Oral glucocorticosteroid-sparing effect of budesonide administered by Turbuhaler: a double-blind, placebo-controlled study in adults with moderate-to-severe chronic asthma. Pulmicort Turbuhaler Study Group. [Budesonide administered via Turbuhaler and a nebulator]. Administration of budesonide once daily by means of turbuhaler to subjects with stable asthma. Importance of the inhalation device on the effect of budesonide. Influence of spacer device on drug delivery to young children with asthma. Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids. Starting with a higher dose of inhaled corticosteroids in primary care asthma treatment. Comparative study of budesonide as a nebulized suspension vs pressurized metered-dose inhaler in adult asthmatics. A double‐blind dose‐response study of budesonide by inhalation in patients with bronchial asthma Long-term effects of budesonide on airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthmatics. Effects of once-daily formoterol and budesonide given alone or in combination on surrogate inflammatory markers in asthmatic adults. Controlled study of linear growth in asthmatic children during treatment with inhaled glucocorticosteroids. Adverse effects of inhaled budesonide (800 micrograms) on growth and collagen turnover in children with asthma: a double-blind comparison of once-daily versus twice-daily administration. Dose-response evaluation of the therapeutic index for inhaled budesonide in patients with mild-to-moderate asthma. The effects of static charge in spacer devices on glucocorticosteroid aerosol deposition in asthmatic patients. Short-term knemometry and urine cortisol excretion in children treated with fluticasone propionate and budesonide: a dose response study. Optimal asthma control, starting with high doses of inhaled budesonide. Low-dose budesonide improves exercise-induced bronchospasm in schoolchildren. A 1-year comparison of turbuhaler vs pressurized metered-dose inhaler in asthmatic patients. Once-daily budesonide inhalation powder (Pulmicort Turbuhaler) maintains pulmonary function and symptoms of asthmatic children previously receiving inhaled corticosteroids. Dose titration of nebulized budesonide in young children. Initial loading (400 micrograms twice daily) versus static (400 micrograms nocte) dose budesonide for asthma management. PLAN Research Group. Clinical comparison of inhaled budesonide delivered either via pressurized metered dose inhaler or Turbuhaler® Dose-response comparison of systemic bioactivity with inhaled budesonide and triamcinolone acetonide in asthmatic adults. Effect of inhaled budesonide on severe steroid-dependent asthma. Differential effects of inhaled budesonide on serum osteocalcin in children and adolescents with asthma. Growth of asthmatic children during treatment with budesonide: a double blind trial. Therapeutic ratio of inhaled corticosteroids in adult asthma. A dose-range comparison between fluticasone propionate and budesonide, measuring their effect on bronchial hyperresponsiveness and adrenal cortex function. Influence of dosing frequency and schedule on the response of chronic asthmatics to the aerosol steroid, budesonide. Budesonide treatment of moderate and severe asthma in children: a dose-response study. Rapid onset of control with budesonide Turbuhaler in patients with mild-to-moderate asthma. Low-dose budesonide with the addition of an increased dose during exacerbations is effective in long-term asthma control. On behalf of the Italian Study Group. Rapid induction of clinical response with a short-term high-dose starting schedule of budesonide nebulizing suspension in young children with recurrent wheezing episodes. The potential value of a 750-ml spacer for the administration of inhaled corticosteroids to children. Once-daily budesonide in mild asthma. Comparison of dose‐response effects of inhaled beclomethasone dipropionate and budesonide in the management of asthma Effects of once daily dosing with inhaled budesonide on airway hyperresponsiveness and airway inflammation following repeated low‐dose allergen challenge in atopic asthmatics Once-daily budesonide: 400 micrograms once daily is as effective as 200 micrograms twice daily in controlling childhood asthma. PETITE Research Group. Nebulized budesonide for the treatment of moderate to severe asthma in infants and toddlers * Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. Measures of systemic activity of inhaled glucocorticosteroids in children: a comparison of urine cortisol excretion and knemometry. High-dose inhaled budesonide in treatment of severe steroid-dependent asthma. Dosage and time effects of inhaled budesonide on bronchial hyperreactivity. Comparison of high and low dose of the inhaled steroid, budesonide, as an initial treatment in newly detected asthma. The insulin–like growth factor axis and collagen turnover in asthmatic children treated with inhaled budesonide Effects of budesonide by means of the Turbuhaler on the hypothalmic-pituitary-adrenal axis in asthmatic subjects: a dose-response study. Systemic effects of inhaled fluticasone propionate and budesonide in adult patients with asthma. Efficacy and safety of budesonide inhalation suspension (Pulmicort Respules) in young children with inhaled steroid-dependent, persistent asthma. Dose-proportional pharmacokinetics of budesonide inhaled via Turbuhaler. Dose-related efficacy of budesonide administered via a dry powder inhaler in the treatment of children with moderate to severe persistent asthma. Adrenal Function in Asthmatic Children Treated with Inhaled Budesonide The influence of orally deposited budesonide on the systemic availability of budesonide after inhalation from a Turbuhaler. Comparison of 3 different doses of budesonide and placebo on the early asthmatic response to inhaled allergen. Once-daily budesonide inhalation suspension for the treatment of persistent asthma in infants and young children. Comparison of the antiasthmatic, oropharyngeal, and systemic glucocorticoid effects of budesonide administered through a pressurized aerosol plus spacer or the Turbuhaler dry powder inhaler. Eosinophil and neutrophil activity in asthma in a one-year trial with inhaled budesonide. The impact of smoking. Budesonide delivered by Turbuhaler is effective in a dose-dependent fashion when used in the treatment of adult patients with chronic asthma.
OBJECTIVE To determine the ability of budesonide via an inhaler ( Pulmicort Turbuhaler ; Astra Draco AB ) to replace oral glucocorticosteroids ( GCSs ) in adult subjects with moderate-to-severe asthma . DESIGN Double-blind , r and omized , and placebo-controlled study , with parallel groups . SETTING Multicenter study in outpatient setting . PARTICIPANTS Eighty men and 79 women , aged 20 to 69 years , with moderate-to-severe asthma and a mean FEV1 of 58.3 % predicted normal . All subjects were receiving oral GCS treatment and 79 % of subjects were also receiving inhaled beclomethasone dipropionate ( BDP ) . The mean daily doses of prednisone at baseline , including converted dose of BDP , for the placebo , budesonide 400 microg , and budesonide 800 microg , respectively , were 19.7 mg , 19.5 mg , and 18.7 mg . MEASUREMENTS AND INTERVENTIONS After a 2-week baseline period , subjects entered a 20-week treatment period , during which the oral dose of prednisone was reduced by forced down-titration at 2-weekly intervals . RESULTS Subjects receiving 400 microg or 800 microg bid of budesonide achieved a significantly greater reduction ( 82.9 % and 79.0 % respectively ) in oral GCS dose compared with placebo-treated subjects ( 27 % ; p<0.001 ) . Two thirds of the subjects receiving budesonide were able to achieve sustained oral corticosteroid cessation , compared with 8 % in the placebo group . Additionally , both doses of budesonide result ed in significant improvement in results of pulmonary function tests and asthma symptoms scores , and a significant decrease in the use of bronchodilator therapy . The mean plasma cortisol levels before and after adrenocorticotropic hormone stimulation increased most toward the normal range in the budesonide-treated groups compared with placebo-treated subjects . CONCLUSION Budesonide administered via Turbuhaler has a significant oral GCS-sparing capacity with maintained or improved asthma control in adult subjects with moderate-to-severe asthma Two hundred and forty-one children with perennial asthma had their normal dose of budesonide ( administered via Nebuhaler ) reduced by 50 % . Asthma control deteriorated in 126 patients to such an extent that budesonide had to be increased to the normal dose . During a subsequent two week run-in these 126 patients were treated with their normal dose of budesonide via Nebuhaler . Thereafter 64 were r and omized to treatment with their normal budesonide therapy and 62 to treatment with half their normal budesonide dose via Turbuhaler for nine weeks . Asthma symptoms , peak-flow measurements , and beta 2-agonist use were recorded . Pulmonary function tests , exercise tests and 24 hour urine sample collection s were performed . There were no differences between the groups in any of the parameters studied during run-in or during the study period , except for use of beta 2-agonist , which was significantly lower in the Turbuhaler-treated group . We conclude that Turbuhaler is more effective than Nebuhaler in the treatment of asthma . Therefore the dose of budesonide should be reduced when patients are switched from Nebuhaler to Turbuhaler treatment BACKGROUND Optimal management of chronic , mild-to-moderate asthma with inhaled  steroids may include use of the lowest possible doses , as recommended in guidelines , and a reduction in the frequency of daily administration for greater convenience . Lower doses and once daily treatment with inhaled steroids must be rigorously evaluated in controlled clinical trials . OBJECTIVES The objective of this study was to assess the efficacy and safety of once daily treatment with budesonide in subjects with stable asthma . METHODS Once daily budesonide was assessed in 309 adult subjects , including those who were and were not using an inhaled steroid at baseline . The subjects were stratified by inhaled steroid use and r and omly assigned to one of 3 treatments : 200 microgram budesonide , 400 microgram budesonide , or placebo administered by means of Turbuhaler once daily in the morning for 6 weeks . Beyond this point , treatment was continued unchanged for another 12 weeks ( maintenance ) in those receiving 200 microgram budesonide once daily and placebo . In those who received 400 microgram budesonide once daily , the dose was reduced to 200 microgram once daily at week 6 and held constant for the remaining 12 weeks ( 400/200 microgram group ) . Primary efficacy endpoints were mean change from baseline in FEV1 and morning peak expiratory flow . RESULTS Once daily budesonide was well tolerated and result ed in significant improvements in all efficacy endpoints , even though baselines were well stabilized . Baseline lung function was elevated with little room for improvement ; however , mean increases in FEV1 during the maintenance period were 0.10 L and 0.11 L in the 200 microgram and 400/200 microgram groups , respectively , versus a decrease of -0.09 L in the placebo arm ( P < .001 ) . Results for peak expiratory flow were similar . Significant improvements in secondary endpoints , including symptoms , beta-agonist use , and quality of life , also developed with budesonide 200 and 400 microgram once daily . CONCLUSION Inhaled budesonide , in doses as low as 200 microgram , may be an appropriate introductory or maintenance dose in subjects with stable , mild-to-moderate asthma Two hundred and forty one children with chronic perennial asthma , who had been treated with budesonide via a metered dose inhaler with a spacer device ( Nebuhaler )  , had their normal dose of budesonide reduced by 50 % to