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: A double blind , r and omised , placebo controlled , crossover trial of prednisolone ( 40 mg/day for 14 days ) was carried out in 33 patients with chronic airflow limitation ( mean age 62 years , mean FEV1 1.01 litres , mean FEV1/FVC ratio 44 % ) , to assess the value of serial peak expiratory flow ( PEF ) measurements , taken five times daily in evaluating treatment response by comparison with other objective measurements and with measurements of symptoms . The mean serial PEF after a one week run in period was 189 1 min-1 , during the second week of placebo 193 1 min-1 , and during the second week on prednisolone 231 1 min-1 . The difference in mean PEF values between placebo and prednisolone was significant ( p less than 0.01 ) . With regard to the response to steroids of the individual patients , 13 of the 33 had a detectable trend of improvement on visual inspection of serial PEF measurements during prednisolone treatment but only one during placebo administration . Of all the objective measurements made after the run in and after each treatment phase ( 12 minute walking distance , FEV1 , forced vital capacity ( FVC ) , serial PEF ) , the serial PEF chart provided the best discrimination between placebo and prednisolone treatment . There was no statistically significant association between steroid induced improvement in serial PEF measurements and in breathlessness , partly because of placebo improvements in symptoms in those who had no improvement in serial PEF values . This study indicates the importance of making objective measurements to identify a genuine steroid response rather than relying on symptomatic improvement alone . The best simple measurement to make is serial PEF during steroid trials . This is more sensitive in detecting a steroid response than are the 12 minute walking distance , FEV1 , or FVC , and is also less likely than these measurements to show spurious placebo responses BACKGROUND A significant minority of patients with COPD have favourable response to corticosteroid treatment . In addition , the benefit of corticosteroid treatment may be outweighed by the side-effects . Long-term administration of inhaled steroids is a safe means of treatment . However , only a few studies have addressed the role of inhaled steroids in patients with COPD , with conflicting results . METHODS Forty-four patients with stable COPD were defined as ' responders to bronchodilators ' ( increase in FEV1 > or = 20 % following administration of  beta 2-agonist ) ( group A ) , and 124 as ' non-responders to bronchodilators ' ( group B ) . All patients were r and omized to receive a 6-week course of either a daily dose of 800 micrograms of inhaled budesonide or placebo , separated by 4 weeks when no medication was taken ; were r and omized again to receive a 6-week course of either 1600 micrograms day-1 of inhaled budesonide , or 800 micrograms day-1 of inhaled budesonide plus placebo ; and were r and omized once again to receive a 6-week course of either 40 mg day-1 of prednisone or placebo . All stages were performed in a double-blind cross-over design . RESULTS Following administration of 800 micrograms day-1 of inhaled budesonide , there was an increase in the mean FEV1 from 1.40 + /- 0.20 to 1.92 + /- 0.22 L ( P < 0.001 ) and a significant decrease in inhaled beta 2 agonist consumption in group A. These changes remained almost stable during the increased dose of inhaled budesonide or during prednisone treatment . The mean FEV1 did not change during the placebo period , or in group B in either treatments . CONCLUSIONS Treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about one-quarter of patients with stable COPD , and this rate increased to about three-quarters in patients who responded to beta 2-agonist inhalation . There was no additional benefit in using a higher dose of inhaled budesonide or prednisone Background : A trial of corticosteroids has been recommended for all patients with chronic obstructive pulmonary disease ( COPD ) , with the subsequent “ response ” determining the treatment selected . This approach assumes that patients can be reliably divided into responder and non-responder groups . We have assessed whether such a separation is statistically valid , which factors influence the change in forced expiratory volume in 1 second ( FEV1 ) after prednisolone , and whether the prednisolone response predicts 3 year changes in FEV1 , health status , or number of exacerbations