Assessment of the Long-term Safety of Inhaled Ciclesonide on Growth in Children With Asthma Effect of inhaled steroids on airway hyperresponsiveness, sputum eosinophils, and exhaled nitric oxide levels in patients with asthma Adrenal function and high dose inhaled corticosteroids for asthma Early asthma prophylaxis, natural history, skeletal development and economy (EASE): a pilot randomised controlled trial. Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. The Dutch Asthma Study Group. Effect of inhaled glucocorticoids in childhood on adult height. Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. Twelve-month safety and efficacy of inhaled fluticasone propionate in children aged 1 to 3 years with recurrent wheezing. Linear growth and bone maturation are unaffected by 1 year of therapy with inhaled flunisolide hydrofluoroalkane in prepubescent children with mild persistent asthma: a randomized, double-blind, placebo-controlled trial. Relations between exhaled nitric oxide and measures of disease activity among children with mild-to-moderate asthma. Long-term safety of fluticasone propionate and nedocromil sodium on bone in children with asthma. One year treatment with salmeterol compared with beclomethasone in children with asthma. The Dutch Paediatric Asthma Study Group. 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. Systemic effects of inhaled corticosteroids on growth and bone turnover in childhood asthma: a comparison of fluticasone with beclomethasone. Osteocalcin, growth, and inhaled corticosteroids: a prospective study. Fluticasone propionate compared with budesonide: a double-blind trial in asthmatic children using powder devices at a dosage of 400 microg x day(-1). Daily versus as-needed inhaled corticosteroid for mild persistent asthma (The Helsinki early intervention childhood asthma study) Canadian Thoracic Society 2012 guideline update: diagnosis and management of asthma in preschoolers, children and adults. Growth during one year of treatment with fluticasone propionate or sodium cromoglycate in children with asthma. A comparison of beclomethasone, salmeterol, and placebo in children with asthma. Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group. Long-term inhaled corticosteroids in preschool children at high risk for asthma. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial 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. Efficacy and safety of inhaled steroid and cromone treatment in school-age children: a randomized pragmatic pilot study. Short-term growth during treatment with inhaled fluticasone propionate and beclomethasone dipropionate. Effect of long-term treatment with an inhaled corticosteroid (budesonide) on airway hyperresponsiveness and clinical asthma in nonsteroid-dependent asthmatics. Low‐dose inhaled budesonide once or twice daily for 27 months in children with mild asthma Long-term effects of budesonide or nedocromil in children with asthma. Effect of short-term treatment with low-dose inhaled fluticasone propionate on airway inflammation and remodeling in mild asthma: a placebo-controlled study. Long-term effect of inhaled corticosteroids on growth rate in adolescents with asthma. A randomized trial of lower leg and height growth in children with asthma treated with inhaled budesonide from a new dry powder inhaler. Aerosol beclomethasone dipropionate compared with theophylline as primary treatment of chronic, mild to moderately severe asthma in children. Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial Linear growth in prepubertal asthmatic children treated with montelukast, beclomethasone, or placebo: a 56-week randomized double-blind study. Adrenal suppression, evaluated by a low dose adrenocorticotropin test, and growth in asthmatic children treated with inhaled steroids. Growth in asthmatic children treated with fluticasone propionate. Fluticasone Propionate Asthma Study Group. Nebulised beclomethasone dipropionate in preschool asthma. The Childhood Asthma Management Program (CAMP): design, rationale, and methods. Childhood Asthma Management Program Research Group. Beclomethasone dipropionate in long-term treatment of asthma in children. Efficacy and safety of high-dose inhaled steroids in children with asthma: a comparison of fluticasone propionate with budesonide. Growth of prepubertal children with mild asthma treated with inhaled beclomethasone dipropionate. Efficacy and safety of inhaled fluticasone propionate chlorofluorocarbon in 2- to 4-year-old patients with asthma: results of a double-blind, placebo-controlled study. One-Year Trial on Safety and Normal Linear Growth with Flunisolide HFA in Children with Asthma Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial. Effects of inhaled fluticasone propionate in children less than 2 years old with recurrent wheezing. Efficacy and safety of three ciclesonide doses vs placebo in children with asthma: the RAINBOW study. Ciclesonide in wheezy preschool children with a positive asthma predictive index or atopy. Knemometry, Urine Cortisol Excretion, and Measures of the Insulin-Like Growth Factor Axis and Collagen Turnover in Children Treated with Inhaled Glucocorticosteroids
OBJECTIVE . To assess the effects of the new inhaled corticosteroid ciclesonide on growth in children with asthma . METHODS . We performed a multicenter , r and omized , double-blind , placebo-controlled study to assess the effects of inhaled ciclesonide on growth in children with mild , persistent asthma . After a 6-month run-in period , 661 prepubertal children who were aged 5.0 to 8.5 years were r and omly assigned to once-daily morning treatment for 1 year with ciclesonide 40 or 160 μg ( ex-actuator ) or placebo , followed by a 2-month follow-up period . The primary end point was the linear growth velocity ( linear regression estimate ) over the double-blind treatment period . Growth was recorded as the median of 4 stadiometer measurements . Adverse events and 10-hour overnight and 24-hour urinary free cortisol levels were also assessed . RESULTS . Mean linear growth velocity during run-in was comparable between groups : 160 μg , 6.20 cm/year ; 40 μg , 6.59 cm/year ; placebo , 6.49 cm/year . Mean differences from placebo ( 5.75 cm/year ) in growth velocity over the double-blind treatment period were −0.02 cm/year for ciclesonide 40 μg and −0.15 cm/year for ciclesonide 160 μg . Both ciclesonide treatments were noninferior to placebo with respect to growth velocity . The overall incidence of adverse events was comparable between groups , and no significant changes in 10-hour overnight or 24-hour urinary free cortisol levels were noted between groups during the double-blind treatment period . CONCLUSIONS . Ciclesonide demonstrated no detectable effect on childhood growth velocity , even at the highest dosage , which may ease concerns about systemic adverse events BACKGROUND Airway hyperresponsiveness , induced sputum eosinophils , and exhaled nitric oxide ( NO ) levels have all been proposed as non-invasive markers for monitoring airway inflammation in patients with asthma . The aim of this study was to compare the changes in each of these markers following treatment with inhaled glucocorticosteroids in a single study . METHODS In a r and omised , double blind , placebo controlled , parallel study 25 patients with mild asthma ( 19–34 years , forced expiratory volume in one second ( FEV1 ) > 75 % predicted , concentration of histamine provoking a fall in FEV1 of 20 % or more ( PC20 ) < 4 mg/ml ) inhaled fluticasone propionate ( 500 μg twice daily ) for four weeks  . PC20 to histamine , sputum eosinophil numbers , and exhaled NO levels were determined at weeks 0 , 2 , and 4 , and two weeks after completing treatment . Sputum was induced by inhalation of hypertonic ( 4.5 % ) saline and eosinophil counts were expressed as percentage non-squamous cells . Exhaled NO levels ( ppb ) were measured by chemiluminescence . RESULTS In the steroid treated group there was a significant increase in PC20 , decrease in sputum eosinophils , and decrease in exhaled NO levels compared with baseline at weeks 2 and 4 of treatment . Subsequently , each of these variables showed significant worsening during the two week washout period compared with week 4 . These changes were significantly different from those in the placebo group , except for the changes in sputum eosinophils and exhaled NO levels during the washout period . There were no significant correlations between the changes in the three markers in either group at any time . CONCLUSIONS Treatment of asthmatic subjects with inhaled steroids for four weeks leads to improvements in airway hyperresponsiveness to histamine , eosinophil counts in induced sputum , and exhaled nitric oxide levels . The results suggest that these markers may provide different information when monitoring anti-inflammatory treatment in asthma OBJECTIVE To investigate effects on adrenal function of fluticasone , a recently released inhaled steroid preparation with lower systemic bioavailability than beclomethasone dipropionate . METHODS 34 children on high doses ( 400 - 909 μg/m2/d ) of inhaled beclomethasone dipropionate or budesonide  were recruited into a double blind , crossover study investigating the effects on adrenal function of beclomethasone and fluticasone propionate , given using a st and ard spacer ( Volumatic ) . The 24 hour excretion rates of total cortisol and cortisol metabolites were determined at baseline ( after a two week run in ) , after six weeks treatment with an equal dose of beclomethasone , and after six weeks of treatment with half the dose of fluticasone , both given through a spacer device . RESULTS The comparison of effects between fluticasone and beclomethasone during treatment periods , although favouring fluticasone in all measured variables , reached significance only after correction for urinary creatinine excretion ( tetrahydrocortisol and 5α-tetrahydrocortisol geometric means : 424 v 341 μg/m2/d ) . The baseline data showed adrenal suppression in the children taking beclomethasone ( total cortisol geometric means : 975 v 1542 μg/d ) and a dose related suppression in the children taking budesonide . Suppressed adrenal function in the children who were taking beclomethasone at baseline subsequently improved with