Cost-Effectiveness of the School-Based Asthma Therapy (SBAT) Program Efficacy and tolerability of formoterol Turbuhaler in children. The safety of twice-daily treatment with fluticasone propionate and salmeterol in pediatric patients with persistent asthma. Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate. Evaluation of Fluticasone Propionate and Fluticasone Propionate/Salmeterol Combination on Exercise in Pediatric and Adolescent Patients with Asthma Budesonide/formoterol maintenance and reliever therapy: an effective asthma treatment option? Comparison of heat-sensitive moxibustion versus fluticasone/salmeterol (seretide) combination in the treatment of chronic persistent asthma: design of a multicenter randomized controlled trial Addition of montelukast or salmeterol to fluticasone for protection against asthma attacks: a randomized, double-blind, multicenter study. Leukotriene antagonists as first-line or add-on asthma-controller therapy. Salmeterol and fluticasone in young children with multiple-trigger wheeze. Addition of salmeterol versus doubling the dose of beclomethasone in children with asthma. The Dutch Asthma Study Group. Factors associated with asthma exacerbations during a long-term clinical trial of controller medications in children. Effect of inhaled glucocorticoids in childhood on adult height. Maintenance asthma treatment with fluticasone/salmeterol combination via Diskus: effect on outcomes in inner-city children enrolled in TennCare. Titrating steroids on exhaled nitric oxide in children with asthma: a randomized controlled trial. Addition of fexofenadine to inhaled corticosteroid therapy to reduce inflammatory biomarkers in atopic asthma. Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment. Effect of formoterol on clinical parameters and lung functions in patients with bronchial asthma: a randomised controlled trial Determining economic feasibility of fluticasone propionate-salmeterol vs montelukast in the treatment of persistent asthma using a net benefit approach and cost-effectiveness acceptability curves. Effect of different antiasthmatic treatments on exercise-induced bronchoconstriction in children with asthma. Benefit from anti-inflammatory treatment during clinical remission of atopic asthma. Traditional and patient-centred outcomes with three classes of asthma medication Salmeterol/fluticasone propionate (50/250 microg) combination is superior to double dose fluticasone (500 microg) for the treatment of symptomatic moderate asthma. Dose-related efficacy and safety of formoterol (Oxis) Turbuhaler compared with salmeterol Diskhaler in children with asthma. Economic assessment of adjustable maintenance treatment with budesonide/formoterol in a single inhaler versus fixed treatment in asthma The effect of adjustable dosing with budesonide/formoterol on health-related quality of life and asthma control compared with fixed dosing Canadian Thoracic Society 2012 guideline update: diagnosis and management of asthma in preschoolers, children and adults. Salmeterol xinafoate in children on high dose inhaled steroids. Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma. Long-term safety and asthma control with budesonide/formoterol versus budesonide pressurized metered-dose inhaler in asthma patients. The safety and clinical benefit of budesonide/formoterol pressurized metered-dose inhaler versus budesonide alone in children. Asthma control over 3 years in a real-life study. Add-on salmeterol compared to double dose fluticasone in pediatric asthma: a double-blind, randomized trial (VIAPAED). A randomized, double-blind trial of the effect of anti-asthma treatment on lung function in children with asthma. Formoterol used as needed in patients with intermittent or mild persistent asthma. Montelukast versus formoterol as second-line therapy in asthmatic children exposed to relevant allergens. Budesonide/formoterol in a single inhaler versus inhaled corticosteroids alone in the treatment of asthma. Low-dose fluticasone propionate with and without salmeterol in steroid-naïve patients with mild, uncontrolled asthma. Down-titration from high-dose combination therapy in asthma: Removal of long-acting beta(2)-agonist. Eformoterol Turbohaler compared with salmeterol by dry powder inhaler in asthmatic children not controlled on inhaled corticosteroids. Efficacy and safety of budesonide/formoterol single inhaler therapy versus a higher dose of budesonide in moderate to severe asthma Effect of fluticasone propionate-salmeterol therapy on seasonal changes in airway responsiveness and exhaled nitric oxide levels in patients with pollen-induced asthma. Efficacy and Safety of Fluticasone Propionate/Salmeterol HFA 134A MDI in Patients with Mild‐to‐Moderate Persistent Asthma A randomised controlled trial of short term growth and collagen turnover in asthmatics treated with inhaled formoterol and budesonide The effectiveness of asthma therapy alternatives and evaluating the effectivity of asthma therapy by interleukin-13 and interferon gamma levels in children. Long-term circadian effects of salmeterol in asthmatic children treated with inhaled corticosteroids. Improving asthma treatment in a managed care population. Fluticasone propionate nasal spray is superior to montelukast for allergic rhinitis while neither affects overall asthma control. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Fluticasone propionate and salmeterol administered via Diskus compared with salmeterol or fluticasone propionate alone in patients suboptimally controlled with short-acting beta2-agonists. Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma. Effect of addition of salmeterol versus doubling the dose of fluticasone propionate on specific airway resistance in children with asthma. [The quality of life of the asthmatic child caregiver]. Budesonide/formoterol improves lung function compared with budesonide alone in children with asthma. Budesonide/Formoterol Pressurized Metered-Dose Inhaler versus Budesonide: A Randomized Controlled Trial in Black Patients with Asthma Efficacy and safety of fluticasone propionate/salmeterol 250/50 mcg Diskus administered once daily. Childhood evaluation of salmeterol tolerance--a double-blind randomized controlled trial. Efficacy and safety of a new pressurised metered-dose inhaler formulation of budesonide/formoterol in children with asthma: a superiority and therapeutic equivalence study. Efficacy and safety of salmeterol/fluticasone propionate delivered via a hydrofluoroalkane metered dose inhaler in Chinese patients with moderate asthma poorly controlled with inhaled corticosteroids. Formoterol, montelukast, and budesonide in asthmatic children: effect on lung function and exhaled nitric oxide. Duration of action of the salmeterol/fluticasone combination inhaler administered in the evening: a randomized controlled trial in childhood asthma. Fluticasone propionate/salmeterol and exercise-induced asthma in children with persistent asthma. Efficacy and safety of formoterol Turbuhaler when added to inhaled corticosteroid treatment in children with asthma. Salmeterol/fluticasone propionate (50/500 microg) in combination in a Diskus inhaler (Seretide) is effective and safe in the treatment of steroid-dependent asthma. Randomized comparison of strategies for reducing treatment in mild persistent asthma. A Comparison of Budesonide/Formoterol Maintenance and Reliever Therapy Versus Conventional Best Practice in Asthma Management in Spain A randomized controlled trial of an asthma clinical pathway for children in general practice Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. Effect of fluticasone/salmeterol administered via a single device on exercise-induced bronchospasm in patients with persistent asthma. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Fixed and adjustable dose asthma action plans based on combination therapy: a pilot study. Combination therapy salmeterol/fluticasone versus doubling dose of fluticasone in children with asthma. A comparison of the effects of oral montelukast and inhaled salmeterol on response to rescue bronchodilation after challenge. Comparable long-term safety and efficacy of a novel budesonide/formoterol pressurized metered-dose inhaler versus budesonide/formoterol Turbuhaler in adolescents and adults with asthma. Pilgrim's progress: the effect of salmeterol in older children with chronic severe asthma. Tailored second-line therapy in asthmatic children with the Arg(16) genotype. Efficacy and safety of fluticasone/formoterol combination therapy in patients with moderate-to-severe asthma. Management of Asthma in School age Children On Therapy (MASCOT): a randomised, double-blind, placebo-controlled, parallel study of efficacy and safety. Efficacy and safety of a recombinant anti‐immunoglobulin E antibody (omalizumab) in severe allergic asthma Salmeterol HFA is as effective as salmeterol CFC in children and adults with persistent asthma. Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial.
BACKGROUND AND OBJECTIVE : Impoverished urban children suffer disproportionately from asthma and underuse preventive asthma medications . The objective of this study was to examine cost-effectiveness ( CE ) of the School-Based Asthma Therapy ( SBAT ) program compared with usual care ( UC ) . METHODS : The analysis was based on the SBAT trial , including 525 children aged 3 to 10 years attending urban preschool or elementary school who were r and omized to either UC or administration of 1 dose of preventive asthma medication at school by the school nurse each school day . The primary outcome was the mean number of symptom-free days ( SFDs ) . The impact of the intervention on medical costs was estimated by using parent-reported child health services utilization data and average national reimbursement rates . We estimated the cost of running the program using wages for program staff . Productivity costs were estimated by using value of parent lost time due to child illness . CE of the SBAT program compared with UC was evaluated based on the incremental CE ratio . RESULTS : The health benefit of the intervention was equal to ∼158 SFD gained per each 30-day period ( P < .05 ) per 100 children . The programmatic expenses summed to an extra $ 4822 per 100 children per month . The net saving due to the intervention ( reduction in medical costs and parental productivity , and improvement in school attendance ) was $ 3240 , result ing in the incremental cost-savings difference of $ 1583 and CE of $ 10 per 1 extra SFD gained . CONCLUSIONS : The SBAT was effective and cost-effective in reducing symptoms in urban children with asthma compared with other existing programs A r and omised , double-blind trial was undertaken to investigate the efficacy and tolerability of formoterol Turbuhaler in children with mild to moderate asthma . After a two-week run-in , 248 children aged 6 - 17 years were r and omised to receive formoterol 4.5 and 9 pmicro b.i.d . or placebo for 12 weeks . Morning PEF ( primary variable ) , was significantly improved versus placebo only in the formoterol 9 pmicro b.i.d . group ( 13 l/min , 95 % CCI 1.9 , 24.2 % ; p = 0 .02 ) . Both formoterol 4.5 and 9 pmicro significantly increased the pre-bronchodilator FEV1 by 5.2 - 6.7 % ( p < 0 .05 ) and reduced use of daytime relief medication versus placebo ( p < 0 .05 ) . Formoterol 9 pmicro significantly reduced night-time reliever use and awakenings due to asthma versus placebo ( p < 0.05 ) . Both doses of formoterol were as well tolerated as placebo . In conclusion , formoterol 4.5 and 9 micro b.i.d . is effective and well tolerated as maintenance therapy in children with mild to moderate asthma BACKGROUND For children older than 5 years with asthma who remain symptomatic despite inhaled corticosteroid ( ICS ) therapy , the preferred treatment is to add an inhaled long-acting beta2-agonist vs increasing the ICS dose . OBJECTIVE To compare the safety of twice-daily treatment with inhaled fluticasone propionate plus the inhaled long-acting beta2-agonist salmeterol with that of fluticasone propionate used alone in children aged 4 to 11 years with persistent asthma . METHODS A r and omized , multicenter , double-blind , active-controlled , parallel-group study in 203 children with persistent asthma who were symptomatic during ICS therapy . Patients received fluticasone propionate-salmeterol ( 100/50 microg ) or fluticasone propionate ( 100 microg ) alone twice daily for 12 weeks . RESULTS The safety profile of fluticasone propionate-salmeterol was similar to that of fluticasone propionate alone . The overall incidence of adverse events was 59 % for fluticasone propionate-salmeterol and 57 % for fluticasone propionate . Both treatments were well tolerated . Two patients receiving fluticasone propionate-salmeterol and 5 receiving fluticasone propionate withdrew from the study because of worsening asthma . Changes in heart rate , blood pressure , and laboratory variables were infrequent and were similar between treatments . No patients had clinical ly significant abnormal electrocardiographic findings during treatment . Geometric mean 24-hour urinary cortisol excretion at baseline and after 12 weeks of treatment was comparable within and between groups ; no patient in either group had abnormally low 24-hour urinary cortisol excretion after 12 weeks of treatment . The incidence of withdrawals due to asthma exacerbations was 2 % in the fluticasone propionate-salmeterol group and 5 % in the fluticasone propionate group . CONCLUSIONS In pediatric patients with persistent asthma , fluticasone propionate-salmeterol twice daily was well tolerated , with a safety profile similar to that of fluticasone propionate used alone OBJECTIVE Intranasal beclomethasone dipropionate ( BDP ) has generally been considered to have no systemic activity at recommended doses , but the potential for long-term effects on growth has not previously been evaluated . This study was undertaken to assess the effects of 1 year of treatment with intranasal BDP on growth in children . STUDY DESIGN In this double-blind , r and omized , parallel-group study , 100 prepubertal children 6 to 9 years old with perennial allergic rhinitis were treated with aqueous BDP 168 microg twice daily ( n = 51 ) or placebo ( n = 49 ) for 1 year . Subjects ' baseline heights were required to be between the 5th and 95th percentile , and skeletal age as determined by left wrist radiograph was required to be within 2 years of chronological age . Washout periods for medications known to affect growth , including other forms of corticosteroids , were established , and these medications were prohibited during the study . However , short courses of oral prednisolone lasting no more than 7 days , and short courses of dermatologic corticosteroids lasting no more than 10 days , were allowed . Height was measured with a stadiometer after 1 , 2 , 4 , 6 , 8 , 10 , and 12 months of treatment . The hypothalamic-pituitary-adrenocortical axis was assessed by measurements of 8 AM basal cortisol concentrations and response to . 25 mg cosyntropin stimulation . The primary safety parameter was the rate of change in st and ing height . Statistical analyses were based on all r and omized subjects who received at least 1 dose of medication ( intent-to-treat principle ) . The rate of change in st and ing height was analyzed for all subjects who entered the study and for those completing the full 12 months of treatment ( n = 80 ) . The rate of change in st and ing height over the 1-year study was calculated as the slope of a linear regression line fitted to each subject 's height measurements over time . Because there was a statistically significant between-group difference in st and ing height at baseline , an analysis of covariance was performed for all analyses of st and ing height data . RESULTS Of the 100 subjects enrolled , 90 completed the study . The 2 treatment groups were generally comparable at baseline ; however , at baseline , mean age and mean height were significantly greater in the BDP treatment group that the in placebo treatment group . In both analyses , overall growth rate was significantly slower in BDP-treated subjects than placebo-treated subjects . The mean change in st and ing height after 1 year was 5.0 cm in the BDP-treated subjects compared with 5.9 cm in the placebo-treated subjects . The difference in growth rates was evident as early as the 1-month treatment visit , suggesting that the effect on growth occurred initially . The growth-suppressive effect of BDP remained consistent across all age and gender subgroups , and among subjects with and without a previous history of corticosteroid use . Use of additional exogenous corticosteroids during the study was similar in both groups and did not affect the results . Because there was a baseline imbalance in height , a supplemental analysis of the differences in pre study growth rates was performed . This analysis found no baseline imbalance in pre study growth rates . To determine whether the difference in growth rates during the study could be attributed to preexisting growth rates , a z score analysis was performed . The heights of both groups were normalized at baseline and at the end of the study using the US National Center for Health Statistics data for mean and st and ard deviations of height . This analysis confirmed that the difference in growth rates between the 2 groups was primarily attributable to the treatment rather than to any preexisting difference in growth . Additional analyses confirmed that the results were not influenced by outlier values . No significant between-group difference were found in the hypothalamic-pituitary-adrenocortical axis assessment s. No unusual adverse events were observed . ( Objective : This study was design ed to demonstrate that four weeks of fluticasone propionate ( FP ) 100 micrograms ( mcg ) combined with salmeterol 50 mcg twice daily ( BID ) via DISKUS ® result ed in protection against bronchospasm induced by activity , as measured by st and ardized exercise challenge testing in pediatric and adolescent subjects who required regular use of inhaled corticosteroids for the treatment of persistent asthma . Methods : Prior to study entry , all patients reported regular use of inhaled corticosteroids ( ICS ) . During screening all patients demonstrated ≥20 % fall in FEV1 following exercise . Results : A total of 231 subjects aged 4 to 17 were r and omized to the two study treatments : 113 to the FP/salmeterol combination group ( FSC ) and 118 to receive FP 100 mcg BID . Of the subjects r and omized , 106 ( 94 % ) subjects in the FSC 100/50 group and 108 ( 92 % ) subjects in the FP 100 group completed the study . At the end of treatment ( Week 4 ) , both FSC and FP  protected against a fall in FEV1 following exercise in patients who at baseline experienced ≥20 % fall in FEV1 following exercise . A mean decrease in FEV1 of 9.9 % was observed in the FSC 100/50 group as compared with a mean decrease of 11.1 % in the FP 100 group ; there was no statistical difference between treatments . Conclusion : Both FSC 100/50 and FP 100 provided protection against an exercised-induced fall in FEV1 ; but statistically significant differences we not noted . Both treatments were well-tolerated over four