determine if they had been overtreated . Within three weeks , asthma control deteriorated in 126 patients to such an extent that budesonide had to be increased to the normal dose . After stabilising their asthma , these children were enrolled in a r and omised , double blind , double dummy , parallel study , performed to compare the effect of budesonide via Nebuhaler with that of half the dose of budesonide via Turbuhaler . The study started with a two week run-in during which patients were treated with their normal dose of budesonide via Nebuhaler . After run-in , 64 children were r and omised to treatment with their normal budesonide treatment and the remaining 62 children to treatment with half their normal dose via Turbuhaler for nine weeks . Throughout the study , patients recorded asthma symptoms , peak flow measurements , and beta 2 agonist use in a diary . Pulmonary function tests , exercise tests , and 24 hour urine sample collection s were performed at hospital visits during run-in and the study period . Apart from beta 2 agonist use , which was significantly lower for patients on Turbuhaler treatment than on Nebuhaler treatment , there were no differences between the groups in any of the parameters studied during run-in or during the study period . Furthermore , there was no trend of deterioration in asthma control when the dose of budesonide was reduced by 50 % when Turbuhaler was the inhalation device . It is concluded that budesonide via Turbuhaler is more effective than via Nebuhaler in the treatment of asthma . Based on this finding , attempts should be made to reduce the dose of budesonide when patients are switched from Nebuhaler to Turbuhaler treatment The budesonide dose delivered to the patient from three different spacer devices ( Nebuhaler = 750 ml , Aerochamber = 140 ml , and Babyspacer = 260 ml ) was assessed by measuring the budesonide dose deposited on a filter inserted between the spacer outlet and the mouth of the patient . Twenty children aged 10 - 25 months were given a single dose of 200 micrograms budesonide from each spacer device in a r and omised crossover study . All spacers had a facemask attached and a one way valve system . The children breathed through the inhalation system for 30 seconds . Furthermore , the minute ventilation of the children through a tightly fitting facemask was measured . The filter dose of budesonide  was significantly lower after Aerochamber treatment ( 39.4 micrograms , range 19 - 67 micrograms ) than after Nebuhaler ( 53.5 micrograms , range 34 - 88 micrograms ) and Babyspacer ( 55.5 micrograms , range 39 - 76 micrograms ) treatment . The minute ventilation of the children varied from 1.4 l/min to 7.0 l/min ( mean 5.0 l/min ) . This was sufficient to empty all spacers within the 30 seconds of inhalation . It is concluded that spacer volume does not seem to be so important for children aged 10 - 25 months as long as spacers with a volume lower than 750 ml are used BACKGROUND It is desirable to prescribe the minimal effective dose of inhaled steroids to control asthma . To ensure that inflammation is suppressed whilst using the lowest possible dose , a sensitive and specific method for assessing airway inflammation is needed . METHODS The usefulness of exhaled nitric oxide ( NO ) , sputum eosinophils , and methacholine airway responsiveness ( PC20 ) for monitoring airway inflammatory changes following four weeks of treatment with an inhaled corticosteroid ( budesonide via Turbohaler ) were compared . Mild stable steroid naive asthmatic subjects were r and omised into two double blind , placebo controlled studies . The first was a parallel group study involving three groups receiving either 100 μg/day budesonide ( n = 8) , 400 μg/day budesonide ( n = 7 ) , or a matched placebo ( n = 6 ) . The second was a crossover study involving 10 subjects r and omised to receive 1600 μg budesonide or placebo . The groups were matched with respect to age , PC20 , baseline FEV1 ( % predicted ) , exhaled NO , and sputum eosinophilia . RESULTS There were significant improvements in FEV1 following 400 μg and 1600 μg budesonide ( 11.3 % and 6.5 % , respectively , p<0.05 ) . This was accompanied by significant reductions in eosinophil numbers in induced sputum ( 0.7 and 0.9 fold , p<0.05 ) . However , levels of exhaled NO were reduced following each budesonide dose while PC20was improved only with 1600 μg budesonide . These results suggest that exhaled NO and PC20 may not reflect the control of airway inflammation as accurately as the number of eosinophils in sputum . There were dose dependent changes in exhaled NO , sputum eosinophils , and PC20 to inhaled budesonide but a plateau response of exhaled NO was found at a dose of 400 μg daily . CONCLUSION Monitoring the number of eosinophils in induced sputum may be the most accurate guide to establish the minimum dose of inhaled steroids needed to control inflammation . This , however , requires further studies involving a larger number of patients The aim of the present study was to examine the efficacy of low-dose inhaled budesonide ( BUD ) administered via Turbuhaler once or twice daily on symptoms , lung function and bronchial hyperreactivity in children with mild asthma . One hundred and sixty-three children ( mean age 9.9 yrs , 56 females/107 males ) with mild asthma ( forced expiratory volume in one second ( FEV1 ) 103 % of predicted , morning peak expiratory flow ( PEF ) 87 % pred , reversibility in FEV1 3 % , fall in FEV1 after exercise 10.4 % from pre-exercise value ) and not previously treated with inhaled steroids , were included in a double-blind , r and omized , parallel-group study . After a two-week run-in period , the children received inhaled BUD 100 microg or 200 microg once daily in the morning , 100 microg twice daily or placebo for 12 weeks . Exercise and methacholine challenges were performed before and at the end of treatment . After 12 weeks of therapy , the fall in FEV1 after an exercise test was significantly less in all three BUD groups ( 43 - 5.1 % ) than in the placebo group ( 8.6 % ) . Bronchial hyperreactivity to methacholine with the provocative dose causing a 20 % fall in FEV1 decreased significantly in the BUD 100 microg twice-daily group compared with placebo ( ratio at the end of treatment 156 % ) . Changes in baseline lung function ( FEV1 and PEF ) were less marked than changes in bronchial responsiveness . In conclusion , low doses of inhaled budesonide , given once or twice daily , provided protection against exercise-induced bronchoconstriction in children with mild asthma and near normal lung function New British guidelines on the treatment of asthma ( 9 ) advocate starting with a higher dose of inhaled corticosteroids in newly detected asthma patients . We investigated whether initiating inhaled steroid treatment with a higher dose is clinical ly more effective than a lower dose in steroid naive patients with asthma . The study had a 13-wk r and omized , double-blind , parallel design : 1-mo treatment with 400 microg budesonide twice a day , or 100 microg budesonide twice a day by dry powder inhaler , and follow-up treatment period of 2 mo with 200 microg budesonide once daily for all patients . Forty patients started with 400 microg budesonide twice daily , 44 with 100 microg budesonide twice daily . Mean age was 32 yr , baseline FEV1 value 84 % predicted , reversibility 9 % from baseline , and mean bronchodilator use 1.6 inhalations/d in the run-in period . After 4 wk of treatment with 400 microg and 100 microg budesonide twice daily mean morning peak expiratory flow ( PEF ) increased 27 L/min ( SD 50 ) , and 38 L/ min ( SD 53 ) , respectively ( p = 0.30 ) ; mean symptom score improved from 1.1 to 0.6 and from 1.1 to 0.5 . These effects were maintained in the 2 mo follow-up . This study suggests that starting inhaled corticosteroids at a higher dose is not superior to a lower dose in the treatment of newly detected asthma The study objective was to compare the effect of budesonide administered as a nebulized suspension as compared to a spray with a spacer in adult asthmatics . In a double-blind , double-dummy crossover study , 26 adult patients with moderately severe unstable asthma were r and omized to three 4-week treatment periods with budesonide 0.8 mg b.i.d . administered by a pressurized metered-dose inhaler ( pMDI ) with spacer ( Nebuhaler ) and budesonide 1 mg and 4 mg b.i.d . administered by a Pari Inhalier Boy jet nebulizer . The nebulizer was activated only during inspiration . The total mass output was similar from the two devices but their fraction of small particles differed by a factor of 2 in favour of pMDI . Effect was evaluated from daily home measurements of peak expiratory flow ( PEF ) , need of beta 2-agonist and symptom scores . Plasma cortisol and budesonide levels were measured in a subgroup of 10 patients . A consistent trend showed the nebulizer treatment to be at least as efficient as the pMDI plus spacer treatment . In actual fact , the apparent order of effect was : 4 mg nebulized suspension treatment > or = 1 mg nebulized suspension treatment > or = 0.8 mg pMDI with spacer treatment . Plasma budesonide and plasma cortisol also exhibited dose-related levels independent of device . The adverse effects reported appeared to be related to the dose rather than delivery device . Accordingly , the effect was related to total mass output , rather than to the small particle fraction of the budesonide aerosol . These results attest to the efficiency of jet-nebulized budesonide suspension , and indicate nebulized budesonide to be equipotent to st and ard budesonide therapy delivered by pMDI with Nebuhaler , provided nebulization is synchronized with inspiration and no loss of aerosol occurs during expiration Budesonide by inhalation and placebo were tested in 18 patients with moderate chronic bronchial asthma . Three dose levels of budesonide were used ( 25 , 100 and 400 μg q.i.d . ) and the patients were to take two puffs q.i.d . in all periods . The active treatment was investigated using double‐blind cross‐over technique , and placebo at the end of the trial . The duration of each treatment period was 2 weeks . The study showed a high drop‐out frequency while on placebo and that the PEF values were influenced in a dose‐dependent way by budesonide . In spite of the double‐blindness the patients had a tendency towards overuse of the trial aerosol on the lowest dose , but they used significantly less than prescribed during the period with the highest dose . No side effects were reported Budesonide 400 micrograms daily , in nonsteroid-dependent asthma , can produce improvements in airway responsiveness and clinical asthma severity , with some patients returning to normal responsiveness and becoming asymptomatic . This study examined whether similar improvements occur when asthmatics , who are dependent upon inhaled steroids , take either a regular maintenance dose of inhaled steroid or twice that amount for a year . Thirty two asthmatics were each stabilized on the minimum amount of inhaled steroid that would keep symptoms non-troublesome . In a double-blind , r and omized manner , half were assigned to remain on a maintenance dose ( MD ) and the rest received twice that dose ( MDx2 ) for one year . Before and monthly throughout the study , airway responsiveness to methacholine was measured and clinical asthma severity assessed by question naire , inhaled bronchodilator use and number of asthma exacerbations . There was a significant improvement in airway responsiveness and clinical asthma severity in both treatment groups . Those on MDx2 showed the greatest improvement but the difference between the two groups did not reach significance . This study provides strong evidence that prolonged use of inhaled steroids is associated with improvement in airway responsiveness and clinical asthma severity in inhaled steroid-dependent asthma with