Salbutamol: comparison of bronchodilating effect of inhaled powder and aerosol in asthmatic subjects. Comparison of a new multidose powder inhaler with a pressurized aerosol in children with asthma. Clinical equivalence of a novel non-chlorofluorocarbon-containing salbutamol sulfate metered-dose inhaler and a conventional chlorofluorocarbon inhaler in patients with asthma. The protective effect of salbutamol inhaled using different devices on methacholine bronchoconstriction. Clinical comparability of albuterol delivered by the breath-actuated inhaler (Spiros) and albuterol by MDI in patients with asthma. Fenoterol inhalation powder as an alternative to treatment with the metered dose inhaler. Proventil HFA prevents exercise-induced bronchoconstriction in children. Comparison of inhaled terbutaline administered by either the Turbuhaler dry powder inhaler or a metered-dose inhaler with spacer in preschool children with asthma. Proventil HFA provides protection from exercise-induced bronchoconstriction comparable to proventil and ventolin. A comparison between aerosol and inhaled powder administration of fenoterol in adult asthmatics. A novel multiple dose powder inhaler. Salbutamol powder and aerosol give equal bronchodilatation with equal doses. The inhalation device influences lung deposition and bronchodilating effect of terbutaline. Equivalence of salbutamol 200 microg four times daily propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. Eastern European study group. The bronchoprotective efficacy of salbutamol inhaled from a new metered-dose powder inhaler compared with a conventional pressurized metered-dose inhaler connected to a spacer. Pilot study of bronchodilator response to inhaled albuterol delivered by metered-dose inhaler and a novel dry powder inhaler. Proventil HFA provides bronchodilation comparable to ventolin over 12 weeks of regular use in asthmatics. Comparison of inhaled salbutamol powder and aerosol in asthmatic patients with low peak expiratory flow level. A comparison of terbutaline inhaled by Turbuhaler and by a chlorofluorocarbon (CFC) inhaler in children with exercise-induced asthma. Albuterol delivered by metered-dose inhaler (MDI), MDI with spacer, and Rotahaler device--a comparison of efficacy and safety. Kinetics of action of salbutamol inhaled from a metered dose inhaler (MDI) and a "Diskhaler". Cumulative dose response study comparing HFA-134a albuterol sulfate and conventional CFC albuterol in patients with asthma. Albuterol aerosol versus albuterol Rotacaps in exercise-induced bronchospasm in children. Dry powder inhalers are bioequivalent to metered-dose inhalers. A study using a new urinary albuterol (salbutamol) assay technique. Safety of long-term treatment with HFA albuterol. Switching patients with asthma from chlorofluorocarbon (CFC) albuterol to hydrofluoroalkane-134a (HFA) albuterol. Comparative assessment of a new breath-actuated inhaler in patients with reversible airways obstruction. Treatment of asthma in pre-school children with inhalation of terbutaline in Turbuhaler compared with Nebuhaler. Turbuhaler: a new device for dry powder terbutaline inhalation. Ventilation effects of fenoterol powder and freon-propelled aerosol in patients with asthma. Bricanyl Turbuhaler in the treatment of asthma: a six week multi-centre study carried out in Sweden, the United Kingdom, Denmark, Norway and Finland. Dose potency relationship of terbutaline inhaled via Turbuhaler or via a pressurized metered dose inhaler. Protection against methacholine bronchoconstriction to assess relative potency of inhaled beta2-agonist. Evaluation of a breath operated powder inhaler. Terbutaline via pressurised metered dose inhaled (P-MDI) and Turbuhaler in highly reactive asthmatic patients. Bronchodilator responses to salbutamol using diskhaler versus metered-dose inhaler. Ipratropium bromide (Atrovent) as inhalation powder. A double-blind study of comparison with ipratropium as a pressure aerosol in patients with reversible airways obstruction. Comparison of inhaled albuterol powder and aerosol in asthma. Equivalence of as-required salbutamol propelled by propellants 11 and 12 or HFA 134a in mild to moderate asthmatics. German Study Group. Comparative efficacy and safety of albuterol sulfate Spiros inhaler and albuterol metered-dose inhaler in asthma. The effect of powder aerosol compared to pressurized aerosol. GR106642X: a new, non-ozone depleting propellant for inhalers. Bronchodilator delivery from Gentlehaler, a new low-velocity pressurized aerosol inhaler. Albuterol treatment for children with asthma: a comparison of inhaled powder and aerosol. A new multiple dose powder inhaler, (Turbuhaler), compared with a pressurized inhaler in a study of terbutaline in asthmatics. Long-term comparison of salbutamol powder with salbutamol aerosol in asthmatic out-patients. Comparison of the bronchodilating efficacies of a novel salbutamol metered dose powder inhaler and a pressurised metered dose aerosol with a spacer. Safety and efficacy of a high cumulative dose of salbutamol inhaled via Turbuhaler or via a pressurized metered-dose inhaler in patients with asthma. Comparison of terbutaline and placebo from a pressurised metered dose inhaler and a dry powder inhaler in a subgroup of patients with asthma. Equivalent bronchodilation with salbutamol given via pMDI or turbuhaler. Easyhaler, a novel multiple dose powder inhaler: clinically equivalent to salbutamol metered dose inhaler and easier to use. Salbutamol by powder or spray inhalation in childhood asthma. A multiple dose powder inhaler (Turbuhaler) compared with a conventional aerosol. An acceptance study in asthmatics. Cumulative dose-response study of non-CFC propellant HFA 134a salbutamol sulfate metered-dose inhaler in patients with asthma. Fenoterol inhalation powder and aerosol in the treatment of asthma. Clinical equivalence of a novel multiple dose powder inhaler versus a conventional metered dose inhaler on bronchodilating effects of salbutamol. Differences in bronchodilating potency of salbutamol in Turbuhaler as compared with a pressurized metered-dose inhaler formulation in patients with reversible airway obstruction. Influence of inspiratory capacity on bronchodilatation via Turbuhaler or pressurized metered-dose inhaler in asthmatic children: a comparison. Clickhaler (a novel dry powder inhaler) provides similar bronchodilation to pressurized metered-dose inhaler, even at low flow rates. Comparison of salbutamol Rotahaler with conventional pressurized aerosol. A double-blind comparison between a new multidose powder inhaler (Turbuhaler) and metered dose inhaler in children with asthma.
In the treatment of asthma salbutamol can be administered as an aerosol with a metered-dose inhaler or as a powder with a breath-actuated device (Rotahaler). The two forms of the drug were compared in a double-blind placebo-controlled study involving 10 asthmatic adults who were known to respond to salbutamol. The bronchodilating effect of the aerosol and the powder at doses of 200 micrograms and of the powder at doses of 200 and 400 micrograms was compared, bronchodilation being measured in terms of forced expiratory volume and vital capacity. The response was far greater to salbutamol than to placebo, but there was no significant difference between the two forms of the drug or between the lower and higher doses of powder. No side effects were observed. Thirteen children with asthma were treated with cumulative doses of terbutaline delivered as a pressurized aerosol and from a new multidose powder inhaler (Turbuhaler) in a randomized cross-over dose-response study. The cumulative dose of terbutaline was 2 mg on each study day. All children used a correct aerosol inhalation technique. At no time was there any difference in forced expiratory volume in 1 s (FEV1), forced midexpiratory flow, forced vital capacity, peak expiratory flow rate, or percent increase in these parameters between the two inhalers. The mean total increases in FEV1 after 2 mg terbutaline were 60% (aerosol) and 62% (Turbuhaler); 90% of these increases were measured after a cumulative dose of 0.5 mg terbutaline. One milligram of terbutaline inhaled from a Nebuhaler at the end of each study day did not result in additional increase of pulmonary functions, indicating that maximal bronchodilation had been achieved with both inhalers. After a cumulative dose of 2 mg terbutaline from the aerosol seven children complained of tremor and one of restlessness. No side effects were reported when the Turbuhaler was used (P less than 0.02). 1989; 7:00-00. New formulations of non-chlorofluorocarbon-containing propellants for pressurized metered-dose inhaler delivery systems must be developed in response to the forthcoming ban on chlorofluorocarbon (CFC) production.
                This study compared the bronchodilator effects of 100, 200, and 300 micrograms (base equivalent) of salbutamol in a novel CFC-free propellant system (Airomir in the 3M CFC-Free System; 3M Pharmaceuticals, St. Paul, Minn.; 108 micrograms of salbutamol sulfate or 90 micrograms of salbutamol base equivalent per inhalation) with that of 100 and 200 micrograms of salbutamol base in a conventional CFC propellant system (Ventolin, CFC-11/12; Allen and Hanburys, Division of Glaxo Inc., Research Triangle Park, N.C.; 90 micrograms of salbutamol base per inhalation) and placebo.
