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 Many patients with asthma have uncontrolled disease despite treatment with inhaled glucocorticoids . One potential cause of the variability in response to treatment is heterogeneity in the role of interleukin-13 expression in the clinical asthma phenotype . We hypothesized that anti-interleukin-13 therapy would benefit patients with asthma who had a pretreatment profile consistent with interleukin-13 activity . METHODS We conducted a r and omized , double-blind , placebo-controlled study of lebrikizumab , a monoclonal antibody to interleukin-13 , in 219 adults who had asthma that was inadequately controlled despite inhaled glucocorticoid therapy .  The primary efficacy outcome was the relative change in prebronchodilator forced expiratory volume in 1 second ( FEV(1 ) ) from baseline to week 12 . Among the secondary outcomes was the rate of asthma exacerbations through 24 weeks . Patient subgroups were prespecified according to baseline type 2 helper T-cell ( Th2 ) status ( assessed on the basis of total IgE level and blood eosinophil count ) and serum periostin level . RESULTS At baseline , patients had a mean FEV(1 )  that was 65 % of the predicted value and were taking a mean dose of inhaled glucocorticoids of 580 μg per day ; 80 % were also taking a long-acting beta-agonist . At week 12 , the mean increase in FEV(1 ) was 5.5 percentage points higher in the lebrikizumab group than in the placebo group ( P = 0.02 ) . Among patients in the high-periostin subgroup , the increase from baseline FEV(1 ) was 8.2 percentage points higher in the lebrikizumab group than in the placebo group ( P = 0.03 ) . Among patients in the low-periostin subgroup , the increase from baseline FEV(1 ) was 1.6 percentage points higher in the lebrikizumab group than in the placebo group ( P = 0.61 ) . Musculoskeletal side effects were more common with lebrikizumab than with placebo ( 13.2 % vs. 5.4 % , P = 0.045 ) . CONCLUSIONS Lebrikizumab treatment was associated with improved lung function . Patients with high pretreatment levels of serum periostin had greater improvement in lung function with lebrikizumab than did patients with low periostin levels . ( Funded by Genentech ; Clinical Trials.gov number , NCT00930163 . ) In athletes , exercise‐induced respiratory symptoms are common and their assessment is time and re source consuming . Objectives To quantify the diagnostic accuracy of selected inflammatory markers in addition to symptoms and signs for predicting pneumonia and to derive a diagnostic tool . Design Diagnostic study performed between 2007 and 2010 . Participants had their history taken , underwent  physical examination and measurement of C reactive protein ( CRP ) and procalcitonin in venous blood  on the day they first consulted , and underwent chest radiography within seven days . Setting Primary care centres in 12 European countries . Participants Adults presenting with acute cough . Main outcome measures Pneumonia as determined by radiologists , who were blind to all other information when they judged chest radiographs . Results Of 3106 eligible patients , 286 were excluded because of missing or inadequate chest radiographs , leaving 2820 patients ( mean age 50 , 40 % men ) of whom 140 ( 5 % ) had pneumonia . Re- assessment of a subset of 1675 chest radiographs showed agreement in 94 % ( κ 0.45 , 95 % confidence interval 0.36 to 0.54 ) . Six published “ symptoms and signs models ” varied in their discrimination ( area under receiver operating characteristics curve ( ROC ) ranged from 0.55 ( 95 % confidence interval 0.50 to 0.61 ) to 0.71 ( 0.66 to 0.76 ) ) . The optimal combination of clinical prediction items derived from our patients included absence of runny nose and presence of breathlessness , crackles and diminished breath sounds on auscultation , tachycardia , and fever , with an ROC area of 0.70 ( 0.65 to 0.75 ) . Addition of CRP at the optimal cut off of > 30 mg/L increased the ROC area to 0.77 ( 0.73 to 0.81 ) and improved the diagnostic classification ( net reclassification improvement 28 % ) . In the 1556 patients classified according to symptoms , signs , and CRP > 30 mg/L as “ low risk ” ( < 2.5 % ) for pneumonia , the prevalence of pneumonia was 2 % . In the 132 patients classified as “ high risk ” ( > 20 % ) , the prevalence of pneumonia was 31 % . The positive likelihood ratio of low , intermediate , and high risk for pneumonia was 0.4 , 1.2 , and 8.6 respectively . Measurement of procalcitonin added no relevant additional diagnostic information . A simplified diagnostic score based on symptoms , signs , and CRP > 30 mg/L result ed in proportions of pneumonia of 0.7 % , 3.8 % , and 18.2 % in the low , intermediate , and high risk group respectively . Conclusions A clinical rule based on symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough performed best in patients with mild or severe clinical presentation . Addition of CRP concentration at the optimal cut off of > 30 mg/L improved diagnostic information , but measurement of procalcitonin  concentration did not add clinical ly relevant information in this group BACKGROUND Asthma diagnosis is based on the presence of symptoms and the demonstration of airflow variability . Airway inflammation measured by fractional exhaled nitric oxide , measured at a flow rate of 50 ml/s ( FE(NO50 ) ) remains a controversial diagnostic tool . AIM To assess the ability of FE(NO50 ) to identify bronchial hyperresponsiveness ( BHR ) to methacholine ( provocative concentration of methacholine causing a 20 % fall in FEV(1 ) ; PC20 M ≤ 16 mg/ml ) and to establish whether or not symptoms relate to FE(NO50 ) and PC20 M in patients with no demonstrated reversibility to β(2 ) -agonist . METHODS We conducted a prospect i ve study on 174 steroid naive patients with respiratory symptoms , forced expiratory volume in 1 s ( FEV(1 ) ) ≥ 70 % predicted and no demonstrated reversibility to β(2 ) -agonist . Patients answered to a st and ardised symptom question naire and underwent FE(NO50 ) and methacholine challenge . Receiver-operating characteristic ( ROC ) curve and logistic regression analysis assessed the relationship between PC20 M and FE(NO50 ) , taking into account covariates ( smoking , atopy , age , gender and FEV(1 ) ) . RESULTS A total of 82 patients had a PC20 M ≤ 16 mg/ml and had significantly higher FE(NO50 ) ( 19 ppb vs. 15 ppb ; p < 0.05 ) . By constructing ROC curve , we found that FE(NO50 ) cut-off value of 34 ppb was able to identify not only BHR with high specificity ( 95 % ) and positive predictive value ( 88 % ) but low sensitivity ( 35 % ) and negative predictive value ( 62 % ) . When combining all variables into the logistic model , FE(NO50 ) ( p = 0.0011 ) and FEV(1 ) ( p < 0.0001 ) were independent predictors of BHR whereas age , gender , smoking and atopy had no influence . The presence of diurnal and nocturnal wheezing was associated with raised FE(NO50 ) ( p < 0.001 and p < 0.05 , respectively ) . CONCLUSION The value of FE(NO50 ) > 34 ppb has high predictive value of PC20 M < 16 in patients with suspected asthma in whom bronchodilating test failed to demonstrate reversibility or was not indicated . However , FE(NO50 ) ≤ 34 ppb does not rule out BHR and should prompt the clinician to ask for a methacholine challenge INTRODUCTION Exercise-induced bronchoconstriction ( EIB ) is present in 40 to 90 % of patients with asthma .  Exhaled NO ( eNO ) levels have been correlated with bronchial hyperresponsiveness to methacholine , and have correlated with the degree of decrease in FEV(1 ) with exercise . The purpose of our study was to examine whether eNO measurements prior to or after exercise could be used as a surrogate marker of exertional bronchoconstriction in a population referred specifically for the evaluation of EIB . METHODS We studied 50 consecutive subjects without a history of asthma who were referred for the clinical evaluation of EIB .  