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: 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 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 Background : Inhaled corticosteroids ( ICS ) are recommended therapy for persistent asthma , although side effects can limit appropriate use . Ciclesonide , a novel ICS , is activated in the lung , thereby reducing systemic activity and side effects . This 12‐week , double‐blind , r and omized , parallel‐group , placebo‐controlled study evaluated the efficacy and safety of ciclesonide in adults with persistent asthma Ciclesonide is a novel inhaled corticosteroid that is converted in the lungs to its active metabolite , desisobutyryl-ciclesonide ( des-CIC ) . The aim of this study was to compare the deposition of ciclesonide , as well as its conversion to des-CIC , in the oropharyngeal cavity with fluticasone propionate ( FP ) following inhalation via hydrofluoroalkane-propelled metered-dose inhalers ( HFA-MDIs ) . Eighteen asthmatics inhaled ciclesonide 800 microg followed by FP 1000 microg or vice versa in an open , r and omized , 2-treatment , 2-sequence study design . The oropharynx was washed out immediately and at 15 , 30 , 45 , and 60 minutes after inhalation . Sample s were analyzed for ciclesonide , des-CIC , and FP using liquid chromatography with t and em mass-spectrometric detection . Concentration-time curves and area under the concentration-time curve ( AUC ) were calculated for each drug . Ciclesonide and FP were recovered in almost all sample s. Within 60 minutes after inhalation , the amounts of both ciclesonide and FP decreased sharply , and low residual levels were detected after 30 minutes . des-CIC was detected in relatively low concentrations , with maximum concentration 30 minutes following inhalation . The AUC(0 - 60 min ) for ciclesonide ( 250.4 nmol x h/L ) and des-CIC ( 37.8 nmol x h/L ) were found to be significantly lower compared with FP ( 636.2 nmol.h/L , P < .001 ) . Approximately 50 % less ciclesonide and 90 % less metabolite were present in the oropharynx compared with FP . Less than 20 % of the residual ciclesonide in the oropharynx was metabolized to des-CIC . These findings indicate that oropharyngeal deposition of ciclesonide is only half that of FP following inhalation from an HFA-MDI . Furthermore , there is little activation of ciclesonide to its active metabolite in the oropharynx , suggesting a decreased likelihood of inhaled ciclesonide-associated oropharyngeal side effects Objective Inhaled corticosteroids may cause  oropharyngeal side effects  if deposited in the oropharynx in active form . Ciclesonide , an inhaled corticosteroid with low glucocorticoid receptor affinity , is activated primarily in the lung by esterases to an active metabolite , desisobutyryl-ciclesonide ( des-CIC ) , with high glucocorticoid receptor affinity . We studied oropharyngeal deposition of ciclesonide , des-CIC , and budesonide . Methods In an open-label , r and omized , two-treatment ( administered in sequence ) , five-period study , 18 healthy subjects received 800 μg ( ex-valve ) inhaled ciclesonide via a hydrofluoroalkane-pressurized , metered-dose inhaler followed by 800 μg budesonide ( Pulmicort ) by a chlorofluorocarbon-pressurized , metered-dose inhaler ( four puffs of 200 μg each , ex-valve ) or vice versa . Oropharyngeal cavity rinsing was performed immediately , or 15 , 30 , 45 , or 60 min after inhalation ( one rinsing per study period ) , and the solutions were analyzed using liquid chromatography with t and em mass spectrometric detection . Results Ciclesonide and budesonide were detected in most oropharyngeal wash sample s. Maximal concentration of each inhaled corticosteroid was reached immediately post-inhalation ; maximal concentrations of ciclesonide and des-CIC were 30 % and 0.67 % , respectively , of budesonide . Oropharyngeal deposition of ciclesonide and budesonide decreased rapidly within 15 min post-inhalation , and less rapidly thereafter . Less than 10 % of the residual ciclesonide in the oropharynx was converted to des-CIC . The molar dose-adjusted amount of des-CIC was 4 % of budesonide ( P < 0.0001 ) . There were no significant adverse events . Conclusion Oropharyngeal deposition of des-CIC was more than one order of magnitude lower than that of budesonide when