Comparison of budesonide and beclomethasone dipropionate in patients with severe chronic asthma: assessment of relative prednisolone-sparing effects

The relative prednisolone-sparing effects of inhaled budesonide 400 micrograms daily and beclomethasone dipropionate (BDP) 400 micrograms daily were compared in a double-blind crossover study of 26 patients with chronic asthma requiring treatment with BDP and oral prednisolone in a daily dose of 5 mg or greater. During each period of the trial budesonide and BDP were inhaled via conventional pressurized inhalers in a dose of 100 micrograms four times daily. Prednisolone was reduced by 1 mg per month from the patient's normal maintenance dose to zero or to the point at which asthmatic symptoms became unacceptable. The mean reduction in prednisolone dose during BDP treatment was 2.65 mg compared with 1.8 mg at the end of the budesonide period. The difference between the prednisolone-sparing properties of BDP and budesonide assessed in this way in this group of patients was statistically significant in favour of BDP. The mean minimum prednisolone doses at the end of the treatment periods were 3.46 mg for BDP and 4.3 mg for budesonide. Since inhaled steroids were not withdrawn the absolute prednisolone-sparing properties of the two drugs were not assessed, and thus a pharmacological potency ratio cannot be derived from the results. It is concluded that BDP is marginally more potent than budesonide in its prednisolone-sparing properties.     

Acute effect of nebulized budesonide in asthmatic children.

The acute anti-inflammatory effects of inhaled steroids at high doses and their use at home and as emergency treatment of acute asthma attacks in children have been evaluated in many clinical studies. However very little is known about their additional bronchodilator response to systemic steroids plus nebulized salbutamol in the early management in children. Asthmatic patients aged between 5-15 years were investigated in a double-blind, placebo-controlled fashion. Both the study group (Group I) and the control group (Group II) received three consecutive doses of nebulized salbutamol (0.15 mg/kg/dose) and one dose of parenteral methylprednisolone (1 mg/kg/dose, intramuscularly). After this treatment, nebulized budesonide (1 mg/dose) was administered to patients in the study group and placebo (nebulized saline) was administered to patients in the control group. Pulmonary index scoring and peak flow meter was performed to both groups before and after the treatment. There were twelve patients in Group I (mean age: 7.90 +/- 2.34 years) and fourteen patients in Group II (mean age: 9.36 +/- 2.55 years). There was no difference between the two groups with respect to age (p = 0.1421), gender (p = 1.000) and inhaled steroid prophylaxis rate (p = 0.2177). No statistically significant difference was detected between the two groups with respect to the pulmonary index score (p = 0.3528). Yet, there was a statistically significant difference between the two groups with respect to the increase in PEFR (p = 0.0155). The positive acute effect of nebulized budesonide in addition to systemic steroids and nebulized salbutamol in improving the spirometric indices in asthmatic children is an encouraging finding for further investigations of its routine use in the pediatric emergency department.     

Double-blind, randomised, controlled trial assessing controller medications in asthma

BACKGROUND: The motive behind conducting this study was to determine if better control of asthma can be achieved by adding a second controller medication and to assess its use to reduce the dose of inhaled steroids. OBJECTIVES: The study aimed to determine whether either oral sustained-release theophylline or montelukast added to inhaled steroids improved clinical symptoms and pulmonary function test parameters when compared to high-dose steroids alone. METHODS: Ninety patients with incompletely controlled asthma were allocated, in a randomised, double-blind fashion, to one of three treatment groups: group A: double dose of inhaled budesonide (400 microg b.i.d.), group B: 400 mg oral sustained-release theophylline plus budesonide (200 microg b.i.d.) and group C: 10 mg montelukast plus budesonide (200 microg b.i.d.). The primary endpoints were forced expiratory volume in 1 s (FEV(1)) and mean morning peak expiratory flow rate (PEFR). RESULTS: All three groups had improved FEV(1) and PEFR at 8 weeks (p < 0.001). Group C increased their PEFR by 18.7 l/min (95% confidence interval, CI, 12.4-25.1) more than group A and by 19.8 l/min (95% CI 13.4-26.1) more than group B (both p = 0.001). Similarly, group C had a 114 ml (95% CI 45-183 ml) greater improvement in FEV(1) than group A and a 95 ml (95% CI 26-164 ml) greater improvement than group B (both p = 0.01). CONCLUSIONS: Addition of montelukast to budesonide is safe and results in greater improvement in pulmonary function test parameters than high-dose budesonide treatment or addition of theophylline.     

