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A randomized, double-blind trial of the effect of treatment with montelukast on bronchial hyperresponsiveness and serum eosinophilic cationic protein (ECP), soluble interleukin 2 receptor (sIL-2R), IL-4, and soluble intercellular adhesion molecule 1 (sICAM-1) in children with asthma. A placebo-controlled, dose-ranging study of montelukast, a cysteinyl leukotriene-receptor antagonist. Montelukast Asthma Study Group. Leukotriene receptor antagonist, montelukast, can reduce the need for inhaled steroid while maintaining the clinical stability of asthmatic patients Comparative Effects of Desloratadine versus Montelukast on Asthma Symptoms and Use of β2-Agonists in Patients with Seasonal Allergic Rhinitis and Asthma Pranlukast, a novel leukotriene receptor antagonist: results of the first European, placebo controlled, multicentre clinical study in asthma. Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study. 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Pranlukast ( 8‐[p‐(4‐phenylbutyloxy ) benzol ] amino‐2‐[tetrazol‐5‐yl]‐4‐oxo‐4H‐1‐benzopyran hemihydrate ) , a selective cysteinyl leukotriene receptor antagonist , has been reported to exhibit not only antileukotrine activity but also pharmacological activity including antieosinophilic effects BACKGROUND It has been reported that pranlukast reduces the antigen induced immediate and late phase asthmatic responses , airway hyperreactivity to acetylcholine , and pulmonary eosinophil accumulation in guinea pigs . A study was undertaken to test the hypothesis that pranlukast may reduce the number of inflammatory cells in the bronchial mucosa of patients with asthma . METHODS A double blind , placebo controlled study was performed in 17 mild to moderate asthmatic subjects to examine changes in inflammatory cell infiltration in response to pranlukast ( 225 mg orally twice per day for four weeks ) . Comparisons of the mean daily β2 agonist use , symptom score , FEV1 percentage predicted , and airway methacholine responsiveness were made before and after treatment . Using fibreoptic bronchoscopy , bronchial biopsy specimens were obtained before and after treatment with either pranlukast ( n = 10 ) or placebo ( n = 7 ) . Immunohistology was performed using monoclonal antibodies for CD3 , CD4 , CD8 , CD68 , NP57 , AA1 , EG1 , EG2 , γGTP and CD19 . RESULTS When the pranlukast and placebo treated groups were compared there were decreases in β2agonist use , symptom score , and airway methacholine responsiveness  after pranlukast but no increase in FEV1 was seen . The clinical response in patients treated with pranlukast was accompanied by a reduction in CD3 ( median difference –37 , 95 % confidence interval ( CI ) –69 to –1 ; p<0.05 ) , CD4 ( median difference –28 , 95 % CI –49 to –8 ; p<0.01 ) , AA1 ( median difference –15 , 95 % CI –26 to 0 ; p<0.05 ) and EG2 positive cells ( 95 % CI –35 to 0 ; p<0.05 ) , but not in EG1 positive eosinophils , γGTP positive cells , and CD19 positive plasma cells . CONCLUSIONS These results support the view that pranlukast may act by inhibition of bronchial inflammation in patients with asthma Background Asthma affects mainly Venezuela ’s urban and poor majority . Exacerbations bring about a high dem and in health services , thus becoming a significant public health problem . In general , asthma control programs ( GINA ) with use of inhaled steroid medications have proven effective , although their implementation in real life remains cumbersome . Montelukast could be a useful and practical tool for these deprived socioeconomic sectors . Methods This real-life pilot study was conducted in a prospect i ve , double blinded , placebo-controlled manner with r and omized and parallel groups . Asthmatics that had never used leukotriene modifiers were recruited and followed-up every three months . The main outcome was the number of exacerbations meriting use of nebulized bronchodilators  administered by the health care system . Results Eighty-eight asthmatic patients were enrolled , between children and adults . Groups were comparable in : demographic data , previous use of other medications , ACT scores , pulmonary functions ( Wright Peak Flow meter ) , allergy status ( Skin Prick Test ) as well as adherence to the prescribed Montelukast treatment . By an intention to treat ( ITT ) , a total of 64 patients were included for analysis . For the three and six months time points the difference between placebo and Montelukast was found to be significant ( p < 0.03 and p < 0.04 , respectively ) . Such trends continued for the rest of the year , but without statistical significance , due to patient attrition . Conclusions This real-life pilot study shows that a simplified strategy with oral Montelukast was practical and effective in controlling exacerbations in an asthmatic population of a vulnerable community from Caracas . Such an approach reinforces the role of primary care in asthma treatment OBJECTIVE Many asthmatic patients are unable to quit cigarettes ; therefore information is needed on treatment options for smokers . This study evaluates 10 mg/d montelukast and 250 μg of fluticasone propionate twice daily , each compared with placebo , in patients with self-reported active smoking ( unable to quit ) and asthma . METHODS Patients ( ages 18 - 55 years , with asthma [ ≥1 year ] , FEV1 of 60 % to 90 % of predicted value , airway reversibility [ ≥12 % ] , and self-reported active smoking [ ≥0.5 to ≤2 packs per day ] ) were r and omized ( after a 3-week , single-blind , placebo , run-in period ) to 1 of 3 parallel , 6-month , double-blind treatment arms . The primary efficacy end point was the percentage of days with asthma control during treatment . Adverse experiences ( AEs ) were also evaluated . RESULTS There were 347 , 336 , and 336 patients r and omized to montelukast , fluticasone , and placebo , respectively . The mean percentage of days with asthma control over 6 months of treatment was 45 % ( montelukast , P < .05 vs placebo ) , 49 % ( fluticasone , P < .001 vs placebo ) , and 39 % ( placebo ) ; the difference between montelukast and fluticasone was not significant ( P = .14 ) . Patients with a smoking history of ≤11 pack years ( the median value ) tended to show more benefit with fluticasone , whereas those with a smoking history of > 11 pack years tended to show more benefit with montelukast  . AEs occurred in similar proportions among treatment groups . CONCLUSIONS In a population of asthmatic patients actively smoking cigarettes , both 10 mg/d montelukast and 250 μg of fluticasone propionate twice daily significantly increased the mean percentage of days with asthma control compared with placebo BACKGROUND Leukotrienes , especially LTC4 , are important inflammatory mediators in allergic and nonallergic inflammation of the entire airways . Of particular interest are numerous theories regarding the pathogenesis of aspirin intolerance with subsequent hyperproduction of leukotrienes and inhibition of cyclooxygenase . OBJECTIVE To examine the influence of the cysteinyl-leukotriene receptor antagonist montelukast on clinical symptoms and inflammatory markers in nasal lavage fluid in patients with bronchial asthma and nasal polyps , and determine its dependency on aspirin sensitization . METHODS Twenty-four patients ( 7 women , 17 men ; median age , 55.5 years ) with nasal polyps and controlled asthma ( n=12 with aspirin intolerance ) were treated with 10 mg montelukast once daily for 6 weeks in a blinded , placebo-controlled fashion . The placebo phase was r and omly assigned 4 weeks before ( n=12 ) or after treatment ( n=12 ) . Symptom score , rhinoendoscopy , rhinomanometry , smears for eosinophils , and nasal lavages for the determination of different mediators were performed . RESULTS Compared to placebo , there were significant improvements in the nasal symptom score and airflow limitation as well as a reduction in the inflammatory mediators in nasal lavage fluid after treatment . Furthermore , reduced eosinophils in nasal smears and peripheral blood were observed 2 and 6 weeks after treatment . CONCLUSION Leukotriene 1 receptor blockade led to a significant decrease in eosinophil inflammation accompanied by a reduction in other mediators such as neurokinin A and substance P in the nasal lavage fluid of patients with nasal polyps and asthma , with or without aspirin intolerance SUMMARY Objective : The objective of this study was to evaluate montelukast 10 mg daily as treatment for allergic rhinitis in patients with symptomatic allergic rhinitis and active asthma during the allergy season . Methods : This was a multicenter study of 831 patients ( ages 15 years–85 years ) with seasonal allergen sensitivity , active symptoms of seasonal allergic rhinitis , and active asthma . Following a single-blind , placebo run-in period of 3 days–5 days , patients were r and omized to oral montelukast 10 mg ( n = 415 ) or placebo ( n = 416 ) daily during the 2-week , double-blind , active-treatment period . Main outcome measures : The primary endpoint was Daily Rhinitis Symptoms score , average of Daytime Nasal Symptoms and Nighttime Symptoms , as