a suggestion that the improvements are dose related OBJECTIVES We wished to evaluate the effects of once-daily combination therapy on surrogate inflammatory markers . METHODS Fifteen patients with atopic persistent asthma were evaluated ( mean age , 32.4 years ; FEV(1 ) , 75.2 % predicted ) in a r and omized , double-blind , double-dummy , placebo-controlled crossover study with a 1-week placebo washout period , comparing the following once-daily nighttime treatments : ( 1 ) formoterol ( FM ) , 12 microg , for 2 weeks and FM , 24 microg , for 2 weeks ; or ( 2 ) budesonide ( BUD ) , 400 microg , for 2 weeks and BUD , 800 microg , for 2 weeks ; or ( 3 ) FM , 12 microg , plus BUD , 400 microg , for 2 weeks and FM , 24 microg , plus BUD , 800 microg , for 2 weeks . Adenosine monophosphate ( AMP ) bronchial challenge , exhaled nitric oxide ( NO ) , and serum eosinophilic cationic protein ( ECP ) were evaluated at 12 h postdosing after administration of each placebo and after 2 and 4 weeks of each treatment . RESULTS The results of AMP challenge ( provocative concentration causing a 20 % fall in FEV(1 ) ) at 4 weeks showed significant ( p<0.05 ) improvements after patients had received all active treatments compared to placebo ( 20 mg/mL ) , with FM plus BUD , 261 mg/mL , being superior ( p<0.05 ) to FM alone , 82 mg/mL , but not to BUD , 201 mg/mL. NO and ECP showed significant ( p<0.05 ) reductions compared to placebo with FM plus BUD or BUD alone but not with FM alone . Combination therapy was associated with optimal patient preference ( rank order , FM plus BUD > FM > BUD ; p<0.0005 ) , highest domiciliary peak expiratory flow , and lowest rescue inhaler usage . All three treatments produced equivalent improvements in spirometry . CONCLUSIONS Patients preferred once-daily combination therapy , but this had no greater effect on inflammatory markers than therapy with BUD alone . FM alone had no anti-inflammatory activity but exhibited bronchoprotection . This emphasizes the importance of first optimizing anti-inflammatory control with inhaled corticosteroids before considering adding a regular long-acting beta(2)-agonist Linear growth was investigated with weekly knemometry in a population of 43 schoolchildren with mild asthma treated with inhaled budesonide .  The design was a r and omized , double-blind , parallel group study with three dose groups of 200 , 400 , and 800 micrograms of budesonide per day . Each dose group received budesonide for 8 consecutive weeks . Placebo was given for either 4 weeks before or after budesonide treatment . Twelve children in the 200-micrograms group , 14 in the 400-micrograms group , and 12 in the 800-micrograms group completed the 12-week study period . There was no significant difference in mean growth velocity among the three dose groups during placebo treatment . Compared with placebo ( growth velocity : 0.39 mm/wk ) , mean lower leg growth velocity was reduced with 0.26 mm/wk ( P less than .001 , t = 5.0 , df = 11 ; 95 % confidence interval 0.14 to 0.37 mm/wk ) in children treated with 800 micrograms of budesonide . There was no statistically significant difference in growth velocity between 200- or 400-micrograms budesonide treatments and placebo . These data indicate that inhaled budesonide can be safely used in doses up to 400 micrograms/d in schoolchildren with asthma BACKGROUND Twice-daily administration of inhaled budesonide ( 400 micrograms ) suppresses short-term growth in children with asthma . OBJECTIVE To compare short-term growth and markers of collagen turnover during treatment with 800 micrograms of inhaled budesonide administered once daily in the morning and 400 micrograms administered twice daily . PATIENTS Twenty-four children with asthma aged 5.6 to 12.5 years . SETTING An outpatient secondary referral center . METHODS A r and omized , double-blind , crossover trial with 2 treatment periods of 4 weeks was conducted , and growth was assessed with a knemometer . The carboxy terminal propeptide of type I procollagen , the amino terminal propeptide of type I procollagen ( PINP ) , the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen , the amino terminal propeptide of type III procollagen ( PIIINP ) , and urinary pyridinoline and deoxypyridinoline were evaluated . RESULTS Mean lower leg growth rate ( P = .04 ) , PINP ( P = .03 ) , and PIIINP ( P < .01 ) were suppressed during twice-daily administration of budesonide , 400 micrograms . Otherwise , no statistically significant differences were detected . CONCLUSIONS As compared with 400 micrograms of inhaled budesonide administered twice daily , 800 micrograms administered once daily in the morning has a sparing effect on short-term growth and collagen turnover 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 Electrostatic charge in plastic spacer devices has been shown in vitro to reduce delivery of asthma medications intended for inhalation , but the effect of static charge on in vivo drug deposition is unknown . A six-way r and omized crossover study was conducted in 10 mild asthmatic patients .  Two plastic spacers ( Nebuhaler and Volumatic ) and one metal spacer ( Nebuchamber ) were tested . The spacers were used either " primed " or " unprimed " . Priming was performed by firing 20 doses of placebo aerosol into a new spacer , hence coating the inner surface with surfactant and minimizing static charge . Unprimed spacers were new and were not treated . Pressurized aerosol canisters delivering budesonide ( 200 microg Pulmicort ) were radiolabelled with the radionuclide 99mTc and lung deposition was measured by gamma scintigraphy . The radiolabel was shown to be a valid marker for the drug substance prior to the clinical phase of the study . Priming significantly increased mean whole lung deposition following inhalation from plastic spacers ( Nebuhaler primed 37.7 % and unprimed 26.7 % , p=0.01 ; Volumatic primed 32.0 % and unprimed 22.1 % , p=0.02 ) . Priming had no effect on the mean whole lung deposition following inhalation from the Nebuchamber ( primed 33.5 % and unprimed 32.9 % ) . Lung deposition in vivo from plastic spacer devices will vary according to the electrostatic charge on the spacer walls . Priming reduces retention of drug on plastic spacer devices and increases lung deposition .  Metal spacers are not susceptible to static charge , which should result in more predictable lung deposition Few thorough comparisons of the systemic effects of inhaled corticosteroids in children are available . The aim of this study was to compare the effect of budesonide and fluticasone propionate on short-term lower leg growth .  Fluticasone propionate , budesonide and placebo were administered for 2 weeks in a r and omized , double-blind , double-dummy , cross-over design . Twenty four children aged 6 - 12 yrs received 200 microg x day(-1 ) of each drug , or placebo .  Another 24 children aged 6 - 12 years received 400 microg x day(-1 ) of each drug , or placebo . Dry powder inhalers were used . Lower leg length was measured by knemometry twice a week during all three treatment periods , and 24 h cortisol excretion in the urine was measured at the end of each period . In the low-dose group , lower leg growth rate was the same during treatment with placebo ( 0.35 mm x week(-1 ) ) , fluticasone propionate ( 0.38 mm x week(-1 ) ) or budesonide ( 0.26 mm x week(-1 ) ) . No significant difference ( p=0.39 ) in lower leg growth rate was found between treatment with 400 microg x day(-1 ) budesonide ( 0.30 mm x week(-1 ) ) and 400 microg fluticasone propionate treatment ( 0.37 mm x week(-1 ) ) . Growth rate during treatment with budesonide , 400 microg x day(-1 ) , was significantly lower than during placebo treatment ( 0.52 mm x week(-1 ) ) . Cortisol excretion in the urine during treatment with 200 microg x day(-1 ) fluticasone propionate was significantly reduced as compared with placebo ( p=0.006 ) , but not when compared with 200 microg x day(-1 ) budesonide ( p=0.07 ) . Budesonide 200 microg x day(-1 ) was not significantly different from placebo . Fluticasone propionate and budesonide , both at 400 microg x day(-1 ) , result ed in a significant reduction in cortisol excretion in the urine as compared with placebo ( p=0.001 ) . It is concluded that , dose-for-dose , budesonide Turbuhaler and fluticasone propionate Diskhaler have similar systemic effects The aim of this study was to determine whether outcomes in poorly controlled asthma can be further improved with a starting dose of inhaled budesonide higher than that recommended in international guidelines . The study had a parallel-group design and included 61 subjects with poorly controlled asthma , r and omized to receive 3,200 microg or 1,600 microg budesonide daily by Turbuhaler for 8 weeks ( double-blind ) , then 1,600 microg x day(-1 ) for 8 weeks ( single-blind ) , followed by 14 months of open-label budesonide dose down-titration using a novel algorithm , with a written asthma crisis plan based on electronic peak expiratory flow monitoring . The primary outcome variable for weeks 1 - 16 was change in airway hyperresponsiveness ( AHR ) , and , for the open-label phase , mean daily budesonide dose . By week 16 , there were large changes from baseline in all outcomes , with no significant differences between the 3,200- and 1,600-microg x day(-1 ) starting dose groups ( AHR increased by 3.2 versus 3.0 doubling doses , p=0.7 ; morning peak flow increased by 134 versus 127 L x min(-1 ) , p=0.8 ) . Subjects starting with 3,200 microg x day(-1 ) were 3.8 times more likely to achieve AHR within the normal range , as defined by a provocative dose of histamine causing a 20 % fall in forced expiratory volume in one second ( PD20 ) of > or = 3.92 micromol by week 16 ( p=0.03 ) [ corrected ] . During dose titration , there was no significant difference in mean budesonide dose ( 1,327 versus 1,325 microg x day(-1 ) , p>0.3 ) . Optimal asthma control was achieved in the majority of subjects ( at completion/withdrawal : median symptoms 0.0 days x week(-1 ) , beta2-agonist use 0.2 occasions x day(-1 ) , and PD20 2.4 micromol ) . In subjects with poorly controlled asthma , a starting dose of 1,600 microg x day(-1 ) budesonide was sufficient to lead to optimal control in most subjects . The high degree of control achieved , compared with previous studies , warrants further investigation The aim of this study was to compare the clinical efficacy of low-dose inhaled budesonide ( once or twice daily ) and placebo , administered via Turbuhaler , on exercise-induced bronchoconstriction ( EIB ) in children with mild asthma . Fifty-seven steroid-naive children ( 7 - 16 years old ; 41 boys , 16 girls ) with EIB participated in this sub- population study according to the following inclusion criterion : a maximum fall in forced expiratory volume in 1 s ( FEV1 ) > or = 10 % after a st and ardized treadmill test . Mean baseline FEV1 was 100.3 % of predicted , and mean maximum fall in FEV1 after the st and ardized exercise test was 22 % . The study was a double-blind , r and omized , parallel-group design . After 2 weeks of run-in , the children received inhaled budesonide 100 microg or 200 microg once daily in the morning , 100 microg twice daily , or placebo , for 12 weeks . After 12 weeks of treatment , the fall in FEV1 after the exercise test was significantly less in all three budesonide groups ( 7.2 - 7.8 % ) vs. placebo ( 16.7 % ) . Daytime symptom scores were significantly lower in all three budesonide groups compared with placebo ( p < 0.02 ) . The three budesonide groups did not differ significantly , and no significant change in lung function was found in any group . Therefore children with mild asthma , but with significant EIB , improved their exercise tolerance and symptom control after 3 months of treatment with a low dose of inhaled budesonide given once or twice daily An open , r and omized , parallel-group study was conducted to