Oral steroid-sparing effect of two doses of nebulized fluticasone propionate and placebo in patients with severe chronic asthma

Inhaled steroids, delivered by metered dose aerosol and dry powder inhalers, have proved effective in reducing the need for oral steroids in patients with oral steroid-dependant asthma. This randomized, double-blind study, compared the efficacy and tolerability of nebulized fluticasone propionate (FP Nebules), 2 mg b.d. (FP 4 mg) and 0.5 mg b.d. (FP 1 mg) with placebo, on the reduction of oral steroid requirement in 301 adult patients with oral steroid-dependent asthma. Primary efficacy was assessed by the reduction in daily oral steroid dose. Secondary efficacy parameters included daily diary card peak expiratory flow (PEF), day and night-time symptoms and clinic lung function measurements. Safety was assessed by adverse event monitoring and serum cortisol levels. After 12 weeks of treatment the adjusted mean +/- SEM reduction in oral prednisolone was significantly greater in the FP 4 mg group (4.44 +/- 0.98 mg day-1) compared with FP 1 mg (2.16 +/- 1.00 mg day-1, P = 0.039) and placebo (1.20 +/- 1.02 mg day-1, P = 0.004). A higher percentage of patients discontinued the use of oral steroids with FP 4 mg (37%) compared with FP 1 mg (26%, P = 0.038) and placebo (18%, P < 0.001). Following treatment, the adjusted mean morning PEF showed a trend in favour of FP 4 mg (280 +/- 41 min-1) compared with placebo (270 +/- 51 min-1, P = 0.053) and the evening PEF was significantly higher with FP 4 mg (305 +/- 41 min-1) compared with FP 1 mg (292 +/- 41 min-1, P = 0.010). FP 4 mg resulted in a significantly higher percentage of days when the patients were free from daytime (P = 0.036) and night-time (P = 0.021) wheeze, compared with placebo. Significantly fewer patients withdrew from the FP 4 mg group compared with the other two groups (vs. FP 1 mg, P = 0.003; vs. placebo, P = 0.032). All three treatments were well tolerated and the incidence of adverse events was similar between the groups. FP Nebules at a daily dose of between 1 and 4 mg are a safe and effective means of reducing the oral steroid requirement of patients with chronic oral steroid dependent asthma.     

Efficacy of once- and twice-daily administration of budesonide via Turbuhaler as initial therapy in patients with mild persistent asthma.

Inhaled glucocorticosteroids such as budesonide have an important role in the management of asthma. Although these agents have traditionally been given twice daily, evidence is accumulating that once-daily treatment may be as effective as twice-daily administration. The efficacy of budesonide Turbuhaler (Astra, Lund, Sweden), 400 micrograms once daily in the evening or 200 micrograms twice daily, was compared in a randomized, double-blind study involving 181 patients (75 men, 106 women; mean age 30.8 years) with mild asthma [mean forced expiratory volume in 1 s (FEV1) 92.8% pred.] who had not previously been treated with inhaled glucocorticosteroids. After a 2-week run-in period, patients were randomized to either regimen and treated for 6 weeks. This was followed by two 8-week open treatment periods, during which all patients received budesonide Turbuhaler, 200 micrograms once daily during the first period and 100 micrograms once daily during the second period. The mean change in morning peak expiratory flow (PEF) during the double-blind treatment period was 16.9 l min-1 in patients receiving once-daily treatment and 17.2 l min-1 in those receiving twice-daily treatment. Similarly, there were no significant differences in evening PEF, symptom scores, bronchodilator use or spirometry data between patients receiving once- and twice-daily treatments. The improvements in morning PEF, symptom scores and bronchodilator use seen during the double-blind treatment period were maintained during the two open treatment periods. It is concluded that once-daily treatment with budesonide Turbuhaler is as effective as an initial therapy twice-daily treatment in patients with mild persistent asthma and that the initial dose can be reduced to maintenance levels (including 100 micrograms) without loss of asthma control.     

