human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    