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 Background : Ciclesonide exhibits clinical efficacy at 160 μg ( ex‐actuator ) once daily but the anti‐inflammatory effects at this dose are not known . We wished to know whether 4 weeks therapy with ciclesonide pMDI 160 μg once daily in the morning exhibited significant anti‐inflammatory effects BACKGROUND There are no data comparing the relative effects of high-dose ciclesonide ( CIC ) and fluticasone propionate ( FP ) on airway and systemic outcomes in patients with moderate persistent asthma . OBJECTIVE We elected to evaluate the relative effects of CIC and FP on the plasma cortisol response to stimulation with human corticotropin-releasing factor ( hCRF ) and bronchial hyperresponsiveness to methacholine as the primary outcome variables , in addition to secondary outcomes of overnight 10-h urinary cortisol ( OUC ) levels , exhaled nitric oxide levels , lung function , symptoms , and quality of life . METHODS Fourteen patients with moderate persistent asthma ( mean FEV(1 ) , 67 % predicted [ prior to each r and omized treatment ] ) completed the study , which had a r and omized , double-blind , double-dummy , crossover design , per protocol . Patients stopped receiving their usual inhaled corticosteroids for the duration of the study and instead began receiving salmeterol , 50 mug twice daily , and montelukast , 10 mg once daily , for the 2-week washout periods prior to each r and omized treatment , in order to prevent dropouts after withdrawal from inhaled corticosteroid therapy . Patients received 4 weeks of either CIC , 200 microg ex-valve ( 160 microg ex-actuator ) four puffs twice daily , plus FP-placebo , four puffs twice daily , or FP , 250 microg ex-valve ( 220 microg ex-actuator ) four puffs twice daily , plus CIC-placebo , four puffs twice daily . Salmeterol and montelukast were withheld for 72 h prior to each postwashout baseline visit , and CIC or FP was withheld for 12 h prior to each posttreatment visit . RESULTS FP , but not CIC , when compared to respective baseline values , significantly suppressed ( p < 0.05 ) plasma cortisol levels as follows : FP prior to receiving hCRF : geometric mean fold difference , 1.2 ; 95 % confidence interval ( CI ) , 1.1 to 1.3 ; CIC prior to receiving hCRF : geometric mean fold difference , 0.9 ; 95 % CI , 0.8 to 1.0 ; FP 30 min after receiving hCRF : geometric mean fold difference , 1.2 ; 95 % CI , 1.1 to 1.3 ; CIC 30 min after receiving hCRF : geometric mean fold difference , 1.0 ; 95 % CI , 0.9 to 1.2 ; OUC after FP administration : geometric mean fold difference , 1.9 ; 95 % CI , 1.4 to 2.6 ; OUC after CIC administration : geometric mean fold difference , 1.2 ; 95 % CI , 0.9 to 1.5 . There was also a significantly lower ( p < 0.05 ) mean value for OUC levels after FP administration than after CIC administration ( geometric mean fold difference , 1.5 ; 95 % CI , 1.1 to 2.0 ) . Therapy with CIC and FP , compared to respective baselines , significantly increased ( p < 0.05 ) the provocative concentration of methacholine causing a 20 % fall in FEV(1 ) , as follows : CIC : doubling dilution difference , 0.8 ; 95 % CI , 0.1 to 1.6 ; FP : doubling dilution difference , 1.0 ; 95 % CI , 0.1 to 2.0 . It also significantly reduced ( p < 0.05 ) exhaled nitric oxide levels , as follows : CIC : geometric mean fold difference , 1.2 ; 95 % CI , 1.1 to 1.3 ; FP : geometric mean fold difference , 1.9 ; 95 % CI , 1.3 to 2.8 . There was no effect on other secondary efficacy outcomes . CONCLUSION FP , 2,000 microg daily , but not CIC , 1,600 microg daily , significantly suppressed hypothalamic-pituitary-adrenal axis outcomes , with OUC levels being lower after FP administration than after CIC administration . Both drugs significantly improved airway outcomes in terms of methacholine bronchial hyperresponsiveness and exhaled nitric oxide levels . The present results would therefore suggest that CIC might confer a better therapeutic ratio than FP when used at higher doses Background : The aim of this clinical trial was to investigate whether repeated inhalation of the new inhaled steroid ciclesonide reduces the early‐phase ( EAR ) and late‐phase ( LAR ) reactions after allergen challenge in patients with mild allergic asthma . Also , this study provides further data on safety and tolerance of ciclesonide STUDY OBJECTIVES Oral corticosteroids ( OCS ) may be associated with systemic adverse events ( AEs ) , which can be reduced by replacing OCS with inhaled corticosteroids ( ICS ) . The potential of ciclesonide , a novel ICS , to reduce OCS use in patients with severe , persistent asthma was evaluated in this study . DESIGN A phase III , 12-week , international , multicenter , double-blind , placebo-controlled , parallel-group study . PATIENTS Adult and adolescent patients ( > or = 12 years old ; n = 141 ) with severe , persistent , oral steroid (prednisone)-dependent asthma . INTERVENTIONS Patients were r and omized to receive ciclesonide ( 640 mug/d or 1,280 microg/d [ ex-actuator ] ) bid or placebo for 12 weeks . Weekly evaluations determined eligibility for prednisone dose reduction based on predetermined criteria . MEASUREMENTS AND RESULTS The  prednisone dose was significantly reduced by 47 % and 63 % in the groups receiving ciclesonide , 640 microg/d , and ciclesonide , 1,280 microg/d , respectively , vs an increase of 4 % in the placebo group ( both p < or = 0.0003 ) at week 12 . By week 12 , prednisone was discontinued by approximately 30 % of patients in the ciclesonide-treated groups , vs 11 % of patients in the placebo group ( both p < or = 0.04 ) . FEV1 improved significantly at week 12 in the ciclesonide treatment groups vs placebo ( p < 0.03 ) . The occurrence of local and systemic AEs was comparable between all treatment groups . CONCLUSION Study results suggest that ciclesonide significantly reduces the need for OCS in patients with severe , persistent asthma , while maintaining asthma control The study addressed the question whether the novel inhaled prodrug corticosteroid ciclesonide is equally effective when inhaled in the morning compared to the evening . For this purpose a double-blind , r and omized , parallel group study was initiated in which 209 asthmatic patients ( forced expiratory volume in one second = 50 - 90 % predicted ) inhaled either 200 microg ciclesonide in the morning or in the evening , for 8 weeks . Efficacy was assessed by means of spirometry as well as daily recordings of morning and evening peak expiratory flow ( PEF ) , symptoms and use of rescue medication . The 24-h urinary cortisol excretion was measured to evaluate any effect on hypothalamic-pituitary-adrenol axis . Ciclesonide significantly improved asthma control . Morning and evening administration was shown to be equally effective for the different spirometry variables , evening PEF , symptoms , use of rescue medication and number of asthma exacerbations . Regarding morning PEF , the improvements after evening dosing were more prominent and equivalence of morning and evening administration could not be demonstrated . No relevant influence on cortisol excretion was found . Overall , the study indicates that ciclesonide can be given either in the morning or in the evening to meet the patients ' preference and individual medical needs , although evening administration may lead to a more pronounced improvement in morning peak expiratory flow The efficacy and systemic effects of ciclesonide , a novel glucocorticosteroid , inhaled via pressurized metered-dose inhaler ( pMDI ) were compared with fluticasone propionate pMDI in 26 patients with asthma , using a r and omized , double blind , placebo-controlled , double dummy , 6-period crossover study design . Treatments were placebo , ciclesonide 320 microg ( ex-actuator dose ) once daily ( o.d . ) , ciclesonide 640 microg o.d . , ciclesonide 640 microg twice daily ( b.i.d . ) , fluticasone propionate 440 microg ( ex-actuator dose ) b.i.d . , and fluticasone propionate 880 microg b.i.d . The primary variable was area under the plasma cortisol concentration-time curve over 24 h ( plasma cortisol AUC(0 - 24 ) , relative to placebo ) derived from sample s taken every 2 h , on the 9th day of treatment . Secondary variables were 24-h urinary cortisol excretion and PC20 for adenosine 5'-monophosphate ( AMP ) ( relative to placebo and expressed in doubling concentrations ) . Ciclesonide did not affect 24-h cortisol secretion .  