Therapeutic comparison of a new budesonide/formoterol pMDI with budesonide pMDI and budesonide/formoterol DPI in asthma

BACKGROUND: Budesonide/formoterol is an effective treatment for both asthma and chronic obstructive pulmonary disease. This study compared the efficacy and safety of a novel hydrofluoroalkane (HFA) pressurised metered-dose inhaler (pMDI) formulation of budesonide/formoterol with that of budesonide pMDI and budesonide/formoterol dry-powder inhaler (DPI; Turbuhaler). METHODS: This was a 12-week, multinational, randomised, double-blind, double-dummy study involving patients aged > or = 12 years with asthma. All patients had a forced expiratory volume in 1 s of 50-90% predicted normal and were inadequately controlled on inhaled corticosteroids (500-1600 microg/day) alone. Following a 2-week run-in, during which they received their usual medication, patients were randomised (two inhalations twice daily) to budesonide pMDI 200 microg, budesonide/formoterol DPI 160/4.5 microg or budesonide/formoterol pMDI 160/4.5 microg. The primary efficacy end-point was change from baseline in morning peak expiratory flow (PEF). RESULTS: In total, 680 patients were randomised, of whom 668 were included in the primary analysis. Therapeutically equivalent increases in morning PEF were observed with budesonide/formoterol pMDI (29.3 l/min) and budesonide/formoterol DPI (32.0 l/min) (95% confidence interval: -10.4 to 4.9; p = 0.48). The increase in morning PEF with budesonide/formoterol pMDI was significantly higher than with budesonide pMDI (+28.7 l/min; p < 0.001). Similar improvements with budesonide/formoterol pMDI vs. budesonide pMDI were seen for all secondary efficacy end-points. Both combination treatments were similarly well tolerated. CONCLUSIONS: Budesonide/formoterol, administered via the HFA pMDI or DPI, is an effective and well-tolerated treatment for adult and adolescent patients with asthma, with both devices being therapeutically equivalent.     

The safety and efficacy of formoterol (Oxis) turbuhaler plus budesonide (Pulmicort) turbuhaler in mild to moderate asthma: a comparison with budesonide Turbuhaler alone and current non-corticosteroid therapy in Russia

Current therapy in Russia for long-term management of asthma is mainly non-steroidal. This provided the opportunity to compare the efficacy and safety of formoterol (Oxis) Turbuhaler plus budesonide (Pulmicort) Turbuhaler with budesonide Turbuhaler alone in adults (n=338) with mild to moderate asthma who had little previous exposure to inhaled corticosteroids. The 12-week study followed a randomised, double-blind, parallel group design and included an open control group of patients who were treated with conventional non-corticosteroid therapy. Patients treated with formoterol plus budesonide benefited from a significantly greater improvement in their pulmonary function and asthma symptoms compared with budesonide alone (95% Cl of difference in mean morning peak expiratory flow [PEF] 8.7-36.3 l/min, p=0.0015). Non-corticosteroid treatment was significantly less effective than formoterol plus budesonide and budesonide alone (95% CIs of differences in mean morning PEF were 36.4-63.6 l/min and 14.1-41.1 l/min, respectively, both p=0.0001). Although the incidence and frequency of adverse events was not significantly different between the groups, formoterol plus budesonide and budesonide alone were better tolerated than non-corticosteroid treatment, and there were fewer incidences of asthma deterioration. Overall, formoterol Turbuhaler plus budesonide Turbuhaler was the safest and most effective treatment.     

Extrafine beclomethasone dipropionate breath-actuated inhaler (400 micrograms/day) versus budesonide dry powder inhaler (800 micrograms/day) in asthma

Hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol breath-actuated inhaler (Qvar Autohaler; BDP-AH) provides an alternative to chlorofluorocarbon metered dose inhalers or dry powder inhalers (DPIs). The aim of this six-week, open-label study was to determine whether BDP-AH demonstrates equivalent asthma control to twice the dose of budesonide (BUD)-DPI (Pulmicort Turbuhaler). Adults with symptomatic asthma inadequately controlled on BUD-DPI 400 micrograms/day and beta-agonist were enrolled. Patients (n = 193) were randomised to receive 400 micrograms/day BDP-AH (n = 98) (two puffs of 100 micrograms/actuation inhaler twice daily) or 800 micrograms/day BUD-DPI (n = 95) (two puffs of 200 micrograms/actuation inhaler twice daily). Both groups showed a statistically significant change from baseline in morning (a.m.) peak expiratory flow (PEF) at weeks 5-6 (p < 0.01), indicating study treatment improved a.m. PEF over prestudy 400 micrograms/day BUD. Changes from baseline in a.m. PEF at weeks 5-6 were 15.9 l/min for BDP-AH and 14.2 l/min for BUD-DPI; the groups were statistically equivalent (90% CI -7.02-10.44; p < -0.001 [equivalence = within +/- 25 l/min]). Other efficacy assessments (evening PEF, FEV1, asthma symptoms, beta-agonist use) confirmed the treatments were clinically equivalent. Thirty-nine (40%) patients on BDP-AH and 35 (37%) on BUD-DPI experienced at least one adverse event (p = 0.767). Four (4%) patients on BDP-AH and 3 (3%) on BUD-DPI reported increased asthma symptoms. BDP-AH at half the daily dose provided equivalent asthma control to BUD-DPI; both treatments were well tolerated.     

