[Long-term corticosteroid therapy as a risk factor of osteoporosis in patients with asthma and chronic bronchitis]. Changes in bronchial reactivity in asthmatic children after treatment with beclomethasone alone or in association with salbutamol. Comparative adrenal suppression with inhaled budesonide and fluticasone propionate in adult asthmatic patients. Inhaled budesonide for treatment of recurrent wheezing in early childhood Effect of continuous treatment with topical corticosteroid on episodic viral wheeze in preschool children. Salbutamol treatment of acute severe asthma in the ED: MDI versus hand-held nebulizer. Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Comparison of fluticasone propionate with beclomethasone dipropionate in moderate to severe asthma treated for one year. International Study Group. Effect of inhaled beclomethasone dipropionate on expression of proinflammatory cytokines and activated eosinophils in the bronchial epithelium of patients with mild asthma. Comparison of a beta 2-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma. One year treatment with salmeterol compared with beclomethasone in children with asthma. The Dutch Paediatric Asthma Study Group. Importance of total serum IgE for improvement in airways hyperresponsiveness with inhaled corticosteroids in asthma and chronic obstructive pulmonary disease. The Dutch CNSLD Study Group. Effect of inhaled budesonide on seasonal changes in sensitivity and maximal response to methacholine in pollen-sensitive asthmatic subjects. Bloodspot cortisol in mild asthma: the effect of inhaled corticosteroids. Osteocalcin, growth, and inhaled corticosteroids: a prospective study. Growth and childhood asthma. Asthma treatment with a new corticosteroid aerosol, budesonide, administered twice daily by spacer inhaler Duration of growth suppressive effects of regular inhaled corticosteroids Assessment of the relative systemic potency of inhaled fluticasone and budesonide. Systemic effects of high dose inhaled steroids: comparison of beclomethasone dipropionate and budesonide in healthy subjects. Growth during one year of treatment with fluticasone propionate or sodium cromoglycate in children with asthma. Inhalation therapy during acute asthma. The role of a combined steroid and beta-stimulant preparation. Pulmicort Turbohaler once daily as initial prophylactic therapy for asthma. Anti-inflammatory action of steroid inhalers. Comparison of budesonide and beclomethasone dipropionate in patients with severe chronic asthma: assessment of relative prednisolone-sparing effects. Effect of triamcinolone acetonide aerosol upon exercise-induced asthma. Effects of 22 months of treatment with inhaled corticosteroids and/or beta-2-agonists on lung function, airway responsiveness, and symptoms in children with asthma. The Dutch Chronic Non-specific Lung Disease Study Group. Increased numbers of dendritic cells in the bronchial mucosa of atopic asthmatic patients: downregulation by inhaled corticosteroids Comparison of the efficacy and safety of inhaled fluticasone propionate 200 micrograms/day with inhaled beclomethasone dipropionate 400 micrograms/day in mild and moderate asthma. Inhaled beclomethasone dipropionate (BDP) prevents seasonal changes in atopic asthmatics. Impact of fluticasone propionate powder on health-related quality of life in patients with moderate asthma. Protective effect of inhaled budesonide against unlimited airway narrowing to methacholine in atopic patients with asthma. Aerosol beclomethasone dipropionate compared with theophylline as primary treatment of chronic, mild to moderately severe asthma in children. Nebulised beclomethasone dipropionate suspension. Nebulized budesonide for the treatment of moderate to severe asthma in infants and toddlers * Measures of systemic activity of inhaled glucocorticosteroids in children: a comparison of urine cortisol excretion and knemometry. Fluticasone propionate in children with moderate asthma. Placebo-controlled immunopathologic study of four months of inhaled corticosteroids in asthma. Long-term follow-up of patients with a history of near fatal episodes; can inhaled corticosteroids reduce the risk of death from asthma? Can the morbidity of asthma be reduced by high dose inhaled therapy? A prospective study. [Inhaled beclomethasone in long-term management of asthma: optimal dose and optimal duration of treatment]. Fluticasone propionate compared with theophylline for mild-to-moderate asthma. Nebulised beclomethasone dipropionate in preschool asthma. Is delayed introduction of inhaled corticosteroids harmful in patients with obstructive airways disease (asthma and COPD)? The Dutch CNSLD Study Group. The Dutch Chronic Nonspecific Lung Disease Study Groups. Effects of inhaled beclomethasone dipropionate and alternate-day prednisone on pituitary-adrenal function in children with chronic asthma. Effects of dose and dosing schedule of inhaled budesonide on bone turnover. Perception of bronchial obstruction in asthmatic patients. Relationship with bronchial eosinophilic inflammation and epithelial damage and effect of corticosteroid treatment. Linear growth of very young asthmatic children treated with high‐dose nebulized budesonide A 12-week dose-ranging study of fluticasone propionate powder in the treatment of asthma. Candidiasis and dysphonia complicating beclomethasone treatment of asthma. Absence of posterior subcapsular cataracts in young patients treated with inhaled glucocorticoids [The effect of the Russian inhalant glucocorticosteroid budesonide on bronchial inflammation and hyperreactivity during the long-term treatment of bronchial asthma patients]. The effect of corticosteroids on methacholine inhalation in symptomatic bronchial asthma. Eosinophil and neutrophil activity in asthma in a one-year trial with inhaled budesonide. The impact of smoking. Effectiveness of fluticasone propionate in patients with moderate asthma: a dose-ranging study.
This work evaluates frequency of steroid induced osteoporosis  according to kind of steroid drugs ( systemic , inhaled ) , dose and duration of treatment . In group of 80 young patients with asthma and chronic bronchitis the following examinations have been used : biochemical markers of bone turnover , X-ray of thoracic lumbar part of vertebral column and bone density in quantitative computed tomography of vertebrae L2-L4 . Osteoporosis appeared in patients chronically treated with systemic steroids ( prednisone ) and in patients treated with inhaled steroids  in typical dose as well . Usefulness of biochemical markers of bone turnover in connection with quantitative computed tomography in diagnostic of steroid induced osteoporosis has been confirmed Airway inflammation is consistently present in patients with severe asthma . The combination of inhaled steroids and bronchodilators may be useful both for treating symptoms and improving the underlying inflammatory condition . We have compared the effect of beclomethasone dipropionate ( BDP ) combined with salbutamol ( S ) , BDP alone , and placebo , on the severity of bronchial responsiveness in 30 children with allergic asthma during the period of specific allergen exposure . In children treated with BDP alone , PC20-FEV1 methacholine was 0.66 + /- 0.54 at the beginning and 1.91 + /- 2.11 at the end of the study period ( p greater than 0.05 ) . In children treated with BDP + S PC20 , methacholine was 1.21 + /- 1.43 at the beginning and 4.22 + /- 3.88 at the end of the study ( p less than 0.05 ) . The group of children treated with placebo had a PC20-FEV1 methacholine of 0.79 + /- 0.61 at the beginning of the study and 0.80 + /- 0.46 at the end of the study . The results of the present study show that maintenance treatment with inhaled beclomethasone combined with salbutamol may lead to greater improvement in bronchial hyperreactivity than treatment with inhaled beclomethasone dipropionate alone BACKGROUND : A study was performed to compare the adrenal suppression caused by inhaled fluticasone propionate and budesonide on a microgram equivalent basis , each given by metered dose inhaler to asthmatic patients . METHODS : Twelve asthmatic patients of mean age 29.9 years , with a forced expiratory volume in one second ( FEV1 ) 92.9 % predicted and forced expiratory flow 25 - 75 % ( FEF25 - 75 ) 69.5 % predicted , on less than or equal to 400 micrograms/day inhaled corticosteroid , were studied in a double blind placebo controlled crossover design comparing single doses of inhaled budesonide 400 , 1000 , 1600 , 2000 micrograms and fluticasone propionate 500 , 1000 , 1500 , 2000 micrograms . Doses were administered at 22.00 hours by metered dose inhaler with mouth rinsing and measurements were made in the laboratory 10 hours later . RESULTS : Serum cortisol levels compared with placebo ( mean 325.2 nmol/l ) were suppressed by fluticasone at doses of 1500 micrograms ( 211.6 nmol/l ) and 2000 micrograms ( 112.3 nmol/l ) and by budesonide at 2000 micrograms ( 243.4 nmol/l ) . Fluticasone propionate 2000 micrograms produced lower absolute serum cortisol levels than budesonide 2000 micrograms ( 95 % CI for difference 42.9 to 219.2 ) . The dose ratio ( geometric mean ) for the relative potency was 2.89 fold ( 95 % CI 1.19 to 7.07 ) . In terms of percentage suppression versus placebo , fluticasone propionate also produced greater effects ( means and 95 % CI for difference ) : budesonide 1600 micrograms ( 16.0 ) versus fluticasone propionate 1500 micrograms ( 40.9 ) ( 95 % CI -0.6 to 50.6 ) , budesonide 2000 micrograms ( 26.0 ) versus fluticasone 2000 micrograms ( 65.2 ) ( 95 % CI 10.5 to 67.8 ) . Individual serum cortisol levels at the two highest doses showed 15 of 24 patients below the normal limit of the reference range ( 150 nmol/l ) for fluticasone and five of 24 for budesonide . Fluticasone propionate also caused greater ACTH suppression than budesonide ( as % versus placebo ) : budesonide 1600 micrograms ( 12.0 ) versus fluticasone propionate 1500 micrograms ( 31.9 ) ( 95 % CI 7.6 to 32.1 ) , budesonide 2000 micrograms ( 13.5 ) versus fluticasone propionate 2000 micrograms ( 44.4 ) ( 95 % CI 13.2 to 48.7 ) . For overnight 10 hour urinary cortisol ( nmol/10 hours ) there was a difference between the lowest doses of the two drugs : budesonide 400 micrograms ( 37.2 ) versus fluticasone propionate 500 micrograms ( 19.9 ) ( 95 % CI 6.9 to 27.8 ) . CONCLUSIONS : Like budesonide the systemic bioactivity of fluticasone propionate is mainly due to lung vascular absorption . Fluticasone propionate exhibited at least twofold greater adrenal suppression than budesonide on a microgram equivalent basis in asthmatic patients 77 children , aged 11 to 36 months ( mean 24 ) with moderately severe recurrent wheezing , were treated with budesonide pressurised aerosol 400 micrograms twice daily or placebo for 12 weeks in a double-blind , parallel-group trial . Aerosols were inhaled from a spacer with a facemask . Budesonide significantly improved symptom scores of wheezing , sleep disturbance , and patient happiness . The frequency of severe exacerbations that required a course of oral prednisolone was also significantly reduced . The treatment effect appeared to be fully established after 6 - 8 weeks and no side-effects could be ascribed to the active treatment . The findings indicate that young children below 3 years of age can inhale a pressurised aerosol from a spacer with a facemask . Use of topically active glucocorticosteroids with this simple device may reduce symptoms and distress in young children with moderately severe recurrent wheeze and dyspnoea , and possibly reduce their requirement for oral steroids Acute episodic wheeze related to viral infections is a common and distressing condition and treatment remains unsatisfactory . Although some benefit from the continuous use of inhaled steroids has been demonstrated in young wheezy children , their effect primarily on acute episodes has not been considered . In this study the effect of budesonide ( 400 micrograms/day ) was assessed in a four month double blind parallel trial , in 41 children ( 0.7 - 6.0 years ) with predominantly episodic viral wheeze . Analysis of the last three months showed no difference between budesonide or placebo in mean daily total symptom score ( median values 0.6 and 0.63 ) , episode number ( mean values 2.6 and 2.4 ) , or score/episode ( mean value 30 and 31 ) . Four months of treatment with inhaled budesonide had no effect on acute episodes of wheeze in this group of children The objectives of this study were to compare the efficacy of salbutamol delivered by either metered-dose inhaler plus spacer ( MDI-spacer ) or by wet nebulization ( NEB ) , and to determine the relationships between physiologic responses and plasma salbutamol concentrations . Asthmatic patients presenting to the emergency department ( ED ) with acute severe asthma ( forced expiratory volume in the first second [ FEV1 ] less than 50 % of predicted ) were enrolled in a r and omized , double-blind , parallel-group study . The MDI-spacer group received salbutamol , delivered via MDI into a spacer device , in four puffs actuated in rapid succession at 10-minute intervals ( 2.4 mg/h ) . The NEB group was treated with nebulized salbutamol , 1.5 mg , via nebulizer at 15-minute intervals ( 6 mg/h ) . Doses were calculated on the basis of the percentage of total dose that reaches the lower airway with both methods . The protocol involved 3 hours of this treatment . Mean peak expiratory flow rate ( PEFR ) and FEV1 improved significantly over baseline values for both groups ( P=.01 ) . However , there were no significant differences between both groups for PEFR and FEV1 at any point studied . The examination of the relationships between cumulative dose of salbutamol and change in FEV1 showed a significant linear relationship ( P=.01 ) for both methods ( MDI r=.97 ; NEB r=.97 ) . The regression equations showed that for every 1 mg of salbutamol by MDI-spacer , 2.5 mg are needed from nebulization to have equal therapeutic response . At the end of treatment , the salbutamol plasma levels were 10.1+/-1.6 ng/ml for the MDI-spacer group and 14.4+/-2.3 ng/ml for the NEB group ( P=.0003 ) . Both groups showed a nonsignificant heart rate decrease . A significant group-by-time interaction means that differences between groups increased with time ( P=.04 ) . Additionally , the NEB group presented a higher incidence of tremor ( P=.03 ) and anxiety ( P=.04 ) , reflecting larger systemic absorption of salbutamol . These data indicate that when doses used are calculated on the basis of the percentage of total drug that reaches the lower airway , there was equivalent bronchodilatation after salbutamol administered by either MDI-spacer or nebulization in patients with acute severe asthma . However , nebulizer therapy produced greater side effects related to the increase in salbutamol absorption and higher plasma level In a controlled prospect i ve study we have measured growth and pulmonary function in children with asthma during long-term treatment with inhaled budesonide  and compared these findings with those obtained from children not treated with corticosteroids . Two hundred and sixteen children were followed at 6 monthly intervals for 1 - 2 years without inhaled budesonide and then for 3 - 6 years on inhaled budesonide .  Sixty-two children treated with theophylline , beta 2-agonists and sodium-cromoglycate but not with inhaled steroids were also followed for 3 - 7 years ( controls ) . During the period of budesonide therapy the mean daily dose decreased from 710 to 430 micrograms ( P < 0.01 ) and no signs of tachyphylaxis to the treatment were seen . Budesonide treatment was associated with a significant reduction in the number of annual hospital admissions due to acute severe asthma ( from 0.03 to 0.004 per child , P < 0.001 ) . In patients not treated with budesonide an annual decrease in % predicted FEV1 of 1 - 3 % was seen . In contrast FEV1 improved significantly with time during budesonide treatment , both compared with the run-in period and with the control group ( P < 0.01 ) . Furthermore , there was a significant ( P = 0.01 ) relationship between the duration of asthma at the start of budesonide and the annual increase in FEV1 during budesonide therapy . After 3 years of treatment with budesonide , children who started this therapy later than 5 years after the onset of asthma had significantly lower FEV1 ( 96 % ) than the children who received budesonide within the first 2 years after the onset of asthma ( 101 % ) ( P < 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND --High dose inhaled glucocorticosteroids are increasingly used in the management of patients with moderate to severe asthma . Although effective , they may cause systemic side effects .  Fluticasone propionate is a topically active inhaled glucocorticosteroid which has few systemic effects at high doses . METHODS --Fluticasone propionate , 1.5 mg per day , was compared with beclomethasone dipropionate at the same dose for one year in patients with symptomatic moderate to severe asthma ; 142 patients received fluticasone propionate and 132 received beclomethasone dipropionate .  The study was multicentre , double blind and of a parallel design . For the first three months patients attended the clinic every four weeks and completed daily diary cards . For the next nine months they were only seen at three monthly intervals in the clinic . RESULTS --During the first three months diary card peak expiratory flow ( PEF ) rate and lung function measurements in the clinic showed significantly greater improvement in patients receiving fluticasone propionate ( difference in morning PEF 15 l/min ( 95 % CI 6 to 25 ) ) , and these differences were apparent at the end of the first week . The improved lung function was maintained throughout the 12 month period and the number of severe exacerbations in patients receiving fluticasone propionate was reduced by 8 % compared with those receiving beclomethasone dipropionate . No significant differences between the two groups were observed in morning plasma cortisol levels , urinary free cortisol levels , or response to synthetic ACTH stimulation . In addition , both the rates of withdrawal and of adverse events were low , and there were fewer exacerbations of asthma with fluticasone propionate than beclomethasone dipropionate . CONCLUSIONS --This study shows that fluticasone propionate in a daily dose of 1.5 mg results in a significantly greater increase in PEF and asthma control than the same dose of beclomethasone dipropionate , with no increase in systemic or other side effects Increasing evidence suggests that cytokines play a role in airway inflammation by attracting and activating inflammatory cells . This may lead to epithelial cell damage and airway hyperresponsiveness . Bronchial provocative concentration of histamine causing a 20 % fall in forced expiratory volume in 1 second was measured in patients with mild asthma , and bronchial biopsy specimens were stained for granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , interleukin (IL)-8 , and activated eosinophils ( EG2 ) in the bronchial epithelium . The effect of inhaled beclomethasone dipropionate was also assessed in a placebo-controlled double-blind manner . There was a correlation between GM-CSF expression and EG2-staining cells ( r = 0.484 p < 0.05 ) in the epithelium . Provocative concentration of histamine causing a 20 % fall in forced expiratory volume in 1 second was correlated with GM-CSF expression ( r = -0.462 , p < 0.05 ) . Treatment with inhaled beclomethasone dipropionate 500 micrograms twice a day led to a significant decrease in both the expression of GM-CSF ( p < 0.01 ) and IL-8 ( p < 0.02 ) and the number of EG2-staining cells ( p < 0.01 ) in the epithelium . The changes in GM-CSF ( r = 0.798 , p < 0.01 ) and IL-8 ( r = 0.653 , p < 0.02 ) expression were correlated with the changes in EG2-staining cells after treatment . These results suggest that GM-CSF may influence eosinophil activation in the epithelium in vivo and participate in the etiology of bronchial hyperresponsiveness in mild asthma . Also , beclomethasone dipropionate may inhibit eosinophil activation partly by downregulating the expression