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: A pilot study was performed to investigate a clinical algorithm using serum-eosinophil cationic protein level ( S-ECP ) as an objective parameter for tapering the anti-inflammatory treatment in chronic childhood asthma . We studied 21 outpatient asthmatic children ( 6 girls and 15 boys , mean age 9 yr , range 3 - 12 yr , all with initial S-ECP > or = 15 microg/l ) over a period of 12 months at monthly intervals . At each visit a short history , clinical examination , blood sample for S-ECP and eosinophil count , lung function tests and drug compliance were assessed . According to the initial S-ECP , patients were allocated to two anti-inflammatory treatment groups : patients with S-ECP between 15 microg/l and 30 microg/l were treated with Budesonide 200 microg twice daily , while patients with S-ECP of 30 microg/l and above received Budesonide 400 microg twice daily . After this induction treatment the anti-inflammatory medication was tapered at monthly intervals according to actually measured S-ECP : patients with S-ECP < 15 microg/l received sodium cromoglycate ( SCG ) 10 mg twice daily per inhalation via spacer , patients with S-ECP > or = 15 microg/l and < 30 microg/l received Budesonide 200 microg twice daily via spacer , and patients with S-ECP > or = 30 microg/l received Budesonide 400 microg twice daily . Prior to inhalation of topical steroids or SCG all patients had to inhale 500 microg Terbutaline twice daily for optimal bronchodilatation . The use of medication was assessed by weighing the metered dose inhaler containers each month . Our results showed a decrease in symptoms ( p = 0.0001 ) and in S-ECP ( p= 0.02 ) and MEF50 % predicted ( p= 0.02 ) after the initial month of Budesonide treatment . During a total of 246 months of investigation there was no need for emergency room treatment or hospital admission , and no need for oral steroids . During the whole study period there was a tendency for inhaled steroids to be more effective than SCG in reduction of markers of airway inflammation , improvement of symptoms and lung function . Inadequate use of medication was related to an increase in S-ECP in all treatment groups . From this open pilot study it is concluded that a clinical algorithm including S-ECP for tapering the anti-inflammatory treatment may be helpful in childhood asthma . These first observations should be confirmed by a controlled long-term study BACKGROUND The aim of the present study was to treat unstable asthma according to exhaled nitric oxide ( eNO ) and induced-sputum eosinophils ( sEos ) levels to assess if this strategy is better than the conventional approach based on symptoms and function to achieve asthma control . METHODS Fourteen patients with mild-to-moderate persistent asthma ( 6 men , 8 women ) were recruited . During the recruitment visit , the patients , previously treated for asthma following Global Initiative for Asthma recommendations , underwent clinical evaluation and pulmonary function tests ( PFTs ) . Then , after 4 weeks of washout from inhaled antiinflammatory treatment , the patients underwent a basal visit performing PFTs , challenge test to methacholine , and determination of eNO and sEos counts .  These procedures were repeated after 3 , 6 , and 12 months while the patients were treated with inhaled steroids in a stepwise fashion according to eNO and sEos values . RESULTS At the end of the study , a significant decrease in eNO and sEos was observed ( 57.2 + /- 32.8 parts per billion [ ppb ] vs 22.1 + /- 10.8 ppb , p < 0.01 ; and 27.1 + /- 27.1 % vs 3.7 + /- 3.5 % , p < 0.01 , respectively ) . A close correlation ( r2 = 0.41 , p < 0.01 ) between the percentage change of eNO and sEos was observed only after 6 months . Patients treated according to the levels of these inflammatory markers had fewer symptoms and fewer exacerbations compared to those the year before when they were conventionally treated . CONCLUSIONS Our results show the usefulness of eNO and sEos for titrating treatment in asthmatic patients in order to achieve better long-term control of the disease . The eNO decrease reflects adequately the reduction of sEos only after 6 months WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Much of the focus of inflammatory surrogates and airway challenges in asthma has been directed towards success of therapy and diagnosis . Few have considered them in the context of guiding dose reduction once sufficient control has been achieved . WHAT THIS STUDY ADDS Adenosine monophosphate ( AMP ) as an indirect bronchial airway challenge , together with non invasive inflammatory surrogate measures were not found to be clinical ly useful when guiding therapy in a group of asthmatic patients through step 3 - 4 in British Thoracic Society asthma guidelines . However , they may still play a role in predicting failure of individual step-down . AIM The aim of the study was to evaluate the usefulness of inflammatory surrogates in determining step-down therapy in asthma . METHODS AMP challenge , serum eosinophil cationic protein ( ECP ) , exhaled nitric oxide ( eNO ) and pulmonary function tests were recorded . Subjects were divided into two groups following