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: Exhaled nitric oxide ( NO ) may be derived from constitutive NO synthase ( NOS ) in normal airways , but the increased concentration in asthma is likely to be derived from inducible NOS expressed in inflamed airways . To investigate this , we administered a nonselective NOS inhibitor , NG-nitro-L-arginine methyl ester ( L-NAME ) , and a selective inhibitor of inducible NOS , aminoguanidine , by nebulization in a double-blind , placebo-controlled manner in both normal subjects and subjects with asthma .  L-NAME result ed in a significant reduction in exhaled NO compared with saline control in eight normal subjects ( maximum fall from baseline , 53 + /- 7.6 % versus 8.9 + /- 6.5 % ; P < 0.05 ) and in seven patients with asthma ( maximum fall , 67 + /- 7.4 % versus 10 + /- 7.4 % versus 10 + /- 9.3 % ; p < 0.05 ) . Aminoguanidine at the same molar concentration decreased exhaled NO in subjects with asthma ( maximum fall , 53 + /- 7.2 % versus 7.1 + /- 10.4 % ; p < 0.05 ) , but caused no significant change in normal volunteers ( maximum fall , 28 + /- 9.3 versus 15 + /- 11 ) . No rise in blood pressure , fall in FEV1 , or adverse effects were observed in either subject group . We have demonstrated that NOS inhibitors can safely be given by inhalation in a single does in normal subjects and subjects with asthma . The raised exhaled NO concentration in patients with asthma may be attributable to induction of NOS , with that in normal subjects reflecting basal constitutive NOS activity Airway inflammation is present in asthma and is thought to play a significant part in the development of airflow obstruction . In chronic obstructive pulmonary disease ( COPD ) , neutrophilic inflammation is present in the airway lumen , whereas the submucosa displays a lymphocytic infiltrate . Less is known about the nature and mechanisms of inflammation in COPD than in asthma . Induced sputum allows noninvasive sampling of respiratory tract secretions from patients and control subjects , allowing characterization of cells and measurement of soluble markers . We exploited this technique in order to compare the presence and quantify specific markers of eosinophil and neutrophil activation in subjects with asthma or COPD , and control subjects .  Differential cell counts showed significantly higher neutrophil percentages in the patients with COPD compared with other groups , while patients with asthma had higher numbers of eosinophils . The neutrophil markers myeloperoxidase ( MPO ) , from primary granules in neutrophils , and human neutrophil lipocalin ( HNL ) , released from secondary granules , were elevated in patients with asthma and COPD compared with control subjects but markedly more so in COPD . The difference between COPD and asthma was more marked for HNL than for MPO suggesting that HNL may be a better marker for discriminating between these conditions . Concentrations of the eosinophil granule protein , eosinophil cationic protein ( ECP ) , and the eosinophil granule-derived enzyme , eosinophil peroxidase ( EPO ) were raised in the patients with asthma and those with COPD Exhaled  nitric oxide ( ENO ) is used increasingly as a surrogate marker of airway inflammation in research protocol s that may incorporate st and ard efficacy measures , such as spirometry before and after bronchodilator , which could affect ENO measurements . In seven healthy volunteers and 11 mild asthmatic subjects , we measured ENO before and serially for 1 h after spirometry . On two additional days in the subjects with asthma , we reexamined the effect of spirometry as before , followed by the serial measurement of ENO for 1 h after two puffs of salbutamol ( 100 microgram/puff ) by metered-dose inhaler or matching placebo . As early as 1 min after spirometry , ENO fell by 13 % and 10 % in the normal and asthmatic subjects , respectively . In both groups , ENO returned to baseline over 1 h. In the asthmatic subjects , salbutamol caused a significant mean increase of the order of 10 parts per billion in ENO ( p < 0.001 ) for 1 h as compared with placebo inhaler . We conclude that spirometry and beta2-agonist may perturb ENO values and recommend that studies control for these factors Nitric  oxide ( NO ) can be measured in exhaled air with the single-breath ( SB ) and tidal-breathing ( TB ) methods . To allow comparison between different