investigate whether asthmatic patients , considered adequately treated with a corticosteroid and /or short-acting beta 2-agonist via pressurized metered-dose inhaler ( pMDI ) , could be transferred to a corresponding nominal dose of budesonide and /or terbutaline via Turbuhaler , an inspiratory flow-driven multidose dry powder inhaler ( Astra Draco ; Lund , Sweden ) , without a decrease in the effect of treatment . One thous and four patients ( 555 women ; mean age , 44 years ; mean peak expiratory flow [ PEF ] , 102 % predicted normal value ) were r and omized and treated with either pMDI ( current therapy ) or Turbuhaler for 52 weeks . The variables studied were asthma-related events , morning PEF , and inhaler-induced clinical symptoms . Asthma-related events were defined in two ways : ( 1 ) sum of health-care contacts plus doublings or additions of steroids , and ( 2 ) number of 2 consecutive days with PEF less than 80 % of baseline . Baseline was obtained from a 2-week run-in period while receiving previous therapy . No statistically significant difference was found in asthma-related events according to definition 1 . According to definition 2 , there was a statistically significant difference between the groups in favor of Turbuhaler ( p = 0.008 ) . The mean number of events was 1.7 with Turbuhaler and 2.2 with pMDI . The mean number of weeks per patient with a PEF less than 90 % of baseline was 4.5 with Turbuhaler compared with 6.0 with pMDI ( p = 0.002 ) . The sum of inhaler-induced symptoms after 1 year of use was statistically significantly lower with Turbuhaler ( 0.40 ) than with pMDI ( 0.75 ) ( p = 0.0001 ) . In conclusion , budesonide and terbutaline in Turbuhaler offered a superior alternative to corticosteroids and bronchodilators delivered by pMDIs in the maintenance treatment of asthma BACKGROUND The incidence of pediatric asthma has increased dramatically over the past few decades , with approximately 5 % of American children affected by the disease . OBJECTIVES To compare the efficacy and safety of once-daily budesonide Turbuhaler with placebo in asthmatic children previously treated with orally inhaled corticosteroids . METHODS This r and omized , double-blind , placebo-controlled , multicenter ( 17 centers ) study included 274 male and female children ( aged 6 to 17 years ) with a history of asthma for at least the previous 6 months . Patients received placebo or budesonide Turbuhaler ( 200 microg or 400 microg ) once daily for 12 weeks . Efficacy variables included mean changes from baseline in forced expiratory volume in 1 second ( FEV1 ) , AM and PM peak expiratory flow rates ( PEFRs ) , nighttime and daytime asthma symptom severity scores , patient discontinuations , use of beta2-agonists as breakthrough medication , forced vital capacity ( FVC ) , and midexpiratory flow rate between 25 % and 75 % of FVC ( FEF25%-75 % ) . Safety was evaluated by adverse events , physical examinations , vital signs , and laboratory tests . RESULTS Baseline characteristics were comparable among treatment groups . Percentage of predicted FEV1 at baseline was 76.6 + /- 6.9 for placebo , 77.5 + /- 7.1 , and 77.0 + /- 7.8 for the budesonide Turbuhaler 200 microg and 400 microg groups , respectively . Significantly ( P < or = 0.024 ) more placebo patients ( 24 % ) discontinued treatment because of disease deterioration or no improvement than budesonide Turbuhaler 200 microg ( 11 % ) or 400 microg patients ( 10 % ) . Patients receiving budesonide Turbuhaler experienced significant improvements in FEV1 compared with patients receiving placebo ( P < or = 0.015 ) . Significant ( P < or = 0.041 ) improvements over placebo also were observed in AM and PM PEFRs , FVC , FEF25%-75 % , nighttime and daytime asthma symptoms , and amount of beta2-agonist used in both budesonide Turbuhaler groups . Adverse events were generally mild or moderate in intensity and similar among treatment groups . CONCLUSIONS Once-daily budesonide Turbuhaler is effective and safe in children with persistent asthma previously maintained on at least twice-daily dosing regimens of inhaled corticosteroids 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 , r and omized , cross-over , dose titration study . After a 1-week run-in , patients were r and omized 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 Pari 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 This double-blind study aim ed to determine whether superior asthma control is achieved with budesonide ( Pulmicort Turbohaler ) at a loading dose ( LD ) ( 400 micrograms b.d . ) for 6 weeks , followed by step down to 400 micrograms nocte for 12 weeks , compared with a static dose ( SD ) ( 400 micrograms nocte ) for 18 weeks . A total of 682 patients ( mean peak expiratory flow rate ( PEFR ) 413 l/min ) , who demonstrated > or = 15 % reversibility in PEFR , were r and omised into the study . After 18 weeks , patients experienced improvements in morning PEFR ( + 45 l/min , both groups ) , symptom score ( LD -0.57 , SD -0.49 , on a scale of 0 - 3 ) , sleep disturbance ( LD -1.21 nights/week , SD -1.06 nights/week ) and beta 2-agonist use ( LD -1.36 puffs/day , SD -1.06 puffs/day ) , within both groups ( each p = 0.0001 ) . At 18 weeks , 82 % ( LD ) and 84 % ( SD ) of patients benefited from no nocturnal wakening in the previous 7 days . Overall , at 18 weeks , asthma control was not significantly different between the groups . After 6 weeks , improvements in morning PEFR ( LD + 36 l/min , SD + 26 l/min ) and beta 2-agonist use ( LD -1.10 puffs/day , SD -0.94 puffs/day ) were greater in the loading dose than in the static dose group ( each p < 0.05 ) . The greater improvement in morning PEFR in the loading dose group was significant by day 7 ( p < 0.05 ) . While both regimens are equally effective in achieving asthma control at 18 weeks , early clinical advantage is gained with initial loading dose budesonide ( 400 micrograms b.d . ) The aim of this open , r and omized cross‐over study was to compare the efficacy and safety of inhaled budesonide administered either via a pressurised metered dose inhaler with a 750 ml spacer attached , or via a new dry powder inhaler , Turbuhaler ® , in 28 patients with stable bronchial asthma . During the 2‐week run‐in period , the patients received their ordinary inhaled steroid treatment . This was followed by two 4–week periods of active treatment with inhaled budesonide given via Turbuhaler or pressurized MDI . The patients were divided into two groups according to their previous , inhaled steroid doses . Group A received 400 μg of budesonide b.i.d , and Group B 800 μg of budesonide b.i.d . Diary cards were used by the patients at home to report asthma symptoms , ( 32‐agonist consumption , and PEF twice daily , as well as the number of coughs experienced in a 5‐min period after steroid inhalation . Budesonide Turbuhaler produced a significantly better effect on morning peak flow than budesonide MDI  . The number of coughs in the 5 min after steroid inhalation was significantly lower with the Turbuhaler than with the MDI . In all other parameters recorded ( e.g. FEV1 , evening PEF , histamine PC20 and other diary measurements ) there were no statistically significant differences between the two devices . Turbuhaler was significantly more appreciated than MDI in all questions of preference . The study showed that budesonide via Turbuhaler was at least as effective and safe as budesonide via a pressurized MDI at daily doses of 800 and 1,600 μg . The absence of additives , the lower incidence of cough after dose intake , the easiness of use , and higher preference , make Turbuhaler a valuable contribution in the treatment of asthmatics BACKGROUND Budesonide ( BUD ) has recently been licensed for treatment of asthma in the United States , whereas triamcinolone acetonide ( TAA ) has been used for many years . OBJECTIVE We sought to evaluate the dose-response effect of inhaled BUD and TAA in terms of adrenal , bone , and blood markers . METHODS Twelve asthmatic subjects ( mean age , 32 years ; mean FEV1 , 91 % of predicted value ) were studied in a r and omized design comparing 3 days of treatment with placebo and low ( 200 micrograms twice daily ) , medium ( 400 micrograms twice daily ) , and high ( 800 micrograms twice daily ) doses of BUD ( Pulmicort Turbuhaler , 100 micrograms ) and TAA ( Azmacort integrated actuator/spacer , 100 micrograms ) with a 7-day period at crossover , when patients received their usual inhaled corticosteroid therapy . Measurements were made at 8 am for serum cortisol , osteocalcin , and blood eosinophils . Measurements were also made for overnight urinary cortisol/creatinine excretion . RESULTS For all measurements there were no significant differences between the 2 treatments at any dose level . Ratios between BUD and TAA ( 95 % CI ) at the highest dose levels were as follows : 8 am serum cortisol , 1.08-fold ( 0.63 to 1 . 85 ) ; urinary cortisol , 1.09-fold ( 0.63 to 1.86 ) ; eosinophils , 0 . 98-fold ( 0.69 to 1.38 ) ; and osteocalcin 1.05-fold ( 0.78 to 1.41 ) . There was no evidence of a significant overall dose-response effect for any parameter of hypothalamo-pituitary-adrenocortical axis activity , with neither drug being significantly different from placebo at any dose . For the 3 dose levels of both drugs , total abnormal low values for 8 am serum cortisol ( ie , < 5.4 micrograms/dL [ < 150 nmol/L ] ) showed 2 of 36 for BUD and 2 of 36 for TAA . There was also no significant overall dose-response effect for eosinophils or osteocalcin , although both drugs were significantly ( P < .05 ) different from placebo at the highest dose : eosinophils ( x10(9)/L ) , placebo : 0.36 , TAA : 0.24 , and BUD : 0.23 ; and osteocalcin ( nmol/L ) , placebo : 1.04 , TAA : 0.73 , and BUD : 0.77 . CONCLUSION There were no significant differences in the systemic bioactivity profiles , in terms of adrenal , blood , and bone markers , between  BUD administered by means of Turbuhaler and TAA administered by means of an integrated actuator/spacer in a dose range of 400 micrograms to 1600 micrograms/day . Both drugs exhibited a significant degree of detectable systemic bioactivity but only at the highest dose of 1600 micrograms/day for effects on eosinophil count and osteocalcin Twenty-four patients with severe steroid-dependent asthma participated in a double-blind cross-over study performed in two centers . After a run-in period of 2 weeks when beclomethasone dipropionate ( BDP ) ( 400 micrograms/day ) was used , the patients were treated for 4 weeks with either a high-dose ( 1600 micrograms/day ) or a low-dose ( 400 micrograms/day ) of budesonide ( Pulmicort ) . Thereafter the doses of budesonide were switched and the treatment continued for a further 4-week period . Patients treated with high-dose budesonide displayed significant improvements in airway functions . In addition , subjective scores for cough , sputum production and dyspnoea were more improved in the high-dose group than in the low-dose group . The need for concomitant beta 2-agonist therapy was also significantly reduced during the high-dose treatment . No significant changes in plasma cortisol levels were detected and no adverse effects of importance were registered . The results indicate that high-dose budesonide treatment improves the clinical status of patients with severe steroid-dependent asthma more than a low-dose therapy but without causing systemic side-effects In recent years , measurement of serum osteocalcin has been introduced for assessment of bone turnover in patients treated with exogenous glucocorticoids .  