high dose inhaled corticosteroids ( ICS ) : Group A fixed dose ICS vs. Group B ICS alone and in combination with add on therapies . RESULTS No differences were seen in inflammatory measures between fixed dose ICS and reduced dose ICS alone or with combination therapies . CONCLUSIONS AMP challenge conferred no additional benefit in guiding step-down therapy . The role of inflammatory surrogates may still play a role in predicting failed step-down on an individual basis Background Previous studies in adults with asthma incorporating the control of sputum eosinophils into management strategies have shown significant reductions in exacerbations . A study was undertaken to investigate whether this strategy would be successful in children with severe asthma . Methods 55 children ( 7–17 years ) with severe asthma were r and omised to either a conventional symptom-based management strategy or to an inflammation-based strategy ( principally sputum eosinophils ) . Children were seen 3-monthly over a 1-year period . Results The annual rate of total and major exacerbations ( courses of oral corticosteroids ) was non-significantly lower in the inflammatory management group compared with the symptom management group ( 3.6 vs 4.8 , incident rate ratio ( IRR ) 0.75 , 95 % CI 0.54 to 1.04 , p=0.082 ; and 1.9 vs 2.7 IRR 0.73 , 95 % CI 0.42 to 1.28 , p=0.274 for total and major exacerbations , respectively ) . Significantly fewer subjects in the inflammatory management group experienced an exacerbation within 28 days of a study visit . There were small non-significant differences in measures of asthma control ( symptom-free days and short-acting β agonist use ) favouring the inflammatory management group . There was no significant difference in the inhaled corticosteroid dose prescribed over the course of the study . Conclusion Incorporating the control of sputum eosinophils into the management algorithm did not significantly reduce overall exacerbations or improve asthma control . Exacerbations were reduced in the short term , suggesting that more frequent measurements would be needed for a clinical ly useful effect and that controlling inflammation may have a role to play in subgroups of children with severe asthma BACKGROUND Treatment decisions in asthma are based on assessment s of symptoms and simple measures of lung function , which do not relate closely to underlying eosinophilic airway inflammation . We aim ed to assess whether a management strategy that minimises eosinophilic inflammation reduces asthma exacerbations compared with a st and ard management strategy . METHODS We recruited 74 patients with moderate to severe asthma from hospital clinics and r and omly allocated them to management either by st and ard British Thoracic Society asthma guidelines ( BTS management group ) or by normalisation of the induced sputum eosinophil count and reduction of symptoms ( sputum management group ) . We assessed patients nine times over 12 months . The results were used to manage those in the sputum management group , but were not disclosed in the BTS group . The primary outcomes were the number of severe exacerbations and control of eosinophilic inflammation , measured by induced sputum eosinophil count . Analyses were by intention to treat . FINDINGS The sputum eosinophil count was 63 % ( 95 % CI 24 - 100 ) lower over 12 months in the sputum management group than in the BTS management group ( p=0.002 ) . Patients in the sputum management group had significantly fewer severe asthma exacerbations than did patients in the BTS management group ( 35 vs 109 ; p=0.01 ) and significantly fewer patients were admitted to hospital with asthma ( one vs six , p=0.047 ) . The average daily dose of inhaled or oral corticosteroids did not differ between the two groups . INTERPRETATION A treatment strategy directed at normalisation of the induced sputum eosinophil count reduces asthma exacerbations and admissions without the need for additional anti-inflammatory treatment One important goal of asthma treatment is to reduce exacerbations . The current authors investigated if the use of sputum cell counts to guide treatment would achieve this goal . A total of 117 adults with asthma were entered into a multicentre , r and omised , parallel group-effectiveness study for two treatment strategies over a 2-yr period . In one strategy ( the clinical strategy : CS ) treatment was based on symptoms and spirometry . In the other ( the sputum strategy : SS ) sputum cell counts were used to guide corticosteroid therapy to keep eosinophils ≤2 % ; symptoms and spirometry were used to identify clinical control , exacerbations and other treatments . Patients were blind to sputum cell counts in both strategies and physicians were blind in the CS , thus removing bias . First , the minimum treatment to maintain control was identified in 107 patients ( Phase 1 ) and then this treatment was continued ( Phase 2 ) for the remaining of the 2 yrs . The primary outcomes were the relative risk reduction for the occurrence of the first exacerbation in Phase 2 and the length of time without exacerbation . The current authors also examined the type and severity of exacerbations and the cumulative dose of inhaled