Effect of the addition of montelukast to inhaled fluticasone propionate on airway inflammation. Leukotriene modifier vs inhaled corticosteroid in mild-to-moderate asthma: clinical and anti-inflammatory effects. Effect of montelukast for treatment of asthma in cigarette smokers. Double-Blind, Randomised, Controlled Trial Assessing Controller Medications in Asthma Leukotriene antagonists as first-line or add-on asthma-controller therapy. Dose reduction of inhaled corticosteroids under concomitant medication with montelukast in patients with asthma A Randomized Trial of Single-Dose Oral Dexamethasone Versus Multidose Prednisolone for Acute Exacerbations of Asthma in Children Who Attend the Emergency Department. Effectiveness of a multi-level asthma intervention in increasing controller medication use: a randomized control trial Effect of montelukast added to inhaled budesonide on control of mild to moderate asthma [Pranlukast allows reduction of inhaled steroid dose without deterioration in lung function in adult asthmatics]. Temperature-controlled laminar airflow in severe asthma for exacerbation reduction (The LASER Trial): study protocol for a randomised controlled trial Effects of adding either a leukotriene receptor antagonist or low-dose theophylline to a low or medium dose of inhaled corticosteroid in patients with persistent asthma. Allergen inhalation challenge, refractoriness and the effects of ibuprofen Failure of montelukast to reduce sputum eosinophilia in high-dose corticosteroid-dependent asthma Addition of Montelukast to Low-Dose Inhaled Corticosteroid Leads to Fewer Exacerbations in Older Patients Than Medium-Dose Inhaled Corticosteroid Monotherapy A phase 1 randomized, double-blind, placebo-controlled, crossover trial of DAS181 (Fludase®) in adult subjects with well-controlled asthma Canadian Thoracic Society 2012 guideline update: diagnosis and management of asthma in preschoolers, children and adults. Addition of montelukast versus double dose of inhaled budesonide in moderate persistent asthma. [Clinical effects of long-term administration of pranlukast, a leukotriene receptor antagonist, on adult patients with bronchial asthma]. Zafirlukast improves asthma control in patients receiving high-dose inhaled corticosteroids. 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Improved control of childhood asthma with low‐dose, short‐term vitamin D supplementation: a randomized, double‐blind, placebo‐controlled trial Cost effectiveness of leukotriene receptor antagonists versus inhaled corticosteroids for initial asthma controller therapy: a pragmatic trial. Montelukast added to fluticasone propionate does not alter inflammation or outcomes. Effects of 24-week add-on treatment with ciclesonide and montelukast on small airways inflammation in asthma. Evaluation of switching low-dose inhaled corticosteroid to pranlukast for step-down therapy in well-controlled patients with mild persistent asthma
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 STUDY OBJECTIVE Evidence for the anti-inflammatory activity of leukotriene receptor antagonists in humans is somewhat limited . There are also no data comparing the anti-inflammatory effects of leukotriene receptor antagonists with those of inhaled corticosteroids . This study was design ed to assess the clinical efficacy and anti-inflammatory effects of leukotriene receptor antagonist plus low-dose inhaled corticosteroids compared to those of a high-dose inhaled corticosteroid in patients with mild-to-moderate asthma . METHODS Forty-nine patients with newly diagnosed asthma were recruited . They were r and omly assigned to groups that received , for a 6-week period , either ( 1 ) budesonide , 600 microg bid ( 1,200 microg/d ) or ( 2 ) budesonide , 200 microg ( 400 microg/d ) , and zafirlukast , 20 mg bid . The variables of asthma control were recorded daily . Sputum induction and methacholine provocation tests were performed . RESULTS The results indicated that the administration of a low-dose inhaled corticosteroid plus zafirlukast was as effective as that of a high-dose inhaled corticosteroid regarding clinical improvement and anti-inflammatory effects ( ie , eosinophil percentage , and eosinophilic cationic protein [ ECP ] and cysteinyl leukotriene C4 levels in induced sputum ) . Nineteen ( group 1 , 8 patients ; group 2 , 11 patients ) of 49 patients ( 38.8 % ) had returned to normal airway responsiveness after treatment . Among these patients , 16 patients ( 84.2 % ) had normal ECP levels and 10 patients ( 52.6 % ) had normal percentages of eosinophils . ECP level , but not the eosinophil percentage , was significantly associated with symptom scores . The peak expiratory flow rate ( PEFR ) showed a significant correlation with the provocative concentration of methacholine causing a 20 % fall in FEV1 ( PC20 ) instead of with symptom scores . CONCLUSIONS The addition of a leukotriene modifier to treatment with low-dose inhaled corticosteroids is equivalent to treatment with high-dose inhaled corticosteroids in patients with newly diagnosed mild-to-moderate asthma . In addition to symptoms and PEFR , the monitoring of ECP and PC20 may be of great value in achieving optimal control of asthma OBJECTIVE Many asthmatic patients are unable to quit cigarettes ; therefore information is needed on treatment options for smokers . This study evaluates 10 mg/d montelukast and 250 μg of fluticasone propionate twice daily , each compared with placebo , in patients with self-reported active smoking ( unable to quit ) and asthma . METHODS Patients ( ages 18 - 55 years , with asthma [ ≥1 year ] , FEV1 of 60 % to 90 % of predicted value , airway reversibility [ ≥12 % ] , and self-reported active smoking [ ≥0.5 to ≤2 packs per day ] ) were r and omized ( after a 3-week , single-blind , placebo , run-in period ) to 1 of 3 parallel , 6-month , double-blind treatment arms . The primary efficacy end point was the percentage of days with asthma control during treatment . Adverse experiences ( AEs ) were also evaluated . RESULTS There were 347 , 336 , and 336 patients r and omized to montelukast , fluticasone , and placebo , respectively . The mean percentage of days with asthma control over 6 months of treatment was 45 % ( montelukast , P < .05 vs placebo ) , 49 % ( fluticasone , P < .001 vs placebo ) , and 39 % ( placebo ) ; the difference between montelukast and fluticasone was not significant ( P = .14 ) . Patients with a smoking history of ≤11 pack years ( the median value ) tended to show more benefit with fluticasone , whereas those with a smoking history of > 11 pack years tended to show more benefit with montelukast  . AEs occurred in similar proportions among treatment groups . CONCLUSIONS In a population of asthmatic patients actively smoking cigarettes , both 10 mg/d montelukast and 250 μg of fluticasone propionate twice daily significantly increased the mean percentage of days with asthma control compared with placebo Background : The motive behind conducting this study was to determine if better control of asthma can be achieved by adding a second controller medication and to assess its use to reduce the dose of inhaled steroids . Objectives : The study aim ed to determine whether either oral sustained-release theophylline or montelukast added to inhaled steroids  improved clinical symptoms and pulmonary function test parameters when compared to high-dose steroids alone . Methods : Ninety patients with incompletely controlled asthma were allocated , in a r and omised , double-blind fashion , to one of three treatment groups : group A : double dose of inhaled budesonide ( 400 µg b.i.d . ) , group B : 400 mg oral sustained-release theophylline plus budesonide ( 200 µg b.i.d . ) and group C : 10 mg montelukast plus budesonide ( 200 µg b.i.d . ) . The primary endpoints were forced expiratory volume in 1 s ( FEV1 ) and mean morning peak expiratory flow rate ( PEFR ) . Results : All three groups had improved FEV1 and PEFR at 8 weeks ( p < 0.001 ) . Group C increased their PEFR by 18.7 l/min ( 95 % confidence interval , CI , 12.4–25.1 ) more than group A and by 19.8 l/min ( 95 % CI 13.4–26.1 ) more than group B ( both p = 0.001 ) . Similarly , group C had a 114 ml ( 95 % CI 45–183 ml ) greater improvement in FEV1 than group A and a 95 ml ( 95 % CI 26–164 ml ) greater improvement than group B ( both p = 0.01 ) . Conclusions : Addition of montelukast to budesonide is safe and results in greater improvement in pulmonary function test parameters  than high-dose budesonide treatment or addition of theophylline BACKGROUND Most r and omized trials of treatment for asthma study highly selected patients under idealized conditions . METHODS We conducted two parallel , multicenter , pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist ( LTRA ) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist ( LABA ) as add-on therapy in patients already receiving inhaled glucocorticoid therapy . Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life ( Mini Asthma Quality of Life Question naire [ MiniAQLQ ] score ≤6 ) or inadequate asthma control ( Asthma Control Question naire [ ACQ ] score ≥1 ) . We r and omly assigned patients to 2 years of open-label therapy , under the care of their usual physician , with LTRA ( 148 patients ) or an inhaled glucocorticoid ( 158 patients ) in the first-line controller therapy trial and LTRA ( 170 patients ) or LABA ( 182 patients ) added to an inhaled glucocorticoid in the add-on therapy trial . RESULTS Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials . At 2 months , differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence ( 95 % confidence interval [ CI ] for an adjusted mean difference , -0.3 to 0.3 ) . At 2 years , mean MiniAQLQ scores approached equivalence , with an adjusted mean difference between treatment groups of -0.11 ( 95 % CI , -0.35 to 0.13 ) in the first-line controller therapy trial and of -0.11 ( 95 % CI , -0.32 to 0.11 ) in the add-on therapy trial . Exacerbation rates and ACQ scores did not differ significantly between the two groups . CONCLUSIONS Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients . Equivalence was not proved at 2 years . The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group . ( Funded by the National Coordinating Centre for Health Technology Assessment U.K. and others ; Controlled Clinical Trials number , IS RCT N99132811 . ) 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 STUDY OBJECTIVE In acute exacerbations of asthma in children , corticosteroids reduce relapses , subsequent hospital admission , and the need for ß2-agonist bronchodilators . Prednisolone is the most commonly used corticosteroid , but prolonged treatment course , vomiting , and a bitter taste