EASE OF HANDLING AND CLINICAL EFFICACY OF FLUTICASONE PROPIONATE ACCUHALER/DISKUS™ INHALER COMPARED WITH THE TURBOHALER™ INHALER IN PAEDIATRIC PATIENTS

A total of 323 children aged 4-11 years who were receiving, or had symptoms indicating a clinical requirement for, inhaled corticosteroid at a daily dose of 400 μg budesonide (BUD) or beclomethasone dipropionate (BDP), or 200 μg fluticasone propionate (FP), were randomised into this multicentre, open-label, parallel group study. Patients received either FP 100 μg b.d. administered via the Accuhaler/Diskus inhaler (n=159) or BUD 200 μg b.d. administered via a Turbohaler inhaler (n=164) for four weeks and recorded daily their morning and evening peak expiratory flow (PEF), asthma symptoms and use of relief medication. Device handling was assessed by a questionnaire, with responses recorded on three- or five-point ordinal scales. The primary efficacy parameter was mean percent predicted morning PEF. The device handling results showed the Accuhaler/Diskus inhaler was rated more favourably than the Turbohaler inhaler in terms of ease of correct inhaler use, ease of telling how many doses were left, ease of knowing whether a dose had been inhaled and overall liking of the device. More patients in the Accuhaler/Diskus group (85%) than in the Turbohaler group (58%) said they would be happy to receive the same device again, while 8% and 25% respectively said they would not be happy to be given it again. In addition, the change from baseline to week 4 of treatment in mean percent predicted morning PEF was greater in the FP Accuhaler/Diskus group, indicating that FP 200 μg daily via Accuhaler/Diskus inhaler is at least as clinically effective as BUD 400 μg daily via the Turbohaler inhaler.     

Equally efficacious asthma management with budesonide 800 micrograms administered by Turbuhaler or with beclomethasone dipropionate > or = 1500 micrograms given through a pressurized metered-dose inhaler with spacer. The French Budesonide Trial Group

To avoid the side effects associated with long-term administration of high doses of inhaled glucocorticosteroids, they should be used at the lowest effective dose. This study compared the clinical efficacy of budesonide given via a dry-powder, inspiratory flow-driven device (Turbuhaler), at a daily dose of 800 micrograms, with beclomethasone dipropionate (BDP) 1500 to 2000 micrograms given via pressurized metered-dose inhaler (pMDI) with spacer to adults requiring the latter dose of BDP to control their asthma. The study was performed as a 2-week run-in, 8-week open, randomized, multicenter, parallel-group design. Adult asthmatics with a forced expiratory volume in 1 second 55% or more of predicted normal and receiving BDP 1500 to 2000 micrograms daily entered the study. After a 2-week run-in, one group continued with BDP and the other was switched to budesonide through the Turbuhaler. After 8 weeks, morning peak expiratory flow (PEF) had increased by 5.9 L/min from a mean of 390 L/min in the budesonide group and by 1.9 L/min from a mean of 402 L/min in the BDP group. No clinically or statistically significant differences between groups were evident with regard to the change in this primary variable. Similarly, only small changes in evening PEF and secondary variables of lung function were seen, with no statistically significant difference between groups. The authors concluded that both treatments were equivalent in managing asthma in adult patients with stable asthma.     

