Assessment of the systemic effects of budesonide inhaled from Easyhaler and from Turbuhaler in healthy male volunteers.

The main objective of this study was to show dose-dependent equivalence in the systemic activity of budesonide 800 microg day(-1) and 1600 microg day(-1) delivered from either Easyhaler or Turbuhaler in healthy male subjects. This single-centre study was carried out according to a randomized, double-blind, double-dummy, five-way crossover design over a 9-week period. All subjects received 1 week of treatment with the following, in randomized order, with a washout week between each treatment: budesonide Easyhaler 800 microg day(-1) plus placebo Turbuhaler; budesonide Easyhaler 1600 microg day(-1) plus placebo Turbuhaler; placebo Easyhaler plus Pulmicort Turbuhaler 800 microg day(-1); placebo Easyhaler plus Pulmicort Turbuhaler 1600 microg day(-1); placebo Easyhaler plus placebo Turbuhaler. The final inhalation of study drug was performed at the study centre, where blood and urine samples were collected. Fifteen subjects were recruited and all completed the study. Mean serum cortisol AUC0-20 values (the primary outcome variable) were comparable for each device at the two dose levels, and met the defined criteria for equivalence (90% CI 0.8-1.25 for between-treatment difference). Budesonide 800 microg day(-1) caused minimal suppression of serum cortisol AUC0-20 values, Budesonide 1600 microg day(-1) statistically significantly suppressed serum cortisol AUC0-20 values compared with placebo. Mean morning serum cortisol values were within the reference range in al treatment groups. At a budesonide dose of 800 microg day(-1) mean urine cortisol/creatinine ratio was statistically significantly higher with Easyhaler than with Turbuhaler, but there was no significant difference between the devices at the 1600 microg day(-1) dose. Serum budesonide concentrations were equivalent for each device at both dose levels. Adverse drug reactions were infrequent and mild in nature and there were no clinically significant changes in laboratory safety variables. In conclusion, in healthy male volunteers, budesonide 800 microg day(-1) and 1600 microg day inhaled from Easyhaler had comparable systemic effects to the same doses inhaled via Turbuhaler.     

Comparison of two budesonide powder inhalers,Easyhaler and Turbuhaler,in steroid-naïve asthmatic patients

The objective of this multicenter study was to compare the clinical efficacy, safety, and acceptability of Easyhaler and Turbuhaler for the delivery of budesonide 200 micrograms/dose twice daily in steroid-na?ve asthmatic patients. Three hundred and twenty-six newly diagnosed, steroid-na?ve adult patients with mild-to-moderate asthma were recruited into this randomized, double-blind, double-dummy, parallel-group study, comprising a 2-week run-in period and 8 weeks of treatment. Patients received budesonide inhalation powder 400 micrograms/day either via Easyhaler (n = 159) or via Turbuhaler (n = 167), plus salbutamol inhalation powder (100 micrograms/dose) via Easyhaler as rescue therapy. The study was completed by 292 patients: 143 in the Easyhaler group and 149 in the Turbuhaler group. The primary outcome variable, mean morning peak expiratory flow (PEF), improved significantly and almost similarly by 36.3 and 30.6 l/min, respectively, from run-in to weeks 7-8. At weeks 7-8, the mean (SE) difference in morning PEF between the two treatments was 7.1 (9.4) l/min (90% CI from -8.4 to 22.6) on per protocol analysis, which was within the defined limits for therapeutic equivalence. There were no significant differences between treatments in terms of secondary efficacy variables or adverse events. However, patients found Easyhaler more acceptable than Turbuhaler. The results show that budesonide via Easyhaler is clinically as effective as Pulmicort Turbuhaler when equal daily doses of budesonide are delivered to steroid-na?ve asthmatic patients. Moreover, patients found Easyhaler more acceptable than Turbuhaler, and a majority would prefer Easyhaler if given a choice.     

Once-daily inhaled budesonide for the treatment of asthma: clinical evidence and pharmacokinetic explanation.