weeks and FSC 100/50 had an adverse event profile comparable to that observed with FP 100 This 12-month dose-titration study assessed the effectiveness of budesonide/formoterol for maintenance plus relief with a control group using salmeterol/fluticasone for maintenance plus salbutamol for relief . Adolescents and adults ( n = 2,143 ; mean forced expiratory volume in one second ( FEV1 ) 73 % predicted ; mean inhaled corticosteroid ( ICS ) 884 µg·day−1 ) were r and omised  to budesonide/formoterol 160/4.5 µg two inhalations b.i.d . plus additional inhalations as needed , or salmeterol/fluticasone 50/250 µg b.i.d . plus salbutamol as needed . Treatment was prescribed open label ; after 4 weeks , physicians could titrate maintenance doses in accordance with normal clinical practice . Maintenance plus as-needed budesonide/formoterol prolonged the time to first severe exacerbation versus salmeterol/fluticasone ( 25 % risk reduction ) . The total number of severe exacerbations was significantly reduced in the budesonide/formoterol group ( 255 versus 329 ) . Both regimens provided sustained improvements in symptoms , as-needed use , quality of life and FEV1 , with differences in favour of the budesonide/formoterol group for as-needed use ( 0.58 versus 0.93 inhalations·day−1 ) and FEV1 ( post-β2-agonist values ) . Mean ICS dose during treatment was similar in both groups ( 653 µg budesonide·day−1 ( maintenance plus as-needed ) versus 583 µg fluticasone·day−1 ) . The simplified strategy using budesonide/formoterol for maintenance and reliever therapy is feasible , safe and at least as effective as salmeterol/fluticasone plus salbutamol Background Asthma is a major health problem and has significant mortality around the world . Although the symptoms can be controlled by drug treatment in most patients , effective low-risk , non-drug strategies could constitute a significant advance in asthma management . An increasing number of patients with asthma are attracted by acupuncture and moxibustion . Therefore , it is of importance that scientific evidence about the efficacy of this type of therapy is regarded . Our past research es suggested heat-sensitive moxibustion might be effective in treatment of asthma . Our objective is to investigate the effectiveness of  heat-sensitive moxibustion  compared with conventional drug treatment . Methods / Design This study is comprised of a multi-centre ( 12 centers in China ) , r and omized , controlled trial with two parallel arms ( A : heat-sensitive moxibustion ; B : conventional drug ) . Group A selects heat- sensitive acupoints from the rectangle region which consist of two outer lateral lines of dorsal Bladder Meridian of Foot-Taiyang , and two horizontal lines of BL13(Fei Shu ) and BL17 ( Ge Shu);6 inch outer the first and second rib gap of anterior chest . Group B treats with fluticasone/salmeterol ( seretide ) . The outcome measures will be assessed over a 3-month period before each clinic visit at days 15 , 30 , 60 , and 90 . Follow-up visit will be at 3 , 6 months after the last treatment session . Adverse event information will be collected at each clinic visit . Discussion This trial will utilize high quality trial method ologies in accordance with CONSORT guidelines . It may provide evidence for the effectiveness of heat-sensitive moxibustion as a treatment for chronic moderate persistent asthma . Moreover , the result may propose a new type moxibustion to control asthma . Trial Registration The trial is registered at Chinese Clinical Trials Registry : BACKGROUND For patients whose asthma is uncontrolled with low-dose inhaled corticosteroids , addition of alternative therapy instead of increasing the steroid dose is recommended by current treatment guidelines . OBJECTIVE To compare montelukast , a once-daily leukotriene receptor antagonist , and salmeterol , a twice-daily , long-acting beta-agonist , concomitantly administered with inhaled fluticasone , according to the percentage of patients without an asthma attack for 1 year . METHODS A r and omized , double-blind , double-dummy , multicenter study was conducted . Adult patients with moderate-to-severe persistent asthma ( ages 14 - 73 years ) receiving inhaled fluticasone ( 220 microg/d ) who remained symptomatic during a 4-week run-in period were r and omized to the addition of salmeterol ( 84 microg/d ) or montelukast ( 10 mg/d ) for 48 weeks . RESULTS Of the 1,473 r and omized patients , 743 were r and omized to montelukast and 730 to salmeterol ; 1,059 patients completed the study . Eighty percent of patients in the montelukast group and 83.3 % of patients in the salmeterol group remained attack free during the 48 weeks of treatment ( relative risk , 1.20 ; 95 % confidence interval , 0.96 - 1.49 ) . Montelukast significantly reduced blood eosinophil counts compared with salmeterol , whereas salmeterol significantly increased prealbuterol forced expiratory volume in 1 second , asthma-specific quality of life , morning peak expiratory flow rate , and decreased nocturnal awakenings compared with montelukast . Differences between treatments were small , and both treatments were generally well tolerated . CONCLUSIONS Addition of montelukast or salmeterol to an inhaled corticosteroid similarly protected most patients from experiencing an asthma attack during a 1-year period , but , based on noninferiority limits , the study was inconclusive with regard to a difference between treatment groups BACKGROUND Most r and omized trials of treatment for asthma study highly selected patients under idealized conditions . METHODS We conducted two parallel , multicenter , pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist ( LTRA ) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist ( LABA ) as add-on therapy in patients already receiving inhaled glucocorticoid therapy . Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life ( Mini Asthma Quality of Life Question naire [ MiniAQLQ ] score ≤6 ) or inadequate asthma control ( Asthma Control Question naire [ ACQ ] score ≥1 ) . We r and omly assigned patients to 2 years of open-label therapy , under the care of their usual physician , with LTRA ( 148 patients ) or an inhaled glucocorticoid ( 158 patients ) in the first-line controller therapy trial and LTRA ( 170 patients ) or LABA ( 182 patients ) added to an inhaled glucocorticoid in the add-on therapy trial . RESULTS Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials . At 2 months , differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence ( 95 % confidence interval [ CI ] for an adjusted mean difference , -0.3 to 0.3 ) . At 2 years , mean MiniAQLQ scores approached equivalence , with an adjusted mean difference between treatment groups of -0.11 ( 95 % CI , -0.35 to 0.13 ) in the first-line controller therapy trial and of -0.11 ( 95 % CI , -0.32 to 0.11 ) in the add-on therapy trial . Exacerbation rates and ACQ scores did not differ significantly between the two groups . CONCLUSIONS Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients . Equivalence was not proved at 2 years . The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group . ( Funded by the National Coordinating Centre for Health Technology Assessment U.K. and others ; Controlled Clinical Trials number , IS RCT N99132811 . ) BACKGROUND Treatment guidelines recommend using an inhaled corticosteroid ( ICS ) plus a long-acting β(2)-agonist ( LABA ) for childhood asthma when the symptoms are not controlled by ICS alone , but the appropriate use of LABAs in children continues to be debated . OBJECTIVE To compare the efficacy of an inhaled salmeterol and fluticasone propionate combination , 50/100 μg twice daily , with fluticasone propionate , 100 μg twice daily , or salmeterol , 50 μg twice daily , in children with multiple-trigger wheeze . METHODS A total of 105 children 4 to 7 years of age with multiple-trigger wheezing based on respiratory symptoms and bronchodilator responsiveness and /or exercise-induced bronchoconstriction without a viral cold were r and omized to salmeterol-fluticasone , fluticasone propionate alone , or salmeterol alone via a metered-dose inhaler and a spacer device for 8 weeks . The primary efficacy outcome was exhaled nitric oxide level . Secondary outcomes were lung function measurements via impulse oscillometry , respiratory symptoms , and rescue medication use . RESULTS The exhaled nitric oxide levels decreased after all treatments , significantly more so after salmeterol-fluticasone and fluticasone than with salmeterol ( adjusted geometric means at 8 weeks : salmeterol-fluticasone , 9.4 ppb ; fluticasone , 9.3 ppb ; salmeterol , 13.9 ppb ; salmeterol-fluticasone vs salmeterol , P = .02 ; fluticasone vs salmeterol , P = .01 ) . No treatment differences were found with respect to respiratory symptoms or median rescue use . Salmeterol-fluticasone result ed in a small but statistically significant improvement in baseline lung function compared with fluticasone . All treatments were equally well tolerated . CONCLUSION The effects of salmeterol-fluticasone and fluticasone were comparable , although lung function improvement was better with salmeterol-fluticasone than with fluticasone alone . There is no obvious benefit in initiation therapy with salmeterol-fluticasone rather than fluticasone alone in the treatment of steroid-naive children with multiple-trigger wheeze . TRIAL REGISTRATION Pathway of clinical trial registry of Helsinki University : http://www.hus.fi/?Path=1;28;2530;9899;9900;23618;23903;33578 Studies in adults revealed that addition of salmeterol to a moderate dose of inhaled corticosteroid result ed in better symptom control and higher PEF compared with doubling the dose of inhaled corticosteroid . The aim of this three group study was to compare the effects of a moderate dose of beclomethasone , the same dose of beclomethasone with salmeterol , and a doubling dose of beclomethasone on lung function and symptoms in children with moderate asthma . A total of 177 children already treated with inhaled corticosteroids , were r and omized in a double-blind parallel study either to salmeterol 50 microg twice daily ( BDP400+salm ) , beclomethasone 200 microg twice daily ( BDP800 ) , or placebo ( BDP400 ) in addition to beclomethasone 200 microg twice daily . No significant differences between groups were found in FEV1 , PD20 methacholine , symptom scores , and exacerbation rates after 1 yr . Salmeterol result ed in slightly better PEF in the first months of treatment . FEV1 , and PD20 methacholine significantly improved in all groups . After 1 yr mean changes in FEV1 , percent predicted were 4.3 % ( 95 % CI 1.3 ; 7.2 ) , 5.8 % ( 95 % CI 2.9 ; 8.7 ) , and 4.3 % ( 95 % CI 2.1 ; 6.5 ) for BDP400+salm , BDP800 , and BDP400 , respectively . Changes in airway responsiveness were 0.60 ( 95 % CI 0.05 ; 1.14 ) , 1.30 ( 95 % CI 0.73 ; 1 . 87 ) , and 0.80 ( 95 % CI 0.33 ; 1.27 ) doubling doses . Growth was significantly slower in the BDP800 group . We conclude that no additional benefit was found of adding either salmeterol or more beclomethasone to a daily dose of 400 microg beclomethasone in this group of children with excellent compliance of medication BACKGROUND Asthma exacerbations are a common cause of critical illness in children . OBJECTIVE To determine factors associated with exacerbations in children with persistent asthma . METHODS Regression modeling was used to identify historical , phenotypic , treatment , and time-dependent factors associated with the occurrence of exacerbations , defined by need for oral corticosteroids or emergency or hospital care in the 48-week Pediatric Asthma Controller Trial study . Children age 6 to 14 years with mild-to-moderate persistent asthma were r and omized to receive either fluticasone propionate 100 microg twice daily ( FP monotherapy ) , combination fluticasone 100 microg AM and salmeterol twice daily , or montelukast 5 mg once daily . RESULTS Of the 285 participants r and omized , 48 % had 231 exacerbations . Using a multivariate analysis , which included numerous demographic , pulmonary , and inflammatory parameters , only a history of an asthma exacerbation requiring a systemic corticosteroid in the past year ( odds ratio [ OR ] , 2.10 ; P < .001 ) was associated with a subsequent exacerbation during the trial . During the trial , treatment with montelukast versus FP monotherapy ( OR , 2.00 ; P = .005 ) , season ( spring , fall , or winter vs summer ; P < or = .001 ) , and average seasonal 5 % reduction in AM peak expiratory flow ( OR , 1.21 ; P = .01 ) were each associated with exacerbations . Changes in worsening of symptoms , beta-agonist use , and low peak expiratory flow track together before an exacerbation , but have poor positive predictive value of exacerbation . CONCLUSION Children with mild-to-moderate persistent asthma with previous exacerbations are more likely to have a repeat exacerbation despite controller treatment . Inhaled corticosteroids are superior to montelukast at modifying the exacerbation risk . Available physiologic measures and biomarkers and diary card tracking are not reliable predictors of asthma exacerbations BACKGROUND The use of inhaled glucocorticoids for persistent asthma causes a temporary reduction in growth velocity in prepubertal children . The result ing decrease in attained height 1 to 4 years after the initiation of inhaled glucocorticoids is thought not to decrease attained adult height . METHODS We measured adult height  in 943 of 1041 participants ( 90.6 % ) in the Childhood Asthma Management Program ; adult height was determined at a mean ( ±SD ) age of 24.9±2.7 years . Starting at the age of 5 to 13 years , the participants had been r and omly assigned to receive 400 μg of budesonide , 16 mg of nedocromil , or placebo daily for 4 to 6 years . We calculated differences in adult height for each active treatment group , as compared with placebo , using multiple linear regression with adjustment for demographic characteristics , asthma features , and height at trial entry . RESULTS Mean adult height was 1.2 cm lower ( 95 % confidence interval [ CI ] , -1.9 to -0.5 ) in the budesonide group than in the placebo group ( P=0.001 ) and was 0.2 cm lower ( 95 % CI , -0.9 to 0.5 ) in the nedocromil group than in the placebo group ( P=0.61 ) . A larger daily dose of inhaled glucocorticoid in the first 2 years was associated with a lower adult height ( -0.1 cm for each microgram per kilogram of body weight ) ( P=0.007 ) . The reduction in adult height in the budesonide group as compared with the placebo group was similar to that seen after 2 years of treatment ( -1.3 cm ; 95 % CI , -1.7 to -0.9 ) . During the first 2 years , decreased growth velocity in the budesonide group occurred primarily in prepubertal participants . CONCLUSIONS The initial decrease in attained height associated with the use of inhaled glucocorticoids in prepubertal children persisted as a reduction in adult height , although the decrease was not progressive or cumulative . ( Funded by the National Heart , Lung , and Blood Institute and the National Center for Research Re sources ; CAMP Clinical Trials.gov number , NCT00000575 . ) Although current national guidelines suggest combination inhaled corticosteroid/long-acting inhaled beta2-agonist as the preferred treatment in moderate and severe persistent asthma for children , trials aim ed at reducing emergency department ( ED ) visits and hospitalizations in minority inner-city children have not been conducted with the combination product of fluticasone/salmeterol via Diskus ( Advair ) . This study assessed the effect of fluticasone/salmeterol combination via Diskus therapy on hospitalizations and ED visits in children with asthma . We conducted a prospect i ve 1-year study with an intervention group compared with a usual care control group . This study took place at an inner-city university-affiliated children 's medical center allergy clinic . Inner-city patients with asthma aged 4 - 17 years with a history of frequent ED visits and hospitalizations for the 2 previous years were enrolled beginning in July 2001 . A control group of inner-city asthmatic patients was identified via hospital medical records . Patients were prescribed fluticasone/salmeterol combination via Diskus ( n = 39 ) for 1 year and were compared with a usual care control group ( n = 39 ) . Although the investigators did not intervene in the control patients , review of their records revealed that all control patients had inhaled corticosteroids prescribed during the intervention period . Outcome measures included ED visits and hospitalizations for 1 year after enrollment versus the mean for acute care visits for 2 years before enrollment in the study . The intervention group had a 20 % reduction in ED visits , which was significant compared with the control group ( p = 0.017 ) ; both groups had significant reductions in hospitalizations . The risk of experiencing an asthma exacerbation ( ED visit or hospitalization ) was reduced by 33 % in the intervention group compared with the control group ( risk ratio , 0.67 ; 95 % confidence interval , 0.49 - 0.90 ; p = 0.005 ) . Our results suggest that fluticasone/salmeterol combination via Diskus is associated with a reduction in risk of acute exacerbations of asthma in inner-city children , including ED visits and hospitalizations RATIONALE Corticosteroids are the antiinflammatory treatment of choice in asthma . Treatment guidelines are mainly symptom-driven but symptoms are not closely related to airway inflammation . The fraction of nitric oxide in exhaled air ( FENO ) is a marker of airway inflammation in asthma . OBJECTIVE We evaluated whether titrating steroids on FENO improved asthma management in children . METHODS Eighty-five children with atopic asthma , using inhaled steroids  , were allocated to a FENO group ( n=39 ) in which treatment decisions were made on both FENO and symptoms , or to a symptom group ( n=46 ) treated on symptoms only .  Children were seen every 3 months over a 1-year period . MEASUREMENTS Symptoms were scored during 2 weeks before visits and 4 weeks before the final visit . FeNO was measured at all visits , and airway hyperresponsiveness and FEV1 were measured at the start and end of the study . Primary endpoint was cumulative steroid dose . RESULTS Changes in steroid dose from baseline did not differ between groups . In the FENO group , hyperresponsiveness improved more than in the symptom group ( 2.5 vs. 1.1 doubling dose , p=0.04 ) . FEV1 in the FENO group improved , and the change in FEV1 was not significantly different between groups . The FENO group had 8 severe exacerbations versus 18 in the symptom group . The change in symptom scores did not differ between groups . FENO increased in the symptom group ; the change in FENO from baseline differed between groups ( p=0.02 ) . CONCLUSION In children with asthma , 1 year of steroid titration on FENO did not result in higher steroid doses and did improve airway hyperresponsiveness and inflammation BACKGROUND We previously showed that H1-antihistamines may shift the PC20 ( provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20 % ) threshold to adenosine monophosphate ( AMP ) challenge but may paradoxically prolong recovery . OBJECTIVES To measure AMP recovery using a constant predetermined AMP PC20 and to evaluate whether fexofenadine use confers add-on effects to treatment with either fluticasone propionate alone or combined fluticasone propionate-salmeterol . METHODS Fourteen atopic patients with mild-to-moderate asthma ( forced expiratory volume in 1 second of 76 % ) completed a double-blind , r and omized , crossover study consisting of 3-week treatment blocks of either fluticasone propionate-salmeterol , 250 microg twice daily , or fluticasone propionate alone , 250 microg twice daily , in conjunction with either fexofenadine , 180 mg once daily , or matched placebo .  