Effectiveness of inhaled bronchodilator delivery systems for elderly patients.

A prospective study of inhaler technique using aerosol metered dose inhalers (MDIs), Rotahalers and a breath-activated device (Aerolin Autohaler) was undertaken to assess how effectively elderly patients use their inhalers. Fifty-one patients aged 67-89 years (mean 77.4 years) were enrolled. Peak flow, FEV1 and FVC were recorded, before and after inhalation of 2.5 mg of salbutamol via a nebulizer, to assess the extent of reversible airways obstruction. Inhaler technique was assessed using a scoring system, based on performance in five aspects of inhaler use. Those with poor technique were randomly allocated to an alternative inhaler and reassessed. Twenty-nine of 51 patients demonstrated reversibility in their airways disease. Twenty-one of 47 had poor technique using an MDI and were given Rotahaler or Aerolin devices to use. Ten of 11 given Aerolin Autohalers improved but seven of ten using Rotahaler showed no improvement (p = 0.006). Subsequently, five of these seven were able to improve their technique with the breath-activated autohaler. The breath-activated Aerolin Autohaler is a better delivery system than Rotahalers for inhaled bronchodilators for elderly patients.     

Breath-actuated inhalers: comparison of terbutaline Turbohaler with salbutamol Rotahaler

Two breath-actuated inhalers, the Turbohaler and the Rotahaler, were compared in 24 patients with chronic asthma using an open, cross-over study design. Patients were treated with terbutaline (500 micrograms) and salbutamol (400 micrograms) four times daily, each trial period lasting three weeks. Mean morning peak expiratory flow (PEF) values were higher during Turbohaler treatment, but were similar 15 min after inhaler use. The Turbohaler was found to be easier to use than the Rotahaler.     

The relative bioavailability of salbutamol to the lung using urinary excretion following inhalation from a novel dry powder inhaler: the effect of inhalation rate and formulation

Each dry powder inhaler has a different resistance so that a respirable dose can be generated from the formulation by the patient's inspiratory effort. It is important to recognize that this effect is achievable. The inspiratory flow characteristics of asthmatics inhaling through a Clickhaler were determined. In a separate study 10 volunteers inhaled separate 2 x 100 microg salbutamol doses from a Clickhaler (ML Laboratories plc U.K.). Two different formulations (one with a high and one with a low respirable fraction) were each inhaled using an inspiratory flow of 30 and 60 l min(-1). A urine sample was collected 30 min post inhalation and then pooled for the next 24 h. The mean (SD) inhalation rate of 24 asthmatics when they inhaled from a Clickhaler was 37.3 (14.6) l min(-1). The mean (SD) urinary salbutamol excretion during the first 30 min, by the volunteers, using the high respirable dose formulation at 30 and 60 l min(-1) was 5.59 (1.87) and 4.62 (1.49) microg respectively (P<0.01). Similar values using the low respirable dose formulation were 4.84 (1.58) and 3.86 (2.14) microg. There was no significant difference between the amounts excreted in the 24 h post-dose. The different 30-min urinary excretions following inhalation of the two formulations suggest a link between the relative bioavailability of salbutamol to the lung and the respirable dose, and that a slow inhalation rate should be used when using a Clickhaler. The patient study shows that this rate is achieved by most asthmatics without further training.     

Comparative assessment of a new breath-actuated inhaler in patients with reversible airways obstruction.

Twenty-five patients with reversible airways obstruction inhaled salbutamol (200 micrograms) from the standard press and breathe-metered dose inhaler or a new breath-actuated metered dose inhaler (Aerolin in the Autohaler inhalation device; 3M Health Care Ltd.) in a single dose, double-blind, double-dummy, 2-period, cross-over study. Forced expiratory volume in 1 s, forced vital capacity and peak expiratory flow rate were measured in the 4-hour period after inhalation. The equivalence of the two inhaler devices was determined by analysis of the peak change and time to peak, with reference to the initial recorded baselines of the measured parameters. The efficacy of the two devices was very similar. The breath-actuated device is likely to benefit inhaler users who suffer from poor co-ordination of actuation and inhalation with a standard inhaler.     

