tiotropium-bromide and Dyspnea

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Drug Combinations; Dyspnea; Forced Expiratory Volume; Glycopyrrolate; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quinuclidines; Salmeterol Xinafoate; Tiotropium Bromide; Treatment Outcome

Topics: Adrenergic beta-2 Receptor Agonists; Benzoxazines; Bronchodilator Agents; Drug Combinations; Dyspnea; Exercise; Humans; Pulmonary Disease, Chronic Obstructive; Quality of Life; Tiotropium Bromide; Treatment Outcome

The objective of this study was to estimate the relative efficacy and safety of fixed-dose combination aclidinium/formoterol 400/12 μg twice daily compared to tiotropium 18 μg once daily in adult patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).. A systematic literature review performed in March 2014, using a predefined search strategy in MEDLINE, EMBASE and Cochrane Library, identified 17 randomized placebo-controlled trials, (tiotropium n = 15; aclidinium/formoterol n = 2). Outcomes of interest were: bronchodilation (peak and trough forced expiratory volume in 1 s (FEV1)), COPD symptoms [Transition Dyspnea Index (TDI) focal score and % of responders (>1 unit improvement)] and Health Related Quality of Life (HRQoL) [St. George's Respiratory Questionnaire (SGRQ) total score and % responders (>4 unit improvement)], % of patients with ≥1 exacerbations, adverse events (AE), serious adverse events (SAE), hospitalization and mortality, all at 24 weeks. In the absence of head-to-head trials between aclidinium/formoterol and tiotropium, a Bayesian indirect treatment comparison (ITC) was used with placebo as common control.. Regarding bronchodilation, aclidinium/formoterol was found to be more efficacious than tiotropium at peak FEV1, with mean difference in change from baseline (DCFB) 143 mL [95% credible interval (CrI): 112, 174] and at trough FEV1 [DCFB 26 mL (95% CrI -2, 55)]. Aclidinium/formoterol is expected to be more efficacious than tiotropium in improving dyspnea symptoms measured by TDI [DCFB 0.54 points (95% CrI 0.09, 0.99); odds ratio (OR) of responders 1.51 (95% CrI 1.11, 2.06)]. SGRQ results are comparable for aclidinium/formoterol versus tiotropium [DCFB -0.52 (95% CrI -2.21, 1.17); OR of responders 1.16 (95% CrI 0.47, 2.87)]. The ITC results suggest similar safety profiles regarding AEs, SAEs and hospitalization.. Based on the ITC, aclidinium/formoterol is expected to be more efficacious than tiotropium in terms of lung function and symptom control while providing comparable HRQoL results and safety profile.. AstraZeneca.

Topics: Bayes Theorem; Bronchodilator Agents; Drug Combinations; Dyspnea; Forced Expiratory Volume; Formoterol Fumarate; Hospitalization; Humans; Odds Ratio; Pulmonary Disease, Chronic Obstructive; Quality of Life; Severity of Illness Index; Tiotropium Bromide; Tropanes

Several new fixed-dose combination bronchodilators have been recently launched, and assessing their efficacy relative to each other, and with open dual combinations is desirable. This network meta-analysis (NMA) assessed the efficacy of umeclidinium and vilanterol (UMEC/VI) with that of available dual bronchodilators in single/separate inhalers.. A systematic literature review identified randomized controlled trials of ≥10 weeks among chronic obstructive pulmonary disease patients (≥40 years), assessing the efficacy of combination bronchodilators in single or separate inhalers. Comparative assessment was conducted on change from baseline in trough forced expiratory volume in 1 second (FEV1), St George's Respiratory Questionnaire (SGRQ) total scores, transitional dyspnea index (TDI) focal scores, and rescue medication use at 12 weeks and 24 weeks using an NMA within a Bayesian framework.. A systematic literature review identified 77 articles of 26 trials comparing UMEC/VI, indacaterol/glycopyrronium (QVA149), formoterol plus tiotropium (TIO) 18 μg, salmeterol plus TIO, or indacaterol plus TIO, with TIO and placebo as common comparators at 12 weeks and approximately 24 weeks. The NMA showed that at 24 weeks, efficacy of UMEC/VI was not significantly different compared with QVA149 on trough FEV1 (14.1 mL [95% credible interval: -14.2, 42.3]), SGRQ total score (0.18 [-1.28, 1.63]), TDI focal score (-0.30 [-0.73, 0.13]), and rescue medication use (0.02 [-0.27, 0.32]); compared with salmeterol plus TIO on trough FEV1 (67.4 mL [-25.3, 159.4]), SGRQ total score (-0.11 [-1.84, 1.61]), and TDI focal score (0.58 [-0.33, 1.50]); and compared with formoterol plus TIO 18 μg on SGRQ total score (-0.68 [-1.77, 0.39]). Results at week 12 were consistent with week 24 outcomes. Due to lack of availability of evidence, no comparison was made with formoterol plus TIO on FEV1 or TDI at 24 weeks.. UMEC/VI has comparable efficacy to other dual-bronchodilator combinations on available efficacy endpoints.

Topics: Bronchodilator Agents; Drug Combinations; Drug Therapy, Combination; Dyspnea; Forced Expiratory Volume; Formoterol Fumarate; Glycopyrrolate; Humans; Indans; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Tiotropium Bromide; Treatment Outcome

Tiotropium bromide is an anticholinergic agent that has gained worldwide acceptance as a first-line, once daily maintenance therapy for patients with moderate-to-severe chronic obstructive pulmonary disease. The purpose of this review is to synthesize the evidence base in the past 10 years on the development of tiotropium and its efficacy compared to other able interventions such as long-acting beta agonists (LABAs), as well as to assess its safety profile and its effects on health-related outcomes in patients with COPD. Treatment with tiotropium bromide has generally improved patients' health-related quality of life, reduced the number of patients suffering from acute exacerbations, decreased the number of hospitalizations, improved dyspnea, and reduced adverse events compared to placebo. In the past decade, several studies have examined the safety and efficacy of tiotropium in comparison to placebo and to LABAs (salmeterol, formoterol, and indacaterol) over periods ranging from 3 months to 48 months of follow-up. Head-to-head comparisons of tiotropium 18μg (once daily) with salmeterol 50μg (twice daily) in well-controlled trials demonstrated that tiotropium was superior in reducing acute exacerbation events and in improving quality of life. In a few short-term studies, indacaterol was comparable to tiotropium in its efficacy in improving health-related outcomes. Although the safety record of tiotropium has been exemplary in comparison to placebo, anticholinergic events such as dry mouth can be encountered in some patients. While the long-term safety of tiotropium when delivered in the HandiHaler® has been well documented, its delivery using the Respimat® Soft Mist Inhaler™ was associated with an elevated risk of cardiovascular complications, including increased mortality when compared to placebo. The exact mechanism for this is not known but is being investigated in a large multinational study that will evaluate the long-term safety of different doses of tiotropium delivered by the Respimat® soft mist inhaler versus the HandiHaler®. Further studies are required to investigate the efficacy and safety of tiotropium in comparison with novel LABAs such as indacaterol and vilanterol, and with other emerging novel anticholinergic agents such as aclidinium bromide and NVA237 (glycopyrronium bromide).

Topics: Adrenergic beta-2 Receptor Agonists; Albuterol; Bronchodilator Agents; Dyspnea; Ethanolamines; Formoterol Fumarate; Humans; Indans; Medication Adherence; Mucociliary Clearance; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Quality of Life; Quinolones; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide

Indacaterol is a once-daily, long-acting β(2)-agonist bronchodilator that improves dyspnoea and health status in patients with moderate-to-severe COPD. While its bronchodilator effects have been shown to be maintained in different patient subgroups, effects on clinical outcomes in certain subgroups are not yet defined.. Post-hoc analysis of pooled clinical study data to investigate efficacy and safety of indacaterol compared with placebo and other long-acting bronchodilators (formoterol, salmeterol, open-label tiotropium) in patient subgroups defined by COPD severity (GOLD stage II or III; n = 4082) and ICS use at baseline (no/yes; n = 4088). Efficacy outcomes were trough (24-h post-dose) FEV(1), dyspnoea (transition dyspnoea index; TDI) and health status (St George's Respiratory Questionnaire; SGRQ) after 26 weeks.. All active treatments significantly improved trough FEV(1) and dyspnoea compared with placebo, and all apart from open-label tiotropium improved health status compared with placebo. Among active treatments, indacaterol 150 μg had the best overall efficacy profile in the GOLD II and no-ICS subgroups. In the GOLD III and ICS subgroups, indacaterol 300 μg had the best overall efficacy, including a marked effect on dyspnoea (1.4-point improvement in TDI total score vs. placebo; p < 0.001). Within subgroups, the incidence of adverse events was similar between treatments.. Indacaterol maintained its efficacy regardless of disease severity or use of concurrent ICS. Indacaterol 150 μg had the best overall efficacy profile in the GOLD stage II patients while, in patients with more severe disease, indacaterol 300 μg provided useful improvements in dyspnoea.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Albuterol; Bronchodilator Agents; Drug Administration Schedule; Drug Therapy, Combination; Dyspnea; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Glucocorticoids; Humans; Indans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Scopolamine Derivatives; Severity of Illness Index; Tiotropium Bromide; Treatment Outcome; Vital Capacity

Topics: Acute Disease; Adrenergic beta-Agonists; Cholinergic Antagonists; Disease Progression; Drug Combinations; Dyspnea; Forced Expiratory Volume; Humans; Pulmonary Disease, Chronic Obstructive; Quality of Life; Scopolamine Derivatives; Tiotropium Bromide

Chronic obstructive pulmonary disease (COPD) is a common disease with a global impact in terms of morbidity and mortality. Patients usually consult their doctor because of symptoms, and among those, dyspnea at rest or under exercise is one of the most common. The sensation of dyspnea is experienced differently among individuals with COPD and may be based on diverse factors, such as muscle fatigue, patient perception, or trapped volumes. Treatment algorithms for COPD emphasize a stepwise approach to therapy depending on the severity of the disease, which, for reasons of convenience, is primarily based on spirometric impairment. Drugs that alter bronchial smooth muscle tone and increase inspiratory capacity have clinical efficacy for the dyspneic patient, most likely based on their effect on lung function, whereas the effects of antiinflammatory therapy with inhaled corticosteroids is more difficult to explain. The following short review aims to give an overview of the available clinical information of clinical trials performed over the last couple of years.

Topics: Adrenergic beta-Agonists; Albuterol; Cholinergic Antagonists; Dyspnea; Humans; Pulmonary Disease, Chronic Obstructive; Recovery of Function; Respiratory Function Tests; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

A systematic review was undertaken to evaluate the efficacy of tiotropium, a long acting anticholinergic drug, on clinical events, symptom scales, pulmonary function, and adverse events in stable chronic obstructive pulmonary disease (COPD).. A systematic search was made of the Cochrane trials database, MEDLINE, EMBASE, CINAHL, and a hand search of 20 respiratory journals. Missing data were obtained from authors and the manufacturer. Randomised controlled trials of > or =12 weeks' duration comparing tiotropium with placebo, ipratropium bromide, or long acting beta2 agonists (LABA) were reviewed. Studies were pooled to yield odds ratios (OR) or weighted mean differences with 95% confidence intervals (CI).. Nine trials (8002 patients) met the inclusion criteria. Tiotropium reduced the odds of a COPD exacerbation (OR 0.73; 95% CI 0.66 to 0.81) and related hospitalisation (OR 0.68; 95% CI 0.54 to 0.84) but not pulmonary (OR 0.50; 95% CI 0.19 to 1.29) or all-cause (OR 0.96; 95% CI 0.63 to 1.47) mortality compared with placebo and ipratropium. Reductions in exacerbations and hospitalisations compared with LABA were not statistically significant. Similar patterns were evident for quality of life and symptom scales. Tiotropium yielded greater increases in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) from baseline to 6-12 months than did placebo, ipratropium, and LABA. Decline in FEV1 over 1 year was 30 ml (95% CI 7 to 53) slower with tiotropium than with placebo and ipratropium (data were not available for LABA). Reports of dry mouth and urinary tract infections were increased with tiotropium.. Tiotropium reduced COPD exacerbations and related hospitalisations, improved quality of life and symptoms, and may have slowed the decline in FEV1. Long term trials are warranted to evaluate the effects of tiotropium on decline in FEV1 and to clarify its role compared with LABA.

