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 AND AIM COPD leads to a progressive decline of pulmonary function . Family physicians treat a substantial number of patients with COPD and are encouraged to start treatment at as early a stage as is possible . This study analyzed the effectiveness of early inhaled corticosteroid treatment on the decline of pulmonary function in COPD patients . PATIENTS AND SETTING Subjects with a rapid decline in lung function ( ie , FEV(1 ) decline , > 80 mL/yr ) who had never before received a diagnosis of asthma or COPD . METHODS Two-year , r and omized , controlled , double-blind clinical trial of fluticasone propionate ( 250 microg bid ; 24 patients ) or placebo ( 25 patients ) , followed by a 7-month open-label study in which all subjects received fluticasone propionate . The primary outcome was the post-bronchodilator therapy FEV(1 , ) and secondary outcomes were respiratory symptoms , exacerbations , health state , quality of life , and health-care utilization . RESULTS After 31 months , there were no statistical differences in post-bronchodilator therapy FEV(1 ) between the intervention group and the control group . No statistical differences were observed for symptoms , exacerbations , or quality of life , although tendencies were consistently in favor of treatment . There was no significant impact on the direct or indirect costs . CONCLUSIONS There are no indications that early treatment with inhaled corticosteroids modifies a rapid decline in lung function or respiratory symptoms and quality of life Background : Airway inflammation in chronic obstructive pulmonary disease ( COPD ) is characterised by infiltration of CD8 + T cells and CD68 + macrophages and an increased number of neutrophils , whereas few studies have described the presence of eosinophils . Although the anti-inflammatory effects of corticosteroids in stable COPD are unclear , recent studies suggest that combination therapy could be beneficial . A study was therefore undertaken to evaluate combined salmeterol/fluticasone propionate ( SFC ) and fluticasone propionate ( FP ) alone on inflammatory cells in the airways of patients with COPD . Methods : Patients were treated in a r and omised , double blind , parallel group , placebo-controlled trial with either a combination of 50 µg salmeterol and 500 µg FP twice daily  ( SFC , n = 19 , 19 men , mean age 62 years ) , 500 µg FP twice daily ( n = 20 , 15 men , mean age 64 years ) or placebo  ( n = 21 , 17 men , mean age 66 years ) for 3 months . At the start and end of treatment bronchoscopy with bronchial biopsies was performed and the numbers of CD8 + T lymphocytes , CD68 + macrophages , neutrophils and eosinophils were measured . Results : CD8 + cells were significantly reduced by SFC compared with placebo ( difference −98.05 cells/mm2 ; 95 % CI −143.14 to −52.9 ; p<0.001 ) . Such a marked effect was not seen with FP alone ( −44.67 cells/mm2 ; 95 % CI −90.92 to 1.57 ; p = 0.06 ) . CD68 + macrophages were also reduced by SFC compared with placebo ( difference −31.68 cells/mm2 ; 95 % CI −61.07 to −2.29 ; p = 0.03 ) but not by FP . SFC did not significantly change neutrophils and eosinophils compared with placebo . Conclusions : SFC has airway anti-inflammatory effects not seen with inhaled corticosteroids alone 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 The aim of the present r and omized , double-blind study was to evaluate the effect of inhaled budesonide on daily symptoms , ventilatory capacity , and airway responsiveness in smokers with chronic bronchitis . Twenty-five subjects with a provocative concentration producing a 20 % fall in forced expiratory volume in one second PC20(FEV1 ) less than 2.0 mg.ml-1 , by bronchial histamine challenge , were included . Eighteen subjects accomplished the entire 12 week study , eight receiving inhaled budesonide 400 micrograms b.i.d . and ten receiving placebo .  