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: PURPOSE Viable bacteria are often isolated from airway secretions in clinical ly stable patients with chronic bronchitis . We hypothesized that the number of organisms and bacterial species might be important modulators of airway inflammation . SUBJECTS AND METHODS We performed quantitative sputum cultures in 160 stable patients [ 55 with chronic obstructive pulmonary disease ( COPD ) and normal serum alpha(1)-antitrypsin levels , 62 with COPD and severe alpha(1)-antitrypsin deficiency ( PiZ ) , and 43 with idiopathic bronchiectasis ] . The results were related to several indicators of the mechanisms and severity of airway inflammation . RESULTS Airway bacterial load correlated with sputum myeloperoxidase level , an indirect measure of neutrophil activation and number ( r = 0.50 , P<0 . 001 ) ; sputum neutrophil chemoattractants [ interleukin-8 level ( r = 0 . 68 , P<0.001 ) and leukotriene B4 level ( r = 0.53 , P<0.001 ) ] ; sputum leukocyte elastase activity ( r = 0.55 , P<0.001 ) ; and albumin leakage from serum to sputum ( r = 0.26 , P<0.01 ) . Markers of inflammation increased at bacterial loads of 10(6 ) to 10(7 ) colony-forming units per milliliter , and increased progressively with increasing bacterial load . For example , the median ( interquartile range ) sputum myeloperoxidase level was 0.3 U/mL ( 0.1 to 0.5 U/mL ) for patients who were not colonized or who had mixed normal oropharyngeal flora alone ; 0.5 U/mL ( 0.2 to 0.7 U/mL ) for patients with 10(5 ) to 10(6 ) colony-forming units per milliliter ( P = 0.07 ) ; 0.5 U/mL ( 0.3 to 1.2 U/mL ) for patients with 10(6 ) to 10(7 ) colony-forming units per milliliter ( P<0.01 ) ; 0.7 U/mL ( 0.3 to 1.2 U/mL ) for patients with 10(7 ) to 10(8 ) colony-forming units per milliliter ( P < 0.005 ) ; and 2.4 U/mL ( 0.7 to 4.8 U/mL ) for patients with 10(8 ) or greater colony-forming units per milliliter ( P<0.0001 ) . The bacterial species influenced airway inflammation ; for example , sputum myeloperoxidase activity was greater ( P<0.005 ) in patients colonized with Pseudomonas aeruginosa [ median 32 U/mL ( interquartile range , 20 to 65 U/mL ) ] than those colonized with nontypeable Hemophilus influenzae [ 4 U/mL ( 2 to 31 U/mL ) ] , which in turn was greater ( P = 0.01 ) than among those colonized with Moraxella catarrhalis [ 1.1 U/mL ( 0.6 to 1.8 U/mL ) ] . We did not find a relation between bacterial load and lung function . CONCLUSIONS The bacterial load and species contribute to airway inflammation in patients with stable chronic bronchitis . Further studies are required to determine the consequences of bacterial colonization on patient morbidity and decline in lung function 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 Chronic obstructive pulmonary disease ( COPD ) patients experiencing frequent exacerbations demonstrate increased stable-state airway inflammation . Tiotropium has been shown to reduce exacerbation frequency , but its effect on airway inflammation is unknown . The aim of the present study was to investigate the effect of tiotropium on sputum inflammatory markers and exacerbation frequency .  Patients ( n = 142 ) were r and omised to receive tiotropium or placebo in addition to their usual medication for 1 yr . Sputum and serum cytokines were assayed by ELISA and exacerbation frequency calculated using a symptom-based diary . There was no difference in the area under the curve for sputum interleukin (IL)-6 or myeloperoxidase between the groups , but sputum IL-8 level was increased in the tiotropium arm . There was no difference between start and end of study in serum IL-6 or C-reactive protein level .  