steroid needed . The duration and number of exacerbations in Phase 1 were similar in both groups . In Phase 2 there were a 126 exacerbations of which 79 occurred in the CS ( 62.7 % ) and 47 ( 37.3 % ) in the SS groups . The majority of the 126 exacerbations ( 101 ; 80.1 % ) were mild . The majority of the 102 exacerbations , where sputum examination was performed before any treatment ( n = 70 ) , were noneosinophilic . In the SS patients , the time to the first exacerbation was longer ( by 213 days ) especially in those considered to need treatment with a long acting β2-agonist ( by 490 days ) , the relative risk ratio was lower ( by 49 % ) , and the number of exacerbations needing prednisone was reduced ( 5 versus 15 ) . This benefit was seen mainly in patients needing treatment with inhaled steroid in a daily dose equivalent to fluticasone > 250 μg , and was due to fewer eosinophilic exacerbations . The cumulative dose of corticosteroid during the trial was similar in both groups . Monitoring sputum cell counts was found to benefit patients with moderate-to-severe asthma by reducing the number of eosinophilic exacerbations and by reducing the severity of both eosinophilic and noneosinophilic exacerbations without increasing the total corticosteroid dose . It had no influence on the frequency of noneosinophilic exacerbations , which were the most common exacerbations Background : The debate as to whether asthma is a single or heterogeneous disease remains unresolved although pathological studies , mostly using fibreoptic bronchoscopy on small numbers of subjects , have emphasised the similarities between different clinical phenotypes . Methods : Lower airway inflammation was assessed non-invasively using induced sputum in 34 normal controls and 259 adults with symptomatic asthma receiving treatment at steps 1–3 of the British Thoracic Society ( BTS ) guidelines . A subgroup of 49 patients treated with as required β2 agonists only who met BTS criteria for a step up in treatment were studied before and 2 months after treatment with inhaled budesonide 400 μg twice daily . Results : There was considerable heterogeneity in induced sputum cell counts , particularly in non-atopic patients . A subgroup of 60 patients had a distinctive sputum cell profile with a neutrophil count higher than our normal range ( > 65.3 % ) and a normal sputum eosinophil count ( < 1.9 % ) . These patients were older , predominantly female , and were more likely to be non-atopic but otherwise had similar clinical and physiological features to the group as a whole . Among the 49 subjects studied 
    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: A pilot study was performed to investigate a clinical algorithm using serum-eosinophil cationic protein level ( S-ECP ) as an objective parameter for tapering the anti-inflammatory treatment in chronic childhood asthma . We studied 21 outpatient asthmatic children ( 6 girls and 15 boys , mean age 9 yr , range 3 - 12 yr , all with initial S-ECP > or = 15 microg/l ) over a period of 12 months at monthly intervals . At each visit a short history , clinical examination , blood sample for S-ECP and eosinophil count , lung function tests and drug compliance were assessed . According to the initial S-ECP , patients were allocated to two anti-inflammatory treatment groups : patients with S-ECP between 15 microg/l and 30 microg/l were treated with Budesonide 200 microg twice daily , while patients with S-ECP of 30 microg/l and above received Budesonide 400 microg twice daily . After this induction treatment the anti-inflammatory medication was tapered at monthly intervals according to actually measured S-ECP : patients with S-ECP < 15 microg/l received sodium cromoglycate ( SCG ) 10 mg twice daily per inhalation via spacer , patients with S-ECP > or = 15 microg/l and < 30 microg/l received Budesonide 200 microg twice daily via spacer , and patients with S-ECP > or = 30 microg/l received Budesonide 400 microg twice daily . Prior to inhalation of topical steroids or SCG all patients had to inhale 500 microg Terbutaline twice daily for optimal bronchodilatation . The use of medication was assessed by weighing the metered dose inhaler containers each month . Our results showed a decrease in symptoms ( p = 0.0001 ) and in S-ECP ( p= 0.02 ) and MEF50 % predicted ( p= 0.02 ) after the initial month of Budesonide treatment . During a total of 246 months of investigation there was no need for emergency room treatment or hospital admission , and no need for oral steroids . During the whole study period there was a tendency for inhaled steroids to be more effective than SCG in reduction of markers of airway inflammation , improvement of symptoms and lung function . Inadequate use of medication was related to an increase in S-ECP in all treatment groups . From this open pilot study it is concluded that a clinical algorithm including S-ECP for tapering the anti-inflammatory treatment may be helpful in childhood asthma . These first observations should be confirmed by a controlled long-term study BACKGROUND The aim of the present study was to treat unstable asthma according to exhaled nitric oxide ( eNO ) and induced-sputum eosinophils ( sEos ) levels to assess if this strategy is better than the conventional approach based on symptoms and function to achieve asthma control . METHODS Fourteen patients with mild-to-moderate persistent asthma ( 6 men , 8 women ) were recruited . During the recruitment visit , the patients , previously treated for asthma following Global Initiative for Asthma recommendations , underwent clinical evaluation and pulmonary function tests ( PFTs ) . Then , after 4 weeks of washout from inhaled antiinflammatory treatment , the patients underwent a basal visit performing PFTs , challenge test to methacholine , and determination of eNO and sEos counts .  