                Twenty-six patients with chronic, stable asthma, who had a forced expiratory volume in 1 second (FEV1) between 50.0% and 75.0% of predicted normal value, entered this randomized, double-blind, double-dummy, 6-period, crossover study. FEV1 was measured before and at multiple time points (ranging from 10 to 480 minutes) after administration of one, two, and three inhalations of salbutamol/CFC-free (100, 200, and 300 micrograms); one and two inhalations of salbutamol/CFC (100 and 200 micrograms); and placebo. Safety parameters included adverse events, heart rate, blood pressure, physical examinations, electrocardiograms, and clinical laboratory tests. Parametric analysis of variance models appropriate for a 6-period crossover design were used, along with multiple comparisons according to Tukey's method.
                All active treatments produced significantly (p < 0.0001) greater bronchodilation than placebo. The bronchodilator effect, as measured by FEV1 (peak percent change, peak as a percent of predicted value, duration, and area under the curve) after two inhalations of salbutamol/CFC-free was clinically comprable to two inhalations of salbutamol/CFC, with no clinically meaningful differences in safety parameters between the two delivery systems or between different dose levels.
                These results suggest that salbutamol/CFC-free may offer a suitable alternative for salbutamol/CFC when the need arises to change from CFC-containing salbutamol products. 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.
                Randomized, double-blind, cross-over, placebo-controlled study.
                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.
                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.
                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.
                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. This study compares the efficacy and safety of one and two actuations of albuterol sulfate powder delivered via a breath-actuated, effort-assisted, investigational inhaler (Spiros, Dura Pharmaceuticals, Inc) and albuterol delivered via a conventional propellant-driven metered dose inhaler (Ventolin, Glaxo, Inc).
                Randomized, double-blind, placebo-controlled, 5-way crossover study.
                Sixty patients with mild-to-moderate asthma (FEV1 59% predicted) were enrolled and 44 completed the study.
                FEV1 values over 6 hours were analyzed by ANCOVA and the Finney relative potency model. The relative potency of the inhalers (albuterol MDI: albuterol DPI) was 1.132 (90% CI, 0.680 to 2.252) indicating 1.132 actuations of albuterol MDI provided the same bronchodilation as one actuation of albuterol DPI. ANCOVA analyses further indicated that there were no significant differences between the two delivery systems with respect to FEV1, FVC, FEF25-75%, or PEF. Both inhalers had similar effects on serum potassium levels, QTc interval, blood pressure, and heart rate.
                In patients with mild-to-moderate asthma in this study, the albuterol DPI was determined to be therapeutically comparable to albuterol MDI in the delivery of one and two actuations of albuterol. Nine adult asthmatics took part in a cumulative dose response comparison of fenoterol (Berotec) inhalation powder and fenoterol metered dose inhaler. The study was carried out as a double-blind investigation using a double-dummy technique. No significant difference was observed in the lung function, in tremor or pulse rate on comparison of the two modes of administration. It is concluded that fenoterol inhalation powder is an effective and freon-free alternative to the metered dose inhaler. Short-acting inhaled beta2-agonists used just prior to exercise are an effective method for preventing exercise-induced bronchoconstriction (EIB) in children. This was a randomized, single-blind, placebo-controlled, four-period crossover study that compared the effectiveness of albuterol formulated in hydrofluoroalkane-134a (HFA) to albuterol formulated in chlorofluorocarbons (CFCs) and to placebo in protecting asthmatic children age 6-11 from EIB. Patients self-administered either HFA albuterol, two different CFC albuterol products, or placebo 30 min prior to exercise challenge. Spirometry was performed predose and 5, 10, 15, 30, 45, 60, 75, and 90 min after the exercise challenge was completed. The smallest percent change from the predose forced expiratory volume in 1 sec (FEV1) after exercise challenge was similar for the three active treatments, and each of the active treatments was significantly better than placebo. Each active treatment had significantly fewer patients unprotected from EIB (unprotected defined as having >20% fall in FEV1 after exercise challenge) than placebo. Changes in heart rate, blood pressure and electrocardiogram (ECG) intervals were similar for the three active treatments following exercise. HFA albuterol is as effective as albuterol products formulated in CFCs and more effective than placebo in protecting asthmatic children from EIB. We compared the bronchodilator response of terbutaline delivered either by a dry powder inhaler, the Turbuhaler, or by a metered-dose inhaler attached to a Nebuhaler inhaler in 10 children with stable asthma who were 3 to 6 years of age. The bronchodilator response did not differ between the two inhalational devices. The dry powder inhaler Turbuhaler is a suitable alternative to a metered-dose inhaler in the delivery of terbutaline to preschool children with stable asthma if adequate inhalational technique is used. During the 1970s, scientists suggested that the growing use of chlorofluorocarbons (CFCs) was contributing to depletion of the stratospheric ozone layer with potentially harmful results. A committee on the ozone layer organized the preparation of the Montreal Protocol. This protocol mandated the cessation of production and use of CFCs by January 1, 1996. The primary exemption to this ban is for the use of CFCs as propellants in metered dose inhalers (MDIs) for the treatment of asthma. Suitable replacement hydrofluoroalkane (HFA) propellants, such as HFA-134a, for use in MDIs have been identified. Albuterol, a selective beta-adrenergic agonist, currently widely available for inhalation asthma therapy, has been reformulated in HFA-134a (Proventil HFA). OBJECTIVE; To compare the efficacy of Proventil HFA to Ventolin, Proventil, and placebo (HFA-134a) MDI in protecting asthmatic patients from exercise-induced bronchoconstriction.
                This was a randomized, single-blind, placebo-controlled, 4-period crossover study of asthmatic patients with documented exercise-induced broncho-constriction. Twenty patients self administered two puffs of either Proventil HFA, Ventolin, Proventil or placebo, from an MDI, 30 minutes prior to performing a standardized exercise challenge at the study site. Spirometry was performed predose and 5, 10, 15, 30, 45, 60, 75, and 90 minutes after completion of the exercise challenge. Heart rate and blood pressure were measured just prior to spirometry and a 12-lead ECG was performed 15 minutes after completion of the exercise challenge for measurement of the QT corrected interval.
                The primary efficacy variable was the smallest percent change from the predose FEV1 following exercise. The smallest percent change from predose FEV1 for Proventil HFA was 2.0 +/- 9.9 SD, similar to the 2.0 +/- 11.4 SD for Ventolin, and the 3.6 +/- 10.2 SD for Proventil. The smallest percent change from predose FEV1 for each of the active treatments was significantly different from placebo, -23.7 +/- 14.5. Twelve of the patients had a > or = 20% fall in FEV1 post-exercise with placebo pretreatment, but only 1, 1, and 0 had > or = 20% FEV1 falls after treatment with Proventil HFA, Ventolin, and Proventil respectively. Changes in heart rate, blood pressure and QT corrected interval were similar for the three active treatments following exercise.