may reduce patient compliance . Dexamethasone has a longer half-life and has been used safely in other acute pediatric conditions . We examine whether a single dose of oral dexamethasone is noninferior to prednisolone in the emergency department ( ED ) treatment of asthma exacerbations in children , as measured by the Pediatric Respiratory Assessment Measure ( PRAM ) at day 4 . METHODS We conducted a r and omized , open-label , noninferiority trial comparing oral dexamethasone ( single dose of 0.3 mg/kg ) with prednisolone ( 1 mg/kg per day for 3 days ) in patients aged 2 to 16 years and with a known diagnosis of asthma or at least 1 previous episode of ß2-agonist-responsive wheeze who presented to a tertiary pediatric ED . The primary outcome measure was the mean PRAM score ( range of 0 to 12 points ) performed on day 4 . Secondary outcome measures included requirement for further steroids , vomiting of study medication , hospital admission , and unscheduled return visits to a health care practitioner within 14 days . RESULTS There were 245 enrollments involving 226 patients . There was no difference in mean PRAM scores at day 4 between the dexamethasone and prednisolone groups ( 0.91 versus 0.91 ; absolute difference 0.005 ; 95 % CI -0.35 to 0.34 ) . Fourteen patients vomited at least 1 dose of prednisolone compared with no patients in the dexamethasone group . Sixteen children ( 13.1 % ) in the dexamethasone group received further systemic steroids within 14 days after trial enrollment compared with 5 ( 4.2 % ) in the prednisolone group ( absolute difference 8.9 % ; 95 % CI 1.9 % to 16.0 % ) . There was no significant difference between the groups in hospital admission rates or the number of unscheduled return visits to a health care practitioner . CONCLUSION In children with acute exacerbations of asthma , a single dose of oral dexamethasone ( 0.3 mg/kg ) is noninferior to a 3-day course of oral prednisolone ( 1 mg/kg per day ) as measured by the mean PRAM score on day 4 Abstract Introduction : Poor self-management by families is an important factor in explaining high rates of asthma morbidity in Puerto Rico , and for this reason we previously tested a family intervention called CALMA that was found effective in improving most asthma outcomes , but not effective in increasing the use of controller medications . CALMA-plus was developed to address this issue by adding to CALMA , components of provider training and screening for asthma in clinics . Methods : Study participants were selected from cl aims Medicaid data in San Juan , Puerto Rico . After screening , 404 children in eight clinics were selected after forming pairs of clinics and r and omizing the clinics ) to CALMA-only or CALMA-plus . Results : For all three primary outcomes at 12 months , the mean differences between treatment arms were small but in the predicted direction . However , after adjusting for clinic variation , the study failed to demonstrate that the CALMA-plus intervention was more efficacious than the CALMA-only intervention for increasing controller medication use , or decreasing asthma symptoms . Both groups had lower rates of asthma symptoms and service utilization , consistent with previous results of the CALMA-only intervention . Conclusions : Compliance of providers with the intervention and training , small number of clinics available and the multiple barriers experienced by providers for medicating may have been related to the lack of difference observed between the groups . Future interventions should respond to the limitations of the present study design and provide more re sources to providers that will increase provider participation in training and implementation of the intervention 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 We undertook a community based case-control study to measure the effect of pranlukast on the reduction of inhaled steroid in adult asthmatics . Forty-one adults completed a run-in period of 4 weeks on 800 microgram of beclomethasone dipropionate ( BDP ) documenting twice daily peak expiratory flow ( PEF ) and symptom score and therapeutic score on a st and ard diary . Forced expiratory volume in one second ( FEV1.0 ) , V50 , V25 was measured once during the run-in period . Patients were then r and omized to receive either pranlukast with 400 microgram of BDP or 400 microgram alone for 8 weeks . There was no difference in the symptom score and therapeutic between the two groups at any time point . However , morning and evening % PEF run-in expressed as a % of the PEF average during the run-in period was significantly lower at 8 weeks in the groups without pranlukast . There were subjects in the group without pranlukast ( 35.3 % ) compared to those with ( 20.8 % ) who had a 10 % or more reduction in % PEF from the run-in period . The patients with an FEV1.0 < 80 % predicted who were r and omized to the control group were more likely ( 5 of 7 ) to have a fall in % PEF run-in and those r and omized to received pranlukast were less likely to have a fall in % PEF run-in though this was not significant ( 2 of 6 ) . In this study , pranlukast has demonstrated steroid sparing effect . Severe asthmatics ( FEV1.0 < 80 % ) who deteriorate after reduction of inhaled steroid may benefit most from pranlukast . Larger studies are now required to explore this important effect Background Asthma affects more than 5 million patients in the United Kingdom . Nearly 500,000 of these patients have severe asthma with severe symptoms and frequent exacerbations that are inadequately controlled with available treatments . The burden of severe asthma on the NHS is enormous , accounting for 80 % of the total asthma cost ( £ 1 billion ) , with frequent exacerbations and expensive medications generating much of this cost . Of those patients with severe asthma , 70 % are sensitised to indoor aeroallergens , and the level of exposure to allergens determines the symptoms ; patients exposed to high levels are therefore most at risk of exacerbations and hospital admissions . The LASER trial aims to assess whether a new treatment , temperature controlled laminar airflow ( TLA ) delivered by the Airsonett ™ device , can reduce the frequency of exacerbations in patients with severe allergic asthma by reducing exposure to aeroallergens overnight . Methods This multicentre study is a placebo-controlled , blinded , r and omised controlled , parallel group trial . A total of 222 patients with a new or current diagnosis of severe allergic asthma will be assigned with a r and om element in a 1:1 ratio to receive either an active device for one year or a placebo device . The primary outcome is the frequency of severe asthma exacerbations occurring over a 12-month period , defined in accordance with the American Thoracic Society/European Respiratory Society ( ATS/ERS ) guidelines . Secondary outcomes include changes in asthma control , lung function , asthma-specific and global quality of life for participants and their carers , adherence to intervention , healthcare re source use and costs , and cost-effectiveness . Qualitative interviews will be conducted to elicit participant ’s and their partner ’s perceptions of the treatment . Discussion Effective measures of allergen avoidance have , to date , proved elusive . The LASER trial aims to address this . The study will ascertain whether home-based nocturnal TLA usage over a 12-month period can reduce the frequency of exacerbations and improve asthma control and quality of life as compared to placebo , whilst being cost-effective and acceptable to adults with poorly controlled , severe allergic asthma . The results of this study will be widely applicable to the many patients with allergic asthma both in the UK and internationally . Trial registration Current controlled trials IS RCT N46346208 ( Date assigned 22 January 2014 ) STUDY OBJECTIVES To evaluate the effect of adding zafirlukast or low-dose theophylline to a beclomethasone dipropionate ( BDP ) extra-fine hydrofluoroalkane aerosol on bronchial hyperresponsiveness as the primary outcome variable . METHODS Twenty-four patients with mild-to-moderate asthma were studied using a r and omized crossover design with the following three treatment blocks : ( 1 ) beclomethasone , 100 microg/d , alone for the first 2 weeks followed by 400 microg/d alone for the next 2 weeks ; ( 2 ) beclomethasone , 100 microg/d , followed by 400 microg/d , with the addition of zafirlukast , 20 mg bid ; ( 3 ) beclomethasone , 100 microg/d , followed by 400 microg/d , with the addition of theophylline , 200 to 300 mg bid . Measurements were made after 2 and 4 weeks of each treatment and at pretreatment baseline . RESULTS The mean trough plasma theophylline concentration was 6.7 mg/L , coinciding with the anti-inflammatory target range ( ie , 5 to 10 mg/L ) . The provocative dose of methacholine causing a 20 % fall in FEV(1 ) ( as doubling dose difference from baseline ) was significantly ( p < 0.05 ) greater with beclomethasone , 100 microg , plus zafirlukast ( 1.1 doubling dose ) but not with beclomethasone , 100 microg , plus theophylline ( 0.7 doubling dose ) compared to beclomethasone , 100 microg alone ( 0.4 doubling dose ) , but not compared to beclomethasone , 400 microg alone ( 1.1 doubling dose ) . There were also significant ( p < 0.05 ) differences between beclomethasone , 100 microg , plus zafirlukast ( but not BDP , 100 microg , plus theophylline ) vs beclomethasone , 100 microg , alone in terms of nitric oxide level , midexpiratory phase of forced expiratory flow , and peak expiratory flow . There were no further significant improvements observed with the addition of zafirlukast or theophylline to beclomethasone , 400 microg . CONCLUSIONS A leukotriene receptor antagonist , but not low-dose theophylline , conferred significant additive anti-inflammatory effects to therapy with a low-dose inhaled corticosteroid but not to that with a medium dose of an inhaled corticosteroid . Thus , optimizing the dose of inhaled corticosteroid as monotherapy would seem to be the logical first step , which is in keeping with current guidelines Abstract Background Bronchoprovocation challenges use direct or indirect acting stimuli to induce airflow obstruction . Indirect stimuli either non-allergic/non-IgE mediated ( e.g. exercise , mannitol ) or allergic/IgE mediated ( i.e. allergen ) trigger mast cells to release bronchoconstricting mediators ( e.g. cysteinyl leukotrienes , histamine ) . Performing repeat challenges within a short timeframe ( e.g. 3 h ) with non-allergic indirect stimuli results in a diminished , refractory response to the second challenge that is inhibited by non-steroidal anti-inflammatory medications . Cross refractoriness occurs