The effects of oxitropium bromide on exercise performance in patients with stable chronic obstructive pulmonary disease. A comparison of three different exercise tests

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.     

Oxitropium bromide. Dose-response and time-response study of a new anticholinergic bronchodilator drug

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.     

Incremental benefit of adding oxitropium bromide to formoterol in patients with stable COPD.

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.     

Bronchodilator reversibility, exercise performance and breathlessness in stable chronic obstructive pulmonary disease.

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.     

Influence of higher than conventional doses of oxitropium bromide on formoterol-induced bronchodilation in COPD

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.     

Bronchodilating effect of oxitropium bromide in heart disease patients with exacerbations of COPD: double-blind, randomized, controlled study

Anti-cholinergic agents are considered the bronchodilator therapy of first-choice in the treatment of patients with stable chronic obstructive pulmonary disease (COPD) associated with heart disease since they may be as effective or more effective than inhaled beta2-agonists and, moreover, they do not interact with cardiac beta-adrenoceptors. The aim of our study was to evaluate the bronchodilator activity of oxitropium bromide in outpatients suffering from exacerbations of COPD associated with heart diseases (ischaemic heart disease and/or arrhythmias). We recruited 50 consecutive outpatients (33 males and 17 females, mean age 68.6 years, 15 current smokers and 35 ex-smokers). Each patient performed body plethismography in basal condition and 30 min after inhalation of 200 microg metered dose inhaler (MDI) oxitropium bromide administered by a device (Fluspacer). FEV1, FVC, MMEF25-75, sRaw and tRaw were evaluated. Thirty minutes after 200 microg oxitropium bromide administration, we observed a significant improvement in FEV1 11.6% +/- 1 (mean +/- SEM) (P<0.01); FVC, MMEF25-75 sRaw variation was respectively: 9.2% +/- 0.6, 31.4 +/- 2.9, -19.9 +/- 1.1. Placebo did not significantly change pulmonary function. Our data suggest that oxitropium bromide bronchodilator activity is effective in exacerbations of COPD.     

The addition of an aerosol anticholinergic to an oral beta agonist plus theophylline in asthma and bronchitis. A double-blind single dose study

In two groups of patients, 15 with asthma and 15 with chronic bronchitis, the bronchodilator effects of ipratropium bromide, of fenoterol plus theophylline, and of the combination of the three drugs, were compared using a double-blind, single-dose, placebo-controlled format. Ipratropium bromide caused rapid bronchodilatation which was not significantly different in asthmatic patients and patients with bronchitis (delta FEV1 = .29 L in one hour in asthmatic patients, .18 L in patients with bronchitis). In contrast, fenoterol plus theophylline induced a considerably greater effect in asthmatic patients (delta FEV1 = .41 L in one hour) than in those with bronchitis (delta FEV1 = .07 in one hour). The use of the three drugs in combination compared with ipratropium bromide alone, or fenoterol plus theophylline alone, resulted in a significant additional bronchodilatation in asthmatic patients. In the patients with bronchitis, the triple combination was clearly superior to fenoterol plus theophylline. A similar trend was present in comparing the triple combination to ipratropium bromide, but the difference did not reach statistical significance. There was no evidence of synergism when ipratropium bromide was combined with fenoterol plus theophylline in that the total bronchodilator effect was approximately additive. Asthmatic patients and the physician were able to distinguish the triple combination from placebo. No such ability was demonstrated with respect to those with bronchitis. All three drugs were well tolerated. Side effects were mostly mild, and none was related to the use of ipratropium.     

A comparison of global questions versus health status questionnaires as measures of the severity and impact of asthma.

This study compared estimates of the severity and impact of asthma recorded using global questions of the type used in diary cards with health status measurements obtained using comprehensive questionnaires. Seventy-four outpatients with asthma, aged 17-76 yrs (mean 48 yrs) participated. Mean+/-SD forced expiratory volume in one second (FEV1) was 72+/-26% predicted. Patients recorded morning and evening peak expiratory flow rate (PEFR) and scaled their responses to the questions: "How has your asthma been today?" (asthma severity) and "How much effect has your asthma had on your life today?" (asthma impact) for 2 weeks. They then completed Juniper's Asthma Quality of Life Questionnaire (AQLQ) and the St George's Respiratory Questionnaire (SGRQ). Diary card scores for asthma impact were less severe than for asthma severity (p<0.0001). Both correlated with AQLQ and SGRQ total scores (r>0.7; p<0.0001). Some patients responded 'none' for asthma severity (n=10) or asthma impact (n=13) on all 14 days of recording. For these patients, FEV1 was <80% predicted, morning PEFR was <90% predicted and their AQLQ and SGRQ scores indicated significant health impairment. Diary card scores for asthma severity and impact were correlated with health status, but these global questions were insensitive in mild disease. Responses to these questions were influenced by their wording, so the number of symptom-free days calculated from diary cards will depend on the questions used. Standardization is required before symptom-free days can be used as a reliable measure of treatment efficacy.     