of GM-CSF and IL-8 in the bronchial epithelium BACKGROUND The presence of airway inflammation even in mild asthma points to the potential value of antiinflammatory therapy . We compared the effect of an inhaled corticosteroid , budesonide , with that of an inhaled beta 2-agonist , terbutaline , in the long-term treatment of newly detected asthma . METHODS We studied 103 patients ( 29 male and 74 female patients 15 to 64 years old ) in whom asthma had appeared within the previous year . The patients were r and omly assigned in blinded fashion to two treatment groups : one to receive 600 micrograms of inhaled budesonide twice a day , and the other to receive 375 micrograms of inhaled terbutaline twice a day . The study period was two years . RESULTS After six weeks of treatment , the patients treated with budesonide  tolerated inhaled histamine  better than the patients treated with terbutaline ( a difference of one doubling dose step , P less than 0.001 ) , and the difference was sustained . Patients ' diaries kept during the first three months of the study and during the last month of the first and second years showed budesonide to be more effective than terbutaline in improving peak expiratory flow in the morning ( average increase from the pretreatment value , 32.8 liters per minute for budesonide vs. 4.8 liters per minute for terbutaline ; P less than 0.001 ) and in the evening ( P less than 0.01 ) . Budesonide was also more effective in reducing the symptoms of asthma ( P less than 0.01 ) and the use of supplemental beta 2-agonist medication ( P less than 0.01 ) . Ten patients were withdrawn from the terbutaline group because treatment was insufficiently effective , whereas only one dropped out of the budesonide group . The adverse reactions to both treatments were few and mild . CONCLUSIONS Antiinflammatory therapy with inhaled budesonide is an effective first-line treatment for patients with newly detected , mild asthma , and it is superior to the use of terbutaline in such patients The aim of this study was to compare the effects of salmeterol and beclomethasone on lung function and symptoms in children with mild to moderate asthma . Sixty-seven children not treated with inhaled corticosteroids were r and omized in a double-blind parallel study either to salmeterol 50 micrograms b.i.d . or beclomethasone 200 micrograms b.i.d . After one year , FEV1 significantly increased in the beclomethasone group , whereas in the salmeterol group there was a small reduction . Differences between groups were 14.2 % predicted ( p < 0.0001 ) and 7.0 % predicted ( p = 0.007 ) for pre- and postbronchodilator FEV1 values , respectively . PD20 methacholine decreased by 0.73 DD ( p = 0.05 ) in the salmeterol group and increased by 2.02 DD ( p < 0.0001 ) in the beclomethasone group . Morning and evening PEF and symptom scores improved in both groups , although more in the beclomethasone group . Asthma exacerbations , for which prednisolone was needed , were more frequent in the salmeterol group ( 17 versus two ) , as were the number of withdrawals due to exacerbations ( six versus one ) . However , growth was significantly slower in the beclomethasone group ( -0.28 SDS ) compared with that in the salmeterol group ( -0.03 SDS ) ( p = 0.001 ) . We conclude that treatment with a moderate dose of beclomethasone is superior to salmeterol in children with mild to moderate asthma and recommend that salmeterol should not be used as monotherapy Airways hyperresponsiveness is a hallmark of asthma , and many patients with COPD also demonstrate hyperresponsiveness . Inhaled corticosteroids improve hyperresponsiveness , but the extent of improvement may vary considerably between patients . This study was design ed to determine which patient characteristics predict these differences in response . Patients with mild to moderately severe obstructive airways disease ( asthma and COPD ) were selected if PC20 < or = 8 mg/ml and FEV1 < 95 % confidence interval of predicted normal . They were followed for 2.5 yr , during which one-third received  inhaled corticosteroids . The independent influences of baseline FEV1/IVC , bronchodilator response , PC20 , smoking habits , allergy , age , and sex on the improvement in airways hyperresponsiveness with inhaled corticosteroids were analyzed . Total serum IgE was taken as a parameter of allergy , next to specific IgE for house dust mite , skin tests , and blood eosinophils . Total serum IgE was found to be the most important and single independent predictor of change in PC20 with inhaled corticosteroids : patients with a higher IgE had a greater increase in PC20 when administered inhaled corticosteroids than those with lower IgE levels . Alternatively , patients with a higher IgE who did not receive corticosteroids had a decrease in PC20 compared with patients with a lower IgE. This effect was most prominent in asthma but was inconsistent in asthmatic bronchitis and COPD . The level of IgE can not be used to predict the response to inhaled corticosteroids in individuals accurately . Total serum IgE is the single most important predictor of change in PC20 with and without inhaled corticosteroids . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of this study was to investigate the effect of inhaled budesonide on modifications of the provocative concentration of agonist causing a 20 % fall in forced expiratory volume in one second ( FEV1 ) ( PC20 ) and maximal response plateau to inhaled methacholine during the pollen season in pollen-sensitive subjects with mild asthma . The effects of inhaled budesonide ( 800 micrograms.day-1 ) on the threshold value ( PC20 ) and maximal response plateau to inhaled methacholine were studied in 28 pollen-sensitive subjects with mild asthma during a pollen season in a r and omized , double-blind , placebo-controlled parallel fashion . They were challenged with methacholine ( up to 200 mg.ml-1 ) in February ( preseasonal assessment ) and during the middle of the pollen season ( in May and again in June ) . Subjects treated with budesonide ( n = 13 ) were protected from the decrease in PC20 seen in the placebo ( n = 15 ) group ( geometric mean PC20 placebo group : preseasonal = 8.51 , May = 2.19 and June = 1.78 mg.ml-1 ; budesonide group : preseasonal = 3.71 , May = 3.23 and June = 2.40 mg.ml-1 ; intergroup differences in doubling concentrations , p < 0.05 ) . Among 10 subjects in the placebo group who reached plateau during the preseasonal assessment , seven lost the plateau in May and six in June . In the budesonide group , among seven subjects who reached plateau during the preseasonal assessment , three lost the plateau in May and four in June . Between-group differences were not significant . We conclude that in pollen-sensitive subjects with mild asthma , inhaled budesonide blocks the effects of natural allergen exposure on the methacholine threshold value . ( ABSTRACT TRUNCATED AT 250 WORDS Bloodspot cortisol , where finger pricked blood is applied to blotting paper , is suitable for repeated measurements in the home environment . The use of bloodspot cortisol measurements in children with asthma and the effect of inhaled corticosteroids on daytime cortisol concentrations were assessed . Twenty children with mild asthma were r and omised to receive double blind either placebo or beclomethasone dipropionate 200 micrograms twice daily . Blood was taken by finger prick at home on waking , and treatment administered . Blood was then taken one hour after treatment , at lunchtime , and in the evening . The area under the curve ( AUC ) for the four time points was calculated as a composite index of daytime cortisol . Mean ( SEM ) bloodspot cortisols fell progressively over the day from 199.2 ( 15.6 ) nmol/l to 58.4 ( 8.9 ) nmol/l . Cortisol in the group treated with beclomethasone dipropionate  was lower at all time points , but was significant only after treatment ( mean ( SEM ) 120.9 ( 14.3 ) v 177.5 ( 21.0 ) nmol/l ) and at lunchtime ( mean ( SEM ) 82.7 ( 12.4 ) v 128.9 ( 12.6 ) nmol/l ) . AUC for the beclomethasone dipropionate treated group was also significantly decreased ( mean ( SEM ) 317 ( 31.4 ) v 446 ( 29.7 ) ) . Beclomethasone dipropionate at a dose of 400 micrograms/day significantly suppresses the daytime cortisol profile OBJECTIVES : To determine the relationship between biochemical markers of bone metabolism and statural growth , and their suitability as surrogate markers of inhaled corticosteroid induced growth suppression . DESIGN : R and omised , double blind , placebo controlled comparison of inhaled beclomethasone dipropionate 200 micrograms twice daily as dry powder for six months . SETTING : Southampton . OUTCOME MEASURES : Serum osteocalcin , urinary deoxypyridinoline , and statural growth . SUBJECTS : 7 to 9 year old children with recurrent wheeze . RESULTS : There were no significant differences in serum osteocalcin between the beclomethasone dipropionate and placebo group measured at baseline or after three and six months ' treatment , while deoxy-pyridinoline was significantly higher in the placebo treated children after three months . Growth was significantly decreased in the beclomethasone dipropionate group over the course of the study . Growth over the six months , both in those receiving beclomethasone dipropionate and those receiving placebo , was significantly correlated with serum osteocalcin measured at three months and six months . CONCLUSION : Although serum osteocalcin shows excellent correlation with growth , it is a poor marker for decreased growth associated with use of inhaled corticosteroids Height and weight were measured every six months in a long term prospect i ve study of 66 children with chronic perennial asthma for a mean 13.1 years . There was no evidence of growth retardation on entry into the study . Growth developed along normal lines in all 66 children until about 10 years , and in 35 of these children growth continued along normal lines throughout the whole period of follow up . Thirty children showed the physiological decelerating growth velocity pattern seen in children with delay in the onset of puberty , and one child