laboratories , a European Respiratory Society task force recently reported guidelines for st and ardization of both methods . To facilitate comparison between laboratories further , this study investigated whether there is a difference between NO values measured with SB and TB methods in subjects with asthma or chronic obstructive pulmonary disease ( COPD ) , and in healthy subjects . Moreover , the differences between groups were studied and the influence of smoking in asthma was assessed . Sixteen atopic nonsmoking asthmatics , 16 atopic currently smoking asthmatics , 16 nonatopic nonsmoking healthy controls , 16 nonatopic exsmokers with COPD and 16 nonatopic exsmoking healthy controls were studied . NO concentrations differed substantially between both methods . Mean NO concentrations were higher with the SB than with the TB method in nonsmoking and in smoking asthmatics and especially so with the higher NO values . Furthermore , NO values with both methods were higher in nonsmoking asthmatics than in nonsmoking healthy subjects . NO was not significantly different between exsmokers with COPD and healthy exsmokers . In conclusion nitric oxide values of the single-breath and tidal-breathing methods are not interchangeable . Both methods can be used to measure differences between groups Systemic hypotension during sepsis is thought to be due to nitric oxide ( NO ) overproduction , but it may also be due to acidosis . We evaluated in healthy rats the consequences of acid infusion on NO and blood pressure .  Sprague-Dawley rats were anesthetized , and ventilated with room air . The animals were r and omized into four groups . Group 1 ( C , n = 10 ) received only normal saline at rates comparable to the other groups . Group 2 ( A1 , n = 10 ) received hydrochloric acid at 0.162 mmol in the first 15 to 30 min , followed by a continuous infusion of 0.058 mmol/h for 5 h. Group 3 ( AG+A1 , n = 6 ) was pretreated with aminoguanidine ( AG , 50 mg/kg ) , and HCl was infused as above . Group 4 ( A2 , n = 7 ) received HCl at twice the rate used in A1 . Nitric oxide concentration in the exhaled gas ( ENO ) , blood gases , and mean arterial pressure were measured every 30 min . Acid infusion in A1 caused the pH to fall gradually from 7.43 + /- 0 . 01 to 7.13 + /- 0.05 . This moderate decrease in pH was associated with a marked increase in ENO ( 1.6 + /- 0.3 to 114.2 + /- 22.3 ppb ) , an increase in plasma nitrite/nitrate ( 17.3 + /- 3.7 to 35.2 + /- 4.3 microM ) , and a significant decrease in blood pressure ( 110.5 + /- 6.3 to 63.3 + /- 15.0 mm Hg ) . Furthermore , acidosis caused lung inflammation , as suggested by the increase in lung myeloperoxidase activity ( 282.2 + /- 24.7 to 679.3 + /- 57.3 U/min/g ) and lung injury score ( 1.7 + /- 0.2 to 3.5 + /- 0.6 ) . Acidosis after AG pretreatment was associated with a similar change in pH , but the increase in ENO , nitrite/nitrate , and systemic hypotension were prevented . Furthermore , lung injury was attenuated by AG , as suggested by a lower myeloperoxidase activity , though lung injury score was not altered . In this model , moderate acidosis causes increases in NO , hypotension , and lung inflammation . Lung inflammation and injury are due in part to acidosis and NO production . This is the first report to show a direct effect of chronic acidosis on NO production and lung injury . These results have profound implication s on the role of acidosis on NO production and lung injury during sepsis BACKGROUND The exhaled nitric oxide ( FeNO ) is a non-invasive marker of airway inflammation in asthma . A very recent statement has suggested FeNO as potential outcome in chronic obstructive pulmonary disease ( COPD ) . Recently , a new h and -held FeNO analyzer ( NIOX MINO ) has been developed . PATIENTS AND METHODS We have evaluated the NIOX MINO  in COPD patients and monitored FeNO levels during 1-year assessment in the outpatient setting .  