Studies in children with asthma on inhaled  glucocorticoids , however , have shown inconsistent results . The aim of the present study is to assess bone turnover in prepubertal children and in adolescents with asthma treated with inhaled budesonide  using three different osteocalcin assays : the Pharmacia Osteocalcin CAP FEIA , the CIS OSTK-PR and CIS IRMA ELSA-OSTEO assays . Two studies were conducted : 1 ) a r and omised double blind two-period crossover study of 22 prepubertal children aged 5 - 12 years . In one period 800 microg budesonide was given once in the morning , in the other 400 microg was given twice daily ; 2 ) a r and omised double blind placebo controlled two period crossover study of inhaled budesonide 400 microg twice daily in fourteen 13 - 16 year old adolescents with pubertal stages II-V. In both studies , treatment periods were of four weeks duration , and blood sample s were collected at the last day of each period . In the prepubertal children none of the osteocalcin assays detected any statistically significant differences between any of the periods . In the adolescent group reduced levels of osteocalcin were seen during budesonide treatment . The suppression reached statistical significance with the CAP FEIA ( P = 0.03 ) and the OSTK-PR ( P = 0.01 ) assays , but not with the ELSA-OSTEO assay ( P = 0.06 ) . Correlation analyses showed statistically significant correlation coefficients varying between 0.58 and 0.91 ( P = 0.03 and P < 0.0001 , respectively ) . The effect of inhaled glucocorticoids on serum osteocalcin may depend on the assay applied , and inhaled glucocorticoids have differential effects in children and adolescents OBJECTIVE --To determine whether the inhaled glucocorticosteroid budesonide has any adverse effect on short term linear growth in children with mild asthma . SETTING --Outpatient clinic in secondary referral centre . PATIENTS --15 children aged 6 - 13 years with normal statural growth velocity during the previous year , no signs of puberty , and no use of systemic or topical steroids in the two months before the study . DESIGN OF INTERVENTIONS --Double blind , r and omised crossover trial with two active periods in which budesonide was given in divided daily doses of 200 micrograms and 800 micrograms . During run in and two washout periods placebo was given . After the second washout period the children received open treatment with 400 micrograms budesonide daily . All periods were of 18 days ' duration . MAIN OUTCOME MEASURE -- Growth of the lower leg as measured twice a week by knemometry . RESULTS --Mean growth velocity of the lower leg was 0.63 mm/week during run in and during washout 0.64 mm/week . Budesonide treatment was associated with a significant dose related reduction of growth velocity : the mean reduction in growth velocity during treatment was 0.11 ( 95 % confidence interval -0.15 0.36 ( 0.13 to 0.59 ) mm/week with 800 micrograms budesonide ( p less than 0.05 ; Page 's test ) . During treatment with 400 micrograms budesonide a reduction of 0.17 ( -0.10 to 0.45 ) mm/week was found . CONCLUSIONS --Treatment with inhaled budesonide is associated with a dose related suppression of short term linear growth in children with mild asthma Inhaled corticosteroids have become the mainstay treatment of bronchial asthma . However , simultaneous evaluations of efficacy and side effects are few . This study aim ed to compare the relative effect of fluticasone propionate ( FP ) and budesonide ( BUD ) on bronchial responsiveness and endogenous cortisol secretion in adults with asthma . The study was double-blind and included 66 adults with asthma , who were r and omized to FP ( n = 33 ) or BUD ( n = 33 ) . Pre study , all participants were clinical ly stable , using inhaled corticosteroids and hyperresponsive to methacholine . Eligible patients were r and omized to three consecutive 2-wk periods with either FP 250 microg twice daily , FP 500 microg twice daily , and FP 1,000 microg twice daily , or BUD 400 microg twice daily , BUD 800 microg twice daily , and BUD 1,600 microg twice daily , delivered by Diskhaler and Turbuhaler , respectively . Before r and omization and at the end of each treatment , bronchial methacholine PD(20 ) , 24-h urinary cortisol excretion ( 24-h UC ) , plasma cortisol , serum osteocalcin , and blood eosinophils were determined . The relative PD(20 ) potency between FP and BUD was 2.51 ( 95 % CI , 1.05 - 5.99 ; p < 0 . 05 ) , while the relative 24-h UC potency was 0.60 ( 95 % CI , 0.44 - 0.83 ; p < 0.01 ) . The differential therapeutic ratio ( FP/BUD ) based on PD(20 ) potency and 24-h UC was 4.18 ( 95 % CI , 1.16 - 15.03 ; p < 0.05 ) . The difference in systemic potency was also seen for plasma cortisol , serum osteocalcin , and blood eosinophils . Therapeutic ratio over a wide dose range , determined by impact on bronchial responsiveness and endogenous corticosteroid production , seems to favor FP The influence of various dosing regimens on the response of asthmatic patients to aerosol steroid was investigated . Budesonide , a topically active corticosteroid like beclomethasone dipropionate , was given q.i.d . or b.i.d . , in the morning or A.M./P.M. , at doses of 400 , 800 , and 1600 micrograms/day . Each patient ( n = 34 ) took every treatment combination for 2 wk . The antiasthmatic and systemic effects , measured by changes in peak expiratory flow rate ( PEFR ) , blood eosinophils , and serum cortisol levels increased approximately linearly on log dose budesonide ( p less than 0.0005 ) . Systemic effects of the drug were nonsignificant at low dosage . At high dosage , morning dosing conserved hypothalamic-pituitary-adrenal function , but at the cost of a marginal reduction in efficacy ( delta PEFR , p = 0.12 ) . Having the dose frequency reduced the antiasthmatic potency of the drug , i.e. , PEFR fell by an amount equivalent to approximately eightfold reduction in daily dosage ( p = 0.002 ) . This effect was not evident when asthma was in remission but became so with asthma in relapse . Overall , the q.i.d . A.M./P.M. regimen showed the best risk-benefit relationships . The data indicate ( 1 ) that reductions in dose frequency made with the hope of improving patient compliance and thus conserving the drug 's long-term efficacy are likely to lead to the reverse effect , ( 2 ) that the clinician can conserve a better balance of risk vs benefit by titrating dosage in terms of puffs per dose rather than doses per day , and ( 3 ) that patients can increase the antiasthmatic efficacy of this aerosol steroid without any increase in drug costs ( or apparent risk ) by simply increasing dosing frequency . These therapeutic considerations probably apply to some or all of the other topically active steroids currently used to treat asthma OBJECTIVE The purpose of the study was to evaluate the dose-response relationships of the inhaled corticosteroid budesonide in a double blind crossover study in 19 children with moderate and severe asthma . METHODS A 2-week placebo treatment period ( run-in ) was followed by three 4-week treatment periods during which 100 , 200 , and 400 micrograms of budesonide were given per day in r and omized order . Urinary cortisol excretion , lung functions , and protection against exercise-induced asthma were assessed at the end of run-in and each treatment period . Furthermore , morning and evening peak expiratory flow rates , day and night symptoms , and use of rescue beta 2-agonists were recorded throughout the study . RESULTS One hundred micrograms of budesonide per day markedly improved symptoms , morning and evening peak expiratory flow rates , and use of rescue beta 2-agonists ( p < 0.01 ) . No further improvement was seen in these parameters with increasing doses of budesonide . In contrast , a significant dose-response effect was found on lung functions measured at the hospital and fall in lung functions after exercise ( p < 0.001 ) ; 200 micrograms was significantly better than 100 micrograms , and 400 micrograms was significantly better than 200 micrograms . About 53 % of the maximum effect against exercise-induced asthma was achieved by the lowest budesonide dose ( p < 0.001 ) , and about 83 % by the highest dose . No significant differences were seen in urinary cortisol excretion between run-in and the various budesonide doses . CONCLUSIONS Low doses of budesonide , which are not associated with any systemic side effects , have a marked antiasthma effect in children . Protection against exercise-induced asthma requires higher doses than achievement of symptom control BACKGROUND Budesonide ( Pulmicort ) is an inhaled corticosteroid with high topical potency but low systemic activity . Turbuhaler is a novel breath-actuated , multi-dose , dry-powder inhaler . OBJECTIVES This study was conducted to determine the efficacy and safety of two different dose regimens of budesonide Turbuhaler , compared with placebo , in adult patients with mild-to-moderate asthma not well-controlled with bronchodilator therapy . METHODS This double-blind , r and omized , placebo-controlled , parallel-group , multicenter study compared the efficacy and safety of 200 microg and 400 microg of budesonide , administered twice daily via Turbuhaler , with placebo , in 273 adult patients ( aged 19 to 70 years ) with mild-to-moderate asthma ( FEV1 67 % of predicted normal ) , not well-controlled with bronchodilator therapy .  Efficacy was assessed by pulmonary function tests and patient assessment s of asthma symptom control . Safety was assessed in terms of adverse events , laboratory evaluations , and physical examinations . RESULTS Two hundred and 400 microg of budesonide bid were significantly more effective than placebo at improving morning PEF ( mean differences from placebo of 43.63 L/min and 40.10 L/min , respectively ; P < .001 ) and FEV1 ( mean differences from placebo of 0.44 L , and 0.50 L , respectively ; P < .001 ) over the 12-week treatment period . Onset of action as assessed by morning PEF was within two days . Basal and stimulated plasma cortisol concentrations were not significantly affected by budesonide treatment compared with placebo . CONCLUSIONS Treatment of adults suffering from mild-to-moderate asthma with budesonide Turbuhaler is well tolerated and results in a rapid onset of asthma control which is maintained over time OBJECTIVES This study was design ed to compare the effects of a 6-month treatment with budesonide 100 microg bid ( low dose ) and 400 microg bid ( st and ard reference dose ) in controlling symptoms and lung function in a group of asthmatics with moderate asthma ( baseline FEV(1 ) > or = 50 % and < or = 90 % of predicted values ) previously treated with inhaled beclomethasone dipropionate ( 500 to 1,000 microg/d ) . Moreover , we investigated whether or not asthma exacerbations could be treated by a short-term increase in the daily dose of budesonide . METHODS After a 2-week run-in period and 1-month treatment with a high dose of budesonide ( 800 microg bid ) , 213 patients with moderate asthma were assigned to r and omized treatments . Daily treatment included budesonide ( bid ) plus an additional treatment in case of exacerbation ( qid for 7 days ) . Treatments were as follows : budesonide 400 microg plus placebo ( group 1 ) ; budesonide 100 microg plus budesonide 200 microg ( group 2 ) ; and budesonide 100 microg plus placebo ( group 3 ) . Symptoms and a peak expiratory flow ( PEF ) diary were recorded and lung function was measured each month . An exacerbation was defined as a decrease in PEF > 30 % below baseline values on 2 consecutive days . RESULTS We found that that 1-month treatment with a high budesonide dose remarkably reduced all asthma symptoms . Moreover , symptoms were under control in all treatment groups throughout the study period . Similarly , lung function improved and remained stable , and no relevant differences between groups were observed . In each treatment group , the majority of patients had no exacerbations . In patients treated with the st and ard budesonide dose ( group 1 ) , the number of exacerbations and days with exacerbations were significantly lower than in group 3 ( intention-to-treat analysis ) . Additionally , patients treated with low budesonide dose plus budesonide ( group 2 ) experienced a significantly lower number of exacerbations and days with exacerbations compared to group 3 ( per- protocol analysis ) . CONCLUSIONS This study demonstrates that when patients with moderate asthma had reached a stable clinical condition with a high dose of budesonide , a low dose of budesonide ( 200 microg/d ) is as effective as the st and ard dose ( 800 microg/d ) in the control of symptoms and lung function over a period of several months . Furthermore , results showed that the addition of inhaled budesonide ( 800 microg/d ) at onset of an asthmatic exacerbation has a beneficial clinical effect BACKGROUND There are no data currently available on the correct schedule for the initiation of treatment with nebulized suspension of budesonide in children with recurrent wheezing episodes . We compared the efficacy and safety of starting with a high dose followed by a stepwise decrease to a continuous low dose . METHODS In a double-blind design , 42 children aged 6 months to 3 years were r and omly allocated to receive either a high starting dose of 1 mg budesonide twice daily followed by a stepwise decrease of 25 % every second day for 1 week ( group A ) or a low dose of 0.25 mg twice daily for 1 week ( group B ) . Efficacy was assessed with daily symptom scores and the systemic effect of the corticosteroids with the adrenocorticotropic hormone test . RESULTS The two groups were comparable for all parameters evaluated . During the first week of treatment , there was a significant decrease in asthmatic symptomatology only in group A : a 59 % decrease for wheezing ( p = 0.0001 ) , 39 % for diurnal cough ( p = 0.036 ) , and 39 % for nocturnal cough ( p = 0.04 ) . Mean time to clinical response was 3.0 days in group A and 5.7 days in group B ( p = 0.02 ) . This early improvement was sustained for the rest of the follow-up period . The high dose starting schedule was not associated with any change in serum cortisol level . CONCLUSIONS The administration of nebulized suspension of budesonide at a high starting dose schedule followed by a rapid ( 1 week ) stepwise decrease yields a significant early improvement in asthma symptoms and causes no change in serum cortisol levels An open , cross-over trial was conducted on 25 asthmatic children , aged 6 - 13 years , who required inhaled steroids . They inhaled Budesonide 200 micrograms twice daily , either directly from the metered dose inhaler or via the pear spacer ( PS ) , for 2 months on each , in r and omized order . The effects of the treatment were monitored with diary cards recording peak expiratory flow rates twice daily , symptoms and treatment taken , and with monthly clinical assessment s including more sensitive lung function studies ( flow-volume loops and single breath nitrogen wash-out tests ) . There was no specifically PS-related improvement in symptoms or in the majority of tests , but the results showed improvement with time when using either method . The improvement was more distinct in some tests reflecting proximal airway calibre ( i.e. , PEFR ) than in tests thought to reflect predominantly peripheral airway calibre ( i.e. , F50 , RV ) . The bronchodilator responsiveness , as shown by the increase in lung function tests after a beta-agonist was given , was significantly greater for FVC during the periods when the PS was used , although there was no significant improvement in FEV2 or PEFR . The improvement in tests reflecting proximal airways may have been due to optimization of the inhalation technique , greater underst and ing of asthma , or better compliance with medication associated with regular attendance for the study . The greater bronchodilator response whilst children were inhaling budesonide by the PS may have been due to increased deposition or better distribution of the steroid but was probably related to a difference between the two groups in initial baseline function tests Inhaled steroid therapy is the most important treatment in the management of chronic asthma and currently twice-daily administration is recommended in mild to moderate asthma . Compliance is often a problem in asymptomatic patients and may lead to reduced disease control . Our aim was to investigate whether budesonide 0.2 mg once daily administered via the Turbuhaler is as effective as 0.1 mg twice daily . A r and omized , double-blind , parallel group study was carried out in which 76 adult patients with mild to moderate asthma ( FEV1 86 % of predicted ) were allocated to budesonide once or twice daily . After a run-in period of 2 weeks on present inhaled steroid treatment ( 0.2 - 0.5 mg day-1 ) there was an 8 week treatment period , followed by a washout period in which patients received no steroid for 4 weeks unless a drop in morning peak flow of at least 20 % occurred or the use of beta 2-agonists increased by 50 % . Both treatment groups improved minimally in peak flow ( 1.7 and 4.31 min-1 in the once-daily and twice-daily groups respectively ) but the differences between the two groups were not significant . Testing the reverse hypothesis revealed clinical equivalence . The 90 % confidence interval of the difference in the change of peak flow from run-in was between + 30 and -30 l min-1 , the limits deemed to be clinical ly relevant . There were no differences in symptom scores , beta 2-agonist use or spirometry measurements between the two groups . In the washout period there was a significant deterioration in peak flow and symptoms . This study shows that 0.2 mg budesonide given once a day is as affective as 0.1 mg given twice daily in patients with mild to moderate asthma The dose‐response effects of inhaled beclomethasone dipropionate ( BDP ) and budesonide ( BUD ) administered b.i.d . with the aid of metered dose aerosols were studied in 128 patients ( 67 men and 61 women , mean age 53 years ) suffering from asthma bronchiale . The study was design ed as a multi‐centre , double‐blind , four‐period cross‐over study , followed by a single‐blind double placebo period . BDP was administered in doses of 400 and 1000 μg , and BUD in doses of 400 and 800 μg . The results in terms of peak expiratory flow ( PEF ) in the morning and evening , daily symptoms score and use of inhaled β2‐agonists did not reveal any clinical ly significant differences between the drugs or between high ( 800 μg BUD , 1000 μg BDP ) and low ( 400 mg BUD/BDP ) doses . However , statistically significant differences were recorded for the corresponding parameters when comparing the placebo with preceding steroid periods . Adverse effects consisting mainly of oropharyngeal c and idiasis , hoarseness and cough occurred in 54 of 468 treatment months ( 12 % ) . The carry‐over effects of inhaled steroids are longer lasting than was previously assumed Repeated low‐dose allergen challenge increases airway hyperresponsiveness and sputum eosinophils  in atopic asthmatics .  Inhaled corticosteroids attenuate the airway responses to high‐dose allergen challenge , but have not been evaluated against repeated low dose challenge One hundred and sixty seven children on 0 - 200 microgram/day of inhaled steroid with asthma symptoms and sub-optimal peak flow values ( less than 90 % of that predicted for their height ) were r and omly allocated either 400 microgram once daily ( nocte with placebo o.m . ) or 200 mircrogram twice daily of budesonide Turbohaler for 8 weeks . Bronchdilator usage and symptoms were reduced in both groups at 4 and 8 weeks compared with baseline . There was a significant increase within both groups in morning and evening PEF after 4 and 8 weeks . The increase in evening PEF after 8 weeks was greater in the once-daily group than in the twice-daily group but there were no other significant differences between the groups ( morning : + 24.6 l/min vs 15.2 l/min , p = 0.059 ; evening : + 19.7 l/min vs + 8.31 l/min ; p = 0.013 ) . Budesonide Turbohaler 400 microgram once daily is therefore as effective as 200 microgram twice daily in achieving asthma control in children Maintenance treatment with nebulized budesonide was studied in young children with asthma not controlled without steroids . In a blind parallel‐group study for 18 weeks , 102 children , mean age 22 ( 5–47 ) months , were r and omized for treatment starting with 0.25 or 1 mg b.i.d . The patients were review ed every 3 weeks , and if symptom control had been achieved the dose was reduced , otherwise it was kept . The clinical effect was very good with both dose regimens . The median time to 7 consecutive days without any asthma symptoms was about 1 month with both , highlighting the importance of the duration of therapy rather than the benefits of a high starting dose . In 18 of 24 children who attained the placebo stage , symptoms had reappeared at the last visit . Although an overall minimal effective maintenance dose could not be demonstrated , 47 % achieved symptom control on 0.25 mg b.i.d . , i.e. fulfilled criteria for further dose reduction . No significant side effects were seen . On average , 25 % of the nominal dose reached the patients BACKGROUND The role of long-acting , inhaled beta2-agonists in treating asthma is uncertain . In a double-blind study , we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide . METHODS After a four-week run-in period of treatment with budesonide ( 800 microg twice daily ) , 852 patients being treated with glucocorticoids  were r and omly assigned to one of four treatments given twice daily by means of a dry-powder inhaler ( Turbuhaler ) : 100 microg of budesonide plus placebo , 100 microg of budesonide plus 12 microg of formoterol , 400 microg of budesonide plus placebo , or 400 microg of budesonide plus 12 microg of formoterol . Terbutaline was permitted as needed . Treatment continued for one year ; we compared the frequency of exacerbations of asthma , symptoms , and lung function in the four groups . A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days . RESULTS The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent , respectively , when formoterol was added to the lower dose of budesonide . The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent , respectively . Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent , respectively . Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide , but the improvements with formoterol were greater . CONCLUSIONS In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids , the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial . The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma Measurement of short term lower leg growth with the knemometer has recently been shown to be a sensitive method for assessment of systemic activity of exogeneous glucocorticosteroids in children with asthma ( 1 ) . It is not known , however , whether short term knemometry is more sensitive than established measures of adrenal function , such as 24 h urine free cortisol excretion . We recently found that  knemometric growth rates were suppressed in a dose-related manner in asthmatic children treated with 200 , 400 and 800,~g of inhaled budesonide ( 2 ) . In the present paper , we report the 24 h urine free cortisol excretion in the same children for comparison with the knemometry data , to evaluate if there is any correlation between the two measures of systemic activity , and to assess which method is the more sensitive Forty-five steroid-dependent asthmatic out patients were treated twice daily for 51 weeks with a new inhalation steroid , budesonide ( BUD ) , using a 750 ml spacer . During the initial 15 weeks the prednisone-sparing effects of a high daily dose ( 1600 micrograms ) and a conventional dose ( 400 micrograms per day ) were compared in a double-blind r and omized trial including 50 patients . During the remaining 36 weeks 45 patients were treated openly with 1600 micrograms daily . All patients used other antiasthmatic drugs which were maintained throughout the study , except for inhalations of beta-2 agonists that could be used whenever needed . All patients but 2 were able to reduce the daily dose of oral prednisone . The mean daily dose decreased from 13.9 mg to 5.3 mg . Eighteen patients ( 40 % ) were able to discontinue oral prednisone . Adrenal gl and function improved considerably as prednisone intake decreased . Oropharyngeal thrush frequency showed no change . No severe side effects were observed In a double-blind study of 2 parallel groups of 15 allergic asthmatic patients each , we investigated whether treatment with inhaled budesonide has a dose- and time-dependent effect on the degree of bronchial hyperreactivity . The patients were r and omly allocated to treatment with either 200 or 800 micrograms budesonide per day for a period of 8 wk . The active treatment period was preceded by a selection period of 3 wk , and a single-blind placebo period of 2 wk . During these initial 5 wk the maintenance treatment of the patients , including cromolyn sodium and inhaled corticosteroids , was withheld .  