oxitropium and Lung-Diseases--Obstructive

We compare the efficacy including spirometry, peak expiratory flow (PEFR) and quality of life and safety of an 8-week treatment with inhaled oxitropium, theophylline or their combination in patients with mild-to-severe chronic obstructive pulmonary disease (COPD). We conducted a multicentre, double-blind, double-dummy randomized, parallel-group study at 29 Italian outpatients clinics. A group of 236 patients with mild-to-severe COPD (baseline FEV1 < or = 70% of predicted value) were recruited. Treatments were as follows: Inhaled oxitropium bromide 200 microg (N=75), sustained-release oral theophylline 300 mg (N=81) or their combination (N=80), taken twice daily. Spirometry (FEV1 and FVC) was evaluated every 4 weeks, and morning and evening PEFR (before and 2-4 h after drug intake) was measured daily. Symptoms, cough and dysponea, were recorded daily. Health status was evaluated at baseline and week 8 using the disease specific St George' Respiratory Questionnaire (SGRQ). Any adverse event occurring during the treatment period was recorded on a diary card. FEV1 and FVC improved in all the groups at 4 and 8 weeks, but the difference between treatment groups did not reach statistically significant levels. Differences between groups in pre-dosing morning and evening PEFR were not significant. Post-dosing morning and evening PEFR were increased and the largest increase was seen in patients treated with both drugs. However, differences between groups was significant only for evening values (P=0.008). The proportion of patients who experienced a decrease in symptoms was high in all groups but no differences among groups were observed. SGRQ total scores decreased in all treatment groups after 8 weeks, particularly in the oxitropium and combination groups. Clinically significant change (> or = 4 units) was only observed in patients treated with oxitropium bromide whether with or without theophylline. Adverse events related to treatments were higher in the group treated with theophylline alone (P < 0.02). We conclude that inhaled oxitropium bromide alone was associated with an improvement in FEV1, PEFR and symptoms in patients with COPD that was not statistically different from that of oral theophylline alone or of the combination of both drugs. Oxitropium bromide in combination with theophylline provided a greater improvement in evening post-dosing PEFR. Oxitropium bromide alone or in combination with theophylline improved the quality of life better than theophyll

Topics: Aged; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Parasympatholytics; Peak Expiratory Flow Rate; Quality of Life; Scopolamine Derivatives; Spirometry; Theophylline

The purpose of the present study was to compare the characteristics of three different exercise tests in evaluating the effects of oxitropium bromide on exercise performance. Thirty-eight males with stable chronic obstructive pulmonary disease (COPD) (FEV(1) = 40.8 +/- 16.5% predicted; mean +/- SD) completed randomized, double-blind, placebo-controlled, crossover studies for each exercise test. The exercise tests were performed 60 min after the inhalation of either oxitropium bromide 400 microg or placebo. The patients performed 6-min walking tests (6MWT) on Days 1 and 2, progressive cycle ergometry (PCE) on Days 3 and 4, and cycle endurance tests at 80% of the maximal workload of PCE on Days 5 and 6. Spirometry was conducted before and at 45 and 90 min after the inhalation. Oxitropium bromide significantly increased FEV(1) as compared with placebo. Oxitropium bromide increased the endurance time significantly, by 19% (p < 0.001), and caused a small but significant increase in the 6-min walking distance by 1% (p < 0.05), but induced no significant increase in maximal oxygen consumption (V O(2)max) in PCE. The responses in these three exercise tests were different, and we conclude that the endurance test was the most sensitive in detecting the effects of inhaled anticholinergic agents on exercise performance in patients with stable COPD. An endurance procedure may be performed to detect clinical changes in evaluating the effects of oxitropium bromide on exercise performance.

Topics: Administration, Inhalation; Aged; Bronchodilator Agents; Cross-Over Studies; Double-Blind Method; Exercise Test; Humans; Lung Diseases, Obstructive; Lung Volume Measurements; Male; Middle Aged; Parasympatholytics; Physical Endurance; Scopolamine Derivatives

Inhaled anticholinergic drugs are often recommended for use as a first-line therapy for patients with COPD because they provide similar or more effective bronchodilating actions, as well as fewer side effects. It is not known, however, which class of bronchodilators is more advantageous for pulmonary hemodynamics, particularly during exercise.. To compare the effects of oxitropium and fenoterol on pulmonary hemodynamics in patients with COPD at rest and during exercise.. The study participants consisted of 20 consecutive male patients with stable COPD, a mean (+/- SD) age of 68+/-8 years old, and an FEV1/FVC ratio of 47.5+/-10.0%.. Eleven patients inhaled two puffs of oxitropium, and nine patients inhaled two puffs of fenoterol. Seven members of each group performed incremental exercise using a cycle ergometer. The hemodynamic measurements with right heart catheterization were performed by taking the average of three consecutive respiratory cycles before and after the administration of inhaled bronchodilators at rest and during exercise.. At rest, despite a similar improvement of spirometric data with the two drugs, fenoterol, not oxitropium, caused significant increases in heart rate and cardiac output, a decrease in pulmonary vascular resistance, and a deteriorated Pao2. During exercise, however, both drugs similarly attenuated elevations in the mean pulmonary arterial pressure (40+/-12 to 38+/-10 mm Hg by oxitropium, and 41+/-9 to 36+/-9 mm Hg by fenoterol), the mean pulmonary capillary wedge pressure, and the mean right atrial pressure.. Our findings indicate that both classes of bronchodilators are equally beneficial in the attenuation of right heart afterload during exercise in patients with COPD.