Topics: Acute Disease; Bronchodilator Agents; Double-Blind Method; Dyspnea; Forced Expiratory Volume; Hospitalization; Humans; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome; Vital Capacity

Forced expiratory volume in 1 second (FEV1) has served as an important diagnostic measurement of chronic obstructive pulmonary disease (COPD) but has not been found to correlate with patient-centered outcomes such as exercise tolerance, dyspnea, or health-related quality of life. It has not helped us understand why some patients with severe FEV1 impairment have better exercise tolerance compared with others with similar FEV1 values. Hyperinflation, or air trapping caused by expiratory flow limitation, causes operational lung volumes to increase and even approach the total lung capacity (TLC) during exercise. Some study findings suggest that a dyspnea limit is reached when the end-inspiratory lung volume encroaches within approximately 500 mL of TLC. The resulting limitation in daily physical activity establishes a cycle of decline that includes physical deconditioning (elevated blood lactic acid levels at lower levels of exercise) and worsening dyspnea. Hyperinflation is reduced by long-acting bronchodilators that reduce airways resistance. The deflation of the lungs, in turn, results in an increased inspiratory capacity. For example, the once-daily anticholinergic bronchodilator tiotropium increases inspiratory capacity, 6-minute walk distance, and cycle exercise endurance time, and it decreases isotime fatigue or dyspnea. Pulmonary rehabilitation and oxygen therapy both reduce ventilatory requirements and improve breathing efficiency, thereby reducing hyperinflation and improving exertional dyspnea. Thus, hyperinflation is directly associated with patient-centered outcomes such as dyspnea and exercise limitation. Furthermore, therapeutic interventions--including pharmacotherapy and lung volume--reduction surgery--that reduce hyperinflation improve these outcomes.

Topics: Bronchodilator Agents; Dyspnea; Exercise; Exercise Tolerance; Health Status; Humans; Inspiratory Capacity; Pulmonary Disease, Chronic Obstructive; Quality of Life; Scopolamine Derivatives; Tiotropium Bromide

In chronic obstructive pulmonary disease (COPD), the rate of decline in forced expiratory volume in 1 second (FEV1) and progression to disability and death are accelerated. COPD management goals include preventing or slowing the progressive loss of lung function, relieving symptoms, improving exercise tolerance and the patient's health status, preventing and treating exacerbations and complications, minimizing side effects of treatment, and reducing mortality. Although lung function is important for diagnosis of COPD and classification of its severity, clinicians and patients are also very interested in symptoms, ability to function, and general well-being (health status). Consequently, increasing attention is being given to these patient-centered outcomes. It is possible to modify patient-centered outcomes; however, it remains to be seen whether doing so can also alter the natural course of the disease and reduce mortality. Two long-term clinical trials--Towards a Revolution in COPD Health (TORCH) and Understanding the Potential Long-Term Impacts on Function with Tiotropium (UPLIFT)--will help to answer the question of whether pharmacologic interventions are effective in changing the clinical course of COPD. The TORCH study examines the long-term effects of combination therapy with an inhaled long-acting beta-agonist (salmeterol) and a corticosteroid (fluticasone) on reduction of all-cause mortality over 3 years. The 4-year UPLIFT study examines the effects of maintenance treatment with the once-daily anticholinergic bronchodilator tiotropium on the yearly rate of decline in trough FEV1 and the yearly rate of decline in FEV1 90 minutes after maximal or near-maximal bronchodilator administration. This article examines the rationale for each of these studies and provides an overview of study methodology as well as preliminary demographic data.

Topics: Acute Disease; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Dyspnea; Female; Fluticasone; Forced Expiratory Volume; Health Status; Humans; Male; Middle Aged; Patient Admission; Patient-Centered Care; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Risk Assessment; Risk Factors; Salmeterol Xinafoate; Scopolamine Derivatives; Severity of Illness Index; Tiotropium Bromide; Treatment Outcome

Topics: Albuterol; Bronchodilator Agents; Clinical Trials as Topic; Dyspnea; Emotions; Exercise; Follow-Up Studies; Forced Expiratory Volume; Health Status; Humans; Interviews as Topic; Ipratropium; Multivariate Analysis; Placebos; Pulmonary Disease, Chronic Obstructive; Quality of Life; Salmeterol Xinafoate; Scopolamine Derivatives; Surveys and Questionnaires; Time Factors; Tiotropium Bromide

Options to treat and prevent episodic wheezing in children are scarce. Our objective was to assess the efficacy of intermittent tiotropium bromide treatment in early childhood episodic wheezing.. This 48-week, randomized, open-label, controlled, parallel-group trial was conducted at 4 hospitals in Finland. Children aged 6 to 35 months with 2 to 4 physician-confirmed episodes of wheeze and/or shortness of breath were considered eligible. Study participants were randomly allocated to receive 1 of 3 treatments: once-daily tiotropium bromide 5 µg for 7 to 14 days during respiratory tract infections and as-needed albuterol sulfate 0.2 mg (n = 27), twice-daily fluticasone propionate 125 µg for 7 to 14 days during respiratory tract infections and as-needed albuterol sulfate 0.2 mg (n = 25), or as-needed albuterol sulfate 0.2 mg alone (n = 28). The primary outcome was efficacy, assessed as intention-to-treat by comparing the proportion of episode-free days (the days lacking symptoms or treatments) between the treatment groups.. The proportion of episode-free days was higher in those receiving intermittent tiotropium bromide (median 97% [interquartile range, 93% to 99%]) than in those receiving intermittent fluticasone propionate (87% [78% to 93%], P = .002), or with as-needed albuterol sulfate alone (88% [79% to 95%], P = .003). Adjustment with allergic sensitization, the baseline number of physician-confirmed episodes of wheeze and/or shortness of breath, or short-course glucocorticoid treatment in the 2 weeks before the enrollment, did not affect the result. Intervention-related adverse events were not seen.. Intermittent tiotropium bromide treatment may be an effective alternative to current therapies for episodic wheezing. Before implementation of use, further research on safety and efficacy is indicated.

Topics: Albuterol; Bronchodilator Agents; Child; Child, Preschool; Double-Blind Method; Dyspnea; Fluticasone; Humans; Respiratory Sounds; Respiratory Tract Infections; Tiotropium Bromide; Treatment Outcome

Hyperinflation has been associated with negative cardiocirculatory consequences in patients with chronic obstructive pulmonary disease (COPD). These abnormalities are likely to worsen when the demands for O. 20 patients (residual volume = 201.6 ± 63.6% predicted) performed endurance cardiopulmonary exercise tests (75% peak) 1 h after placebo or tiotropium/olodaterol 5/5 μg via the Respimat® inhaler (Boehringer Ingelheim, Ingelheim am Rhein, Germany). Cardiac output was assessed by signal-morphology impedance cardiography. Near-infrared spectroscopy determined quadriceps blood flow (indocyanine green dye) and intra-muscular oxygenation.. Tiotropium/olodaterol was associated with marked lung deflation (p < 0.01): residual volume decreased by at least 0.4 L in 14/20 patients (70%). The downward shift in the resting static lung volumes was associated with less exertional inspiratory constraints and dyspnoea thereby increasing exercise endurance by ~50%. Contrary to our premises, however, neither central and peripheral hemodynamics nor muscle oxygenation improved after active intervention compared to placebo. These results were consistent with those found in a subgroup of patients showing the largest decrements in residual volume (p < 0.05).. The beneficial effects of tiotropium/olodaterol on resting and operating lung volumes are not translated into enhanced cardiocirculatory responses to exertion in hyperinflated patients with COPD. Improvement in exercise tolerance after dual bronchodilation is unlikely to be mechanistically linked to higher muscle blood flow and/or O

Topics: Aged; Aged, 80 and over; Benzoxazines; Bronchodilator Agents; Cardiac Output; Case-Control Studies; Cross-Over Studies; Cross-Sectional Studies; Drug Combinations; Dyspnea; Exercise Test; Exercise Tolerance; Female; Hemodynamics; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Oxygen; Physical Exertion; Placebos; Pulmonary Atelectasis; Pulmonary Disease, Chronic Obstructive; Quadriceps Muscle; Regional Blood Flow; Residual Volume; Spectroscopy, Near-Infrared; Tiotropium Bromide

The 3-min constant speed shuttle test (CSST) was used to examine the effect of tiotropium/olodaterol compared with tiotropium at reducing activity-related breathlessness in patients with chronic obstructive pulmonary disease (COPD).This was a randomised, double-blind, two-period crossover study including COPD patients with moderate to severe pulmonary impairment, lung hyperinflation at rest and a Mahler Baseline Dyspnoea Index <8. Patients received 6 weeks of tiotropium/olodaterol 5/5 µg and tiotropium 5 µg in a randomised order with a 3-week washout period. The speed for the 3-min CSST was determined for each patient such that an intensity of breathing discomfort ≥4 ("somewhat severe") on the modified Borg scale was reached at the end of a completed 3-min CSST.After 6 weeks, there was a decrease in the intensity of breathlessness (Borg dyspnoea score) at the end of the 3-min CSST from baseline with both tiotropium (mean -0.968, 95% CI -1.238- -0.698; n=100) and tiotropium/olodaterol (mean -1.325, 95% CI -1.594- -1.056; n=101). The decrease in breathlessness was statistically significantly greater with tiotropium/olodaterol

Topics: Administration, Inhalation; Aged; Benzoxazines; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Drug Combinations; Dyspnea; Exercise Test; Exercise Tolerance; Female; Forced Expiratory Volume; Humans; Internationality; Lung; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Recovery of Function; Severity of Illness Index; Time Factors; Tiotropium Bromide; Treatment Outcome; Vital Capacity

Tiotropium bromide has been widely used in clinical practice, while theophylline is another treatment option for chronic obstructive pulmonary disease (COPD). However, only a few relevant studies have investigated the long-term outcomes and efficacy of both in patients with COPD. We evaluated the effects of tiotropium and low-dose theophylline on stable COPD patients of groups B and D.. Eligible participants (n = 170) were randomized and received either tiotropium 18 µg once daily with theophylline 100 mg twice daily (Group I) or tiotropium 18 µg once daily (Group II) for 6 months. COPD assessment test (CAT), modified Medical Research Council (mMRC) dyspnea scores and pulmonary function tests were measured before randomization and during the treatment.. After 6 months of treatment, the CAT scores in both groups decreased significantly (11.41 ± 3.56 and 11.08 ± 3.05, p < 0.0001). The changes of CAT (p = 0.028) and mMRC scores (p = 0.049) between the two groups differed after 1 month of treatment. In Group I, forced expiratory flow after 25% of the FVC% predicted (MEF. Tiotropium combined with low-dose theophylline significantly improved the symptoms and general health of patients with stable COPD of groups B and D after 6 months of follow-up. Additionally, this therapy also improved the indicators of small airway function.. Chinese Clinical Trial Registry (Registry ID: ChiCTR1800019027).

Topics: Aged; Bronchodilator Agents; Drug Therapy, Combination; Dyspnea; Female; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Theophylline; Tiotropium Bromide

The long-term safety and efficacy of a novel Co-Suspension™ Delivery Technology glycopyrrolate (GP)/formoterol fumarate (FF) 18/9.6 μg fixed-dose combination metered dose inhaler (GFF MDI) were investigated in a 28-week safety extension study (PINNACLE-3, NCT01970878) of two randomized controlled Phase III trials (PINNACLE-1 and -2; NCT01854645 and NCT01854658) in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD).. Subjects completing 24 weeks' treatment with GFF MDI, GP MDI, FF MDI (all twice-daily) or open-label tiotropium 18 μg (once-daily) in PINNACLE-1 or -2 were randomly selected to continue treatment for 28 weeks. The target enrollment for PINNACLE-3 was 850 subjects. Safety and efficacy were evaluated over 52 weeks.. Of 3274 subjects randomized to active treatment in PINNACLE-1 or -2, 892 entered PINNACLE-3. Incidences of adverse events, serious adverse events and major adverse cardiovascular events were similar across treatment groups with no unexpected safety findings. For change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV. Results confirmed the long-term safety and tolerability of GFF MDI 18/9.6 μg twice-daily in subjects with moderate-to-very severe COPD. Improvements in efficacy endpoints were also sustained over 52 weeks.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aged; Bronchodilator Agents; Drug Therapy, Combination; Drug Tolerance; Dyspnea; Female; Forced Expiratory Volume; Formoterol Fumarate; Glycopyrrolate; Humans; Male; Metered Dose Inhalers; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Smoking; Tiotropium Bromide; Treatment Outcome

In this pooled analysis, we compared the effect of indacaterol/glycopyrronium (IND/GLY) by sex versus other commonly used chronic obstructive pulmonary disease (COPD) treatments and placebo. Male and female patients with moderate-to-very-severe COPD who had participated in six randomized controlled trials were included in the analysis. Baseline demographics and disease characteristics were analyzed by sex, and any differences noted. The effects of IND/GLY versus salmeterol/fluticasone (SFC), glycopyrronium, tiotropium and placebo, on lung function and the patient-reported outcomes (health status, dyspnea, rescue medication use and symptoms) were assessed by sex after 26 weeks treatment. The analysis population comprised 4719 men and 1389 women. Most baseline parameters differed significantly between men and women. Nonetheless, despite these differences in baseline characteristics, IND/GLY significantly improved lung function versus placebo (p < 0.0001) and all active comparators (p < 0.01) in men and women. Overall, IND/GLY showed better improvement in dyspnea and health status compared with all other treatments in both sex. Greater reduction of rescue medication use was observed with IND/GLY versus placebo and other treatments (all p < 0.01 expect IND/GLY versus SFC). Although some variability was observed, improvements in health status, dyspnea, rescue medication use and symptoms were generally larger in women than in men. Irrespective of sex, IND/GLY provided superior efficacy to monotherapy or SFC in both men and women. Small differences in efficacy response by sex were observed, which should be evaluated further in prospective clinical studies. Nevertheless, the benefits observed with IND/GLY confirm dual bronchodilator as the preferred therapy in patients with moderate-to-very-severe COPD regardless of sex.

