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, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years. 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). Addition of montelukast or salmeterol to fluticasone for protection against asthma attacks: a randomized, double-blind, multicenter study. Effects of montelukast on surrogate inflammatory markers in corticosteroid-treated patients with asthma. Montelukast, a leukotriene receptor antagonist, reduces the concentration of leukotrienes in the respiratory tract of children with persistent asthma. Airway and systemic effects of hydrofluoroalkane formulations of high-dose ciclesonide and fluticasone in moderate persistent asthma. Oral Montelukast, Inhaled Beclomethasone, and Placebo for Chronic Asthma An economic evaluation of combination treatment with budesonide and formoterol in patients with mild-to-moderate persistent asthma. Dose reduction of inhaled corticosteroids under concomitant medication with montelukast in patients with asthma Comparison of second controller medications in addition to inhaled corticosteroid in patients with moderate asthma. Fluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast. Effect of montelukast added to inhaled budesonide on control of mild to moderate asthma Combination therapy with a long-acting beta-agonist and a leukotriene antagonist in moderate asthma. Determining economic feasibility of fluticasone propionate-salmeterol vs montelukast in the treatment of persistent asthma using a net benefit approach and cost-effectiveness acceptability curves. Salmeterol powder provides significantly better benefit than montelukast in asthmatic patients receiving concomitant inhaled corticosteroid therapy. Traditional and patient-centred outcomes with three classes of asthma medication Formoterol protects against platelet-activating factor-induced effects in asthma Montelukast versus fluticasone: effects on lung function, airway responsiveness and inflammation in moderate asthma Salmeterol response is not affected by beta2-adrenergic receptor genotype in subjects with persistent asthma. Failure of tacrolimus to prevent aspirin-induced respiratory reactions in patients with aspirin-exacerbated respiratory disease. Salmeterol/Fluticasone Propionate versus Fluticasone Propionate Plus Montelukast Once-daily budesonide/formoterol in a single inhaler in adults with moderate persistent asthma. A randomized, double-blind trial of the effect of anti-asthma treatment on lung function in children with asthma. Zafirlukast improves asthma control in patients receiving high-dose inhaled corticosteroids. The salmeterol/fluticasone combination is more effective than fluticasone plus oral montelukast in asthma. Effect of treatment with zileuton, a 5-lipoxygenase inhibitor, in patients with asthma. A randomized controlled trial. Zileuton Clinical Trial Group. A randomized, double‐blind trial of the effect of glucocorticoid, antileukotriene and bβ‐agonist treatment on IL‐10 serum levels in children with asthma Cost-effectiveness of eformoterol Turbohaler versus salmeterol Accuhaler in children with symptomatic asthma. Evaluation of salmeterol or montelukast as second-line therapy for asthma not controlled with inhaled corticosteroids. Oral Montelukast Compared with Inhaled Salmeterol To Prevent Exercise-Induced Bronchoconstriction Comparison of fluticasone propionate-salmeterol combination therapy and montelukast in patients who are symptomatic on short-acting beta(2)-agonists alone. Effects of hydrofluoroalkane formulations of ciclesonide 400 microg once daily vs fluticasone 250 microg twice daily on methacholine hyper-responsiveness in mild-to-moderate persistent asthma. The effectiveness of asthma therapy alternatives and evaluating the effectivity of asthma therapy by interleukin-13 and interferon gamma levels in children. Efficacy and safety of low-dose fluticasone propionate compared with zafirlukast in patients with persistent asthma. Nebulized budesonide inhalation suspension compared with cromolyn sodium nebulizer solution for asthma in young children: results of a randomized outcomes trial. Cost-Effectiveness Comparison of Salmeterol/Fluticasone Propionate versus Montelukast in the Treatment of Adults with Persistent Asthma Addition of Formoterol or Montelukast to Low-Dose Budesonide: An Efficacy Comparison in Short- and Long-Term Asthma Control Antitussive Effect of the Leukotriene Receptor Antagonist Zafirlukast in Subjects with Cough-Variant Asthma* Effects of 2 weeks of treatment with fluticasone propionate 100 mcg b.d. by comparison with zafirlukast 20 mg b.d. on bronchial hyper-responsiveness in patients with mild to moderate asthma. Comparison of bronchoprotective and bronchodilator effects of a single dose of formoterol delivered by hydrofluoroalkane and chlorofluorocarbon aerosols and dry powder in a double blind, placebo-controlled, crossover study. Add-on therapy with montelukast or formoterol in patients with the glycine-16 beta2-receptor genotype. 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. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. Comparison of inhaled salmeterol and oral zafirlukast in patients with asthma. Effects of fluticasone vs. fluticasone/salmeterol on airway calibre and airway hyperresponsiveness in mild persistent asthma. Randomized comparison of strategies for reducing treatment in mild persistent asthma. A comparison of the effects of oral montelukast and inhaled salmeterol on response to rescue bronchodilation after challenge. One-year safety and efficacy of budesonide/formoterol in a single inhaler (Symbicort Turbuhaler) for the treatment of asthma. Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of chronic asthma: a multicenter, randomized, double-blind trial. Montelukast Clinical Research Study Group. Fluticasone propionate/salmeterol combination compared with montelukast for the treatment of persistent asthma. Montelukast added to inhaled beclomethasone in treatment of asthma. Montelukast/Beclomethasone Additivity Group. Equivalent asthma control and systemic safety of inhaled budesonide delivered via HFA-134a or CFC propellant in a broad range of doses. Efficacy and safety of low-dose fluticasone propionate compared with montelukast for maintenance treatment of persistent asthma. Low-dose inhaled fluticasone propionate versus oral zafirlukast in the treatment of persistent asthma. Salmeterol HFA is as effective as salmeterol CFC in children and adults with persistent asthma. Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial. Additive bronchoprotective and bronchodilator effects with single doses of salmeterol and montelukast in asthmatic patients receiving inhaled corticosteroids.
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 BACKGROUND The greatest prevalence of asthma is in preschool children ; however , the clinical utility of asthma therapy for this age group is limited by a narrow therapeutic index , long-term tolerability , and frequency and /or difficulty of administration .  Inhaled corticosteroids and inhaled cromolyn are the most commonly prescribed controller therapies for young children with persistent asthma , although very young patients may have difficulty using inhalers , and dose delivery can be variable . Moreover , reduced compliance with inhaled therapy relative to orally administered therapy has been reported . One potential advantage of montelukast is the ease of administering a once-daily chewable tablet ; additionally , no tachyphylaxis or change in the safety profile has been evidence d after up to 140 and 80 weeks of montelukast therapy in adults and pediatric patients aged 6 to 14 years , respectively . To our knowledge , this represents the first large , multicenter study to address the effects of a leukotriene receptor antagonist in children younger than 5 years of age with persistent asthma , as well as one of the few asthma studies that incorporated end points vali date d for use in preschool children . OBJECTIVE Our primary objective was to determine the safety profile of montelukast , an oral leukotriene receptor antagonist , in preschool children with persistent asthma . Secondarily , the effect of montelukast on exploratory measures of asthma control was also studied . DESIGN AND STATISTICAL ANALYSIS : We conducted a double-blind , multicenter , multinational study at 93 centers worldwide : including 56 in the United States , and 21 in countries in Africa , Australia , Europe , North America , and South America . In this study , we r and omly assigned 689 patients ( aged 2 - 5 years ) to 12 weeks of treatment with placebo ( 228 patients ) or 4 mg of montelukast as a chewable tablet ( 461 patients ) after a 2-week placebo baseline period . Patients had a history of physician-diagnosed asthma requiring use of beta-agonist and a predefined level of daytime asthma symptoms . Caregivers answered questions twice daily on a vali date d , asthma-specific diary card and , at specified times during the study , completed a vali date d asthma-specific quality -of-life question naire . Physicians and caregivers completed a global evaluation of asthma control at the end of the study . Efficacy end points included : daytime and overnight asthma symptoms , daily use of beta-agonist , days without asthma , frequency of asthma attacks , number of patients discontinued because of asthma , need for rescue medication , physician and caregiver global evaluations of change , asthma-specific caregiver quality of life , and peripheral blood eosinophil counts . Although exploratory , the efficacy end points were predefined and their analyses were written in a data analysis plan before study unblinding . At screening and at study completion , a complete physical examination was performed . Routine laboratory tests were drawn at screening and weeks 6 and 12 , and su bmi tted to a central laboratory for analysis . Adverse effects were collected from caregivers at each clinic visit . An intention-to-treat approach , including all patients with a baseline measurement and at least 1 postr and omization measurement , was performed for all efficacy end points . An analysis -of-variance model with terms for treatment , study center and stratum ( inhaled/nebulized corticosteroid use , cromolyn use , or none ) was used to estimate treatment group means and between-group differences and to construct 95 % confidence intervals . Treatment-by-age , -sex , -race , -radioallergosorbent test , -stratum , and - study center interactions were evaluated by including each term separately . Fisher 's exact test was used for between-group comparisons of the frequency of asthma attacks , discontinuations from the study because of worsening asthma , need for rescue medication , and the frequencies of adverse effects . Because of an imbalance in baseline values for eosinophil counts for the 2 treatment groups , an analysis of covariance was performed on the eosinophil change from baseline with the patient 's baseline as covariate . STUDY PARTICIPANTS Of the 689 patients enrolled , approximately 60 % were boys and 60 % were white . Patients were relatively evenly divided by age : 21 % , 24 % , 30 % , and 23 % were aged 2 , 3 , 4 , and 5 years , respectively . For 77 % of the patients , asthma symptoms first developed during the first 3 years of life . During the placebo baseline period , patients had asthma symptoms on 6.1 days/week and used beta-agonist on 6.0 days/week . RESULTS In over 12 weeks of treatment of patients aged 2 to 5 years , montelukast administered as a 4-mg chewable tablet produced significant improvements compared with placebo in multiple parameters of asthma control including : daytime asthma symptoms ( cough , wheeze , trouble breathing , and activity limitation ) ; overnight asthma symptoms ( cough ) ; the percentage of days with asthma symptoms ; the percentage of days without asthma ; the need for beta-agonist or oral corticosteroids ; physician global evaluations ; and peripheral blood eosinophils . The clinical benefit of montelukast was evident within 1 day of starting therapy . Improvements in asthma control were consistent across age , sex , race , and study center , and whether or not patients had a positive radioallergosorbent test . Montelukast demonstrated a consistent effect regardless of concomitant use of inhaled/nebulized corticosteroid or cromolyn therapy . Caregiver global evaluations , the percentage of patients experiencing asthma attacks , and improvements in quality -of-life scores favored montelukast , but were not significantly different from placebo . There were no clinical ly meaningful differences between treatment groups in overall frequency of adverse effects or of individual adverse effects , with the exception of asthma , which occurred significantly more frequently in the placebo group . There were no significant differences between treatment groups in the frequency of laboratory adverse effects or in the frequency of elevated serum transaminase levels .  