Topics: Administration, Inhalation; Bronchodilator Agents; Carbon Dioxide; Exercise; Exercise Test; Fenoterol; Hemodynamics; Humans; Lung Diseases, Obstructive; Male; Oxygen; Parasympatholytics; Respiration; Scopolamine Derivatives; Spirometry

The effects of the long-acting beta(2)-agonist formoterol, the anticholinergic drug oxitropium bromide, and their combination were compared in 16 patients with partially reversible stable COPD. On each of 4 study days patients inhaled both drugs separated by 180 min in alternate sequence, with formoterol being administered in two doses (formoterol 12 microg + oxitropium bromide 200 microg; oxitropium bromide 200 microg + formoterol 12 microg; formoterol 24 microg + oxitropium bromide 200 microg; oxitropium bromide 200 microg + formoterol 24 microg). FEV(1)and FVC were measured baseline and after 30, 60, 120, 180, 210, 240, 300 and 360 min. In terms of onset of action, formoterol performed better than oxitropium bromide. Within the first 180 min after inhalation formoterol 24 microg was the most effective drug (maximal change in FEV(1): formoterol 24 microg = 25.6%, formoterol 12 microg = 21.1%, oxitropium bromide = 18.2%). Increased bronchodilation was obtained when the second drug was added, the sequence formoterol 24 microg + oxitropium bromide being the most effective (maximal change in FEV(1)over baseline: formoterol 24 microg + oxitropium bromide 28.8%, oxitropium bromide + formoterol 24 microg 20.9%, formoterol 12 microg + oxitropium bromide 26.6%, oxitropium bromide + formoterol 12 microg 22.5%). Significant improvement in pulmonary function may be achieved by giving two different bronchodilators in stable COPD patients. The sequence formoterol 24 microg + oxitropium bromide 200 microg seems to be the most effective.

Topics: Administration, Inhalation; Aged; Bronchoconstriction; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Parasympatholytics; Scopolamine Derivatives

An earlier study documented that, in patients with chronic obstructive pulmonary disease (COPD), addition of ipratropium bromide at the clinically recommended dose (40 microg) does not produce any further bronchodilation than that achieved with salmeterol 50 microg alone. However, the dose of ipratropium bromide needed to produce near maximal bronchodilation is several times higher than the customary dosage. The full therapeutic potential of combined salmeterol plus an anticholinergic drug can therefore only be established using doses higher than those currently recommended in the marketing of these agents. A study was undertaken to examine the possible acute effects of higher than conventional doses of an anticholinergic agent on the single dose salmeterol induced bronchodilation in patients with stable and partially reversible COPD.. Thirty two outpatients received 50 microg salmeterol or placebo. Two hours after inhalation a dose-response curve to inhaled oxitropium bromide (100 microg/puff) or placebo was constructed using one puff, one puff, two puffs, and two puffs-that is, a total cumulative dose of 600 microg oxitropium bromide. Dose increments were given at 20 minute intervals with measurements being made 15 minutes after each dose. On four separate days all patients received one of the following: (1) 50 microg salmeterol + 600 microg oxitropium bromide; (2) 50 microg salmeterol + placebo; (3) placebo + 600 microg oxitropium bromide; (4) placebo + placebo.. Salmeterol induced a good bronchodilation (mean increase 0.272 l; 95% CI 0.207 to 0.337) two hours after its inhalation. Oxitropium bromide elicited an evident dose-dependent increase in forced expiratory volume in one second (FEV(1)) and this occurred also after pretreatment with salmeterol with a further mean maximum increase of 0.152 l (95% CI of differences 0.124 to 0.180).. This study shows that acute pretreatment with 50 microg salmeterol does not block the possibility of inducing more bronchodilation with an anticholinergic agent when a higher than normal dosage of the muscarinic antagonist is used.

Topics: Administration, Inhalation; Aged; Albuterol; Bronchodilator Agents; Cholinergic Antagonists; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Scopolamine Derivatives; Smoking; Vital Capacity

We examined the influence of higher than conventional doses of oxitropium bromide on formoterol-induced bronchodilation in patients with partially reversible stable COPD. Twenty outpatients inhaled one or two puffs of formoterol (12 microg puff(-1)), or placebo. Two hours after inhalation, a dose-response curve to inhaled oxitropium bromide (100 microg puff(-1)) or placebo was constructed using one puff, one puff, two puffs and two puffs, for a total cumulative dose of 600 microg oxitropium bromide. Doses were given at 20-min intervals and measurements made 15 min after each dose. On six separate days, all patients received one of the following: (1) formoterol 12 microg + oxitropium bromide 600 microg, (2) formoterol 12 microg + placebo, (3) formoterol 24 microg + oxitropium bromide 600 microg, (4) formoterol 24 microg + placebo, (5) placebo + oxitropium bromide 600 microg, or (6) placebo + placebo. Both formoterol 12 microg and 24 microg induced a good bronchodilation (formoterol 12 microg, 0.19-0.20 l; formoterol 24 microg 0.22-0.24 l). The dose-response curve of oxitropium, but not placebo, showed an evident increase in FEV1, with a further significant increase of respectively 0.087 l and 0.082 l after the formoterol 12 microg and formoterol 24 microg pre-treatment. This study shows that improved pulmonary function in patients with stable COPD may be achieved by adding oxitropium 400-600 microg to formoterol. There is not much difference in bronchodilation between combining oxitropium with formoterol 12 microg or 24 microg. In any case, formoterol 24 microg alone seems sufficient to achieve the same bronchodilation induced by oxitropium 600 microg alone in most patients.

