The safety of twice-daily treatment with fluticasone propionate and salmeterol in pediatric patients with persistent asthma. Effect of the addition of montelukast to inhaled fluticasone propionate on airway inflammation. Montelukast and fluticasone compared with salmeterol and fluticasone in protecting against asthma exacerbation in adults: one year, double blind, randomised, comparative trial Montelukast or salmeterol combined with an inhaled steroid in adult asthma: design and rationale of a randomized, double-blind comparative study (the IMPACT Investigation of Montelukast as a Partner Agent for Complementary Therapy-trial). FeNO as a Marker of Airways Inflammation: The Possible Implications in Childhood Asthma Management Double-Blind, Randomised, Controlled Trial Assessing Controller Medications in Asthma Addition of montelukast or salmeterol to fluticasone for protection against asthma attacks: a randomized, double-blind, multicenter study. Leukotriene antagonists as first-line or add-on asthma-controller therapy. Effects of montelukast on surrogate inflammatory markers in corticosteroid-treated patients with asthma. Long‐term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older Montelukast as add-on therapy with inhaled corticosteroids alone or inhaled corticosteroids and long-acting beta-2-agonists in the management of patients diagnosed with asthma and concurrent allergic rhinitis (the RADAR trial). Titrating steroids on exhaled nitric oxide in children with asthma: a randomized controlled trial. Fluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast. A randomized open-label comparative study of montelukast versus theophylline added to inhaled corticosteroid in asthmatic children. The at-risk registers in severe asthma (ARRISA) study: a cluster-randomised controlled trial examining effectiveness and costs in primary care Montelukast improves asthma control in asthmatic children maintained on inhaled corticosteroids. Comparison of the cost-effectiveness of budesonide and sodium cromoglycate in the management of childhood asthma in everyday clinical practice. Effects of 2 inhaled corticosteroids on growth: results of a randomized controlled trial. Effects of adding either a leukotriene receptor antagonist or low-dose theophylline to a low or medium dose of inhaled corticosteroid in patients with persistent asthma. Effect of different antiasthmatic treatments on exercise-induced bronchoconstriction in children with asthma. Randomized open comparison of montelukast and sublingual immunotherapy as add-on treatment in moderate persistent asthma due to birch pollen. Failure of montelukast to reduce sputum eosinophilia in high-dose corticosteroid-dependent asthma Home telemonitoring (forced expiratory volume in 1 s) in children with severe asthma does not reduce exacerbations Effect of montelukast added to inhaled corticosteroids on fractional exhaled nitric oxide in asthmatic children Effects of a Short Course of Pranlukast Combined with Systemic Corticosteroid on Acute Asthma Exacerbation Induced by Upper Respiratory Tract Infection Traditional and patient-centred outcomes with three classes of asthma medication The effect of montelukast on eosinophil apoptosis: induced sputum findings of patients with mild persistent asthma. Canadian Thoracic Society 2012 guideline update: diagnosis and management of asthma in preschoolers, children and adults. A Randomized Controlled Trial on the Effect of Montelukast on Sputum Eosinophil Cationic Protein in Children with Corticosteroid-Dependent Asthma Montelukast as an Add-On Therapy to Inhaled Corticosteroids in the Treatment of Severe Asthma in Elderly Patients Addition of montelukast versus double dose of inhaled budesonide in moderate persistent asthma. The Back to School asthma study: the effect of montelukast on asthma burden when initiated prophylactically at the start of the school year. A randomized, double-blind trial of the effect of anti-asthma treatment on lung function in children with asthma. Effect of budesonide and montelukast in asthmatic children exposed to relevant allergens Comparative efficacy and safety of low-dose fluticasone propionate and montelukast in children with persistent asthma. Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing. Zafirlukast improves asthma control in patients receiving high-dose inhaled corticosteroids. Impact of add-on pranlukast in stable asthma; the additive effect on peripheral airway inflammation. Exhaled nitric oxide in the management of childhood asthma: a prospective 6-months study. A randomized, double‐blind trial of the effect of glucocorticoid, antileukotriene and bβ‐agonist treatment on IL‐10 serum levels in children with asthma Effects of montelukast compared to double dose budesonide on airway inflammation and asthma control. Evaluation of salmeterol or montelukast as second-line therapy for asthma not controlled with inhaled corticosteroids. A randomised controlled trial of short term growth and collagen turnover in asthmatics treated with inhaled formoterol and budesonide The effectiveness of asthma therapy alternatives and evaluating the effectivity of asthma therapy by interleukin-13 and interferon gamma levels in children. Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma Comparative efficacy and anti-inflammatory profile of once-daily therapy with leukotriene antagonist or low-dose inhaled corticosteroid in patients with mild persistent asthma. Repeated dosing effects of mediator antagonists in inhaled corticosteroid-treated atopic asthmatic patients. Clinical trial of low-dose theophylline and montelukast in patients with poorly controlled asthma. A randomized, open labeled, comparative study to assess the efficacy and safety of controller medications as add on to inhaled corticosteroid and long-acting β2 agonist in the treatment of moderate-to-severe persistent asthma. Budesonide/formoterol improves lung function compared with budesonide alone in children with asthma. Tapering dose of inhaled budesonide in subjects with mild-to-moderate persistent asthma treated with montelukast: a 16-week single-blind randomized study. "Real-world" effectiveness of daily controller medicine in children with mild persistent asthma. Leukotriene receptor antagonist, montelukast, can reduce the need for inhaled steroid while maintaining the clinical stability of asthmatic patients A comparison of short-term treatment with inhaled fluticasone propionate and zafirlukast for patients with persistent asthma. Addition of leukotriene antagonists to therapy in chronic persistent asthma: a randomised double-blind placebo-controlled trial Add-on therapy with montelukast or formoterol in patients with the glycine-16 beta2-receptor genotype. The effect of montelukast versus usual care on health care resource utilization in children aged 2 to 5 years with asthma. Comparisons of the complementary effect on exhaled nitric oxide of salmeterol vs montelukast in asthmatic children taking regular inhaled budesonide. Formoterol, montelukast, and budesonide in asthmatic children: effect on lung function and exhaled nitric oxide. Montelukast added to budesonide in children with persistent asthma: a randomized, double-blind, crossover study. Linear growth in prepubertal asthmatic children treated with montelukast, beclomethasone, or placebo: a 56-week randomized double-blind study. Comparison of inhaled salmeterol and oral zafirlukast in patients with asthma. Placebo-controlled study of montelukast and budesonide on short-term growth in prepubertal asthmatic children. Effect of montelukast or salmeterol added to inhaled fluticasone on exercise-induced bronchoconstriction in children. Randomized comparison of strategies for reducing treatment in mild persistent asthma. Low-dose fluticasone propionate compared with montelukast for first-line treatment of persistent asthma: a randomized clinical trial. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Effects of montelukast (MK-0476); a potent cysteinyl leukotriene receptor antagonist, on bronchodilation in asthmatic subjects treated with and without inhaled corticosteroids. A comparison of the effects of oral montelukast and inhaled salmeterol on response to rescue bronchodilation after challenge. The effects of add-on zafirlukast treatment to budesonide on bronchial hyperresponsiveness and serum levels of eosinophilic cationic protein and total antioxidant capacity in asthmatic patients. The Efficacy of Montelukast during the Allergy Season in Pediatric Patients with Persistent Asthma and Seasonal Aeroallergen Sensitivity The effect of montelukast and different doses of budesonide on IgE serum levels and clinical parameters in children with newly diagnosed asthma. Inhaled corticosteroids in children with persistent asthma: dose-response effects on growth. Attenuation of the September Epidemic of Asthma Exacerbations in Children: A Randomized, Controlled Trial of Montelukast Added to Usual Therapy Evaluation of theophylline or pranlukast, a cysteinyl leukotriene receptor 1 antagonist, as add-on therapy in uncontrolled asthmatic patients with a medium dose of inhaled corticosteroids. Comparing outcomes in patients with persistent asthma: a registry of two therapeutic alternatives* Montelukast added to inhaled beclomethasone in treatment of asthma. Montelukast/Beclomethasone Additivity Group. Treatment effectiveness of inhaled corticosteroids and leukotriene modifiers for patients with asthma: an analysis from managed care data. A proof of concept study to evaluate putative benefits of montelukast in moderate persistent asthmatics. Asthma in Head Start children: effects of the Breathmobile program and family communication on asthma outcomes. Low-dose inhaled fluticasone propionate versus oral zafirlukast in the treatment of persistent asthma. Effect of montelukast and fluticasone propionate on airway mucosal blood flow in asthma. Effects of adding a leukotriene antagonist or a long-acting beta(2)-agonist in asthmatic patients with the glycine-16 beta(2)-adrenoceptor genotype. Cost effectiveness of leukotriene receptor antagonists versus inhaled corticosteroids for initial asthma controller therapy: a pragmatic trial. Montelukast added to fluticasone propionate does not alter inflammation or outcomes.
BACKGROUND For children older than 5 years with asthma who remain symptomatic despite inhaled corticosteroid ( ICS ) therapy , the preferred treatment is to add an inhaled long-acting beta2-agonist vs increasing the ICS dose . OBJECTIVE To compare the safety of twice-daily treatment with inhaled fluticasone propionate plus the inhaled long-acting beta2-agonist salmeterol with that of fluticasone propionate used alone in children aged 4 to 11 years with persistent asthma . METHODS A r and omized , multicenter , double-blind , active-controlled , parallel-group study in 203 children with persistent asthma who were symptomatic during ICS therapy . Patients received fluticasone propionate-salmeterol ( 100/50 microg ) or fluticasone propionate ( 100 microg ) alone twice daily for 12 weeks . RESULTS The safety profile of fluticasone propionate-salmeterol was similar to that of fluticasone propionate alone . The overall incidence of adverse events was 59 % for fluticasone propionate-salmeterol and 57 % for fluticasone propionate . Both treatments were well tolerated . Two patients receiving fluticasone propionate-salmeterol and 5 receiving fluticasone propionate withdrew from the study because of worsening asthma . Changes in heart rate , blood pressure , and laboratory variables were infrequent and were similar between treatments . No patients had clinical ly significant abnormal electrocardiographic findings during treatment . Geometric mean 24-hour urinary cortisol excretion at baseline and after 12 weeks of treatment was comparable within and between groups ; no patient in either group had abnormally low 24-hour urinary cortisol excretion after 12 weeks of treatment . The incidence of withdrawals due to asthma exacerbations was 2 % in the fluticasone propionate-salmeterol group and 5 % in the fluticasone propionate group . CONCLUSIONS In pediatric patients with persistent asthma , fluticasone propionate-salmeterol twice daily was well tolerated , with a safety profile similar to that of fluticasone propionate used alone The aim of the study was to investigate the effect of addition of montelukast to inhaled fluticasone propionate ( FP ) therapy , compared with FP therapy alone ( 100 microg twice a day ) on airway immunopathology in individuals with mild asthma . Twenty-eight subjects received FP ( 100 microg twice a day ) or FP ( 100 microg twice a day ) plus montelukast ( 10 mg at night ) for 8 weeks and were then crossed over to the alternate treatment for a further 8 weeks . Physiological measurements and bronchial biopsies were obtained at + /- 2 days before treatment and + /- 2 days at the end of each treatment period . A two-period crossover analysis was performed and the mean and SE were calculated . There was no significant difference in percent predicted FEV1 ( p = 0.51 ) or PC20 mg/ml ( p = 0.81 ) between the two treatment regimes after 8 weeks of therapy . There was no difference in the efficacy of either treatment in decreasing T cell ( p = 0.97 ) , CD45RO+ ( p = 0.37 ) , mast cell ( p = 0.37 ) , or activated eosinophils ( p = 0.55 ) numbers in bronchial biopsies . There was no significant difference in the percentage area stained for IFN-gamma ( p = 0.76 ) or interleukin-4 ( p = 0.61 ) between treatments . Reduction of inflammatory cell numbers in the bronchial mucosa achieved with FP plus montelukast was not significantly different from the reduction observed with FP alone in individuals with mild asthma Abstract Objectives To assess the effect of montelukast versus salmeterol added to inhaled fluticasone propionate on asthma exacerbation in patients whose symptoms are inadequately controlled with fluticasone alone . Design and setting A 52 week , two period , double blind , multicentre trial during which patients whose symptoms remained uncontrolled by inhaled corticosteroids were r and omised to add montelukast or salmeterol .  Participants Patients ( 15 - 72 years ; n = 1490 ) had a clinical history of chronic asthma for ≥ 1 year , a baseline forced expiratory volume in one second ( FEV 1 ) value 50 - 90 % predicted , and a β agonist improvement of ≥ 12 % in FEV 1 . Main outcome measures The primary end point was the percentage of patients with at least one asthma exacerbation . Results 20.1 % of the patients in the group receiving montelukast and fluticasone  had an asthma exacerbation compared with 19.1 % in the group receiving salmeterol and fluticasone ; the difference was 1 % ( 95 % confidence interval -3.1 % to 5.0 % ) . With a risk ratio ( montelukast-fluticasone/salmeterol-fluticasone ) of 1.05 ( 0.86 to 1.29 ) , treatment with montelukast and fluticasone was shown to be non-inferior to treatment with salmeterol and fluticasone . Salmeterol and fluticasone  significantly increased FEV 1 before a β agonist was used and morning peak expiratory flow compared with montelukast and fluticasone ( P ≤ 0.001 ) , whereas FEV 1 after a β agonist was used and improvements in asthma specific quality of life and nocturnal awakenings were similar between the groups . Montelukast and fluticasone significantly ( P = 0.011 ) reduced peripheral blood eosinophil counts compared with salmeterol and fluticasone . Both treatments were generally well tolerated . Conclusion The addition of montelukast in patients whose symptoms remain uncontrolled by inhaled fluticasone could provide equivalent clinical control to salmeterol Asthma patients who continue to experience symptoms despite taking regular inhaled corticosteroids  represent a management challenge . Leukotrienes play a key role in asthma pathophysiology , and since pro-inflammatory leukotrienes are poorly suppressed by corticosteroids it seems rational to add a leukotriene receptor antagonist ( LTRA ) when a low to moderate dose of inhaled corticosteroids does not provide sufficient disease control . Long acting beta2-agonist ( LABA ) treatment represents an alternative to LTRAs and both treatment modalities have been shown to provide additional disease control when added to corticosteroid treatment . To compare the relative clinical benefits of adding either a LTRA or a LABA to asthma patients inadequately controlled by inhaled corticosteroids , a r and omized , double-blind , multi-centre , 48-week study will be initiated at approximately 120 centres throughout Europe , Latin America , Middle East , Africa and the Asia-Pacific region in early 2000 . The study will compare the oral LTRA montelukast with the inhaled LABA salmeterol , each administered on a background of inhaled fluticasone , on asthma attacks , quality of life , lung function , eosinophil levels , healthcare utilization , and safety , in approximately 1200 adult asthmatic patients . The requirements for study enrollment include a history of asthma , FEV1 or PEFR values between 50 % and 90 % of the predicted value together with > or = 12 % improvement in FEV1 after beta-agonist administration , a minimum pre-determined level of asthma symptoms and daily beta-agonist medication . The study will include a 4-week run-in period , during which patients previously taking inhaled corticosteroids are switched to open-label fluticasone ( 200 microg daily ) , followed by a 48-week double-blind , treatment period in which patients continuing to experience abnormal pulmonary function and daytime symptoms are r and omized to receive montelukast ( 10 mg once daily ) and salmeterol placebo , or inhaled salmeterol ( 100 microg daily ) and montelukast placebo . All patients will continue with inhaled fluticasone ( 200 microg daily ) . During the study , asthma attacks , overnight asthma symptoms , and morning peak expiratory flow rate will be assessed using patient diary cards ; quality of life will also be assessed using an asthma-specific quality -of life question naire . The results of this study are expected to provide physicians with important clinical evidence to help them make a rational and logical treatment choice for asthmatic patients experiencing breakthrough symptoms on inhaled corticosteroids The aim of this study was to verify FeNO usefulness , as a marker of bronchial inflammation , in the assessment of therapeutic management of childhood asthma . We performed a prospect i ve 1-year r and omized clinical trial evaluating two groups of 32 children with allergic asthma : “ GINA group ” , in which therapy was assessed only by GINA guidelines and “ FeNO group ” , who followed a therapeutic program assessed also on FeNO measurements .  