Comparison of the bronchodilator effects of salbutamol delivered via a metered-dose inhaler with spacer, a dry-powder inhaler, and a jet nebulizer in patients with chronic obstructive pulmonary disease

The aim of this study was to compare the bronchodilator effects of salbutamol delivered via three different devices: a dry-powder inhaler (DPI), a metered-dose inhaler (MDI) with a large-volume spacer and a jet nebulizer (NEB) in patients with stable chronic obstructive pulmonary disease (COPD). Ten male patients with stable COPD [age: 67.2 +/- 3.8 years, forced expiratory volume in 1 s (FEV1): 1.56 +/- 0.32 liters] were studied in a randomized, double-blind and crossover manner. Each patient received 200 or 1, 000 microg salbutamol via an MDI with an InspirEaseTM spacer, a RotahalerTM, or a DeVilbiss 646(TM) nebulizer (NEB), or matching placebo on 7 separate days. Spirometry was performed before and 15, 30, 60, 90, 120, and 240 min after inhalation. With the 200- microg dose, only DPI produced a small but greater response in maximum FEV1 and in area under the time-response curve (AUC-FEV1) compared with placebo. With the 1,000- microg dose, DPI and MDI produced equally greater improvements in both maximum FEV1 and AUC-FEV1 than NEB. An equal bronchodilating effect can be obtained using either DPI or MDI with a spacer device, whereas the NEB was less effective when the same dose was administered.     

Rapid onset of bronchodilation in COPD: a placebo-controlled study comparing formoterol (Foradil Aerolizer) with salbutamol (Ventodisk)

Formoterol fumarate is a beta2-agonist bronchodilator that combines a fast onset of action with a long duration of action. Its fast onset of action is well documented in asthma but has not been directly compared with that of salbutamol in patients with chronic obstructive pulmonary disease (COPD). This randomized, double-blind, placebo-controlled study was conducted to assess the bronchodilatory effects over the first 3 h after inhalation of single doses of formoterol 24 microg delivered via the Aerolizer dry powder inhaler device (double-blind), or salbutamol 400 microg delivered by a Diskhaler dry powder inhaler (single-blind) in patients with COPD. A total of 24 patients with COPD were randomized [mean age 61.6 +/- 7.8 years, mean forced expiratory volume in 1 sec (FEV1) 1.38 +/- 0.32 l and 45.8 +/- 9.6% of predicted]. Inhalation of formoterol or salbutamol resulted in similar increases in FEV from 0 to 3 h post-dose. Both drugs produced similar bronchodilation by 5 min, which became almost maximal by 30 min. The primary efficacy variable, the area under the curve (AUC) of the FEV increase above predose baseline from 0 to 30 min (AUC(0-30 min)), demonstrated significant effects for formoterol (mean 5.89 +/- 4.67 l min(-1)), and salbutamol (mean 6.06 +/- 4.34 l min(-1)), which were not statistically different from each other but statistically significantly higher (P<0.0001) than that observed with placebo (-0.32 +/- 2.59 l min(-1)). In addition, both formoterol and salbutamol produced similar and rapid increases in forced vital capacity (FVC). In summary, this study confirms the rapid onset of action of formoterol and indicates that the onset of action of formoterol and salbutamol are similar in 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)     

Additive benefits of tiotropium in COPD patients treated with long-acting beta agonists and corticosteroids