                Proventil HFA provides protection against exercise-induced bronchoconstriction comparable to Ventolin and Proventil and protection superior to placebo. Proventil HFA has a safety profile similar to Ventolin when used to prevent exercise-induced bronchoconstriction. Eleven adult asthmatics were given fenoterol either as a metered aerosol dose or as an inhaled powder with appropriate controls, in a randomised double-blind fashion. The increase in FEV1 was the same after both dosage forms and no side effects occurred indicating that powder inhalation is a safe and effective alternative to aerosol inhalation in the treatment of asthma with sympathomimetics. Twenty adult patients with stable asthma were treated with cumulatively increasing doses of salbutamol delivered from a metered dose inhaler (MDI) and from a novel multiple dose powder inhaler (MDPI), Easyhaler, in a randomized 3-period crossover study. Four doses of salbutamol (delivered doses to the patient: 90, 90, 180, 360 micrograms; cumulative dose of 720 micrograms) were administered during each of the three study days and were inhaled every 30 minutes. Drug doses were released from the powder inhaler either before or during inhalation. Spirometry was performed at the beginning of each study day and 20 minutes after each dose. The lung function parameters after cumulative dosing of salbutamol were equal during each study day. The maximal percentage changes in forced expiratory volumes in one second after 720 micrograms of salbutamol were 24% with the MDI and 23% and 24% with the Easyhaler inhaler, respectively. Ten patients reported mild side effects when using the MDI, three when the powder was released before inhalation and five when the MDPI was actuated during inhalation. No significant changes in heart rate or blood pressure were observed during the study. We conclude that the novel multiple dose powder inhaler is clinically equally effective and slightly better tolerated than conventional metered dose inhaler when equal doses of salbutamol are inhaled by asthmatic patients. The development of new inhalation devices for asthma drugs raises the issue of the relationship between pulmonary deposition and therapeutic effect of inhaled drugs in patients with obstructive lung diseases. We thus conducted a randomized, double-blind and double-dummy, four-period crossover study in 13 patients with moderate asthma (mean age 36 yr; FEV1 59% of predicted), who inhaled 0.25 and 0.5 mg terbutaline sulphate on separate occasions either via a pressurized metered dose inhaler (pMDI) or Turbuhaler (TBH). Pulmonary deposition was 8.1 +/- 2.7% and 8.3 +/- 2.3%, respectively, of the nominal dose for pMDI and 19.0 +/- 7.3%, and 22.0 +/- 8.1% for TBH. The FEV1 increase after 0.25 mg terbutaline sulphate via TBH was significantly greater than after 0.25 mg via pMDI. No significant differences in FEV1 increase were observed between 0.25 mg via TBH, 0.5 mg via pMDI, or 0.5 mg via TBH. Other lung function variables showed similar dose- and device-related changes. We concluded that: (1) the dose of terbutaline sulphate deposited in the lungs is dependent on which inhalation system is used; (2) TBH delivers about twice the amount of drug to the lungs as the pMDI; and (3) the observed difference in deposition is reflected in the bronchodilating effect. The phasing out of chlorofluorocarbons (CFCs) requires the development of an alternative non-ozone depleting propellant for use in pressurized metered dose inhalers (pMDIs). The present study assessed the effects on tolerability and efficacy of a switch from the currently available formulation containing the CFC propellants 11 and 12 to an alternative non-CFC formulation using the propellant hydrofluoroalkane (HFA) 134a in patients with mild to moderate asthma. After a 4-week run-in period during which patients received salbutamol 200 microg four times daily from a CFC pMDI, 547 patients were randomized to 12 weeks of treatment with salbutamol 200 microg four times daily administered from either an HFA 134a pMDI (Ventolin CFC-free; 277 patients) or CFC pMDI (Ventolin, 270 patients). At the end of this period, all patients then received a further 4 weeks of treatment with the same dose of salbutamol via a CFC pMDI (run-out period). On the basis that high doses of beta2-agonists are known to increase heart rate, change in heart rate was selected as the primary outcome variable. Small increases in heart rate were observed during the treatment period and these changes were comparable in both groups; the 90% confidence interval for the treatment differences was within the predefined limits for clinical equivalence (+/- 10 beats min(-1)). The incidence of adverse events was similar in both groups and there were no reports of paradoxical bronchospasm. Furthermore, daily PEF measurements showed comparability in terms of lung function. Symptom scores and use of additional bronchodilator were also similar in both groups. These results demonstrate that salbutamol (800 microg day(-1)), formulated with HFA 134a is equivalent to the current CFC formulation in terms of tolerability and efficacy. The aim of this study was to compare the efficacy of 100 micrograms of salbutamol inhaled from a new metered-dose powder inhaler (MDPI, Leiras Taifun, Finland) with that of a same dose of salbutamol inhaled from a conventional pressurized metered-dose inhaler with a large volume spacer (pMDI + S) in protecting against methacholine (Mch) induced bronchoconstriction. This was a 3 day, randomized, cross-over, partly blinded, placebo-controlled multicentre study where the pMDI + S was used as an open control. Twenty-six asthmatic outpatients with a baseline FEV1 > or = 60% of predicted and with bronchial hyperreactivity (PD20 FEV1 < or = 890 micrograms of Mch) were studied. On each study day the patients underwent an Mch provocation 30 min after inhaling placebo from the MDPI or a dose of 100 micrograms of salbutamol from the MDPI and from the pMDI + S. PD20 FEV1 and dose-response slope [DRS; maximal change in FEV1 (%)/dose of Mch (mumol)] were used to evaluate efficacy. The median values of PD20 FEV1 were 250, 622 and 1737 micrograms after placebo MDPI, salbutamol pMDI + S and salbutamol MDPI, respectively. The corresponding DRS values were -11.0%, -4.5% and -2.0% mumol-1. With both parameters, all differences were statistically significant (P < 0.05). In conclusion, 100 micrograms of salbutamol inhaled from Leiras Taifun MDPI offers better protection against Mch-induced bronchoconstriction than 100 micrograms of salbutamol from a pMDI connected to a large volume spacer device. The metered-dose inhaler is currently one of the most prescribed methods of delivering drugs to the lungs. In the United States, most currently marketed metered dose inhalers use chlorofluorocarbons as the system propellant and require patient breath coordination. These factors lead to the need for a delivery system that is independent of propellants and patient coordination.
                To compare the magnitude and time course of bronchodilation between albuterol delivered by Ventolin metered dose inhaler and albuterol sulfate powder (Rotacaps) delivered by a novel dry powder inhaler that generates a respirable drug aerosol over a range of inspiratory flow rates.
                A single-center, single-dose, randomized, placebo-controlled, partial-blind, 3-way crossover study was conducted in an outpatient asthma Clinical Research Center. Twelve mild to moderate asthmatic patients 12 to 36 years of age participated in this study that involved three treatments, each separated by three to eight days, consisting of 2 puffs (90 micrograms/puff) albuterol by Ventolin metered-dose inhaler, two inhalations (100 micrograms/puff) albuterol sulfate powder (Rotacaps) by dry powder inhaler, and two inhalations (12.5 mg/inhalation) lactose powder by dry powder inhaler. Spirometry, blood pressure, and heart rate were measured at 30 minutes, 15 minutes, and immediately before treatment and then at 15, 30, 45, 60, 90, 120, 180, 240, and 300 minutes after each treatment. Serum potassium and glucose, and electrocardiograms were measured at 30 minutes before, and 30, 60, 90, and 180 minutes after each treatment. Endpoints were compared with analysis of variance.
                Five patients (one metered-dose inhaler and four dry powder inhaler) did not respond with > 15% FEV1 increase over baseline within 30 minutes. Metered-dose inhaler and dry powder inhaler mean FEV1 results, respectively, for 11 and 8 responders were 15 minutes in onset, 202.9 and 185.4 minutes in duration, 24.8% and 25.1% maximum change, and 18.6 and 18.2 area-under-FEV1-bronchodilation-curve. Statistical analysis of all patients and responders-only revealed both active treatments to be different from placebo (P = .0018), but not different from each other (P = .1291). No safety endpoints were significantly different among all three treatments (P > .10 for all safety endpoints).
                In this study, the dry powder inhaler safely and effectively delivered a commercially available albuterol sulfate powder (Rotacaps) into human lungs with bronchodilation comparable to Ventolin metered-dose inhaler. To compare the bronchodilator effectiveness of albuterol reformulated in the chlorofluorocarbon-free propellant hydrofluoroalkane (HFA)134a (Proventil HFA) to that of Ventolin and HFA placebo over 12 weeks of regular dosing.
                Randomized, double-blind, double-dummy, parallel group, placebo-controlled, multi-center trial of asthmatics requiring inhaled beta-adrenergic bronchodilators for symptom control.
                Treatment qid with Proventil HFA, Ventolin, or HFA-134a placebo for 12 weeks.
                At weeks 0, 4, 8, and 12, spirometry was performed predose and serially over 6 h after dosing with study drug. Bronchodilator efficacy variables, based on FEV1 response to study drug, were proportion of responders, time to onset of effect, peak percent change, time to peak effect, duration of effect, and area under the curve (AUC).
                Demographic and baseline characteristics were similar for patients randomized to Proventil HFA (193), Ventolin (186), and HFA-134a placebo (186). No significant differences were found between the Proventil HFA and Ventolin treatment groups for any FEV1 efficacy variable, either predose or during 6 h of serial spirometry, at weeks 0, 4, 8, and 12. For all efficacy variables, except time to onset of effect, the Proventil HFA and Ventolin results were significantly greater than placebo. Time to onset of effect for the HFA-134a placebo group is misleading; only 13 patients (7%) were found to be responders in the intent-to-treat database. These efficacy results were found to be consistent across subgroup analyses of inhaled and nasal corticosteroid use, age (18 to 35 and 36 to 66 years), sex, race, weight (<60, 60 to 100, and >100 kg), and baseline FEV1 (< or =55% and >55% predicted). The peak FEV1 effect, duration of FEV1 effect, and AUC for FEV1 were all significantly smaller at weeks 4, 8, and 12 than week 0 for both the Proventil HFA and Ventolin treatment groups.