BACKGROUND: Budesonide, a widely used inhaled corticosteroid (ICS) with a favorable therapeutic ratio, is available via a dry powder inhaler (Pulmicort Turbuhaler) and as a suspension for nebulization (Pulmicort Respules). METHODS: MEDLINE and an AstraZeneca database were searched to identify relevant controlled clinical trials published between 1986 and 2002 using the key words budesonide OR inhaled corticosteroid, AND once daily. RESULTS: Thirty-four controlled clinical studies involving once-daily administration of budesonide to asthmatic patients were identified. Excluding long-term studies, this review presents data from 23 controlled studies for 4466 adults or adolescents and 1532 children with asthma and demonstrates efficacy of budesonide in both corticosteroid-na?ve patients and patients previously treated with ICS. Once-daily administration of budesonide achieves clinical efficacy comparable with that of twice-daily regimens in patients with mild-to-moderate asthma and is equally effective when given in the morning or evening. Once-daily administration simplifies treatment regimens and may improve patient compliance. The tolerability profiles of budesonide once-daily via Turbuhaler or as budesonide inhalation suspension are good and comparable with those for twice-daily dosing. CONCLUSIONS: Once-daily budesonide is effective and well tolerated as initial treatment for adults and children with mild asthma and as maintenance therapy in patients with more severe asthma once asthma control has been achieved.     

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

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

Efficacy of budesonide Turbuhaler compared with that of beclomethasone dipropionate pMDI in Japanese patients with moderately persistent asthma

OBJECTIVE: The aim of the study was to compare the efficacy and safety of budesonide Turbuhaler with that of beclomethasone dipropionate (BDP) pMDI. METHODOLOGY: Three hundred and fifty adult asthma patients (mean age 52.7 years, mean baseline morning peak expiratory flow (PEF) 294 L/min (< 80% predicted normal)), taking BDP via pressurized metered-dose inhaler (pMDI), 400 microg daily for at least 2 months, were randomized in an open 6 week study to receive daily doses of either budesonide 100 microg or 400 microg twice daily via Turbuhaler or continued treatment with BDP, 100 microg four times daily. The primary efficacy variable was the mean change in morning PEF from baseline to the end of treatment. Outcome was also assessed using symptom scores and investigators' assessments employed in Japanese clinical trials. RESULTS: At the end of the 6 week treatment period, mean morning PEF improved significantly from baseline in both budesonide groups, 16 L/min and 33 L/min in the 200 microg and 800 microg groups, respectively, but not in the BDP group, 5 L/min. There was no significant difference between 200 microg budesonide and 400 microg BDP treatment in the effect on PEF (P = 0.29), but 800 microg budesonide was significantly superior to BDP (P < 0.001). Final assessment of improvement and usefulness ratings showed that both budesonide treatments were significantly superior to BDP (P < 0.001). All treatments were well tolerated. CONCLUSION: Budesonide Turbuhaler (200 microg) was as effective as 400 microg BDP pMDI. The efficacy of budesonide was improved significantly by increasing the dosage to 800 microg daily. The study design shows the importance of including a higher dose treatment group when comparing two formulations of inhaled corticosteroids in order to determine whether the treatments to be compared are on the steep part of the dose-response curve. Without that information, comparative studies are usually inconclusive.     

Efficacy and Tolerability of Budesonide Clickhaler® and Turbuhaler® in Adult Asthma

New dry powder inhalers should be clinically comparable with established devices to ensure the continuity of effective therapy for asthma patients. This randomized, open, parallel group study compared the clinical efficacy and tolerability of budesonide delivered via Clickhaler® or Turbuhaler® dry powder inhalers in adults with mild to moderate stable asthma. Following a 4-week stabilizing period using budesonide Turbuhaler adults aged 18 years or older, who had been treated with inhaled corticosteroids for at least the previous 12 weeks, were randomized to receive budesonide twice daily (≤ 1600 µg/day) via either Clickhaler (n = 110) or Turbuhaler (n = 112) for 12 weeks. Morning peak expiratory flow (PEF), evening PEF, asthma symptoms, and use of inhaled short-acting β₂-agonist were recorded daily by the patients on diary cards. Lung function and tolerability data were recorded at clinic visits following 4, 8, and 12 weeks' treatment. Efficacy was measured primarily by mean change from the run-in baseline in weekly morning PEF. Of the 222 patients randomized to treatment, 167 completed the study according to the protocol. Repeated-measures analysis of covariance indicated that the devices were clinically equivalent; a treatment difference of ? 2.3 L/min separated the group mean changes in weekly morning PEF (95% confidence interval ? 7.9 to 3.3). Secondary analyses also supported clinical comparability. This study demonstrates the comparable clinical efficacy and tolerability of budesonide Clickhaler and Turbuhaler devices in adult patients with stable asthma.     