between indirect stimuli . It follows that repeat bronchoprovocation with allergen might exhibit refractoriness that might be altered by ibuprofen . We assessed the response to a second allergen challenge performed 24 h after an initial allergen challenge to determine if the response is refractory . If refractoriness developed , the study aim ed to determine whether a single dose of ibuprofen would alter the refractory response to the second allergen challenge . In the absence of a refractory response , the study design allowed for the assessment of the effect of ibuprofen on allergen challenge outcomes , including indices of airway inflammation . Methods Thirteen mild atopic asthmatics were enrolled in a r and omized , double-blind , placebo controlled , cross-over study . Ibuprofen ( 400 mg ) or placebo was administered 1 h prior to the first of two allergen challenges , performed 24 h apart . Blood and sputum eosinophils , airway responsiveness to methacholine and levels of fractional exhaled nitric oxide were assessed before and 7 h after each allergen challenge . All data were log transformed and differences in geometric means were analyzed by paired t-tests . Results After placebo , early asthmatic responses for the two challenges were not significantly different ( p = 0.82 ) . A single 400 mg dose of ibuprofen decreased both the early ( p = 0.03 ; n = 12 ) and late asthmatic responses ( p = 0.03 ; n = 3 ) . Conclusion Allergen challenges conducted 24 h apart do not exhibit refractoriness . Single dose ibuprofen inhibits early and late asthmatic responses to allergen bronchoprovocation . Ibuprofen should be withheld for at least 24 h prior to investigations utilizing allergen bronchoprovocation . Trial registration clinical trials.gov # Sputum eosinophilia is a sensitive predictor of benefit from corticosteroid treatment . Montelukast is a cysteinyl leukotriene antagonist , which also reduces sputum and blood eosinophils . The present study examined the possibility that montelukast has an added eosinophil-lowering effect in subjects with asthma who are corticosteroid responsive but relatively corticosteroid resistant . A total of 14 clinical ly stable adults with asthma requiring minimum treatment with a high-dose inhaled steroid or prednisone , with baseline sputum eosinophilia ( ≥5 % ) , were r and omised to receive 4 weeks of 10 mg montelukast or placebo daily in a double-blind crossover trial . The primary outcome was the effect of treatment on the percentage of sputum eosinophils . Secondary outcomes were changes in the blood eosinophil count , symptoms , forced expiratory volume in one second , peak expiratory flow and the need for salbutamol . The median ( interquartile range , i.e. 75th–25th centile ) for sputum eosinophils at baseline was 15.7 % ( 22 ) . The effect of adding montelukast was not significantly different from that of placebo , sputum eosinophils being 9.3 % ( 18.9 ) after montelukast and 11.3 % ( 22.8 ) after placebo . No difference was detected on secondary outcomes . No crossover interactions were observed . In conclusion , the addition of montelukast to existing high-dose corticosteroid therapy in subjects with asthma with elevated sputum eosinophils does not provide additional attenuation of airway eosinophilia Purpose There have been few reports regarding the efficacy of antiasthmatics in older patients . To compare the efficacy of the addition of montelukast to low-dose inhaled budesonide ( MON-400BUD ) versus increasing the dose of inhaled steroid ( 800BUD ) on asthma control in older asthmatics . Methods A r and omized , open-label , parallel- design ed trial was conducted for 12 weeks . The primary endpoint was the rate of patients who reached " well-controlled asthma status " after the 12-week treatment period . Additionally , asthma exacerbations , sputum inflammatory cells , asthma control test ( ACT ) and physical functioning scale ( PFS ) , and adverse reactions were monitored . Results Twenty-four ( 36.9 % ) and 22 ( 34.9 % ) subjects in the MON-400BUD ( n=65 ) and 800BUD ( n=63 ) groups had well-controlled asthma at the end of the study , respectively . The numbers of asthma exacerbations requiring oral corticosteroid treatment ( 20 vs 9 , respectively , P=0.036 ) and the development of sore throat ( 22 vs 11 , respectively , P=0.045 ) were significantly higher in the 800BUD group than in the MON-400BUD group . Body mass index and changes in ACT , FEV1 % , 6-min walk distance and PFS from baseline were all significant determinants for distinguishing subjects with well-controlled and partly controlled asthma from those with uncontrolled asthma ( P<0.05 ) at the end of the study . Conclusions The efficacy of 12-week treatment with MON-400BUD in older asthmatics was comparable to that of 800BUD on asthma control but associated with reduced frequency of asthma exacerbations requiring oral steroids and sore throat events . Changes in ACT and PFS can be useful predictors of asthma control status in older patients Background Influenza virus ( IFV ) infection is associated with increased morbidity and mortality in people with underlying lung disease . Treatment options for IFV are currently limited and antiviral resistance is a growing concern . DAS181 , an inhaled antiviral with a unique mechanism of action , has shown promise in early clinical trials involving generally healthy human subjects . This study was undertaken to assess the safety and tolerability of DAS181 in individuals with underlying reactive airway disease . Methods This was a r and omized , double-blind , placebo-controlled , crossover phase 1 study of DAS181-F02 . Dry particle inhaler administration of 10 mg was done on 3 consecutive days in ten adult volunteers with well-controlled asthma . The primary outcome was the frequency of adverse events ( AEs ) , grade 1 or higher that occurred during each study period . Results There were 280 AEs among ten evaluable subjects ( 56.8 % active ; 43.2 % placebo ) ; 90.7 % were grade 1 . No grade 3 or higher AEs occurred . A statistically significant association between exposure to DAS181 and experiencing any AE , a grade 1 AE , or a grade 2 AE was not detected . Overall , the majority of AEs were classified as possibly related ( 35.7 % ) , unlikely related ( 38.9 % ) , or unrelated ( 15.4 % ) to study drug administration . However , there was a statistically significant association between exposure to DAS181 and experiencing a definitely or probably related AE . Respiratory effects , including dyspnea , dry cough , and chest discomfort related to respirations , accounted for all of the definitely related AEs and one of the most common probably related AEs . Conclusions DAS181 was safe in this small study of otherwise healthy subjects with well-controlled asthma . However , the generalizability of these results is limited by the small sample size and generally mild nature of the subjects ’ asthma at baseline . The increased association of respiratory events classified as probably or definitely related to DAS181 administration suggests caution may need to be employed when administering DAS181 to individuals with less stable reactive airway disease . Further investigation in a controlled setting of the safety and efficacy of DAS181 in a larger population of asthmatic subjects with varying disease activity is warranted . Trial Registration Clinical Trials.gov NCT01113034Trial Registration Date : April 27 , BACKGROUND In 2010 , the Canadian Thoracic Society ( CTS ) published a Consensus Summary for the diagnosis and management of asthma in children six years of age and older , and adults , including an up date d Asthma Management Continuum . The CTS Asthma Clinical Assembly subsequently began a formal clinical practice guideline up date process , focusing , in this first iteration , on topics of controversy and ⁄or gaps in the previous guidelines . METHODS Four clinical questions were identified as a focus for the up date d guideline : the role of noninvasive measurements of airway inflammation for the adjustment of anti-inflammatory therapy ; the initiation of adjunct therapy to inhaled corticosteroids ( ICS ) for uncontrolled asthma ; the role of a single inhaler of an ICS⁄long-acting beta(2)-agonist combination as a reliever , and as a reliever and a controller ; and the escalation of controller medication for acute loss of asthma control as part of a self-management action plan . The expert panel followed an adaptation process to identify and appraise existing guidelines on the specified topics . In addition , literature search es were performed to identify relevant systematic review s and r and omized controlled trials . The panel formally assessed and grade d the evidence , and made 34 recommendations . RESULTS The up date d guideline recommendations outline a role for inclusion of assessment of sputum eosinophils , in addition to st and ard measures of asthma control , to guide adjustment of controller therapy in adults with moderate to severe asthma . Appraisal of the evidence regarding which adjunct controller therapy to add to ICS and at what ICS dose to begin adjunct therapy in children and adults with poor asthma control supported the 2010 CTS Consensus Summary recommendations . New recommendations for the adjustment of controller medication within written action plans are provided . Finally , priority areas for future research were identified . CONCLUSIONS The present clinical practice guideline is the first up date of the CTS Asthma Guidelines following the Canadian Respiratory Guidelines Committee 's new guideline development process . Tools and strategies to support guideline implementation will be developed and the CTS will continue to regularly provide up date s reflecting new evidence BACKGROUND Although current guidelines suggest the use of inhaled corticosteroids as the first line therapy in persistent asthma , the concerns about high-dose corticosteroids may limit their usage . We aim ed to investigate the efficacy of inhaled budesonide plus oral montelukast versus a double dose of inhaled budesonide . METHODOLOGY Thirty patients with moderate asthma took part in the study . Following a 2-week run in period , the patients were r and omized into two groups to receive 400 microg/day of inhaled budesonide plus 10 mg/day of montelukast ( BUD + M group ) or 800 microg/day of inhaled budesonide ( high BUD group ) . The patients were evaluated at 2-week intervals ( during a total treatment period of 6 weeks ) for symptom scores , asthma exacerbations , lung function , use of short-acting beta2 agonist , blood eosinophil counts and adverse events . RESULTS At the end of the study , morning and daytime symptom scores were significantly reduced within