OBJECTIVE AND BACKGROUND: The addition of an alternative class of long-acting bronchodilator is recommended for COPD patients who do not respond satisfactorily to monotherapy. The aim of this study was to investigate the additive benefit of tiotropium in severe COPD and to establish whether the improvement in lung function in these patients can be predicted from their acute bronchodilator response to ipratropium or salbutamol. METHODOLOGY: Forty-six patients with severe COPD treated with inhaled long-acting beta(2) agonists and corticosteroids (LABA/CS) were enrolled. Their prebronchodilator FEV(1) was less than 50% of the predicted value. Tiotropium (18 microg, once daily) was added via a dry-powder inhaler device. After a month of treatment, tiotropium was stopped but their previous medication was continued. Patients were reassessed a month later. Acute bronchodilator response to ipratropium and salbutamol was assessed prior to tiotropium treatment. Pulmonary function and health status were evaluated. RESULTS: Adding tiotropium significantly improved FVC, FEV(1) and inspiratory capacity (IC). The increase in FVC was significantly associated with an increase in IC (r = 0.36, P = 0.019) and a decrease in residual volume (r =-0.56, P < 0.001). Total scores of St. George Respiratory Questionnaire scores were significantly improved after adding tiotropium treatment (P < 0.001). After tiotropium withdrawal, FVC, FEV(1) and IC decreased markedly. Bronchodilator response to ipratropium did not predict the tiotropium-mediated improvement in FEV(1) or FVC. CONCLUSIONS: Adding tiotropium to inhaled LABA/CS can yield clinical benefits in lung function and improved quality of life in COPD patients, as both drugs act through separate yet complementary pathways to maintain airway calibre.     

Contribution of ipratropium bromide to the bronchodilator test in patients with chronic obstructive pulmonary disease.

The aim of the study was to analyze the bronchodilator test (BDT) response to ipratropium bromide (IB) in patients with chronic obstructive pulmonary disease (COPD) who do not respond to inhaled terbutaline. Sixty patients with stable COPD who showed a negative response to BDT, defined as an increase of less than 160 ml in the forced expiratory volume in the first second (FEV1) after inhaling 1500 microg of terbutaline, were recruited. Each patients randomly received 200 microg of IB or placebo in a single blinded fashion, and a spirometric study was made at 30 and 60 min. The increase in absolute values of FEV1 at 30 and 60 min after IB was significantly higher than after placebo. The means +/- SD were 126 +/- 93 vs. 70 +/- 96 ml at 30 min and 148 +/- 120 vs. 74 +/- 132 ml at 60 min (P=0.01). The BDT was positive in 57% of patients who received IB, considering a positive response as an increase of FEV1 greater than 160 ml (P=0.01). We conclude that the BDT was positive with high doses of IB in more than half of COPD patients who did not respond to terbutaline alone.     

Acute bronchodilator trials in chronic obstructive pulmonary disease.

Short-term trials of bronchodilator drugs are widely used to assess patients with stable chronic obstructive pulmonary disease (COPD), but there is an uncertainty about the equivalence of the FEV1 response to beta-agonists and anticholinergic drugs, their relative ability to identify patients likely to improve with corticosteroids, the most appropriate way to express the results of these tests, and whether age or allergic status affects the beta-agonist and anticholinergic response differently. We studied 100 consecutive patients with stable COPD (mean FEV1, 0.96 +/- 0.48 L; mean age, 62 +/- 8 yr). Spirometry was measured before and after either 5 mg of nebulized salbutamol or 500 micrograms of nebulized ipratropium bromide and repeated after 2 wk of 30 mg of oral prednisolone daily. Total IgE, specific RAST, and skin prick testing values were recorded. Using modified American Thoracic Society response criteria, 33 patients failed to bronchodilate after the acute trials, 16 responded only to nebulized salbutamol, 17 to nebulized ipratropium, and 34 to both drugs. Twenty-two patients improved after corticosteroids. This was usually detected by a positive acute trial response (salbutamol 90% specific; ipratropium 84% specific). Baseline FEV1 differed between days, and in those who responded on only 1 day, this variation correlating with the response to ipratropium (r = 0.66). Expressing the response criterion as a percentage change in the available bronchodilatation increased the numbers responding with a high baseline FEV1, and vice versa. Neither age nor allergic status was related to the change in FEV1 after either drug in these patients. In COPD patients, testing with high-dose nebulized bronchodilators identifies a substantial number of partially reversible patients whatever age it is employed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dose response to ipratropium as a nebulized solution in patients with chronic obstructive pulmonary disease. A three-center study