fluticasone and beclomethasone during treatment periods . CONCLUSIONS Fluticasone is less likely to suppress adrenal function than beclomethasone at therapeutically equivalent doses . The baseline data also support the cl aim that spacer devices should be used for the administration of high doses of inhaled topical steroids OBJECTIVES ( 1 ) To establish recruitment rates of newly presenting asthmatic children . ( 2 ) To establish acceptability of study protocol s. ( 3 ) To pilot age-specific quality of life ( QoL ) assessment . ( 4 ) To assess short-term ( 6 months ) outcomes of inhaled corticosteroids ( ICS ) treatment . ( 5 ) To refine sample size calculations for a definitive study . DESIGN A r and omised pragmatic longitudinal trial design was used , with no blinding or placebo , to examine early ICS introduction similar to its use in practice . Subjects were assessed at entry , 3 and 6 months . SETTING Subjects were recruited from six general practice s. Children under 6 years were assessed at the Craig Research and Investigation Unit , Royal Aberdeen Children 's Hospital , or their family home , and subjects 6 years and over were assessed at their general practice . SUBJECTS Children ( aged 6 months-16 years ) with symptoms suggestive of asthma/wheeze that had commenced no longer than 12 months before were identified retrospectively and prospect ively from general practice s. Subjects were also required to be naïve to prophylactic therapy with no other lung disease/concomitant illness . INTERVENTIONS Subjects were r and omised to ss2-agonist ( ss2-only group ) or ss2-agonist and ICS ( ICS group ) for 6 months . Physicians could later prescribe ICS in controls if needed . MAIN OUTCOME MEASURES ( 1 ) Pulmonary function . ( 2 ) Asthma symptom diary . ( 3 ) Symptomatic health status question naire . ( 4 ) Caregiver 's and child 's QoL. ( 5 ) Growth . ( 6 ) Bone mass . ( 7 ) Bone turnover . ( 8) Economic issues . RESULTS Of over 15,000 children yielded from general practice records , 11 % had symptoms suggestive of asthma/wheeze , and two-thirds of these already used ICS . Of the remaining , 141 subjects met the criterion of early asthma , and 86 were r and omised . Two-thirds of those r and omised were < 6 years old , the males : females ratio was 2:1 , and 67 % had a family history of atopy . RESULTS - PHYSIOLOGICAL DEVELOPMENT : Pulmonary function did not significantly improve in the older children . Although tidal breathing measures in the pre-school children were significantly higher at 6 months in the ss2-only group , there was great variability . Incidence of wheeze and night-time cough reduced equally in both groups . Reduction of night-time symptom score and reliever use , and increase in symptom-free days were only significant in the ss2-only group . No significant differences were found in growth and bone mass between the two groups , but bone metabolism was significantly reduced at 6 months in the ICS group . RESULTS - PSYCHOLOGICAL DEVELOPMENT : The caregiver 's QoL question naire was sensitive to child symptom changes over 3 months , but absolute impact of child symptoms on their QoL varied , whereas the child-centred question naire was not sensitive to change . RESULTS - ECONOMICS : There were no significant differences in medical consultation costs between the groups , but , as expected , prescription costs in the ICS group were higher over 6 months . Combined healthcare costs were significantly higher for patients assigned to ICS , but there were no significant differences in any effectiveness measures between the groups . CONCLUSIONS Most ( 96 % ) of the proposed sample was recruited , and the low drop-out rate ( 8 % ) demonstrated acceptability of the study protocol . Most children first presenting with symptoms suggestive of asthma were < 6 years old and represented a group biased towards mild to moderate asthma , or virally induced wheeze . The caregiver 's QoL question naire was found to better reflect a child 's symptom changes than a child-centred instrument . In the short term , no adverse effects were seen on growth , but ICS treatment significantly reduced bone metabolism . Most of the young children with asthma/wheeze improved over time with ss2-agonist treatment alone , and clinical benefits of early ICS intervention amongst these children were not detected ; however , there was inadequate power in this pilot study to establish this . ( Studies in adults revealed that addition of salmeterol to a moderate dose of inhaled corticosteroid result ed in better symptom control and higher PEF compared with doubling the dose of inhaled corticosteroid . The aim of this three group study was to compare the effects of a moderate dose of beclomethasone , the same dose of beclomethasone with salmeterol , and a doubling dose of beclomethasone on lung function and symptoms in children with moderate asthma . A total of 177 children already treated with inhaled corticosteroids , were r and omized in a double-blind parallel study either to salmeterol 50 microg twice daily ( BDP400+salm ) , beclomethasone 200 microg twice daily ( BDP800 ) , or placebo ( BDP400 ) in addition to beclomethasone 200 microg twice daily . No significant differences between groups were found in FEV1 , PD20 methacholine , symptom scores , and exacerbation rates after 1 yr . Salmeterol result ed in slightly better PEF in the first months of treatment . FEV1 , and PD20 methacholine significantly improved in all groups . After 1 yr mean changes in FEV1 , percent predicted were 4.3 % ( 95 % CI 1.3 ; 7.2 ) , 5.8 % ( 95 % CI 2.9 ; 8.7 ) , and 4.3 % ( 95 % CI 2.1 ; 6.5 ) for BDP400+salm , BDP800 , and BDP400 , respectively . Changes in airway responsiveness were 0.60 ( 95 % CI 0.05 ; 1.14 ) , 1.30 ( 95 % CI 0.73 ; 1 . 87 ) , and 0.80 ( 95 % CI 0.33 ; 1.27 ) doubling doses . Growth was significantly slower in the BDP800 group . We conclude that no additional benefit was found of adding either salmeterol or more beclomethasone to a daily dose of 400 microg beclomethasone in this group of children with excellent compliance of medication BACKGROUND The use of inhaled glucocorticoids for persistent asthma causes a temporary reduction in growth velocity in prepubertal children . The result ing decrease in attained height 1 to 4 years after the initiation of inhaled glucocorticoids is thought not to decrease attained adult height . METHODS We measured adult height  in 943 of 1041 participants ( 90.6 % ) in the Childhood Asthma Management Program ; adult height was determined at a mean ( ±SD ) age of 24.9±2.7 years . Starting at the age of 5 to 13 years , the participants had been r and omly assigned to receive 400 μg of budesonide , 16 mg of nedocromil , or placebo daily for 4 to 6 years . We calculated differences in adult height for each active treatment group , as compared with placebo , using multiple linear regression with adjustment for demographic characteristics , asthma features , and height at trial entry . RESULTS Mean adult height was 1.2 cm lower ( 95 % confidence interval [ CI ] , -1.9 to -0.5 ) in the budesonide group than in the placebo group ( P=0.001 ) and was 0.2 cm lower ( 95 % CI , -0.9 to 0.5 ) in the nedocromil group than in the placebo group ( P=0.61 ) . A larger daily dose of inhaled glucocorticoid in the first 2 years was associated with a lower adult height ( -0.1 cm for each microgram per kilogram of body weight ) ( P=0.007 ) . The reduction in adult height in the budesonide group as compared with the placebo group was similar to that seen after 2 years of treatment ( -1.3 cm ; 95 % CI , -1.7 to -0.9 ) . During the first 2 years , decreased growth velocity in the budesonide group occurred primarily in prepubertal participants . CONCLUSIONS The initial decrease in attained height associated with the use of inhaled glucocorticoids in prepubertal children persisted as a reduction in adult height , although the decrease was not progressive or cumulative . ( Funded by the National Heart , Lung , and Blood Institute and the National Center for Research Re sources ; CAMP Clinical Trials.gov number , NCT00000575 . ) 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 Short-term studies have shown that inhaled corticosteroids may reduce the growth of children with asthma . However , the effect of long-term treatment on adult height is uncertain . METHODS We conducted a prospect i ve study in children with asthma to examine the effect of long-term treatment with inhaled budesonide on adult height . We report on 211 children who have attained adult height : 142 budesonide-treated children with asthma , 18 control patients with asthma who have never received inhaled corticosteroids , and 51 healthy siblings of patients in the budesonide group , who also served as controls . RESULTS The children in the budesonide group attained adult height after a mean of 9.2 years of budesonide treatment ( range , 3 to 13 ) at a mean daily dose of 412 microg ( range , 110 to 877 ) . The mean cumulative dose of budesonide was 1.35 g ( range , 0.41 to 3.99 ) . The mean differences between the measured and target adult heights were + 0.3 cm ( 95 percent confidence interval , -0.6 to + 1.2 ) for the budesonide-treated children , -0.2 cm ( 95 percent confidence interval , -2.4 to + 2.1 ) for the control children with asthma , and + 0.9 cm ( 95 percent confidence interval , -0.4 to + 2.2 ) for the healthy siblings . The adult height depended significantly ( P<0.001 ) on the child 's height before budesonide treatment . Although growth rates were significantly reduced during the first years of budesonide treatment , these changes in growth rate were not significantly associated with adult height . CONCLUSIONS Children with asthma who have received long-term treatment with budesonide attain normal adult height OBJECTIVE Our aim was to compare the 12-month safety and efficacy of fluticasone propionate ( FP ) and sodium cromoglycate ( SCG ) in children aged 1 to 3 years with mild to moderate recurrent wheeze . METHODS The study was a r and omized , parallel-group , open-label multicenter study of 625 children , aged 1 to 3 years , with recurrent wheeze r and omized in a 3:1 ratio to treatment for 52 weeks with FP ( 100 microg twice daily ) via metered-dose inhaler and Babyhaler spacer device or SCG ( 5 