Evaluation of a clinical algorithm involving serum eosinophil cationic protein for guiding the anti-inflammatory treatment of bronchial asthma in childhood. Usefulness of exhaled nitric oxide and sputum eosinophils in the long-term control of eosinophilic asthma. Proof of concept study to evaluate step-down therapy with inhaled corticosteroid alone or additive therapy on surrogate inflammatory markers in asthma. Use of sputum eosinophil counts to guide management in children with severe asthma Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids Monitoring sputum eosinophils in mucosal inflammation and remodelling: a pilot study An inhaled steroid improves markers of airway inflammation in patients with mild asthma. Benefits of induced sputum for the evaluation of therapeutic efficacy in patients with bronchial asthma. The Combined Impact of Exhaled Nitric Oxide and Sputum Eosinophils Monitoring in Asthma Treatment: A Prospective Cohort Study. Asthma severity, recommended changes of inhaled therapy and exhaled nitric oxide in children: a prospective, blinded trial. Accuracy of eosinophils and eosinophil cationic protein to predict steroid improvement in asthma Acute anti-inflammatory effects of inhaled budesonide in asthma: a randomized controlled trial. Induced sputum and bronchoalveolar lavage as tools for evaluating the effects of inhaled corticosteroids in patients with asthma. Step-down compared to fixed-dose treatment with inhaled fluticasone propionate in asthma. Clinical use of noninvasive measurements of airway inflammation in steroid reduction in children. [A study on a therapeutic protocol to improve the control of persistent asthma by monitoring sputum eosinophil counts]. Use of exhaled nitric oxide measurements to guide treatment in chronic asthma. Eosinophil markers in blood, serum, and urine for monitoring the clinical course in childhood asthma: impact of budesonide treatment and withdrawal. [Induced sputum--means for detecting bronchial inflammation in children with atopic bronchial asthma and treatment monitoring]. Eosinophils and eosinophilic cationic protein in induced sputum and blood: effects of budesonide and terbutaline treatment. Strategy Aimed at Reduction of Sputum Eosinophils Decreases Exacerbation Rate in Patients with Asthma Analysis of induced sputum before and after withdrawal of treatment with inhaled corticosteroids in asthmatic patients
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 before and after inhaled budesonide , 11 patients had an isolated sputum neutrophilia . Following treatment , these patients showed significantly less improvement in visual analogue symptom scores ( –5.5 v –19.4 mm ; mean difference 13.9 ; 95 % CI 0.7 to 27.0 ) , forced expiratory volume in 1 second ( FEV1 ) ( –0.08 v 0.13 l ; mean difference 0.21 ; 95 % CI 0.03 to 0.39 ) , and concentration of methacholine provoking a fall in FEV1 of 20 % or more ( PC20 ) ( 0.15 v 1.29 doubling doses ; mean difference 1.11 ; 95 % CI 0.13 to 2.15 ) than the remaining 38 patients . Conclusions : These results suggest the presence of a distinct subgroup of patients with mild to moderate asthma who have predominantly neutrophilic airway inflammation and who respond less well to treatment with inhaled corticosteroids Normalisation of eosinophil counts in sputum of asthmatic patients reduces eosinophilic exacerbations . However , the effect of this strategy on airway remodelling remains to be determined . We compared bronchial inflammation and collagen deposition after 2 yrs of treatment guided by either sputum eosinophils ( sputum strategy , SS ) or by clinical criteria ( clinical strategy , CS ) . As a pilot study , 20 mild asthmatic patients were r and omly assigned to CS or SS strategies . Bronchial biopsies were obtained when minimum treatment needed to maintain control was identified and this was continued for 2 yrs . Biopsies were immunostained for inflammatory cells , mucin 5A ( MUC5A ) and collagen . The mean dose of inhaled corticosteroids at the start and end of the study was similar in both SS and CS groups . Forced expiratory volume in 1 s increased in both groups at the study end . In SS , mucosal lymphocyte and eosinophil counts , but not neutrophils , were reduced at the