during placebo or fluticasone propionate treatment . Methods : Oral prednisolone 0.6 mg/kg was given for 14 days to 524 patients with COPD before r and omised treatment for 3 years with fluticasone propionate or placebo . Factors relating to change in FEV1 after prednisolone were investigated using multiple regression . The response to prednisolone was entered into separate mixed effects models of decline in FEV1 and health status during the 3 years of the study . Results : The post-bronchodilator FEV1 increased by a mean 60 ml ( CI 46 to 74 ) after prednisolone with a wide unimodal distribution . Current smoking was the factor most strongly associated with the change in FEV1 after prednisolone , with an increase of 35 ml in current smokers and 74 ml in confirmed ex-smokers ( p<0.001 ) . There was no relationship between the change in FEV1 after prednisolone  and the response to inhaled bronchodilators , baseline FEV1 , atopic status , age , or sex . The response to prednisolone  , however expressed , was unrelated to the subsequent change in FEV1 over the following 3 years on either placebo or fluticasone propionate . Regression to the mean effects explained much of the apparent prednisolone response . The significant effect of treatment on decline in health status was not predicted by the prednisolone response . Conclusion : Patients with COPD can not be separated into discrete groups of corticosteroid responders and non-responders . Current smoking reduces the FEV1 response to prednisolone . Prednisolone testing is an unreliable predictor of the benefit from inhaled fluticasone propionate in individual patients One hundred and twenty seven adults considered on clinical grounds to have non-asthmatic chronic airflow obstruction entered a r and omised , double blind , placebo controlled , crossover trial comparing the physiological response to inhaled beclomethasone dipropionate 500 micrograms thrice daily with oral prednisolone 40 mg a day , both given for two weeks . One hundred and seven patients completed the study . Response was assessed as change in FEV1 and FVC measured on the last treatment day , and as change in mean peak expiratory flow ( PEF ) over the final seven days of treatment from home PEF recordings performed five times daily . A full response to treatment was defined as an increase in FEV or FVC , or an increase in mean daily PEF over the final seven days of treatment , of at least 20 % from baseline values . An improvement in one measurement of at least 15 % , or of 10 % in any two measurements , was defined as a partial treatment response . Response to placebo showed a significant order effect , suggesting a carry over effect of active treatment of at least three weeks . Response to active treatment was therefore related to initial baseline values , and compared with placebo by considering responses in the first treatment phase only . A full response to oral prednisolone ( 16/38 ) was significantly more common than to placebo ( 3/35 ) . The number of full responses to inhaled beclomethasone ( 8/34 ) did not differ significantly from the number responding to oral prednisolone or placebo in the first treatment phase , though full and partial responses to inhaled beclomethasone ( 12/34 ) were significantly more common than those to placebo ( 4/35 ) . When all three treatment phases were considered 44/107 patients showed a full response to one or both forms of corticosteroid treatment , a response to prednisolone ( 39 ) occurring more frequently than to inhaled beclomethasone ( 26 ) . Only 21 of the 44 responders showed a response to both forms of treatment . Inhaled beclomethasone dipropionate 500 micrograms thrice daily was inferior to oral prednisolone 40 mg per day , but better than placebo , in producing improvement in physiological measurements in patients thought to have nonasthmatic chronic airflow obstruction . It was , however , an effective alternative in over half of those showing a response to prednisolone STUDY OBJECTIVE To determine the effectiveness of treatment with corticosteroids in patients with COPD . METHODS In this study , we investigated the effect of a 2-year treatment with corticosteroids on clinical symptoms and the decline of lung function in 58 nonallergic patients with COPD . Subjects were treated in a double-blind , r and omized , placebo-controlled , parallel way with inhaled budesonide ( bud ) , 1,600 micrograms/d ; inhaled budesonide , 1,600 micrograms/d , plus oral prednisolone , 5 micrograms/d ( bud + pred ) ; or placebo ( plac ) .  