mg 4 times daily ) via metered-dose inhaler and Nebuhaler spacer device , respectively . RESULTS There was no significant difference in mean adjusted growth rates between the 2 groups : 84.0 mm/year in the FP group versus 86.4 mm/year in the SCG group ( difference FP-SCG : -2.4 mm/year ; 95 % confidence interval : -6.6 to 1.8 ) . Growth comparisons were independent of age , gender , previous use of steroid , or whether measured as length and /or height . Serum and urinary cortisol concentrations showed a statistically significant suppression of 10 % and 14 % , respectively , but the number of patients with serum cortisol levels below the lower normal limit was reduced during the trial . Both treatments were well tolerated . The most common drug-related adverse events were cough ( 2 % FP vs 1 % SCG ) and hoarseness ( 1 % FP vs 0 % SCG ) . One incident of cataract was observed at baseline and 1 after FP treatment ; the latter had resolved after 12 months . The efficacy of FP was superior to SCG with fewer cases of symptom worsening , exacerbations , and requirements for oral steroid treatment and more symptom-free days and days without use of rescue treatment . CONCLUSIONS Twelve months of treatment with inhaled FP ( 100 microg twice daily ) in preschool children aged 1 to 3 years with recurrent wheeze has no effect on growth and no other clinical ly important side effects but is more efficacious than SCG BACKGROUND Inhaled corticosteroids ( ICS ) are the preferred long-term therapy for subjects with persistent asthma . However , concerns remain about potential effects of long-term ICS use on growth in children . OBJECTIVE To determine the effect of 1 year of inhalation therapy with flunisolide hydrofluoroalkane ( HFA ) on growth velocity and bone maturation in children with mild persistent asthma . METHODS In this double-blind , placebo-controlled study , 218 prepubescent ( Tanner Stage 1 ) children with mild persistent asthma ranging in age from 4 to 10 years were evaluated . After a 2-week run-in period , subjects were r and omized ( 1:1 ) to 2 puffs flunisolide HFA twice daily ( 85 μg/puff ) or placebo for 52 weeks . Height was assessed by stadiometry at each visit . Growth velocity ( cm/52 weeks ) was estimated by the slope of the linear regression of height over time . An independent assessor scored h and and wrist radiographs for bone development pretreatment and at week 52 . Analysis of covariance was used for all efficacy endpoints . RESULTS The 2 treatment groups were similar at baseline for sex , race , age , weight , and height . At the end of double-blind treatment , mean growth velocity was 6.01 ± 1.84 cm/52 weeks for flunisolide HFA ( n = 106 ) and 6.19 ± 1.30 cm/52 weeks for placebo ( n = 112 ) ( P = .425 ) . Mean advancement in bone age during the 1-year study was similar for the 2 groups : 0.93 ± 0.46 years for flunisolide HFA ( n = 70 ) and 1.01 ± 0.41 years for placebo ( n = 75 ) ( P = .128 ) . CONCLUSIONS In this study , flunisolide HFA did not suppress growth or bone maturation at the highest approved dose for children with persistent asthma OBJECTIVE Exhaled nitric oxide ( FE(NO ) ) was evaluated in children with asthma after 4 to 6 years of treatment with budesonide , nedocromil , or albuterol  as needed . STUDY DESIGN FE(NO ) , spirometry , total eosinophil count , and serum eosinophil cationic protein levels were obtained from 118 children at the Denver site of the Childhood Asthma Management Program upon completion of treatment and after a 2- to 4-month washout . RESULTS Budesonide-treated patients had significantly lower median ( 1st , 3rd quartile ) FE(NO ) ( 21.5 [ 13.2 , 84.4 ] vs 62.5 [ 26.2 , 115.0 ] ppb , P < .01 ) and eosinophil cationic protein levels ( 17.4 [ 10.1 , 24.3 ] vs 24.0 [ 15.4 , 33.9 ] mg/dL , P = .05 ) compared with placebo , whereas no differences were noted between nedocromil and placebo groups . After washout , FE(NO ) levels were similar between the three treatments . FE(NO ) levels significantly correlated with degree of bronchial hyperresponsiveness , bronchodilator reversibility , allergen skin prick tests , serum IgE , and total eosinophil count . FE(NO ) levels were also higher in patients with nocturnal symptoms and in patients requiring beta-agonist use at least once weekly . CONCLUSIONS Budesonide therapy was more effective than nedocromil in reducing FE(NO ) . Unfortunately , the effects of long-term budesonide were not sustained after its discontinuation . FE(NO ) may be a complementary tool to current practice guidelines in assessing asthma control and medication response OBJECTIVE Inhaled corticosteroids are recommended as first-line therapy for pediatric asthma . However , few controlled long-term studies have investigated their effect on bone mineral density ( BMD ) and growth . METHODS Children who were aged 6 to 14 years and had persistent asthma were r and omized to 24 months ' treatment with fluticasone propionate ( FP ) 200 micro g/d or nedocromil sodium ( NS ) 8 mg/d ( if uncontrolled , maximum doses of 400 micro g/d and 16 mg/d , respectively ) . BMD was assessed blind and analyzed at a central facility on the basis of dual-energy x-ray absorptiometry measurements of the lumbar spine and femoral neck at months 0 , 6 , 12 , and 24 . Height was measured at months 0 , 12 , and 24 . Efficacy parameters ( lung function , asthma control , occurrence of exacerbations ) were measured every 3 months . RESULTS In total , 174 children were r and omized to treatment ( 87 received FP , and 87 received NS ) . At month 24 , the adjusted mean percentage increase in lumbar spine BMD was 11.6 % in the FP group compared with 10.4 % in NS-treated children ( 95 % confidence interval for treatment difference : -0.7 % to 3.1 % ) . The corresponding increases in femoral neck BMD were 8.9 % and 8.5 % , respectively . There was no significant difference in growth between the 2 groups : adjusted mean growth rates were 6.1 cm/y with FP and 5.8 cm/y with NS . FP was significantly superior for every efficacy parameter investigated and was similarly well tolerated as NS . CONCLUSIONS The long-term effects of FP and NS on BMD accrual and growth are similar among children with asthma . The benefit : risk ratio of FP may be considered superior to that of NS 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 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 Inhaled steroids are frequently used in childhood asthma , but concerns based on limited objective evidence remain , regarding long-term side-effects . In this study the systemic effects of st and ard doses of inhaled steroids in childhood asthma were assessed , comparing beclomethasone dipropionate ( BDP ) with fluticasone propionate ( FP ) . The study was prospect i ve , r and omized and double-blind . Twenty-three steroid-naive children with moderately severe asthma , aged 5 - 10 yrs , were allocated either BDP ( 400 microg x day(-1 ) or FP ( 200 microg x day(-1 ) ) using a metered-dose inhaler with a spacer . Asthma control was assessed at regular intervals over 20 months . Fasting morning blood and overnight urine sample s were collected for estimation of serum cortisol , serum 1-carboxyterminal telopeptide ( ICTP ) , serum osteocalcin and urine deoxypyridinoline ( DPD ) . Bone mineral density ( BMD ) was measured at each visit . None of the markers of bone turnover showed any change during the study period . BMD increased at normal rates with age . Serum cortisol significantly decreased on BDP , but not on FP . A significant difference in growth rates was found between the groups , with a slower rate of growth towards the end of the observation period in the BDP group . In conclusion when taken in a relatively modest dose over a period of time , beclomethasone dipropionate had significant effects on the hypothalamic-pituitary-adrenal axis and statural growth in childhood asthma . These systemic effects were not seen with an equipotent dose of fluticasone propionate 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 The aim of this study was to compare fluticasone propionate ( FP ) with budesonide ( BUD ) at a dose of 400 microg x day(-1 ) in the treatment of children with asthma . Two hundred and twenty nine children with mild-to-moderate asthma , currently receiving 200 - 400 microg x day(-1 ) of inhaled corticosteroid  , were r and omized to receive either 400 microg x day(-1 ) of FP from the Diskhaler ( registered trade mark of the Glaxo Group of Companies ) or 400 microg x day(-1 ) of BUD from the Turbuhaler ( registered trade mark of Astra Pharmaceuticals Ltd ) for 8 weeks , in a parallel-group , double-blind , double-dummy study . Primary efficacy was assessed by measurement of daily peak expiratory flow ( PEF ) . In addition , pulmonary function tests were performed at each clinic visit and a self-administered patient-centred question naire was completed by one parent of each patient at the start and end of study treatment . Mean morning PEF increased following treatment both with FP and BUD , but was significantly higher following treatment with FP during Weeks 1 - 4 ( p=0.015 ) and Weeks 1 - 8 ( p=0.019 ) . Similar results were found for mean evening PEF and percentage predicted morning and evening PEF . Children receiving FP experienced significantly less disruption in their physical activities ( i.e. sports , games ) because of their asthma compared to children treated with BUD ( p=0.03 ) . Mean cortisol levels increased in both groups , but the increase was significantly higher in the FP group at 4 weeks ( p=0.022 ) . Serum and urine markers of bone formation and resorption changed very little and showed no consistent pattern of change . Fluticasone propionate at a dosage of 400 microg x day(-1 ) from the Diskhaler provided a more rapid and greater improvement in lung function in children with mild-to-moderate asthma than BUD 400 microg day(-1 ) from the Turbuhaler . Both treatments were well-tolerated , with a similar safety profile Objective : To compare the effect of inhaled budesonide given daily or as-needed on  mild persistent childhood asthma .  