Short-term variability in FeNO was compared using a NIOX MINO and a stationary chemiluminescence analyzer ( NOA , Sensormedics ) in healthy volunteers and COPD patients on two consecutive months . Long-term FeNO variability was assessed on a cohort of 70 COPD out patients measuring FeNO for 1 year . The intra-individual FeNO coefficient of variation ( eNOCoV ) was taken as index FeNO long-term variability . RESULTS In COPD there were no significant differences between NIOX MINO and NOA FeNO values recorded at baseline and 1 month later . Ninety five percent limits of agreement between NIOX MINO and NOA were-2.7 and 1.9ppb with significant reliability ( r=0.96 , p<0.0001 ) . Mean FeNO at baseline was 15.0+/-9.5ppb . Over the 1-year period the overall mean FeNO was 15.5+/-10.1ppb . The long-term eNOCoV was 33.9+/-16.4 % ( range 8.1 - 83.1 % ) , and it was significantly associated with exacerbation rate ( r=0.57 , p<0.0001 ) . CONCLUSION FeNO electrochemical h and -held analyzer is feasible in COPD showing good agreement with stationary chemiluminescence analyzer . COPD patients exhibit a wide range of FeNO levels and a high variability of FeNO over time , which was positively associated with the number of exacerbations The aim of the study was to evaluate the exhaled nitric oxide ( F(ENO ) ) in clinical ly stable chronic obstructive pulmonary disease ( COPD ) , its relationship to the severity of the disease , pulmonary function , smoking status , reversibility of airflow limitation , and ICS therapy . The study was conducted in 47 patients with COPD and 40 healthy controls .  Flow/volume spirometry and F(ENO ) measurement were performed before and after 2 months of ICS therapy .  F(ENO ) were significantly elevated in current smokers and ex-smoking COPD patients . In both groups of COPD patients inhaled corticosteroids ( ICS ) therapy caused a significant decrease in F(ENO ) without significant changes in FEV1 . A positive correlation between initial F(ENO ) and postbronchodilator FEV1 ( % predicted ) was observed in the group of ex-smoking COPD patients , but not in the currently smoking COPD group . In both groups of COPD patients , the initial level of F(ENO ) correlated with the reversibility of airway obstruction , the increase in postbronchodilator FEV1 and the decrease in F(ENO ) following ICS treatment . F(ENO ) increases in patients with stable COPD . ICS therapy decreased elevated F(ENO ) levels in these patients without statistically significant changes in lung function . The selection of COPD patients with increased F(ENO ) level and partial reversibility of airway obstruction should be helpful in terms of proposed ICS treatment 
    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: Exhaled nitric oxide ( NO ) may be derived from constitutive NO synthase ( NOS ) in normal airways , but the increased concentration in asthma is likely to be derived from inducible NOS expressed in inflamed airways . To investigate this , we administered a nonselective NOS inhibitor , NG-nitro-L-arginine methyl ester ( L-NAME ) , and a selective inhibitor of inducible NOS , aminoguanidine , by nebulization in a double-blind , placebo-controlled manner in both normal subjects and subjects with asthma .  L-NAME result ed in a significant reduction in exhaled NO compared with saline control in eight normal subjects ( maximum fall from baseline , 53 + /- 7.6 % versus 8.9 + /- 6.5 % ; P < 0.05 ) and in seven patients with asthma ( maximum fall , 67 + /- 7.4 % versus 10 + /- 7.4 % versus 10 + /- 9.3 % ; p < 0.05 ) . Aminoguanidine at the same molar concentration decreased exhaled NO in subjects with asthma ( maximum fall , 53 + /- 7.2 % versus 7.1 + /- 10.4 % ; p < 0.05 ) , but caused no significant change in normal volunteers ( maximum fall , 28 + /- 9.3 versus 15 + /- 11 ) . No rise in blood pressure , fall in FEV1 , or adverse effects were observed in either subject group . We have demonstrated that NOS inhibitors can safely be given by inhalation in a single does in normal subjects and subjects with asthma . The raised exhaled NO concentration in patients with asthma may be attributable to induction of NOS , with that in normal subjects reflecting basal constitutive NOS activity Airway inflammation is present in asthma and is thought to play a significant part in the development of airflow obstruction . In chronic obstructive pulmonary disease ( COPD ) , neutrophilic inflammation is present in the airway lumen , whereas the submucosa displays a lymphocytic infiltrate . Less is known about the nature and mechanisms of inflammation in COPD than in asthma . Induced sputum allows noninvasive sampling of respiratory tract secretions from patients and control subjects , allowing characterization of cells and measurement of soluble markers . We exploited this technique in order to compare the presence and quantify specific markers of eosinophil and neutrophil activation in subjects with asthma or COPD , and control subjects .  