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Bronchi; Bronchodilator Agents; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Formoterol Fumarate; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Parasympatholytics; Scopolamine Derivatives; Single-Blind Method

There have been suggestions that corticosteroid treatment might improve bronchodilator responses in chronic obstructive pulmonary disease (COPD). We have studied bronchodilator responses to salbutamol and to oxitropium bromide in 20 patients with stable moderate to severe COPD. Dose responses to the two bronchodilators were tested before and after 3 week courses of placebo and 30 mg prednisolone. Thirteen patients were taking inhaled corticosteroids. There were no significant changes in numbers of responses or maximum bronchodilator effects from either bronchodilator, although there was a trend towards higher maximum levels after 3 weeks of prednisolone. Spirometry measured at home each morning before and after oxitropium bromide showed no difference between prednisolone and placebo periods. This study provides no evidence for a significant effect on bronchodilator responses to beta-agonists or anticholinergic agents from 3 weeks of oral prednisolone in moderately severe COPD.

Topics: Aged; Aged, 80 and over; Albuterol; Bronchodilator Agents; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Forced Expiratory Volume; Glucocorticoids; Humans; Lung; Lung Diseases, Obstructive; Male; Middle Aged; Parasympatholytics; Prednisolone; Scopolamine Derivatives; Smoking

Anti-cholinergic agents are generally regarded as the bronchodilator therapy of first choice in the treatment of stable chronic obstructive pulmonary disease (COPD), considering that they may be more effective than in inhaled beta 2-agonist. However, results of the authors' recent studies conflict to some extent with this suggestion because they demonstrate that this is true only for short acting beta 2-agonists but not for long-acting beta 2-agonists. Oxitropium bromide is an anti-cholinergic drug that has been shown to produce a similar degree of bronchodilation to that obtained with ipratropium bromide, but with a longer-lasting effect. In the present study, the time course of inhaled oxitropium bromide bronchodilation in comparison to that of inhaled salmeterol in a group of patients with partially reversible COPD was evaluated. Twelve male patients with moderate to severe COPD participated in the study. The study had a single-bind, cross-over, randomized design. The bronchodilator activity of 50 micrograms salmeterol hydroxynaphthoate, 200 and 400 micrograms oxitropium bromide and placebo, which were all inhaled from a metered-dose inhaler, was investigated on several non-consecutive days. The highest FVC and FEV1, obtained from one or the other of the reproducible curves, were kept for analysis. Measurements were performed at the following times: immediately before inhalation of treatment, and at 15, 30, 60, 120, 180, 240, 300, 360, 480, 600 and 720 min after inhalation of the individual treatment. Salmeterol tended to have a delayed time to peak effect, but had a longer duration of effect than oxitropium. The response to salmeterol exceeded the response to 200 micrograms oxitropium for 12 h, but its responses were significantly (P < 0.05) greater than those to 200 micrograms oxitropium from 10 to 12 h. From 3 to 12 h, salmeterol also surpassed 400 micrograms oxitropium but differences were not significant (P < 0.05). The mean FEV1 area under the curve was significantly (P < 0.05) larger after salmeterol when compared to 200 micrograms oxitropium bromide, but there was no significant difference (P < 0.05) between salmeterol and 400 micrograms oxitropium bromide. No significant changes in pulse rate, blood pressure or electrocardiograms were found among the four groups as compared with placebo group. These findings confirm and extend what has been demonstrated by the authors' previous studies, and show that salmeterol compares conveniently with anti-

Topics: Aged; Albuterol; Area Under Curve; Bronchodilator Agents; Cross-Over Studies; Dose-Response Relationship, Drug; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Parasympatholytics; Respiratory Function Tests; Salmeterol Xinafoate; Scopolamine Derivatives; Single-Blind Method

We examined whether a pretreatment with formoterol, oxitropium bromide, or salmeterol might modify the dose-response curves to inhaled salbutamol in patients with stable and partially reversible chronic obstructive pulmonary disease (COPD). Sixteen outpatients with partially reversible, stable COPD received 24 microg formoterol, 50 microg salmeterol, 200 microg oxitropium bromide, or placebo on four non-consecutive days. Spirometric testing was performed immediately before inhalation of treatment and after 2 h. A dose-response curve to inhaled salbutamol was then constructed using doses of 100, 100, 200 microg and 400 microg--that is, a total cumulative dose of 800 microg. Dose increments were given at 20 min intervals with measurements being made 15 min after each dose. Formoterol, salmeterol, or oxitropium bromide elicited a significant increase in forced expiratory volume in one second (FEV1) compared with placebo (mean differences (L) = placebo 0.05; formoterol 0.34; salmeterol 0.27; oxitropium bromide 0.23). Dose-dependent increases in FEV1 were seen (mean values (L) before salbutamol and after a cumulative dose of 100, 200, 400, and 800 microg = placebo: 1.06, 1.28, 1.35, 1.39, 1.41; formoterol: 1.33, 1.37, 1.41, 1.44, 1.44; salmeterol: 1.30, 1.33, 1.36, 1.39, 1.42; oxitropium bromide: 1.27, 1.34, 1.37, 1.41, 1.40). Statistical analysis revealed no significant differences in FEV1 and forced vital capacity (FVC) responses to salbutamol after therapy with formoterol, salmeterol, or oxitropium bromide compared with placebo. This study clearly shows that a pretreatment with a conventional dose of formoterol, salmeterol, or oxitropium bromide does not preclude the possibility of inducing a further bronchodilation with salbutamol in patients suffering from partially reversible chronic obstructive pulmonary disease.