end of the study . In CS , only activated eosinophil and neutrophil counts decreased . MUC5A staining decreased in SS but not CS . No change in collagen deposition underneath the basement membrane was observed in either strategy . Treatment strategies that normalise sputum eosinophils also reduce mucosal inflammatory cells and MUC5A expression , but do not change subepithelial collagen deposition in mild to moderate asthma Airway inflammation can be demonstrated in mildly asthmatic patients who are not treated with inhaled steroids . Current guidelines recommend that inhaled steroids should be introduced in mild asthmatics who use an inhaled beta2-agonist more than once daily . It was postulated that inhaled steroids can have anti-inflammatory effects in patients with even milder disease . The effect of 4 weeks of treatment with budesonide ( 800 microg twice daily by Turbohaler ) was studied in 10 steroid-naive mildly asthmatic patients ( forced expiratory volume in one second ( FEV1 ) = 96+/-1.4 % predicted ) who required an inhaled beta2-agonist less than one puff daily , in a double-blind , placebo-controlled , crossover fashion .  Spirometry , exhaled nitric oxide ( NO ) , bronchial responsiveness ( provocative concentration causing a 20 % fall in FEV1 ( PC20 ) ) , and sputum induction  were performed before and after each treatment period . Following budesonide treatment , there were significant improvements in FEV1 , and PC20 , in association with a significant reduction in the percentage of eosinophils in induced sputum . Exhaled NO levels tended towards reduction , but the change was nonsignificant . There were also nonsignificant reductions in sputum eosinophil cationic protein and tumour necrosis factor-alpha levels . In conclusion inhaled budesonide can lead to improvements in noninvasive markers of airway inflammation , in association with a small improvement in lung function , even in mildly asthmatic patients who require an inhaled beta2-agonist less than once daily . This suggests a potential benefit of inhaled corticosteroids , even in relatively asymptomatic asthma Airway inflammation is a major factor in the pathogenesis of asthma . Inducing sputum by hypertonic saline is a noninvasive method of assessment of the airway inflammation in asthmatic patients . To investigate sputum induction as a method for assessing airway inflammation and to evaluate the effect of inhaled beclomethasone dipropionate ( BDP ) in asthmatic patients , we examined the bronchial hyperresponsibility ( BHR ) , pulmonary function and differential cell counts in induced sputum of the patients before and after BDP therapy .  In asthmatic patients , the percentage of eosinophils in induced sputum was significantly higher than that in non-asthmatic subjects . Ten patients with atopic asthma ( four men and six women ; mean [ + /- SD ] age , 30.5 + /- 12.4 years ) participated . Their mean percentage of eosinophils ( % eosinophils ) in induced sputum fell from 22.9 + /- 7.2 % to 13.9 + /- 8.3 % ( p < 0.05 ) by 3 months of BDP treatment . The percentage of eosinophils in induced sputum before BDP treatment was significantly correlated with the ratio of the forced expiratory volume in one second to the forced vital capacity ( FEV1 % ) at baseline ( r = -0.75 , p < 0.05 ) , but not with log Dmin at baseline ( p = 0.18 ) . The change in FEV1 % between at baseline and post-treatment correlated significantly with the change in the sputum eosinophil percentage ( r = -0.79 , p < 0.01 ) . In addition , there was a significant correlation between the change of log Dmin and the change of the sputum eosinophil percentage ( r = -0.64 , p < 0.05 ) . In conclusion , analysis of induced sputum is a safe , noninvasive , repeatable and useful method to assess the clinical condition of bronchial inflammation in patients with bronchial asthma BACKGROUND Inhaled corticosteroids ( ICS ) treatment for asthma control is generally focused on lung function and symptoms , but inadequately correlated with airway inflammation . OBJECTIVE To compare asthma control in a group of patients whose treatment was based on fraction of exhaled nitric oxide ( FENO ) and sputum eosinophils ( intervention group ) with a group in whom treatment