Clinical assessment ( history , physical examination , and spirometry ) was carried out every 2 months . The rate of decline in FEV1 was assessed by calculating individual regression co-efficients from linear regression of FEV1 on time for each subject . RESULTS Eleven patients dropped out . The number of withdrawals due to pulmonary problems was significantly higher in the plac group ( n = 5 out of 18 ) than in the actively treated groups ( n = 2 out of 40 ) . Treatment with corticosteroids significantly reduced pulmonary symptoms . Median decline of FEV1 was 60 mL/yr in the plac group , 40 mL/yr in the bud + pred group , and 30 mL/yr in the bud group . Variation was large and differences were not statistically significant . No treatment effect was found on frequency or duration of exacerbations , possibly because of the high number of withdrawals due to pulmonary deterioration in the plac group . Treatment with a combination of inhaled plus oral corticosteroids was not more effective than inhaled corticosteroids alone . Morning plasma cortisol levels remained within the normal range in all three groups . CONCLUSIONS Our study shows beneficial effects of long-term daily treatment with inhaled corticosteroids in patients with COPD with regard to symptoms and drop out due to pulmonary problems . Lung function decline tends to decrease during treatment with inhaled corticosteroids . The observed effects are limited but warrant further studies on the effectiveness of corticosteroids in larger numbers of patients with COPD A double-blind crossover trial of prednisolone was conducted in 70 patients of chronic obstructive lung disease ( COLD ) . Emphysema dominated the clinical picture in 38 , rest being chronic bronchitis with varying degrees of air trapping . None of the patients had clinical asthma . All the patients had obtained maximal benefit from an optimal dose of bronchodilators prior to entering the study . Prednisolone in a dose of 0.8 mg/kg was prescribed in a double blind crossover manner with identical appearing placebo tablets . Patients were evaluated on a weekly basis for an objective as well as a subjective response and side effects of therapy . Thirty-four patients demonstrated a statistically significant improvement in pulmonary functions . In 20 others only subjective response was observed . A good objective response was predicted by a pre- study variability in FEV1 , disease duration of less than 10 years and a history of smoking less than 50 pack years Evans , J. A. , Morrison , I. M. , and Saunders , K. B. (1974).Thorax , 29 , 401 - 406 . A controlled trial of prednisone , in low dosage , in patients with chronic airways obstruction . Ten men with chronic airways obstruction took part in a double-blind controlled cross-over trial of 5 mg prednisone , daily for a week , versus placebo .  All patients had breathlessness as their main complaint , and chronic cough with sputum for 2 to 30 years ; five had evidence of emphysema on the chest radiograph . None had a personal or family history of asthma . For the group , mean forced expiratory volume in one second was 1·11 1 . , and mean forced vital capacity was 2·28 1 . Six patients had abnormally high levels of arterial Pco2 ( 46 - 52 mmHg ) . When the ` placebo ' and ` prednisone ' measurements were compared there was no significant change in forced expiratory volumes , bronchodilator effect on forced expiratory volumes , or blood gas tensions . Inspiratory airways resistance measured by body plethysmography was significantly higher , or ` worse ' , on prednisone ( mean 4·2 cmH2O per 1/sec ) than on placebo ( mean 3·2 ) Many patients with irreversible chronic obstructive pulmonary disease ( COPD ) cl aim symptomatic improvement with steroid therapy , despite a lack of objective improvement in their spirometric data . To determine if steroids actually increase the exercise capacity of these individuals , 13 clinical ly stable patients ( mean age , 63 + /- 4 years ; 12 male patients ) were given methylprednisolone ( 32 mg once daily ) or placebo in a r and omized double-blind crossover fashion . Spirometric data and minute ventilation , oxygen consumption ( VO2 ) , carbon dioxide production , and heart rate during incremental exercise were measured at each visit . Methylprednisolone did not produce a significant change in any of the measured parameters . Three patients had an increase in maximal VO2 of greater than 2 ml/kg/min during therapy 