Topics: Adrenergic beta-Agonists; Adult; Albuterol; Bronchi; Bronchodilator Agents; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Ethanolamines; Forced Expiratory Volume; Formoterol Fumarate; Heart Rate; Humans; Lung Diseases, Obstructive; Parasympatholytics; Salmeterol Xinafoate; Scopolamine Derivatives; Spirometry; Vital Capacity

To investigate the long-term effects of the inhaled anticholinergic bronchodilator, oxitropium bromide (OTB), on lung function, exercise capacity, and dyspnea in patients with chronic obstructive pulmonary disease (COPD), spirometry and symptom-limited exercise testing before and 1, 6, and 12 months after the regular use of OTB (600 micrograms/day) were performed in 12 patients with the use of OTB (mean age 69.9 +/- 3.1 years; FEV1/FVC 53.3 +/- 1.6%) as well as in 12 control patients who were not treated with OTB (Mean age 68.8 +/- 2.8 years; FEV1/FVC 52.6 +/- 1.9%). The dyspnea was evaluated by the slope of the regression line between Borg scale and oxygen uptake (Vo2) during exercise (Borg scale slope: BSS). At 1, 6, and 12 months after the start of OTB, the forced expiratory volume in one second (FEV1) and the exercise capacity (maximal Vo2) were greater than the pretreatment values and the dyspnea index (BSS) was significantly improved compared with the pretreatment value, while these parameters slightly worsened in the control patients over one year. In conclusion, the chronic use of an inhaled anticholinergic bronchodilator may provide beneficial improvements in expiratory flow rate, exercise performance, and dyspnea in mild to moderate COPD patients over one year.

Topics: Administration, Inhalation; Aged; Cholinergic Antagonists; Dyspnea; Exercise Test; Exercise Tolerance; Follow-Up Studies; Humans; Lung Diseases, Obstructive; Male; Respiratory Function Tests; Scopolamine Derivatives; Treatment Outcome

To test the effects of the inhaled anticholinergic drug, oxitropium bromide (OTB), on exercise capacity and dyspnoea in elderly patients (more than 75 years old) with chronic obstructive pulmonary disease (COPD), we performed cycle exercise testing on 12 elderly patients with COPD [mean age 78.7 (SD 1.1) years; FEV1% 41.3 (2.0)%] as well as 12 middle-aged COPD patients [mean age 60.1 (1.0) years; FEV1% 38.9 (2.4)%] before and after inhalation of OTB or placebo in a double-blind and placebo-controlled design. Spirometry was repeated immediately before and 30 min after OTB or placebo inhalation. Dyspnoea was quantitatively evaluated using the slope of the regression line between Borg scale and oxygen uptake (VO2) during exercise (Borg scale slope: BSS). After OTB inhalation, spirometric indices, exercise capacity as indexed by maximal VO2, and dyspnoea index (BSS) were improved compared with pre-inhalation value in both the elderly and middle-aged patients. The magnitude of improvements in these indices in the elderly patients was not different from that in the middle-aged. We conclude that the inhaled anticholinergic drug produces useful improvements in dyspnoea and exercise capacity in both elderly and middle-aged COPD patients.

Topics: Administration, Inhalation; Aged; Aged, 80 and over; Airway Resistance; Cholinergic Antagonists; Double-Blind Method; Exercise Test; Female; Geriatric Assessment; Humans; Lung Diseases, Obstructive; Lung Volume Measurements; Male; Middle Aged; Quality of Life; Scopolamine Derivatives

Inhaled anticholinergics and beta agonists are widely used in the treatment of patients with chronic obstructive pulmonary disease (COPD). However, dosage requirements have not been thoroughly evaluated and comparative dose-response data for these agents are limited.. Twenty men with stable COPD of mean (SD) age 69.4 (5.8) years and FEV1 0.93 (0.38) litres were studied in randomised, double blind, crossover, placebo controlled experiments. All of the patients received two, four, eight, and 16 puffs of ipratropium bromide (20 micrograms/puff), flutropium bromide (30 micrograms/puff), oxitropium bromide (100 micrograms/puff), fenoterol (200 micrograms/puff), or placebo in random order on five separate days. Doses were administered by a metered dose inhaler at intervals of 60 minutes to give cumulative doses of two, six, 14, and 30 puffs. Five mg of nebulised salbutamol was administered 60 minutes after the patient had received the final 16 puffs of each regimen. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), heart rate, and blood pressure were measured five minutes before each treatment and 30 minutes after treatment with nebulised salbutamol.. FEV1 and FVC reached a plateau after administration of a cumulative dose of 14 puffs of ipratropium bromide (280 micrograms) or flutropium bromide (420 micrograms), and after six puffs of oxitropium bromide (600 micrograms). There were no differences with respect to maximum increases in FEV1 and FVC amongst the three anticholinergic agents. However, after six puffs oxitropium bromide produced a greater increase in FEV1 than either ipratropium bromide or flutropium bromide. Fenoterol caused a greater increase in both FEV1 and FVC than the three anticholinergic agents after six puffs, as well as a greater increase in pulse rate. Oxitropium bromide produced a greater increase in pulse rate than the other anticholinergics after 14 puffs. The incidence of side effects was dose-related and notable adverse effects were reported after 30 puffs of ipratropium bromide, 14 puffs of oxitropium bromide, and two puffs of fenoterol.. Oxitropium bromide produced a greater bronchodilator effect than either ipratropium bromide or flutropium bromide when used at doses of less than six puffs, without apparent side effects. There were, however, no differences in maximal response between these drugs. Fenoterol may have a greater peak bronchodilator effect than the anticholinergic agents but it causes more adverse effects, even at lower doses. Depending upon the balance between efficacy and side effects, oxitropium bromide may be preferred in the treatment of patients with COPD.