Cough decreased significantly in the actively treated group during the treatment period , but no change could be demonstrated in expectoration , dyspnoea , or sleep disturbances . No changes in any of these symptoms were found in the placebo group , and no differences in symptoms scores were found between the groups . No significant differences in ventilatory capacity or bronchial responsiveness could be demonstrated . In conclusion , a moderately high dose of inhaled steroid in eight subjects with chronic bronchitis did not improve the symptom scores , ventilatory capacity , or airway responsiveness to any clinical ly relevant degree Background : Chronic obstructive pulmonary disease ( COPD ) is characterised by both an accelerated decline in lung function and periods of acute deterioration in symptoms termed exacerbations . The aim of this study was to investigate whether these are related . Methods : Over 4 years ,  peak expiratory flow ( PEF ) and symptoms were measured at home daily by 109 patients with COPD ( 81 men ; median ( IQR ) age 68.1 ( 63–74 ) years ; arterial oxygen tension ( Pao2 ) 9.00 ( 8.3–9.5 ) kPa , forced expiratory volume in 1 second ( FEV1 ) 1.00 ( 0.7–1.3 ) l , forced vital capacity ( FVC ) 2.51 ( 1.9–3.0 ) l ) ; of these , 32 ( 29 men ) recorded daily FEV1 . Exacerbations were identified from symptoms and the effect of frequent or infrequent exacerbations ( > or < 2.92 per year ) on lung function decline was examined using cross sectional , r and om effects models . Results : The 109 patients experienced 757 exacerbations . Patients with frequent exacerbations had a significantly faster decline in FEV1 and peak expiratory flow ( PEF ) of –40.1 ml/year ( n=16 ) and –2.9 l/min/year ( n=46 ) than infrequent exacerbators in whom FEV1 changed by –32.1 ml/year ( n=16 ) and PEF by –0.7 l/min/year ( n=63 ) . Frequent exacerbators also had a greater decline in FEV1 if allowance was made for smoking status . Patients with frequent exacerbations were more often admitted to hospital with longer length of stay . Frequent exacerbations were a consistent feature within a patient , with their number positively correlated ( between years 1 and 2 , 2 and 3 , 3 and 4 ) . Conclusions : These results suggest that the frequency of exacerbations contributes to long term decline in lung function of patients with moderate to severe COPD Despite the success of inhaled steroids in controlling asthma , the benefit in patients with chronic obstructive pulmonary disease ( COPD ) remains controversial . Five subjects with moderate to severe emphysema due to alpha 1-antitrypsin deficiency ( phenotype PiZ ) were followed with daily home spirometry in a 2 x 8 weeks , r and omized double-blind , placebo-controlled , crossover study of inhaled budesonide 0.8 mg b.i.d . In three of the five patients , there was a statistically significant increase in the mean forced expiratory volume in 1 s ( FEV1 ) , and in two of these patients , there was also a statistically significant increase in the mean forced vital capacity ( FVC ) during budesonide treatment . A significant diurnal variation in FEV1 and FVC was found in three and two patients , respectively , but did not change significantly during treatment . These findings emphasize the need for renewed evaluation of inhaled steroids in the treatment of patients with emphysema , and indicate that individual patients may have significant clinical improvement BACKGROUND --Despite effective treatments , the morbidity and mortality of obstructive airways disease ( asthma and COPD ) remains high . Home monitoring of peak expiratory flow ( PEF ) is increasingly being advocated as an aid to better management of obstructive airways disease . The few available studies describing effects of treatment on the level and variation of PEF have involved relatively small numbers of subjects and did not use control groups . METHODS -- Patients aged 18 - 60 years were selected with PC20 < or = 8 mg/ml and FEV1 < 95 % confidence interval of predicted normal . They were r and omised to receive , in addition to a beta 2 agonist , either an inhaled corticosteroid ( BA+CS ) , an anticholinergic ( BA+AC ) , or a placebo ( BA+PL ) .  