Long-term assessment of efficacy and safety of L1, an oral iron chelator, in transfusion dependent thalassaemia: Indian trial

From August 1989 to May 1991, 52 patients with transfusion dependent thalassaemia major received L1 (1,2-dimethyl-3- hydroxypyrid-4-one), the oral iron chelator, for a period of 3-21 months (mean +/- SD: 14.2 +/- 6.8). Mean (+/- SD) urinary iron excretion varied from 6.2 +/- 4.6 mg/d on 25 mg/kg/d of L1 to 42.3 +/- 37.1 mg/d on 100 mg/kg/d of L1. Mean (+/- SD) drop in S ferritin was 1465 +/- 990 micrograms/l after 5.0 +/- 0.8 months to 3641.2 +/- 2299.3 micrograms/l after 20.1 +/- 0.9 months of therapy. There was no evidence of neutropenia, thrombocytopenia, ear or eye toxicity. L1-related arthralgia, which was reversible on dose reduction or stoppage, was seen in 20 patients (38.5%), while minor gastrointestinal (GI) tract symptoms occurred in seven (3.5%) cases. We conclude that although L1 is an effective iron chelator, further studies are required to understand the mechanism of L1 related arthralgia and also to find a safer but effective dose on which incidence of L1 related arthralgia is minimal.     

Highdose inhaled steroid therapy and the cortisol stress response to acute severe asthma

Systemic absorption of inhaled corticosteroids taken in high doses (> or = 1500 micrograms beclomethasone dipropionate or budesonide daily), may cause suppression of the hypothalamo-pituitary-adrenal axis. Patients taking long-term high dose inhaled steroid therapy might therefore be at risk of adrenal crisis at times of stress. Plasma cortisol levels were measured in 24 adults with severe acute asthma who had not received treatment with systemic corticosteroids prior to hospital attendance. Seven were not taking inhaled steroids, four were taking 600-1200 micrograms and 13 were taking 1500-2400 micrograms beclomethasone dipropionate or budesonide daily. Plasma cortisol levels in these 13 (median 594 nmol l-1, interquartile range 399-620 nmol l-1) were similar to levels in those taking lower dose/no inhaled steroids (median 512 nmol l-1, interquartile range 287-1050 nmol l-1): there was no relationship between inhaled steroid dose and cortisol level. Nine of the 24 patients failed to achieve plasma cortisol values > 500 nmol l-1 (the normal response to an insulin stress test). When compared with the remaining 15, they had less severe asthma as indicated by higher arterial oxygen tension (P < 0.01) and peak expiratory flow (P < 0.03). Patients taking long-term high dose inhaled corticosteroids appear to be able to mount an appropriate adrenocortical response to the stress of severe acute asthma.     

Budesonide/formoterol in a single inhaler for maintenance and relief in mild-to-moderate asthma: a randomized, double-blind trial