We performed a dose-response study of ipratropium bromide as a nebulized solution in patients with stable chronic obstructive pulmonary disease (COPD) using a double-blind crossover format. Five doses from 0.05 to 0.6 mg of ipratropium bromide as a nebulized solution, the standard dose of ipratropium bromide by metered-dose inhaler, 40 micrograms, and placebo were given in random order on separate days. End points were the maximal increase in FEV1 and FVC, and the area under the FEV1 and FVC curves in the 8 h after administration of each of the seven treatments. Forty-two patients completed all seven study days. By each of the above end points for FEV1, 0.4 and 0.6 mg of nebulized ipratropium bromide achieved significantly more bronchodilatation than did each of the other treatments. These two doses were not significantly different from each other, suggesting that the optimal dose in this patient population is 0.4 mg. After this dosage, the FEV1 increased by 440 +/- 194 (mean +/- 1 SD) ml at peak effect between 1 and 2 h, and significant bronchodilatation persisted for 6.5 h. Ipratropium bromide by metered-dose inhaler (40 micrograms) was equivalent to approximately 0.1 mg by nebulized solution and achieved only 63 to 73% of the bronchodilatation achieved by optimal doses of the nebulized solution. In terms of FVC, all treatments with ipratropium were significantly better than with placebo. The area under the FVC curve was significantly greater after 0.4 and 0.6 mg of nebulized solution than after other treatments. No significant adverse experiences occurred with any of the treatments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quality of life measurements and bronchodilator responsiveness in prescribing nebulizer therapy in COPD

Nebulized bronchodilators are widely regarded as the optimal treatment for maintenance therapy in patients with severe chronic obstructive pulmonary disease (COPD). The aim of the study was to assess whether detailed physiological, functional and quality of life-related measurements can assist in determining the requirement for nebulized bronchodilator therapy in patients with moderate to severe COPD. This was an unblinded, randomized, crossover study that compared intermediate (120 mcg ipratropium bromide and 600 mcg of salbutamol using metered dose inhaler (MDI) and spacer) and high dose (nebulized 500 mcg ipratropium bromide and 2.5 mg salbutamol) bronchodilator therapy, on physiological, functional and quality of life-related measurements in patients with COPD. A total of 25 patients (12 female), mean (SD) age 68 (7) years, FEV(1) 45 (10) % predicted completed the study. There was no statistically significant difference between the treatments in the pre- and post-bronchodilator lung function values, six-minute walk distance, breathlessness score or quality of life questionnaires. Fifteen patients preferred bronchodilator therapy with nebulizer and 10 with MDI and spacer. In 20 patients at least one positive response in quality of life score, lung function or six-minute walk, was observed on the preferred treatment. Only a proportion of patients with moderate or severe COPD prefer nebulized bronchodilator therapy. This study found that none of the parameters singly or in combination were consistently predictive of patients' preference for nebulized bronchodilator therapy. Therefore, we suggest that clinicians institute a trial of stepping up to an intermediate dose of bronchodilators prior to introducing nebulized therapy.     

A comparison of responses to albuterol delivered by two aerosol devices

Nineteen outpatients with stable obstructive pulmonary disease (mean forced expiratory volume in one second [FEV1], 1.00 + 0.10 L) were evaluated for airway response to albuterol (salbutamol) administered by metered-dose inhaler and Bosch ultrasonic nebulizer (BUSN). Albuterol administered by metered-dose inhaler but not by nebulizer caused a significant increase in FEV1 and the mean forced expiratory flow over the middle half of the forced vital capacity (FEF25-75%) (p less than 0.02). Absolute increase from baseline of FEV1 and FEF25-75% was significantly greater for metered-dose inhaler (0.21 +/- 0.05 L; 0.32 +/- 0.13 L/sec) compared to ultrasonic nebulizer (0.07 +/- 0.03 L; 0.03 +/- 0.04 L/sec) (p less than 0.02). In 11 subjects (mean FEV1, 1.08 + 0.14 L), the placebo effect of inhalation of the diluent from the metered-dose inhaler (Freon) and the ultrasonic nebulizer (isotonic saline solution) was determined. Freon produced the mean increase of 1.5 percent, whereas the ultrasonic aerosol of isotonic saline solution resulted in a mean decrease of 8 percent in FEV1. Therefore, the inferior response to albuterol administered by ultrasonic nebulizer was at least in part due to the superimposed broncho-constriction occurring with ultrasonically administered saline solution. The metered-dose inhaler was more effective than the ultrasonic nebulizer for administration of albuterol in stable obstructive pulmonary disease, and the latter device is not recommended. A specific ultrasonic nebulizer should be prescribed only if its superiority to a metered-dose inhaler can be objectively documented.     

