Tiotropium Research Articles

Cardiovascular safety of mometasone/indacaterol and mometasone/indacaterol/glycopyrronium once-daily fixed-dose combinations in asthma: pooled analysis of phase 3 trials.

To evaluate cardiovascular safety of two new inhaled fixed-dose combinations for treatment of asthma: (i) the inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) mometasone furoate/indacaterol acetate (MF/IND), (ii) the ICS/LABA/long-acting muscarinic antagonist (LAMA) MF/IND/glycopyrronium bromide (GLY). Patient-level data were pooled from four randomized trials, including 52-week studies PALLADIUM (n=2216) and IRIDIUM (n=3092), 24-week study ARGON (n=1426), and 12-week study QUARTZ (n=802). Cardio-/cerebrovascular (CCV) event frequencies were examined in the following comparisons: (1) LABA effect: pooled-dose MF/IND vs. pooled-dose MF; (2) LAMA effect: pooled-dose MF/IND/GLY vs. pooled-dose MF/IND; (3) ICS-dose effects: (a) high-dose MF/IND vs. medium-dose MF/IND, (b) high-dose MF/IND/GLY vs. medium-dose MF/IND/GLY; (4) intra-class effects: (a) high-dose MF/IND vs. Fluticasone/Salmeterol (F/S), (b) high-dose MF/IND/GLY vs. F/S+Tiotropium (TIO). Risk estimates (percentage of patients with ≥1 CCV event) and risk differences (RDs) with 95% confidence intervals (CIs) were calculated for each comparison. The frequency of CCV events was low, without notable differences between comparison groups. Risk estimates and corresponding RDs (95% CIs) were as follows: (1) pooled-dose MF/IND =2.35%, pooled-dose MF =2.18%, RD=0.17% (-1.00%, 1.34%); (2) pooled-dose MF/IND/GLY=3.65%, pooled-dose MF/IND=3.77%, RD=-0.12% (-1.63%, 1.39%); (3a) high-dose MF/IND=3.69%, medium-dose MF/IND=3.35%, RD=0.34% (-1.25%, 1.94%); (3b) high-dose MF/IND/GLY=2.84%, medium-dose MF/IND/GLY=2.02%, RD=0.82% (-0.49%, 2.13%); (4a) high-dose MF/IND=3.69%, F/S=2.82%, RD=0.87% (-0.66%, 2.40%); (4b) high-dose MF/IND/GLY=1.26%, F/S+TIO=1.05%, RD=0.21% (-1.26%, 1.68%). There was no evidence of increased cardiovascular risk attributable to the addition of IND to MF or addition of GLY to MF/IND. Similarly, no evidence of increased cardiovascular risk was observed with an increase in the ICS-dose or relative to F/S±TIO.

Availability, cost, and affordability of asthma and chronic obstructive pulmonary disease medications in The Gambia

Objectives:Guidelines for asthma and chronic obstructive pulmonary disease (COPD) have undergone significant changes. Specifically, inhaled corticosteroids (ICSs) either alone or in combination with a long-acting beta2-agonist (LABA) are now first-line treatment for asthma, while long-acting muscarinic antagonists alone or in combination with LABAs are first-line treatment of COPD. Data on local availability, cost, and affordability of these medicines in The Gambia are unknown.Materials and Methods:We surveyed all registered pharmacists in Gambia and calculated affordability indices relative to the prevailing wage of the lowest government worker.Results:Eight out of 18 registered pharmacists responded to the survey. Respondents were responsible for stocking 19 out 26 registered pharmacies in the country, resulting in a response rate of 44%. Salbutamol inhalers were widely available, stocked by the central medical stores and 6 out of 8 surveyed pharmacists. Only one pharmacist reported stocking beclometasone 50 mcg, budesonide 100 mcg, and fluticasone propionate 125 mcg inhalers. Aminophylline was stocked by 4/8 pharmacists. The price of salbutamol 100 mcg inhaler was Gambian Dalasi (GMD) 200 (US$ 4, 4 days’ wages), while ipratropium bromide 20 mcg cost GMD 675 (US$ 14, 15 days’ wages). ICS maintenance inhalers at private pharmacies cost 15, 26, and 28 days’ wages for beclomethasone 50 mcg, fluticasone propionate 125 mcg, and budesonide 100 mcg, respectively. Combination of ICS/LABA inhaler was 26 days’ wages while tiotropium bromide 18 mcg affordability was 95 days’ wages.Conclusion:Guideline recommended medications for the management of asthma and COPD in The Gambia are unavailable, expensive, and unaffordable.