Tiotropium was associated with a 52 % reduction in exacerbation frequency ( 1.17 versus 2.46 exacerbations·yr−1 ) . Of patients on tiotropium , 43 % experienced at least one exacerbation , compared with 64 % on placebo  . The total number of exacerbation days was reduced compared with placebo ( 17.3 versus 34.5 days ) . Tiotropium  reduces exacerbation frequency in chronic obstructive pulmonary disease , but this effect does not appear to be due to a reduction in airway or systemic inflammation In order to describe the outcomes of patients hospitalized with an acute exacerbation of severe chronic obstructive pulmonary disease ( COPD ) and determine the relationship between patient characteristics and length of survival , we studied a prospect i ve cohort of 1,016 adult patients from five hospitals who were admitted with an exacerbation of COPD and a PaCO2 of 50 mm Hg or more . Patient characteristics and acute physiology were determined . Outcomes were evaluated over a 6 mo period . Although only 11 % of the patients died during the index hospital stay , the 60-d , 180-d , 1-yr , and 2-yr mortality was high ( 20 % , 33 % , 43 % , and 49 % , respectively ) . The median cost of the index hospital stay was $ 7,100 ( $ 4,100 to $ 16,000 ; interquartile range ) . The median length of the index hospital stay was 9 d ( 5 to 15 d ) . After discharge , 446 patients were readmitted 754 times in the next 6 mo . At 6 mo , only 26 % of the cohort were both alive and able to report a good , very good , or excellent quality of life . Survival time was independently related to severity of illness , body mass index ( BMI ) , age , prior functional status , PaO2/FI(O2 ) , congestive heart failure , serum albumin , and the presence of cor pulmonale . Patients and caregivers should be aware of the likelihood of poor outcomes following hospitalization for exacerbation of COPD associated with hypercarbia BACKGROUND AND OBJECTIVE To evaluate whether changes in regular physical activity ( PA ) in patients with chronic obstructive pulmonary disease ( COPD ) affect the rate of hospitalizations for COPD exacerbation ( e COPD ) . METHODS Five hundred forty-three ambulatory clinic patients being treated for COPD were prospect ively identified . PA was self-reported by patients , and the level was established by the distance they walked ( km/day ) at least 3 days per week . Hospitalizations were recorded from hospital data bases . All patients with at least a 2-year follow-up after enrollment were included in the analysis . The response variable was the number of hospitalizations for e COPD within the 3-year period from 2 to 5 years after study enrollment . RESULTS Three hundred ninety-one survivors were studied . Mean forced expiratory volume in 1 s was 52 % ( ±14 % ) of the predicted value . Patients who maintained a lower level of PA had an increased rate of hospitalization ( odds ratio 1.901 ; 95 % confidence interval 1.090 - 3.317 ) . After having had the highest level of PA , those patients who decreased their PA in the follow-up showed an increasing rate of hospitalizations ( odds ratio 2.134 ; 95 % confidence interval 1.146 - 3.977 ) . CONCLUSIONS Patients with COPD with a low level of PA or who reduced their PA over time were more likely to experience a significant increase in the rate of hospitalization for e COPD . Changes to a higher level of PA or maintaining a moderate or high level of PA over time , with a low intensity activity such as walking for at least 3 - 6 km/day , could reduce the rate of hospitalizations for e COPD RATIONALE Increased bacterial concentration ( load ) in the lower airways and new bacterial strain acquisition have been posited as mechanisms for chronic obstructive pulmonary disease ( COPD ) exacerbations .  