                Proventil HFA provided bronchodilation comparable to Ventolin and superior effects to HFA-134a placebo over 12 weeks of regular dosing. There was a diminution in bronchodilator response to both Proventil HFA and Ventolin after 4 weeks of use. The short-term bronchodilator effects of dry salbutamol powder and a pressurized salbutamol aerosol were compared in 22 patients with severe asthma, on 3 consecutive mornings, in a double-dummy cross-over study. Only patients with peak expiratory flow (PEF) rate lower than 250 l/min, were recruited. PEF measurement was employed to assess changes in ventilatory function induced by inhalation of the drugs. No significant difference was found between the PEF changes induced by the dry salbutamol powder (400 micrograms) and the pressurized aerosol (200 micrograms). Both forms of the drug produced a significant rise in mean PEF values. The study shows that even in asthmatic patients with poor ventilation, a dry powder inhaler and pressurized aerosol are effective means of drug delivery to the lungs. The present study compared the bronchodilating effect of inhalation from the Turbuhaler (0.5 mg terbutaline x 2) with the effect of inhalation from the chlorofluorocarbon (CFC) inhaler (0.25 mg terbutaline x 4) in children aged 9-17 years with reproducible, exercise-induced asthma (EIA). The treatments were given on two occasions, 5 min apart (terbutaline 0.5 mg + 0.5 mg). The study was performed as a double-blind, double-dummy, and placebo-controlled trial in 12 asthmatic children. The study was conducted on three separate days. The bronchoconstriction was induced by steady running on a treadmill. Forced expiratory volume in 1 s (FEV1.0), vital capacity (VC), and volume of trapped gas (VTG) were measured before and after the exercise test and after treatment. The study showed that the same amount of terbutaline inhaled from the Turbuhaler or from a CFC inhaler is equally effective for reversing EIA, and that the Turbuhaler is possibly more effective for treating spasm in small airways. A randomized double-blind, triple crossover study was conducted on 20 asthmatic patients (7 males and 13 females; age 40.9 +/- 14.2 Caucasians, 11 blacks, and 1 oriental. Criteria for admission included FEV1 < or = 80% of predicted when inhaled beta-agonists were witheld for at least 6 hrs and oral beta-agonists for 12 hr, in addition to at least 15% increase in FEV1, 15 min after treatment with albuterol with spacer delivery. Each of the study patients were tested on each of 3 separate days (within the same week) at baseline, 15, 30, 60, 120, 180, 240, 300, and 360 min post treatment. On each day albuterol was delivered by one of the 3 delivery devices and the other two methods delivered placebo. Albuterol was administered at the maximum recommended dosages of two puffs for MDI. Two puffs for MDI with spacer, and two capsules for Rotahaler. Spirometry, blood pressure and heart rate were measured at each testing interval. The mean percentage in FEV1 was higher in Rotahaler group compared to MDI with spacer (p < 0.001) and no significant difference in FEV1 was found between Rotahaler and MDI alone (p = 0.31). No significant changes in heart rate or blood pressure were associated with albuterol delivery by any of the three methods. Albuterol inhaled as a microfine powder was more effective than the same drug delivered as an aerosol by either MDI or MDI with spacer. In a double-blind cross-over study, 12 patients with reversible airways obstruction were treated with 200 micrograms salbutamol base in aerosol or 400 micrograms of powder following methacholine-induced bronchoconstriction. Salbutamol was inhaled either from a conventional metered dose inhaler (MDI) or from an inhaler (Diskhaler) utilizing the powdered form of the drug. The efficacy of both forms was identical whether assessed in terms of FEV1 or vital capacity. The ratio of the increase in FEV1 or vital capacity after bronchodilatation to the decrease during the prior bronchoconstriction was 1.4, indicating that both FEV1 and vital capacity improved over baseline following bronchodilatation. In six subjects, the onset of action of the powder form was more rapid, and in four the MDI acted more rapidly. In the group as a whole, the mean time constant for the action of salbutamol was identical (3.8 min) for the two forms. It is concluded that salbutamol powder has a similar efficacy and time course of action as the aerosol, probably because both formulations produce similar sized particles of the drug. As a result of the pending ban on chlorofluorocarbon production, the non-chlorofluorocarbon propellant 1,1,1,2-tetrafluoroethane (HFA-134a) is being evaluated as a replacement for CFCs in metered-dose inhalers.
                This cumulative dose response study compared the safety and bronchodilator efficacy of 16 cumulative inhalations of albuterol sulfate in an HFA-134a, CFC-free propellant system (108 microg of albuterol sulfate, equivalent to 90 microg of albuterol base) with that of equivalent doses of albuterol in a conventional CFC propellant system.
                Twenty-two patients with at least a 12-month history of stable asthma, who were currently taken an inhaled beta-adrenergic bronchodilator, and who had a FEV1 between 40% and 80% of predicted, were enrolled in this randomized, modified-blind, two-period crossover study. One, 1, 2, 4, and 8 inhalations of study drug were self-administered at 30-minute intervals, resulting in 16 cumulative inhalations. Pulmonary function and safety measures were assessed after each dosing interval.
                A significant dose response was found for HFA-134a albuterol sulfate and CFC albuterol with regard to changes in FEV1, serum potassium, heart rate, and blood pressure after 16 cumulative inhalations. No significant differences were demonstrated between HFA-134a albuterol sulfate and CFC albuterol for any FEV1 or safety parameter at any cumulative dose level. No clinically meaningful laboratory or physical examination abnormalities were found with administration of either HFA-134a albuterol sulfate or CFC albuterol.
                HFA-134a albuterol sulfate provides bronchodilation comparable to CFC albuterol and has a similar safety profile. The purpose of this study was to determine the safety and effectiveness of albuterol aerosol 180 micrograms and albuterol powder 200 micrograms in the prevention of exercise-induced bronchospasm in children. Forty-six patients aged 4-11 years with asthma and exercise-induced bronchospasm were enrolled in this randomized, double-blind, single-dose, three-way crossover study comparing albuterol aerosol, albuterol powder, and placebo. Exercise challenge was performed at the screening visit for qualifying and baseline determinations of pulmonary function and then 15 min after drug administration at each of three visits. Prevention of exercise-induced bronchospasm was assessed by comparing across all treatment groups the percentage change in FEV1 from pre- to postexercise, the percentage of patients protected by treatment, postexercise minimum FEV1, and postexercise change in FEV1. Safety was assessed by observation of clinical adverse events, laboratory tests, physical examination, electrocardiogram and rhythm strips, vital signs, and pulmonary auscultation. Forty-four patients completed the study. Mean postexercise FEV1 decreased 6% from preexercise values when patients were treated with either albuterol formulation; FEV1 decreased 23% when patients were treated with placebo. Exercise-induced bronchospasm was prevented in 95% of patients when treated with albuterol powder, in 91% treated with albuterol aerosol, and in 57% treated with placebo. Patients maintained significantly higher mean minimum FEV1 values after treatment with albuterol powder and albuterol aerosol than when treated with placebo. Treatment with either albuterol formulation produced a significantly smaller decrease in mean FEV1 from pre- to postexercise than treatment with placebo. No drug-related adverse events were reported, and safety assessments were within normal limits.(ABSTRACT TRUNCATED AT 250 WORDS) Metered-dose inhalers (MDIs) are extensively used to deliver drugs to the lungs but are driven by chlorofluorocarbon (CFC) propellants. The worldwide phasing out of CFCs within the next 5 to 10 years presents difficulties to the pharmaceutical industry. The mean +/- SD relative lung bioavailability of albuterol to the lung following inhalation of 400 micrograms of albuterol from an MDI, the Rotahaler and Diskhaler in 10 well-trained volunteers, was 2.83 (0.78), 1.72 (0.99), and 2.64 (1.23)%, respectively, expressed as a percentage of the nominal dose. The delivery of albuterol to the lungs from the MDI and Diskhaler was similar. In nine asthmatic subjects, the relative lung bioavailability of albuterol following inhalation with the MDI and Diskhaler was 1.19 (0.79) and 2.38 (1.46)%, respectively, expressed as a percentage of the nominal dose. There was no difference in reversibility 30 min after administration of the dose by the two methods. Similar lung deposition from the Diskhaler in volunteers probably is due to efficient MDI technique, which was absent in the asthmatic subjects. The Diskhaler does not rely on coordination during inhalation and therefore is easier to use. Chlorofluorocarbons (CFCs) used as propellants in metered-dose inhalers deplete stratospheric ozone, which results in serious public health concerns. Albuterol has been reformulated in the non-ozone-depleting propellant, hydrofluoroalkane-134a (HFA albuterol).
                The primary objective was to compare the safety of HFA albuterol to an albuterol product formulated in chlorofluorocarbon propellants (CFC albuterol) during 1 year of treatment in asthmatics. Bronchodilator efficacy of the two products was assessed as a secondary objective.
                The results from two open-label, parallel-group trials of similar design in asthmatics requiring short-acting beta-agonists for symptom control were combined. Patients took two puffs bid of either HFA albuterol or CFC albuterol for 1 year. Additional puffs of study drug were allowed as needed to control asthma symptoms. Adverse events were recorded at clinic visits. Patients self-administered study drug at quarterly visits and underwent serial spirometry during a 6-h period postdose. Bronchodilator efficacy variables, based on FEV1 response to study drug, were proportion of responders, time to onset of effect, peak percent change, time to peak effect, duration of effect, and area under the curve. Differences between products and changes over time in efficacy variables were assessed using an analysis of variance model. Regression analyses with FEV1 as a covariate were performed post-hoc to analyze changes in bronchodilator efficacy over time.
                Demographic and baseline characteristics were similar for patients receiving HFA albuterol (n = 337) and CFC albuterol (n = 132). Total reported adverse events were similar for the two treatments. Differences in only four individual adverse events were noted: the HFA albuterol group reported more gastroenteritis and dizziness; the CFC albuterol group reported more epistaxis and expectoration. Adverse events attributed to study drug use were infrequent. No serious adverse events were related to study drug use. Predose FEV1 at quarterly visits increased to a small extent in both groups from month 0 to month 12. The bronchodilator efficacy of HFA albuterol was comparable to that of CFC albuterol at the quarterly visits, but decreased from baseline for both products over the 12 months of treatment. Use of inhaled corticosteroids, nasal corticosteroids, or theophylline did not explain the increase in predose FEV1 over time and did not protect patients from developing reduced bronchodilator efficacy by month 12. The change in predose FEV1 did not entirely account for the reduced bronchodilator efficacy over time.