self-rated by patients on a 0–3 scale on daily diaries . Results : Montelukast  reduced the Daily Rhinitis Symptoms score : difference between montelukast and placebo in mean change from baseline was –0.12 [ 95 % CI –0.18 , –0.06 ; p ≤ 0.001 ] . Similar improvements were seen in Daytime Nasal Symptoms ( –0.14 [ –0.21 , –0.07 ; p ≤ 0.001 ] ) and Nighttime Symptoms ( –0.10 [ –0.16,–0.04 ; p ≤ 0.001 ] ) . Improvements ( p < 0.05 ) were seen in Daytime Eye Symptoms and in the secondary endpoints of Global Evaluations of AR by Patient and by Physician , and Rhinoconjunctivitis Quality of Life . In exploratory analyses , improvement in rhinitis symptoms was numerically ( though not statistically ) larger in patients with greater levels of asthma at study start . Montelukast provided benefit in the Global Evaluations of Asthma by Patient and by Physician : mean differences were –0.24 [ –0.41 , –0.06 ; p = 0.008 ] and –0.17 [ –0.33,–0.01 ; p = 0.037 ] . Similarly , as-needed β-agonist use ( puffs/day ) was reduced with montelukast ( p ≤ 0.005 ) . Conclusion : Montelukast provides significant relief from symptoms of seasonal allergic rhinitis , while also conferring a benefit for asthma , in patients with both allergic rhinitis and asthma For patients with persistent asthma , the National Asthma Education and Prevention Program recommends the regular use of controller medications to provide long-term control , together with as-needed use of rescue medications ( 1 ) . Inhaled corticosteroids are currently the most commonly used controller medications ( 1 ) . Although inhalation into the airway has advantages in terms of both safety and efficacy , problems with compliance with inhaled agents may limit their real-world effectiveness , especially in elderly and pediatric patients ( 2 , 3 ) . Cysteinyl leukotrienes are important pro-inflammatory mediators of asthma ( 4 ) . Recent clinical studies of leukotriene receptor antagonists ( 5 - 7 ) and a 5-lipoxygenase inhibitor ( 8) have shown these agents to have clinical benefit in patients with chronic asthma , and treatment guidelines now consider these agents alternative , first-line controller medications ( 1 ) . Recent studies showed that montelukast , a potent and specific leukotriene receptor antagonist ( 9 ) , had efficacy in adult ( over a 12-week period ) and pediatric ( over an 8-week period ) patient with chronic asthma and had a tolerability profile similar to that of placebo ( 10 - 12 ) . To date , no comparisons of leukotriene receptor antagonists and inhaled corticosteroids have been published . Our placebo-controlled , parallel-group study , which was primarily design ed to compare the effect of montelukast with that of placebo in a phase III clinical development trial , also compared montelukast and inhaled beclomethasone in patients with chronic asthma who require the daily use of a controller medication . Methods Patients Healthy , nonsmoking , male and female patients 15 years of age and older were eligible to participate if they had had asthma for at least 1 year before the initial study evaluation . Each patient also had to have 1 ) an FEV1 between 50 % and 85 % of predicted value , 2 ) an increase of at least 15 % in absolute FEV1 after the use of inhaled -agonist on at least two of three visits during period 1 [ see below ] , 3 ) a daytime asthma symptom score of at least 64 [ of a possible 336 ] , and 4 ) average daily use of at least one puff of as-needed , short-acting , inhaled -agonist ( salbutamol )  . Patients were excluded from the study if they had used inhaled and oral corticosteroids , cromolyn , or nedocromil within 4 weeks before the initial evaluation ; had used long-acting -agonists , antimuscarinics , and newly instituted theophylline within 2 weeks before the initial evaluation ; or had used long-acting antihistamines ( for example , they could not have used astemizole within 3 months of the initial evaluation , and they could not have used terfenadine or loratadine within 2 weeks of the initial evaluation ) . Intermittent use of short-acting antihistamines was allowed , and immunotherapy was permitted if it had been started at least 6 months before the initial study evaluation and if the monthly dose remained constant . Protocol Our r and omized , double-dummy , placebo-controlled , parallel-group trial had a 2-week , single-blind placebo run-in period ( period 1 ) ; a 12-week , double-blind treatment period ( period 2 ) ; and a 3-week , double-blind placebo washout period [ period 3 ] . Eligible patients were r and omly assigned to one of three treatment regimens : 1 ) montelukast , 10 mg once daily in the evening ; 2 ) inhaled beclomethasone , 200 g twice daily ; or 3 ) placebo . The ratio of montelukast recipients to beclomethasone recipients to placebo recipients was 3:2:2 , with a blocking factor of 7 , according to a single , computer-generated allocation schedule . Patients , investigators , and coordinating center staff were blinded to the treatment schedule until all corrections to the data base were completed . During period 3 , a subset of patients originally assigned to receive active treatment ( approximately 40 , as determined by the allocation schedule ) was switched to placebo in a blinded manner . The other patients originally assigned to receive active treatment continued to receive that treatment . This allowed us to assess withdrawal from therapy . The study was done at 36 clinical centers in 19 countries in Europe , Africa , Australia , Central America , and South America . The study protocol and informed consent were approved by local ethics review committees . All participants gave written informed consent before participation ; consent of parents or guardians was obtained for patients younger than 18 years of age . Patients were recruited from the patient pool of each clinical study center and through local newspaper advertisements . Medication The study medication consisted of 10-mg montelukast film-coated tablets , placebo tablets that were identical in appearance to the montelukast tablets , beclomethasone ( 100 g/puff ) in inhalers ( Allen & Hanburys , Stockley Park , United Kingdom ) , and placebo in inhalers identical to those used for beclomethasone . Patients were instructed to take one tablet at bedtime and to take two puffs from the inhaler ( using the AeroChamber spacer device [ Clement Clark , Columbus , Ohio ] ) at bedtime and in the morning . Short-acting , inhaled -agonist ( salbutamol , 100 g/puff ) ( Allen & Hanburys ) was to be used as needed . Patients with worsening episodes of asthma that required additional therapy were treated with oral corticosteroids according to a st and ard protocol . Patients who had more than two worsening episodes of asthma requiring corticosteroid therapy were dropped from the study . Measurements Central ized spirometry training was done according to st and ard American Thoracic Society criteria before the start of the study .  Spirometry  was done at each visit after inhaled -agonist therapy had been withheld for at least 6 hours , theophylline therapy had been withheld for at least 24 hours , and antihistamine therapy had been withheld for at least 48 hours . At least three spirometry maneuvers were done , and the largest FEV1 was reported . Spirometry data were transmitted electronically to a central data base and monitored continuously for quality , and feedback was given to the study centers ( 13 ) . If quality was not maintained , sites were visited by coordinating center personnel . Answers to four questions on daytime asthma symptoms and one question on nocturnal awakenings were collected on a daily diary card , as were morning and evening peak expiratory flow rate and daily use of as-needed salbutamol . With respect to daytime asthma symptoms , patients used a 7-point scale ( on which 0 means best and 6 means worst ) to rate the severity of symptoms , their frequency , the degree to which they were bothersome , and their impact on daily activities . These ratings were combined into a mean daily score . Nocturnal awakenings were evaluated by the patient 's response ( on a four-point scale ) to a single question ( 14 ) . The validation of these questions has been published elsewhere ( 14 ) . Peak expiratory flow was measured in the morning and in the evening immediately before study medication was taken . The best of three measurements was recorded . Prespecified end points other than peak expiratory flow included peripheral blood eosinophil counts , global evaluations by physicians and patients ( on a 7-point scale , on which 6 means very much worse and 0 means very much better ) ( 7 ) , and asthma-specific quality of life ( 15 ) . Asthma outcome end points , including asthma attacks ( defined as worsening asthma requiring oral corticosteroid treatment or an unscheduled visit to a physician , emergency department , or hospital ) , percentage of days with asthma exacerbations , and percentage of asthma-control days ( as defined elsewhere [ 11 , 16 ] ) , were also evaluated . The diary card , the Asthma Quality -of-Life Question naire ( 15 ) , and the global evaluation questions were translated from English into appropriate