Approximately 90 % of the patients completed the study . CONCLUSIONS Oral montelukast ( 4-mg chewable tablet ) administered once daily is effective therapy for asthma in children aged 2 to 5 years and is generally well tolerated without clinical ly important adverse effects . Similarly , in adults and children aged 6 to 14 years , montelukast improves multiple parameters of asthma control . Thus , this study confirms and extends the benefit of montelukast to younger children with persistent asthma 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 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 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 Leukotrienes are bronchoactive mediators secreted by inflammatory cells in the respiratory mucosa on exposure to asthma triggers . OBJECTIVE We investigated the effect of montelukast , a leukotriene receptor antagonist , on the release of leukotrienes in the respiratory mucosa of children with persistent asthma . METHOD Twenty-three children aged 6 to 11 years with moderately severe asthma were treated in a cross-over design starting , after a 2-week run in period , with either montelukast ( n = 12 ) or cromolyn ( n = 11 ) for 4 weeks with a 2-week washout period between treatments . Twelve of them were then treated with either montelukast or beclomethasone for 6 months . The use of beta(2)-agonists was recorded on a diary card . The concentration of leukotriene C(4 ) ( LTC(4 ) ) was measured by HPLC in nasal washes obtained before and at the end of each treatment period . Eosinophilic cationic protein ( ECP ) was measured in the nasal washes by RIA . RESULTS The LTC(4 ) concentration significantly decreased in the children treated for the first 4 weeks with montelukast , from 5.03 + /- 1.17 to 1.42 + /- 0.33 ng/mL ( P < .005 ) , and a nonsignificant increase was noted in children treated with cromolyn , from 3.37 + /- 1.11 to 5.88 + /- 2.17 ng/mL ( P = .17 ) . ECP concentration also decreased in the children receiving montelukast ( P = .12 ) . The concentration of LTC(4 ) remained low after 3 and 6 months of treatment with montelukast ( 0.8 + /- 0.7 and 1.0 + /- 0.3 microg/mL ) and was lower than with beclomethasone . Children treated with montelukast required significantly fewer beta(2)-agonists ( P < .04 ) , CONCLUSION Montelukast reduces the concentration of leukotrienes in the respiratory tract of children with persistent asthma parallel to reduction in ECP and clinical improvement . This effect was not observed when the same children were treated with cromolyn BACKGROUND There are no data comparing the relative effects of high-dose ciclesonide ( CIC ) and fluticasone propionate ( FP ) on airway and systemic outcomes in patients with moderate persistent asthma . OBJECTIVE We elected to evaluate the relative effects of CIC and FP on the plasma cortisol response to stimulation with human corticotropin-releasing factor ( hCRF ) and bronchial hyperresponsiveness to methacholine as the primary outcome variables , in addition to secondary outcomes of overnight 10-h urinary cortisol ( OUC ) levels , exhaled nitric oxide levels , lung function , symptoms , and quality of life . METHODS Fourteen patients with moderate persistent asthma ( mean FEV(1 ) , 67 % predicted [ prior to each r and omized treatment ] ) completed the study , which had a r and omized , double-blind , double-dummy , crossover design , per protocol . Patients stopped receiving their usual inhaled corticosteroids for the duration of the study and instead began receiving salmeterol , 50 mug twice daily , and montelukast , 10 mg once daily , for the 2-week washout periods prior to each r and omized treatment , in order to prevent dropouts after withdrawal from inhaled corticosteroid therapy . Patients received 4 weeks of either CIC , 200 microg ex-valve ( 160 microg ex-actuator ) four puffs twice daily , plus FP-placebo , four puffs twice daily , or FP , 250 microg ex-valve ( 220 microg ex-actuator ) four puffs twice daily , plus CIC-placebo , four puffs twice daily . Salmeterol and montelukast were withheld for 72 h prior to each postwashout baseline visit , and CIC or FP was withheld for 12 h prior to each posttreatment visit . RESULTS FP , but not CIC , when compared to respective baseline values , significantly suppressed ( p < 0.05 ) plasma cortisol levels as follows : FP prior to receiving hCRF : geometric mean fold difference , 1.2 ; 95 % confidence interval ( CI ) , 1.1 to 1.3 ; CIC prior to receiving hCRF : geometric mean fold difference , 0.9 ; 95 % CI , 0.8 to 1.0 ; FP 30 min after receiving hCRF : geometric mean fold difference , 1.2 ; 95 % CI , 1.1 to 1.3 ; CIC 30 min after receiving hCRF : geometric mean fold difference , 1.0 ; 95 % CI , 0.9 to 1.2 ; OUC after FP administration : geometric mean fold difference , 1.9 ; 95 % CI , 1.4 to 2.6 ; OUC after CIC administration : geometric mean fold difference , 1.2 ; 95 % CI , 0.9 to 1.5 . There was also a significantly lower ( p < 0.05 ) mean value for OUC levels after FP administration than after CIC administration ( geometric mean fold difference , 1.5 ; 95 % CI , 1.1 to 2.0 ) . Therapy with CIC and FP , compared to respective baselines , significantly increased ( p < 0.05 ) the provocative concentration of methacholine causing a 20 % fall in FEV(1 ) , as follows : CIC : doubling dilution difference , 0.8 ; 95 % CI , 0.1 to 1.6 ; FP : doubling dilution difference , 1.0 ; 95 % CI , 0.1 to 2.0 . It also significantly reduced ( p < 0.05 ) exhaled nitric oxide levels , as follows : CIC : geometric mean fold difference , 1.2 ; 95 % CI , 1.1 to 1.3 ; FP : geometric mean fold difference , 1.9 ; 95 % CI , 1.3 to 2.8 . There was no effect on other secondary efficacy outcomes . CONCLUSION FP , 2,000 microg daily , but not CIC , 1,600 microg daily , significantly suppressed hypothalamic-pituitary-adrenal axis outcomes , with OUC levels being lower after FP administration than after CIC administration . Both drugs significantly improved airway outcomes in terms of methacholine bronchial hyperresponsiveness and exhaled nitric oxide levels . The present results would therefore suggest that CIC might confer a better therapeutic ratio than FP when used at higher doses 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 Patients with mild asthma may benefit from increasing their inhaled corticosteroid dose , adding a long-acting beta2-agonist , or both . This study assessed the cost-effectiveness of these options . Patients aged > or = 12 years with mild-to-moderate persistent asthma ( n = 1272 ) were r and omised to twice-daily , double-blind treatment with budesonide 100 microg , budesonide 100 microg plus formoterol 4.5 microg , budesonide 200 microg , or budesonide 200 microg plus formoterol 4.5 microg for 12 months . Clinical variables included lung function , number of symptom-free days and number of severe exacerbations . Data on medication use , hospitalisation , visits to health professionals and time off work due to asthma were combined with Swedish unit cost data ( 1999 ) to estimate the mean annual cost per patient . Budesonide 200 microg plus formoterol 4.5 microg had the greatest efficacy and effectiveness .  Budesonide 200 microg plus formoterol 4.5 microg was both more effective and less costly than budesonide 100 microg plus formoterol 4.5 microg , so a cost-effectiveness ratio was not calculated for this comparison . The cost-effectiveness ratio for budesonide 200 microg plus formoterol 4.5 microg compared with budesonide 200 microg alone was SEK 21 per symptom-free days gained . The combination of budesonide and formoterol in mild-to-moderate persistent asthma improved effectiveness at modest additional cost 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 The objective of this study was to compare the efficacy and safety of the second controller medications ( long-acting beta2-agonist , leukotriene receptor antagonist and sustained-release theophylline ) used in addition to inhaler corticosteroid treatment in moderate persistent asthma . A total of 64 patients with asthma , in the moderate persistent asthma category , were divided into three groups . Patients , all of whom were concurrently using inhaled corticosteroid ( Budesonide 400 microg twice daily ) , were treated for 3 months with either inhaled formoterol 9 microg twice daily ( first group ) , oral zafirlukast 20 mg twice daily ( second group ) , or sustained-release theophylline 400 mg once daily ( third group ) . All of the patients were subjected to assessment s on the subject of peak expiratory flow ( PEF ) variability , forced expiratory volume in 1 sec ( FEV1 ) , asthma symptom scores ( daytime and night-time ) , supplemental terbutalin use , asthma exacerbations and adverse events . Over the 3-month treatment period . In all of the three groups , significant improvements were recorded in the lung function , asthma symptom scores and supplemental terbutalin use criteria , as a result oftreatments applied . Formoterol treatment result ed in significantly greater and earlier improvements compared with the other two groups in several criteria : PEF variability ( 17.9 + /- 2.5 ; 21.9 + /- 3.2 ; 23.7 + /- 3.3 ; P < 0.001 ) ; asthma symptom score ( daytime ) ( 1.6 + /- 0.5 ; 1 + /- 0.5 ; 2.0 + /- 0,5 ; P < 0.05 ) ; asthma symptom score ( night-time ) ( 1.2 + /- 0.4 ; 2.2 + /- 0.5 ; 16 + /- 0.6 ; P < 0001 ) ; and supplement alter butalin  use ( 1.2 + /- 0.3 ; 1.8 + /- 0.5 ; 1.7 + /- 0.5 ; P < 0.05 ) . However , at the end of the treatment , in all of the three groups studied , improvements were attained in overall asthma control and there was no statistical difference among the groups . Although there were no side effects which required the discontinuation of the treatment , it was observed that the maximum side effect was in the second group ( 20 % , 31.6 % and 20 % , respectively ) . In conclusion , in patients who still have symptoms on treatment with inhaled corticosteroids , the addition of a long-acting beta2-agonist , leukotriene antagonists or sustained-release theophylline to the treatment is a logical approach , and , in addition to inhaled corticosteroids , any one of these second controller medications may be chosen in patients with moderate asthma 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 : 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 RATIONALE Long-acting beta-agonists ( LABAs ) and inhaled corticosteroids administered together appear to be complementary in terms of effects on  asthma control .  