Asthma Severity score ( ASs ) , Asthma Exacerbation Frequency ( AEf ) , and Asthma Therapy score ( ATs ) were evaluated at the start of the study ( T1 ) , 6 months ( T2 ) , and 1 year after ( T3 ) . ASs and AEf significantly decreased only in the FeNO group at times T2 and T3 ( p[T1-T2 ] = 0.0001 , and p[T1-T3 ] = 0.01 ; p[T1-T2 ] = 0.0001 ; and p[T1-T3 ] < 0.0001 , resp . ) . After six months of follow-up , we found a significant increase of patients under inhaled corticosteroid and /or antileukotrienes  in the GINA group compared to the FeNO group ( P = .02 ) . Our data show that FeNO measurements , might be a very useful additional parameter for management of asthma , which is able to avoid unnecessary inhaled corticosteroid and antileukotrienes therapies , however , mantaining a treatment sufficient to obtain a meaningful improvement of asthma Background : The motive behind conducting this study was to determine if better control of asthma can be achieved by adding a second controller medication and to assess its use to reduce the dose of inhaled steroids . Objectives : The study aim ed to determine whether either oral sustained-release theophylline or montelukast added to inhaled steroids  improved clinical symptoms and pulmonary function test parameters when compared to high-dose steroids alone . Methods : Ninety patients with incompletely controlled asthma were allocated , in a r and omised , double-blind fashion , to one of three treatment groups : group A : double dose of inhaled budesonide ( 400 µg b.i.d . ) , group B : 400 mg oral sustained-release theophylline plus budesonide ( 200 µg b.i.d . ) and group C : 10 mg montelukast plus budesonide ( 200 µg b.i.d . ) . The primary endpoints were forced expiratory volume in 1 s ( FEV1 ) and mean morning peak expiratory flow rate ( PEFR ) . Results : All three groups had improved FEV1 and PEFR at 8 weeks ( p < 0.001 ) . Group C increased their PEFR by 18.7 l/min ( 95 % confidence interval , CI , 12.4–25.1 ) more than group A and by 19.8 l/min ( 95 % CI 13.4–26.1 ) more than group B ( both p = 0.001 ) . Similarly , group C had a 114 ml ( 95 % CI 45–183 ml ) greater improvement in FEV1 than group A and a 95 ml ( 95 % CI 26–164 ml ) greater improvement than group B ( both p = 0.01 ) . Conclusions : Addition of montelukast to budesonide is safe and results in greater improvement in pulmonary function test parameters  than high-dose budesonide treatment or addition of theophylline BACKGROUND For patients whose asthma is uncontrolled with low-dose inhaled corticosteroids , addition of alternative therapy instead of increasing the steroid dose is recommended by current treatment guidelines . OBJECTIVE To compare montelukast , a once-daily leukotriene receptor antagonist , and salmeterol , a twice-daily , long-acting beta-agonist , concomitantly administered with inhaled fluticasone , according to the percentage of patients without an asthma attack for 1 year . METHODS A r and omized , double-blind , double-dummy , multicenter study was conducted . Adult patients with moderate-to-severe persistent asthma ( ages 14 - 73 years ) receiving inhaled fluticasone ( 220 microg/d ) who remained symptomatic during a 4-week run-in period were r and omized to the addition of salmeterol ( 84 microg/d ) or montelukast ( 10 mg/d ) for 48 weeks . RESULTS Of the 1,473 r and omized patients , 743 were r and omized to montelukast and 730 to salmeterol ; 1,059 patients completed the study . Eighty percent of patients in the montelukast group and 83.3 % of patients in the salmeterol group remained attack free during the 48 weeks of treatment ( relative risk , 1.20 ; 95 % confidence interval , 0.96 - 1.49 ) . Montelukast significantly reduced blood eosinophil counts compared with salmeterol , whereas salmeterol significantly increased prealbuterol forced expiratory volume in 1 second , asthma-specific quality of life , morning peak expiratory flow rate , and decreased nocturnal awakenings compared with montelukast . Differences between treatments were small , and both treatments were generally well tolerated . CONCLUSIONS Addition of montelukast or salmeterol to an inhaled corticosteroid similarly protected most patients from experiencing an asthma attack during a 1-year period , but , based on noninferiority limits , the study was inconclusive with regard to a difference between treatment groups BACKGROUND Most r and omized trials of treatment for asthma study highly selected patients under idealized conditions . METHODS We conducted two parallel , multicenter , pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist ( LTRA ) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist ( LABA ) as add-on therapy in patients already receiving inhaled glucocorticoid therapy . Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life ( Mini Asthma Quality of Life Question naire [ MiniAQLQ ] score ≤6 ) or inadequate asthma control ( Asthma Control Question naire [ ACQ ] score ≥1 ) . We r and omly assigned patients to 2 years of open-label therapy , under the care of their usual physician , with LTRA ( 148 patients ) or an inhaled glucocorticoid ( 158 patients ) in the first-line controller therapy trial and LTRA ( 170 patients ) or LABA ( 182 patients ) added to an inhaled glucocorticoid in the add-on therapy trial . RESULTS Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials . At 2 months , differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence ( 95 % confidence interval [ CI ] for an adjusted mean difference , -0.3 to 0.3 ) . At 2 years , mean MiniAQLQ scores approached equivalence , with an adjusted mean difference between treatment groups of -0.11 ( 95 % CI , -0.35 to 0.13 ) in the first-line controller therapy trial and of -0.11 ( 95 % CI , -0.32 to 0.11 ) in the add-on therapy trial . Exacerbation rates and ACQ scores did not differ significantly between the two groups . CONCLUSIONS Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients . Equivalence was not proved at 2 years . The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group . ( Funded by the National Coordinating Centre for Health Technology Assessment U.K. and others ; Controlled Clinical Trials number , IS RCT N99132811 . ) We evaluated whether montelukast conferred additive effects in patients with asthma receiving fluticasone/salmeterol ( FP/SM ) combination and FP alone . Twenty-two patients with mild to moderate asthma completed a double-blind , placebo-controlled study . After a 2-week run-in using FP 250 microg/SM 50 microg 1 puff twice daily , patients entered a r and omized crossover period to receive additional montelukast 10 mg daily or placebo for 3 weeks each . For the first 2 weeks , they received FP/SM 1 puff BID , and then they received FP 250 microg 1 puff BID for the 3rd week . The primary outcome was adenosine monophosphate challenge threshold and recovery time ; secondary outcomes included surrogate inflammatory markers and lung function . Compared with FP/SM run-in , adding montelukast to FP/SM was better ( p < 0.05 ) than placebo for inflammatory markers but not for lung function . For adenosine monophosphate threshold , recovery , exhaled nitric oxide , and blood eosinophils , there were 1.4 ( 95 % confidence interval , 1.1 - 1.8 ) geometric mean fold , 10 minutes ( 3 - 17 minutes ) , 2.1 parts per billion ( 0.2 - 3.9 parts per billion ) , and 88 ( 34 - 172 ) x 10(6)/L differences , respectively . The combination of FP plus montelukast was superior to FP/SM for inflammatory markers but was inferior for lung function . Thus , in patients taking FP/SM or FP , montelukast conferred complimentary effects on surrogate inflammatory markers , which were dissociated from lung function . Further studies are required to evaluate whether these effects of montelukast translate into clinical benefits Background Leukotriene receptor antagonists have demonstrated clinical benefits in chronic asthma studies of up to 3 months in duration . The effects of these agents over extended periods of time have not been reported OBJECTIVE To evaluate the effectiveness of montelukast as add-on therapy for patients diagnosed with asthma and concurrent allergic rhinitis who remain uncontrolled while receiving inhaled corticosteroid ( ICS ) monotherapy or ICS/long-acting beta-2-agonist ( LABA ) therapy  in a community practice setting . DESIGN An eight-week , multicentre , open-label , observational study . Patients were 15 years of age or older and , while treated with an ICS or ICS/LABA , had allergic rhinitis and uncontrolled asthma symptoms by at least two criteria as per the Canadian Asthma Consensus Guidelines . The primary outcome measure was the percentage of patients with controlled asthma symptoms after eight weeks of treatment with montelukast 10 mg once daily added to ICS or ICS/LABA therapy . RESULTS In total , 1004 patients participated in the survey phase of the study . Of these patients , 319 continued in the treatment phase and 301 ( 94.4 % ) completed the eight-week assessment . At baseline , all patients had uncontrolled asthma symptoms based on the Canadian Asthma Consensus Guidelines ; at the eight-week assessment , 229 patients ( 76.1 % ) achieved asthma control . According to the Asthma Control Question naire ( as determined by scores of 0.75 or less ) , 164 patients ( 54.7 % ) achieved well-controlled asthma at week 8 . The mean ( + /- SD ) Asthma Control Question naire score decreased from 2.03+/-0.80 to 0.92+/-0.80 ( P<0.001 ) for all patients , representing a clinical ly significant improvement . A statistically and clinical ly significant reduction in the overall Mini Rhinitis Quality of Life Question naire score was achieved with a decrease from 2.57+/-1.20 to 1.12+/-1.00 ( -1.45+/-1.35 ; P<0.001 ) . Patient and physician satisfaction rates with montelukast add-on therapy were also significantly increased when compared with baseline treatment . CONCLUSION Montelukast add-on therapy is effective for managing asthma and allergic rhinitis symptoms in patients who were previously uncontrolled with ICS or ICS/LABA treatment RATIONALE Corticosteroids are the antiinflammatory treatment of choice in asthma . Treatment guidelines are mainly symptom-driven but symptoms are not closely related to airway inflammation . The fraction of nitric oxide in exhaled air ( FENO ) is a marker of airway inflammation in asthma . OBJECTIVE We evaluated whether titrating steroids on FENO improved asthma management in children . METHODS Eighty-five children with atopic asthma , using inhaled steroids  , were allocated to a FENO group ( n=39 ) in which treatment decisions were made on both FENO and symptoms , or to a symptom group ( n=46 ) treated on symptoms only .  Children were seen every 3 months over a 1-year period . MEASUREMENTS Symptoms were scored during 2 weeks before visits and 4 weeks before the final visit . FeNO was measured at all visits , and airway hyperresponsiveness and FEV1 were measured at the start and end of the study . Primary endpoint was cumulative steroid dose . RESULTS Changes in steroid dose from baseline did not differ between groups . In the FENO group , hyperresponsiveness improved more than in the symptom group ( 2.5 vs. 1.1 doubling dose , p=0.04 ) . FEV1 in the FENO group improved , and the change in FEV1 was not significantly different between groups . The FENO group had 8 severe exacerbations versus 18 in the symptom group . The change in symptom scores did not differ between groups . FENO increased in the symptom group ; the change in FENO from baseline differed between groups ( p=0.02 ) . CONCLUSION In children with asthma , 1 year of steroid titration on FENO did not result in higher steroid doses and did improve airway hyperresponsiveness and inflammation BACKGROUND Asthma is a disease of chronic inflammation and bronchoconstriction . Inhaled corticosteroids ( ICSs ) provide important anti-inflammatory treatment but may not provide optimal control of asthma when taken alone . Two therapeutic alternatives for enhanced asthma control are to substitute the combination of fluticasone propionate ( FP ) and salmeterol ( FP/Salm Combo ) through the Diskus inhaler or to add montelukast to existing ICS therapy . OBJECTIVE We compared the efficacy and safety of FP/Salm Combo through the Diskus inhaler versus montelukast added to FP ( FP + montelukast ) in patients whose symptoms were suboptimally controlled with ICS therapy . METHODS We performed a multicenter , double-blind , double-dummy , parallel-group , 12-week study in 447 patients with asthma who were symptomatic at baseline while receiving low-dose FP .  Patients were treated for 12 weeks with one of the following : ( 1 ) combination of FP 100 microg plus salmeterol 50 microg twice daily through the Diskus inhaler , or ( 2 ) FP 100 microg twice daily through the Diskus inhaler plus oral montelukast 10 mg once daily . RESULTS FP/Salm Combo treatment provided better overall asthma control than FP + montelukast with significantly greater improvements in morning peak expiratory flow ( + 24.9 L/min vs + 13.0 L/min , P < .001 ) , evening peak expiratory flow ( + 18.9 L/min vs + 9.6 L/min , P < .001 ) , and forced expiratory volume in 1 second ( + 0.34 L vs + 0.20 L , P < .001 ) , as well as a change in the percentage of days with no albuterol use ( + 26.3 % vs + 19.1 % , P = .032 ) and the shortness of breath symptom score ( -0.56 vs -0.40 , P = .017 ) . The groups had comparable improvements in chest tightness , wheeze , and overall symptom scores . Asthma exacerbation rates were significantly lower ( P = .031 ) in the FP/Salm Combo group ( 4 patients , 2 % ) than in the FP + montelukast group ( 13 patients , 6 % ) . Adverse event profiles were comparable . CONCLUSION Symptomatic patients on low-dose ICS therapy had significantly greater improvement in asthma control when switched to the FP/Salm Combo than when montelukast was added to ICS therapy BACKGROUND Inhaled corticosteroids ( ICSs ) are widely used in combination with other classes of drugs for treatment of childhood asthma . The efficacy and the safety of montelukast added to low-dose ICS therapy were compared with those of sustained-release theophylline added to low-dose ICS therapy in asthmatic children in the present study . METHODS Following the 2-week run-in period , 6-to 14-year old patients receiving treatment with ICSs  were r and omized to treatment for 4 weeks with either montelukast 5 mg once daily or sustained release theophylline 5 - 8 mg/kg ( dry syrup ) or 100 - 200 mg ( tablet ) twice daily . Patients also received a fixed dose of ICS throughout the run-in and treatment periods . The primary efficacy endpoint was the change from baseline in peak expiratory flow ( PEF ) at Week 2 . RESULTS A significant increase in morning PEF was observed in the add-on montelukast group as compared with the add-on theophylline group at Week 2 ( change from baseline of 22.8 L/minvs . 8.7 L/min ; p = 0.041 for between-group difference ) and at Week 4 ( 31.0 L/minvs . 9.8 L/min ; p = 0.012 ) . A significant increase in evening PEF was observed in the add-on montelukast group as compared with the add-on theophylline group at Week 4 ( 24.7 L/minvs . 8.7 L/min ; p = 0.027 ) . There were no significant differences between the treatment groups in incidences of clinical and laboratory adverse experiences . CONCLUSIONS The results indicate that montelukast added to low-dose ICS is an effective and safe option for the treatment of asthma in children Background Patients at risk of severe exacerbations contribute disproportionally to  asthma mortality , morbidity and costs . We evaluated the effectiveness and costs of using ‘ asthma risk registers ’ for these patients in primary care . Methods In a cluster-r and omised trial , 29 primary care practice s identified 911 at-risk asthma patients using British asthma guideline criteria ( severe asthma plus adverse psychosocial characteristics ) . Intervention practice s added electronic alerts to identified patients ' records to flag their at-risk status and received practice -based training about using the alerts to improve patient access and opportunistic management . Control practice s continued routine care . Numbers of patients experiencing the primary outcome of a moderate-severe exacerbation ( result ing in death , hospitalisation , accident and emergency attendance , out-of-hours contact , or a course/boost in oral prednisolone for asthma ) , other healthcare and medication usage , and costs over 1 year were derived from practice -based records . Results There was no significant effect on exacerbations ( control : 46.5 % ; intervention : 53.6 % , OR , 95 % CI 1.30 , 0.93 to 1.80 ) . However , this composite outcome masked relative reductions in intervention patients experiencing hospitalisations ( OR 0.50 , 95 % CI 0.26 to 0.94 ) , accident and emergency ( OR 0.74 , 95 % CI 0.42 to 1.31 ) and out-of-hours contacts ( OR 0.79 , 95 % CI 0.45 to 1.37 ) ; and a relative increase in prednisolone prescription for exacerbations ( OR 1.31 , 95 % CI 0.92 to 1.85 ) . Furthermore , prescription of nebulised short-acting β-agonists reduced and long-acting β-agonists increased for intervention relative to control patients . The adjusted mean per patient healthcare cost was £ 138.21 lower ( p=0.837 ) among intervention practice s. Conclusion Using asthma risk registers in primary care did not reduce treated exacerbations , but reduced hospitalisations and increased prescriptions of recommended preventative therapies without increasing costs BACKGROUND Because of potential toxicities of inhaled corticosteroid ( ICS ) use in pediatric asthma , alternative or steroid-sparing therapy is desirable . There are no previous studies evaluating montelukast 's  steroid-sparing effects in children with asthma . OBJECTIVE To evaluate whether ( 1 ) montelukast as add-on therapy improves asthma symptom control and ( 2 ) montelukast provides steroid-sparing effects in children with asthma treated with low to moderate doses of ICS therapy . METHODS In a double-blind , placebo-controlled trial , 36 children ages 6 to 14 years with symptomatic asthma maintained on a stable low to moderate dose of ICSs  were r and omly assigned to receive montelukast or matching placebo for 24 weeks after a run-in period of 2 weeks ( period I ) . During the trial , subjects kept daily asthma diary cards and monthly spirometry was performed . After a 4 week add-on period ( period II ) , the subjects completed a 20-week ( period III ) ICS tapering period based on a predetermined protocol . RESULTS In period II , the difference in the number of rescue-free days was significantly higher in the montelukast group ( P = 0.0001 ) , and the number of rescue-free days per week was also significantly higher in montelukast-treated subjects compared with placebo subjects ( P = 0.002 ) . In period III , the percentage reduction in ICS dose was not significant between montelukast and placebo ( P = 0.10 ) , but the montelukast group experienced an average 17 % decrease in ICS dose and the control group experienced an average 64 % increase in ICS dose . CONCLUSIONS Montelukast treatment significantly increased the number of rescue-free days in symptomatic children with asthma BACKGROUND Budesonide and sodium cromoglycate are both recommended as maintenance therapy for childhood asthma . OBJECTIVE To compare the cost-effectiveness of these two treatment strategies in clinical practice , in an open-label , pharmacoeconomic clinical trial . METHODS Health economics were evaluated in 138 children , ages 5 to 11 years , with unstable asthma not previously treated with corticosteroids or cromones . The asthma was stabilized during 4 to 6 weeks with budesonide 200 to 400 microg twice daily . The children were then r and omly allocated to one of the two treatment strategies aim ing at maintaining asthma control for 12 months ; budesonide 400 microg/day ( N = 69 ) or sodium cromoglycate 60 mg/day ( N = 69 ) . If asthma control was judged unsatisfactory , the doses were increased or the children were switched to the alternate treatment . RESULTS In children continuing on the same treatment , the degree of asthma control was similar in the two groups at study end . To maintain asthma control , 42 % of cromoglycate children switched to budesonide , and then experienced a 14 % increase in symptom-free days . No budesonide patient had to switch therapy because of lack of asthma control . Although not statistically significant , total annual cost per patient was 24 % ( Swedish kronor 4195 ; US $ 487 ; Euro 485 ) lower in the budesonide than the cromoglycate group , mainly due to a lower cost for asthma medication . CONCLUSIONS A budesonide strategy for continued maintenance treatment , after an initial period of stabilizing treatment with budesonide , result ed in lower costs and less drug switches than did a strategy with sodium cromoglycate OBJECTIVE To compare the long-term effect of treatment with fluticasone propionate or beclomethasone dipropionate on growth in asthmatic children . DESIGN Prospect i ve , multicenter , r and omized , double-blind , parallel-group study . SETTING Children requiring regular treatment with inhaled corticosteroids and with a sexual maturity rating of Tanner stage 1 ( prepubertal ) . PATIENTS Three hundred forty-three children aged 4 to 11 years with asthma . The growth population ( excluding patients with protocol violations likely to affect growth measurements ) included 277 patients . INTERVENTIONS Fluticasone propionate or beclomethasone dipropionate , both at a dosage of 200 microg administered twice daily via a dry powder inhaler ( Diskhaler ) for 12 months . MAIN OUTCOME MEASURES Growth velocity , lung function , and serum and urinary cortisol levels . RESULTS The adjusted mean growth velocity in the fluticasone group was significantly greater than that in the beclomethasone group ( 5.01 [ SE , 0.14 ] vs 4.10 [ SE , 0.15 ] cm/y ; difference , 0.91 cm ; 95 % confidence interval , 0.63 - 1.20 cm ; P<.001 ) . Both treatments improved lung function , with significant differences in favor of fluticasone .  