had an early menarche . The tendency for delay in the onset of puberty was significant for both boys and girls and was noted to be independent of severity of asthma . Once puberty finally began in these children , complete catch up growth result ed in the attainment of the predicted adult height . Long term prophylactic inhalation of beclomethasone dipropionate in 26 children in a dosage up to 600 mcg/day before puberty and 400 mcg/day during puberty was shown not to affect growth . It is concluded that asthma had no direct influence on growth in height but was associated with delay in the onset of puberty . The pre-adolescent physiological deceleration of growth velocity that occurs in these children gives the impression of growth retardation In a double-blind crossover trial a new corticosteroid aerosol , budesonide , delivered by spacer inhaler twice daily , was found to be at least as effective in controlling  childhood asthma  as beclomethasone dipropionate administration four times a day . The twice daily dosage schedule of the new preparation offers considerable advantages for compliance with therapy in schoolchildren . Previous studies have shown that lung deposition of aerosol is increased by the use of a tube spacer between the pressurised aerosol inhaler and the mouth . This technique of administration may improve the efficacy of corticosteroids in the treatment of asthma The growth of 50 children receiving regular inhaled corticosteroids  was segregated into divisions of six weeks from the start of treatment and compared with their growth when not receiving regular corticosteroids using a r and om effects regression model . Growth suppression was most marked during the initial six weeks after starting treatment , with most suppression occurring during the initial 18 weeks . Thereafter the children ’s growth was similar to their growth when not receiving treatment . These findings have important consequences for patterns of treatment of asthma in children Studies using dry powder devices have suggested that fluticasone propionate ( FP ) has a greater systemic effect than budesonide ( BUD ) . The aim of the present study was to investigate and compare the relative systemic potency of FP and BUD from their respective pressurized metered-dose inhalers ( pMDIs ) . A placebo-controlled , open , r and omized , cross-over study was conducted in 21 healthy male volunteers .  Placebo , BUD ( 200 , 400 and 1,000 micrograms b.i.d . ) and FP ( 200 , 375 and 1,000 micrograms b.i.d . ) were inhaled for 4 days , with a wash-out period of at least 3 days between treatments . Blood sample s for cortisol analysis were drawn during the last 24 h of each treatment period . Cortisol levels , measured as 24 h pooled plasma cortisol , were statistically significantly lower ( p = 0.0001 ) for all dose levels during FP pMDI treatment ( 21 , 39 and 84 % suppression from placebo ) than during BUD pMDI treatment ( 1 , 3 and 27 % suppression from placebo ) . The relative systemic potency  FP : BUD was 3.7:1 ( 95 % confidence interval ( 95 % CI ) 2.9 - 4.8 ) ) . The relative systemic potency based on the single 08:00 h sample s was 5.2:1 ( 95 % CI 3.0 - 9.3 ) . In conclusion , in healthy male volunteers using pressurized metered-dose inhalers , fluticasone propionate was shown to have a stronger systemic effect than budesonide ACKGROUND -- Systemic absorption of inhaled corticosteroids may adversely influence the function of the hypothalamo-pituitary-adrenal axis , bone metabolism , and circulating leucocytes . These changes can be used to assess the safety of different types and modes of administration of these drugs . METHODS --The study was a r and omised , double dummy , crossover design with nine healthy adults . It compared the effects of beclomethasone dipropionate and budesonide ( given by metered dose aerosols with and without their respective large volume spacers ( Volumatic and Nebuhaler ) attached ) on serum cortisol , 24 hour urinary free cortisol , and plasma osteocalcin concentrations , and circulating neutrophils and lymphocytes . Subjects inhaled the drug ( 1 mg ) and matching placebo at 0900 and 2200 hours on each of six study days . Blood sample s were taken hourly for six hours after the morning dose and at the end of the study period . RESULTS --All results were within the reference ranges . Both drugs caused similar reductions in serum cortisol four to six hours after inhalation . These changes were not affected by the use of a large spacer and did not persist at 24 hours . Use of spacers tended to increase the haematological effects of the steroids . Beclomethasone dipropionate inhaled through a Volumatic provoked a rise in circulating neutrophils compared with placebo although lymphocyte numbers were unaffected . Budesonide did not influence neutrophil numbers but did reduce circulating lymphocytes , numbers of which were further reduced when the Nebuhaler was used . There were no significant changes in plasma osteocalcin concentration or 24 hour urinary free cortisol excretion with budesonide , with or without a spacer . Beclomethasone dipropionate inhaled without a spacer reduced urinary cortisol and plasma osteocalcin at 24 hours ; however , use of the Volumatic protected against these effects . CONCLUSIONS --Attaching a Volumatic reduces the systemic effects of 2 mg aerosol beclomethasone dipropionate on the hypothalamo-pituitary-adrenal axis and circulating osteocalcin concentrations . This study did not establish whether the Nebuhaler reduces the systemic effects of budesonide . When large spacers are used , 2 mg per day of beclomethasone dipropionate and budesonide seem to be equivalent in terms of unwanted effects The aim of this study was to compare accurately measured growth over 12 months in asthmatic children treated with either fluticasone propionate ( FP ) 50 micrograms twice daily ( b.i.d . ) or sodium cromoglycate ( SCG ) 20 mg four times daily ( q.i.d . ) . After a 2-week run-in , asthmatic children aged 4 - 10 years from 15 UK centers were r and omized in a 3:4 ratio to open-label FP ( n = 52 ) or SCG ( n = 70 ) . After 8 weeks , those whose asthma was not adequately controlled were switched from SCG to FP or withdrawn .  St and ing height was measured ( Holtain stadiometry ) at baseline , after 8 weeks and at 6 weeks intervals thereafter for 1 year . Morning peak flows ( PEFam ) were recorded by patients for 2 weeks during baseline , and 1 week before each visit during treatment . Urinary free cortisol ( 24 h ) was measured at baseline , 6 months , and 1 year . After 8 weeks , 22 patients were withdrawn from SCG group ( and were switched to FP ) , and five patients were withdrawn from the FP group due to poor asthma control  . A further 21 and 11 patients were withdrawn from the SCG and FP groups , respectively , during the course of the study . There were no significant differences between patients who received FP and SCG for 1 year ( n = 34 and n = 26 , respectively ) in terms of height velocity adjusted for age and gender ( HV ) , or height velocity st and ard deviation scores adjusted for gender ( HVSDS ) . Mean HV ( mean HVSDS ) were 6.0 cm/yr ( 0.1 ) and 6.5 cm/yr ( 0.5 ) for FP and SCG , respectively . There were no treatment differences in mean 24 h urinary free cortisol levels at 6 and 12 months . Mean % predicted PEFam improved over 1 year in both groups but to a greater degree in the FP group . We concluded that growth was normal in mildly asthmatic children receiving FP ( 50 micrograms bid ) for 1 year . There were fewer withdrawals and lung function improved to a greater extent in FP treated patients than in patients receiving SCG A compound consisting of a beta-stimulant , salbutamol ( Ventolin ; Allen & Hanburys ) ( 100 micrograms/puff ) , and a steroid , beclomethasone dipropionate ( Becotide ; Allen & Hanburys ) ( 50 micrograms/puff ) , was studied to test the hypothesis that the corticosteroid could enhance the bronchodilator properties of the beta-stimulant during chronic asthma and simulated acute attacks ( antigen challenge ) . Conventional doses ( 200 micrograms and 100 micrograms of salbutamol and beclomethasone respectively ) were compared using a schedule which included a second administration 1 hour later . The results obtained on the baseline bronchial responsiveness of chronic asthmatics  and during the delayed asthmatic response ( simulated acute asthma ) were similar . The compound was as effective as salbutamol alone but not more so . A significantly greater bronchodilator response was recorded in all patients after the second administration of both the compound and salbutamol alone . The practical advantages of having one rather than two inhalers are evident , but the appropriate application of this compound agent , probably in a prophylactic role , must be defined In a double-blind , r and omized , parallel-group clinical trial , 340 asthmatic patients aged 12 - 70 years received budesonide 400 micrograms once daily in the morning , budesonide 400 micrograms once daily in the evening , budesonide 200 micrograms twice daily or placebo , for 12 weeks in addition to inhaled short-acting beta 2-agonists used as required ( p.r.n . ) . Budesonide was given as Pulmicort Turbohaler .  