    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: A double blind , r and omised , placebo controlled , crossover trial of prednisolone ( 40 mg/day for 14 days ) was carried out in 33 patients with chronic airflow limitation ( mean age 62 years , mean FEV1 1.01 litres , mean FEV1/FVC ratio 44 % ) , to assess the value of serial peak expiratory flow ( PEF ) measurements , taken five times daily in evaluating treatment response by comparison with other objective measurements and with measurements of symptoms . The mean serial PEF after a one week run in period was 189 1 min-1 , during the second week of placebo 193 1 min-1 , and during the second week on prednisolone 231 1 min-1 . The difference in mean PEF values between placebo and prednisolone was significant ( p less than 0.01 ) . With regard to the response to steroids of the individual patients , 13 of the 33 had a detectable trend of improvement on visual inspection of serial PEF measurements during prednisolone treatment but only one during placebo administration . Of all the objective measurements made after the run in and after each treatment phase ( 12 minute walking distance , FEV1 , forced vital capacity ( FVC ) , serial PEF ) , the serial PEF chart provided the best discrimination between placebo and prednisolone treatment . There was no statistically significant association between steroid induced improvement in serial PEF measurements and in breathlessness , partly because of placebo improvements in symptoms in those who had no improvement in serial PEF values . This study indicates the importance of making objective measurements to identify a genuine steroid response rather than relying on symptomatic improvement alone . The best simple measurement to make is serial PEF during steroid trials . This is more sensitive in detecting a steroid response than are the 12 minute walking distance , FEV1 , or FVC , and is also less likely than these measurements to show spurious placebo responses BACKGROUND A significant minority of patients with COPD have favourable response to corticosteroid treatment . In addition , the benefit of corticosteroid treatment may be outweighed by the side-effects . Long-term administration of inhaled steroids is a safe means of treatment . However , only a few studies have addressed the role of inhaled steroids in patients with COPD , with conflicting results . METHODS Forty-four patients with stable COPD were defined as ' responders to bronchodilators ' ( increase in FEV1 > or = 20 % following administration of  beta 2-agonist ) ( group A ) , and 124 as ' non-responders to bronchodilators ' ( group B ) . All patients were r and omized to receive a 6-week course of either a daily dose of 800 micrograms of inhaled budesonide or placebo , separated by 4 weeks when no medication was taken ; were r and omized again to receive a 6-week course of either 1600 micrograms day-1 of inhaled budesonide , or 800 micrograms day-1 of inhaled budesonide plus placebo ; and were r and omized once again to receive a 6-week course of either 40 mg day-1 of prednisone or placebo . All stages were performed in a double-blind cross-over design . RESULTS Following administration of 800 micrograms day-1 of inhaled budesonide , there was an increase in the mean FEV1 from 1.40 + /- 0.20 to 1.92 + /- 0.22 L ( P < 0.001 ) and a significant decrease in inhaled beta 2 agonist consumption in group A. These changes remained almost stable during the increased dose of inhaled budesonide or during prednisone treatment . The mean FEV1 did not change during the placebo period , or in group B in either treatments . CONCLUSIONS Treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about one-quarter of patients with stable COPD , and this rate increased to about three-quarters in patients who responded to beta 2-agonist inhalation . There was no additional benefit in using a higher dose of inhaled budesonide or prednisone Background : A trial of corticosteroids has been recommended for all patients with chronic obstructive pulmonary disease ( COPD ) , with the subsequent “ response ” determining the treatment selected . This approach assumes that patients can be reliably divided into responder and non-responder groups . We have assessed whether such a separation is statistically valid , which factors influence the change in forced expiratory volume in 1 second ( FEV1 ) after prednisolone , and whether the prednisolone response predicts 3 year changes in FEV1 , health status , or number of exacerbations