Experience of using double bronchodilation therapy in patients with COPD

Chronic obstructive pulmonary disease (COPD) is currently one of the most socially significant diseases that leads to a significant decrease in the daily activity and productivity of patients, as well as their rapid invalidization. In this regard, its treatment remains the most important problem of medicine. Currently, the main goals of treatment of patients with COPD are: relief of symptoms, improvement of exercise tolerance, improvement of General health, prevention and effective treatment of complications, prevention and effective treatment of exacerbations, prevention of disease progression, and reduction of mortality. The article presents a clinical case from the practice of a patient with COPD who received olodaterol + Tiotropium bromide. In view of the patient’s low adherence to therapy, further progression of the disease was observed, which led to a significant violation of airway patency during spirometry, and a decrease in exercise tolerance. The patient was assigned a new representative of combined drugs with 24-hour action - Vilanterol + Umeclidinium 22/55 mcg, with a new method of drug delivery. After 6 months of therapy with Vilanterol + Umeclidinium, the patient’s exercise tolerance increased, lung function improved, and quality of life improved.

ЕФЕКТИВНІСТЬ КОМБІНОВАНОГО ЛІКУВАННЯ ХВОРИХ НА БРОНХІАЛЬНУ АСТМУ З НЕЙТРОФІЛЬНИМ ТИПОМ ЗАПАЛЕННЯ

THE EFFICACY OF COMBINED THERAPY IN PATIENTS WITH NEUTROPHILIC BRONCHIAL ASTHMA Yu. I. Feshchenko, L. A. Iashyna, G. L. Gumeniuk, V. I. Ignatieva, M. A. Polianska, S. G. Opimakh, I. V. Zvol, S. M. Moskalenko, N. A. Vlasova, L. A. Halai State organization «F. G. Yanovsky National institute of phthisiology and pulmonology National Academy of medical sciences of Ukraine» , Kyiv, Ukraine Abstract. Background: Issues of neutrophilic bronchial asthma remain unresolved and the investigations of the pathogenesis and treatment of this disease endotype are currently continuing. The aim of the study: This study aimed to develop the technology of the treatment of the neutrophilic asthma with the use of available drugs in Ukraine. Methods. The study involved 30 patients with neutrophilic asthma. The first (control) group consisted of 15 patients who received standard therapy with a combination of budesonide and formoterol. The second (main) group consisted of 15 patients who received the treatment according the technology (ultrafine beclomethasone dipropionate, formoterol, tiotropium bromide and additionally for the first 10 days — inhalation of 10.0 % acetylcysteine solution through a nebulizer). All patients were surveyed with the Asthma Control Test (ACT), the Asthma Control Questionnaire (ACQ). The quality of life of patients was assessed by a St. George’s Respiratory Questionnaire. All patients underwent spirometry and a 6-minute walking test (6MWT). Results: In the prescription of complex therapy to patients with neutrophilic asthma clinical and functional efficacy was achieved in 93.3 % of patients. There were observed statistically significant increase in the ACT from (14.3 ± 1.3) to (20.3 ± 0.8) points (p < 0.05), a decrease in the ACQ from (2.3 ± 0.2) ) to (1.1 ± 0.1) points (p < 0.05), clinically significant reduction in the number of symptoms from (71.4 ± 5.6) points to (51.3  5.0) points, p < 0.05 according to the results of the St. George’s Respiratory Questionnaire, and a statistically significant increase in MEF50 from (28.9 ± 4.5) % to (41.6 ± 4.2) %, p < 0.05, MEF25 — from (19.1 ± 2.9) % to (27.6 ± 2.6) %, p < 0.05 and FEV1 /FVC from (67.2 ± 3.5) % to (76.1 ± 2.3) %, p < 0.05 after 3 months of complex treatment, as well as a statistically significant increase in the number of meters passed in the 6MWT from (266.3 ± 16.2) m to (312.0 ± 14.4) m, p < 0.05, reduction of shortness of breath on the Borg scale before test from (2.5  0.3) points to (1.5 ± 0.1) points, p < 0.05 and after the test — from (4.1 ± 0.3) points to (3.1 ± 0.3) points, p < 0.05. Conclusions: The technology of treatment of patients with neutrophilic asthma allows to improve the control of the asthma symptoms and quality of life of the patients, bronchial patency at the small airways and reduce fixed bronchial obstruction, as well as increase exercise tolerance. Key words: bronchial asthma, neutrophilic inflammation, combined therapy.