Bacterial concentrations are higher during exacerbation than during stable disease ; however , these studies are cross sectional and devoid of strain typing . OBJECTIVES To determine if the increased bacterial concentrations function as a separate mechanism for exacerbation induction independent of new strain acquisition . METHODS In a prospect i ve , longitudinal cohort of patients with COPD , the relationship between exacerbation occurrence , sputum bacterial concentrations , and new strain acquisition was examined . MEASUREMENTS AND MAIN RESULTS Clinical information , quantitative sputum cultures , and molecular typing of potential bacterial pathogen isolates . Over 81 months , 104 subjects completed 3,009 clinic visits , 560 ( 19.6 % ) during exacerbations and 2,449 ( 80.4 % ) during stable disease . Among preexisting strains , sputum concentrations of Nontypeable Haemophilus influenzae and Haemophilus haemolyticus were not different in exacerbation versus stable disease . Moraxella catarrhalis ( stable , 10(8.38 + /- 0.13 ) [ mean + /- SEM ] vs. exacerbation , 10(7.78 + /- 0.26 ) ; p = 0.02 ) and Streptococcus pneumoniae ( stable , 10(8.42 + /- 0.21 ) vs. exacerbation , 10(7.76 + /- 0.52 ) ; p = 0.07 ) concentrations were lower during exacerbations compared with stable periods . Concentrations of new strains of H. influenzae ( stable , 10(7.28 + /- 0.15 ) vs. exacerbation , 10(7.76 + /- 0.17 ) ; p = 0.04 ) and M. catarrhalis ( stable , 10(7.85 + /- 0.15 ) vs. exacerbation , 10(8.37 + /- 0.14 ) ; p = 0.02 ) , were increased during exacerbations ; however , the differences were small . CONCLUSIONS Change in bacterial load is unlikely to be an important mechanism for exacerbations . Better underst and ing of the host-pathogen interaction , rather than enumerating bacteria in respiratory sample s , is required to provide new insights into bacterial infection in COPD BACKGROUND The role of bacterial pathogens in acute exacerbations of chronic obstructive pulmonary disease is controversial . In older studies , the rates of isolation of bacterial pathogens from sputum were the same during acute exacerbations and during stable disease . However , these studies did not differentiate among strains within a bacterial species and therefore could not detect changes in strains over time . We hypothesized that the acquisition of a new strain of a pathogenic bacterial species is associated with exacerbation of chronic obstructive pulmonary disease . 
    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: PURPOSE Viable bacteria are often isolated from airway secretions in clinical ly stable patients with chronic bronchitis . We hypothesized that the number of organisms and bacterial species might be important modulators of airway inflammation . SUBJECTS AND METHODS We performed quantitative sputum cultures in 160 stable patients [ 55 with chronic obstructive pulmonary disease ( COPD ) and normal serum alpha(1)-antitrypsin levels , 62 with COPD and severe alpha(1)-antitrypsin deficiency ( PiZ ) , and 43 with idiopathic bronchiectasis ] . The results were related to several indicators of the mechanisms and severity of airway inflammation . RESULTS Airway bacterial load correlated with sputum myeloperoxidase level , an indirect measure of neutrophil activation and number ( r = 0.50 , P<0 . 001 ) ; sputum neutrophil chemoattractants [ interleukin-8 level ( r = 0 . 68 , P<0.001 ) and leukotriene B4 level ( r = 0.53 , P<0.001 ) ] ; sputum leukocyte elastase activity ( r = 0.55 , P<0.001 ) ; and albumin leakage from serum to sputum ( r = 0.26 , P<0.01 ) . Markers of inflammation increased at bacterial loads of 10(6 ) to 10(7 ) colony-forming units per milliliter , and increased progressively with increasing bacterial load . For example , the median ( interquartile range ) sputum myeloperoxidase level was 0.3 U/mL ( 0.1 to 0.5 U/mL ) for patients who were not colonized or who had mixed normal oropharyngeal flora alone ; 0.5 U/mL ( 0.2 to 0.7 U/mL ) for patients with 10(5 ) to 10(6 ) colony-forming units per milliliter ( P = 0.07 ) ; 0.5 U/mL ( 0.3 to 1.2 U/mL ) for patients with 10(6 ) to 10(7 ) colony-forming units per milliliter ( P<0.01 ) ; 0.7 U/mL ( 0.3 to 1.2 U/mL ) for patients with 10(7 ) to 10(8 ) colony-forming units per milliliter ( P < 0.005 ) ; and 2.4 U/mL ( 0.7 to 4.8 U/mL ) for patients with 10(8 ) or greater colony-forming units per milliliter ( P<0.0001 ) . The bacterial species influenced airway inflammation ; for example , sputum myeloperoxidase activity was greater ( P<0.005 ) in patients colonized with Pseudomonas aeruginosa [ median 32 U/mL ( interquartile range , 20 to 65 U/mL ) ] than those colonized with nontypeable Hemophilus influenzae [ 4 U/mL ( 2 to 31 U/mL ) ] , which in turn was greater ( P = 0.01 ) than among those colonized with Moraxella catarrhalis [ 1.1 U/mL ( 0.6 to 1.8 U/mL ) ] . We did not find a relation between bacterial load and lung function . CONCLUSIONS The bacterial load and species contribute to airway inflammation in patients with stable chronic bronchitis . Further studies are required to determine the consequences of bacterial colonization on patient morbidity and decline in lung function 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 Chronic obstructive pulmonary disease ( COPD ) patients experiencing frequent exacerbations demonstrate increased stable-state airway inflammation . Tiotropium has been shown to reduce exacerbation frequency , but its effect on airway inflammation is unknown . The aim of the present study was to investigate the effect of tiotropium on sputum inflammatory markers and exacerbation frequency .  Patients ( n = 142 ) were r and omised to receive tiotropium or placebo in addition to their usual medication for 1 yr . Sputum and serum cytokines were assayed by ELISA and exacerbation frequency calculated using a symptom-based diary . There was no difference in the area under the curve for sputum interleukin (IL)-6 or myeloperoxidase between the groups , but sputum IL-8 level was increased in the tiotropium arm . There was no difference between start and end of study in serum IL-6 or C-reactive protein level .  Tiotropium was associated with a 52 % reduction in exacerbation frequency ( 1.17 versus 2.46 exacerbations·yr−1 ) . Of patients on tiotropium , 43 % experienced at least one exacerbation , compared with 64 % on placebo  . The total number of exacerbation days was reduced compared with placebo ( 17.3 versus 34.5 days ) . Tiotropium  reduces exacerbation frequency in chronic obstructive pulmonary disease , but this effect does not appear to be due to a reduction in airway or systemic inflammation In order to describe the outcomes of patients hospitalized with an acute exacerbation of severe chronic obstructive pulmonary disease ( COPD ) and determine the relationship between patient characteristics and length of survival , we studied a prospect i ve cohort of 1,016 adult patients from five hospitals who were admitted with an exacerbation of COPD and a PaCO2 of 50 mm Hg or more . Patient characteristics and acute physiology were determined . Outcomes were evaluated over a 6 mo period . Although only 11 % of the patients died during the index hospital stay , the 60-d , 180-d , 1-yr , and 2-yr mortality was high ( 20 % , 33 % , 43 % , and 49 % , respectively ) . The median cost of the index hospital stay was $ 7,100 ( $ 4,100 to $ 16,000 ; interquartile range ) . The median length of the index hospital stay was 9 d ( 5 to 15 d ) . After discharge , 446 patients were readmitted 754 times in the next 6 mo . At 6 mo , only 26 % of the cohort were both alive and able to report a good , very good , or excellent quality of life . Survival time was independently related to severity of illness , body mass index ( BMI ) , age , prior functional status , PaO2/FI(O2 ) , congestive heart failure , serum albumin , and the presence of cor pulmonale . Patients and caregivers should be aware of the likelihood of poor outcomes following hospitalization for exacerbation of COPD associated with hypercarbia BACKGROUND AND OBJECTIVE To evaluate whether changes in regular physical activity ( PA ) in patients with chronic obstructive pulmonary disease ( COPD ) affect the rate of hospitalizations for COPD exacerbation ( e COPD ) . METHODS Five hundred forty-three ambulatory clinic patients being treated for COPD were prospect ively identified . PA was self-reported by patients , and