during placebo or fluticasone propionate treatment . Methods : Oral prednisolone 0.6 mg/kg was given for 14 days to 524 patients with COPD before r and omised treatment for 3 years with fluticasone propionate or placebo . Factors relating to change in FEV1 after prednisolone were investigated using multiple regression . The response to prednisolone was entered into separate mixed effects models of decline in FEV1 and health status during the 3 years of the study . Results : The post-bronchodilator FEV1 increased by a mean 60 ml ( CI 46 to 74 ) after prednisolone with a wide unimodal distribution . Current smoking was the factor most strongly associated with the change in FEV1 after prednisolone , with an increase of 35 ml in current smokers and 74 ml in confirmed ex-smokers ( p<0.001 ) . There was no relationship between the change in FEV1 after prednisolone  and the response to inhaled bronchodilators , baseline FEV1 , atopic status , age , or sex . The response to prednisolone  , however expressed , was unrelated to the subsequent change in FEV1 over the following 3 years on either placebo or fluticasone propionate . Regression to the mean effects explained much of the apparent prednisolone response . The significant effect of treatment on decline in health status was not predicted by the prednisolone response . Conclusion : Patients with COPD can not be separated into discrete groups of corticosteroid responders and non-responders . Current smoking reduces the FEV1 response to prednisolone . Prednisolone testing is an unreliable predictor of the benefit from inhaled fluticasone propionate in individual patients One hundred and twenty seven adults considered on clinical grounds to have non-asthmatic chronic airflow obstruction entered a r and omised , double blind , placebo controlled , crossover trial comparing the physiological response to inhaled beclomethasone dipropionate 500 micrograms thrice daily with oral prednisolone 40 mg a day , both given for two weeks . One hundred and seven patients completed the study . Response was assessed as change in FEV1 and FVC measured on the last treatment day , and as change in mean peak expiratory flow ( PEF ) over the final seven days of treatment from home PEF recordings performed five times daily . A full response to treatment was defined as an increase in FEV or FVC , or an increase in mean daily PEF over the final seven days of treatment , of at least 20 % from baseline values . An improvement in one measurement of at least 15 % , or of 10 % in any two measurements , was defined as a partial treatment response . Response to placebo showed a significant order effect , suggesting a carry over effect of active treatment of at least three weeks . Response to active treatment was therefore related to initial baseline values , and compared with placebo by considering responses in the first treatment phase only . A full response to oral prednisolone ( 16/38 ) was significantly more common than to placebo ( 3/35 ) . The number of full responses to inhaled beclomethasone ( 8/34 ) did not differ significantly from the number responding to oral prednisolone or placebo in the first treatment phase , though full and partial responses to inhaled beclomethasone ( 12/34 ) were significantly more common than those to placebo ( 4/35 ) . When all three treatment phases were considered 44/107 patients showed a full response to one or both forms of corticosteroid treatment , a response to prednisolone ( 39 ) occurring more frequently than to inhaled beclomethasone ( 26 ) . Only 21 of the 44 responders showed a response to both forms of treatment . Inhaled beclomethasone dipropionate 500 micrograms thrice daily was inferior to oral prednisolone 40 mg per day , but better than placebo , in producing improvement in physiological measurements in patients thought to have nonasthmatic chronic airflow obstruction . It was , however , an effective alternative in over half of those showing a response to prednisolone STUDY OBJECTIVE To determine the effectiveness of treatment with corticosteroids in patients with COPD . METHODS In this study , we investigated the effect of a 2-year treatment with corticosteroids on clinical symptoms and the decline of lung function in 58 nonallergic patients with COPD . Subjects were treated in a double-blind , r and omized , placebo-controlled , parallel way with inhaled budesonide ( bud ) , 1,600 micrograms/d ; inhaled budesonide , 1,600 micrograms/d , plus oral prednisolone , 5 micrograms/d ( bud + pred ) ; or placebo ( plac ) .  