Effect of Pulmonary Rehabilitation Combined with Tiotropium Bromide on BODE Index in Clinical Stable Patients with Chronic Obstructive Pulmonary Disease

Effect of Pulmonary Rehabilitation Combined with Tiotropium Bromide on BODE Index in Clinical Stable Patients with Chronic Obstructive Pulmonary Disease

ТРАНСФОРМУВАЛЬНИЙ ФАКТОР РОСТУ-β1 У ХВОРИХ НА БРОНХІАЛЬНУ АСТМУ: ПАТОГЕНЕТИЧНІ, КЛІНІЧНІ ТА ТЕРАПЕВТИЧНІ АСПЕКТИ (ОГЛЯД ЛІТЕРАТУРИ ТА ВЛАСНІ РЕЗУЛЬТАТИ ДОСЛІДЖЕННЯ)

The goal of our research was to analyze the role of transforming growth factor-β1 (TGF-β1 ) in airway remodeling, inflammation, clinical course, treatment efficacy in patients with bronchial asthma (BA) according to the literature data, as well as determination of this biomarkers level in the blood of BA patients. Material and research methods. The publications is containing the results of studies on the role of TGF-β1 in the course of BA have been analyzed. The level of TGF-β1 in the blood was determined within enzyme-linked immunosorbent assay using kits “IBL International GMBH, Germany” in 553 BA patients and in 95 healthy individuals. Results. The article presents data about TGF-β1 influence on the processes of airway remodeling in BA patients, its role in microcirculation disorders, mucus production, eosinophilic inflammation and severity of clinical symptoms of the disease. The level of TGF-β1 expression was associated with disease control, severity and duration of the disease, despite conflicting data that require further study. In addition, there were presented recent research data about TGF-β1 as a marker of airway remodeling and as a therapeutic target in the treatment of BA patients. Glucocorticoids, tiotropium bromide, methylxanthines, selective inhibitors of TGF-β1 , resveratrol, simvastatin and montelukast and their mechanisms of influence were presented in detail. Significantly higher level of TGF-β1 in the blood of patients with BA was found (38.5 ± 0.7) pg/ml compared with healthy individuals (33.9 ± 1.0) pg /ml, p = 0.007. Conclusion. A significantly higher level of TGF-β1 was revealed in the blood of BA patients. In our opinion, a differentiated analysis of the content of this marker depending on the phenotype of the disease is important, which would explain the conflicting results of different studies, deepen understanding of its pathophysiological and clinical role in order to develop methods for slowing airway remodeling. Key words: bronchial asthma, transforming growth factor-β1 (TGF-β1), airway remodeling.

Effect of Tiotropium Soft Mist Inhalers on Dynamic Changes in Lung Mechanics of Patients with Chronic Obstructive Pulmonary Disease Receiving Mechanical Ventilation: A Prospective Pilot Study.

The effects of tiotropium bromide soft mist inhalers (SMIs) in patients with chronic obstructive pulmonary disease (COPD) receiving mechanical ventilation remain unexplored. This study investigated the dynamic effects of a tiotropium SMI on lung mechanics and gas exchange in these patients. We analyzed 11 mechanically ventilated and hemodynamically stable patients with COPD who experienced acute exacerbation and were ready to be weaned from the ventilator. Two puffs of tiotropium (2.5 μg/puff) were administered with a T-adaptor connected to the ventilator circuit. Lung mechanics—peak inspiratory pressure, plateau pressure, mean airway pressure, maximum respiratory resistance (Rrs), and gas exchange function—were analyzed. The two-puff tiotropium SMI treatment led to the greatest reduction in Rrs at 6 h, with the Rrs returning to baseline gradually, and significantly improved the PaO2/FiO2 ratio at 24 h. Compared with baseline values, tiotropium SMI had the strongest effect on Rrs between hours 3 and 6 but did not significantly affect hemodynamic parameters. Tiotropium SMI administration in mechanically ventilated patients with COPD achieved the greatest reduction in Rrs at 6 h and significantly improved the PaO2/FiO2 ratio at 24 h. Future studies should investigate whether the bronchodilation effect can be improved with increased dosage or frequency.

Direct Switch from Tiotropium to Indacaterol/Glycopyrronium in Chronic Obstructive Pulmonary Disease Patients in Korea.