Adverse events were similar in both groups , and there were no significant differences in effect on serum and urinary cortisol levels . CONCLUSIONS The more favorable risk-benefit ratio of fluticasone indicates that this agent is preferable to beclomethasone for the long-term treatment of children with asthma , especially if moderate doses are required STUDY OBJECTIVES To evaluate the effect of adding zafirlukast or low-dose theophylline to a beclomethasone dipropionate ( BDP ) extra-fine hydrofluoroalkane aerosol on bronchial hyperresponsiveness as the primary outcome variable . METHODS Twenty-four patients with mild-to-moderate asthma were studied using a r and omized crossover design with the following three treatment blocks : ( 1 ) beclomethasone , 100 microg/d , alone for the first 2 weeks followed by 400 microg/d alone for the next 2 weeks ; ( 2 ) beclomethasone , 100 microg/d , followed by 400 microg/d , with the addition of zafirlukast , 20 mg bid ; ( 3 ) beclomethasone , 100 microg/d , followed by 400 microg/d , with the addition of theophylline , 200 to 300 mg bid . Measurements were made after 2 and 4 weeks of each treatment and at pretreatment baseline . RESULTS The mean trough plasma theophylline concentration was 6.7 mg/L , coinciding with the anti-inflammatory target range ( ie , 5 to 10 mg/L ) . The provocative dose of methacholine causing a 20 % fall in FEV(1 ) ( as doubling dose difference from baseline ) was significantly ( p < 0.05 ) greater with beclomethasone , 100 microg , plus zafirlukast ( 1.1 doubling dose ) but not with beclomethasone , 100 microg , plus theophylline ( 0.7 doubling dose ) compared to beclomethasone , 100 microg alone ( 0.4 doubling dose ) , but not compared to beclomethasone , 400 microg alone ( 1.1 doubling dose ) . There were also significant ( p < 0.05 ) differences between beclomethasone , 100 microg , plus zafirlukast ( but not BDP , 100 microg , plus theophylline ) vs beclomethasone , 100 microg , alone in terms of nitric oxide level , midexpiratory phase of forced expiratory flow , and peak expiratory flow . There were no further significant improvements observed with the addition of zafirlukast or theophylline to beclomethasone , 400 microg . CONCLUSIONS A leukotriene receptor antagonist , but not low-dose theophylline , conferred significant additive anti-inflammatory effects to therapy with a low-dose inhaled corticosteroid but not to that with a medium dose of an inhaled corticosteroid . Thus , optimizing the dose of inhaled corticosteroid as monotherapy would seem to be the logical first step , which is in keeping with current guidelines BACKGROUND Exercise-induced bronchoconstriction occurs in a large proportion of children with asthma , limiting everyday activities important for their physical and social development . OBJECTIVE The purpose of this r and omized , double-blind , placebo-controlled study was to compare the ability of different patterns of antiasthmatic treatment , recommended in childhood asthma , to protect patients from exercise-induced bronchoconstriction . METHODS Children 6 to 18 years of age with atopic asthma were r and omized to a 4-week , placebo-controlled , double-blind trial . Patients were r and omly allocated to receive daily 200 microg budesonide ( twice daily , 100 microg per dose ) + 9 microg formoterol ( twice daily , 4.5 microg per dose ; n = 20 ) ; 200 microg budesonide + 5 or 10 mg montelukast ( once daily at bedtime ; n = 20 ) ; 5 or 10 mg montelukast ( n = 20 ) ; 200 microg budesonide ( n = 20 ) ; or placebo ( n = 20 ) . A st and ardized treadmill exercise challenge was performed before and after treatment . RESULTS Exercise-induced bronchoconstriction , reflected by area under the curve for the FEV1 values from exercise over the 20-minute period and by maximum percent fall in FEV1 after exercise , was significantly diminished after 4 weeks in all active treatment groups , and compared with placebo . Exercise-induced bronchoconstriction protection improved more significantly in the budesonide + montelukast and montelukast groups compared with other therapeutic options . CONCLUSION These data indicate differences in effects on exercise-induced bronchoconstriction between therapeutic options recommended in childhood asthma . Control of childhood asthma with exercise-induced bronchoconstriction can be obtained by using regular controller treatment BACKGROUND No studies have directly compared the effects of immunotherapy and antileukotrienes due to the long time required to appreciate the clinical effects of immunotherapy . We compared the effect of montelukast ( MK ) and SLIT added to st and ard therapy in moderate asthma over 5 years . METHODS Open r and omized controlled trial . Patients with moderate asthma ( and rhinitis ) solely due to birch pollen were r and omized to receive either MK ( 10 mg/d ) or birch sublingual immunotherapy ( SLIT ) in the pollen seasons , in addition to formoterol/fluticasone . All the patients also received salbutamol and cetirizine as rescue medications . Asthma and rhinitis symptoms were recorded on diary cards from February to May at baseline and after 3 and 5 years of study . In-season nasal eosinophils and bronchial hyperresponsiveness were also evaluated . RESULTS Thirty-three adult patients were enrolled and 29 completed the study . The groups were homogeneous at baseline . Bronchial and nasal symptom scores were lower at 3 and 5 years compared to baseline in the SLIT group . Bronchial hyperresponsiveness and bronchodilator use decreased significantly in both groups at 5 years , but only in the SLIT group at 3 years . In the SLIT group there was a significant decrease in nasal eosinophils compared to baseline and to the MK group . CONCLUSION In patients with birch pollen-induced moderate asthma and rhinitis , the addition of SLIT provides a greater clinical benefit than that of MK Sputum eosinophilia is a sensitive predictor of benefit from corticosteroid treatment . Montelukast is a cysteinyl leukotriene antagonist , which also reduces sputum and blood eosinophils . The present study examined the possibility that montelukast has an added eosinophil-lowering effect in subjects with asthma who are corticosteroid responsive but relatively corticosteroid resistant . A total of 14 clinical ly stable adults with asthma requiring minimum treatment with a high-dose inhaled steroid or prednisone , with baseline sputum eosinophilia ( ≥5 % ) , were r and omised to receive 4 weeks of 10 mg montelukast or placebo daily in a double-blind crossover trial . The primary outcome was the effect of treatment on the percentage of sputum eosinophils . Secondary outcomes were changes in the blood eosinophil count , symptoms , forced expiratory volume in one second , peak expiratory flow and the need for salbutamol . The median ( interquartile range , i.e. 75th–25th centile ) for sputum eosinophils at baseline was 15.7 % ( 22 ) . The effect of adding montelukast was not significantly different from that of placebo , sputum eosinophils being 9.3 % ( 18.9 ) after montelukast and 11.3 % ( 22.8 ) after placebo . No difference was detected on secondary outcomes . No crossover interactions were observed . In conclusion , the addition of montelukast to existing high-dose corticosteroid therapy in subjects with asthma with elevated sputum eosinophils does not provide additional attenuation of airway eosinophilia Some children with severe asthma develop frequent exacerbations despite intensive treatment . We sought to assess the outcome ( severe exacerbations and healthcare use , lung function , quality of life and maintenance treatment ) of a strategy based on daily home spirometry with teletransmission to an expert medical centre and whether it differs from that of a conventional strategy . 50 children with severe uncontrolled asthma were enrolled in a 12-month prospect i ve study and were r and omised into two groups : 1 ) treatment managed with daily home spirometry and medical feedback ( HM ) and 2 ) conventional treatment ( CT ) .  The children ’s mean age was 10.9 yrs ( 95 % confidence interval 10.2–11.6 ) . 44 children completed the study ( 21 in the HM group and 23 in the CT group ) . The median number of severe exacerbations per patient was 2.0 ( interquartile range 1.0–4.0 ) in the HM group and 3.0 ( 1.0–4.0 ) in the CT group ( p=0.38 with adjustment for age ) . There were no significant differences between the two groups for unscheduled visits ( HM 5.0 ( 3.0–7.0 ) , CT 3.0 ( 2.0–7.0 ) ; p=0.30 ) , lung function ( pre-&bgr;2-agonist forced expiratory volume in 1 s ( FEV1 ) p=0.13 ) , Paediatric Asthma Quality of Life Question naire scores ( p=0.61 ) and median daily dose of inhaled corticosteroids ( p=0.86 ) . A treatment strategy based on daily FEV1 monitoring with medical feedback did not reduce severe asthma exacerbations The aim of this prospect i ve , self-controlled , single-blind study was to assess the effect of montelukast added to maintenance therapy with inhaled corticosteroids ( ICS ) on fractional exhaled nitric oxide ( FENO ) in asthmatic children . Thirty-five children ( age 11.2±0.4 yrs ( mean±sem ) ) with mild-to-moderate persistent asthma treated with low to medium doses of ICS and FENO>20 parts per billion ( ppb ) were included . The patients were r and omly assigned to two groups : 17 patients continued ICS ( group C ) and 18 had montelukast added to ICS for 3 weeks ( group M ) . FENO measurements were performed in both groups at baseline ( T1 ) and after 3 weeks ( T2 ) , and in group M also after 2 weeks of washout . FENO was measured by a chemiluminescence analyser using an on-line method ( 50 mL·s−1 ) with nitric oxide-free air . The overall mean daily dose of ICS was equivalent to 530±58 µg·day−1 of beclomethasone in group M and to 564±55 µg·day−1 of beclomethasone in group C. There were no significant differences in baseline FENO and forced expiratory volume in one second ( FEV1 ) between the two groups . After 3 weeks there was a significant reduction of FENO values in patients of group M ( T1 52.2±7.8 ppb , T2 36.1±4.6 ppb ) but no significant changes in group C ( T1 43.5±6.0 ppb , T2 47.8±9.4 ppb ) . In group M after 2 weeks of montelukast  withdrawal , FENO rose to baseline values ( 55.6±8.7 ppb ) . In conclusion , after montelukast treatment there is a fractional exhaled nitric oxide reduction in asthmatic children receiving maintenance therapy with inhaled corticosteroids . This suggests an anti-inflammatory effect of montelukast additive to that of inhaled corticosteroids Background . Upper respiratory tract infections ( URIs ) represent the most frequent cause of acute asthma exacerbation .  Systemic corticosteroid ( CS ) is presently recommended for URI-induced asthma exacerbation , although it might inhibit cellular immunity against respiratory virus infection . Objectives . To determine the effects of adding a short course ( 2 weeks ) of a leukotriene receptor antagonist ( LTRA ) to systemic CS on URI-induced acute asthma exacerbation . Methods . Twenty-three adult asthmatics ( mean age , 42.8 ± 9.8 y ; Male : Female , 10:13 ) with URI-induced acute asthma exacerbation confirmed by a question naire and physical findings were r and omly assigned to receive either oral prednisolone ( PSL ) alone or oral PSL plus the LTRA pranlukast ( PRL ) for 2 weeks ( PSL + PRL ) . The cumulative doses of PSL and the amount of time required to clear asthma-related symptoms were determined . Levels of respiratory syncytial virus ( RSV ) RNA and influenza viral ( IV ) antigen in nasopharyngeal swabs were also determined . Results . Adding PRL significantly reduced the cumulative dose of PSL  and tended to reduce the time required to clear asthma-related symptoms . Either RSV or IV was detected in about one-third of the patients . Conclusion . The combination of an LTRA and CS might be more useful than CS alone for treating URI-induced acute exacerbation of asthma and reducing the cumulative CS dose Lung function is commonly used as the primary endpoint in asthma clinical trials , but it may not reflect changes which are important to patients . The present study compared changes in , and relationships between , traditional and patient-centred end-points during treatment with three classes of asthma medication . Subjects with mild-to-moderate asthma were r and omised to double-blind , double-dummy crossover treatment with eformoterol 12 µg b.i.d . or montelukast 10 mg q.d . , then single-blind treatment with fluticasone 250 µg b.i.d./placebo capsules , with 6-week treatment periods and 1-week washouts .  Individual “ traditional ” end-points ( symptoms , reliever use , forced expiratory volume in one second per cent predicted , morning peak expiratory flow , airway hyperresponsiveness ) and “ patient-centred ” end-points ( asthma control question naire , quality of life , patient global assessment s ) were assessed . Principal component analysis and linear modelling were used to explore overall rank orders for treatment , and relationships between outcomes . A total of 58 subjects were r and omised . The rank order of benefit from eformoterol and fluticasone differed for three factors derived from principal component analysis ( eformoterol > fluticasone for symptom/reliever use factor , fluticasone > eformoterol for lung function factor , eformoterol = fluticasone for patient-centred factor ) . Montelukast was ranked third for all three factors . A significant relationship between patient-based variables and lung function was found only for montelukast treatment . In asthma treatment , traditional end-points do not fully capture patient-centred benefits , and the relationship between end-points differs with medication class BACKGROUND Apoptosis may be important in limiting airway eosinophilia . Treatment with leukotriene antagonists decreases the number of eosinophils in both peripheral blood and sputum . AIM To assess the effect of montelukast on eosinophil apoptosis in a group of patients with mild persistent asthma ( MPA ) and to compare this effect with the apoptotic effect of fluticasone propionate ( FP ) . METHODS R and omly selected patients with MPA ( n = 22 ) who had not taken anti-inflammatory therapy within the preceding 12 months were included in the study . The sputum induction procedure was performed and the patients were divided into two groups : group 1 ( n = 10 ) received FP 250 microg/day and group 2 ( n = 22 ) received montelukast 10 mg/day orally for 4 weeks . Sputum induction was repeated after the treatment period . The result ing cytospin slides were stained by Wright 's stain and morphologic changes in apoptotic eosinophils were assessed by the use of light microscopy by two blinded expert pathologists . Serum soluble Fas lig and ( sFasL ) concentrations were measured by an ELISA method at baseline and after treatment in both groups , as well as in a group of healthy subjects . RESULTS In within-group comparisons , the apoptotic ratio ( AR ) increased at the end of the study period in group 1 ( p = 0.05 ) . In the group treated with FP the ratio of sputum eosinophils significantly decreased ( p = 0.02 ) , and the AR significantly increased ( p < 0.005 ) . No differences were found in the two study groups in serum sFasL levels at the end of the treatment period compared with baseline values ( p > 0.05 ) . CONCLUSION Our findings demonstrate that 4 weeks ' treatment with a CysLT receptor antagonist ( montelukast ) result ed in an increase in eosinophil apoptosis comparable to that produced by FP , suggesting that induction of apoptosis may be a potential mechanism for the mode of action of CysLT receptor antagonists in asthma BACKGROUND In 2010 , the Canadian Thoracic Society ( CTS ) published a Consensus Summary for the diagnosis and management of asthma in children six years of age and older , and adults , including an up date d Asthma Management Continuum . The CTS Asthma Clinical Assembly subsequently began a formal clinical practice guideline up date process , focusing , in this first iteration , on topics of controversy and ⁄or gaps in the previous guidelines . METHODS Four clinical questions were identified as a focus for the up date d guideline : the role of noninvasive measurements of airway inflammation for the adjustment of anti-inflammatory therapy ; the initiation of adjunct therapy to inhaled corticosteroids ( ICS ) for uncontrolled asthma ; the role of a single inhaler of an ICS⁄long-acting beta(2)-agonist combination as a reliever , and as a reliever and a controller ; and the escalation of controller medication for acute loss of asthma control as part of a self-management action plan . The expert panel followed an adaptation process to identify and appraise existing guidelines on the specified topics . In addition , literature search es were performed to identify relevant systematic review s and r and omized controlled trials . The panel formally assessed and grade d the evidence , and made 34 recommendations . RESULTS The up date d guideline recommendations outline a role for inclusion of assessment of sputum eosinophils , in addition to st and ard measures of asthma control , to guide adjustment of controller therapy in adults with moderate to severe asthma . Appraisal of the evidence regarding which adjunct controller therapy to add to ICS and at what ICS dose to begin adjunct therapy in children and adults with poor asthma control supported the 2010 CTS Consensus Summary recommendations . New recommendations for the adjustment of controller medication within written action plans are provided . Finally , priority areas for future research were identified . CONCLUSIONS The present clinical practice guideline is the first up date of the CTS Asthma Guidelines following the Canadian Respiratory Guidelines Committee 's new guideline development process . Tools and strategies to support guideline implementation will be developed and the CTS will continue to regularly provide up date s reflecting new evidence Previous adult studies demonstrated the clinical efficacy of an additional treatment with leukotriene receptor antagonists on steroid-dependent asthma , but there is little knowledge about anti-inflammatory add-on effects within the lung . In this study , we hypothesized that steroid-treated children exhibit a decrease in bronchial inflammation in induced sputum under additional treatment with montelukast .  