Efficacy and safety of salmeterol/fluticasone propionate delivered via a hydrofluoroalkane metered dose inhaler in Chinese patients with moderate asthma poorly controlled with inhaled corticosteroids

A randomised, open-label, multicentre study compared the efficacy and tolerability of salmeterol 25 microg/fluticasone propionate 125 microg (two puffs, twice daily) delivered via a hydrofluoroalkane metered-dose inhaler (HFA-MDI) and salmeterol 50microg/fluticasone propionate 250 microg (one puff, twice daily) delivered via a Diskus inhaler in Chinese patients with moderate asthma uncontrolled with inhaled corticosteroids (ICSs). Morning peak expiratory flow (PEF) was the primary efficacy endpoint. Secondary endpoints included evening PEF, forced expiratory volume in 1 s, day and night symptom scores, rescue medication and patient self-evaluation of efficacy. Safety was assessed according to adverse events recorded. Both treatments were equipotent and significantly improved morning PEF (HFA-MDI 40 l/min; Diskus 42 l/min; p < 0.05) and all secondary endpoints (p < 0.05) from baseline, over 1-4 weeks. Similarly, both treatments were well tolerated. Salmeterol/fluticasone propionate delivered via an HFA-MDI or Diskus inhaler provides a choice of efficacious delivery systems in Chinese patients whose asthma is poorly controlled on ICSs alone.     

Budesonide/formoterol in a single inhaler (Symbicort) reduces healthcare costs compared with separate inhalers in the treatment of asthma over 12 months

This open, multinational, randomised, parallel-group, six-month extension conducted in the Swedish centres of a previous six-month study compared the costs of a total of 12 months of treatment with budesonide/formoterol in a single inhaler with budesonide plus formoterol separate inhalers in 320 adults with asthma. Patients received budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 mg delivered doses, two inhalations b.i.d., or corresponding doses of budesonide (Pulmicort Turbuhaler) plus formoterol (Oxis Turbuhaler). Direct costs and indirect costs were estimated. Budesonide/formoterol treatment was associated with reduced healthcare service utilisation and statistically significant reductions in direct (SEK1595, p=0.0004) and total costs (SEK1884, p=0.043) per person per year compared with budesonide plus formoterol. Budesonide/formoterol reduced the average annual emergency room admission cost per person by SEK489.7 (31% of direct cost reduction) and physician costs by SEK235.4 (15%).The direct cost of study, relief and other medication was reduced by SEK893.8 (47% of total reduction). There were no statistically significant differences in efficacy and safety parameters following treatment with budesonide/formoterol from single or separate inhalers, other than a significantly lower proportion of withdrawals with the single inhaler (9.2% vs 19.4%, p=0.008). In summary, budesonide/formoterol treatment from a single inhaler reduced 12-month treatment costs compared with separate inhalers, while maintaining at least as good control of asthma.     

Formoterol 12 microg BID administered via single-dose dry powder inhaler in adults with asthma suboptimally controlled with salmeterol or on-demand salbutamol: a multicenter,randomized, open-label,parallel-group study

BACKGROUND: Although salmeterol and formoterol are both long-acting beta(2) adrenergic receptor agonist bronchodilators, there are distinct differences between them that could translate into differences in clinical response in some patients. OBJECTIVE: The goal of this study was to examine the efficacy of formoterol in patients with moderate to severe persistent asthma that was suboptimally controlled with an inhaled corticosteroid (ICS) combined with on-demand salbutamol (albuterol in the United States) with or without salmeterol. METHODS: This multicenter, 4-week, randomized, open-label, parallel-group study included adult patients (age >/=18 years) with suboptimally controlled asthma (mean salbutamol use, >/=2 puffs/d via pressurized metered-dose inhaler [100 microg/puff]). Patients were randomized in a 2:1 ratio to receive formoterol 12 microg BID via single-dose dry powder inhaler plus on-demand salbutamol or to continue their existing treatment with either on-demand salbutamol alone or salmeterol 50 microg BID via multidose dry powder inhaler plus on-demand salbutamol. ICS regimens were unchanged during the trial. The primary efficacy variable was evening predose peak expiratory flow (PEF). Secondary variables included further measures of asthma symptom control.RESULTS: A total of 6239 adult patients entered the study; data from 6155 patients were available for analysis. Patients who were switched from salmeterol to formoterol reported a significant increase in mean (SD) evening predose PEF compared with patients who continued their existing treatment (402.9 [112.1] vs 385.5 [107.5] Umin, respectively; P < 0.001). Similarly, patients who were switched from on-demand salbutamol alone to formoterol plus on-demand salbutamol reported a significant increase in mean evening predose PEF compared with those who continued treatment with on-demand salbutamol alone (409.3 [105.6] vs 385.0 [105.3] L/min, respectively; P < 0.001). The results for the secondary efficacy measures mirrored the significant improvements seen in patients switched to formoterol compared with those who continued to receive on-demand salbutamol alone or salmeterol plus on-demand salbutamol. CONCLUSION: In this study, formoterol significantly improved lung function and control of asthma symptoms and decreased use of rescue medication in patients whose asthma had been suboptimally controlled with an ICS in combination with on-demand salbutamol with or without salmeterol.     