In patients with COPD, treatment with a combination of formoterol and ipratropium is more effective than a combination of salbutamol and ipratropium : a 3-week, randomized, double-blind, within-patient, multicenter study

STUDY OBJECTIVES: To compare the efficacy of adding formoterol or salbutamol to regular ipratropium bromide treatment in COPD patients whose conditions were suboptimally controlled with ipratropium bromide alone. DESIGN: A randomized, double-blind, double-dummy, two-period, crossover clinical trial. SETTING: Twenty-four clinics and university medical centers in nine countries. PATIENTS: One hundred seventy-two patients with baseline FEV(1) < or = 65% predicted, with FEV(1) reversibility to salbutamol not exceeding the normal variability of the measurement, and symptomatic despite regular treatment with ipratropium bromide. INTERVENTIONS: Each patient received two treatments in random order: either inhaled formoterol dry powder, 12 microg bid, in addition to ipratropium bromide, 40 microg qid for 3 weeks, followed by salbutamol, 200 microg qid, in addition to ipratropium, 40 microg qid for 3 weeks, or vice versa. MEASUREMENTS AND RESULTS: Efficacy end points included morning premedication peak expiratory flow (PEF) during the last week of treatment (primary end point), the area under the curve (AUC) for FEV(1) measured for 6 h after morning dose on the last day of treatment, and symptom scores (from daily diary recordings). Morning PEF and the AUC for FEV(1) were significantly better for formoterol/ipratropium than for salbutamol/ipratropium (p = 0.0003 and p < 0.0001, respectively). The formoterol/ipratropium combination also induced a greater improvement in mean total symptom scores (p = 0.0042). The safety profile of the two treatments was comparable. CONCLUSIONS: In COPD patients requiring combination bronchodilator treatment, the addition of formoterol to regular ipratropium treatment is more effective than the addition of salbutamol.     

Effects of replacing oxitropium with tiotropium on pulmonary function in patients with COPD: a randomized study

BACKGROUND: Inhaled bronchodilators are first line drugs in the treatment of chronic obstructive pulmonary disease (COPD). Tiotropium bromide is a recently introduced long-acting anticholinergic agent able to reduce dyspnoea and COPD exacerbations and to improve pulmonary function and quality of life. We designed a study to compare the short-term efficacy of tiotropium bromide with that of oxitropium bromide in improving pulmonary function in patients with COPD. METHODS: Eighty patients were randomized either to continue oxitropium 800 mcg/day or to receive tiotropium 18 mcg/day. Seventy-six (39 in the tiotropium and 37 in the oxitropium group) completed the study. Plethysmography was performed at baseline and after 72 h in all patients. The changes in functional parameters in the two groups were compared by the Mann-Whitney U-test. RESULTS: There were no differences between the two groups regarding age (72.5 vs. 74.2 years), male/female ratio (25/14 vs. 23/14) and pulmonary function at baseline. The changes in spirometric parameters were significantly greater in tiotropium- than in oxitropium-treated patients: mean forced expiratory volume in 1s (FEV(1)) increased significantly by 15% vs. 3% (P=0.017), mean FVC by 10.5% vs. 2.2% (P=0.044), and FEF 25, 50, and 75 by 34% vs. 14% (P<0.05), 33% vs. 7% (P<0.05), and 50% vs. 6% (P<0.0001), respectively; mean FRC and RV decreased nonsignificantly by 7.5% and 10% with tiotropium vs. 4.3% and 6.5% with oxitropium, respectively. CONCLUSION: The replacement of oxitropium with tiotropium significantly increases pulmonary function in patients with COPD. The improvement involves also small airways that have not been investigated thus far.     