was based on clinical score ( control group ) . Study design and primary outcome : R and omized parallel-group longitudinal 24-month study including 5 visits every 6 months . A combination of asthma exacerbation rate and symptom score at 24 months was the primary outcome . PARTICIPANTS Fourteen patients with eosinophilic asthma per group were included . RESULTS In the intervention group , exacerbation rate/patient/year was reduced at 12 months ( 0.82 ) ( -73 % ) and , to a greater extent at 24 months ( 0.5 ) ( -84 % ) compared with baseline ( 3.21 , p<0.01 ) . In the control group , a significant reduction in exacerbation rate/patient/year was only observed between month 12 ( 3.0 ) and 24 ( 2.0 , -33 % , p<0.01 ) . At 24 months , exacerbation rate was lower ( -75 % ) in the intervention ( 0.5 ) than in the control group ( 2.0 , p<0.05 ) . Compared with baseline , mean symptom scores at 24 months were reduced in both groups ( intervention group : -72 % ; control group : - 60 % ) , but were lower in the intervention ( 8.1±1.0 , p<0.05 ; -27 % ) than in the control group ( 11±2.6 ) . ICS dose gradually increased in both groups throughout the study , with no between-group differences . CONCLUSION Compared with conventional strategy , longitudinal monitoring of FENO and sputum eosinophils improves eosinophilic asthma control in terms of reduced symptoms and exacerbations without additional increase e in ICS treatment Orally  exhaled nitric oxide ( ENO )  correlates with several variables of airway inflammation and might be useful to direct asthma therapy . If this is true , ENO should correlate with disease severity and the therapeutic decisions made . - In 74 children with allergic asthma ( age 9.7 years , range 4 - 16 ) disease severity was determined by history , clinical symptoms , and lung function and inhaled therapy was adjusted according to the NIH criteria .  ENO was also measured , but the patients , their parents and the physicians who made the therapeutic decision were left unaware of the results . 31 healthy children served as controls .  ENO was higher in asthmatics than in controls , but did not differ with asthma severity . ENO was weakly correlated with the changes in asthma therapy recommended ( r = 0.303 , P = 0.009 ) . ENO values above normal ( > 13 ppb ) had a sensitivity of 0.67 and a specificity of 0.65 to predict a step up in therapy . Due to the non-normal distribution of ENO there was a substantial overlap between the different groups . The lack of correlation with disease severity and the weak prediction of physician recommended inhaled therapy , suggest that ENO may be of some value to guide asthma therapy . Studies using ENO to direct therapy are necessary for a definite answer Background There is a large variability in clinical response to corticosteroid treatment in patients with asthma . Several markers of inflammation like eosinophils and eosinophil cationic protein ( ECP ) , as well as exhaled nitric oxide ( NO ) , are good c and i date s to predict clinical response Corticosteroids can have acute effects on airway function and methacholine airway responsiveness in asthma as early as 6 h after dosing , suggesting there may be an acute anti-inflammatory effect of inhaled corticosteroid in asthma . This study aim ed to determine the effects of a single dose of inhaled budesonide on sputum eosinophils and mast cells in adults with asthma , and to examine whether the mechanism of clearance of eosinophils was by apoptosis . A r and omized , double-blind , placebo-controlled , crossover study was conducted . At the screening visit , adults with stable asthma ( n = 41 ) ceased inhaled corticosteroid therapy for 4 d and those with significant sputum eosinophilia ( > or = 7 % ) were r and omized ( n = 26 ) to a single dose of budesonide 2,400 microg or placebo via Turbuhaler , on two separate study days . Symptoms and lung function were followed for 6 h , then sputum was induced and airway responsiveness to hypertonic saline determined . Sputum eosinophils ( mean , SE ) were significantly lower 6 h after budesonide ( 25 % , 4.5 ) , compared with placebo ( 37 % , 6.2 , p < 0.05 ) . There was a 2.2-fold ( 95 % CI 1.45 to 3.33 ) improvement in airway responsiveness with