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 compare the efficacy and safety of once-daily inhaled ciclesonide 40 mug ( CIC40 ) , 80 mug ( CIC80 ) , and 160 mug ( CIC160 ) with placebo in children with persistent asthma of all severities . STUDY DESIGN Overall , 1031 children age 4 to 11 years were r and omized into 2 identical double-blinded , placebo-controlled , parallel group studies consisting of a run-in phase followed by 12 weeks of treatment . Both studies were design ed to allow for a prespecified integrated analysis . The primary outcome variable was change in forced expiratory volume in 1 second ( FEV(1 ) ) percent predicted between baseline and study end ; treatment comparisons were assessed using analysis of covariance . Additional endpoints included asthma symptom scores , daily albuterol use , and safety , including hypothalamic-pituitary-adrenal ( HPA ) axis function . RESULTS Baseline characteristics were comparable ; 59.4 % of patients had moderate asthma , and 24.1 % had severe asthma . All ciclesonide doses were associated with greater improvements in baseline to week 12 FEV(1 ) percent predicted versus placebo ( CIC40 , 11.97 ; CIC80 , 13.58 , P < .05 ; CIC160 , 14.17 , P < .01 ) . Significant improvements in asthma symptoms ( P < .01 ) and reductions in albuterol use were reported . Ciclesonide was well tolerated with no effect on HPA axis function . CONCLUSIONS In this integrated analysis , ciclesonide was effective and well tolerated in children with persistent asthma 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 BACKGROUND Onset of bronchodilation of budesonide/formoterol in one pressurized metered-dose inhaler ( pMDI ) has not been evaluated in asthma . OBJECTIVE To evaluate time to onset of clinical ly significant bronchodilation ( > or = 15 % improvement in forced expiratory volume in 1 second ) and patient-perceived onset of effect ( OE ) in patients previously receiving inhaled corticosteroids . METHODS In two 12-week studies , patients 12 years and older with moderate to severe ( study 1 ; n = 596 ) and mild to moderate ( study 2 ; n = 480 ) persistent asthma received budesonide/formoterol pMDI , budesonide pMDI plus formoterol dry powder inhaler ( study 1 only ) , budesonide pMDI , formoterol dry powder inhaler , or placebo . Postdose time to 15 % or greater improvement in forced expiratory volume in 1 second and patient-perceived OE ( assessed in a subset of patients 18 years and older [ study 1 , n=553 ; study 2 , n=405 ] ) were evaluated [ corrected ] RESULTS More budesonide/formoterol-treated patients achieved onset of clinical ly significant bronchodilation within 15 minutes ( median , 13 minutes ) of administration at r and omization vs those taking budesonide or placebo ( P < .001 ) . More patients receiving budesonide/formoterol vs budesonide and placebo reported feeling their study medication begin to work right away ( P < or = .004 ; end of week 1 ) . Similar results ( P < .001 ) were observed for patient satisfaction with how quickly they felt their medication begin to work ( except budesonide/formoterol vs budesonide , study 1 [ P = .073 ] ) . Time to onset of clinical ly significant bronchodilation and patient-perceived OE of budesonide/formoterol and formoterol were similar . CONCLUSION Budesonide/formoterol demonstrated a more rapid onset of clinical ly significant bronchodilation and a greater percentage of patients who perceived their medication working right away vs budesonide or placebo 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 Environmental tobacco smoke ( ETS ) negatively affects children with asthma . The prevalence of ETS exposure among children with poor asthma control may be changing . Importantly , the mechanisms by which ETS worsens asthma control are poorly understood . OBJECTIVE We describe how ETS affects gastroesophageal reflux ( GER ) , respiratory infections , and leukotriene production among children with poor asthma control . METHODS We analyzed data from 306 children between 6 and 17 years of age with poorly controlled asthma enrolled in a 6-month clinical trial . We evaluated prevalence and determinants of ETS exposure by interview , question naire , and urinary cotinine and the association of ETS exposure on leukotriene production , respiratory infections , GER , lung function , and asthma control . We used multivariable linear , logistic , and Poisson regressions to assess outcomes . RESULTS ETS prevalence estimates ranged from 6 % to 30 % . Children with domestic indoor exposure had worse asthma control ( c-Asthma Control Test , 17.8 vs 21.5 ; P = .04 ) , worse FEV1 % predicted ( 84.1 vs 90.7 ; P = .02 ) , and a trend for increased mean urinary leukotriene E4 . ETS from any setting was associated with increased symptomatic respiratory infections ( adjusted incidence rate ratio : 1.30 ; P = .02 ) . However , children exposed to ETS did not have symptoms or pH probe results , suggestive of heightened GER . CONCLUSIONS Domestic smoking exposure was associated with both higher rates of symptomatic respiratory infection and poorer asthma control despite generally intensive controller therapy . ETS exposure is common among asthmatic children with poor control and may worsen asthma control by promoting respiratory infections . Further investigation is required to eluci date ETS mechanisms in poor asthma control 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  