Patients , design and interventions : 176 children aged 5–10 years with newly detected asthma were r and omly assigned to three treatment groups : ( 1 ) continuous budesonide ( 400 μg twice daily for 1 month , 200 μg twice daily for months 2–6 , 100 μg twice daily for months 7–18 ) ; ( 2 ) budesonide , identical treatment to group 1 during months 1–6 , then budesonide for exacerbations as needed for months 7–18 ; and ( 3 ) disodium cromoglycate ( DSCG ) 10 mg three times daily for months 1–18 . Exacerbations were treated with budesonide 400 μg twice daily for 2 weeks . Main outcome measures : Lung function , the number of exacerbations and growth . Results : Compared with DSCG the initial regular budesonide treatment result ed in a significantly improved lung function , fewer exacerbations and a small but significant decline in growth velocity . After 18 months , however , the lung function improvements did not differ between the groups . During months 7–18 , patients receiving continuous budesonide treatment had significantly fewer exacerbations ( mean 0.97 ) , compared with 1.69 in group 2 and 1.58 in group 3 . The number of asthma-free days did not differ between regular and intermittent budesonide treatment . Growth velocity was normalised during continuous low-dose budesonide and budesonide therapy given as needed . The latter was associated with catch-up growth . Conclusions : Regular use of budesonide afforded better asthma control but had a more systemic effect than did use of budesonide as needed . The dose of ICS could be reduced as soon as asthma is controlled . Some children do not seem to need continuous ICS treatment BACKGROUND In 2010 , the Canadian Thoracic Society ( CTS ) published a Consensus Summary for the diagnosis and management of asthma in children six years of age and older , and adults , including an up date d Asthma Management Continuum . The CTS Asthma Clinical Assembly subsequently began a formal clinical practice guideline up date process , focusing , in this first iteration , on topics of controversy and ⁄or gaps in the previous guidelines . METHODS Four clinical questions were identified as a focus for the up date d guideline : the role of noninvasive measurements of airway inflammation for the adjustment of anti-inflammatory therapy ; the initiation of adjunct therapy to inhaled corticosteroids ( ICS ) for uncontrolled asthma ; the role of a single inhaler of an ICS⁄long-acting beta(2)-agonist combination as a reliever , and as a reliever and a controller ; and the escalation of controller medication for acute loss of asthma control as part of a self-management action plan . The expert panel followed an adaptation process to identify and appraise existing guidelines on the specified topics . In addition , literature search es were performed to identify relevant systematic review s and r and omized controlled trials . The panel formally assessed and grade d the evidence , and made 34 recommendations . RESULTS The up date d guideline recommendations outline a role for inclusion of assessment of sputum eosinophils , in addition to st and ard measures of asthma control , to guide adjustment of controller therapy in adults with moderate to severe asthma . Appraisal of the evidence regarding which adjunct controller therapy to add to ICS and at what ICS dose to begin adjunct therapy in children and adults with poor asthma control supported the 2010 CTS Consensus Summary recommendations . New recommendations for the adjustment of controller medication within written action plans are provided . Finally , priority areas for future research were identified . CONCLUSIONS The present clinical practice guideline is the first up date of the CTS Asthma Guidelines following the Canadian Respiratory Guidelines Committee 's new guideline development process . Tools and strategies to support guideline implementation will be developed and the CTS will continue to regularly provide up date s reflecting new evidence 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 BACKGROUND An inhaled glucocorticoid is currently the medication of choice for long-term control of persistent asthma in children . The role of long-acting beta2-adrenergic-receptor agonists , such as salmeterol , needs to be defined . METHODS We conducted a r and omized , double-blind , placebo-controlled , parallel-group , one-year study of 241 children ( mean [ + /-SD ] age , 9.3+/-2.4 years ) with clinical ly stable asthma and less than one month of prior glucocorticoid use . We compared inhaled beclomethasone dipropionate ( 200 microg twice daily ) with salmeterol xinafoate ( 50 microg twice daily ) and placebo ( lactose ) . The primary outcome measure , airway responsiveness ( as assessed with a methacholine challenge ) was evaluated before treatment ; after 3 , 6 , 9 , and 12 months of treatment ( 12 and 36 hours after study medications had been withheld ) ; and 2 weeks after the end of treatment . Spirometry , symptoms , use of rescue medication ( 200 microg of albuterol inhaled as needed ) , and adverse effects were also assessed . RESULTS During months 1 through 12 overall , beclomethasone was associated with significantly less airway hyperresponsiveness than salmeterol ( P= 0.003 ) or placebo ( P<0.001 ) . This effect was lost two weeks after treatment had been stopped . As compared with placebo , beclomethasone was associated with less variability between morning and evening in the peak expiratory flow ( P=0.002 ) , as was salmeterol ( P=0.02 ) . Beclomethasone was also associated with a reduced need for albuterol as rescue therapy ( P<0.001 ) and fewer withdrawals because of asthma exacerbations ( P=0.03 ) , but salmeterol was not ( P=0.09 and 0.55 , respectively ) . During months 1 through 12 , linear growth was 3.96 cm in the children receiving beclomethasone , as compared with 5.40 cm in the salmeterol group ( P=0.004 ) and 5.04 cm in the placebo group ( P=0.018 ) . Height was not measured after treatment ended . CONCLUSIONS Beclomethasone was effective in reducing airway hyperresponsiveness and in controlling symptoms of asthma , but it was associated with decreased linear growth . Salmeterol was not as effective as beclomethasone in reducing airway hyperresponsiveness or in controlling symptoms ; however , it was an effective bronchodilator and was not associated with rebound airway hyperresponsiveness , masking of symptoms , or adverse effects BACKGROUND It is unknown whether inhaled corticosteroids can modify the subsequent development of asthma in preschool children at high risk for asthma . METHODS We r and omly assigned 285 participants two or three years of age with a positive asthma predictive index to treatment with fluticasone propionate ( at a dose of 88 mug twice daily ) or masked placebo for two years , followed by a one-year period without study medication . The primary outcome was the proportion of episode-free days during the observation year . RESULTS During the observation year , no significant differences were seen between the two groups in the proportion of episode-free days , the number of exacerbations , or lung function . During the treatment period , as compared with placebo use , use of the inhaled corticosteroid was associated with a greater proportion of episode-free days ( P=0.006 ) and a lower rate of exacerbations ( P<0.001 ) and of supplementary use of controller medication ( P<0.001 ) . In the inhaled-corticosteroid group , as compared with the placebo group , the mean increase in height was 1.1 cm less at 24 months ( P<0.001 ) , but by the end of the trial , the height increase was 0.7 cm less ( P=0.008 ) . During treatment , the inhaled corticosteroid reduced symptoms and exacerbations but slowed growth , albeit temporarily and not progressively . CONCLUSIONS In preschool children at high risk for asthma , two years of inhaled-corticosteroid therapy did not change the development of asthma symptoms or lung function during a third , treatment-free year . These findings do not provide support for a subsequent disease-modifying effect of inhaled corticosteroids after the treatment is discontinued . ( Clinical Trials.gov number , NCT00272441 . ) BACKGROUND Although inhaled glucocorticosteroids are recommended for persistent asthma , their long-term effect on recent onset , mild , persistent asthma has yet to be established . METHODS We did a r and omised , double-blind clinical trial in 7241 patients in 32 countries to assess the effects of budesonide  in patients who had had mild persistent asthma for less than 2 years and who had not had previous regular treatment with glucocorticosteroids . Patients aged 5 - 66 years received either budesonide or placebo once daily for 3 years in addition to their usual asthma medications . The daily budesonide dose was 400 microg , or 200 microg for children younger than 11 years . The primary outcome was time to first severe asthma-related event , and analysis was by intention to treat . FINDINGS 198 of 3568 patients on placebo and 117 of 3597 on budesonide had at least one severe asthma exacerbation ; hazard ratio 0.56 ( 95 % CI 0.45 - 0.71 , p<0.0001 ) . Patients on budesonide had fewer courses of systemic corticosteroids and more symptom-free days than did those on placebo . Compared with placebo , budesonide increased postbronchodilator forced expiratory volume in 1 s ( FEV1 ) from baseline by 1.48 % ( p<0.0001 ) after 1 year and by 0.88 % ( p=0.0005 ) after 3 years ( expressed as percent of the predicted value ) . The corresponding increase in prebronchodilator FEV1 was 2.24 % after 1 year and 1.71 % after 3 years ( p<0.0001 at both timepoints ) . The effect of treatment on all outcome variables was independent of the baseline lung function ( prebronchodilator or postbronchodilator ) or baseline medication . In children younger than 11 years , 3-year growth was reduced in the budesonide group by 1.34 cm . The reduction was greatest in the first year of treatment ( 0.58 cm ) than years 2 and 3 ( 0.43 cm and 0.33 cm , respectively ) . INTERPRETATION Long-term , once-daily treatment with low-dose budesonide decreases the risk of severe exacerbations and improves asthma control in patients with mild persistent asthma of recent onset 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 In the treatment of asthma , inhaled steroids are more effective than cromolyn , whereas the latter offers extreme safety . The aim of the present pilot study was to evaluate , contemporarily , efficacy and safety