Topics: Aged; Bronchodilator Agents; Drug Combinations; Dyspnea; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Glycopyrrolate; Health Status; Humans; Indans; Male; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinolones; Severity of Illness Index; Sex Factors; Tiotropium Bromide; Vital Capacity

Chronic obstructive pulmonary disease is associated with significant morbidity and mortality. Trials of maintenance chronic obstructive pulmonary disease treatments focus on improvement in lung function and reductions in exacerbations, while patients are much more concerned about symptoms and health status. Our aim was to investigate the effects of tiotropium + olodaterol on patient-reported health outcomes, breathlessness and night-time rescue medication use in patients with chronic obstructive pulmonary disease, compared to placebo, tiotropium or olodaterol monotherapy. Two pairs of replicate, phase III studies of 12 (OTEMTO 1 + 2) and 52 weeks' (TONADO 1 + 2) duration were evaluated, in which patients received either tiotropium + olodaterol 2.5/5 or 5/5 μg, tiotropium 2.5 or 5 μg, olodaterol 5 μg or placebo, all delivered once daily via Respimat inhaler. Patient-reported outcomes included breathlessness assessed by transition dyspnoea index focal score, health status assessed by St George's Respiratory Questionnaire total score and night-time rescue medication use at 12 or 24 weeks. Outcomes from the pooled study data are reported. Overall, 1621 and 5162 patients were treated in the OTEMTO and TONADO trials, respectively. Significantly larger improvements in St George's Respiratory Questionnaire and transition dyspnoea index focal scores were observed and a greater proportion of patients were responders to therapy (based on minimum clinically important differences in St George's Respiratory Questionnaire and transition dyspnoea index) with tiotropium + olodaterol compared to either monotherapy or to placebo. Tiotropium + olodaterol 5/5 µg significantly reduced night-time rescue medication usage.. COMBINED INHALER PROVES EFFECTIVE: Results from four in-depth studies show that a combined inhaler is very effective for treatment of moderate to severe chronic lung disease. Alleviating the symptoms of chronic obstructive pulmonary disease (COPD), particularly sleep disturbance, is crucial to enhancing patients' quality of life. Gary Ferguson at the Pulmonary Research Institute of Southeast Michigan, together with other scientists across the USA and Germany, analysed data from four large-scale studies to evaluate the efficacy of STIOLTO Respimat, a combination of two bronchodilators-tiotropium, and olodaterol, which tackle airway obstruction and breathlessness, improving long-term lung function. They found that the new drug combination triggered significant improvements in patients' quality of life and levels of breathlessness. Use of night-time rescue medication in patients on STIOLTO Respimat was considerably reduced. A greater number of patients responded positively to the combined inhaler than to monotherapy.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Benzoxazines; Bronchodilator Agents; Double-Blind Method; Drug Therapy, Combination; Dyspnea; Female; Forced Expiratory Volume; Health Status; Humans; Male; Middle Aged; Patient Reported Outcome Measures; Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide; Vital Capacity

Studies have shown that tiotropium once daily reduces lung hyperinflation and dyspnea during exercise and improves exercise tolerance in patients with COPD. Mechanisms underlying the effects of the muscarinic receptor antagonist tiotropium on COPD have not been fully understood.. In this study, we investigated whether improvement in neural respiratory drive is responsible for reducing dyspnea during exercise and improving exercise tolerance in COPD.. Twenty subjects with severe COPD were randomized into two groups: no treatment (Control, n = 10, 63.6 ± 4.6 years, FEV1 29.6 ± 13.3%pred) or inhaled tiotropium 18 μg once daily for 1 month (n = 10, 66.5 ± 5.4 years, FEV1 33.0 ± 11.1%pred). All subjects were allowed to continue their daily medications other than anti-cholinergics during the study. Constant cycle exercise with 75% of maximal workload and spirometry were performed before and 1 month after treatment. Diaphragmatic EMG (EMGdi) and respiratory pressures were recorded with multifunctional esophageal catheter. Efficiency of neural respiratory drive, defined as the ratio of minute ventilation (VE) and diaphragmatic EMG (VE/EMGdi%max), was calculated. Modified British Medical Research Council Dyspnea Scale (mMRC) was used for the evaluation of dyspnea before and after treatment.. There was no significant difference in spirometry before and after treatment in both groups. Diaphragmatic EMG decreased significantly at rest (28.1 ± 10.9% vs. 22.6 ± 10.7%, P < 0.05) and mean efficiency of neural respiratory drive at the later stage of exercise increased (39.8 ± 2.9 vs. 45.2 ± 3.9, P < 0.01) after 1-month treatment with tiotropium. There were no remarkable changes in resting EMGdi and mean efficiency of neural respiratory drive post-treatment in control group. The score of mMRC decreased significantly (2.5 ± 0.5 vs. 1.9 ± 0.7, P < 0.05) after 1-month treatment with tiotropium, but without significantly difference in control group.. Tiotropium significantly reduces neural respiratory drive at rest and improves the efficiency of neural respiratory drive during exercise, which might account for the improvement in exercise tolerance in COPD.

Topics: Aged; Dyspnea; Exercise Test; Exercise Tolerance; Forced Expiratory Volume; Humans; Middle Aged; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Severity of Illness Index; Spirometry; Tiotropium Bromide

In chronic obstructive pulmonary disease (COPD), there is a poor correlation between forced expiratory volume in 1 s (FEV1) and dyspnea following bronchodilator use. Better correlations have been observed between inspiratory lung function parameters (ILPs) and dyspnea, which drives our interest in ILPs. However, the acute and prolonged effects of long-acting bronchodilators and oral corticosteroids on ILPs have not been well investigated. Therefore, the aim of this study was to investigate the effects of these treatments on the ILPs, FEV1, dyspnea (visual analog scale (VAS)) and clinical COPD questionnaire (CCQ).. Twenty-eight stable COPD patients had their ILPs and FEV1 measured both before and 2 h after the use of a single dose of 18 mcg bronchodilator tiotropium and 50 mcg salmeterol. Thereafter, the patients were randomized to 2 weeks of treatment with 30 mg oral prednisolone once daily or oral placebo in combination with daily treatment with these two bronchodilators. Four weeks after the cessation of the randomized treatment, the ILPs and FEV1 were again measured. After each intervention, any change in the VAS score was assessed.. With both bronchodilators, significant improvements in ILPs were demonstrated (p < 0.005), with the exception of changes in ILPs inspiratory capacity (IC) and forced inspiratory flow at 50% of the vital capacity (FIF50) after tiotropium inhalation. After 2 weeks of treatment with prednisolone, significant differences were found for ILP forced inspiratory volume in 1 s (FIV1) and FEV1 compared with placebo. These differences were no longer present 4 weeks after the cessation of prednisolone. Significant relationships between ILPs and VAS scores were only found after 2 weeks of treatment with prednisolone or placebo.. After a single dose of long-acting bronchodilator salmeterol, significant improvements are observed in all ILPs and in FIV1 and PIF after tiotropium. Two weeks of oral corticosteroid treatment improved the FIV1 and FEV1. The dyspnea VAS score was only significantly correlated with the ILPs after 2 weeks of oral corticosteroid treatment.

Topics: Administration, Oral; Aged; Aged, 80 and over; Albuterol; Bronchodilator Agents; Delayed-Action Preparations; Double-Blind Method; Dyspnea; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Inspiratory Capacity; Male; Middle Aged; Prednisolone; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Salmeterol Xinafoate; Scopolamine Derivatives; Surveys and Questionnaires; Time Factors; Tiotropium Bromide

We evaluated the effect of QVA149, a dual bronchodilator combining indacaterol and glycopyrronium, on direct patient-reported dyspnoea in patients with moderate-to-severe chronic obstructive pulmonary disease. In this multicentre, blinded, double-dummy, three-period crossover study, 247 patients were randomised to once-daily QVA149 110/50 μg, placebo or tiotropium 18 μg. Superiority of QVA149 versus placebo (primary objective) and tiotropium (secondary objective) was assessed for improvement in dyspnoea via the self-administered computerised (SAC) version of the Baseline and Transition Dyspnoea Index after 6 weeks. Secondary end-points included lung function, rescue medication use and safety. After 6 weeks, the SAC Transition Dyspnoea Index total score was significantly higher with QVA149 versus placebo (least squares mean (LSM) treatment difference 1.37, p<0.001) and tiotropium (LSM treatment difference 0.49, p=0.021). QVA149 provided significant improvements in lung function, with higher forced expiratory volume in 1 s area under the curve from 0-4 h post-dose versus placebo and tiotropium at day 1 and week 6 (all p<0.001). Rescue medication use was significantly lower with QVA149 versus placebo (p<0.001) and tiotropium (p=0.002). All treatments were well tolerated. Once-daily QVA149 provided superior improvements in patient-reported dyspnoea and lung function versus placebo and tiotropium. These benefits were associated with improvements in other symptoms and reduced use of rescue medication.

Topics: Adult; Aged; Area Under Curve; Bronchodilator Agents; Cross-Over Studies; Drug Combinations; Dyspnea; Female; Forced Expiratory Volume; Glycopyrrolate; Humans; Indans; Male; Middle Aged; Powders; Pulmonary Disease, Chronic Obstructive; Quinolones; Scopolamine Derivatives; Spirometry; Tiotropium Bromide; Treatment Outcome

This randomized, double-blind, Phase IIIb study evaluated the 24-hour bronchodilatory efficacy of aclidinium bromide versus placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).. Patients received aclidinium 400 μg twice daily (morning and evening), tiotropium 18 μg once daily (morning), or placebo for 6 weeks. The primary endpoint was change from baseline in forced expiratory volume in 1 second area under the curve for the 24-hour period post-morning dose (FEV1 AUC0-24) at week 6. Secondary and additional endpoints included FEV1 AUC12-24, COPD symptoms (EXAcerbations of chronic pulmonary disease Tool-Respiratory Symptoms [E-RS] total score and additional symptoms questionnaire), and safety.. Overall, 414 patients were randomized and treated (FEV1 1.63 L [55.8% predicted]). Compared with placebo, FEV1 AUC0-24 and FEV1 AUC12-24 were significantly increased from baseline with aclidinium (∆ = 150 mL and 160 mL, respectively; p < 0.0001) and tiotropium (∆ = 140 mL and 123 mL, respectively; p < 0.0001) at week 6. Significant improvements in E-RS total scores over 6 weeks were numerically greater with aclidinium (p < 0.0001) than tiotropium (p < 0.05) versus placebo. Only aclidinium significantly reduced the severity of early-morning cough, wheeze, shortness of breath, and phlegm, and of nighttime symptoms versus placebo (p < 0.05). Adverse-event (AE) incidence (28%) was similar between treatments. Few anticholinergic AEs (<1.5%) or serious AEs (<3%) occurred in any group.. Aclidinium provided significant 24-hour bronchodilation versus placebo from day 1 with comparable efficacy to tiotropium after 6 weeks. Improvements in COPD symptoms were consistently numerically greater with aclidinium versus tiotropium. Aclidinium was generally well tolerated.