Peak expiratory flow rate ( PEFR ) increased by 20 to 30 1 min-1 in each of the active treatment groups , significantly more than in the placebo group ( P < 0.01 ) . There were no significant differences between the active treatment groups . Symptom improvement and decreased beta 2-agonist use reflected the PEFR data . Incidences of adverse events in the active treatment groups were similar to those observed in the placebo group . Budesonide 400 micrograms given once daily morning or evening is equieffective with the same total daily dose given twice daily in the treatment of mild to moderate stable asthmatics With mucosal inflammation contributing to the pathogenesis of asthma , it is increasingly accepted that long term steroid inhalers may induce remission in chronic long st and ing asthmatics . The present study involved 44 stable asthmatics who were r and omly given either beclomethasone dipropionate inhaler ( 50 ug ) 2 puffs qds or salbutamol inhaler ( 100 mcg ) 2 puffs tds in addition to their oral bronchodilators . Pulmonary function testing , bronchoalveolar lavage and complete blood count were done at basal and weekly intervals and at the end of the study . The absolute eosinophil count showed a significant drop in the beclomethasone group as compared to the salbutamol group . Serial lung functions showed a significant improvement in the pre-bronchodilator PEFR and the pre-bronchodilator FVC in the beclomethasone group as compared to the salbutamol group . There was no significant change in the lavage eosinophil count pre and post-bronchodilator in both groups . Steroid inhalers are thus useful in long term management of bronchial asthma especially with respect to reducing bronchodilator requirement The relative  prednisolone-sparing effects of inhaled budesonide 400 micrograms daily and beclomethasone dipropionate ( BDP ) 400 micrograms daily were compared in a double-blind crossover study of 26 patients with chronic asthma requiring treatment with BDP and oral prednisolone in a daily dose of 5 mg or greater . During each period of the trial budesonide and BDP were inhaled via conventional pressurized inhalers in a dose of 100 micrograms four times daily . Prednisolone was reduced by 1 mg per month from the patient 's normal maintenance dose to zero or to the point at which asthmatic symptoms became unacceptable . The mean reduction in prednisolone dose during BDP treatment was 2.65 mg compared with 1.8 mg at the end of the budesonide period . The difference between the  prednisolone-sparing properties of BDP and budesonide assessed in this way in this group of patients was statistically significant in favour of BDP . The mean minimum prednisolone doses at the end of the treatment periods were 3.46 mg for BDP and 4.3 mg for budesonide . Since inhaled steroids were not withdrawn the absolute  prednisolone-sparing properties of the two drugs were not assessed , and thus a pharmacological potency ratio can not be derived from the results . It is concluded that BDP is marginally more potent than budesonide in its prednisolone-sparing properties The effect of triamcinolone acetonide aerosol upon exercise-induced asthma was compared with that of placebo in a double-blind , crossover study in 11 asthmatic children . Measurement of pulmonary function before and after treatment and before and after exercise disclosed inhibition of exercise-induced asthma in only three of nine children in whom exercise after inhalation of placebo caused bronchospasm In a r and omized double-blind multicenter clinical study , 116 children with asthma were r and omly assigned to treatment with an inhaled beta-2-agonist ( salbutamol 0.2 mg ) plus an inhaled corticosteroid ( budesonide 0.2 mg ) three times a day ( BA+CS ) or to an inhaled beta-2-agonist ( salbutamol 0.2 mg ) plus a placebo three times a day ( BA+PL ) . After a median follow-up time of 22 months , 26 patients receiving BA+PL ( 45 % ) had withdrawn from r and omized treatment , mainly because of asthma symptoms , compared with three withdrawals in the patients receiving BA+CS ( p less than 0.0001 ) . The FEV1 , expressed as a percentage of the predicted value for age , sex , and height , showed an absolute increase of 7.0 % after 2 months of BA+CS compared with a decrease of 4.0 % after 2 months of BA+PL . This 11 % difference in percent predicted FEV1 ( 95 % confidence interval , 7 to 15 % ; p less than 0.0001 ) was then maintained after a median follow-up period of 22 months . Postbronchodilator FEV1 showed an absolute increase of 3.7 % predicted within 2 months in patients receiving BA+CS and an absolute decrease of 1.1 % predicted in children receiving BA+PL ( p = 0.0005 ) . Thereafter , this difference between the two treatment groups was maintained . Average peak expiratory flow rate ( PEFR ) increased from baseline by 36.6 L/min in the BA+CS group compared with 3.7 L/min in the BA+PL group ( p = 0.003 ) . This difference then remained for the median follow-up time of 22 months . ( ABSTRACT TRUNCATED AT 250 WORDS Background Dendritic cells ( DC ) are the most potent antigen‐presenting cells ( APC ) and stimulators of T cells . Dendritic cells are also likely to be essential for the initiation of allergic immune responses in the lung . However , there are not many data on the presence of dendritic cells in the airways of patients with atopic asthma and on the effects of corticosteroid‐treatment  on such dendritic cells This study was design ed to compare the efficacy and safety of a new inhaled corticosteroid , fluticasone propionate at a total daily dose of 200 micrograms , with beclomethasone dipropionate 400 micrograms/day in childhood asthma . A total of 398 asthmatic children ( aged 4 - 19 years ) were r and omised to receive either fluticasone propionate 200 micrograms daily or beclomethasone dipropionate 400 micrograms daily for six weeks inhaled via a spacer device from a metered dose inhaler . During the study the patients recorded morning and evening peak expiratory flow rate ( PEFR ) , symptom scores , and use of beta 2 agonist rescue medication . In addition , clinic visit PEFR and forced expiratory volume in one second were measured . Safety was assessed by recording all adverse events and by performing routine biochemistry and haematology screens including plasma cortisol concentration before and after treatment . For the purpose s of analysis the diary card data were grouped into three periods : week 3 ( days 15 - 21 ) , week 6 ( days 36 - 42 ) , and weeks 1 - 6 ( days 1 - 42 ) . The results showed no significant difference between treatments on most efficacy parameters . However , there were significant differences in changes from baseline in favour of fluticasone propionate for % predicted morning PEFR both at week 3 ( fluticasone propionate 6.1 % , beclomethasone dipropionate 3.9 % ) and at week 6 ( fluticasone propionate 8.3 % , beclomethasone dipropionate 5 . 9 % ) and % predicted evening PEFR at week 6 ( fluticasone propionate 7.3 % , beclomethasone dipropionate 4.9 % and over weeks 1 - 6 ( fluticasone propionate 5.5 % , beclomethasone dipropionate 3.6 % . Comparison between groups showed that the group receiving fluticasone propionate had a lower % of days with symptom-free exercise at week 6 ( fluticasone propionate 87 % , beclomethasone dipropionate 81 % ) and % days without rescue medication at week 6 ( fluticasone propionate 87 % , beclomethasone dipropionate 80 % ) and over weeks 1 - 6 ( fluticasone propionate 80 % , beclomethasone dipropionate 73 % ) . Except for a higher incidence of sore throat in the fluticasone propionate group , the two treatments did not differ with regard to safety . There was no evidence of adrenal suppression with either treatment . In conclusion , fluticasone propionate 200 microgram daily ws at least as effective and as well tolerated as beclomethasone dipropionate 400 microgram daily in childhood asthma Inhaled corticosteroids are most effective drugs currently available for the treatment of bronchial asthma . They have been shown to reduce airway inflammation and hyperresponsiveness . The aim of this study was to assess the preventive effect of inhaled steroid therapy in seasonal asthma . In a double-blind study , two groups of 10 allergic asthmatics were r and omly assigned to receive inhaled beclomethasone dipropionate ( BDP ) , 500 micrograms b.i.d . , or a matched placebo , two puffs b.i.d . The patients used inhaled salbutamol as needed . At the beginning of the study , and every month between February and June , the following parameters were assessed : lung function ( forced expiratory volume in one second ( FEV1 ) ; airway responsiveness ( provocative dose of methacholine producing a 20 % fall in forced expiratory volume in one second ( PD20 ) ) , serum eosinophil cationic protein ( ECP ) ; and blood eosinophil count . All subjects recorded daily asthma symptoms , beta 2-agonist consumption and peak expiratory flow ( PEF ) values . In the placebo group , all parameters except FEV1 worsened significantly during the pollen season compared with preseasonal values ( p < 0.001 ) . BDP produced complete protection , although a slight change from baseline was found for symptom score ( p < 0.01 ) , beta 2-agonist consumption ( p < 0.01 ) , and eosinophil number ( p < 0.05 ) in May , when the pollen load was highest . These data provide evidence that beclomethasone dipropionate treatment is able to inhibit the seasonal changes occurring during natural exposure in asthmatics . This preventive effect is probably due to the anti-inflammatory action of beclamethasone dipropionate , as documented by its effect on serum markers of airway inflammation Because biological indicators alone do not adequately represent the comprehensive health status of a patient with asthma , we also assessed patients ' health-related quality of life ( HRQOL ) in a r and omized , double-blind , placebo-controlled study of the effects of the inhaled corticosteroid fluticasone propionate ( FP ) . A total of 342 patients with moderate asthma were treated twice daily for 12 weeks with FP powder ( 50 , 100 , or 250 micrograms ) or placebo . At regular intervals , patients completed the Medical Outcomes Study Short Form-36 , acute version ( SF-36A ) , a general health status question naire measuring eight dimensions of HRQOL ; the 20-item Living with Asthma ( LWA-20 ) question naire , a disease-specific instrument measuring HRQOL ; and three additional questions related to sleep loss and number of nighttime awakenings . Each of the three FP groups compared with placebo had significantly higher scores at study endpoint on the Physical Functioning ( p < 0.001 ) and Role-Physical ( p < or = 0.0001 ) dimensions of the SF-36A ; the FP 100- or 250-micrograms groups compared with placebo also had significantly higher scores on General Health Perceptions ( p < 0.03 ) , Vitality ( p < 0.007 ) , and Mental Health ( p < 0.02 ) . At endpoint , all three FP groups compared with placebo had significantly better scores on the LWA question naire ( p < 0.05 ) and on the sleep-related items ( p < 0.0001 ) . These data , collected using both a general health status question naire and an asthma-specific question naire , demonstrate that fluticasone propionate powder can improve HRQOL in patients with mild-to-moderate asthma BACKGROUND Patients with asthma who have moderate to severe airway hyperresponsiveness often demonstrate progressive , unlimited airway narrowing in response to inhaled bronchoconstrictor stimuli , which is likely to be due to inflammatory changes within the airway wall . It is unknown whether regular therapy with inhaled steroids can limit this excessive response . OBJECTIVE We investigated the effect of inhaled budesonide on the development of a plateau on the dose-response curve to methacholine in patients with asthma who did not show such a plateau before the study . METHODS Thirty-one atopic patients with asthma ( age , 19 to 31 years ; FEV1 > 70 % of predicted value ; PC20 < 8 mg/ml ) with documented absence of a maximal-response plateau to methacholine on two occasions during the run-in period , participated in a double-blind , placebo-controlled , parallel study . St and ardized methacholine challenges were performed at -1 , 0 , 4 , 8 , and 12 weeks of treatment with inhaled budesonide , 800 microg two times a day , or corresponding placebo , and after a 2-week washout period . Airway response was measured by FEV1 ( percent fall from baseline ) . A maximal-response plateau was considered if three or more consecutive data points fell within a 5 % response range . RESULTS Thirty patients completed the study . There was a steady increase in the number of budesonide-treated patients exhibiting a maximal-response plateau on the dose-response curve from zero of 15 patients at run-in to nine of 14 patients at week 12 , as compared with four of 16 patients in the placebo group ( p = 0.03 , chi square test ) . This was accompanied by a significant improvement in PC20 in the budesonide group as compared with the placebo group ( p < 0.01 at week 12 ) , whereas the changes in FEV1 were not significantly different between the groups ( p = 0.77 at week 12 ) . CONCLUSION Regular treatment with the inhaled corticosteroid budesonide limits maximal airway narrowing in response to methacholine by introducing a plateau on the dose-response curve in patients with asthma , who were initially characterized by the absence of a plateau . This indicates that inhaled steroids are likely to reduce the hazard of unlimited airway narrowing in asthma OBJECTIVE To compare the benefits and adverse reactions of theophylline and beclomethasone ( BDP ) in the long-term control of mild to moderate chronic asthma in children . DESIGN Multicentered , double-blind , double-placebo , r and omized , controlled trial . PATIENTS One hundred ninety-five children between the ages of 6 and 16 years with mild to moderate asthma . INTERVENTION Treatment with either BDP , 84 micrograms four times a day , or sustained-release theophylline administered twice daily in doses adjusted for optimum control of symptoms . MAIN OUTCOME MEASURES Daily diary record of symptoms , peak flow rates , supplemental bronchodilator and glucocorticoid treatment , doctor and hospital visits , absence from work and school , and side effects . RESULTS Aerosol BDP and sustained-release theophylline were effective primary treatments for mild to moderate chronic asthma . Beclomethasone result ed in comparable symptom control with less bronchodilator use and fewer courses of systemic steroids than did theophylline .  Side effects were observed significantly more frequently with theophylline than with BDP .  Growth velocity suppression was noted with BDP and was more pronounced in boys . Suppression was not associated with alterations in cortisol measurements either at baseline or following stimulation . CONCLUSION Both theophylline and BDP are effective therapy for mild to moderate asthma . Caution must be used with the administration of  BDP in children because of possible growth velocity suppression We compared nebulised beclomethasone dipropionate suspension against placebo in 16 children with moderately severe asthma in double blind crossover fashion . Three children withdrew due to deterioration while on placebo .  Of the remaining 13 , eight were better on beclomethasone and five on placebo . These trends in favour of nebulised beclomethasone were not significant and do not suggest that the suspension is as effective as inhaled powder or aerosol topical steroid formulation 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 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 Inhaled corticosteroids are considered to be effective and safe to treat children with asthma . These drugs , often used as maintenance treatment , can , however , influence the HPA-axis , which might be reflected by the serum and urine cortisol concentration . The aim of the present study was to investigate the efficacy and safety of fluticasone propionate ( FP ) 100 microg administered twice a day via a Diskhaler for 3 mo . FP was tested in a double-blind r and omized placebo-controlled parallel trial in a group of 34 children with moderate asthma who did not use inhaled steroids for at least 4 wk prior to the study . At home , symptoms and peak flow recordings ( PEFR ) were noted in a diary . At each visit lung function was measured , and serum and urinary cortisol were determined . During treatment , wheezing decreased and PEFR values increased in the FP group . FEV1 and PC20-histamine increased and the reversibility decreased in the FP group . All changes were significant , with the exception of the change in nocturnal PEFR . Four weeks after cessation of FP all parameters returned to pretreatment values . Serum cortisol did not change significantly in either treatment group . The decrease in urinary cortisol in the FP group was significant only if it was compared with the increase in urinary cortisol in the placebo group . We conclude that FP 100 microg given twice a day is effective in children with moderate stable asthma .  Suppression of the HPA-axis by FP 100 microg given twice daily , although not likely , can not be ruled out by this study since the absence of a significant decrease in urinary cortisol in the FP group could be due to an insufficient number of patients . Additional studies are required to solve this problem The effect of prolonged inhaled corticosteroid treatment on bronchial immunopathology was assessed in 25 nonsmoking mildly asthmatic subjects previously receiving intermittent inhaled beta 2-agonist alone .  Inhaled beclomethasone dipropionate ( BDP ) , 500 micrograms twice per day or placebo was administered for 4 mo in a double-blind parallel group study . Histamine bronchial provocation , fiberoptic bronchoscopic biopsy  , and  bronchoalveolar lavage ( BAL ) were performed before and after treatment . There was no difference in bronchial responsiveness or lung function between groups . In patients treated with BDP compared with placebo , there was a significant reduction in toluidine blue-staining mast cells ( p = 0.028 ) and total ( p = 0.005 ) and activated eosinophils ( p = 0.05 ) in biopsies but no difference in eosinophils or eosinophil cationic protein in BAL . Granulocyte-macrophage colony-stimulating factor expression was significantly reduced in the bronchial epithelium , and the thickness of Type III collagen deposition in the bronchial lamina reticularis reduced from 29.7 + /- 4.4 to 19.8 + /- 3.4 microns ( mean + /- 95 % confidence interval ) ( p = 0.04 ) . No change in helper or activated helper T cells occurred . Prolonged BDP treatment reduces inflammatory infiltration , proinflammatory cytokine expression , and subepithelial collagen deposition , a recognized abnormality in asthma We retrospectively studied the use of inhaled corticosteroids in patients who experienced near fatal episodes ( NFE ) to determine whether such therapy reduces the risk of death .  Forty-eight patients who had near fatal episodes of asthma between January 1981 and December 1989 were divided into two groups . Group A comprised 19 patients who received beclomethasone dipropionate ( BDP ) daily ( mean dose of BDP:687 micrograms/day : 200 - 2,000 ) following NFE , and Group B , 28 patients who did not take BDP or who took less than 6 mg BDP/month . During the follow-up period ( Group A:82.9 months , Group B:66.2 months ) , no patients in Group A died , but eight deaths occurred in Group B ( mean period between near fatal episode and death was 31.5 months : 12 - 66 ) . These results suggest that the regular use of inhaled corticosteroids , even at low doses , may reduce the risk of death in patients who experience NFE A community based , prospect i ve study of the value of high dose inhaled therapy for the reduction of the morbidity of asthma has been undertaken . One hundred and sixty adults with airflow obstruction were treated for up to 9 months with increasing doses of salbutamol . Two thirds of the patients also received increasing doses of beclomethasone dipropionate in a ' partially double-blind ' manner . The FEV1 rose by at least 10 per cent of that predicted in one third of the total patients and the overall mean domiciliary peak expiratory flow rates rose by approximately 50 l/min-1 . All chronic symptoms were abolished in half of the patients and acute attacks of asthma in the majority . Asthma was controlled in a greater proportion of patients more effectively and rapidly by a combination of inhaled steroids and beta agonist than by salbutamol alone , particularly when inhaled steroids were started in relatively high dosage We studied the usefulness of 24 weeks of therapy with inhaled beclomethasone dipropionate ( BDP ) in the management of mild and moderately severe asthma in adults . To determine the optimal dose and treatment duration , the patients were divided into three groups . Patients in group I ( n = 10 ) were treated with bronchodilators but no BDP .  Patients in group II ( n = 12 ) received bronchodilators and 450 micrograms/day of BDP .  