The efficacy of bisoprolol fumarate tablets combined with tiotropium bromide powder aerosol inhalation in the treatment of patients with chronic obstructive pulmonary disease complicated with pulmonary heart disease at the acute exacerbation stage / 中国医师杂志

Objective:To study the efficacy of bisoprolol fumarate tablets combined with tiotropium bromide powder aerosol inhalation in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with pulmonary heart disease and its effect on high-sensitivity C-reactive protein (hs-CRP) and brain natriuretic peptide (BNP).Methods:From June 2016 to October 2021, 96 patients with AECOPD complicated with pulmonary heart disease admitted to the Affiliated Hospital of Jining Medical University were randomly divided into a control group and an observation group with 48 patients in each group. The patients in both groups were treated with oxygen inhalation, expectorant, cough relieving, asthma relieving and empirical antibiotics. The control group was treated with atomized inhalation of tiotropium bromide powder, and the observation group was treated with bisoprolol fumarate tablets on the basis of the control group. The left ventricular ejection fraction (LVEF), 6-minute walking distance (6MWD), 1 s forced expiratory volume (FEV 1), forced vital capacity (FVC), serum hs-CRP, BNP and other factors were compared between the two groups after treatment, and the total effective rate and adverse drug reaction of the two groups were counted. Results:After treatment, the total effective rates of the observation group and the control group were 91.67%(44/48) and 77.08%(37/48), respectively, with a statistically significant difference ( P<0.05). After treatment, the LVEF of the observation group and the control group were (43.15±6.04)% and (38.96±5.67)% respectively, the 6MWD was (294.86±30.11)m and (261.35±25.88)m, the FEV 1 was (2.36±0.69)L and (1.75±0.52)L, the FVC was (3.58±0.51)L and (2.96±0.45)L, the hs-CRP was (4.47±1.25)mg/L and (7.86±2.01)mg/L, and the BNP was (418.25±32.25)ng/ml and (496.52±43.21)ng/ml; ESR was (16.78±2.11)mm/h and (21.02±1.69)mm/h, ET-1 was (54.26±6.45)ng/ml and (73.21±8.24)ng/ml, and Interleukin 6 was (22.63±8.45)ng/L and (31.85±12.24)ng/L, respectively, with statistical significance ( P<0.05). The total incidence of adverse drug reaction in the observation group and the control group was 8.33%(4/48) and 4.17%(2/48), respectively, with no statistically significant difference ( P>0.05). Conclusions:Bisoprolol fumarate tablets combined with tiotropium bromide powder aerosol inhalation in the treatment of AECOPD complicated with cor pulmonale can improve the heart and lung function of patients, regulate the expression level of hs-CRP, BNP and other factors, improve the efficacy, and do not increase adverse reactions.

Effects of acupoint application therapy with Chinese medicine combined with tiotropium bromide inhalation on quality of life in patients with stable chronic obstructive pulmonary disease / 中国基层医药

Objective:To investigate the effects of acupoint application therapy with Chinese medicine combined with tiotropium bromide inhalation on quality of life in patients with stable chronic obstructive pulmonary disease (COPD).Methods:A total of 109 patients with stable COPD admitted to People's Hospital of Gaomi from March 2019 to May 2020 were included in this study. They were randomly divided into a control group ( n = 54) and an observation group ( n = 55). Both groups were given tiotropium bromide powder inhalation and acupoint application therapy ( Dazhui, Shenque, Feishu, Pishu, Shenshu and Zusanli). Chinese medicine ointment was applied in the observation group, but not in the control group. All patients were treated for 6 consecutive months. Before and after treatment, pulmonary function indicators [forced expiratory volume in the first second (FEV 1), the percentage of expiratory volume in the first second (FEV 1%), forced vital capacity (FVC), FEV 1/FVC], modified Medical Research Council (mMRC) dyspnea scale score, and the Saint George's Respiratory Questionnaire (SGRQ) score were compared between the two groups before and after treatment to evaluate therapeutic efficacy and quality of life. Results:Before and after treatment, there were no significant differences in FEV 1, FEV 1% and FEV 1/FVC between the two groups (all P > 0.05). After treatment, mMRC score and SGRQ total score in the observation group were (1.91 ± 0.27) points and (38.54 ± 8.18) points, respectively, which were significantly lower than (2.43 ± 0.33) points and (43.12 ± 7.86) points in the control group ( t = 4.93, 4.47, both P < 0.05). The number of exacerbations and the number of hospitalizations were (0.42 ± 0.09) times/6 months and (0.27 ± 0.05) times/6 months in the observation group and they were (0.69 ± 0.17) times/6 months and (0.47 ± 0.13) times/6 months in the control group. There were significant differences in these indices between the two groups ( t = 3.90, 3.85, P < 0.05). Conclusion:Acupoint application therapy with Chinese medicine combined with tiotropium bromide inhalation has a good therapeutic effect on stable COPD. The combined therapy can reduce the number of acute attacks and improve patient's quality of life. This study is scientific and innovative.