administered by the respective metered-dose inhalers . This may explain the low frequency of oropharyngeal side effects of ciclesonide in clinical studies AIMS There are no data comparing the relative efficacy of hydrofluoroalkane ( HFA ) formulations of ciclesonide ( CIC ) and fluticasone propionate ( FP ) on airway hyper-responsiveness , in mild-to-moderate persistent asthma . We therefore elected to evaluate the comparative efficacy of HFA pressurized metered-dose inhaler formulations of CIC and FP , assessing methacholine challenge , in addition to exhaled nitric oxide , lung function , diary cards and quality of life . METHODS Nineteen mild-to-moderate asthmatic patients completed the study per protocol in r and omized , double-blind , double-dummy , crossover fashion . Patients were required to stop their usual inhaled corticosteroid therapy for the duration of the study . Patients were commenced instead on salmeterol ( SM ) 50 microg one puff twice daily + montelukast ( ML ) 10 mg once daily for 2-week washout periods prior to each r and omized treatment , in order to prevent dropouts . Patients received 4 weeks of either CIC 200 microg two puffs once daily ( 08.00 h ) + CIC-placebo ( PL ) two puffs once daily ( 20.00 h ) + FP-PL two puffs twice daily ( 08.00 h and 20.00 h ) , or FP 125 microg two puffs twice daily ( 08.00 h and 20.00 h ) + CIC-PL two puffs twice daily ( 08.00 h and 20.00 h ) . SM + ML were withheld for 72 h prior to post-washout visits and CIC or FP was withheld for 24 h prior to study visits . RESULTS There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC20 as doubling dilution ( dd ) shift from respective baseline ; mean difference : 0.4 dd ( 95 % CI -0.4 , 1.2 ) . Moreover , there was no difference between treatments for the sequence of CIC first vs FP second ; mean difference : 0.2 dd ( 95 % CI -1.3 , 1.7 ) or FP first vs CIC second ; mean difference : 0.9 dd ( 95 % CI -0.1 , 1.8 ) . There were also no differences for other secondary outcomes between treatments , either respective or irrespective of sequence , as change from baseline . CONCLUSIONS There were no differences between 4 weeks of CIC  
    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: 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 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 Background : Inhaled corticosteroids ( ICS ) are recommended therapy for persistent asthma , although side effects can limit appropriate use . Ciclesonide , a novel ICS , is activated in the lung , thereby reducing systemic activity and side effects . This 12‐week , double‐blind , r and omized , parallel‐group , placebo‐controlled study evaluated the efficacy and safety of ciclesonide in adults with persistent asthma Ciclesonide is a novel inhaled corticosteroid that is converted in the lungs to its active metabolite , desisobutyryl-ciclesonide ( des-CIC ) . The aim of this study was to compare the deposition of ciclesonide , as well as its conversion to des-CIC , in the oropharyngeal cavity with fluticasone propionate ( FP ) following inhalation via hydrofluoroalkane-propelled metered-dose inhalers ( HFA-MDIs ) . Eighteen asthmatics inhaled ciclesonide 800 microg followed by FP 1000 microg or vice versa in an open , r and omized , 2-treatment , 2-sequence study design . The oropharynx was washed out immediately and at 15 , 30 , 45 , and 60 minutes after inhalation . Sample s were analyzed for ciclesonide , des-CIC , and FP using liquid chromatography with t and em mass-spectrometric detection . Concentration-time curves and area under the concentration-time curve ( AUC ) were calculated for each drug . Ciclesonide and FP were recovered in almost all sample s. Within 60 minutes after inhalation , the amounts of both ciclesonide and FP decreased sharply , and low residual levels were detected after 30 minutes . des-CIC was detected in relatively low concentrations , with maximum concentration 30 minutes following inhalation . The AUC(0 - 60 min ) for ciclesonide ( 250.4 nmol x h/L ) and des-CIC ( 37.8 nmol x h/L ) were found to be significantly lower compared with FP ( 636.2 nmol.h/L , P < .001 ) . Approximately 50 % less ciclesonide and 90 % less metabolite were present in the oropharynx compared with FP . Less than 20 % of the residual ciclesonide in the oropharynx was metabolized to