Once versus twice daily formoterol via Novolizer for patients with moderate to severe COPD--a double-blind, randomised, controlled trial

STUDY OBJECTIVES: To evaluate in patients with moderate to severe COPD whether a single morning dose of 24 microg formoterol from the Novolizer is not inferior to two divided doses of 12 microg formoterol inhaled in the morning and in the evening. DESIGN: Randomised, double blind, active-controlled, parallel-group, multi-centre study with a 2-week run-in period and a 12-week treatment phase. SETTING: Forty-seven outpatient centres in Germany, including private practices. PARTICIPANTS: N=321 symptomatic patients with moderate to severe COPD aged 40-70 years with an FEV1 of 30-80% predicted and the requirement of 3-12 actuations of salbutamol per day on 5 days during the run-in period. TREATMENT: Eligible patients were randomised to inhale formoterol either (a) as a single 24 microg dose in the morning (OD) or (b) in two divided 12 microg doses in the morning and in the evening (b.i.d.). MEASUREMENTS AND RESULTS: The mean age was 60.3 (SD 7.3) years, and mean baseline pre-dose FEV1 was 1.5l (0.5l) or 50% (12%) of predicted, respectively. After 12 weeks of treatment, pre-dose FEV(1) improved in both groups (mean: OD, +104 ml, b.i.d., +135 ml, mean difference between groups: 31 ml). The 95% CI exceeded the pre-determined margin of 100ml by 2 ml, so that the statistical hypothesis of non-inferiority of once daily dosing was not confirmed. No statistically significant differences were seen for improvements in PEF, MEF75, MEF50, and MEF25. COPD symptoms, percentage of symptom-free days and quality of life (SGRQ) improved in both groups to a similar degree. There were no relevant differences in the incidence of adverse events. CONCLUSIONS: Based on a comparable efficacy and tolerability, the dosing schedule with formoterol via Novolizer as once daily in the morning seems to be an alternative compared to twice daily treatment. The primary endpoint suggests the equivalence of both treatment schedules from a clinical perspective. This regimen can be considered as an alternative therapeutic approach for a subgroup of COPD patients and may help to improve patient compliance.     

A novel, short, and simple questionnaire to measure health-related quality of life in patients with chronic obstructive pulmonary disease.

A novel, short, and simple questionnaire, the Airways Questionnaire 20 (AQ20), has been developed to measure and quantify disturbances in the health-related quality of life (HRQoL) of patients with asthma or chronic obstructive pulmonary disease (COPD). The AQ20 has 20 items with yes/no responses, and should take 2 min to complete and score. The purpose of this study was to assess the discriminative properties and responsiveness of the AQ20 in patients with COPD. First, in a cross- sectional study, 165 patients with mild-to-severe COPD (mean age, 69 +/- 7 yr; FEV1, 40 +/- 16% of predicted) completed the AQ20, the St. George's Respiratory Questionnaire (SGRQ), the Chronic Respiratory Disease Questionnaire (CRQ), pulmonary function tests, a progressive cycle ergometer exercise test, and an assessment of their dyspnea and anxiety. The score distribution of the AQ20 was skewed toward the mild end of the scale, whereas the SGRQ and CRQ showed a normal distribution. The AQ20 showed a moderately strong correlation with the maximal oxygen uptake and the assessment of dyspnea (Spearman's correlation coefficients [rs] = -0.49, -0.60, respectively), but a weak correlation with the FEV1 (rs = -0.18). Moderate to strong correlations were also recognized between the AQ20 and SGRQ and CRQ (rs = -0.80, -0.72, respectively). Multiple regression analysis revealed that dyspnea and anxiety accounted for 43% of the variance in the AQ20, almost the same as in the SGRQ and CRQ. Second, longitudinal changes over time in the FEV1, AQ20, SGRQ, and CRQ were examined in 86 patients with newly detected COPD (mean age, 69 +/- 8 yr; FEV1, 45 +/- 19% of predicted). All three measures showed significant improvements in their scores over a 3-mo period after initiating medical intervention. The change in the AQ20 showed a moderate to strong correlation with each dimension of the SGRQ and CRQ (rs = 0.56, -0.52, respectively), but no significant correlation was noted with the FEV1. In conclusion, the AQ20 may have discriminative properties and responsiveness that are similar to more complex questionnaires such as the SGRQ and CRQ. Because it is short and can be quickly answered and scored, the AQ20 may be useful in studies with limited time for HRQoL assessments.     