Lung Function and Health Status in Patients of Chronic Obstructive Pulmonary Disease on Treatment with Tiotropium

Introduction: Chronic obstructive pulmonary disease (COPD) is a group of chronic and slowly progressive respiratory disordercharacterized by reduced maximum expiratory flow during forced exhalation. Tiotropium, a long-acting antimuscarinic agent,has well-known documented effect on improving lung function and quality of life (QOL). There are many studies globally ontiotropium and its effect on lung function, but limited studies available in our Indian set up. Hence, we planned this study.Materials and Methods: Patients were recruited from chest clinic and outpatient department from the Department of Medicineof University College of Medical Sciences and GTB Hospital. It was a prospective observational cohort study conducted fromNovember 2017 to April 2019. Tiotropium was given as meter dose inhaler in dose of 18 µg per dose, in schedule as prescribedby the Global Initiative for Chronic Obstructive Lung Disease-2017 guidelines. Patients were followed up for 3 months withperiodic assessment of lung functions, Saint George’s Respiratory Questionnaire (SGRQ) score, and symptoms assessment.Results: A total of 65 patients were recruited for study which included 57 (87.7%) males and 8 (12.3%) females. Among thepulmonary function tests measured, there is a significant change in mean forced expiratory volume (FEV1) at the end of followup period compared to FEV1 at baseline. There is a significant change in mean forced vital capacity at the end of follow-upstudy compared to start of the study. There was no significant change in mean SGRQ score after 1 month of start of drug,but significant statistical change observed at end of the 3rd month of the study compared to the 1st month that implies SGRQscore decreased and patients health status and QOL improved. There is a significant change in mean SGRQ score at the endof follow-up study compared to baseline. In our study, 16 patients (24.6%) complained of dry mouth, 7 (10.7%) complained ofpharyngitis or throat irritation, and 3 (4.6%) patients complained of constipation.Conclusion: There was a statistically significant change in lung functions and improvement in QOL scores as assessed bySGRQ at the end of the study compared to baseline by use of inhaled tiotropium in COPD patients

Legal demands of the tiotropium bromide for treatment of chronic obstructive pulmonary disease and their financial impact for the State of Paraná, Brazil / Demandas judiciais do uso de brometo tiotrópio para o tratamento da doença pulmonar obstrutiva crônica e o impacto financeiro para o Estado do Paraná, Brasil

ABSTRACT Objective To analyze the legal demands of tiotropium bromide to treat chronic obstructive pulmonary disease. Methods We included secondary data from the pharmaceutical care management systems made available by the Paraná State Drug Center. Results Public interest civil action and ordinary procedures, among others, were the most common used by the patients to obtain the medicine. Two Health Centers in Paraná (Londrina and Umuarama) concentrated more than 50% of the actions. The most common specialty of physicians who prescribed (33.8%) was pulmonology. There is a small financial impact of tiotropium bromide on general costs with medicines of the Paraná State Drug Center. However, a significant individual financial impact was observed because one unit of the medicine represents 38% of the Brazilian minimum wage. Conclusion Our study highlights the need of incorporating this medicine in the class of long-acting anticholinergic bronchodilator in the Brazilian public health system.

RESUMO Objetivo Analisar as demandas judiciais do brometo de tiotrópio para tratar a doença pulmonar obstrutiva crônica. Métodos Foram considerados dados secundários dos sistemas gerenciais de assistência farmacêutica, disponibilizados pelo Centro de Medicamentos do Paraná. Resultados Ações civis públicas e ações ordinárias, de procedimento comum, entre outras, foram as mais praticadas pelos pacientes para obter o medicamento. Duas Regionais de Saúde do Paraná (Londrina e Umuarama) concentraram mais de 50% das ações. Quanto à especialidade dos médicos prescritores, 33,8% eram pneumologistas. Verificou-se discreto impacto financeiro do brometo de tiotrópio nos gastos gerais com medicamentos pelo Centro de Medicamentos do Paraná. Entretanto, também houve relevante impacto financeiro individual, pois uma unidade do medicamento consome 38% do salário mínimo. Conclusão O estudo aponta para a necessidade de incorporação deste medicamento da classe broncodilatadores anticolinérgicos de longa duração, no Sistema Único de Saúde.

Meta-analysis of the Effectiveness of Inhaled Corticosteroids Combined with Tiotropium Bromide versus Inhaled Corticosteroids Alone in the Treatment of Asthmatic-COPD Overlap Syndrome / 中国药房

