果：治疗后噻托溴铵组的总有效率为97.6 %,高于对照组的85.7 % (P<0.05)。两组治疗后的氧合指数高于治疗前(P<0.05),噻托溴铵组高于对照组(P<0.05)。两组治疗后的FEV₁与FVC值高于治疗前(P<0.05),噻托溴铵组高于对照组(P<0.05)。两组治疗后的血清NO值高于治疗前(P<0.05),血清VEGF值低于治疗前(P<0.05),噻托溴铵组与对照组对比差异也都有统计学意义(P<0.05)。结论：噻托溴铵辅助治疗呼吸窘迫综合征能抑制血清VEGF的表达与促进NO的释放,改善患者的肺功能与氧合状况,从而提高治疗效果。     

Tiotropium in asthma: back to the future of anticholinergic treatment

Asthma is among the most common chronic diseases worldwide; however, despite progresses in the understanding of the patho-physiological mechanisms and advances in the development of new therapeutic options and strategies, the disease remains uncontrolled in a not trivial proportion of subjects. Thus, the need of new molecules to treat the underlying biological and functional abnormalities and to control symptoms is strongly advocated by clinicians. In this scenario, the most recent GINA guidelines have included the use of tiotropium bromide in the most severe and uncontrolled forms of the disease, in addition to treatment with inhaled corticosteroid plus long acting beta adrenergic agents. Indeed, a large body of evidence has accumulated to support the use of tiotropium bromide in asthma. The current review paper provides a state of the art systematic revision of findings on the efficacy and safety of tiotropium in the adult and paediatric asthma population. To this aim, electronic searches were undertaken in the most common scientific databases from the date of inception to March 2017. Robust and high quality evidence showed that tiotropium is effective and safe in both adults and children/adolescents. Predictive markers of response have been also suggested, as well as cost–benefit analyses reported. The tiotropium bronchodilator effect seems to be not solely related to the reduction of the smooth muscle tone. However, the observations on anti-inflammatory properties or reduction in mucus production, despite highly interesting, have been only demonstrated in in vitro studies and animal models, therefore advocating for further specifically designed investigations.     

Tiotropium might improve survival in subjects with COPD at high risk of mortality

Background

Inhaled therapies reduce risk of chronic obstructive pulmonary disease (COPD) exacerbations, but their effect on mortality is less well established. We hypothesized that heterogeneity in baseline mortality risk influenced the results of drug trials assessing mortality in COPD.

Methods

The 5706 patients with COPD from the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) study that had complete clinical information for variables associated with mortality (age, forced expiratory volume in 1 s, St George’s Respiratory Questionnaire, pack-years and body mass index) were classified by cluster analysis. Baseline risk of mortality between clusters, and impact of tiotropium were evaluated during the 4-yr follow up.

Results

Four clusters were identified, including low-risk (low mortality rate) patients (n = 2339; 41%; cluster 2), and high-risk patients (n = 1022; 18%; cluster 3), who had a 2.6- and a six-fold increase in all-cause and respiratory mortality compared with cluster 2, respectively. Tiotropium reduced exacerbations in all clusters, and reduced hospitalizations in high-risk patients (p < 0.05). The beneficial effect of tiotropium on all-cause mortality in the overall population (hazard ratio, 0.87; 95% confidence interval, 0.75–1.00, p = 0.054) was explained by a 21% reduction in cluster 3 (p = 0.07), with no effect in other clusters.

Conclusions

Large variations in baseline risks of mortality existed among patients in the UPLIFT® study. Inclusion of numerous low-risk patients may have reduced the ability to show beneficial effect on mortality. Future clinical trials should consider selective inclusion of high-risk patients.     

Tiotropium (Spiriva): mechanistical considerations and clinical profile in obstructive lung disease