Twenty-five asthmatic children aged 6 to 14 y , who had been taking inhaled corticosteroids ( 400–800 μg/d budesonide ) regularly for at least 12 wk , were r and omized to receive additional treatment with either montelukast ( 5 mg orally , once daily ) or placebo over a 4-wk period . As primary efficacy variable , eosinophil cationic protein ( ECP ) in induced sputum as direct measurement of bronchial inflammation was assessed before and after treatment . To assure a baseline level of inflammation , an ECP concentration above 100 μg/L was required . Sputum eosinophil count , concentration of exhaled nitric oxide , urinary excretion of eosinophil protein X , and quality -of-life items were considered as secondary outcome variables . After treatment with montelukast  , ECP in sputum was significantly reduced  ( montelukast : median −975 μg/L [ 5 to 95 % confidence interval : −4295 to 583 μg/L ] ; placebo : 561 μg/L [ −1335 to 3320 μg/L ] ; p < 0.01 ) and the quality -of-life score had significantly improved ( p < 0.05 ) compared with placebo . Partly explained by low baseline levels , no statistically significant change in concentration of exhaled nitric oxide ( p > 0.05 ) , urinary excretion of eosinophil protein X ( p > 0.05 ) , or eosinophil count ( p > 0.05 ) was found . In conclusion , add-on treatment with montelukast can suppress sputum ECP in children with steroid-dependent asthma , while at the same time an improvement in quality of life items occurs Background . Severe asthma remains a worldwide medical problem . However , this disease has not been adequately explored in the elderly . This study was performed to determine how the addition of montelukast to antiasthmatic therapy improves the control of severe asthma in elderly patients . Methods . Elderly patients ( > 60 years old ) with diagnoses of severe asthma were observed over 24 months of therapy : the first 12 months using inhaled corticosteroids ( ICS ) and long-acting beta-agonists ( LABA ) and the second 12 months with oral montelukast added in two-thirds of the patients , with the remaining third representing the control group . The primary efficacy endpoint of the study was the percentage of days without asthma symptoms in the first 12 months of treatment compared with the percentage after adding montelukast therapy . Results . A total of 512 elderly , asthmatic patients were included in the study : seventy-one ( 13.9 % ) patients had well-controlled asthma , 211 ( 41.2 % ) had partly controlled asthma , and 230 ( 44.9 % ) had uncontrolled asthma . During the first year of treatment using ICS and LABA , an increase in the median percentage of days without asthma was observed from 50.1 % to 62.1 % , as well as a decrease in the percentage of days with short beta-receptor agonist use , from 52.2 % to 46.8 % . These differences were significantly greater after 12 months , when montelukast was added to the therapy ( 78.4 % and 39.5 % , respectively ) . This improvement was not observed in the control group . After 2 years of observation , the median number of asthma exacerbation incidents per patient decreased from 1.6 per year to 1.2 per year when montelukast was added . Conclusion . Severe asthma in elderly patients is very poorly treated , with this population exhibiting very low compliance with antiasthmatic therapy . Adding montelukast provides benefits and improved control ; however , it does not resolve severe asthma control problems BACKGROUND Although current guidelines suggest the use of inhaled corticosteroids as the first line therapy in persistent asthma , the concerns about high-dose corticosteroids may limit their usage . We aim ed to investigate the efficacy of inhaled budesonide plus oral montelukast versus a double dose of inhaled budesonide . METHODOLOGY Thirty patients with moderate asthma took part in the study . Following a 2-week run in period , the patients were r and omized into two groups to receive 400 microg/day of inhaled budesonide plus 10 mg/day of montelukast ( BUD + M group ) or 800 microg/day of inhaled budesonide ( high BUD group ) . The patients were evaluated at 2-week intervals ( during a total treatment period of 6 weeks ) for symptom scores , asthma exacerbations , lung function , use of short-acting beta2 agonist , blood eosinophil counts and adverse events . RESULTS At the end of the study , morning and daytime symptom scores were significantly reduced within the groups . Although there was a significant decrease in the frequency of short-acting beta2 agonist use in the BUD + M group , the decrease in the high BUD group was not significant . During the study period , no patient in either group experienced an asthma exacerbation . Blood eosinophil levels significantly declined in both the BUD + M ( 0.87 + /- 0.31 % ) and high BUD groups ( 0.67 + /- 0.29 % ) as compared with baseline levels ( BUD + M = 2.60 + /- 0.65 % , high BUD group = 2.60 + /- 0.47 % ; P < 0.05 ) . CONCLUSION Our results suggest that the addition of montelukast to low-dose inhaled budesonide is as effective as a double dose of inhaled budesonide in asthma control BACKGROUND Pediatric asthma hospitalizations peak in early autumn . OBJECTIVE To determine the effectiveness of montelukast therapy in reducing the asthma burden in children when initiated prophylactically on school return . METHODS This was a r and omized , multicenter , double-blind , placebo-controlled study of children with asthma aged 6 to 14 years . No minimum asthma symptoms were required , and patients could continue inhaled corticosteroid ( ICS ) use . Montelukast , 5 mg , chewable tablet ( n = 580 ) or matching placebo ( n = 582 ) was taken the night before the first day of school and nightly thereafter for 8 weeks . The primary end point was the percentage of days with worsening asthma , defined by one of the following : ( 1 ) increased beta-agonist use , ( 2 ) increased daytime symptoms , ( 3 ) awake " all night , " ( 4 ) oral corticosteroid rescue or increased ICS use for worsening asthma , or ( 5 ) unanticipated health care utilization . RESULTS The reduction in the percentage of days with worsening asthma with montelukast use versus placebo use was not significant ( 24.3 % vs 27.2 % , P = .07 ) . Prespecified subgroup analyses demonstrated nonsignificant trends favoring montelukast therapy in boys and older children but no effect by baseline ICS use or history of cold symptoms . Post hoc analysis showed a nonsignificant trend favoring montelukast therapy in reducing worsening asthma days for children commencing school after August 15 compared with earlier commencement . CONCLUSIONS Montelukast use was not significantly more effective than was placebo use in reducing the percentage of days with worsening asthma when initiated at the start of the school year . The effect of montelukast treatment on the fall peak in asthma burden may depend on sex , age , and the date of school return BACKGROUND Pulmonary function tests ( PFTs ) and especially spirometry measures are useful tools in evaluating early response to treatment of asthma in children mainly due to their worldwide availability . The aim of our study was to determine the effects of anti-asthma treatment in children , equally on FEV(1 ) , FEF25 - 75 % , R(int ) and SR(aw ) values . METHODS Children 6 - 18 years of age with moderate atopic asthma were r and omized to 4-week , placebo-controlled , double-blind trial . Patients were r and omly allocated to receive 200 microg budesonide ( B ) ( n=29 ) , 5 or 10 mg ( according to age ) montelukast ( M ) ( n=29 ) , 200 microg B + 5 or 10 mg M ( n=29 ) , 200 microg B + 9 microg formoterol ( F ) ( n=29 ) or placebo ( n=27 ) . FEV(1 , ) FEF25 - 75 % , R(int ) , SR(aw ) were measured before and after treatment . RESULTS R(int ) , SR(aw ) , FEV(1 ) improved significantly in all active treatment groups while FEF25 - 75 % improved significantly only in BM group and M group . Combination therapy , showed significantly greater effects on R(int ) than monotherapy : BM group compared to B group ( P=0.01 ) and M group ( P=0.03 ) and BF group compared to B group ( P=0.01 ) and M group ( P=0.04 ) . CONCLUSION This study shows that using single parameter for monitoring asthma can be misleading . Using combination of lung function techniques provides better assessment of treatment . Results of our study confirm this hypothesis . The best effect on large and small airways was achieved with combined anti-inflammatory therapy Background : Montelukast has been shown to be effective in controlling the increase in exhaled NO in asthmatic children re‐exposed to house dust mite ( HDM ) . This study compared the effect of low dose inhaled budesonide and oral montelukast in preventing the expected relapse of airway inflammation and reactivity in a group of 24 mild asthmatic children allergic to HDM after a brief period of exposure to relevant allergens OBJECTIVE To evaluate efficacy , safety , health outcomes , and cost-effectiveness of fluticasone propionate ( FP ) versus montelukast ( MON ) in 342 children ( 6 to 12 years of age ) with persistent asthma . STUDY DESIGN R and omized , double-blind , 12-week study of treatment with FP inhalation powder 50 mug twice daily or MON chewable 5 mg once daily for 12 weeks . RESULTS Compared with MON , FP significantly increased mean percent change from baseline FEV1 ( forced expiratory volume in 1 second ) ( P=.002 ) , morning PEF ( peak expiratory flow ) ( P=.004 ) , evening PEF ( P=.020 ) , and percent rescue-free days ( P=.002 ) at end point , and it significantly reduced nighttime symptom scores ( P < .001 ) and mean total ( P=.018 ) , and nighttime ( P < .001 ) albuterol use . Withdrawals from the study were more frequent with MON ( 21 % ) than with FP ( 13 % ) . Adverse events ( 69 % vs 71 % ) and mean end point to baseline 12-hour urinary cortisol excretion ratios were similar . Parents and physicians were more satisfied with FP treatment than with MON ( P=.006 and P=.016 , respectively , at Week 12 ) . Mean total daily asthma-related cost per patient in the FP group was approximately one-third of that in the MON group ( $ 1.25 vs $ 3.49 ) . CONCLUSION FP was significantly more effective than MON in improving pulmonary function , asthma symptoms , and rescue albuterol use . Both therapies had similar safety profiles . Parent- and physician-reported satisfaction ratings were higher with FP treatment , and asthma-related costs were lower BACKGROUND Acute wheezing illnesses in preschoolers require better management strategies to reduce morbidity . OBJECTIVES We sought to examine the effectiveness of episodic use of an inhaled corticosteroid and a leukotriene receptor antagonist in preschoolers with intermittent wheezing . METHODS In a r and omized , double-blind , placebo-controlled 12-month trial , 238 children aged 12 to 59 months with moderate-to-severe intermittent wheezing received 7 days of either budesonide inhalation suspension ( 1 mg twice daily ) , montelukast ( 4 mg daily ) , or placebo in addition to albuterol with each identified respiratory tract illness ( RTI ) . Proportion of episode-free days ( EFDs ) during the 12-month trial was the primary outcome . RESULTS The 3 treatment groups did not differ in proportions of EFDs , with adjusted mean EFDs of 76 % ( 95 % CI , 70 % to 81 % ) for budesonide , 73 % ( 95 % CI , 66 % to 79 % ) for montelukast , and 74 % ( 95 % CI , 65 % to 81 % ) for conventional therapy ( P = .66 ) . The 3 groups did not differ in oral corticosteroid use , health care use , quality of life , or linear growth . However , during RTIs , budesonide and montelukast therapy led to modest reductions in trouble breathing ( 38 % [ P = .003 ] and 37 % [ P = .003 ] , respectively ) and interference with activity scores ( 32 % [ P = .01 ] and 40 % [ P = .001 ] , respectively ) that were most evident in those with positive asthma predictive indices . CONCLUSIONS In preschool children with moderate-to-severe intermittent wheezing , episodic use of either budesonide or montelukast early in RTIs , when added to albuterol , did not increase the proportion of EFDs or decrease oral corticosteroid use over a 12-month period . However , indicators of severity of acute illnesses were reduced , particularly in children with positive asthma predictive indices Not all asthma can be adequately controlled , despite the use of high-dose inhaled corticosteroids . Because cysteinyl-leukotrienes ( Cys-LT ) have been implicated in the pathogenesis of asthma , we hypothesized that the leukotriene receptor antagonist zafirlukast , in combination with high-doses of inhaled corticosteroids , might be efficacious in severe asthma . In a double-blind , parallel group study , 368 chronic adult asthmatic patients treated with inhaled corticosteroids ( 1,000 to 4,000 microgram/d ) , who had a predefined level of asthma symptoms during the run in period of the study , were r and omly assigned to receive additional treatment with a high dose of zafirlukast ( 80 mg twice daily ) ( n = 180 ) or placebo ( n = 188 ) for 6 wk . Compared with placebo , zafirlukast produced a significant improvement over baseline in the primary study endpoint of mean morning peak expiratory flow rate ( PEFR ) ( 18.7 L/min versus 1.5 L/min , p < 0.001 ) , as well as in evening PEFR ( p < 0.01 ) , FEV(1 ) ( p < 0.05 ) , daytime symptom score ( p < 0.001 ) , and beta(2)-agonist use ( p < 0.001 ) . Furthermore , zafirlukast significantly reduced the risk of an exacerbation of asthma ( odds ratio [ OR ] : 0.61 ; 95 % confidence interval [ CI ] : 0.38 to 0.99 ) and the risk of patients requiring a further increase in asthma controller therapy ( OR : 0.4 ; 95 % CI : 0.2 to 0.8 ) . In conclusion , in patients taking high-dose inhaled corticosteroids , zafirlukast improves pulmonary function and asthma symptoms , and reduces the risk of an asthma exacerbation , suggesting that the contribution of leukotrienes to asthma symptoms and exacerbations is not adequately controlled by high-dose inhaled corticosteroids BACKGROUND The importance of airway inflammation has been highlighted in the pathophysiology of asthma . Even in controlled asthmatics treated with inhaled corticosteroid ( ICS ) , residual airway inflammation is reported . Systemic therapy with oral leukotriene receptor antagonist , pranlukast , may have additive effects to improve asthma control . METHODS Twenty-five controlled asthmatics treated with ICS or ICS plus long-acting β2-agonist ( LABA )  were enrolled for a r and omized crossover trial evaluating the effect of additional oral pranlukast . The patients were assigned to two groups receiving ICS ( + LABA ) or ICS ( + LABA ) + pranlukast for 8 weeks . After washout period , two groups were switched over for another 8 weeks . Fraction of exhaled nitric oxide ( FeNO ) , lung function tests , peak expiratory flow ( PEF ) and asthma control test ( ACT ) were evaluated at the beginning and end of each period . Central airway NO flux ( J'(awNO ) ) and peripheral airway/alveolar NO concentration ( C(ANO ) ) were measured and adjusted for axial NO back-diffusion . RESULTS FEV1 , % predicted , forced expired flow ( FEF ) ( 25 - 75 ) , % predicted , morning PEF and ACT were significantly increased after the addition of pranlukast . Oral pranlukast administration significantly decreased both C(ANO ) and corrected C(ANO ) . CONCLUSIONS The addition of oral pranlukast to ICS or ICS + LABA therapy may improve asthma control with reducing distal airway inflammation . TRIAL REGISTRATION UMIN 000003781 Fractional exhaled nitric oxide ( FeNO ) is elevated in asthma and reflects eosinophilic airway inflammation . The aim of this prospect i ve , r and omized , single-blind study was to examine whether the inclusion of repeated FeNO measurements into asthma monitoring leads to an improvement in asthma outcome . Forty-seven children with mild to moderate asthma were allocated to a FeNO group ( n = 22 ) and to a control group ( n = 25 ) . In the FeNO group therapy was based on symptoms ,  beta-agonist use , lung function , and FeNO whereas in the control group therapy was based on symptoms , beta-agonist use and lung function only . Patients performed five visits in 6 weeks intervals . Frequency of respiratory symptoms , beta-agonist use , FEV(1)% predicted and the frequency of exacerbations were similar between groups . Patients in the FeNO group received higher doses of inhaled corticosteroids ( ICS )  ( control group : median ( interquartile range ) : 241 microg ( 26 - 607 microg ) ; FeNo group : 316 microg ( 200 - 500 microg ) and had significantly higher MEF(50)% predicted ( control group : median ( interquartile range ) : 68.5 % ( 55.8 - 83.1 % ) ; FeNO group : 83.2 % ( 62.9%-98.3 % ) . At a cut-off point of 22.9 ppb FeNO the best predictive value for exacerbations with a sensitivity of 80 % and specificity of 60 % was found . Significant relationships were observed between FeNO and dose of ICS ( beta = -8.77 ; P < 0.002 ) , beta-agonist use 2 weeks prior to a visit ( beta = 0.11 ; P < 0.05 ) , asthma symptoms ( beta = 0.02 ; P < 0.0001 ) , and bronchial hyperresponsiveness ( beta = 0.04 ; P = 0.02 ) . In conclusion , FeNO was related to important markers of asthma control . A therapy regimen aim ed at lowering FeNO in children with asthma improved parameters of small airway function , but was not able to improve clinical markers of asthma control Background Levels of an immunoregulatory and anti‐inflammatory cytokine IL‐10 are reduced in asthmatic airways , potentially contributing to more intense inflammation . Triamcinolone has anti‐inflammatory properties and the anti‐inflammatory effects of montelukast and formoterol have been discussed Many patients with asthma remain symptomatic with impaired airway function on inhaled steroids . This study investigates the relationship between the clinical effect seen in response to additional treatment and the effect on airway inflammatory indices .  Seventy-five adult asthmatic patients , incompletely controlled on 800 mcg budesonide/day  , were r and omised following a 4 week run-in period , to a double-blind , multi-centre controlled clinical trial of doubling inhaled corticosteroid ( budesonide 1600 mcg/day ) or adding 10 mg montelukast for 12 weeks . Induced sputum was collected at baseline and end of treatment and analysed for eosinophil and neutrophil percentages , leukotrienes C4 , D4 and E4 , IL-8 , Eosinophil Cationic Protein ( ECP ) and histamine . Sputum evidence of inflammation ( 2.0 % eosinophils ) was seen in only 29 % of these patients and the percentage of eosinophils and other markers of airway inflammation did not change over the study period in either treatment group . There were significant improvements in am PEF ( montelukast : 31.7 L/min , budesonide : 32.3 L/min ) and quality of life with both treatments . We conclude that while both treatments showed similar improvements in lung function and quality of life , there was no evidence from these sputum markers measured that the effects were mediated via a reduction in airway inflammation or that the level of pre-treatment markers was associated with outcome OBJECTIVE To assess the addition of a leukotriene receptor antagonist and a long-acting beta(2)-agonist as second-line therapy in asthma . DESIGN Placebo-controlled , double-dummy , crossover study . SETTING Outpatient clinic . PATIENTS Twenty patients with persistent asthma not controlled with inhaled corticosteroid therapy . INTERVENTIONS Montelukast 10 mg once daily , or salmeterol , 50 microg bid , each for 2 weeks with 1-week run-in and washout placebo periods . MEASUREMENTS AND RESULTS Adenosine monophosphate ( AMP ) bronchial challenge , blood eosinophil count ( EOS ) , exhaled nitric oxide , and lung function after both placebo periods and after the first and last doses of each active treatment . Patients recorded their domiciliary peak expiratory flow ( PEF ) , asthma symptoms , and rescue bronchodilator requirement ( RES ) twice daily throughout the study . For the primary end point of the provocative concentration of AMP causing a 20 % fall in FEV(1 ) , compared to placebo ( 47.5 + /- 13.0 mg/mL ) , there were significant differences with the first ( 114.1 + /- 36.9 mg/mL ) and last ( 94.2 + /- 30.4 mg/mL ) doses of montelukast as well as the first ( 160.1 + /- 64.5 mg/mL ) but not the last ( 70.1 + /- 23.7 mg/mL ) dose of salmeterol . Only montelukast produced significant suppression of the EOS . Neither drug affected exhaled nitric oxide levels . There were significant improvements with the first doses of salmeterol for all parameters of lung function . After 2 weeks of treatment , there were significant improvements with both drugs for RES and morning PEF . There were no significant differences between drugs for any end points except EOS . CONCLUSIONS Montelukast and salmeterol exhibited significant improvements in asthma control when given as second-line therapy . Montelukast also produced significant effects on AMP challenge and EOS suggesting anti-inflammatory activity AIMS To determine effects on short term growth and collagen turnover of adding formoterol ( Eformoterol ) to half the glucocorticoid dose in children with asthma , treated with inhaled budesonide ( Pulmicort Turbuhaler ) . DESIGN A r and omised double blind , placebo controlled crossover study with two six-week periods . SETTING Outpatient clinic in secondary referral centre . SUBJECTS A total of 27 prepubertal children aged 6–13 years . INTERVENTIONS Formoterol 12 μg and dry powder budesonide 100 μg twice daily in one period ; placebo and dry powder budesonide 200 μg twice daily in the other . OUTCOME MEASURES Primary outcome measures were lower leg growth rate , and serum and urine markers of type I and type III collagen turnover . Secondary outcome measures were inflammation markers in serum , and parameters of asthma control . RESULTS During budesonide 200 μg twice daily treatment , mean lower leg growth rate was 0.14 mm/week ( p = 0.02 ) lower than during the formoterol and budesonide period . Similar statistically significant effects on markers of collagen turnover were found , whereas inflammation markers and asthma control did not vary statistically significantly between the two periods . CONCLUSIONS In children treated with inhaled glucocorticoids  , halving the dose and adding formoterol is associated with faster short term growth and an increase in markers of collagen turnover , with no loss of asthma control This study evaluated the superiority of combination therapy over steroid therapy alone by using clinical and laboratory data including interleukin (IL)-13 and interferon ( IFN ) gamma , which participate in the characteristic inflammation and have not been studied to evaluate the efficiency of asthma treatment sufficiently . Moderate persistent asthma patients , aged 7 - 17 years were included in the study . Patients were r and omized to three groups . Group 1 used inhaled budesonide , group 2 used inhaled budesonide plus inhaled formoterol fumarate , and group 3 used inhaled budesonide and oral montelukast sodium therapy . At the beginning and at the end of the 2nd month a detailed physical examination and clinical evaluation ; total IgE levels and total eosinophil count in peripheral venous blood , serum IL-13 , and IFN-gamma levels ; pulmonary function tests ; and an assessment question naire ( Pediatric Asthma Quality -of-Life Question naire with St and ardized Activities [ PAQLQ{S } ] were performed . Sixty-seven patients completed the study .  