Topics: Aged; Area Under Curve; Bronchodilator Agents; Circadian Rhythm; Cough; Disease Progression; Double-Blind Method; Dry Powder Inhalers; Dyspnea; Female; Forced Expiratory Volume; Headache; Humans; Male; Middle Aged; Muscarinic Antagonists; Patient Preference; Pharyngitis; Pulmonary Disease, Chronic Obstructive; Respiratory Sounds; Scopolamine Derivatives; Surveys and Questionnaires; Time Factors; Tiotropium Bromide; Tropanes; Xerostomia

Tiotropium partially relieves exertional dyspnea and reduces the risk of congestive heart failure in chronic obstructive pulmonary disease (COPD) patients. However, its effect on the sympathetic activation response to exercise is unknown.. This study aimed to determine whether tiotropium use results in a sustained reduction in sympathetic activation during exercise.. We conducted a 12-week, open-label (treatments: tiotropium 18 μg or oxitropium 0.2 mg × 3 mg), crossover study in 17 COPD patients. Treatment order was randomized across subjects. The subjects underwent a pulmonary function test and two modes of cardiopulmonary exercise (constant work rate and incremental exercise) testing using a cycle ergometer, with measurement of arterial catecholamines after each treatment period.. Forced expiratory volume in 1 second and forced vital capacity were significantly larger in the tiotropium treatment group. In constant exercise testing, exercise endurance time was longer, with improvement in dyspnea during exercise and reduction in dynamic hyperinflation in the tiotropium treatment group. Similarly, in incremental exercise testing, exercise time, carbon dioxide production, and minute ventilation at peak exercise were significantly higher in the tiotropium treatment group. Plasma norepinephrine concentrations and dyspnea intensity were also lower during submaximal isotime exercise and throughout the incremental workload exercise in the tiotropium treatment group.. Tiotropium suppressed the increase of sympathetic activation during exercise at the end of the 6-week treatment, as compared with the effect of oxipropium. This effect might be attributed to improvement in lung function and exercise capacity and reduction in exertional dyspnea, which were associated with decreases in respiratory frequency and heart rate and reduced progression of arterial acidosis.

Topics: Aged; Cholinergic Agents; Cholinergic Antagonists; Cross-Over Studies; Dyspnea; Exercise Tolerance; Female; Heart Failure; Heart Function Tests; Humans; Male; Physical Exertion; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

In COPD, improvements in lung mechanics following bronchodilator, measured using the forced oscillation technique (FOT), are more sensitive than spirometry at detecting improvement in lung function following bronchodilator. The relationship between these improvements in lung mechanics and improvements in functional outcomes, such as exertional dyspnoea, following bronchodilator, in COPD is unknown.. 17 COPD subjects were recruited into a double blind placebo controlled randomised cross over study. Dyspnoea was induced using a standardised six-minute walk test (6 MWT), and measured by borg score throughout the test. Measurement of respiratory system conductance (Grs), respiratory system reactance (Xrs), inspiratory capacity (IC) and spirometry were made at baseline and 1 h after a single dose of either 18 μg of tiotropium bromide plus 200 μg salbutamol, or placebo.. Subjects had a mean baseline FEV(1) of 45.5 ± 11.0% predicted. The bronchodilator induced reduction in exertional dyspnoea correlated significantly with the increase in Grs (r(s) = 0.59, p = 0.01) and approached significance with FEV(1) (r(s) = 0.45, p = 0.07) but not with FVC (r(s) = 0.30, p = 0.24), Xrs (r(s) = 0.19, p = 0.47) or IC (r(s) = -0.08, p = 0.78). Increase in Grs was the best and sole predictor of reduction in exertional dyspnoea, explaining 41% of the variance. There was no additional contribution to the model from the increase in FEV(1) or IC.. Bronchodilator induced improvements in exertional dyspnoea in moderate to severe COPD are predicted by improvements in Grs, measured by FOT, independent of improvements in spirometry or hyperinflation. The findings suggest that FOT may be useful for measuring response to bronchodilator in COPD.

Topics: Aged; Aged, 80 and over; Albuterol; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Dyspnea; Exercise Test; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Oscillometry; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Respiratory Mechanics; Scopolamine Derivatives; Spirometry; Tiotropium Bromide; Walking

The current mainstream treatment for COPD is bronchodilators alone or in combination. The effects of a beta(2)-agonist, tulobuterol, administered transdermally, have been reported to last for 24h. However, there are no reports on the efficacy of tulobuterol combined with an anticholinergic. In this study, we investigated the efficacy and safety of transdermal tulobuterol combined with inhaled tiotropium in COPD.. After a 2-week run-in period, 103 stable COPD patients aged >or=40 years were randomized into two groups: inhaled tiotropium (18microg, Tio group) or transdermal tulobuterol (2mg) combined with inhaled tiotropium (18microg, Tio+Tulo group) for 8 weeks. Primary endpoints were pulmonary function and severity of dyspnea. The St. George's Respiratory Questionnaire (SGRQ) score was a secondary endpoint.. In both groups, FEV(1) and FVC as well as dyspnea improved significantly after 8 weeks. In a comparison of both groups, percentage changes in IC and morning and evening peak expiratory flow were significantly greater in the Tio+Tulo group than in the Tio group. In addition, significant improvement in SGRQ score was observed in the Tio+Tulo group only. The risk of adverse events related to the study drugs was not increased.. In COPD patients, additional administration of transdermal tulobuterol to inhaled tiotropium produced significant benefits in dyspnea and SGRQ score as well as pulmonary function. These benefits may be due to a reduction in pulmonary hyperinflation resulting from improvement of peripheral airflow obstruction through tulobuterol via the systemic circulation.

Topics: Administration, Cutaneous; Administration, Inhalation; Aged; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Dyspnea; Female; Humans; Japan; Male; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory Function Tests; Scopolamine Derivatives; Surveys and Questionnaires; Terbutaline; Tiotropium Bromide; Treatment Outcome

The synergistic interactions between pharmacotherapy and pulmonary rehabilitation has been provided, but it remains to be established whether this may also apply to more severe patients.. We have examined whether tiotropium enhances the effects of exercise training in patients with advanced COPD (FEV(1)

Topics: Aged; Albuterol; Androstadienes; Bronchodilator Agents; Combined Modality Therapy; Drug Administration Schedule; Drug Synergism; Dyspnea; Exercise Tolerance; Female; Fluticasone; Humans; Male; Pilot Projects; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Clinical information on 24-h spirometric efficacy of combining tiotropium and salmeterol compared to single-agent therapy is lacking in patients with COPD.. A randomized, double-blind, four-way crossover study of 6-week treatment periods comparing combination therapy of tiotropium 18 microg plus qd or bid salmeterol 50 microg versus single-agent therapy. Serial 24-h spirometry (FEV(1), FVC), effects on dyspnea (TDI focal score) and rescue salbutamol use were evaluated in 95 patients.. Tiotropium plus qd salmeterol was superior to tiotropium or salmeterol alone in average FEV(1) (0-24h) by 72 mL and 97 mL (p<0.0001), respectively. Compared to this qd regimen, combination therapy including bid salmeterol provided comparable daytime (0-12h: 12 mL, p=0.38) bronchodilator effects, but significantly more bronchodilation during the night-time (12-24h: 73 mL, p<0.0001). Clinically relevant improvements in TDI focal score were achieved with bronchodilator combinations including salmeterol qd or bid (2.56 and 2.71; p<0.005 versus components). Symptom benefit of combination therapies was also reflected in less need for reliever medication. All treatments were well tolerated.. Compared to single-agent therapy, combination therapy of tiotropium plus salmeterol in COPD provided clinically meaningful improvements in airflow obstruction and dyspnea as well as a reduction in reliever medication.

Topics: Adult; Airway Obstruction; Albuterol; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Dyspnea; Female; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Salmeterol Xinafoate; Scopolamine Derivatives; Spirometry; Tiotropium Bromide; Treatment Outcome

Indacaterol is the first once-daily, long-acting inhaled beta(2)-agonist bronchodilator studied in patients with chronic obstructive pulmonary disease (COPD).. To demonstrate greater efficacy of indacaterol versus placebo on FEV(1) at 24 hours post dose (trough) after 12 weeks, to compare efficacy with placebo and tiotropium, and to evaluate safety and tolerability over 26 weeks.. Patients with moderate-to-severe COPD were randomized to double-blind indacaterol 150 or 300 microg or placebo, or open-label tiotropium 18 microg, all once daily, for 26 weeks. The primary efficacy outcome was trough FEV(1) at 12 weeks. Additional analyses (not adjusted for multiplicity) included transition dyspnea index (TDI), health status (St George's Respiratory Questionnaire [SGRQ]), and exacerbations. Serum potassium, blood glucose, and QTc interval were measured.. A total of 1,683 patients (age, 63.3 yr; post-bronchodilator FEV(1), 56% predicted; FEV(1)/FVC, 0.53) were randomized to the four treatment arms. Trough FEV(1) at Week 12 increased versus placebo by 180 ml with both indacaterol doses and by 140 ml with tiotropium (all P < 0.001 vs. placebo). At Week 26, for indacaterol 150/300 microg, respectively, versus placebo, TDI increased (1.00/1.18, P < 0.001) and SGRQ total score decreased (-3.3/-2.4, P < 0.01); corresponding results with tiotropium were 0.87 (P < 0.001) for TDI and (-1.0, P = not significant) for SGRQ total score. The incidence of adverse events, low serum potassium, high blood glucose, and prolonged QTc interval was similar across treatments.. Indacaterol was an effective once-daily bronchodilator and was at least as effective as tiotropium in improving clinical outcomes for patients with COPD. Clinical trial registered with clinicaltrials.gov (NCT 00463567).

Topics: Administration, Inhalation; Blood Glucose; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Dyspnea; Electrocardiography; Female; Forced Expiratory Volume; Health Status; Humans; Indans; Male; Middle Aged; Potassium; Pulmonary Disease, Chronic Obstructive; Quinolones; Scopolamine Derivatives; Spirometry; Tiotropium Bromide

It is currently unclear whether the additive effects of a long-acting beta(2)-agonist (LABA) and the antimuscarinic tiotropium bromide (TIO) on resting lung function are translated into lower operating lung volumes and improved exercise tolerance in patients with chronic obstructive pulmonary disease (COPD).. On a double-blind and cross-over study, 33 patients (FEV(1) = 47.4 +/- 12.9% predicted) were randomly allocated to 2-wk formoterol fumarate 12 microg twice-daily (FOR) plus TIO 18 microg once-daily or FOR plus placebo (PLA). Inspiratory capacity (IC) was obtained on constant-speed treadmill tests to the limit of tolerance (Tlim).. FOR-TIO was superior to FOR-PLA in increasing post-treatment FEV(1) and Tlim (1.34 +/- 0.42 L vs. 1.25 +/- 0.39 L and 124 +/- 27% vs. 68 +/- 14%, respectively; p < 0.05). FOR-TIO slowed the rate of decrement in exercise IC compared to FOR-PLA (Deltaisotime-rest = -0.27 +/- 0.40 L vs. -0.45 +/- 0.36 L, p < 0.05). In addition, end-expiratory lung volume (% total lung capacity) was further reduced with FOR-TIO (p < 0.05). Of note, patients showing greater increases in Tlim with FOR-TIO (16/26, 61.6%) had more severe airways obstruction and lower exercise capacity at baseline. Improvement in Tlim with FOR-TIO was also related to larger increases in FEV(1) (p < 0.05).. Compared to FOR monotherapy, FOR-TIO further improved effort-induced dynamic hyperinflation and exercise endurance in patients with moderate-to-severe COPD. These beneficial consequences were more likely to be found in severely-disabled patients with larger resting functional responses to the combination therapy.. Clinicaltrials.gov Identifier: NCT00680056 [ClinicalTrials.gov].

Topics: Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Dyspnea; Ethanolamines; Exercise Tolerance; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide; Total Lung Capacity; Treatment Outcome

Current guidelines support using in combination more than one class of long-acting bronchodilator for COPD patients whose symptoms are not controlled by mono-therapy. This 2-week, multi-center (34 sites), randomized, modified-blind, parallel group study evaluated the efficacy and safety of concomitant treatment with nebulized arformoterol (the formoterol(R,R)-isomer) BID and tiotropium DPI QD.. COPD patients (mean FEV(1) 1.37L, 45.4% predicted) were randomized to receive mono-therapy (either arformoterol 15microg BID [n=76] or tiotropium 18microg QD [n=80]), or combined therapy (sequential dosing of arformoterol 15microg BID and tiotropium 18microg QD [n=78]). Changes in pulmonary function, dyspnea, and rescue levalbuterol use were evaluated, as were safety outcomes.. Mean FEV(1)AUC(0-24) (the primary endpoint) improved similarly from baseline for arformoterol (0.10L) and tiotropium (0.08L) treatment groups and greater for the combined therapy group (0.22L; all p-values <0.005). Peak FEV(1), peak FVC, 24-h trough FEV(1), and inspiratory capacity also improved similarly for the mono-therapies and greatest for the combined therapy. Dyspnea (mean transition dyspnea index) improved similarly for arformoterol (+2.3) and tiotropium (+1.8) and greatest with combined therapy (+3.1; p-values <0.05). Levalbuterol use decreased for all treatment groups (range -1.8 to -2.5 actuations/day). All treatments had similar frequency of adverse events.. In this study, the combination of nebulized arformoterol 15microg BID plus tiotropium 18microg DPI QD was the most effective in improving pulmonary function and disease symptoms. Mono-therapy improvement with arformoterol or tiotropium was similar. All three treatments were well tolerated.