One hundred and forty one of these subjects with moderately severe obstructive airways disease completed seven periods of two weeks of morning and afternoon PEF measurements at home during 18 months of blind follow up . RESULTS --Improvements in PEF occurred within the first three months of treatment with BA+CS and was subsequently maintained : the mean ( SE ) increase in morning PEF was 51 ( 8) l/min in the BA+CS group compared with no change in the other two groups . Similarly , afternoon PEF increased by 22 ( 7 ) l/min . Diurnal variation in PEF ( amplitude % mean ) decreased from 18.0 % to 10.2 % in the first three months of treatment with BA+CS . Within-subject relations between changes in diurnal variation in PEF and changes in PC20 were found to be predominantly negative ( median rho-0.40 ) but with a large scatter . Relations between diurnal variation in PEF and changes in symptom scores , FEV1 , and bronchodilator response were even weaker . CONCLUSIONS --In patients with moderately severe obstructive airways disease , PEF rates and variation are greatly improved by inhaled corticosteroids . Since the relation of diurnal PEF variation with PC20 , symptoms , FEV1 , and bronchodilator response were all weak , these markers of disease severity may all provide different information on the actual disease state . PEF measurements should be used in addition to the other markers but not instead of them Cross-sectional studies have suggested that asthmatic patients receiving high dose inhaled corticosteroids and intermittent courses of oral corticosteroids  have reduced bone mass . This prospect i ve 2-yr study was undertaken to evaluate changes in bone density of patients receiving high doses of inhaled corticosteroids . Patients ( n = 33 ) ( males aged 18 - 50 yrs , females aged 18 - 40 yrs ) on inhaled corticosteroids 1,000 - 2,000 microg x day(-1 ) , were r and omized in a double-blind fashion to either fluticasone propionate ( FP ) 1,000 microg x day(-1 ) or beclomethasone dipropionate ( BDP ) 2,000 microg x day(-1 ) . In parallel , three open control groups of the same age range were studied : asthmatics ( n = 8) receiving low dose inhaled corticosteroids ( < or = 400 microg x day(-1 ) ) ( group A ) ; chronic , severe asthmatics ( n = 8) receiving oral corticosteroids ( > or = 10 mg x day(-1 ) ( group B ) ; and healthy untreated volunteers ( n = 7 ) ( group C ) . Bone densitometry scans 
    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 AND AIM COPD leads to a progressive decline of pulmonary function . Family physicians treat a substantial number of patients with COPD and are encouraged to start treatment at as early a stage as is possible . This study analyzed the effectiveness of early inhaled corticosteroid treatment on the decline of pulmonary function in COPD patients . PATIENTS AND SETTING Subjects with a rapid decline in lung function ( ie , FEV(1 ) decline , > 80 mL/yr ) who had never before received a diagnosis of asthma or COPD . METHODS Two-year , r and omized , controlled , double-blind clinical trial of fluticasone propionate ( 250 microg bid ; 24 patients ) or placebo ( 25 patients ) , followed by a 7-month open-label study in which all subjects received fluticasone propionate . The primary outcome was the post-bronchodilator therapy FEV(1 , ) and secondary outcomes were respiratory symptoms , exacerbations , health state , quality of life , and health-care utilization . RESULTS After 31 months , there were no statistical differences in post-bronchodilator therapy FEV(1 ) between the intervention group and the control group . No statistical differences were observed for symptoms , exacerbations , or quality of life , although tendencies were consistently in favor of treatment . There was no significant impact on the direct or indirect costs . CONCLUSIONS There are no indications that early treatment with inhaled corticosteroids modifies a rapid decline in lung function or respiratory symptoms and quality of life Background : Airway inflammation in chronic obstructive pulmonary disease ( COPD ) is characterised by infiltration of CD8 + T cells and CD68 + macrophages and an increased number of neutrophils , whereas few studies have described the presence of eosinophils . Although the anti-inflammatory effects of corticosteroids in stable COPD are unclear , recent studies suggest that combination therapy could be beneficial . A study was therefore undertaken to evaluate combined salmeterol/fluticasone propionate ( SFC ) and fluticasone propionate ( FP ) alone