tiotropium-bromide and Airway-Obstruction

Many patients with asthma remain symptomatic despite treatment with inhaled corticosteroids (ICS) with or without long-acting β2-agonists (LABAs). Tiotropium add-on to ICS plus a LABA has been shown to improve lung function and reduce exacerbation risk in patients with symptomatic asthma.. To determine whether the efficacy of tiotropium add-on therapy is dependent on patients' baseline characteristics.. Two randomized, double-blind, parallel-group, twin trials (NCT00772538 and NCT00776984) of once-daily tiotropium Respimat(®) 5 μg add-on to ICS plus a LABA were performed in parallel in patients with severe symptomatic asthma. Exploratory subgroup analyses of peak forced expiratory volume in 1 s (FEV1), trough FEV1, time to first severe exacerbation, time to first episode of asthma worsening, and seven-question Asthma Control Questionnaire responder rate were performed to determine whether results were influenced by baseline characteristics.. 912 patients were randomized: 456 received tiotropium and 456 received placebo. Tiotropium improved lung function, reduced the risk of asthma exacerbations and asthma worsening, and improved asthma symptom control, compared with placebo, independent of baseline characteristics including gender, age, body mass index, disease duration, age at asthma onset, and FEV1 % predicted at screening and reversibility.. Once-daily tiotropium 5 μg compared with placebo improved lung function, reduced the risk of asthma exacerbations and asthma worsening, and improved asthma symptom control, independent of a broad range of baseline characteristics, as add-on to ICS plus LABAs in patients with severe symptomatic asthma.. ClinicalTrials.gov; numbers NCT00772538 and NCT00776984 URL: www.clinicaltrials.gov.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Aged; Airway Obstruction; Asthma; Bronchodilator Agents; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Hypersensitivity; Male; Middle Aged; Severity of Illness Index; Smoking; Tiotropium Bromide

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

Some patients with asthma have poorly controlled disease despite the use of high-dose inhaled corticosteroids (ICS), long-acting β2 agonists (LABAs) and antileukotrienes. The aim of the study was to assess the effectiveness of tiotropium as an add-on therapy to the standard treatment with high-dose ICS/LABA on asthma control and lung function in patients with severe asthma.. Of the 633 asthmatic patients, 64 (10.1%) patients with severe asthma who were add-on treated at least for 3 months were evaluated. Number of exacerbations, emergency department visits, hospitalizations and lung functions of patients belonging to 12 months before starting add-on treatment were compared with those of 12 months after starting add-on treatment.. The mean duration of add-on tiotropium treatment was 8.3 ± 0.5 months. For patients with severe asthma that was poorly controlled with standard combination therapy, tiotropium improved asthma control in 42.2%, decreased the number of emergency department visits in 46.9% and decreased the number of hospitalizations in 50.0% of them. The mean baseline forced expiratory volume in 1 s before add-on tiotropium was 57.5 ± 1.9% and forced vital capacity was 74.3 ± 15.6%. However, after 12 months of add-on tiotropium treatment, these rates became 65.5 ± 1.9% and 82.5 ± 15.1%, respectively. The addition of tiotropium significantly improved the percentages of the number of emergency department visits, the number of hospitalizations (P < 0.05).. Our study has suggested that, for patients with poorly controlled asthma despite of the use of ICS/LABA, the addition of tiotropium to standard care may be beneficial.

Topics: Administration, Inhalation; Adult; Aged; Airway Obstruction; Anti-Asthmatic Agents; Asthma; Bronchodilator Agents; Drug Administration Schedule; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Male; Prednisone; Retrospective Studies; Theophylline; Tiotropium Bromide; Treatment Outcome

Topics: Acetates; Administration, Inhalation; Adult; Airway Obstruction; Asthma; Atherosclerosis; Bronchodilator Agents; Bronchoscopy; Child; Cyclopropanes; Glucocorticoids; Humans; Hyperthermia, Induced; Leukotriene Antagonists; Quinolines; Scopolamine Derivatives; Sulfides; Tiotropium Bromide