OBJECTIVE：To systematically e valuate the effectiveness of inhaled corticosteroids combined with tiotropium bromide versus inhaled corticosteroids alone in the treatment of asthmatic-COPD overlap syndrome ，and to provide evidence-based reference for clinical use. METHODS ：Retrieved from PubMed ，Web of Science ，Embase，Cochrane Library ，CBM，CNKI， VIP，Wanfang database ，during the establishment of the database to Nov. 2019，randomized controlled trials （RCT）about inhaled corticosteroids combined with tiotropium bromide （trial group ）versus inhaled corticosteroids alone （control group ）in the treatment of asthmatic-COPD overlap syndrome were collected. After data extraction of included literatures met inclusion criteria ，quality evaluation with modified Jadad scale ，Meta-analysis was performed for response rate ，forced expiratory volume in the first second （FEV1），forced vital capacity （FVC），FEV1/FVC，inspiratory fraction （IC/TLC），residual to total ratio （RV/TLC），asthma symptom（ACT）score，chronic obstructive pulmonary symptom （CAT）score，the times of acute exacerbations by Rev Man 5.3.0 software. RESULTS ：A total of 25 RCTs were included ，involving 2 828 patients. The results of Meta-analysis showed that the response rate [RR ＝1.16，95％CI（1.10，1.22），P＜0.001]，FEV1[MD＝0.44，95％CI（0.35，0.54），P＜0.001]，FVC [MD ＝0.70， 95％CI（0.46，0.95），P＜0.001]，FEV1/FVC [MD= 8.79，95％CI（6.22，11.37），P＜0.001]，IC/TLC [MD ＝4.93，95％CI（3.01， 6.85），P＜0.001]，RV/TLC [MD ＝－9.22，95％CI（－9.79，－8.66），P＜0.001]，ACT score [MD ＝5.38，95％CI（4.30，6.47）， P＜0.001]，CAT score [MD ＝－3.67，95％CI（－4.89，－2.45），P＜0.001] and the times of acute exacerbations [MD ＝－1.49， 95％CI（－2.82，－0.17），P＝0.03] in trial group were significantly higher than control group ，with statistical significance. CONCLUSIONS：Compared with inhaled corticosteroids alone ，inhaled hormone combined with tiotropium bromide can improve the response rate and pulmonary function ，but increase the times of acute exacerbation of patients with asthmatic-COPD overlap syndrome.

A comparative study on efficacy and safety of glycopyrronium bromide + salmeterol/fluticasone and tiotropium bromide + salmeterol/fluticasone in hronic obstructive pulmonary disease

Objective: To compare the effect of tiotropium bromide and glycopyrronium bromide in the treatment of chronic obstructive pulmonary disease. Methods: This was an open labeled Randomized controlled trial study. Patients diagnosed with COPD according to the Global Initiative for chronic Obstructive Lung Disease (GOLD) strategy were included in the study. The patients were divided in two groups and each group had 100 patients. Group A- COPD patients on Tiotropium bromide + Salmeterol/Fluticasone; Group B – COPD patient on Glycopyrronium bromide + Salmeterol/Fluticasone. Tiotropium bromide: 18 mcg OD, Glycopyrronium bromide: 50 mcg OD along with Salmeterol 50 mcg/Fluticasone 100mcg was given. Results: The mean age of patients of Group A and Group B was 56.28±7.78 and 57.64±8.06 years respectively. Baseline variables were comparable between the groups. There was significant (p<0.05) difference in PFT parameters between the groups at 12 and 24 weeks except for FEV1/FVC. The mean change was higher in Group B compared to Group A from 0 week to 24 weeks. There was clinical improvement among all the patients in both the groups. Conclusion: Once-daily GLY demonstrated similar effects to TIO when combined with SAL/FP in patients with moderate and severe COPD.

Add-on Tiotropium in Chinese Patients With Moderate Asthma: A Pooled Subgroup Analysis of MezzoTinA-Asthma 1 and 2

PURPOSE: Asthma affects approximately 30 million patients in China; however, tiotropium data for Chinese patients is limited. This study aimed to assess the efficacy and safety of tiotropium in Chinese patients with moderate symptomatic asthma. METHODS: A post hoc subgroup analysis was conducted on 430 Chinese patients pooled from two 24-week, replicate phase 3 trials (NCT01172808 and NCT01172821), in which they received once-daily tiotropium 2.5 µg (Tio R2.5) or 5 µg (Tio R5) (n = 106 or 109, respectively), twice-daily salmeterol 50 µg (Sal 50) (n = 110), or placebo (n = 105), while maintaining inhaled corticosteroids (ICS). The co-primary endpoints assessed in week 24 were forced expiratory volume in 1 second (FEV1) peak0–3h response, trough FEV1 response, and responder rate as assessed using the Asthma Control Questionnaire (ACQ). RESULTS: For both FEV1 peak0–3h responses and trough FEV1 responses, the mean treatment differences were greater for Tio R2.5, Tio R5, and Sal 50 compared with placebo at 0.249 L, 0.234 L, and 0.284 L, and 0.172 L, 0.180 L, and 0.164 L, respectively (P< 0.001). The ACQ responder rate in placebo, Tio R2.5, Tio R5, and Sal 50 was 58.7%, 62.3%, 59.3%, and 69.1%, respectively. Furthermore, 11 (2.6%) of 430 patients had serious adverse events (Tio R5, n = 4; Tio R2.5, n = 1; Sal 50, n = 1; and placebo, n = 5). CONCLUSIONS: Once-daily tiotropium, as add-on to medium-dose ICS, was effective and well tolerated for Chinese patients with moderate symptomatic asthma, consistent with the main analysis.