The elements of asthma control achieved by LABAs ( improved lung function ) and leukotriene receptor antagonists ( LTRAs ; protection against exacerbations ) may be complementary as well . OBJECTIVE We sought to determine whether the combination of the LTRA montelukast and the LABA salmeterol could provide an effective therapeutic strategy for asthma . METHODS AND MEASUREMENTS In a r and omized , placebo-controlled , crossover study of 192 subjects with moderate asthma , we compared the clinical efficacy of regular treatment over 14 weeks with the combination of montelukast and salmeterol to that with the combination of beclomethasone and salmeterol in moderate asthma . The primary efficacy outcome was time to treatment failure . MAIN RESULTS Three months after the r and omization of the last subject , the Data and Safety Monitoring Board determined that the primary research question had been answered and terminated the trial . The combination of montelukast and salmeterol was inferior to the combination of beclomethasone and salmeterol as judged by protection against asthma treatment failures ( p = 0.0008 ) , lung function ( 26 L/min difference in a.m. peak expiratory flow rate , p = 0.011 ) , asthma control score ( 0.22 difference in Asthma Control Question naire score , p = 0.038 ) , and markers of inflammation and airway reactivity . CONCLUSIONS Patients with moderate asthma similar to those we studied should not substitute the combination of an LTRA and an LABA for the combination of inhaled corticosteroid and an LABA BACKGROUND The choice of treatment can have a major impact on the total costs associated with asthma care . OBJECTIVE To determine the relative cost-effectiveness of twice-daily treatment with inhaled fluticasone propionate-salmeterol via Diskus , 100/50 microg , with that of once-daily treatment with oral montelukast as initial maintenance therapy in patients with persistent asthma uncontrolled with a short-acting beta2-agonist alone . METHODS Data from a r and omized , double-blind , double-dummy , 12-week clinical trial were analyzed . Efficacy end points included ( 1 ) symptom-free days ( SFDs ) during the 12-week period and ( 2 ) a 12 % or greater increase in forced expiratory volume in 1 second ( FEV1 ) from baseline . The economic analysis was performed from a payer 's perspective , and hence only direct costs were included in the analysis . The incremental cost-effectiveness ratio ( ICER ) , which is the mean difference in average costs divided by the mean difference in average effectiveness , was calculated for both effectiveness outcomes ( SFDs and FEV1 ) . RESULTS For the SFDs end point , the ICER for fluticasone propionate-salmeterol vs montelukast was $ 2.87 ( 95 % confidence interval , -$1.08 to $ 6.65 ) , indicating that it costs , on average , an extra $ 2.87 per day for an additional SFD with fluticasone propionate-salmeterol than with montelukast . With regard to FEV1 , the ICER was $ 1.79 ( 95 % confidence interval , -$0.72 to $ 3.86 ) , indicating that it costs , on average , an extra $ 1.79 per day to achieve a lung function improvement of 12 % or greater from baseline with fluticasone propionate-salmeterol than with montelukast . At a widely acceptable ceiling ratio of $ 9.95 per day , the probability of fluticasone propionate-salmeterol being more cost-effective than montelukast was 99.8 % for SFDs and was almost 100 % for an FEV1 improvement of 12 % of greater . CONCLUSIONS Treating 2 main components of asthma , inflammation and smooth muscle dysfunction , using fluticasone propionate-salmeterol is more cost-effective than using a single mediator antagonist alone , such as montelukast , as initial maintenance therapy for persistent asthma in patients treated with a short-acting beta2-agonist only STUDY OBJECTIVES Comparison of inhaled salmeterol powder vs oral montelukast treatment in patients with persistent asthma who remained symptomatic while receiving inhaled corticosteroids . DESIGN R and omized , double-blind , double-dummy , parallel-group , multicenter trials of 12-week duration . SETTING Out patients in private and university-affiliated clinics . PATIENTS Male and female patients > or = 15 years of age with a diagnosis of asthma ( baseline FEV(1 ) of 50 to 80 % of predicted ) and symptomatic despite receiving inhaled corticosteroids . INTERVENTIONS Inhaled salmeterol xinafoate powder , 50 microg bid , or oral montelukast , 10 mg qd . MEASUREMENTS AND RESULTS Treatment with salmeterol powder result ed in significantly greater improvements from baseline compared with montelukast for most efficacy measurements , including morning peak expiratory flow ( 35.0 L/min vs 21.7 L/min ; p < 0.001 ) , percentage of symptom-free days ( 24 % vs 16 % ; p < 0.001 ) , and the percentage of rescue-free days ( 27 % vs 20 % ; p = 0.002 ) . Total supplemental albuterol use was decreased significantly more in the salmeterol group compared with the montelukast group ( - 1.90 puffs per day vs - 1.66 puffs per day ; p = 0.004 ) and nighttime awakenings per week decreased significantly more with salmeterol than with montelukast ( - 1.42 vs - 1.32 ; p = 0.015 ) . Patients treated with inhaled salmeterol were significantly more satisfied with their treatment regimen and how well , how fast , and how long it worked than were patients who were treated with oral montelukast . The safety profiles for the two treatments were similar . CONCLUSION In patients with persistent asthma who remain symptomatic while receiving inhaled corticosteroids , adding inhaled salmeterol powder provided significantly greater improvement in lung function and asthma symptoms and was preferred by patients over oral montelukast 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 Platelet-activating factor ( PAF ) is an inflammatory mediator that provokes neutropaenia , bronchoconstriction and gas exchange defects due to exudation of bulk plasma within the airways . While the inhibitory effects of short-acting β2‐agonists on PAF‐induced disturbances have been consistently shown , those of long-acting β2‐agonists are less convincing . To further explore the mechanisms involved in PAF challenge in asthma , 12 patients ( forced expiratory volume in one second , 90±4 % predicted ) were investigated 2 h after inhaled formoterol ( 18 µg )  , in a double-blind , placebo-controlled , crossover design following PAF ( 18 µg ) inhalation . Compared with the placebo , at 5 min , premedication with formoterol  reduced PAF-induced cough and dyspnoea , and attenuated increased respiratory system resistance ( by 67 % ) and arterial deoxygenation ( by 50 % ) . Likewise , ventilation-perfusion ( V′A/Q′ ) ine quality improved , as reflected by the dispersion of pulmonary blood flow ( by 63 % ) and an overall index of V′A/Q′ heterogeneity ( by 71 % ) . In contrast , PAF-induced facial flushing , neutropaenia and subsequent rebound neutrophilia remained unchanged . The improvement in gas exchange abnormalities shown after platelet-activating factor in patients with asthma pretreated with formoterol at the recommended clinical dose may reflect , in addition to its class effects , an anti-exudative effect of formoterol in the airways Whether leukotriene receptor antagonists exhibit adequate anti-inflammatory effects in the treatment of asthma is still a controversial issue . The aim of the present study was to perform a direct comparison of the effects of a 4-week treatment with either montelukast ( 10 mg , once a day ) or low-dose inhaled fluticasone ( 100 µg b.i.d . ) on functional and inflammatory parameters in steroid-naïve patients with moderate asthma . Forty patients ( forced expiratory volume in one second ( FEV1 ) , 60–80 % predicted ) were studied in a double-blind , r and omised , crossover design . Treatment periods were separated by 3–8 weeks of washout . At the beginning and end of each period , FEV1 , airway responsiveness to inhaled methacholine  ( provocative concentration causing a 20 % fall in FEV1 ( PC20 ) ) , the level of exhaled nitric oxide ( NO ) and sputum differential cell counts were determined . Only short-acting β2-agonists were allowed for relief of symptoms . FEV1 increased by 0.50±0.07 L ( mean±sem ) after fluticasone and by 0.37±0.07 L after montelukast ( p<0.001 , each ) , and PC20 by 1.33±0.13 ( p<0.001 ) and 0.15±0.17 ( ns ) doubling doses , respectively . Correspondingly , percentages of sputum eosinophils were reduced by factor 2.7 ( p<0.01 ) and 1.4 ( nonsignificant ( ns ) ) , and the levels of exhaled NO ( at 50 mL·s−1 ) by factor 2.1 ( p<0.01 ) and 1.1 ( ns ) . These data indicate a comparable bronchodilator action of montelukast and fluticasone in patients with moderate asthma , but additional attenuation of airway inflammation by fluticasone as detectable through noninvasive methods BACKGROUND Recent studies suggest that there might be an association between albuterol use and worsening asthma in patients homozygous for arginine ( Arg/Arg ) at codon 16 of the beta-receptor . However , it is not known whether similar responses occur in Arg/Arg patients receiving long-acting beta2-agonists . OBJECTIVE We sought to evaluate the effects of variation in the beta2-adrenergic receptor gene ( ADRB2 ) on clinical response to salmeterol administered with fluticasone propionate . METHODS Subjects ( n = 183 ) currently receiving short-acting beta2-agonists were r and omized to twice-daily therapy with salmeterol , 50 microg , administered with fluticasone propionate , 100 microg , in a single inhaler or daily therapy with montelukast for 12 weeks , followed by a 2- to 4-day run-out period . RESULTS There was sustained and significant improvement ( P < .001 ) over baseline in all measures of asthma control in subjects receiving salmeterol , regardless of Arg16Gly genotype . Morning peak expiratory flow in subjects with the Arg/Arg genotype showed 89.0 + /- 16.1 L/min improvement over baseline compared with 93.7 + /- 12.7 L/min for Gly/Gly subjects and 92.5 + /- 11.9 L/min for Arg/Gly subjects . Pairwise changes were similar for Arg/Arg compared with Gly/Gly or Arg/Gly genotypes ( estimated differences , 4.7 L/min and 3.5 L/min , respectively ) . Responses did not appear to be modified by haplotype pairs . During the run-out period , all subjects had predictable and similar decreases in measures of asthma control , with no differences between genotypes . CONCLUSION Response to salmeterol does not vary between ADRB2 genotypes after chronic dosing with an inhaled corticosteroid . CLINICAL IMPLICATION S Analyses from this study indicate that genetic polymorphisms leading to Arg16Gly sequence changes within the beta2-adrenergic receptor do not affect patients ' responses to recommended asthma therapy with salmeterol and fluticasone propionate BACKGROUND In patients with aspirin-exacerbated respiratory disease ( AERD ) , pretreatment with asthma controller medications ( leukotriene modifiers , inhaled or systemic corticosteroids , and salmeterol ) partially modifies the severity of aspirin-induced asthmatic reactions . OBJECTIVE A recent study showed that pretreatment with tacrolimus completely prevented aspirin-induced respiratory reactions and might allow silent aspirin desensitization . METHODS Ten patients with rhinosinusitis , nasal polyps , and asthma had a history of asthma attacks after ingesting