budesonide . No significant difference was seen on mast cells , apoptotic eosinophils , symptoms , or lung function . In conclusion , a single dose of inhaled corticosteroids has beneficial effects on airway inflammation and airway hyperresponsiveness as early as 6 h after dosing . This may be clinical ly useful as therapy during mild exacerbations of asthma Changes in airway inflammation can be studied with bronchoalveolar lavage , but the widespread use of this procedure is limited by its invasiveness . The aim of this study was to evaluate the usefulness of induced sputum as a non-invasive alternative to bronchoalveolar lavage for study ing changes in airway inflammation in patients with asthma . Thirty patients were treated for 12 weeks with an inhaled corticosteroid ( fluticasone propionate ( FP ) , 250 microg twice daily ) or a short-acting beta-agonist ( salbutamol ( Sb ) , 400 microg twice daily ) in a double-blind , double-dummy , r and omized parallel group study . Sputum induction with hypertonic saline solution was performed twice before treatment and after 4 , 8 , 10 , and 11 weeks of treatment . Bronchoalveolar lavage fluid divided into two pools ( first 60 mL portion as bronchoalveolar lavage/bronchial wash ( BAL/BW ) and subsequent 80 mL as bronchoalveoalar lavage ( BAL ) ) was obtained before and after 12 weeks of treatment . Changes in cell differentials and plasma-protein leakage ( alpha2-macroglobulin , albumin , and their ratio ( relative coefficient of excretion , RCE ) ) were analyzed in induced sputum and were compared with changes in BAL/BW and BAL . During treatment with FP , the PC20histamine ( interpolated concentration of histamine that caused a fall in FEV1 of 20 % of the baseline value ) increased ( P < .0001 ) , and the percentage of eosinophils ( P = .004 ) , levels of ( alpha2-macroglobulin ( P = .09 ) and RCE ( P = .007 ) decreased in sputum . These changes were different from those in the Sb group ( PC20histamine P < .0001 , eosinophils P= .004 , alpha2-macroglobulin P= .003 , RCE P = .01 ) , in which alpha2-macroglobulin showed a significant increase ( P = .015 ) . Changes in the percentage of eosinophils and in the levels of alpha2-macroglobulin in sputum were associated with changes in the PC20histamine ( Rs = -0.59 , P = .007 and Rs = -0.47 , P = .03 , respectively ) . These correlations did not reach significance in BAL/BW and BAL fluid . The statistical power to detect changes in induced sputum was higher for the percentage of eosinophils and similar for plasma protein leakage as compared with analysis of BAL/BW and BAL fluid . We conclude that the analysis of induced sputum is a useful , non-invasive alternative to bronchoalveolar lavage for assessing the effects of antiinflammatory drugs in asthma BACKGROUND Inhaled corticosteroids ( ICSs ) are an effective treatment of asthma even when administered at a low dose . Once asthma is controlled , current guidelines recommend that the dose of ICS be reduced to the lowest possible and effective dose . Although the most appropriate strategy for the stepping down has not yet been defined , quantification of sputum eosinophils and bronchial hyperresponsiveness ( BHR ) are indeed measures of asthma control . OBJECTIVE To compare the efficacy of step-down and fixed-dose strategies in the control of BHR to methacholine and eosinophilic inflammation patients with mild-to-moderate asthma . METHODS We performed a double-blind , r and omized study to compare inhaled fluticasone propionate ( FP ) , 1,000 microg/d , then reduced to 200 microg/d ( group 1 ; n = 18 ) to a fixed dose of FP , 200 microg/d ( group 2 ; n = 17 ) administered for 6 weeks and then 8 weeks in reducing the provocative dose of methacholine causing a 20 % fall in FEV1 ( PD20 ) and sputum eosinophils in 35 patients . The duration of the efficacy was also followed subsequently after 8 weeks of placebo treatment . RESULTS PD20 remarkably increased with both treatment strategies , but differences between groups were not significant . Sputum eosinophils ( median values , percentage ) at baseline and after each treatment period were not different ( group 1 , 16.4 to 1.0 to 2.7 % ; group 2 , 16.7 to 2.8 to 2.8 % , respectively ) . The percentages of