Efficacy and Tolerability of Budesonide Clickhaler® and Turbuhaler® in Adult Asthma

New dry powder inhalers should be clinically comparable with established devices to ensure the continuity of effective therapy for asthma patients. This randomized, open, parallel group study compared the clinical efficacy and tolerability of budesonide delivered via Clickhaler® or Turbuhaler® dry powder inhalers in adults with mild to moderate stable asthma. Following a 4-week stabilizing period using budesonide Turbuhaler adults aged 18 years or older, who had been treated with inhaled corticosteroids for at least the previous 12 weeks, were randomized to receive budesonide twice daily (≤ 1600 µg/day) via either Clickhaler (n = 110) or Turbuhaler (n = 112) for 12 weeks. Morning peak expiratory flow (PEF), evening PEF, asthma symptoms, and use of inhaled short-acting β₂-agonist were recorded daily by the patients on diary cards. Lung function and tolerability data were recorded at clinic visits following 4, 8, and 12 weeks' treatment. Efficacy was measured primarily by mean change from the run-in baseline in weekly morning PEF. Of the 222 patients randomized to treatment, 167 completed the study according to the protocol. Repeated-measures analysis of covariance indicated that the devices were clinically equivalent; a treatment difference of - 2.3 L/min separated the group mean changes in weekly morning PEF (95% confidence interval - 7.9 to 3.3). Secondary analyses also supported clinical comparability. This study demonstrates the comparable clinical efficacy and tolerability of budesonide Clickhaler and Turbuhaler devices in adult patients with stable asthma.     

The role of budesonide in adults and children with mild-to-moderate persistent asthma.

Asthma, a chronic and potentially life-threatening disease of the airways, affects patients of all ages. Inhaled corticosteroids (ICS) are the recommended first-line therapy for patients with persistent asthma. To review the clinical efficacy and tolerability data available on budesonide in the treatment of mild-to-moderate persistent asthma, a MEDLINE database search was performed for 1996-2003 using the following key words: budesonide, inhaled corticosteroid, efficacy, safety, systemic. When administered once or twice daily, budesonide effectively controls asthma in children, adolescents, and adults with mild-to-moderate asthma. Budesonide can be delivered effectively via a dry powder inhaler (Pulmicort Turbuhaler) in patients aged > or = 6 years or as an inhalation suspension (Pulmicort Respules) in children as young as 12 months. With over 20 years' clinical exposure, budesonide has been demonstrated to be well tolerated in the treatment of chronic asthma in patients as young as 12 months. Specifically, at doses required to treat mild or moderate persistent asthma, budesonide does not affect hypothalamic-pituitary-adrenal axis function, bone mineral density, cataract formation, or final adult height. As Pulmicort Turbuhaler, budesonide is the only ICS to achieve a Food and Drug Administration pregnancy category B rating. Early intervention with budesonide is recommended in asthma management: maximum benefit from therapy is reported in patients treated within 2 years of disease recognition. Budesonide is effective and well tolerated in the control of mild-to-moderate persistent asthma in patients aged 12 months and older. There is no evidence for variation in efficacy in population subgroups.     

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

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

A comparison of the lung deposition of budesonide from Easyhaler, Turbuhaler and pMDI plus spacer in asthmatic patients

Inhaled corticosteroids in pressurized metered does inhalers (pMDIs) are often delivered via a large volume spacer device, but these are bulky and inconvenient. Dry powder inhalers (DPIs) provide a highly portable and convenient propellant-free alternative to pMDIs for asthma maintenance therapy However, each DPI could have unique in vivo delivery characteristcs. In order to quantify the total and regional lung deposition of budesonide (200 microg) from (a) Easyhaler, (b) Turbuhaler and (c) pMDI plus Nebuhaler 750 ml spacer, a three-way randomized cross-over study was carried out in 12 mild to moderate asthmatic patients. Deposition was quantified by the imaging technique of gamma scintigraphy Optimal inhalation techniques were used throughout. Mean (SD) whole lung deposition (% metered dose) was similar for Easyhaler [18.5 (7.8) %] and Turbuhaler [21.8 (8.2) %], but was significantly higher for pMDI plus Nebuhaler [44.1 (10.0) %, P < 0.01]. The regional distribution patterns in the lungs were predominantly central for all three devices. Nebuhaler reduced oropharyngeal deposition significantly compared with the two DPIs. Easyhaler showed comparable deposition to Turbuhaler and hence drugs delivered by Easyhaler would be expected to have a similar clinical effect to those delivered by Turbuhaler in asthma maintenance therapy.     