BackgroundMany chronic obstructive pulmonary disease (COPD) patients receiving monotherapy continue to experience symptoms, exacerbations and poor quality of life. This study aimed to assess the efficacy and safety of direct switch from once-daily tiotropium (TIO) 18 μg to indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily in COPD patients in Korea.MethodsThis was a randomized, open-label, parallel group, 12-week trial in mild-to-moderate COPD patients who received TIO 18 μg once daily for ≥12 weeks prior to study initiation. Patients aged ≥40 years, with predicted post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥50%, post-bronchodilator FEV1/forced vital capacity <0.7 and smoking history of ≥10 pack-years were included. Eligible patients were randomized in a 1:1 ratio to either IND/GLY or TIO. The primary objective was to demonstrate superiority of IND/GLY over TIO in pre-dose trough FEV1 at week 12. Secondary endpoints included transition dyspnea index (TDI) focal score, COPD assessment test (CAT) total score, and rescue medication use following the 12-week treatment, and safety assessment.ResultsOf the 442 patients screened, 379 were randomized and 347 completed the study. IND/GLY demonstrated superiority in pre-dose trough FEV1 versus TIO at week 12 (least squares mean treatment difference [Δ], 50 mL; p=0.013). Also, numerical improvements were observed with IND/GLY in the TDI focal score (Δ, 0.31), CAT total score (Δ, −0.81), and rescue medication use (Δ, −0.09 puffs/day). Both treatments were well tolerated by patients.ConclusionA direct switch from TIO to IND/GLY provided improvements in lung function and other patient-reported outcomes with an acceptable safety profile in patients with mild-to-moderate airflow limitation.

Prospects for the development of inhalation drugs for the provision of pre-hospital assistance to affected by hazardous chemical substances

Abstract. Pharmacological agents are analyzed, in respect of which it is advisable to develop dosage forms for inhalation use as medical means of protection at the prehospital stage of medical evacuation in case of damage by emergency-hazardous chemicals. It was found that the inhalation intake of hazardous chemicals, especially with a pronounced pulmonotoxic, irritating and generally poisonous effect, is highly likely to develop post-intoxication complications associated with damage to the lung parenchyma, and death. For the therapy of such intoxications, it is advisable to administrate drugs in a dosage form for inhalation administration, which have several advantages: high bioavailability, rapid onset of effect, and severity of local action in various parts of tracheobronchial tree. The data of experimental and clinical studies of the effectiveness of drugs belonging to various pharmacological groups allow us to recommend for the further development of inhaled forms of means of prevention and treatment of toxic pulmonary edema (fluticasone, roflumilast, rolipram). Bronchodilators and donors of sulfhydryl groups (ipratropium bromide, tiotropium bromide, atropine sulfate, fenoterol, salbutamol, formoterol, unitiol dimercaprol) are referred to means of correction of respiratory disorders of various etiologies. Diazepam, midazolam, clonazepam, lorazepam are considered to be the most likely anticonvulsants from the enzodiazepine-class suitable for inhalation. Acetylcysteine, hydroxycobalamin can be used to combat hypoxia. The principal possibility of inhalation application of bioscavengers (acetylcholinesterase, butyrylcholinesterase) for the treatment of cholinopositive symptoms of toxic genesis is shown. Existing methods and means of delivery allow the use of these drugs at the prehospital stage of medical evacuation as part of single dose metered powder inhalers.

&lt;p&gt;Frequency of Tiotropium Bromide Use and Clinical Features of Patients with Severe Asthma in a Real-Life Setting: Data from the Severe Asthma Network in Italy (SANI) Registry&lt;/p&gt;

PurposePatients with uncontrolled asthma despite high doses of inhaled corticosteroid therapy plus another controller are defined as severe asthmatics. Tiotropium bromide respimat (TBR) is the only long-acting muscarinic antagonists (LAMA) approved for severe asthma. The aim of this study was to explore the frequency of severe asthmatics treated with TBR and characterize their clinical features in a real-life, registry-based setting.Materials and MethodsBaseline data from the Severe Asthma Network in Italy (SANI) registry have been analyzed to determine the use of TBR and other LAMA, and to compare clinical, functional and inflammatory features associated with the use of LAMA.ResultsAmong a total of 698 enrolled patients, 35.9% were treated with LAMA (23.3% TBR, 4.5% tiotropium bromide handihaler, 4.5% aclidinium, 3.4% glycopyrronium bromide 0.3% umeclidinium bromide). Age of asthma onset was higher in patients taking LAMA, whom, compared to others were more frequently former smokers. They also had a higher annual exacerbation rate, experienced worst asthma control, worst disease-related quality of life and poorer lung function. Bronchiectasis was more frequently found in LAMA users (25.9% vs 13.1%).ConclusionTBR is still underused in severe asthma in a real-life setting, while a relevant proportion of patients are treated with other LAMA that are not approved for severe asthma treatment. Patients taking LAMA have features characteristic of even more severe asthma.