eNO levels were measured prior to exercise challenge and every 5 min for a total of 30 min after exercise . Forced expiratory flows were measured prior to and serially after exercise challenge . RESULTS Seven subjects had a decrease in FEV(1 ) of > or = 15 % with exercise . The mean eNO level prior to exercise was 41 parts per billion ( ppb ) [ median + /- SD , 23 + /- 42.2 ppb ] in the EIB group and 25.6 ppb ( median , 19.95 + /- 18.47 ppb ) in the group without EIB . A receiver operator characteristic curve yielded a value of 0.636 . When using an eNO level of < 12 ppb , the sensitivity , specificity , negative predictive value , and positive predictive value for EIB were 1.0 , 0.31 , 0.19 , and 1.0 , respectively ; therefore , no one with a baseline eNO of < 12 ppb demonstrated EIB . CONCLUSIONS No subjects with very low pre-exercise eNO levels ( < 12 ppb ) demonstrated bronchial hyperresponsiveness to exercise . eNO measurement may obviate the need for bronchoprovocation testing in patients who complain of exertional dyspnea BACKGROUND Whole-body plethysmography ( WBP ) with bronchial challenge testing to measure the ( specific ) airway resistance , (s)R(AW ) , is considered to be a more sensitive diagnostic procedure than spirometry , which can only measure the forced expiratory volume in one second ( FEV1 ) . The evidence for the added diagnostic value of WBP is not yet conclusive . METHODS In a prospect i ve diagnostic study , we carried out WBP with bronchial challenge testing as well as a bronchodilation test in 400 patients with suspected asthma from June 2010 to October 2011 . The bronchial provocation test was considered positive if the FEV1 fell by at least 20 % and /or the airway resistance doubled , with an increase of the sR(AW ) to at least 2.0 kPA × s and /or of the R(AW ) to 0.5 kPA × s/L. Follow-up evaluation was performed one year later . RESULTS The prevalence of asthma in the 302 patients who completed follow-up was 27.5 % .  The sensitivity of WBP with sR(AW ) measurement for asthma was 95.2 % ( 95 % confidence interval [ CI ] 88.3%-98.1 % ) , and its specificity was 81.7 % ( 95 % CI 76.1%-86.3 % ) . The sensitivity of FEV1 was 44.6 % ( 95 % CI 34.4%-55.3 % ) , and its specificity was 91.3 % ( 95 % CI 86.6%-94.4 % ) . The negative predictive value ( NPV ) of WBP with sR(AW ) measurement was 97.8 % ( 95 % CI 94.5%-99.1 % ) , while that of FEV1 was 81.3 % ( 95 % CI 76.0%-85.7 % ) . The positive predictive value ( PPV ) of WBP with sR(AW ) measurement was 66.4 % ( 95 % CI 57.5%-74.2 % ) , while that of FEV1 was 66.1 % ( 95 % CI 53.0%-77.1 % ) . CONCLUSION With sR(AW ) measurement , asthma can be ruled out with high certainty . Improving the positive predictive value of testing for asthma remains a challenge , however , as sR(AW ) measurement does not yield any increase in specificity BACKGROUND The fraction of exhaled NO ( FeNO ) is valuable for the follow-up of asthmatic patients . However , its usefulness as a screening tool for asthma is not established . METHODS We screened a population of 961 university students with a modified European Community Respiratory Health Survey question naire that has been previously used for the screening of respiratory symptoms related to asthma . All subjects with a positive answer to at least one question ( n = 149 ) were su bmi tted to FeNO measurement with a portable nitric oxide analyzer . Subsequently , they were su bmi tted to spirometry and evaluated by a physician blinded to FeNO measurements . Seventy students with no respiratory symptoms served as control subjects . RESULTS Asthma was diagnosed in 63 subjects , and allergic rhinitis was diagnosed in 57 subjects . Asthmatics presented higher Fe 