Recovery after a predetermined AMP PC20 challenge was measured ( primary outcome ) , along with exhaled nitric oxide levels , plasma eosinophil cationic protein levels , peripheral eosinophil counts , pulmonary function , diary card outcomes , and quality of life ( all secondary outcomes ) . RESULTS There were no differences in any of the primary or secondary outcomes when fexofenadine was added to treatment with either fluticasone propionate-salmeterol or fluticasone propionate alone . The mean AMP recovery time was 25.0 vs 23.4 minutes for fexofenadine and placebo , respectively , as add-on to fluticasone-salmeterol and 22.5 vs 23.9 minutes , respectively , as add-on to fluticasone alone . CONCLUSION Fexofenadine did not affect recovery to a fixed dose of AMP challenge or any other surrogate inflammatory markers when given as add-on therapy to corticosteroid-treatedatopic asthmatic patients OBJECTIVES The long-acting beta2-adrenergic agonist salmeterol prevents exercise-induced asthma , but tolerance may develop to its bronchoprotective effect . We wanted to ascertain if the development of tolerance could be prevented by using a low-dose treatment regimen of 50 microg once daily , instead of the usual dose of 50 microg twice daily , in adolescents receiving regular glucocorticoid inhalations . Methods . In a r and omized , double-blind , 2x28-day crossover study , we administered salmeterol ( 50 microg ) or placebo once daily via a metered-dose inhaler and Nebulizer Chronolog device to monitor compliance . Exercise challenge tests were performed 1 and 9 hours after salmeterol or placebo inhalation on the 1st and 28th day of each treatment period . The primary outcome variable was the maximum decrease in percent predicted FEV1 postexercise . RESULTS Fourteen subjects with a mean age of 13.1 years completed the study . The first dose of salmeterol had an excellent bronchoprotective effect against exercise-induced asthma at 1 and 9 hours . After the 28th consecutive daily dose of salmeterol , the bronchoprotective effect was significantly greater than that of placebo at 1 hour , but not at 9 hours . CONCLUSIONS We conclude that a single 50-microg dose of salmeterol has an excellent protective effect against exercise-induced asthma for at least 9 hours , but that this effect may wane during regular once-daily salmeterol treatment , despite the reduced frequency of dosing and despite concomitant use of inhaled glucocorticoids AIMS To determine the role of formoterol in the treatment of children with bronchial asthma who are symptomatic despite regular use of inhaled corticosteroids . METHODS A r and omised , double blind , parallel group , placebo controlled study to investigate the effects of inhaled formoterol ( 12 μg twice a day ) in 32 children with moderate to severe bronchial asthma . The study consisted of two week run in periods and six week treatment periods , during both of which the patients continued their regular anti-inflammatory drugs . The efficacy parameters were symptom scores , bronchodilator use , daily peak expiratory flow rates ( PEFR ) , methacholine hyper-reactivity , forced expiratory volume in one second ( FEV1 ) , lung volumes , and airway conductance . RESULTS Formoterol treatment for six weeks decreased symptom scores , PEFR variability , and the number of rescue salbutamol doses , and increased morning and evening PEFR significantly . No adverse reactions were seen . CONCLUSION These findings suggest that inhaled formoterol is effective in controlling chronic asthma symptoms in children who are symptomatic despite regular use of inhaled corticosteroids BACKGROUND The choice of treatment can have a major impact on the total costs associated with asthma care . OBJECTIVE To determine the relative cost-effectiveness of twice-daily treatment with inhaled fluticasone propionate-salmeterol via Diskus , 100/50 microg , with that of once-daily treatment with oral montelukast as initial maintenance therapy in patients with persistent asthma uncontrolled with a short-acting beta2-agonist alone . METHODS Data from a r and omized , double-blind , double-dummy , 12-week clinical trial were analyzed . Efficacy end points included ( 1 ) symptom-free days ( SFDs ) during the 12-week period and ( 2 ) a 12 % or greater increase in forced expiratory volume in 1 second ( FEV1 ) from baseline . The economic analysis was performed from a payer 's perspective , and hence only direct costs were included in the analysis . The incremental cost-effectiveness ratio ( ICER ) , which is the mean difference in average costs divided by the mean difference in average effectiveness , was calculated for both effectiveness outcomes ( SFDs and FEV1 ) . RESULTS For the SFDs end point , the ICER for fluticasone propionate-salmeterol vs montelukast was $ 2.87 ( 95 % confidence interval , -$1.08 to $ 6.65 ) , indicating that it costs , on average , an extra $ 2.87 per day for an additional SFD with fluticasone propionate-salmeterol than with montelukast . With regard to FEV1 , the ICER was $ 1.79 ( 95 % confidence interval , -$0.72 to $ 3.86 ) , indicating that it costs , on average , an extra $ 1.79 per day to achieve a lung function improvement of 12 % or greater from baseline with fluticasone propionate-salmeterol than with montelukast . At a widely acceptable ceiling ratio of $ 9.95 per day , the probability of fluticasone propionate-salmeterol being more cost-effective than montelukast was 99.8 % for SFDs and was almost 100 % for an FEV1 improvement of 12 % of greater . CONCLUSIONS Treating 2 main components of asthma , inflammation and smooth muscle dysfunction , using fluticasone propionate-salmeterol is more cost-effective than using a single mediator antagonist alone , such as montelukast , as initial maintenance therapy for persistent asthma in patients treated with a short-acting beta2-agonist only BACKGROUND Exercise-induced bronchoconstriction occurs in a large proportion of children with asthma , limiting everyday activities important for their physical and social development . OBJECTIVE The purpose of this r and omized , double-blind , placebo-controlled study was to compare the ability of different patterns of antiasthmatic treatment , recommended in childhood asthma , to protect patients from exercise-induced bronchoconstriction . METHODS Children 6 to 18 years of age with atopic asthma were r and omized to a 4-week , placebo-controlled , double-blind trial . Patients were r and omly allocated to receive daily 200 microg budesonide ( twice daily , 100 microg per dose ) + 9 microg formoterol ( twice daily , 4.5 microg per dose ; n = 20 ) ; 200 microg budesonide + 5 or 10 mg montelukast ( once daily at bedtime ; n = 20 ) ; 5 or 10 mg montelukast ( n = 20 ) ; 200 microg budesonide ( n = 20 ) ; or placebo ( n = 20 ) . A st and ardized treadmill exercise challenge was performed before and after treatment . RESULTS Exercise-induced bronchoconstriction , reflected by area under the curve for the FEV1 values from exercise over the 20-minute period and by maximum percent fall in FEV1 after exercise , was significantly diminished after 4 weeks in all active treatment groups , and compared with placebo . Exercise-induced bronchoconstriction protection improved more significantly in the budesonide + montelukast and montelukast groups compared with other therapeutic options . CONCLUSION These data indicate differences in effects on exercise-induced bronchoconstriction between therapeutic options recommended in childhood asthma . Control of childhood asthma with exercise-induced bronchoconstriction can be obtained by using regular controller treatment STUDY OBJECTIVES Subjects with atopic asthma often experience a disappearance of symptoms around puberty . However , airway inflammation and remodeling may persist . It is unknown whether those findings warrant prolonged anti-inflammatory treatment despite the absence of symptoms . In this study , we investigated whether a short course of combined anti-inflammatory treatment would , also in this specific patient population , diminish airway inflammation and /or remodeling . DESIGN A double-blind , r and omized placebo-controlled trial was conducted in 28 asymptomatic subjects with a history of atopic asthma , with established bronchial hyperresponsiveness to methacholine ( MCh ) as non-invasive indicator of ongoing airway pathology . INTERVENTIONS Intervention consisted of the salmeterol/fluticasone propionate combination ( SFC ) product ( 50/250 microg bid via the Diskus inhaler ) or placebo for 3 months . MEASUREMENTS The change in lung function ( FEV1 ) , bronchial response to MCh and adenosine monophosphate ( AMP ) , the fraction of nitric oxide in exhaled air ( FENO ) and quality of life ( QOL ) scores were measured . Also , bronchial biopsies were taken and cryo sections immunostained for eosinophils ( major basic protein , MBP ) and mast cells ( tryptase and chymase ) before and after treatment . The change in reticular basement membrane ( RBM ) thickness , one of the parameters of airway remodeling , was also determined . RESULTS SFC treatment improved hyperresponsiveness to MCh ( P = 0.014 ) as well as AMP ( P = 0.011 ) , and reduced FENO ( P < 0.001 ) significantly as compared with placebo . Lung function tended to improve ( NS ) . Furthermore , SFC treatment reduced tryptase in the subepithelium of bronchial biopsy specimens ( P = 0.01 ) , and slightly reduced RBM thickness ( P = 0.05 ) . However , eosinophils in (sub)epithelium were not significantly affected ; neither were chymase levels , blood eosinophils or QOL scores . CONCLUSIONS We found that 3 months of treatment with fluticasone propionate and salmeterol reduced airway hyperresponsiveness , FENO and tryptase density in the airway mucosa as markers of airway inflammation . MBP density in the airway mucosa and QOL were , however , unchanged . The clinical relevance of these findings , especially with respect to the long-term outcome , has not been determined yet Lung function is commonly used as the primary endpoint in asthma clinical trials , but it may not reflect changes which are important to patients . The present study compared changes in , and relationships between , traditional and patient-centred end-points during treatment with three classes of asthma medication . Subjects with mild-to-moderate asthma were r and omised to double-blind , double-dummy crossover treatment with eformoterol 12 µg b.i.d . or montelukast 10 mg q.d . , then single-blind treatment with fluticasone 250 µg b.i.d./placebo capsules , with 6-week treatment periods and 1-week washouts .  Individual “ traditional ” end-points ( symptoms , reliever use , forced expiratory volume in one second per cent predicted , morning peak expiratory flow , airway hyperresponsiveness ) and “ patient-centred ” end-points ( asthma control question naire , quality of life , patient global assessment s ) were assessed . Principal component analysis and linear modelling were used to explore overall rank orders for treatment , and relationships between outcomes . A total of 58 subjects were r and omised . The rank order of benefit from eformoterol and fluticasone differed for three factors derived from principal component analysis ( eformoterol > fluticasone for symptom/reliever use factor , fluticasone > eformoterol for lung function factor , eformoterol = fluticasone for patient-centred factor ) . Montelukast was ranked third for all three factors . A significant relationship between patient-based variables and lung function was found only for montelukast treatment . In asthma treatment , traditional end-points do not fully capture patient-centred benefits , and the relationship between end-points differs with medication class QUESTIONS UNDER STUDY if patients with asthma remain symptomatic in spite of chronic treatment with inhaled corticosteroids ( ICS ) , increasing the ICS dosage or adding another drug to the treatment regimen are possible therapeutic alternatives . We compared the efficacy and safety of combined salmeterol fluticasone therapy ( SFC , 50/250 microg twice daily ) with twice the dose of fluticasone propionate ( FP , 500 microg b.i.d . ) in symptomatic asthmatics . METHODS this prospect i ve , double-blind study was conducted in 76 study centres . 365 symptomatic patients with moderate asthma aged > 18 years and receiving ICS in a dose equivalent to 1000 microg beclomethasone propionate per day were r and omly assigned to receive either salmeterol xinafoate ( 50 microg ) and fluticasone propionate ( 250 microg ) in a single dry powder inhaler ( Diskus ) or 500 microg FP twice daily . The primary efficacy endpoint was morning peak expiratory flow rate ( PEFR ) . Secondary measurements included forced expiratory volume in 1 second ( FEV1 ) , asthma symptom scores , and use of rescue medication . RESULTS combined salmeterol fluticasone therapy result ed in significantly greater improvements in PEFR and symptom control than doubling the dose of FP . At week 12 , morning PEFR had increased by 52 L/min from baseline in patients on SFC and by 36 L/min in subjects receiving FP . The adjusted difference between groups was 16.6 L/min ( 95 % confidence interval , 1.1 to 32.0 L/min ) . In the SFC group , the percentage of symptom-free days increased from baseline by 49 % of days as compared with 38 % of days after FP ( adjusted difference : 12.6 % of days , 95 % CI 4.0 to 20.7 ) . Quality of life improved to a greater degree after SFC therapy , and patients regarded study drugs as superior to their previous asthma medication . Adverse event profiles were similar between groups . CONCLUSIONS the combination of salmeterol 50 microg and fluticasone 250 microg in a single dry powder inhaler was superior to twice the dose of FP ( 500 microg ) . It seems justified to add salmeterol rather than increasing the ICS dose if symptomatic asthmatics require supplementary therapy To compare the dose-related bronchodilator efficacy and tolerability of formoterol ( Oxis ) Turbuhaler with salmeterol Diskhaler and placebo in children with asthma . A single-dose , r and omized , double-blind , incomplete crossover study of 68 children ( 7 - 17 years ) , with moderate-to-severe asthma , 82 % receiving inhaled corticosteroids .  Patients received four of six treatments [ 4.5 , 9 , 18 , or 36 microg formoterol ( 6 , 12 , 24 or 48 microg metered doses ) , 50 microg salmeterol ( metered dose ) or placebo ] at 12-h visits , separated by > or =3 days . Forced expiratory volume in 1 s ( FEV1 ) , pulse , blood pressure , electrocardiogram , adverse events and urine formoterol  were assessed . The therapeutic ratio of formoterol vs. salmeterol was estimated from the efficacy and systemic effects results . All active treatments significantly improved FEV1 compared with placebo . Formoterol 9 - 36 microg provided dose-related increases over salmeterol in lung function : average 12-h FEV1 ( increases of 4.9 - 8.7 % , p < 0.001 ) and FEV1 at 12 h post-dose ( 7.0 - 12.2 % , p < 0.001 ) . The onset of effect of formoterol was also significantly faster than salmeterol for doses > or = 9 microg . Salmeterol 50 microg was estimated to be equieffective to 3.3 microg formoterol for 12-h average FEV1 and the estimated equieffective dose for a variety of systemic effects was 7.8 - 13.5 microg formoterol . All treatments were well tolerated .  Formoterol ( Oxis ) Turbuhaler 4.5 - 36 microg provided dose-related improvements in bronchodilator efficacy in children with asthma . Formoterol > or = 9 microg provided superior bronchodilator efficacy over 12 h compared with salmeterol Diskhaler 50 microg with no increase in systemic effects Abstract Objectives : To compare the costs and effectiveness of adjustable maintenance dosing with budesonide/formoterol in a single inhaler versus fixed dosing in adults with asthma . Methods : In this prospect i ve , r and omised , open-label , parallel-group , multicentre trial conducted in Germany , patients with asthma received budesonide/formoterol 160µg/4.5 µg in a single inhaler ( Symbicort ® Turbuhaler ® ) with two inhalations twice daily for a 4-week run-in period . Patients were then r and omised to either adjustable maintenance dosing ( one inhalation twice daily , stepping up to four inhalations twice daily for 1 week if asthma worsened ; n = 1679 ) or fixed dosing ( two inhalations twice daily ; n = 1618 ) for 12 weeks . The primary efficacy variable was the change in health-related quality of life ( HR-QOL ) , measured using the Asthma Quality of Life Question naire ( st and ardised ) during the r and omised treatment period . Re source utilisation data were collected in parallel and combined with German unit costs to estimate direct and indirect costs ( year 2001 values ) . Results : Both treatment regimens were equally effective in maintaining HR-QOL and asthma control during the r and omised treatment period . However , overall , patients in the adjustable maintenance dosing group took fewer daily inhalations of budesonide/formoterol  than those in the fixed-dosing group ( mean : 2.63 vs 3.82 inhalations ; p < 0.001 ) . Adjustable maintenance dosing was associated with significantly lower asthma-related direct costs  compared with fixed dosing ( mean : € 221 vs € 292 ; p < 0.001 ) . This pattern was maintained when patients were stratified into those with peak expiratory flow ( PEF ) of 60 % to < 80 % predicted normal and those with PEF of ≥80 % predicted normal and when total costs were considered . Conclusion : Adjustable maintenance dosing with budesonide/formoterol in a single inhaler maintained HR-QOL in adult patients with asthma at a significantly lower cost than fixed dosing SUMMARY Background : Budesonide/formoterol in a single inhaler is an effective therapy for asthma . We investigated whether adjustable maintenance dosing with budesonide/formoterol could maintain health-related quality of life ( HRQL ) and asthma control . Patients / methods : Asthma patients ( n = 4025 ) received budesonide/formoterol ( Symbicort * 160/4.5 µg ) 2 inhalations twice daily ( bid ) for 4 weeks during run-in of this open , multicentre study . Patients were r and omised to adjustable dosing ( budesonide/formoterol 1 inhalation bid ; stepping up to 2 or 4 inhalations bid for 1 week if asthma worsened ) or fixed dosing ( budesonide/formoterol 2 inhalations bid ) , for 12 weeks . Change in HRQL ( st and ardised Asthma Quality of Life Question naire , AQLQ[S ] , score ) during r and omised treatment was the primary efficacy variable . Secondary variables included asthma control ( peak expiratory flow [ PEF ] , symptom-severity score , nocturnal awakenings , reliever-medication use ) and study -medication intake . Results : Clinical ly significant ( ≥ 0.5 ) improvements in AQLQ(S ) score ( mean 0.73 ) , morning and evening PEF ( mean 42.5 and 24.8 L/min , respectively ) , and symptom-severity score ( mean 0.36 ) were achieved during run-in . The improvements were maintained in both groups although , overall , adjustable-dosing patients took fewer daily inhalations of budesonide/formoterol than fixed-dosing patients ( mean 2.63 versus 3.82 , p < 0.001 ) . Conclusion : Adjustable maintenance dosing with budesonide/formoterol  maintains HRQL and asthma control as effectively as fixed dosing and is associated with a reduced drug load overall 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 Current UK and international guidelines on asthma management recommend that , in pediatric patients still symptomatic on treatment with high-dose inhaled corticosteroids , consideration should be given to the introduction of regular twice daily long-acting beta 2-agonists . OBJECTIVE The purpose of this study was to assess the efficacy and safety of inhaled salmeterol xinafoate 50 micrograms bid via the Diskhaler when added to the existing treatment of children with moderate to severe asthma . METHODS A 12-week multicenter , double-blind , placebo-controlled , parallel group study was conducted at 78 hospital centers throughout the United Kingdom , involving 210 asthmatic children aged between 4 and 16 years of age .  