Comparable effects of inhaled fluticasone propionate and budesonide on the HPA-axis in adult asthmatic patients

This randomized, double-blind, double-dummy, multicentre cross-over study compared the effects on the hypothalamic-pituitary-adrenal (HPA) axis of fluticasone propionate (750 microg twice daily given via the Diskus) and budesonide (800 microg twice daily given via the Turbuhaler). Two treatment periods of 2 weeks each were preceded by a 2-week run-in period and separated by a 2-week washout period. During run-in and washout, patients received beclomethasone dipropionate (BDP) or budesonide at a constant dose of 1500-1600 microg day(-1). Sixty patients aged 18-75 years with moderate to severe asthma not fully controlled by treatment with 1500-1600 microg day(-1) budesonide or BDP entered run-in and 45 completed the study. HPA axis suppression was assessed by morning serum cortisol (area under the curve from 08.00 to 10.30 hours) and 12-h nocturnal urinary cortisol excretion, measured at the end of run-in (baseline 1), at the end of washout (baseline 2), and at the end of each treatment period. Neither budesonide nor fluticasone produced significant suppression of either parameter compared to baselines. Only a few patients had serum-cortisol and urinary cortisol values below the normal range, before and after treatment. This shows that the patients did not have adrenal suppression before entering the study. The ratio between the AUC serum cortisol measured after fluticasone treatment and after budesonide treatment was 0.99 (95% CI 0.92-1.06), indicating equivalent effects on the HPA axis. This result was achieved after having omitted two patients' results, due to their very sensitive reaction to budesonide, but not to fluticasone. Two exacerbations of acute asthma occurred during budesonide treatment and none during fluticasone treatment. Both treatments were well tolerated. In conclusion, budesonide 1600 microg day(-1) via Turbuhaler and fluticasone propionate 1500 microg day(-1) via Diskus had no clinical effects on the HPA axis in patients with moderate to severe asthma.     

Once-daily budesonide inhalation powder (Pulmicort Turbuhaler) is effective and safe in adults previously treated with inhaled corticosteroids.

This 12-week, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of budesonide 400 microg administered once daily via Turbuhaler in adults previously treated with at least twice-daily dosing of inhaled corticosteroids. Pulmonary function (FEV1, PEF, FVC, FEF(25-75%)), asthma symptom scores, quality of life, and breakthrough medication use were significantly (p < 0.05) different in patients receiving once-daily budesonide Turbuhaler compared to placebo, and significantly (p < 0.001) more patients receiving placebo discontinued the study. Adverse events were similar between study groups. Once-daily administration of budesonide Turbuhaler was safe and efficacious in patients previously treated with inhaled corticosteroids.     

Dose-response evaluation of the therapeutic index for inhaled budesonide in patients with mild-to-moderate asthma

PURPOSE: Inhaled corticosteroids have beneficial effects on pulmonary function and inflammation in patients with asthma, but they also cause systemic adverse effects, such as adrenal suppression. We evaluated the therapeutic index of inhaled corticosteroids in asthmatic patients by comparing their dose-response effects on lung function, surrogate markers of airway inflammation, and tests of adrenal function. SUBJECTS AND METHODS: After a 10-day placebo run-in, we evaluated the effects of 200 microg, 400 microg, and 800 microg of inhaled budesonide, each dose given twice daily sequentially for 3 weeks in 26 patients, aged 35 +/- 12 years (mean +/- SD), with mild-to-moderate asthma. Measurements were made of bronchial reactivity, exhaled nitric oxide (a marker of airway inflammation), spirometry, serum eosinophilic cationic protein concentration, and 10-hour overnight urinary cortisol excretion. Plasma cortisol levels were measured at 8 AM and after stimulation with human corticotropin releasing factor. RESULTS: For measurements of pulmonary function and exhaled nitric oxide, there was a plateau in the mean response to budesonide between 400 microg (low dose) and 800 microg (medium dose) per day, whereas for eosinophilic cationic protein and bronchial challenge, maximal benefits occurred between 800 and 1,600 microg (high dose) per day. Effects on plasma cortisol levels showed maximal suppression at 1,600 microg of budesonide per day. The proportion of patients with an optimal therapeutic index, in terms of a good airway response (fourfold decrease in bronchial hyperreactivity) and minimal systemic response (overnight urinary cortisol greater than 20 nmol), was similar at low-dose (46%) and at high-dose (52%) budesonide. The proportion of patients with a suboptimal therapeutic index, a good airway response with a marked systemic response (overnight urinary cortisol greater than 20 nmol), increased from 4% at low dose to 38% at high dose. CONCLUSIONS: In patients with mild-to-moderate atopic asthma, there were dose-related effects of budesonide on surrogate markers of inflammation (bronchial hyperreactivity and serum eosinophilic cationic protein), although higher doses were associated with adrenal suppression and a decrease in the therapeutic index.     