local language s and were vali date d for linguistic equivalence and cultural differences ( 17 ) . Patient compliance with study therapy was determined by weighing inhalers and counting tablets . The weight of a full canister was determined by averaging the weights of at least 50 canisters of beclomethasone and placebo . A st and ard puff weight was determined by repeatedly actuating and weighing 10 canisters . Laboratory safety tests , including hematologic tests , serum biochemistry analysis , and urinalysis , were done at prespecified visits , and the results were analyzed by a central laboratory . The central laboratory also determined eosinophil counts with an automated cell counter . Statistical Analysis Our primary objective was to compare montelukast with placebo with respect to two prespecified primary end points : FEV1 and daytime symptom score . Other objectives were to compare beclomethasone with placebo and to compare montelukast with beclomethasone in a stepwise manner in accordance with the Dunnet-Tamhane approach , with the comparison of montelukast and beclomethasone prespecified as an estimation of the difference using 95 % CIs ( 18 ) . No multiplicity adjustments were made for each of the secondary end points , which were prespecified as supportive . The analysis for each efficacy end point included all patients who had a measurement taken at baseline and at least one measurement taken after r and omization . Treatment responses were calculated as the average change or percentage change from baseline to period 2 ; the baseline value was the average value for period 1 . With SAS software ( SAS Institute , Inc. , Cary , North Carolina ) , we used an analysis of variance ( ANOVA ) model to estimate treatment group means and between-group differences and to construct 95 % CIs by using the least-square means and the differences in least-square means . The model contained factors for treatment , study center , and stratum ( theophylline use ) . The consistency of the treatment effect across study centers , strata , and subgroups ( which were formed according to sex , age , ethnicity , history of allergic rhinitis , and history of exercise-induced asthma ) was assessed by interaction testing done using the ANOVA model with an OBJECTIVE Leukotrienes ( LTs ) are involved in airway eosinophilic inflammation in patients with asthma . We examined the effects of a cysteinyl LT 1-receptor antagonist , montelukast , on sputum eosinophil levels , and the correlation between sputum eosinophils and bronchodilatation in patients with asthma . DESIGN Double-blind , r and omized , crossover study . SETTING University hospital and private hospital . PATIENTS Twenty-nine patients with mild-to-moderate asthma . INTERVENTIONS Montelukast , 10 mg , and placebo tablet , once daily , each for 4 weeks . MEASUREMENTS Sputum eosinophils analyzed using hypertonic saline solution-induced sputum and airway hyperresponsiveness to histamine were evaluated before and after treatment . In addition , morning and evening peak expiratory flow ( PEF ) , asthma symptoms , and peripheral blood eosinophil levels were assessed . RESULTS The percentage of eosinophils in sputum decreased from 24.6 + /- 12.3 % at baseline to 15.1 + /- 11.8 % after montelukast treatment , for a change of - 9.5 + /- 12.7 % ( n = 20 ) . During placebo administration , the percentage of eosinophils fell from 21.3 + /- 12.1 % to 21.0 + /- 11.5 % , result ing in a decrease of - 0.3 + /- 10.8 % ( n = 20 ) . There was a statistically significant difference in the change in sputum eosinophil levels between these two periods ( p < 0.005 ) . The number of peripheral blood eosinophils also significantly decreased after montelukast treatment ( 314.1 + /- 237.6/mL ) compared with placebo ( 413.1 + /- 232.1/mL ; p < 0.005 , n = 21 ) . Although morning and evening PEF values were significantly improved from baseline after montelukast treatment ( p < 0.01 , n = 20 ) , asthma symptoms and airway responsiveness to histamine were not significantly altered . Furthermore , there was no significant correlation between the decrease in sputum eosinophils and the increase in PEF . CONCLUSION These results suggest that montelukast has anti-inflammatory effects on the airway in patients with asthma , and that its bronchodilatory effect is not solely dependent on a decrease in airway eosinophilia The present study aim ed at comparing the effects of a dose reduction of inhaled corticosteroids on lung function , indirect measures of airway inflammation and clinical scores during treatment with a leucotriene receptor antagonist . In 50 patients ( mean forced expiratory volume in one second ( FEV1 ) 94 % predicted ) , steroid doses ( 800 µg beclomethasone dipropionate ) were first reduced to 50 % and then to 25 % , for 6 weeks each . One group received a placebo and the other group received montelukast ( 10 mg ) . The first reduction did not cause significant effects . During the second , FEV1 and peak expiratory flow decreased in both groups ( p<0.001 ) . Daytime symptoms were not altered with placebo but were reduced by montelukast ( p<0.05 ) . Night-time symptoms were slightly elevated with placebo ( p<0.05 ) but not montelukast , as well as the use of supplemental salbutamol  . Changes in provocative concentration of methacholine causing a 20 % fall in FEV1 ( PC20 ) , sputum eosinophils and exhaled nitric oxide were mostly nonsignificant for both placebo and montelukast . These data demonstrate that a 75 % reduction in the dose of steroid given to patients with asthma led to a deterioration in lung function not prevented by montelukast , whereas changes in clinical state seemed to favour montelukast treatment . It therefore appears that potential effects of montelukast , in the presence of low-dose steroids , could not be attributed to single indices of lung function or airway inflammation Background : Controlled clinical trials on the effects of leukotriene antagonists on asthma‐like symptoms , bronchial hyperresponsiveness and airway inflammation have not been performed in elite athletes STUDY OBJECTIVES We have previously found that vascular endothelial growth factor ( VEGF ) levels in induced sputum were increased in asthmatic patients , and that its levels were closely associated with the degree of airway obstruction and microvascular permeability . Therefore , this study was design ed to examine the effects of pranlukast , a selective leukotriene receptor antagonist , on VEGF levels in induced sputum from steroid-untreated or steroid-treated asthmatic patients . DESIGN Double-blind , r and omized , placebo-controlled , crossover study . SETTING University hospital . PARTICIPANTS Twenty-three asthmatic patients ( steroid-untreated , 13 patients ; steroid-treated , 10 patients ) and 10 healthy control subjects . INTERVENTIONS All asthmatic patients received 4-weeks of therapy with pranlukast ( 225 mg bid ) , and sputum induction was performed before and after the 4-week treatment course . MEASUREMENTS AND RESULTS In steroid-untreated asthmatic patients , the mean percentage of eosinophils ( % EOS ) and mean eosinophil cationic protein ( ECP ) levels in induced sputum were significantly decreased after 4 weeks of pranlukast administration ( % EOS : before , 16.7 % [ SD , 7.1 % ] ; after , 12.3 % [ SD , 4.0 % ] ; p = 0.03 ; ECP levels : before , 774 ng/mL [ SD , 258 ng/mL ] ; after , 564 ng/mL [ SD , 204 ng/mL ] ; p = 0.034 ) . Moreover , VEGF levels in the induced sputum and the airway vascular permeability index also were decreased after pranlukast administration ( VEGF levels : before , 5,670 pg/mL [ SD , 1,780 pg/mL ] ; after , 4,380 pg/mL [ SD , 1,540 pg/mL ] ; p = 0.026 ; airway vascular permeability index : before , 0.032 [ SD , 0.012 ] ; after , 0.017 [ SD , 0.006 ] ; p = 0.01 ) . In addition , the change in airway vascular permeability index from before to after pranlukast administration was significantly correlated with the change in VEGF levels ( r = 0.782 ; p = 0.007 ) . However , in steroid-treated asthmatic patients there was no significant difference in mean VEGF levels in induced sputum between placebo administration ( before , 3,640 pg/mL [ SD , 1,020 pg/mL ] ; after , 3,640 pg/mL [ SD , 960 pg/mL ] and pranlukast administration ( before , 3,660 pg/mL [ SD , 940 pg/mL ] ; after , 2,950 pg/mL [ SD , 890 pg/mL ] ) . CONCLUSIONS Pranlukast administration decreased airway microvascular permeability through , at least in part , a decrease in airway VEGF levels in steroid-untreated asthmatic patients . However , it is likely that pranlukast administration added little efficacy to inhaled corticosteroid therapy for reduction in airway VEGF levels Background : Proinflammatory leukotrienes , which are not completely inhibited by inhaled corticosteroids , may contribute to asthmatic problems . A 16 week multicentre , r and omised , double blind , controlled study was undertaken to study the efficacy of adding oral montelukast , a leukotriene receptor antagonist , to a constant dose of inhaled budesonide . Methods : A total of 639 patients aged 18–70 years with forced expiratory volume in 1 second ( FEV1 ) ≥55 % predicted and a