    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 Many patients with asthma have uncontrolled disease despite treatment with inhaled glucocorticoids . One potential cause of the variability in response to treatment is heterogeneity in the role of interleukin-13 expression in the clinical asthma phenotype . We hypothesized that anti-interleukin-13 therapy would benefit patients with asthma who had a pretreatment profile consistent with interleukin-13 activity . METHODS We conducted a r and omized , double-blind , placebo-controlled study of lebrikizumab , a monoclonal antibody to interleukin-13 , in 219 adults who had asthma that was inadequately controlled despite inhaled glucocorticoid therapy .  The primary efficacy outcome was the relative change in prebronchodilator forced expiratory volume in 1 second ( FEV(1 ) ) from baseline to week 12 . Among the secondary outcomes was the rate of asthma exacerbations through 24 weeks . Patient subgroups were prespecified according to baseline type 2 helper T-cell ( Th2 ) status ( assessed on the basis of total IgE level and blood eosinophil count ) and serum periostin level . RESULTS At baseline , patients had a mean FEV(1 )  that was 65 % of the predicted value and were taking a mean dose of inhaled glucocorticoids of 580 μg per day ; 80 % were also taking a long-acting beta-agonist . At week 12 , the mean increase in FEV(1 ) was 5.5 percentage points higher in the lebrikizumab group than in the placebo group ( P = 0.02 ) . Among patients in the high-periostin subgroup , the increase from baseline FEV(1 ) was 8.2 percentage points higher in the lebrikizumab group than in the placebo group ( P = 0.03 ) . Among patients in the low-periostin subgroup , the increase from baseline FEV(1 ) was 1.6 percentage points higher in the lebrikizumab group than in the placebo group ( P = 0.61 ) . Musculoskeletal side effects were more common with lebrikizumab than with placebo ( 13.2 % vs. 5.4 % , P = 0.045 ) . CONCLUSIONS Lebrikizumab treatment was associated with improved lung function . Patients with high pretreatment levels of serum periostin had greater improvement in lung function with lebrikizumab than did patients with low periostin levels . ( Funded by Genentech ; Clinical Trials.gov number , NCT00930163 . ) In athletes , exercise‐induced respiratory symptoms are common and their assessment is time and re source consuming . Objectives To quantify the diagnostic accuracy of selected inflammatory markers in addition to symptoms and signs for predicting pneumonia and to derive a diagnostic tool . Design Diagnostic study performed between 2007 and 2010 . Participants had their history taken , underwent  physical examination and measurement of C reactive protein ( CRP ) and procalcitonin in venous blood  on the day they first consulted , and underwent chest radiography within seven days . Setting Primary care centres in 12 European countries . Participants Adults presenting with acute cough . Main outcome measures Pneumonia as determined by radiologists , who were blind to all other information when they judged chest radiographs . Results Of 3106 eligible patients , 286 were excluded because of missing or inadequate chest radiographs , leaving 2820 patients ( mean age 50 , 40 % men ) of whom 140 ( 5 % ) had pneumonia . Re- assessment of a subset of 1675 chest radiographs showed agreement in 94 % ( κ 0.45 , 95 % confidence interval 0.36 to 0.54 ) . Six published “ symptoms and signs models ” varied in their discrimination ( area under receiver operating characteristics curve ( ROC ) ranged from 0.55 ( 95 % confidence interval 0.50 to 0.61 ) to 0.71 ( 0.66 to 0.76 ) ) . The optimal combination of clinical prediction items derived from our patients included absence of runny nose and presence of breathlessness , crackles and diminished breath sounds on auscultation , tachycardia , and fever , with an ROC area of 0.70 ( 0.65 to 0.75 ) . Addition