the level was established by the distance they walked ( km/day ) at least 3 days per week . Hospitalizations were recorded from hospital data bases . All patients with at least a 2-year follow-up after enrollment were included in the analysis . The response variable was the number of hospitalizations for e COPD within the 3-year period from 2 to 5 years after study enrollment . RESULTS Three hundred ninety-one survivors were studied . Mean forced expiratory volume in 1 s was 52 % ( ±14 % ) of the predicted value . Patients who maintained a lower level of PA had an increased rate of hospitalization ( odds ratio 1.901 ; 95 % confidence interval 1.090 - 3.317 ) . After having had the highest level of PA , those patients who decreased their PA in the follow-up showed an increasing rate of hospitalizations ( odds ratio 2.134 ; 95 % confidence interval 1.146 - 3.977 ) . CONCLUSIONS Patients with COPD with a low level of PA or who reduced their PA over time were more likely to experience a significant increase in the rate of hospitalization for e COPD . Changes to a higher level of PA or maintaining a moderate or high level of PA over time , with a low intensity activity such as walking for at least 3 - 6 km/day , could reduce the rate of hospitalizations for e COPD RATIONALE Increased bacterial concentration ( load ) in the lower airways and new bacterial strain acquisition have been posited as mechanisms for chronic obstructive pulmonary disease ( COPD ) exacerbations .  Bacterial concentrations are higher during exacerbation than during stable disease ; however , these studies are cross sectional and devoid of strain typing . OBJECTIVES To determine if the increased bacterial concentrations function as a separate mechanism for exacerbation induction independent of new strain acquisition . METHODS In a prospect i ve , longitudinal cohort of patients with COPD , the relationship between exacerbation occurrence , sputum bacterial concentrations , and new strain acquisition was examined . MEASUREMENTS AND MAIN RESULTS Clinical information , quantitative sputum cultures , and molecular typing of potential bacterial pathogen isolates . Over 81 months , 104 subjects completed 3,009 clinic visits , 560 ( 19.6 % ) during exacerbations and 2,449 ( 80.4 % ) during stable disease . Among preexisting strains , sputum concentrations of Nontypeable Haemophilus influenzae and Haemophilus haemolyticus were not different in exacerbation versus stable disease . Moraxella catarrhalis ( stable , 10(8.38 + /- 0.13 ) [ mean + /- SEM ] vs. exacerbation , 10(7.78 + /- 0.26 ) ; p = 0.02 ) and Streptococcus pneumoniae ( stable , 10(8.42 + /- 0.21 ) vs. exacerbation , 10(7.76 + /- 0.52 ) ; p = 0.07 ) concentrations were lower during exacerbations compared with stable periods . Concentrations of new strains of H. influenzae ( stable , 10(7.28 + /- 0.15 ) vs. exacerbation , 10(7.76 + /- 0.17 ) ; p = 0.04 ) and M. catarrhalis ( stable , 10(7.85 + /- 0.15 ) vs. exacerbation , 10(8.37 + /- 0.14 ) ; p = 0.02 ) , were increased during exacerbations ; however , the differences were small . CONCLUSIONS Change in bacterial load is unlikely to be an important mechanism for exacerbations . Better underst and ing of the host-pathogen interaction , rather than enumerating bacteria in respiratory sample s , is required to provide new insights into bacterial infection in COPD BACKGROUND The role of bacterial pathogens in acute exacerbations of chronic obstructive pulmonary disease is controversial . In older studies , the rates of isolation of bacterial pathogens from sputum were the same during acute exacerbations and during stable disease . However , these studies did not differentiate among strains within a bacterial species and therefore could not detect changes in strains over time . We hypothesized that the acquisition of a new strain of a pathogenic bacterial species is associated with exacerbation of chronic obstructive pulmonary disease . 
    Output:
    