Double-blind, randomised, controlled trial assessing controller medications in asthma

BACKGROUND: The motive behind conducting this study was to determine if better control of asthma can be achieved by adding a second controller medication and to assess its use to reduce the dose of inhaled steroids. OBJECTIVES: The study aimed to determine whether either oral sustained-release theophylline or montelukast added to inhaled steroids improved clinical symptoms and pulmonary function test parameters when compared to high-dose steroids alone. METHODS: Ninety patients with incompletely controlled asthma were allocated, in a randomised, double-blind fashion, to one of three treatment groups: group A: double dose of inhaled budesonide (400 microg b.i.d.), group B: 400 mg oral sustained-release theophylline plus budesonide (200 microg b.i.d.) and group C: 10 mg montelukast plus budesonide (200 microg b.i.d.). The primary endpoints were forced expiratory volume in 1 s (FEV(1)) and mean morning peak expiratory flow rate (PEFR). RESULTS: All three groups had improved FEV(1) and PEFR at 8 weeks (p < 0.001). Group C increased their PEFR by 18.7 l/min (95% confidence interval, CI, 12.4-25.1) more than group A and by 19.8 l/min (95% CI 13.4-26.1) more than group B (both p = 0.001). Similarly, group C had a 114 ml (95% CI 45-183 ml) greater improvement in FEV(1) than group A and a 95 ml (95% CI 26-164 ml) greater improvement than group B (both p = 0.01). CONCLUSIONS: Addition of montelukast to budesonide is safe and results in greater improvement in pulmonary function test parameters than high-dose budesonide treatment or addition of theophylline.     

Effects of Inhalation or Incubation of Oxitropium Bromide on Diaphragm Muscle Contractility in Mice

BackgroundAlthough oxitropium bromide is used clinically as an anticholinergic drug (i.e., parasympathetic antagonist) to relax airway smooth muscle, we examined whether it has or does not have any effects on diaphragm muscle.MethodsThree treatment sets, an oxitropium bromide inhalation only group, an oxitropium bromide inhalation plus endotoxin injection group (in vivo) and an oxitropium bromide incubation group (in vitro) were studied as to diaphragm muscle contractile properties.ResultsOxitropium bromide inhalation shifted force-frequency curves upward at 2 h after inhalation (p < 0.05) and inhibited the decrease of force-frequency curves due to endotoxin injection in vivo. Incubation with oxitropium bromide of untreated diaphragm muscle and diaphragm muscle injected with endotoxin did not increase the force-frequency curves dose-dependently in vitro; however, it caused both types of muscle to be fatigue resistant.ConclusionsWe speculate that the increment of muscle contractility with the inhalation of oxitropium bromide was induced by the antagonization of musucarinic acetylcholine receptors (mAChR). In addition, the changes of fatigue resistance provoked by oxitropium bromide, which also is speculated to antagonize mAChR, may be beneficial in the treatment of patients with COPD.     

A comparison of bronchodilating drugs in the treatment of stable COPD]

The purpose of this study was to establish the optimal bronchodilating drug among therapies currently available for clinical treatment of the stable phase of chronic obstructive pulmonary disease (COPD). The efficacy of ipratropium bromide 40 micrograms, salbutamol 200 micrograms, and ipratropium bromide 40 micrograms plus salbutamol 200 micrograms was compared in 14 patients with COPD. Daily PEFR was obtained during the last seven days of a 2 week period incorporating drug inhalation four times daily. FEV1 and FVC were assessed on the final day of the treatment period. In the absence of bronchodilating medication, FEV1 was 1.27 +/- 0.13 l (52.9 +/- 5.1% pred). With ipratropium bromide 40 micrograms alone, FEV1 was 1.43 +/- 0.13 l (59.8 +/- 5.3% pred). A similar value was obtained for salbutamol 200 micrograms: 1.45 +/- 0.14 l (61.0 +/- 5.4% pred). However, FEV1 following the administration of ipratropium bromide 40 micrograms in combination with salbutamol 200 micrograms was 1.51 +/- 0.13 l (63.6 +/- 5.3% pred). The percent increase in FEV1 (compared to the value obtained without medication) was significantly higher with combined ipratropium bromide 40 micrograms plus salbutamol 200 micrograms (122.2 +/- 3.8%) than with either ipratropium bromide 40 micrograms (114.8 +/- 5.5%) or salbutamol 200 micrograms (116.5 +/- 4.4%) alone. Furthermore, the daily post-dilator PEFR improved significantly more with the combined therapy four times a day (311 +/- 29 l/min) than with either ipratropium bromide 40 micrograms (296 +/- 30 l/min) or salbutamol 200 micrograms (303 +/- 29 l/min) therapy alone. There was no discernible difference between results obtained with ipratropium bromide 40 micrograms versus salbutamol 200 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of medication and quality of life among patients with COPD