the groups . Although there was a significant decrease in the frequency of short-acting beta2 agonist use in the BUD + M group , the decrease in the high BUD group was not significant . During the study period , no patient in either group experienced an asthma exacerbation . Blood eosinophil levels significantly declined in both the BUD + M ( 0.87 + /- 0.31 % ) and high BUD groups ( 0.67 + /- 0.29 % ) as compared with baseline levels ( BUD + M = 2.60 + /- 0.65 % , high BUD group = 2.60 + /- 0.47 % ; P < 0.05 ) . CONCLUSION Our results suggest that the addition of montelukast to low-dose inhaled budesonide is as effective as a double dose of inhaled budesonide in asthma control Eighty-one adult patients with bronchial asthma who suffered asthmatic episodes in spite of treatment with 400 mg/day of BDP  were placed on pranlukast therapy for 4 weeks . Group I , which showed a 5 % or greater increase in PEFR , continued oral pranlukast medication for an additional two years . Those patients who did not show an increase of 5 % or greater in PEFR after 4 weeks of pranlukast therapy were instructed to continue the medication for another year . Group II , which exhibited a 5 % or greater increase in PEFR after a one-year period continued medication for one more year . Medication was suspended for Group III , which failed to show improvement in PEFR after one year , and the group was placed under observation for the following year . Group I improved significantly in PEFR and exhibited a reduction in the frequency of b2 inhalation , the number of night visits to a medical facility , the amount of steroids inhaled , and the quantity of oral steroids given at regular intervals ; and the Group I peripheral eosinophil count , serum ECP level , and FEV1.0 ameliorated . After one year , Group II also showed significant improvement in PEFR and a reduction in both the peripheral eosinophil count and the serum ECP level . This group 's PEFR continued to improve after two years . One year after medication was suspended , Group III showed a significant increase in the number of night visits to a medical facility and a rise in the serum ECP level . These findings indicated the efficacy of pranlukast Not all asthma can be adequately controlled , despite the use of high-dose inhaled corticosteroids . Because cysteinyl-leukotrienes ( Cys-LT ) have been implicated in the pathogenesis of asthma , we hypothesized that the leukotriene receptor antagonist zafirlukast , in combination with high-doses of inhaled corticosteroids , might be efficacious in severe asthma . In a double-blind , parallel group study , 368 chronic adult asthmatic patients treated with inhaled corticosteroids ( 1,000 to 4,000 microgram/d ) , who had a predefined level of asthma symptoms during the run in period of the study , were r and omly assigned to receive additional treatment with a high dose of zafirlukast ( 80 mg twice daily ) ( n = 180 ) or placebo ( n = 188 ) for 6 wk . Compared with placebo , zafirlukast produced a significant improvement over baseline in the primary study endpoint of mean morning peak expiratory flow rate ( PEFR ) ( 18.7 L/min versus 1.5 L/min , p < 0.001 ) , as well as in evening PEFR ( p < 0.01 ) , FEV(1 ) ( p < 0.05 ) , daytime symptom score ( p < 0.001 ) , and beta(2)-agonist use ( p < 0.001 ) . Furthermore , zafirlukast significantly reduced the risk of an exacerbation of asthma ( odds ratio [ OR ] : 0.61 ; 95 % confidence interval [ CI ] : 0.38 to 0.99 ) and the risk of patients requiring a further increase in asthma controller therapy ( OR : 0.4 ; 95 % CI : 0.2 to 0.8 ) . In conclusion , in patients taking high-dose inhaled corticosteroids , zafirlukast improves pulmonary function and asthma symptoms , and reduces the risk of an asthma exacerbation , suggesting that the contribution of leukotrienes to asthma symptoms and exacerbations is not adequately controlled by high-dose inhaled corticosteroids BACKGROUND Systemic reactions are related to the pathogenesis of Aspirin Exacerbated Respiratory Disease ( AERD ) . With this work we wanted to study the changes in the systemic levels of inflammatory mediators in both baseline and after oral aspirin challenge in patients with and without AERD . METHODS Patients with nasal polyposis and asthma with AERD ( n=20 ) and without ( n=18 ) were orally challenged with aspirin in a single-blind placebo controlled study . Serum sample s and urine were collected before and 6h after placebo and aspirin oral challenges .  Serum levels of inflammatory mediators were assayed by using the Luminex technology and ELISA . The concentrations of 9-alpha , 11-beta prostagl and in F2 , and leukotriene E4 ( uLTE4 ) were measured in urine sample s by ELISA . The expression of T-cell surface markers was analyzed in peripheral blood mononuclear cells isolated before and after the challenges . RESULTS AERD patients showed significantly higher baseline levels of s-IL-5R-alpha , uLTE4 and percentage of CD4(+)CD25(+)CD127(pos ) and CD4(+)CD45RA(-)CD45RO(+ ) but decreased levels of TGF-β1 and number of CD4(+)CD25(+)CD127(neg ) cells  . Aspirin challenge induced the release of uLTE4 , IL-6 and increased the number of CD4(+)CD45RA(-)CD45RO(+ ) memory T-cells only in AERD patients but failed to reduce the levels of sCD40L as observed in non-AERD subjects . Further , IL-8 and sIL-5R-alpha levels directly correlated with the PD20ASA and the effects of aspirin  on IL-6 and number of memory T-cells was more pronounced in subjects showing more strong reaction ( bronchial and nasal ) . CONCLUSIONS AERD patients have a differential baseline inflammatory pattern that supports the role inflammation as underlying mechanism of the disease . Systemic response to oral aspirin challenge was related to an increase in serum IL-6 and the number of circulating memory T-cells in AERD patients Insufficient data exist to evaluate the comparative effects of inhaled corticosteroids ( ICS ) versus leukotriene receptor antagonist ( LTRA ) on airway inflammation and quality of life ( QoL ) . The aim of the study was to compare the effectiveness of montelukast compared to budesonide at different doses on QoL and bronchial reactivity in mild-asthmatic adult patients . 45 subjects with bronchial asthma were r and omly assigned to a different treatment and divided in 3 treatment groups : A : 400 μg of budesonide twice a day ; B : 10 mg of montelukast daily ; C : 10 mg of montelukast daily plus 400 μg of budesonide twice a day . At the beginning of the study and at the end of the treatment period ( 16 weeks ) all patients underwent complete clinical evaluation , pulmonary function testing and methacholine challenge test ( MCHt ) . In group A the increase from baseline was 153.4 % , in group C was 133.2 % , and in group B 247.7 % , the latter increase being statistically significant compared to that in the other 2 groups ( p < 0.005 Wilcoxon test ) . In all domains the improvement in quality of life in the group treated with montelukast ( group B ) was significantly greater than that in the group treated with both medications ( group C ) : in particular , the improvement was consistent in the symptoms ( p < 0.01 ) and emotions ( p < 0.01 ) domains , and weaker in the physical activity ( p < 0.05 ) . A similar difference was observed between group B and A , but only in the symptoms ( p<0.01 ) , emotions ( p<0.01 ) , and environmental stimuli domains ( p<0.05 ) . The personal perception of their own disease is important for a correct therapeutic management of asthma . In order to optimize the treatment , a complete adherence of the patient to the treatment itself is required , to be achieved through simplification of therapeutic schedule and easy administration of medications . Montelukast may be considered a valid alternative in the treatment of mild-persistent asthma , both for the clinical and functional benefits and for the great advantage of the once-daily dosage , which consistently improves the compliance with the chronic treatment of the disease OBJECTIVE Leukotriene antagonists are increasingly used in asthma management . Pranlukast is a new , orally active , selective inhibitor of CysLt1 leukotriene receptor . The present clinical trial was performed to study the effect and safety of pranlukast in mild-to-moderate asthma . METHODOLOGY A r and omized , double-blind , placebo-controlled , parallel group study was performed in eight medical centres in Korea . Mild-to-moderate asthma patients who had been treated with beta2-agonists and /or inhaled corticosteroids were studied . The patients ' symptoms were evaluated by asthma diary and twice-daily peak flow monitoring . RESULTS Of the 206 patients enrolled , 197 were eligible for analysis . The pranlukast group ( n = 98 ) showed statistically significant improvement in asthma symptoms , including asthma attack rate , daily living score , and morning and evening asthma scores .  Pranlukast significantly reduced the consumption of beta2-agonist . Compared with the placebo group , forced vital capacity ( FVC ) and forced expiratory volume in 1 s ( FEV1 ) were not significantly higher in the pranlukast group . Morning and evening peak expiratory flow ( PEF ) were significantly increased after pranlukast treatment at weeks 2 and 4 ( 380.8 + /- 10.1 L/min at baseline , 394.5 + /- 10.1 at week 2 , 396.3 + /- 10.4 at week 4 ) . There were no serious adverse reactions . CONCLUSION Pranlukast , an oral leukotriene antagonist , was well tolerated and was effective for the management of mild-to-moderate asthma BACKGROUND Zafirlukast is a leukotriene receptor antagonist that was invented to treat patients with chronic asthma . METHODS To evaluate whether the zafirlukast improved the peak expiratory flow rate ( PEFR ) and clinical symptoms , 31 asthmatic patients with moderate persistent asthma who received regular inhaled corticosteroid were r and omly divided into the study group ( N = 17 ) . They received the zafirlukast 20 mg bid for 4 weeks , and the control group ( N = 14 ) received a placebo . Daily morning and evening PEFR and St. George 's Respiratory Question naire ( SGRQ ) scoring were recorded respectively . The levels of serum IgE and urine leukotriene E4 before and after treatment were measured using enzyme linked immunosorbent assay and enzyme immunoassay kits . RESULTS In the zafirlukast treated group , the morning PEFR was significantly improved from 314.4 + /- 20.6 to 340.6 + /- 18.3 L/min ( N = 17 , p < 0.05 ) after 4 weeks of treatment , while the control group did not show any significant changes . The zafirlukast group had significant improvement in their symptom scores of SGRQ from 48.6 + /- 4.6 to 33.8 + /- 4.7 ( N = 17 , p < 0.05 ) . However , the placebo did not improve the symptom scores . CONCLUSION Leukotriene receptor antagonists effectively improved symptoms and benefited lung function for moderate persistent asthmatic patients who had received regular treatments with inhaled steroids BACKGROUND Symptoms often deteriorate in well-controlled asthmatics after a step down in inhaled beclomethasone dipropionate ( iBDP ) therapy if the serum concentration of eosinophil cationic protein ( sECP ) is high . This deterioration is significantly abrogated by pranlukast , a leukotriene receptor antagonist , or by seratrodast , a thromboxane A2 receptor antagonist . However , these results were based on short-term ( less than 6 months ) observations . METHODS We studied 35 well-controlled adult asthmatics . We assigned the patients into different groups according to their sECP levels before the step down : ( i ) group A , sECP < 25 microg/L ; ( ii ) group B , sECP > or = 25 microg/L ; and ( iii ) group C ,  sECP > or = 25 microg/L but patients treated with pranlukast or seratrodast .  