Expression of Muscarinic Receptors and the Effect of Tiotropium Bromide in Aged Mouse Model of Chronic Asthma / 결핵및호흡기질환

BACKGROUND: Efficacy and safety of tiotropium bromide, a muscarinic receptor antagonist, in treatment of asthma have been reported. However, its effect on airway remodeling in chronic asthma of the elderly has not been clearly verified. The objective of this study was to investigate the effect of tiotropium and expression of muscarinic receptors as its related mechanism in an aged mouse model of chronic asthma with airway remodeling. METHODS: BALB/c female mice age 6 weeks, 9 and 15 months were sensitized and challenged with ovalbumin (OVA) for three months. Tiotropium bromide was administered during the challenge period. Airway hyperresponsiveness (AHR) and pulmonary inflammation were measured. Parameters of airway remodeling, and expression levels of M2 and M3 receptors were examined. RESULTS: Total cell with eosinophils, increased in the OVA groups by age, was decreased significantly after treatment with tiotropium bromide, particularly in the age group of 15 months. AHR and levels of interleukin (IL)-4, IL-5, and IL-13 were decreased, after tiotropium administration. In old aged group of 9- and 15-months-treated groups, hydroxyproline contents and levels of α-smooth muscle actin were attenuated. Tiotropium enhanced the expression of M2 but decreased expression of M3 in all aged groups of OVA. CONCLUSION: Tiotropium bromide had anti-inflammatory and anti-remodeling effects in an aged mouse model of chronic asthma. Its effects seemed to be partly mediated by modulating expression M3 and M2 muscarinic receptors. Tiotropium may be a beneficial treatment option for the elderly with airway remodeling of chronic asthma.

Analysis of the efficacy of tiotropium bromide combined with BiPAP in treatment of patients with AECOPD / 中国基层医药

Objective@#To analyze the efficacy of tiotropium bromide combined with bi level positive airway pressure ventilation(BiPAP) in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD).@*Methods@#From 2014 to 2016, 60 patients with AECOPD in Tongde Hospital were selected in the research, and were randomly divided into the control group and observation group according to the digital table, with 30 cases in each group.The control group was given BiPAP treatment on the basis of conventional treatment, and the observation group was given tiotropium bromide combined with BiPAP treatment.The therapeutic effects, pulmonary function, arterial blood gas analysis, serum inflammatory factors and quality of life were compared between the two groups after 12 weeks of continuous treatment.@*Results@#After treatment, the total effective rate of the control group was 76.67%, which of the observation group was 96.67%, the difference between the two groups was statistically significant(χ2=5.192, P<0.05). Before treatment, one second forced expiratory volume(FEV1), forced expiratory volume in one second/forced vital capacity(FEV1/FVC), one second forced expiratory volume percentage(FEV1%) between the two groups showed no statistically significant differences(all P>0.05). After treatment, the FEV1, FEV1/FVC and FEV1% in the observation group were (2.73±0.63)L, (77.53±10.68)%, (73.85±11.21)%, respectively, which were higher than those in the control group [(2.02±0.57)L, (68.57±11.25)%, (64.38±12.74)%], the differences between the two groups were statistically significant(t=4.577, 3.163, 3.056, all P<0.05). Before treatment, the oxygen partial pressure(PaO2), partial pressure of carbon dioxide(PaCO2) between the two groups showed no statistically significant differences(all P>0.05). After treatment, the PaO2 of the observation group [(80.48±15.64)mmHg] was higher than that of the control group[(66.05±12.05)mmHg], the PaCO2 of the observation group [(53.11±8.38) mmHg] was lower than that of the control group [(60.33±9.95)mmHg], the differences between the two groups were statistically significant(t=4.003, 3.039, all P<0.05). Before treatment, the serum interleukin 6(IL-6), tumor necrosis factorα(TNF-α), high sensitive C reactive protein(hs-CRP) levels between the two groups showed no significant differences(all P>0.05). After treatment, the levels of serum IL-6, TNF-alpha and hs-CRP in the observation group were (85.83±27.35)ng/L, (85.35±29.15)ng/L, (2.25±0.64)mg/L, respectively, which were lower than those in the control group [(102.57±32.65)ng/L, (101.45±32.14)ng/L, (2.88±0.78)mg/L], there were significant differences between two groups(t=2.152, 2.032, 3.420, all P<0.05). Before treatment, the quality of life questionnaire(SF-36) score between the two groups had no statistically significant difference(P>0.05). After treatment, the SF-36 score of the observation group[(92.48±8.64)points]was higher than the control group[(79.22±17.04)points], there was statistically significant difference between the two groups(t=3.095, P<0.05).@*Conclusion@#Tiotropium bromide combined with BiPAP has better curative effect in the treatment of AECOPD, it can help to improve the patients' lung function and blood gas index, regulate the body's inflammatory state, so that patients get better quality of life, it is worthy of clinical application.