STUDY OBJECTIVES: To determine the medications prescribed to patients with chronic obstructive pulmonary disease (COPD) and their relationship to health-related quality of life (HRQL). METHODS: Cross-sectional study of 611 consecutive patients with stable, mild-to-severe COPD who attended at the respiratory service of a single hospital during a 1-year period. HRQL was evaluated using the St. George Respiratory Questionnaire (SGRQ) and the Short Form 36-item (SF-36) questionnaires. Linear regression analysis was used to determine the influence of the number or type of medication on the total SGRQ score, adjusting by disease severity and other relevant variables. RESULTS: Significant differences were observed among the number of drugs prescribed according to dyspnea levels, percentage of predicted FEV1 (FEV1%), SGRQ scores and some areas of SF-36. Fifty-nine percent of patients with an FEV1%>50% were prescribed inhaled corticosteroids (ICS). Those who took an ICS had a worse HRQL than patients with an FEV1%>50% who did not receive ICS. CONCLUSIONS: A relationship exists between the number of medicines prescribed to patients with COPD and their HRQL, measured by the total SGRQ score, after adjustment by severity of the disease. Within the group of patients who should not have been prescribed ICS, there are subgroups that might benefit from this medication.     

Tiotropium Bromide

Tiotropium bromide (Spiriva) is a long-acting anticholinergic bronchodilator that maintains bronchodilation for at least 24 hours, allowing once-daily administration. The active moiety is the tiotropium cation (tiotropium); tiotropium bromide 22.5 micrograms is equivalent to 18 micrograms of tiotropium cation. Greater improvements in lung function from baseline (primary endpoint mean trough FEV(1)) were observed with inhaled tiotropium 18 micrograms once daily than with placebo in 6-month and 1-year randomized, double-blind trials in patients with COPD. Tiotropium improved lung function (trough FEV(1) response) more effectively than ipratropium bromide (ipratropium) 40 micrograms four times daily in 1-year clinical trials, and was at least as effective as salmeterol 50 micrograms 12-hourly in 6-month trials. Preliminary data suggest that tiotropium alone or in combination with once-daily formoterol has a greater bronchodilator effect than twice-daily formoterol in patients with COPD. Improvements in patients' perception of health-related quality of life (HR-QOL) or dyspnea were greater with tiotropium than with placebo or ipratropium, and were similar to those with salmeterol. Reductions in the frequency and severity of acute exacerbations and in the use of rescue medication were also greater with tiotropium than with ipratropium or placebo. There was no evidence of tachyphylaxis with tiotropium during 1-year clinical trials. Inhaled tiotropium was generally well tolerated in clinical trials. Apart from dry mouth, the type and incidence of adverse events with tiotropium were similar to those with ipratropium, salmeterol or placebo in patients with COPD. In conclusion, inhaled tiotropium 18 micrograms once daily improved lung function, dyspnea, and HR-QOL, and decreased the incidence of acute COPD exacerbations and the use of rescue medication relative to placebo or ipratropium in clinical trials in patients with COPD. Tiotropium was at least as effective as salmeterol in terms of bronchodilator efficacy and improvements in dyspnea or HR-QOL. With the exception of dry mouth, the tolerability profile of tiotropium was similar to that with placebo, ipratropium, or salmeterol. Consequently, inhaled tiotropium is likely to be a valuable option for first-line, long-term maintenance therapy in the management of bronchoconstriction in patients with symptomatic COPD. Tiotropium bromide has a quaternary ammonium structure and acts as an anticholinergic bronchodilator; the active moiety is the tiotropium cation (tiotropium). A 22.5 micrograms dose of tiotropium bromide provides 18 micrograms of tiotropium. Orally inhaled tiotropium bromide antagonizes the muscarinic M(1), M(2), and M(3) receptors located in airway smooth muscle, reversing vagally mediated bronchoconstriction. Receptor binding assays and in vitro tests indicate that tiotropium bromide is kinetically selective for M(1) and M(3) receptors over the M(2) receptor, unlike ipratropium bromide, which is nonselective. Animal and in vitro studies showed that tiotropium bromide was more potent ( approximate, equals 20-fold) than ipratropium bromide in displacing [(3)H]N-methylscopolamine (NMS) from muscarinic receptors, and had a more sustained protective effect (>70% inhibition) against NMS binding. Tiotropium bromide was a more potent inhibitor of bronchial contraction than atropine ( approximate, equals 23-fold), and had a slower onset and markedly longer duration of action than atropine or an equipotent dose of ipratropium bromide. Aerosol particle penetration is improved with tiotropium, without delaying mucus clearance from the lungs. Tiotropium 4.5-36 micrograms once daily for 4 weeks increased mean trough and average FEV(1) and FVC and mean PEFR values from baseline compared with placebo, with no evidence of tachyphylaxis. Improvements in trough FEV(1) from baseline with tiotropium 4.5-36 micrograms were not dose dependent. Based on a lack of dose response, the optimal once-daily tiotropium dosage is 18 micrograms. Steady-state trough FEV(1) values are achieved within 48 hours of commencing tiotrochodilation (for >/=24 hours) and an attenuation of the nocturnal decline in FEV(1) that were unaffected by timing of the daily tiotropium dose were seen in