Topics: Administration, Inhalation; Aged; Albuterol; Bronchodilator Agents; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Dyspnea; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome; Vital Capacity

In chronic diseases such as chronic obstructive pulmonary disease (COPD), patients may not perceive all of the benefits of drug therapy until withdrawal. Thus, we evaluated the effect of tiotropium withdrawal on clinical variables.. COPD subjects who participated in two identical 1-year, prospective, double-blind, placebo-controlled studies of tiotropium 18 microg once daily who completed a 3-week visit following discontinuation of therapy were included in this analysis. Outcomes measured included dyspnea (transition dyspnea index [TDI]), Peak Expiratory Flow Rate (PEFR), health status (St George's Respiratory Questionnaire [SGRQ]), and rescue beta2-agonist use.. Overall, the tiotropium group exhibited significant improvements in clinical parameters at the end of therapy. Of the entire cohort of 921 patients, 713 patients (77%) completed 3-weeks post-withdrawal evaluation. Patients in the tiotropium group had 1.1 unit worsening in TDI, decreased in PEFR, health status and reduced beta(2)-agonist medication following treatment discontinuation, while the placebo group remained relatively stable.. The withdrawal of tiotropium results in worsening of COPD over a three-week interval. There was no evidence of a rebound effect in response to tiotropium withdrawal.

Topics: Aged; Bronchodilator Agents; Dyspnea; Epidemiologic Methods; Female; Forced Expiratory Volume; Humans; Male; Pulmonary Disease, Chronic Obstructive; Quality of Life; Scopolamine Derivatives; Tiotropium Bromide; Withholding Treatment

Current guidelines for the treatment of chronic obstructive pulmonary disease (COPD) recommend the use of long-acting bronchodilators in the maintenance management of COPD. Combining bronchodilators that work through different mechanisms is recommended in patients with continuous symptoms. We conducted this study to confirm and further investigate the efficacy and safety of nebulized formoterol as an add-on therapy to maintenance tiotropium in patients with COPD. This randomized, double-blind, placebo-controlled, parallel-group study (NCT00507234) was conducted at 24 US sites from March to October 2007 in 155 patients aged > or =40 years with post-bronchodilator forced expiratory volume in 1 second (FEV(1)) > or =25% to <65% predicted normal. COPD patients receiving open-label tiotropium bromide 18 microg once daily during a 1- to 2-week run-in period were randomized to receive either formoterol fumarate inhalation solution 20 microg or placebo by nebulization twice daily for 6 weeks while continuing treatment with tiotropium. Outcomes included serial spirometry, inspiratory capacity (IC), baseline dyspnoea index/transition dyspnoea index (BDI/TDI), daily symptom scores, salbutamol (albuterol) use and health status measured by the St George's Respiratory Questionnaire (SGRQ). The primary efficacy endpoint was standardized absolute FEV(1) area under the curve over 3 hours (AUC(0-3)) at week 6. Treatment groups (formoterol plus tiotropium, n = 78; placebo plus tiotropium, n = 77) were comparable at baseline. At 6 weeks, FEV(1) AUC(0-3) was significantly greater in the formoterol group compared with the placebo group (1.57 vs 1.38 L [p < 0.0001]). Similarly, formoterol plus tiotropium improved other lung function measures, including FEV(1), forced vital capacity and post-dose IC at day 1, and maintained efficacy through week 6. Formoterol plus tiotropium decreased rescue albuterol use throughout the study (p < 0.05). Mean TDI, SGRQ and most symptom scores did not differ between the two treatment groups. Overall, 37% of formoterol plus tiotropium recipients experienced adverse events versus 51% of those receiving placebo plus tiotropium. The addition of nebulized formoterol to tiotropium in maintenance treatment of COPD provided clinically meaningful, statistically significant and sustained improvements in pulmonary function without additional adverse effects.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Aged; Albuterol; Area Under Curve; Bronchodilator Agents; Drug Therapy, Combination; Dyspnea; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Scopolamine Derivatives; Spirometry; Tiotropium Bromide

Evaluation of tiotropium efficacy in patients with mild chronic obstructive pulmonary disease (COPD) defined by the 2003 Swedish Society of Respiratory Medicine guidelines (post-bronchodilator FEV1/FVC <70%; FEV1 >60% predicted).. In this 12-week, randomised, double-blind, placebo-controlled study of tiotropium 18 mcg once daily versus placebo, respiratory function was assessed on Days 1, 15 and 85 (baseline: pre-dose Day 1).. Mean+/-SD baseline FEV1 (% predicted) was 73.4+/-12.5 (tiotropium, n=107; placebo, n=117). Tiotropium significantly improved change from baseline in area under the curve from pre-dose to 2 hours post-dose (AUC0-2 h) FEV1 versus placebo, by 166+/-26 mL (mean+/-SE) at study end (p<0.0001). With tiotropium, there were significant increases in the change in AUC0-2 h FVC versus baseline, and trough FEV1 and FVC, versus placebo, on all test days (p<0.01). Adverse event rates were similar.. Compared with placebo, tiotropium improved lung function in patients with mild COPD.

Topics: Bronchodilator Agents; Double-Blind Method; Dyspnea; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Scopolamine Derivatives; Severity of Illness Index; Spirometry; Tiotropium Bromide; Vital Capacity

To determine which timing of therapy with formoterol (FOR) and/or tiotropium (TIO) shows the greater and more continuous functional improvement during 24 h in patients with moderate to severe COPD.. In this randomised, blind, crossover study 80 patients with stable COPD (40 moderate and 40 severe) received 5 different bronchodilator 30-day treatments in a random order. Treatments (Tr) were: Tr1: TIO 18 microg once-daily (8 am); Tr2: TIO 18 microg (8 am) + FOR 12 microg (8 pm); Tr3: FOR 12 microg twice-daily (8 am and 8 pm); Tr4: TIO 18 microg (8 am) + FOR 12 microg twice-daily (8 am and 8 pm); Tr5: FOR 12 microg twice-daily (8 am and 8 pm) + TIO 18 microg (8 pm). Spirometries were performed during 24 h (13 steps) on Day1 and Day30. End-points were: gain of FEV(1) (DeltaFEV(1)) from baseline of the Day1 and Day30, AUC (Area Under Curve), Dyspnoea Index, and as-needed use of salbutamol.. Sixty-eight patients completed all treatments. The greater and continuous daily functional improvement was showed during Tr4 and Tr5 (Day1 +135.8 mL and +119.1 mL; Day30 +160.2 mL, and +160.5 mL, respectively). Daily means of DeltaFEV(1) were significantly different between single-drug treatments and combination therapy. Dyspnoea was greater in single-drug treatments. Less use of rescue salbutamol was reported in Tr4 (0.80 puffs/die) and Tr5 (0.71 puffs/die).. In patients with moderate to severe COPD, combination therapy with tiotropium administered in the morning (Tr4) was the most effective; in patients with prevailing night-symptoms, treatment with tiotropium in the evening (Tr5) reduced symptoms and use of salbutamol. Tr5 showed less variability of FEV(1) during the 24 h (CV=0.256). These results are relevant for opening new ways in clinical practice.

Topics: Aged; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Dyspnea; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Exercise training improves exercise tolerance in chronic obstructive pulmonary disease (COPD). Tiotropium 18 microg once daily induces sustained bronchodilation throughout the day and reduces hyperinflation, one of the pathophysiological factors contributing to exertional dyspnea in COPD patients.. To determine whether tiotropium enhances the effects of exercise training in patients with COPD.. Multicenter, 25 week randomized, double-blind, placebo-controlled, parallel-group study.. Twelve Italian Pulmonary Units practicing pulmonary rehabilitation.. Two hundred thirty four COPD patients (196 males; mean age: 67.4 +/- 7.6; forced expiratory volume at 1 second (FEV1): 41.4 +/- 13.0% predicted) were randomised to tiotropium 18 microg or placebo inhalation capsules taken once daily. Both groups underwent a 8 week pulmonary rehabilitation program (PR) consisting of 3 exercise training session per week.. Baseline, at the end of PR and after 12 weeks, patients completed pulmonary function testing, six minute walking test (6MWT), the Baseline and Transition Dyspnea Index (BDI and TDI), and the St. George's Respiratory Questionnaire (SGRQ).. Relative to placebo, tiotropium had larger trough and post-study drug FEV1 responses on all test days. At the end of and 12 weeks following PR, patients on tiotropium showed no statistically significant differences in 6MWT compared to patients on placebo. Compared to the period immediately prior to PR, the mean improvement in 6MWT was only 29.7 meters (7.1%) for the combined cohort. Mean TDI focal scores at the end of PR were 3.60 for tiotropium and 2.25 for placebo (p < 0.01). At 12 weeks after PR, TDI focal scores were 2.71 for tiotropium and 2.11 for placebo (p = 0.16). Reduction in all four SGRQ component scores, indicating an improvement in health-related quality of life, was observed for the tiotropium group over the duration of the study compared to placebo but the differences were not statistically significant. During the study period, there were fewer exacerbations and exacerbation days in the tiotropium group.. Although significant improvements were observed with perceived dyspnea, compared to placebo, the addition of tiotropium to pulmonary rehabilitation did not improve the 6MWT.

Topics: Aged; Bronchodilator Agents; Cholinergic Antagonists; Combined Modality Therapy; Double-Blind Method; Dyspnea; Exercise Therapy; Exercise Tolerance; Female; Forced Expiratory Volume; Hospitalization; Humans; Italy; Lung; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Scopolamine Derivatives; Surveys and Questionnaires; Time Factors; Tiotropium Bromide; Treatment Outcome; Walking

Although combination therapy with bronchodilators is recommended for chronic obstructive pulmonary disease (COPD), there is insufficient evidence for the efficacy of some combinations of long-acting bronchodilators.. We investigated the effects of a combination therapy with tiotropium and theophylline in COPD patients.. In a 12-week, open-labeled, parallel-group randomized study, pulmonary functions and dyspnea scores were compared between the combination and theophylline alone therapy at baseline, and 4 and 8 weeks after randomization in COPD.. Sixty-one COPD patients completed the trial (31 combination therapy, 30 theophylline alone; mean age 70 years; 58 males; mean dyspnea score 2.0 and forced expiratory volume in one second (FEV1) 1.5 L [62.5% predicted]). FEV1 in the combination group, but not in the theophylline alone, was significantly increased at 4 (1.56 +/- 0.13 L, p < 0.001) and 8 weeks (1.60 +/- 0.13 L, p < 0.001) from the baseline (1.40 +/- 0.12 L). In the combination group, but not the theophylline alone group, the dyspnea score was significantly improved after 4 (p < 0.01) and 8 weeks (p <0.05) compared with baseline. In 17 patients who did not receive theophylline at screening, treatment with 4 or 8 weeks of theophylline alone did not improve dyspnea score or FEV1.. Addition of tiotropium therapy to theophylline treatment can improve dyspnea and pulmonary function in COPD. Although this study did not assess whether there was any benefit of adding theophylline to patients treated with tiotropium, tiotropium can be a useful addition in COPD already treated with theophylline.

Topics: Aged; Bronchodilator Agents; Drug Therapy, Combination; Dyspnea; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Theophylline; Tiotropium Bromide; Treatment Outcome

A combination of bronchodilators may be effective in the treatment of chronic obstructive pulmonary disease (COPD). We examined the effect of adding a long-acting anti-cholinergic agent (tiotropium) to a transdermal-type beta(2)-agonist (tulobuterol) on dyspnea as well as pulmonary function.. In a multicentre, randomized, parallel design study, 60 COPD patients treated with the transdermal beta(2)-agonist tulobuterol were divided into a tiotropium added group (Tulo+Tio group, n=40) or transdermal beta(2)-agonist tulobuterol alone group (Tulo group, n=20), and then treated for 4 weeks after a 2 week run-in period. Pulmonary function and a dyspnea (Medical Research Council (MRC)) scale were assessed before and after the treatment. Daily peak expiratory flow (PEF) monitoring was also performed.. After 4 weeks, the Tulo+Tio group showed a significant increase in pulmonary function compared with the Tulo group; DeltaFVC (0.31+/-0.06 L vs. 0.06+/-0.05 L, p< 0.01), DeltaFEV(1) (0.15+/-0.03 L vs. -0.02+/-0.02 L, p<0.0001), and DeltaPEF (41.0+/-5.1 L/min vs. 0.5+/-3.5 L/min, p<0.0001). The MRC dyspnea scale was also significantly improved in Tulo+Tio, but not in Tulo group.. These results suggest that tiotropium caused a significant improvement in both pulmonary function and dyspnea in COPD patients already treated with the transdermal beta(2)-agonist tulobuterol.