aspirin and nonsteroidal anti-inflammatory drugs . All underwent baseline oral aspirin challenges and had typical respiratory reactions . They were then r and omized to receive tacrolimus ( 0.1 mg/kg weight ; 8 patients ) or placebo ( 2 patients ) in a double-blind protocol before rechallenge with aspirin using the previous provoking dose of aspirin . In addition , respiratory reactions sustained by 50 consecutive patients with AERD during 2004 were recorded , analyzed , and compared with the tacrolimus/placebo-treated patients to determine whether there were any differences . RESULTS Tacrolimus pretreatment failed to block respiratory reactions to provoking doses of aspirin in 5 of 8 patients with AERD , and in the other 3 patients did not block higher doses of aspirin . The results of oral aspirin challenges in the control population of 50 patients were compared with either the baseline or postchallenge data from the tacrolimus-pretreated or placebo-pretreated patients with AERD , and there were no significant differences . CONCLUSIONS Use of tacrolimus as add-on pretreatment to prevent reactions to aspirin in patients with AERD or to achieve the goal of silent aspirin desensitization could not be accomplished Introduction and objective Asthma , owing to its chronic nature , is associated with a substantial economic burden . Healthcare providers need to compare the cost effectiveness of alternative asthma treatment options to ensure that they obtain the best value for money from the re sources they control . The objective of the current study was to compare the cost effectiveness of salmeterol/fluticasone propionate in combination with fluticasone propionate plus montelukast in patients with symptomatic asthma uncontrolled with inhaled corticosteroid ( ICS ) monotherapy . Study design and methods Direct healthcare re source data were prospect ively collected during a double-blind , r and omized , 12-week clinical study of inhaled salmeterol/fluticasone propionate 50/100 µg twice daily ( n = 356 ) and inhaled fluticasone propionate 100 µg twice daily plus oral montelukast 10 mg daily ( n = 369 ) . Re sources were costed in Dutch guilders ( NLG ) from the perspective of The Netherl and s healthcare system using 1999/2000 prices , but have been presented in US dollars and euros . The primary effectiveness measure was the proportion of successfully treated weeks ( based on mean morning PEF values ) . Secondary measures were episode-free days , symptom-free days , and symptom-free nights . Results Salmeterol/fluticasone propionate was more effective than fluticasone propionate plus montelukast as measured by the proportion of successfully treated weeks mean 63.3 % vs 39.0 % ; median difference 25 % ; p < 0.001 ) . Salmeterol/fluticasone propionate was also more effective than fluticasone propionate plus montelukast according to the secondary effectiveness measures . The mean total direct daily healthcare costs per patient were 16 % higher with fluticasone propionate plus montelukast than with salmeterol/fluticasone propionate mainly due to higher drug costs in the former group ( $ US2.25 vs 1.94 ; € 1.92 vs 1.66 , respectively ; the NLG was fixed against the euro at a rate of € 1 = NLG2.2 on 31 December 1998 ; $ US1 = NLG1.883 , June 2003 ; $ US1 = € 0.848 , June 2003 ) . Incremental cost-effectiveness analyses showed that salmeterol/fluticasone propionate was dominant over fluticasone propionate plus montelukast and sensitivity analyses showed these results to be robust . ConclusionS almeterol/fluticasone propionate is a more cost-effective treatment option than fluticasone propionate plus montelukast for patients with symptomatic asthma uncontrolled by ICS Patients with moderate persistent asthma ( n = 523 ; mean FEV1 77.4 % ) not fully controlled with inhaled corticosteroids ( ICS ; 400 - 1000 microg/day ) were r and omized to receive either once-daily budesonide/formoterol ( 160/4.5 microg , two inhalations ) ; or twice-daily budesonide/formoterol ( 160/4.5 microg , one inhalation ) ; or budesonide ( 400 microg ) once-daily for 12 weeks . Once-daily dosing was administered in the evening and twice-daily dosing was administered in the morning and evening . All patients received twice-daily budesonide ( 200 microg ) during a 2-week run-in . Compared with budesonide alone , change in mean morning and evening peak expiratory flow was greater in the once-daily budesonide/formoterol group ( 27 and 171 min(-1 ) , respectively ; P < 0.001 ) and twice-daily budesonide/formoterol group ( 23 and 24 l min(-1 ) , respectively ; P < 0.001 ) . Night awakenings , symptom-free days , reliever-use-free days and asthma-control days were all improved during once-daily budesonide/formoterol therapy vs. budesonide ( P < or = 0.05 ) . Similar improvements were also seen with twice-daily budesonide/formoterol ( P < or = 0.05 ) . The risk of a mild exacerbation was reduced after once- and twice-daily budesonide/formoterol vs. budesonide ( 38 % and 35 % , respectively ; P < 0.002 ) . All treatments were well tolerated . Budesonide/formoterol , once- or twice-daily , in a single inhaler improved asthma symptoms and exacerbations compared with budesonide . In the majority of patients with moderate persistent asthma requiring ICS and long-acting beta-agonists , once-daily formoterol/budesonide provided sustained efficacy over 24 h , similar to twice-daily dosing 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 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 The aim of this study was to compare the efficacy and safety of salmeterol/fluticasone propionate combination product ( SFC ) with fluticasone propionate ( FP ) plus oral montelukast ( M ) over 12 weeks in symptomatic asthma patients . The study was a multinational , r and omised , double-blind , double-dummy , parallel-group design in patients aged > or = 15 years . After a 4-week run-in during which all patients received FP 100 microg twice daily , patients were r and omised to inhaled SFC ( 50/100 microg ) twice daily or inhaled FP 100 microg twice daily and oral M 10 mg once daily . Patients kept daily records of their peak expiratory flow ( PEF ) symptom scores and use of rescue medication . Over the 12-week treatment period , the adjusted increase in mean morning PEF was significantly greater in the SFC group ( 36 l/min ) than the FP/M group ( 19 l/min ; P < 0.001 ) . The improvement in FEV1 was also significantly greater in the SFC group ( mean treatment difference 0.11 l ; P < 0.001 ) . SFC provided significantly better control of daytime and night-time symptoms and there were fewer exacerbations . Patients in the SFC group were also significantly more likely to have a rescue-free day . Both treatments were equally well tolerated . Combination therapy with FP plus salmeterol ( SFC ) produced significantly greater improvements in lung function and asthma control than the addition of montelukastto FP OBJECTIVE To study the effect of 3 months of treatment with zileuton , an inhibitor of the enzymatic pathway ( 5-lipoxygenase ) leading to leukotriene formation , on disease control in patients with mild to moderate asthma . DESIGN R and omized , double-blind , parallel-group study in 401 patients . A 10-day placebo lead-in was followed by a double-blind treatment period of 13 weeks . SETTING Asthma study clinics in university hospitals and private practice s. PATIENTS OR OTHER PARTICIPANTS Patients with mild to moderate asthma ( forced expiratory volume in the first second [ FEV1 ] , 40 % to 80 % of predicted ) whose only treatment was inhaled beta-agonists . INTERVENTIONS Treatment with 600 mg or 400 mg of zileuton or placebo ( each taken four times daily . ) MAIN OUTCOME MEASURES Frequency of asthma exacerbation requiring treatment with corticosteroids , use of inhaled beta-agonists , pulmonary function tests , asthma symptom assessment , and quality -of-life evaluation . Safety was evaluated by monitoring adverse events . RESULTS Only eight ( 6.1 % ) of 132 patients receiving 600 mg of zileuton four times a day required  corticosteroid treatment  for asthma vs 21 ( 15.6 % ) of 135 patients receiving placebo ( P=.02 ) , giving a relative risk of 2.6 . At the time of expected peak drug concentration , the average FEV1 improved 15.7 % in the 600-mg zileuton group vs 7.7 % in the placebo group ( P=.006 ) . Quality -of-life assessment s significantly improved in the 600-mg zileuton group and not in the placebo group ( P=.007 for the overall score ) . Elevations in liver function tests ( more than three times normal ) , all of which reversed with drug withdrawal , occurred in five patients ( P=.03 vs placebo ) , three patients ( P=.12 vs placebo ) , and no patients treated with 600 mg of zileuton , 400 mg of zileuton , or placebo , respectively . CONCLUSIONS Three months of 5-lipoxygenase inhibition produced a significant improvement in asthma control . These data indicate that 5-lipoxygenase products of arachidonic acid metabolism are mediators of inflammation with an important role in the biology of asthma 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 We conducted an economic evaluation in a UK setting based on a 12-week prospect i ve r and omized open-label parallel-group comparison of eformoterol Turbohaler 12 microg b. i.d . with salmeterol Accuhaler 50 microg b. i.d . in children aged 6 - 17 with symptomatic asthma receiving inhaled corticosteroids and short-acting beta2-agonists .  The principal effectiveness measure was percentage of symptom-free days with no short-acting beta2-agonist use during the study period . Asthma-related medication , unscheduled physician contacts and hospitalizations were collected prospect ively and cost to the UK NHS calculated using year 2,000 prices . The economic evaluation included 73 patients in the eformoterol group and 72 patients in the salmeterol group . The mean age of patients was 11.6 years ( eformoterol ) and 11.8 years ( salmeterol ) . The mean percentage of symptom-free days with no short-acting beta2-agonist use was 39 % in the eformoterol group and 30 % in the salmeterol group . Mean per patient daily cost was 1.15 pounds in the eformoterol group and 1.39 pounds in the salmeterol group . Both cost and effectiveness differences favoured eformoterol ( P < 0.05 ; one-sided ) . Sensitivity analysis confirmed the results to be robust to changes in effectiveness , price and re source utilisation parameters . Eformoterol delivered by Turbohaler was found to be significantly more effective and less expensive than salmeterol Accuhaler in this study 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 Exercise-induced bronchoconstriction is common in patients with chronic asthma ( 1 ) . Airway cooling or desiccation during exercise may trigger activation of mast cells and release of such mediators as histamine and cysteinyl leukotrienes , result ing in bronchospasm ( 1 , 2 ) . Cysteinyl leukotrienes ( LTC4 , LTD4 , and LTE4 ) , synthesized from arachidonic acid through the 5-lipoxygenase pathway , are potent bronchoconstrictors , with an effect greater than 1000 times that of histamine ( 3 - 5 ) . Several research ers have demonstrated an increase in urinary concentrations of LTE4 after exercise ( 6 , 7 ) . Prophylaxis against exercise-induced bronchoconstriction with inhaled mast cell-stabilizing agents and short-acting -agonists must be administered 15 to 30 minutes before exercise . The long-acting inhaled -agonist salmeterol protects against exercise-induced bronchoconstriction for up to 12 hours , thus providing more flexibility in the dosing schedule for active patients with asthma ( 8 , 9 ) . However , in some patients , tolerance to salmeterol develops with long-term use , and the level of bronchoprotection diminishes by 6 to 9 hours ( 10 - 12 ) . Montelukast sodium , a leukotriene receptor antagonist , is a potent oral medication for the treatment of asthma . The leukotriene receptor antagonists have demonstrated a significant bronchoprotective effect with exercise after one or two doses ( 13 , 14 ) . In patients with exercise-induced bronchoconstriction , short-term treatment with montelukast ( Singulair , Merck & Co. , Inc. , Whitehouse Station , New Jersey ) given once daily diminished the postexercise response , as described by the area under the FEV1 time curve ( AUC0 - 60 min ) , by more than 50 % , even at the end of the dosing interval ( 20 to 24 hours after administration ) ( 15 , 16 ) . Furthermore , tolerance to the bronchoprotective effects of montelukast did not occur with long-term administration ( 17 ) . We sought to test the hypothesis that the bronchoprotective effects of montelukast were greater than those of salmeterol in patients with chronic asthma who experienced exercise-induced bronchoconstriction . Methods Design We conducted a r and omized , parallel-group study consisting of a 2-week , single-blind placebo baseline period followed by an 8-week , double-blind treatment period with montelukast sodium ( 10-mg tablet taken orally once in the evening ) or inhaled salmeterol ( 50-g aerosol formulation [ 2 puffs ] taken twice daily ) . Seventeen clinical study sites participated in the trial . To mask formulation differences , a double-dummy treatment regimen was used . Each patient received one tablet daily ( active agent or matching placebo ) or one inhaler twice daily ( active agent or matching placebo ) for both the single-blind and double-blind treatment periods . A computer-generated allocation schedule with a blocking factor of 4 was produced by the statistician . Each center was given a block of allocation numbers that were assigned sequentially to consecutive r and omly assigned patients . Spirometric measurements were obtained before and after st and ardized exercise challenges at the beginning and end of the baseline period , within the first 3 days of the double-blind treatment period , and at weeks 4 and 8 of the treatment period . Additional measurements were physical examination , vital signs , electrocardiography , chest radiography , and laboratory tests ( hematology , chemistry profile , and urinalysis ) . At each visit , all spontaneously reported adverse events were recorded . The protocol was approved by the institutional review board of each site , and written informed consent was obtained from each patient . Inclusion Criteria Male and female patients 15 to 45 years of age with a history of chronic asthma were enrolled . All patients had an FEV1 of at least 65 % of the predicted value at rest and a decrease in FEV1 of at least 20 % after a st and ardized exercise challenge on two occasions during the baseline period . All patients had been nonsmokers for at least 1 year and had a smoking history of less than 15 pack-years . Exclusion Criteria Persons who had upper respiratory infection or exacerbation of asthma requiring emergency care within the past month or were hospitalized for asthma in the past 3 months were excluded . Use of oral or inhaled corticosteroids , theophylline , cromolyn sodium , nedocromil , oral -agonist , and long-acting antihistamines was prohibited before and during the study . Use of inhaled albuterol for symptomatic relief of asthma and use of short-acting antihistamines were permitted . Evaluations A st and ard spirometer ( Puritan-Bennett PB100/PB110 , Puritan-Bennett , Wilmington , Massachusetts ) was used to obtain all spirometric measurements according to American Thoracic Society st and ard criteria ( 18 ) . Patients had to have discontinued use of inhaled short-acting -agonists for 6 hours before the visit . Exercise testing was done in the early afternoon near the trough of effect for both drugs according to a method described elsewhere ( 17 ) . Measurements were obtained 20 and 5 minutes before exercise ( prechallenge period ) . Exercise challenge was performed only if the average FEV1 in the prechallenge period was greater than 65 % of predicted ; otherwise , the test was rescheduled . Patients  exercised on a treadmill while inhaling room temperature , compressed , dry air . During the first test , the speed and gradient of the treadmill were adjusted to achieve 80 % to 90 % of the patient 's age-predicted maximum heart rate . The setting s were maintained for a total of 6 minutes ; the same setting s were used for future tests . This level of exercise has been used to quantify the level of bronchoconstriction associated with regular exercise ( 19 ) . Serial spirometric measurements were obtained at 0 , 5 , 10 , 15 , 30 , 45 , and 60 minutes after exercise ( postexercise period ) . Additional measurements were carried out at 15-minute intervals for up to 90 minutes if the patient 's FEV1 had not returned to within 5 % of the prechallenge value by 60 minutes . If the patient 's FEV1 did not return to the prechallenge value by 90 minutes after exercise , a rescue dose of inhaled -agonist was administered at the discretion of the study investigator . Statistical Analysis An all- patients -treated analysis , which included patients with a baseline visit and at least one post-r and omization visit , was performed . The change from baseline in the maximal percentage decrease in FEV1 after exercise at the end of 8 weeks of treatment was the primary end point . Analysis of variance was used to compare the two treatment groups . The analysis of variance model included terms for treatment , center , and the interaction of treatment and center . Ninety-five percent CIs for within-group means and the difference between groups were constructed to assess the magnitude of the treatment effect . Analysis of variance on the ranked data was used to analyze percentage inhibition for all end points . In the event of early termination of the exercise challenge because of administration of rescue medication , the largest percentage decrease in FEV1 achieved before administration of rescue medication was used in the analysis . Secondary end points were change from baseline for maximal percentage decrease in FEV1 at days 1 to 3 and week 4 , the time required after maximal decrease in FEV1 to return within 5 % of prechallenge values ( time to recovery ) , and the AUC0 - 60 min at all visits . The mean of the 20- and 5-minute prechallenge measurements was used as the pre-exercise FEV1 value . If a patient required rescue with inhaled -agonist during the postexercise period , the last recorded FEV1 value was used and carried forward for all subsequent readings and 100 minutes was entered for the end point of time to recovery . The AUC0 - 60 min was calculated by using the trapezoidal method . If a patient 's FEV1 did not decrease below 95 % of the prechallenge value , the time to recovery was assigned a value of zero . The persistence of effect over time was assessed by using a repeated- measures fixed-effects model with terms for center , treatment group , time , and the interaction of treatment group and time to calculate the rate of change over the treatment period . Persistence of effect was defined as a slope of zero . The magnitude of the slopes for each treatment group was estimated , and 95 % CIs were calculated . An overall test of equal slopes between the treatment groups was examined , and a 95 % CI on the difference in slopes between treatment groups was provided . The number and percentage of patients requiring rescue medication  during or at the end of the exercise test were summarized by treatment group at each time point . In addition , the number and percentage of patients whose decrease in FEV1 from pre-exercise levels was less than 10 % , 10 % to 20 % , 20 % to 40 % , and greater than 40 % were summarized by treatment group for each visit . The overall incidence of adverse events and laboratory abnormalities was assessed by using the Fisher exact test , and within-group changes in the number of laboratory abnormalities were assessed by using the McNemar test . Descriptive statistics were provided by treatment group for patient demographic characteristics , clinical characteristics , and baseline profile . The study was design ed with a sample size of 160 patients ( 80 patients per treatment group ) to have 95 % power ( two-sided test at = 0.05 ) to detect a 7 % difference in the mean change in maximal percentage decrease in FEV1 between treatments . All statistical analyses were performed by using SAS software , version 6 ( SAS Institute , Inc. , Cary , North Carolina ) . Role of the Funding Source Funding for this trial was provided by Merck & Co. , Inc. , Whitehouse Station , New Jersey . Personnel from Merck U.S. Human Health , Clinical Development department played a significant role in the design , conduct , and analysis of the trial . The trial was conducted in accordance with guidelines for clinical trials of investigational agents established by U.S. regulatory authorities . Results The objective of this study was to determine whether initial maintenance therapy for the treatment of inflammation and bronchoconstriction associated with persistent asthma is more effective with a combination product ( 100 microg of fluticasone propionate and 50 microg of salmeterol [ FSC ] ) administered twice daily through the Diskus device ( GlaxoWellcome , Research Triangle Park , NC ) or with montelukast at 10 mg once daily . A 12-wk , r and omized , double-blind , double-dummy , multicenter study was conducted with 423 patients 15 yr of age and older with asthma and who were symptomatic while receiving short-acting beta(2)-agonists alone . At end point , FSC result ed in significantly greater increases in morning predose FEV(1 ) ( 0.54 + /- 0.03 vs. 0.27 + /- 0.03 L ) , morning peak expiratory flow ( PEF ) ( 89.9 + /- 6.7 vs. 34.2 + /- 4.7 L/min ) , evening PEF ( 69.9 + /- 5.8 vs. 31.1 + /- 4.5 L/min ) , the percentage of symptom-free days ( 48.9 + /- 2.9 vs. 21.7 + /- 2.5 % ) , the percentage of rescue-free days ( 53.0 + /- 2.8 vs. 26.2 + /- 2.5 % ) , and the percentage of nights with no awakenings ( 23.0 + /- 2.5 vs. 15.5+/-2.4 % ) compared with montelukast ( p < or = 0.001 , all comparisons ) . FSC significantly reduced asthma symptom scores ( -1.0 + /- 0.1 vs. -0.6 + /- 0.1 ) , rescue albuterol use ( -3.3 + /- 0.2 vs. -1.9 + /- 0.2 puffs/d ) , and the number of exacerbations ( 0 vs. 11 ) compared with montelukast ( p < 0.001 ) . Both treatments were well tolerated . In summary , treatment of the two main components of asthma ( inflammation and bronchoconstriction ) with fluticasone propionate and salmeterol in a combination product was a more effective initial maintenance treatment strategy than treatment with montelukast , a single-mediator antagonist AIMS There are no data comparing the relative efficacy of hydrofluoroalkane ( HFA ) formulations of ciclesonide ( CIC ) and fluticasone propionate ( FP ) on airway hyper-responsiveness , in mild-to-moderate persistent asthma . We therefore elected to evaluate the comparative efficacy of HFA pressurized metered-dose inhaler formulations of CIC and FP , assessing methacholine challenge , in addition to exhaled nitric oxide , lung function , diary cards and quality of life . METHODS Nineteen mild-to-moderate asthmatic patients completed the study per protocol in r and omized , double-blind , double-dummy , crossover fashion . Patients