randomized, double-blind, placebo-controlled studies in patients with stable COPD. The drug improved static and dynamic lung hyperinflation (evidenced by reduced trapped air volume and increased tidal volume and end-of-exercise inspiratory capacity), and improved exertional dyspnea (during activities of daily living and exertion) and exercise tolerance compared with placebo in randomized, double-blind studies. In patients with stable COPD, improved sleep-related oxygen desaturation that was unaffected by the timing of the daily dose was seen with tiotropium but not with placebo. Clinically significant treatment-related disorders of conduction or rhythm, or changes in heart rate were not observed with tiotropium in this patient group. Mean maximal plasma concentrations (C(max)) were observed within 5 minutes of inhalation of a single dose of tiotropium 18 micrograms in patients with COPD. Plasma drug levels declined to minimum concentrations (C(min)) within 1 hour of treatment in healthy volunteers. Mean steady-state C(max) concentrations (16 ng/L) were achieved after 2-3 weeks of once-daily inhaled tiotropium 18 micrograms in elderly patients with COPD; tiotropium does not appear to accumulate once steady-state has been achieved.The estimated absolute bioavailability of tiotropium at steady state in healthy volunteers was approximately 20-25%, and approximately 72% of the drug is bound to plasma proteins. Excretion of tiotropium is predominantly renal (through active secretion by the kidneys), although in vitro studies suggest that cytochrome P450 (CYP) oxidation (possibly involving CYP2D6 and CYP3A4 enzymes) may have a minor role. In patients with COPD, renal excretion of the unchanged drug at 24 hours (Ae(24)) was approximately 7%. The mean plasma elimination half-life after single or multiple doses in healthy volunteers and elderly patients with COPD was approximately 5-6 days. The renal clearance and urinary excretion of tiotropium decrease with increasing age; however, these changes are not considered to be clinically significant. Because of altered steady-state C(max), C(min), area under the concentration-time curve, and Ae(24) values, caution is required with tiotropium administration in patients with moderate-to-severe renal impairment. The pharmacokinetics of tiotropium in patients with severe renal or hepatic impairment have not been studied. Tiotropium does not interact with drugs such as cimetidine or ranitidine, which are also eliminated by active renal secretion. Orally inhaled tiotropium bromide has been evaluated as a bronchodilator for the management of patients with COPD in randomized, double-blind 6-month and 1-year trials, and in several shorter studies. In clinical trials, COPD was diagnosed according to the American Thoracic Society guidelines. The bronchodilator effect was expressed as the trough FEV(1) response (the mean change in FEV(1) from baseline measured 1 hour prior to and immediately before a scheduled dose), and was the primary endpoint in all but two clinical trials. The bronchodilator effect with tiotropium 18 micrograms once daily was superior to that with placebo in several well designed trials in patients with COPD. Moreover, greater improvements in mean peak and average FEV(1) responses occurred with tiotropium but not with placebo. Mean trough, peak, and average FVC responses, and weekly mean morning and evening PEFR values were also improved to a greater extent with tiotropium than with placebo. Tiotropium demonstrated a greater bronchodilator effect than ipratropium bromide (hereafter referred to as ipratropium when used at approved dosages) 40 micrograms four times daily in two 1-year trials in patients with COPD. Mean peak and average FEV(1), mean trough FVC responses, and weekly mean morning and evening PEFR values were also increased to a greater extent with tiotropium than with ipratropium. In one of the two 6-month trials that compared the efficacy of tiotropium with that of inhaled salmeterol 50 micrograms twice daily, greater improvements from baseline in mean trough, peak, and average FEV(1) and FVC responses were seen with tiotropium than with salmeterol. Increases in weekly mean evening, but not morning, PEFR values were generally greater with tiotropium than salmeterol. In the second trial, improvement in the primary endpoint (mean trough FEV(1) response from baseline) with tiotropium or salmeterol was similar, although peak and average responses were superior with tiotropium. Preliminary results from a 6-week crossover study in patients with COPD suggested that tiotropium alone or in combination with once-daily formoterol improved mean trough and average FEV(1) and trough FVC values from baseline to a greater extent than twice-daily formoterol. More patients achieved a clinically important improvement (increase of >/=1 unit) in the transitional dyspnea index focal score (a measure of dyspnea-related impairment) with tiotropium than with placebo in the 1-year trials. Tiotropium was superior to ipratropium in 1-year trials, and was at least as effective as salmeterol in 6-month trials, in achieving a clinically important improvement in focal scores. Tiotropium recipients experienced fewer COPD exacerbations than placebo or ipratropium recipients and had fewer and shorter COPD-related hospitalizations compared with placebo recipients. Unlike salmeterol, tiotropium lengthened the time to onset of the first exacerbation and decreased the number of exacerbations compared with placebo in two 6-month trials. Similar proportions of tiotropium, salmeterol, and placebo recipients required COPD-related hospitalizations. (ABSTRACT TRUNCATED)     