minimum predefined level of asthma symptoms during a 2 week placebo run in period were r and omised to receive montelukast 10 mg ( n=326 ) or placebo ( n=313 ) once daily for 16 weeks . All patients received a constant dose of budesonide ( 400–1600 μg/day ) by Turbuhaler throughout the study . Results : Mean FEV1 at baseline was 81 % predicted . The median percentage of asthma exacerbation days was 35 % lower ( 3.1 % v 4.8 % ; p=0.03 ) and the median percentage of asthma free days was 56 % higher ( 66.1 % v 42.3 % ; p=0.001 ) in the montelukast group than in the placebo group . Patients receiving concomitant treatment with montelukast had significantly ( p<0.05 ) fewer nocturnal awakenings and significantly ( p<0.05 ) greater improvements in β agonist use and morning peak expiratory flow rate ( PEFR ) . Conclusions : For patients with mild airway obstruction and persistent asthma symptoms  despite budesonide treatment , concomitant treatment with montelukast significantly improves asthma control 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 Background : Inhaled corticosteroids and leukotriene receptor antagonists reduce airway eosinophilia and have been used as first line anti-inflammatory therapy for mild persistent asthma . Methods : A multicentre , r and omised , placebo controlled , parallel group study was performed to compare the anti-inflammatory effects of fluticasone propionate and montelukast as measured by sputum eosinophils in 50 adults with symptomatic steroid naive asthma and sputum eosinophilia of ⩾3.5 % . Results : Eighteen patients received low dose fluticasone ( 250 μg/day ) , 19 received montelukast ( 10 mg/day ) , and 13 were given placebo for 8 weeks . Fluticasone treatment result ed in a greater reduction in sputum eosinophils ( geometric mean ( SD ) 11.9 (2.3)% to 1.7 (5.1)% ) than montelukast ( 10.7 (2.3)% to 6.9 (3.8)% ; p = 0.04 ) or placebo ( 15.4 (2.4)% to 7.8 (4.2)% ; p = 0.002 ) , and improvement in FEV1 ( mean ( SD ) 2.6 ( 0.9 ) l to 3.0 ( 0.9 ) l ) than montelukast ( 2.8 ( 0.7 ) l to 2.8 ( 0.9 ) l ; p = 0.02 ) or placebo ( 2.4 ( 0.8 ) l to 2.4 ( 0.9 ) l ; p = 0.01 ) . Treatment with fluticasone  suppressed sputum eosinophilia within a week while montelukast only attenuated it . The effect of montelukast was maximal at 1 week and was maintained over 4 weeks . The effect of fluticasone was maintained over 8 weeks while that of montelukast was not . Conclusions : Montelukast is not as effective as low dose fluticasone in reducing or maintaining an anti-inflammatory effect in steroid naïve eosinophilic asthma Leukotrienes are pro-inflammatory mediators which may contribute to tissue , sputum , and blood eosinophilia seen in allergic and inflammatory diseases , including asthma . Montelukast is a cysteinyl leukotriene1 ( CysLT1 ) receptor antagonist which improves asthma control ; the aim of this study was to investigate its effect on induced sputum eosinophils .  Montelukast 10 mg ( n=19 ) or placebo ( n=21 ) were administered orally once in the evening for 4 weeks to 40 chronic adult asthmatic patients , aged 19 - 64 yrs , in a double-blind , r and omized , parallel group study . Patients were included if , at pre study , they had > 5 % sputum eosinophils , symptomatic asthma with a forced expiratory volume in one second > or = 65 % of the predicted value and were being treated only with " as needed " inhaled beta2-agonists . In addition to sputum eosinophils , blood eosinophils and clinical endpoints were also assessed . Four weeks of montelukast treatment decreased sputum eosinophils from 7.5 % to 3.9 % ( 3.6 % decrease , 95 % confidence interval ( CI ) -16.6 - 0.4 ) . In contrast , placebo treatment was associated with an increase in sputum eosinophils from 14.5 % to 17.9 % ( 3.4 % increase , 95 % CI -3.5 - 9.8 ) . The least squares mean difference between groups ( -11.3 % , 95 % CI -21.1-(-1.4 ) ) was significant ( p=0.026 ) . Compared with placebo , montelukast significantly reduced blood eosinophils ( p=0.009 ) , asthma symptoms ( p=0.001 ) and beta2-agonist use ( p<0.001 ) while significantly increasing morning peak expiratory flow ( p=0.001 ) . Montelukast was generally well tolerated in this study , with a safety profile similar to the placebo . These results demonstrate that montelukast decreases airway eosinophilic inflammation in addition to improving clinical parameters . Its efficacy in the treatment of chronic asthma may be due , in part , to the effect on airway inflammation The distribution of responses in study population s provides a novel method of comparing the benefit of two treatments . This 6‐week , r and omised , placebo-controlled , double-blind study compared the effectiveness of oral montelukast with inhaled beclomethasone in chronic asthma by assessing the distribution and overlap of patient responses to therapy , as measured by a clinical outcome ( asthma control days ) . A total of 730 adult patients with asthma , age 15–65 yrs , with a forced expiratory volume in one second ( FEV1 ) at baseline of 50–85 % of predicted and ≥15 % improvement in FEV1 after inhaled β‐agonist were enrolled . After a 2–week placebo run-in period , patients were r and omly allocated to receive montelukast ( 10 mg once daily ) , inhaled beclomethasone ( 200 µg twice daily ) or placebo . The primary end-point ( per cent of asthma control days ) was compared between treatments as the overlap in the response distributions . The overlap of the distribution of responses between the montelukast and beclomethasone groups was 89 % for per cent asthma control days and 96 % for change from baseline in FEV1 . The mean ( ±sd ) per cent asthma control days in the montelukast and beclomethasone groups was significantly higher than that in the placebo group ( placebo 40.0±35.8 , montelukast 50.7±37.1 , beclomethasone 57.9±36.1 ) . The mean differences between montelukast and placebo , beclomethasone and placebo , and montelukast and beclomethasone were significant . The mean per cent change ( ±sd ) from baseline in FEV1 was 12.1±18.7 and 13.9±20.8 in the montelukast and beclomethasone groups , respectively , and significantly greater than that in the placebo group ( 6.4±20.1 ) ; there was no significant difference between the montelukast and beclomethasone groups in mean values or response distribution . There was also no difference among treatment groups in the frequency of adverse experiences . A comparison of the response distribution is an important approach to comparing therapies ; montelukast and beclomethasone provided similar response distributions for the end-point of per cent asthma control days over a 6‐week treatment period BACKGROUND Antileukotriene agents have been shown to be beneficial in chronic asthma . Although patients with cough variant asthma have cough with minimal wheezing and dyspnea , airway hyperresponsiveness from chronic inflammation is believed to be the underlying mechanism . OBJECTIVE To evaluate the effectiveness of montelukast , a leukotriene receptor antagonist , in the treatment of cough variant asthma . METHODS Fourteen patients with cough variant asthma participated in a r and omized , double-blind , placebo-controlled trial with a 7- to 10-day baseline period and a 4-week treatment period with montelukast , 10 mg , or placebo daily . Inclusion criteria were ( 1 ) chronic cough with a duration of at least 4 weeks with minimal or no wheezing or dyspnea and ( 2 ) forced expiratory volume in 1 second of 50 % to 85 % of predicted and reversibility of 12 % with use of an inhaled beta-agonist or forced expiratory volume in 1 second greater than 85 % and positive methacholine challenge results . Patients fulfilled the minimum criteria for cough frequency and symptom scores for r and omization . RESULTS Eight patients received montelukast and 6 received placebo . The primary efficacy variable , mean percentage change from baseline in cough frequency , was significantly improved by the second week , and by the fourth week the mean percentage change from baseline was 75.7 % for the treatment group and 20.7 % for the placebo group . CONCLUSIONS The leukotriene receptor antagonist montelukast seems to be effective in the treatment of cough variant asthma . Larger studies are recommended to confirm this effect The efficacy of the oral leukotriene-receptor antagonist zafirlukast was assessed as maintenance therapy for patients with mild-to-moderate asthma . A total of 762 patients aged 12 to 76 years were enrolled in a 13-week , multicenter , double-masked , placebo-controlled , parallel-group trial and r and omly assigned to receive either zafirlukast ( 20 mg twice daily ) or placebo . Patients were maintained on as-needed beta-agonist therapy throughout the study and had to have a cumulative daytime asthma symptoms score > or = 8 ( on a daily scale of 0 to 3 ) over 7 consecutive days before r and omization . Efficacy was assessed by changes in symptoms , beta-agonist use , and pulmonary function . Safety was assessed by adverse experiences , laboratory test results , physical examination , and electrocardiography .  