                HFA albuterol has a safety profile similar to that of CFC albuterol during chronic, scheduled use, and both drugs are well tolerated. HFA albuterol and CFC albuterol provided comparable bronchodilator efficacy, but bronchodilator efficacy decreased for both products with 1 year of use. Chlorofluorocarbon (CFC) propellants deplete stratospheric ozone. Production and use of CFCs, except for certain critical exemptions, has been prohibited by the Montreal Protocol. Use of CFCs as propellants in metered-dose inhalers (MDIs) is still allowed, but the U.S. Food and Drug Administration is planning the transition to alternative propellants for use in MDIs. Hydrofluoroalkane-134a (HFA), a non-ozone-depleting propellant, has been used to reformulate albuterol (HFA albuterol). This study evaluates whether comparable safety and efficacy continues for 12 weeks after patients with asthma are switched from CFC albuterol to HFA albuterol. Patients with asthma stabilized on CFC albuterol during a 12-week safety and efficacy trial were randomized to either continue receiving CFC albuterol or to be switched to receive HFA albuterol in a yearlong safety and efficacy trial. Safety and efficacy were compared over the first 12 weeks of the yearlong trial between patients who had remained on CFC albuterol and those who had been switched to HFA albuterol. Bronchodilator efficacy was evaluated by serial spirometry for 6 hr after the patients self-administered the study drug in the clinic. Safety was assessed by measuring changes in pulse rate, blood pressure, and electrocardiogram (ECG) intervals after dosing with study drug, monitoring adverse events, and performing prestudy and poststudy laboratory testing and physical examinations. No significant differences in bronchodilator efficacy between the patients continuing to receive CFC albuterol and those switched to HFA albuterol were found in the 12 weeks after the switch. No differences between the two products were found for changes in pulse rate, blood pressure, and ECG intervals. Adverse event profiles were similar for the two products, except the patients remaining on CFC albuterol reported increased asthma symptoms and rhinitis significantly more often than the patients switched to HFA albuterol. No clinically meaningful changes in laboratory tests or physical examinations were found in either treatment group. Patients with asthma switched from CFC albuterol to HFA albuterol receive comparable bronchodilation with a similar safety profile as those continuing to receive CFC albuterol. 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. The aim of this study was to evaluate the efficacy, safety and preference of pre-school children with regard to two different devices for treatment of bronchial asthma with terbutaline. Turbuhaler, a powder inhaler preloaded with pure terbutaline for inhalation, was compared with a pressurized metered dose inhaler, attached to a Nebuhaler. The study had an open, cross-over randomized design. Each treatment period consisted of 2 weeks. Diary cards were filled in every morning and evening by the parents regarding PEF, asthma symptoms, extra inhalations of terbutaline, and side effects. Twenty-one children (mean age 3.9 years) were included in the study. A highly significant (P less than 0.001) increase in peak expiratory flow (PEF) was obtained after inhalation with both devices. The PEF values in the mornings after inhalation of terbutaline with Turbuhaler were significantly higher (P = 0.046) than those with Nebuhaler. Further, the PEF baseline values in the evenings before inhalation were also significantly higher (P = 0.03) with Turbuhaler. No difference was found in asthma symptoms and extra medication between the two devices. Side effects were mild and few with both devices. The parents found Turbuhaler easier to handle and 19 of 21 preferred this device for future use. The aim of this study was to compare bronchodilator response and adverse effects of terbutaline when administered with the metered dose inhaler (MDI) Bricanyl and with the dry powder inhaler Bricanyl Turbuhaler (BT). Nine adult patients with bronchial asthma participated. The study was of an open crossover design. At 30-min intervals the patients inhaled increasing doses of terbutaline (0.25 mg to 5.0 mg cumulated) from either the conventional MDI or from the BT. After each inhalation FEV1, FVC, heart rate, muscle tremor and adverse effects were recorded. Both treatments, BT and MDI, resulted in a dose-related increase in lung function, without any statistical difference. Taste sensation, muscle tremor and increase in heart rate were observed in both groups. Because of the design of the BT one may assume that inhalation failure can be avoided. The efficacy of fenoterol powder (Berotec, Boehringer-Ingelheim) was investigated in ten patients with moderate or severe asthma. Double-blind comparison to placebo powder showed a significant difference (p less than 0.05) between 30 to 180 min after a single dose of 0.2 mg. There was no difference between fenoterol powder and aerosol (0.2 mg). No adverse effects were encountered. Two hundred and fifty eight adult patients with bronchial asthma participated in an open, parallel group study of 8 wks duration. During a 2 wk run-in period the beta 2-agonist terbutaline (0.5 mg q.i.d) was delivered via a pressurized freon aerosol, Bricanyl metered dose inhaler (MDI). During the following 6 wks, one third of the patients continued with MDI and two thirds with the same dose of terbutaline in the form of dry powder, Bricanyl Turbuhaler. There were no statistically significant differences in the increases in peak expiratory flow rate (PEFR) after inhalation between the two treatment groups. The asthma symptom scores decreased in the Turbuhaler group during the study but remained the same in the MDI group. No difference in use of extra trial medication during the day was found. During the night, the difference was statistically significant in favour of Turbuhaler (p less than 0.05). Turbuhaler was well accepted and easy to use. As compared with the MDI used during run-in, 50% of the patients in the Turbuhaler group preferred to use Turbuhaler and 26% MDI, whilst 24% had no preference. In conclusion, Turbuhaler was at least as effective as MDI during the whole Turbuhaler life-span (6 wks). The relative dose potency of cumulative doses of terbutaline sulfate inhaled via Turbuhaler and via a pressurized metered dose inhaler was estimated with respect to lung efficacy and systemic effect.
                The study was an open, crossover, randomized, multicenter study including 31 adult patients with asthma [forced expiratory volume in one second (FEV1), 65% of predicted]. The patients inhaled terbutaline doses of 0.125, 0.125, 0.25, 0.5, 1.0, and 2.0 mg (a total of 4 mg) at 30-minute intervals. Lung function [FEV1, forced vital capacity (FVC), forced expiratory flow at 75% of FVC (FEF75%), and peak expiratory flow (PEF)], and systemic effect variables (serum potassium, tremor, pulse, blood pressure) were monitored prior to the first inhalation and 15 to 25 minutes after each inhaled dose.
                The mean relative dose potency of terbutaline inhaled via Turbuhaler compared with pressurized metered dose inhaler was 1.5 (95% confidence interval: 1.2 to 1.8) with respect to FEV1 and serum potassium, respectively. The corresponding relative dose potencies for PEF, FVC, and FEF75% were 1.0, 1.2, and 1.6, respectively, with no statistically significant difference between the two devices. No differences between the devices were evident with regard to blood pressure and pulse.