aspects of different asthma treatment modalities . In 75 school-age children ( mean age 9.5 years ; range 5.5 - 14.7 years ) , treatment of asthma was started with budesonide ( BUD , n = 30 ) , fluticasone propionate ( FP , n = 30 ) or cromones ( CROM , n = 15 ) . BUD was used at a dose of 800 microg/day during the first 2 months and at 400 microg/day thereafter . The respective FP doses were 500 and 200 microg/day . Efficacy of the treatment was assessed by measuring forced expiratory volume in 1 second ( FEV1 ) and by evaluating the use of bronchodilators . Side-effects of the treatment were evaluated by following growth of the children and by performing low-dose adrenocorticotropin ( ACTH ) testing . At 4 months FEV1 had improved by a mean of 8.2 % in the BUD group and by 5.4 % in the FP group ( p < 0.01 vs. baseline in both groups ; NS between BUD and FP groups ) . The use of bronchodilators had decreased from five doses/week to one dose/week in the BUD group ( p < 0.05 ) , and from three doses/week to one dose/week in the FP group ( p < 0.01 ) ( NS between the groups ) . In the CROM group , the FEV1 value and the use of bronchodilators did not change . The treatment was unsuccessful on the basis of FEV1 decrease and increased bronchodilator use in , respectively , 30 and 15 % of the BUD- , 20 and 7 % of the FP- , and 50 and 47 % of the CROM-treated children . Therefore , to prevent one treatment failure in the CROM group , between three and five children would need to move to treatment with steroids . The treatment had measurable systemic effects on the basis of height st and ard deviation ( SD ) score decrease and minor adrenocortical suppression in , respectively , 60 and 30 % of the BUD- , 27 and 17 % of the FP- , and 20 and 0 % of the CROM-treated children . Therefore , to avoid systemic effects in one steroid-treated child , three BUD- and six to 14 FP-treated children would need to move to treatment with CROM . In conclusion , in school-age children asthma should be treated first with inhaled steroids . It is probable that the best combination of efficacy and safety can be achieved by using low steroid doses Short-term lower leg growth was investigated with twice weekly knemometry measurements in 19 schoolchildren with mild asthma during treatment with daily doses of 200 micrograms fluticasone propionate  , 400 micrograms , and 800 micrograms beclomethasone dipropionate from a dry powder inhaler . The design was a r and omised , double blind , crossover trial . After a run in period of four days ( period 1 ) the children were allocated to a sequence of active treatments in periods 2 , 4 , and 6 . In periods 3 and 5 ( wash out ) placebo was given . All periods except the run in were two weeks long . The mean lower leg growth velocities during the wash out periods were 0.61 and 0.80 mm/week . Mean growth velocities during treatment with fluticasone propionate and low and high doses of beclomethasone dipropionate were 0.34 , 0.09 , and 0.06 mm/week respectively . Compared with fluticasone propionate , treatment with beclomethasone dipropionate 400 and 800 micrograms/day was associated with a statistically significant reduction in growth velocity Several short-term studies have shown that inhaled steroids can reduce airway hyper-responsiveness in asthma . To evaluate whether prolonged treatment can bring about full recovery , this double-blind , r and omized , controlled trial examined the effect of budesonide , 400 micrograms daily for 1 yr , on airway hyperresponsiveness . The time course and characteristics of improvements and associated changes in clinical asthma severity were also evaluated . Thirty-two stable adult asthmatics , requiring bronchodilators alone , were selected . Before and monthly throughout the study , airway responsiveness to methacholine was measured and clinical asthma severity assessed by question naire , daily bronchodilator use , and number of asthma exacerbations . Patients receiving budesonide  showed a fourfold mean improvement in airway responsiveness compared with those receiving placebo ( p less than 0.0005 ) , whose responsiveness remained very stable . Fifteen of the 16 budesonide subjects improved and 5 returned to the normal range . Largest improvements occurred during the first 3 months but , in some , were still progressing slowly at 1 yr . Improvements in responsiveness were accompanied by significant improvements in asthma symptoms , bronchodilator use , and number of asthma exacerbations . The results show that regular , prolonged use of inhaled steroid can produce marked improvements in airway hyperresponsiveness , sometimes with full resolution , and these improvements are accompanied by clinical ly significant improvements in clinical asthma This study is an extended follow‐up for 24 months of a 12‐week trial to study the long‐term clinical efficacy of low‐dose inhaled budesonide ( BUD ) once or twice daily in children with mild asthma . A total of 122 children ( mean age 9.7 years , girls/boys ; 42/80 ) with mild asthma ( FEV1 103.7 % of predicted , reversibility in FEV1 3.5 % , and fall in FEV1 afterexercise 12.2 % ) , not previously treated with inhaled steroids , were included in a double‐blind , r and omized , parallel‐group study . The children were treated with inhaled BUD 100 or 200 µg administered via Turbuhaler ® once daily in the morning , 100 µg twice daily , or placebo for 27 months . Exercise and methacholine challenges were performed at 3‐month intervals the first year and at 6‐month intervals the second year , in a total of seven visits . A significant dose‐response effect favoring BUD 200 µg daily ( vs 100 µg daily ) was found when comparing changes in FEV1 , FEF25 % , and FEV50 % ; the fall in FEV1 after an exercise test ; and the effect on blood eosinophils . Bronchial hyperreactivity to methacholine decreased significantly on three visits in patients treated with BUD 200 µg daily compared to placebo . Growth rate was not significantly affected except in children aged 7–11 years at baseline after 12 months of treatment . In conclusion , 100 or 200 µg daily of inhaled BUD for 27 months is safe and effective in protecting against exercise‐induced asthma and achieving nearly normal lung function . Baseline lung function was not significantly affected in this group of children with mild asthma BACKGROUND Antiinflammatory therapies , such as inhaled corticosteroids or nedocromil , are recommended for children with asthma , although there is limited information on their long-term use . METHODS We r and omly assigned 1041 children from 5 through 12 years of age with mild-to-moderate asthma to receive 200 microg of budesonide ( 311 children ) , 8 mg of nedocromil ( 312 children ) , or placebo ( 418 children ) twice daily . We treated the participants for four to six years . All children used albuterol for asthma symptoms . RESULTS There was no significant difference between either treatment and placebo in the primary outcome , the degree of change in the forced expiratory volume in one second ( FEV1 , expressed as a percentage of the predicted value ) after the administration of a bronchodilator . As compared with the children assigned to placebo , the children assigned to receive budesonide had a significantly smaller decline in the ratio of FEV1 to forced vital capacity ( FVC , expressed as a percentage ) before the administration of a bronchodilator ( decline in FEV1:FVC , 0.2 percent vs. 1.8 percent ) . The children given budesonide also had lower airway responsiveness to methacholine , fewer hospitalizations ( 2.5 vs. 4.4 per 100 person-years ) , fewer urgent visits to a caregiver ( 12 vs. 22 per 100 person-years ) , greater reduction in the need for albuterol for symptoms , fewer courses of prednisone , and a smaller percentage of days on which additional asthma medications were needed . As compared with placebo , nedocromil significantly reduced urgent care visits ( 16 vs. 22 per 100 person-years ) and courses of prednisone . The mean increase in height in the budesonide group was 1.1 cm less than in the placebo group ( 22.7 vs. 23.8 cm , P=0.005 ) ; this difference was evident mostly within the first year . The height increase was similar in the nedocromil and placebo groups . CONCLUSIONS In children with mild-to-moderate asthma , neither budesonide nor nedocromil is better than placebo in terms of lung function , but inhaled budesonide improves airway responsiveness and provides better control of asthma than placebo or nedocromil . The side effects of budesonide are limited to a small , transient reduction in growth velocity In a double-blind , parallel-group study , we examined the effect of short-term treatment with inhaled fluticasone propionate ( FP ) in a group of 20 nonsmoking asthmatic patients who required only beta2-agonists to control their symptoms . We administered FP ( 250 microg twice daily ) or matched placebo for 6 wk . Methacholine challenge was performed before treatment , after 3 wk , and at the end of treatment . Each patient underwent bronchoscopy with bronchoalveolar lavage ( BAL ) and bronchial biopsy before and after treatment . Eight patients in the placebo group and nine patients in the FP group completed the study .  