Spirometry  and inhalation provocation tests with methacholine were carried out , and the symptom score was recorded every 2 wk . The methacholine provocation concentrations ( geometric mean ) causing a decrease in FEV1 of 20 % ( PC20 ) in the 200 and 800 micrograms/day treatment groups just before the active treatment period were 0.90 and 0.91 mg/ml , respectively . These values increased significantly to 1.21 and 1.84 mg/ml after 2 wk of treatment ( p less than 0.05 and p less than 0.001 , respectively ) and to 1.55 and 2.74 mg/ml after 8 wk of treatment ( p less than 0.01 and p less than 0.001 ) . During the whole study period budesonide in a dosage of 800 micrograms/day induced a significantly larger change in PC20 than in a dosage of 200 micrograms/day . The FEV1 before treatment was 91 + /- 3 % ( SEM ) and 84 + /- 2 % of the predicted value in the 200 and 800 micrograms/day treatment groups , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS 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 r and omly 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 Serum concentrations of growth hormone – dependent insulin – like growth factor I ( IGF – I ) and insulinlike growth factor binding protein–3 ( IGFBP–3 ) , the carboxy terminal propeptide of type I procollagen ( PICP ) , the carboxy terminal pyridinoline cross – linked telopeptide of type I collagen ( ICTP ) and the amino terminal propeptide of type III procollagen ( PIIINP ) were studied in 14 prepubertal children with asthma ( mean age 9.7 years ) during treatment with inhaled budesonide .  The study design was a r and omized , crossover trial with two double – blind treatment periods ( 200 and 800 μg ) and one open , non – r and omized treatment period ( 400 μg ) . All periods were 18 days ’ duration . Budesonide treatment was associated with a dose – related suppressive trend in serum concentrations of PIIINP when the 400 μg period was included ( p < 0.01 ; z = –2.7 ) and when it was excluded from the calculations ( p < 0.01 ; z = –2.6 ) , indicating reduced synthesis of type III collagen . A similar trend was observed in ICTP levels when the 400 μg period was excluded from the calculations ( p= 0.05 ; z = –1.9 ) . No other statistically significant variations were seen BACKGROUND As a general phenomenon , corticosteroids may suppress the activity in the hypothalamic-pituitary-adrenal ( HPA ) axis . The adrenal stimulation test is a commonly used method to assess the relative risk of exogenous corticosteroids to induce systemic side effects . OBJECTIVES This clinical trial was performed to assess the effects of budesonide on the HPA axis ( at 800 , 1600 , or 3200 microg/day , given as a twice daily regimen , administered by means of the Turbuhaler ) in adult patients with mild , non-steroid-dependent asthma . METHODS Sixty-four asthmatic patients received budesonide or placebo by inhalation or 10 mg/day oral prednisone once daily as a positive control in a double-blind , double-dummy , r and omized , placebo-controlled , parallel-group , multicenter study . Plasma cortisol concentration was measured to assess the effect on the HPA axis before and during a 6-hour infusion of synthetic adrenocorticotropic hormone ( ACTH ) , cosyntropin . RESULTS After 6 weeks of treatment , plasma cortisol concentrations after adrenal stimulation by cosyntropin infusion had fallen by 4 % in the placebo group ; by 13 % , 11 % , and 27 % in the budesonide groups ( 800 , 1600 , and 3200 microg/day , respectively ) ; and by 35 % in the prednisone group . The decrease was significant only in the 3200 microg/day budesonide ( p = 0.03 ) and prednisone ( p = 0.005 ) groups . Over the same time period , decreases in basal plasma cortisol concentrations were 1 % in the placebo group ; 19 % , 19 % , and 34 % in the three budesonide groups ; and 37 % in the prednisone group . Only in the prednisone group was the decrease significant ( p = 0.03 vs placebo ) . CONCLUSIONS In this study budesonide inhaled by means of the Turbuhaler , at doses recommended for clinical use ( 800 or 1600 microg/day ) , did not produce any statistically significant suppression of the HPA axis compared with placebo We assessed the systemic effects of budesonide ( BUD ) and fluticasone propionate ( FP ) in 23 patients with asthma , using a double-blind , placebo-controlled , double-dummy , and cross-over design . The following five treatments were given in a r and omized order for 1 wk with a washout period in between of 2 wk : ( 1 ) placebo ; ( 2 ) FP , 200 micrograms twice a day , inhaled from a Diskhaler ; ( 3 ) FP , 1,000 micrograms twice a day , inhaled from a Diskhaler ; ( 4 ) BUD , 200 micrograms twice a day , inhaled from a Turbuhaler ; and ( 5 ) BUD , 800 micrograms twice a day , inhaled from a Turbuhaler . The primary variable was the area under the curve of serum cortisol versus time ( AUC0 - 20 ) , derived from serum sample s taken every 2 h over a 20-h period following the last evening dose at 10:00 P.M. The lower doses of BUD and FLU did not cause any adrenal suppression . Compared with placebo , however , FP ( 1 , 000 micrograms , twice daily and BUD ( 800 micrograms , twice daily ) decreased the AUC0 - 20 by 34 and 16 % , respectively . Fluticasone ( 1,000 micrograms , twice daily ) was more suppressive than BUD ( 800 micrograms , twice daily ) ( p = 0.0006 ) . The FEV1 , measured the morning after the last inhalation , was significantly higher after the active treatments , compared with placebo ( p < 0.02 ) , but did not differ between all active treatments . We conclude that high doses of BUD and FP ( in particular the latter ) , inhaled via their respective dry powder inhalers for 1 wk , result in a measurable systemic activity in patients with asthma BACKGROUND Inhaled glucocorticosteroids are indicated for the treatment of persistent asthma ; however , many young children are unable to effectively use currently available inhalers . OBJECTIVE We sought to evaluate the efficacy and safety of 3 different twice daily doses of budesonide inhalation suspension ( Pulmicort Respules ) in inhaled steroid-dependent asthmatic children . METHODS This was a 12-week , r and omized , double-blind , placebo-controlled , parallel-group study involving 178 children ( age range , 4 to 8 years ) at 17 centers in the United States .  Budesonide inhalation suspension doses of 0.25 mg , 0.50 mg , or 1.0 mg twice daily were administered by means of a jet nebulizer and air compressor system .  Efficacy was assessed by recording at home nighttime and daytime asthma symptom scores , use of rescue medication , pulmonary function tests , and treatment discontinuation because of worsening symptoms . Safety was assessed by reported adverse events and changes in baseline and adrenocorticotrophic hormone-stimulated plasma cortisol levels in a subset of patients . RESULTS Baseline demographics , symptom scores , and pulmonary function data were similar across treatment groups . All doses of budesonide inhalation suspension were superior to placebo in improving nighttime and daytime asthma symptom scores ( P < /=.026 ) , reducing use of breakthrough medication ( P < /=.032 ) , and improving morning peak expiratory flow ( P < /=.030 ) . The number of dropouts because of worsening asthma was also significantly fewer in the budesonide groups ( P < /=.015 ) . There were no differences between doses of budesonide . Adverse events and basal and adrenocorticotrophic hormone-stimulated cortisol responses were not different between budesonide and placebo groups . CONCLUSION Budesonide inhalation suspension , 0.25 mg , 0.50 mg , and 1.0 mg twice daily , is an effective and safe treatment for young children with inhaled steroid-dependent , persistent asthma AIMS The present pharmacokinetic study was undertaken to determine the dose proportionality of three different doses of budesonide-400 microg , 800 microg or 1600 microg administered twice daily by a dry-powder inhaler ( Turbuhaler ) in adult patients with mild asthma . METHODS A total of 38 patients received budesonide by inhalation , 13 received 400 microg twice daily , 12 received 800 microg twice daily and 13 received 1600 microg twice daily . Mean FEV1 at inclusion was 3.4 , 4.0 and 3.9 l min-1 in the three groups , respectively .  Blood sample s were taken after a single dose , and after 3 weeks of daily treatment , for pharmacokinetic evaluation . Plasma concentrations of budesonide  were determined by liquid chromatography plus mass spectrometry . RESULTS Eleven evaluable patients remained in each dose group . Mean time to peak budesonide plasma concentration ( tmax ) was short ( 0.28 - 0.40 h ) and did not differ between treatment groups .  Budesonide concentrations declined rapidly thereafter , indicating efficient pulmonary absorption and rapid elimination with a half-life of approximately 3 h. Cmax was 1 . 4(2.0 ) nmol l-1 ( single ( repeated ) doses ) , 2.6(3.6 ) nmol l-1 and 5 . 4(6.4 ) nmol l-1 after 400 , 800 and 1600 microg twice daily , respectively . The corresponding results for the area under the plasma concentration vs time curve ( AUC ) were 271(325 ) , 490(628 ) and 915(1096 ) nmol l-1 min . Ninety percent confidence intervals for pairwise dose-normalized Cmax and AUC comparisons between groups were large but contained unity in all cases , thus indicating dose-proportional pharmacokinetics . Regression on analysis supported these findings . Mean AUC after repeated doses ( AUC(0,12 h , RD ) ) was on average 23 % higher than the mean AUC after single doses ( AUC(0 , infinity , SD)(P=0.04 ) with no significant differences between doses , indicating slight accumulation following bid dosing . CONCLUSIONS In this relatively small study , budesonide inhaled via Turbuhaler appeared to have dose-proportional pharmacokinetics , both within and above the clinical ly recommended dose range for asthmatic patients OBJECTIVE To determine the efficacy and safety of budesonide delivered by an inhalation-driven dry powder inhaler ( Turbuhaler ) in children with moderate to severe persistent asthma . STUDY DESIGN In our r and omized , double-blind , placebo-controlled , parallel-group , multicenter study , a total of 404 children with asthma , who were aged 6 to 18 years and who had been receiving inhaled glucocorticosteroid therapy  , were r and omly assigned to receive either 100 , 200 , or 400 micrograms of budesonide or placebo twice daily for 12 weeks . At baseline , mean forced expiratory volume in 1 second ( FEV1 ) was 74.6 % ( range , 30.7 % to 123.3 % ) of the predicted normal value . RESULTS Patients in each of the three budesonide treatment groups showed significant dose-related improvements in lung function ( morning peak expiratory flow and FEV1 ) , in asthma symptoms , and with a significant decrease in inhaled beta 2-agonist use in comparison with placebo . Improvements were evident within 2 weeks and were maintained throughout the 12 weeks . Budesonide treatment had no significant effect on hypothalamic-pituitary-adrenal axis function , and the incidence of reported adverse events was similar in all treatment groups . CONCLUSION Budesonide administered via a dry powder inhaler provided dose-related improvements in lung function and clinical status and was well tolerated by children ( 6 to 18 years of age ) with moderate to severe persistent asthma Bisgaard , H. , Pedersen S. , Damkjær Nielsen M and Østerballe O. ( Department of Paediatrics , University Hospital of Copenhagen , County of Gentofte , Copenhagen ; Department of Paediatrics , County Hospital of Kolding ; Department of Clinical Physiology , University Hospital of Copenhagen , County of Glostrup , Copenhagen ; Department of Paediatrics , County Hospital of Viborg , Denmark ) . Adrenal function in asthmatic children treated with inhaled budesonide .  