Differential cell counts showed significantly higher neutrophil percentages in the patients with COPD compared with other groups , while patients with asthma had higher numbers of eosinophils . The neutrophil markers myeloperoxidase ( MPO ) , from primary granules in neutrophils , and human neutrophil lipocalin ( HNL ) , released from secondary granules , were elevated in patients with asthma and COPD compared with control subjects but markedly more so in COPD . The difference between COPD and asthma was more marked for HNL than for MPO suggesting that HNL may be a better marker for discriminating between these conditions . Concentrations of the eosinophil granule protein , eosinophil cationic protein ( ECP ) , and the eosinophil granule-derived enzyme , eosinophil peroxidase ( EPO ) were raised in the patients with asthma and those with COPD Exhaled  nitric oxide ( ENO ) is used increasingly as a surrogate marker of airway inflammation in research protocol s that may incorporate st and ard efficacy measures , such as spirometry before and after bronchodilator , which could affect ENO measurements . In seven healthy volunteers and 11 mild asthmatic subjects , we measured ENO before and serially for 1 h after spirometry . On two additional days in the subjects with asthma , we reexamined the effect of spirometry as before , followed by the serial measurement of ENO for 1 h after two puffs of salbutamol ( 100 microgram/puff ) by metered-dose inhaler or matching placebo . As early as 1 min after spirometry , ENO fell by 13 % and 10 % in the normal and asthmatic subjects , respectively . In both groups , ENO returned to baseline over 1 h. In the asthmatic subjects , salbutamol caused a significant mean increase of the order of 10 parts per billion in ENO ( p < 0.001 ) for 1 h as compared with placebo inhaler . We conclude that spirometry and beta2-agonist may perturb ENO values and recommend that studies control for these factors Nitric  oxide ( NO ) can be measured in exhaled air with the single-breath ( SB ) and tidal-breathing ( TB ) methods . To allow comparison between different laboratories , a European Respiratory Society task force recently reported guidelines for st and ardization of both methods . To facilitate comparison between laboratories further , this study investigated whether there is a difference between NO values measured with SB and TB methods in subjects with asthma or chronic obstructive pulmonary disease ( COPD ) , and in healthy subjects . Moreover , the differences between groups were studied and the influence of smoking in asthma was assessed . Sixteen atopic nonsmoking asthmatics , 16 atopic currently smoking asthmatics , 16 nonatopic nonsmoking healthy controls , 16 nonatopic exsmokers with COPD and 16 nonatopic exsmoking healthy controls were studied . NO concentrations differed substantially between both methods . Mean NO concentrations were higher with the SB than with the TB method in nonsmoking and in smoking asthmatics and especially so with the higher NO values . Furthermore , NO values with both methods were higher in nonsmoking asthmatics than in nonsmoking healthy subjects . NO was not significantly different between exsmokers with COPD and healthy exsmokers . In conclusion nitric oxide values of the single-breath and tidal-breathing methods are not interchangeable . Both methods can be used to measure differences between groups Systemic hypotension during sepsis is thought to be due to nitric oxide ( NO ) overproduction , but it may also be due to acidosis . We evaluated in healthy rats the consequences of acid infusion on NO and blood pressure .  Sprague-Dawley rats were anesthetized , and ventilated with room air . The animals were r and omized into four groups . Group 1 ( C , n = 10 ) received only normal saline at rates comparable to the other groups . Group 2 ( A1 , n = 10 ) received hydrochloric acid at 0.162 mmol in the first 15 to 30 min , followed by a continuous infusion of 0.058 mmol/h for 5 h. Group 3 ( AG+A1 , n = 6 ) was pretreated with aminoguanidine ( AG , 50 mg/kg ) , and HCl was infused as above . Group 4 ( A2 , n = 7 ) received HCl at twice the rate used in A1 . Nitric oxide concentration in the exhaled gas ( ENO ) , blood gases , and mean arterial pressure were measured every 30 min . Acid infusion in A1 caused the pH to fall gradually from 7.43 + /- 0 . 