Bronchodilating effects of salbutamol from a novel inhaler Airmax

This randomized, placebo-controlled, evaluator-blind, five-way crossover study compared the equivalence in terms of FEV1 response to single ascending cumulative doses of salbutamol (100-400 micrograms) from Airmax, a new multidose dry powder inhaler, in comparison with placebo, the same dose from a standard pressurized metered dose inhaler (Ventolin) or at double the dose from the dry powder inhalers Diskhaler and Accuhaler. Sixty-one adult asthmatic subjects with FEV150-80% predicted and > or = 15% increase in FEV1 to salbutamol took part. Equivalence was declared if the 95% CI for the ratio of the FEV1 responses to the two treatments was within the range 90-111%. Following the cumulative four doses, FEV1 (1) changes pre-dose to the highest dose were: 2.53-3.31, 2.47-3.30, 2.51-3.35, 2.52-3.31 and 2.57-2.55 for Airmax salbutamol, salbutamol Ventolin, salbutamol Diskhaler, salbutamol Accuhaler and placebo, respectively. The 95% CIs for the ratio of Airmax salbutamol to each of the active devices were within +/- 5% demonstrating a 1:1 dose equivalence between Airmax salbutamol and Ventolin and a 1:2 dose equivalence between each of the other two salbutamol dry powder devices. Adverse events profiles were similar for all treatments. In conclusion, the novel multidose inhaler Airmax salbutamol is as efficacious and safe as the pressurized metered dose inhaler without the need for co-ordinating actuation and inhalation and with the added benefit of a dose counter.     

Long-term comparison of salbutamol powder with salbutamol aerosol in asthmatic out-patients.

Salbutamol dry powder was compared with salbutamol aerosol in 38 asthmatic patients. The study was double-blind and took place over six months. Salbutamol powder in a dose of 200 micrograms per capsule was able to control asthma as well as the aerosol, but some patients needed to increase the frequency of dosage when using the powder. The device used for powder administration, the Rotahaler, was well accepted and was preferred to the pressurized aerosol by one-third of patients. Dry powder administered by Rotahaler allows salbutamol to be given by inhalation to many patients previously using aerosols inefficiently.     

New formulation metered dose inhaler increases breath alcohol levels.

A new, chlorofluorocarbon-free metered dose inhaler containing salbutamol, with small amounts of ethanol as a co-solvent, has recently been released. We evaluated the effect on breath alcohol levels of two inhalations from this metered dose inhaler. In 10 volunteers, breath alcohol levels rose to 17.9 micrograms 100 ml-1 breath after an inhalation with a good technique, and to 35 micrograms 100 ml-1 breath (the current legal limit for driving in the UK) after a poor inhalation. Breath alcohol levels were reduced by the use of a spacer device, and in all cases fell to near zero after 2 min. In patients who have just used this type of metered dose inhaler, breath alcohol measurements should be defferred for at least 2 min.     

Protection against methacholine-induced bronchospasm: salbutamol pMDI versus Clickhaler DPI.

Passive dry-powder inhalers (DPIs) have been developed as an alternative to pressurised metered-dose inhalers (pMDIs) to improve aerosol delivery on inhalation and eliminate the need for propellants. However, new DPI formulations of generic drugs must be rigorously compared with conventional pMDI therapy. This randomised, double-blind, double-dummy, placebo-controlled, seven-way crossover study evaluated bronchoprotection from methacholine challenge in order to compare a novel salbutamol DPI (Clickhaler) with a reference salbutamol pMDI (Ventolin). Adult asthma patients with airway hyperresponsiveness to methacholine (provocative concentration of methacholine causing a 20% fall in the forced expiratory volume in one second (PC20) <4 mg x mL(-1)) were treated on separate days with 0, 100, 200 or 400 microg of salbutamol via the DPI or pMDI. Methacholine challenge was performed before and after salbutamol treatment and the PC20 ratios analysed by Finney's bioassay to test for therapeutic equivalence of the inhalers. Eighteen patients completed the study and showed significant dose-related responses to salbutamol. The relative potency of DPI:pMDI was 1.29 (90% confidence interval 1.04-1.63). There were no treatment differences in safety (cardiac frequency, blood pressure, adverse events). Methacholine-challenge methodology provides a sensitive bioassay and has demonstrated therapeutic equivalence of the salbutamol Clickhaler dry-powder inhaler with the conventional salbutamol pressurised metered-dose inhaler.     

Multiple inhalers confuse asthma patients.