Patients in group III ( n = 17 ) received bronchodilators and 900 micrograms/day of BDP . BDP was inhaled via a large spacer ( Volumatic ) . Asthma scores were measured before treatment began , and again every 2 weeks for the duration of the study ( 26 weeks ) . Peak expiratory flows ( PEF ) were measured before treatment began , 2 weeks after treatment had begun , and again every four weeks until the end of the study . Vital capacity , FEV1 , and bronchial reactivity to methacholine were measured before treatment began , and again 12 weeks and 24 weeks after it had begun . Adrenocortical function in patients in group III was measured with a rapid ACTH test , at the same time as the pulmonary functions were measured . The results were : 1 ) Asthma scores decreased more in patients who received the higher dose of BDP than in those who received the lower dose , especially during the second 12 weeks . 2 ) After two weeks of treatment , % PEF had increased significantly in both groups that received BDP , but after six weeks of treatment there was no further improvement . % PEF did not improve in the group given bronchodilators only . 3 ) In the patients whose baseline % PEF was less than 80 % , only the higher dose of BDP significantly increased % PEF . 4 ) Only the higher dose of BDP increased the % VC , the FEV1 % , and the PD20 for methacholine . 5 ) Asthma type and severity were not related to the usefulness of BDP therapy . 6 ) Results of the rapid ACTH test indicated that the higher dose of BDP did not suppress adrenocortical function . These data indicate that 900 micrograms of BDP per day is more effective than 450 micrograms/day as initial therapy for long-term management of mild or moderate asthma in adults , and that the dose of BDP should be review ed after 3 months of treatment . Patients in whom asthma is well-controlled may tolerate a reduction in dose , and those in whom asthma is not well-controlled may require a higher dose BACKGROUND The inhaled corticosteroid , fluticasone propionate , was compared with the oral bronchodilator theophylline in the maintenance treatment of asthma . OBJECTIVE The objective of the present study was to compare the efficacy and safety of twice-daily inhaled fluticasone propionate , 50 micrograms , and fluticasone propionate , 100 micrograms , with that of theophylline in the maintenance treatment of mild-to-moderate asthma . METHODS In this r and omized , double-blind , placebo-controlled , parallel-group study , 353 adult and adolescent patients with asthma inadequately controlled with inhaled beta-agonist therapy alone received fluticasone propionate , 50 micrograms , or fluticasone propionate , 100 micrograms , by metered-dose inhaler ; theophylline capsules ; or placebo twice daily for 12 weeks . Only inhaled albuterol was permitted as needed for acute symptoms . RESULTS Both fluticasone propionate groups had a significantly greater probability of remaining in the study ( ie , meeting asthma stability criteria ) than did either the theophylline or placebo group ( P < or = .008 ) ; 39 % and 51 % in the theophylline and placebo groups , respectively , were withdrawn due to lack of treatment efficacy compared with 14 % and 21 % in the fluticasone propionate , 50 micrograms , and fluticasone propionate , 100 micrograms , groups . Both fluticasone propionate groups experienced significantly greater improvement in FEV1 and PEF compared with patients in the theophylline or placebo group ( P < or = .004 ) . The incidence of potentially drug-related adverse events was significantly greater in the theophylline group ( 25 % ) than in the placebo group ( 11 % ) ( P = .031 ) , while there were no differences between placebo and fluticasone propionate , 50 micrograms , ( 18 % ) or fluticasone propionate 100 micrograms , ( 22 % ) . CONCLUSION Twice daily treatment with inhaled fluticasone propionate 50 micrograms or 100 micrograms was significantly more effective than theophylline in the treatment of mild-to-moderate asthma Twenty nine young children with severe recurrent asthma were given nebulised beclomethasone dipropionate or normal saline in a double blind manner over a six month period . Progress was monitored using diary score cards . Those receiving beclomethasone had lower symptom scores , had more symptom free days , and required less additional treatment with bronchodilator agents . The code needed to be broken more frequently if normal saline was used . Over the study period height and weight increases in the two groups were similar , and no serious side effects were noted BACKGROUND The institution of inhaled corticosteroids is generally advocated for effective treatment of patients with asthma . It is yet unknown what is the best time to start inhaled corticosteroid therapy and especially whether delayed introduction is harmful . PHASE 1 : In a previous study in patients with asthma and COPD , we found that 2.5 years of treatment with a beta 2-agonist plus inhaled corticosteroid ( BA + CS ) was more effective in improving the FEV1 and the provocative concentration of histamine causing a 20 % reduction in FEV1 ( PC20 ) than treatment with a beta 2-agonist plus anticholinergic ( BA + AC ) or placebo ( BA + PL ) . PHASE 2 : We extended this study with 6 months to investigate whether delayed introduction of inhaled CS therapy ( 800 micrograms beclomethasone dipropionate ) in the groups previously not treated with inhaled CS ( BA + /- AC ) could also improve FEV1 and PC20 to the same degree . A distinction was made between patients with predominantly asthma ( high baseline reversibility , delta FEV1 > or = 9 % of predicted ) , and predominantly COPD ( low baseline reversibility , delta FEV1 < 9 % of predicted ) . RESULTS Improvement of FEV1 percent predicted by inhaled CS  was comparable both in the asthmatics between phase 1 ( 13.8 % predicted ) and phase 2 ( 8.5 % predicted ; p = 0.31 ) as well as in the patients with COPD ( 2.5 % and 1.5 % predicted , respectively ) . PC20 , however , increased significantly more in the asthmatics in phase 1 ( 1.77 doubling concentration [ DC ] ) than in phase 2 ( 0.79 DC ; p = 0.03 ) . Improvement of PC20 in the patients with COPD was not significantly higher in phase 1 ( 0.74 DC ) than in phase 2 ( 0.00 DC ; p = 0.19 ) . CONCLUSIONS Our study indicates that although delayed introduction of inhaled CS in asthmatics leads to similar improvements in FEV1 , improvements in PC20 are significantly less . These findings in patients with longer-existing asthma concur with other findings in newly detected asthma . We suggest that institution of inhaled CS therapy should not be postponed in asthmatics with documented airways obstruction and reversibility Two corticosteroid regimens , alternate-day prednisone and inhaled beclomethasone dipropionate , have been more acceptable than daily oral corticosteroids for treatment of chronic asthma . To compare the effect of these regimens on hypothalamic-pituitary-adrenal function , 20 children with asthma were evaluated while receiving 20 to 40 mg of prednisone on alternate mornings or 400 to 800 microgram per day of inhaled beclomethasone dipropionate in divided daily doses ; seven children requiring only non-corticosteroid medication served as controls . Early-morning serum cortisol concentration , urinary free-cortisol excretion and the 11-desoxycortisol response to metyrapone were decreased to a similar degree among children receiving both corticosteroid regimens in comparison with the control patients and were lowest when alternate-day prednisone and inhaled beclomethasone dipropionate were given together . Thus , inhaled beclomethasone dipropionate appears similar to alternate-day prednisone in its effect on hypothalamic-pituitary-adrenal function when used alone ; the effect is additive when the two are used together To assess whether the use of larger than usual doses of inhaled steroid to treat severe asthma may adversely affect bone turnover and whether such an effect may be mitigated by altering the dose schedule , we investigated the effects of budesonide ( BUD ) on serum osteocalcin and the urinary output of hydroxyproline and calcium .  Healthy adults were administered 1.2 or 2.4 mg of BUD per day ( N = 40 ) or placebo ( N = 8) in a crossover , double-blind comparison of morning versus diurnal dosing schedules for 1 month each . Both BUD doses reduced the 24-hour urinary free-cortisol output ( p less than 0.001 ) and serum osteocalcin ( p less than 0.001 ) . The larger dose reduced the morning serum cortisol levels ( p = 0.002 ) . Neither dose increased the 8 AM urinary calcium or hydroxyproline output . Osteocalcin and plasma cortisol levels were higher on morning than on diurnal dosing ( p = 0.01 ) . The 24-hour urinary free-cortisol output was the same with either schedule ( p = 0.96 ) . Additional study is required to assess the clinical importance of the inhibitory effect of BUD on bone formation , as evidence d by the reduction in osteocalcin levels . Of concern is the possibility of serious bone complications result ing from the long-term use of inhaled steroid , particularly in growing children or patients in whom other risk factors for osteoporosis are present . The clinical advantage , if any , of morning dosing remains question able We studied the perception of bronchoconstriction in asthmatic subjects who were r and omly treated with inhaled beta 2 agonist given either alone ( n = 9 ) or associated with inhaled corticosteroids ( n = 9 ) .  