Morning peak expiratory flow ( PEF ) , evening PEF , night-time and daytime symptoms and relief medication usage were recorded daily by the patient or parent over a 12-week treatment period . RESULTS Compared with placebo , the addition of salmeterol xinafoate to existing high dose inhaled corticosteroid treatment significantly improved mean morning PEF expressed as percent predicted ( PEF-PP ) during the first 4 weeks of treatment ( median increase 6.5 percentage points P < .001 ) . This effect persisted throughout the 12-week treatment period ( P < .05 ) . Both groups demonstrated an overall improvement in mean morning PEF-PP , 7.5 percentage points for salmeterol xinafoate and 4 percentage points for placebo .  The mean evening PEF-PP followed a similar although less pronounced trend which was significant only during the first 4 weeks of treatment ( P = .014 ) . Daytime relief medication and recorded symptoms were reduced significantly in both groups . There was a greater improvement in the number of symptom-free days during the first 4 weeks ( P < .01 ) and the last 4 weeks ( P < .05 ) of treatment for salmeterol xinafoate . The overall incidence and nature of minor adverse events was similar in both groups . CONCLUSIONS This study demonstrates that the addition of salmeterol xinafoate to inhaled corticosteroid therapy in symptomatic asthmatic children significantly improves morning PEF-PP , and reduces their symptoms and use of relief medication Asthma control is improved by combining inhaled corticosteroids with long-acting beta2-agonists . However , fluctuating asthma control still occurs . We hypothesized that in patients receiving low maintenance dose budesonide/formoterol ( bud/form ) , replacing short-acting beta2-agonist ( SABA ) reliever with as-needed bud/form would provide rapid symptom relief and simultaneous adjustment in antiinflammatory therapy , thereby reducing exacerbations . In this double-blind , r and omized , parallel-group study , 2,760 patients with asthma aged 4 - 80 years ( FEV1 60 - 100 % predicted ) received either terbutaline 0.4 mg as SABA with bud/form 80/4.5 microg twice a day ( bud/form + SABA ) or bud 320 microg twice a day ( bud + SABA ) or bud/form 80/4.5 microg twice a day with 80/4.5 microg as-needed ( bud/form maintenance + relief ) . Children used a once-nocte maintenance dose . Bud/form maintenance + relief prolonged time to first severe exacerbation ( p < 0.001 ; primary endpoint ) , result ing in a 45 - 47 % lower exacerbation risk versus bud/form + SABA ( hazard ratio , 0.55 ; 95 % confidence interval , 0.44 , 0.67 ) or bud + SABA ( hazard ratio , 0.53 ; 95 % confidence interval 0.43 , 0.65 ) . Bud/form maintenance + relief also prolonged the time to the first , second , and third exacerbation requiring medical intervention ( p < 0.001 ) , reduced severe exacerbation rate , and improved symptoms , awakenings , and lung function compared with both fixed dosing regimens Safety concerns have been raised regarding the regular use of long-acting beta(2)-adrenergic agonists ( LABAs ) alone or with inhaled corticosteroids ( ICSs ) . The purpose of this study was to examine the long-term safety of budesonide/formoterol pressurized metered-dose inhaler ( pMDI ) . This 52-week , double-blind study ( SD-039 - 0728 ; n=708 ) included patients > or=12 years of age with moderate to severe persistent asthma previously receiving ICSs .  After 2 weeks on budesonide pMDI 320 microg twice daily ( b.i.d . ) , patients were r and omized 3:1:1 overall to budesonide/formoterol pMDI 640/18 microg b.i.d . , budesonide/formoterol pMDI 320/9 microg b.i.d . , or budesonide pMDI 640 microg b.i.d . The incidence of adverse events ( AEs ) was similar across the groups . Drug-related AEs ( > or=2 % overall ) were oral c and idiasis , tremor , and pharyngolaryngeal pain . No clinical ly meaningful differences in laboratory , electrocardiogram , or Holter monitor variables were observed . The percentage of patients with > or=1 asthma exacerbation was significantly lower ( p=0.006 ) with budesonide/formoterol 640/18 ( 12.2 % ) and numerically lower with budesonide/formoterol 320/9 ( 14.4 % ) versus budesonide ( 21.8 % ) . The number of asthma exacerbations per patient-treatment year was lower with budesonide/formoterol 640/18 ( 0.174 ; p=0.004 ) and budesonide/formoterol 320/9 ( 0.185 ; p=0.049 ) versus budesonide ( 0.315 ) . Improvements in forced expiratory volume in 1 second and diary variables were significantly greater ( p<0.001 ) with both budesonide/formoterol doses versus budesonide . Budesonide/formoterol 640/18 and 320/9 microg b.i.d . showed an acceptable safety profile relative to budesonide , with no significant or unexpected patterns of abnormalities observed by adding a LABA to budesonide for up to 1 year in this patient population . Improvements in asthma control were shown with both doses of budesonide/formoterol versus budesonide Few studies have evaluated inhaled corticosteroid (ICS)/long-acting beta(2)-adrenergic agonist combination therapy in asthmatic children . This study was design ed to evaluate the safety ( primary ) and clinical benefits ( secondary ) of budesonide/formoterol pressurized metered-dose inhaler ( pMDI ) versus budesonide dry powder inhaler ( DPI ) in children with persistent asthma . This was a 26-week , multicenter , r and omized , open-label U.S. study of 187 children 6 - 11 years of age previously receiving ICS .  After 1 week of usual ICS therapy , subjects received twice-daily budesonide/formoterol pMDI 160/4.5 micrograms x 2 inhalations ( 320/9 micrograms ; n = 124 ) or budesonide DPI 200 micrograms x 2 inhalations ( 400 micrograms [ 320 micrograms delivered ex-mouthpiece ] ; n = 63 ) . Budesonide/formoterol and budesonide were well tolerated with a similar incidence of adverse events ( AEs ) ( 84.6 % and 85.7 % , respectively ) , most of mild or moderate intensity . Treatment-related AE incidence was low ( 5.4 % ) and similar across groups ( budesonide/formoterol , 4.9 % ; budesonide , 6.3 % ) . No clinical ly important treatment differences were observed for 12-lead electrocardiograms , hematology , serum glucose and potassium , and 24-hour urinary cortisol . Compared with budesonide , budesonide/formoterol decreased health care use ( urgent care visits and interference with daily activities [ child ] or work [ caregiver ] ; p < or = 0.012 ) and improved health-related quality of life ( Pediatric Asthma Quality of Life Question naire [ st and ardized ] and Pediatric Asthma Caregiver Quality of Life Question naire overall scores ; p < or = 0.006 ) and pulmonary function ( predose forced expiratory volume in 1 second and forced expiratory flow during the middle half of exhalation ; p < or = 0.007 ) . In this 26-week study of asthmatic children ( 6 - 11 years ) , safety profiles were similar and clinical benefits were greater with budesonide/formoterol than with budesonide This was a 3-year " real-life " study , during which patients ' medication was increased and decreased to achieve sustained asthma control .  Patients ( 282 ) were r and omised to receive treatment with SAL 50microg , FP 250microg , or SFC 50/250microg via a Diskustrade mark inhaler , bid . A 12-month double-blind period was followed by a 2-year open phase . The physician increased or decreased patients ' medication to achieve and maintain asthma control at regular clinical assessment s using criteria based on the asthma treatment guidelines . On completion 73 % ( 168/229 ) of the subjects were receiving SFC to maintain control of their asthma , compared with 21 % ( 49/229 ) receiving FP and 5 % ( 12/229 ) receiving SAL . Odds ratio for requiring increased treatment were 2.66 ( p=0.002 ) for patients initially r and omised to FP and 9.38 ( p<0.0001 ) SAL , compared with SFC . Time until 25 % of patients first required an increase in study medication was 6months for patients initially treated with SAL compared to 12months for FP and 21months for SFC . Symptoms and use of rescue medication improved first , followed rapidly by PEF with the greatest improvements occurring over the first year . Airway hyperresponsiveness continued to improve throughout the study . The majority of patients achieved and maintained control of asthma over a 3-year period with physician-driven medication changes . Patients treated with SFC were more likely to achieve control than patients treated with FP or SAL alone . Continuing improvements in airway hyperresponsiveness indicate the importance of maintaining treatment after clinical control of symptoms and lung function are achieved RATIONALE In asthmatic children whose symptoms are uncontrolled on st and ard doses of inhaled corticosteroids ( ICS ) , guidelines recommend to either increase the ICS dose or to add further controller medication , e.g. a long acting ss2-agonist ( LABA ) . The aim of this study was to compare the efficacy and safety of doubling the dose of ICS ( fluticasone proprionate FP 200 microg twice daily ) with adding a long-acting beta-2 agonist to the ICS ( SFC , salmeterol 50 microg/ FP 100 microg twice daily ) in children with uncontrolled asthma . METHODS Children between 4 and 16 years of age were eligible for this multicenter , r and omized , double blind , double dummy , parallel-group study . During a 14-day run-in phase , all children inhaled FP 100 microg b.i.d . Patients with persistent symptoms on > or = 7 of 14 days were r and omized to 8 weeks treatment with a Diskus(R ) containing either SFC 50 microg/100 microg b.i.d . or FP 200 microg b.i.d .. The primary endpoint was the mean change in morning ( a.m. ) PEF from baseline . The initial statistical hypothesis of non-inferiority of SFC vs. FP was confirmed in an adaptive interim analysis , so that the study was terminated prematurely . RESULTS 441 patients from 39 centers entered the run-in phase , and 64 % of these were r and omized to treatment ( N = 138 to SFC and N = 145 to FP ) . After 8 weeks , patients on SFC had significantly better results for primary and secondary endpoints : The mean increase in morning PEF was 30.4 + /- 34.1 L/min in the SFC group and 16.7 + /- 35.8 L/min in the fluticasone group , and the mean ( 95 % CI ) improvement from baseline a.m. PEF in the ITT group was significantly larger after SFC ( + 8.6 L/min , CI : [ 1.3 ; infinity ] ) . Patients in the SFC group experienced 8.7 % ( CI : [ 1.2;16.3 ] ) more days without asthma symptoms and 8.0 % ( CI : [ 0.6;15.3 ] ) more days without salbutamol than patients receiving FP . Good asthma control was achieved for a longer period in the SFC ( 3.4 + /- 2.7 weeks ) group than in the FP group ( 2.7 + /- 2.7 , P = 0.02 ) . Both treatments were generally well tolerated . Asthma exacerbations were recorded in 3 and 6 and SAEs in 2 and 1 patients from the SFC and FP groups , respectively . CONCLUSIONS In children with persistent asthma inadequately controlled on low dose ICS alone , adding a long acting beta-2-agonist to ICS in a single inhaler was more effective than doubling the ICS dose . These results support recommendations of adding LABA to low-dose ICS as the preferred controller option for children older than 4 years with symptomatic asthma BACKGROUND Pulmonary function tests ( PFTs ) and especially spirometry measures are useful tools in evaluating early response to treatment of asthma in children mainly due to their worldwide availability . The aim of our study was to determine the effects of anti-asthma treatment in children , equally on FEV(1 ) , FEF25 - 75 % , R(int ) and SR(aw ) values . METHODS Children 6 - 18 years of age with moderate atopic asthma were r and omized to 4-week , placebo-controlled , double-blind trial . Patients were r and omly allocated to receive 200 microg budesonide ( B ) ( n=29 ) , 5 or 10 mg ( according to age ) montelukast ( M ) ( n=29 ) , 200 microg B + 5 or 10 mg M ( n=29 ) , 200 microg B + 9 microg formoterol ( F ) ( n=29 ) or placebo ( n=27 ) . FEV(1 , ) FEF25 - 75 % , R(int ) , SR(aw ) were measured before and after treatment . RESULTS R(int ) , SR(aw ) , FEV(1 ) improved significantly in all active treatment groups while FEF25 - 75 % improved significantly only in BM group and M group . Combination therapy , showed significantly greater effects on R(int ) than monotherapy : BM group compared to B group ( P=0.01 ) and M group ( P=0.03 ) and BF group compared to B group ( P=0.01 ) and M group ( P=0.04 ) . CONCLUSION This study shows that using single parameter for monitoring asthma can be misleading . Using combination of lung function techniques provides better assessment of treatment . Results of our study confirm this hypothesis . The best effect on large and small airways was achieved with combined anti-inflammatory therapy OBJECTIVE To study the effectiveness and safety of as-needed treatment of formoterol compared with the short-acting alternative terbutaline . METHODS Two double-blind , 12-month , parallel-group , non-inferiority trials comparing as-needed use of formoterol ( Oxis ) 4.5 microg and terbutaline ( Bricanyl ) 0.5 mg via dry-powder inhaler ( Turbuhaler ) , one in 675 patients with intermittent and one in 455 patients with mild persistent asthma , overall 6 - 87 years of age .  Peak expiratory flow ( PEF ) , symptoms , rescue medication use , exacerbations , airway responsiveness ( metacholine challenge ; subgroup of 127 patients ) , systemic effects ( high single-dose test ; subgroup of 87 patients ) , and safety ( adverse events ) were assessed . RESULTS Formoterol 4.5 microg was as effective as terbutaline 0.5 mg with regard to morning PEF ( non-inferiority ; lower 95 % confidence interval limit above -10 L/min ) . Metacholine sensitivity , exacerbation rates or use of rescue medication did not differ between treatments . Formoterol 54 microg was shown to give less systemic effects than terbutaline 6 mg . Both treatments were safe and well tolerated . CONCLUSIONS Formoterol 4.5 microg used as needed was at least as effective and safe as terbutaline 0.5 mg used as needed in intermittent and mild persistent asthma , and was associated with less systemic effects when administered as high single doses In sensitive asthmatic children , the exposure to relevant allergens causes a deterioration of lung function and symptoms associated with an increase of inflammatory indices . The aim of this single-blind r and omized add-on study was to compare the effects of montelukast or formoterol added to low-dose budesonide in asthmatic allergic children exposed to relevant allergens . Twenty children ( 5 female subjects and 15 male subjects , aged 6 - 12 years ) were enrolled .  Lung function and airway inflammatory indices ( exhaled nitric oxide [ eNO ] and sputum eosinophils ) were evaluated at T0 when children were not exposed to relevant allergens and at T1 after 15 days of natural effective allergen exposure . At T1 , pulmonary function tests and sputum eosinophils remained stable in both of the groups , without significant differences in comparison with T0 at baseline . Furthermore , formoterol plus budesonide was effective in preventing the expected increase in eNO from 26.46 + /- 2.62 ppb at T0 to 29.33 + /- 9.28 ppb at T1 ( not significant ) . However , in the group receiving montelukast plus budesonide , there was a significant decrease of eNO from baseline ( 30.78 + /- 6.87 ppb ) to T1 ( 18.17 + /- 6.60 ppb ) ( p < .05 ) . In allergic asthmatic children , the use of montelukast or formoterol combined with budesonide could offer a durable protective effect on symptoms , lung function , and inflammatory indices The aim of this study was to evaluate the efficacy ( expressed as effect on lung function ) and tolerability of Symbicort ( budesonide/formoterol in a single inhaler ) in children with asthma . This was a double-blind , double-dummy , r and omized , parallel-group , multicenter trial . After a 2 - 4-week run-in period , 286 asthmatic children ( 177 boys , 109 girls ; mean age , 11 years ; mean forced expiratory volume in 1 sec ( FEV(1 ) ) , 75 % predicted normal ) , previously treated with inhaled corticosteroids ( average dose 548 microg/day ) , were r and omized to 12 weeks ' treatment with either budesonide/formoterol 80/4.5 microg , two inhalations twice daily ( n = 148 ) , or an equivalent dose of budesonide 100 microg , two inhalations twice daily ( n = 138 ) . Efficacy variables included morning and evening peak expiratory flow ( PEF ) , spirometery , asthma symptoms , and use of rescue medication ( beta(2)-agonists ) . Serial FEV(1 ) assessment s were carried out on a subgroup of children ( budesonide/formoterol , n = 41 ; budesonide , n = 40 ) at r and omization and at week 12 . Relative to baseline , morning PEF ( primary variable ) increased to a significantly greater extent with budesonide/formoterol than with budesonide alone ( 7.22 % predicted normal vs 3.45 % predicted normal ; P < 0.001 ) . Evening PEF also increased significantly with budesonide/formoterol ( 6.13 % predicted normal vs. 2.73 % predicted normal ; P < 0.001 ) , as did mean FEV(1 ) and serial FEV(1 ) measured over 12 hr ( both P < 0.05 ) . Similar improvements in asthma symptoms and rescue medication use were observed in both groups . The two treatment groups were similar in terms of their adverse-event profile and rates of discontinuation . Budesonide/formoterol in a single inhaler provided rapid improvements in PEF and FEV(1 ) compared to inhaled budesonide alone . These improvements were sustained throughout the study period . Budesonide/formoterol was well-tolerated in children with moderate persistent asthma BACKGROUND The role of combination ICS/LABA as initial controller therapy in mild , persistent asthma is uncertain . Therefore , the objective of this study was to compare the efficacy of initial controller therapy with fluticasone propionate ( FP ) 100 microg twice daily to the efficacy of fluticasone propionate/salmeterol xinafoate ( FSC ) 100/50 microg twice daily in patients with persistent asthma symptoms while using as-needed SABA alone . METHODS This r and omized , double-blind , parallel-group study was conducted at 45 general practice and 15 specialist centers . A total of 526 adult patients were r and omized to receive FP or FSC for 24 weeks . The primary efficacy endpoint was change in morning peak expiratory flow ( PEF ) from baseline . Secondary efficacy endpoints included symptom- and rescue-free days ; asthma exacerbation rate ; asthma-related health-care utilization ; and the onset of effect . Safety was assessed by monitoring adverse events . RESULTS Mean morning PEF was significantly greater in the FSC versus the FP group ( P<0.001 ) ; this greater effect was evident as early as the first week of treatment ( P<0.001 ) . The percentages of symptom-free days and rescue-free days in the FSC group were 7.7 % ( P=0.009 ) and 8.4 % ( P=0.001 ) higher than the FP group , respectively . Trends toward lower exacerbation-related health care-utilization for FSC versus FP were not statistically significant and exacerbation rates were not significantly different . The incidence of adverse events was low with both treatments . CONCLUSIONS : Treatment with FSC was a more effective initial controller therapy than FP monotherapy in ICS-naïve patients who had uncontrolled asthma while using as-needed SABA alone BACKGROUND Asthma guidelines recommend reducing inhaled corticosteroids ( ICS ) to the minimum effective dose , but the timing of long-acting beta(2)-agonist ( LABA ) withdrawal is unclear . Recent FDA guidelines recommend LABA withdrawal once asthma is well-controlled . This 13-month double-blind study of patients taking high-dose combination therapy investigated the effect of discontinuation of LABA before ICS down-titration . METHODS Adults using salmeterol/fluticasone combination ( SFC ) 50/500 microg bd were r and omized to SFC 50/500 microg bd or  fluticasone propionate ( FP ) 500 microg bd , with subsequent ICS down-titration 8-weekly using a clinical algorithm . The primary outcome was mean daily FP dose , including ICS for exacerbations . RESULTS 82 subjects were r and omized . Asthma was well-controlled at baseline , with mean FEV(1 ) 84.8 % predicted and Asthma Control Question naire ( ACQ ) score 0.9 . There was no significant difference in mean daily FP dose ( SFC : 721 microg , FP:816 microg , p = 0.3 ) , but final dose was lower with SFC ( 534 microg cf . 