Objective To investigate the effects of TiotropiumBromide on airway inflammation in a rat model of chronic obstructive pulmonary disease( COPD) . Methods Thirty Wistar rats were randomly divided into three groups. Group A received normal breeding as normal control. Group B and group C received LPS( 200 μg, intratracheally injected at the 1st and the 14th day) and tobacco exposure( from the 2nd day to the 30th day except the 14th day) to establish COPD model. And group C received a nebulized dose of Tiotropium Bromide( 0. 12 mmol / L, 10 minutes) 30 minutes before the tobacco exposure each time. Airway resistance and compliance were measured before sacrificed. Histological examination was performed with Hematoxylin-Eosin staining. The concentrations of IL-8 and LTB4 , total and differential cells counts in bronchoalveolar lavage fluid( BALF) were examined, and the concentrations of IL-8 and LTB4 in blood serum were also examined by ELISA. Results Severe lung inflammation and decreased lung function were demonstrated in the rats in the group B compared with those in the group A. The inflammatory cell counts in BALF, and the levels of IL-8 and LTB4 in BALF and serum were significantly increased in the group B compared with those in the group A. Tiotropium Bromide administration improved the parameters above. Conclusions The results suggest that Tiotropium Bromide can alleviate the lung inflammation and improve the lung function in a rat COPD model. These effects may be exerted through reducing the mediators of inflammation.
Objective To investigate the therapeutic effects of tiotropium in the treatment of stable COPD ( chronic obstructive pulmonary disease) patients of group D. Methods Sixty-two subjects with stable COPD in group D classified by combined COPD assessment in GOLD 2011, were randomly divided into a treatment group ( n = 32) and a control group ( n = 30) . The treatment group was treated with tiotropium ( 18 μg, inhalation, once daily) plus salmeterol /fluticasone ( 50/500 μg, inhalation, twice a day)and the control group was treated only with salmeterol / fluticasone ( 50/500 μg, inhalation, twice a day) . The exercise tolerance, dyspnea score and lung function were measured before and 1, 8,24, and 48 weeks after the treatment respectively. Results 8, 24, 48 weeks after the treatment respectively, there were improvements of 6 minute walk test and the dyspnea score of medical research council scale( MRC) in both groups than before treatment, and which was better in the treatment group. Compared with baseline and the control group, significantly greater improvements in the FVC, FEV1 and FEV1% pred were seen in the treatment group at all time points. In the control group, FVC, FEV1 and FEV1% pred 1 and 8 weeks after treatment were higher than those before treatment, but there was no significant difference after treatment of 24 and 48 weeks.Conclusion Combination treatment with tiotropium and salmeterol / fluticasone inhalation results in greater therapeutic benefits than salmeterol / fluticasone inhalation alone in stable COPD patients of group D.
Objective To observe the effects of salmeterol / fluticasone combined with tiotropium in the treatment of sever to very sever COPD. Methods Eighty patients with severe to very severe stable COPD were recruited from outpatient of Central Hospital of Cangzhou between May 2008 and October 2009. The subjects were randomly divided into a salmeterol /fluticasone group and a combination group. The salmeterol / fluticasone group received salmeterol / fluticasone propionate, and the combination group received the combination therapy of tiotropium and salmeterol / fluticasone propionate. All patients had received the treatment for 12 months. At baseline and at the end of 1-month, 3-month, 6-month, 12-month, lung function ( FEV1 , IC and FVC) , six-minute walk distance and the St. George’s Respiratory Questionnaire ( SGRQ) score were assessed. The number of exacerbations and the time to the first exacerbation were also recorded. Results At every visit, lung function ( FEV1 , IC and FVC) , six-minute walk distance and the SGRQ score were improved in both groups compared with baseline ( Plt;0. 05) , especially in the combination group ( Plt;0.05) . Compared with the salmeterol /fluticason, the combination therapy with tiotropium significantly decreased the incidence of exacerbations and prolonged the time to the first exacerbation ( Plt;0.05) . And there was no significant difference between two groups in adverse effects ( Pgt;0.05) . Conclusions The combination therapy with salmeterol / fluticasone propionate and tiotropium was superior to salmeterol / fluticasone propionate in treatment of sever to very severe stable COPD patients in improving lung function, exercise tolerance, and quality of life, without additional adverse effects.
Objective To investigate whether long term bronchodilator tiotropium has an acute bronchodilator effect on COPD patients. Methods 46 patients with stable COPD were enrolled in the study.Lung function test was performed before and at 10 min, 20 min, 1 h after inhaling tiotropium. FEV1 , FVC,FEV1/FVC, PEF25% -75% were measured by ambulatory spirometer. The patients were followed up after 1 month.Results The mean FEV1 was ( 1. 110 ±0. 34) L before inhaling tiotropiumand ( 1. 172 ±0. 359) L, ( 1. 221 ±0. 391) L, ( 1. 225 ±0. 392) L at 10 min,20 min, 1 h after inhaling tiotropium, respectively. FEV1 at 1 h after inhaling tiotropiumsignificantly increased compared with that before inhaling tiotropium. FVC also increased and reached highest at 1 h after inhaling tiotropium. PEF25%-75% at 1 h after inhaling tiotropium increased, but there was no significance difference compared with that before inhaling tiotropium. Mean FEV1 was 1. 287 Lafter 1 month, with significant difference compared with baseline. Conclusion Tiotropium can release the symptoms and improve compliance of COPD patients for its acute bronchodilator effect on COPD patients.