A comparison of several agents with two delivery systems for the prevention of airway narrowing induced by nebulised pentamidine isethionate

Bronchial narrowing is the major side effect of inhaled nebulised pentamidine isethionate, used for the prophylaxis and treatment of Pneumocystis carinii pneumonia. Several agents and delivery systems were assessed for prophylaxis of bronchial narrowing in HIV-positive males receiving regular nebulised pentamidine isethionate. In a previous study we found the mean maximum fall in FEV1 with nebulised pentamidine alone to be 21%. FEV1 was measured before and after inhaling nebulised pentamidine, preceded by one of the following bronchodilator/immunoregulatory agents: Terbutaline metered dose inhaler (500 micrograms), nebulised salbutamol (5 mg), nebulised ipratropium bromide (500 micrograms), nebulised sodium cromoglycate (20 mg), and nedocromil sodium metered dose inhaler (4 mg). Each agent was administered once only to ten different subjects. Nebulised salbutamol gave most effective prophylaxis against bronchial narrowing induced by nebulised pentamidine (mean maximum fall in FEV1 = 5% vs. 21%, P less than 0.001). Terbutaline given by metered dose inhaler was significantly less effective than high dose terbutaline (10 mg) given by nebuliser, demonstrated in the previous study (mean maximum fall in FEV1 = 14% vs. 6%, P less than 0.05). Mean maximum falls in FEV1 for ipratropium bromide, sodium cromoglycate and nedocromil sodium were 16, 17 and 16%, respectively. High dose beta 2-agonists administered by nebuliser give more effective prophylaxis against nebulised pentamidine-induced bronchial narrowing than either lower doses given by metered dose inhaler, anticholinergics or immunoregulatory drugs.     

Inhaled formoterol versus ipratropium bromide in chronic obstructive pulmonary disease

BACKGROUND: Short-acting anticholinergic bronchodilator, ipratropium bromide has been recommended as first-line drug in chronic obstructive pulmonary disease (COPD). More recently, long acting beta2-agonist (LABA) bronchodilators such as formoterol have been shown to be useful in COPD. Limited information is available on the relative efficacy of these two drugs in COPD. METHODOLOGY: A randomised, double-blind, cross-over, placebo-controlled study was carried out. Forty-four stable patients with COPD received single doses of formoterol (12 microg), ipratropium bromide (40 microg) or placebo, administered through a metered-dose inhaler on three consecutive days in a random order. Spirometry, static lung volumes, pulse rate and blood pressure, and assessment of sensation of dyspnoea at rest using a visual analog scale (Borg Scale) were recorded at baseline. Subsequently, these were repeated for assessment of response: spirometry at 5, 30 and 60 minutes and static lung volumes, pulse rate, blood pressure and dyspnoea measurement at 60 minute. RESULTS: Formoterol resulted in greater immediate improvement in lung function, with the change in FEV1 at 5 min being greater than that observed with ipratropium. The changes in static lung volumes were similar between the two but superior to placebo. Both the drugs reduced dyspnoea. Formoterol produced a significantly greater increase in heart rate and systolic blood pressure as compared to ipratropium, although the magnitude of these changes was small and clinically unimportant. CONCLUSIONS: Single therapeutic doses of formoterol and ipratropium bromide are equally effective in improving lung function and reducing dyspnoea. However, formoterol appears to be a better bronchodilator producing a faster improvement in lung function.     