    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 compare the efficacy and safety of once-daily inhaled ciclesonide 40 mug ( CIC40 ) , 80 mug ( CIC80 ) , and 160 mug ( CIC160 ) with placebo in children with persistent asthma of all severities . STUDY DESIGN Overall , 1031 children age 4 to 11 years were r and omized into 2 identical double-blinded , placebo-controlled , parallel group studies consisting of a run-in phase followed by 12 weeks of treatment . Both studies were design ed to allow for a prespecified integrated analysis . The primary outcome variable was change in forced expiratory volume in 1 second ( FEV(1 ) ) percent predicted between baseline and study end ; treatment comparisons were assessed using analysis of covariance . Additional endpoints included asthma symptom scores , daily albuterol use , and safety , including hypothalamic-pituitary-adrenal ( HPA ) axis function . RESULTS Baseline characteristics were comparable ; 59.4 % of patients had moderate asthma , and 24.1 % had severe asthma . All ciclesonide doses were associated with greater improvements in baseline to week 12 FEV(1 ) percent predicted versus placebo ( CIC40 , 11.97 ; CIC80 , 13.58 , P < .05 ; CIC160 , 14.17 , P < .01 ) . Significant improvements in asthma symptoms ( P < .01 ) and reductions in albuterol use were reported . Ciclesonide was well tolerated with no effect on HPA axis function . CONCLUSIONS In this integrated analysis , ciclesonide was effective and well tolerated in children with persistent asthma 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 BACKGROUND Onset of bronchodilation of budesonide/formoterol in one pressurized metered-dose inhaler ( pMDI ) has not been evaluated in asthma . OBJECTIVE To evaluate time to onset of clinical ly significant bronchodilation ( > or = 15 % improvement in forced expiratory volume in 1 second ) and patient-perceived onset of effect ( OE ) in patients previously receiving inhaled corticosteroids . METHODS In two 12-week studies , patients 12 years and older with moderate to severe ( study 1 ; n = 596 ) and mild to moderate ( study 2 ; n = 480 ) persistent asthma received budesonide/formoterol pMDI , budesonide pMDI plus formoterol dry powder inhaler ( study 1 only ) , budesonide pMDI , formoterol dry powder inhaler , or placebo . Postdose time to 15 % or greater improvement in forced expiratory volume in 1 second and patient-perceived OE ( assessed in a subset of patients 18 years and older [ study 1 , n=553 ; study 2 , n=405 ] ) were evaluated [ corrected ] RESULTS More budesonide/formoterol-treated patients achieved onset of clinical ly significant bronchodilation within 15 minutes ( median , 13 minutes ) of administration at r and omization vs those taking budesonide or placebo ( P < .001 ) . More patients receiving budesonide/formoterol vs budesonide and placebo reported feeling their study medication begin to work right away ( P < or = .004 ; end of week 1 ) . Similar results ( P < .001 ) were observed for patient satisfaction with how quickly they felt their medication begin to work ( except budesonide/formoterol vs budesonide , study 1 [ P = .073 ] ) . Time to onset of clinical ly significant bronchodilation and patient-perceived OE of budesonide/formoterol and formoterol were similar . CONCLUSION Budesonide/formoterol demonstrated a more rapid onset of clinical ly significant bronchodilation and a greater percentage of patients who perceived their medication working right away vs budesonide or placebo 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 Environmental tobacco smoke ( ETS ) negatively affects children with asthma . The prevalence of ETS exposure among children with poor asthma control may be changing . Importantly , the mechanisms by which ETS worsens asthma control are poorly understood . OBJECTIVE We describe how ETS affects gastroesophageal reflux ( GER ) , respiratory infections , and leukotriene production among children with poor asthma control . METHODS We analyzed data from 306 children between 6 and 17 years of age with poorly controlled asthma enrolled in a 6-month clinical trial . We evaluated prevalence and determinants of ETS exposure by interview , question naire , and urinary cotinine and the association of ETS exposure on leukotriene production , respiratory infections , GER , lung function , and asthma control . We used multivariable linear , logistic , and Poisson regressions to assess outcomes . RESULTS ETS prevalence estimates ranged from 6 % to 30 % . Children with domestic indoor exposure had worse asthma control ( c-Asthma Control Test , 17.8 vs 21.5 ; P = .04 ) , worse FEV1 % predicted ( 84.1 vs 90.7 ; P = .02 ) , and a trend for increased mean urinary leukotriene E4 . ETS from any setting was associated with increased symptomatic respiratory infections ( adjusted incidence rate ratio : 1.30 ; P = .02 ) . However , children exposed to ETS did not have symptoms or pH probe results , suggestive of heightened GER . CONCLUSIONS Domestic smoking exposure was associated with both higher rates of symptomatic respiratory infection and poorer asthma control despite generally intensive controller therapy . ETS exposure is common among asthmatic children with poor control and may worsen asthma control by promoting respiratory infections . Further investigation is required to eluci date ETS mechanisms in poor asthma control 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  
    Output:
    