Topics: Aged; Atropine Derivatives; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Fenoterol; Forced Expiratory Volume; Histamine H1 Antagonists; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Nebulizers and Vaporizers; Scopolamine Derivatives; Vital Capacity

Twelve patients suffering from partially reversible chronic obstructive pulmonary disease (COPD) took past in a single blind, randomised, 4-way cross-over trial to determine the optimal dose and duration of action of the anticholinergic agent oxitropium bromide (OTB) inhaled as a nebulised solution. Single doses of 500, 1000, 1500 and 2000 micrograms nebulised OTB were compared during a 6 hour-observation period. Lung function test results indicated that 500 and 1000 micrograms OTB only induced slight bronchodilatation, whereas 1500 and 2000 micrograms OTB produced a significantly greater increase in mean FEV1 compared to 500 micrograms. There was a trend for 2000 micrograms to be superior to 1000 micrograms, but 2000 micrograms and 1500 micrograms were not significantly different. Significant bronchodilatation (> 15% rise in FEV1 from baseline) persisted for 6 h after 1500 micrograms. A significant decrease in airway resistance (Raw) was observed following inhalation of 2000 micrograms. The mean decrease in Raw was 33% after 30 min, 20% after 4 h and 12% after 6 h. In this trial, 2000 micrograms OTB administered by an ultrasonic nebuliser was the optimal dose, but a satisfactory result was also obtained with 1500 micrograms.

Topics: Administration, Inhalation; Aged; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Nebulizers and Vaporizers; Parasympatholytics; Respiratory Function Tests; Scopolamine Derivatives; Single-Blind Method; Time Factors

Inhaled anticholinergics may be the first-line therapy for stable COPD. However, the effect of inhaled anticholinergic agents on exercise capacity is still controversial. Fourteen patients with stable COPD (age, 64.6 +/- 5.9 years) completed a randomized, double-blind placebo-controlled crossover trial. All the patients were studied by symptom-limited progressive cycle ergometry before and 90 min after the inhalation of either oxitropium bromide, 800 micrograms, or an identical placebo. Spirometry was assessed before and after each exercise test. While FEV1 averaged 0.85 +/- 0.34 L at 90 min after the inhalation of placebo, FEV1 was 1.01 +/- 0.41 L at 90 min after the inhalation of oxitropium, 800 micrograms (significant from placebo, p < 0.001). The maximal workload of 94.0 +/- 25.8 W after oxitropium administration was significantly greater than the 87.6 +/- 24.7 W measured after placebo (p < 0.01). The maximal minute ventilation was 40.2 +/- 12.3 L/min after oxitropium inhalation and 36.8 +/- 10.5 after placebo inhalation (p < 0.05). The differences in maximal oxygen consumption, maximal carbon dioxide production, and maximal heart rate between oxitropium and placebo inhalation also were statistically significant (p < 0.05, p < 0.05, and p < 0.01, respectively). There was a significant correlation between the change in maximal workload and the change in FEV1 before and after inhalation (r = 0.625, p < 0.01). The inhalation of oxitropium bromide, 800 micrograms, can improve the exercise capacity of patients with stable COPD. It is suggested that the effect is due to the bronchodilation induced by this drug.

Topics: Administration, Inhalation; Aged; Cross-Over Studies; Double-Blind Method; Exercise Test; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Parasympatholytics; Scopolamine Derivatives; Spirometry; Vital Capacity

Oxitropium bromide is a novel anticholinergic bronchodilator agent. The purpose of this study was to compare the bronchodilating and cardiovascular effects of oxitropium (0.2 mg), fenoterol (0.4 mg), combined oxitropium and fenoterol (0.2 mg and 0.4 mg, respectively) over a 10-h test period. Fourteen patients with chronic obstructive pulmonary disease (COPD) (FEV1, 0.95 +/- 0.38L) were studied in a randomized, double-blind, placebo-controlled trial. Combined oxitropium and fenoterol produced significantly greater improvements in FEV1 over a time span of 15 min to 10 h and in the area under the time-FEV1 curve (AUC) than either oxitropium or fenoterol alone. The effects of oxitropium on both FEV1 and AUC values were similar to those of fenoterol. Oxitropium resulted in a greater increase in FEV1 than the placebo even after 10 h. In contrast; fenoterol produced a significant improvement in the FEV1 for only 15 min to 4 h. Oxitropium showed no adverse cardiovascular effects, whereas fenoterol was associated with an increased heart rate at 15 min and 1 h after the administration. We conclude that oxitropium bromide is an effective and safe bronchodilator for even elderly patients with COPD.

Topics: Aged; Double-Blind Method; Female; Fenoterol; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Parasympatholytics; Scopolamine Derivatives

To examine the effects of bronchodilators on maximal exercise capacity and their correlation with airflow during exercise in patients with chronic obstructive pulmonary disease (COPD), we conducted a double-blind, randomized comparison between inhaled fenoterol (beta 2-agonist) and oxitropium bromide (anticholinergic agent) in 8 patients with stable COPD (mean age 73 years, mean FEV1 1.1 L, mean FEV1% 50%). Only oxitropium bromide resulted in statistically significant improvement in FEV1 40 min after inhalation. On maximal exercise, fenoterol did not affect oxygen uptake (VO2 max), minute ventilation (VEmax), respiratory frequency (Rfmax), ventilatory efficacy (VEmax/VO2 max), peak expiratory flow during exercise (PEFmax), heart rate (HRmax) and dyspnea (Borg Scale Slope). After oxitropium bromide, dyspnea during exercise and HRmax decreased significantly, but PEFmax and other parameters did not change significantly compared with control. There was no correlation between changes in dyspnea during exercise and changes in FEV1 and PEFmax after oxitropium bromide inhalation. We conclude that inhaled oxitropium bromide, an anticholinergic agent, reduces dyspnea during exercise in patients with COPD. This favorable effect was not due to change of airflow limitation during exercise, and other factors can thus influence reduction of dyspnea during exercise in these patients.