This study investigated the influence of the use of different types of inhalers on the adequacy of inhalation technique among adult asthmatics. Three hypotheses were tested: first, patients using only one type of inhaler will demonstrate adequate inhalation technique more often than those with two or more types. Secondly, patients using a combination of dry powder inhalers (DPIs) will demonstrate correct inhalation technique more often than those using the combination of a metered dose inhaler (MDI) and a DPI. Thirdly, some inhalers or combinations of inhalers are more prone to erroneous inhalation technique than others. Adult outpatients with asthma who regularly used inhaled steroid therapy (n=321) participated in the study. The inhalers investigated were MDIs on the one hand, and the DPIs Turbuhaler, Diskhaler, Cyclohaler, Inhaler Ingelheim and Rotahaler on the other. Of 208 adult asthmatics with only one inhaler, 71% made no inhalation errors versus 61% of 113 patients with two or more different inhalers. Of patients with a combination of DPIs 68% performed all essential checklist items correctly, versus 54% of patients with the combination of "regular" MDI and DPI. Patients using only the Diskhaler made fewest errors. Whenever possible, only one type of inhaler should be prescribed. If a combination is unavoidable, combinations of DPIs are preferable to MDI and DPI. The Diskhaler seems to be the most foolproof device.     

Impact of training on use of inhalational techniques of different inhaler devices: A single institutional cross sectional observation study

ObjectiveTo assess the impact of training on use of inhalational techniques of different inhaler devices in spirometry proved cases of COPD and Bronchial Asthma in a tertiary care centre.MethodsA total of 128 spirometry proved cases of Asthma and COPD were enrolled. They were equally distributed in four groups comprising of 32 patients each according to their inhalation devices namely pMDI, Rotahaler, Accuhaler and Turbohaler. Patients were asked to demonstrate their inhalation technique and errors were noted according to their inhaler specific checklist. Patients were also interviewed regarding their knowledge about inhalation devices. Training about proper inhalation techniques was given to every participant. Rechecking of inhalation technique was again done at the second visit after 2 wks in the similar manner. Correct and incorrect steps of inhalation technique again evaluated by filling the checklist of the individual device to see post training improvement.ResultIn our study, out of total cases more than one third of the patients were >60 yrs of age (41.4%) and most of the patients were males (62.5%). During the interview at first visit, almost 92% patients claimed to know how to use the inhalation device correctly but in reality most of the patients (around 96.1%) had committed at least one mistakes in their inhalation technique among all the inhalation steps. Errors were noted in different steps of inhalation including the essential steps among all the four devices. Statistically significant improvement in inhalation techniques including the essential steps were found among all the four devices after educational intervention and demonstration of sequential steps involved in particular inhaler.ConclusionOur study confirmed a significant increase in the percentage of improvement in inhalation technique after proper demonstration and training about the inhalation devices. Inhalation technique including essential steps of inhalation significantly improved in all the four devices used.     

The efficacy of a new salbutamol metered-dose powder inhaler in comparison with two other inhaler devices

An open cross-over and randomized study was carried out in order to compare the efficacy and safety of inhaled salbutamol delivered from a new 50 microg dose(-1) metered-dose dry powder inhaler Taifun, and a commercially available 50 microg dose(-1) dry powder inhaler Turbuhaler, and a conventional 100 microg dose(-1) pressurized metered-dose inhaler with a spacer (pMDI+S). Twenty-one patients, aged 21-70 years, with stable asthma and with demonstrated reversibility upon inhalation of salbutamol were included in the study. On three separate study days, the patients received a total dose of 400 microg of salbutamol from the dry powder inhalers and a dose of 800 microg from the pMDI+S in a cumulative fashion: 1,1, 2 and 4 doses at 30 min intervals. The percent change in forced expiratory volume in 1 sec (FEV1), was used as the primary efficacy variable. Salbutamol inhaled via the Taifun produced greater bronchodilation than the other devices. The difference in percent change in FEV1 between the Taifun and the other devices was statistically significant at the two first dose levels, but diminished towards the higher doses when the plateau of the dose-response curve was reached. The estimated relative dose potency of the Taifun was approximately 1.9- and 2.8-fold compared to the Turbuhaler and the pMDI+S, respectively. The Taifun caused a slight, but clinically insignificant, decrease in serum potassium concentration. There were no significant changes in the other safety parameters (blood pressure, heart rate and electrocardiogram recordings) with any of the used devices. In conclusion, this study indicates that salbutamol inhaled via the Taifun is more potentthan salbutamol inhaled from the other devices tested. In practise, a smaller total dose of salbutamol from theTaifun is needed to produce a similar bronchodilatory response. All treatments were equally well tolerated.     