Bronchial responsiveness to methacholine decreased significantly only after 6 wk of treatment with FP ( p < 0.05 ) . When we compared the FP group with the placebo group , we observed a significant decrease only in the number of cells expressing intracellular adhesion molecule-1 ( ICAM-1 ) and MAC-1 ( p < 0.04 and p < 0.03 , respectively ) . Moreover , we saw that the tryptase level in BAL decreased ( p < 0.001 ) , whereas the eosinophil cationic protein ( ECP ) level did not change significantly . Additionally , the number of eosinophils and mast cells in the lamina propria in bronchial biopsies specimens was significantly smaller in the FP group than in the placebo group ( p < 0.02 and p < 0.01 , respectively ) . Additionally , in the FP group , we found that basement-membrane thickness was significantly decreased when compared with that of the placebo group ( p < 0.05 ) . In conclusion , our results show that short-term treatment with low-dose FP reduces inflammatory cell infiltration into the lamina propria in bronchial biopsy specimens . Moreover , short-term low-dose FP treatment might control the intensity of airway remodeling in mild asthma BACKGROUND Growth in stature in asthmatic adolescents may be delayed compared to normals as a result of treatment with inhaled corticosteroids ( CS ) or because of a delay in puberty . However , growth rates in asthmatic children have never been studied when treatment with CS was r and omized and when growth was compared with that of matched healthy control subjects . OBJECTIVE To assess the long-term effect of CS treatment on growth rates in asthmatic adolescents . METHODS Participants were 40 asthmatic teenagers ( mean age 12.8 years ) who received r and omized treatment with 0.2 mg of albuterol ( salbutamol ) with either placebo three times a day ( BA + PL ) or 0.2 mg of budesonide three times a day ( BA + CS ) for a median period of 22 months in a double-blind controlled study . Growth rates were compared with those of 80 control subjects who were matched for sex , age , height , and duration of follow-up . RESULTS Growth rates in male patients , but not in female patients , were significantly less than in control subjects ( P < .05 ) , a finding consistent with a delay of puberty due to asthma . The mean difference ( 95 % confidence interval ) in growth rates between patients treated with BA+PL and their controls was -0.70 ( -1.62 , 0.22 ) cm/y ; that between patients treated with BA + CS and their controls was -0.44 ( -1.25 , 0.37 ) cm/y . The observed mean ( SEM ) case-control difference between treatment groups was + 0.27 ( 0.58 ) cm/y in favor of BA + CS . CONCLUSION Growth retardation observed in adolescents with asthma may be due to a delay in puberty but not to the prescription of 0.6 mg of budesonide daily Short-term knemometry is a highly sensitive and accurate method for non-invasive assessment of systemic activity of inhaled corticosteroids in children with asthma . However , there are no r and omized data available to eluci date the relation between inhaled corticosteroid suppressed short-term lower leg and height growth . The aim of the present study was to assess the relation between short-term lower leg and 1-yr height growth in children with asthma treated with inhaled budesonide from the new Pulairmax inhaler 200 μg once daily in the morning or montelukast 5 mg once daily . A total of 52 pre-pubertal children with asthma were included in a r and omized open-label parallel group study . Length of the lower leg and height were measured by  knemometry and stadiometry  , respectively , at study entry and after 2 , 4 , 12 , 20 , 28 , 36 , 44 and 52 wks . Lower leg and height growth rates were significantly lower in the budesonide than in the montelukast group ( p < 0.0001 ) . Mean 2-wks lower leg growth rate was 0.17 mm/wk in the budesonide and 0.39 mm/wk in the montelukast treated children ( p = 0.02 ) . Mean 1-yr height growth rate was 5.51 cm/yr in the budesonide and 6.51 cm/yr in the montelukast group [ 95 % CI : ( 0.20 ; 1.79 ) ] . There was a strong linear correlation between lower leg and height growth in both groups , rho = 0.96 ( budesonide ) and 0.98 ( montelukast ) . In conclusion , 1-yr height growth suppression  of budesonide 200 μg administered via the Pulairmax inhaler once daily in the morning was indicated from suppressed short-term lower leg growth providing evidence that short-term knemometry is able to predict 1-yr height growth suppression of inhaled corticosteroids . Short-term knemometry should be performed as part of the safety assessment s of new inhaled corticosteroids and inhalation devices in children with asthma before long-term height growth evaluations are initiated 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 BACKGROUND Daily inhaled corticosteroids are an effective treatment for mild persistent asthma , but some children have exacerbations even with good day-to-day control , and many discontinue treatment after becoming asymptomatic . We assessed the effectiveness of an inhaled corticosteroid ( beclomethasone dipropionate ) used as rescue treatment . METHODS In this 44-week , r and omised , double-blind , placebo-controlled trial we enrolled children and adolescents with mild persistent asthma aged 5 - 18 years from five clinical centres in the USA . A computer-generated r and omisation sequence , stratified by clinical centre and age group , was used to r and omly assign participants to one of four treatment groups : twice daily beclomethasone with beclomethasone plus albuterol as rescue ( combined group ) ; twice daily beclomethasone with placebo plus albuterol as rescue ( daily beclomethasone group ) ; twice daily placebo with beclomethasone plus albuterol as rescue ( rescue beclomethasone group ) ; and twice daily placebo with placebo plus albuterol as rescue ( placebo group ) . Twice daily beclomethasone treatment was one puff of beclomethasone ( 40 μg per puff ) or placebo given in the morning and evening . Rescue beclomethasone treatment was two puffs of beclomethasone or placebo for each two puffs of albuterol ( 180 μg ) needed for symptom relief . The primary outcome was time to first exacerbation that required oral corticosteroids . A secondary outcome measured linear growth . Analysis was by intention to treat . This study is registered with clinical trials.gov , number NCT00394329 . RESULTS 843 children and adolescents were enrolled into this trial , of whom 288 were assigned to one of four treatment groups ; combined ( n=71 ) , daily beclomethasone ( n=72 ) , rescue beclomethasone ( n=71 ) , and placebo (n=74)-555 individuals were excluded during the run-in , according to predefined criteria . Compared with the placebo group ( 49 % , 95 % CI 37 - 61 ) , the frequency of exacerbations was lower in the daily ( 28 % , 18 - 40 , p=0·03 ) , combined ( 31 % , 21 - 43 , p=0·07 ) , and rescue ( 35 % , 24 - 47 , p=0·07 ) groups . Frequency of treatment failure was 23 % ( 95 % CI 14 - 43 ) in the placebo group , compared with 5·6 % ( 1·6 - 14 ) in the combined ( p=0·012 ) , 2·8 % ( 0 - 10 ) in the daily ( p=0·009 ) , and 8·5 % ( 2 - 15 ) in the rescue ( p=0·024 ) groups . Compared with the placebo group , linear growth was 1·1 cm ( SD 0·3 ) less in the combined and daily arms ( p<0·0001 ) , but not the rescue group ( p=0·26 ) . Only two individuals had severe adverse events ; one in the daily beclomethasone group had viral meningitis and one in the combined group had bronchitis . INTERPRETATION Children with mild persistent asthma should not be treated with rescue albuterol alone and the most effective treatment to prevent exacerbations is daily inhaled corticosteroids . Inhaled corticosteroids as rescue medication with albuterol might be an effective step-down strategy for children with well controlled , mild asthma because it is more effective at reducing exacerbations than is use of rescue albuterol alone . Use of daily inhaled corticosteroid treatment and related side-effects such as growth impairment can therefore be avoided . FUNDING National Heart , Lung and Blood Institute BACKGROUND Antileukotrienes and inhaled corticosteroids are asthma controller agents widely used in the treatment of pediatric asthma . OBJECTIVE To evaluate the effects of montelukast and beclomethasone on linear growth in prepubertal asthmatic children for 1 year . METHODS This was a 30-center study of boys ( 6.4 - 9.4 years old ) and girls ( 6.4 - 8.4 years old ) at Tanner stage I with mild , persistent asthma . After a placebo run-in period , 360 patients were r and omized in equal ratios to double-blind , double-dummy treatment with 5 mg of montelukast , 200 microg of beclomethasone twice daily ( positive control ) , or placebo for 56 weeks ; 90 % of the patients completed the study . The primary end point was linear growth velocity , measured using a stadiometer . RESULTS Linear growth rates were similar between the montelukast and placebo groups ; the mean difference for the year was 0.03 cm . The mean growth rate with beclomethasone was significantly less than with placebo ( -0.78 cm ) or montelukast ( 0.81 cm ) ( P < .001 for both ) . Median percentage of days with beta-agonist use was greater with placebo ( 14.58 % ) vs montelukast ( 10.55 % ) or beclomethasone ( 6.65 % ) ( P < .05 for all ) . More patients used oral corticosteroid rescue with placebo ( 34.7 % ) than with montelukast ( 25.0 % ) or beclomethasone ( 23.5 % ) . An imbalance in bone marker levels was seen with beclomethasone but not with montelukast . CONCLUSION In prepubertal asthmatic children , montelukast did not affect linear growth , whereas the growth rate with beclomethasone was significantly decreased during 1 year of treatment The aim of the present study was to evaluate the prevalence of adrenal suppression and growth retardation in children using moderate doses of budesonide or fluticasone propionate . Seventy-five asthmatic children were r and omly divided into three treatment groups : 30 to the fluticasone propionate ( FP ) , 30 to the budesonide ( BUD ) , and 15 to the  cromone ( CROM ) group .  