of CRP at the optimal cut off of > 30 mg/L increased the ROC area to 0.77 ( 0.73 to 0.81 ) and improved the diagnostic classification ( net reclassification improvement 28 % ) . In the 1556 patients classified according to symptoms , signs , and CRP > 30 mg/L as “ low risk ” ( < 2.5 % ) for pneumonia , the prevalence of pneumonia was 2 % . In the 132 patients classified as “ high risk ” ( > 20 % ) , the prevalence of pneumonia was 31 % . The positive likelihood ratio of low , intermediate , and high risk for pneumonia was 0.4 , 1.2 , and 8.6 respectively . Measurement of procalcitonin added no relevant additional diagnostic information . A simplified diagnostic score based on symptoms , signs , and CRP > 30 mg/L result ed in proportions of pneumonia of 0.7 % , 3.8 % , and 18.2 % in the low , intermediate , and high risk group respectively . Conclusions A clinical rule based on symptoms and signs to predict pneumonia in patients presenting to primary care with acute cough performed best in patients with mild or severe clinical presentation . Addition of CRP concentration at the optimal cut off of > 30 mg/L improved diagnostic information , but measurement of procalcitonin  concentration did not add clinical ly relevant information in this group BACKGROUND Asthma diagnosis is based on the presence of symptoms and the demonstration of airflow variability . Airway inflammation measured by fractional exhaled nitric oxide , measured at a flow rate of 50 ml/s ( FE(NO50 ) ) remains a controversial diagnostic tool . AIM To assess the ability of FE(NO50 ) to identify bronchial hyperresponsiveness ( BHR ) to methacholine ( provocative concentration of methacholine causing a 20 % fall in FEV(1 ) ; PC20 M ≤ 16 mg/ml ) and to establish whether or not symptoms relate to FE(NO50 ) and PC20 M in patients with no demonstrated reversibility to β(2 ) -agonist . METHODS We conducted a prospect i ve study on 174 steroid naive patients with respiratory symptoms , forced expiratory volume in 1 s ( FEV(1 ) ) ≥ 70 % predicted and no demonstrated reversibility to β(2 ) -agonist . Patients answered to a st and ardised symptom question naire and underwent FE(NO50 ) and methacholine challenge . Receiver-operating characteristic ( ROC ) curve and logistic regression analysis assessed the relationship between PC20 M and FE(NO50 ) , taking into account covariates ( smoking , atopy , age , gender and FEV(1 ) ) . RESULTS A total of 82 patients had a PC20 M ≤ 16 mg/ml and had significantly higher FE(NO50 ) ( 19 ppb vs. 15 ppb ; p < 0.05 ) . By constructing ROC curve , we found that FE(NO50 ) cut-off value of 34 ppb was able to identify not only BHR with high specificity ( 95 % ) and positive predictive value ( 88 % ) but low sensitivity ( 35 % ) and negative predictive value ( 62 % ) . When combining all variables into the logistic model , FE(NO50 ) ( p = 0.0011 ) and FEV(1 ) ( p < 0.0001 ) were independent predictors of BHR whereas age , gender , smoking and atopy had no influence . The presence of diurnal and nocturnal wheezing was associated with raised FE(NO50 ) ( p < 0.001 and p < 0.05 , respectively ) . CONCLUSION The value of FE(NO50 ) > 34 ppb has high predictive value of PC20 M < 16 in patients with suspected asthma in whom bronchodilating test failed to demonstrate reversibility or was not indicated . However , FE(NO50 ) ≤ 34 ppb does not rule out BHR and should prompt the clinician to ask for a methacholine challenge INTRODUCTION Exercise-induced bronchoconstriction ( EIB ) is present in 40 to 90 % of patients with asthma .  Exhaled NO ( eNO ) levels have been correlated with bronchial hyperresponsiveness to methacholine , and have correlated with the degree of decrease in FEV(1 ) with exercise . The purpose of our study was to examine whether eNO measurements prior to or after exercise could be used as a surrogate marker of exertional bronchoconstriction in a population referred specifically for the evaluation of EIB . METHODS We studied 50 consecutive subjects without a history of asthma who were referred for the clinical evaluation of EIB .  