We began the study with a step down in iBDP therapy ( initial step down ) , then followed the clinical course of the asthma for 2 years . During the study period , we decreased , increased or maintained the iBDP dose on the basis of the stepwise approach described in the National Institutes of Health guidelines . We monitored the time and frequency of exacerbation and evaluated the  iBDP dose required to control the asthma symptoms . RESULTS The rates of exacerbation after the step down were high in groups A and B. In group A , the conditions were again qualified for the step down in all patients , but this was not the case for most group B patients . From 15 to 21 months after the initial step down , the average dose of iBDP required to control symptoms was significantly higher in group B than in group A patients ( P = 0.0127 - 0.0373 ) . The exacerbation rate in group C after 12 months tended to be lower than in the other two patient groups ( P = 0.0743 ) . In group C , the average dose of iBDP  from 9 to 24 months after the initial step down was significantly lower than before the step down ( P < 0.0001 ) and was not significantly different from the mean dose of iBDP in groups A or B. CONCLUSIONS High sECP in well-controlled asthma may indicate the necessity for a higher iBDP dose over a long period than when the sECP concentration is not high . Even if sECP is high , pranlukast or seratrodast help to prevent exacerbation of asthma and enable successful step down in iBDP therapy for at least 2 years thereafter Many patients with asthma remain symptomatic with impaired airway function on inhaled steroids . This study investigates the relationship between the clinical effect seen in response to additional treatment and the effect on airway inflammatory indices .  Seventy-five adult asthmatic patients , incompletely controlled on 800 mcg budesonide/day  , were r and omised following a 4 week run-in period , to a double-blind , multi-centre controlled clinical trial of doubling inhaled corticosteroid ( budesonide 1600 mcg/day ) or adding 10 mg montelukast for 12 weeks . Induced sputum was collected at baseline and end of treatment and analysed for eosinophil and neutrophil percentages , leukotrienes C4 , D4 and E4 , IL-8 , Eosinophil Cationic Protein ( ECP ) and histamine . Sputum evidence of inflammation ( 2.0 % eosinophils ) was seen in only 29 % of these patients and the percentage of eosinophils and other markers of airway inflammation did not change over the study period in either treatment group . There were significant improvements in am PEF ( montelukast : 31.7 L/min , budesonide : 32.3 L/min ) and quality of life with both treatments . We conclude that while both treatments showed similar improvements in lung function and quality of life , there was no evidence from these sputum markers measured that the effects were mediated via a reduction in airway inflammation or that the level of pre-treatment markers was associated with outcome BACKGROUND Roflumilast , a selective phosphodiesterase 4 inhibitor , has been shown to provide modest improvements in lung function in patients with mild-to-moderate asthma , but its efficacy in patients with moderate-to-severe asthma has not been assessed . We hypothesized that this drug might provide benefit if combined with montelukast , a leukotriene receptor antagonist , in patients whose symptoms are uncontrolled by inhaled corticosteroids and long-acting β-agonists . OBJECTIVE We sought to examine the efficacy , safety , and mode of action of the addition of roflumilast and montelukast versus montelukast alone in patients with moderate-to-severe asthma . METHODS In a phase 2 , r and omized , double-blind , placebo-controlled , multiple-dose , 2-sequence , crossover study , 64 patients were r and omized to receive 500 μg of roflumilast plus montelukast followed by placebo plus 10 mg of montelukast ( sequence AB ) or placebo plus 10 mg of montelukast followed by 500 μg of roflumilast plus 10 mg of montelukast ( sequence BA ) . All patients had a diagnosis of bronchial asthma inadequately controlled by at least a medium-dose inhaled corticosteroid plus a long-acting β-agonist . RESULTS The analysis of FEV1 change from baseline to week 4 showed a statistically significant and clinical ly meaningful treatment difference of 100 mL for roflumilast plus montelukast versus placebo plus montelukast . Also , improvements in patient-reported outcomes and a reduction in urinary leukotriene E4 levels were observed during roflumilast plus montelukast treatment compared with placebo plus montelukast  treatment . Adverse events were consistent with the known safety profile of roflumilast . CONCLUSION The combination of roflumilast with montelukast compared with montelukast  alone improved lung function and asthma control in patients with moderate-to-severe asthma and deserves further study for this indication Background : Inhaled corticosteroids ( ICS ) affect many inflammatory pathways in asthma but have little impact on cysteinyl leukotrienes . This may partly explain persistent airway inflammation during chronic ICS treatment and failure to achieve adequate asthma control in some patients . This double blind , r and omised , parallel group , non-inferiority , multicentre 16 week study compared the clinical benefits of adding montelukast to budesonide with doubling the budesonide dose in adults with asthma . Methods : After a 1 month single blind run in period , patients inadequately controlled on inhaled budesonide ( 800 μg/day ) were r and omised to receive montelukast 10 mg + inhaled budesonide 800 μg/day ( n=448 ) or budesonide 1600 μg/day ( n=441 ) for 12 weeks . Results : Both groups showed progressive improvement in several measures of asthma control compared with baseline . Mean morning peak expiratory flow ( AM PEF ) improved similarly in the last 10 weeks of treatment compared with baseline in both the montelukast + budesonide group and in the double dose budesonide group ( 33.5 v 30.1 l/min ) . During days 1–3 after start of treatment , the change in AM PEF from baseline was significantly greater in the montelukast + budesonide group than in the double dose budesonide group ( 20.1 v 9.6 l/min , p<0.001 ) , indicating faster onset of action in the montelukast group . Both groups showed similar improvements with respect to “ as needed ” β agonist use , mean daytime symptom score , nocturnal awakenings , exacerbations , asthma free days , peripheral eosinophil counts , and asthma specific quality of life .  Both montelukast + budesonide and double dose budesonide were generally well tolerated . Conclusion : The addition of montelukast to inhaled budesonide is an effective and well tolerated alternative to doubling the dose of inhaled budesonide in adult asthma patients experiencing symptoms and inadequate control on budesonide alone This paper presents the resulţs of Montelukast sodic therapy in 16 asthmatic patients , in a prospect i ve study . Montelukast sodic was given in severe chronic asthma treated by inhaled or systemic steroids before . Patients were followed up for three months regarding : clinical symptoms , respiratory function ( FEV ) , blood and sputum eozinophyls . Short term therapy showed a great improvement in day and night symptoms , a reduction of sputum and blood eozinophyls and an increased FEV . Long term therapy could be protective for asthma exacerbations and will provide constant good life quality of asthmatics BACKGROUND Asthma treatment guidelines recommend addition of controller medications for patients with poorly controlled asthma . We compared the effectiveness of once-daily oral controller therapy with either an antileukotriene receptor antagonist ( montelukast ) or low-dose theophylline added to existing medications in patients with poorly controlled asthma . METHODS We conducted a r and omized , double-masked , placebo-controlled trial in 489 participants with poorly controlled asthma r and omly assigned to  placebo , theophylline ( 300 mg/d ) , or montelukast ( 10 mg/d ) . Participants were monitored for 24 wk to measure the rate of episodes of poor asthma control ( EPACs ) defined by decreased peak flow , increased beta-agonist use , increased oral corticosteroid use , or unscheduled health care visits . OBSERVATIONS There was no significant difference in EPAC rates ( events/person/yr ) compared with placebo : low-dose theophylline , 4.9 ( 95 % confidence interval [ CI ] , 3.6 - 6.7 ; not significant ) ; montelukast , 4.0 ( 95 % CI , 3.0 - 5.4 ; not significant ) ; and placebo , 4.9 ( 95 % CI , 3.8 - 6.4 ) . Both montelukast and theophylline caused small improvements in prebronchodilator FEV(1 ) of borderline significance . Nausea was more common with theophylline only during the first 4 wk of treatment . Neither treatment improved asthma symptoms or quality of life . However , in patients not receiving inhaled corticosteroids , addition of low-dose theophylline significantly ( p < 0.002 ) improved asthma control and symptoms as well as lung function . CONCLUSIONS Neither montelukast nor low-dose theophylline lowered the EPAC rate of poor asthma control in patients with poorly controlled asthma despite improved lung function . For patients not using inhaled corticosteroids , low-dose theophylline improved asthma symptom control more than montelukast or placebo , and provides a safe and low-cost alternative asthma treatment BACKGROUND Results from phase III clinical trials in adults and phase II clinical trials in children and adolescents demonstrate that tiotropium is an effective treatment when added to inhaled corticosteroid ( ICS ) maintenance therapy . OBJECTIVE We sought to assess the efficacy and safety of once-daily tiotropium