724 microg , p = 0.005 ) . ICS dose was reduced by > or=80 % in 41 % SFC and 15 % FP patients . Ambulatory lung function was significantly higher with SFC , but there were no differences between groups in rescue beta(2)-agonist use , clinic spirometry , airway responsiveness , ACQ , sputum eosinophils or FeNO . Baseline airway responsiveness , and pre-reduction blood eosinophils , were significant predictors of mean daily FP dose and dose reduction failure respectively . CONCLUSIONS Many patients prescribed high-dose combination therapy may be over-treated . Substantial reductions in dose can be achieved with a clinical algorithm , reaching lower FP doses with SFC than FP without losing asthma control or increasing disease activity . TRIAL REGISTRATION This study was commenced before m and atory registration of clinical trials The aim of the study was to compare the efficacy of the inhaled long-acting beta2-agonists eformoterol and salmeterol when added to existing inhaled corticosteroid ( ICS ) therapy in symptomatic asthmatic children . This r and omized , 12-week , parallel-group study , performed in a primary care setting , included 156 children and adolescents ( aged 6 - 17 years ) with moderate persistent asthma . Patients were r and omized to open-label eformoterol ( Oxis ) Turbohaler 9 microg ( delivered dose ) or salmeterol Accuhaler 50 microg , both b.i.d , added to current ICS . Assessment s included : changes in daytime reliever beta2-agonist therapy ( primary variable ) , total 24-h reliever use , lung function , clinic and diary symptom scores , patient and carer health-related quality of life ( HRQL ) and adverse events . Daytime reliever use decreased significantly ( p < 0.001 ) from baseline by 65 % and 52 % , respectively in the eformoterol and salmeterol treatment groups . Compared with salmeterol , eformoterol produced a greater decrease in daytime ( -0.46 inhalations/day ; p = 0.081 ) and 24-h ( -0.70 inhalations/day ; p = 0.043 ) reliever use . The percentage of patients who did not require any reliever medication during the study was significantly higher in the eformoterol group ( p < 0.05 vs. salmeterol at weeks 8 and 12 ) . Clinic and diary card peak expiratory flow and symptom measures all improved from baseline in both treatment arms . There was a significantly greater effect in favour of eformoterol for the reduction in clinic-assessed overall night-time symptoms ( p < 0.05 vs. salmeterol ) . Clinical ly relevant improvements in patient-assessed HRQL occurred during treatment with eformoterol and salmeterol , but carer-assessed HRQL was improved to a clinical ly relevant extent , only with eformoterol . Both treatments were well tolerated . In children and adolescents with moderate persistent asthma , add-on therapy with eformoterol was well tolerated and at least as effective as salmeterol SUMMARY Objectives : This study evaluated the efficacy and safety of a novel asthma management strategy – budesonide/formoterol for both maintenance and symptom relief ( Symbicort Single Inhaler Therapy * ) – compared with a higher maintenance dose of budesonide in patients with moderate to severe asthma . Methods : This was a 12-month , r and omised , double-blind , parallel-group study . Symptomatic patients with asthma ( n = 1890 ; mean age 43 years [ range 11 years–80 years ] , mean baseline forced expiratory volume in 1 s [ FEV1 ] 70 % of predicted , mean inhaled corticosteroid [ ICS ] dose 746 µg/day ) received either budesonide ( 160 µg , 2 inhalations twice daily ) plus terbutaline 0.4 mg as needed or a daily maintenance dose of budesonide/formoterol ( 160/4.5 µg , 2 inhalations once daily ) with additional inhalations of budesonide/formoterol 160/4.5 µg as needed . Time to first severe exacerbation ( hospitalisation/emergency room [ ER ] treatment or systemic steroids due to asthma worsening or a fall in morning peak expiratory flow [ PEF ] to ≤ 70 % of baseline on 2 consecutive days ) was the primary outcome variable . Results : A total of 1890 patients were r and omised , of whom 1563 ( 83 % ) had severe asthma .  The time to first severe exacerbation was prolonged by budesonide/formoterol single inhaler therapy ( p < 0.001 ) compared with a higher dose of budesonide . The risk of having a severe exacerbation was 39 % lower with budesonide/ formoterol single inhaler therapy compared with budesonide ( p < 0.001 ) . The number needed to treat to prevent one severe exacerbation per year  with budesonide/formoterol compared with budesonide was 5 . The budesonide/formoterol group had 45 % fewer severe exacerbations requiring medical intervention per patient compared with the budesonide group ( p < 0.001 ) . Budesonide/formoterol patients had fewer hospitalisations/ER treatments ( 15 vs 25 events , respectively [ descriptive statistics ] ) and fewer treatment days with systemic steroids ( 1776 days vs 3177 days , respectively [ descriptive statistics ] ) compared with budesonide patients . Budesonide/formoterol single inhaler therapy patients used less as-needed medication compared with budesonide patients ( 0.90 vs 1.42 inhalations/day ; p < 0.001 ) . The mean daily ICS dose was lower in the budesonide/formoterol group than in the budesonide group ( 466 µg/day vs 640 µg/day ) . Over the 12-month study period , the budesonide/formoterol group achieved asthma control sufficient to not require any additional as-needed medication on 60 % of days . Overall , budesonide/formoterol single inhaler therapy gave 31 more asthma control days ( a night and day with no asthma symptoms and no as-needed medication use ) per patient-year and 12 additional undisturbed nights per patient-year compared with a higher dose of budesonide . Both treatments were well tolerated . Conclusion : Budesonide/formoterol single inhaler therapy has the potential to provide a complete asthma management approach with one inhaler , demonstrating a high level of efficacy in patients with moderate to severe asthma BACKGROUND There has been concern that in allergic asthmatic patients there might be an interactive effect on inflammation between regular salmeterol use and exposure to allergens , result ing in increased airway responsiveness . OBJECTIVE To determine the effects of salmeterol on allergen-induced changes in airway responsiveness and exhaled nitric oxide ( ENO ) levels in allergic asthmatic patients concomitantly taking inhaled corticosteroids . METHODS Forty-two asthmatic patients sensitized to pollen allergens were r and omly allocated to treatment with fluticasone propionate-salmeterol ( n=21 ) or fluticasone propionate alone ( n=21 ) . Spirometry , the methacholine provocation concentration causing a 20 % decline in forced expiratory volume in 1 second ( PC20 ) , the adenosine 5'-monophosphate ( AMP ) PC20 , and ENO levels were measured before and at the height of the pollen season after 6 weeks of treatment . RESULTS Changes in the methacholine PC20 , the AMP PC20 , and ENO levels were not significantly different between treatment groups . No significant changes in the AMP PC20 were observed among the fluticasone propionate-salmeterol and fluticasone propionate groups during natural pollen exposure . However , a significant increase in the methacholine PC20 was observed in the fluticasone propionate-salmeterol group ( P = .03 ) and in the fluticasone propionate group ( P = .04 ) ; ENO concentrations decreased significantly in both groups during natural allergen exposure ( P = .009 and .005 ) . CONCLUSIONS In patients with pollen-induced asthma , treatment with either fluticasone propionate or fluticasone propionate-salmeterol is associated with significant reductions in methacholine responsiveness and ENO concentrations , even during natural pollen exposure . Furthermore , at least in patients with mild asthma , natural allergen exposure and the regular use of fluticasone propionate-salmeterol are not associated with a greater increase in ENO levels and airway responsiveness than natural allergen exposure and fluticasone propionate use alone The objective of this study was to compare the efficacy and safety of fluticasone propionate ( FP ) ( 44 µg)/salmeterol ( 21 µg ) delivered as two inhalations twice daily via a single hydrofluoroalkane ( HFA 134a ) metered dose inhaler ( MDI ) ( FSC ) with that of placebo HFA 134a ( PLA ) , fluticasone propionate 44 µg chlorofluorocarbon ( CFC ) alone and salmeterol 21 µg CFC alone ( S ) in patients ( n = 360 ) with persistent asthma previously treated with β2‐agonists ( short‐ or long‐acting ) or inhaled corticosteroids ( ICS ) . After 12 weeks of treatment , patients treated with FSC had a significantly greater increase ( p ≤ 0.006 ) in mean FEV1 AUC(bl ) compared with PLA , FP , or S. At end point , mean change from baseline in morning predose FEV1 for FSC ( 0.58 L ) was significantly ( p ≤ 0.004 ) greater than PLA ( 0.14 L ) , FP ( 0.36 L ) , and S ( 0.25 L ) . Patients treated with FSC also had a significantly higher probability of remaining in the study without being withdrawn due to worsening asthma ( 2 % ) compared with those in the PLA ( 29 % ) and S ( 25 % ) groups ( p < 0.001 ) . Finally , treatment with FSC result ed in significantly ( p ≤ 0.007 ) greater improvements in morning and evening peak expiratory flow , need for rescue albuterol , and asthma symptom scores compared with FP , S , and PLA . The safety profile of FSC was also similar to FP or S alone . Initial maintenance treatment of the two main components of asthma , inflammation , and smooth muscle dysfunction ( e.g. , bronchoconstriction ) , with FSC results in greater overall improvements in asthma control compared with treatment of either individual component alone AIMS To determine effects on short term growth and collagen turnover of adding formoterol ( Eformoterol ) to half the glucocorticoid dose in children with asthma , treated with inhaled budesonide ( Pulmicort Turbuhaler ) . DESIGN A r and omised double blind , placebo controlled crossover study with two six-week periods . SETTING Outpatient clinic in secondary referral centre . SUBJECTS A total of 27 prepubertal children aged 6–13 years . INTERVENTIONS Formoterol 12 μg and dry powder budesonide 100 μg twice daily in one period ; placebo and dry powder budesonide 200 μg twice daily in the other . OUTCOME MEASURES Primary outcome measures were lower leg growth rate , and serum and urine markers of type I and type III collagen turnover . Secondary outcome measures were inflammation markers in serum , and parameters of asthma control . RESULTS During budesonide 200 μg twice daily treatment , mean lower leg growth rate was 0.14 mm/week ( p = 0.02 ) lower than during the formoterol and budesonide period . Similar statistically significant effects on markers of collagen turnover were found , whereas inflammation markers and asthma control did not vary statistically significantly between the two periods . CONCLUSIONS In children treated with inhaled glucocorticoids  , halving the dose and adding formoterol is associated with faster short term growth and an increase in markers of collagen turnover , with no loss of asthma control This study evaluated the superiority of combination therapy over steroid therapy alone by using clinical and laboratory data including interleukin (IL)-13 and interferon ( IFN ) gamma , which participate in the characteristic inflammation and have not been studied to evaluate the efficiency of asthma treatment sufficiently . Moderate persistent asthma patients , aged 7 - 17 years were included in the study . Patients were r and omized to three groups . Group 1 used inhaled budesonide , group 2 used inhaled budesonide plus inhaled formoterol fumarate , and group 3 used inhaled budesonide and oral montelukast sodium therapy . At the beginning and at the end of the 2nd month a detailed physical examination and clinical evaluation ; total IgE levels and total eosinophil count in peripheral venous blood , serum IL-13 , and IFN-gamma levels ; pulmonary function tests ; and an assessment question naire ( Pediatric Asthma Quality -of-Life Question naire with St and ardized Activities [ PAQLQ{S } ] were performed . Sixty-seven patients completed the study .  Serum IL-13 levels and PAQLQ(S ) scores before the therapy and serum IL-13 levels after the therapy were significantly different between the groups and other parameters did not show any significant differences . Serum IgE level was decreased after the therapy in group I and increased in groups 2 and 3 , but the difference was insignificant . In all groups total eosinophil levels were decreased insignificantly . After the therapy , IL-13 levels were decreased in groups 1 and 2 and increased in group 3 , but the difference was not statistically significant . When compared with the levels before the therapy IFN-gamma levels were decreased after the therapy but the difference was not statistically significant . When the improvement rates for IgE , total eosinophil , IL-13 , and IFN-gamma levels and each parameter of respiratory function tests were compared , there were no significant differences between the therapy groups . In all groups PAQLQ(S ) scores were significantly improved after the therapy . Our results showed that steroid and other agent combinations do not have any superiority to steroids only ; but according to pulmonary function tests and clinical indicators , all three therapy models are effective . These results suggested that the inhalation steroids , as the oldest agents , are still preserving their place and importance in asthma therapy The present study was set up to investigate whether salmeterol in children with asthma already treated with inhaled corticosteroids ( ICS )  leads to a sustained bronchodilator effect and decreased bronchial responsiveness , both during the day and night . Furthermore , we investigated whether cessation of salmeterol leads to a rebound increase in bronchial responsiveness .  Forty children with asthma ( aged 7 - 15 yrs ) using ICS participated in a r and omized , double-blind , parallel study . They received either twice daily 50 micrograms salmeterol or placebo .  FEV1 and provocative concentration of methacholine that caused a 20 % fall in FEV1 ( PC20 ) were measured at 4:00 P.M. and 4:00 A.M. at baseline and after 16 wk . The same measurements were performed at 4:00 P.M. at 8 h after the first dose , and after 1 and 8 wk . After cessation of the study drug , FEV1 and PC20 were measured at 12 and 20 h and after 1 wk . Overall mean FEV1 from 1 to 16 wk of treatment was significantly higher in the salmeterol group than in the placebo group ( difference , 4.9 + /- 2.0 % , p = 0.01 ) . Evolution in time of FEV1 did not differ significantly between the two groups ( p = 0.09 ) . Overall mean PC20 from 1 to 16 wk of treatment was not significantly higher with salmeterol than with placebo ( difference , 0.7 + /- 0.4 doubling dose [ DD ] p = 0.07 ) ; evolution in time of PC20 did not differ significantly between the two groups ( p = 0.58 ) . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To identify and educate members of ConnectiCare , Inc & Affiliates , a regional managed care organization , who were not using asthma medications as recommended by the National Heart , Lung , and Blood Institute , by means of a nurse-administered 6-month telephonic case management intervention called the Asthma Treatment Awareness Project . STUDY DESIGN A r and omized controlled design was used to evaluate intervention and control groups . Self-selected members who opted in , opted out , or did not respond to an invitation to participate were included in the analysis . METHODS Changes in asthma medication use , physician office visits , emergency department visits , hospitalizations , and quality of life were measured . A change in asthma medication use was measured using an asthma medication index ranging from 0 to 1.00 , with a higher score indicating a better prescribing pattern . RESULTS There was significant improvement in asthma medication use for all groups , but the asthma medication index increase of 0.176 for the intervention group was nearly 2 times the 0.091 increase for the control group . This difference remained significant ( P = .04 ) after using analysis of variance to control for age and the preintervention asthma medication index . There was also a significant increase in overall quality of life for the intervention group ( P = .04 ) but not for the control group . CONCLUSION Individualized telephonic case management from a specially trained registered nurse may be effective in improving asthma medication use and quality of life in subjects that do not use asthma medications according to National Heart , Lung , and Blood Institute guidelines BACKGROUND Asthma and allergic rhinitis are both highly prevalent diseases and often coexist in patients . OBJECTIVE To investigate the effect of rhinitis therapy on asthma outcomes in adult and adolescent patients with both seasonal allergic rhinitis ( SAR ) and persistent asthma . METHODS A total of 863 patients ( mean baseline FEV1 81 % predicted ) were r and omized to receive open-label fluticasone propionate/salmeterol ( FSC ) , 100/50 microg bid for 4 weeks , plus either blinded fluticasone propionate aqueous nasal spray ( FPANS ) 200 microg/d , montelukast 10 mg/d , or placebo . Patients kept daily records of peak expiratory flow ( PEF ) , asthma , and rhinitis symptoms and rescue albuterol use . RESULTS FPANS added to FSC result ed in superior outcomes for daytime total nasal symptom scores ( D-TNSS ) and individual daytime nasal specific symptoms ( congestion , rhinorrhea , sneezing , and itching ) compared with montelukast plus FSC and placebo plus FSC ( p < or = 0.001 ) . Montelukast plus FSC was superior to placebo plus FSC only for D-TNSS and itching and sneezing . Morning PEF , asthma symptoms , and rescue albuterol use improved significantly ( p < or = 0.001 ) in all treatment groups , but improvements were comparable across the treatment groups . CONCLUSION In patients with persistent asthma treated with FSC , the addition of montelukast or FPANS for the treatment of SAR result ed in no additional improvements in overall asthma control compared with FSC alone . However , FPANS provided superior rhinitis control compared with montelukast . These data suggest that asthma and rhinitis should each be optimally treated The optimal treatment for mild asthma is uncertain . We assessed the effects of adding a long-acting inhaled beta-agonist , formoterol , to low doses of an inhaled corticosteroid , budesonide , for 1 yr in subjects with mild asthma , receiving no or only a small dose of inhaled corticosteroid . The 698 corticosteroid free patients ( Group A ) were assigned to twice daily treatment with 100 microg budesonide , 100 microg budesonide plus 4.5 microg formoterol , or placebo .  The 1,272 corticosteroid-treated patients ( Group B ) were assigned to twice daily treatment with 100 microg budesonide , 100 microg budesonide plus 4.5 microg formoterol , 200 microg budesonide , or 200 microg budesonide plus 4.5 microg formoterol . The main outcome variables were time to the first severe asthma exacerbation and poorly controlled asthma days . In Group A , budesonide alone reduced the risk for severe exacerbations by 60 % and poorly controlled days by 48 % ; adding formoterol increased lung function with no change in other end points . By contrast , in Group B , adding formoterol reduced the risk for the first severe exacerbation and for poorly controlled days by 43 and 30 % , respectively . Thus , in corticosteroid-free patients , low dose inhaled budesonide alone reduced severe exacerbations and improved asthma control , and in patients already receiving inhaled corticosteroid , adding formoterol was more effective than doubling the corticosteroid dose BACKGROUND Optimal therapy for many patients with persistent asthma requires control of both main components of this disease : inflammation and bronchoconstriction . OBJECTIVES To compare the efficacy and safety of initiating maintenance therapy with an inhaled , long-acting beta2-agonist and an inhaled corticosteroid administered from a single device with that of the individual agents alone . METHODS A 12-week , r and omized , double-blind study was conducted in patients 12 years and older with persistent asthma who were symptomatic while taking as-needed , short-acting beta2-agonists alone . Treatments were administered twice daily via the Diskus device : salmeterol , 50 microg ; fluticasone propionate , 100 microg ; or fluticasone propionate , 100 microg , with salmeterol , 50 microg . RESULTS Of 555 patients screened , 267 were r and omly assigned to treatment . At end point , fluticasone propionate and salmeterol significantly increased predose forced expiratory volume in 1 second ( FEV1 ) compared with salmeterol alone ( 0.51 + /- 0.05 L vs 0.38 + /- 0.04 L , P = .04 ) . Fluticasone propionate and salmeterol significantly increased area under the serial FEV1 curve at treatment week 12 relative to predose FEV1 ( baseline ) on treatment day 1 ( AUCb1 , 8.4 + /- 0.6 L/h ; P < or = .02 ) compared with salmeterol ( 6.2 + /- 0.5 L/h ) and fluticasone propionate ( 7.0 + /- 0.6 L/h ) . Fluticasone propionate and salmeterol were significantly ( P < or = .02 ) more effective than the individual agents used alone in improving morning and evening peak expiratory flow rate and asthma symptoms . In addition , fluticasone propionate and salmeterol effectively reduced rescue albuterol use ( P < or = .04 ) . All treatments were well tolerated . CONCLUSIONS In patients symptomatic while taking short-acting beta2-agonists alone , initial maintenance treatment of the 2 main components of asthma , inflammation and smooth muscle dysfunction , with fluticasone propionate and salmeterol , 100 and 50 microg , administered via the Diskus results in greater improvements in overall asthma control compared with treatment of either component alone OBJECTIVES A fixed combination of long-acting beta(2)-agonists ( LABA ) plus inhaled corticosteroids ( ICS ) has never been proven to reduce asthma exacerbations vs ICS alone in children . This 12-month , double-blind , r and omized study in 341 children ( age range , 4 to 11 years ) with asthma uncontrolled on ICS investigated whether a novel regimen using budesonide/formoterol for maintenance and reliever therapy ( Symbicort maintenance and relief therapy [ SMART ] ) [ Symbicort ; AstraZeneca R&D , Lund , Sweden ] could reduce exacerbations . METHODS Patients received SMART ( budesonide/formoterol 80/4.5 microg qd maintenance plus additional inhalations for symptom relief ) , budesonide/formoterol 80/4.5 microg qd for maintenance ( fixed combination ) , or higher-dose budesonide 320 microg qd ( fixed-dose budesonide ) . Blinded as-needed medication ( terbutaline 0.4 microg ) was provided in both fixed-dose groups . RESULTS SMART prolonged the time to first exacerbation vs fixed-dose budesonide ( p = 0.02 ) and fixed-dose combination ( p < 0.001 ) . Rates of exacerbation requiring medical intervention were reduced by 70 to 79 % with SMART vs fixed-dose budesonide and fixed-dose combination ( 0.08/patient vs 0.28/patient and 0.40/patient , respectively ; both p < 0.001 ) . Mild exacerbation days and awakenings were significantly lower with SMART ; yearly growth improved by 1.0 cm vs fixed-dose budesonide ( p < 0.01 ) . CONCLUSION The SMART regimen using budesonide/formoterol for both maintenance and as-needed symptom relief reduces the exacerbation rate compared with both fixed-dose combination and higher fixed-dose ICS alone in children with asthma Based primarily on extrapolation from adult studies , current pediatric asthma guidelines advise the addition of long-acting beta₂-agonists for children symptomatic on low/moderate-dose inhaled corticosteroids before increasing the corticosteroid dose . This study was design ed to compare the effect of combination salmeterol/fluticasone propionate ( SFC ) with doubling the dose of fluticasone propionate ( FP ) on specific airway resistance ( sR(aw ) ) in moderate/severe persistent asthmatic children . A double-blind , r and omized , controlled study was performed ; children with asthma ( 4 - 11 years old ; sR(aw ) > 1.3 kPa·s ) were r and omized after a 2-week run-in ( FP , 100 μg , b.i.d . ) to either SFC ( 50 μg/100 μg b.i.d . ) or FP ( 200 μg b.i.d . ) via Diskus ( GlaxoSmithKline , Stockley Park , U.K. ) for 6 weeks . Lung function ( sR(aw)-plethysmography and forced expiratory volume in 1 second [ FEV₁ ] ) was measured before run-in , at r and omization , after 3 weeks , at the end of 6-week treatment , and after 48-hour washout . Symptom scores and rescue medication use were recorded throughout . Thirty-five children entered run-in and 24 were r and omized ( mean age , 7.3 ± 2.2 years ; 50 % boys ) . All children showed an improvement in sR(aw ) . After adjusting for age , gender , and baseline sR(aw , ) children receiving SFC had a significantly greater improvement in sR(aw ) compared with those receiving FP ( adjusted means ratio [ 95 % confidence interval { CI } ] , 0.81 [ 0.68 - 0.97 ] ; p = 0.021 ) . There was a significant interaction between treatment and gender ( sR(aw ) , adjusted geometric mean [ 95 % CI ] kPa·s , SFC versus FP : boys , 1.25 [ 1.10 - 1.41 ] [ n = 7 ] versus 1.87 [ 1.61 - 2.17 ] [ n = 5 ] ; girls , 1.29 [ 1.10 - 1.52 ] [ n = 5 ] versus 1.29 [ 1.13 - 1.47 ] [ n = 7 ] ; p = 0.008 ) . There were no differences in FEV₁ , symptoms , or rescue medication use between the groups . Addition of salmeterol provides greater improvement in sR(aw ) than doubling the dose of FP in children with moderate/severe persistent asthma UNLABELLED Despite better underst and ing of the pathophysiology of asthma , the application of better drugs ( potent anti-inflammatory medications and beta2 adrenergics with long-lasting effects ) , some symptoms persist and the illness itself , at the same time with exacerbation , may compromise the integrity of the patient . This calls for an evaluation of the impact of the ailment in different aspects of daily life of patients and of his/her caregivers . To address these situations , quality -of-life question naires for patients and caregivers were design ed . With this study , our objective was to make up a quality -of-life question naire to be filled out by caregivers of asthmatic children treated with one of two therapeutic schemes : with inhaled steroids ( EI ) , or the EI plus prolonged action bronchodilator ( BAP ) . MATERIAL S AND METHODS Controlled , experimental , and comparative clinical trial polling asthmatic child caregivers , applying a question naire design ed by Elizabeth Juniper ( PACQLQ ) . Patients and caregivers were r and omized in two groups : group A was treated with IE ( Beclomethasone ) plus BAP ( Salmeterol ) during a 6-week period , followed by a 2-week wash-out period followed by a 6-week period with only IE . Group B were treated only with EI followed by a 2-week period of wash-out and a six-week period with IE plus BAP . Caregivers filled in the question naires at the beginning , and at second , fourth , and sixth weeks of treatment . RESULTS We included 30 patients and their caregivers who were r and omized in two groups . Values in every group showed significant improvement in quality of life , as compared to basal values . Values between groups showed greater improvement in groups who received EI plus BAP at the beginning . CONCLUSIONS Our study shows that administering treatment for asthma improves significantly the caregiver 's appreciation of quality of life with respect to the PACQLQ question naire . The group that received EI therapy plus BAP at the beginning showed greater improvement . These results coincide with those published to date . We recommend the use of question naires at the beginning of the treatment as part of the integral evaluation of every patient with asthma UNLABELLED We aim ed to compare the efficacy and safety of budesonide/formoterol ( Symbicort ) with budesonide alone ( Pulmicort ) or budesonide ( Pulmicort ) and formoterol ( Oxis ) administered via separate inhalers in children with asthma . In a 12 wk , double-blind study , a total of 630 children with asthma ( mean age 8 yr [ 4 - 11 yr ] ; mean forced expiratory volume in 1 s ( FEV(1 ) ) 92 % predicted ; mean inhaled corticosteroid dose 454 microg/day ) were r and omized to : budesonide/formoterol ( 80/4.5 microg , two inhalations twice daily ) ; a corresponding dose of budesonide alone ( 100 microg , two inhalations twice daily ) ; or a corresponding dose of budesonide ( 100 microg , two inhalations twice daily ) and formoterol ( 4.5 microg , two inhalations twice daily ) ( budesonide + formoterol in separate inhalers ) . The primary efficacy variable was the change from baseline to treatment ( average of the 12-wk treatment period ) in morning peak expiratory flow ( PEF ) . Other changes in lung function and asthma symptoms were assessed , as was safety .  Budesonide/formoterol significantly improved morning PEF , evening PEF and FEV(1 ) compared with budesonide ( all p < 0.001 ) ; there was no significant difference between budesonide/formoterol and budesonide + formoterol in separate inhalers for these variables . All other diary card variables improved from baseline in all treatment groups ; there were no significant between-group differences . Adverse-event profiles were similar in all groups ; there were no serious asthma-related adverse events in any treatment group . CONCLUSION budesonide/formoterol significantly improved  lung function in children ( aged 4 - 11 yr ) with asthma compared with budesonide alone . Budesonide/formoterol is a safe and effective treatment option for children with asthma Objective . Concerns exist that responses to long-acting β2-adrenergic agonists in black patients may differ from the general population . The efficacy and safety of budesonide/formoterol ( BUD/FM ) pressurized metered-dose inhaler ( pMDI ) versus budesonide dry powder inhaler ( BUD DPI ) were evaluated in adolescent and adult black asthma patients . Methods . This 12-week , r and omized , double-blind , multicenter , phase IV US study was conducted in 311 self-reported black patients aged ≥12 years with moderate to severe persistent asthma , previously receiving medium- to high-dose inhaled corticosteroid . After 2 weeks on BUD 90 μg × 2 inhalations twice daily ( bid ) , symptomatic patients were r and omized to BUD/FM 160/4.5 μg × 2 inhalations bid or BUD 180 μg × 2 inhalations bid . Results . Improvement in predose forced expiratory volume in 1 second from baseline to the treatment mean ( primary variable ) was greater with BUD/FM versus BUD ( 0.16 vs. 0.07 L ; p = .008 ) ; this effect was also observed at weeks 2 , 6 , and end of treatment ( p ≤ .032 ) . Greater improvements ( p < .001 ) in peak expiratory flow with BUD/FM versus BUD were seen at first measurement and maintained during 12 weeks ( morning : 25.34 vs. 7.53 L/minute , respectively ; evening : 21.61 vs. 7.67 L/minute , respectively ) ; greater improvements in daily asthma symptom score and rescue medication use were also observed ( p ≤ .039 ) . Both treatments were well tolerated , with similar safety profiles . Conclusions . In this population of black asthma patients , BUD/FM pMDI result ed in greater improvements in pulmonary function and asthma control versus BUD DPI , with similar safety profiles BACKGROUND The twice daily administration of an inhaled corticosteroid ( ICS ) and long-acting beta(2)-agonist ( LABA ) has been shown to be effective in achieving asthma control . The once daily administration of an ICS/LABA may be a treatment option for some patients . OBJECTIVE To assess the effectiveness of fluticasone propionate (FP)/salmeterol via a single inhaler ( FSC ) administered once daily compared with FP once daily , FSC twice daily , or placebo . METHODS A 12-week , r and omized , double-blind multicenter study conducted in 844 patients > or = 12 years of age who were symptomatic while using a short-acting beta(2)-agonist alone . Blinded treatments included : FSC 250/50 mcg once daily in the evening ( FSC 250/50 QD ) , FP 250 mcg once daily in the evening ( FP 250 QD ) , FSC 100/50 mcg twice daily ( FSC 100/50 mcg BID ) , or placebo . All treatments were delivered via the Diskus device . RESULTS All treatments demonstrated greater improvements in efficacy measures compared with placebo . Overall , the greatest improvements were observed in the patients receiving FSC , either once or twice daily , compared with the FP 250 QD group . The two FSC treatments were similar except that QD dosing did not maintain improvements in lung function for 24h compared with twice daily dosing . All treatments were well tolerated . No suppression of HPA axis , as assessed by 24-h urinary cortisol excretion , was observed in any of the active treatment groups . CONCLUSION In patients symptomatic on a short-acting beta(2)-agonist alone , FSC 100/50 mcg BID was shown to provide better efficacy than a higher strength ( FSC 250/50 mcg ) administered once daily . However , a once daily regimen was effective and may be a valuable treatment option for some patients . Registered at ( http://ctr.gsk.co.uk/welcome.asp ) ( SAS30022 ) Long acting beta(2)-agonists ( LABA ) are widely used in children with asthma . Data from adults suggest that there is tachyphylaxis particularly to the bronchoprotective effects of LABA . There are no data in children . To determine whether LABA are subject to tachyphylaxis in school-aged children . Children were eligible for participation if they remained symptomatic on 400 microg of beclometasone dipropionate equivalent/day . Participants undertook a 4-wk run in period with open-label fluticasone 100 microg BD via Diskus . Children were then r and omized to receive fluticasone 100 microg BD or salmeterol/fluticasone 50/100 microg BD via Diskus in a double-blind manner . Children underwent spirometry , cold air challenge and salbutamol reversibility testing at baseline , 4 and 8 wk . 37/42 children completed the study . There were significant improvements in basal FEV1 ( % predicted ) in the salmeterol/fluticasone group ( n = 21 ) ( + 6.4 % ( 95 % CI : 2.4 - 10.5 ) p = 0.0033 ) but not in the fluticasone group ( n = 16 ) [ + 1.2 ( 95 % CI : -3.4 to 5.8 ) p = 0.5900 ] . There was a non-significant reduction in fall in FEV1 provoked by cold air in both groups . There was a significant lessening in the acute salbutamol response after 8 wk in the salmeterol/fluticasone group [ -11.4 % ( 95 % CI : -17.6 to -5.2 ) p = 0.0010 ] but not in the fluticasone group [ -1.6 % ( 95 % CI : -9.8 to 6.6 ) p = 0.6827 ] . Salmeterol/fluticasone therapy significantly improves basal FEV(1 )  in asthmatic children however , there is negligible additional bronchoprotection by week 4 of treatment and there is significant attenuation of salbutamol responsiveness when compared with fluticasone alone . Some of this reduction in salbutamol response may relate to the concurrent improvements in baseline lung function AIM This paediatric asthma study evaluated the efficacy and safety of a novel hydrofluoroalkane pressurised metered-dose inhaler ( pMDI ) formulation of budesonide/formoterol versus budesonide pMDI and budesonide/formoterol dry-powder inhaler ( DPI ) . METHODS The study was a 12-week , multinational , double-blind trial involving children ( aged 6 - 11 years ) with symptomatic asthma on inhaled corticosteroids ( 375 - 1000 microg/day ) , with a history of exercise-induced bronchoconstriction and peak expiratory flow ( PEF ) > or = 50 % of predicted . Patients were r and omised ( two inhalations twice daily ) to budesonide pMDI 100 microg , budesonide/formoterol DPI 80/4.5 microg or budesonide/formoterol pMDI 80/4.5 microg . The primary endpoint was change from baseline in morning PEF . RESULTS Overall , 622 patients were r and omised .  