were required to stop their usual inhaled corticosteroid therapy for the duration of the study . Patients were commenced instead on salmeterol ( SM ) 50 microg one puff twice daily + montelukast ( ML ) 10 mg once daily for 2-week washout periods prior to each r and omized treatment , in order to prevent dropouts . Patients received 4 weeks of either CIC 200 microg two puffs once daily ( 08.00 h ) + CIC-placebo ( PL ) two puffs once daily ( 20.00 h ) + FP-PL two puffs twice daily ( 08.00 h and 20.00 h ) , or FP 125 microg two puffs twice daily ( 08.00 h and 20.00 h ) + CIC-PL two puffs twice daily ( 08.00 h and 20.00 h ) . SM + ML were withheld for 72 h prior to post-washout visits and CIC or FP was withheld for 24 h prior to study visits . RESULTS There was no significant difference between CIC vs. FP for the primary outcome of methacholine PC20 as doubling dilution ( dd ) shift from respective baseline ; mean difference : 0.4 dd ( 95 % CI -0.4 , 1.2 ) . Moreover , there was no difference between treatments for the sequence of CIC first vs FP second ; mean difference : 0.2 dd ( 95 % CI -1.3 , 1.7 ) or FP first vs CIC second ; mean difference : 0.9 dd ( 95 % CI -0.1 , 1.8 ) . There were also no differences for other secondary outcomes between treatments , either respective or irrespective of sequence , as change from baseline . CONCLUSIONS There were no differences between 4 weeks of CIC 400 microg once daily and FP 250 microg twice daily on methacholine hyper-responsiveness in mild-to-moderate persistent asthma . Longer-term studies are indicated to evaluate their relative efficacy on asthma exacerbations 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 To compare the efficacy and safety of fluticasone propionate and zafirlukast in patients with relatively stable persistent asthma who were previously treated with inhaled corticosteroids and short-acting beta(2)-agonists . A total of 440 patients ( > or = 12 years of age ) previously treated with inhaled corticosteroids ( beclomethasone dipropionate or triamcinolone acetonide ) and short-acting beta(2)-agonists  were included in this r and omized double-blind study . After an 8-day run-in period , patients were treated with fluticasone ( 88 microg ) or zafirlukast ( 20 mg ) twice daily for 6 weeks . Outcome measures included pulmonary function ( forced expiratory volume in 1 second [ FEV(1 ) ] , peak expiratory flow [ peak flow ] ) , albuterol use , asthma symptoms , withdrawals due to lack of efficacy , and asthma exacerbations . Patients treated with fluticasone ( n = 224 ) experienced greater mean increases in FEV(1 ) ( 0.24 L vs. 0.08 L , P < 0.001 ) , morning peak flow ( 30 L/min vs. 6 L/min , P < 0.001 ) , and evening peak flow ( 23 L/min vs. 5 L/min , P < 0.001 ) during the study than did those treated with zafirlukast ( n = 216 ) . Fluticasone-treated patients had significantly greater increases in the mean percentages of symptom-free days ( 22 % vs. 8 % , P < 0.001 ) , rescue-free days ( 23 % vs. 10 % , P = 0.002 ) , nights with uninterrupted sleep ( < 1 % vs. -5 % , P = 0.006 ) , and fewer asthma exacerbations ( 1 % vs. 6 % , P = 0.005 ) . Fewer fluticasone-treated patients were withdrawn due to lack of efficacy ( 2 % vs. 13 % , P < 0.001).Inhaled fluticasone was more effective than zafirlukast in maintaining or improving asthma control in patients with relatively stable asthma who were switched from low-dose inhaled corticosteroids OBJECTIVE The availability of antiinflammatory asthma medications for infants and young children has been limited . The objective of this study was to compare effects of nebulized budesonide inhalation suspension and cromolyn sodium nebulizer solution on asthma-related health outcomes in young children with asthma . METHODS We conducted a r and omized , parallel-group , 52-week , open-label study in 36 US clinical sites . Patients included 335 children who were 2 to 6 years of age and had persistent asthma that had been treated with at least 1 long-term control medication ; 287 children ( 86 % ) completed the study . Patients received budesonide inhalation suspension , 0.5 mg daily ( n = 168 ) , or cromolyn sodium nebulizer solution , 20 mg 4 times daily ( n = 167 ) , for 8 weeks , followed by dose titration at the investigator 's discretion . The main outcome measure was the rate of asthma exacerbations over 52 weeks . Secondary measures included times to first asthma exacerbation and first use of additional asthma therapy , asthma symptom scores , rescue medication use , and health care re source use . RESULTS The budesonide group had a mean ( median ) asthma exacerbation rate of 1.23 ( 0.99 ) per year compared with 2.41 ( 1.85 ) for the cromolyn group , significantly longer times to first exacerbation and first use of additional long-term asthma medication , greater improvements in asthma symptom scores , reduced use of rescue medication , and fewer urgent care visits . Both treatments were well tolerated . CONCLUSIONS Budesonide inhalation suspension was more effective than nebulized cromolyn sodium in young children with persistent asthma . Both treatments were well tolerated with similar adverse event profiles Abstract Objective : To compare the relative cost effectiveness of salmeterol (50μg)/ fluticasone propionate ( 100μg ) with that of oral montelukast ( 10 mg ) as initial maintenance therapy in patients with persistent asthma uncontrolled on short-acting β2-agonist therapy alone . Study design : A cost-effectiveness analysis was performed based on effectiveness and re source utilisation data that was prospect ively collected from a r and omised , double-blind , double-dummy , 12-week trial . Patients and methods : Patients ( > 15 years of age ) who had asthma for at least 6 months . Effectiveness measurements in this analysis included improvement in forced expiratory volume in 1 second ( FEV1 ) and symptom-free days ( SFDs ) . Cost of asthma drug treatment as well as costs related to an asthma exacerbation were used in the cost analysis . The study assumed a payer ’s perspective . All costs are in 2001 US dollars . Results : Of the 423 patients eligible for the study , 211 were r and omised to salmeterol/fluticasone propionate and 212 to montelukast . Treatment with salmeterol/fluticasone propionate result ed in a significantly higher proportion of patients who achieved a 12 % increase in FEV1 ( successful treatment ) [ salmeterol/fluticasone propionate : 71 % vs montelukast : 39 % ; p < 0.001 ] and percentage of SFDs  ( salmeterol/fluticasone propionate : 46.8 % vs montelukast : 21.5 % ; p < 0.001 ) compared with montelukast . The mean daily costs per successfully treated patient were lower in the salmeterol/fluticasone propionate group ( $ US5.03 , 95 % CI $ US4.61 to $ US5.50 ) compared with the montelukast group ( $ US8.25 , 95 % CI $ US6.98 to $ US9.93 ) . Furthermore , per patient mean daily cost per SFD was lower with salmeterol/fluticasone propionate ( $ US7.63 , 95 % CI $ US6.90 to $ US8.50 ) compared with montelukast ( $ US14.89 , 95 % CI $ US12.36 to $ US17.98 ) . Incremental cost-effectiveness ratios ( ICERs ) showed that the additional costs to achieve these benefits with salmeterol/fluticasone propionate were minimal . With regards to improvement in lung function , the ICER was $ US1.33 ( 95 % CI $ US0.80 to $ US2.02 ) and with regards to SFD , the ICER was $ US1.69 ( 95 % CI $ US1.01 to $ US2.48 ) . Sensitivity analysis demonstrated the stability of the results over a range of assumptions . Conclusions : From a third-party payer perspective , this analysis shows that based on increased efficacy and only a slight increase in cost , twice-daily treatment with salmeterol/fluticasone propionate is more cost effective than once-daily treatment with montelukast as initial maintenance therapy for persistent asthma . This finding complements the results of the clinical analyses indicating that treatment of both inflammation and bronchoconstriction with products such as salmeterol/fluticasone propionate may be more cost effective as initial maintenance asthma therapy than the use of leukotriene modifiers such as montelukast Background : Asthma is a chronic inflammatory disease of the airways . Inhaled corticosteroids are very important in anti-inflammatory treatment , but to a great extent they can not control asthma alone . In addition to corticosteroids , long-acting β2 agonists and leukotriene antagonists are used for asthma control . Objective : In this study , the effect of the addition of formoterol and montelukast on asthma control in patients with moderately persistent asthma who were symptomatic while using a low dose of inhaled budesonide  was compared . Methods : At the beginning of the study , 40 symptomatic patients with moderately persistent asthma used  400 µg/day budesonide for a 4-week training period , and were then divided r and omly into two groups , each composed of 20 persons . For the first group ’s treatment regime , inhaled formoterol ( 9 µg ) twice a day was added , and for the second group ’s treatment regime , one-dose oral montelukast ( 10 µg ) was added . These patients were followed up for 8 weeks . The patients ’ peak expiratory flow ( PEF ) values measured in the morning and at night , changes in PEF , forced expiratory volume in 1 s , asthma symptom score and the symptom-relieving therapy used during the 12-week study period were recorded and evaluated in the clinic at the very beginning and at the end of each period . Results : Before the study , the morning PEF value of the group for whom formoterol was added to budesonide ( FB ) was 266.3 ± 59.3 liters/min , and in the group for whom montelukast was added to budesonide ( MB ) , it was 262.8 ± 53.8 liters/min ( p > 0.05 ) . After the 8-week treatment period , the morning PEF values were found to be 320.5 ± 54.4 liters/min in the FB group and 293.3 ± 52.4 liters/min in the MB group ; at the end of the study , it was seen that although there was an increase in morning PEF of 54.2 ± 15.2 liters/min in the FB group , there was an increase of only 30.5 ± 25.3 liters/min in the MB group ( p < 0.0001 ) . Before the study , night PEF values were 287 ± 56.6 liters/min in the FB group and 283 ± 48.5 liters/min in the MB group ( p > 0.05 ) . At the end of the treatment , the night PEF values were found to be 331.5 ± 56.1 liters/min in the FB group and 310 ± 53.1 liters/min in the MB group . At the end of the study , it was observed that although there was an increase in night PEF of 44.5 ± 23.3 liters/min in the FB group , there was an increase of only 27 ± 24.1 liters/min in the MB group ( p < 0.001 ) . Although asthma symptom scores and the use of symptom-relieving drugs showed similarities between the two groups at the beginning of the study , after treatment , the FB group had better results than the MB group with respect to these two parameters ( p < 0.0001 for both ) . It was also seen that the two treatments are tolerated equally well . Conclusion : FB treatment , which causes a considerable improvement in lung function , showed better asthma control than MB treatment in patients with moderately persistent asthma Cough-variant asthma ( CVA ) occurs in a subgroup of asthmatics whose sole or predominant respiratory symptom is cough . Although bronchodilators are often sufficient to treat CVA , refractory cough may require therapy with inhaled or systemic corticosteroids . In a r and omized , double-blind , placebo-controlled , crossover study , we examined the effect of a 14-day course of the leukotriene receptor antagonist zafirlukast on subjective cough score and cough-reflex