Zafirlukast significantly decreased daytime asthma symptoms scores ( -26.5 % ) , nighttime awakenings ( -19.8 % ) , mornings with asthma ( -29.0 % ) , and beta-agonist use ( -22.3 % ) and significantly increased morning peak expiratory flow rate ( 6.9 % ) and forced expiratory volume in 1 second ( 6.3 % ) compared with placebo .  Changes in symptoms , beta-agonist use , and pulmonary function occurred within 2 days of zafirlukast treatment and continued throughout the trial . Zafirlukast was well tolerated . Pharyngitis and headache were the most common adverse events , occurring with similar frequency in both the zafirlukast and placebo groups . No clinical ly significant changes were observed in laboratory test results , findings on physical examination , or electrocardiographic findings . We conclude that zafirlukast produces early and sustained effects in the treatment of mild-to-moderate asthma Background Evidence has demonstrated that the distal lung , which includes airways of < 2 mm in diameter and lung parenchyma , constitutes an important component of asthma pathology . Cysteinyl leukotrienes ( CysLTs ) are potent proinflammatory mediators and bronchoconstrictors involved in the asthmatic process . Guidelines recommend the leukotriene‐modifying agents for asthma treatment . We hypothesized that a leukotriene receptor antagonist with an inhaled corticosteroid ( ICS ) and long‐acting & bgr;2 agonist ( LABA ) combination would improve small airways function in moderate‐to‐severe asthmatics evaluated by physiological tests and high‐resolution computed tomography ( H RCT ) analysis . This study was performed at a tertiary university hospital in Beijing . Methods This was a r and omized , double‐blind , parallel study performed in 38 patients with moderate‐to‐severe asthma treated with salmeterol/fluticasone ( SFC ) plus montelukast ( SFC+M ) or SFC plus placebo over 24 weeks . Small airway function was assessed by physiological studies and H RCT image analysis . Results Montelukast significantly improved air trapping as expressed by the residual volume (RV)/total lung capacity ( TLC ) . Over 24 weeks of treatment , RV/TLC was improved by (15.41±6.67)% in patients receiving SFC+M while RV/TLC was decreased by (8.57±10.26)% in patients receiving SFC alone , the difference between the two groups was significant ( P=0.02 ) . There was a trend towards a significant difference in forced expiratory volume in the first second (FEV1)/forced vital capacity ( FVC ) in the SFC+M group compared to that in the SFC group ( (17.87±8.17)% vs. (12.28±9.20)% , P=0.056 ) . There was no significant change in percentage wall area ( WA% ) after 24 weeks of add‐on treatment with montelukast . Patients receiving SFC+M showed significant improvement in the ratio of CT‐determined values at full expiration to those at full inspiration ( E/I ratio ) ( 0.894±0.005 vs. 0.871±0.003 , P=0.002 ) . Conclusion We have shown , using lung function tests and H RCT image technique , that add‐on therapy with montelukast  improves distal lung function reflected by air trapping , but not airway wall thickness in moderate‐to‐severe asthma . ( Clinical Trials.gov number , NCT00699062 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 is a widely used controller agent in childhood asthma . It is modestly effective in reducing symptoms , decreasing the need for rescue albuterol , and improving forced expiratory volume in 1 second ( FEV1 ) . OBJECTIVE To determine whether montelukast therapy improves peripheral airway obstruction as measured by lung volumes , air trapping , airway resistance ( Raw ) , and specific conductance ( Sgaw ) . METHODS Twenty-one children aged 9 to 18 years with mild-to-moderate asthma were r and omized into a double-blind , placebo-controlled study to receive montelukast ( 5 or 10 mg ) or matching placebo daily for 8 weeks . Symptoms and albuterol  use were recorded twice daily , and  exhaled nitric oxide measurement , forced oscillometry , spirometry , and body box plethysmography  ( before and after beta-agonist use ) were performed at r and omization and at 2 , 4 , 6 , and 8 weeks . Circulating eosinophil counts and serum eosinophil cationic protein ( ECP ) levels were obtained at r and omization and at 8 weeks . RESULTS Montelukast-treated patients had lower residual volume ( P = .05 ) , residual volume-total lung capacity ratio ( P = .04 ) , Raw ( P = .02 ) , Sgaw ( P = .03 ) , and serum ECP levels ( P = .02 ) at 8 weeks compared with those treated with placebo . There was a trend toward reduced daytime and nighttime albuterol use , although the difference did not reach statistical significance . There were no significant differences in FEV1 , FEV1-forced vital capacity ratio , exhaled nitric oxide levels , or daytime and nighttime symptom scores between the 2 groups . CONCLUSIONS Montelukast therapy was associated with less air trapping , hyperinflation , and Raw and better Sgaw compared with placebo . Lower serum ECP levels , a surrogate measure of airway inflammation , were associated with improvements in lung function BACKGROUND Zafirlukast is a leukotriene receptor antagonist that was invented to treat patients with chronic asthma . METHODS To evaluate whether the zafirlukast improved the peak expiratory flow rate ( PEFR ) and clinical symptoms , 31 asthmatic patients with moderate persistent asthma who received regular inhaled corticosteroid were r and omly divided into the study group ( N = 17 ) . They received the zafirlukast 20 mg bid for 4 weeks , and the control group ( N = 14 ) received a placebo . Daily morning and evening PEFR and St. George 's Respiratory Question naire ( SGRQ ) scoring were recorded respectively . The levels of serum IgE and urine leukotriene E4 before and after treatment were measured using enzyme linked immunosorbent assay and enzyme immunoassay kits . RESULTS In the zafirlukast treated group , the morning PEFR was significantly improved from 314.4 + /- 20.6 to 340.6 + /- 18.3 L/min ( N = 17 , p < 0.05 ) after 4 weeks of treatment , while the control group did not show any significant changes . The zafirlukast group had significant improvement in their symptom scores of SGRQ from 48.6 + /- 4.6 to 33.8 + /- 4.7 ( N = 17 , p < 0.05 ) . However , the placebo did not improve the symptom scores . CONCLUSION Leukotriene receptor antagonists effectively improved symptoms and benefited lung function for moderate persistent asthmatic patients who had received regular treatments with inhaled steroids 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 BACKGROUND Asthma and allergic rhinitis are both highly prevalent diseases and often coexist in patients . OBJECTIVE To investigate the effect of rhinitis therapy on asthma outcomes in adult and adolescent patients with both seasonal allergic rhinitis ( SAR ) and persistent asthma . METHODS A total of 863 patients ( mean baseline FEV1 81 % predicted ) were r and omized to receive open-label fluticasone propionate/salmeterol ( FSC ) , 100/50 microg bid for 4 weeks , plus either blinded fluticasone propionate aqueous nasal spray ( FPANS ) 200 microg/d , montelukast 10 mg/d , or placebo . Patients kept daily records of peak expiratory flow ( PEF ) , asthma , and rhinitis symptoms and rescue albuterol use . RESULTS FPANS added to FSC result ed in superior outcomes for daytime total nasal symptom scores ( D-TNSS ) and individual daytime nasal specific symptoms ( congestion , rhinorrhea , sneezing , and itching ) compared with montelukast plus FSC and placebo plus FSC ( p < or = 0.001 ) . Montelukast plus FSC was superior to placebo plus FSC only for D-TNSS and itching and sneezing . Morning PEF , asthma symptoms , and rescue albuterol use improved significantly ( p < or = 0.001 ) in all treatment groups , but improvements were comparable across the treatment groups . CONCLUSION In patients with persistent asthma treated with FSC , the addition of montelukast or FPANS for the treatment of SAR result ed in no additional improvements in overall asthma control compared with FSC alone . However , FPANS provided superior rhinitis control compared with montelukast . These data suggest that asthma and rhinitis should each be optimally treated BACKGROUND New drug evaluations in patients with mild asthma are sometimes complicated by enrollment of patients whose disease is too mild to show improvement with therapy . A peak expiratory flow ( PEF ) variability criterion may help to more clearly define a mild asthmatic population . OBJECTIVE To evaluate the effectiveness of zafirlukast ( 20 mg twice daily ) and cromolyn sodium ( 1600 microg four times daily ) compared with placebo as first-line therapy for mild asthma using a retrospective analysis , which stratified patients by PEF variability ( < 10 % or > or = 10 % ) . STUDY DESIGN Symptomatic patients ( daytime asthma symptoms score > or = 8) were r and omized to 13 weeks of treatment in a double-blind , double-dummy , placebo-controlled , parallel-group , multicenter trial . PATIENTS AND METHODS Patients ( n = 287 ) were nonsmokers ( age > or = 12 years ) with reversible airway disease , a forced expiratory volume in one second ( FEV1 ) of > or = 55 % of predicted , and previous treatment with beta2-agonist or theophylline only . Assessment s included changes from