Inhaled antimuscarinics, often called anticholinergics in clinical medicine, are established as first line bronchodilators in COPD. Tiotropium has been developed as a new generation antimuscarinic following ipratropium. Tiotropium is a specific, highly potent antimuscarinic, demonstrating very slow dissociation from muscarinic receptors. Dissociation from M2-receptors is faster than from M3 or M1, which in functional in vitro studies, appeared as kinetic receptor subtype selectivity of M3 and M1 over M2. The high potency and slow receptor dissociation found its clinical correlate in significant and long lasting bronchodilatation and bronchoprotection in patients with COPD and asthma. In asthma, protection against methacholine challenge exceeded the study period of 48 hours. In COPD, bronchodilatation of about 80% of the plateau was demonstrated after the first dose. Following chronic once daily inhalation for 28 days, the improvement in pulmonary function was sustained and there was a further increase in peak effects, but more importantly a rising baseline, achieving steady state within 2 weeks. Tiotropium achieves very stable long lasting effects with comparatively low variation of bronchodilatation between peak and trough (the level before the next administration). Stable 24 hour effectiveness profiles the compound as the first once daily bronchodilator. Clinical correlates of kinetic receptor subtype selective blockade remain to be shown. Plasma levels of tiotropium at trough are in the low pg/ml range and are unlikely to explain the sustained effectiveness in the airways. Slow dissociation from muscarinic receptors is likely to be responsible for the long duration of action.     

Comparison of Clinical Efficacy and Safety between Indacaterol and Tiotropium in COPD: Meta-Analysis of Randomized Controlled Trials

Two once-daily inhaled bronchodilators, indacaterol and tiotropium, are widely used as first-line therapy in stable COPD patients. This study was performed to compare the clinical efficacy and safety between indacaterol and tiotropium in patients with moderate-to-severe COPD. MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched to identify all published randomized controlled trials (RCTs). The primary outcome was trough forced expiratory volume in 1 second (FEV₁) at week 12. Four RCTs were eligible for inclusion (three RCTs with moderate-to-severe COPD patients and one RCT with only severe COPD patients). Trough FEV₁ at weeks 12 and 26 were not significantly different between indacaterol and tiotropium by the standardized mean difference with 0.014 (95% CI, -0.036, 0.063, I²= 23.5%) and with 0.037 (95% CI, -0.059 to 0.133, I²= 0%) along with differences in means of 0.003L and 0.014L, respectively. Indacaterol and tiotropium also showed similar St. George`s Respiratory Questionnaire (SGRQ) total scores and percentages of patients with SGRQ improvement (≥ 4 units) at week 26. The incidences of nasopharyngitis, serious cardiovascular events, and serious adverse events were not different between indacaterol and tiotropium, while those of cough (OR = 1.68, P < 0.001, and RR = 1.63) and COPD worsening (OR = 1.18, P = 0.003, and RR = 1.12) were higher for indacaterol than tiotropium. However, when one study with only severe COPD patients was removed from the meta-analysis, the difference in the incidence of COPD worsening between indacaterol and tiotropium became non-significant (OR = 1.13, P = 0.204, and RR = 1.09). The clinical efficacy and serious adverse events between indacaterol and tiotropium were equivocal in patients with moderate-to-severe COPD. Cough is a common complaint associated with indacaterol, and COPD worsening needs to be carefully monitored in severe COPD patients when treated with indacaterol.     

Tiotropium bromide (Ba 679 BR), a novel long-acting muscarinic antagonist for the treatment of obstructive airways disease

Tiotropium bromide (Ba 679 BR) is a novel potent and long-lasting muscarinic antagonist that has been developed for the treatment of chronic obstructive airways disease (COPD). Binding studies with [3H]tiotropium bromide in human lung have confirmed that this is a potent muscarinic antagonist with equal affinity for M1-, M2- and M3-receptors and is approximately 10-fold more potent than ipratropium bromide. Tiotropium bromide dissociates very slowly from lung muscarinic receptors compared with ipratropium bromide. In vitro tiotropium bromide has a potent inhibitory effect against cholinergic nerve-induced contraction of guinea-pig and human airways, that has a slower onset than atropine or ipratropium bromide. After washout, however, tiotropium bromide dissociates extremely slowly compared with the dissociation of atropine and ipratropium bromide. Measurement of acetylcholine (ACh) release from guinea-pig trachea shows that tiotropium bromide, ipratropium bromide and atropine all increase ACh release on neural stimulation and that this effect is washed out equally quickly for the three antagonists. This confirms binding studies to transfected human muscarinic receptors which suggested that tiotropium bromide dissociates slowly from M3-receptors (on airway smooth muscle) but rapidly from M2 autoreceptors (on cholinergic nerve terminals). Clinical studies with inhaled tiotropium bromide confirm that it is a potent and long-lasting bronchodilator in COPD and asthma. Furthermore, it protects against cholinergic bronchoconstriction for > 24 h. This suggests that tiotropium bromide will be a useful bronchodilator, particularly in patients with COPD, and may be suitable for daily dosing. The selectivity for M3- over M2-receptors may also confer a clinical advantage.