Systematic review and Meta-analysis on efficacy and safety of Buzhong Yiqi Decoction for stable chronic obstructive pulmonary disease

To systematically review the efficacy and safety of Buzhong Yiqi Decoction in the treatment of stable chronic obstructive pulmonary disease(COPD) at the stable stage. Three English databases and four Chinese databases were systematically searched from the database establishment to August 1, 2020. Randomized controlled trials(RCTs) were screened according to the pre-determined inclusion and exclusion criteria, and then the data were extracted. Methodological quality of the included studies was assessed based on Cochrane bias risk tool, and RevMan 5.3 was used for data analysis. A total of 389 articles were retrieved and finally 18 RCTs were included in this study, involving 1 566 patients, and the overall quality of the included studies was not high. Meta-analysis showed that, in terms of improving 6-minute walk distance(6 MWD), and delaying the decline of forced expiratory volume in one second(FEV_1) or its % in the expected value as well as the decline in ratio of FEV_1 to forced vital capacity(FVC), Buzhong Yiqi Decoction alone or in combination with conventional Western medicine was superior to conventional therapy Western medicine alone. Subgroup analysis showed that, in terms of reducing traditional Chinese medicine symptom scores, Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment. In terms of reducing the grade of modified medical research council(mMRC), Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment. In terms of improving 6 MWD, Buzhong Yiqi Decoction combined with conventional treatment or Tiotropium Bromide Powder for Inhalation was superior to conventional treatment alone or Tiotropium Bromide Powder for Inhalation alone. In terms of delaying the decline of FEV_1 or its % in the expected value, Buzhong Yiqi Decoction combined with conventional treatment or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation or Tiotropium Bromide Powder for Inhalation was superior to conventional treatment or Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation or Tiotropium Bromide Powder for Inhalation alone, and Buzhong Yiqi Decoction alone was superior to Theophylline alone. In terms of delaying the decline in FEV_1/FVC, Buzhong Yiqi Decoction combined with conventional treatment was superior to conventional treatment, and Buzhong Yiqi Decoction alone was superior to Theophylline alone. Meta-analysis of other outcome measures was not available and no conclusion can be drawn due to the inclusion of only one study. As some studies did not mention the adverse reactions, no safety comments can be made for Buzhong Yiqi Decoction alone or combined with conventional Western medicine. Due to the limitations of the quality and quantity of included studies, the conclusions of this research should be treated with caution. The efficacy of Buzhong Yiqi Decoction for stable COPD still needs more high-quality studies for confirmation, and its safety needs to be further verified.

A simple and economic chromatographic method for simultaneous determination of six bronchodilator drugs in pharmaceutical dosage forms

Chronic obstructive pulmonary disease is a major cause of morbidity and mortality worldwide. Combining an inhaled anticholinergic and a β2-agonist are a convenient way of delivering treatment, obtaining better lung function and improved symptoms. We aimed to develop and validate a reliable HPLC method for the simultaneous determination of the anticholinergics; ipratropium bromide, glycopyrronium bromide and tiotropium bromide in addition to the β2-agonists; bambuterol hydrochloride, formoterol fumarate and indacaterol maleate. The chromatographic separation was achieved on a Phenomenex Luna phenyl-hexyl (250 × 4.6 mm i.d., 5 μm) column and a mobile phase composed of 0.2% phosphoric acid (pH 3.0)/methanol/acetonitrile (66:12:22, v/v/v). The analysis was performed at a flow rate of 1 mL/min with UV detection at 210 nm. Method validation showed that calibration curves were linear within the range from 0.5 to 30.0 μg/mL with a correlation coefficient > 0.998. Intraday and interday precision and accuracy evaluated by relative standard deviation were lower than 2%. The limits of detection were in the ranges of 0.037–0.152 μg/mL. The developed method which is rapid, sensitive and highly efficient was applied for the analysis of the six bronchodilators in single and combined formulations saving money, solvents and chemicals. In addition, the environmental impact of the proposed method was evaluated using a suitable analytical Eco-Scale.