Topics: Administration, Inhalation; Aerosols; Aged; Aged, 80 and over; Double-Blind Method; Exercise Tolerance; Fenoterol; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Parasympatholytics; Pulmonary Ventilation; Scopolamine Derivatives

Although exercise induced desaturation can occur in patients with chronic obstructive pulmonary disease (COPD), little is known about its frequency during everyday exercise, or how it relates to dyspnoea or prior drug treatment.. The effects of 200 micrograms inhaled oxitropium bromide, an anticholinergic bronchodilator drug, on spirometric values, dyspnoea score, and oxygen saturation during corridor walking and cycle ergometry were studied in a double blind, randomised, placebo controlled study.. Oxitropium produced a small increase in forced expired volume in one second (FEV1) from 0.76 (0.28) 1 to 0.93 (0.69) 1 and in six minute walking distance from 311 (93) m to 332 (86) m, but did not change progressive cycle exercise duration. Resting and end exercise breathlessness levels were reduced in both forms of exercise after oxitropium. Resting oxygen saturation fell significantly after active bronchodilator from 92.9% (3.7%) to 92.0% (4.1%) but the nadir saturation during exercise was unchanged. The patients desaturated more during corridor walking than cycle ergometry [walking 7.8% (4.4%), cycle ergometry 2.1% (2.1%)]. Baseline walking distance was related to FVC, resting breathlessness and resting oxygen saturation (multiple r2 = 0.46) but only resting saturation correlated with end exercise breathlessness (r2 = -0.25). Improvements in symptoms or exercise performance after oxitropium could not be predicted by changes in spirometric indices or oxygen saturation.. In patients with COPD arterial oxygen desaturation during self-paced walking is common, of greater severity than that during cycle ergometry, but is unaffected by inhaled oxitropium bromide. The factors that predict initial performance are not appropriate markers of functional improvement after an active bronchodilator drug.

Topics: Double-Blind Method; Dyspnea; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Parasympatholytics; Physical Exertion; Scopolamine Derivatives; Vital Capacity; Walking

To elucidate the effect of oxitropium bromide (OTB), an anticholinergic drug, on dyspnea and gas exchange during exercise in patients with chronic obstructive pulmonary disease (COPD), we performed the cycle exercise test on 19 patients with COPD (mean age, 72.0 +/- 1.9 years; mean FEV1, 1.28 +/- 0.07 L) before and after inhalation of OTB, 300 micrograms, or placebo, 300 micrograms, in randomized fashion. Spirometry was performed immediately before and 30 min after inhalation of either OTB or placebo. Dyspnea during exercise was evaluated using the Borg scale (BS) and the slope of the regression between BS and oxygen uptake (VO2) during exercise (Borg scale slope: BSS). Arterial oxygen saturation (SaO2) was continuously monitored by pulse oximeter during and after exercise. We also measured the recovery time, which was defined as the time to recover decreases in SaO2 after exercise. After OTB, spirometric indices were improved (delta FEV1 16.8 +/- 0.9 percent) and maximal VO2 during exercise increased significantly (from 986 +/- 46 ml/min to 1,156 +/- 55 ml/min, p < 0.01), but not after placebo. The maximal scores of BS and the BSS were significantly decreased after OTB, but not after placebo. Although the SaO2 at rest and during exercise did not differ with or without either OTB or placebo, the recovery time after OTB (77.3 +/- 6.8 s) was significantly shorter than that before administration (98.4 +/- 14.6 s) (p < 0.01). We conclude that the inhaled OTB produces small but significant improvement both in dyspnea during exercise and in exercise performance in stable COPD and may contribute to improve the quality of life in some patients with COPD. However, gas exchange during exercise of COPD patients is little affected by OTB.

Topics: Administration, Inhalation; Aged; Aged, 80 and over; Double-Blind Method; Dyspnea; Exercise Test; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Oxygen; Parasympatholytics; Pulmonary Gas Exchange; Scopolamine Derivatives; Vital Capacity

The effects of an antimuscarinic agent, oxitropium bromide (200 micrograms), a beta-2 adrenoceptor agonist, fenoterol (200 micrograms), and their combination, were compared in ten patients with chronic obstructive pulmonary disease and ten patients with bronchial asthma, in a placebo-controlled, single blind crossover trial. In patients with chronic obstructive pulmonary disease, oxitropium and fenoterol produced a significant and similar degree of bronchodilatation. The duration of the bronchodilator effect was 3 h after oxitropium and 4 h after fenoterol, respectively. The combination of oxitropium and fenoterol produced a significantly greater degree of bronchodilatation than either drug alone. The duration of bronchodilatation in combination was 7 h and was considerably longer than that of each drug alone. In patients with bronchial asthma, oxitropium and fenoterol also caused bronchodilatation. Their combination produced a significantly greater degree of bronchodilatation than when either drug was used. The duration of the bronchodilator effects were 5 h after oxitropium, 4 h after fenoterol and 5 h after the combination. We conclude that the combination of oxitropium and fenoterol causes greater bronchodilatation in patients with chronic obstructive pulmonary disease and bronchial asthma than when compared to each drug alone. In the former, the duration of bronchodilatation is additionally prolonged. These combination effects may be of value in the clinical management of these common respiratory disorders.