baseline to endpoint in daytime and nocturnal asthma symptoms , beta2-agonist use , PEF , and FEV1 . Response to treatment was assessed by predetermined diary card and FEV1 criteria . Safety was determined from adverse events and laboratory test results . RESULTS No significant treatment effects were seen across efficacy measures for patients with PEF variability < 10 % . For patients with PEF variability > or = 10 % , both active treatments significantly ( P < .05 ) decreased the daytime asthma symptoms score , nighttime awakenings , and beta2-agonist use , and increased morning PEF and FEV1 compared with placebo . Response to diary card criteria was 70 % and 75 % for zafirlukast and cromolyn , respectively ; response to FEV1 criteria was 47 % for both treatments . All treatments were tolerated well by patients . CONCLUSIONS Zafirlukast and cromolyn are effective first-line therapies for mild asthma , with both therapies producing greater benefits in patients whose PEF variability was > or = 10 % . In prospect i ve trials to evaluate therapies in patients with mild asthma , it may be worthwhile to include PEF variability with a 10 % cutoff either as an inclusion criteria or as a tool for subset analysis BACKGROUND Anti-inflammatory properties of leukotriene modifiers and their effect on bronchial hyperresponsiveness have not been studied in children with asthma . OBJECTIVE The primary objective of this study was to determine the changes in serum levels of inflammatory mediators , clinical efficacy , and bronchial hyperresponsiveness after treatment with montelukast . METHODS In this double-blind , r and omized , placebo-controlled trial , 39 children with mild-to-moderate atopic asthma were r and omly allocated to receive montelukast or placebo for 6 weeks . Main outcome measures were changes in serum concentrations of soluble interleukin 2 receptor ( sIL-2R ) , IL-4 , and soluble intercellular adhesion molecule 1 ( sICAM-1 ) ; peripheral blood eosinophil count ; and eosinophilic cationic protein ( ECP ) . Asthma severity score , FEV(1 ) , and bronchial hyperreactivity ( BHR ) for histamine were secondary end points . RESULTS Compared to placebo , serum concentrations of IL-4 , sICAM-1 , and ECP and eosinophil blood counts significantly decreased after 6 weeks of treatment with montelukast . Montelukast significantly improved asthma control and FEV(1 ) .  Montelukast result ed in within-group significant decrease in levels of serum sIL-2R ( 611 vs. 483 pg/mL ) , IL-4 ( 0.123 vs 0.102 pg/mL ) , sICAM-1 ( 280 vs. 244 ng/mL ) , and ECP ( 74 vs. 59 microg/mL ) and in eosinophil blood counts ( 349 vs. 310 cells/mm(3 ) ) . Mean FEV(1 ) value changed from 85 % of predicted to 95 % ( P < .001 ) and for histamine ( PC(20)H ) from 2.8 mg/mL to 3.8 mg/mL ( P < .001 ) after treatment with montelukast . There was no significant difference between montelukast and placebo recipients in the serum concentrations of sIL-2R and PC(20)H after treatment . CONCLUSION Montelukast provides clinical benefit to patients with chronic asthma and decreases bronchial hyperresponsiveness .  Montelukast caused a statistically significant decrease of serum concentrations in cytokine , ICAM-1 , and ECP and peripheral blood eosinophil counts over the 6-week treatment period . This observation raises the possibility that leukotriene receptor antagonists , such as montelukast , may have effects on parameters of asthmatic inflammation BACKGROUND The cysteinyl leukotrienes are important mediators of bronchial asthma . The clinical effect of montelukast , a potent cysteinyl leukotriene-receptor antagonist , was investigated in a r and omized , placebo-controlled , multicenter , parallel-group , dose-ranging study . METHODS After a 3-week , single-blind , placebo run-in period , 343 asthmatic patients ( FEV1 40 % to 80 % of the predicted value with an improvement in FEV1 of at least 15 % [ absolute value ] after receiving inhaled beta-agonists on at least two occasions ) were r and omly assigned to one of six treatment groups : placebo ; 10 , 100 , or 200 mg once daily montelukast in the evening ; or 10 or 50 mg twice daily montelukast for a 6-week , double-blind treatment period followed by a 1-week placebo washout period . All patients used inhaled , short-acting beta-agonists as needed . RESULTS All montelukast doses caused similar and significant differences compared with placebo in asthma control endpoints . The least-square mean difference between pooled montelukast groups and placebo in the percentage change from baseline in morning FEV1 ( 10.30 % ; 95 % CI : 5.56 to 15.04 ) , as-needed beta-agonist use ( -0.98 puffs ; 95 % CI : -1.53 to -0.44 ) , morning peak expiratory flow rate ( 18.80 L/min ; 95 % CI : 8.62 to 28.98 ) , physicians ' and patients ' global evaluations , and asthma-specific quality -of-life scores were all significant ( p < or = 0.050 ) . The incidence of adverse experiences was not dose related and was similar between placebo and montelukast treatment . CONCLUSION Montelukast caused a significant improvement in chronic asthma at an oral , once daily evening dose as low as 10 mg Background Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma Background : Asthma and seasonal allergic rhinitis ( SAR ) are recognized as manifestations of a single airway disease . Desloratadine has demonstrated efficacy in treating SAR symptoms , including nasal obstruction . Methods : Safety and efficacy of desloratadine and montelukast each were assessed in a double-blind , placebo-controlled trial of patients with SAR and symptoms of asthma , who were assigned r and omly to once-daily treatment with desloratadine 5 mg , montelukast 10 mg , or placebo for 4 weeks . Change from baseline of AM/PM reflective total asthma symptom severity scores ( TASS ) , FEV1 , individual asthma symptom scores , and β2-agonist usage were assessed . Results : Desloratadine and montelukast each were associated with statistically significant reductions from baseline in the mean TASS averaged over the 4-week period ( p ≤0.022 vs. placebo ) . Individual asthma symptom scores also improved significantly for both therapies ( p ≤ 0.05 ) . Patients treated with desloratadine or montelukast demonstrated improvement from baseline in FEV1  versus placebo ; significant improvement was seen in a subset of patients with baseline FEV1 < 80 % of predicted normal ( both p < 0.05 ) . Both active therapies significantly reduced β2-agonist use ( both p < 0.01 ) . Improvements for both therapies were comparable for all efficacy parameters ; they were tolerated well with adverse event profiles similar to placebo . Conclusions : Asthma symptoms and β2-agonist were improved significantly in patients with concomitant SAR and asthma treated with desloratadine 5 mg as well as montelukast 10 mg once daily . Both therapies significantly improved FEV1 in a subset of patients with FEV1 < 80 % of predicted normal at entry . Improvements in asthma symptoms were comparable for both active treatment groups BACKGROUND Leukotriene receptor antagonists have been shown to protect against bronchoconstriction induced by antigens , exercise , and cold air . There are relatively few clinical studies reported in patients with asthma . The present study is the first clinical evaluation of pranlukast ( SB 205312 , ONO-1078 ) outside Japan in patients with asthma . METHODS A r and omised , double blind , placebo controlled , parallel group , multicentre four week study of the safety and tolerability of oral pranlukast , 225 or 337.5 mg twice daily , was performed in patients with mild to moderate asthma . Preliminary efficacy data were obtained ; the main efficacy variables evaluated were forced expiratory volume in one second ( FEV1 ) and morning domiciliary ( home ) peak expiratory flow rates ( PEFR ) . Clinic PEFR and daytime and night-time asthma symptom scores were also recorded . RESULTS Compared with the placebo group the improvement in morning home PEFR was statistically significant at all time points for patients receiving pranlukast 337.5 mg twice daily and at weeks 1 and 2 for those treated with pranlukast in a dose of 225 mg twice daily . Mean morning home PEFR increased by 10.8 to 18.61/min ( 95 % CI 0.2 to 29.3 l/min ) in patients treated with pranlukast compared with a slight deterioration in those given placebo .  FEV1 significantly increased within one hour after the first dose of pranlukast compared with baseline and this increase was maintained for eight hours . Improvements in trough FEV1-that is , at the end of the dosing interval-were statistically significant for the group treated with pranlukast 225 mg twice daily compared with placebo at week 4 . Mean increases in FEV1 ranged from 210 ml to 340 ml ( 95 % CI 60 to 500 ml ) at trough in the pranlukast group . Patients treated with pranlukast also showed improvements in summary symptom and night-time asthma scores .  