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 Endothelin (ET)-l is a bronchoconstrictor peptide produced in the airways . It has been implicated in the pathogenesis of asthma and virally mediated airway inflammation and may play a role in exacerbations of chronic obstructive pulmonary disease ( COPD ) . METHODS Seventy one patients with COPD were followed prospect ively and sample d for  plasma and sputum ET-1 levels when stable and during an exacerbation . Sputum was also examined for cytokines , human rhinovirus , and Chlamydia pneumoniae . RESULTS Plasma ET-1 levels were available for 67 patients with stable COPD ( mean ( SD ) 0.58 ( 0.31 ) pg/ml ) ; 28 pairs of stable-exacerbation plasma sample s had a mean stable ET-1 level of 0.54 ( 0.30 ) pg/ml rising to 0.67 ( 0.35 ) pg/ml at exacerbation ( mean difference 0.13 , 95 % confidence interval ( CI ) 0.04 to 0.21 , p = 0.004 ) . Plasma ET-1 levels in the 67 patients with stable COPD were inversely correlated with baseline forced expiratory volume in one second ( FEV1;r = –0.29 , p = 0.022 ) and forced vital capacity ( FVC ; r = –0.38 , p = 0.002 ) . The change in plasma ET-1 levels during an exacerbation correlated with the change in oxygen saturation ( Sao 2;r = –0.41 , p = 0.036 ) . In 14 stable-exacerbation pairs of sputum sample s median stable ET-1 levels were 5.37 ( 0.97–21.95 ) pg/ml rising to 34.68 ( 13.77–51.95 ) pg/ml during an exacerbation ( mean difference 25.14 , 95 % CI 3.77 to 46.51 , p = 0.028 ) . This increase in sputum ET-1 levels correlated with the increase in plasma ET-1 levels ( r = 0.917 , p = 0.001 ) and sputum interleukin (IL)-6 levels ( r = 0.718 , p = 0.013 ) . CONCLUSIONS Sputum levels of ET-1 rise in COPD patients during an exacerbation and this is reflected by a smaller rise in plasma ET-1 levels . ET-1 may have a role in mediating airway inflammatory changes during exacerbations of COPD Chronic bronchitis is associated with airways obstruction and inflammation . In order to determine whether aerosolized beclomethasone can modulate airway inflammation and diminish airway obstruction , subjects with chronic bronchitis performed spirometry and underwent bronchoalveolar lavage ( BAL ) before and after receiving 6 wk of therapy ( five puffs four times a day ) with either aerosolized beclomethasone ( n = 20 ) or placebo ( n = 10 ) in a double-blinded , r and omized fashion . All subjects received aerosolized albuterol before each use of the study medications . Before BAL , the airways were visually assessed for the appearance of inflammation and assigned a score , the bronchitis index . BAL was performed by instilling five 20-ml aliquots of saline into each of three sites and pooling and separately analyzing the returns from the first aliquots to yield a " bronchial sample . " The bronchial lavages were repeated in an additional three sites to increase the volume of fluid available for analysis . The fluid was prepared for cytologic examination by cytocentrifugation . Albumin ( as a measure of epithelium permeability ) and lactoferrin and lysozyme ( as measures of serous cell activity ) were measured in unconcentrated BAL fluid by enzyme-linked immunosorbent assay , and concentrations in epithelial lining fluid were estimated using urea as an internal marker for dilution . After treatment , the beclomethasone group , but not the placebo group , showed improvement in FVC ( p = 0.02 ) , FEV1 ( p = 0.002 ) , and 25 to 75 % forced expiratory flow ( p = 0.006 ) . Associated with the improvement in spirometry , the bronchitis index fell ( 13.5 + /- 1.0 versus 10.75 + /- 1.1 , p = 0.02 ) in the beclomethasone-treated group , but not the placebo-treated group . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of this double-blind single center study ( the COPE study ) was to investigate the effect of discontinuation of the inhaled corticosteroid fluticasone propionate ( FP ) on exacerbations and health-related quality of life in patients with chronic obstructive pulmonary disease . After 4 months of treatment with FP ( 1,000 microg/day ) , 244 patients were r and omized to either continue FP or to receive placebo for 6 months : 123 patients continued FP ( FP group ) , and 121 received placebo ( placebo group ) . In the FP group , 58 ( 47 % ) patients developed at least one exacerbation compared with 69 ( 57 % ) in the placebo group . The hazard ratio of a first exacerbation in