Bronchodilator response to inhaled beta-2 agonist and anticholinergic drugs in patients with bronchiectasis

OBJECTIVE: An increase in incidence of reversible airflow obstruction and bronchial hyperresponsiveness occurs in patients with bronchiectasis. We conducted a study to assess the efficacy of bronchodilators in the treatment of bronchiectasis. METHODOLOGY: Twenty-four patients with confirmed bronchiectasis were studied. Each patient inhaled fenoterol 400 microg administered by metered dose inhaler via a spacer after a baseline lung function and a lung function test was repeated 30 min later. This was followed by a second dose of fenoterol 5 mg via nebulizer and another lung function test 30 min later. A repeat study was done at least 24 h later with ipratropium bromide 40 microg by metered dose inhaler and 500 microg by a nebulizer. RESULTS: The results showed a significant improvement from baselines (mean percentage change +/- SD) of peak expiratory flow rate (PEF) by 8.5 +/- 8.72% and 15.3 +/- 11.63%, forced expiratory volume in 1 s (FEV1) by 8.77 +/- 9.69% and 10.2 +/- 12.2% and forced vital capacity (FVC) by 10.25 +/- 11.61% and 10.09 +/- 10.88% after low- and high-dose fenoterol, respectively. The improvements after low- and high-dose ipratropium bromide for PEE FEV1 and FVC were 9.89 +/- 9.35% and 14.39 +/- 12.82%, 9.38 +/- 10.41% and 13.52 +/- 17.09%, and 8.03 +/- 10.85% and 9.63 +/- 13.85%, respectively. Eleven patients (45.8%) responded to one or both bronchodilators significantly (> 15% improvement in FEV1). Five patients (20%) responded to both, three (12%) to fenoterol alone and another three (12%) to ipratropium bromide alone. CONCLUSION: There is significant bronchodilator response in a subset of patients with bronchiectasis and patients with bronchiectasis should therefore undergo bronchodilator testing. Skin prick testing against a panel of nine allergens done on each individual yielded a positive result in 13 patients (54.2%).     

Formoterol Turbuhaler as reliever medication in patients with acute asthma.

The aim of this study was to compare the efficacy and safety of formoterol versus salbutamol as reliever medication in patients presenting at an emergency dept with acute asthma. A randomised, double-blind, double-dummy, parallel group study was performed in four Australian emergency treatment centres. The study included a total of 78 adult patients (mean baseline forced expiratory volume in one second (FEV1) 1.83 L; 59% predicted) with acute asthma. Based on the expected dose equivalence of formoterol Turbuhaler 4.5 microg (delivered dose) and salbutamol pressurised metered-dose inhaler 200 microg (metered dose), patients received a total of formoterol Turbuhaler 36 microg (delivered) or salbutamol pressurised metered-dose inhaler with spacer 1,600 microg (metered), divided into two equal doses at 0 and 30 min. FEV1, peak expiratory flow and systemic beta2-agonist effects were monitored for 4 h. The primary variable was FEV1% pred at 45 min. At 45 min, mean increases in FEV1 expressed in % pred were 6.6% and 9.3%, respectively, with a small adjusted mean difference in favour of salbutamol (3.0%, 95% confidence interval -2.0-8.0). Transient increases in systemic beta2-agonist effects occurred predominantly with salbutamol, although no significant treatment differences were observed. Eight patients discontinued due to adverse events. In this study of patients presenting at emergency depts with acute asthma, formoterol Turbuhaler 36 microg was well tolerated and, as rescue therapy, had an efficacy that was not different from that of salbutamol pressurised metered-dose inhaler with spacer 1,600 microg in the number of patients studied.     

Effect of different inhaled bronchodilators on recovery from methacholine-induced bronchoconstriction in asthmatic children.