patients in whom sputum eosinophilia was normalized ( < or = 3 % ) were as follows : group 1 , 69 % and 60 % ; group 2 , 50 % and 57 % . After placebo treatment , sputum eosinophils were still " normalized " in approximately one third of patients . CONCLUSION Step-down and fixed-dose strategies with FP improved PD20 and sputum eosinophilia to a similar degree . The effect on sputum eosinophils persisted longer than that on methacholine The use of noninvasive methods of monitoring airway inflammation , such as exhaled nitric oxide ( eNO ) and induced sputum , has been shown to improve asthma monitoring and optimize treatment in adult patients with asthma . There is a lack of comparable data in children . Forty children with stable asthma eligible for inhaled steroid reduction  were review ed every 8 weeks , and their inhaled steroid dose halved if clinical ly indicated . eNO , sputum induction combined with bronchial hyperreactivity testing , and exhaled breath condensate collection were performed at each visit to predict success or failure of reduction of inhaled steroids . Thirty of 40 ( 75 % ) children tolerated at least one dose reduction , 12 of 40 ( 30 % ) were successfully weaned off , and in total , 15 of 40 ( 38 % ) children experienced loss of asthma control . Treatment reduction was successful in all children who had no eosinophils in induced sputum  before the attempted reduction . Using multiple logistic regression , increased eNO ( odds ratio , 6.3 ; confidence interval , 3.75 - 10.58 ) and percentage of sputum eosinophils ( odds ratio , 1.38 ; confidence interval , 1.06 - 1.81 ) were significant predictors of failed reduction . These findings suggest that monitoring airway inflammation may be useful in optimizing treatment in children with asthma OBJECTIVE To evaluate the clinical applicability of a therapeutic protocol aim ing to improve the control of asthma by reducing the eosinophil ( EOS ) counts in induced sputum . METHODS A prospect i ve , r and omized and controlled study was conducted from February 2005 to February 2006 . Forty-one patients with persistent asthma in the outpatient clinic were enrolled and r and omly allocated to management groups either by minimization of the induced sputum EOS ( Group A , n = 20 ) or by st and ard clinical guidelines ( Group B , n = 21 ) . The baseline data were collected after a 2-week run-in period . The doses of inhaled or oral glucocorticoids were adjusted according to sputum EOS count ( Group A ) or according to symptoms and lung functions ( Group B ) . The patients were followed up for a total of 6 months , during which the patients were assessed for 4 times , at day 15 , and at the end of the 2(nd ) , 4(th ) and 6(th ) month . Sputum induction and EOS counts were performed at the 2(nd ) , 3(rd ) and 4(th ) visits . The primary result was the total number of acute exacerbations . Rescue use of short-acting beta(2)-agonists , symptom scores , lung functions , use of glucocorticoids , and the number of sputum EOS counts were also compared between the groups . RESULTS In a study period of 6 months , the total numbers of acute exacerbations in Group A and Group B were 11 and 26 respectively , the difference being significant ( t = 6.34 , P = 0.026 ) . beta(2)-agonist use , symptom score , PEF variability , FEV(1 ) , and the average daily dose of inhaled glucocorticoids were not different between the two groups at any visits . The sputum EOS percentage at baseline and at the end of study in Group A was 0.067 ( 0.015 , 0.169 ) and 0.048 ( 0.015 , 0.150 ) respectively , the decrease being significant ( F = 3.39 , P = 0.02 ) , but in Group B was 0.040 ( 0.014 , 0.133 ) and 0.045 ( 0.012 , 0.236 ) respectively ( F = 1.07 , P = 0.37 ) . CONCLUSION A treatment strategy directed at reducing the number of the induced sputum EOS count is clinical ly feasible and effective for the adjustment of glucocorticoids and therefore for a better control of asthma BACKGROUND International guidelines for the treatment of asthma recommend adjusting the dose of inhaled corticosteroids on the basis of symptoms , bronchodilator requirements , and the results of pulmonary-function tests . Measurements of the fraction of exhaled nitric oxide ( FE(NO ) ) constitute