The comparisons of the efficacy of two fixed dose combinations, i.e. Salmeterol and Fluticasone vs. Formoterol and Tiotropium bromide in moderate to severe COPD patients

Background: Bronchodilators are essential for symptomatic management of all stages of chronic obstructive pulmonary disease (COPD). For patients whose COPD is not sufficiently controlled by monotherapy, combining a ß2-agonist with either inhaled steroid or anticholinergic drug is a convenient way of delivering treatment. Currently, there is no documentation to say that one drug is superior to other or the contrary, but a combination of two drugs is more effective than giving single drug alone in patients suffering from COPD.Methods: The study was prospective, open labelled, randomized, comparative interventional clinical study conducted by the Departments of Pharmacology and Medicine, Basaveshwara Medical College and Hospital, Chitradurga in 60 moderates to severe COPD patients.Results: Both the treatments i.e. Salmeterol/Fluticasone and Tiotropium/Formoterol were equally effective as far as the improvement of the lung functions and Borg dyspnoea score are concerned. The difference in improvement with the combination of Salmeterol/Fluticasone was not statistically significant (p>0.05) compared to the combination of Tiotropium/Formoterol. However, Salmeterol/Fluticasone was found to be better than Tiotropium/Formoterol in improving the lung function of moderate to severe COPD patients.Conclusions: Salmeterol/Fluticasone is efficacious and better than Tiotropium /Formoterol combination for maintenance therapy in moderate to severe COPD patients.

Índice de hospitalização e custos associados à doença pulmonar obstrutiva crônica (DPOC) entre estados que padronizaram versus que não padronizaram o tiotrópio ­ dados do mundo real / Hospitalization rates and costs associated with chronic obstructive pulmonary disease among states standardized versus not standardized tiotropium ­ real-world data

Objetivo: Avaliar, por meio de dados do mundo real (DATASUS) e análises estatísticas, o impacto da inclusão do tiotrópio no tratamento da doença pulmonar obstrutiva crônica (DPOC), comparando o índice de hospitalização e custos associados à internação nos estados que possuem o tiotrópio padronizado em suas diretrizes de tratamento comparados aos estados que não o incluem. Método: Estudo retrospectivo histórico realizado entre 2013 e 2015, a partir de dados obtidos do DATASUS, portais de compras públicas estaduais e Secretarias de Saúde Estaduais. Todos os índices foram normalizados pelo número da população, de acordo com os dados atualizados do IBGE. Foi utilizado o teste Z para avaliar a significância estatística dos resultados. Resultados: A análise combinada do grupo com tiotrópio apresentou 52,4% menos hospitalizações em comparação ao grupo sem tiotrópio (90,0/100.000 versus 43,3/100.000, respectivamente, p < 0,01). O gasto total para o sistema único de saúde com hospitalização por DPOC foi de R$ 2,3 milhões e R$ 4,8 milhões para o grupo com tiotrópio vs. grupo sem tiotrópio, respectivamente (p = 0,0003). Houve diferença significativa entre os grupos quanto ao número total e gastos totais de internação por DPOC, nos estados nos quais o tiotrópio estava padronizado e nos estados sem o tiotrópio padronizado. Conclusão: A análise dos resultados sugere redução significativa no número de internações por DPOC e seus respectivos gastos nos estados nos quais o tiotrópio está padronizado.

Objective: To evaluate the impact of the inclusion of tiotropium in the treatment of chronic obstructive pulmonary disease (COPD) using real world data (DATASUS) and statistical analyzes, comparing hospitalization rates and costs associated with hospitalization in states where tiotropium is reimbursed in their treatment guidelines compared to states where tiotropium is not included. Method: A retrospective historical study conducted between 2013 and 2015, based on data obtained from DATASUS, state public purchasing portals and State Health Secretariats. All indexes were normalized by the number of the population, according to the IBGE updated data. The Z tests were used to evaluate the statistical significance of the results. Results: The combined analysis of the tiotropium reimbursed group presented 52.4% fewer hospitalizations compared to the tiotropium non-reimbursed group (90.0/100,000 versus 43.3/100,000, respectively). The total expenditure for the public healthcare system with hospitalization for COPD was R$ 2.3 million and R$ 4.8 million for the tiotropium group vs. the non-tiotropium group, respectively. Statistical analysis, both in total number and total costs of hospitalization for COPD, showed a statistically significant difference in the states in which tiotropium was reimbursed vs non-reimbursed. Conclusion: Analysis of the results suggests a significant reduction in the number of hospitalizations due to COPD in the states in which tiotropium is reimbursed, as well as a reduction in the total expenditure related to hospitalizations associated with COPD.

The Role of Tiotropium+Olodaterol Dual Bronchodilator Therapy in the Management of Chronic Obstructive Pulmonary Disease / 결핵

Bronchodilator therapy is central to the management of chronic obstructive pulmonary disease and are recommended as the preferred treatment by the Global Obstructive Lung Disease Initiative (GOLD). Long acting anti-muscarinics (LAMA) and long acting β₂ agonists (LABA) are both more effective than regular short-acting drugs but many patients remain symptomatic despite monotherapy with these drugs. Combination therapy with LAMA and LABA increases the therapeutic benefit while minimizing dose-dependent side effects of long-acting bronchodilator therapy. The TOviTO programme has investigated the benefits of treatment with a combination of tiotropium and olodaterol administered via a single inhaler. Tiotropium+olodaterol 5/5 µg significantly improved forced expiratory volume in 1 second (FEV₁) area under the curve from 0 to 3 hours, trough FEV₁ health status and breathlessness versus the mono-components and placebo. Tiotropium+olodaterol 5/5 µg also increased endurance time and reduced dynamic hyperinflation during constant work rate cycle ergometry. On the basis of these and other studies the 2017 GOLD report recommends escalating to dual bronchodilator therapy in patients in groups B and C if they remain symptomatic or continue to have exacerbations and as initial therapy for patients in group D.