Topics: Aged; Asthma; Bronchodilator Agents; Drug Therapy, Combination; Female; Fenoterol; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Parasympatholytics; Scopolamine Derivatives; Single-Blind Method

Partial bronchodilator reversibility can be demonstrated in many patients with stable chronic obstructive pulmonary disease (COPD), but its relevance to exercise capacity and symptoms is uncertain. Previous data suggest that anticholinergic bronchodilators do not improve exercise tolerance in such patients. We studied 32 patients with stable COPD, mean age 65 yrs, in a double-blind, placebo-controlled, cross-over trial of the inhaled anticholinergic drug, oxitropium bromide. From the within and between day placebo spirometry, we derived the spontaneous variation in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) of this population (FEV1 140 ml; FVC 390 ml) and considered responses beyond this to be significant. Oxitropium bromide increased baseline FEV1 from 0.70 (0.28) l (mean (SD)) to 0.88 (0.36) l. The 6 min walking distance increased by 7% compared with placebo, whilst resting breathlessness scores fell from 2.0 to 1.23 at rest and 4.09 to 3.28 at the end of exercise after the active drug. Improvements in walking distances and symptoms were unrelated to changes in either FEV1 or FVC, indicating that routine reversibility testing is not a good predictor of symptomatic benefit in these patients.

Topics: Aged; Bronchi; Bronchodilator Agents; Double-Blind Method; Dyspnea; Exercise; Female; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Parasympatholytics; Scopolamine Derivatives; Time Factors; Vital Capacity

Topics: Adolescent; Adult; Aged; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Parasympatholytics; Scopolamine Derivatives

The efficacy and side effects of oxitropium bromide, a new anticholinergic bronchodilator drug, were tested in a double-blind placebo-control study. Twenty-four men, aged 58 to 72 years, with chronic partially reversible obstruction of the airways were used as subjects. Three doses of oxitropium were tested (100 micrograms, 200 micrograms, and 300 micrograms) to determine the optimum dose by metered-dose inhaler. A comparison was also made between oxitropium, fenoterol (400 micrograms), and a combination of oxitropium (200 micrograms) and fenoterol (400 micrograms). Fenoterol produced a greater degree of maximal bronchodilatation than each of the three doses of oxitropium, and its effect was more rapid in onset (30 vs 120 minutes to peak effect); however, the duration of action of oxitropium was greater than that of fenoterol (ie, the forced expiratory volume in one second [FEV1] remained within 5 percent of peak FEV1 for three hours, compared to one hour). Oxitropium in the 100 micrograms dose was inferior to 200 micrograms and 300 micrograms in subjective efficacy scores, peak percent change in FEV1, forced vital capacity, (FVC), mean forced expiratory flow over the middle half of the FVC, and duration of action; there was no difference between 200 micrograms and 300 micrograms. The oxitropium-fenoterol combination had a rapid onset of action, and a greater peak effect was achieved than for oxitropium alone. The main unwanted effect was a mildly unpleasant taste. Anticholinergic effects were not seen in this group of elderly men. Oxitropium bromide therefore is an effective bronchodilator with slow onset but prolonged activity and few side effects when used in patients with moderately severe obstruction of the airways. An appropriate dose appears to be 200 micrograms. Addition of oxitropium to fenoterol appears to offer even greater efficacy.

Topics: Aged; Bronchodilator Agents; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Fenoterol; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Parasympatholytics; Scopolamine Derivatives; Time Factors

Oxitropium bromide (OB) is a quaternary ammonium congener of hyoscine with anticholinergic properties. We studied its bronchodilating properties in 14 patients with chronic obstructive lung disease without features of asthma in whom theophylline and other bronchodilators were withheld. Five doses of OB(20, 40, 100, 200, and 400 micrograms) as well as 150 micrograms of isoproterenol (ISO) and placebo were administered by metered-dose inhaler on separate occasions in a double-blind fashion. Pulmonary function (flow volume loops and airways resistance), blood pressure, and pulse rate were measured at baseline and periodically for eight hours after drug administration. Onset of bronchodilator effect was within five minutes for OB (P less than .025). Duration of action of OB was at least eight hours (P less than .025). The dose response characteristics of OB were examined by correlating the log dose with the areas under the time-FEV1 curve (r = .97, P less than .01), the time-forced vital capacity curve (r = .98, P less than .01), and the time-SGAW curve (r = .83, P less than 0.1). For FEV1, doses of 40 to 400 micrograms were significantly better than placebo and 100 to 400 micrograms were better than ISO (P less than .01). For forced vital capacity, all doses of OB were better than placebo (P less than .05). For SGAW, the response to the 100- and 400-micrograms doses were significantly better than placebo and isoproterenol (P less than .05). There were no significant effects of OB on pulse, blood pressure, or electrocardiogram. No side effects were noted from the use of OB.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Pressure; Bronchodilator Agents; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Heart Rate; Humans; Lung Diseases, Obstructive; Male; Parasympatholytics; Plethysmography; Pulse; Random Allocation; Respiration; Scopolamine Derivatives; Spirometry; Theophylline; Time Factors

Twenty-four elderly male patients with moderate-to-severe chronic airway obstruction took part in a double-blind, placebo-controlled, randomized dose-response and response-duration comparison of a new inhaled anticholinergic bronchodilator oxitropium bromide and the inhaled beta-agonist bronchodilator fenoterol hydrobromide. On 6 separate days lung function changes and side effects were monitored for 8 h after either placebo, oxitropium 100, 200 and 300 micrograms, fenoterol 400 micrograms, or oxitropium 200 micrograms plus fenoterol 400 micrograms. Fenoterol alone and in combination with oxitropium produced a rapid peak effect (mean delta FEV1 = 41.6 and 39.5%, respectively at 30 min). Oxitropium alone had a slow onset of action (peak delta FEV1 seen at 120 min: 100 micrograms = 22.7%, 200 micrograms = 29.9%, 300 micrograms = 28.2%). However, mean FEV1 remained within 5% of peak for 60 min after fenoterol, but for 180 min after each dose of oxitropium and after fenoterol plus oxitropium. No differences between oxitropium 200 and 300 micrograms were seen; however, these doses produced more prolonged bronchodilatation than did oxitropium 100 micrograms. The fenoterol-plus-oxitropium combination produced even more prolonged bronchodilatation. The only side effect, seen with each inhaler was a mildly unpleasant taste. No anticholinergic effects were seen. We conclude that oxitropium is an effective bronchodilator with slow onset but prolonged duration of action. In combination with fenoterol it produced both rapid and prolonged bronchodilatation in patients with chronic airflow obstruction.