Respimat added to ICSs with or without a leukotriene receptor antagonist in a phase III trial in adolescent patients with moderate symptomatic asthma . METHODS In this 48-week , double-blind , placebo-controlled , parallel-group study , 398 patients aged 12 to 17 years were r and omized to receive 5 μg ( 2 puffs of 2.5 μg ) or 2.5 μg ( 2 puffs of 1.25 μg ) of once-daily tiotropium or placebo ( 2 puffs ) administered through the Respimat device every evening , each as add-on treatment to ICS background therapy , with or without a leukotriene receptor antagonist ; long-acting β2-agonist therapy was not permitted during the study . RESULTS Improvement in peak FEV1 within 3 hours after dosing at 24 weeks ( primary end point ) was statistically significant with both tiotropium doses compared with placebo : 5 μg of tiotropium , 174 mL ( 95 % CI , 76 - 272 mL ) ; 2.5 μg of tiotropium , 134 mL ( 95 % CI , 34 - 234 mL ) . Significant improvements in trough FEV1 at week 24 ( a secondary end point ) were observed with the 5-μg dose only . Trends for improvement in asthma control and health-related quality of life over the 48-week treatment period were observed . CONCLUSIONS Once-daily tiotropium  significantly improved lung function and was safe and well tolerated when added to at least ICS maintenance therapy in adolescent patients with moderate symptomatic asthma . Larger responses were observed with the 5-μg tiotropium dose OBJECTIVE To observe the clinical efficacy of treating chronic persistent bronchial asthma ( CPBA ) children with abnormal myocardial enzyme spectrum ( AMES ) by Yupingfeng Powder ( YP ) combined routine therapy . METHODS From January 2010 to December 2012 , 156 CPBA children patients with AMES were r and omly assigned to the treatment group ( 80 cases ) and the control group ( 76 cases ) . All patients received routine treatment ( inhaled corticosteroids and /or leukotriene regulator ) . Besides , those in the treatment group took YP . The treatment duration was 3 months . The scores of children asthma control test ( C-ACT ) , pulmonary function ( FEV,% and PEF% ) , myocardial enzyme spectrum were observed before and after treatment , and 3 months before and after treatment . The myocardial enzyme spectrum of 40 healthy children at the baby clinics during the same period were recruited as the control . RESULTS Compared with the control group , creatine kinase isoenzyme ( CK-MB ) , creatine kinase(CK ) , and lactate dehydrogenase ( LDH ) increased in the two treatment groups ( P < 0.01 ) , but there was no statistical difference in AST ( P > 0.05 ) . Compared with before treatment in the same group , CK-MB , CK , LDH , and AST decreased in the treatment group after treatment and 3 months after treatment ( P < 0.01 ) . CK-MB , CK , LDH , and AST decreased in the control group 3 months after treatment ( P < 0.01 , P < 0.05).Compared with after treatment , CK decreased in the control group 3 months after treatment ( P < 0.01 ) . C-ACT score , FEV(1),% , and PEF% all increased in the two groups after treatment and 3 months after treatment ( P < 0.01 , P < 0.05 ) . Compared with after treatment in the same group , CK decreased in the control group 3 months after treatment ( P < 0 . 01 ) . Compared with the control group in the same period , post-treatment CK-MB and CK decreased ( P < 0 . 01 , P < 0 . 05 ) , while post-treatment C-ACT score , FEV , % , and PEF% increased ( P < 0.05 ) in the treatment group ( P < 0.05 ) . CONCLUSION YP could strengthen specific and non-specific immunity of the organism , and improve clinical symptoms and the level of myocardial enzyme spectrum We studied 51 atopic non-smoking subjects who were divided to four treatments groups : ( A ) montelukast 10 mg daily , ( B ) budesonide 400 microg twice a day ( bid ) , ( C ) montelukast 10 mg daily plus budesonide 400 microg bid and ( D ) budesonide 800 microg bid . Bronchial responsiveness was assessed before and after 12 weeks of treatment . The bronchial responsiveness , evaluated by means of PC(20 ) values , showed a strong significant increase in groups B , C and D , and a weak but significant rise in group A , when compared to basal data . Regarding other pulmonary parameters ( FEV(1 ) , PEF ) there were no significant differences among the groups after 12 weeks of therapy . A statistical significance was founded after therapy between group A and C ( p < 0.05 ) , but not between the group B and D treated with only budesonide at different doses . No significant differences was observed in the side effect pattern among the various treatments . The study data demonstrated that administration of montelukast provided an important and additional effect on bronchial hyperresponsiveness . Oral administration represents a significant advantage over the majority of other anti-asthmatic drugs . Our results confirm the anti-inflammatory properties of both the inhaled corticosteroid ( ICS ) and montelukast and the possible role of these drugs can have on airway remodelling . While currently low dose ICS remains the reference drug as a controller in mild-moderate persistent asthma , montelukast may be viewed as a possible option , either in monotherapy or in association Pharmacological therapy with inhaled steroids ( IS ) is currently considered the gold-st and ard of treatment for mild-persistent asthma . Leukotriene receptor antagonist drugs ( LTRAs ) play an important role associated with IS , allowing dose tapering and maintaining control of asthma symptoms . The aim of this study was to determine the effectiveness of montelukast ( MON ) to allow tapering of the inhaled dose of budesonide ( BUD ) in patients with mild-moderate persistent asthma . This 16-wk single-blind r and omized study included 40 asthmatic patients divided in 2 treatment groups . After a run-in period ( 4 wk ) , in which all patients inhaled 400 microg of BUD twice daily ( bid ) , group A ( 20 patients ) received MON ( oral , 10 mg/day ) combined with inhaled BUD ( 400 microg/bid ) , while group B ( 20 patients ) was treated with BUD for the whole period of the study . In both groups , at every 4 wk the dose of BUD was halved . After 12 wk of treatment the mean value of forced expiratory volume during the first sec ( FEV1 , as % of predicted value ) was significantly greater in group A compared with group B ( 94 + /- 7.5 vs 83.1 + /- 6.9 ; p<0.005 ) . The mean values of peak expiratory flow ( PEF ) , the percentages of asthmatic exacerbations , and the use of beta2-short-acting agonist ( SABA ) were similar in the 2 groups at 4 , 8 , and 12 wk . In conclusion , in patients with mild-moderate persistent asthma , MON therapy is useful in tapering the dose of IS in order to reduce its side effects and to maintain the clinical stability of the disease Background Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma OBJECTIVES To explore the influence of zafirlukast on pulmonary functions and quality of life ( QOL ) in patients with mild-to-moderate asthma at the stage of attack and at the stable stage . METHODS Patients at the stage of attack were r and omly divided into two groups : Group one is zafirlukast 20 mg twice daily plus inhaled the half quantity of glucocorticoid(budelade ) of the Global Initiative for Asthma ( GINA ) st and ard quantity , long-effection aminophyllin 0.2 g twice daily and inhaled salbutamol when necessary ; Group two : inhaled budelade of GINA st and ard quantity , long-effection aminophyllin 0.2 g twice daily and inhaled salbutamol when necessary ) . Patients ' peak expiratory flow (PEF)/PEF predicted value % and delta PEFR% were determined at the second week and the forth week before and after the treatment . On the st and ard treatment , patients with the stable stage were added zafirlukast 20 mg twice a day . PEF values in the morning and evening and QOL were evaluated . RESULTS After treating with zafirlukast , the PEF/PEF predicted value % and delta PEFR% in Group one were higher and lower than those of Group two respevtively . These changes were appeared in two days and were peaked in two weeks and the peak had been gone on for more than 4 weeks , but these were no significant difference between the Groups ( P > 0.05 ) ; PEF values in the morning and evening in patients with the stable asthma increased 5.9 % and 4.6 % respectively and their QOL were improved in asthma symptoms , limitative activities , avoiding stimuli , and reacting on stimuli . CONCLUSION Zafirlukast can improve pulmonary function , reduce the inhalation quantity of steroid in patients with mild-to-moderate asthma , and play an important role in treating and improving QOL in patients with the stable asthma Abstract Objective : To determine the ability of montelukast , a leukotriene receptor antagonist , to allow tapering of inhaled corticosteroids in clinical ly stable asthmatic patients . Design : Double blind , r and omised , placebo controlled , parallel group study . After a single blind placebo run in period , during which ( at most ) two inhaled corticosteroids dose decreases occurred , qualifying , clinical ly stable patients were allocated r and omly to receive montelukast ( 10 mg tablet ) or matching placebo once daily at bedtime for up to 12 weeks . Setting : 23 academic asthma centres in United States , Canada , and Europe . Participants : 226 clinical ly stable patients with chronic asthma receiving high doses of inhaled corticosteroids ( 113 r and omised to montelukast and 113 to placebo ) . Interventions : Every 2 weeks , the inhaled corticosteroids dose was tapered , maintained , or increased ( rescue ) based on a st and ardised clinical score . Main outcome measures : Last tolerated dose of inhaled corticosteroids . Results : Compared with placebo , montelukast allowed significant ( P=0.046 ) reduction in the inhaled corticosteroid dose ( montelukast 47 % v placebo 30 % ; least square mean difference 17.6 % , 95 % confidence interval 0.3 to 34.8 ) . Fewer patients on montelukast ( 18 ( 16 % ) v 34 ( 30 % ) placebo , P=0.01 ) required discontinuation because of failed rescue . Conclusions : Montelukast reduces the need for inhaled corticosteroids among patients requiring moderate to high doses of corticosteroid to maintain asthma control . Key messages Leukotriene receptor antagonists have complementary action to inhaled corticosteroids in asthma Many patients receive higher doses of inhaled corticosteroids than clinical ly required In this placebo controlled trial , montelukast allowed significant reduction of inhaled corticosteroid doses Fewer patients receiving montelukast had failed rescue than patients receiving OBJECTIVES To compare the effects of addition of montelukast or salmeterol to inhaled corticosteroids ( ICS ) on the response