Clinical practice guidelines on the diagnosis and treatment of patients with arterial hypertension and chronic obstructive pulmonary disease

One of the most common comorbid condition in people over 40 years old is: arterial hypertension (AH) and chronic obstructive pulmonary disease (COPD). The frequency of AH in patients with COPD varies from 6.8 to 76.3%, in average 34.3%. COPD is detected in every fourth patient with hypertension in the age group of 2564 years. The current trend towards an increase in life expectancy and therefore growing pool of elder cohort, will lead to a higher number of patients with comorbid disorders. Diagnosis and treatment of AH and COPD are determined by current clinical recommendations for both nosologies, however, a number of mutual pathophysiological mechanisms lead to a more severe course of these diseases with frequent exacerbations. The choice of antihypertensive therapy in patients with AH in combination with COPD should be given to drugs that can provide an adequate decrease in blood pressure in hypoxic conditions, especially at night and early morning hours, that have prolonged effect or could be prescribed in the evening, and to those that dont worsen bronchial obstruction or exacerbate hypoxia. Patients with AH and COPD should be given recommendations on lifestyle changes, especially smoking cessation. As initial therapy calcium channel blockers, angiotensin receptor blockers or angiotensin-converting enzyme inhibitors should be considered. Calcium channel blockers/renin-angiotensin system blockers should be considered as the first line for combination therapy. Thiazide, thiazide-like diuretics orb1-selective adrenergic blockers could be prescribed in case of insufficient antihypertensive response or depending on different clinical scenarios. Bronchodilators are the baseline therapy in COPD with concomitant AH. According to modern concepts, prescription of combination therapy with different mechanisms of action is the most proven and justified approach, which leads to a decrease in the frequency of exacerbations of COPD and amelioration of the symptoms. The choice of bronchodilator in the case of a COPD and AH combination, should take into account the proven long-term safety regarding the risk of cardiovascular complications. Tiotropium bromide as the monotherapy, including as a liquid inhaler and aclidinium/formoterol, tiotropium/oladeterol as combination therapy showed cardiovascular safety in the long-term studies. The escalation of COPD therapy with the need of inhaled steroids requires careful monitoring of blood pressure and, possibly, a revision of antihypertensive treatment leading to its escalation as well. COPD has many phenotypes requiring different medications, eg.: roflumilast, theophylline, macrolides and mucoactive drugs, that could also require tighter blood pressure control on patients with COPD and AH.

Application of acetylcysteine in inhalation form in complex treatment of patients with bronchial asthma with neutrophilic type of inflammation