Fluticasone propionate suppressed cortisol secretion as demonstrated by a decrease in plasma cortisol AUC(0 - 24 ) , relative to placebo , by 29 % ( 95 % CI 15 - 41 ) and 59 % ( 95 % CI 51 - 66 ) with 440 and 880 microg b.i.d . , respectively . PC20 more than doubled with each active treatment , but no statistically significant dose-response effect could be established . It was concluded that moderate to high doses of fluticasone propionate suppressed cortisol secretion , that ciclesonide did not suppress cortisol secretion , and that all active treatments decreased hyperresponsiveness to AMP Fifty-three adult asthmatic subjects requiring 800 micrograms or more of inhaled beclomethasone dipropionate  were enrolled in a double-blind parallel group study of 6-month duration to compare the efficacy and side effects of inhaled budesonide in doses of 800 , 1,200 , and 1,600 micrograms given two or four times a day ( BID or QID ) . After a two-week observation period to establish baseline , subjects were given the same dose of budesonide as they would be for beclomethasone dipropionate ; however , the frequency regimen ( BID or QID ) was r and omly allocated . Subjects were asked to fill in diary cards describing their asthmatic symptoms , need for medication , and throat symptoms . They were assessed by a physician every 4 wk , at which time  spirometry  was performed . Throat swabs were done at every other monthly visit . Cortisol and response to cortisol after synthetic ACTH injection were assessed at the beginning and end of the trial . Thirty-six subjects , half in each group , completed the study . Those on the BID regimen had almost twice as many days with nocturnal asthma and cough and almost three times as many days with disability due to asthma . There were also twice as many relapses in the BID regimen as judged by the clinician . These relapses mainly occurred toward the end of the study . The maximal daily swings in peak expiratory flow rates were slightly greater in the BID group , although this difference was not physiologically significant . Spirometry , cortisol secretion , and the response after synthetic ACTH injection were not significantly different in either 
    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 Background : Ciclesonide exhibits clinical efficacy at 160 μg ( ex‐actuator ) once daily but the anti‐inflammatory effects at this dose are not known . We wished to know whether 4 weeks therapy with ciclesonide pMDI 160 μg once daily in the morning exhibited significant anti‐inflammatory effects BACKGROUND There are no data comparing the relative effects of high-dose ciclesonide ( CIC ) and fluticasone propionate ( FP ) on airway and systemic outcomes in patients with moderate persistent asthma . OBJECTIVE We elected to evaluate the relative effects of CIC and FP on the plasma cortisol response to stimulation with human corticotropin-releasing factor ( hCRF ) and bronchial hyperresponsiveness to methacholine as the primary outcome variables , in addition to secondary outcomes of overnight 10-h urinary cortisol ( OUC ) levels , exhaled nitric oxide levels , lung function , symptoms , and quality of life . METHODS Fourteen patients with moderate persistent asthma ( mean FEV(1 ) , 67 % predicted [ prior to each r and omized treatment ] ) completed the study , which had a r and omized , double-blind , double-dummy , crossover design , per protocol . Patients stopped receiving their usual inhaled corticosteroids for the duration of the study and instead began receiving salmeterol , 50 mug twice daily , and montelukast , 10 mg once daily , for the 2-week washout periods prior to each r and omized treatment , in order to prevent dropouts after withdrawal from inhaled corticosteroid therapy . Patients received 4 weeks of either CIC , 200 microg ex-valve ( 160 microg ex-actuator ) four puffs twice daily , plus FP-placebo , four puffs twice daily , or FP , 250 microg ex-valve ( 220 microg ex-actuator ) four puffs twice daily , plus CIC-placebo , four puffs twice daily . Salmeterol and montelukast were withheld for 72 h prior to each postwashout baseline visit , and CIC or FP was withheld for 12 h prior to each posttreatment visit . RESULTS FP , but not CIC , when compared to respective baseline values , significantly suppressed ( p < 0.05 ) plasma cortisol levels as follows : FP prior to receiving hCRF : geometric mean fold difference , 1.2 ; 95 % confidence interval ( CI ) , 1.1 to 1.3 ; CIC prior to receiving hCRF : geometric mean fold difference , 0.9 ; 95 % CI , 0.8 to 1.0 ; FP 30 min after receiving hCRF : geometric mean fold difference , 1.2 ; 95 % CI , 1.1 to 1.3 ; CIC 30 min after receiving hCRF : geometric mean fold difference , 1.0 ; 95 % CI , 0.9 to 1.2 ; OUC after FP administration : geometric mean fold difference , 1.9 ; 95 % CI , 1.4 to 2.6 ; OUC after CIC administration : geometric mean fold difference , 1.2 ; 95 % CI , 0.9 to 1.5 . There was also a significantly lower ( p < 0.05 ) mean value for OUC levels after FP administration than after CIC administration ( geometric mean fold difference , 1.5 ; 95 % CI , 1.1 to 2.0 ) . Therapy with CIC and FP , compared to respective baselines , significantly increased ( p < 0.05 ) the provocative concentration of methacholine causing a 20 % fall in FEV(1 ) , as follows : CIC : doubling dilution difference , 0.8 ; 95 % CI , 0.1 to 1.6 ; FP : doubling dilution difference , 1.0 ; 95 % CI , 0.1 to 2.0 . It also significantly reduced ( p < 0.05 ) exhaled nitric oxide levels , as follows : CIC : geometric mean fold difference , 1.2 ; 95 % CI , 1.1 to 1.3 ; FP : geometric mean fold difference , 1.9 ; 95 % CI , 1.3 to 2.8 . There was no effect on other secondary efficacy outcomes . CONCLUSION FP , 2,000 microg daily , but not CIC , 1,600 microg daily , significantly suppressed hypothalamic-pituitary-adrenal axis outcomes , with OUC levels being lower after FP administration than after CIC administration . Both drugs significantly improved airway outcomes in terms of methacholine bronchial hyperresponsiveness and exhaled nitric oxide levels . The present results would therefore suggest that CIC might confer a better therapeutic ratio than FP when used at higher doses Background : The aim of this clinical trial was to investigate whether repeated inhalation of the new inhaled steroid ciclesonide reduces the early‐phase ( EAR ) and late‐phase ( LAR ) reactions after allergen challenge in patients with mild allergic asthma . Also , this study provides further data on safety and tolerance of ciclesonide STUDY OBJECTIVES Oral corticosteroids ( OCS ) may be associated with systemic adverse events ( AEs ) , which can be reduced by replacing OCS with inhaled corticosteroids ( ICS ) . The potential of ciclesonide , a novel ICS , to reduce OCS use in patients with severe , persistent asthma was evaluated in this study . DESIGN A phase III , 12-week , international , multicenter , double-blind , placebo-controlled , parallel-group study . PATIENTS Adult and adolescent patients ( > or = 12 years old ; n = 141 ) with severe , persistent , oral steroid (prednisone)-dependent asthma . INTERVENTIONS Patients were r and omized to receive ciclesonide ( 640 mug/d or 1,280 microg/d [ ex-actuator ] ) bid or placebo for 12 weeks . Weekly evaluations determined eligibility for prednisone dose reduction based on predetermined criteria . MEASUREMENTS AND RESULTS The  prednisone dose was significantly reduced by 47 % and 63 % in the groups receiving ciclesonide , 640 microg/d , and ciclesonide , 1,280 microg/d , respectively , vs an increase of 4 % in the placebo group ( both p < or = 0.0003 ) at week 12 . By week 12 , prednisone was discontinued by approximately 30 % of patients in the ciclesonide-treated groups , vs 11 % of patients in the placebo group ( both p < or = 0.04 ) . FEV1 improved significantly at week 12 in the ciclesonide treatment groups vs placebo ( p < 0.03 ) . The occurrence of local and systemic AEs was comparable between all treatment groups . CONCLUSION Study results suggest that ciclesonide significantly reduces the need for OCS in patients with severe , persistent asthma , while maintaining asthma control The study addressed the question whether the novel inhaled prodrug corticosteroid ciclesonide is equally effective when inhaled in the morning compared to the evening . For this purpose a double-blind , r and omized , parallel group study was initiated in which 209 asthmatic patients ( forced expiratory volume in one second = 50 - 90 % predicted ) inhaled either 200 microg ciclesonide in the morning or in the evening , for 8 weeks . Efficacy was assessed by means of spirometry as well as daily recordings of morning and evening peak expiratory flow ( PEF ) , symptoms and use of rescue medication . The 24-h urinary cortisol excretion was measured to evaluate any effect on hypothalamic-pituitary-adrenol axis . Ciclesonide significantly improved asthma control . Morning and evening administration was shown to be equally effective for the different spirometry variables , evening PEF , symptoms , use of rescue medication and number of asthma exacerbations . Regarding morning PEF , the improvements after evening dosing were more prominent and equivalence of morning and evening administration could not be demonstrated . No relevant influence on cortisol excretion was found . Overall , the study indicates that ciclesonide can be given either in the morning or in the evening to meet the patients ' preference and individual medical needs , although evening administration may lead to a more pronounced improvement in morning peak expiratory flow The efficacy and systemic effects of ciclesonide , a novel glucocorticosteroid , inhaled via pressurized metered-dose inhaler ( pMDI ) were compared with fluticasone propionate pMDI in 26 patients with asthma , using a r and omized , double blind , placebo-controlled , double dummy , 6-period crossover study design . Treatments were placebo , ciclesonide 320 microg ( ex-actuator dose ) once daily ( o.d . ) , ciclesonide 640 microg o.d . , ciclesonide 640 microg twice daily ( b.i.d . ) , fluticasone propionate 440 microg ( ex-actuator dose ) b.i.d . , and fluticasone propionate 880 microg b.i.d . The primary variable was area under the plasma cortisol concentration-time curve over 24 h ( plasma cortisol AUC(0 - 24 ) , relative to placebo ) derived from sample s taken every 2 h , on the 9th day of treatment . Secondary variables were 24-h urinary cortisol excretion and PC20 for adenosine 5'-monophosphate ( AMP ) ( relative to placebo and expressed in doubling concentrations ) . Ciclesonide did not affect 24-h cortisol secretion .  Fluticasone propionate suppressed cortisol secretion as demonstrated by a decrease in plasma cortisol AUC(0 - 24 ) , relative to placebo , by 29 % ( 95 % CI 15 - 41 ) and 59 % ( 95 % CI 51 - 66 ) with 440 and 880 microg b.i.d . , respectively . PC20 more than doubled with each active treatment , but no statistically significant dose-response effect could be established . It was concluded that moderate to high doses of fluticasone propionate suppressed cortisol secretion , that ciclesonide did not suppress cortisol secretion , and that all active treatments decreased hyperresponsiveness to AMP Fifty-three adult asthmatic subjects requiring 800 micrograms or more of inhaled beclomethasone dipropionate  were enrolled in a double-blind parallel group study of 6-month duration to compare the efficacy and side effects of inhaled budesonide in doses of 800 , 1,200 , and 1,600 micrograms given two or four times a day ( BID or QID ) . After a two-week observation period to establish baseline , subjects were given the same dose of budesonide as they would be for beclomethasone dipropionate ; however , the frequency regimen ( BID or QID ) was r and omly allocated . Subjects were asked to fill in diary cards describing their asthmatic symptoms , need for medication , and throat symptoms . They were assessed by a physician every 4 wk , at which time  spirometry  was performed . Throat swabs were done at every other monthly visit . Cortisol and response to cortisol after synthetic ACTH injection were assessed at the beginning and end of the trial . Thirty-six subjects , half in each group , completed the study . Those on the BID regimen had almost twice as many days with nocturnal asthma and cough and almost three times as many days with disability due to asthma . There were also twice as many relapses in the BID regimen as judged by the clinician . These relapses mainly occurred toward the end of the study . The maximal daily swings in peak expiratory flow rates were slightly greater in the BID group , although this difference was not physiologically significant . Spirometry , cortisol secretion , and the response after synthetic ACTH injection were not significantly different in either 
    Output:
    