to rescue beta2-agonist use after exercise-induced bronchoconstriction . METHODS A double-blind , placebo-controlled study was performed at 16 centers in the United States . Patients with asthma ( n = 122 , ages 15 - 58 ) whose symptoms were uncontrolled on Low-dose inhaled fluticasone and who had a history of exercise-induced worsening of asthma were r and omized to receive either montelukast ( 10 mg once daily ) , salmeterol ( 50microg twice daily ) , or placebo for 4 weeks . St and ardized spirometry  after exercise challenge and beta2-agonist rescue was performed at baseline , week 1 and 4 . RESULTS Maximum achievable forced expiratory volume in 1 s ( FEV1 ) percent predicted after rescue beta2-agonist improved in the montelukast ( + 1.5 % ) and placebo ( + 1.2 % ) groups at 4 weeks , but diminished in the salmeterol ( -3.9 % ) group ( P < 0.001 ) . Although pre-exercise FEV1 was greatest with salmeterol ( P = 0.10 ) , patients taking montelukast had significantly greater protection from an exercise-induced decrease in FEV1 than those taking salmeterol ( P < 0.001 ) . Both the magnitude and rate of rescue bronchodilation were greater with montelukast compared with salmeterol ( P < 0.001 ) . Five minutes after rescue beta2-agonist , 92 % of patients taking montelukast and 68 % of those taking placebo had recovered to pre-exercise levels , whereas only 50 % of those taking salmeterol had recovered to pre-exercise levels . CONCLUSION In patients whose asthma symptoms remain uncontrolled using ICS , addition of montelukast permits a greater and more rapid rescue bronchodilation with a short-acting beta2-agonist than addition of salmeterol and provides consistent and clinical ly meaningful protection against exercise-induced bronchoconstriction Bronchial hyperresponsiveness to 5-adenosine mono-phosphate ( AMP ) is a marker of airway inflammation . Inhaled corticosteroids and antileukotrienes are used as anti-inflammatory drugs for the treatment of asthma . To find out if these two drugs exert their protection in an additive fashion , we compared the effects of acute treatment with inhaled beclomethasone ( BDP ) and montelukast ( ML ) , alone or in combination , on methacholine and AMP induced bronchoconstriction . 15 asthmatic patients undertook methacholine and AMP challenges at baseline and after receiving ML or BDP , alone or in combination , in a r and omized , double-blind , double-dummy placebo-controlled , crossover design . BDP pretreatment significantly increased the AMP PC(20 ) value ( 68.34+/-15.9mg/mL ) as compared to placebo ( 22.87+/-5.7mg/mL ) . Combined treatment , BDP plus ML , afforded a further significant increase of AMP PC(20 ) ( 154.57+/-55.0mg/mL ) as compared to each single treatment . The significant protection exerted by combined treatment as compared to each single active treatment was also demonstrated by the change of AMP PC(20 ) doubling dose as compared to placebo and each single active treatment . Our findings suggest that these two agents exert their acute additive protection against AMP induced bronchoconstriction acting on distinct inflammatory pathways and their combined use might provide greater protection against inflammatory response elicited by AMP than either drug alone Mild persistent asthma is most effectively controlled with inhaled corticosteroids . Leukotriene receptor antagonists have complementary effects to corticosteroids on inflammation control . The additional effect of a leukotriene receptor antagonist , zafirlukast , was investigated in stable asthma patients under control with inhaled budesonide .  We conducted a r and omised , double-blind , placebo-controlled , single center trial to investigate the effects of add-on zafirlukast treatment to budesonide , on symptom score , pulmonary function , bronchial responsiveness , and serum levels of eosinophilic cationic protein ( ECP ) and antioxidant capacity in stable asthmatic patients under control with inhaled budesonide . The present study included 21 mild or moderate asthmatic patients ( 8 males and 13 females ) , who were stable at least for 6 weeks with inhaled budesonide ( 400 microg/day ) .  Serum total antioxidant capacity ( TAC ) and ECP levels were measured , and symptom scoring , spirometry , and bronchial provocation with methacholine were performed . Then , the patients were r and omised to use either placebo or oral zafirlukast ( 40 mg/day ) in addition to budesonide for 6 weeks . At the 6th week , symptom scoring , spirometry , and bronchial provocation tests were repeated and serum TAC and ECP levels were measured again . After add-on zafirlukast treatment to budesonide , forced expiratory volume in 1 second ( FEV(1 ) ) , TAC and ECP values did not change significantly ( p > 0.05 ) but bronchial hyperresponsiveness and symptom score decreased significantly ( p = 0.022 ) compared to baseline . Thus , in stable asthmatic patients , add-on zafirlukast treatment to budesonide improves symptoms and decreases bronchial hyperresponsiveness BACKGROUND AND OBJECTIVES : The use of written asthma action plans ( WAAPs ) has been associated with reduced asthma-related morbidity , but there are concerns about their complexity . We developed a health literacy – informed , pictogram- and photograph-based WAAP and examined whether providers who used it , with no training , would have better asthma counseling quality compared with those who used a st and ard plan . METHODS : Physicians at 2 academic centers r and omized to use a low-literacy or st and ard action plan ( American Academy of Allergy , Asthma and Immunology ) to counsel the hypothetical parent of child with moderate persistent asthma ( regimen : Flovent 110 μg 2 puffs twice daily , Singulair 5 mg daily , Albuterol 2 puffs every 4 hours as needed ) . Two blinded raters independently review ed counseling transcriptions . Primary outcome measures : medication instructions presented with times of day ( eg , morning and night vs number of times per day ) and inhaler color ; spacer use recommended ; need for everyday medications , even when sick , addressed ; and explicit symptoms used . RESULTS : 119 providers were r and omly assigned ( 61 low literacy , 58 st and ard ) . Providers who used the low-literacy plan were more likely to use times of day ( eg , Flovent morning and night , 96.7 % vs 51.7 % , P < .001 ; odds ratio [ OR ] = 27.5 ; 95 % confidence interval [ CI ] , 6.1–123.4 ) , recommend spacer use ( eg , Albuterol , 83.6 % vs 43.1 % , P < .001 ; OR = 6.7 ; 95 % CI , 2.9–15.8 ) , address need for daily medications when sick ( 93.4 % vs 34.5 % , P < .001 ; OR = 27.1 ; 95 % CI , 8.6–85.4 ) , use explicit symptoms ( eg , “ ribs show when breathing , ” 54.1 % vs 3.4 % , P < .001 ; OR = 33.0 ; 95 % CI , 7.4–147.5 ) . Few mentioned inhaler color . Mean ( SD ) counseling time was similar ( 3.9 [ 2.5 ] vs 3.8 [ 2.6 ] minutes , P = .8 ) . CONCLUSIONS : Use of a low-literacy WAAP improves the quality of asthma counseling by helping providers target key issues by using recommended clear communication principles A few studies compared the additional effects of oral controller medicines on pulmonary function in asthmatic patients on a moderate dose of inhaled steroids . The aim of this study was to compare the additional effects of two oral asthma controllers , a leukotriene receptor antagonist and a sustained released theophylline ( Theo ) , with a moderate dose of inhaled steroid on  peak expiratory flow ( PEF ) and asthma-related symptoms . A total of 67 adult asthmatic patients with PEF < 80 % predicted during a 2-week run-in period with 800 microg/day of beclomethasone dipropionate  were r and omized to receive either pranlukast , 450 mg/day ( n = 33 ) , or sustained released Theo , 200 mg/day ( n = 34 ) , for 4 weeks . Pranlukast and Theo did not significantly alter the symptom scores , use of rescue beta2-agonist , and daily PEF variability . However , both agents significantly increased both morning and evening PEF compared with the run-in periods . The effects of both medications were comparable . For asthmatic patients even on a moderate dose of inhaled steroids , the addition of either leukotriene receptor antagonist or sustained released Theo does not improve asthma-related symptoms but significantly and equally increases PEF The aim of this study was to investigate the effects of leukotriene receptor antagonists ( LTRAs ) on the premenstrual exacerbation of asthma ( PMA ) . Twenty-four female patients with mild asthma were enrolled in the study . Patients were followed for three menstrual cycles and separated into two groups based on whether they exibit premenstrual worsening of asthma symptoms ( n = 11 ) or not ( n = 13 ) . During the first month all were treated with only inhaled steroids ( IS ) ( run-in period ) ; during the second month they received IS plus placebo ; and during the third month they were given IS plus montelukast . Furthermore , they were advised to use beta 2 -agonists as needed . Peak expiratory flow rate ( PEFR ) and symptom scores were recorded during the 3 months . Pulmonary function tests ( PFT ) and the levels of oestrogen , progesterone , luteinizing hormone ( LH ) , and follicle-stimulating hormone ( FSH ) were measured a week before the begining of the menstrual period . At the end of the 3-month period , it was observed that following therapy with montelukast , the patients with PMA showed significant improvement in PEFR variability and symptom scores when compared with the placebo group . Baseline FSH levels were higher , but FSH and other hormone levels and PFTs did not change in these groups . However , in the group without PMA there was no difference between the montelukast or placebo groups in PEFR variability , symptom scores , PFTs , and hormone levels . Based on the data in h and , it could be stated that LTRAs have ensured the control of symptoms and improved PEFR variability in patients with PMA by supressing inflammation . We are of the view that LTRAs would be a right choice in the treatment of patients with PMA BACKGROUND Although inhaled steroids are used as the first line of therapy in asthmatic patients , symptoms of asthma do not improve completely in some patients . OBJECTIVE To investigate the effects of pranlukast , a cysteinyl leukotriene receptor 1 antagonist , in patients with moderate/severe asthma , when combined with beclomethasone dipropionate ( BDP ) . METHODS Protocol 1 : After a 2-week observation period , 41 patients with moderate asthma were divided into those receiving BDP at 1,600 microg/day or 800 microg/day + pranlukast ( 450 mg/day ) . The effect of treatment was evaluated by measuring AM peak expiratory flow rate , symptom score , frequency of beta2-agonists , and