Background. Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease of the airways. On the base of this heterogeneity, among other factors, a significant role is played by the type of inflammation (eosinophilic, neutrophilic or malogranulocytic). In this regard it is offered to allocate separate endotypes of the disease. BA with a neutrophilic type of inflammation is characterized by more severe course with the presence of obstruction at the level of small bronchi and fixed bronchoobstruction. In the presence of disorders at the level of small bronchi, it is advisable to prescribe anti-inflammatory drugs in delivery devices that can create a high concentration of drugs in the peripheral departments (eg, Respimat, inhaled inhalers, fine aerosols). Mucolytics disrupt the structure of the mucus gel, thereby reducing its viscosity and elasticity and, thus, improving the viscoelastic properties of sputum, which facilitate airway clearance and promote the targeted delivery of bronchodilators and anti-inflammatory drugs to the small bronchi.&#x0D; Objective. To evaluate the effectiveness of the use of ultrafine-particle glucocorticoid tiotropium bromide through Respimat in standard therapeutic doses and inhalation of a10 % solution of acetylcysteine with a nebulizer once a day for 10 days as basic therapy.&#x0D; Materials and methods. The diagnosis of BA with the neutrophilic type of inflammation was established in patients, whose results of the blood analysis by microscopy showed the level of neutrophils ≥4000 in 1 μl. The effectiveness of treatment of patients having BA with neutrophilic type of inflammation was studied in 30 patients. First (control) group consisted of 15 patients (5 men and 10 women, mean age – 53.2±4.9 years, FEV1 after test with a bronchodilator – 50.6±16.3 %, FEV1/FVC – 66.4±17,8), who received as a standard therapy a combined drug – 320 mcg of budesonide and 9 mcg of formoterol – twice a day in complex treatment. Second (main) group consisted of 15 patients (9 men and 6 women, mean age – 53.6±3.8 years, FEV1 – 51.5±4.7 %, FEV1/FVC – 67,2±3,5), who were administered the inhalation of 250 μg of ultrafine-particle beclomethasone dipropionate and 12 μg of formoterol twice a day, 5 mcg tiotropium bromide as inhalations through the delivery device respimat once a day for 3 months. In the complex treatment, the inhalation of acetylcysteine (3 ml of 10 % solution) with a nebulizer once a day in the morning (duration of an inhalation session – 10 min) for 10 days was additionally prescribed.&#x0D; Results and discussion. After 3 months in patients of group 2, the effectiveness of treatment was 93.3 %. There was a statistically significant increase in the total score of the test for asthma control (ACT) from 14.3±1.3 to 20.3±0.8 points (p&lt;0.05), a decrease in the total score evaluation of the questionnaire for the control of asthma symptoms (ACQ) from 2.3±0.2 to 1.1±0.1 points (p&lt;0.05), which indicated an improvement in the control of asthma symptoms and a reduction in exacerbations; clinically significant decrease in the number of symptoms from 71.4±5.6 to 51.3±5.0 points (p&lt;0.05) according to the results of the St. George’s Hospital quality of life questionnaire, which indicated an improvement in the quality of life of patients; an increase in MEF50 from 28.9±4.5 % to 41.6±4.2 %, MEF25 from 19.1±2.9 % to 27.6±2.6 % and FEV1/FVC from 67.2±3.5 % to 76.1±2.3 %, which indicated an improvement in bronchial patency at the level of small bronchi and a decrease in fixed bronchial obstruction; an increase in the number of passed meters 6MWT from 266.3±16.2 to 312.0±14.4 m, a decrease in shortness of breath on the Borg scale from 2.5±0.3 to 1.5±0.1 points before the test and from 4.1±0.3 to 3.1±0.3 points after the test, which testified to the increase of tolerance to physical activity. The complex therapy was well tolerated by patients and was not accompanied by the development of side effects. In patients of the control group, statistically significant dynamics of the studied indicators was not detected.&#x0D; Conclusions. Prescription to patients with BA with the neutrophilic type of inflammation according to the severity of the disease as a basic therapy of ultrafine-particle inhaled glucocorticoid tiotropium bromide through a modern technical device Respimat in a standard therapeutic dose, and formoterol 12 μg twice a day for 10 days led to a positive dynamics of clinical symptoms of asthma, improved respiratory function, increased tolerance to physical activity, and improved the quality of life, thus, resulted in the effectiveness of treatment of patients with BA with the neutrophilic type of inflammation being 93.3 %.

SINGLE-INHALER TRIPLE THERAPY FLUTICASONE FUROATE/UMECLIDINIUM/VILANTEROL COMPARED WITH TIOTROPIUM MONOTHERAPY IN COPD: A POST HOC ANALYSIS BY AIRFLOW LIMITATION

SINGLE-INHALER TRIPLE THERAPY FLUTICASONE FUROATE/UMECLIDINIUM/VILANTEROL COMPARED WITH TIOTROPIUM MONOTHERAPY IN COPD: A POST HOC ANALYSIS BY AIRFLOW LIMITATION

DEVELOPMENT AND VALIDATION OF UV-SPECTROSCOPIC METHOD FOR ESTIMATION OF TIOTROPIUM BROMIDE IN API AND PHARMACEUTICAL DOSAGE FORM

Objective: The current work intended towards the developed and validated UV spectrophotometric method for the estimation of Tiotropium Bromide in API and pharmaceutical formulation.&#x0D; Methods: The UV spectrum of tiotropium bromide in methanol shows maximum absorbance at 230 nm. Calibration curve method was used for the estimation of tiotropium bromide in API and pharmaceutical formulation.&#x0D; Results: Maximum absorbance obtained in 230 nm. Calibration curve plotted in concentration range 20-120 µm/ml exhibit the linearity relationship with line equation y=0.0057x+0.3319. The Accuracy was found to be 80-100.5%. The precision %RSD=0.1110, and the limit of detection(LOD)=4.12and limit of quantification (LOQ= 12.50. The method was found to comply all the validation parameters as per the ICH guideline in indicating the sensitivity of the method analyte.&#x0D; Conclusion: This method is used as satisfactory for the routine analysis of tiotropium bromide in API and pharmaceutical dosage forms.