Increases in morning PEF with budesonide/formoterol pMDI and budesonide/formoterol DPI were therapeutically equivalent ( 29.5 versus 30.2l/min , respectively ; 95 % confidence interval : -6.0 to 4.6 ; P=0.78 , also confirmed by per- protocol analysis ) . Improvements in secondary efficacy endpoints with both budesonide/formoterol formulations were not significantly different . Significantly greater improvement was achieved with budesonide/formoterol pMDI versus budesonide pMDI for morning PEF ( + 9.6l/min ; P<0.001 ) and other lung function parameters . The safety profile of budesonide/formoterol pMDI was favourable and similar to that of budesonide/formoterol DPI and budesonide pMDI . CONCLUSION Budesonide/formoterol , administered via the therapeutically equivalent hydrofluoroalkane pMDI or DPI , is an effective and well-tolerated treatment for children with asthma A r and omised , open-label , multicentre study compared the efficacy and tolerability of salmeterol 25 microg/fluticasone propionate 125 microg ( two puffs , twice daily ) delivered via a hydrofluoroalkane metered-dose inhaler ( HFA-MDI ) and salmeterol 50microg/fluticasone propionate 250 microg ( one puff , twice daily ) delivered via a Diskus inhaler in Chinese patients with moderate asthma uncontrolled with inhaled corticosteroids ( ICSs ) .  Morning peak expiratory flow ( PEF ) was the primary efficacy endpoint . Secondary endpoints included evening PEF , forced expiratory volume in 1 s , day and night symptom scores , rescue medication and patient self-evaluation of efficacy . Safety was assessed according to adverse events recorded . Both treatments were equipotent and significantly improved morning PEF ( HFA-MDI 40 l/min ; Diskus 42 l/min ; p < 0.05 ) and all secondary endpoints ( p < 0.05 ) from baseline , over 1 - 4 weeks . Similarly , both treatments were well tolerated . Salmeterol/fluticasone propionate delivered via an HFA-MDI or Diskus inhaler provides a choice of efficacious delivery systems in Chinese patients whose asthma is poorly controlled on ICSs alone BACKGROUND It has been proposed that asthma control may be achieved in part by minimizing airway inflammation . The simultaneous effects of inhaled steroids associated with long-acting beta-agonists and leukotriene antagonists on pulmonary function and airway inflammation are still largely unexplored in children with moderate persistent asthma . OBJECTIVES The aim of this study was to investigate the effects of add-on therapy with long-acting beta-agonists and leukotriene antagonists on FEV1 and exhaled nitric oxide levels ( FENO ) in children . METHODS Forty-eight steroid-naïve atopic asthmatic children , 7 - 11 years of age , were r and omly treated in four groups for two consecutive one-month periods , as follows : ( 1 ) first month : budesonide 200 microg twice daily ; second month : budesonide 400 microg twice daily ; ( 2 ) first month : budesonide 200 microg twice daily+formoterol 9 microg twice daily ; second month : budesonide 200 microg twice daily+montelukast 5 mg once daily ; ( 3 ) first month : budesonide 200 microg twice daily+montelukast 5 mg once daily ; second month budesonide 200 microg+formoterol 9 microg twice daily ; ( 4 ) first and second month : budesonide 400 microg twice daily . RESULTS All treatments result ed in a significant increase in lung function and a decrease in FENO compared with values at baseline . Budesonide+montelukast in combination was the most effective treatment for reducing FENO levels . CONCLUSION This study demonstrates that add-on therapy with montelukast plus low-dose budesonide is more effective than the addition of long-acting beta-agonists or doubling the dose of budesonide for controlling FENO in asthmatic children OBJECTIVE AND BACKGROUND To investigate the duration of bronchodilator action of a salmeterol/fluticasone combination ( SFC ) inhaler when administered in the evening to children with asthma . METHODOLOGY DESIGN A double-blind , placebo-controlled , cross-over study . SETTING Hospital inpatient . SUBJECTS Fourteen children aged between 4 and 11 years with mild to moderate asthma ( FEV(1 ) > 60 % predicted ) who exhibited a 15 % increase in FEV(1 ) with bronchodilator . INTERVENTIONS SUBJECTS inhaled , in r and om order , either SFC ( 100/50 microg ) or placebo , via accuhaler , at 20.00 hours on two separate occasions with at least 3 days between study days . OUTCOME MEASURES Lung function measurements including FEV(1 ) , PEF , specific airways conductance ( sGaw ) and maximum expiratory flow at 25 - 75 % of vital capacity were measured at baseline , 2 , 12 , 16 , 20 and 24 h. RESULTS For all lung function parameters SFC result ed in significantly greater bronchodilation than placebo for at least 20 h after inhalation . At 24 h , the increase in FEV(1 ) and PEF compared with placebo was 0.08 L ( 95 % confidence interval : -0.18 to 0.02 , P = 0.16 ) and 27 L/min ( 95 % confidence interval : -47 to -6 , P = 0.004 ) , respectively . CONCLUSIONS The single administration of SFC via an accuhaler in the evening result ed in significant bronchodilation for at least 20 h in children with asthma RATIONALE Exercise is a common trigger in children with persistent asthma and inhaled corticosteroids have been shown to effectively treat clinical manifestations of persistent asthma , including protection from decrements in lung function caused by exercise . The goal of this study was to evaluate the effectiveness of fluticasone propionate/salmeterol 100/50 mcg compared with fluticasone propionate 100 mcg for the prevention of airflow limitation triggered by st and ardized exercise challenge in pediatric and adolescent patients with persistent asthma . METHODS Multicenter , r and omized , double-blind , parallel group trial of 248 subjects with persistent asthma ( age 4 - 17 years ) r and omized to receive fluticasone propionate/salmeterol ( 100/50 mcg twice daily ) or fluticasone propionate alone ( 100 mcg twice daily ) via Diskus for 4 weeks . Exercise challenge tests were performed during screening and approximately 8 hr after administration of the blinded study medication on Treatment Day 28 . RESULTS After 4 weeks of therapy both treatments provided protection following exercise challenge . The protection estimated by the maximal fall in FEV(1 ) was significantly better for fluticasone propionate/salmeterol ( 9.5 + /- 0.8 % [ mean + /- SE ] ) compared with fluticasone propionate alone ( 12.7 + /- 1.1 % , P = 0.021 ) . Statistically significant differences were not observed for asthma rescue-free days and asthma symptom-free days . CONCLUSION Chronic dosing with fluticasone propionate/salmeterol in a single device provides superior protection compared with an inhaled corticosteroid alone in protecting against exercise-induced asthma in children with persistent asthma This double-blind , placebo-controlled , r and omized , parallel-group , multicenter study was conducted in 302 children aged 6 - 11 years with asthma not optimally treated with inhaled corticosteroids alone . Patients continued with their existing dose of inhaled corticosteroids and in addition received placebo , formoterol 4.5 microg or formoterol 9 microg b.i.d . , for 12 weeks ( all delivered via Turbuhaler ) . Terbutaline was available as reliever medication . The primary efficacy variable was change from baseline in morning peak expiratory flow ( PEF ) ; secondary efficacy variables included forced expiratory volume in 1 sec ( FEV(1 ) ) , serial PEF measured over 12 hr , evening PEF , asthma symptom score , and quality of life . Compared with placebo , formoterol 4.5 microg and 9 microg improved morning PEF by 8 l/min ( P = 0.035 ) and 11 l/min ( P = 0.0045 ) , respectively . Evening PEF and FEV(1 ) were also significantly increased compared with placebo , with no statistically significant difference between formoterol doses . Lung-function improvements compared with placebo were greater in the middle of the day . Twelve-hour average serial PEF after 3 months increased by 24 l/min ( 95 % CI , 9 , 39 l/min ) in the formoterol 9-microg group , and by 14 l/min ( 95 % CI , 0 , 29 l/min ) in the formoterol 4.5-microg group . The incidence of severe exacerbations in both formoterol groups was numerically lower than in the placebo group , indicating that formoterol may have the potential to improve exacerbation control in children . Both formoterol doses were well-tolerated , and tolerance to the drug 's bronchodilator effect was not observed . Formoterol provided sustained improvements in lung function and was well-tolerated in children with asthma suboptimally treated with inhaled corticosteroids alone This multicentre double-blind , double-dummy study compared the safety and efficacy of a new combination Diskus inhaler containing both salmeterol 50 microg and fluticasone propionate 500 microg ( Seretide , GlaxoWellcome , France ) with the same doses of the two drugs delivered via separate Diskus inhalers and with the same dose of fluticasone propionate alone .  Patients were eligible for study entry if they had received an inhaled corticosteroid continuously for 12 weeks prior to run-in , and had received treatment with  beclomethasone dipropionate or budesonide 1500 - 2000 microg day(-1 ) or fluticasone propionate 750 - 1000 microg day(-1 ) for at least 4 weeks prior to run-in . In total , 503 patients receiving inhaled corticosteroids were r and omized to 28 weeks ' treatment with either salmeterol/fluticasone propionate ( 50/500 microg ) via a single Diskus inhaler ( combination ) and placebo , or salmeterol 50 microg and fluticasone propionate 500 microg administered via separate Diskus inhalers ( concurrent ) , or fluticasone propionate 500 microg and placebo . All treatments were administered twice daily , mean morning peak expiratory flow rate ( PEFR ) and asthma symptoms were measured for the first 12 weeks and safety data were collected throughout the 28-week study . Over weeks 1 to 12 , improvement in adjusted mean morning PEFR was 35 and 33 l min(-1 ) , respectively , in the combination and concurrent therapy treatment groups ( 12 and 10 % increase from baseline , respectively ) . The mean difference between treatments was -3 l min(-1 ) ( 90 % confidence interval -10.4 l min(-1 ) ) which was within the criteria for clinical equivalence . However , the combination therapy was statistically significantly superior to fluticasone propionate alone for mean morning PEFR ( P<0.001 ) and other measures of lung function , whilst clinical equivalence of the combination and concurrent therapies was observed . All three treatments were well tolerated . In addition , there were no differences between the three treatments in either the c.hange in serum cortisol or urinary cortisol concentrations , which , for each treatment group , were no significantly different from baseline at the end of the treatment period . Thus , the combination of salmeterol and fluticasone propionate in a single inhaler is as well tolerated and effective in achieving asthma control in steroid-dependent patients as the separate administration of the two drugs , and both combination and concurrent therapy are superior to administration of the same dose of corticosteroid alone BACKGROUND Treatment guidelines recommend the use of inhaled corticosteroids in patients with asthma who have persistent symptoms and the " stepping down " of therapy to the minimum needed to maintain control of asthma . Whether patients with asthma that is well controlled with the use of inhaled corticosteroids twice daily can receive a step-down treatment with once-daily montelukast ( our primary hypothesis ) or once-daily fluticasone propionate plus salmeterol ( our secondary hypothesis ) has not yet been determined . METHODS We r and omly assigned 500 patients with asthma that was well controlled by inhaled fluticasone ( 100 microg twice daily ) to receive continued  fluticasone ( 100 microg twice daily ) ( 169 patients ) , montelukast ( 5 or 10 mg each night ) ( 166 patients ) , or fluticasone ( 100 microg ) plus salmeterol ( 50 microg ) each night ( 165 patients ) . Treatment was administered for 16 weeks in a double-blind manner . The primary outcome was the time to treatment failure . RESULTS Approximately 20 % of patients assigned to receive continued fluticasone or switched to treatment with fluticasone plus salmeterol had treatment failure , as compared with 30.3 % of subjects switched to montelukast . The hazard ratio for both comparisons was 1.6 ( 95 % confidence interval , 1.1 to 2.6 ; P=0.03 ) . The percentage of days on which patients were free of asthma symptoms ( 78.7 to 85.8 % ) was similar across the three groups . CONCLUSIONS Patients with asthma that is well controlled with the use of twice-daily inhaled fluticasone can be switched to once-daily fluticasone plus salmeterol without increased rates of treatment failure . A switch to montelukast results in an increased rate of treatment failure and decreased asthma control ; however , patients taking montelukast remained free of symptoms on 78.7 % of treatment days . ( Clinical Trials.gov number , NCT00156819 [ Clinical Trials.gov ] . ) Objective . To study the effectiveness and safety in a real-life setting of budesonide/formoterol ( Symbicort ) Maintenance And Reliever Therapy ® ( Symbicort SMART ® ) , a simplified management approach with one inhaler , compared with conventional best practice ( CBP ) with multiple inhalers in patients with persistent asthma . Design . Open-label r and omized controlled parallel-group trial , 6-month treatment . Participants . A total of 654 adult patients , with persistent asthma receiving treatment with inhaled corticosteroids ( ICS ) , either alone or in conjunction with long-acting β2-agonist .  Main outcome measures . Time to first severe asthma exacerbation and number of severe asthma exacerbations . Results . No difference between groups was seen in time to first severe exacerbation ( p = .2974 ) . Exacerbation rates were low in both groups . A total of 22 patients in the Symbicort SMART group experienced a total of 24 severe asthma exacerbations , and 31 patients in the CBP group experienced a total of 34 severe asthma exacerbations ( annual rate 0.16 vs. 0.22 , p = .2869 ) . The mean daily dose of ICS expressed in beclomethasone dipropionate equivalent was significantly lower in the Symbicort SMART group ( including as-needed use ) versus the CBP group ( 799 μg vs.1184 μg ; p < .001 ) . Mean scores in Asthma Control Question naire , five- question version , improved significantly in the SMART group compared with the CBP group ( p =  .0292  ) . Symbicort SMART and CBP were equally well tolerated . The mean drug cost per patient per 6 months was lower for the patients in the SMART group compared with patients receiving CBP ( € 295.32 vs. € 387.98 , p < .0001 ) . Conclusions . A simplified regimen using budesonide/formoterol maintenance and reliever therapy ( Symbicort SMART ) was at least as effective at improving clinical control compared with CBP with a significantly lower ICS dose and lower drug costs Aims : To evaluate the effect of the implementation of an asthma clinical pathway on asthma in children in general practice . Methods : A r and omized , controlled trial involving 270 general practitioners . One group of general practitioners implemented the asthma clinical pathway for children ( intervention group ) and the control group continued with their usual asthma medical care management . The main outcome measures were admissions to hospital for asthma and attendance at the Children 's Emergency Department . Compliance with the guidelines was assessed by examining asthma drug prescriptions . Results : Admissions to hospital for asthma dropped 40 % in the intervention group , by 33 % in the control group and by 22 % in general practitioners not participating in the trial . The differences between the intervention and control and between the intervention and non‐participating general practitioners were not statistically significant . The decrease in attendance at the Children 's Emergency Department decreased by 25 % , 30 % and 19 % , respectively , but this was not statistically significant . There was a significant decrease in prescriptions for oral relievers , dry powder relievers  in the under 6s , mast cell stabilizers and methylxanthines  in both control and intervention groups . However , only for oral relievers was there a significant difference between the intervention group and control , with the decrease larger in the intervention group ( p<0.001 ) BACKGROUND For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids ( ICS ) , evidence to guide step-up therapy is lacking . METHODS We r and omly assigned 182 children ( 6 to 17 years of age ) , who had uncontrolled asthma while receiving 100 microg of fluticasone twice daily , to receive each of three blinded step-up therapies in r and om order for 16 weeks : 250 microg of fluticasone twice daily ( ICS step-up ) , 100 microg of fluticasone plus 50 microg of a long-acting beta-agonist twice daily ( LABA step-up ) , or 100 microg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily ( LTRA step-up ) . We used a triple-crossover design and a composite of three outcomes ( exacerbations , asthma-control days , and the forced expiratory volume in 1 second ) to determine whether the frequency of a differential response to the step-up regimens was more than 25 % . RESULTS A differential response occurred in 161 of 165 patients who were evaluated ( P<0.001 ) . The response to LABA step-up therapy was most likely to be the best response , as compared with responses to LTRA step-up ( relative probability , 1.6 ; 95 % confidence interval [ CI ] , 1.1 to 2.3 ; P=0.004 ) and ICS step-up ( relative probability , 1.7 ; 95 % CI , 1.2 to 2.4 ; P=0.002 ) . Higher scores on the Asthma Control Test before r and omization ( indicating better control at baseline ) predicted a better response to LABA step-up ( P=0.009 ) . White race predicted a better response to LABA step-up , whereas black patients were least likely to have a best response to LTRA step-up ( P=0.005 ) . CONCLUSIONS Nearly all the children had a differential response to each step-up therapy . LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up . However , many children had a best response to ICS or LTRA step-up therapy , highlighting the need to regularly monitor and appropriately adjust each child 's asthma therapy . ( Clinical Trials.gov number , NCT00395304 . BACKGROUND Exercise is a common trigger of asthma symptoms in patients with persistent asthma . OBJECTIVE To evaluate the protective effect of fluticasone/salmeterol against exercise-induced bronchospasm . METHODS Multicenter , r and omized , double-blind , parallel-group trial of 192 asthma patients who used moderate-dose inhaled corticosteroids . Patients ( aged 12 - 50 years ; mean forced expiratory volume in 1 second [ FEV1 ] , 78 % of predicted at baseline ) were r and omized to receive fluticasone/salmeterol ( 250/50 microg twice daily ) or fluticasone alone ( 250 microg twice daily ) via Diskus for 4 weeks . Exercise challenge tests were performed 1 and 8.5 hours after administration of the first ( day 1 ) and last ( week 4 ) doses of blinded study medication . RESULTS On