ObjectiveTo investigate the changes of interleukin-8 (IL-8), tumor necrosis factor-α(TNF-α) and phospholipase A2 (PLA2) in serum, bronchoalveolar lavage fluid (BALF) and lung tissue of COPD rats and the effects of tiotropium.To identify the anti-inflammatory function of tiotropium. MethodsRat COPD model was established by passive smoking as well as intratracheal instillation of lipopolysaccharide(LPS).Thirty male SD rats were randomly divided into a control group, a COPD group and a tiotropium bromide treatment group (n=10 in each group).The pathologic changes of the lung tissue and airway were observed by HE staining.The total and differential cell counts in BALF were observed.The levels of IL-8, TNF-α, PLA2 in serum, BALF and lung tissue were measured by enzyme-linked immunosorbent assay. ResultsHE staining revealed that the rat COPD model was successfully established.The COPD group appeared obvious emphysema, while the treatment group appeared mild emphysema.The total inflammatory cells, the proportion of neutrophils and lymphocyte, and the levels of IL-8, TNF-α, PLA2 in serum, BALF and lung tissue in the COPD group were obviously higher than those in the control group (P < 0.01).The total inflammatory cells, the proportion of neutrophils and lymphocyte, and the levels of IL-8, TNF-α, PLA2 in serum, BALF and lung tissue in the treatment group were significantly lower than those in the COPD group but higher than those in the control group (P < 0.01). ConclusionsTiotropium bromide can reduce the levels of IL-8, TNF-α, PLA2 in serum, BALF and lung tissue of COPD rats by reducing the leakage of inflammatory cells, and alleviate the airway inflammation and the degree of emphysema.
Objective To systematically evaluate the efficacy and safety of tiotropium plus budesonide/formoterol compared with tiotropium in Chinese patients with chronic obstructive pulmonary disease (COPD). Methods PubMed (from 1980 to March, 2015), Wiley Online Library (from 1990 to March, 2015), Elsevier (from 1990 to March, 2015), CNKI(from 1990 to March, 2015), VIP(from 1990 to March, 2015) and WanFang Data(from 1990 to March, 2015) were searched for randomized controlled trials (RCTs) of tiotropium plus budesonide/formoterol compared with tiotropium in treating Chinese patients with COPD from the establishment of the database to March 2015. The quality of included studies was assessed according to Cochrane Methods 5.1 for Systematic Review, and Meta-analysis was conducted by RevMan 5.3 software. Results Atotal of 9 studies involving 503 patients were included. Compared with the tiotropium therapy group, tiotropium plus budesonide/formoterol in treating Chinese patients with COPD can more significantly improve FEV1 (MD=0.10, 95%CI 0.05 to 0.15, P<0.000 01), FEV1%pred (MD=4.27, 95%CI 2.44 to 6.09, P<0.000 01), FEV1/FVC (MD=3.48, 95%CI 3.21 to 3.74, P<0.000 01), mMRC (MD=-0.27, 95%CI -0.38 to -0.17, P<0.000 01), CAT (MD=-0.91, 95%CI -1.74 to -0.08, P=0.03), 6MWT (MD=27.64, 95%CI 11.76 to 37.53, P<0.000 01) and the frequency of repeated exacerbations (OR=0.25, 95%CI 0.08 to 0.76, P=0.01) while no significant difference was found between two groups in SGRQ (MD=-5.11, 95%CI -11.57 to 1.36, P=0.12). There was no significant differences in adverse reaction rates (OR=1.33, 95%CI 0.65 to 2.73, P=0.44) between the tiotropium plus budesonide/formoterol group and the control group. Conclusions Tiotropium plus budesonide/formoterol is effective in treating Chinese patients with COPD. It can effectively improve treatment efficiency and does not increase the incidence of adverse drug reactions. However, due to the limitation of both quantity and quality of included studies, this conclusion should be further confirmed by more high quality and large sample studies.