Tolerability of a high dose of budesonide/formoterol in a single inhaler in patients with asthma

This randomised, double-blind, double-dummy, crossover, placebo-controlled study assessed the acute tolerability of budesonide/formoterol in a single inhaler (Symbicort Turbuhaler, AstraZeneca) administered as a high dose. Fourteen patients with asthma receiving budesonide/formoterol maintenance treatment (two inhalations of 160/4.5 microg twice daily) inhaled 10 additional doses of budesonide/formoterol 1600/45 microg (total daily dose including morning dose of maintenance treatment 1920/54 microg) or formoterol 45 microg (Oxis Turbuhaler, AstraZeneca; total daily dose including morning dose of maintenance treatment 54 microg formoterol) or placebo in addition to the morning dose of maintenance treatment on 3 separate study days. Serum potassium, pulse rate, blood pressure and ECG were assessed at regular intervals over a 12-h period following dosing. Blood glucose and plasma lactate were assessed over 3 h following dosing. Changes in serum potassium, pulse rate, blood pressure, QTc, blood glucose and plasma lactate occurring with budesonide/formoterol, though statistically significantly different from placebo (P<0.05), were considered clinically unimportant. No clinically relevant differences were identified between active treatments. In conclusion, budesonide/formoterol in a single inhaler is well tolerated at high doses such as might be used by patients using budesonide/formoterol for relief of symptoms of asthma.     

Comparison of high and low dose of the inhaled steroid, budesonide, as an initial treatment in newly detected asthma

The importance of early initiation of inhaled steroids even in mild asthma has been documented in several studies. It is not, however, clear whether the treatment should be started with a high or a low dose of the inhaled steroid. We have compared the effects of high and low dose inhaled steroid, budesonide, in patients with newly detected asthma. We studied 101 adult patients with newly detected bronchial asthma who were without inhaled steroid or any regular pharmacological treatment for their asthma. The patients were randomly allocated to two treatment groups: one to receive 800 microg inhaled budesonide per day and the other to receive 200 microg inhaled budesonide per day. The drugs were given with a Turbuhaler dry powder inhaler. During the 3-month treatment period, no significant differences between the treatment groups were noted in morning or evening PEF values, in spirometric parameters, in asthmatic symptoms or in the use of rescue beta2-agonists. The decrease in bronchial hyperresponsiveness was, however, more marked in the high dose budesonide group, reaching a borderline significance (P=0.10 high vs. low dose budesonide). In addition, in serum markers of asthmatic inflammation significant differences were shown between the treatment groups. The decrease in the number of blood eosinophils during the treatment was more marked in the high dose budesonide group (P=0.02; high vs. low dose budesonide). In serum ECP no change was observed in the low dose budesonide group, but a marked decrease in the high-dose budesonide group (P=0.008; high vs. low dose budesonide). The change was even more marked with regard to serum EPX (P=0.005; high vs. low dose budesonide). Our results support the view that the treatment of newly detected asthma should be started with a high dose of inhaled steroid. The low dose may not be enough to suppress asthmatic inflammation despite good clinical primary response.     

Efficacy of inhaled budesonide and oral theophylline in asthmatic subjects.