des-CIC . These findings indicate that oropharyngeal deposition of ciclesonide is only half that of FP following inhalation from an HFA-MDI . Furthermore , there is little activation of ciclesonide to its active metabolite in the oropharynx , suggesting a decreased likelihood of inhaled ciclesonide-associated oropharyngeal side effects Objective Inhaled corticosteroids may cause  oropharyngeal side effects  if deposited in the oropharynx in active form . Ciclesonide , an inhaled corticosteroid with low glucocorticoid receptor affinity , is activated primarily in the lung by esterases to an active metabolite , desisobutyryl-ciclesonide ( des-CIC ) , with high glucocorticoid receptor affinity . We studied oropharyngeal deposition of ciclesonide , des-CIC , and budesonide . Methods In an open-label , r and omized , two-treatment ( administered in sequence ) , five-period study , 18 healthy subjects received 800 μg ( ex-valve ) inhaled ciclesonide via a hydrofluoroalkane-pressurized , metered-dose inhaler followed by 800 μg budesonide ( Pulmicort ) by a chlorofluorocarbon-pressurized , metered-dose inhaler ( four puffs of 200 μg each , ex-valve ) or vice versa . Oropharyngeal cavity rinsing was performed immediately , or 15 , 30 , 45 , or 60 min after inhalation ( one rinsing per study period ) , and the solutions were analyzed using liquid chromatography with t and em mass spectrometric detection . Results Ciclesonide and budesonide were detected in most oropharyngeal wash sample s. Maximal concentration of each inhaled corticosteroid was reached immediately post-inhalation ; maximal concentrations of ciclesonide and des-CIC were 30 % and 0.67 % , respectively , of budesonide . Oropharyngeal deposition of ciclesonide and budesonide decreased rapidly within 15 min post-inhalation , and less rapidly thereafter . Less than 10 % of the residual ciclesonide in the oropharynx was converted to des-CIC . The molar dose-adjusted amount of des-CIC was 4 % of budesonide ( P < 0.0001 ) . There were no significant adverse events . Conclusion Oropharyngeal deposition of des-CIC was more than one order of magnitude lower than that of budesonide when administered by the respective metered-dose inhalers . This may explain the low frequency of oropharyngeal side effects of ciclesonide in clinical studies AIMS There are no data comparing the relative efficacy of hydrofluoroalkane ( HFA ) formulations of ciclesonide ( CIC ) and fluticasone propionate ( FP ) on airway hyper-responsiveness , in mild-to-moderate persistent asthma . We therefore elected to evaluate the comparative efficacy of HFA pressurized metered-dose inhaler formulations of CIC and FP , assessing methacholine challenge , in addition to exhaled nitric oxide , lung function , diary cards and quality of life . METHODS Nineteen mild-to-moderate asthmatic patients completed the study per protocol in r and omized , double-blind , double-dummy , crossover fashion . Patients were required to stop their usual inhaled corticosteroid therapy for the duration of the study . Patients were commenced instead on salmeterol ( SM ) 50 microg one puff twice daily + montelukast ( ML ) 10 mg once daily for 2-week washout periods prior to each r and omized treatment , in order to prevent dropouts . Patients received 4 weeks of either CIC 200 microg two puffs once daily ( 08.00 h ) + CIC-placebo ( PL ) two puffs once daily ( 20.00 h ) + FP-PL two puffs twice daily ( 08.00 h and 20.00 h ) , or FP 125 microg two puffs twice daily ( 08.00 h and 20.00 h ) + CIC-PL two puffs twice daily ( 08.00 h and 20.00 h ) . SM + ML were withheld for 72 h prior to post-washout visits and CIC or FP was withheld for 24 h prior to study visits . RESULTS There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC20 as doubling dilution ( dd ) shift from respective baseline ; mean difference : 0.4 dd ( 95 % CI -0.4 , 1.2 ) . Moreover , there was no difference between treatments for the sequence of CIC first vs FP second ; mean difference : 0.2 dd ( 95 % CI -1.3 , 1.7 ) or FP first vs CIC second ; mean difference : 0.9 dd ( 95 % CI -0.1 , 1.8 ) . There were also no differences for other secondary outcomes between treatments , either respective or irrespective of sequence , as change from baseline . CONCLUSIONS There were no differences between 4 weeks of CIC  
    Output:
    