sensitivity to inhaled capsaicin in eight subjects with CVA refractory to inhaled beta agonists , and in five subjects refractory to inhaled corticosteroids . Seven of eight subjects experienced significant subjective and objective improvement in cough after treatment with zafirlukast . Mean ( ± SEM ) cough score improved from 7.75 ± 0.56 to 3.25 ± 0.84 ( p = 0.0006 ) . Cough sensitivity to capsaicin was suppressed by zafirlukast in all subjects . Patients with CVA may represent a distinct subgroup of asthmatics whose afferent cough receptors within the respiratory epithelium are hypersensitive relative to those of patients with the typical form of asthma . Zafirlukast appears to be particularly effective in treating CVA by inhibiting the sensitivity of these receptors . Leukotriene receptor antagonists may offer an alternative to corticosteroids for the treatment of CVA refractory to inhaled bronchodilators This study was design ed to compare the effects of low-dose inhaled fluticasone propionate ( 100 mcg twice daily ) with those of the leukotriene antagonist , zafirlukast ( 20 mg twice daily ) , on bronchial hyper-responsiveness . The study recruited 30 patients ( nine men , 21 women ; mean age 45 years ) with forced expiratory volume in 1 sec ( FEV1 ) > 50 % and airway reversibility to salbutamol > or = 15 % . This was a single centre , double-blind , double-dummy cross-over study , composed of two successive 2-week treatment periods , each preceded by a 2 - 4 week single-blind placebo period . Following 2 weeks of treatment with fluticasone propionate and zafirlukast , the mean provocational concentration causing a 20 % fall in FEV1 ( PC20 ) histamine was 1.61 mg ml(-1 ) ( SD 2.34 ) and 0.99 mg ml(-1 ) ( SD 1.74 ) respectively . Taking baseline differences into account , the difference between treatments was equivalent to 0.77 doubling doses of histamine ( 95 % CI , 0.05 - 1.50 ; P=0.037 ) . Morning peak flow values were significantly higher ( 17 l min(-1 ) ; P=0.049 ) after treatment with fluticasone propionate during the second week of treatment . Both treatments were well tolerated . The results of this short-term study show that compared with zafirlukast , a low dose of fluticasone propionate offers greater clinical benefit and is more cost effective BACKGROUND In response to the phasing out of chlorofluorocarbon ( CFC ) inhalers , a metered dose hydrofluoroalkane ( HFA ) formulation , Modulite ( Chiesi Farmaceutici S.p . A , Parma , Italy ) , to be delivered with a pressurized metered dose inhaler ( pMDI ) , has been developed . Modulite is a HFA formulation technology that has been design ed to provide stable and uniform dose delivery of HFA-based formulations to enable an easy transition from CFC to HFA inhalers . OBJECTIVES The aim of this study was to compare the bronchoprotective and bronchodilator effects of a single dose of 12 microg of formoterol from the HFA Modulite inhaler with the Foradil Aerolizer ( dry powder inhaler , DPI ) and the Foradil CFC inhalers ( Novartis Health Consumer , Basel , Switzerl and ) . METHODS This was a double blind , double dummy , r and omized , placebo-controlled , crossover study conducted in 38 subjects with mild to moderate asthma ( mean forced expiratory volume in 1 s [ FEV1 ] 87.5 % predicted ) . The primary endpoint was methacholine challenge provocative dose required for 20 % fall in the FEV1 ( PD20 ) 90 min post dose . Bronchodilation was assessed with spirometry ( FEV1 , FVC , FEF25 - 75 ) and impulse oscillometry ( resistance at 5 and 20 Hz , reactance at 5 Hz and resonant frequency ) over the 90 min post dose . In a subset of 12 subjects formoterol plasma levels , serum potassium and glucose were determined up to 480 min post dose . RESULTS The three formoterol formulations demonstrated significant ( P < or = 0.05 ) improvements in bronchoprotection compared to placebo and non-inferiority of the HFA preparation compared to the CFC and DPI preparations was demonstrated . Geometric mean PD20 values were 0.51 mg with HFA , 0.62 mg with DPI , 0.62 mg with CFC and 0.2 mg with placebo . The log transformed mean differences in PD20 doubling dose between HFA and ( a ) DPI was -0.28 ( 95 % CI -0.84 - 0.29 , P = 0.57 ) ( b ) CFC was -0.28 ( 95 % CI -0.84 - 0.28 , P = 0.57 ) and ( c ) placebo was 1.38 ( 95 % CI 0.82 - 1.94 , P < 0.001 ) . Serum potassium , glucose and formoterol plasma profiles were comparable for the CFC , HFA and DPI devices . CONCLUSION Our findings of similar efficacy , pharmacokinetics and systemic effects of the HFA formoterol inhaler compared to the CFC and DPI preparations supports the potential use of this novel formulation in the treatment of 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 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 BACKGROUND The role of long-acting , inhaled beta2-agonists in treating asthma is uncertain . In a double-blind study , we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide . METHODS After a four-week run-in period of treatment with budesonide ( 800 microg twice daily ) , 852 patients being treated with glucocorticoids  were r and omly assigned to one of four treatments given twice daily by means of a dry-powder inhaler ( Turbuhaler ) : 100 microg of budesonide plus placebo , 100 microg of budesonide plus 12 microg of formoterol , 400 microg of budesonide plus placebo , or 400 microg of budesonide plus 12 microg of formoterol . Terbutaline was permitted as needed . Treatment continued for one year ; we compared the frequency of exacerbations of asthma , symptoms , and lung function in the four groups . A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days . RESULTS The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent , respectively , when formoterol was added to the lower dose of budesonide . The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent , respectively . Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent , respectively . Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide , but the improvements with formoterol were greater . CONCLUSIONS In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids , the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial . The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma 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 AIMS Inhaled corticosteroids alone or in combination with long acting beta2-agonists are indicated for use in mild persistent asthmatics . We set out to evaluate effects on airway hyperresponsiveness ( AHR ) and airway calibre using hydrofluoroalkane fluticasone/salmeterol ( FP/SM ) vs. double the dose of fluticasone alone ( FP ) . METHODS Fourteen mild persistent asthmatics completed a r and omized double-blind crossover study with 1-week run-in and washout periods prior to treatments . Subjects received 3 weeks of FP 250 microg or FP 125 microg/SM 25 microg as 1 puff twice daily .  Methacholine PD20 and lung function were measured after both baseline and treatment periods . RESULTS There were no significant differences in baseline values prior to r and omized treatments . Compared with pooled baseline , FP/SM and FP conferred improvements ( P < 0.05 ) on methacholine PD20 : 2.5 ( 95 % confidence interval 1.7 , 3.2 ) and 1.6 ( 0.8 - 2.3 ) doubling dose improvements , respectively ; between FP/SM vs. FP there was a 0.9 ( 0.4 , 1.4 ) doubling dose difference ( P < 0.05 ) . For forced expiratory volume in 1 s ( FEV1 ) , forced mid-expiratory flow ( FEF25 - 75 ) and morning peak expiratory flow ( PEF ) , FP/SM but not FP conferred improvements ( P < 0.05 ) compared with pooled baseline , with FP/SM being greater than FP ( P < 0.05 ) : differences in FEV1 of 7.2 % ( 3.8 , 10.6 ) predicted , FEF25 - 75 of 11.2 % ( 6.3 , 16.1 ) predicted , and morning PEF of 17 L x min(-1)(1 - 32 ) . CONCLUSIONS FP/SM conferred improvements on AHR and airway calibre , while twice the dose of FP improved only AHR in patients with mild asthma . The differential effects of FP/SM and FP suggest separate but complementary actions of the two moieties on airway inflammation and smooth muscle stabilization . This may explain the beneficial effects of combination inhalers on exacerbations 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 ] . ) 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 BACKGROUND A budesonide/formoterol single inhaler has been developed for convenient treatment of patients whose asthma is inadequately controlled by inhaled glucocorticosteroids alone . OBJECTIVES To compare long-term safety and efficacy of budesonide/formoterol single inhaler with budesonide plus formoterol via separate inhalers in adults with asthma . METHODS In this open , r and omized , parallel-group 6-month extension conducted in a subset of centres from a previous 6-month study , patients ( n=321 ) received two inhalations bid of budesonide/formoterol ( Symbicort Turbuhaler ) 160/4.5 microg delivered dose or corresponding doses of budesonide ( Pulmicort Turbuhaler ) plus formoterol ( Oxis Turbuhaler ) via separate inhalers . RESULTS Significantly fewer patients receiving budesonide/formoterol single inhaler withdrew compared with budesonide plus formoterol ( 9 vs. 19 % , P=0.008 ) . Incidence and severity of AEs were low and similar in both groups . No clinical ly important differences between groups , or changes , were identified in laboratory measurements , vital signs or ECG . Treatments produced similar improvements in lung function , ACQ scores and Mini AQLQ domains that were maintained throughout 12 months . CONCLUSIONS Budesonide/formoterol in a single inhaler is as safe and effective in the long-term treatment of asthma as budesonide plus formoterol via separate inhalers . The lower number of withdrawals with budesonide/formoterol may reflect better adherence to treatment compared with budesonide plus formoterol 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 Asthma is a chronic disease characterized by inflammation and bronchoconstriction . Medications that are able to effectively treat both components are advantageous . OBJECTIVE To compare the efficacy of an inhaled corticosteroid and a long-acting beta2-agonist combination product with a leukotriene antagonist for initial maintenance therapy in patients who were symptomatic while receiving short-acting beta2-agonists alone . METHODS A 12-week , r and omized , double-blind , double-dummy , multicenter study was conducted in 432 patients 15 years of age and older with persistent asthma who were symptomatic on short-acting beta2-agonists alone . Fluticasone propionate 100 microg and salmeterol 50 microg combination product ( FSC ) twice daily or montelukast 10 mg once daily was administered . RESULTS At endpoint , compared with montelukast , FSC significantly increased morning predose forced expiratory volume in 1 second ( 0.61 + /- 0.03 L vs 0.32 + /- 0.03 L ) , morning peak expiratory flow rate ( peak expiratory flow rate ; 81.4 + /- 5.9 L/minute vs 41.9 + /- 4.8 L/minute ) , evening peak expiratory flow rate ( 64.6 + /- 5.3 L/minute vs 38.8 + /- 4.7 L/minute ) , the percentage of symptom-free days ( 40.3 + /- 2.9 % vs 27.0 + /- 2.7 % ) , the percentage of rescue-free days ( 53.4 + /- 2.8 % vs 26.7 + /- 2.5 % ) , and the percentage of nights with no awakenings ( 29.8 + /- 2.5 % vs 19.6 + /- 2.1 % ) ( P < or = 0.011 , all comparisons ) . At endpoint , FSC significantly reduced asthma symptom scores ( -1.0 + /- 0.1 vs -0.7 + /- 0.1 ) and rescue albuterol use ( -3.6 + /- 0.2 puffs/day vs -2.2 + /- 0.2 puffs/day ) compared with montelukast ( P < 0.001 ) . At endpoint , patients treated with FSC also had a significantly