the placebo group compared with the FP group was 1.5 ( 95 % confidence interval [ CI ] 1.1 - 2.1 ) . In the placebo group 26 patients ( 21.5 % ) experienced rapid recurrent exacerbations and were subsequently unblinded and prescribed FP compared with 6 patients ( 4.9 % ) in the FP group ( relative risk = 4.4 ; 95 % CI 1.9 - 10.3 ) . Over a 6-month period , a significant difference in favor of the FP group was observed in the total score ( + 2.48 95 % CI 0.37 - 4.58 ) , activity domain ( + 4.64 95 % CI 1.60 - 7.68 ) , and symptom domain ( + 4.58 95 % CI 1.05 - 8.10 ) of the St. George 's Respiratory Question naire . This study indicates that discontinuation of FP in patients with chronic obstructive pulmonary disease is associated with a more rapid onset and higher recurrence-risk of exacerbations and a significant deterioration in aspects of Health-Related Quality of Life Oxidative stress in the lung is important in the pathogenesis of COPD . Published data indicate that glucocorticoids inhibit blood cells in their capacity to produce reactive oxygen species ( ROS ) . We investigated the effect of Fluticasone propionate ( FP ) on the ROS production capabilities of pulmonary cells . Bronchoalveolar lavage ( BAL ) was performed in smoking COPD patients , before and after a six month , placebo-controlled treatment with FP . BAL cells were stimulated with phorbol myristrate acetate ( PMA ) alone , and together with superoxide dismutase ( SOD ) . From kinetic plots of ferricytochrome-c conversion we calculated the maximal rate of superoxide production : V(max ) . We also examined BAL cell subsets and performed correlation analyses on ROS production and relevant clinical determinants . Paired results were obtained from 6 FP- and 9 placebo-treated patients . No significant change of V(max ) was found in both patient groups . Also BAL cellularity was unchanged . Correlation analyses showed a significant ( inverse ) association of V(max ) with the number of cigarettes smoked per day . We concluded that a potent inhaled glucocorticoid had no effect on the ROS production capability of BAL cells from smoking COPD patients . Apparently , heavy smoking impaired the ability of alveolar macrophages to produce ROS , which was not further decreased by FP STUDY OBJECTIVE To investigate possible changes in cells and molecular mediators of airway inflammation following inhaled steroid treatment of stable COPD patients . DESIGN Six-week open preliminary prospect i ve study . SETTING A university respiratory disease clinic . PATIENTS : Stable COPD patients with mild disease . INTERVENTION Six-week treatment with inhaled beclomethasone ( 1.5 mg die ) . MEASUREMENTS The levels of interleukin (IL)-8 , myeloperoxidase , eosinophilic cationic protein and tryptase , and cell numbers in bronchial lavage specimens were determined , and the symptom score , the endoscopic bronchitis index , and functional parameters were recorded . RESULTS After treatment there were significant reductions in the lavage levels of IL-8 ( [ mean + /- SEM ] 1,603.4 + /- 331.2 vs 1,119.2 + /- 265.3 pg/mL , respectively ; p = 0 . 01 ) and myeloperoxidase ( 1,614.5 + /- 682.3 vs 511.2 + /- 144.2 microg/L , respectively ; p = 0.05 ) , in cell numbers ( 250.6 + /- 27.7 vs 186.3 + /- 11.5 cells x 10(3)/mL , respectively ; p = 0.04 ) , neutrophil proportion ( 59.7 + /- 14.3 % vs 31.5 + /- 10.1 % ; p = 0.01 ) , symptom score ( 4.5 + /- 0.6 vs 1.4 + /- 0.5 ; p = 0.01 ) , and bronchitis index ( 8.5 + /- 0.8 vs 5.5 + /- 0.7 ; p = 0.007 ) . CONCLUSIONS In stable patients with COPD , inhaled steroid treatment may induce changes on some cellular and molecular parameters of airway inflammation Inhaled corticosteroids are widely prescribed for the treatment of stable chronic obstructive pulmonary disease ( COPD ) , despite lack of proven efficacy . Because COPD involves airway inflammation and probable protease-antiprotease imbalance , we examined the effect of high dose fluticasone propionate on markers of activity of both pathogenetic mechanisms . Thirteen patients with COPD were treated with fluticasone propionate ( 500 microg twice a day ) for 4 wk , delivered via MDI and spacer , in a double-blind crossover study . There was no clinical benefit in terms of lung function or symptom scores , and induced sputum inflammatory cells , percentage neutrophils , and IL-8 levels were unchanged . Sputum supernatant elastase activity , matrix metalloproteinase (MMP)-1 , MMP-9 , and the antiproteases secretory leukoprotease inhibitor ( SLPI ) and tissue inhibitor of metalloproteinase (TIMP)-1 were similarly unaffected by treatment . These results add to previous evidence that inhaled steroids have no anti-inflammatory action in stable COPD . Furthermore , inhaled steroids do not appear to redress the protease-antiprotease imbalance that is thought to be important in the pathogenesis of airway obstruction The effects of fluticasone propionate ( FP ) on sputum chemotactic activity , elastase inhibitory potential , albumin concentrations , and peripheral neutrophil function were studied in a group of patients with clinical ly stable , smoking-related chronic bronchitis and emphysema . Seventeen patients ( 50 to 75 yr of age ) were entered into a double-blind , placebo-controlled study of 1.5 mg inhaled FP/d for 8 wk . Following treatment with FP the chemotactic activity of the sputum sol phase was lower than the corresponding values for the placebo group ( p < 0.01 ) . Values fell from a mean of 21.75 ( + /- 1.58 ) during the run-in period to 18.37 ( + /- 1.46 ; p < 0.01 ) after 4 wk and 17.63 ( + /- 1.86 ; p < 0.05 ) after 8 wk treatment returning to 22.08 ( + /- 1.26 ) cell/field after the washout period . The neutrophil elastase inhibitory capacity of the sputum sol phase increased ( p < 0.025 ) with treatment from a mean of 0.177 microM elastase inhibited/L ( + /- 0.05 ) pretreatment to 0.413 microM ( + /- 0.054 ) after 4 wk and 0.415 microM ( + /- 0.054 ) after 8 wk returning to 0.270 microM ( + /- 0.07 ) after the washout period . Treatment with FP did not result in a change in the peripheral neutrophil functions studied or sputum albumin and myeloperoxidase concentrations . The results suggest that FP may play a protective role in these patients through a reduction in the chemotactic activity of lung secretions and potentially a reduction in the recruitment of neutrophils to the lung , and also by directly affecting the proteinase/antiproteinase balance , in favor of antiproteinases , within lung secretions BACKGROUND The efficacy of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease ( C 
    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 Endothelin (ET)-l is a bronchoconstrictor peptide produced in the airways . It has been implicated in the pathogenesis of asthma and virally mediated airway inflammation and may play a role in exacerbations of chronic obstructive pulmonary disease ( COPD ) . METHODS Seventy one patients with COPD were followed prospect ively and sample d for  plasma and sputum ET-1 levels when stable and during an exacerbation . Sputum was also examined for cytokines , human rhinovirus , and Chlamydia pneumoniae . RESULTS Plasma ET-1 levels were available for 67 patients with stable COPD ( mean ( SD ) 0.58 ( 0.31 ) pg/ml ) ; 28 pairs of stable-exacerbation plasma sample s had a mean stable ET-1 level of 0.54 ( 0.30 ) pg/ml rising to 0.67 ( 0.35 ) pg/ml at exacerbation ( mean difference 0.13 , 95 % confidence interval ( CI ) 0.04 to 0.21 , p = 0.004 ) . Plasma ET-1 levels in the 67 patients with stable COPD were inversely correlated with baseline forced expiratory volume in one second ( FEV1;r = –0.29 , p = 0.022 ) and forced vital capacity ( FVC ; r = –0.38 , p = 0.002 ) . The change in plasma ET-1 levels during an exacerbation correlated with the change in oxygen saturation ( Sao 2;r = –0.41 , p = 0.036 ) . In 14 stable-exacerbation pairs of sputum sample s median stable ET-1 levels were 5.37 ( 0.97–21.95 ) pg/ml rising to 34.68 ( 13.77–51.95 ) pg/ml during an exacerbation ( mean difference 25.14 , 95 % CI 3.77 to 46.51 , p = 0.028 ) . This increase in sputum ET-1 levels correlated with the increase in plasma ET-1 levels ( r = 0.917 , p = 0.001 ) and sputum interleukin (IL)-6 levels ( r = 0.718 , p = 0.013 ) . CONCLUSIONS Sputum levels of ET-1 rise in COPD patients during an exacerbation and this is reflected by a smaller rise in plasma ET-1 levels . ET-1 may have a role in mediating airway inflammatory changes during exacerbations of COPD Chronic bronchitis is associated with airways obstruction and inflammation . In order to determine whether aerosolized beclomethasone can modulate airway inflammation and diminish airway obstruction , subjects with chronic bronchitis performed spirometry and underwent bronchoalveolar lavage ( BAL ) before and after