STUDY OBJECTIVE: To compare a novel asthma management strategy--budesonide/formoterol in a single inhaler for both maintenance therapy and symptom relief--with a higher dose of budesonide plus as-needed terbutaline. METHODS: This was a 6-month, randomized, double-blind, parallel-group study in patients with mild-to-moderate asthma (n = 697; mean age, 38 years [range, 11 to 79 years]; mean baseline FEV1, 75% of predicted; mean inhaled corticosteroid [ICS] dosage, 348 microg/d). Following a 2-week run-in period, all patients received two blinded, dry powder inhalers, one containing maintenance medication and one containing medication to be used as needed for the relief of symptoms. Patients were randomized to receive either budesonide/formoterol (80 microg/4.5 microg, two inhalations qd) for maintenance plus additional inhalations as needed for symptom relief, or budesonide (160 microg, two inhalations qd) for maintenance medication plus terbutaline (0.4 mg) as needed. The primary efficacy variable was morning peak expiratory flow (PEF). RESULTS: Patients receiving budesonide/formoterol showed greater improvements in morning PEF than patients receiving budesonide (increases of 34.5 L/min vs 9.5 L/min, respectively; p < 0.001). The risk of having a severe exacerbation (hospitalization/emergency department [ED] treatment, oral steroids for asthma, or a > or = 30% decrease from baseline in morning PEF on 2 consecutive days) was 54% lower with budesonide/formoterol vs budesonide (p = 0.0011). Budesonide/formoterol patients experienced 90% fewer hospitalizations/ED treatments due to asthma than budesonide patients (1 vs 10, respectively; p = 0.026). The increased efficacy with budesonide/formoterol was achieved with less ICS than was used in the budesonide group (mean dose, 240 microg/d vs 320 microg/d, respectively) and with 77% fewer oral steroid treatment days vs budesonide (114 days vs 498 days, respectively). Both treatments were well tolerated. CONCLUSIONS: Budesonide/formoterol for both maintenance and relief improves asthma control with a lower steroid load compared with a higher dose of budesonide plus terbutaline.     

The response to inhaled and oral steroids in patients with stable chronic obstructive pulmonary disease

BACKGROUND: A significant minority of patients with COPD have favourable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side-effects. Long-term administration of inhaled steroids is a safe means of treatment. However, only a few studies have addressed the role of inhaled steroids in patients with COPD, with conflicting results. METHODS: Forty-four patients with stable COPD were defined as 'responders to bronchodilators' (increase in FEV1 > or = 20% following administration of beta 2-agonist) (group A), and 124 as 'non-responders to bronchodilators' (group B). All patients were randomized to receive a 6-week course of either a daily dose of 800 micrograms of inhaled budesonide or placebo, separated by 4 weeks when no medication was taken; were randomized again to receive a 6-week course of either 1600 micrograms day-1 of inhaled budesonide, or 800 micrograms day-1 of inhaled budesonide plus placebo; and were randomized once again to receive a 6-week course of either 40 mg day-1 of prednisone or placebo. All stages were performed in a double-blind cross-over design. RESULTS: Following administration of 800 micrograms day-1 of inhaled budesonide, there was an increase in the mean FEV1 from 1.40 +/- 0.20 to 1.92 +/- 0.22 L (P < 0.001) and a significant decrease in inhaled beta 2 agonist consumption in group A. These changes remained almost stable during the increased dose of inhaled budesonide or during prednisone treatment. The mean FEV1 did not change during the placebo period, or in group B in either treatments. CONCLUSIONS: Treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about one-quarter of patients with stable COPD, and this rate increased to about three-quarters in patients who responded to beta 2-agonist inhalation. There was no additional benefit in using a higher dose of inhaled budesonide or prednisone.     

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.     

Dose titration of nebulized budesonide in young children

We compared the clinical effect of the glucocorticoid budesonide delivered from two nebulizers Aiolos® and Pari LL® in 38 children less than 4 years of age (mean age, 20.2 months) with chronic wheeze. The design was a controlled, single-blind, randomized, cross-over, dose titration study. After a 1-week run-in, patients were randomized to treatment with 1 mg budesonide b.i.d. for 2 weeks from either an Aiolos® or a Pari LL® nebulizer. This was followed by a gradual dose reduction period during which the budesonide dose was reduced at 2-week intervals until unacceptable asthma symptoms appeared or the placebo level was reached. The patient was then switched to budesonide 1 mg b.i.d. from the other nebulizer for 2 weeks, after which the dose was reduced at 2-week intervals as described for the first period. Patients who completed the study on placebo for 2 weeks without deterioration of their asthma were not included in the statistical analysis. During Period # 1 the minimum effective dose of budesonide was 2 mg/day in 9 patients, 1 mg/day in 10 patients, and 0.5 mg/day in 13 patients. In Period #2 the corresponding figures were 14, 5, and 13 patients. Six patients were excluded after the first period because their asthma control did not deteriorate during dose reduction and when finishing on placebo for 2 weeks. For both nebulizers the reduction in budesonide dose was associated with a small increase in symptoms and use of rescue terbutaline. The mean dose of budesonide delivered to the patient by the Aiolos® was twice as large as that delivered by the Parl LL®: 26% vs. 13% of the nominal dose assessed by the filter method. Nevertheless, no statistically significant difference in clinical effect or mean minimal effective dose (1.1 mg for Aiolos® and 1.2 mg for Pari LL®) could be detected between the two nebulizers. No serious adverse events were observed. We conclude that the minimal effective dose of nebulized budesonide varies from 0.5 to 2.0 mg/day in young children with asthma. A higher drug delivery, as assessed by the filter method, does not necessarily result in better clinical control or lower minimal effective dose. Further studies are needed to assess whether this is due to insufficient sensitivity of the study design in detecting a difference in clinical effect, or whether measurements of drug delivery by the filter method do not reflect lung deposition or clinical effect in young children with wheezing. Pediatr Pulmonol. 1997;23:270–277. © 1997 Wiley-Liss, Inc.     