Serum IL-13 levels and PAQLQ(S ) scores before the therapy and serum IL-13 levels after the therapy were significantly different between the groups and other parameters did not show any significant differences . Serum IgE level was decreased after the therapy in group I and increased in groups 2 and 3 , but the difference was insignificant . In all groups total eosinophil levels were decreased insignificantly . After the therapy , IL-13 levels were decreased in groups 1 and 2 and increased in group 3 , but the difference was not statistically significant . When compared with the levels before the therapy IFN-gamma levels were decreased after the therapy but the difference was not statistically significant . When the improvement rates for IgE , total eosinophil , IL-13 , and IFN-gamma levels and each parameter of respiratory function tests were compared , there were no significant differences between the therapy groups . In all groups PAQLQ(S ) scores were significantly improved after the therapy . Our results showed that steroid and other agent combinations do not have any superiority to steroids only ; but according to pulmonary function tests and clinical indicators , all three therapy models are effective . These results suggested that the inhalation steroids , as the oldest agents , are still preserving their place and importance in asthma therapy Background : Inhaled corticosteroids ( ICS ) affect many inflammatory pathways in asthma but have little impact on cysteinyl leukotrienes . This may partly explain persistent airway inflammation during chronic ICS treatment and failure to achieve adequate asthma control in some patients . This double blind , r and omised , parallel group , non-inferiority , multicentre 16 week study compared the clinical benefits of adding montelukast to budesonide with doubling the budesonide dose in adults with asthma . Methods : After a 1 month single blind run in period , patients inadequately controlled on inhaled budesonide ( 800 μg/day ) were r and omised to receive montelukast 10 mg + inhaled budesonide 800 μg/day ( n=448 ) or budesonide 1600 μg/day ( n=441 ) for 12 weeks . Results : Both groups showed progressive improvement in several measures of asthma control compared with baseline . Mean morning peak expiratory flow ( AM PEF ) improved similarly in the last 10 weeks of treatment compared with baseline in both the montelukast + budesonide group and in the double dose budesonide group ( 33.5 v 30.1 l/min ) . During days 1–3 after start of treatment , the change in AM PEF from baseline was significantly greater in the montelukast + budesonide group than in the double dose budesonide group ( 20.1 v 9.6 l/min , p<0.001 ) , indicating faster onset of action in the montelukast group . Both groups showed similar improvements with respect to “ as needed ” β agonist use , mean daytime symptom score , nocturnal awakenings , exacerbations , asthma free days , peripheral eosinophil counts , and asthma specific quality of life .  Both montelukast + budesonide and double dose budesonide were generally well tolerated . Conclusion : The addition of montelukast to inhaled budesonide is an effective and well tolerated alternative to doubling the dose of inhaled budesonide in adult asthma patients experiencing symptoms and inadequate control on budesonide alone BACKGROUND Current guidelines advocate the use of preventative anti-inflammatory therapy for mild persistent asthma . OBJECTIVE We compared the efficacy and anti-inflammatory profiles of a leukotriene receptor antagonist and a low dose of inhaled corticosteroid in patients with mild persistent asthma . METHODS Twenty-one adult patients with mild asthma received 4 weeks of either once-daily inhaled hydrofluoroalkane triamcinolone acetonide ( 450 microg/day ex-actuator dose ) or oral montelukast ( 10 mg/day ) in a r and omized , placebo-controlled , single-blinded crossover study . Measurements were made before and after 2 and 4 weeks of each treatment . RESULTS At the endpoint ( after 4 weeks ) , triamcinolone and montelukast had improved the primary outcome ( provocative dose of methacholine required to produce a 20 % fall in FEV(1 ) ) in comparison with placebo ( P < .05 ) , there being no difference between the treatments ( 1.09-fold ; 95 % CI 0.73 to 1.63 ) . Triamcinolone was better than placebo or montelukast for effects on all other surrogate inflammatory markers ( P < .05 ) , including exhaled nitric oxide , blood eosinophils , serum eosinophil cationic protein , plasma intracellular circulating adhesion molecule 1 , and plasma E-selectin . Both treatments improved ( P < .05 ) morning and evening peak flow , nighttime beta2-agonist use , and symptoms in comparison with placebo , though triamcinolone was better than montelukast ( P < .05 ) with regard to peak flow . Triamcinolone produced suppression ( P < .05 ) of overnight urinary cortisol/creatinine and serum osteocalcin . CONCLUSION Once-daily inhaled corticosteroid and leukotriene antagonist improved the primary outcome variable of bronchial hyperresponsiveness to a similar degree BACKGROUND The anti-inflammatory effects of repeated dosing with mediator antagonists as add-on therapy to that with inhaled corticosteroids ( ICSs ) in patients with asthma remain to be fully established . OBJECTIVE We elected to evaluate the effects of repeated dosing with fexofenadine ( FEX ) and montelukast ( ML ) at clinical ly recommended doses in ICS-treated asthmatic patients using adenosine monophosphate ( AMP ) bronchial challenge as the primary outcome . METHODS Eighteen atopic asthmatic patients receiving a mean ( + /- SEM ) dose of 631 + /- 104 micro g daily of ICSs , which remained unchanged throughout the entire study , were r and omized in double-blind , cross-over fashion to receive FEX , 180 mg , ML , 10 mg , or placebo ( PL ) for 1 week . There was a 1-week washout period prior to each r and omized treatment . Measurements of the provocative concentration of a substance ( ie , AMP ) causing a 20 % fall in FEV(1 ) ( PC(20 ) ) were made after each washout period and r and omized treatment period . RESULTS The values for AMP PC(20 ) after the washout period prior to each r and omized treatment were not significantly different ( FEX , 74 + /- 15 mg/mL ; ML , 73 + /- 18 mg/mL ; PL , 71 + /- 19 mg/mL ) . There were significant improvements ( p < 0.05 ) in AMP PC(20 ) with the use of FEX ( 127 + /- 38 mg/mL ) and ML ( 121 + /- 27 mg/mL ) compared to PL ( 78 + /- 23 mg/mL ) . Spontaneous recovery after AMP challenge , as determined by area under the 60-min time-response curve , was significantly enhanced ( p < 0.05 ) with the use of ML ( 352 + /- 95%.min [ corrected ] ) compared to FEX ( 758 + /- 140%.min ) and PL ( 683 + /- 134%.min [ corrected ] ) . Both FEX and ML significantly suppressed ( p < 0.05 ) the levels of exhaled nitric oxide , while only ML significantly reduced ( p < 0.05 ) the peripheral blood eosinophil count compared to PL . Morning and evening peak expiratory flow were significantly higher ( p < 0.05 ) , and the frequency of salbutamol rescue was significantly reduced ( p < 0.05 ) with FEX and ML compared to PL . CONCLUSION Repeated dosing with FEX and ML as add-on therapy improved AMP PC(20 ) and other surrogate inflammatory markers along with asthma diary outcomes in ICS-treated atopic asthmatic patients . Further studies are indicated to evaluate the long-term add-on effects of FEX on asthma exacerbations BACKGROUND Asthma treatment guidelines recommend addition of controller medications for patients with poorly controlled asthma . We compared the effectiveness of once-daily oral controller therapy with either an antileukotriene receptor antagonist ( montelukast ) or low-dose theophylline added to existing medications in patients with poorly controlled asthma . METHODS We conducted a r and omized , double-masked , placebo-controlled trial in 489 participants with poorly controlled asthma r and omly assigned to  placebo , theophylline ( 300 mg/d ) , or montelukast ( 10 mg/d ) . Participants were monitored for 24 wk to measure the rate of episodes of poor asthma control ( EPACs ) defined by decreased peak flow , increased beta-agonist use , increased oral corticosteroid use , or unscheduled health care visits . OBSERVATIONS There was no significant difference in EPAC rates ( events/person/yr ) compared with placebo : low-dose theophylline , 4.9 ( 95 % confidence interval [ CI ] , 3.6 - 6.7 ; not significant ) ; montelukast , 4.0 ( 95 % CI , 3.0 - 5.4 ; not significant ) ; and placebo , 4.9 ( 95 % CI , 3.8 - 6.4 ) . Both montelukast and theophylline caused small improvements in prebronchodilator FEV(1 ) of borderline significance . Nausea was more common with theophylline only during the first 4 wk of treatment . Neither treatment improved asthma symptoms or quality of life . However , in patients not receiving inhaled corticosteroids , addition of low-dose theophylline significantly ( p < 0.002 ) improved asthma control and symptoms as well as lung function . CONCLUSIONS Neither montelukast nor low-dose theophylline lowered the EPAC rate of poor asthma control in patients with poorly controlled asthma despite improved lung function . For patients not using inhaled corticosteroids , low-dose theophylline improved asthma symptom control more than montelukast or placebo , and provides a safe and low-cost alternative asthma treatment BACKGROUND The goal of asthma therapy is to achieve clinical control and near normal lung functions . Many patients with persistent asthma fail to achieve this goal with a single controller medication add on to a inhaled corticosteroid . We have checked whether another controller medication add on to inhaled corticosteroid and long-acting β2 agonist helps in achieving the asthma goal or not . OBJECTIVES To identify the effect of controller medication add on to inhaled corticosteroid and the long-acting β2 agonist on the clinical symptom , lung function , and compliance in patients with asthma . MATERIAL S AND METHODS We conducted a r and omized , open-labeled , comparative trial in 50 participants with moderate-to-severe persistent asthma . The study duration was of 10 weeks . During the first two weeks of the run-in period all the participants received a dry powder inhaler drug delivery of budesonide ( 400 mcg/day ) and formoterol ( 12 mcg/day ) combination . At the end of the run-in period the participants were r and omly allocated into three groups : group A ( n = 16 ) received oral montelukast ( 10 mg/day ) ; group B ( n = 17 ) received oral doxophylline ( 400 mg/day ) , and group C ( n = 17 ) received inhaled budesonide ( 400 mcg ) as add on to the above-mentioned drugs of the run-in period . The primary outcome was improvement in forced expiratory volume at 1 second ( FEV1 ) . RESULTS All the participants of the three groups had significant improvement in FEV1 ( P < 0.001 ) and asthma symptoms at the end of 10 weeks . The mean increase in FEV1 ( % of predicted ) from the baseline , in groups A , B , and C was : 24.6 ; 21.33 , and 19.86 % , respectively . CONCLUSIONS All add on controller medications helped , with a significant improvement of lung functions and asthma symptoms UNLABELLED We aim ed to compare the efficacy and safety of budesonide/formoterol ( Symbicort ) with budesonide alone ( Pulmicort ) or budesonide ( Pulmicort ) and formoterol ( Oxis ) administered via separate inhalers in children with asthma . In a 12 wk , double-blind study , a total of 630 children with asthma ( mean age 8 yr [ 4 - 11 yr ] ; mean forced expiratory volume in 1 s ( FEV(1 ) ) 92 % predicted ; mean inhaled corticosteroid dose 454 microg/day ) were r and omized to : budesonide/formoterol ( 80/4.5 microg , two inhalations twice daily ) ; a corresponding dose of budesonide alone ( 100 microg , two inhalations twice daily ) ; or a corresponding dose of budesonide ( 100 microg , two inhalations twice daily ) and formoterol ( 4.5 microg , two inhalations twice daily ) ( budesonide + formoterol in separate inhalers ) . The primary efficacy variable was the change from baseline to treatment ( average of the 12-wk treatment period ) in morning peak expiratory flow ( PEF ) . Other changes in lung function and asthma symptoms were assessed , as was safety .  Budesonide/formoterol significantly improved morning PEF , evening PEF and FEV(1 ) compared with budesonide ( all p < 0.001 ) ; there was no significant difference between budesonide/formoterol and budesonide + formoterol in separate inhalers for these variables . All other diary card variables improved from baseline in all treatment groups ; there were no significant between-group differences . Adverse-event profiles were similar in all groups ; there were no serious asthma-related adverse events in any treatment group . CONCLUSION budesonide/formoterol significantly improved  lung function in children ( aged 4 - 11 yr ) with asthma compared with budesonide alone . Budesonide/formoterol is a safe and effective treatment option for children with asthma Pharmacological therapy with inhaled steroids ( IS ) is currently considered the gold-st and ard of treatment for mild-persistent asthma . Leukotriene receptor antagonist drugs ( LTRAs ) play an important role associated with IS , allowing dose tapering and maintaining control of asthma symptoms . The aim of this study was to determine the effectiveness of montelukast ( MON ) to allow tapering of the inhaled dose of budesonide ( BUD ) in patients with mild-moderate persistent asthma . This 16-wk single-blind r and omized study included 40 asthmatic patients divided in 2 treatment groups . After a run-in period ( 4 wk ) , in which all patients inhaled 400 microg of BUD twice daily ( bid ) , group A ( 20 patients ) received MON ( oral , 10 mg/day ) combined with inhaled BUD ( 400 microg/bid ) , while group B ( 20 patients ) was treated with BUD for the whole period of the study . In both groups , at every 4 wk the dose of BUD was halved . After 12 wk of treatment the mean value of forced expiratory volume during the first sec ( FEV1 , as % of predicted value ) was significantly greater in group A compared with group B ( 94 + /- 7.5 vs 83.1 + /- 6.9 ; p<0.005 ) . The mean values of peak expiratory flow ( PEF ) , the percentages of asthmatic exacerbations , and the use of beta2-short-acting agonist ( SABA ) were similar in the 2 groups at 4 , 8 , and 12 wk . In conclusion , in patients with mild-moderate persistent asthma , MON therapy is useful in tapering the dose of IS in order to reduce its side effects and to maintain the clinical stability of the disease BACKGROUND Unmeasured confounders and selection bias can significantly influence the results of retrospective observational analyses of asthma therapy . OBJECTIVE To evaluate the efficacy of oral montelukast and inhaled fluticasone propionate in a r and omized , prospect i ve 12-month " real-world " observational analysis of children with mild persistent asthma . METHODS Children ( n = 104 ) between 6 and 15 years of age with mild asthma as determined by forced expiratory volume in 1 second , symptoms , and evaluation by an experienced pediatric allergist or pulmonologist , who were not currently receiving controller therapy , were r and omly assigned to fluticasone or montelukast on an alternating basis . Subjects were asked to complete a question naire at 6 and 12 months ; otherwise , medical care was identical to that of similar managed care patients . Outcome parameters were evaluated after 12 months by cl aims data base analysis . An acute asthma attack requiring emergent care was the primary outcome parameter . Measures of adherence , symptoms , and asthma control , as measured by the pediatric Asthma Therapy Assessment Question naire , were secondary outcome parameters . RESULTS Demographics , spirometry , symptoms at enrollment , emergent care visits , asthma hospitalizations , routine office visits , and symptoms at study completion were not significantly different between study groups . Adherence , as evaluated by the number of controller fills , was significantly ( P = 0.0003 ) better for montelukast ( 7.65 + /- 3.01 ) than fluticasone ( 5.46 + /- 3.01 ) . Similar numbers of subjects in each study group required beta-agonists and oral prednisone . CONCLUSIONS These results suggest that oral montelukast and inhaled fluticasone have similar real-world efficacies in the treatment of children with mild asthma , possibly as a result of the significantly better adherence with oral montelukast therapy compared with inhaled fluticasone Background Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma PURPOSE To compare the short-term efficacy and safety of low-dose fluticasone propionate with that of oral zafirlukast therapy for patients previously treated with beta-2-agonists alone , and to evaluate the potential therapeutic benefit of switching from zafirlukast to a low-dose inhaled corticosteroid . SUBJECTS AND METHODS This study consisted of a 4-week r and omized , double-blind treatment period followed by a 4-week open-label period . Two hundred ninety-four patients > or = 12 years old with asthma previously uncontrolled with beta-2-agonists alone were r and omly assigned to treatment with low-dose inhaled fluticasone ( 88 microg twice daily ) or oral zafirlukast ( 20 mg twice daily ) . After 4 weeks , all patients discontinued their double-blind therapy and received open-label fluticasone ( 88 microg twice daily ) . Outcomes included pulmonary function , asthma symptoms , albuterol use , asthma exacerbations , and adverse events . RESULTS During the double-blind treatment period , fluticasone patients had significantly greater improvements in morning peak flow ( 29.3 L/min vs. 18.3 L/min ) , percentage of symptom-free days ( 19.8 % vs. 11.6 % ) , and daily albuterol use ( -1.8 puffs per day vs. -1.1 puffs per day ) compared with zafirlukast patients ( P < or = 0.025 , each comparison ) . During the open-label treatment period , patients switched from zafirlukast to fluticasone experienced additional improvements in morning peak flow ( 17.2 L/min ) , evening peak flow ( 13.6 L/min ) , and FEV(1 ) ( 0.11 liter ) and daily albuterol use ( -0.9 puffs daily ) compared with values obtained at the end of the double-blind treatment period ( P < or = 0.001 , each comparison ) . CONCLUSION Low-dose fluticasone was more effective than zafirlukast in improving pulmonary function and symptoms in patients with persistent asthma . In addition , switching patients from zafirlukast to fluticasone further improved clinical outcomes BACKGROUND Controlled trials suggest that leukotriene receptor antagonists can improve lung function and reduce requirement for oral or inhaled corticosteroids in patients with asthma . We aim ed to assess whether montelukast , a leukotriene receptor antagonist , can improve symptoms or lung function in patients with chronic asthma with symptoms already taking corticosteroids . METHODS We did a double-blind , placebo-controlled , crossover , r and omised add-on study in which 100 patients with asthma and symptoms despite treatment with inhaled corticosteroids and additional therapy were given 10 mg montelukast sodium for 14 days in an outpatient clinic setting . Outcome measures were symptoms and peak flow diaries . FINDINGS 72 patients had diary data for analysis . Compared with placebo , addition of montelukast did not result in any significant change in symptom scores ( mean difference between the last 7 days of each treatment period 0.05 ; 95 % CI --0.86 to 1.14 ) , rescue inhaled beta(2 ) agonist use ( mean difference in puffs per day 0.41 ; -0.29 to 0.57 ) , or twice daily peak expiratory flow ( PEF ) measurements ( mean difference in morning PEF 1.18 L/min ; -14.29 to 17.14 ) , and mean difference in evening peak flow ( -0.50 ; -17.42 to 12.86 ) . When treatment response was defined as a 15 % or greater increase in mean peak flow readings , there were four responders to montelukast and seven responders to placebo . INTERPRETATION Based on PEF data from our previous studies of a similar patient group we would have expected to detect changes of more than 5 % . Used as additional therapy in a hospital outpatient clinic setting , montelukast did not provide such additional benefit in patients with moderate or severe asthma AIMS We assessed whether montelukast or formoterol provides additive effects to asthmatics not controlled on inhaled corticosteroids , by study ing patients who were considered to be genetically susceptible to beta2-receptor down regulation and subsensitivity , and who expressed the homozygous glycine-16 beta2-receptor genotype . METHODS Fifteen corticosteroid-treated , mild to moderate persistent asthmatics received montelukast 10 mg once daily or formoterol 9 micro g twice daily for 2 weeks , separated by a 2-week placebo run-in and washout , in a double-blind , double-dummy , r and omized crossover design . Bronchoprotection against adenosine monophosphate ( AMP ) challenge ( primary endpoint ) , spirometry and blood eosinophils were measured at trough after placebo , first and last doses . RESULTS For AMP PC20vs placebo , there were sustained significant ( P < 0.05 ) doubling dilution improvements following first ( 1.1 ; 95 % CI 0.4 , 1.9 ) and last ( 1.0 ; 95 % CI 0.3 , 1.8 ) doses of montelukast , and following first ( 1.3 ; 95 % CI 0.1 , 2.6 ) but not last ( 0.3 ; 95 % CI -0.9 , 1.6 ) doses of formoterol .  