The effect of tiotropium bromide powder on the sleep quality and lung function in patients with moderate and severe chronic obstructive pulmonary disease in stable period / 中国医师进修杂志

Objective To explore the influence of tiotropium bromide powder inhalant or budesonide powder inhalant on sleep quality and lung function in patients with moderate and severe chronic obstructive pulmonary disease (COPD) in stable period. Methods Sixty-three patients with moderate and severe COPD in stable period were divided into 2 groups by random sortition method:tiotropium bromide group(31 cases,the patients inhaled tiotropium bromide powder inhalant 5 μg/time, 1 time/12 h) and budesonide group (32 cases, the patients inhaled budesonide powder inhalant 200 μg/time, 1 time/12 h). All patients were treated for 3 months. The lung function monitoring and polysomnography were detected before and after treatment. Results Seven patients withdrawn: 3 patients were in tiotropium bromide group,and 4 patients were in budesonide group.The forced expired volume in 1 second(FEV1),forced vital capacity(FVC),FEV1/FVC,peak expiratory flow(PEF)and forced expiratory flow from 25% to 75% (MMEF) after treatment in 2 group were significantly improved compared with those before treatment, and there were statistical differences (P<0.05). The FEV1, FVC and FEV1/FVC levels after treatment in tiotropium bromide group were significantly higher than those in budesonide group: (2.29 ± 0.43) L vs. (2.01 ± 0.42) L, (4.19 ± 0.26) L vs. (3.93 ± 0.23) L and (52.03 ± 10.45) % vs. (49.73 ± 10.21) %, and there were statistical differences (P<0.05). The percentages of S1 phase,S2 phase,rapid eye movement(REM)phase and activity apnea-hypopnea index (AHI)after treatment in 2 groups were significantly improved compared with those before treatment,and the indexes in tiotropium bromide group were significantly better than those in budesonide group:(29.99 ± 8.43)% vs. (26.91 ± 11.66)%, (48.99 ± 10.26)% vs. (45.45 ± 10.13)%, (14.83 ± 8.36)% vs. (13.33 ± 7.44)% and (8.70 ± 5.11) times/h vs. (11.72 ± 10.09) times/h, and there were statistical differences(P<0.05).Conclusions Tiotropium bromide has better effect in promoting the lung function and sleep quality compared with budesonide in patients with moderate and severe COPD in stable period.

The effect of exercise combined with bailing capsules on chronic stationary obstructive pulmonary disease / 中华物理医学与康复杂志

Objective To observe and compare the effect of Cordyceps sinensis ( bailing ) capsules com-bined with weight-bearing breathing exercises, and weight-bearing breathing exercises combined with tiotropium bro-mide and seretide, on patients with stable but moderate-to-severe chronic obstructive pulmonary disease (COPD). Methods Sixty-three patients with moderate-to-severe COPD were randomly divided into an observation group and a control group. Both groups performed weight-bearing breathing exercises, supplemented in the observation group with the oral administration of bailing capsules. The control group instead inhaled tiotropium bromide and seretide. Six-mi-nute walking distance, the COPD assessment test ( CAT scores) and concentrations of interleukin-6 ( IL-6) , interleu-kin-8 ( IL-8) and tumor necrosis factor-α ( TNF-α) were observed after 1 ( T1) , 30 ( T2) and 58 ( T3) days of the treatments. Results At T1 there were no significant differences between the two groups in any of the measurements ( P≤0.05) . At T2, there were still no significant differences except that a significant decrease in IL-8 and TNF-αlevels was observed in the control group. At T3 the average CAT scores had decreased significantly in both groups compared to before the treatment but there was no significant difference between the two groups. In the observation group, the average 6MWT distance had increased significantly compared to before the treatment and compared to the control group, where there was no significant improvement. The average IL-6, IL-8 and TNF-αreadings of the control group were significantly lower than those of the observation group at T3 and compared to before the treatment. No sig-nificant changes in those indicators were observed in the observation group at T3. Conclusions Bailing capsules combined with weight-breathing exercises are more effective for relieving dyspnea symptoms and improving exercise capacity than weight-breathing exercises combined with tiotropium bromide and seretide. However, in controlling air-way inflammation and airway hyper-responsiveness, the triple inhalation combined with weight-bearing breathing exer-cises is more effective.