The aim of present study was to evaluate clinical, functional, and anti-inflammatory effects of inhaled budesonide and oral theophylline treatments in patients with mild to moderate asthma. The study included 38 patients. After a 10-day run-in period, the patients were randomly assigned into two groups. Group 1 received inhaled budesonide (Pulmicort Turbuhaler) 800 microg/day for 4 weeks. Group 2 received oral theophylline (Talotren tablets, 200 mg twice daily) for 4 weeks. Inhaled budesonide therapy was accompanied by a significant decrease in serum interleukin (IL)-5 levels (p < 0.0005) and blood, sputum, and nasal eosinophil counts (p < 0.005). It produced a significant reduction in daytime (p < 0.01) and nighttime (p < 0.005) symptom scores and an increase in morning (p < 0.005) and evening (p < 0.05) peak expiratory flow (PEF) and forced expiratory volume in I sec (FEV1) values (p < 0.01). Theophylline therapy was associated with a significant decrease in blood (p < 0.02) and nasal (p < 0.01) eosinophil counts and serum IL-5 levels (p < 0.01). It resulted in significant improvements in daytime and nighttime symptom scores (p < 0.05), and morning PEF and FEV1 values (p < 0.05). These changes were more significant in group I than in group 2. There was no statistically significant difference between the two groups with respect to post-treatment values. Our results confirm the role of inhaled corticosteroids in the treatment of asthma and are consistent with the recommendation that theophylline exerts an anti-inflammatory effect. Further studies should be conducted to determine long-term benefits of theophylline.     

Randomized comparison of the efficacy and safety of ciclesonide and budesonide in adolescents with severe asthma

BACKGROUND: The aim of the study was to investigate the efficacy and safety of ciclesonide compared with budesonide in adolescents with severe asthma. METHODS: In this randomized, double-blind, double-dummy, parallel-group study, patients aged 12-17 years with severe asthma were treated with budesonide 400 microg once daily (QD) in a 2-week run-in period. At randomization, eligible patients were assigned 2:1 to ciclesonide 320 microg QD (ex-actuator) or budesonide 800 microg QD (metered dose), respectively, in the evening. Forced expiratory volume in 1s (FEV(1)) was the primary variable. Patients recorded asthma symptom score and rescue medication use in diaries. Safety assessments included adverse events (AEs) and 24-h urine cortisol. RESULTS: Four hundred and three patients were randomized. Ciclesonide 320 microg QD and budesonide 800 microg QD significantly increased FEV(1) (least-squares mean: 505 and 536 mL, respectively; both p<0.0001 versus baseline) in the intention-to-treat (ITT) population. Lower limits of the 95% confidence intervals (ITT: -138 mL; per-protocol: -122 mL) were above the non-inferiority limit (-150 mL). Median percentage of days without asthma symptoms and without rescue medication use was 84% with ciclesonide and 85% with budesonide. AEs were unremarkable, with no cases of confirmed candidiasis. Median creatinine-adjusted urine cortisol significantly decreased with budesonide treatment (15.9-13.7 nmol cortisol/mmol creatinine; p=0.0086 versus baseline), but not with ciclesonide (p=0.1125). CONCLUSIONS: Ciclesonide 320 microg QD showed similar efficacy to budesonide 800 microg QD in adolescents with severe asthma. Ciclesonide was well tolerated and, unlike budesonide, had no effect on urine cortisol levels. CLINICAL TRIAL REGISTRATION NUMBER: EudraCT No.: 2004-001233-41.     

Efficacy and safety of high-dose budesonide/formoterol (Symbicort) compared with budesonide administered either concomitantly with formoterol or alone in patients with persistent symptomatic asthma

OBJECTIVE AND BACKGROUND: Budesonide/formoterol 160/4.5 microg, two inhalations bd, is an effective and well-tolerated maintenance therapy for patients not controlled on inhaled corticosteroids alone. The authors assessed the efficacy and safety of a higher dose of budesonide/formoterol in patients with persistent symptomatic asthma. METHODS: This was a 24-week, double-blind, double-dummy randomized study. Budesonide/formoterol 320/9 microg, two inhalations bd (1280/36 microg/day), was compared with corresponding doses of budesonide during weeks 1-12 and budesonide plus formoterol via separate inhalers during weeks 1-24. Efficacy was assessed during weeks 1-12; the primary variable was morning PEF. Safety was assessed over weeks 1-24. RESULTS: Patients (n=456; aged 12-79 years) had a mean reversibility in FEV1 of 28% and mean pre-study inhaled corticosteroid dose of 1038 microg/day. Mean morning PEF increased by 37 L/min and 36 L/min with budesonide/formoterol and budesonide plus formoterol, respectively, versus an increase of 5 L/min with budesonide (P<0.001 for both vs. budesonide). Budesonide/formoterol increased time to first mild exacerbation (P<0.005) versus budesonide. Budesonide/formoterol and budesonide plus formoterol had similar efficacy. All treatments were well tolerated and the incidence of class-related adverse events was similarly low in all groups. Changes in serum potassium and plasma cortisol were comparable across treatments. CONCLUSIONS: High-dose budesonide/formoterol (320/9 microg, two inhalations bd) is effective and well tolerated in patients with persistent symptomatic asthma. The findings also support the safety of regular high-dose formoterol (36 microg/day).     