Budesonide/formoterol (Symbicort) is well tolerated and effective in patients with moderate persistent asthma

The aim of this study was to compare the safety and efficacy of budesonide/formoterol 160/4.5 microg, two inhalations twice daily, with that of the mono-products administered at the same daily doses via separate inhalers. A total of 586 patients (mean age 45 years) was included in this six-month, open, randomised, multicentre study. Patients received either budesonide/formoterol (n=390) or budesonide plus formoterol (n=190). Safety was assessed by adverse events, vital signs and laboratory values. Efficacy was evaluated using spirometry tests, the Mini Asthma Quality of Life Questionnaire and the Asthma Control Questionnaire. Both treatments were well tolerated, with no differences in safety parameters between the groups. Mean FEV1 increased by 5-6% over baseline in both groups. There was no significant difference in the change from baseline between the groups using the disease-specific questionnaires. Asthma exacerbations occurred with low frequency in both groups. Withdrawal rates were also comparable between the groups (p=0.085). Budesonide/formoterol in a single inhaler was as effective and as well tolerated as budesonide plus formoterol via separate inhalers.     

Comparison of the efficacy of formoterol and salmeterol in patients with reversible obstructive airway disease: a multicenter, randomized, open-label trial

BACKGROUND: Beta2-adrenergic agonists are frequently used for the prevention and relief of bronchospasm in patients with reversible obstructive airway disease. Formoterol and salmeterol are long-acting beta2-agonists. In addition to its long duration of action, formoterol has been reported to have an onset of action similar to that of albuterol. OBJECTIVE: This study compared the effects on lung function of regular twice-daily inhalation of formoterol or salmeterol in adults with moderate to moderately severe persistent asthma who were receiving daily inhaled corticosteroids. METHODS: In this 6-month, multicenter, open-label, parallel-group study, patients with moderate or moderately severe asthma were randomized to receive either formoterol 12 microg BID or salmeterol 50 microg BID. The primary end point was mean morning peak expiratory flow (PEF) measured 5 minutes after dosing and entered in a patient diary each day during the first 4 weeks of treatment. Secondary end points included mean morning and evening predose PEF and number of episode-free days recorded in the patient diaries during the first 4 weeks of treatment, use and time of rescue medication, symptom scores, and overall mean morning predose PEF (spirometric measurements made by the physician during scheduled visits) for the entire treatment period. Safety assessments included spontaneously reported adverse events and vital signs. RESULTS: A total of 528 patients were randomized to study treatment, 262 to formoterol and 266 to salmeterol. There were no significant differences in demographic or baseline characteristics between treatment groups, except in the proportion of current smokers in the formoterol group (4.6%) compared with the salmeterol group (1.5%; P = 0.039). Based on the information recorded in patients' diaries, those receiving formoterol showed significant improvement in mean morning PEF measured 5 minutes after dosing (P < 0.001), reduced use of rescue medication (P < 0.03), and an increased number of episode-free days (P < 0.04) compared with patients receiving salmeterol. Mean predose morning and evening PEF and symptom scores based on diary data and mean morning predose PEF based on measurements obtained during office visits were comparable between the 2 treatment groups throughout the study. CONCLUSIONS: In this open-label trial, patients randomized to formoterol treatment had greater improvement in mean PEF 5 minutes after dosing, required significantly less rescue medication (fewer actuations of albuterol), and experienced more episode-free days compared with patients receiving salmeterol. Thus, although both formoterol and salmeterol are long-acting beta2-agonists, formoterol had a more rapid onset of action.     

Handling of inhaler devices in actual pulmonary practice: metered-dose inhaler versus dry powder inhalers

BACKGROUND: Handling of inhaler devices such as pressurized metered-dose inhalers (MDIs) and dry-powder inhalers (DPIs) in actual pulmonary practice is not well studied. OBJECTIVE: The aim of this study was to evaluate patients' proper handling of inhaler devices during actual pulmonary practice. METHODS: Prospective observational evaluations were conducted at 3 pulmonary clinics in Jordan, from February 2006 until August 2006. MDI (without spacer), Turbuhaler, Diskus, and Aerolizer devices were studied. Incorrect handling was defined as improper technique in any of the predefined essential steps. RESULTS: Patients (n = 300) were recruited and 525 inhaler-device handling technique evaluations were completed. Diskus inhaler had the lowest rate of incorrect handling (7/103, 6.8%) and MDI had the highest rate of incorrect handling (144/193, 74.6%). Turbuhaler and Aerolizer were handled incorrectly by 63/146 (43.2%) and 14/83 (16.9%) patients, respectively. DPI had a lower rate of incorrect handling, when compared with the MDI (p < 0.001). Among the DPI devices, the Diskus had the lowest rate of incorrect handling (p < 0.031). CONCLUSIONS: In actual pulmonary clinical practice the majority of patients were unable to use MDI correctly, whereas correct handling of DPI devices was variable. Regular checking of inhalation technique and proper teaching by health care providers is crucial for optimum use of most inhaler devices.     