Pranlukast was well tolerated , and no drug related changes in haematological and biochemical variables were observed . CONCLUSIONS Pranlukast , an oral leukotriene receptor antagonist , is well tolerated and is effective for the treatment of asthma . It increased FEV1 within one hour of dosing , improved patient summary symptom and night-time asthma scores , and reduced the use of rescue bronchodilators , thus providing further evidence of a role for leukotrienes in the pathogenesis of asthma BACKGROUND Clinical trials in children with moderate-to-severe persistent asthma are limited . OBJECTIVE We sought to determine whether azithromycin or montelukast are inhaled corticosteroid sparing . METHODS The budesonide dose ( with salmeterol [ 50 microg ] twice daily ) necessary to achieve control was determined in children 6 to 17 years of age with moderate-to-severe persistent asthma . After a budesonide-stable period of 6 weeks , children were r and omized in a double-masked , parallel , multicenter study to receive once-nightly azithromycin , montelukast , or matching placebos plus the established controlling dose of budesonide ( minimum , 400 microg twice daily ) and salmeterol twice daily . Primary outcome was time from r and omization to inadequate asthma control after sequential budesonide dose reduction . RESULTS Of 292 children screened , only 55 were r and omized .  Inadequate adherence to study medication ( n = 80 ) and improved asthma control under close medical supervision ( n = 49 ) were the major reasons for r and omization failure . A futility analysis was requested by the Data Safety Monitoring Board . In data available for analyses , no differences were noted for either treatment compared with placebo in time to inadequate control status ( median : azithromycin , 8.4 weeks [ 95 % confidence limit , 4.3 - 17.3 ] ; montelukast , 13.9 weeks [ 95 % confidence limit , 4.7 - 20.6 ] ; placebo , 19.1 weeks [ 95 % confidence limit , 11.7-infinity ] ) , with no difference between the groups ( log-rank test , P = .49 ) . The futility analysis indicated that even if the planned sample size was reached , the results of this negative study were unlikely to be different , and the trial was prematurely terminated . CONCLUSION Based on these results , neither azithromycin nor montelukast is likely to be an effective inhaled corticosteroid-sparing alternative in children with moderate-to-severe persistent asthma OBJECTIVE The objective of our study was to compare the efficacy and safety of fluticasone propionate ( an inhaled corticosteroid ) with zafirlukast ( a leukotriene modifier ) for persistent asthma . STUDY DESIGN In this r and omized placebo-controlled , parallel-group , double-blind , double-dummy trial , patients underwent an 8- to 14-day run-in period followed by 12 weeks of treatment with inhaled fluticasone propionate ( 88 mg twice daily by metered-dose inhaler ) , oral zafirlukast ( 20 mg twice daily ) , or placebo . POPULATION We included a total of 338 persistent asthma patients , 12 years of age or older , using short-acting b2-agonists alone . OUTCOMES measured Efficacy outcomes included changes in pulmonary function , asthma symptoms , rescue albuterol use , nighttime awakenings due to asthma , and quality of life . Safety outcomes included asthma exacerbations , adverse events , and clinical ly significant laboratory test results . RESULTS After 12 weeks of treatment , patients taking fluticasone propionate experienced significantly greater improvements in all clinical parameters ( symptom scores , percentages of symptom-free and albuterol-free days , albuterol use , and nighttime awakenings ) compared with patients taking zafirlukast ( P < .05 ) or placebo ( P < .05 ) . Treatment with fluticasone propionate result ed in significantly greater improvements in pulmonary function compared with zafirlukast ( P < .05 ) or placebo ( P < .05 ) . Fewer fluticasone propionate patients ( 4 % ) had an exacerbation requiring oral corticosteroids compared with those taking zafirlukast ( 12 % ) or placebo ( 10 % ) . CONCLUSIONS Inhaled fluticasone propionate is more effective than zafirlukast in controlling asthma symptoms , improving pulmonary function , and improving quality of life for patients who are symptomatic with the use of short-acting b2-agonists alone STUDY OBJECTIVES The distal airways are likely to contribute to asthma pathobiology and symptoms but have rarely been specifically evaluated in relation to systemic oral therapy . We hypothesized that treatment with montelukast , an oral cysteinyl-leukotriene receptor antagonist , would improve both proximal and distal lung physiology in patients with mild asthma . DESIGN R and omized , double-blind , crossover design . SETTING Academic referral center . PATIENTS Subjects with mild asthma limited to using short-acting inhaled beta(2)-agonists . INTERVENTIONS Nineteen subjects with mild asthma underwent a baseline assessment of lung function , lung mechanics , and symptoms , followed by r and omization to therapy with montelukast , 10 mg taken in the evening , or placebo in a crossover , double-blind fashion . Each treatment phase lasted 4 weeks , with a 2-week washout period . A repeat evaluation was performed during the last week of each treatment phase . MEASUREMENTS AND RESULTS Montelukast result ed in improvement in ( mean + /- SD ) proximal and distal lung function parameters ( change in FEV(1 ) : montelukast , 0.16 + /- 0.06 L ; placebo , -0.05 + /- 0.05 L ; p = 0.008 ) ; change in specific conductance : montelukast , 7.2 + /- 2.9 % predicted ; placebo , -17 + /- 8 % predicted ; p = 0.007 ; change in % predicted residual volume [ RV ] : montelukast , 18.4 + /- 8.3 % predicted ; placebo , 3.0 + /- 2.9 % predicted ; p = 0.05 ) . Improvement in symptoms ( ie , wheeze and chest tightness ) correlated with improvements in RV while receiving montelukast , but not while receiving placebo ( Pearson coefficients : 0.55 and 0.66 , respectively ; p < 0.008 and 0.04 , respectively ) . CONCLUSIONS The systemically acting oral agent montelukast improves proximal and distal lung physiology . Improvements in distal lung function correlate with improvements in asthma symptoms The efficacy of 6 wk of therapy with oral ICI 204,219 , a selective leukotriene D4 ( LTD4 ) receptor antagonist , was evaluated in subjects with moderate asthma during a multicenter , double-blind , r and omized , placebo-controlled , dose-ranging study . Subjects who entered the trial had been chronically treated for asthma with beta agonist alone or in combination with theophylline . Subjects were r and omized to treatment with twice daily doses of ICI 204,219  ( 5 , 10 , or 20 mg ) or  placebo if they had an FEV1 between 40 and 75 % of predicted values without bronchodilator therapy and a daytime asthma score > 10 ( range 0 to 21 per wk ) for 7 consecutive d.  Efficacy was evaluated from the results of symptom assessment s , pulmonary function tests , and rescue medication use .  Of 276 subjects r and omized to treatment , 266 ( 10 mg , n = 66 ; 20 mg , n = 67 ; 40 mg , n = 67 ; placebo , n = 66 ) were analyzed for efficacy . Diary card assessment s showed that treatment with increasing doses of ICI 204,219 linearly improved five efficacy criteria without increasing the number or severity of adverse events . The 40 mg dose was more effective than placebo ( p < 0.05 ) in reducing nighttime awakenings , first morning asthma symptoms , the daytime asthma score , and albuterol use and in increasing evening peak expiratory flow ( PEF ) rates as well as FEV1 . Compared with baseline measurements , the 40 mg dose decreased awakenings by 46 % , albuterol use by 30 % , and daytime symptoms by 26 % and increased FEV1 by 11 % . ICI 204,219 improves objective and subjective measures of asthma severity in moderately ill asthmatic subjects and may provide a new treatment option for the disease Abstract Objective : To determine the ability of montelukast , a leukotriene receptor antagonist , to allow tapering of inhaled corticosteroids in clinical ly stable asthmatic patients . Design : Double blind , r and omised , placebo controlled , parallel group study . After a single blind placebo run in period , during which ( at most ) two inhaled corticosteroids dose decreases occurred , qualifying , clinical ly stable patients were allocated r and omly to receive montelukast ( 10 mg tablet ) or matching placebo once daily at bedtime for up to 12 weeks . Setting : 23 academic asthma centres in United States , Canada , and Europe . Participants : 226 clinical ly stable patients with chronic asthma receiving high doses of inhaled corticosteroids ( 113 r and omised to montelukast and 113 to placebo ) . Interventions : Every 2 weeks , the inhaled corticosteroids dose was tapered , maintained , or increased ( rescue ) based on a st and ardised clinical score . Main outcome measures : Last tolerated dose of inhaled corticosteroids . Results : Compared with placebo , montelukast allowed significant ( P=0.046 ) reduction in the inhaled corticosteroid dose ( montelukast 47 % v placebo 30 % ; least square mean difference 17.6 % , 95 % confidence interval 0.3 to 34.8 ) . Fewer patients on montelukast ( 18 ( 16 % ) v 34 ( 30 % ) placebo , P=0.01 ) required discontinuation because of failed rescue . Conclusions : Montelukast reduces the need for inhaled corticosteroids among patients requiring moderate to high doses of corticosteroid to maintain asthma