                The results suggest that Turbuhaler is more efficient in the delivery of inhaled terbutaline to the lungs compared with the conventional pressurized metered dose inhaler. The purposes of this study were to estimate the relative dose potency (RP) of two formulations of salbutamol pressurized metered-dose inhalers (Proventil-HFA and Ventolin-CFC MDIs) to protect against methacholine bronchoconstriction, to validate this method and provide recommendations. The protective effects of 100-, 200-, and 400-micrograms doses of Proventil-HFA were compared with the same doses of Ventolin-CFC in 18 adult asthmatics (mean FEV1, 92% predicted; mean baseline PC20 methacholine, 1.8 mg/ml), in a dose-level blind, balanced, eight-period, crossover, placebo-controlled study. The log-transformed PC20 values after each dose of the drugs were compared by repeated-measures analysis of variance (ANOVA). A significant dose-effect was present (p < 0.0001). Using the Finney assay, the RP of Proventil-HFA compared with Ventolin-CFC was 1.08 (90% CI, 0.81-1.46) (80% power). This was also estimated using a nonlinear Emax model to validate the Finney method. The most precise estimate of RP was obtained with the comparison between 100- and 200-micrograms doses (RP, 1.00; 90% CI, 0.77-1.31). There were no adverse events resulting from the drugs or methacholine. We conclude that Proventil-HFA salbutamol is bioequivalent to Ventolin-CFC salbutamol. Bronchoprotection to methacholine is a valid method of demonstrating bioequivalence. By this method, 100- and 200-micrograms doses of salbutamol inhalations from an MDI will suffice. A randomized, double-blind, double-dummy crossover study on 42 asthmatics was carried out to compare the single dose effects of salbutamol administered from the widely used metered dose inhaler and a breath operated system (Diskhaler). The bronchodilator response (change in forced expiratory volume in the first second) was almost identical for the two systems. The Diskhaler system however, since it is breath operated, obviates the need for hand-breath coordination. There is some concern over the environmental consequences of chlorofluorocarbons (CFCs) used in pressurized metered-dose inhalers (p-MDIs). Turbuhaler was designed to deliver a drug as a dry powder without administering additives directly to the airways. The aim of this study was to evaluate the comparative irritant and bronchodilating effects of the same dose of terbutaline delivered by a p-MDI and via Turbuhaler. Ten symptomatic, asthmatic patients, with highly reactive airways (provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20) < 0.2 mg.ml-1), inhaled, on separate days, 0.25 mg terbutaline via p-MDI or Turbuhaler. Changes in airway calibre were followed as specific airways conductance (sGaw). On a third day, patients inhaled from a placebo p-MDI containing all constituents except terbutaline. The study was conducted in a single-blind fashion and in random order. There were no significant differences in baseline sGaw on any of the study days. Inhalation of terbutaline from the p-MDI produced a transient percentage fall in sGaw at 1 min, reaching a mean maximum +/- SD of 17 +/- 8% at 10 s and then returning to baseline value after 20 s, followed by a progressive increase in sGaw to a maximum of 39 +/- 45% above baseline at 45 min. In contrast, inhalation of terbutaline via Turbuhaler caused no significant bronchoconstriction (fall in sGaw, 3 +/- 16%) at 10 s and achieved a greater increase in sGaw, reaching 63 +/- 51% at 45 min, although just failing to reach statistical significance compared to terbutaline p-MDI inhalation.(ABSTRACT TRUNCATED AT 250 WORDS) In adults inhaling salbutamol via metered-dose inhalers (MDls) 200 microg doses are recommended, but with diskhalers the manufacturer advocates 400 rather than 200 microg doses. To assess this advice, a partially double-blind, placebo-controlled salbutamol dose response, crossover study (also incorporating MDI doses) was conducted in 12 mild/moderate asthmatics. After active treatment, mean peak expiratory flow rate (PEFR) increments yielded no clinically or statistically significant differences; compared to placebo, respective median differences in PEFR increments (95% Cls) were 10 (-10, 50), 20 (0, 50), and 15 (0, 30) following 400 and 200 microg via diskhalers and 200 microg via MDls. Diskhalers are a suitable alternative for patients with poor MDI technique, but the use of 400 rather than 200 microg salbutamol doses is not supported by evidence. The bronchospasmolytic effects of 40 micrograms ipratropium bromide (Atrovent) given either as an aerosol (2 puffs of 20 micrograms) or as a powder inhalation were compared in a double-blind cross-over study. Following a randomisation list the drug was given on 2 successive days to 20 patients with stable bronchospasm in whom it had previously been shown that the bronchial obstruction was reversible after administration of 40 micrograms ipratropium bromide as an aerosol (with an increase over the baseline value of the FEV1 of at least 15% 1 h after drug administration). The effects of the two presentations of ipratropium bromide were followed by respiratory function tests from 15 min to 6 h after administration of the drug. With both formulations excellent bronchospasmolytic effects were noted in each of the parameters measured. The peak of the effects was noted approximately 1 h after the inhalations. Six hours later there was still a significant improvement in comparison with the baseline values. There was no significant difference between the results with the two different formulations. Inhalation powder of ipratropium bromide was well tolerated and there were no complaints of irritation or coughing. It would appear, therefore, to be a valuable alternative to the pressure aerosol. In this multicenter, randomized, double-blind study comparing the efficacy and safety of aerosolized albuterol with the dry powder formulation, 231 patients with chronic reversible obstructive airway disease were randomly allocated to receive either placebo albuterol aerosol followed immediately by active albuterol powder (200 micrograms) or active albuterol aerosol (two puffs, 180 micrograms) followed immediately by placebo lactose powder four times a day for a period of 12 weeks. No statistically significant differences were found between the powder and aerosol formulations with respect to pulmonary function, length of time mean FEV1 remained greater than or equal to 15% above baseline, physicians' assessments of patients' clinical response, or patients' subjective symptom scores. There were also no significant differences between treatment groups in cardiovascular effects, laboratory values, or adverse events. Among patients who expressed a preference for one of the delivery systems, half preferred using the powder. Results of this study demonstrate that 200 micrograms of albuterol powder is as safe and effective as 180 micrograms of albuterol aerosol. This randomized, double-blind, parallel-group study compared the efficacy and tolerability of as-required salbutamol 100 microg administered from either a chlorofluorocarbon (CFC) pressurized metered dose inhaler (pMDI; Ventolin) or from a non-CFC hydrofluoroalkane (HFA) 134a pMDI (Ventolin CFC-free) in patients with mild to moderate asthma. All patients (n = 423) continued with their standard asthma therapy, and recorded their daily use of study medication, morning and evening peak expiratory flow (PEF) and symptom scores, throughout the 4-week treatment period. Clinic lung function was measured at 2-week intervals. The median daily use of inhaled study medication remained constant at four actuations per day throughout the study in both treatment groups and statistical analysis indicated that the two formulations were equivalent. Small improvements in both treatment groups were reported in mean morning and evening PEF, clinic forced expiratory volume in 1 sec and clinic PEF and there were no significant differences between the two groups. Both formulations were well tolerated. This study indicates that as-required salbutamol 100 microg administered via a HFA 134a pMDI is as effective and safe as the currently available CFC-propelled formulation. To compare the long-term efficacy and safety of albuterol administration using a Spiros Inhalation System (Dura Pharmaceuticals; San Diego, CA) dry powder inhaler (DPI) and albuterol (Ventolin; Glaxo Wellcome; Research Triangle Park, NC) administration using a metered-dose inhaler (MDI) in patients with asthma.
                This was a phase III, 12-week, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, multicenter study of 283 adolescent and adult patients with mild to moderate asthma. The patients were randomized into one of three treatment groups: the Spiros group, who were given 108 microg/actuation of albuterol sulfate equivalent to 90 microg of albuterol base; the MDI group, who were given 90 microg/actuation of albuterol; and the placebo group.
                Over the length of the study, the Spiros and MDI groups were comparable in all FEV1 parameters. Both active treatment groups were superior to the placebo group for each FEV1 parameter at all visits. With the exception of differences at treatment week 0 for the maximum percent change in the FEV1, the duration of effect, and the area under the curve at baseline, there were no statistically significant differences between the Spiros and MDI groups for any FEV1 parameters. Using a repeated-measures analysis, the FEV1 parameters at week 0 for the Spiros group were not statistically significantly different from the parameters at weeks 4, 8, and 12. The same analysis effect at week 0 for the MDI group was greater for maximum percent change in the FEV1 from baseline (weeks 4, 8, and 12) and duration of effect. Adverse events and changes in clinical laboratory values, vital signs, ECG results, and physical examinations were reported with similar incidence in each of the three treatment groups.
                Both active treatments were superior to the placebo treatment. The Spiros DPI was well tolerated and was as effective as the albuterol MDI in treating patients with moderate asthma. A comparison was performed between inhalation of salbutamol as a powder aerosol or as a pressurized aerosol. Seven intrinsic asthmatics, well-trained in inhalation technique, were studied in an open randomized crossover comparison of the two different modes of administration. Five doses were inhaled of salbutamol from the pressurized aerosol, 0.1-2.4 mg, and five doses as a powder aerosol from a Rotahaler, 0.2-4.8 mg. The FEV1 dose-response curves were almost identical indicating bronchodilating equipotency between the two modes of administration. A preliminary report is given of the effects on morning cortisol of inhalation of beclomethasone dipropionate as a powder aerosol or as a pressurized aerosol in 10 healthy volunteers trained in inhalation technique. Morning cortisol decreased to the same degree after both modes of administration and the decrease was dose-dependent when beclomethasone dipropionate was given in the doses 200 micrograms, 500 micrograms and 1000 micrograms q.i.d. Thus, in patients with a good inhalation technique the powder aerosol does not seem to be better than the pressurized aerosol. We think, however, that it could be offered as an alternative to patients with poor inhalation technique. nan We have compared radioaerosol deposition pattern and bronchodilator response following inhalation of 100 micrograms of albuterol from a correctly used conventional metered dose inhaler (MDI) to those from Gentlehaler, a new compact low-velocity pressurized aerosol device (Schering Corporation), in a group of ten asthmatic patients (mean baseline FEV1 52 percent; reversibility > 15 percent). Whole lung deposition (mean 18.8 percent of dose by conventional MDI, mean 19.9 percent of dose by