Acta Paediatr Sc and 80 : 213 , 1 . The aim of this pharmacokinetic study was to evaluate to what extent oropharyngeal deposition of drug contributes to the systemic availability of budesonide inhaled from a dry powder inhaler ( Turbuhaler ) . 2 . The design was a r and omized cross-over study in eight children aged 7 - 13 years . The plasma concentrations of the two epimers of budesonide ( 22R and 22S ) after inhalation of 1 mg budesonide from a Turbuhaler were compared with the plasma concentrations obtained when the absorption of the drug deposited in the oropharynx was blocked by drinking and rinsing the mouth with charcoal before and after the inhalation . 3 . The plasma concentrations of budesonide  were significantly reduced by the charcoal treatment ( P < 0.01 ) and the area under the time vs plasma concentration curve 0 - 4 h was significantly reduced from 9.5 to 8.0 mmol l-1 h for 22S ( P < 0.01 ) and from 7.6 to 5.7 mmol l-1 h for 22R ( P < 0.01 ) . 4 . The plasma concentrations and the AUCs after both Turbuhaler administrations were markedly higher than those obtained in earlier studies using other inhalers suggesting a higher intrapulmonary deposition of drug after Turbuhaler treatment . 5 . It is concluded that oropharyngeal deposition of drug accounts for about 20 % of the total systemic availability of budesonide inhaled from Turbuhaler . Thus , the main contribution to the system comes from budesonide absorbed in the airways BACKGROUND A simple laboratory method to evaluate relative potency of inhaled corticosteroids in asthma would be valuable . Single-dose studies with the allergen-induced late asthmatic response have failed to show a useful dose-response relationship . Treatment for several days with inhaled corticosteroids will also inhibit the allergen-induced early asthmatic response . METHODS Twelve atopic asthmatic subjects were studied during a season when no medications were required except ipratropium  bromide  as needed . These subjects had positive allergen and methacholine inhalation tests and FEV1 greater than 70 % of predicted value . A double-blind , r and omized , cross-over study compared placebo and budesonide 100 , 200 , and 400 microg administered by means of Turbuhaler twice daily for 7 days with 6-day washout periods . Methacholine PC20  was measured before and after 6 days of treatment , and allergen PC15 was measured after 7 days of treatment . RESULTS The allergen PC15 ( n = 11 ) was significantly larger ( P = .0001 ) for all doses of budesonide compared with placebo , but there was no significant difference between the 3 doses of budesonide , and no dose response was demonstrated . The methacholine PC20 was significantly larger after all budesonide treatments compared with placebo ( P = .024 ) , but there was no difference between the 3 doses . There was a progressive increase in the allergen PC15 chronologically ( sequence effect ) that was not explained by improvement in FEV1 or airway responsiveness ; sequence effects were not seen for FEV1 or for pretreatment or posttreatment methacholine PC20 . Statistical adjustment for sequence effect did not alter allergen PC15 statistics . CONCLUSION A 7-day course of budesonide administered by means of Turbuhaler at 200 , 400 , or 800 microg per day provided marked and significant inhibition of the allergen-induced early asthmatic response compared with placebo . There was , however , no difference between the 3 doses . Therefore this method with these doses is not useful for providing assessment of relative potency BACKGROUND Inhaled glucocorticosteroids ( GCS ) are the most effective long-term controller medications for the treatment of persistent asthma . Currently , however , available delivery devices limit their use in young children . A nebulized formulation of budesonide has been developed to address the needs of infants and young children . OBJECTIVE To evaluate the efficacy and safety of once-daily budesonide inhalation suspension in children 6 months to 8 years old with mild persistent asthma not on inhaled GCS . METHODS Three hundred fifty-nine children were r and omized to receive once-daily budesonide inhalation suspension ( 0.25 mg , 0.50 mg , or 1.0 mg ) or placebo via a Pari LC-Jet Plus nebulizer for 12 weeks . Efficacy assessment s included nighttime/daytime asthma symptoms , pulmonary function ( subset of patients ) , rescue medication use , and treatment discontinuations . Safety was based on adverse events and assessment of HPA-axis function . RESULTS Demographics , baseline characteristics , asthma symptoms , and pulmonary function were similar across treatment groups . Mean nighttime/daytime asthma symptom scores were 1.19 + /- 0.63 and 1.34 + /- 0.53 , respectively . Mean duration of asthma was 36.3 months and mean FEV1 was 81.3 % of predicted with 27.7 % reversibility . Following 12 weeks of treatment , all budesonide inhalation suspension doses produced significant improvements in nighttime/daytime symptoms ( P < or = .049 ) and significant decreases in rescue medication use ( P < or = .038 ) compared with placebo . Significant improvements ( P < or = .044 ) in FEV1 were observed in the 0.5- and 1.0-mg budesonide inhalation suspension groups . There were no differences between doses of budesonide inhalation suspension . Adverse events and basal and ACTH-stimulated cortisol levels were similar among all groups . CONCLUSION Once-daily administration of budesonide inhalation suspension was well tolerated and effective for the treatment of mild persistent asthma in infants and young children not adequately controlled with bronchodilators or non-GCS antiinflammatory treatments To determine therapeutically and systemically equivalent dosages of budesonide inhaled through the Turbuhaler dry powder inhalation device ( Astra Pharma Production AB , Södertälje , Sweden ) or pressurized metered-dose inhaler ( pMDI ) plus Nebuhaler spacer ( Astra Pharma Production AB ) , we compared these devices in a r and omized , open , parallel-group trial . Adults with moderate to severe asthma inhaled budesonide ( 0.4 , 0.8 , 1.6 , and 2.4 mg/day ) , for 2 weeks at each dose level , through the Turbuhaler ( n = 30 ) or pMDI + Nebuhaler ( n = 28 ) . Dose-dependent effects were demonstrated on asthma symptoms ( p = 0.0001 ) , daily peak expiratory flow ( p = 0.02 ) , blood eosinophils ( p = 0.0001 ) , urinary cortisol output per day ( p = 0.0001 ) , serum cortisol ( p = 0.006 ) , serum osteocalcin ( p = 0.0001 ) , and the oropharyngeal C and ida colony count ( p = 0.0007 . analysis of covariance ) . The ratio of the responses to the two inhalation devices approximated 1.0 for each index measured ; that is , no significant between-device difference was found ( p > or = 0.29 ) . However , the 95 % confidence limits for the ratio of their respective systemic effects on osteocalcin production were 0.83 to 1.48 . Thus in adults who use inhalation devices efficiently and have optimally controlled asthma , conversions from the pMDI + Nebuhaler to the Turbuhaler may reasonably be made at milligram equivalent doses of budesonide , then down-titrated to minimize possible systemic effects . Because earlier studies have shown that the Turbuhaler can double intrapulmonary drug delivery in comparison with a pMDI without a spacer , a 50 % dose reduction may be indicated when converting from a pMDI to the Turbuhaler The object of this investigation was to study the long-term effects of antiasthma treatment on blood markers of inflammation and lung function in adult asthmatic subjects . For this purpose 85 allergic and nonallergic asthmatic subjects were r and omized into three groups , which were given high-dose ( 1,600 micrograms/d ) inhaled budesonide , low-dose ( 400 micrograms/d ) inhaled budesonide , and oral theophylline ( 600 mg/d ) , respectively , and were followed for 11 mo with testing of lung function and blood sampling for the assay in serum of eosinophil cationic protein ( ECP ) , eosinophil protein x/eosinophil derived neurotoxin ( EPX/EDN ) as eosinophil markers , and myeloperoxidase ( MPO ) and lactoferrin ( LF ) as neutrophil markers . Lung functions ( FEV1 % predicted , and histamine PC20 ) and the eosinophil markers ECP and EPX/EDN were improved and reduced , respectively , by budesonide in a dose-dependent and temporally parallel fashion . Theophylline did not alter lung functions but reduced ECP and EPX/EDN after prolonged treatment . The treatment efficacy of budesonide was attributed solely to an effect on nonsmoking asthmatic subjects , since neither lung functions nor eosinophil markers changed in smokers even with high-dose budesonide . MPO but not LF was reduced after several months of treatment in all three groups , but only in nonsmokers . We conclude that ECP and EPX/EDN may be used to monitor antiinflammatory treatment in asthmatic patients , and that smoking asthmatic subjects are resistant to inhaled corticosteroids BACKGROUND Airway inflammation is a hallmark of asthma , therefore current treatment recommendations include the use of inhaled glucocorticosteroids ( GCS ) . However , there is little evidence that the effects of inhaled GCS are dose dependent . OBJECTIVES The objective of this study was to assess the efficacy and safety of a second-generation GCS , budesonide , delivered by Turbuhaler , in adults with chronic asthma . METHODS In a 12-week , r and omized , double-blind , multicenter , parallel-group study , 473 subjects 18 to 70 years of age received either placebo or budesonide ( 200 , 400 , 800 , or 1600 microg total daily dose ) administered twice daily . Primary efficacy end points were mean change from baseline for FEV1 and morning peak expiratory flow . Safety was assessed by reported adverse events and by a cosyntropin-stimulation test . RESULTS The mean baseline FEV1 was 63 % to 66 % of predicted normal value between groups . All doses of budesonide were more effective than placebo ( p < 0.001 ) . The mean changes in morning peak expiratory flow were 12 , 22 , 27 , and 30 L/min in the 200 , 400 , 800 , and 1600 microg budesonide total daily dose groups , respectively , and -27 L/min for the placebo group . A statistically significant dose-response effect for the mean change from baseline over the 12-week study was seen for both morning peak expiratory flow and FEV1 .  Budesonide-treated subjects also demonstrated significant reduction in asthma symptoms and bronchodilator use compared with placebo . There were no clinical ly significant differences in treatment-related adverse experiences among groups . CONCLUSIONS Budesonide administered by Turbuhaler exhibited a dose response and was effective at low doses . It was well tolerated and significantly more effective than placebo
BACKGROUND Inhaled budesonide ( BUD ) is available in a range of doses for treating chronic asthma .
OBJECTIVES To quantitatively assess the efficacy and safety of budesonide at different doses in order to establish whether a clinical ly significant dose response profile exists .