Salmeterol/fluticasone propionate combination therapy 50/250 microg twice daily is more effective than budesonide 800 microg twice daily in treating moderate to severe asthma

Three hundred and fifty-three asthmatic patients who remained symptomatic despite treatment with budesonide 800-1200 microg day(-1) (or equivalent) were randomized to a new combination therapy comprising salmeterol 50 microg and fluticasone propionate 250 microg (Seretide, Advair, Viani 50/250 microg) twice daily or budesonide 800 microg twice daily for 24 weeks. Patients kept daily records of their morning and evening peak expiratory flow (PEF), daytime and night-time symptom scores and daytime and night-time use of rescue salbutamol. Mean morning PEF increased by 451 min(-1) (baseline 361 l min(-1)) in the salmeterol/fluticasone propionate combination (SFC) group and by 19 l min(-1) (baseline 358 l min(-1)) in the budesonide group over the 24 weeks. The adjusted mean morning PEF over weeks 1 to 24 was significantly greater in the SFC group, despite the > three-fold lower corticosteroid dose (406 vs. 380 l min(-1); P < 0.001). A significantly greater improvement in evening PEF was also seen in the SFC group (adjusted mean 416 vs. 398 l min(-1); P<0.001). SFC also provided significantly better control of daytime symptoms and a significantly greater reduction in the requirement for rescue salbutamol compared with budesonide. These results demonstrate that SFC 50/250 microg twice daily is superior to budesonide 800 microg twice daily in the management of patients with moderate to severe asthma who are symptomatic on their existing dose of corticosteroid.     

High-Dose Inhaled Budesonide May Substitute for Oral Therapy After an Acute Asthma Attack

Patients attending the emergency room with acute asthma, participating in a study comparing salbutamol (albuterol in the United States) via a dry powder inhaler (Turbuhaler®) with pressurized metered-dose inhaler (pMDI), were included in this 1-week follow-up study with the aim of assessing whether inhaled budesonide via Turbuhaler may be an alternative to prednisolone tablets after an acute asthma attack. Eighty-one patients with a mean age of 38 years and forced expiratory volume in 1 sec (FEV₁) of 64% predicted normal value after treatment with salbutamol were randomized in this double-blind, double-dummy, parallel-group study. The doses given were budesonide 1600 μg b.i.d. or prednisolone in daily doses from 40 mg (day 1) decreased to 5 mg (day 7). FEV₁ was recorded before and after the 7-day treatments and peak expiratory flow (PEF) morning and evening, clinical symptoms (visual analogue scale 0-100), and doses of rescue medication (terbutalineTurbuhaler 0.25 mg/dose) were recorded daily. The mean increase in FEV, from baseline to day 7 was 1 7.3% in the budesonide Turbuhaler group and 1 7.6% in the prednisolone group. Mean values of morning PEF increased from day 1 to day 7 by 67 L/min in the budesonide Turbuhaler group and by 57 L/min in the prednisolone group (not significant). There were no statistically significant differences between the groups in clinical symptoms and in the number of doses of rescue medication. Because of disease deterioration, five patients in the Turbuhaler group and three in the prednisolone group needed additional symptomatic as well as corticosteroid treatment. Inhaled budesonide in high doses may be a substitute for oral therapy as follow-up treatment after an acute asthma attack.     