Gentlehaler), regional lung deposition, and bronchodilator response were similar for the two devices, but oropharyngeal deposition was halved by Gentlehaler. The spray velocity from Gentlehaler was less than 2 m s-1 compared with a velocity of greater than 30 m s-1 commonly found in the conventional device. Gentlehaler may therefore play a valuable role in inhalation therapy, notably by reducing "cold Freon" problems (respiratory inhibition) in pressurized aerosol delivery, and by reducing oropharyngeal losses of inhaled corticosteroids. A dose-ranging study and a 12-week treatment study were conducted in children with asthma, aged 4 to 12 years, to assess the efficacy and safety of albuterol inhaled as either an aerosol or as dry powder. Both studies were double-blind and placebo-controlled with randomized assignment to treatment. The dose-ranging study in 30 patients indicated that similar single doses of albuterol aerosol and powder had comparable effects with the intermediate doses (i.e., 180 micrograms of aerosol and 200 micrograms of powder) providing effective bronchodilation with minimal adverse effects. In the subsequent 12-week, parallel-group study, 204 children received albuterol as either aerosol, 180 micrograms, or powder, 200 micrograms four times a day. Both formulations were equally effective with no untoward cardiovascular effects and only one incident of mild tremor. Among those children who expressed a preference for one of the delivery systems, significantly more children preferred the powder (44% versus 26%, p less than 0.01). Albuterol taken four times a day as either aerosol or dry powder is both effective and well tolerated in children with asthma. Twelve adult asthmatic patients participated in an open, randomized, cross-over comparison between cumulatively increasing doses of terbutaline sulphate administered via the multiple dose powder inhaler (Turbuhaler) or via a pressurized inhaler. Turbuhaler and the pressurized inhaler showed equipotency both with respect to bronchodilatation and side effects. Both treatments produced a significant increase in pulmonary function measurements, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). No increase in pulse rate was seen with either treatment but there was an increase in tremor at higher doses with both treatments. Inhalation of beta-agonists via Turbuhaler seems to be an effective way of treating asthma. 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. In a two-day, randomised, double-blind, double-dummy, cross-over multicenter study, the bronchodilating effect of 100 micrograms of salbutamol (CAS 18559-94-9) inhaled from a new metered dose powder inhaler (MDPI; Taifun) was compared with that of an identical dose of salbutamol inhaled from a conventional pressurised metered dose inhaler connected to a spacer (pMDI + S). Thirty-six non-smoking, adult asthmatic outpatients with a baseline forced expiratory volume in 1 s (FEV1) between 35 and 70% of the predicted value participated in the study. After inhalation of the study medication pulmonary function, FEV1 and airway resistance (R(aw)), blood pressure (BP), and heart rate (HR) were measured up to 6 h. Area under the FEV1 vs. time curve (AUCFEV1) was used as the primary efficacy parameter, and the 90% confidence intervals (CI) were used to judge clinical equivalence. Other efficacy parameters were used in supportive analyses as secondary parameters. Both treatments produced a clear improvement in pulmonary function. The mean +/- SD AUCFEV1 were 893 +/- 281 and 889 +/- 2761.min after MDPI and pMDI + S, respectively. The 90% CI for the relative efficacy of the MDPI is from 98 to 103% of that of the pMDI + S. Also the other efficacy parameters gave similar results without significant differences: the mean +/- SD values of percent increase in FEV1 were 47.2 +/- 19.3 and 44.7 +/- 20.8, the maximum absolute value of FEV1 were 2.87 +/- 0.77 and 2.86 +/- 0.77, the maximum percent decrease in R(aw) 53.2 +/- 20.5 and 55.0 +/- 19.1, and the minimum absolute value of R(aw) 0.27 +/- 0.11 and 0.30 +/- 0.12 kPa.s.l-1 for the MDPI and pMDI + S, respectively. The salbutamol doses had no significant effect on BP or HR, and were equally well tolerated. Furthermore, 57.5% of the patients preferred the MDPI, 35% the pMDI + S, and 7.5% considered that there was no difference between the devices. In conclusion, this study demonstrates that the new MDPI is as effective and safe a device as a conventional pMDI connected to a spacer in administering inhaled salbutamol for asthmatic patients. Further, most patients considered the MDPI easier to handle, and preferred it over the pMDI + S. An open, crossover and randomized study was carried out to compare the safety and efficacy of salbutamol inhaled using the dry-powder inhaler Turbuhaler, and using a pressurized metered-dose inhaler (pMDI). Twelve patients with moderate to severe asthma, aged 47-68 years, were included in the study. On two separate days, patients received a total dose of 1600 micrograms of salbutamol administered in a cumulative dose fashion: 100, 100, 200, 400 and 800 micrograms at 3-min intervals. Salbutamol inhaled via Turbuhaler caused a larger decrease in serum potassium concentration than did salbutamol inhaled via pMDI. The estimated relative dose potency of the hypokalaemic effect of salbutamol Turbuhaler vs salbutamol pMDI was 2.0 with a 95% confidence interval of 1.3-3.6. Turbuhaler caused a small (but statistically significantly greater than with pMDI) increase in heart rate, QTc interval and tremor. Blood pressure was unaffected by the treatments. No adverse events of clinical relevance were reported. The estimated relative dose potency of the bronchodilating effect (FEV1) of salbutamol Turbuhaler vs salbutamol pMDI was 3.0 with a 95% confidence interval of 1.8-5.8. In conclusion, salbutamol inhaled via Turbuhaler was more potent and seemed to have a better therapeutic ratio than salbutamol inhaled via pMDI. Both treatments were equally well tolerated. Reversibility after administration of an inhaled bronchodilator is not always demonstrable in patients with asthma. Bronchodilator aerosol-induced bronchoconstriction has also been reported to occur in some patients.
                Fifteen selected patients showing < 10% improvement in forced expiratory volume in one second (FEV1) when tested with four doses of salbutamol (0.1 mg/dose) or terbutaline (0.25 mg/dose) from a pressurised metered dose inhaler (MDI) participated in two randomised, double blind studies. They received 2.0 mg terbutaline (4 x 2 doses of 0.25 mg) or a corresponding placebo from an MDI connected to a 750 ml spacer, and 1.0 mg (2 x 0.5 mg) terbutaline or placebo from a multidose dry powder inhaler free of additives (Turbohaler).
                Inhalation of placebo MDI resulted in a mean (SD) decrease in FEV1 of 20.5 (14.1)% (range -42.9% to +2.6%). In 14 patients inhalation of 2.0 mg terbutaline MDI with spacer resulted in < 10% improvement (mean increase 3.1 (6.0)%). One mg of terbutaline via a Turbohaler resulted in improvements in FEV1 of > 15% in eight patients (mean increase 16.0 (9.7)%). The improvement was < 10% in four patients. Use of placebo Turbohaler did not affect airway calibre (mean change 0.2 (2.9)%).
                Additives of MDIs may cause bronchoconstriction in some patients with asthma. In these patients inhalation from a pressurised metered dose inhaler is more likely to decrease the bronchodilator response than inhalation from an additive-free inhaler. The frequency of this phenomenon is unknown. Several breath-activated multidose powder devices for inhaled anti-asthma drugs are now available. Some of these inhalers have been argued to give higher drug deposition in the airways than conventional pressurized metered dose inhalers (pMDI). The aim of the present study was to compare the efficacy and safety of salbutamol given via pMDI or Turbuhaler (both 100 microgram per inhalation). Adult asthmatic patients of either sex (n = 22) and with reversible airflow obstruction were included in a randomized, placebo-controlled study. On the study days, salbutamol was given with increasing doses (200 to 3,200 microgram cumulative) or placebo, via pMDI or Turbuhaler. A dose-related increase in FEV1 was observed after administration of salbutamol given via either device, versus placebo. The improvement in FEV1 was similar whether salbutamol was given via pMDI or Turbuhaler, at microgram equivalent doses. After a total cumulative dose of 3,200 microgram, mean FEV1 for Turbuhaler was 2.98 (change from baseline of 23.1%), for pMDI 2.93 (change from baseline of 23.6%), and for placebo 2.36 (change from baseline of 0. 42%). Changes in potassium, glucose, and heart rate did not show any significant differences between pMDI and Turbuhaler. We conclude that the efficacy of salbutamol is comparable when the drug is given via the Turbuhaler or pMDI. Twenty-one adult asthmatic patients participated in a trial to compare the clinical equivalence of a single dose of salbutamol inhaled either from a novel multiple dose powder inhaler (MDPI), Easyhaler, or from a conventional metered dose inhaler (MDI). The trial was carried out as a randomized, double-blind, crossover study. The study involved 2 study days with a 6-hour follow-up period of spirometric indices. In addition, blood pressure and heart rate were measured immediately before each lung function test. Our data indicate that salbutamol treatment with the MDPI achieves values which are equivalent to those achieved with the conventional pressurized MDI as regards improving pulmonary function and tolerability. The mean maximum forced expiratory volume in 1 s (FEV1) after the powder dose was 2.44 +/- 0.96 liters and after the aerosol dose 2.45 +/- 0.93 liters. The mean area under the curve of absolute FEV1 values was 822 +/- 340 and 829 +/- 335, respectively. The mean percent change from the baseline in FEV1, forced vital capacity and peak expiratory flow following administration of the preparations was of equal magnitude in both cases. The treatments tested had no effect on blood pressure or heart rate and were well tolerated. A further important finding was that most patients found the MDPI easier or no more difficult to use than the conventional MDI and this probably facilitates the transition from pressurized MDIs to the novel MDPI. Forty-three children from 3-16 years of age suffering from moderate bronchial asthma completed a double-blind cross-over study on the clinical effect of inhaled salbutamol (Ventoline) powder (0.2 mg/dosis) compared with spray (0.1 mg/dosis) over two 4-week periods. Both administrations gave significant improvement in air flow meter (AFM) results. There was no significant difference between the periods on active powder or spray regarding daily symptom scores, adjuvant medication or AFM values. The powder caused cough in four children but in 12 of 28 children it was considered as easy or easier to accept as the spray; nine of these 12 children were younger than 10 years of age. It is concluded that salbutamol inhaled as a powder is a useful alternative when using a spray is difficult or unwanted. Nineteen patients with asthma completed an open, randomized, crossover study in which 0.5 mg terbutaline sulphate was administered either via Turbuhaler or via the metered dose inhaler (MDI) for 2-week periods. The clinical effect of the two treatment forms was comparable; both provided adequate bronchodilator therapy. Patients also considered Turbuhaler and MDI equally effective, with a small preference for the MDI. Turbuhaler seems to be a valuable alternative to bronchodilator MDI therapy. This study compares the safety and efficacy of HFA 134a salbutamol sulfate (Airomir in the 3M CFC-free system [3M Pharmaceuticals]) and CFC 11/12 salbutamol (Ventolin [Allen & Hanburys]) in a cumulative dose-response (1, 1, 2, 4, 8 inhalations at 30-min intervals) study in asthmatic patients.