Fluticasone/Formoterol Combination Therapy Compared With Monotherapy in Adolescent and Adult Patients With Mild to Moderate Asthma

Objectives

This study investigated the efficacy and tolerability of a new asthma therapy combining fluticasone propionate and formoterol fumarate (fluticasone/formoterol)*, administered twice daily (BID) via a single aerosol inhaler, compared with fluticasone propionate (fluticasone) or formoterol fumarate (formoterol) administered alone, in patients with mild to moderate asthma.

Methods

Patients aged ≥12 years were evenly randomized to 12 weeks of treatment with fluticasone/formoterol (100/10 µg BID), fluticasone (100 µg BID), or formoterol (10 µg BID), in this multicenter, double-blind, parallel-group, study. The 2 coprimary end points were: (1) change in forced expiratory volume in 1 second (FEV₁) from morning predose at baseline to predose at week 12 for the comparison of the combination product with formoterol alone; and (2) change in FEV₁ from morning predose at baseline to 2 hours postdose at week 12 for the comparison of the combination product with fluticasone alone. The secondary objective was to demonstrate the efficacy of fluticasone/formoterol using other pulmonary function tests and clinical end points. Tolerability was assessed based on adverse events, clinical laboratory tests and vital sign evaluations.

Results

Statistically significant differences were demonstrated for the 2 coprimary end points. Fluticasone/formoterol combination therapy showed significantly greater improvements from baseline to end of study in the change in predose FEV₁ compared with formoterol (least squares [LS] mean treatment difference, 0.118 L [95% CI, 0.034–0.201; P = 0.006]) and the change in predose compared with 2 hours postdose FEV₁ versus fluticasone (LS mean treatment difference, 0.122 L [95% CI, 0.040–0.204; P = 0.004]). Statistical analyses of the secondary efficacy endpoints revealed that evaluations of lung function, asthma exacerbations, asthma symptoms, rescue medication use and asthma control were supportive overall of the superior efficacy of fluticasone/formoterol combination therapy compared with its individual components; were supportive overall of the efficacy of fluticasone/formoterol combination therapy compared with its individual components. Since the secondary endpoints were analyzed using the sequential gatekeeper approach, only the mean change from baseline to final week in morning peak expiratory flow rate between the combination-therapy and formoterol groups returned statistically significant results (least squares mean difference, 20.05 [95% CI, 7.631-32.472; P = 0.002]). The fluticasone/formoterol combination therapy had a good tolerability profile over the 12-week treatment period.

Conclusions

Fluticasone/formoterol had a good tolerability profile and showed statistically superior efficacy for the two co-primary endpoints compared to fluticasone or formoterol, in adolescents and adults with mild to moderate asthma. ClinicalTrials.gov identifier: NCT00394199.     

Budesonide/formoterol adjustable maintenance dosing reduces asthma exacerbations versus fixed dosing

A guided, adjustable-dosing regimen with budesonide/formoterol was investigated in asthma patients. In a randomised, open, multicentre study, 1034 patients received budesonide/ formoterol (Symbicort, Turbuhaler,) 80/4.5 microg or 160/4.5 microg (depending on pre-study inhaled corticosteroid dose) two inhalations twice daily for four weeks, followed by adjustable or fixed maintenance dosing for six months. Patients receiving adjustable dosing stepped down to one inhalation twice daily if symptoms were controlled and could, if symptoms worsened, step up to four inhalations twice daily for one or two weeks according to a self-guided management plan. The primary efficacy variable was occurrence of exacerbations. Compared with fixed dosing, adjustable dosing was associated with fewer patients experiencing exacerbations (6.2% vs 9.5%, NNT 30, p<0.05), fewer daily inhalations of budesonide/formoterol (2.35 vs 3.95, p<0.001), lower costs (six-month saving Euros 98, p<0.001) and was similarly well tolerated. Adjustable maintenance dosing with budesonide/formoterol provides more effective asthma control than fixed dosing, and reduces costs.     