Topics: Administration, Cutaneous; Administration, Inhalation; Adrenergic beta-Agonists; Aged; Bronchodilator Agents; Drug Synergism; Dyspnea; Female; Forced Expiratory Volume; Humans; Male; Peak Expiratory Flow Rate; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Scopolamine Derivatives; Terbutaline; Tiotropium Bromide

We explored the additive effect of titrated oral theophylline in patients with stable chronic obstructive pulmonary disease (COPD) who received both tiotropium, 18mug od, and formoterol, 12mug bid. Thirty-six patients with moderate-to-severe COPD were enrolled in this two-period trial. They were initially treated with formoterol+tiotropium for 4 weeks. After this first period, they were divided in two groups of 18 patients. Both groups continued with the initial treatment for further 4 weeks, but the first group received also placebo whereas the second group received oral theophylline. The combination therapy with formoterol+tiotropium induced a significant improvement in mean predose FEV(1) and FVC at the end of the first period, and a significant reduction in dyspnea score as measure by a visual analogic scale and in use of rescue salbutamol. The second period of treatment elicited a significant further improvement in lung function and reduction in dyspnea score and salbutamol use in both groups. On the contrary, differences in improvements in FEV(1) and FVC and reduction in dyspnea score and salbutamol use between theophylline and placebo arms at the end of the second treatment period were not significant, although 5 patients reported an important relief in dyspnea during the theophylline administration period. These findings question the importance of adding theophylline in stable COPD patients already treated with two long-acting bronchodilators, but also indicate the possibility that some of them can benefit from theophylline because of a symptomatic improvement.

Topics: Aged; Albuterol; Bronchodilator Agents; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Dyspnea; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Male; Middle Aged; Pilot Projects; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Single-Blind Method; Theophylline; Tiotropium Bromide; Treatment Outcome; Vital Capacity

Exercise limitation and exertional dyspnea are important symptoms of chronic obstructive pulmonary disease (COPD), which may be partially relieved by tiotropium. Although the mechanism of relief is multifactorial, improved dynamic ventilatory mechanics appear to be important. It is not however known whether tiotropium may also act by improving cardiovascular function during exercise.. We conducted a randomized, placebo-controlled crossover study in 18 COPD subjects with a FEV(1) 40+/-3% predicted (mean+/-SEM). Subjects inhaled either tiotropium 18 microg or placebo once daily for 7-10 days then the other intervention for a further 7-10 days after a 35-day washout period. Subjects performed constant work rate cycle exercise at 75% of maximum after each treatment period. Heart rate, blood pressure, oxygen uptake, operating lung volumes and breathing pattern were measured.. Heart rate was 7 beats/min lower at rest and throughout exercise with tiotropium compared to placebo (p=0.001). Oxygen uptake was unchanged throughout exercise. Oxygen pulse on exercise was greater by 7.4% (p<0.01) and systolic blood pressure was lower by 7 mmHg (p=0.03). The cardiac rate pressure product was reduced by 7.6% (p<0.01) with tiotropium. Exercise endurance tended to be greater with tiotropium. Reduction in heart rate on exercise correlated with an increase in inspiratory reserve volume (r=-0.50, p=0.04).. Tiotropium may improve cardiac as well as pulmonary function during exercise in COPD. We suggest that this effect may be due, in part, to improved cardiopulmonary interaction as a result of mechanical unloading of the ventilatory muscles however further study is required.

Topics: Blood Pressure; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Dyspnea; Exercise Test; Exercise Tolerance; Female; Heart Rate; Humans; Male; Middle Aged; Oxygen Consumption; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

During constant-work-rate exercise in chronic obstructive pulmonary disease, dyspnea increases steeply once inspiratory reserve volume (IRV) falls to a critical level that prevents further expansion of tidal volume (Vt). We studied the effects of this mechanical restriction on the quality and intensity of exertional dyspnea and examined the impact of an anticholinergic bronchodilator. In a randomized, double-blind, crossover study, 18 patients with chronic obstructive pulmonary disease (forced expiratory volume in 1 s = 40 +/- 3%predicted; mean +/- SE) inhaled tiotropium 18 mug or placebo once daily for 7-10 days each. Pulmonary function tests and symptom-limited cycle exercise at 75% of each patient's maximal work capacity were performed 2 h after dosing. Dyspnea intensity (Borg scale), operating lung volumes, breathing pattern, and esophageal pressure (n = 11) were measured during exercise. Dynamic hyperinflation reached its maximal value early in exercise and was associated with only mild increases in dyspnea intensity and the effort-displacement ratio, which is defined as the ratio between tidal swings of esophageal pressure (expressed relative to maximum inspiratory pressure) and Vt (expressed relative to predicted vital capacity). After a minimal IRV of 0.5 +/- 0.1 liter was reached, both dyspnea and the effort-displacement ratio rose steeply until an intolerable level was reached. Tiotropium did not alter dyspnea-IRV relationships, but the increase in resting and exercise inspiratory capacity was associated with an improved effort-displacement ratio throughout exercise. Once a critically low IRV was reached during exercise, dyspnea rose with the disparity between respiratory effort and the Vt response. Changes in dyspnea intensity after tiotropium were positively correlated with changes in this index of neuromechanical coupling.

Topics: Administration, Inhalation; Bronchodilator Agents; Double-Blind Method; Dyspnea; Exercise; Exercise Test; Female; Humans; Male; Middle Aged; Physical Exertion; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation; Respiratory Mechanics; Scopolamine Derivatives; Tiotropium Bromide

Use of maintenance bronchodilator therapy is currently recommended in symptomatic patients with Chronic obstructive pulmonary disease (COPD) and in those with Stage II or greater COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Because no prospective data describe when rescue therapy alone is insufficient or the optimal time to start maintenance therapy, it is unclear whether maintenance therapy has benefits in milder disease. To explore potential benefits we asked: Does once-daily tiotropium improve lung function, health status, and/or symptoms in "undertreated" COPD patients (i.e., those who are not receiving maintenance bronchodilator therapy) or patients considered by their health care providers as having milder disease?. A post-hoc analysis of data from COPD patients participating in two, 1-year, placebo-controlled trials with tiotropium was performed. Patients were defined as "undertreated" if they received no respiratory medication or only as-needed short-acting beta-agonists prior to enrollment. Measures included serial spirometry, Transition Dyspnea Index (TDI), and St. George's Respiratory Questionnaire (SGRQ).. Of 921 patients enrolled, 218 (23.7%) were "undertreated": 130 received tiotropium; 88 received placebo. Demographics for the two treatment groups were comparable. Tiotropium-treated patients had significantly improved forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) compared with patients using placebo on all study days. Additionally, TDI and SGRQ scores significantly improved with tiotropium compared with placebo.. Once-daily tiotropium provides significant improvement in lung function, health status, and dyspnea when used as maintenance therapy in undertreated COPD patients who were not previously receiving maintenance bronchodilator therapy.

Topics: Aged; Bronchodilator Agents; Double-Blind Method; Dyspnea; Female; Forced Expiratory Volume; Health Status; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome; Vital Capacity

Pulmonary rehabilitation (PR) improves exercise tolerance in COPD patients. Tiotropium is a once-daily, inhaled anticholinergic bronchodilator that provides sustained 24-h improvements in airflow and lung hyperinflation reduction. We hypothesized that ventilatory mechanics improvements from tiotropium would permit enhanced ability to train muscles of ambulation and therefore augment exercise tolerance benefits of PR.. In a randomized, double-blind, placebo-controlled trial (tiotropium, n = 47; placebo, n = 44), tiotropium (18 microg qd) was administered to COPD patients participating in 8 weeks of PR (treadmill training three times a week; >/= 30 min per session) at 17 sites. Study drug was administered 5 weeks prior to, 8 weeks during, and 12 weeks following PR. The primary end point was treadmill walking (0% incline) endurance time at 80% of maximum speed attained in an initial incremental test. The transition dyspnea index (TDI), St. George's respiratory questionnaire (SGRQ), and rescue albuterol use were secondary end points.. Mean age of the 93 participants was 67 years, 57% were men, and mean FEV(1) was 0.88 L (34% predicted).. Mean endurance time differences (tiotropium minus placebo) prior to PR, at the end of PR, and 12 weeks after PR were 1.65 min (p = 0.183), 5.35 min (p = 0.025), and 6.60 min (p = 0.018), respectively. Mean TDI focal scores at the end of PR were 1.75 for tiotropium and 0.91 for placebo (p > 0.05). At 12 weeks after PR, TDI focal scores were 1.75 for tiotropium and 0.08 for placebo (p < 0.05). Relative to placebo, tiotropium improved SGRQ total scores by 3.86 at the end of PR and 4.44 at 12 weeks after PR (p > 0.05). Mean albuterol use declined following PR plus tiotropium, compared to PR alone (p

Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Bronchodilator Agents; Cholinergic Antagonists; Double-Blind Method; Dyspnea; Exercise Test; Exercise Therapy; Exercise Tolerance; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Scopolamine Derivatives; Tiotropium Bromide; Vital Capacity

The aim of this study was to test the hypothesis that use of tiotropium, a new long-acting anticholinergic bronchodilator, would be associated with sustained reduction in lung hyperinflation and, thereby, would improve exertional dyspnoea and exercise performance in patients with chronic obstructive pulmonary disease. A randomised, double-blind, placebo-controlled, parallel-group study was conducted in 187 patients (forced expiratory volume in one second 44 +/- 13% pred): 96 patients received 18 microg tiotropium and 91 patients received placebo once daily for 42 days. Spirometry, plethysmographic lung volumes, cycle exercise endurance and exertional dyspnoea intensity at 75% of each patient's maximal work capacity were compared. On day 42, the use of tiotropium was associated with the following effects at pre-dose and post-dose measurements as compared to placebo: vital capacity and inspiratory capacity (IC) increased, with inverse decreases in residual volume and functional residual capacity. Tiotropium increased post-dose exercise endurance time by 105 +/- 40 s (21%) as compared to placebo on day 42. At a standardised time near end-exercise (isotime), IC, tidal volume and minute ventilation all increased, whilst dyspnoea decreased by 0.9 +/- 0.3 Borg scale units. In conclusion, the use of tiotropium was associated with sustained reductions of lung hyperinflation at rest and during exercise. Resultant increases in inspiratory capacity permitted greater expansion of tidal volume and contributed to improvements in both exertional dyspnoea and exercise endurance.

Topics: Aged; Analysis of Variance; Cholinergic Antagonists; Double-Blind Method; Dyspnea; Exercise Test; Exercise Tolerance; Female; Humans; Lung Volume Measurements; Male; Middle Aged; Physical Endurance; Plethysmography; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Spirometry; Tiotropium Bromide

Ths object of this study was to examine validity, meaningful effect sizes, and patterns of response of the Transition Dyspnea Index (TDI) in a clinical trial cohort of chronic obstructive pulmonary disease (COPD) patients. The design was a retrospective analysis of data from a randomized, double-blind placebo-controlled clinical trial. We analyzed fifty clinical investigation sites in United States. There were 921 patients with stable COPD. Tiotropium 18 microg dry powder or matching placebo was used. Patients were allowed to remain on usual care less ipratropium bromide. Construct validity was demonstrated by significant correlations (P <.05) between Baseline Dyspnea Index (BDI) and other baseline measures, as well as between TDI and changes in other measures at the end of 1 year. Concurrent validity was observed by the significant correlation between TDI and dyspnea diary responses. Changes in TDI focal score were in the range of one unit when the group was stratified by a minimal change in the physician's global evaluation. Significantly less (P <.05) supplemental albuterol was observed in the group of responders defined by a one-unit improvement in TDI. Responders also had few exacerbations and better health status. The validity of the TDI is supported in a large clinical trial setting. A one-unit change in the TDI focal score represented the minimal important difference.