High-dose beclomethasone: oral steroid-sparing effect in severe asthmatic patients

One hundred and twenty four patients with severe asthma requiring maintenance treatment with oral corticosteroids were included in a multicentre, double-blind, randomized study comparing the effects of inhaled beclomethasone dipropionate (BDP) (250 micrograms.puff-1), beginning with 1,000 micrograms daily, vs placebo (P). Pulmonary function was assessed and dosage of prednisone and BDP (or P) were adjusted every 15 days according to a clinical score. Our results showed, after 3 months: 1) A greater drop-out rate in the P group than in the BDP group (36 vs 6%, respectively, p less than 0.01); 2) A total weaning from prednisone in 76% of patients in the BDP group (mean BDP dosage = 1,270 +/- 340 micrograms.day-1, mean +/- SD), vs 34% in the P group (p less than 0.001). The mean daily dosage of prednisone was reduced from 17 +/- 7.5 mg to 3.1 +/- 7.4 mg in the BDP group vs 15.6 +/- 7.7 mg to 9.1 +/- 9.4 mg in the P group (p less than 0.001) without any relationship between the steroid-sparing effect and the initial dosage of prednisone; 3) Mean change in forced expiratory volume in one second (FEV1) was +7 +/- 21% from the initial value in the BDP group vs -6 +/- 20% in the P group; p less than 0.01. Thus, in patients with severe asthma requiring oral corticosteroids, high-dose BDP has an important oral steroid-sparing effect not related to the initial dosage of oral steroids and allows a better control of airway obstruction than oral corticosteroids alone.     

Differential effects of inhaled budesonide and oral prednisolone on serum osteocalcin

Inhaled glucocorticosteroids have been developed for the treatment of asthma in an attempt to minimize the suppression of endogenous adrenal function that complicates oral or injected steroid usage, but it is unclear whether this strategy leads to reduced systemic complications in other areas, such as the skeleton. In this study we evaluated serum osteocalcin levels as a marker of skeletal metabolism in healthy volunteers treated with oral and inhaled steroids alone and in response to an oral calcitriol stimulation test. Forty subjects, aged 33 +/- 9 (mean +/- SD) yr were randomized to receive either high or low dose oral prednisolone (40 vs. 10 mg/day) or inhaled budesonide (3.2 vs. 0.8 mg/day). Each dose of budesonide is known to have a greater antiasthmatic potency than the dose of prednisolone with which it was compared. In addition 10 control subjects received placebos containing no active steroid drugs. During the second week of treatment, half of the subjects in each of the 4 steroid-treated groups and all subjects in the control group received oral calcitriol (2.0 micrograms/day). There was a marked dose-dependent reduction in serum cortisol levels, but this reduction was significantly less pronounced during budesonide treatment, such that low dose budesonide was without effect. During the first week of steroid therapy there were significant dose-dependent reductions in serum osteocalcin (P = 0.003), but this reduction was not significantly different between budesonide and prednisolone treatments. In response to calcitriol, serum osteocalcin increased by 35% in the control group (P = 0.06). Osteocalcin levels increased by 56% and 50% in the low dose budesonide and prednisolone groups and by 106% in the high dose budesonide group, but did not change in the high dose prednisolone group. The osteocalcin response to calcitriol was significantly higher in the budesonide groups (P = 0.03, by analysis of variance). High dose prednisolone caused increases in serum 1,25-dihydroxyvitamin D3 (P less than 0.02), urinary calcium excretion (P = 0.07), and urinary hydroxyproline (P less than 0.01). None of these changes was seen during budesonide therapy. There are as yet no data for these variables after long term use of inhaled budesonide in asthmatic patients, but our acute studies suggest that this potent topical glucocorticoid may have considerably less impact on the skeleton than oral prednisolone, even if used at doses high enough to suppress endogenous adrenal function.     