Two hundred fourteen children with mild to moderate asthma were studied to determine bronchodilator effects 5 min after administration of five different metered dose inhaler (MDI) aerosol formulations available in our country, and results were compared to placebo. Methacholine bronchial challenge was performed by the tidal breathing method, using increasing concentrations until a fall in forced expired volume in 1 s (FEV(1)) >/=20% was achieved (PC20). Immediately after FEV(1) had fallen 20% or more, children were randomly allocated into 1 of 6 groups to receive: salbutamol 200 microg (S), fenoterol 200 microg (F), salbutamol 200 microg + beclomethasone 100 microg (S + B), fenoterol 200 microg + ipratropium bromide 80 microg (F + IB), salmeterol 50 microg (SM), and placebo (P). The bronchodilator effect was determined by measuring FEV(1) 5 min after inhalation of medications. Nonparametric tests were used for statistical analysis. The six groups were similar in anthropometric and in respiratory characteristics. All five inhaled aerosols containing beta-agonists caused a significant bronchodilator effect as compared to placebo. However, the effect was significantly greater in the groups treated with F or F + IB (P < 0.05) compared to other formulations. We conclude that the five types of aerosols used in this study are able to reverse methacholine-induced bronchoconstriction 5 min after inhalation of a bronchodilator.     

A randomized study of tiotropium Respimat Soft Mist inhaler vs. ipratropium pMDI in COPD

The aim of these studies was to compare the efficacy and the safety of tiotropium, delivered via Respimat Soft Mist Inhaler (SMI), a novel multi-dose, propellant-free inhaler, with ipratropium pressurized metered-dose inhaler (pMDI) in chronic obstructive pulmonary disease (COPD) patients. Two identical, 12-week, multi-national, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled studies were performed. COPD patients were randomized to treatment with either inhaled tiotropium (5 or 10 microg) via Respimat SMI administered once daily, ipratropium (36 microg) pMDI QID or placebo. The primary endpoint was the mean trough forced expiratory volume in 1s (FEV(1)) response after 12 weeks of treatment. Secondary endpoints included other spirometry measures and rescue medication use. A total of 719 patients were randomized; the majority were male (69%) with a mean pre-bronchodilator FEV(1) (% predicted) of 40.7%. The mean treatment differences between tiotropium 5 and 10 microg and placebo for the primary endpoint (mean trough FEV(1) response at week 12) were 0.118 and 0.149L, respectively (both P<0.0001). Treatment differences between tiotropium 5 and 10 microg and ipratropium were 0.064L (P=0.006) and 0.095L (P<0.0001). The increases in peak FEV(1), FEV(1) AUC((0-6h)) and FVC for both tiotropium doses were statistically superior to placebo (P<0.01) and higher than ipratropium. All active treatments significantly reduced the rescue medication use compared with placebo, but only tiotropium 10 microg was statistically superior to ipratropium (P=0.04). The incidence of adverse events was comparable across groups. In conclusion, tiotropium 5 and 10 microg daily, delivered via Respimat SMI, significantly improved lung function compared with ipratropium pMDI and placebo.     

Comparison of acute bronchodilator effects of inhaled ipratropium bromide and salbutamol in bronchial asthma.

Both salbutamol (sal) and ipratropium (ipra) are effective bronchodilators in asthma patients. However, the issue of their relative status remains unresolved and the clinical factors affecting the responses have also not been adequately defined. The two drugs were compared in 44 asthmatics in a double-blind, randomized crossover, placebo-controlled study. There were four test days on which each patient received the following sequences of drugs: sal-sal-ipra, sal-sal-placebo, ipra-ipra-sal, and ipra-ipra-placebo. Baseline forced expiratory volume in 1 sec (FEV1) was similar on the four days. The change in FEV1 produced by salbutamol when given as the first bronchodilator was 0.50 +/- 0.30 L as compared to a change of 0.39 +/- 0.27 L produced by ipratropium (p < 0.01). Both salbutamol and ipratropium resulted in statistically similar further improvements in FEV1 when given as the second drug. There was, however, a wide patient-to-patient variability in response, with some patients showing greater improvement with salbutamol and others with ipratropium. Younger patients showed a greater response to salbutamol as compared to older patients, while no such difference was observed with ipratropium. Males responded better to both the drugs as compared to females. It was concluded that both salbutamol and ipratropium are effective bronchodilators in asthma patients, although the overall response to salbutamol appears to be superior. However, some patients may respond better to one or other of the two drugs. Sequential administration of the two drugs may be a justified therapeutic approach as some patients show have further improvement with use of the second drug.     