Efficacy and tolerability of formoterol Turbuhaler in children

A randomised, double-blind trial was undertaken to investigate the efficacy and tolerability of formoterol Turbuhaler in children with mild to moderate asthma. After a two-week run-in, 248 children aged 6-17 years were randomised to receive formoterol 4.5 and 9 pmicro b.i.d. or placebo for 12 weeks. Morning PEF (primary variable), was significantly improved versus placebo only in the formoterol 9 pmicro b.i.d. group (13 l/min, 95% CCI 1.9, 24.2%; p = 0 .02). Both formoterol 4.5 and 9 pmicro significantly increased the pre-bronchodilator FEV1 by 5.2-6.7% (p < 0 .05) and reduced use of daytime relief medication versus placebo (p < 0 .05). Formoterol 9 pmicro significantly reduced night-time reliever use and awakenings due to asthma versus placebo (p < 0.05). Both doses of formoterol were as well tolerated as placebo. In conclusion, formoterol 4.5 and 9 micro b.i.d. is effective and well tolerated as maintenance therapy in children with mild to moderate asthma.     

Formoterol as dry powder oral inhalation compared with salbutamol metered-dose inhaler in acute exacerbations of chronic obstructive pulmonary disease

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are managed with increased doses or frequency of the patient's existing bronchodilator therapy. The use of formoterol in the treatment of mild acute exacerbations of COPD has been suggested; however, a comparison of cumulative doses of formoterol with salbutamol, the gold standard bronchodilator agent for this pathologic condition, is still lacking. OBJECTIVE: The aim of the study was to compare the inhaled beta2-agonists salbutamol (rapid onset, short duration of action) and formoterol (rapid onset, long duration of action), both used as needed in patients attending outpatient clinics because of mild acute exacerbations of COPD (Anthonisen exacerbation type I or II). METHODS: A dose-response curve to formoterol via Turbuhaler or salbutamol via pressurized metered-dose inhaler (pMDI) was constructed. On 2 consecutive days, the patients received, in randomized order, both of the following active dose regimens: A = 12 + 12 + 24 microg formoterol via Turbuhaler (48-microg cumulative metered dose); B = 200 + 200 + 400 microg salbutamol via pMDI (800-microg cumulative metered dose). Dose increments were given at 30-minute intervals, with measurements made 25 minutes after each dose. The maximum forced expiratory volume in 1 second (FEV1) value during the dose-response curve to formoterol or salbutamol was chosen as the primary outcome variable to compare the 2 treatments. Oxygen saturation by pulse oximetry (SpO2) and pulse rate were also measured at each assessment period. Every adverse event, either reported spontaneously by the patients or observed by the investigators, was recorded. RESULTS: Sixteen patients (2 women, 14 men) aged 51 to 77 years (most older than 65 years) participated in the study. Both formoterol and salbutamol induced a large, significant, dose-dependent increase in FEV1, inspiratory capacity (IC), and forced vital ca- pacity (FVC). There was no significant difference between FEV1, IC, and FVC values after 48 microg formoterol and 800 microg salbutamol. There was no significant difference in FEV1 after 24 microg formoterol and 800 microg salbutamol; however, the difference in FEV1 after 24 and 48 microg formoterol was significant. Neither heart rate (mean differences from baseline after 48 microg formoterol, 1.9 beats/min [95% CI, -3.4, 7.2] and 800 microg salbutamol, 3.7 beats/min [95% CI, -1.1, 8.5]) nor SpO2 (mean percentage differences from baseline after 48 microg formoterol, -0.37% [95% CI, -1.22, 0.47] and 800 microg salbutamol, -0.75% [95% CI, -1.73, 0.23]) changed significantly. However, SpO2 decreased below 90% in 2 patients after the highest dose of formoterol and in 1 patient after the highest dose of salbutamol. CONCLUSIONS: In this small, selected group of patients with mild acute exacerbations of COPD, formoterol via Turbuhaler induced a fast bronchodilation that was dose dependent and not significantly different from that caused by salbutamol. Furthermore, formoterol appeared to be as well tolerated as salbutamol.     

Bronchodilation of formoterol administered with budesonide: device and formulation effects