on inflammatory cells in the airways of patients with COPD . Methods : Patients were treated in a r and omised , double blind , parallel group , placebo-controlled trial with either a combination of 50 µg salmeterol and 500 µg FP twice daily  ( SFC , n = 19 , 19 men , mean age 62 years ) , 500 µg FP twice daily ( n = 20 , 15 men , mean age 64 years ) or placebo  ( n = 21 , 17 men , mean age 66 years ) for 3 months . At the start and end of treatment bronchoscopy with bronchial biopsies was performed and the numbers of CD8 + T lymphocytes , CD68 + macrophages , neutrophils and eosinophils were measured . Results : CD8 + cells were significantly reduced by SFC compared with placebo ( difference −98.05 cells/mm2 ; 95 % CI −143.14 to −52.9 ; p<0.001 ) . Such a marked effect was not seen with FP alone ( −44.67 cells/mm2 ; 95 % CI −90.92 to 1.57 ; p = 0.06 ) . CD68 + macrophages were also reduced by SFC compared with placebo ( difference −31.68 cells/mm2 ; 95 % CI −61.07 to −2.29 ; p = 0.03 ) but not by FP . SFC did not significantly change neutrophils and eosinophils compared with placebo . Conclusions : SFC has airway anti-inflammatory effects not seen with inhaled corticosteroids alone 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 The aim of the present r and omized , double-blind study was to evaluate the effect of inhaled budesonide on daily symptoms , ventilatory capacity , and airway responsiveness in smokers with chronic bronchitis . Twenty-five subjects with a provocative concentration producing a 20 % fall in forced expiratory volume in one second PC20(FEV1 ) less than 2.0 mg.ml-1 , by bronchial histamine challenge , were included . Eighteen subjects accomplished the entire 12 week study , eight receiving inhaled budesonide 400 micrograms b.i.d . and ten receiving placebo .  Cough decreased significantly in the actively treated group during the treatment period , but no change could be demonstrated in expectoration , dyspnoea , or sleep disturbances . No changes in any of these symptoms were found in the placebo group , and no differences in symptoms scores were found between the groups . No significant differences in ventilatory capacity or bronchial responsiveness could be demonstrated . In conclusion , a moderately high dose of inhaled steroid in eight subjects with chronic bronchitis did not improve the symptom scores , ventilatory capacity , or airway responsiveness to any clinical ly relevant degree Background : Chronic obstructive pulmonary disease ( COPD ) is characterised by both an accelerated decline in lung function and periods of acute deterioration in symptoms termed exacerbations . The aim of this study was to investigate whether these are related . Methods : Over 4 years ,  peak expiratory flow ( PEF ) and symptoms were measured at home daily by 109 patients with COPD ( 81 men ; median ( IQR ) age 68.1 ( 63–74 ) years ; arterial oxygen tension ( Pao2 ) 9.00 ( 8.3–9.5 ) kPa , forced expiratory volume in 1 second ( FEV1 ) 1.00 ( 0.7–1.3 ) l , forced vital capacity ( FVC ) 2.51 ( 1.9–3.0 ) l ) ; of these , 32 ( 29 men ) recorded daily FEV1 . Exacerbations were identified from symptoms and the effect of frequent or infrequent exacerbations ( > or < 2.92 per year ) on lung function decline was examined using cross sectional , r and om effects models . Results : The 109 patients experienced 757 exacerbations . Patients with frequent exacerbations had a significantly faster decline in FEV1 and peak expiratory flow ( PEF ) of –40.1 ml/year ( n=16 ) and –2.9 l/min/year ( n=46 ) than infrequent exacerbators in whom FEV1 changed by –32.1 ml/year ( n=16 ) and PEF by –0.7 l/min/year ( n=63 ) . Frequent exacerbators also had a greater decline in FEV1 if allowance was made for smoking status . Patients with frequent exacerbations were more often admitted to hospital with longer length of stay . Frequent exacerbations were a consistent feature within a patient , with their number positively correlated ( between years 1 and 2 , 2 and 3 , 3 and 4 ) . Conclusions : These results suggest that the frequency of exacerbations contributes to long term decline in lung function of patients with moderate to severe COPD Despite the success of inhaled steroids in