Blood eosinophils ( x 10(6 ) l(-1 ) ) were significantly ( P < 0.05 ) suppressed after the last dose of montelukast ( -71 ; 95 % CI -3 , -140 ) compared with placebo , while formoterol exhibited a nonsignificant rise ( 20 ; 95 % CI -92 , 132 ) . Neither treatment significantly improved FEV1 , FEF25 - 75 or PEF after 2 weeks . CONCLUSIONS In genetically susceptible patients with the homozygous glycine-16 genotype , montelukast , but not formoterol , conferred sustained anti-inflammatory properties in addition to inhaled corticosteroid , which were dissociated from changes in lung function after 2 weeks . Thus , assessing lung function may miss potentially beneficial anti-inflammatory effects of montelukast when used as add-on therapy BACKGROUND Limited clinical data are available on the long-term effects of asthma controller therapy on the utilization of health care re sources in pediatric patients with asthma . OBJECTIVE The objective of this study was to compare the effects of long-term treatment with montelukast and usual care on health care re source use in children with asthma . METHODS Pediatric patients aged 2 to 5 years with asthma who had completed a 3-month , double-blind , double-dummy clinical trial comparing montelukast 4 mg and placebo  were asked to participate in an open-label , controlled extension study comparing montelukast 4 mg and usual care . Usual care was defined as cromolyn or inhaled corticosteroid therapy Health care re source utilization was measured in terms of oral corticosteroid use and numbers of physician visits , emergency department visits , and hospitalizations . RESULTS Of 618 patients who completed the primary phase of the study , 516 ( 83.5 % ) participated in the extension study Data from 506 patients ( 302 without previous asthma maintenance therapy , 204 with ) were included in the analysis . During the extension phase , patients who received montelukast and had not used previous asthma maintenance therapy were followed for a mean of 329.5 days ; those who received usual care and CONCLUSION In this open-label study , pediatric patients aged 2 to 5 years with mild to moderate persistent asthma receiving long-term therapy with montelukast had similar rates of asthma-related health care re source utilization compared with those receiving usual care with cromolyn or inhaled corticosteroids BACKGROUND Inhaled , long-acting beta2-agonists or antileukotrienes are alternatives as add-on therapy for asthmatic children taking regular inhaled steroids . Any complementary effects would be relevant to the choice between these alternatives . Exhaled nitric oxide ( FeNO ) may reflect these effects . OBJECTIVE To compare the control of FeNO provided by salmeterol or montelukast add-on therapy in asthmatic children undergoing regular maintenance treatment with a daily dose of 400 microg of budesonide .  METHODS The study included children with increased FeNO despite regular treatment with budesonide , 400 microg/d , and normal lung function .  Montelukast , 5 mg/d , salmeterol , 50 microg twice daily , or placebo was compared as add-on therapy to budesonide , 400 microg , in a r and omized , double-blind , double-dummy , crossover study . RESULTS Twenty-two children completed the trial . The geometric mean FeNO level was 20 ppb ( 95 % confidence interval [ CI ] , 15 - 27 ppb ) after salmeterol , which was significantly higher than after montelukast ( mean , 15 ppb ; 95 % CI , 11 - 18 ppb ; P = 0.002 ) and placebo ( mean , 15 ppb ; 95 % CI , 10 - 21 ppb ; P = 0.03 ) . There was no difference in FeNO between the montelukast and placebo groups . Mean forced expiratory volume in 1 second ( FEV1 ) was significantly increased after salmeterol ( mean , 2.63 L ; 95 % CI , 2.34 - 2.91 L ) compared with placebo ( mean , 2.48 L ; 95 % CI , 2.19 - 2.77 L ) . Montelukast ( mean , 2.57 L ; 95 % CI , 2.33 - 2.80 L ) was no different than placebo . CONCLUSIONS The FeNO levels were significantly higher after salmeterol add-on treatment compared with both placebo and montelukast add-on treatment . Salmeterol significantly improved lung function ( FEV1 ) compared with placebo and nonsignificantly compared with montelukast . Montelukast failed to reduce FeNO and improve lung function compared with placebo in this group of children taking regular budesonide , 400 microg BACKGROUND It has been proposed that asthma control may be achieved in part by minimizing airway inflammation . The simultaneous effects of inhaled steroids associated with long-acting beta-agonists and leukotriene antagonists on pulmonary function and airway inflammation are still largely unexplored in children with moderate persistent asthma . OBJECTIVES The aim of this study was to investigate the effects of add-on therapy with long-acting beta-agonists and leukotriene antagonists on FEV1 and exhaled nitric oxide levels ( FENO ) in children . METHODS Forty-eight steroid-naïve atopic asthmatic children , 7 - 11 years of age , were r and omly treated in four groups for two consecutive one-month periods , as follows : ( 1 ) first month : budesonide 200 microg twice daily ; second month : budesonide 400 microg twice daily ; ( 2 ) first month : budesonide 200 microg twice daily+formoterol 9 microg twice daily ; second month : budesonide 200 microg twice daily+montelukast 5 mg once daily ; ( 3 ) first month : budesonide 200 microg twice daily+montelukast 5 mg once daily ; second month budesonide 200 microg+formoterol 9 microg twice daily ; ( 4 ) first and second month : budesonide 400 microg twice daily . RESULTS All treatments result ed in a significant increase in lung function and a decrease in FENO compared with values at baseline . Budesonide+montelukast in combination was the most effective treatment for reducing FENO levels . CONCLUSION This study demonstrates that add-on therapy with montelukast plus low-dose budesonide is more effective than the addition of long-acting beta-agonists or doubling the dose of budesonide for controlling FENO in asthmatic children OBJECTIVE We tested the hypothesis that adding montelukast to budesonide would improve asthma control in children with inhaled glucocorticoid-dependent persistent asthma . STUDY DESIGN In a multicenter , r and omized , double-blind , crossover study , we compared the benefit of adding montelukast , 5 mg , or placebo once daily to budesonide , 200 microg , twice daily . RESULTS After a 1-month run-in with budesonide , 200 microg , twice daily , 279 children were r and omized to montelukast or placebo .  The mean + /- SD age was 10.4 + /- 2.2 years , the mean forced expiratory volume in 1 second ( FEV(1 ) ) was 77.7 % + /- 10.6 % predicted , and reversibility was 18.1 % + /- 12.9 % . Compared with adding placebo to budesonide , adding montelukast produced significant improvements in mean percent change from baseline FEV(1 ) ( P = .062 [ P = .010 for per- protocol analysis ] ) , mean absolute change from baseline FEV(1 ) ( P = .040 ) , mean increase from baseline in morning ( P = .023 ) and evening ( P = .012 ) peak expiratory flows , decrease in exacerbation days by approximately 23 % ( P < .001 ) , decreased beta2-agonist use ( P = .013 ) , and reduced blood eosinophil counts ( P < .001 ) . The treatments did not differ significantly with regard to safety . CONCLUSIONS Montelukast , 5 mg , added to budesonide improved asthma control significantly , indicated by a small additive effect on lung function and a clinical ly relevant decrease in asthma exacerbation days BACKGROUND Antileukotrienes and inhaled corticosteroids are asthma controller agents widely used in the treatment of pediatric asthma . OBJECTIVE To evaluate the effects of montelukast and beclomethasone on linear growth in prepubertal asthmatic children for 1 year . METHODS This was a 30-center study of boys ( 6.4 - 9.4 years old ) and girls ( 6.4 - 8.4 years old ) at Tanner stage I with mild , persistent asthma . After a placebo run-in period , 360 patients were r and omized in equal ratios to double-blind , double-dummy treatment with 5 mg of montelukast , 200 microg of beclomethasone twice daily ( positive control ) , or placebo for 56 weeks ; 90 % of the patients completed the study . The primary end point was linear growth velocity , measured using a stadiometer . RESULTS Linear growth rates were similar between the montelukast and placebo groups ; the mean difference for the year was 0.03 cm . The mean growth rate with beclomethasone was significantly less than with placebo ( -0.78 cm ) or montelukast ( 0.81 cm ) ( P < .001 for both ) . Median percentage of days with beta-agonist use was greater with placebo ( 14.58 % ) vs montelukast ( 10.55 % ) or beclomethasone ( 6.65 % ) ( P < .05 for all ) . More patients used oral corticosteroid rescue with placebo ( 34.7 % ) than with montelukast ( 25.0 % ) or beclomethasone ( 23.5 % ) . An imbalance in bone marker levels was seen with beclomethasone but not with montelukast . CONCLUSION In prepubertal asthmatic children , montelukast did not affect linear growth , whereas the growth rate with beclomethasone was significantly decreased during 1 year of treatment BACKGROUND Salmeterol , a long-acting beta2 -agonist , and zafirlukast , a leukotriene receptor antagonist , are both indicated for the treatment of asthma in adolescent and adult patients . OBJECTIVE We sought to compare the effect of 4 weeks of treatment with inhaled salmeterol xinafoate versus oral zafirlukast in the treatment of persistent asthma . METHODS This was a r and omized , double-blind , double-dummy , parallel-group , multicenter clinical trial . Patients , over 80 % of whom were on a concurrent inhaled corticosteroid regimen , were treated for 4 weeks with either inhaled salmeterol xinafoate 42 microgram twice daily administered by means of a metered-dose inhaler or oral zafirlukast 20 mg twice daily . The primary efficacy measure was morning peak expiratory flow ( PEF ) ; secondary efficacy measures included evening PEF , asthma symptom scores , supplemental albuterol use , nighttime awakenings , sleep symptoms , asthma exacerbations , and FEV1 . RESULTS Both inhaled salmeterol and oral zafirlukast result ed in within-group improvements from baseline in measures of pulmonary function , asthma symptoms , and supplemental albuterol use . Salmeterol treatment result ed in significantly greater improvements from baseline compared with zafirlukast for most efficacy measurements , including morning PEF ( 29.6 vs 13.0 L/min ; P < /= .001 ) , percentage of symptom-free days ( 22.4 % vs 8.8 % ; P < /= .001 ) , and percentage of days and nights with no supplemental albuterol use ( 30.5 % vs 11.3 % ; P < /= .001 ) . There were no differences in safety profiles as assessed by adverse event monitoring . CONCLUSION In patients with persistent asthma , most of whom were concurrently using inhaled corticosteroids , treatment with inhaled salmeterol provided significantly greater improvement than oral zafirlukast in overall asthma control over the 4-week treatment period BACKGROUND Inhaled corticosteroids and anti-leukotriene agents are widely used in the treatment of pediatric asthma . Although data on the effect of corticosteroids on growth are available , there are few such data on anti-leukotriene agents . The aim of this study was to assess the influence of montelukast on short-term lower leg growth rate ( LLGR ) in prepubertal children with asthma . METHODS Forty-two boys ( 6- to 12-year old ) and 29 girls ( 6- to 11-year old ) with mild asthma were r and omized to 1 of 2 crossover arms , with two treatment sequences per arm : montelukast 5 mg once daily/placebo or inhaled dry powder budesonide 200 microg twice daily/placebo . Budesonide was used as a positive control to ensure that the method was sensitive enough to detect a suppression of LLGR . The 3-week double-blind treatment period was followed by a 3-week washout . Primary outcome was LLGR over the 3-week treatment , measured by knemometry . RESULTS Ninety-four percent of patients completed the study .  Mean LLGR was similar between patients receiving montelukast and placebo treatments : mean difference , -0.02 mm/week [ 95 % confidence interval -0.14 , 0.11 ] . Mean LLGR in patients receiving budesonide was significantly less than for those receiving placebo ( difference of -0.16 mm/week [ -0.25 , -0.06 ] , P = 0.002 ) . Mean LLGR was similar for patients taking placebo in the two arms ( 0.43 and 0.44 mm/week ) . CONCLUSION Montelukast 5 mg did not significantly affect short-term LLGR in prepubertal children OBJECTIVES To evaluate the effect of montelukast , 5 mg , or inhaled salmeterol , 50 microg , added to inhaled fluticasone in reducing the maximum percentage decrease in forced expiratory volume in 1 second ( FEV1 ) after a st and ardized exercise challenge and response to rescue bronchodilation with albuterol in children aged 6 to 14 years with persistent asthma and exercise-induced bronchoconstriction ( EIB ) . METHODS R and omized , double-blind , double-dummy , multicenter , 2-period , 4-week , crossover study conducted between December 22 , 2005 and November 14 , 2008 at 30 centers in Europe , Asia , Mexico , and South America . Patients with asthma receiving inhaled corticosteroids  demonstrated an FEV1 of 70 % or higher of the predicted value and EIB ( defined as a decrease in FEV1 > or = 15 % compared with preexercise baseline FEV1 on 2 occasions before r and omization ) . St and ardized exercise challenges were performed at baseline ( prer and omization ) and at the end of each active treatment period . RESULTS Of 154 patients r and omized , 145 completed the study .  Montelukast , compared with salmeterol , significantly reduced the mean maximum percentage decrease in FEV1 ( 10.6 % vs 13.8 % ; P = .009 ) , mean area under the curve for the first 20 minutes after exercise ( 116.0 % x min vs 168.8 % x min ; P = .006 ) , and median time to recovery ( 6.0 vs 11.1 minutes ; P = .04 ) . Response to albuterol rescue after exercise challenge was significantly greater ( P < .001 ) with montelukast . Montelukast and salmeterol were generally well tolerated . CONCLUSIONS Attenuation and response of EIB to albuterol rescue after exercise challenge were significantly better with montelukast than with salmeterol after 4 weeks of treatment BACKGROUND Treatment guidelines recommend the use of inhaled corticosteroids in patients with asthma who have persistent symptoms and the " stepping down " of therapy to the minimum needed to maintain control of asthma . Whether patients with asthma that is well controlled with the use of inhaled corticosteroids twice daily can receive a step-down treatment with once-daily montelukast ( our primary hypothesis ) or once-daily fluticasone propionate plus salmeterol ( our secondary hypothesis ) has not yet been determined . METHODS We r and omly assigned 500 patients with asthma that was well controlled by inhaled fluticasone ( 100 microg twice daily ) to receive continued  fluticasone ( 100 microg twice daily ) ( 169 patients ) , montelukast ( 5 or 10 mg each night ) ( 166 patients ) , or fluticasone ( 100 microg ) plus salmeterol ( 50 microg ) each night ( 165 patients ) . Treatment was administered for 16 weeks in a double-blind manner . The primary outcome was the time to treatment failure . RESULTS Approximately 20 % of patients assigned to receive continued fluticasone or switched to treatment with fluticasone plus salmeterol had treatment failure , as compared with 30.3 % of subjects switched to montelukast . The hazard ratio for both comparisons was 1.6 ( 95 % confidence interval , 1.1 to 2.6 ; P=0.03 ) . The percentage of days on which patients were free of asthma symptoms ( 78.7 to 85.8 % ) was similar across the three groups . CONCLUSIONS Patients with asthma that is well controlled with the use of twice-daily inhaled fluticasone can be switched to once-daily fluticasone plus salmeterol without increased rates of treatment failure . A switch to montelukast results in an increased rate of treatment failure and decreased asthma control ; however , patients taking montelukast remained free of symptoms on 78.7 % of treatment days . ( Clinical Trials.gov number , NCT00156819 [ Clinical Trials.gov ] . ) BACKGROUND Both inhaled corticosteroids and leukotriene modifiers are used in the maintenance treatment of persistent asthma . OBJECTIVE The goal was to compare the efficacy and safety of low-dose fluticasone propionate ( FP ) and montelukast as first-line maintenance therapy in symptomatic patients by using short-acting beta2-agonists alone to treat persistent asthma . METHODS In this multicenter , r and omized , double-blind , double-dummy , parallel-group study , 533 patients ( > 15 years old ) with persistent asthma who remained symptomatic while taking short-acting beta2-agonists alone were treated with FP ( 88 microg [ 2 puffs of 44 microg ] twice daily ) or montelukast ( 10 mg once daily ) for 24 weeks . RESULTS Compared with treatment with montelukast , treatment with FP result ed in significantly greater improvements at endpoint in morning predose FEV(1 ) ( 22.9 % vs 14.5 % , P < .001 ) , forced midexpiratory flow ( 0.66 vs 0.41 L/sec , P < .001 ) , forced vital capacity ( 0.42 vs 0.29 L , P = .002 ) , morning peak expiratory flow ( PEF ) ( 68.5 vs 34.1 L/min , P < .001 ) , and evening PEF ( 53.9 vs 28.7 L/min , P < .001 ) . Similar improvements in PEF were observed in patients with milder asthma ( > 70%-80 % predicted FEV(1 ) ) . At endpoint , FP was more effective than montelukast at decreasing rescue albuterol use ( 3.1 puffs/day vs 2.3 puffs/day , P < .001 ) , asthma symptom scores ( -0.85 [ 48.6 % decrease ] vs -0.60 [ 30.5 % ] , P < .001 ) , and nighttime awakenings due to asthma ( -0.64 awakenings/night [ 62 % decrease ] vs -0.48 awakenings/night [ 47.5 % ] , P = .023 ) , and FP increased the percentage of symptom-free days ( 32.0 % vs 18.4 % of days , P < .001 ) compared with montelukast . The adverse event and asthma exacerbation profiles for FP and montelukast were similar . CONCLUSIONS Low-dose FP is more effective than montelukast as first-line maintenance therapy for patients with persistent asthma who are undertreated and remain symptomatic while taking short-acting beta2-agonists alone BACKGROUND For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids ( ICS ) , evidence to guide step-up therapy is lacking . METHODS We r and omly assigned 182 children ( 6 to 17 years of age ) , who had uncontrolled asthma while receiving 100 microg of fluticasone twice daily , to receive each of three blinded step-up therapies in r and om order for 16 weeks : 250 microg of fluticasone twice daily ( ICS step-up ) , 100 microg of fluticasone plus 50 microg of a long-acting beta-agonist twice daily ( LABA step-up ) , or 100 microg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily ( LTRA step-up ) . We used a triple-crossover design and a composite of three outcomes ( exacerbations , asthma-control days , and the forced expiratory volume in 1 second ) to determine whether the frequency of a differential response to the step-up regimens was more than 25 % . RESULTS A differential response occurred in 161 of 165 patients who were evaluated ( P<0.001 ) . The response to LABA step-up therapy was most likely to be the best response , as compared with responses to LTRA step-up ( relative probability , 1.6 ; 95 % confidence interval [ CI ] , 1.1 to 2.3 ; P=0.004 ) and ICS step-up ( relative probability , 1.7 ; 95 % CI , 1.2 to 2.4 ; P=0.002 ) . Higher scores on the Asthma Control Test before r and omization ( indicating better control at baseline ) predicted a better response to LABA step-up ( P=0.009 ) . White race predicted a better response to LABA step-up , whereas black patients were least likely to have a best response to LTRA step-up ( P=0.005 ) . CONCLUSIONS Nearly all the children had a differential response to each step-up therapy . LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up . However , many children had a best response to ICS or LTRA step-up therapy , highlighting the need to regularly monitor and appropriately adjust each child 's asthma therapy . ( Clinical Trials.gov number , NCT00395304 . STUDY OBJECTIVE To compare the safety of salmeterol xinafoate or placebo added to usual asthma care . DESIGN A 28-week , r and omized , double-blind , placebo-controlled , observational study . SETTING Study subjects were seen once in the study physician 's office for screening and were provided all blinded study medication for the entire study period . Follow-up by telephone was scheduled every 4 weeks . PARTICIPANTS Subjects ( > 12 years old ) with asthma as judged by the study physician were eligible . Individuals with a history of long-acting beta2-agonist use were excluded . INTERVENTIONS Salmeterol , 42 mug bid via metered-dose inhaler ( MDI ) , and placebo bid via MDI . MEASUREMENTS AND RESULTS Following an interim analysis in 26,355 subjects , the study was terminated due to findings in African Americans and difficulties in enrollment . The occurrence of the primary outcome , respiratory-related deaths , or life-threatening experiences was low and not significantly different for salmeterol vs placebo ( 50 vs 36 ; relative risk [ RR ] = 1.40 ; 95 % confidence interval [ CI ] , 0.91 to 2.14 ) . There was a small , significant increase in respiratory-related deaths ( 24 vs 11 ; RR , 2.16 ; 95 % CI , 1.06 to 4.41 ) and asthma-related deaths ( 13 vs 3 ; RR , 4.37 ; 95 % CI , 1.25 to 15.34 ) , and in combined asthma-related deaths or life-threatening experiences ( 37 vs 22 ; RR , 1.71 ; 95 % CI , 1.01 to 2.89 ) in subjects receiving salmeterol vs placebo . The imbalance occurred largely in the African-American sub population : respiratory-related deaths or life-threatening experiences ( 20 vs 5 ; RR , 4.10 ; 95 % CI , 1.54 to 10.90 ) and combined asthma-related deaths or life-threatening experiences ( 19 vs 4 ; RR , 4.92 ; 95 % CI , 1.68 to 14.45 ) in subjects receiving salmeterol vs placebo . CONCLUSIONS For the primary end point in the total population , there were no significant differences between treatments . There were small , but statistically significant increases in respiratory-related and asthma-related deaths and combined asthma-related deaths or life-threatening experiences in the total population receiving salmeterol . Subgroup analyses suggest the risk may be greater in African Americans compared with Caucasian subjects . Whether this risk is due to factors including but not limited to a physiologic treatment effect , genetic factors , or patient behaviors leading to poor outcomes remains unknown BACKGROUND Cysteinyl leukotriene release in association with airway inflammation is a feature of clinical asthma . The acute effects of montelukast ( MK-0476 ) , a potent , orally administered , specific cysteinyl leukotriene receptor antagonist , on airways obstruction was assessed in patients with mild to moderately severe asthma . METHODS Twenty two asthmatic subjects were r and omised to receive montelukast , 100 mg or 250 mg , or placebo in a double blind , three period , crossover trial . Ten of the patients were using concomitant inhaled corticosteroids . RESULTS Montelukast increased the forced expiratory volume in one second ( FEV1 ) from predose baseline values compared with placebo , the percentage point differences between montelukast and placebo being 8.6 % ( 95 % CI 3.6 to 13.6 ) and 8.5 % ( 95 % CI 3.5 to 13.5 ) for the 100 mg and 250 mg doses , respectively . CONCLUSION Single oral doses of montelukast 100 mg and 250 mg produced significant increases in FEV1 irrespective of the concurrent use of inhaled corticosteroids in asthmatic subjects with airflow limitation OBJECTIVES To compare the effects of addition of montelukast or salmeterol to inhaled corticosteroids ( ICS ) on the response to rescue beta2-agonist use after exercise-induced bronchoconstriction . METHODS A double-blind , placebo-controlled study was performed at 16 centers in the United States . Patients with asthma ( n = 122 , ages 15 - 58 ) whose symptoms were uncontrolled on Low-dose inhaled fluticasone and who had a history of exercise-induced worsening of asthma were r and omized to receive either montelukast ( 10 mg once daily ) , salmeterol ( 50microg twice daily ) , or placebo for 4 weeks . St and ardized spirometry  after exercise challenge and beta2-agonist rescue was performed at baseline , week 1 and 4 . RESULTS Maximum achievable forced expiratory volume in 1 s ( FEV1 ) percent predicted after rescue beta2-agonist improved in the montelukast ( + 1.5 % ) and placebo ( + 1.2 % ) groups at 4 weeks , but diminished in the salmeterol ( -3.9 % ) group ( P < 0.001 ) . Although pre-exercise FEV1 was greatest with salmeterol ( P = 0.10 ) , patients taking montelukast had significantly greater protection from an exercise-induced decrease in FEV1 than those taking salmeterol ( P < 0.001 ) . Both the magnitude and rate of rescue bronchodilation were greater with montelukast compared with salmeterol ( P < 0.001 ) . Five minutes after rescue beta2-agonist , 92 % of patients taking montelukast and 68 % of those taking placebo had recovered to pre-exercise levels , whereas only 50 % of those taking salmeterol had recovered to pre-exercise levels . CONCLUSION In patients whose asthma symptoms remain uncontrolled using ICS , addition of montelukast permits a greater and more rapid rescue bronchodilation with a short-acting beta2-agonist than addition of salmeterol and provides consistent and clinical ly meaningful protection against exercise-induced bronchoconstriction Mild persistent asthma is most effectively controlled with inhaled corticosteroids . Leukotriene receptor antagonists have complementary effects to corticosteroids on inflammation control . The additional effect of a leukotriene receptor antagonist , zafirlukast , was investigated in stable asthma patients under control with inhaled budesonide .  We conducted a r and omised , double-blind , placebo-controlled , single center trial to investigate the effects of add-on zafirlukast treatment to budesonide , on symptom score , pulmonary function , bronchial responsiveness , and serum levels of eosinophilic cationic protein ( ECP ) and antioxidant capacity in stable asthmatic patients under control with inhaled budesonide . The present study included 21 mild or moderate asthmatic patients ( 8 males and 13 females ) , who were stable at least for 6 weeks with inhaled budesonide ( 400 microg/day ) .  Serum total antioxidant capacity ( TAC ) and ECP levels were measured , and symptom scoring , spirometry , and bronchial provocation with methacholine were performed . Then , the patients were r and omised to use either placebo or oral zafirlukast ( 40 mg/day ) in addition to budesonide for 6 weeks . At the 6th week , symptom scoring , spirometry , and bronchial provocation tests were repeated and serum TAC and ECP levels were measured again . After add-on zafirlukast treatment to budesonide , forced expiratory volume in 1 second ( FEV(1 ) ) , TAC and ECP values did not change significantly ( p > 0.05 ) but bronchial hyperresponsiveness and symptom score decreased significantly ( p = 0.022 ) compared to baseline . Thus , in stable asthmatic patients , add-on zafirlukast treatment to budesonide improves symptoms and decreases bronchial hyperresponsiveness Objective . To determine the effect of montelukast on asthma during the allergy season in children with persistent asthma and seasonal aeroallergen sensitivity . Design . This 3-week double-blind , placebo-controlled , parallel-group multicenter study compared daily montelukast 5 mg chewable tablets and placebo in patients 6–14 years of age with forced expiratory volume in 1 second ( FEV1 ) ≥ 60 and ≤ 85 % predicted , persistent asthma that is also active during allergy season , and documented sensitivity to seasonal allergens . Concomitant inhaled corticosteroid use was permitted in up to 40 % of enrolled patients . The primary endpoint was the percentage change from baseline in FEV1 over 3 weeks of treatment . Additional endpoints included the percentage change from baseline in β -agonist use , average changes in daytime and nighttime symptom score , AM and PM peak expiratory flow rate ( PEFR ) , investigator 's global asthma evaluation , and parent/guardian global asthma evaluation at the end of the treatment period . Adverse experiences ( AEs ) were collected to assess safety and tolerability . Results . A total of 421 patients were r and omized to montelukast ( N = 203 ) or placebo ( N = 218 ) . For the primary endpoint , the percentage change from baseline FEV1  , montelukast was not significantly different from placebo ( least squares mean 9.53 % vs. 9.15 % , respectively ; p = 0.810 ) . Compared with placebo , montelukast was associated with significantly lower ( better ) investigator 's global asthma evaluation ( LS mean 2.71 vs. 2.98 ; p < 0.05 ) and parent/guardian global asthma evaluation ( LS mean : 2.63 vs. 2.90 ; p < 0.05 ) scores . There were no significant differences between treatment groups for the other efficacy evaluations . Both treatments were well tolerated , with no significant differences observed in AE rates . Conclusion . Montelukast did not significantly improve FEV1 compared with placebo over three weeks of treatment during the allergy season in pediatric patients with seasonal allergen sensitivity . ( Clinical Trials.gov identifier : NCT00289874 BACKGROUND Since IgE is considered to play a crucial role in allergic immune responses , the reduction of free IgE level has been an attractive target in the treatment of allergic diseases . The present study was conducted to determine the effects of a 6-month treatment with different doses of inhaled budesonide and montelukast sodium in children with newly diagnosed atopic asthma . METHODS In this r and omized , double-blind , double-dummy trial , 51 children with newly diagnosed asthma and sensitivity to house-dust mites were r and omly allocated to receive budesonide ( in two different doses 400 or 800 mcg ) or montelukast for 6 months . The primary end point was the level of serum total and specific IgE before and after treatment . The secondary end points were clinical parameters and forced expiratory volume in 1s ( FEV1 ) . RESULTS After 6 months of treatment , a high dose of inhaled corticosteroid and montelukast , significantly decreased levels of total and specific IgE. Medium dose of inhaled corticosteroid had no effect on total and specific IgE serum level . Clinical score and FEV1 significantly improved after 6 months of treatment with medium ( P = 0.002 ) and high dose ( P = 0.001 ) of inhaled budesonide and montelukast ( P = 0.002 ) . There were no differences between groups in changes of all clinical parameters after treatment . CONCLUSION Only high doses of inhaled corticosteroids and montelukast decreased the serum IgE levels . Perhaps long-term treatment with montelukast will be beneficial to asthma patients by decreasing IgE levels BACKGROUND Inhaled corticosteroids ( ICS ) are the first-line treatment for children with persistent asthma . Their potential for growth suppression remains a matter of concern for parents and physicians . OBJECTIVES To assess whether increasing the dose of ICS is associated with slower linear growth , weight gain and skeletal maturation in children with asthma . SEARCH METHODS We search ed the Cochrane Airways Group Specialised Register of trials ( CAGR ) and the Clinical Trials.gov website up to March 2014 . SELECTION CRITERIA Studies were eligible if they were parallel-group r and omised trials evaluating the impact of different doses of the same ICS using the same device in both groups for a minimum of three months in children one to 17 years of age with persistent asthma . DATA COLLECTION AND ANALYSIS Two review authors ascertained method ological quality independently using the Cochrane Risk of bias tool . The primary outcome was linear growth velocity . Secondary outcomes included change over time in growth velocity , height , weight , body mass index and skeletal maturation . MAIN RESULTS Among 22 eligible trials , 17 group comparisons were derived from 10 trials ( 3394 children with mild to moderate asthma ) , measured growth and contributed data to the meta- analysis . Trials used ICS ( beclomethasone , budesonide , ciclesonide , fluticasone or mometasone ) as monotherapy or as combination therapy with a long-acting beta2 -agonist and generally compared low ( 50 to 100 μg ) versus low to medium ( 200 μg ) doses of hydrofluoroalkane (HFA)-beclomethasone equivalent over 12 to 52 weeks . In the four comparisons reporting linear growth over 12 months , a significant group difference was observed , clearly indicating lower growth velocity in the higher ICS dose group of 5.74 cm/y compared with 5.94 cm/y on lower-dose ICS ( N = 728 school-aged children ; mean difference (MD)0.20 cm/y , 95 % confidence interval ( CI ) 0.02 to 0.39 ; high- quality evidence ): No statistically significant heterogeneity was noted between trials contributing data . The ICS molecules ( ciclesonide , fluticasone , mometasone ) used in these four comparisons did not significantly influence the magnitude of effect ( X(2 ) = 2.19 ( 2 df ) , P value 0.33 ) . Subgroup analyses on age , baseline severity of airway obstruction , ICS dose and concomitant use of non-steroidal antiasthmatic drugs were not performed because of similarity across trials or inadequate reporting . A statistically significant group difference was noted in unadjusted change in height from zero to three months ( nine comparisons ; N = 944 children ; MD 0.15 , 95 % CI -0.28 to -0.02 ; moderate- quality evidence ) in favour of a higher ICS dose . No statistically significant group differences in change in height were observed at other time points , nor were such differences in weight , bone mass index and skeletal maturation reported with low quality of evidence due to imprecision . AUTHORS ' CONCLUSIONS In prepubescent school-aged children with mild to moderate persistent asthma , a small but statistically significant group difference in growth velocity was observed between low doses of ICS and low to medium doses of HFA-beclomethasone equivalent , favouring the use of low-dose ICS . No apparent difference in the magnitude of effect was associated with three molecules reporting one-year growth velocity , namely , mometasone , ciclesonide and fluticasone . In view of prevailing parents ' and physicians ' concerns about the growth suppressive effect of ICS , lack of or incomplete reporting of growth velocity in more than 86 % ( 19/22 ) of eligible paediatric trials , including those using beclomethasone and budesonide , is a matter of concern . All future paediatric trials comparing different doses of ICS with or without placebo should systematic ally document growth . Findings support use of the minimal effective ICS dose in children with asthma . PLAIN LANGUAGE SUMMARY Does altering the dose of inhaled corticosteroids make a difference in growth among  children with asthma ? BACKGROUND Asthma guidelines recommend inhaled corticosteroids ( ICS ) as the first choice of treatment for children with persistent asthma that is not well controlled when only a reliever inhaler is used to treat symptoms . Steroids work by reducing inflammation in the lungs and are known to control underlying symptoms of asthma . However , parents and physicians remain concerned about the potential negative effect of ICS on growth . REVIEW QUESTION Does altering the dose of inhaled corticosteroids make a difference in the growth of children with asthma ? WHAT EVIDENCE DID WE FIND ? : We studied whether a difference could be seen in the growth of children with persistent asthma who were using different doses of the same ICS molecule and the same delivery device . We found 22 eligible trials , but only 10 of them measured growth or other measures of interest . Overall , 3394 children included in the review combined 17 group comparisons ( i.e. 17 groups of children with mild to moderate asthma using a particular dose and type of steroid in 10 trials ) . Trials used different ICS molecules ( beclomethasone , budesonide , ciclesonide , fluticasone or mometasone ) either on their own or in combination with a long-acting beta2 -agonist ( a drug used to open up the airways ) and generally compared low doses of corticosteroids ( 50 to 100 μg ) with low to medium ( 200 μg ) doses of corticosteroids ( converted in μg HFA-beclomethasone equivalent ) over 12 to 52 weeks . RESULTS We found a small but statistically significant group difference in growth over 12 months between these different doses clearly favouring the lower dose of ICS . The type of corticosteroid among newer molecules ( ciclesonide , fluticasone , mometasone ) did not seem to influence the impact on growth over one year . Differences in corticosteroid doses did not seem to affect the change in height , the gain in weight , the gain in bone mass index and the maturation of bones . QUALITY OF THE EVIDENCE : This review is based on a small number of trials that reported data and were conducted on children with mild to moderate asthma . Only 10 of 22 studies measured the few outcomes of interest for this review , and only four comparisons reported growth over 12 months . Our confidence in the quality of evidence is high for this outcome , however it is low to moderate for several other outcomes , depending on the number of trials reporting these outcomes . Moreover , a few outcomes were reported only by a single trial ; as these findings have not been confirmed by other trials , we down grade d the evidence for these outcomes to low quality . An insufficient number of trials have compared the effect of a larger difference in dose , for example , between a high dose and a low dose of ICS and of other popular molecules such as budesonide and beclomethasone over a year or longer of treatment . CONCLUSIONS We report an evidence -based ICS dose-dependent reduction in growth velocity in prepubescent school-aged children with mild to moderate persistent asthma . The choice of ICS molecule ( mometasone , ciclesonide or fluticasone ) was not found to affect the level of growth velocity response over a year . The effect of corticosteroids on growth was not consistently reported : among 22 eligible trials , only four comparisons reported the effects of corticosteroids on growth over one year . In view of parents ' and clinicians ' concerns , lack of or incomplete reporting of growth is a matter of concern given the importance of the topic . We recommend that growth be systematic ally reported in all trials involving children taking ICS for three months or longer . Until further data comparing low versus high ICS dose and trials of longer duration are available , we recommend that the minimal effective ICS dose be used in all children with asthma BACKGROUND . A recurring epidemic of asthma exacerbations in children occurs annually in September in North America when school resumes after summer vacation . OBJECTIVE . Our goal was to determine whether montelukast , added to usual asthma therapy , would reduce days with worse asthma symptoms and unscheduled physician visits of children during the September epidemic . PATIENTS AND METHODS . A total of 194 asthmatic children aged 2 to 14 years , stratified according to age group ( 2–5 , 6–9 , and 10–14 years ) and gender , participated in a double-blind , r and omized , placebo-controlled trial of the addition of montelukast to usual asthma therapy between September 1 and October 15 , 2005 . RESULTS . Children r and omly assigned to receive montelukast experienced a 53 % reduction in days with worse asthma symptoms compared with placebo ( 3.9 % vs 8.3 % ) and a 78 % reduction in unscheduled physician visits for asthma ( 4 [ montelukast ] vs 18 [ placebo ] visits ) . The benefit of montelukast was seen both in those using and not using regular inhaled corticosteroids and among those reporting and not reporting colds during the trial . There were differences in efficacy according to age and gender . Boys aged 2 to 5 years showed greater benefit from montelukast ( 0.4 % vs 8.8 % days with worse asthma symptoms ) than did older boys , whereas among girls the treatment effect was most evident in 10- to 14-year-olds ( 4.6 % [ montelukast ] vs 17.0 % [ placebo ] ) , with nonsignificant effects in younger girls . CONCLUSIONS . Montelukast added to usual treatment reduced the risk of worsened asthma symptoms and unscheduled physician visits during the predictable annual September asthma epidemic . Treatment-effect differences observed between age and gender groups require additional investigation A few studies compared the additional effects of oral controller medicines on pulmonary function in asthmatic patients on a moderate dose of inhaled steroids . The aim of this study was to compare the additional effects of two oral asthma controllers , a leukotriene receptor antagonist and a sustained released theophylline ( Theo ) , with a moderate dose of inhaled steroid on  peak expiratory flow ( PEF ) and asthma-related symptoms . A total of 67 adult asthmatic patients with PEF < 80 % predicted during a 2-week run-in period with 800 microg/day of beclomethasone dipropionate  were r and omized to receive either pranlukast , 450 mg/day ( n = 33 ) , or sustained released Theo , 200 mg/day ( n = 34 ) , for 4 weeks . Pranlukast and Theo did not significantly alter the symptom scores , use of rescue beta2-agonist , and daily PEF variability . However , both agents significantly increased both morning and evening PEF compared with the run-in periods . The effects of both medications were comparable . For asthmatic patients even on a moderate dose of inhaled steroids , the addition of either leukotriene receptor antagonist or sustained released Theo does not improve asthma-related symptoms but significantly and equally increases PEF ABSTRACT Objective : Clinical trials have demonstrated improved efficacy of fluticasone propionate/ salmeterol ( 100/50 mcg ) in a single device ( FSC ) compared with montelukast ( 10 mg ) ( MON ) . This study was design ed to assess asthma control , asthma-related quality of life , asthma-related emergency department ( ED ) visit/hospitalization , treatment-related satisfaction , and productivity losses in patients newly started on FSC or MON . Research design and methods : Patients who were newly prescribed FSC or MON during a regularly scheduled office visit were enrolled in a prospect i ve observational study by nearly 500 physicians from eight managed care plans .  