Clinical assessment ( history , physical examination , and spirometry ) was carried out every 2 months . The rate of decline in FEV1 was assessed by calculating individual regression co-efficients from linear regression of FEV1 on time for each subject . RESULTS Eleven patients dropped out . The number of withdrawals due to pulmonary problems was significantly higher in the plac group ( n = 5 out of 18 ) than in the actively treated groups ( n = 2 out of 40 ) . Treatment with corticosteroids significantly reduced pulmonary symptoms . Median decline of FEV1 was 60 mL/yr in the plac group , 40 mL/yr in the bud + pred group , and 30 mL/yr in the bud group . Variation was large and differences were not statistically significant . No treatment effect was found on frequency or duration of exacerbations , possibly because of the high number of withdrawals due to pulmonary deterioration in the plac group . Treatment with a combination of inhaled plus oral corticosteroids was not more effective than inhaled corticosteroids alone . Morning plasma cortisol levels remained within the normal range in all three groups . CONCLUSIONS Our study shows beneficial effects of long-term daily treatment with inhaled corticosteroids in patients with COPD with regard to symptoms and drop out due to pulmonary problems . Lung function decline tends to decrease during treatment with inhaled corticosteroids . The observed effects are limited but warrant further studies on the effectiveness of corticosteroids in larger numbers of patients with COPD A double-blind crossover trial of prednisolone was conducted in 70 patients of chronic obstructive lung disease ( COLD ) . Emphysema dominated the clinical picture in 38 , rest being chronic bronchitis with varying degrees of air trapping . None of the patients had clinical asthma . All the patients had obtained maximal benefit from an optimal dose of bronchodilators prior to entering the study . Prednisolone in a dose of 0.8 mg/kg was prescribed in a double blind crossover manner with identical appearing placebo tablets . Patients were evaluated on a weekly basis for an objective as well as a subjective response and side effects of therapy . Thirty-four patients demonstrated a statistically significant improvement in pulmonary functions . In 20 others only subjective response was observed . A good objective response was predicted by a pre- study variability in FEV1 , disease duration of less than 10 years and a history of smoking less than 50 pack years Evans , J. A. , Morrison , I. M. , and Saunders , K. B. (1974).Thorax , 29 , 401 - 406 . A controlled trial of prednisone , in low dosage , in patients with chronic airways obstruction . Ten men with chronic airways obstruction took part in a double-blind controlled cross-over trial of 5 mg prednisone , daily for a week , versus placebo .  All patients had breathlessness as their main complaint , and chronic cough with sputum for 2 to 30 years ; five had evidence of emphysema on the chest radiograph . None had a personal or family history of asthma . For the group , mean forced expiratory volume in one second was 1·11 1 . , and mean forced vital capacity was 2·28 1 . Six patients had abnormally high levels of arterial Pco2 ( 46 - 52 mmHg ) . When the ` placebo ' and ` prednisone ' measurements were compared there was no significant change in forced expiratory volumes , bronchodilator effect on forced expiratory volumes , or blood gas tensions . Inspiratory airways resistance measured by body plethysmography was significantly higher , or ` worse ' , on prednisone ( mean 4·2 cmH2O per 1/sec ) than on placebo ( mean 3·2 ) Many patients with irreversible chronic obstructive pulmonary disease ( COPD ) cl aim symptomatic improvement with steroid therapy , despite a lack of objective improvement in their spirometric data . To determine if steroids actually increase the exercise capacity of these individuals , 13 clinical ly stable patients ( mean age , 63 + /- 4 years ; 12 male patients ) were given methylprednisolone ( 32 mg once daily ) or placebo in a r and omized double-blind crossover fashion . Spirometric data and minute ventilation , oxygen consumption ( VO2 ) , carbon dioxide production , and heart rate during incremental exercise were measured at each visit . Methylprednisolone did not produce a significant change in any of the measured parameters . Three patients had an increase in maximal VO2 of greater than 2 ml/kg/min during therapy 
    Output:
    