FP doses were 500 microg/day during the first 2 months and 200 microg/day thereafter . The respective BUD doses were 800 and 400 microg/day . A low dose ACTH ( 0.5 microg/1.73 m2 ) test was performed before treatment and 2 , 4 , and 6 months later . The test was considered abnormal if the stimulated serum cortisol concentration was more than 2 SD lower than the pretreatment mean ( < 330 nmol/L ) . The low dose ACTH test was abnormal after both the high and low steroid doses in 23 % of the children . At the 4 month measurement there were more abnormal tests in the BUD ( n = 9 ) than in the FP ( n = 5 ) group ( P < 0.05 ) . At that time also the stimulated concentration of serum cortisol was lower in the BUD than in the CROM group ( P < 0.01 ) , whereas the difference between the FP and CROM groups was not significant . During the study year the mean decrease in height SD score was 0.23 in the children treated with BUD , 0.03 in the children treated with FP , and 0.09 in the children treated with CROM ; the difference between the BUD and FP groups was significant ( P < 0.05 ) . In conclusion , the low dose ACTH test revealed mild adrenal suppression in a quarter of the children using moderate doses of inhaled steroids . A FP dose of 200 microg/day caused less adrenal and growth suppression than did a BUD dose of 400 microg/day OBJECTIVE To determine whether inhaled fluticasone propionate has long-term effects on growth in children with persistent asthma . STUDY DESIGN In a double-blind , r and omized , parallel-group , multicenter study , 325 prepubescent children with persistent asthma and normal growth rates were treated with placebo or inhaled fluticasone propionate powder 50 microg or 100 microg administered twice daily by a breath-actuated device for 1 year . Growth was evaluated monthly , whereas other safety variables and pulmonary function were evaluated periodically . RESULTS The prepubescent patients showed no statistically significant differences in mean height , mean growth velocity , or mean skeletal age between any of the treatment groups at any time . Over a period of 1 year , mean height ( + /- SE ) increased 6.15 + /- 0.17 cm in the placebo group , 5.94 + /- 0.16 cm in the fluticasone propionate 50 microg group , and 5.73 + /- 0.13 cm in the fluticasone propionate 100 microg group ( p = 0.308 , overall ) . CONCLUSIONS Prepubescent children treated with fluticasone propionate 50 microg and 100 microg administered twice daily for 1 year grew at rates similar to placebo-treated control subjects and at rates equal to expected growth velocity for age 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 The Childhood Asthma Management Program ( CAMP ) is a multicenter , r and omized , double-masked clinical trial design ed to determine the long-term effects of three inhaled treatments for mild to moderate childhood asthma : budesonide ( a glucocorticoid used daily ) and albuterol ( a short-acting beta-agonist bronchodilator used as needed ) ; nedocromil ( a nonsteroid anti-inflammatory agent used daily ) and albuterol ; and placebo and albuterol .  One thous and forty-one children ( 32 % from ethnic minority groups ) , aged 5 to 12 years at screening , are currently participating . The primary outcome measure is lung growth as indicated by postbronchodilator forced expiratory volume in 1 second ( FEV1 ) percent of predicted , observed over 5- to 6-year period . The trial also assesses differences between treatment groups with respect to airway responsiveness , morbidity , physical growth and development , and psychological growth and development . This report describes the design of the trial , the rationale for the design choices made , and the methods used to carry out the trial Beclomethasone dipropionate was found to be effective in reducing symptoms of asthma in children . There was no measurable influence on pulmonary function . An 18-month follow-up did not show untoward side effects on adrenal function , growth , serum electrolytes , and hepatic and renal functions with a dose of 100 mug three times daily . The treatment predisposes to the colonization with C and ida albicans in the oropharynx OBJECTIVE To compare the efficacy and adverse effects of inhaled fluticasone propionate ( FP ) , 400 microgram/d , with those of budesonide ( BUD ) , 800 microgram/d , in children with moderate to severe asthma . METHODS Three hundred thirty-three children , ages 4 to 12 years , receiving inhaled corticosteroids  were enrolled in a double-blind , double-dummy , r and omized , parallel-group study . After a 2-week run-in phase , 166 children received FP and 167 received BUD for 20 weeks . The primary outcome variable was mean morning peak expiratory flow ; the 2 treatments were to be regarded as equivalent if the 90 % CI for the treatment difference was within + /- 15 L/min . Pulmonary function , height , and diary cards were assessed at each visit ; and morning serum cortisol levels were determined before and after treatment . RESULTS Baseline peak expiratory flow was similar , FP 236 + /- 72 ( SD ) L/min and BUD 229 + /- 74 , increasing after treatment to 277 + /- 41 and 257 + /- 28 , a difference between treatments of 12 L/min ( 90 % CI 6 - 19 L/min ; P = .002 ) . Symptom control and use of rescue medication were the same . Cortisol levels after treatment were 199 nmol/L ( FP ) and 183 nmol/L ( BUD ) ( treatment ratio = 1.09 ; 90 % CI 0.98 - 1.21 ; P = .172 ) . Linear growth was less in those receiving BUD ( mean difference , 6.2 mm ; 95 % CI 2.9 - 9.6 ; P = .0003 ) . CONCLUSION FP at half the dose was superior to BUD in improving peak expiratory flow and comparable in controlling symptoms . Growth was reduced with BUD compared with FP , but there was no difference in serum cortisol suppression or hepatic or renal function Poorly controlled severe asthma can lead to  growth impairment in childhood . In children with mild asthma , it is less clear whether treatment influences growth or adrenal function . We determined in a r and omized , double-blind , placebo-controlled , community-based study , the effect of inhaled beclomethasone dipropionate ( BDP ) 400 micrograms/day for 7 mo on the linear growth and adrenal function of 94 children 7 to 9 yr of age .  Height was measured at least monthly during treatment , and adrenal function assessed by overnight urinary cortisol at baseline and after 3 and 6 mo of treatment . Mean regressed daily growth was significantly decreased during the treatment period in the BDP-treated group , 0.79 versus 1.14 mm/wk ( difference 0.35 mm/wk ; 95 % CI -0.46 to -0.25 ; p < 0.0001 ) . At the end of the 7 mo , the BDP-treated children had grown significantly less than the children on placebo : mean of 2.66 versus 3.66 cm ( difference 1.0 cm ; 95 % CI -1.36 to -0.64 cm ; p < 0.0001 ) . Growth was significantly decreased in both males and females . During a washout period of 4 mo , there was no significant catch-up growth .  BDP had no effect on overnight urinary cortisol production .  BDP at a dose taken by many children significantly decreases statural growth in children with mild asthma , and this effect is unlikely to be mediated through the hypothalamo-pituitary-adrenal axis BACKGROUND Current asthma guidelines recommend inhaled glucocorticoids administered via pressurized metered-dose inhaler ( MDI ) with a holding chamber as the preferred therapy for young children with asthma . OBJECTIVE To evaluate the efficacy and safety of fluticasone propionate chlorofluorocarbon MDI use in preschool-aged children with asthma . METHODS R and omized , double-blind , placebo-controlled , parallel-group study of 332 children aged 24 to 47 months with asthma .  Fluticasone propionate chlorofluorocarbon , 44 or 88 microg twice daily , or placebo ( chlorofluorocarbon propellant alone ) administered for 12 weeks via MDI with a valved holding chamber and an attached face mask . The primary efficacy measure was average change in 24-hour daily asthma symptom scores . Safety assessment s included adverse events , 12-hour urinary cortisol excretion , and growth . RESULTS Treatment failure ( ie , asthma exacerbation ) occurred in approximately half as many fluticasone propionate-treated patients ( 13%-14 % ) as placebo-treated patients ( 24 % ) . Compared with placebo users , patients treated with fluticasone propionate , 88 microg twice daily , had a 13 % greater improvement in the mean proportion of symptom- and albuterol-free days ( P = .02 ) ; asthma symptom scores and albuterol use were also significantly reduced . Patients treated with fluticasone propionate , 44 microg twice daily , had greater improvements than placebo-treated patients ; however , differences did not reach statistical significance . At end point , the growth velocities of fluticasone propionate-treated patients were within the range of those of placebo-treated patients . No clinical ly relevant changes in 12-hour overnight urinary cortisol excretion were observed . CONCLUSION Compared with placebo use , fluticasone propionate , 88 microg administered twice daily , significantly reduced asthma exacerbations , asthma symptoms , and rescue albuterol use and was well tolerated , with no clinical ly relevant systemic effects , as measured by growth velocity or 12-hour urinary cortisol excretion levels Flunisolide hydrofluoroalkane ( HFA ) has efficacy equivalent to that of flunisolide chlorofluorocarbon ( CFC ) at one third the dose of the CFC formulation , a reduction from 250 pg/puff for flunisolide CFC to 85 pg/puff for flunisolide HFA . Flunisolide HFA delivers a smaller particle size ( 1.2 pim ) in solution , result ing in improved lung deposition as compared with flunisolide CFC ( 3.8 pm ) , which is delivered in suspension . An added built-in spacer has reduced oropharyngeal deposition that may result in fewer adverse events and make it easier to use . The objective of this study was to compare the year-long safety of flunisolide HFA ( daily dosage 340 pg ) with that of CFC beclomethasone dipropionate ( BDP ) ( daily dosage 336 pg ) and cromolyn sodium ( daily dosage 6,400 pg ) in children 4 - 11 years old with mild-to-moderate asthma . The effects of these drugs on linear growth and growth velocity were also compared . The study was a 1-year open-label , parallel-group trial . Changes in physical examinations ( including growth ) , adverse events , vital signs , electrocardiograms , cosyntropin stimulation tests , mouth and throat cultures for C and ida albicans , and laboratory findings were analyzed . Patients 4 - 5 years old received flunisolide HFA only . In total , 235 children were evaluated ( 152 receiving flunisolide HFA , 39 BDP , and 44 cromolyn )  . The incidence of adverse events was comparable among treatment groups ; most were mild or moderate and considered unrelated to treatment . Among patients 6 - 11 years old , mean changes from baseline height at week 52 were 6.2 cm for the flunisolide HFA and cromolyn groups and 5.1 cm for the BDP group . Thus growth in children receiving flunisolide HFA was unaffected by 1 year of treatment . Changes from baseline in other parameters , including response to cosyntropin stimulation , were insignificant and similar among the 3 treatment groups . At the dosages studied , and following 1 year of treatment , flunisolide HFA with its small particle size and built-in spacer is safe and well tolerated in children 4 - 11 years old . There are no adverse effects associated with HFA , including linear growth in children 6 - 11 years old when compared with BDP and  