BACKGROUND: Previous single-dose crossover studies have established therapeutic equivalence of formoterol when administered at the same nominal dose via a dry powder inhaler (DPI) or pressurized hydrofluoroalkane (HFA) metered-dose inhaler (pMDI). Demonstration of equivalent bronchodilation for formoterol administered as formoterol DPI or combined with budesonide in one pMDI (budesonide/formoterol pMDI) would indicate that the greater clinical efficacy of the budesonide/formoterol pMDI combination is due to the budesonide contribution and not to differences in formoterol formulation or delivery device. OBJECTIVE: To determine whether the formoterol-related bronchodilatory effects of formoterol DPI and budesonide/formoterol pMDI are similar, despite formoterol formulation and delivery device differences. METHODS: This was a multicenter, open-label, five-period crossover study conducted in 201 adult patients with stable asthma. The study included a screening visit, a 7- to 14-day run-in period, during which patients were treated with budesonide pMDI (80 microg per inhalation, two inhalations twice daily), and a randomized treatment period that included five single-day treatment periods, during which patients received single-dose crossover treatments, each of which was separated by a 3- to 14-day washout period. Patients were randomized to five of seven single-dose treatments (one, two, or four inhalations of budesonide/formoterol pMDI 80/4.5 microg; four inhalations of budesonide pMDI 80 microg plus one, two, or four inhalations of formoterol DPI 4.5 microg; or four inhalations of budesonide pMDI 80 microg alone). At clinic visits, the budesonide pMDI dose was coordinated with the budesonide dose delivered via the budesonide/formoterol pMDI such that all patients received a 320-microg dose of budesonide. The primary variable was average forced expiratory volume in 1 s (FEV1) from the area under the curve divided by time from 12-h serial spirometry. RESULTS: Average 12-h FEV1 values were similar, regardless of delivery device, among treatments with the same nominal formoterol doses and dose-ordered within each device; mean FEV1 values were significantly higher for treatments containing formoterol versus budesonide alone. The formoterol dose potency ratio for budesonide/formoterol pMDI:formoterol DPI (0.97; 95% confidence interval, 0.73-1.27) demonstrated clinical equivalence in bronchodilation at the same formoterol dose. CONCLUSION: Budesonide/formoterol pMDI affords equivalent formoterol-related bronchodilatory effects versus formoterol DPI at formoterol doses of 4.5, 9, and 18 microg, indicating that practitioners can expect and patients will experience similar bronchodilation from the same dose of formoterol whether it is delivered as monotherapy via a DPI or as combination therapy with budesonide via one pMDI.     

Twelve-week, randomized, placebo-controlled, multicenter study of the efficacy and tolerability of budesonide and formoterol in one metered-dose inhaler compared with budesonide alone and formoterol alone in adolescents and adults with asthma

BACKGROUND: The addition of the long-acting beta(2)-adrenergic agonist formoterol to low- to moderate-dose budesonide has shown clinical efficacy in patients with persistent asthma. Combination therapy with budesonide/formoterol in 1 pressurized metered-dose inhaler (pMDI) has been found to have greater efficacy than its monocomponents in patients with moderate to severe persistent asthma, but it has not been assessed in patients with mild to moderate persistent asthma. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of budesonide and formoterol delivered via 1 pMDI (budesonide/formoterol pMDI), budesonide pMDI, formoterol dry powder inhaler (DPI), and placebo. METHODS: This 12-week, multicenter, double-blind, randomized, placebo-controlled, double-dummy study was conducted at 56 centers across the United States. Patients aged > or =12 years with mild to moderate persistent asthma treated with inhaled corticosteroids (ICSs) for > or =4 weeks before screening and who had a forced expiratory volume in 1 second (FEV(1)) of > or =60% to < or =90% of predicted normal at screening were eligible. After 2 weeks (current asthma therapy discontinued), patients received twice-daily budesonide/formoterol pMDI 80/4.5 microg x 2 inhalations (160/9 microg), budesonide pMDI 80 microg x 2 inhalations (160 microg), formoterol DPI 4.5 microg x 2 inhalations (9 microg), or placebo. The coprimary efficacy variables were changes from baseline in morning predose FEV(1) and 12-hour mean FEV(1) (from serial spirometry) after administration of the morning dose of study medication. Tolerability was assessed based on adverse events (AEs); routine laboratory assessments; electrocardiography; 24-hour Holter monitor assessments; and physical examinations, including vital signs (eg, systolic and diastolic blood pressure and heart rate). AEs were recorded manually by the patient in paper notebooks and reviewed at each clinic visit by the investigator and during a final follow-up phone call. RESULTS: A total of 480 patients were randomized (299 females, 181 males; mean age, 36 years; mean FEV(1), 2.4 L; budesonide/formoterol pMDI, 123 patients; budesonide pMDI, 121; formoterol DPI, 114; placebo, 122). At end of treatment, the mean increases from baseline in predose FEV(1) were greater with budesonide/formoterol pMDI versus budesonide pMDI, formoterol DPI, and placebo (0.37 vs 0.23, 0.17, and 0.03 L, respectively; all, P<0.005). 0.005). After administration of the first dose and at weeks 2 and 12, mean increases in 12-hour mean FEV(1) were significantly greater with budesonide/formoterol pMDI (0.41, 0.47, and 0.50 L, respectively) versus budesonide pMDI (0.17, 0.30, and 0.32 L) and placebo (0.15, 0.12, and 0.12 L) (all, P < 0.001). Fewer patients receiving budesonide/formoterol pMDI met criteria for (18.7%; P < 0.001) or withdrew because of (7.3%; P < or = 0.010) worsening asthma versus formoterol DPI (42.1% and 18.4%, respectively) and placebo (56.6% and 32.8%); results were similar between budesonide pMDI (21.5% and 6.6%, respectively) and budesonide/formoterol pMDI. Three patients experienced serious AEs; none was considered related to study medication. The proportions of withdrawals due to worsening asthma were not significantly different between the budesonide/formoterol pMDI and budesonide pMDI groups. CONCLUSIONS: In this population of adults and adolescents with mild to moderate persistent asthma previously treated with ICSs, twice-daily budesonide/formoterol pMDI was associated with significantly increased pulmonary function versus its monocomponents. All study drugs were generally well tolerated.     