receiving 6 wk of therapy ( five puffs four times a day ) with either aerosolized beclomethasone ( n = 20 ) or placebo ( n = 10 ) in a double-blinded , r and omized fashion . All subjects received aerosolized albuterol before each use of the study medications . Before BAL , the airways were visually assessed for the appearance of inflammation and assigned a score , the bronchitis index . BAL was performed by instilling five 20-ml aliquots of saline into each of three sites and pooling and separately analyzing the returns from the first aliquots to yield a " bronchial sample . " The bronchial lavages were repeated in an additional three sites to increase the volume of fluid available for analysis . The fluid was prepared for cytologic examination by cytocentrifugation . Albumin ( as a measure of epithelium permeability ) and lactoferrin and lysozyme ( as measures of serous cell activity ) were measured in unconcentrated BAL fluid by enzyme-linked immunosorbent assay , and concentrations in epithelial lining fluid were estimated using urea as an internal marker for dilution . After treatment , the beclomethasone group , but not the placebo group , showed improvement in FVC ( p = 0.02 ) , FEV1 ( p = 0.002 ) , and 25 to 75 % forced expiratory flow ( p = 0.006 ) . Associated with the improvement in spirometry , the bronchitis index fell ( 13.5 + /- 1.0 versus 10.75 + /- 1.1 , p = 0.02 ) in the beclomethasone-treated group , but not the placebo-treated group . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of this double-blind single center study ( the COPE study ) was to investigate the effect of discontinuation of the inhaled corticosteroid fluticasone propionate ( FP ) on exacerbations and health-related quality of life in patients with chronic obstructive pulmonary disease . After 4 months of treatment with FP ( 1,000 microg/day ) , 244 patients were r and omized to either continue FP or to receive placebo for 6 months : 123 patients continued FP ( FP group ) , and 121 received placebo ( placebo group ) . In the FP group , 58 ( 47 % ) patients developed at least one exacerbation compared with 69 ( 57 % ) in the placebo group . The hazard ratio of a first exacerbation in the placebo group compared with the FP group was 1.5 ( 95 % confidence interval [ CI ] 1.1 - 2.1 ) . In the placebo group 26 patients ( 21.5 % ) experienced rapid recurrent exacerbations and were subsequently unblinded and prescribed FP compared with 6 patients ( 4.9 % ) in the FP group ( relative risk = 4.4 ; 95 % CI 1.9 - 10.3 ) . Over a 6-month period , a significant difference in favor of the FP group was observed in the total score ( + 2.48 95 % CI 0.37 - 4.58 ) , activity domain ( + 4.64 95 % CI 1.60 - 7.68 ) , and symptom domain ( + 4.58 95 % CI 1.05 - 8.10 ) of the St. George 's Respiratory Question naire . This study indicates that discontinuation of FP in patients with chronic obstructive pulmonary disease is associated with a more rapid onset and higher recurrence-risk of exacerbations and a significant deterioration in aspects of Health-Related Quality of Life Oxidative stress in the lung is important in the pathogenesis of COPD . Published data indicate that glucocorticoids inhibit blood cells in their capacity to produce reactive oxygen species ( ROS ) . We investigated the effect of Fluticasone propionate ( FP ) on the ROS production capabilities of pulmonary cells . Bronchoalveolar lavage ( BAL ) was performed in smoking COPD patients , before and after a six month , placebo-controlled treatment with FP . BAL cells were stimulated with phorbol myristrate acetate ( PMA ) alone , and together with superoxide dismutase ( SOD ) . From kinetic plots of ferricytochrome-c conversion we calculated the maximal rate of superoxide production : V(max ) . We also examined BAL cell subsets and performed correlation analyses on ROS production and relevant clinical determinants . Paired results were obtained from 6 FP- and 9 placebo-treated patients . No significant change of V(max ) was found in both patient groups . Also BAL cellularity was unchanged . Correlation analyses showed a significant ( inverse ) association of V(max ) with the number of cigarettes smoked per day . We concluded that a potent inhaled glucocorticoid had no effect on the ROS production capability of BAL cells from smoking COPD patients . Apparently , heavy smoking impaired the ability of alveolar macrophages to