Agreement between two methods for assessing bioequivalence of inhaled salbutamol

For inhaled medications, bioequivalence testing is becoming increasingly important owing to the availability of many inhalation devices. We evaluated agreement between the Finney bioassay and the Emax model in the assessment of bioequivalence of salbutamol administered via a metered-dose inhaler with a spacer (pMDI+ Volumatic) or via a dry-powder inhaler (Diskus) in asthmatic patients with methacholine-induced bronchoconstriction. Eighteen patients inhaled methacholine until FEV 1 decreased by approximately 35% of control. Following inhalation of placebo, 200 and 400 mcg salbutamol through the pMDI+ Volumatic or the Diskus, changes in FEV 1 were repeatedly measured over a 60-min observation period. Bioequivalence of salbutamol administered via the two inhalation devices was assessed by calculating the relative potency of each device by using the Finney 2-by-2 parallel regression analysis and the non-linear, Emax model. Agreement between these methods in calculating relative potency was evaluated by using the Bland-Altman method. After salbutamol FEV 1 values were similar irrespective of the device employed, and greater (P<0.01) than those after placebo. However, assessment of relative potencies obtained with both the Finney (1.97, 90% CI 1.62-2.32) and the Emax (2.25, 90% CI 1.90-2.60) methods revealed that twice the salbutamol dose was needed to reverse methacholine-induced bronchoconstriction when the drug was inhaled via the Diskus than via the pMDI+ Volumatic. The mean difference in relative potency (-0.28, 90% CI -0.001 to -0.56) calculated with both methods did not significantly differ from zero, and none of the individual differences exceeded the limits of agreement. The Finney and the Emax methods provide comparable results in the evaluation of bioequivalence of different salbutamol formulations. The pMDI+ Volumatic is twice as efficient as the Diskus in lung delivery of salbutamol in asthma patients.     

Salbutamol metered-dose inhaler with spacer for hyperkalemia: how fast? How safe?

OBJECTIVE: To determine the efficacy of inhaled salbutamol (rapidly delivered, using a metered-dose inhaler with a spacer device [MDI-S]) in lowering the serum potassium levels in patients with hyperkalemia. DESIGN: A randomized, double-blind, placebo-controlled trial. PATIENTS: Seventeen chronic renal failure patients referred to the Nephrology Unit between October 1, 1997 and March 31, 1998 for hemodialysis were randomized. INTERVENTION AND RESULTS: Group 1 received salbutamol followed by a placebo. Group 2 received a placebo followed by salbutamol. Each patient inhaled 1,200 microg salbutamol or a placebo through an MDI-S within 2 min. Blood samples were obtained repeatedly before inhalation and after 1, 3, 5, 10, and 60 min. The pulse rate and blood pressure were repeatedly measured. Insulin levels were examined in a subset of patients (n = 10) before, and 1 and 5 min following inhalation. Salbutamol's known side effects, palpitation, tachycardia tremor, and headache, were recorded. Potassium levels rose after 1 min following the completion of treatment and then decreased steadily thereafter. A rise of > or = 0.1 mEq/L was seen in 10 of 17 patients (59%) during the treatment period and there was no change (0%) seen during the placebo period (p < 0.0001). Within 3 min after inhalation of salbutamol, potassium levels declined as a function of time. Potassium levels in those patients taking the placebo did not change as a function of time (p < 0.001). The difference between the placebo and the salbutamol-treated periods reached significance after 5 min (p < 0.05). The serum glucose levels rose following inhalation of salbutamol, with a significant rise after 3 min. The heart rate rose significantly within the first 5 min following inhalation. Serum insulin levels remained unchanged 1 min after inhalation; however, after 5 min, a significant elevation was detected. CONCLUSION: Salbutamol inhalation of 1,200 microg, using an MDI-S, has a relatively rapid onset of action that induces a consistent reduction in serum potassium levels, starting 3 to 5 min following delivery. Unexpectedly, a paradoxical elevation was detected in serum potassium levels in the first minutes following inhalation. This effect, although minor (0.15 mEq/L above baseline), may cast some doubt on the role of salbutamol inhalation as the first treatment for excessive hyperkalemia.     