Once-daily dosing with budesonide/formoterol compared with twice-daily budesonide/formoterol and once-daily budesonide in adults with mild to moderate asthma

Adherence to maintenance therapy is often poor in patients with asthma. Simplifying dosing regimens has the potential to improve both adherence and asthma-related morbidity. In this 12-week, randomized, double-blind, double-dummy, parallel-group study, 617 patients with mild to moderate persistent asthma (mean forced expiratory volume in 1s [FEV1] 78.5% predicted) who were not optimally controlled on inhaled corticosteroids (200-500 microg/day) were randomized to once-daily budesonide/formoterol (80/4.5 microg, 2 inhalations in the evening), twice-daily budesonide/formoterol (80/4.5 microg, 1 inhalation), or a corresponding dose of budesonide once-daily (200 microg, 1 inhalation in the evening). All patients received budesonide (100 microg twice daily) during a 2-week run-in. Changes in mean morning peak expiratory flow (PEF) were similar for od budesonide/formoterol (23.4 l/min) and twice-daily budesonide/formoterol (24.1 l/min), and both were greater than with budesonide (5.5 l/min; both P<0.001). Evening PEF, symptom-free days, reliever-free days, and asthma control days were improved with budesonide/formoterol therapy vs. budesonide (P<0.05 vs. budesonide for all variables). All treatments were well tolerated. Budesonide/formoterol administered once daily in the evening is a convenient treatment regimen that is as effective in improving asthma control as twice-daily dosing in patients with mild to moderate persistent asthma.     

High-Dose Inhaled Budesonide May Substitute for Oral Therapy After an Acute Asthma Attack

Patients attending the emergency room with acute asthma, participating in a study comparing salbutamol (albuterol in the United States) via a dry powder inhaler (Turbuhaler®) with pressurized metered-dose inhaler (pMDI), were included in this 1-week follow-up study with the aim of assessing whether inhaled budesonide via Turbuhaler may be an alternative to prednisolone tablets after an acute asthma attack. Eighty-one patients with a mean age of 38 years and forced expiratory volume in 1 sec (FEV₁) of 64% predicted normal value after treatment with salbutamol were randomized in this double-blind, double-dummy, parallel-group study. The doses given were budesonide 1600 μg b.i.d. or prednisolone in daily doses from 40 mg (day 1) decreased to 5 mg (day 7). FEV₁ was recorded before and after the 7-day treatments and peak expiratory flow (PEF) morning and evening, clinical symptoms (visual analogue scale 0–100), and doses of rescue medication (terbutalineTurbuhaler 0.25 mg/dose) were recorded daily. The mean increase in FEV, from baseline to day 7 was 1 7.3% in the budesonide Turbuhaler group and 1 7.6% in the prednisolone group. Mean values of morning PEF increased from day 1 to day 7 by 67 L/min in the budesonide Turbuhaler group and by 57 L/min in the prednisolone group (not significant). There were no statistically significant differences between the groups in clinical symptoms and in the number of doses of rescue medication. Because of disease deterioration, five patients in the Turbuhaler group and three in the prednisolone group needed additional symptomatic as well as corticosteroid treatment. Inhaled budesonide in high doses may be a substitute for oral therapy as follow-up treatment after an acute asthma attack.     

Budesonide turbuhaler delivered once daily improves health-related quality of life in adult patients with non-steroid-dependent asthma.

Budesonide inhalation powder via the dry-powder multidose inhaler Turbuhaler (budesonide Turbuhaler) has been shown to improve lung function and symptoms in adults with asthma. In this double-blind, placebo-controlled, multicenter trial, we evaluated the effects of once-daily budesonide Turbuhaler on health-related quality of life (HRQL) in 177 adults (aged 18-70 years) with non-steroid-dependent asthma. Patients were randomized to receive budesonide Turbuhaler (400 micrograms) once daily or placebo for 12 weeks. HRQL was assessed at baseline and weeks 4 and 12 using the Asthma Quality of Life Questionnaire (AQLQ). In addition to assessment based on the four AQLQ domains (activity limitations, asthma symptoms, emotional function, and response to exposure to environmental stimuli), AQLQ overall scores were analyzed for both treatment groups. Compared with placebo, patients using budesonide Turbuhaler once daily had statistically significant (p < 0.001) improvements from baseline to weeks 4 and 12 in AQLQ overall scores. Statistically significant improvements from baseline to weeks 4 and 12 in all four individual domains also were observed in the budesonide Turbuhaler group compared with placebo. Differences between the two treatment groups in mean changes from baseline in AQLQ overall, asthma symptoms, and emotional function reached the level required for patients to achieve a minimal important difference of change (> or = 0.5 U) at week 12. A retrospective analysis of the data showed that approximately 70% of patients treated with budesonide Turbuhaler experienced a minimal important difference of change in AQLQ overall scores. Overall, improvements in AQLQ correlated significantly (p < or = 0.04) with improvements in forced expiratory volume in 1 second, morning peak expiratory flow measurements, asthma symptoms, and breakthrough bronchodilator use at the study end. Thus, patients with corticosteroid-na?ve asthma can experience improved HRQL when using budesonide Turbuhaler.     

Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial

Nebulized budesonide has been used successfully to treat acute asthma exacerbation, and we hypothesized that it could also be effective for exacerbations of chronic obstructive pulmonary disease (COPD). In this multicenter, double-blind, randomized, placebo-controlled trial, the efficacy of nebulized budesonide (Pulmicort Respules/Nebuamp), oral prednisolone, and placebo was compared in 199 patients with acute exacerbations of COPD requiring hospitalization. Patients received from randomization (H(0)) to 72 h (H(72)), 2 mg of budesonide every 6 h (n = 71), 30 mg of oral prednisolone every 12 h (n = 62), or placebo (n = 66). All received standard treatment, including nebulized beta(2)-agonists, ipratropium bromide, oral antibiotics, and supplemental oxygen. The mean change (95% confidence interval) in postbronchodilator FEV(1) from H(0) to H(72) was greater with active treatments than with placebo: budesonide versus placebo, 0.10 L (0.02 to 0.18 L); prednisolone versus placebo, 0.16 L (0.08 to 0.24 L). The difference in FEV(1) between budesonide and prednisolone was not significant, -0.06 L (-0.14 to 0.02 L). The occurrence of serious adverse events was similar for all groups. Budesonide had less systemic activity than prednisolone as indicated by a higher incidence of hyperglycemia observed with prednisolone. Both budesonide and prednisolone improved airflow in COPD patients with acute exacerbations when compared with placebo. Nebulized budesonide may be an alternative to oral prednisolone in the treatment of nonacidotic exacerbations of COPD but further studies should be done to evaluate its long-term impact on clinical outcomes after an initial episode of COPD exacerbation.     

Effect of disease duration on dose-response of inhaled budesonide in asthma

BACKGROUND: Inhaled corticosteroids (ICS) represent first-line treatment in persistent asthma with clinical studies showing benefits of initiating therapy early. Whether treatment should be started with a high or low dose remains controversial. We investigated the importance of disease duration on the response to the starting dose of the ICS, budesonide, in asthma patients not previously treated with ICS. METHODS: Forty patients with newly detected asthma (symptoms for <12 months) and 41 patients with established asthma (mean duration 5.2 years, range 2-11) were randomized (double-blind, parallel-group) to treatment with budesonide Turbuhaler 100 or 400microg twice daily or placebo for 12 weeks. RESULTS: For morning peak expiratory flow (mPEF), all four budesonide treatments resulted in statistically significant improvements from baseline and, after 12 weeks, the changes in all four groups were statistically significantly greater than placebo. In patients receiving early treatment, no significant differences were seen between budesonide doses. In patients with established symptoms, 800microg/day improved mPEF significantly more than 200microg/day. The 800microg/day dose in the early treatment group improved mPEF significantly more than in the delayed treatment group. Changes in forced expiratory volume in 1s (FEV1), the concentration of inhaled histamine causing a 20% drop in FEV1, and use of as-needed medication behaved in very similar ways to mPEF. Asthma symptoms were reduced in all budesonide groups without a difference between doses. CONCLUSION: In patients with newly detected asthma treated early the initial ICS dose is not important. In contrast, in patients with symptoms for a longer duration a high starting dose improves airway function and hyperresponsiveness significantly better than a low dose.