cromolyn sodium BACKGROUND More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children . OBJECTIVE The Pediatric Asthma Controller Trial ( PACT ) compared the effectiveness of 3 regimens in achieving asthma control . METHODS A total of 285 children ( ages 6 - 14 years ) with mild-moderate persistent asthma on the basis of symptoms , and with FEV(1 ) > or= 80 % predicted and methacholine FEV(1 ) PC(20 ) < or= 12.5 mg/mL , were r and omized to 1 of 3 double-blind 48-week treatments : fluticasone 100 microg twice daily ( fluticasone monotherapy ) , fluticasone 100 microg/salmeterol 50 microg in the morning and salmeterol 50 mug in the evening ( PACT combination ) , and montelukast 5 mg in the evening . Outcomes included asthma control days ( primary outcome ) , exacerbations , humanistic measurements , and pulmonary function measurements . RESULTS Fluticasone monotherapy and PACT combination were comparable in many patient-measured outcomes , including percent of asthma control days , but fluticasone monotherapy was superior for clinic-measured FEV(1)/forced vital capacity ( P = .015 ) , maximum bronchodilator response ( P = .009 ) , exhaled nitric oxide ( P < .001 ) , and PC(20 ) ( P < .001 ) . Fluticasone monotherapy was superior to montelukast for asthma control days ( 64.2 % vs 52.5 % ; P = .004 ) and for all other control outcomes . Growth over 48 weeks was not statistically different ( fluticasone , 5.3 cm ; PACT combination , 5.3 cm ; montelukast , 5.7 cm ) . CONCLUSION Both fluticasone monotherapy and PACT combination achieved greater improvements in asthma control days than montelukast . However , fluticasone monotherapy was superior to PACT combination in achieving other dimensions of asthma control . Growth was similar in all groups . CLINICAL IMPLICATION S Therefore , of the regimens tested , the PACT study findings favor fluticasone monotherapy in treating children with mild-moderate persistent asthma with FEV(1 ) > or= 80 % predicted , confirming current guideline recommendations Our objective was to evaluate the efficacy and safety of two doses of fluticasone propionate ( FP ) in young children with recurrent wheezing and risk factors for asthma . Our study design was a r and omized , double-blind , placebo-controlled comparison of inhaled FP 50 mcg twice daily ( FP 100 ) and 125 mcg twice daily ( FP 250 ) , for 6 months . Outcome measures included number of wheezing episodes , days on albuterol , height st and ard deviation score ( height SDS ) , osteocalcin ( OC ) , bone alkaline phosphatase fraction ( AKP ) , insulin-like growth factor-binding protein 3 ( IGFBP-3 ) , and serum levels of cortisol ( SC ) .  Our subjects were 30 patients , aged 7 - 24 months .  Mean wheezing episodes were 6.0 + /- 1.9 , 1.9 + /- 1.9 , and 2.8 + /- 1.2 ; mean days of albuterol use were 24.3 + /- 1.3 , 6.5 + /- 0.8 , and 9.1 + /- 0.8 , per patient for placebo , FP100 , and FP250 groups , respectively . There was a significant reduction in clinical outcome in the two FP groups compared to placebo ( P < 0.01 ) . No significant correlations were found between FP dosage and height SDS , OC , AKP , IGFBP-3 , and SC . In conclusion , in young children with asthmatic symptoms , FP at 50 and 125 mcg b.i.d . for 6 months significantly improved respiratory symptoms without causing significant side effects on growth and bone metabolism OBJECTIVE To evaluate the efficacy and safety of three doses of ciclesonide ( with or without spacer ) in children with persistent asthma . PATIENTS AND METHODS This was a multicentre , double-blind , placebo-controlled , 12-week study of ciclesonide 40 , 80 or 160 μg ( once daily pm ) . Children ( 6 - 11 years ) were r and omised 1:1 to treatment via a metered dose inhaler ( MDI ) or MDI plus spacer . The primary variable was change from baseline in mean morning peak expiratory flow ( PEF ) . Secondary variables included : time to first lack of efficacy ( LOE ) , asthma control , forced expiratory volume in 1 s ( FEV(1 ) ) , asthma symptom score and quality of life ( QoL ) . Safety assessment s included : adverse events ( AEs ) , urinary cortisol excretion and body height . RESULTS In total , 1073 children received treatment . At endpoint , mean morning PEF significantly improved with all doses of ciclesonide vs. placebo . There was no difference over placebo in time to first LOE , but ciclesonide was superior to placebo on asthma control , symptom score , FEV(1 ) and QoL. There were no differences between the spacer or non-spacer subgroups . The incidences of AEs were comparable between treatment groups ( approximately 35 % ) and there were no between-group differences in body height or urinary cortisol . CONCLUSIONS Ciclesonide 40 - 160 μg once daily is effective and well tolerated in children with persistent asthma ; its efficacy and safety are unaffected by the use of a spacer . clinical trials.gov registration number : NCT00384189 BACKGROUND Few large-scale studies have examined inhaled corticosteroid treatment in preschool children with recurrent wheeze . We assessed the effects of ciclesonide in preschool children with recurrent wheeze . METHODS We included children 2 - 6 yrs with recurrent wheeze and a positive asthma predictive index or aeroallergen sensitization to , excluding patients with episodic viral wheezing . After a 2 - 4-week baseline period , patients with ongoing symptoms or rescue medication use were r and omised to once-daily ciclesonide 40 , 80 , 160 μg or placebo for 24 weeks . RESULTS The number of wheeze exacerbations requiring systemic corticosteroids  was unexpectedly low in all groups : 25 ( 10.2 % ) in placebo group , as compared to 11 ( 4.4 % ) , 18 ( 7.3 % ) , and 17 ( 6.7 % ) in ciclesonide 40 , 80 , and 160 μg , respectively . The difference in time to first exacerbation was not significantly different between groups ( p = 0.786 ) , but the difference in exacerbation rates between placebo and the pooled ciclesonide groups was ( p = 0.03 ) . Large and significant ( p < 0.0001 ) improvements in symptom scores and rescue medication use occurred in all groups , including placebo . Improvements in FEV(1 ) and FEF(25 - 75 ) ( measured in 284 4 - 6 yr olds ) were larger in the ciclesonide than in the placebo group . No differences in safety parameters ( adverse events , height growth , serum and urinary cortisol levels ) between ciclesonide and placebo were observed . CONCLUSIONS In preschool children with recurrent wheeze and a positive asthma predictive index  , ciclesonide modestly reduces wheeze exacerbation rates and improves lung function . A large placebo response and unexpected selection of patients with mild disease may have affected outcomes , highlighting the heterogeneity of preschool wheezing disorders Correlations between knemometric ( lower leg length ) growth rates and urine free cortisol excretion , respectively , and serum concentrations of IGF-I , IGF binding protein-3 , osteocalcin , carboxy terminal propeptide of type I collagen(PICP ) , carboxy terminal pryridinoline cross-linked telopeptide of type I procollagen ( ICTP ) , and amino terminal propeptide of type III procollagen(PIIINP ) were investigated in 17 asthmatic children aged 7 - 14 y during treatment with fluticasone propionate , 200 μg , and beclomethasone dipropionate , 400 and 800 μg/d , taken from dry powder inhalers . The study was a double blind , crossover trial with three active treatment periods and two wash-out periods . All periods were 15 d long . Overnight urine free cortisol/creatinine × 106 did not correlate with knemometric growth rates or any of the serum markers . Significant correlations ( Pearson 's correlation coefficient , P ) between knemometric growth rates and IGF-I ( 0.41 ; 0.006 ) , IGFBP-3 ( 0.35 ; 0.02 ) , PICP ( 0.44 ; 0.003 ) , ICTP ( 0.35 ; 0.001 ) , and PIIINP ( 0.46 ; 0.002 ) were found . Compared with fluticasone propionate , 200 μg , beclomethasone dipropionate , 400 and 800 μg , caused significant suppression of lower leg growth rate ( F = 12.41;p = 0.002 , and F = 23.30 ; p = 0.0001 , respectively ) and of urine free cortisol/creatinine × 106(F = 10.52 ; p = 0.003 , and F = 13.74;p = 0.001 ) . Beclomethasone , 800 μg , caused suppression of PICP compared with fluticasone propionate , 200 μg ( F = 8.31;p = 0.008 ) , and beclomethasone , 400 μg ( F = 7.53;p = 0.01 ) . Both low ( F = 6.82 ; p = 0.02 ) and high ( F = 23.35 ; p = 0.0001 ) doses of beclomethasone were associated with reduced concentrations of ICTP , the high dose being the most suppressive ( F = 4.42 ; p = 0.05 ) . Beclomethasone 400(F = 9.75 ; p = 0.004 ) and 800 μg ( F = 23.61;p = 0.0001 ) result ed in reduced levels of PIIINP . Reduced short-term knemometric growth rates in children treated with inhaled glucocorticosteroids reflect suppressive effects on type I and type III collagen turnover
BACKGROUND Treatment guidelines for asthma recommend inhaled corticosteroids ( ICS ) as first-line therapy for children with persistent asthma .
Although ICS treatment is generally considered safe in children , the potential systemic adverse effects related to regular use of these drugs have been and continue to be a matter of concern , especially the effects on linear growth .
OBJECTIVES To assess the impact of ICS on the linear growth of children with persistent asthma and to explore potential effect modifiers such as characteristics of available treatments ( molecule , dose , length of exposure , inhalation device ) and of treated children ( age , disease severity , compliance with treatment ) .
However , additional studies are needed to better characterise the molecule dependency of growth suppression , particularly with newer molecules ( mometasone , ciclesonide ) , to specify the respective role of molecule , daily dose , inhalation device and patient age on the effect size of ICS , and to define the growth suppression effect of ICS treatment over a period of several years in children with persistent asthma .
PLAIN LANGUAGE SUMMARY Do inhaled corticosteroids reduce growth in children with persistent asthma ?
Review question : We review ed the evidence on whether inhaled corticosteroids ( ICS ) could affect growth in children with persistent asthma , that is , a more severe asthma that requires regular use of medications for control of symptoms .