Salbutamol via Easyhaler is at least as effective as salbutamol via Turbuhaler in the treatment of histamine-induced bronchoconstriction

The aim of this study was to compare the clinical efficacy and acceptability of salbutamol inhaled via Easyhaler and Turbuhaler multi-dose dry powder inhalers in the treatment of histamine-induced bronchoconstriction. Thirty-two adult patients with asthma and/or bronchial hyper-reactivity were included in the study, which was carried out according to a randomized, double-blind, double-dummy, cross-over design. Histamine challenge test was performed on 2 study days separated by at least 7 days. The challenge test was continued until a > or = 20% fall in forced expiratory volume in 1 sec (FEV1) was achieved. The patients then inhaled a single 100 microg dose of salbutamol from Easyhaler, or from Turbuhaler. FEV1 was assessed by flow-volume spirometry before and after histamine challenge and 1.5, 3, 5, 10, 15, 20, 30 and 60 min after salbutamol inhalation. The primary efficacy variable was the maximum percentage change in FEV1 from the post-challenge value. The secondary efficacy variable was area under the curve (AUC) of FEV1. At the end of the study, acceptability of salbutamol Easyhaler was evaluated using a questionnaire and Easyhaler was also compared with the inhalation device the patient had used earlier. Twenty-six patients completed the study. Both salbutamol Easyhaler and salbutamol Turbuhaler produced a rapid and significant increase in FEV1, with maximum percentage changes being 43.9% (+/-15.3) and 40.5% (+/-21.9) from the post-challenge value, respectively. There were no significant differences between the two inhalation devices in terms of changes in FEV1 or AUC of FEV1. The use of Easyhaler and getting a new dose from Easyhaler was considered to be very easy by 65% and easy by 35% of the patients. None considered it difficult. Of 16 patients who had used Turbuhaler earlier, 19% considered Easyhaler much better, 44% better, and 38% the same as Turbuhaler, and none considered it worse. In conclusion, the results show that salbutamol Easyhaler was at least as effective as salbutamol Turbuhaler in the treatment of histamine-induced bronchoconstriction. In addition, the patients considered Easyhaler very easy or easy to use. The majority of patients who reported Turbuhaler as their own inhaler considered Easyhaler better or much better than Turbuhaler.     

Clinical equivalence trial on budesonide delivered either by the Novolizer multidose dry powder inhaler or the Turbuhaler in asthmatic patients

BACKGROUND AND OBJECTIVES: To investigate the therapeutic equivalence of the two formulations of the glucocorticosteroid budesonide delivered either by the budesonide Novolizer, i.e. a multidose dry powder inhaler, or by the Pulmicort Turbuhaler in asthmatic patients in terms of efficacy, safety and tolerability during a 12-week treatment. METHODS: A total of 315 patients were randomised in this open, multicentre study. Inclusion criteria comprised previously diagnosed bronchial asthma of mild to moderate persistent intensity (ranging from 60% to a maximum of 90% predicted FEV(1)), need for anti-inflammatory therapy, inhalation of beta(2)-sympathomimetics on an as needed to regular basis, reversibility of airway obstruction of >12% after inhalation of 2 actuations of 100 microg salbutamol. Primary variable was FEV(1), secondary were other pulmonary function test variables, PC(20)FEV(1) for histamine challenge, morning and evening PEFR, salbutamol usage, asthma symptoms, reactions after inhalation, standard safety variables. RESULTS: The comparison of the FEV(1) at study endpoint indicated that the Novolizer was at least as efficacious as the Turbuhaler (p < 0.001). All other variables of the pulmonary function tests as well as the asthma symptoms, nocturnal awakenings, PEFR measurements, or salbutamol usage indicated no relevant difference. Only 1 patient (Turbuhaler discontinued prematurely due to lack of efficacy. None of the other safety variables (adverse events, laboratory variables, vital signs, etc.) indicated any difference between the groups. CONCLUSIONS: The budesonide Novolizer is therapeutically equivalent to the Pulmicort Turbuhaler for the long-term treatment of patients with mild to moderate persistent asthma.     

Reproducibility of Bronchodilator Response for a Reservoir Dry Powder Inhaler Following Routine Clinical Use

The performance of dry powder inhaler (DPI) devices, particularly reservoir DPIs, may be influenced by environmental conditions. This study compared the bronchodilator efficacy and in vitro aerosol characteristics of salbutamol, delivered via a novel reservoir DPI (Clickhaler®) and a conventional pressurized metered-dose inhaler (MDI) before and after use of the DPI in clinical practice. Following a screening visit, patients received cumulative doses of salbutamol (100, 200, and 400 ug) via DPI or MDI on separate days in a double-blind, crossover design before and after a 4-week period, during which the DPI was used as the patients' first-line bronchodilator. Lung function responses (forced expiratory volume in 1 sec [FEV₁], forced vital capacity [FVC], and peak expiratory flow [PEF]) to salbutamol delivered by DPI and MDI and in vitro aerosol characteristics were not significantly different before and after the period of DPI patient use. DPI performance, assessed in vivo and in vitro, is maintained following an extended period of patient use.     