A health-related quality-of-life comparison of formoterol (Oxis) Turbuhaler plus budesonide (Pulmicort) Turbuhaler with budesonide Turbuhaler alone and noncorticosteroid treatment in asthma: a randomized clinical study in Russia

BACKGROUND: In Russia, current therapy for the long-term management of asthma is mainly nonsteroidal. This situation provides the opportunity to evaluate new asthma treatments in a patient cohort with little previous exposure to inhaled corticosteroids. OBJECTIVES: To compare the effect of formoterol (Oxis) Turbuhaler plus budesonide (Pulmicort) Turbuhaler with budesonide Turbuhaler alone, on the health-related quality of life (HRQL) of patients with mild to moderate asthma. METHODS: A double-blind, parallel-group, randomized, 12-week study compared formoterol Turbuhaler plus budesonide Turbuhaler and budesonide Turbuhaler alone with an open control group of the investigator's choice of noncorticosteroid therapy. Patients completed the Short Form 36 (SF-36) and the Asthma Quality of Life Questionnaire (AQLQ). RESULTS: The improvement in HRQL scores for patients treated with noncorticosteroids was significantly less (p < 0.05) than those treated with formoterol plus budesonide and budesonide alone in all domains of the SF-36 and AQLQ with one marginal exception (budesonide versus investigator's choice, SF-36, Mental Component Scale, p = 0.053). Improvements in HRQL scores of formoterol plus budesonide, compared with budesonide alone, although generally higher, were not significantly different. Formoterol plus budesonide was more effective in improving lung function and reducing both symptoms and the need for relief terbutaline inhalation. CONCLUSION: Formoterol Turbuhaler plus budesonide Turbuhaler and budesonide Turbuhaler alone significantly improved the HRQL of patients with mild to moderate asthma compared with noncorticosteroid treatment.     

Ciclesonide is more effective than budesonide in the treatment of persistent asthma

BACKGROUND: Ciclesonide is a lung-activated inhaled corticosteroid that provides effective control of persistent asthma. The objective of this study was to compare the efficacy and safety of once-daily ciclesonide versus once-daily budesonide in patients with asthma. METHODS: A total of 399 patients with asthma were randomised to receive once-daily ciclesonide 320 microg ex-actuator (equivalent to 400 microg ex-valve) or once-daily budesonide 400 microg for 12 weeks. The primary endpoint was forced expiratory volume in 1s (FEV(1)). Additional efficacy variables included forced vital capacity (FVC), peak expiratory flow (PEF), asthma symptoms, use of rescue medication and time to onset of effect. Adverse events were monitored throughout the study. RESULTS: Both ciclesonide and budesonide significantly increased FEV(1) from baseline (416 and 321 ml, respectively; p<0.0001). The increase in FEV(1) was significantly greater in ciclesonide-treated patients (95% confidence interval: 0.016-0.174; p=0.019 versus budesonide). Similarly, ciclesonide and budesonide significantly improved FVC and PEF from baseline (p<0.0001), and significantly greater increases occurred with ciclesonide (p=0.034 and 0.019 versus budesonide, respectively). Analysis of morning PEF revealed an earlier onset of action for ciclesonide versus budesonide; a significant improvement was seen by day 2 (p=0.039 versus baseline) with ciclesonide compared with day 7 for budesonide (p=0.047 versus baseline). Adverse events occurred with a similar incidence in both treatment groups. Neither treatment caused significant changes in urinary cortisol levels. CONCLUSION: Once-daily ciclesonide was more effective than once-daily budesonide in improving FEV(1), FVC and PEF. Ciclesonide also had an earlier onset of action than budesonide in patients with persistent asthma. Both ciclesonide and budesonide had good safety and tolerability profiles.