produce ROS , which was not further decreased by FP STUDY OBJECTIVE To investigate possible changes in cells and molecular mediators of airway inflammation following inhaled steroid treatment of stable COPD patients . DESIGN Six-week open preliminary prospect i ve study . SETTING A university respiratory disease clinic . PATIENTS : Stable COPD patients with mild disease . INTERVENTION Six-week treatment with inhaled beclomethasone ( 1.5 mg die ) . MEASUREMENTS The levels of interleukin (IL)-8 , myeloperoxidase , eosinophilic cationic protein and tryptase , and cell numbers in bronchial lavage specimens were determined , and the symptom score , the endoscopic bronchitis index , and functional parameters were recorded . RESULTS After treatment there were significant reductions in the lavage levels of IL-8 ( [ mean + /- SEM ] 1,603.4 + /- 331.2 vs 1,119.2 + /- 265.3 pg/mL , respectively ; p = 0 . 01 ) and myeloperoxidase ( 1,614.5 + /- 682.3 vs 511.2 + /- 144.2 microg/L , respectively ; p = 0.05 ) , in cell numbers ( 250.6 + /- 27.7 vs 186.3 + /- 11.5 cells x 10(3)/mL , respectively ; p = 0.04 ) , neutrophil proportion ( 59.7 + /- 14.3 % vs 31.5 + /- 10.1 % ; p = 0.01 ) , symptom score ( 4.5 + /- 0.6 vs 1.4 + /- 0.5 ; p = 0.01 ) , and bronchitis index ( 8.5 + /- 0.8 vs 5.5 + /- 0.7 ; p = 0.007 ) . CONCLUSIONS In stable patients with COPD , inhaled steroid treatment may induce changes on some cellular and molecular parameters of airway inflammation Inhaled corticosteroids are widely prescribed for the treatment of stable chronic obstructive pulmonary disease ( COPD ) , despite lack of proven efficacy . Because COPD involves airway inflammation and probable protease-antiprotease imbalance , we examined the effect of high dose fluticasone propionate on markers of activity of both pathogenetic mechanisms . Thirteen patients with COPD were treated with fluticasone propionate ( 500 microg twice a day ) for 4 wk , delivered via MDI and spacer , in a double-blind crossover study . There was no clinical benefit in terms of lung function or symptom scores , and induced sputum inflammatory cells , percentage neutrophils , and IL-8 levels were unchanged . Sputum supernatant elastase activity , matrix metalloproteinase (MMP)-1 , MMP-9 , and the antiproteases secretory leukoprotease inhibitor ( SLPI ) and tissue inhibitor of metalloproteinase (TIMP)-1 were similarly unaffected by treatment . These results add to previous evidence that inhaled steroids have no anti-inflammatory action in stable COPD . Furthermore , inhaled steroids do not appear to redress the protease-antiprotease imbalance that is thought to be important in the pathogenesis of airway obstruction The effects of fluticasone propionate ( FP ) on sputum chemotactic activity , elastase inhibitory potential , albumin concentrations , and peripheral neutrophil function were studied in a group of patients with clinical ly stable , smoking-related chronic bronchitis and emphysema . Seventeen patients ( 50 to 75 yr of age ) were entered into a double-blind , placebo-controlled study of 1.5 mg inhaled FP/d for 8 wk . Following treatment with FP the chemotactic activity of the sputum sol phase was lower than the corresponding values for the placebo group ( p < 0.01 ) . Values fell from a mean of 21.75 ( + /- 1.58 ) during the run-in period to 18.37 ( + /- 1.46 ; p < 0.01 ) after 4 wk and 17.63 ( + /- 1.86 ; p < 0.05 ) after 8 wk treatment returning to 22.08 ( + /- 1.26 ) cell/field after the washout period . The neutrophil elastase inhibitory capacity of the sputum sol phase increased ( p < 0.025 ) with treatment from a mean of 0.177 microM elastase inhibited/L ( + /- 0.05 ) pretreatment to 0.413 microM ( + /- 0.054 ) after 4 wk and 0.415 microM ( + /- 0.054 ) after 8 wk returning to 0.270 microM ( + /- 0.07 ) after the washout period . Treatment with FP did not result in a change in the peripheral neutrophil functions studied or sputum albumin and myeloperoxidase concentrations . The results suggest that FP may play a protective role in these patients through a reduction in the chemotactic activity of lung secretions and potentially a reduction in the recruitment of neutrophils to the lung , and also by directly affecting the proteinase/antiproteinase balance , in favor of antiproteinases , within lung secretions BACKGROUND The efficacy of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease ( C 
    Output:
    