ObjectiveTo systematically evaluate the efficacy and safety of budesonide/formoterol combined with tiotropium versus budesonide/formoterol alone for Chinese patients with COPD. MethodsWe electronically searched databases including PubMed, EMbase, The Cochrane Library (Issue 3, 2015), CNKI, VIP and WanFang Data to collect randomized controlled trials (RCTs) about budesonide/formoterol combined with tiotropium vs. budesonide/formoterol alone for Chinese COPD patients from inception to March 2015. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was conducted by RevMan 5.3 software. ResultsA total of 15 studies involving 1123 Chinese patients were included. The results of meta-analysis showed that, compared with the budesonide/formoterol alone group, the budesonide/formoterol plus tiotropium group could significantly improve the levels of FEV1 (MD=0.19, 95%CI 0.12 to 0.25, P<0.00001), FVC (MD=0.35, 95%CI 0.14 to 0.57, P=0.001), FEV1% (MD=5.96, 95%CI 4.48 to 7.43, P<0.00001), FEV1% pred (MD=6.82, 95%CI 2.21 to 11.43, P=0.004), FEV1/FVC (MD=7.72, 95%CI 5.69 to 9.75, P<0.00001), mMRC (MD=-0.43, 95%CI -0.52 to -0.33, P<0.00001), CAT (MD=-1.45, 95%CI -2.26 to -0.64, P=0.0005), SGRQ (MD=-7.05, 95%CI -9.16 to -4.94, P<0.00001) and 6MWT (MD=32.52, 95%CI 16.68 to 48.37, P<0.00001). While there was no significant difference in adverse reaction rates between the two groups (OR=1.77, 95%CI 0.79 to 3.98, P=0.16). ConclusionCurrent evidence shows that budesonide/formoterol plus tiotropium can improve lung function and clinical symptom in Chinese patients with COPD. Due to the limited quality and quantity of included studies, more high quality studies are needed to verify the above conclusion.
ObjectiveTo systematically review the efficacy and safety of indacaterol compared with tiotropium in the treatment of chronic obstructive pulmonary disease (COPD).MethodsWe electronically searched databases including PubMed, EMbase, The Cochrane Library, CNKI, VIP and WanFang Data to collect randomized controlled trials (RCTs) about indacaterol versus tiotropium for COPD patients from inception to November 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.1 software.ResultsA total of 10 RCTs involving 10 415 patients were included, 5 686 patients were in tiotropium group and 4 729 patients in tiotropium group. The results of meta-analysis showed that there was no significant difference between both groups for improving trough forced expiratory volume in one second pulmonary function (FEV1) (MD=0.00, 95%CI –0.03 to 0.03, P=0.79). In the subgroup analysis, it was found that indacaterol had a significant advantage over tiotropium in improving FEV1 over the first 2 weeks (MD=–0.05, 95%CI –0.10 to 0.00, P=0.03). As to the transition dyspnoea index, indoruterol was superior to tiotropium (RR=1.09, 95%CI 1.05 to 1.14, P<0.000 1). Although there was no significant difference of two groups in the St George's respiratory questionnaire score (SGRQ) (MD=–0.48, 95%CI –1.42 to 0.47, P=0.32), indoruterol could significantly improve it among patients whose SGRQ score was greater than or equal 4 than tiotropium (RR=1.13, 95%CI 1.05 to 1.22, P=0.002). Indoruterol had lower overall incidence of adverse reactions (RR=1.05, 95%CI 1.01 to 1.09, P=0.01) , but there was no significant difference between two groups in severe adverse events (RR=1.02, 95%CI 0.89 to 1.16, P=0.81).ConclusionIndacaterol and tiotropium are similar in improving lung function in COPD patients, however, the indacaterol is better than tiotropium in TDI and SGRQ. There is no significant difference for the serious adverse reactions in two groups. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
Objective To systematically evaluate the efficacy and safety of salmeterol/fluticasone combined with tiotropium versus salmeterol/fluticasone alone for Chinese patients with chronic obstructive pulmonary disease (COPD). Methods The databases including PubMed, EMbase, The Cochrane Library (Issue 4, 2017), CNKI, VIP and WanFang Data were electronically searched to collect randomized controlled trials (RCTs) about salmeterol/fluticasone combined with tiotropium vs. salmeterol/fluticasone alone for Chinese COPD patients from inception to April 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was conducted by RevMan 5.3 software. Results A total of 30 RCTs involving 3 121 Chinese patients were included. The results of meta-analysis showed that, compared with the salmeterol/fluticasone alone group, the salmeterol/fluticasone plus tiotropium group could significantly improve the levels of FEV1[MD=0.30, 95%CI(0.22, 0.39), P<0.000 01], FVC [MD=0.31, 95%CI (0.23, 0.40), P<0.000 01] and FEV1/FVC [MD=9.07, 95%CI (6.69, 11.44), P<0.000 01]. While there was no significant difference in adverse reaction rates between the two groups [OR=1.17, 95%CI (0.83, 1.66), P=0.37]. Conclusions Current evidence shows that salmeterol/fluticasone plus tiotropium can improve lung function in Chinese patients with COPD. Due to the limited quality and quantity of included studies, more high quality studies are needed to verify the above conclusion.
Objective To investigate the effect of inhaled anticholinergics on heart rate recovery (HRR) in patients with stable chronic obstructive pulmonary disease (COPD). Methods Sixty clinically stable patients with stage Ⅱ-Ⅳ COPD according to the Global Initiative for Chronic Obstructive Lung Disease guidelines were recruited. HRR was analyzed in this study between 28 patients who had received tiotropium≥1 year and 32 patients who never used anticholinergics as control, so as to reflect parasympathetic reactivity of the heart. Results HRR was significantly lower in the subjects with tiotropium than that in the controls [(16±6) beats/min vs. (22±8) beats/min, P<0.05]. Multivariate regression analysis revealed that anticholinergics medication could be used as an independent predictor of HRR in the COPD patients. Conclusion Anticholinergics can affect cardiac autonomic function of stable COPD patients.