Inhalation injury contributes to the morbidity and mortality of burn victims. In humans and in an ovine model of combined smoke inhalation and burn injury, bronchospasm and acute airway obstruction contribute to progressive pulmonary insufficiency. This study tests the hypothesis that muscarinic receptor antagonist therapy with tiotropium bromide, an M1 and M3 muscarinic receptor antagonist, will decrease the airway constrictive response and acute bronchial obstruction to improve pulmonary function compared to injured animals without treatment.. Randomized, prospective study involving 32 sheep.. Large-animal intensive care research laboratory.. The study consisted of six groups: a sham group (n=4, instrumented noninjured), a control group (n=6, injured and not treated), and tiotropium bromide-treated groups, including both preinjury and postinjury nebulization protocols. Treatments for these groups included nebulization with 36 μg of tiotropium bromide 1 hr before injury (n=6) and postinjury nebulization protocols of 18 μg (n=6), 36 μg (n=6), and 72 μg (n=4) administered 1 hr after injury. All treated groups received an additional 14.4 μg every 4 hrs for the 24-hr study period.. Pretreatment with tiotropium bromide significantly attenuated the increases in ventilatory pressures, pulmonary dysfunction, and upper airway obstruction that occur after combined smoke inhalation and burn injury. Postinjury treatments with tiotropium bromide were as effective as pretreatment in preventing pulmonary insufficiency, although a trend toward decreased obstruction was present only in all post-treatment conditions. There was no improvement noted in pulmonary function in animals that received a higher dose of tiotropium bromide.. This study describes a contribution of acetylcholine to the airway constrictive and lumenal obstructive response after inhalation injury and identifies low-dose nebulization of tiotropium bromide as a potentially efficacious therapy for burn patients with severe inhalation injury.

Topics: Airway Obstruction; Animals; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Dose-Response Relationship, Drug; Injury Severity Score; Muscarinic Antagonists; Pulmonary Gas Exchange; Random Allocation; Reference Values; Respiratory Distress Syndrome; Respiratory Function Tests; Risk Factors; Scopolamine Derivatives; Sheep; Sheep, Domestic; Smoke Inhalation Injury; Statistics, Nonparametric; Tiotropium Bromide; Treatment Outcome

This study evaluated the bronchodilating activity of the beta(2)-agonist carmoterol and the muscarinic M(3)-antagonist tiotropium, given intratracheally alone or in combination in anaesthetized artificially ventilated normal and actively sensitized guinea-pigs. Carmoterol (0.3-100pmol) and tiotropium (10-1000pmol) were superfused (0.01ml/min) for 5min before challenges with acetylcholine (20mug/kg i.v.), histamine (10mug/kg i.v.) or ovalbumin (5mg/kg i.v.). Both compounds given alone were markedly active against all the challenges. Tiotropium resulted more effective towards cholinergic challenge and carmoterol was very potent against histamine and ovalbumin-induced reaction, being effective already at 1pmol. In the presence of tiotropium, the bronchodilating activity of carmoterol was significantly augmented. The ED(50) value of carmoterol on the acetylcholine challenge was reduced by about 10 and 28 times (0.1 and 0.3pmol of tiotropium), that on the histamine one by 4.5 and 13 times (1 and 3pmol of tiotropium) and that on the ovalbumin-induced one by 8 and 25 times (10 and 30pmol of tiotropium). A positive interaction was also evident when other parameters were evaluated. The histamine-induced release of thromboxane B(2) was markedly reduced (56%, P<0.001) by combining completely ineffective doses of the two drugs (0.3 and 3pmol for carmoterol and tiotropium, respectively). In ovalbumin-challenged animals the time to death, amounting in control animals to 7.2+/-0.9min, was dose-dependently prolonged up to achieve complete protection from death with combination of 1 and 30pmol of carmoterol and tiotropium, respectively. The favorable interaction between carmoterol and tiotropium can represent a good option in the control of bronchopulmonary diseases marked by an increase of airway resistances.

Topics: Acetylcholine; Adrenergic beta-2 Receptor Agonists; Airway Obstruction; Airway Resistance; Amphetamines; Animals; Bronchoconstriction; Bronchodilator Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Guinea Pigs; Histamine; Hydroxyquinolines; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Male; Ovalbumin; Quinolones; Scopolamine Derivatives; Survival Analysis; Thromboxane B2; Tiotropium Bromide; Treatment Outcome