These procedures were repeated after 3 , 6 , and 12 months while the patients were treated with inhaled steroids in a stepwise fashion according to eNO and sEos values . RESULTS At the end of the study , a significant decrease in eNO and sEos was observed ( 57.2 + /- 32.8 parts per billion [ ppb ] vs 22.1 + /- 10.8 ppb , p < 0.01 ; and 27.1 + /- 27.1 % vs 3.7 + /- 3.5 % , p < 0.01 , respectively ) . A close correlation ( r2 = 0.41 , p < 0.01 ) between the percentage change of eNO and sEos was observed only after 6 months . Patients treated according to the levels of these inflammatory markers had fewer symptoms and fewer exacerbations compared to those the year before when they were conventionally treated . CONCLUSIONS Our results show the usefulness of eNO and sEos for titrating treatment in asthmatic patients in order to achieve better long-term control of the disease . The eNO decrease reflects adequately the reduction of sEos only after 6 months WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Much of the focus of inflammatory surrogates and airway challenges in asthma has been directed towards success of therapy and diagnosis . Few have considered them in the context of guiding dose reduction once sufficient control has been achieved . WHAT THIS STUDY ADDS Adenosine monophosphate ( AMP ) as an indirect bronchial airway challenge , together with non invasive inflammatory surrogate measures were not found to be clinical ly useful when guiding therapy in a group of asthmatic patients through step 3 - 4 in British Thoracic Society asthma guidelines . However , they may still play a role in predicting failure of individual step-down . AIM The aim of the study was to evaluate the usefulness of inflammatory surrogates in determining step-down therapy in asthma . METHODS AMP challenge , serum eosinophil cationic protein ( ECP ) , exhaled nitric oxide ( eNO ) and pulmonary function tests were recorded . Subjects were divided into two groups following high dose inhaled corticosteroids ( ICS ) : Group A fixed dose ICS vs. Group B ICS alone and in combination with add on therapies . RESULTS No differences were seen in inflammatory measures between fixed dose ICS and reduced dose ICS alone or with combination therapies . CONCLUSIONS AMP challenge conferred no additional benefit in guiding step-down therapy . The role of inflammatory surrogates may still play a role in predicting failed step-down on an individual basis Background Previous studies in adults with asthma incorporating the control of sputum eosinophils into management strategies have shown significant reductions in exacerbations . A study was undertaken to investigate whether this strategy would be successful in children with severe asthma . Methods 55 children ( 7–17 years ) with severe asthma were r and omised to either a conventional symptom-based management strategy or to an inflammation-based strategy ( principally sputum eosinophils ) . Children were seen 3-monthly over a 1-year period . Results The annual rate of total and major exacerbations ( courses of oral corticosteroids ) was non-significantly lower in the inflammatory management group compared with the symptom management group ( 3.6 vs 4.8 , incident rate ratio ( IRR ) 0.75 , 95 % CI 0.54 to 1.04 , p=0.082 ; and 1.9 vs 2.7 IRR 0.73 , 95 % CI 0.42 to 1.28 , p=0.274 for total and major exacerbations , respectively ) . Significantly fewer subjects in the inflammatory management group experienced an exacerbation within 28 days of a study visit . There were small non-significant differences in measures of asthma control ( symptom-free days and short-acting β agonist use ) favouring the inflammatory management group . There was no significant difference in the inhaled corticosteroid dose prescribed over the course of the study . Conclusion Incorporating the control of sputum eosinophils into the management algorithm did not significantly reduce overall exacerbations or improve asthma control . Exacerbations were reduced in the short term , suggesting that more frequent measurements would be needed for a clinical ly useful effect and that controlling inflammation may have a role to play in subgroups of children with severe asthma BACKGROUND Treatment decisions in asthma are based on assessment s of symptoms and simple measures of lung function , which do not relate closely to underlying eosinophilic airway inflammation . We aim ed to assess whether a management strategy that minimises eosinophilic inflammation reduces asthma exacerbations compared with a st and ard management strategy . METHODS We recruited 74 