a noninvasive marker that may be a useful alternative for the adjustment of inhaled-corticosteroid treatment . METHODS In a single-blind , placebo-controlled trial , we r and omly assigned 97 patients with asthma who had been regularly receiving treatment with inhaled corticosteroids  to have their corticosteroid dose adjusted , in a stepwise fashion , on the basis of either FE(NO ) measurements or an algorithm based on conventional guidelines . After the optimal dose was determined ( phase 1 ) , patients were followed up for 12 months ( phase 2 ) . The primary outcome was the frequency of exacerbations of asthma ; the secondary outcome was the mean daily dose of inhaled corticosteroid .  RESULTS Forty-six patients in the FE(NO ) group and 48 in the group whose asthma was treated according to conventional guidelines ( the control group ) completed the study . The final mean daily doses of fluticasone  , the inhaled corticosteroid that was used , were 370 microg per day for the FE(NO ) group ( 95 percent confidence interval , 263 to 477 ) and 641 microg per day for the control group ( 95 percent confidence interval , 526 to 756 ; P=0.003 ) , a difference of 270 microg per day ( 95 percent confidence interval , 112 to 430 ) . The rates of exacerbation were 0.49 episode per patient per year in the FE(NO ) group ( 95 percent confidence interval , 0.20 to 0.78 ) and 0.90 in the control group ( 95 percent confidence interval , 0.31 to 1.49 ) , representing a nonsignificant reduction of 45.6 percent ( 95 percent confidence interval for mean difference , -78.6 percent to 54.5 percent ) in the FE(NO ) group . There were no significant differences in other markers of asthma control , use of oral prednisone , pulmonary function , or levels of airway inflammation ( sputum eosinophils ) . CONCLUSIONS With the use of FE(NO ) measurements , maintenance doses of inhaled corticosteroids may be significantly reduced without compromising asthma control BACKGROUND Markers of airway inflammation are needed for prediction of asthma deterioration and evaluation of disease severity . Few studies have focused on the dynamics of airway inflammation as reflected by the activity of the eosinophils and their proteins after withdrawal of inhaled corticosteroids . OBJECTIVE Our goal was to investigate the effect of withdrawal of inhaled budesonide on eosinophil count in blood and eosinophil proteins in serum and urine and to relate the levels of these markers to the risk of symptoms of asthma , increased bronchial hyperresponsiveness , and deterioration of lung function . METHODS Thirty-three children were r and omly selected to continue or discontinue use of inhaled budesonide  in a double-blind , placebo-controlled study . They were followed up for 4 months with regular analysis of blood , serum , and urine sample s ; lung function ; and methacholine challenges . Eosinophil activity markers were analyzed . Age-matched healthy children provided reference data for all parameters measured . RESULTS The eosinophil number in blood and eosinophil protein levels in serum ( serum eosinophil cationic protein [ ECP ] and serum eosinophil peroxidase [ EPO ] ) increased significantly in the withdrawal group , and the difference between the groups was significant ( P = .02 for all ) . Twenty-nine percent of the children in the withdrawal group remained symptom free . This subgroup had eosinophil counts at baseline below 350/microL , a serum ECP level below 15 microg/L , and a serum EPO level below 25 microg/L , each of which was related to a low risk of exacerbation ( relative risk = 0.37 , 0.48 , and 0.37 respectively ; P < .05 for all ) . All eosinophil markers were lower in the healthy children than in the symptom-free children with asthma . CONCLUSION Our data indicate that eosinophil count and /or ECP and EPO levels can be used to estimate the short-term risk of deterioration and the need for corticosteroid treatment in cases of mild and moderate allergic asthma Induced sputum is a very recent technique for exploration of bronchial inflammation in asthma . Since 1992 , it has significantly improved as a method and as clinical and fundamental research tool for asthma . It is currently recognized that this method is well tolerated and can be used in all asthma patients , except those with FEV1 less than 11 .  