Lung deposition of salbutamol in healthy human subjects from the MAGhaler dry powder inhaler

The MAGhaler (Mundipharma GmbH) is a multidose dry powder inhaler (DPI) containing a novel formulation of drug and lactose compacted by an isostatic pressing technique (GGU GmbH). On actuation, a precise dose is metered from a compacted ring-shaped drug tablet. In this study, the lung deposition of salbutamol from this device has been assessed. Ten healthy non-smoking subjects completed a two-way cross-over study assessing the pulmonary deposition of salbutamol (200 microg) from the MAGhaler at high (60 l/min) and low (30 l/min) peak inhaled flow rates (PIFRs), representing maximal and sub-maximal inspiratory efforts. The formulation was radiolabelled with 99mTc, and lung and oropharyngeal depositions were quantified by gamma scintigraphyThe mean (SD)% ofthe delivered dose deposited in the lungs was 26.4 (4.3)% at 60 l/min and 21.1 (5.1)% at 30 l/min (P < 0.05), corresponding to mean lung depositions of 52.8 and 42.2 microg salbutamol, respectively. The distribution of drug within different lung regions did not vary significantly with inhaled flow rate. The data provided proof of concept for the novel inhaler device and the innovative drug formulation. In comparison with previous deposition data obtained with other DPIs, the lung deposition was relatively high, relatively reproducible (coefficient of variation 16% at 60 l/min) and relatively insensitive to the change in peak inhaled flow rate.     

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.     

The protective effect of salbutamol inhaled using different devices on methacholine bronchoconstriction

STUDY OBJECTIVE: To determine the protective effect of salbutamol, 100 microg, inhaled by different devices (pressurized metered-dose inhaler [pMDI; Ventolin; GlaxoWellcome; Greenford, UK], pMDI + spacer [Volumatic; GlaxoWellcome], or breath-activated pMDI [Autohaler; 3M Pharmaceuticals; St. Paul, MN]) on bronchoconstriction induced by methacholine. DESIGN: Randomized, double-blind, cross-over, placebo-controlled study. PATIENTS: Eighteen subjects with stable, moderate asthma, asymptomatic, receiving regular treatment with salmeterol, 50 microg bid, and inhaled beclomethasone dipropionate, 250 microg bid, in the last 6 months, with high hyperreactivity to methacholine (baseline provocative dose of methacholine causing a 20% fall in FEV(1) [PD(20)] geometric mean [GM], 0.071 mg). Subjects were classified into two groups: subjects with incorrect (n = 5) pMDI inhalation technique, and subjects with correct (n = 13) inhalation technique. METHODS AND MEASUREMENTS: After cessation of therapy for 3 days, all subjects underwent four methacholine challenge tests, each test 1 week apart, each time 15 min after inhalation of salbutamol, 100 microg (via pMDI, pMDI + spacer, or Autohaler), or placebo. The protective effect on methacholine challenge test was evaluated as the change in the PD(20), and expressed in terms of doubling doses of methacholine in comparison with placebo treatment. RESULTS: The PD(20) was significantly higher after salbutamol inhalation than after placebo inhalation, but no significant difference was observed among the three different inhalation techniques. Only when salbutamol was inhaled via pMDI + spacer, PD(20) was slightly but not significantly higher (pMDI GM, 0.454 mg; pMDI + spacer GM, 0.559 mg; and Autohaler GM, 0.372 mg; not significant [NS]) than other inhalation techniques. Similar results (mean +/-SEM) were obtained with doubling doses of methacholine (pMDI, 2 +/- 0.47; pMDI + spacer, 3 +/- 0.35; and Autohaler, 2.4 +/- 0.40; NS). No significant difference was found among techniques when subjects with correct or incorrect inhalation technique were separately considered. CONCLUSIONS: Our data show that the protective effect of salbutamol, 100 microg, on methacholine-induced bronchoconstriction is not affected by the different inhalation techniques, although inhalation via pMDI + spacer tends to improve the bronchoprotective ability of salbutamol. These data confirm the clinical efficacy of salbutamol, whatever the device, and the patient's inhalation technique.     

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.