Topics: Adult; Aged; Aged, 80 and over; Bronchodilator Agents; Double-Blind Method; Dyspnea; Female; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Scopolamine Derivatives; Severity of Illness Index; Tiotropium Bromide; Treatment Outcome

A study was undertaken to record exacerbations and health resource use in patients with COPD during 6 months of treatment with tiotropium, salmeterol, or matching placebos.. Patients with COPD were enrolled in two 6-month randomised, placebo controlled, double blind, double dummy studies of tiotropium 18 micro g once daily via HandiHaler or salmeterol 50 micro g twice daily via a metered dose inhaler. The two trials were combined for analysis of heath outcomes consisting of exacerbations, health resource use, dyspnoea (assessed by the transitional dyspnoea index, TDI), health related quality of life (assessed by St George's Respiratory Questionnaire, SGRQ), and spirometry.. 1207 patients participated in the study (tiotropium 402, salmeterol 405, placebo 400). Compared with placebo, tiotropium but not salmeterol was associated with a significant delay in the time to onset of the first exacerbation. Fewer COPD exacerbations/patient year occurred in the tiotropium group (1.07) than in the placebo group (1.49, p<0.05); the salmeterol group (1.23 events/year) did not differ from placebo. The tiotropium group had 0.10 hospital admissions per patient year for COPD exacerbations compared with 0.17 for salmeterol and 0.15 for placebo (not statistically different). For all causes (respiratory and non-respiratory) tiotropium, but not salmeterol, was associated with fewer hospital admissions while both groups had fewer days in hospital than the placebo group. The number of days during which patients were unable to perform their usual daily activities was lowest in the tiotropium group (tiotropium 8.3 (0.8), salmeterol 11.1 (0.8), placebo 10.9 (0.8), p<0.05). SGRQ total score improved by 4.2 (0.7), 2.8 (0.7) and 1.5 (0.7) units during the 6 month trial for the tiotropium, salmeterol and placebo groups, respectively (p<0.01 tiotropium v placebo). Compared with placebo, TDI focal score improved in both the tiotropium group (1.1 (0.3) units, p<0.001) and the salmeterol group (0.7 (0.3) units, p<0.05). Evaluation of morning pre-dose FEV(1), peak FEV(1) and mean FEV(1) (0-3 hours) showed that tiotropium was superior to salmeterol while both active drugs were more effective than placebo.. Exacerbations of COPD and health resource usage were positively affected by daily treatment with tiotropium. With the exception of the number of hospital days associated with all causes, salmeterol twice daily resulted in no significant changes compared with placebo. Tiotropium also improved health related quality of life, dyspnoea, and lung function in patients with COPD.

Topics: Administration, Inhalation; Albuterol; Bronchodilator Agents; Double-Blind Method; Dyspnea; Female; Forced Expiratory Volume; Hospitalization; Humans; Male; Metered Dose Inhalers; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Salmeterol Xinafoate; Scopolamine Derivatives; Tiotropium Bromide; Vital Capacity

To compare the bronchodilator efficacy and safety of tiotropium and placebo.. A 3-month, randomized, double-blind, placebo-controlled, multicenter trial.. Outpatient.. Four hundred seventy patients with stable COPD (mean FEV(1) = 38.6% predicted).. Tiotropium 18 microg (N = 279) or placebo (N = 191) given once daily via a lactose-based dry-powder inhaler device.. Spirometry was evaluated on days 1, 8, 50, and 92. Data were expressed as the mean trough (ie, before morning dose; 23 to 24 h after previous dose) and average response observed in the 3 h after the dose was received. Tiotropium produced significant improvement in trough FEV(1) and FVC, averaging 12% greater than baseline on day 8; these improvements were maintained on days 50 and 92. The average postdose FEV(1) was 16% greater than baseline on day 1 and 20% greater than baseline on day 92; FVC was 17% greater than baseline on day 1 and 19% greater than baseline on day 92. Tiotropium was significantly more effective than placebo in both trough and average FEV(1) and FVC response (p < 0.001). These spirometric effects were corroborated by significant improvements in daily morning and evening peak expiratory flow rate, as well as a reduction in "as-needed" albuterol use. Symptoms of wheezing and shortness of breath were significantly less in patients receiving tiotropium, and the physician global assessment noted overall improvements with those treated with tiotropium relative to placebo. The most common reported adverse event after tiotropium was dry mouth (9.3% vs 1.6% relative to placebo; p < 0.05).. These data demonstrate that tiotropium is a safe and effective once-daily anticholinergic bronchodilator and should prove useful as first-line maintenance therapy in COPD.

Topics: Aged; Albuterol; Bronchodilator Agents; Cholinergic Antagonists; Double-Blind Method; Dyspnea; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Lung; Lung Diseases, Obstructive; Male; Nebulizers and Vaporizers; Peak Expiratory Flow Rate; Placebos; Respiratory Sounds; Safety; Scopolamine Derivatives; Spirometry; Tiotropium Bromide; Vital Capacity; Xerostomia

This study investigated the efficacy and safety of budesonide/formoterol (B/F) and tiotropium combination in the management of chronic obstructive pulmonary disease (COPD) in Chinese patients.Between January 2015 and November 2017, 113 eligible Chinese patients with COPD were included and divided into an intervention group and a control group. Sixty-three patients in the intervention group underwent B/F combined tiotropium, while 50 patients in the control group received tiotropium alone. The primary outcome was severity of dyspnea on exertion (DOE), measured by the 6-minute walk test (6MWT) scale. The secondary outcomes included lung function, measured by the forced expiratory volume in 1 second (FEV1), quality of life, measured by the St. George's Respiratory Questionnaire (SGRQ), and adverse events. All outcomes were measured at the end of 12-week treatment.B/F and tiotropium combination showed greater efficacy in DOE (P < .01), lung function (P < .01), and quality of life (P < .01), compared with tiotropium alone at the end of 12-week treatment. In addition, adverse events in both groups were similar and tolerable.The findings suggest that B/F and tiotropium combination can be used as an effective treatment in Chinese patients with COPD.

Topics: Aged; Anti-Asthmatic Agents; Asian People; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Drug Therapy, Combination; Dyspnea; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory Function Tests; Retrospective Studies; Severity of Illness Index; Tiotropium Bromide; Treatment Outcome; Walk Test

The long-acting muscarinic antagonist tiotropium received an indication for the treatment of asthma from the FDA in 2015.. This paper summarizes much of the published findings on tiotropium and asthma and explores the heterogeneity of the asthma population vis-à-vis recent changes in guidelines for management of COPD. The accompanying case study provides an illustration of how tiotropium might be added to a patient's regimen appropriately.. Tiotropium has been shown in many studies to be beneficial to patients with asthma as an add-on medication. It should be considered as an agent by the clinician managing patients with both allergic and non-allergic asthma.

Topics: Administration, Inhalation; Asthma; Cholinergic Agents; Dyspnea; Female; Guidelines as Topic; Humans; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quality of Life; Tiotropium Bromide

Micronodular lesions are common findings in lung imaging. As an important differential diagnosis, we describe a case of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia; it is notable that the diagnosis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia is often delayed. This case provides supporting evidence to establish lung biopsy by cryotechnique as the option of first choice when considering a diagnostic strategy for micronodular lung lesions.. We report a case of a 65-year-old white woman who presented with obstructive symptoms of chronic coughing and dyspnea confirmed by conventional lung function tests. A computed tomography scan presented disseminated micronodules in all the lobes of her lungs. With the help of bronchoscopic cryobiopsy it was possible to obtain a high yield sample of lung parenchyma. On histologic examination, the micronodules correlated with a diffuse neuroendocrine cell hyperplasia. In the context of clinical symptoms, radiological aspects, and histomorphological aspects we made the diagnosis of a diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Obstructive symptoms were treated with inhaled steroids and beta-2-mimetics continuously. A comparison between current computed tomography scans of our patient and scans of 2014 revealed no significant changes. Last ambulatory checks occurred in January and May of 2016. The course of disease and the extent of limitation of lung function have remained stable.. The diagnosis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia is best made in a multidisciplinary review including clinical presentation, lung imaging, and histomorphological aspects. This report and current literature indicate that transbronchial lung cryobiopsy can be used as a safe and practicable tool to obtain high quality biopsies of lung parenchyma in order to diagnose micronodular lesions of the lung.

Topics: Aged; Albuterol; Anti-Inflammatory Agents; Biopsy; Bronchodilator Agents; Budesonide; Cough; Cryosurgery; Dyspnea; Female; Formoterol Fumarate; Humans; Hyperplasia; Lung; Lung Diseases, Interstitial; Neuroendocrine Cells; Prognosis; Respiratory Function Tests; Thoracic Surgery, Video-Assisted; Tiotropium Bromide; Tomography, X-Ray Computed; Treatment Outcome

Although the prevalence of chronic obstructive pulmonary disease (COPD) increases with age, no specific therapeutic approaches are available till date for the elderly population.. To assess the efficacy and safety of once-daily indacaterol 150 and 300 μg in elderly patients with moderate to severe COPD.. Data were pooled from 11 randomized, double-blind, placebo- and active-controlled studies (8445 patients with COPD). The patient population was stratified into age groups: young (≥40-<65 years; 52.3%), elderly (≥65-<75 years; 36.4%), and very elderly (≥75 years; 11.4%). The efficacy outcomes included improvements in trough forced expiratory volume in 1 s (FEV. At Week 12, the mean improvement in FEV. This pooled analysis suggests that the efficacy and safety of indacaterol treatment is similar between elderly and younger patients with COPD.

Topics: Adrenergic beta-2 Receptor Agonists; Aged; Aged, 80 and over; Bronchodilator Agents; Clinical Trials, Phase III as Topic; Double-Blind Method; Dyspnea; Female; Forced Expiratory Volume; Formoterol Fumarate; Health Status; Humans; Indans; Male; Middle Aged; Netherlands; Prevalence; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic; Salmeterol Xinafoate; Severity of Illness Index; Smoking; Tiotropium Bromide; Treatment Outcome; Vital Capacity

Poor adherence to inhaled medications in COPD patients seems to be associated with an increased risk of death and hospitalization. Knowing the determinants of nonadherence to inhaled medications is important for creating interventions to improve adherence.. To identify disease-specific and health-related quality of life (HRQoL) factors, associated with adherence to inhaled corticosteroids (ICS) and tiotropium in COPD patients.. Adherence of 795 patients was recorded over 3 years and was deemed optimal at >75%-≤125%, suboptimal at ≥50%-<75%, and poor at <50% (underuse) or >125% (overuse). Health-related quality of life was measured with the Clinical COPD Questionnaire and the EuroQol-5D questionnaire.. Patients with a higher forced expiratory volume in 1 second (FEV1)/vital capacity (VC) (odds ratio [OR] =1.03) and ≥1 hospitalizations in the year prior to inclusion in this study (OR =2.67) had an increased risk of suboptimal adherence to ICS instead of optimal adherence. An increased risk of underuse was predicted by a higher FEV1/VC (OR =1.05). Predictors for the risk of overuse were a lower FEV1 (OR =0.49), higher scores on Clinical COPD Questionnaire-question 3 (anxiety for dyspnea) (OR =1.26), and current smoking (OR =1.73). Regarding tiotropium, predictors for suboptimal use were a higher FEV1/VC (OR =1.03) and the inability to perform usual activities as asked by the EuroQol-5D questionnaire (OR =3.09). A higher FEV1/VC also was a predictor for the risk of underuse compared to optimal adherence (OR =1.03). The risk of overuse increased again with higher scores on Clinical COPD Questionnaire-question 3 (OR =1.46).. Several disease-specific and quality of life factors are related to ICS and tiotropium adherence, but a clear profile of a nonadherent patient cannot yet be outlined. Overusers of ICS and tiotropium experience more anxiety.