Eosinophilic activation in asthma can be very well highlighted by cellular and biochemical analysis of expectoration . Thus , biologic arguments can be added to clinical signs in asthma exacerbations . Clinical evolution under corticosteroids can be biologically proved by this technique .  Sputum analysis  is useful also for differential diagnosis , sometimes difficult , between asthma and COPD BACKGROUND There is a need for easily measurable markers of airway inflammation to guide the use of anti-inflammatory treatment in asthma .  Eosinophilic cationic protein ( ECP ) levels in sputum and blood correlate with clinical severity , and serial measurements of ECP have been proposed as a suitable c and i date . AIMS AND METHODS Our aim was to confirm that sputum and serum ECP measurements would provide a more sensitive indicator of responses to asthma treatment than eosinophil counts per se , in a r and omized , placebo-controlled , crossover study of terbutaline , budesonide , and their combination in patients with chronic persistent asthma . We compared the changes in eosinophil counts and ECP in induced sputum and blood during each treatment period . RESULTS Budesonide and combined treatment caused a significant reduction in sputum eosinophils ( -2.7 % and -2.3 % , respectively , P < 0.05 ) . Sputum eosinophils increased with terbutaline ( + 3.9 % , P = 0.049 ) . In contrast , the changes for sputum ECP were not significant . There was a similar treatment effect on blood eosinophils , but not for serum ECP . Correlations between sputum and blood eosinophils were significant with and without budesonide , but were nonsignificant between sputum and blood ECP during the active treatments . Correlations between sputum eosinophils and ECP , and between blood eosinophils and serum ECP were greatest during treatment with placebo or terbutaline alone : budesonide weakened or abolished these relationships . CONCLUSIONS Compared with eosinophil counts , ECP measurements in either induced sputum or serum failed to reflect treatment-related changes in chronic asthma . We conclude that ECP is not a sensitive or reliable means of evaluating airway inflammation , and can not be recommended for assessing responses to anti-inflammatory therapy Under Global Initiative for Asthma guidelines , the clinical control of disease activity and the adjustment of treatment in patients with asthma are based on symptoms , use of rescue medication , lung function and peak expiratory flow measurement ( st and ard strategy ) . We investigated whether a strategy to reduce the number of sputum eosinophils ( EOS strategy ) gives better clinical control and a lower exacerbation rate compared with the st and ard strategy .  Fifty-five patients with moderate to severe asthma entered this open , r and omized , parallel-group study and visited the out-patient department every 3 months for 18 months . The dose of corticosteroids was adjusted according to the st and ard strategy or the percentage of sputum eosinophils ( EOS strategy ) . During the study period , the EOS strategy led to a significantly lower incidence of asthma exacerbations compared with the st and ard strategy group ( 0.22 and 0.78 exacerbations per year per patient , respectively ) . There were significant differences between the strategies in time to first exacerbation To assess whether sputum eosinophilia predicts the recurrence of asthma symptoms after withdrawal of therapy in moderate stable asthmatics on low‐dose inhaled corticosteroids
BACKGROUND Asthma severity and control can be measured both subjectively and objective ly .
Sputum analysis for evaluation of percentage of sputum eosinophilia directly measures airway inflammation , and is one method of objective ly monitoring asthma .
Using sputum analysis to adjust or tailor asthma medications is potentially superior to traditional methods based on symptoms and spirometry .
OBJECTIVES To evaluate the efficacy of tailoring asthma interventions based on sputum analysis in comparison to traditional methods ( usually symptom-based with or without spirometry/peak flow ) for asthma-related outcomes in children and adults .