Topics: Administration, Inhalation; Aged; Dose-Response Relationship, Drug; Drug Combinations; Fenoterol; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Scopolamine Derivatives; Time Factors; Vital Capacity

Topics: Adolescent; Bronchodilator Agents; Child; Cromolyn Sodium; Double-Blind Method; Dyspnea; Female; Fenoterol; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Physical Exertion; Random Allocation; Scopolamine Derivatives

12 patients with obstructive airway diseases took part in a double-blind study in which 0.02 and 0.2 mg of Ba 253 as metered aerosols were compared with a placebo. Both doses of Ba 253 elicited a significant fall of mean total airway resistance compared to the placebo, and this fall was still discernible even 8 h after inhalation. Under the higher dose, the maximum response was significantly greater and it occurred about 2 h after inhalation; the response was still significantly more pronounced 8 h after inhalation. There was no objective evidence of local or systemic side effects attributable to a vagus-blocking effect. In the light of published reports and our own experience, when Ba 253 is inhaled in the stated doses it appears to be equivalent to ipratropium bromide as regards potency, duration of action, tolerance and therapeutic safety margin.

Topics: Aerosols; Airway Resistance; Bronchial Spasm; Dose-Response Relationship, Drug; Drug Evaluation; Female; Humans; Lung Diseases, Obstructive; Male; Scopolamine Derivatives; Time Factors

Topics: Administration, Inhalation; Adrenergic beta-Agonists; Aged; Albuterol; Bronchodilator Agents; Dose-Response Relationship, Drug; Humans; Lung Diseases, Obstructive; Parasympatholytics; Salmeterol Xinafoate; Scopolamine Derivatives

We studied the bronchodilatory effect of tiquizium bromide [3-(di-2-thienylmethylene)-5 methyl-trans-quinolizidinium bromide; TQZ], an antimuscarinic agent, on airway smooth muscle in vitro, and also in patients with chronic obstructive pulmonary disease (COPD).. In the first experiment, canine tracheal smooth muscle was used to measure the pA2 of TQZ in vitro. The selectivity of TQZ in vitro. The selectivity of TQZ for muscarinic receptor subtypes was also examined with a radioligand binding assay.. The pA2 value of TQZ was 8.75. The pKi values of TQZ for M1, M2, and M3 were 8.70, 8.94, and 9.11, respectively. In an open pilot experiment, the effects of TQz inhalation were studied in seven patients with COPD (seven men, mean age 68.5 years). TQZ significantly increased forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) in a dose-dependent manner. The mean maximum increases in FVC and FEV1 caused by inhaled TQZ (2.0 mg) were 24% and 29%, respectively, and they were measured 1 h after the drug had been inhaled. The FVC and FEV1 were still significantly higher than the control values even 8 h after the drug had been inhaled. No adverse effects were observed after inhalation of TQZ.. These data suggest that TQZ is an effective antimuscarinic agent, and that it causes significant bronchodilation in patients with COPD.

Topics: Acetylcholine; Aged; Animals; Atropine; Atropine Derivatives; Bronchodilator Agents; Cerebral Cortex; Dogs; Dose-Response Relationship, Drug; Female; Forced Expiratory Volume; Heart Atria; Humans; In Vitro Techniques; Ipratropium; Lung Diseases, Obstructive; Male; Muscarinic Antagonists; Muscle Contraction; Muscle, Smooth; Quinolizines; Quinuclidinyl Benzilate; Radioligand Assay; Scopolamine Derivatives; Trachea; Vital Capacity

Topics: Dyspnea; Exercise; Humans; Lung Diseases, Obstructive; Parasympatholytics; Respiratory Function Tests; Scopolamine Derivatives

Topics: Dyspnea; Exercise Tolerance; Humans; Lung Diseases, Obstructive; Parasympatholytics; Perception; Scopolamine Derivatives

We studied the effects of the inhaled anticholinergic agent oxitropium bromide (Ox) on pulmonary hemodynamics in eleven patients with chronic obstructive pulmonary disease. All the patients underwent right heart catheterization and seven of them underwent an incremental ergometer exercise test while in the supine position. Pulmonary hemodynamics and arterial blood gases were measured at rest and during maximal exercise, before and 30 minutes after inhalation of 2 puffs (200 micrograms) of Ox. Inhalation of Ox did not significantly change pulmonary hemodynamics at rest. The mean pulmonary arterial pressure and the mean pulmonary capillary wedge pressure during exercise decreased significantly (from 40.3 +/- 4.6 to 37.7 +/- 3.9 mmHg, and from 20.4 +/- 3.5 to 17.1 +/- 2.7 mmHg, respectively, mean +/- SE). However, neither cardiac output nor pulmonary vascular resistance changed with inhalation of the drug, at rest or during exercise. We therefore conclude that this commonly used dose of Ox does not directly affect the pulmonary vascular system. The small but significant decreases in pulmonary arterial pressure and pulmonary capillary wedge pressure with Ox may have been indirect effects, caused by bronchodilation.

Topics: Administration, Inhalation; Aged; Aged, 80 and over; Cholinergic Antagonists; Hemodynamics; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Pulmonary Circulation; Scopolamine Derivatives