control . Key messages Leukotriene receptor antagonists have complementary action to inhaled corticosteroids in asthma Many patients receive higher doses of inhaled corticosteroids than clinical ly required In this placebo controlled trial , montelukast allowed significant reduction of inhaled corticosteroid doses Fewer patients receiving montelukast had failed rescue than patients receiving 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 OBJECTIVES To determine the clinical effect of oral montelukast sodium , a leukotriene receptor antagonist , in asthmatic patients aged 15 years or more . DESIGN R and omized , multicenter , double-blind , placebo-controlled , parallel-group study . A 2-week , single-blind , placebo run-in period was followed by a 12-week , double-blind treatment period ( montelukast sodium , 10 mg , or matching placebo , once daily at bedtime ) and a 3-week , double-blind , washout period . SETTING / PATIENTS Fifty clinical centers r and omly allocated 681 patients with chronic , stable asthma to receive placebo or montelukast after demonstrating a forced expiratory volume in 1 second 50 % to 85 % of the predicted value , at least a 15 % improvement in forced expiratory volume in 1 second ( absolute value ) after inhaled beta-agonist administration , a minimal predefined level of daytime asthma symptoms , and inhaled beta-agonist use . Twenty-three percent of the patients used concomitant inhaled corticosteroids . PRIMARY END POINTS : Forced expiratory volume in 1 second and daytime asthma symptoms . RESULTS Montelukast improved airway obstruction ( forced expiratory volume in 1 second , morning and evening peak expiratory flow rate ) and patient-reported end points ( daytime asthma symptoms , " as-needed " beta-agonist use , nocturnal awakenings ) ( P<.001 compared with placebo ) . Montelukast provided near-maximal effect in these end points within the first day of treatment . Tolerance and rebound worsening of asthma did not occur . Montelukast improved outcome end points , including asthma exacerbations , asthma control days ( P<.001 compared with placebo ) , and decreased peripheral blood eosinophil counts ( P<.001 compared with placebo ) . The incidence of adverse events and discontinuations from therapy were similar in the montelukast and placebo groups . CONCLUSIONS Montelukast , compared with placebo , significantly improved asthma control during a 12-week treatment period . Montelukast was generally well tolerated , with an adverse event profile comparable with that of placebo BACKGROUND Previous trials demonstrated the effectiveness of the leukotriene receptor antagonist zafirlukast in patients with mild-to-moderate asthma . OBJECTIVES We sought to assess the efficacy and safety of zafirlukast and its effect on patients ' quality of life ( QOL ) during a 13-week , double-blind , placebo-controlled , multicenter trial in adults and adolescents with moderate reversible airflow obstruction . METHODS Patients ( age range , 12 to 68 years ) with total daytime asthma symptoms scores of 10 or greater over 7 consecutive days ( maximum , 21/wk ) , FEV1 45 % or greater but less than or equal to 80 % of predicted value ( > /=6 hours after beta2 -agonist ) , and reversible airway disease were r and omized to 20 mg zafirlukast twice daily ( nZ = 231 ) or placebo twice daily ( nP = 223 ) . Efficacy was assessed from changes in daytime and nocturnal symptoms , beta2 -agonist use , nasal congestion score , and pulmonary function . QOL was evaluated with a disease-specific Asthma Quality of Life Question naire . Safety was determined from adverse event information and clinical laboratory test results . RESULTS Zafirlukast was significantly ( P < .001 ) more effective than placebo , with reductions from baseline in the daytime asthma symptoms score ( -23 % ) , nighttime awakenings with asthma ( -19 % ) , and beta2 -agonist use ( -24 % ) and improvements from baseline in morning ( + 25 L/min ) and evening ( + 18 L/min ) peak expiratory flow rates . Compared with placebo , zafirlukast significantly ( P < /=.018 ) improved scores for QOL domains ( activity limitations , symptoms , emotional function , and exposure to environmental stimuli ) and overall QOL , with a significantly greater proportion of zafirlukast-treated patients demonstrating clinical ly meaningful improvements ( > /=0.5-unit change from baseline ; P < /=.037 ) . The safety profile of zafirlukast was clinical ly indistinguishable from that of placebo . CONCLUSIONS Zafirlukast is effective and well tolerated and improves QOL in the long-term treatment of patients with moderate reversible airflow obstruction Leukotriene antagonists block the proinflammatory actions of leukotrienes ( LT ) and have been introduced as new treatments for asthma . Conventional therapy with glucocorticosteroids does not inhibit the bio synthesis of leukotrienes . We therefore tested whether addition of the leukotriene receptor antagonist montelukast was of therapeutic benefit in a group of aspirin-intolerant patients with asthma of whom 90 % already were treated with moderate to high doses of glucocorticosteroids .  Under double-blind conditions , 80 aspirin-intolerant patients with asthma were r and omized to receive 4 wk oral treatment of either 10 mg of montelukast or placebo once daily at bedtime . Pulmonary function was measured as forced expiratory volume in 1 s ( FEV(1 ) ) once a week in the clinic and daily as morning and evening peak expiratory flow rate ( PEFR ) . Asthma symptoms and use of rescue bronchodilator were also recorded daily . Asthma specific quality of life ( QoL ) was assessed before and after the treatments . The group receiving montelukast showed a remarkable improvement of their asthma , whereas the group given placebo showed no change . Thus , from equal baseline values , the mean difference between the groups over the 4-wk treatment period was 10.2 % for FEV(1 ) and 28.0 L for morning PEFR ( p for both < 0.001 ) . The improved pulmonary function in the group receiving montelukast occurred at the same time as 27 % less bronchodilator was used ( p < 0.05 ) , and it was associated with fewer asthma symptoms than in the group given placebo , including 1.3 nights more of sleep per week and 54 % fewer asthma exacerbations ( p < 0.05 ) . There was also an improvement in asthma-specific QoL ( p < 0.05 ) . The therapeutic response to montelukast was consistent across patients with different baseline characteristics and did not correlate with baseline urinary LTE(4 ) . Addition of a leukotriene receptor antagonist such as montelukast improves asthma in aspirin-intolerant patients over and above what can be achieved by glucocorticosteroids BACKGROUND Information that enhances expectations about drug effectiveness improves the response to placebos for pain . Although asthma symptoms often improve with placebo , it is not known whether the response to placebo or active treatment can be augmented by increasing expectation of benefit . OBJECTIVE The study objective was to determine whether response to placebo or a leukotriene antagonist ( montelukast ) can be augmented by messages that increase expectation of benefit . METHODS A r and omized 20-center controlled trial enrolled 601 asthmatic patients with poor symptom control who were assigned to one of 5 study groups . Participants were r and omly assigned to one of 4 treatment groups in a factorial design ( ie , placebo with enhanced messages , placebo with neutral messages , montelukast with enhanced messages , or montelukast with neutral messages ) or to usual care . Assignment to study drug was double masked , assignment to message content was single masked , and usual care was not masked . The enhanced message aim ed to increase expectation of benefit from the drug . The primary outcome was mean change in daily peak flow over 4 weeks . Secondary outcomes included lung function and asthma symptom control . RESULTS Peak flow and other lung function measures were not improved in participants assigned to the enhanced message groups versus the neutral messages groups for either montelukast or placebo ; no differences were noted between the neutral placebo and usual care groups . Placebo-treated participants had improved asthma control with the enhanced message but not montelukast-treated participants ; the neutral placebo group did have improved asthma control compared with the usual care group after adjusting for baseline difference . Headaches were more common in participants provided messages that mentioned headache as a montelukast side effect . CONCLUSIONS Optimistic drug presentation augments the placebo effect for patient-reported outcomes ( asthma control ) but not lung function . However , the effect of montelukast was not enhanced by optimistic messages regarding treatment effectiveness
BACKGROUND Leukotriene-receptor antagonists ( LTRAs ) are recommended as an alternative treatment in patients with mild asthma , but their effect compared with placebo is unclear .
PURPOSE To determine the benefits and harms of LTRAs as monotherapy or in combination with inhaled corticosteroids compared with placebo in adults and adolescents with asthma .