01 to 7.13 + /- 0.05 . This moderate decrease in pH was associated with a marked increase in ENO ( 1.6 + /- 0.3 to 114.2 + /- 22.3 ppb ) , an increase in plasma nitrite/nitrate ( 17.3 + /- 3.7 to 35.2 + /- 4.3 microM ) , and a significant decrease in blood pressure ( 110.5 + /- 6.3 to 63.3 + /- 15.0 mm Hg ) . Furthermore , acidosis caused lung inflammation , as suggested by the increase in lung myeloperoxidase activity ( 282.2 + /- 24.7 to 679.3 + /- 57.3 U/min/g ) and lung injury score ( 1.7 + /- 0.2 to 3.5 + /- 0.6 ) . Acidosis after AG pretreatment was associated with a similar change in pH , but the increase in ENO , nitrite/nitrate , and systemic hypotension were prevented . Furthermore , lung injury was attenuated by AG , as suggested by a lower myeloperoxidase activity , though lung injury score was not altered . In this model , moderate acidosis causes increases in NO , hypotension , and lung inflammation . Lung inflammation and injury are due in part to acidosis and NO production . This is the first report to show a direct effect of chronic acidosis on NO production and lung injury . These results have profound implication s on the role of acidosis on NO production and lung injury during sepsis BACKGROUND The exhaled nitric oxide ( FeNO ) is a non-invasive marker of airway inflammation in asthma . A very recent statement has suggested FeNO as potential outcome in chronic obstructive pulmonary disease ( COPD ) . Recently , a new h and -held FeNO analyzer ( NIOX MINO ) has been developed . PATIENTS AND METHODS We have evaluated the NIOX MINO  in COPD patients and monitored FeNO levels during 1-year assessment in the outpatient setting .  Short-term variability in FeNO was compared using a NIOX MINO and a stationary chemiluminescence analyzer ( NOA , Sensormedics ) in healthy volunteers and COPD patients on two consecutive months . Long-term FeNO variability was assessed on a cohort of 70 COPD out patients measuring FeNO for 1 year . The intra-individual FeNO coefficient of variation ( eNOCoV ) was taken as index FeNO long-term variability . RESULTS In COPD there were no significant differences between NIOX MINO and NOA FeNO values recorded at baseline and 1 month later . Ninety five percent limits of agreement between NIOX MINO and NOA were-2.7 and 1.9ppb with significant reliability ( r=0.96 , p<0.0001 ) . Mean FeNO at baseline was 15.0+/-9.5ppb . Over the 1-year period the overall mean FeNO was 15.5+/-10.1ppb . The long-term eNOCoV was 33.9+/-16.4 % ( range 8.1 - 83.1 % ) , and it was significantly associated with exacerbation rate ( r=0.57 , p<0.0001 ) . CONCLUSION FeNO electrochemical h and -held analyzer is feasible in COPD showing good agreement with stationary chemiluminescence analyzer . COPD patients exhibit a wide range of FeNO levels and a high variability of FeNO over time , which was positively associated with the number of exacerbations The aim of the study was to evaluate the exhaled nitric oxide ( F(ENO ) ) in clinical ly stable chronic obstructive pulmonary disease ( COPD ) , its relationship to the severity of the disease , pulmonary function , smoking status , reversibility of airflow limitation , and ICS therapy . The study was conducted in 47 patients with COPD and 40 healthy controls .  Flow/volume spirometry and F(ENO ) measurement were performed before and after 2 months of ICS therapy .  F(ENO ) were significantly elevated in current smokers and ex-smoking COPD patients . In both groups of COPD patients inhaled corticosteroids ( ICS ) therapy caused a significant decrease in F(ENO ) without significant changes in FEV1 . A positive correlation between initial F(ENO ) and postbronchodilator FEV1 ( % predicted ) was observed in the group of ex-smoking COPD patients , but not in the currently smoking COPD group . In both groups of COPD patients , the initial level of F(ENO ) correlated with the reversibility of airway obstruction , the increase in postbronchodilator FEV1 and the decrease in F(ENO ) following ICS treatment . F(ENO ) increases in patients with stable COPD . ICS therapy decreased elevated F(ENO ) levels in these patients without statistically significant changes in lung function . The selection of COPD patients with increased F(ENO ) level and partial reversibility of airway obstruction should be helpful in terms of proposed ICS treatment 
    Output:
    