                Randomized, single-blind, two-period cross-over study.
                Twenty-four stable mild to moderate asthmatics.
                At all cumulative inhalations, the changes in FEV1 (absolute, percent, and percent predicted) and FVC were equivalent. There was also no significant difference in heart rate, serum potassium level, BP, 12-lead ECG, Holter monitor recordings, or adverse events. Both HFA 134a salbutamol sulfate and CFC 11/12 salbutamol displayed a significant dose-response for FEV1, FEF25-75%, FVC, serum potassium, heart rate, and systolic BP.
                HFA 134a salbutamol sulfate and CFC 11/12 salbutamol produced clinically and statistically similar airway responses and side effects. These results indicate that HFA 134a salbutamol sulfate would be a safe and effective substitute for CFC 11/12 salbutamol. Twenty patients with asthma were studied. They were given either fenoterol powder or fenoterol MDI for 2-week periods using a double-blind cross-over design. Identical doses of fenoterol (0.2-0.4 mg 2-4 times daily) were given to an individual patient throughout the 4-week study period. Both forms of treatment produced an almost identical bronchodilation, and there were no statistically significant differences in symptoms or side effects. It is concluded that fenoterol powder and fenoterol aerosol are equally effective. In this study the bronchodilating effect of salbutamol (CAS 18559-94-9) after administration a single-dose (100 micrograms) from a novel multiple dose powder inhaler (MDPI; Easyhaler) and from a conventional metered dose inhaler (MDI) was compared. Forty adult asthmatic patients participated in a double-blind, randomized, cross-over, multicenter study with double-dummy technique. The study comprised two study days with a 4-h follow-up period of spirometric indices and measurements of blood pressure and heart rate. Both the powder and aerosol treatments caused a clear increase in spirometric parameters. The mean (SD) maximum forced exspiratory volume in one second (FEV1) after powder delivery was 2.82 (1.13) l and after aerosol 2.77 (1.03) l. The mean percentual change from the baseline in FEV1 was equal after both preparations. The mean area under the curve (AUC) of the absolute FEV1 values was 616 (264) and 609 (240) l x min after the powder and aerosol delivery, respectively. The treatments had no clinically significant effects on blood pressure or heart rate and were equally well tolerated. Thus the clinical effects indicate therapeutical bioequivalence of the powder and aerosol treatments. Furthermore, most patients found the handling of the MDPI device easier than or equal to that of the conventional MDI, which in all probability increase the patient compliance, which is one of the corner stones in the inhalation therapy of bronchial asthma. Two studies are presented, with the aim of establishing the dose potency ratio for salbutamol given via Turbuhaler and via a pressurized metered-dose inhaler (pMDI). Both studies were of a double-blind, randomized design. Outpatients with mild-to-moderate chronic reversible airway obstruction were given single doses of salbutamol administered via Turbuhaler and via pMDI. Efficacy and safety variables were measured before and during 6 h after each dose. The first study was a four-way crossover study including 12 patients. The salbutamol doses given were: 50, 100 and 2x100 microg via Turbuhaler and 2x100 microg via pMDI (Ventolin). The study showed that 2x100 microg of salbutamol inhaled via Turbuhaler is more potent than 2x100 microg salbutamol inhaled via a pMDI, and that 100 microg salbutamol via Turbuhaler is at least as potent as 2x100 microg salbutamol inhaled via a pMDI. The second study including 50 patients was a placebo-controlled five-way crossover, study. Two doses of salbutamol via Turbuhaler, 50 and 2x100 microg, and via pMDI, 100 and 2x200 microg, were given. There was a dose-dependent response in forced expiratory volume in one second (FEV1) for both inhalers. Adjusted for differences in baseline FEV1 values, the estimated relative dose potency for Turbuhaler versus pMDI was 1.98:1 (95% confidence interval 12-3.2). These studies showed that the same bronchodilating effect can be achieved when half the dose of salbutamol given via a conventional pressurized metered-dose inhaler is given via Turbuhaler. This study was designed to compare the bronchodilatatory effect of terbutaline inhaled through Turbuhaler (TH) or pressurized metered-dose inhaler (pMDI) in young asthmatics, and to assess the possible relationship between patients' inspiratory capacity and bronchodilatation for both devices. One hundred and eighteen asthmatics (aged 4 10/12-20 6/12 years) with bronchial obstruction (mean Vmax 50%: 59.5% pred, SD 17.8% pred) were allocated at random to two groups of 59 patients to inhale 0.5 mg terbutaline either by TH or by pMDI (and placebo by dummy of the other device). In- and expiratory spirometry and bodyplethysmography were conducted before and 10 min after inhalation. Bronchodilatation was effective [change in airways resistance (delta RAW) -50%, change in forced expiratory volume in 1 s (delta FEV1)+15%, delta Vmax 50% or 25% + 25% of baseline] in 41 of 59 patients with pMDI (69.5%) and 33 of 59 patients with TH (55.9%). The effect on Vmax 50% was significantly better with pMDI than with TH. Turbuhaler users with higher inspiratory flow [forced inspiratory volume in 1 s (FIV1), forced inspiratory flow at 50% vital capacity (FIF50)] reached better bronchodilatation, while bronchodilatatory effect was not correlated with inspiratory performance in MDI users. Peak inspiratory flow (PIF) did not correlate well with bronchodilatation by TH. When using TH for bronchodilatation, the effectiveness of terbutaline depends upon the degree of inspiratory capacity. This can lead to impaired bronchodilatatory effect in subgroups of obstructive young asthmatics with low inspiratory flow. In contrast, when using a pMDI, inspiratory capacity does not seem to influence the effectiveness of terbutaline. Comparison of the bronchodilator response to an albuterol novel dry powder inhaler (DPI) (Clickhaler [CH]; ML Laboratories PLC; St. Albans, UK) activated at various inspiratory flow rates and to an albuterol pressurized metered-dose inhaler (pMDI) by patients with moderate to moderately severe stable asthma.
                Randomized, double-blind, placebo-controlled comparison of the bronchodilator response to albuterol DPI (200 microg) at inspiratory flow rates of approximately 15, 30, and 60 L/min in patients with stable asthma with demonstrated reversibility to albuterol. Active (albuterol via pMDI inhaled at 30 L/min) and placebo controls were included.
                Single center study at the chest/allergy unit of a teaching hospital in Canada.
                Sixteen patients with moderate to moderately severe stable asthma.
                Efficacy end points were FEV1, FVC, FEV1/FVC, maximum expiratory flow, and forced expiratory flow between 25% and 75% of vital capacity. Safety end points included heart rate, BP, and tremor. There was no significant difference between the bronchodilator response to albuterol via the CH at 15, 30, and 60 L/min inspiratory flow rate and, at all flow rates, no significant difference was found comparing albuterol CH with the pMDI. All of the techniques for delivering albuterol provided significantly better bronchodilatation than placebo. Adverse events were minimal and did not differ between CH and pMDI or between the various flow rates inhaled through the CH.
                A novel passive albuterol DPI (CH) provides a similar bronchodilator response at 15, 30, and 60 L/min inspiratory flow rates compared with a pMDI used optimally. Salbutamol in a powder aerosol from the Rotahaler insufflator was compared, with equal doses of the conventional pressurized aerosol by dose-response curves and in a 1 month open trial, in the treatment of asthma patients with good inhalation technique. Results were not significantly different in either study. A further group of asthma patients, who were known to be incapable of using pressurized aerosols effectively, were shown to benefit from treatment with the Rotahaler. This device should increase the value of the sympathomimetic drugs to the minority of asthma patients who cannot use conventional aerosols correctly. Turbuhaler is a ready-loaded multiple dose inhaler which does not require co-ordination between release of dose and inhalation. 57 children with asthma participated in this clinical trial to compare the clinical effect and acceptance of terbutaline sulphate via Turbuhaler with that of metered dose inhaler (MDI). The trial consisted of two parts. In the first part of the study, which made use of a double-blind cross-over design, the clinical effect and number of treatment occasions with Turbuhaler were compared with those of MDI. In the second part, which was open, all patients were treated with Turbuhaler for 2 weeks. At the end of this period the patients were asked to make a subjective assessment of effect and to state their preference. There was no difference in clinical effect and number of treatment occasions between Turbuhaler and MDI. A majority of the patients thought Turbuhaler had the best effect and was easy to use.
In patients with stable asthma, short-acting beta-2 bronchodilators in standard CFC-pMDI's are as effective as any other devices. The effect of HFA-pMDI on requirement for oral corticosteroid courses to treat acute exacerbations should be confirmed. Effectiveness studies that use an intention-to-treat analysis are required.