Patient survey data were collected at baseline and at months 1 , 3 , 6 , and 12 , to measure study outcomes . ED visits/inpatient stays were reported from commercial cl aims data . Multivariate analyses assessed 12‐month outcomes , controlling for several baseline patient characteristics . Results : A total of 1414 patients ≥ 15 years old were enrolled in the registry ( FSC , n = 1061 ; MON , n = 353 ) , 90 % of which completed a 12‐month survey . FSC patients had significantly greater improvement in both asthma control and quality of life , and reported significantly higher satisfaction with their medication ( p = 0.003 ) and fewer days at work/school with asthma symptoms ( p = 0.04 ) than MON . Other parameters of productivity losses such as missed work/school days due to asthma were not significantly different between the two groups . FSC use was also significantly associated with a lower risk of an asthma-related ED visit/hospitalization compared with MON ( odds ratio = 0.35 , 95 % confidence interval : 0.15–0.92 ) . Conclusion : In a 12‐month office-based observational study , patients age 15 and older with persistent asthma , newly started on FSC , improved in symptom , quality of life , treatment , and utilization-related outcomes compared with patients newly started on MON . These results should be interpreted in light of the inherent limitations of non-r and omized , uncontrolled studies The primary objective of this study was to determine whether montelukast , an oral leukotriene receptor antagonist , provides additional clinical benefit to the effect of inhaled corticosteroids . A total of 642 patients with chronic asthma ( FEV(1 ) 50 to 85 % of predicted value and at least a predefined level of asthma symptoms ) incompletely controlled with inhaled beclomethasone  , 200 microg twice daily using a spacer device , during the 4-wk run-in period were r and omly allocated , in a double-blind , double-dummy manner to one of four treatment groups : ( 1 ) montelukast 10 mg plus continuing inhaled beclomethasone ; ( 2 ) placebo tablet plus continuing inhaled beclomethasone ; ( 3 ) montelukast 10 mg and inhaled placebo ( after blind beclomethasone removal ) ; and ( 4 ) placebo tablet and inhaled placebo ( after blind beclomethasone removal ) . The primary endpoints were FEV(1 ) and daytime asthma symptoms score .  Montelukast provided significant ( p < 0.05 ) clinical benefit in addition to inhaled beclomethasone by improving FEV(1 ) , daytime asthma symptom scores , and nocturnal awakenings . Blind removal of beclomethasone in the presence of placebo tablets caused worsening of asthma control , demonstrating that patients received clinical benefit from inhaled corticosteroids . Blind removal of beclomethasone in the presence of montelukast result ed in less asthma control but not to the level of the placebo group . All treatments were well tolerated ; clinical and laboratory adverse experiences were generally similar to placebo treatment in this study . In conclusion , montelukast provided additional asthma control to patients benefitting from , but incompletely controlled on , inhaled beclomethasone We compared measures of treatment effectiveness when inhaled corticosteroids ( ICSs ) or leukotriene modifiers ( LMs ) were used as controller monotherapy for asthma . Asthma patients aged 6 - 55 years initiating ICS or LM monotherapy between July 1998 and June 1999 ( index prescription ) were identified using a managed care cl aims data base . Asthma-related hospitalizations , emergency department ( ED ) visits , and use of short-acting beta-agonists and oral corticosteroids ( OCSs )  were assessed as proxies for treatment effectiveness . Propensity score was used to adjust for baseline differences between treatment cohorts . The change in the annual rate of cl aims from the preindex to postindex period for each measure was compared across treatment groups . Logistic regression models of the postindex composite events ( hospitalization and /or ED ) and OCS use were estimated . Nine hundred sixty patients were initiated on  LMs ( n = 153 ) and ICSs ( n = 807 ) . The mean annual rate of cl aims for OCSs increased in the ICS group ( 0.2 ) but was unchanged in the LM group ( adjusted mean difference in change , 0.2 ; 95 % CI , 0.05 - 0.4 ; p = 0.01 ) . The mean annual rate of cl aims for short-acting beta-agonists increased in both the ICS and LM groups by 1.1 and 0.5 , respectively ( adjusted mean difference in change , 0.6 ; 95 % CI , -0.06 . 1.1 ; p = 0.08 ) . Similar changes in annualized rates of cl aims for hospitalizations and ED visits were observed between treatment groups . In logistic regression models , greater odds of postindex OCS use was observed among the ICS group ( odds ratio for ICS versus LM = 1.7 ; 95 % CI , 1.04 - 2.8 ; p = 0.04 ) . No association between treatment groups and postindex hospitalization and /or ED events was observed . In this managed care population , patients treated with ICSs or LMs had similar measures of treatment effectiveness , as measured by asthma-related health care re source use AIMS Whether chronic dosing with montelukast confers benefit in patients with moderate to severe asthma remains to be fully established . A proof of concept study was performed evaluating putative benefits with montelukast in moderate persistent asthmatics who were taken off inhaled corticosteroids ( ICS ) and switched to  salmeterol . The latter was done to dissociate the effects of montelukast from ICS . METHODS Twenty moderate to severe persistent asthmatics completed a r and omized double-blind crossover study . Subjects received montelukast 10 mg daily or placebo for 2 weeks each . This was preceded by a 2-week run-in when ICS were discontinued and salmeterol started , and used on a regular basis throughout the study . Measurements were made after run-in and after both r and omized treatments . RESULTS There were no significant sequence effects for responses as to whether placebo or montelukast were given first or second . Methacholine PD20 values after run-in , first and second placebo were 63 micro g , 60 micro g and 64 micro g , respectively ( corresponding to 2 , 4 and 6 weeks of ICS washout , respectively ) . Lung function deteriorated pre vs post run-in , which was significant ( P < 0.05 ) for FEF25 - 75 % predicted . Montelukast conferred significant ( P < 0.05 ) improvements as change from post run-in compared with placebo in methacholine PD20 , FEV1 % predicted , FEF25 - 75 % predicted , diurnal peak expiratory flow , symptoms and salbutamol use . For the primary outcome of methacholine PD20 , this amounted to a 1.6-fold difference ( 95 % CI 1.1 , 2.5 ) . CONCLUSIONS In moderate persistent asthmatics switched from taking ICS to salmeterol alone , adding montelukast conferred significant benefits on all parameters of asthma control . Further studies are indicated to evaluate whether montelukast exhibits additive effects to ICS/long-acting beta2-adrenoceptor agonist combination inhalers upon clinical ly important outcomes BACKGROUND Asthma morbidity and mortality rates are high among young inner-city children . Lack of routine primary care provider visits , poor access to care , and poor patient-physician communication might be contributing factors . OBJECTIVE This study evaluated the effects of providing Breathmobile services only , a Facilitated Asthma Communication Intervention ( FACI ) only , or both Breathmobile plus FACI on asthma outcomes relative to st and ard care . METHODS Children with asthma ( n = 322 ; mean age , 4 years ; 53 % male ; 97 % African American ) were recruited from Head Start programs in Baltimore City and r and omized into 4 groups . Outcome measures included symptom-free days ( SFDs ) , urgent care use ( emergency department visits and hospitalizations ) , and medication use ( courses of oral steroids and proportion taking an asthma controller medication ) , as reported by caregivers at baseline , 6-month , and 12-month assessment s. Generalized estimating equations models were conducted to examine the differential treatment effects of the Breathmobile and FACI compared with st and ard care . RESULTS Children in the combined treatment group ( Breathmobile plus FACI ) had an increase of 1.7 ( 6.6 % ) SFDs that was not maintained at 12 months . In intent-to-treat analyses the FACI-only group had an increase in the number of emergency department visits at 6 months , which was not present at 12 months or in the post hoc as-treated analyses . No significant differences were found between the intervention groups compared with those receiving st and ard care on all other outcome measures . CONCLUSIONS Other than a slight improvement in SFDs at 6 months in the Breathmobile plus FACI group , the intervention components did not result in any significant improvements in asthma management or asthma morbidity BACKGROUND Few studies have compared the efficacy of inhaled corticosteroids and leukotriene modifiers for the treatment of persistent asthma . OBJECTIVE Our purpose was to compare the efficacy of a low dose of inhaled fluticasone propionate ( FP ) with that of oral zafirlukast in the treatment of persistent asthma previously treated with short-acting beta(2)-agonists alone . METHODS A 12-week , r and omized , double-blind , double-dummy , multicenter study was conducted in 451 patients aged 12 years and older with asthma who were symptomatic on short-acting beta(2)-agonists alone . After an 8- to 14-day run-in period , patients were r and omized to treatment with FP 88 microg twice daily or zafirlukast 20 mg twice daily . RESULTS Treatment with FP was more effective than treatment with zafirlukast in increasing morning FEV(1 ) ( by 0.42 L vs 0.20 L over baseline , P < .001 ) , morning peak expiratory flow ( by 49.94 L/min vs 11.68 L/min over baseline , P < . 001 ) , and evening PEF ( by 38.91 L/min vs 10.50 L/min over baseline , P < .001 ) . Statistically significant differences between the two treatments in FEV(1 ) were noted after the first observation ( week 4 ) and in morning and evening peak expiratory flow by week 2 . Mean change in percentage of symptom-free days was greater with FP than with zafirlukast ( 28.5 % of days vs 15.6 % of days , P < .001 ) and FP significantly increased the percentage of rescue-free days by 40.4 % of days compared with 24.2 % of days with zafirlukast ( P < .001 ) . Treatment with FP significantly reduced albuterol use by 2.39 puffs per day compared with 1.45 puffs per day ( P < .001 ) and increased the percentage of nights with no awakenings by 21.2 % of nights compared with 8.0 % of nights with zafirlukast ( P < .001 ) . CONCLUSION The clinical effectiveness of a low dose of FP as first-line therapy in patients with persistent asthma who are symptomatic on beta(2)-agonists alone is superior to that of zafirlukast Asthma is associated with an increase in airway blood flow ( Qaw ) , presumably as a manifestation of airway inflammation . We therefore determined the effect of the antiinflammatory agents montelukast ( ML ) and fluticasone propionate ( FP ) on Qaw in 12 patients with mild intermittent asthma . Using a double-blind approach , Qaw along with FEV(1 ) and Vmax(50 ) were determined before and after a 2-week treatment period with either ML ( 10 mg/day ) , FP ( 440 microg/day ) , or 10 mg of ML plus 440 microg of FP daily , separated by 2-week washout periods . Mean ( + /- SEM ) Qaw ranged from 68 + /- 4.2 to 71.8 + /- 5.9 microl x minute(-1 ) x ml(-1 ) anatomic dead space before the treatment periods . ML , FP , and ML plus FP decreased mean Qaw by 21.5 , 20.8 , and 26.9 % , respectively ( p < 0.05 for all ) . No significant difference was observed among the three regimens . FEV(1 ) and Vmax(50 ) were not changed by any of the treatments . We conclude that at the dosages used , ML and FP are equipotent in reducing Qaw in patients with mild asthma , and that the magnitude of the response is not greater if the two drugs are combined . The results also suggest that the vascular effects of these agents can be assessed independent of their effects on airway function PURPOSE In the United Kingdom , about 40 % of patients with asthma are homozygous for the glycine-16 beta(2)-adrenoceptor polymorphism , which predisposes them to agonist-induced down-regulation and desensitization of the beta(2)-adrenoceptor . We assessed the effects of adding treatment with either a long-acting beta(2)-agonist ( inhaled formoterol , 12 microg twice daily ) or a leukotriene receptor antagonist ( oral zafirlukast , 20 mg twice daily ) to inhaled corticosteroid therapy in patients with this genotype . SUBJECTS AND METHODS We enrolled 24 patients with mild to moderate asthma who were being treated with inhaled corticosteroids . Patients were r and omly assigned to receive one of three treatments ( placebo , zafirlukast , or formoterol in addition to inhaled corticosteroids ) for 1 week each in a crossover fashion , separated by a 1-week placebo run-in and washout period . Measurements of bronchoprotection ( measured as the provocative dose of methacholine that produced a 20 % decline in forced expiratory volume in 1 second [ FEV(1 ) ] ) , exhaled nitric oxide ( a surrogate marker of airway inflammation ) , and symptoms were made before each treatment and 12 hours after the last dose of each treatment . RESULTS Both formoterol and zafirlukast were equally effective in maintaining asthma control compared with placebo : the geometric mean-fold difference in the methacholine provocative dose was 1.5-fold ( 95 % confidence interval [ CI ] : 1.1- to 2.2-fold ) for zafirlukast and 1.9-fold ( 95 % CI : 1.2- to 2.9-fold ) for formoterol . As compared with placebo , zafirlukast caused a significant suppression in exhaled nitric oxide ( 1.7-fold difference in geometric mean values , 95 % CI : 1.1- to 2.6-fold ) but formoterol did not ( 1.2-fold difference , 95 % CI : 0.8- to 1.9-fold ) . Diary cards showed significant ( P < 0.05 ) improvements in the peak flow with formoterol ( morning and evening ) and zafirlukast ( evening ) as compared with placebo . CONCLUSIONS Formoterol and zafirlukast maintained asthma control in patients who might be genetically predisposed to fare worse with long-acting beta(2)-agonists . The reduction in exhaled nitric oxide with zafirlukast suggests that it may have anti-inflammatory effects in addition to those seen with inhaled corticosteroids BACKGROUND Information is lacking on the relative effectiveness and cost effectiveness -- in a primary -care setting --of leukotriene receptor antagonists ( LTRAs ) as an alternative to inhaled corticosteroids ( ICS ) for initial asthma controller therapy . OBJECTIVE To compare the cost effectiveness of LTRAs versus ICS for patients initiating asthma controller therapy . METHODS An economic evaluation was conducted alongside a 2-year , pragmatic , r and omized controlled trial set in 53 primary -care practice s in the UK . Patients aged 12 - 80 years with asthma and symptoms requiring regular anti-inflammatory therapy ( n = 326 ) were r and omly assigned to LTRAs ( n = 162 ) or ICS ( n = 164 ) . The main outcome measures were the incremental costs per point improvement in the Mini Asthma Quality of Life Question naire , per point improvement in the Asthma Control Question naire and per QALY gained from the UK NHS and societal perspectives . RESULTS Over 2 years , re source use was similar between the two treatment groups , but the cost to society per patient was significantly higher for the LTRA group , at pounds sterling 711 versus pounds sterling 433 for the ICS group ( adjusted difference pounds sterling 204 ; 95 % CI 74 , 308 ) [ year 2005 values ] . Cost differences were driven primarily by differences in prescription drug costs , particularly study drug costs . There was a nonsignificant ( imputed , adjusted ) difference between treatment groups , favouring ICS , in QALYs gained at 2 years of -0.073 ( 95 % CI -0.143 , 0.010 ) . Therapy with LTRAs was , on average , a dominated strategy , and , at a threshold for willingness to pay of pounds sterling 30,000 per QALY gained , the probability of LTRAs being cost effective compared with ICS was approximately 3 % from both societal and NHS perspectives . CONCLUSIONS There is a very low probability of LTRAs being cost effective in the UK , at 2005 values , compared with ICS for initial asthma controller therapy . TRIAL REGISTRATION UK National Research Register N0547145240 ; Controlled Clinical Trials IS RCT N99132811 BACKGROUND Airway inflammation is a key pathological feature of asthma which underlies its clinical presentation . OBJECTIVES To examine whether adding a leukotriene modifier to an inhaled corticosteroid produces further clinical and /or anti-inflammatory benefits in patients symptomatic on short-acting beta(2)-agonists . METHODS Patients uncontrolled on short-acting beta(2)-agonists were treated for 12 weeks with either fluticasone propionate ( 100mcg BD ) or fluticasone propionate ( 100mcg BD ) and montelukast ( 10 mg QD ) in a r and omized , double-blind , parallel group study . Bronchoscopy with endobronchial biopsy and bronchoalveolar lavage ( BAL ) was performed before and after treatment to compare effects on airway inflammation . RESULTS Of 103 subjects enrolled , 89 subjects completed treatment and 82 subjects had matched pair biopsy sample s.  Submucosal eosinophil counts , the primary endpoint , and asthma control improved to similar extents after both treatments ( p < or=0.008 ) . Both treatments significantly reduced submucosal mast cell , CD3 + , CD4 + , CD8 + and CD25 + cell counts . Submucosal mast cell reduction was greater in the fluticasone propionate plus montelukast group . There were no differences between treatments in BAL markers of inflammation or thickness of sub-epithelial collagen . CONCLUSIONS Low-dose fluticasone propionate significantly improves clinical disease control and reduces airway inflammation in asthma patients uncontrolled with short-acting beta(2)-agonists without further improvement when montelukast is added to low-dose fluticasone propionate
BACKGROUND In the treatment of children with mild persistent asthma , low-dose inhaled corticosteroids ( ICS ) are recommended as the preferred monotherapy ( referred to as step 2 of therapy ) .
In children with inadequate asthma control on low doses of ICS  ( step 2 ) , asthma management guidelines recommend adding an anti-leukotriene agent to existing ICS as one of three therapeutic options to intensify therapy ( step 3 ) .
OBJECTIVES To compare the efficacy and safety of the combination of anti-leukotriene agents and ICS to the use of the same , an increased , or a tapering dose of ICS in children and adolescents with persistent asthma who remain symptomatic despite the use of maintenance ICS .
In addition , we wished to determine the characteristics of people or treatments , if any , that influenced the magnitude of response attributable to the addition of anti-leukotrienes .