Efficacy and safety of tiotropium bromide in chronic obstructive pulmonary disease: a systematic review of randomized clinical trials / Eficácia e segurança do brometo de tiotrópio na doença pulmonar obstrutiva crônica. Revisão sistemática de ensaios clínicos randomizados

Chronic obstructive pulmonary disease (COPD) is among the most prevalent pulmonary diseases. This study aimed at assessing the efficacy and safety of anticholinergic tiotropium bromide (TB) in Chronic obstructive pulmonary disease patients. This is a systematic review of randomized clinical trials performed in the Brazilian Cochrane Center. Electronic database searched: Cochrane library, Medline, LILACS, Pubmed. There were no language, date or other restrictions. Participants: Patients with Chronic obstructive pulmonary disease. Intervention: tiotropium bromide. Comparison: Other bronchodilators or placebo. Outcomes: Mortality, Chronic obstructive pulmonary disease exacerbation, hospitalizations, adverse effects. Results: 14 studies were included in this systematic review. Mortality was lower in the tiotropium bromide group when compared with the salmeterol group [statistical significance: relative risk (RR) 0.16, confidence interval 95% (CI) 0.03 to 0.89, number needed to treat (NNT) of 100]. There was not a statistical difference in the mortality outcome in the comparison between tiotropium bromide and placebo groups (RR 0.88, CI 0.74 to 1.06). Chronic obstructive pulmonary disease exacerbation decreases significantly in the tiotropium bromide group when compared to placebo (statistical significance: RR 0.85, CI 0.77 to 0.93, NNT 25), but in comparison to the salmeterol group there was no statistical difference (RR 0.93, CI 0.80 to 1.08). The number of hospitalizations was lower in the tiotropium bromide group than in the placebo group (statistical significance:RR 0.77, CI 0.59 to 0.99, NNT 50). The results indicate that tiotropium bromide is an effective once-daily bronchodilator. Tiotropium bromide was associated with consistent health benefits, including reduced chronic obstructive pulmonary disease exacerbations, hospitalizations and even mortality when compared with salmeterol.(AU)

A doença pulmonar obstrutiva crônica está entre as doenças pulmonares mais prevalentes. O objetivo deste estudo foi verificar a eficácia e segurança do brometo de tiotrópio em pacientes com doença pulmonar obstrutiva crônica. Trata-se de revisão sistemática de ensaios clínicos randomizados realizada no Centro Cochrane do Brasil. A estratégia de busca eletrônica foi realizada nos nas bases LILACS, MEDLINE, Biblioteca Cochrane, PubMed. Não houve restrições à linguagem e nem à data. Participaram pacientes com doença pulmonar obstrutiva crônica. A intervenção foi o uso de brometo de tiotrópio comparado a outros broncodilatadores ou placebo. Os desfechos analisados foram mortalidade, exacerbações da doença pulmonar obstrutiva crônica, hospitalização e efeitos adversos. A mortalidade foi menor no grupo brometo de tiotrópio quando comparado com o grupo salmeterol (significância estatística: risco relativo de 0,16; intervalo de confiança de 95% de 0,03-0,89, número necessário para tratar de 100). Não houve diferença estatística no desfecho mortalidade na comparação entre os grupos brometo de tiotrópio e placebo (risco relativo de 0,88; intervalo de confiança de 95% de 0,74-1,06). As exacerbações da doença pulmonar obstrutiva crônica diminuíram significantemente no grupo brometo de tiotrópio quando comparado ao placebo (significância estatística: risco relativo de 0,85; intervalo de confiança de 95% de 0,77-0,93; número necessário para tratar de 25), porém, quando comparado ao salmeterol não obteve significância estatística (risco relativo de 0,93; intervalo de confiança de 95% 0,80-1,08). O número de hospitalizações foi menor no grupo brometo de tiotrópio do que no grupo placebo (significância estatística: risco relativo de 0,77; intervalo de confiança de 95% 0,59-0,99; número necessário para tratar de 50). Os resultados indicam que o brometo de tiotrópio é um broncodilatador eficaz em dose única diária. O brometo de tiotrópio traz benefícios à saúde com resultados consistentes, incluindo redução de exacerbações da doença pulmonar obstrutiva crônica, internações e até mesmo a mortalidade quando comparados com salmeterol.(AU)

Novel dry powder inhalation carrier:drug-carried lactose microparticles with flower shape and nanoporous structure / 药学学报

This work was designed to study a novel dry powder inhalation (DPI) carrier for drug loading and release of tiotropium bromide (asthma medicine). The synthesized lactose drug-carrier with a flower shape was crystalline. The carrier with a micro-meso-macroporous structure had advantages of high pore surface area, high capacity of drug loading and fast release of drug. In the study of loading tiotropium bromide, the drug was distributed at the core of carrier using the solution-based method, while the morphology was changed a little and the amount of loaded drug was 5% (w/w). Using the crystallization-based method, the drug was distributed at the shell of carrier, while the morphology was changed a lot and the amount of loaded drug was 49% (w/w). In addition, with the impact of carrier structure, the drug release rate was increased first and then decreased thereafter using the solution-based method, while the drug release rate was decreased first and then increased thereafter using the crystallization-based method. Thus, the lactose microparticles can be used as a novel drug carrier for dry powder inhalation.