eNO levels were measured prior to exercise challenge and every 5 min for a total of 30 min after exercise . Forced expiratory flows were measured prior to and serially after exercise challenge . RESULTS Seven subjects had a decrease in FEV(1 ) of > or = 15 % with exercise . The mean eNO level prior to exercise was 41 parts per billion ( ppb ) [ median + /- SD , 23 + /- 42.2 ppb ] in the EIB group and 25.6 ppb ( median , 19.95 + /- 18.47 ppb ) in the group without EIB . A receiver operator characteristic curve yielded a value of 0.636 . When using an eNO level of < 12 ppb , the sensitivity , specificity , negative predictive value , and positive predictive value for EIB were 1.0 , 0.31 , 0.19 , and 1.0 , respectively ; therefore , no one with a baseline eNO of < 12 ppb demonstrated EIB . CONCLUSIONS No subjects with very low pre-exercise eNO levels ( < 12 ppb ) demonstrated bronchial hyperresponsiveness to exercise . eNO measurement may obviate the need for bronchoprovocation testing in patients who complain of exertional dyspnea BACKGROUND Whole-body plethysmography ( WBP ) with bronchial challenge testing to measure the ( specific ) airway resistance , (s)R(AW ) , is considered to be a more sensitive diagnostic procedure than spirometry , which can only measure the forced expiratory volume in one second ( FEV1 ) . The evidence for the added diagnostic value of WBP is not yet conclusive . METHODS In a prospect i ve diagnostic study , we carried out WBP with bronchial challenge testing as well as a bronchodilation test in 400 patients with suspected asthma from June 2010 to October 2011 . The bronchial provocation test was considered positive if the FEV1 fell by at least 20 % and /or the airway resistance doubled , with an increase of the sR(AW ) to at least 2.0 kPA × s and /or of the R(AW ) to 0.5 kPA × s/L. Follow-up evaluation was performed one year later . RESULTS The prevalence of asthma in the 302 patients who completed follow-up was 27.5 % .  The sensitivity of WBP with sR(AW ) measurement for asthma was 95.2 % ( 95 % confidence interval [ CI ] 88.3%-98.1 % ) , and its specificity was 81.7 % ( 95 % CI 76.1%-86.3 % ) . The sensitivity of FEV1 was 44.6 % ( 95 % CI 34.4%-55.3 % ) , and its specificity was 91.3 % ( 95 % CI 86.6%-94.4 % ) . The negative predictive value ( NPV ) of WBP with sR(AW ) measurement was 97.8 % ( 95 % CI 94.5%-99.1 % ) , while that of FEV1 was 81.3 % ( 95 % CI 76.0%-85.7 % ) . The positive predictive value ( PPV ) of WBP with sR(AW ) measurement was 66.4 % ( 95 % CI 57.5%-74.2 % ) , while that of FEV1 was 66.1 % ( 95 % CI 53.0%-77.1 % ) . CONCLUSION With sR(AW ) measurement , asthma can be ruled out with high certainty . Improving the positive predictive value of testing for asthma remains a challenge , however , as sR(AW ) measurement does not yield any increase in specificity BACKGROUND The fraction of exhaled NO ( FeNO ) is valuable for the follow-up of asthmatic patients . However , its usefulness as a screening tool for asthma is not established . METHODS We screened a population of 961 university students with a modified European Community Respiratory Health Survey question naire that has been previously used for the screening of respiratory symptoms related to asthma . All subjects with a positive answer to at least one question ( n = 149 ) were su bmi tted to FeNO measurement with a portable nitric oxide analyzer . Subsequently , they were su bmi tted to spirometry and evaluated by a physician blinded to FeNO measurements . Seventy students with no respiratory symptoms served as control subjects . RESULTS Asthma was diagnosed in 63 subjects , and allergic rhinitis was diagnosed in 57 subjects . Asthmatics presented higher Fe 
    Output:
    