Topics: Activities of Daily Living; Administration, Inhalation; Adrenal Cortex Hormones; Aged; Anxiety; Bronchodilator Agents; Chi-Square Distribution; Cholinergic Antagonists; Dyspnea; Female; Forced Expiratory Volume; Humans; Lung; Male; Medication Adherence; Middle Aged; Multivariate Analysis; Netherlands; Odds Ratio; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Quality of Life; Risk Factors; Smoking; Surveys and Questionnaires; Time Factors; Tiotropium Bromide; Treatment Outcome; Vital Capacity

Guidelines for chronic obstructive pulmonary disease (COPD) recommend that treatment choices be based partly on symptoms.. A post-hoc analysis of pooled data from clinical studies compared the efficacy and safety of once-daily inhaled bronchodilators indacaterol (150 and 300 μg) and open-label tiotropium (18 μg) according to baseline dyspnoea severity on the modified Medical Research Council (mMRC) scale in patients with COPD (mMRC scores <2 = 'less dyspnoea'; scores ≥2 = 'more dyspnoea'). Outcomes were assessed after 26 weeks.. The analysis included 3177 patients. In patients with less dyspnoea: indacaterol (both doses) improved 24-h post-dose ('trough') forced expiratory volume in 1 s (FEV1), transition dyspnoea index (TDI) and St George's Respiratory Questionnaire (SGRQ) total scores at week 26 and reduced the risk of COPD exacerbations vs placebo; and open-label tiotropium improved trough FEV1 and TDI total score vs placebo at week 26. In patients with more dyspnoea: indacaterol (both doses) improved trough FEV1, TDI and SGRQ total scores at week 26; indacaterol 300 μg was the only treatment to improve the TDI total score by more than the minimum clinically important difference (≥1 point) vs placebo; and open-label tiotropium improved trough FEV1, TDI total score at week 26 and decreased the risk of COPD exacerbations vs placebo. In both subgroups, all treatments were well tolerated.. In patients with less dyspnoea, all treatments had similar effects. Indacaterol 300 μg may be a useful treatment option for patients with COPD who experience more severe breathlessness.

Topics: Bronchodilator Agents; Delayed-Action Preparations; Dose-Response Relationship, Drug; Dyspnea; Forced Expiratory Volume; Humans; Indans; Patient Acuity; Pulmonary Disease, Chronic Obstructive; Quinolones; Randomized Controlled Trials as Topic; Scopolamine Derivatives; Tiotropium Bromide

Recently, tiotropium Respimat® Soft Mist™ Inhaler has been developed. Respimat is a multidose and propellant-free kit. The aerosol generated from Respimat improved lung drug deposition and required a lower dose of drug than HandiHaler®. The aim of this study is to assess the effect of switching from tiotropium HandiHaler to Respimat in patients with chronic obstructive pulmonary disease (COPD).. Thirty-four patients with COPD who received 18 μg of tiotropium delivered by the HandiHaler once daily were enrolled in this study between May and September 2010. Symptoms, adverse events, pulmonary functions, and usability of inhaler devices were assessed before and 12 weeks after switching from HandiHaler to 5 μg of tiotropium delivered by the Respimat. Symptoms and adverse events were also assessed 4 and 12 weeks after switching. Dyspnea was evaluated using the British Medical Research Council dyspnea scale. The usability of inhaler devices was scored using a 12-step checklist.. Twenty-nine patients were followed until 12 weeks after switching. The median FEV1 (forced expiratory volume in 1 sec) values before and 12 weeks after switching to Respimat were 1.41 L and 1.60 L, respectively. Dry mouth appeared to improve after switching to Respimat. Cough just after inhalation was observed in seven patients until 4 weeks after switching. However, six patients overcame cough as they got used to Respimat. Regarding the handling of inhaler devices, patients were not good at breathing out before inhalation and holding their breath just after inhalation both with HandiHaler and with Respimat. However, in general, both inhalers were considered to be easy to use. Twenty-one patients replied that handling of Respimat was easier than that of HandiHaler.. There was no major problem in switching from tiotropium HandiHaler to Respimat. Respimat and HandiHaler showed similar effects and usability. However, we should be aware of cough just after inhalation with Respimat.

Topics: Administration, Inhalation; Aged; Aged, 80 and over; Bronchodilator Agents; Cohort Studies; Cough; Dyspnea; Equipment Design; Follow-Up Studies; Forced Expiratory Volume; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide; Xerostomia

Topics: Bronchodilator Agents; Dyspnea; Humans; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide; Withholding Treatment

The Visual Simplified Respiratory Questionnaire (VSRQ) was designed to assess health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD). It contains eight items: dyspnea, anxiety, depressed mood, sleep, energy, daily activities, social activities and sexual life. Psychometric properties were assessed during a clinical trial that evaluated the impact of tiotropium on HRQoL of COPD patients. These included the determination of structure, internal consistency reliability, concurrent validity with the St George's Respiratory Questionnaire (SGRQ), test - retest reliability, clinical validity and responsiveness to change over two weeks. Minimal important difference (MID) was calculated; cumulative response curves (CRC) were based on the dyspnea item. Psychometric analyses showed that VSRQ structure was unidimensional. The questionnaire demonstrated good internal consistency reliability (Cronbach's alpha = 0.84), good concurrent validity with SGRQ (Spearman = -0.70) and clinical validity, good test-retest reproducibility (ICC = 0.77), and satisfactory responsiveness (standardized response mean = 0.57; Guyatt's statistic = 0.63). MID was 3.4; CRC median value of the 'minimally improved' patients was 3.5. In conclusion, VSRQ brevity and satisfactory psychometric properties make it a good candidate for large studies to assess HRQoL in COPD patients. Further validation is needed to extend its use in clinical practice.

Topics: Activities of Daily Living; Aged; Anxiety; Cholinergic Antagonists; Depression; Dyspnea; Female; Humans; Lung; Male; Middle Aged; Psychometrics; Pulmonary Disease, Chronic Obstructive; Quality of Life; Reproducibility of Results; Respiration; Scopolamine Derivatives; Severity of Illness Index; Sexual Behavior; Sleep; Social Behavior; Surveys and Questionnaires; Time Factors; Tiotropium Bromide; Treatment Outcome

Topics: Arrhythmias, Cardiac; Bronchodilator Agents; Dyspnea; Forced Expiratory Volume; Humans; Pulmonary Disease, Chronic Obstructive; Quality of Life; Scopolamine Derivatives; Smoking; Smoking Cessation; Tiotropium Bromide

The use of one or more long-acting bronchodilators is key in the maintenance therapy of chronic obstructive pulmonary disease (COPD). This analysis pooled the results of two double-blind studies evaluating the efficacy and safety of adding nebulized formoterol fumarate inhalation solution (FFIS) to maintenance tiotropium (TIO) treatment.. Following a run-in period of 7-14 days with once-daily TIO 18 microg, COPD subjects (> or =25% to <65% predicted forced expiratory volume in 1 second [FEV(1)]) were randomized to twice-daily FFIS 20 microg (n=145) or nebulized placebo (PLA, n=140) while continuing on maintenance TIO for 6 weeks. Efficacy was measured using serial spirometry, transition dyspnea index (TDI), rescue albuterol use, and St. George's Respiratory Questionnaire (SGRQ).. The mean standardized area under the curve for FEV(1) over 3 hours (FEV(1)AUC(0-3)), the primary efficacy variable, was significantly higher in the FFIS/TIO group than the PLA/TIO group on day 1 (140 mL difference, P<0.0001) and week 6 (192 mL difference, P<0.0001). Mean TDI scores in the FFIS/TIO and PLA/TIO groups were 1.97 and 0.67, respectively (P=0.0001). Mean albuterol use declined in the FFIS/TIO group from 2.6 to 1.5 puffs/day compared with little change in the PLA/TIO group (P<0.0001). SGRQ scores were similar between treatment groups with the exception of the symptoms score, which improved in the FFIS/TIO group (-5.8) compared with PLA/TIO (-1.0), and more FFIS/TIO-treated subjects experienced a clinically significant improvement in total SGRQ score. More PLA/TIO-treated subjects than FFIS/TIO-treated subjects experienced adverse events (AEs) (45.7% vs. 31.0%) and COPD exacerbations (7.9% vs. 3.4%).. The addition of FFIS to maintenance TIO treatment for moderate to severe COPD results in significantly improved FEV(1) and dyspnea, decreased rescue medication use, and a lower incidence of AEs and COPD exacerbations. The addition of FFIS to TIO yields clinically and statistically significant benefits for COPD patients and might be of long-term benefit.

Topics: Aged; Albuterol; Bronchodilator Agents; Double-Blind Method; Drug Therapy, Combination; Dyspnea; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic; Respiratory Function Tests; Scopolamine Derivatives; Tiotropium Bromide

Patients with COPD are frequently prescribed inhaled corticosteroids (ICS); however, it is unclear whether the treatment with ICS might modify responses to inhaled bronchodilators. Two 6-month, randomized, placebo-controlled, double-blind, double-dummy, parallel-group studies of tiotropium 18 microg once daily, compared with salmeterol, 50 microg bid, had been conducted in patients with moderate-to-severe COPD. Efficacy was assessed by spirometry, transition dyspnea index (TDI), St. George's Respiratory Questionnaire (SGRQ), and exacerbations. Data from both studies were combined to form subgroups with regard to concurrent use of ICS. 796 patients receiving ICS were separately analyzed from 390 patients not receiving ICS. Mean age was 64 years, and pre-bronchodilator FEV1 was 1.06 L (ICS group) and 1.13 L (non-ICS group). Both bronchodilators increased morning mean +/- SE pre-dose FEV1 compared with placebo (ICS groups: tiotropium 110 +/- 20 mL, salmeterol 80 +/- 20 mL; non-ICS groups: tiotropium 150 +/- 30 mL, salmeterol 110 +/- 30 mL; p > 0.05 for tiotropium vs salmeterol). Improvements in TDI and SGRQ and frequency of exacerbations also tended to be more profound for tiotropium. Treatment with tiotropium in patients with moderate-to-severe COPD was superior to salmeterol in lung function, irrespective of concurrent use of ICS.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Adult; Albuterol; Bronchodilator Agents; Cholinergic Antagonists; Drug Therapy, Combination; Dyspnea; Forced Expiratory Volume; Health Status; Humans; Lung; Middle Aged; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Retrospective Studies; Salmeterol Xinafoate; Scopolamine Derivatives; Time Factors; Tiotropium Bromide; Treatment Outcome

Topics: Airway Resistance; Bronchodilator Agents; Dyspnea; Exercise Test; Functional Residual Capacity; Humans; Inspiratory Capacity; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide

Topics: Bronchodilator Agents; Dyspnea; Evidence-Based Medicine; Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Scopolamine Derivatives; Tiotropium Bromide

Expiratory flow limitation, air-trapping and hyperinflation are well-known problems in COPD patients. Due to dyspnea during exercise COPD patients often avoid physical activity, which is one of the most important parameters of quality of life. In studies with long-acting bronchodilators, e.g., the anticholinergic agent tiotropiumbromide, a reduction of expiratory flow limitation, hyperinflation and dyspnea could be demonstrated. This was followed by an increase in physical activity. Increase in inspiratory capacity and reduction of functional residual capacity correlated well with the improvement of exercise capacity. In conclusion, bronchodilators such as tiotropiumbromide are able to reduce hyperinflation in COPD patients.

Topics: Bronchodilator Agents; Dyspnea; Exercise; Humans; Pulmonary Disease, Chronic Obstructive; Pulmonary Ventilation; Scopolamine Derivatives; Tiotropium Bromide

Dyspnoea is a primary symptom of chronic obstructive pulmonary disease (COPD). The baseline (BDI) and transition (TDI) dyspnoea indices are commonly used instruments to assess breathlessness and the impact of intervention. Its validity and pattern of response in multinational clinical trials has not been established. In a retrospective analysis of a cohort of 997 COPD patients who received tiotropium, salmeterol or placebo, in addition to usual care, the validity and pattern of response of the BDI and TDI were examined. The BDI was significantly correlated with the dyspnoea diary (DD) score and the symptom and activity components of the St. George's respiratory questionnaire (SGRQ), establishing concurrent validity. Furthermore, the TDI was also correlated with the changes in DD, SGRQ symptom and activity scores. Construct validity was established by the association between baseline forced expiratory volume in one second (FEV1) and BDI and AFEVI with TDI. Physician's global evaluation (PGE) was significantly associated with BDI as well as APGE with TDI. Significant correlations have also been observed when the cohorts were classified according to native English and native non-English speaking countries. A change in PGE of 1 category (i.e. 2 units on an 8-point scale) was associated with a mean TDI of approximately 1 unit (0.9-1.3 mean focal score), lending further support to the clinical significance of this change inherent in the instrument's descriptors. TDI responders (i.e. focal score < or = 1 unit) used less supplemental salbutamol, had fewer exacerbations and had significantly improved health status as measured by impacts and total SGRQ scores compared with nonresponders. In conclusion, the transition dyspnoea index is a valid instrument when used in a multinational clinical trial and the patterns of response confirm a 1-unit change in the transition dyspnoea index focal score as being clinically important.

Topics: Albuterol; Bronchodilator Agents; Cohort Studies; Double-Blind Method; Dyspnea; Female; Humans; Internationality; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Retrospective Studies; Salmeterol Xinafoate; Scopolamine Derivatives; Severity of Illness Index; Tiotropium Bromide