controlling asthma , the benefit in patients with chronic obstructive pulmonary disease ( COPD ) remains controversial . Five subjects with moderate to severe emphysema due to alpha 1-antitrypsin deficiency ( phenotype PiZ ) were followed with daily home spirometry in a 2 x 8 weeks , r and omized double-blind , placebo-controlled , crossover study of inhaled budesonide 0.8 mg b.i.d . In three of the five patients , there was a statistically significant increase in the mean forced expiratory volume in 1 s ( FEV1 ) , and in two of these patients , there was also a statistically significant increase in the mean forced vital capacity ( FVC ) during budesonide treatment . A significant diurnal variation in FEV1 and FVC was found in three and two patients , respectively , but did not change significantly during treatment . These findings emphasize the need for renewed evaluation of inhaled steroids in the treatment of patients with emphysema , and indicate that individual patients may have significant clinical improvement BACKGROUND --Despite effective treatments , the morbidity and mortality of obstructive airways disease ( asthma and COPD ) remains high . Home monitoring of peak expiratory flow ( PEF ) is increasingly being advocated as an aid to better management of obstructive airways disease . The few available studies describing effects of treatment on the level and variation of PEF have involved relatively small numbers of subjects and did not use control groups . METHODS -- Patients aged 18 - 60 years were selected with PC20 < or = 8 mg/ml and FEV1 < 95 % confidence interval of predicted normal . They were r and omised to receive , in addition to a beta 2 agonist , either an inhaled corticosteroid ( BA+CS ) , an anticholinergic ( BA+AC ) , or a placebo ( BA+PL ) .  One hundred and forty one of these subjects with moderately severe obstructive airways disease completed seven periods of two weeks of morning and afternoon PEF measurements at home during 18 months of blind follow up . RESULTS --Improvements in PEF occurred within the first three months of treatment with BA+CS and was subsequently maintained : the mean ( SE ) increase in morning PEF was 51 ( 8) l/min in the BA+CS group compared with no change in the other two groups . Similarly , afternoon PEF increased by 22 ( 7 ) l/min . Diurnal variation in PEF ( amplitude % mean ) decreased from 18.0 % to 10.2 % in the first three months of treatment with BA+CS . Within-subject relations between changes in diurnal variation in PEF and changes in PC20 were found to be predominantly negative ( median rho-0.40 ) but with a large scatter . Relations between diurnal variation in PEF and changes in symptom scores , FEV1 , and bronchodilator response were even weaker . CONCLUSIONS --In patients with moderately severe obstructive airways disease , PEF rates and variation are greatly improved by inhaled corticosteroids . Since the relation of diurnal PEF variation with PC20 , symptoms , FEV1 , and bronchodilator response were all weak , these markers of disease severity may all provide different information on the actual disease state . PEF measurements should be used in addition to the other markers but not instead of them Cross-sectional studies have suggested that asthmatic patients receiving high dose inhaled corticosteroids and intermittent courses of oral corticosteroids  have reduced bone mass . This prospect i ve 2-yr study was undertaken to evaluate changes in bone density of patients receiving high doses of inhaled corticosteroids . Patients ( n = 33 ) ( males aged 18 - 50 yrs , females aged 18 - 40 yrs ) on inhaled corticosteroids 1,000 - 2,000 microg x day(-1 ) , were r and omized in a double-blind fashion to either fluticasone propionate ( FP ) 1,000 microg x day(-1 ) or beclomethasone dipropionate ( BDP ) 2,000 microg x day(-1 ) . In parallel , three open control groups of the same age range were studied : asthmatics ( n = 8) receiving low dose inhaled corticosteroids ( < or = 400 microg x day(-1 ) ) ( group A ) ; chronic , severe asthmatics ( n = 8) receiving oral corticosteroids ( > or = 10 mg x day(-1 ) ( group B ) ; and healthy untreated volunteers ( n = 7 ) ( group C ) . Bone densitometry scans 
    Output:
    