Methacholine and bradykinin challenges , bronchoalveolar lavage , and bronchial biopsies were performed in all subjects . After each dose of agonist , breathlessness was assessed using a visual analog scale ( VAS ) and the forced expiratory volume in 1 s ( FEV1 ) was measured . The relationship between VAS scores and FEV1 and the slope of the regression line of VAS scores on the corresponding FEV1 ( VAS/FEV1 slope ) were analyzed for each agonist . Subjects without corticosteroids had good perception of methacholine but poor perception of bradykinin-induced bronchoconstriction . In subjects with corticosteroids , bronchoconstriction was well perceived whatever the agonist . VAS/FEV1 slopes for bradykinin but not for methacholine correlated negatively with the magnitude of eosinophilic inflammation in airway mucosa . VAS/FEV1 slopes for each agonist correlated positively with the percentage of basement membrane covered by airway epithelium . We conclude that in asthmatic patients perception of bronchoconstriction is related to eosinophilic inflammation and to epithelial damage in airways and that corticosteroid treatment is associated with improved perception of bronchoconstriction induced by bradykinin , a mediator endogenously produced in asthma The aim of this open study was to observe linear growth in young children with asthma treated with nebulized budesonide . Infants and young children ( < 3 years old ) with severe uncontrolled asthma were studied . They were treated with nebulized budesonide ( 1‐4mgday‐1 ) and treated for at least 6 months . Height st and ard deviation scores ( HtSDS ) were measured before ( “ pre‐ measurements ” ) immediately prior to commencing nebulized budesonide therapy ( baseline ) and after at least 6 months of therapy ( “ post‐ measurements ” ) . The mean HtSDS score at pretreatment was ‐0.21 and at baseline had fallen further to ‐0.46 . The mean HtSDS increased to ‐0.17 when the post‐ measurements were made ( p= 0.035 ) after at least 6 months of nebulized budesonide therapy . Treatment with nebulized budesonide for longer than 6 months in very young children with severe asthma was not associated with reduced linear growth Fluticasone propionate ( FP ) administered via metered-dose inhaler is a potent corticosteroid effective in the treatment of asthma . To evaluate the efficacy and safety of FP powder administered via a breath-activated inhaler ( Diskhaler ) , a multicenter , double-blind , r and omized , placebo-controlled , parallel-group study was conducted in adolescent and adult patients ( n = 331 ) with mild-to-moderate asthma previously treated with beta 2-agonist therapy alone . Patients received FP powder 50 , 100 , or 250 micrograms or placebo twice daily for 12 weeks . FP-treated patients compared with placebo-treated patients had significantly ( p < 0.001 ) greater improvements in morning predose forced expiratory volume in 1 sec ( 21 - 22 % increase vs. 9 % ) . Improvement in morning peak flow rate were also significantly ( p < 0.001 ) greater with FP than with placebo ( 8 - 10 % increase vs. 2 % increase ) . There was also a significant overall treatment difference in the frequency of inhaled albuterol use ( p < 0.001 ) and number of nighttime awakenings due to asthma ( p = 0.005 ) . There were no statistically significant difference among the FP treatment groups in any outcome measure . Physicians ' global assessment s also indicated significant ( p < 0.001 ) differences in efficacy , with 67 - 74 % of FP-treated patients rated as having " effective " or " very effective " treatment compared with 41 % of placebo-treated patients . Significant beneficial effects of FP were observed in lung function and diary card parameters after just 1 week of treatment . Adverse events were similar across treatment groups and primarily related to local irritation . Effect on hypothalamic-pituitary-adrenal axis function was minimal . In summary , all three dosages of inhaled FP powder were well tolerated and improved various asthma-related variables . Improvements in pulmonary function , beyond those achieved with beta 2-agonist therapy alone , were maintained for the duration of the 12-week study Abstract Oropharyngeal c and idiasis and dysphonia were assessed in 34 asthma patients whose risk of local complications of aerosol steroid therapy was considered to be higher than usual because of the doses of beclomethasone used for treatment of asthma ( 1,080 ± 360 μg/day ) . Cultures and examinations of the oropharynx were collated with symptom and medication-use records over a period of 2 yr . Positive cultures for C and ida were found in 40 % of the group before starting beclomethasone . Colonization of the oropharynx , clinical thrush , and dysphonia each increased in direct relationship to the daily dose of beclomethasone over a range from 200 to 1,600 μg/day . However , at peak prevalence , clinical thrush affected only 13 % of the total group , i.e. , about one quarter of the number with asymptomatic oropharyngeal c and idiasis . Thrush was not increased by occasional use of trimethoprim-sulfamethoxazole or erythromycin . Dysphonia was a more common symptom , affecting up to 50 % of the group , and occasionally was severe or persistent . It was related to the aerosolized steroid and not to the Freon propellants . Chronic voice stress appeared to be an important contributing factor to its onset or persistence . Although dysphonia and thrush were both related to beclomethasone usage , they did not appear to be directly related to one another , and they required different treatments ( voice rest and nystatin ) . These complications diminished in severity with time and did not limit beclomethasone dosage in any patient . Therefore , they need not preclude the long-term use of beclomethasone , even in high dosage when required The prevalence of posterior subcapsular cataracts in young patients receiving inhaled glucocorticoids for treatment of chronic asthma is unknown . In a cross-sectional study , slit-lamp examinations were done on 95 consecutive young patients who were taking inhaled beclomethasone or budesonide .  No posterior subcapsular cataracts were found . The median age of the patients was 13.8 ( range 5.8 - 24.8 ) . The median dose of inhaled beclomethasone or budesonide  was 750 micrograms/day ( range 300 - 2000 ) , or 12.9 micrograms/kg per day ( range 7.5 - 34.2 ) . The median duration of treatment was 5 years ( range 1 - 15 ) . 77 % of the patients had not used  oral glucocorticoids  in the year preceding the examination . This study suggests that routine screening for posterior subcapsular cataracts in this patient population is not warranted 11 patients with severe bronchial asthma entered a r and omized trial of glucocorticosteroid budesonide of Russian produce . Of them 6 patients received  inhalations of budesonide ( 800 micrograms/day for 6 months ) , 5 control patients did not receive the drug . As shown by investigations of external respiration and bronchoalveolar lavage with estimation of cytogram , metacholine provocative tests , fiber bronchoscopy , budesonide inhalations relieved clinical symptoms of asthma , bronchial hyperreactivity and inflammation Abstract The airway responses of 11 symptomatic patients with asthma to  metacholine inhalation  were determined before and after a two-week course of corticosteroids and compared with those of 5 patients with chronic obstructive pulmonary disease and 4 individuals without respiratory illness . A significant increase in response to cholinergic stimulation as measured by a fall in the FEV 1 occurred after corticosteroids only in the asthmatic group . The mechanism of this response is not clear 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 This study was undertaken to evaluate the efficacy and safety of fluticasone propionate , an inhaled corticosteroid , in adolescents and adults with moderate asthma who were previously taking inhaled corticosteroids . After a 2-week , open-label screening period , a double-masked , r and omized , parallel-group , dose-ranging study was conducted over 12 weeks in 21 outpatient centers throughout the United States . Patients ( N = 304 ) > or = 12 years of age with moderate asthma previously treated with inhaled corticosteroids and beta-sympathomimetic bronchodilators were enrolled . Patients were assigned to receive placebo or fluticasone propionate 100 , 250 , or 500 micrograms twice daily via a metered-dose inhaler without a spacer device . These doses refer to the amount of fluticasone propionate released from the valve of the metered-dose inhaler ; the corresponding doses released from the activator of the metered-dose inhaler are 88 micrograms , 220 micrograms , and 440 micrograms , respectively . Between baseline and end point , mean values of forced expiratory volume in 1 second decreased 0.31 L in the placebo group and improved 0.39 L , 0.30 L , and 0.43 L in patients receiving 100-micrograms , 250-micrograms , and 500-micrograms fluticasone propionate , respectively . The differences between placebo and all treatment groups were statistically significant . More patients were withdrawn from placebo ( 72 % ) than from fluticasone propionate ( 13 % to 16 % ) because of failure to meet predetermined asthma stability criteria . Differences in baseline-to-end point changes in morning peak expiratory flow rate , physician overall assessment s and patient-rated assessment of symptoms , and albuterol use for symptom control also significantly favored each fluticasone propionate group over placebo . There were essentially no differences in efficacy among the three fluticasone propionate groups . Treatment-related adverse events occurred in 8 % of placebo-treated patients and 13 % to 15 % of fluticasone propionate-treated patients ; these events were mainly localized to the oropharynx/ larynx . A 12-week course of fluticasone propionate ( 100 , 250 , and 500 micrograms twice daily ) was well tolerated and more effective than placebo based on maintenance of asthma stability , pulmonary function tests , physician and patient assessment s , and rescue bronchodilator use . No dose-related effects were observed with the dosages of fluticasone propionate used in this study
BACKGROUND Inhaled steroids play a central role in the management of childhood asthma .
There is concern about their side effects , especially on growth .
However asthma may also cause growth retardation .
Growth rates are not stable , so r and omised controlled parallel group studies are needed to assess the impact of inhaled steroids on growth .
This review is confine to one inhaled steroid , beclomethasone , that is known to have significant levels of systemic absorption .
OBJECTIVES To determine whether inhaled beclomethasone cause significant delay in the linear growth of children with asthma .