daily variability of peak expiratory flow rate . Protocol 2 : 39 patients participated in this study including those with moderate asthma on 800 microg/day BDP ( group I ) , severe asthma on BDP at 1,600 microg/day ( group II ) , and severe asthma on 1,600 microg/day BDP + 5 to 20 mg prednisolone ( group III ) . Patients of all groups were additionally treated with pranlukast . RESULTS Protocol 1 : Both treatment regimens result ed in improvement in each clinical parameter . There were no significant differences in the effects of two treatment regimens . Protocol 2 : Pranlukast was effective in group I and II , but not in group III . In groups I and II , pranlukast tended to be more effective when BDP was introduced within the first year of onset of asthma . CONCLUSIONS Pranlukast is effective for patients with moderate asthma and those patients with severe asthma who are not treated with oral steroids . Pranlukast is more effective in patients treated with BDP early after onset 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 To test whether the leukotriene antagonist ONO-1078 ( pranlukast ) prevents asthma exacerbations during reduction of high-dose inhaled corticosteroid , we conducted a r and omized , double-blind , placebo-controlled study in 79 asthma patients requiring high doses ( 1,500 microg/d or more ) of inhaled beclomethasone dipropionate ( BDI ) for clinical control ( duration of asthma , 11.0 + /- 3.1 yr ; duration of BDI treatment , 0.5 + /- 0.3 yr ; FEV1 percentage of predicted , 80.7 + /- 2.0 % ) . After a 2-wk run-in period , the doses of BDI were halved , while the patients were assigned to receive orally ONO-1078 , 450 mg twice daily , or placebo . In the placebo group FEV1 decreased by 0.33 + /- 0.20 L after 6 wk ( p < 0.001 ) . Likewise , morning and evening PEF decreased by 46 + /- 7 L/min and 18 + /- 6 L/min , respectively . By contrast these variables were sustained above baseline in the ONO-1078 group . The number of daytime and nighttime asthma symptoms and the use of beta2-agonist increased in the placebo group , whereas they remained unchanged in the ONO-1078 group . In the placebo group concentrations of serum eosinophil cationic protein and exhaled nitric oxide increased ( p = 0.007 and p = 0.025 , respectively ) , compared with no change in the ONO-1078 group . Therefore , the leukotriene antagonist ONO-1078 prevents the asthma deterioration provoked by a 6-wk reduction of the dose of inhaled BDI into half In our prior r and omized trial on preventing influenza , asthma attacks as a secondary outcome occurred less often in the vitamin D group than in the placebo group . We aim ed to clarify whether low‐dose , short‐term vitamin D supplementation , in addition to st and ard treatments , improves control of childhood asthma BACKGROUND Information is lacking on the relative effectiveness and cost effectiveness -- in a primary -care setting --of leukotriene receptor antagonists ( LTRAs ) as an alternative to inhaled corticosteroids ( ICS ) for initial asthma controller therapy . OBJECTIVE To compare the cost effectiveness of LTRAs versus ICS for patients initiating asthma controller therapy . METHODS An economic evaluation was conducted alongside a 2-year , pragmatic , r and omized controlled trial set in 53 primary -care practice s in the UK . Patients aged 12 - 80 years with asthma and symptoms requiring regular anti-inflammatory therapy ( n = 326 ) were r and omly assigned to LTRAs ( n = 162 ) or ICS ( n = 164 ) . The main outcome measures were the incremental costs per point improvement in the Mini Asthma Quality of Life Question naire , per point improvement in the Asthma Control Question naire and per QALY gained from the UK NHS and societal perspectives . RESULTS Over 2 years , re source use was similar between the two treatment groups , but the cost to society per patient was significantly higher for the LTRA group , at pounds sterling 711 versus pounds sterling 433 for the ICS group ( adjusted difference pounds sterling 204 ; 95 % CI 74 , 308 ) [ year 2005 values ] . Cost differences were driven primarily by differences in prescription drug costs , particularly study drug costs . There was a nonsignificant ( imputed , adjusted ) difference between treatment groups , favouring ICS , in QALYs gained at 2 years of -0.073 ( 95 % CI -0.143 , 0.010 ) . Therapy with LTRAs was , on average , a dominated strategy , and , at a threshold for willingness to pay of pounds sterling 30,000 per QALY gained , the probability of LTRAs being cost effective compared with ICS was approximately 3 % from both societal and NHS perspectives . CONCLUSIONS There is a very low probability of LTRAs being cost effective in the UK , at 2005 values , compared with ICS for initial asthma controller therapy . TRIAL REGISTRATION UK National Research Register N0547145240 ; Controlled Clinical Trials IS RCT N99132811 BACKGROUND Airway inflammation is a key pathological feature of asthma which underlies its clinical presentation . OBJECTIVES To examine whether adding a leukotriene modifier to an inhaled corticosteroid produces further clinical and /or anti-inflammatory benefits in patients symptomatic on short-acting beta(2)-agonists . METHODS Patients uncontrolled on short-acting beta(2)-agonists were treated for 12 weeks with either fluticasone propionate ( 100mcg BD ) or fluticasone propionate ( 100mcg BD ) and montelukast ( 10 mg QD ) in a r and omized , double-blind , parallel group study . Bronchoscopy with endobronchial biopsy and bronchoalveolar lavage ( BAL ) was performed before and after treatment to compare effects on airway inflammation . RESULTS Of 103 subjects enrolled , 89 subjects completed treatment and 82 subjects had matched pair biopsy sample s.  Submucosal eosinophil counts , the primary endpoint , and asthma control improved to similar extents after both treatments ( p < or=0.008 ) . Both treatments significantly reduced submucosal mast cell , CD3 + , CD4 + , CD8 + and CD25 + cell counts . Submucosal mast cell reduction was greater in the fluticasone propionate plus montelukast group . There were no differences between treatments in BAL markers of inflammation or thickness of sub-epithelial collagen . CONCLUSIONS Low-dose fluticasone propionate significantly improves clinical disease control and reduces airway inflammation in asthma patients uncontrolled with short-acting beta(2)-agonists without further improvement when montelukast is added to low-dose fluticasone propionate BACKGROUND Eosinophilic inflammation of the small airways is a key process in asthma that often smolders in treated patients . The long-term effects of add-on therapy on the persistent inflammation in the small airways remain unknown . OBJECTIVE To examine the effects of add-on therapy with either ciclesonide , an inhaled corticosteroid with extrafine particles , or montelukast on small airway inflammation . METHODS Sixty patients with stable asthma receiving inhaled corticosteroid treatment were enrolled in a r and omized , open-label , parallel comparison study of 24-week add-on treatment with ciclesonide or montelukast . Patients were r and omly assigned to 3 groups : ciclesonide ( n = 19 ) , montelukast ( n = 22 ) , or no add-on as controls ( n = 19 ) . At baseline and at weeks 4 , 12 , and 24 , extended nitric oxide analysis ; pulmonary function tests , including impulse oscillometry ; blood eosinophil counts ; and asthma control tests ( ACTs ) were performed . RESULTS A total of 18 patients in the ciclesonide group , 19 in the montelukast group , and 15 in the control group completed the study and were analyzed . With repeated- measures analysis of variance , ciclesonide produced a significant decrease in alveolar nitric oxide and a significant improvement in ACT scores over time . Montelukast produced significant decreases in alveolar nitric oxide concentrations and blood eosinophil counts over time and slightly improved ACT scores , whereas no such changes were observed in the control group . Alveolar nitric oxide concentrations with ciclesonide and reactance area at low frequencies with montelukast produced greater improvements over time compared with control . CONCLUSION Ciclesonide add-on therapy and montelukast add-on therapy may act differently , but both separately can improve small airway abnormalities and provide better asthma control . TRIAL REGISTRATION umin.ac.jp/ctr Identifier : UMIN000001083 Abstract Objective : Treatment guidelines for asthma recommend step-down therapy for well-controlled asthma patients . However , the precise strategy for step-down therapy has not been well defined . We investigated whether well-controlled patients with mild persistent asthma can tolerate a step-down therapy of either a reduced dose of inhaled corticosteroid ( ICS ) or a switch to a leukotriene receptor antagonist ( LTRA ) , pranlukast hydrate . Methods : We recruited 40 adult patients with mild persistent asthma who were well-controlled for at least 3 months with a low-dose ICS therapy .  The patients were r and omly assigned to either an ICS dose reduction or a switch to pranlukast for 6 months . Results : FeNO levels in the pranlukast group were significantly increased over that in the ICS group . There were no significant differences between the two groups for lung function , FOT , at the endpoint . The percentage of patients with controlled asthma was 72.2 % in the pranlukast group and 90 % in the ICS group . No statistically significant difference between the two groups in the percentages of patients with treatment failure was observed . Conclusions : Patients with mild persistent asthma that is well-controlled by a low dose of ICS can be switched to pranlukast safely for at least 6 months . However , 27.8 % of the pranlukast group failed to maintain well-control , and FeNO levels increased with the switch to pranlukast at 6 months . This study was been limited by the small sample size and should therefore be considered preliminary . Further studies are needed to investigate the therapeutic efficacy of LTRA monotherapy as a step-down therapy
BACKGROUND Asthma management guidelines recommend low-dose inhaled corticosteroids ( ICS ) as first-line therapy for adults and adolescents with persistent asthma .
The addition of anti-leukotriene agents to ICS offers a therapeutic option in cases of suboptimal control with daily ICS .
OBJECTIVES To assess the efficacy and safety of anti-leukotriene agents added to ICS compared with the same dose , an increased dose or a tapering dose of ICS ( in both arms ) for adults and adolescents 12 years of age and older with persistent asthma .
Also , to determine whether any characteristics of participants or treatments might affect the magnitude of response .