Influence of Baduanjin on lung function, exercise capacity, and quality of life in patients with mild chronic obstructive pulmonary disease

Introduction:Chronic obstructive pulmonary disease (COPD) is an illness characterized by progressive aggravation of airflow limitation, which seriously affects patients’ quality of life, and even life-threatening. The lung function of COPD patients is chronically and progressively deteriorated. Among them, the lung function of early COPD patients deteriorates rapidly, and forced expiratory volume in 1 second (FEV1) declines faster than other stages. If diagnosed early and effectively treated in time, it can greatly affect the prognosis. As a traditional exercise regimen, Baduanjin can improve lung function, exercise capacity, and quality of life of COPD patients. However, high-quality evidence-based medical evidence is so far be lacking to confirm the effectiveness of Baduanjin in reducing or preventing mild COPD lung function decline.Methods:This study is a randomized controlled trial, 192 patients with mild COPD were randomly divided into experimental group and control group. Both of them will receive basic treatment (health education and Tiotropium bromide), the experimental group will receive Baduanjin exercise training, and the control group will be told to maintain the original lifestyle and control the exercise. The Baduanjin exercise will last for 24 weeks and will be followed up for 72 weeks. The primary outcome is the change in lung function, including FEV1, FEV1/forced vital capacity (FVC), and FEV1/predicted. The secondary results included COPD assessment test, 6-minute walk test, St. George Respiratory Questionnaire, and Dyspnea Scale. Safety will also serve as assessing during the test.Discussion:The results of this trial will provide that traditional Baduanjin exercises can prevent COPD lung function deterioration, and provide a simple, inexpensive, and daily pulmonary rehabilitation measure for the patients with mild COPD.

Comparison of tiotropium delivery with the ODAPT adapter and a valved holding chamber

RATIONALE: Facemasks are commonly used by certain patients requiring assistance for aerosol medication delivery. Adapters are used as connectors between facemasks and inhalers. The valved holding chamber (VHC) is commonly prescribed with pressurized metered dose inhalers (pMDIs) to improve medication delivery. Recently, the VHC has been used with the Respimat Soft Mist Inhaler (SMI), which is a propellant-free inhaler. The ODAPT soft mist adapter was previously designed to serve as a connector for facemasks used with the Respimat SMI. OBJECTIVE The purpose of this in vitro study is to compare the Respimat medication delivery and losses using facemasks when connected separately to 1) the VHC and 2) the ODAPT adapter. METHODS Tiotropium was delivered via the Spiriva Respimat SMI with add-ons (either ODAPT adapter or VHC) and without add-ons under different humidity levels (40–50% and >90%) at 28.3 L/min using an 8-stage Andersen cascade impactor. The particle deposition was assessed via UV-visible spectrophotometry. MEASUREMENTS AND MAIN RESULTS: Under ambient humidity conditions, 7.39% and 19.10% loss of fine particle fraction (FPF) were found using the ODAPT adapter and VHC, respectively. However, for higher humidity, mimicking humidity levels in the lungs, a loss of medication of 16.74% and 30.20% was found using the ODAPT adapter and VHC, respectively. Significant differences were found in medication delivery using the two different connectors, where higher medication losses were found using the VHC. CONCLUSION The ODAPT adapter connected to the Respimat SMI was shown to provide higher medication deposition and to minimize drug losses.

Pharmacoeconomic analysis of tiotropium bromide and olodaterol fixed combination as maintenance therapy for patients with COPD in the Russian Federation

Aim. To assess the economic efficacy of a fixed combination tiotropium bromide+olodaterol (T+O) in comparison with other medications, included in the Vital and Essential Drugs List (VEDL), for the maintenance triple therapy of chronic obstructive pulmonary disease (COPD). Materials and Methods. A Markov model was used for the estimation of direct medical costs associated with different medications. Costminimization and budget impact analyses were performed. Results. The drug costs for T+O were the lowest among all compared treatment strategies. The cost savings in favor of T+O were 24.82% [15.86–29.95%]. The application of T+O strategy in 4,101 target patients led to a decrease in the total direct medical costs under the state programs of guarantees of free medical care by 13.13% in 3 years, which will make T+O therapy available to 643 more patients in the first year and 1,624 patients in three years. Conclusion. A fixed combination T+O is a preferred efficient option for maintenance triple treatment for patients with COPD in comparison with other drugs from VEDL, because it is associated with lower total costs and equal efficacy.

The Effect of Salmeterol, Tiotropium Bromide and its Combination in Patients with Acute Exacerbation Of Chronic Obstructive Pulmonary Disease

The Effect of Salmeterol, Tiotropium Bromide and its Combination in Patients with Acute Exacerbation Of Chronic Obstructive Pulmonary Disease