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.     

The role of domiciliary nebulizers in managing patients with severe COPD

The difficulty of assessing nebulizer responses in chronic obstructive pulmonary disease (COPD) has been demonstrated before. This study aims to re-examine both the role of domiciliary nebulizers in COPD and also bronchodilator (BD) assessment in individuals. In a double-blind, randomized, cross-over trial, 19 stable patients with severe COPD were given the following medication 6-hourly for 2-week periods: (1) nebulized salbutamol 2.5 mg with ipratropium 0.5 mg and placebo inhalers (MDI) with spacer; (2) placebo nebules and inhaled salbutamol 400 microg with ipratropium 80 microg via MDI with spacer; (3) inhaled salbutamol 400 microg with ipratropium 80 microg via MDI with spacer (but no placebo nebulized drugs). Both nebulized and MDI drugs produced highly significant improvements in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), specific airways conductance, 6-min walking distance (6MWD) and residual volume. There were no significant differences between BD responses obtained after active nebulized and active MDI BDs. From the diary cards, 2 weeks of active nebulized BDs produced a slightly higher median peak expiratory flow (PEF) than active MDI BDs (236 and 219 l m(-1), respectively, P=0.01) and slightly less extra inhaler use (0.8 and 1.1 puffs, respectively, P<0.05) but no significant difference in dyspnoea or quality of life (QOL) scores. There were significant correlations between domiciliary PEF and acute BD-induced changes in FVC and 6MWD, and also between domiciliary dyspnoea scores and acute changes in both total lung capacity and 6MWD. In conclusion, nebulized medication conferred little clinical advantage over the regular use of inhalers with spacers in this group of patients with severe COPD. However, acute changes in total lung capacity, FVC and 6MWD may be useful predictors of the longer-term effects of nebulized BDs in individual patients.     

Efficacy of nebulized flunisolide combined with salbutamol and ipratropium bromide in stable patients with moderate-to-severe chronic obstructive pulmonary disease

BACKGROUND: The efficacy of nebulized corticosteroids in the prevention of exacerbation of chronic obstructive pulmonary disease (COPD) has been poorly studied. OBJECTIVE: To evaluate the efficacy and tolerability of nebulized flunisolide (1 mg) + salbutamol/ipratropium bromide (1,875/375 microg) b.i.d. in comparison with placebo + salbutamol/ipratropium bromide. METHODS: This was a randomized, parallel-group, double-blind study on 114 patients with COPD of moderate-to-severe degree. The main outcome was the frequency of severe exacerbations over a 6-month period. Before and after treatment, respiratory symptoms, forced expiratory volume in 1 s (FEV(1)), shuttle walking test distance and St. George's Respiratory Questionnaire scores were evaluated. RESULTS: The total number of exacerbations was slightly lower in the flunisolide group compared to the placebo group (19 vs. 34, p = 0.054); the number of patients experiencing at least one exacerbation during the study was also decreased (16 vs. 26, p = 0.059). In particular, type 3 Anthonisens's exacerbations were significantly reduced by flunisolide (p = 0.044). In the placebo group, scores were higher than in the flunisolide group but nonsignificant for dyspnea, cough, sputum amount and purulence. FEV(1) was significantly increased compared to baseline in both groups, and the area under the FEV(1)-time curve during the 6-month period was significantly greater in the flunisolide group (5.2 +/- 10.6 vs. 2.1 +/- 5.0, flunisolide vs. placebo, respectively; p = 0.047). For shuttle walking test distance and scores of the St. George's Respiratory Questionnaire, no significant difference between the baseline evaluation and the end of the study was observed in both groups. CONCLUSIONS: Nebulized flunisolide is a good alternative to other inhaled corticosteroids when added to nebulized salbutamol/ipratropium bromide in the long-term treatment of moderate-to-severe COPD 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.