Real-life use of inhaler devices for chronic obstructive pulmonary disease in primary care

The correct use of inhalation devices is an inclusion criterion in many comparative studies. However, patients can make errors, thus compromising the effectiveness of their own inhaler. The aim of the study is to evaluate inhaler use by patients with chronic obstructive pulmonary disease (COPD) [n = 984]. General practitioners assessed inhalation technique, using a specific checklist previously established for each inhaler model (Aerolizer, Autohaler, Diskus, a pressurised metered-dose inhaler (pMDI) or a Turbuhaler). A total of 24% of the patients using a pMDI did not make an error compared with 34-40% of those using breath-actuated devices. The frequency of critical errors varied according to the device: 11.5-14.9% of the subjects using an Aerolizer, Autohaler or Diskus versus 37.4% and 38.1% of the patients using a pMDI and a Turbuhaler, respectively. The proper use of the Turbuhaler is often overestimated (24.7%) compared with the pMDI (2.1%). The development of educational programmes for patients and prescribers is needed to improve the management of COPD.     

Beclomethasone dipropionate Easyhaler is as effective as budesonide Turbohaler in the control of asthma and is preferred by patients. German Study Group

This randomised, crossover study compared the efficacy, safety, acceptability and patient preference of two multidose powder inhalers (MDPIs)--beclomethasone dipropionate Easyhaler (BDP-EH) and budesonide Turbohaler (BUD-TH)--in 79 stable asthmatics who used inhaled steroids but had no experience of MDPIs. After eight weeks' treatment a mean increase in morning PEF of 16 l/min from a baseline of 356 +/- 112 l/min was observed for each treatment. Similar improvements occurred in evening PEF, FEV1, FVC and asthma symptoms. Both treatments had only minimal effect on morning serum cortisol levels. Compliance with both treatments was high (> 97%) but almost twice as many patients favoured the EH (59%) compared with the TH (33%); 7% rated the devices equally. Scores of device acceptability were significantly in favour of the EH (p = 0.001). BDP-EH and BUD-TH showed comparable efficacy and safety in the treatment of asthma. Each MDPI had a high rate of compliance, but patients registered greater preference for the EH than the TH.     

Switch to non-CFC inhaled corticosteroids: a comparative efficacy study of HFA-BDP and CFC-BDP metered-dose inhalers

Inhaled corticosteroids, such as beclomethasone dipropionate (BDP), recommended for the treatment of persistent, mild, moderate, or severe asthma, have traditionally been administered via chlorofluorocarbon (CFC) propellant. The imminent phasing out of CFCs from pharmaceutical preparations due to the Montreal Protocol means patients will have to switch to a CFC-free alternative. One such preparation is hydrofluoroalkane-BDP (HFA-BDP), a press-and-breathe metered-dose inhaler. This 8-week, open-label, multicentre study assessed asthma control in patients switching from CFC-BDP to HFA-BDP (QVAR). Patients with asthma, stabilised on 400-1600 micrograms/day CFC-BDP, were randomised to HFA-BDP (354 patients; 75%) at half their current daily dose of CFC-BDP, or to CFC-BDP (119 patients; 25%). HFA-BDP efficacy was found to be equivalent to that of CFC-BDP in that no statistically significant difference was observed between the two groups in the mean change from baseline in a.m. PEF (95% CI within +/- 11 l/min). No statistically significant differences were observed between the two groups for increased asthma symptoms or acute asthma episodes. We conclude that asthma control was maintained over 8 weeks, with few asthma exacerbations, in patients switching from previous CFC-BDP therapy to HFA-BDP at half the dose.