patients with moderate to severe asthma from hospital clinics and r and omly allocated them to management either by st and ard British Thoracic Society asthma guidelines ( BTS management group ) or by normalisation of the induced sputum eosinophil count and reduction of symptoms ( sputum management group ) . We assessed patients nine times over 12 months . The results were used to manage those in the sputum management group , but were not disclosed in the BTS group . The primary outcomes were the number of severe exacerbations and control of eosinophilic inflammation , measured by induced sputum eosinophil count . Analyses were by intention to treat . FINDINGS The sputum eosinophil count was 63 % ( 95 % CI 24 - 100 ) lower over 12 months in the sputum management group than in the BTS management group ( p=0.002 ) . Patients in the sputum management group had significantly fewer severe asthma exacerbations than did patients in the BTS management group ( 35 vs 109 ; p=0.01 ) and significantly fewer patients were admitted to hospital with asthma ( one vs six , p=0.047 ) . The average daily dose of inhaled or oral corticosteroids did not differ between the two groups . INTERPRETATION A treatment strategy directed at normalisation of the induced sputum eosinophil count reduces asthma exacerbations and admissions without the need for additional anti-inflammatory treatment One important goal of asthma treatment is to reduce exacerbations . The current authors investigated if the use of sputum cell counts to guide treatment would achieve this goal . A total of 117 adults with asthma were entered into a multicentre , r and omised , parallel group-effectiveness study for two treatment strategies over a 2-yr period . In one strategy ( the clinical strategy : CS ) treatment was based on symptoms and spirometry . In the other ( the sputum strategy : SS ) sputum cell counts were used to guide corticosteroid therapy to keep eosinophils ≤2 % ; symptoms and spirometry were used to identify clinical control , exacerbations and other treatments . Patients were blind to sputum cell counts in both strategies and physicians were blind in the CS , thus removing bias . First , the minimum treatment to maintain control was identified in 107 patients ( Phase 1 ) and then this treatment was continued ( Phase 2 ) for the remaining of the 2 yrs . The primary outcomes were the relative risk reduction for the occurrence of the first exacerbation in Phase 2 and the length of time without exacerbation . The current authors also examined the type and severity of exacerbations and the cumulative dose of inhaled steroid needed . The duration and number of exacerbations in Phase 1 were similar in both groups . In Phase 2 there were a 126 exacerbations of which 79 occurred in the CS ( 62.7 % ) and 47 ( 37.3 % ) in the SS groups . The majority of the 126 exacerbations ( 101 ; 80.1 % ) were mild . The majority of the 102 exacerbations , where sputum examination was performed before any treatment ( n = 70 ) , were noneosinophilic . In the SS patients , the time to the first exacerbation was longer ( by 213 days ) especially in those considered to need treatment with a long acting β2-agonist ( by 490 days ) , the relative risk ratio was lower ( by 49 % ) , and the number of exacerbations needing prednisone was reduced ( 5 versus 15 ) . This benefit was seen mainly in patients needing treatment with inhaled steroid in a daily dose equivalent to fluticasone > 250 μg , and was due to fewer eosinophilic exacerbations . The cumulative dose of corticosteroid during the trial was similar in both groups . Monitoring sputum cell counts was found to benefit patients with moderate-to-severe asthma by reducing the number of eosinophilic exacerbations and by reducing the severity of both eosinophilic and noneosinophilic exacerbations without increasing the total corticosteroid dose . It had no influence on the frequency of noneosinophilic exacerbations , which were the most common exacerbations Background : The debate as to whether asthma is a single or heterogeneous disease remains unresolved although pathological studies , mostly using fibreoptic bronchoscopy on small numbers of subjects , have emphasised the similarities between different clinical phenotypes . Methods : Lower airway inflammation was assessed non-invasively using induced sputum in 34 normal controls and 259 adults with symptomatic asthma receiving treatment at steps 1–3 of the British Thoracic Society ( BTS ) guidelines . A subgroup of 49 patients treated with as required β2 agonists only who met BTS criteria for a step up in treatment were studied before and 2 months after treatment with inhaled budesonide 400 μg twice daily . Results : There was considerable heterogeneity in induced sputum cell counts , particularly in non-atopic patients . A subgroup of 60 patients had a distinctive sputum cell profile with a neutrophil count higher than our normal range ( > 65.3 % ) and a normal sputum eosinophil count ( < 1.9 % ) . These patients were older , predominantly female , and were more likely to be non-atopic but otherwise had similar clinical and physiological features to the group as a whole . Among the 49 subjects studied 
    Output:
    