噻托溴铵联合沙美特罗替卡松治疗慢性阻塞性肺疾病稳定期患者的疗效观察

目的 观察噻托溴铵联合沙美特罗替卡松对慢性阻塞性肺疾病(COPD)稳定期的治疗效果.方法 采用随机、双盲的方法将62例COPD患者分为观察组和对照组,观察组给予噻托溴铵和沙美特罗替卡松治疗,对照组给予沙美特罗替卡松治疗,分别对两组患者治疗前后呼吸困难评分和肺功能检测进行比较.结果 治疗两个月后,与对照组比较观察组肺功能FEV1、FVC、FEV1/FVC%,呼吸困难评分改善差异有统计学意义(P＜0.05).结论 噻托溴铵与沙美特罗替卡松联合吸入治疗COPD,疗效优于沙美特罗替卡松单药治疗.     

噻托溴胺粉吸入剂对稳定期COPD患者运动耐量及肺功能的疗效

目的探讨稳定期COPD患者予噻托溴胺粉吸入剂治疗后运动耐量及肺功能的改善作用。方法 60例稳定期COPD患者,随机分成治疗组、对照组以及空白对照组。观察三组治疗不同时期肺功能的变化和St Georges呼吸问卷(SGRQ)情况,进行6 min步行试验观察运动耐力的变化。结果用药6个月后治疗组患者咳嗽、咳痰、气促等症状明显好转,前后比较(P<0.05),用药6个月后治疗组FEV1、FVC、FEV1/FVC及FEV1占预计值(%)、运动耐力较对照组及空白对照组改善,三组比较差异有显著性(P<0.05)。治疗组运动耐力(6MWT)增加,SGRQ评分比较治疗组明显下降(P<0.05)。结论吸入噻托溴胺粉吸入剂对稳定期COPD患者运动耐量及肺功能有改善作用,并可以减少急性发作次数,改善患者生活质量,且副反应少。     

噻托溴铵联合沙美特罗/丙酸氟替卡松治疗慢性阻塞性肺疾病稳定期患者的疗效观察

目的 观察沙美特罗/丙酸氟替卡松(舒利迭)联合噻托溴铵粉吸入剂(思力华)对慢性阻塞性肺疾病(COPD)缓解期的治疗效果.方法 采用随机、双肓的方法将85例COPD患者分为观察组和对照组,观察组A组给予噻托溴铵和沙美特罗/丙酸氟替卡松治疗,对照组B组给予沙美特罗/内酸氟替卡松治疗.分别对两组患者治疗前后的呼吸困难的评分、...