Observation on the effect of tiotropium bromide inhalation combined with psychological intervention on stable period of chronic obstructive pulmonary disease / 中国生化药物杂志

Objective To investigate the clinical effect of Tiotropium Bromide Powder for Inhalation combined with mental intervention in the treatment of chronic obstructive pulmonary disease in stable period. Methods 80 patients with stable chronic obstructive pulmonary disease treated in our hospital from January 2015 to January 2017were divided into two groups according to the different treatment methods.The control group was treated with conventional methods, the observation group was treated with routine + Tiotropium Bromide Powder for Inhalation + psychological intervention therapy.The clinical curative effect and the improvement of clinical symptoms were recorded and analyzed. Results The clinicalcurative effect of the observation group was better than that of the control group, the improvement of clinical symptoms was better than that of the control group,the difference was statistically significant (P<0.05). Conclusion The effect of chronic obstructive pulmonary disease patients choose conventional treatment+Tiotropium Bromide Powder for Inhalation + psychological intervention mode is significant, can improve clinical symptoms, improve the therapeutic effect and prognosis in the near future and far, worthy of clinical widely used In the treatment of patients with chronic obstructive pulmonary disease in stable phase.

Tiotropium bromide combined with salmeterol/fluticasone on the treatment of 122 cases with asthma COPD overlap syndrome / 中国生化药物杂志

Objective To evaluate the clinical efficacy of tiotropium combined with salmeterol/fluticasone on the treatment of the patients with asthma COPD overlap syndrome. Methods 122 patients with asthma COPD overlap syndrome were divided into 2 groups by randomized envelope, the experimental group and the control group. The experimental group were given tiotropium bromide combined with salmeterol/fluticasone. The control group were received compound ipratropium bromide combined with salmeterol/fluticasone. The clinical effect was observed. Results Before treatment, there was no significant difference in lung function between the two groups. After treatment, the improvement of pulmonary function indexes in the experimental group was significantly higher than that in the control group (P<0.05). And the number of acute attack and attack time in the experimental group were also better than those in the control group (P<0.05). Conclusion Tiotropium combined with Shah Mette Lo/fluticasone is effective on the treatment of asthma COPD overlap syndrome, and has some clinical advantages in improving lung function and reducing the frequency of attack.

Tiotropium bromide powder for inhalation combined with psychological intervention on the treatment effect of chronic obstructive pulmonary disease in stable period / 中国生化药物杂志

Objective To study in patients with stable chronic obstructive pulmonary disease treatment, the use of Tiotropium Bromide Powder for Inhalation treatment combined with psychological intervention effect.Methods In 40 cases of patients with stable chronic obstructive pulmonary disease treatment using tiotropium bromide powder for inhalation, and classified as the control group, the other 40 patients in the control group based on the use of psychological intervention combined with treatment the treatment, and classified as the observation group, two groups of patients were in our hospital from January 2016 to January 2017.Results There was no significant difference in anxiety and depression of patients in the two groups before intervention, after the intervention group patients in the observation group improved significantly better;two groups of patients before intervention PaCO2, there was no significant difference in PaO2 index, after group intervention of patients in the observation group improved significantly better;compared two groups of patients with the treatment efficiency, the obvious observation group were higher, there were significant differences (P<0.05).Conclusion Tiotropium Bromide Powder for Inhalation combined psychological intervention treatment of patients with stable chronic pulmonary disease blocking was observed, which can improve the patient's condition, and improve the treatment effect, the patient's mental state adjustment also has a positive effect, it is worthy of reference.

Clinical Observation of Tiotropium Bromide Combined with Salmeterol Fluticasone Aerosol in the Treat-ment of Elderly Severe COPD / 中国药房

OBJECTIVE:To observe the clinical efficacy and safety of tiotropium bromide combined with Salmeterol flutica-sone aerosol in the treatment of severe COPD in elderly patients. METHODS:A total of 90 elderly patients with severe COPD se-lected from May 2013 to May 2015 in our hospital as research objects were divided into control group and observation group ac-cording to random number table,with 45 cases in each group. Control group was given Salmeterol xinafonate and fluticasone propi-onate aerosol 1 press/time,bid;observation group was additionally given Tiotropium bromide powder for inhalation 18 μg,qd,on the basis of control group. Both groups were treated for 8 weeks. The short-term clinical efficacy,dyspnea score,pulmonary venti-lation function indexes [FVC,EFV1,EFV1%],blood gas analysis indexes [p(O2),p(CO2)] and QLI score before and after treat-ment were observed in 2 groups. The re-hospitalization time and the occurrence of ADR were compared between 2 groups. RE-SULTS:The total response rate of short-term treatment in observation group was 97.78%,which was significantly higher than 80.00% of control group,with statistical significance (P0.05). After treatment,dyspnea scores and p(CO2) of 2 groups were decreased significantly,while pulmonary ventilation function indexes,p??????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????(O2)and QLI scores were increased significantly;the observation group was significantly better than the control group,with statis-tical significance(P<0.05). The re-hospitalization time of observation group was significantly less than that of control group,with statistical significance(P<0.05). There was no statistical significance in the incidence of ADR between 2 groups(P<0.05). CON-CLUSIONS:Tiotropium bromide assisted with Salmeterol fluticasone aerosol show significant therapeutic efficacy for elderly se-vere COPD,and effectively relieve dyspnea symptom,improve pulmonary ventilation function and quality of daily life,reduce the re-hospitalization risk and do not increase the incidence of ADR.