greater improvement in quality of life scores and were more satisfied with their treatment compared with montelukast-treated patients ( P < or = 0.001 ) . Both treatments were well tolerated . CONCLUSIONS Initial maintenance therapy with FSC provides greater improvement in asthma control and patient satisfaction than montelukast 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 The aim of the present study was to demonstrate an equivalent asthma control and safety of inhaled budesonide 200 microg unit-dose via a spacer device ( Jet Spacer , Chiesi Farmaceutici S.p . A. ) given with an HFA-134a or CFC propellant in stable patients treated with inhaled corticosteroids . A total number of 270 patients , 134 in the HFA-134a group and 136 in the CFC group , completed a 2-week run-in period and were then r and omised to receive a daily dose of inhaled budesonide ( low dose : 400 microg , medium dose : 800 microg , high dose : 1200 or 1600 microg ) , defined on the basis of the dose of previous inhaled steroids given twice daily for 12 weeks . Morning and evening PEFR , intake of rescue salbutamol , number of day-time and night-time asthma attacks , number of night-time awakenings due to asthma and clinical symptoms were recorded daily by patients on diary cards . Pulmonary function tests ( FEV1 , FVC , PEFR and MEF50 ) and vital signs were measured at the clinics at study entry , at the start of treatment and after 2 , 4 , 8 and 12 weeks thereafter . Morning serum cortisol ( 8.00 - 10.00 AM ) was measured at baseline and in the final visit . Adverse events and vital signs were recorded throughout the total study period . Small increases vs. baseline for lung function ( more markedly in the high-dose subsets ) and significant decreases of symptoms and use of rescue salbutamol were similarly observed in both groups . Equivalence was demonstrated for the primary endpoint morning PEFR ( difference between means = -1.51 l/min ; 95 % CI : -9.40 - 6.37 l/min ; pre-defined limits : + /- 42.16 l/min , i.e. + /- 10 % of the reference LSM ) as well as for evening PEFR and FEV1 , both in the ITT population or on a per- protocol basis . No statistically significant differences between groups were observed in any of the other efficacy variables . A similar proportion of drug-related adverse events was observed in the two groups , without drug-related serious events in either group . No evidence of adrenal depletion was also noted with both propellants . In conclusion , the budesonide HFA-134a formulation given with a spacer device provided an equivalent asthma control with that of a corresponding CFC product , when administered in stable patients treated with inhaled corticosteroids in a broad range of daily doses . The use of the new propellant did not modify the safety profile of inhaled budesonide OBJECTIVE To compare the long-term effects of an inhaled corticosteroid with those of a leukotriene modifier on measures of clinical efficacy , subject preference , and safety in patients with persistent asthma . PATIENTS AND METHODS Between November 17 , 1998 , and May 26 , 2000 , we conducted a multicenter , r and omized , double-blind , double-dummy , parallel-group study of patients aged 15 years or older with persistent asthma . The patients were symptomatic while taking short-acting beta2-agonists alone  and were treated with fluticasone propionate ( 88 microg [ 2 puffs of 44 microg ] twice daily ) or montelukast ( 10 mg/d ) for 24 weeks . Measures of pulmonary function , asthma symptoms , albuterol use , nighttime awakenings , physician assessment s of efficacy , patient satisfaction , asthma-related quality of life , and safety were evaluated . RESULTS A total of 522 patients were r and omized to receive fluticasone or montelukast , and 395 patients completed the study . At end point , treatment with fluticasone significantly improved pulmonary function , asthma symptom scores , the percentage of symptom-free days , rescue albuterol use , and the number of nighttime awakenings due to asthma when compared with montelukast ( P < or = .002 , each comparison ) . Significantly more patients were satisfied with fluticasone therapy ( 83 % ) compared with montelukast therapy ( 66 % ) ( P<.001 ) , and fluticasone therapy was rated as effective by a significantly greater portion of physicians ( 67 % ) than was montelukast therapy ( 54 % ) ( P<.001 ) . Treatment with fluticasone significantly improved asthma-related quality -of-life measures compared with montelukast ( P < or = .01 ) . The incidence of asthma exacerbations was similar in the fluticasone ( 19 patients , 7 % ) and montelukast ( 21 patients , 8 % ) treatment groups , although slightly more patients in the montelukast group were withdrawn from the study because of asthma exacerbations ( 6 % vs 4 % , respectively ) . CONCLUSION Long-term treatment with a low dose of inhaled fluticasone is more effective than oral montelukast as first-line maintenance therapy for the treatment of persistent asthma 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 In accordance with the Montreal Protocol 1987 , initiatives to phase out and replace ozone-depleting chlorofluorocarbon ( CFC ) propellants with non-ozone-depleting propellants in metered-dose inhalers ( MDIs ) in the treatment of asthma and chronic obstructive pulmonary disease are underway . In view of this , two multi-centre , r and omised , parallel-group , double-blind studies were conducted to compare the safety and efficacy of salmeterol xinafoate delivered by an MDI using the hydrofluoroalkane ( HFA ) 134a propellant with the licensed CFC formulation ( Serevent ) in asthmatic population s of children ( 4 - 11 years ) and adults ( 12 years ) . Patients on a stable dose of inhaled corticosteroids with a scope for improvement based on mean morning peak expiratory flow ( PEF ) and symptoms were r and omised to receive salmeterol HFA MDI 50 microg twice daily or salmeterol CFC MDI 50 microg twice daily for 12 weeks . The primary efficacy variable was mean morning PEF and secondary variables included other lung function parameters , symptom scores , use of relief medication and safety assessment s. The difference between the treatments in adjusted mean morning PEF ( salmeterol HFA-salmeterol CFC ) were 2.5 and -3.2 L/min for per- protocol population s of children and adults , respectively . The lower limit of 95 % confidence intervals for both population s was within the pre-defined limit ( -15 L/min ) set for non-inferiority . Similar results were observed in intent-to-treat ( ITT ) population s. In children , the two formulations result ed in a lack of any statistically significant difference in secondary efficacy parameters . A significant difference at endpoint in clinic forced expiratory volume in 1s was reported in favour of the HFA formulation in the adult population , although the magnitude of this effect was not considered clinical ly significant . The incidences of adverse events ( AEs ) were similar for both formulations and population s , and no safety concerns were generated . Together these data demonstrate salmeterol HFA MDI to be as effective as salmeterol CFC MDI in adults and children BACKGROUND More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children . OBJECTIVE The Pediatric Asthma Controller Trial ( PACT ) compared the effectiveness of 3 regimens in achieving asthma control . METHODS A total of 285 children ( ages 6 - 14 years ) with mild-moderate persistent asthma on the basis of symptoms , and with FEV(1 ) > or= 80 % predicted and methacholine FEV(1 ) PC(20 ) < or= 12.5 mg/mL , were r and omized to 1 of 3 double-blind 48-week treatments : fluticasone 100 microg twice daily ( fluticasone monotherapy ) , fluticasone 100 microg/salmeterol 50 microg in the morning and salmeterol 50 mug in the evening ( PACT combination ) , and montelukast 5 mg in the evening . Outcomes included asthma control days ( primary outcome ) , exacerbations , humanistic measurements , and pulmonary function measurements . RESULTS Fluticasone monotherapy and PACT combination were comparable in many patient-measured outcomes , including percent of asthma control days , but fluticasone monotherapy was superior for clinic-measured FEV(1)/forced vital capacity ( P = .015 ) , maximum bronchodilator response ( P = .009 ) , exhaled nitric oxide ( P < .001 ) , and PC(20 ) ( P < .001 ) . Fluticasone monotherapy was superior to montelukast for asthma control days ( 64.2 % vs 52.5 % ; P = .004 ) and for all other control outcomes . Growth over 48 weeks was not statistically different ( fluticasone , 5.3 cm ; PACT combination , 5.3 cm ; montelukast , 5.7 cm ) . CONCLUSION Both fluticasone monotherapy and PACT combination achieved greater improvements in asthma control days than montelukast . However , fluticasone monotherapy was superior to PACT combination in achieving other dimensions of asthma control . Growth was similar in all groups . CLINICAL IMPLICATION S Therefore , of the regimens tested , the PACT study findings favor fluticasone monotherapy in treating children with mild-moderate persistent asthma with FEV(1 ) > or= 80 % predicted , confirming current guideline recommendations OBJECTIVE We wished to evaluate whether the combination of a leukotriene receptor antagonist and long-acting beta(2)-agonist might confer additive beneficial effects in terms of bronchoprotection and bronchodilatation , in mild to moderate asthmatic patients who were suboptimally controlled on inhaled corticosteroids alone . METHODS Twelve asthmatic patients were enrolled into a single-blind , placebo-controlled , crossover study , receiving additive therapy as either of the following : ( 1 ) montelukast alone , 10 mg ( ML(10 ) ) ; ( 2 ) inhaled salmeterol alone , 50 microg ( SM(50 ) ) ; ( 3 ) ML(10 ) and SM(50 ) ; ( 4 ) ML(10 ) and inhaled salmeterol , 100 microg ( SM(100 ) ) ; or ( 5 ) placebo inhaler and tablet . Trough measurements were made of adenosine monophosphate ( AMP ) bronchial challenge ( the provocative concentration of a drug [ AMP ] causing a fall of > /= 20 % in FEV(1 ) [ PC(20 ) ] ) as the primary end point , and spirometry , following single doses of either placebo or active treatments ( 12 h after salmeterol , and 24 h after monteleukast , respectively ) . RESULTS Compared to placebo , all active treatments led to significant improvements ( p < 0.05 ) in geometric mean AMP-PC(20 ) :  placebo , 42 mg/mL ; ML(10 ) , 106 mg/mL ; SM(50 ) , 115 mg/mL ; ML(10 ) and SM(50 ) , 183 mg/mL ; and ML(10 ) and SM(100 ) , 247 mg/mL. The effects of montelukast and salmeterol were numerically additive , with ML(10 ) and SM(100 ) being significantly different ( p < 0.05 ) from ML(10 ) alone . For mean FEV(1 ) and forced expiratory flow rate between 25 % and 75 % of vital capacity , there were significant differences ( p < 0.05 ) between both combination therapies vs ML(10 ) alone . CONCLUSIONS Our results suggest additive benefits of a single dose of a long-acting beta(2)-agonist and leukotriene antagonist , in terms of bronchoprotection and bronchodilation . Further studies in more severe asthmatics are required to evaluate long-term clinical effects
BACKGROUND Patients who continue to experience asthma symptoms despite taking regular inhaled corticosteroids ( ICS )  represent a management challenge .
Leukotriene receptor antagonists ( LTRA ) and long-acting beta(2)-agonists ( LABA ) agents may both be considered as add-on therapy to inhaled corticosteroids ( ICS ) .
OBJECTIVES We compared the efficacy and safety profile of adding either daily LABA or LTRA in asthmatic patients who remained symptomatic on ICS .