day 1 and at week 4 , mean + /- SEM values for the maximal percentage decline in FEV1 1 hour after drug administration were 11.4 % + /- 1.5 % and 10.9 % + /- 1.5 % for fluticasone/salmeterol compared with 20.0 % + /- 1.7 % and 18.4 % + /- 1.8 % for fluticasone ( P < .001 ) . At 8.5 hours , mean + /- SEM values on day 1 and at week 4 were 11.6 % + /- 1.4 % and 8.9 % + /1.1 % , respectively , for fluticasone/salmeterol and 12.6 % + /- 1.6 % and 12.9 % + /- 1.4 % , respectively , for fluticasone ( P = .01 at week 4 ) . More fluticasone-treated patients did not complete the 8.5-hour exercise challenges ( 36 % on day 1 and 33 % at week 4 ) compared with the fluticasone/salmeterol group ( 18 % each ) ( P < or = .01 ) . Improvements in peak expiratory flow rate and albuterol rescue-free days were significantly greater with fluticasone/salmeterol vs fluticasone over weeks 1 to 4 ( P < or = .03 ) . CONCLUSIONS Consistent with the improvements in other measures of asthma control , long-term fluticasone/salmeterol therapy also provided protection against exercise-induced bronchospasm in patients with persistent asthma STUDY OBJECTIVE To compare the safety of salmeterol xinafoate or placebo added to usual asthma care . DESIGN A 28-week , r and omized , double-blind , placebo-controlled , observational study . SETTING Study subjects were seen once in the study physician 's office for screening and were provided all blinded study medication for the entire study period . Follow-up by telephone was scheduled every 4 weeks . PARTICIPANTS Subjects ( > 12 years old ) with asthma as judged by the study physician were eligible . Individuals with a history of long-acting beta2-agonist use were excluded . INTERVENTIONS Salmeterol , 42 mug bid via metered-dose inhaler ( MDI ) , and placebo bid via MDI . MEASUREMENTS AND RESULTS Following an interim analysis in 26,355 subjects , the study was terminated due to findings in African Americans and difficulties in enrollment . The occurrence of the primary outcome , respiratory-related deaths , or life-threatening experiences was low and not significantly different for salmeterol vs placebo ( 50 vs 36 ; relative risk [ RR ] = 1.40 ; 95 % confidence interval [ CI ] , 0.91 to 2.14 ) . There was a small , significant increase in respiratory-related deaths ( 24 vs 11 ; RR , 2.16 ; 95 % CI , 1.06 to 4.41 ) and asthma-related deaths ( 13 vs 3 ; RR , 4.37 ; 95 % CI , 1.25 to 15.34 ) , and in combined asthma-related deaths or life-threatening experiences ( 37 vs 22 ; RR , 1.71 ; 95 % CI , 1.01 to 2.89 ) in subjects receiving salmeterol vs placebo . The imbalance occurred largely in the African-American sub population : respiratory-related deaths or life-threatening experiences ( 20 vs 5 ; RR , 4.10 ; 95 % CI , 1.54 to 10.90 ) and combined asthma-related deaths or life-threatening experiences ( 19 vs 4 ; RR , 4.92 ; 95 % CI , 1.68 to 14.45 ) in subjects receiving salmeterol vs placebo . CONCLUSIONS For the primary end point in the total population , there were no significant differences between treatments . There were small , but statistically significant increases in respiratory-related and asthma-related deaths and combined asthma-related deaths or life-threatening experiences in the total population receiving salmeterol . Subgroup analyses suggest the risk may be greater in African Americans compared with Caucasian subjects . Whether this risk is due to factors including but not limited to a physiologic treatment effect , genetic factors , or patient behaviors leading to poor outcomes remains unknown OBJECTIVE The use of combination inhaled corticosteroid/long-acting beta-agonist therapy within the framework of a self-management plan has yet to be investigated . METHODOLOGY In this r and omized open-label study , 69 adult asthmatic patients taking > or= 1,000 microg per day of beclomethasone dipropionate ( BDP ) or equivalent were treated for 3 months with Symbicort Turbuhaler ( 200 microg budesonide/6 microg formoterol ) . Patients were assigned to one of two self-management plans , based on either a fixed or adjustable dose regimen . The primary outcome variable was episode-free days . RESULTS Both regimens result ed in good asthma control , at least comparable to that obtained with previous high dose inhaled corticosteroid therapy . There were no significant differences in clinical outcome measures between the regimens . The mean ( + /- SD ) usage of Symbicort  was similar for the fixed and adjustable dose regimens ( 3.8 + /- 0.68 vs 3.6 + /- 1.54 puffs per day , respectively ) . CONCLUSION We conclude that Symbicort is effective when administered as either a fixed or adjustable dose regimen as part of a self-management plan RATIONALE For children with symptomatic asthma despite low to moderate doses of inhaled corticosteroids , evidence is still lacking whether to add a long-acting bronchodilator or to increase the dose of inhaled corticosteroids . OBJECTIVE To evaluate whether salmeterol/fluticasone propionate ( SFP ) , 50/100 μg twice a day , is noninferior regarding symptom control compared with fluticasone propionate ( FP ) , 200 μg twice a day Diskus in children with symptomatic asthma . METHODS A multicenter , r and omized , parallel-group , double-blind study was performed comparing SFP and FP treatment during 26 weeks on asthma control and lung function . MEASUREMENTS AND MAIN RESULTS A total of 158 children , 6 - 16 years old , still symptomatic on FP , 100 μg twice a day , during a 4-week run-in period , were included .  Percentage of symptom-free days during the last 10 weeks of the treatment period did not differ between treatment groups ( per protocol analysis : adjusted mean difference [ FP minus SFP ] 2.6 % ; 95 % confidence interval , -8.1 to 13.4 ) . Both groups showed substantial improvements of about 25 percent points in symptom-free days ( both P < 0.001 from baseline ) . Lung function measurements ( FEV(1 ) , FVC , PEF rate , and maximal expiratory flow ) did not differ between groups except for a slight advantage in maximal expiratory flow in the SFP group at 1 week . No differences were found between FP and SFP regarding exacerbation rates , adverse events , or growth . CONCLUSIONS In our study the efficacy on symptom control and lung function of the combination of a long-acting bronchodilator with inhaled corticosteroid is equal to doubling the dose of the inhaled corticosteroid in children still symptomatic on a moderate dose of inhaled corticosteroid 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 Budesonide/formoterol in one inhaler is an established therapy for asthma and chronic obstructive pulmonary disease . The long-term safety and efficacy profile of a novel hydrofluoroalkane ( HFA ) pressurized metered-dose inhaler ( pMDI ) formulation of budesonide/formoterol was compared with that of budesonide/formoterol in a dry powder inhaler ( DPI ; Turbuhaler ) . This multinational , 52-week , r and omized , open , parallel-group study included patients aged > or = 12 years with asthma who had a forced expiratory volume in 1s ( FEV1 ) > or = 50 % of predicted normal ; all patients used inhaled corticosteroids ( 400 - 1200 microg/day ) and needed additional short-acting beta 2-agonist therapy . Patients were r and omized to receive budesonide/formoterol pMDI or DPI 160/4.5 microg , two inhalations twice daily . Safety endpoints included assessment of adverse events and laboratory parameters . Efficacy endpoints included change from baseline in FEV1 and time to first severe asthma exacerbation .  Overall , 673 patients ( 446pMDI , 227DPI ) were included . There were no clinical ly significant differences between treatment groups in the nature , incidence or severity of adverse events or laboratory parameters . The number of patients experiencing adverse events was comparable in the pMDI ( 332/446 [ 74 % ] ) and DPI ( 175/227 [ 77 % ] ) groups ; the most commonly reported adverse event was upper respiratory tract infection . The proportion of patients discontinuing as a result of adverse events was low in both groups ( pMDI 12/446 [ 3 % ] , DPI 2/227 [ 1 % ] ) . Lung function was improved to a similar extent in both groups and there was no detectable difference in time to first severe asthma exacerbation . The novel HFA pMDI formulation of budesonide/formoterol is an equally well tolerated and effective treatment for adults and adolescents with asthma as the budesonide/formoterol DPI Twenty-four children aged 12 - 17 years entered a r and omized , double-blind placebo-controlled study investigating the use of salmeterol in chronic severe asthma . In addition to their usual medication , the children were given either placebo or 100 micrograms salmeterol b.d . by dry powder inhalation . Treatment was continued throughout one term at a residential school for asthma . Symptom scores , peak expiratory flow rates , spirometry and quality -of-life scores were compared between the two treatment groups . One child withdrew during the run-in period . Twelve pupils received placebo and 11 pupils received salmeterol . There were consistent improvements in favour of salmeterol , reaching statistical significance for morning and evening peak flow rates and spirometry when measured on four occasions during the study period . There were no medication-related adverse events recorded and no pulse rate changes . Salmeterol ( 100 micrograms b.d . ) is well tolerated and efficacious in older children with chronic severe asthma The Arg(16 ) β(2 ) receptor genotype confers increased susceptibility to exacerbations in asthmatic children taking regular LABA ( long-acting β(2 ) agonists ) . We therefore evaluated using montelukast as an alternative to salmeterol as tailored second-line asthma controller therapy in children expressing this susceptible genotype . A total of 62 persistent asthmatic children with the homozygous Arg16 genotype were r and omized to receive salmeterol ( 50 μg , b.i.d . ) or montelukast ( 5 or 10 mg , once daily ) as an add-on to inhaled fluticasone for 1 year . School absences ( the primary outcome ) were reduced with montelukast compared with salmeterol { difference in score=-0.40 [ 95 % CI ( confidence interval ) , -0.22 to -0.58 ] ; P=0.005}. Salbutamol  use was also reduced with montelukast compared with salmeterol [ difference in score=-0.47 ( 95 % CI , -0.16 to -0.79 ) ; P<0.0001 ] . Greater improvements occurred in both symptom and quality of life scores with montelukast against salmeterol , whereas there was no difference in FEV(1 ) ( forced expiratory volume in 1 s ) . In conclusion , montelukast may be suitable as tailored second-line controller therapy instead of salmeterol in asthmatic children expressing the susceptible Arg(16 ) genotype , a move towards a personalized medicine approach to management BACKGROUND The inhaled corticosteroid , fluticasone propionate , and the long-acting β(2)-adrenergic agonist , formoterol fumarate , are both highly effective treatments for bronchial asthma . This study ( NCT00393952/EudraCT number : 2006 - 005989 - 39 ) compared the efficacy and safety of fluticasone/formoterol combination therapy ( flutiform ( ® ) ; 250/10 μg ) administered twice daily ( b.i.d . ) via a single aerosol inhaler , with the individual components ( fluticasone 250 μg b.i.d . ; formoterol 10 μg b.i.d . ) , in adult and adolescent patients with moderate-to-severe asthma . METHODS This was a 12-week , double-blind , r and omised , parallel-group , multicentre , placebocontrolled phase 3 study . The co- primary efficacy endpoints were : i ) the mean change in the forced expiratory volume in the first second ( FEV(1 ) ) from morning pre-dose at baseline to pre-dose at week 12 ( fluticasone/formoterol 250/10 μg vs. formoterol ) , ii ) the mean change in FEV(1 ) from morning pre-dose at baseline to 2 h post-dose at week 12 ( fluticasone/formoterol 250/10 μg vs. fluticasone ) , and iii ) the number of patients who discontinued prematurely due to lack of treatment efficacy  ( fluticasone/formoterol 250/10 μg vs. placebo ) . The secondary endpoints included measures of lung function , disease control , and asthma symptoms . Safety was assessed based on adverse events , vital signs , and clinical laboratory evaluations . RESULTS Overall , 395 ( 70.9 % ) patients completed the study . Fluticasone/formoterol 250/10 μg b.i.d . was superior to the individual components and placebo for all three co- primary endpoints and demonstrated numerically greater improvements for multiple secondary efficacy analyses . Fluticasone/formoterol combination therapy had a good safety profile over the 12 weeks . CONCLUSION Fluticasone/formoterol combination therapy will provide clinicians with an efficacious alternative treatment option for patients with moderate-to-severe asthma BACKGROUND Asthma affects one in eight children in the UK . National management guidelines have been available for many years but , unlike in adults , studies in children have been few , with their method ologies often based on inappropriate adult models . Sound medical evidence in support of the national guidelines for asthma management in children is lacking . The MASCOT study has been developed to address this need . OBJECTIVES To determine whether adding salmeterol or montelukast to low-dose inhaled corticosteroids ( ICSs ) can reduce the number of exacerbations requiring treatment with oral corticosteroids in children with uncontrolled asthma . DESIGN A r and omised , double-blind , placebo-controlled trial with a 4-week run-in period on a fluticasone propionate inhaler ( 100 µg twice daily ) with inhaler technique correction . Patients who met the post run-in period eligibility criteria were r and omised in the ratio of 1 : 1 : 1 and were followed for 48 weeks . SETTING Secondary care hospitals based in Engl and and Scotl and with recruitment from primary and secondary care . PARTICIPANTS Children aged 6 - 14 years with asthma requiring frequent short-acting beta-2 agonist relief , with symptoms of asthma result ing in nocturnal wakening and /or asthma that has interfered with usual activities . INTERVENTIONS Three groups were compared : ( 1 ) inhaled fluticasone propionate 100 µg twice daily plus placebo tablet once daily ; ( 2 ) inhaled fluticasone propionate 100 µg and salmeterol 50 µg twice daily ( combination inhaler ) plus placebo tablet once daily ; and ( 3 ) inhaled fluticasone propionate 100 µg twice daily plus montelukast 5-mg tablet once daily . MAIN OUTCOME MEASURES The primary outcome was the number of exacerbations requiring treatment with oral corticosteroids over 48 weeks . Secondary outcome measures included quality of life as measured by the Paediatric Asthma Quality of Life Question naire with St and ardised Activities [ PAQLQ(S ) ] and the Paediatric Asthma Caregiver 's Quality of Life Question naire ( PACQLQ ) ; time from r and omisation to first exacerbation requiring treatment with a short course of oral corticosteroids ; school attendance ; hospital admissions ; amount of rescue beta-2 agonist therapy prescribed ; time from r and omisation to treatment withdrawal ( because of lack of efficacy or side effects ) ; lung function at 48 weeks ( as assessed by spirometry ) ; cost-effectiveness ; adverse events . RESULTS The study was closed prematurely because of poor recruitment and the target sample size of 450 was not achieved . In total , 898 children were screened to enter the trial , 166 were registered for the 4-week run-in period and 63 were r and omised ( group 1 : 19 , group 2 : 23 , group 3 : 21 ) , with 38 contributing data for the primary outcome analysis . There were no significant differences between groups for any of the outcomes . Adverse events were similar between the groups except for nervous system disorders , which were more frequently reported on fluticasone plus montelukast . CONCLUSIONS Based on the results of the MASCOT study it is not possible to conclude whether adding salmeterol or montelukast to ICSs can reduce the number of exacerbations requiring treatment with oral corticosteroids in children with uncontrolled asthma . TRIAL REGISTRATION Current Controlled Trials IS RCT N03556343 . FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 17 , No. 4 . See the HTA programme website for further project information Background Patients with severe asthma are often inadequately controlled on existing anti‐asthma therapy , constituting an unmet clinical need In accordance with the Montreal Protocol 1987 , initiatives to phase out and replace ozone-depleting chlorofluorocarbon ( CFC ) propellants with non-ozone-depleting propellants in metered-dose inhalers ( MDIs ) in the treatment of asthma and chronic obstructive pulmonary disease are underway . In view of this , two multi-centre , r and omised , parallel-group , double-blind studies were conducted to compare the safety and efficacy of salmeterol xinafoate delivered by an MDI using the hydrofluoroalkane ( HFA ) 134a propellant with the licensed CFC formulation ( Serevent ) in asthmatic population s of children ( 4 - 11 years ) and adults ( 12 years ) . Patients on a stable dose of inhaled corticosteroids with a scope for improvement based on mean morning peak expiratory flow ( PEF ) and symptoms were r and omised to receive salmeterol HFA MDI 50 microg twice daily or salmeterol CFC MDI 50 microg twice daily for 12 weeks . The primary efficacy variable was mean morning PEF and secondary variables included other lung function parameters , symptom scores , use of relief medication and safety assessment s. The difference between the treatments in adjusted mean morning PEF ( salmeterol HFA-salmeterol CFC ) were 2.5 and -3.2 L/min for per- protocol population s of children and adults , respectively . The lower limit of 95 % confidence intervals for both population s was within the pre-defined limit ( -15 L/min ) set for non-inferiority . Similar results were observed in intent-to-treat ( ITT ) population s. In children , the two formulations result ed in a lack of any statistically significant difference in secondary efficacy parameters . A significant difference at endpoint in clinic forced expiratory volume in 1s was reported in favour of the HFA formulation in the adult population , although the magnitude of this effect was not considered clinical ly significant . The incidences of adverse events ( AEs ) were similar for both formulations and population s , and no safety concerns were generated . Together these data demonstrate salmeterol HFA MDI to be as effective as salmeterol CFC MDI in adults and children BACKGROUND More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children . OBJECTIVE The Pediatric Asthma Controller Trial ( PACT ) compared the effectiveness of 3 regimens in achieving asthma control . METHODS A total of 285 children ( ages 6 - 14 years ) with mild-moderate persistent asthma on the basis of symptoms , and with FEV(1 ) > or= 80 % predicted and methacholine FEV(1 ) PC(20 ) < or= 12.5 mg/mL , were r and omized to 1 of 3 double-blind 48-week treatments : fluticasone 100 microg twice daily ( fluticasone monotherapy ) , fluticasone 100 microg/salmeterol 50 microg in the morning and salmeterol 50 mug in the evening ( PACT combination ) , and montelukast 5 mg in the evening . Outcomes included asthma control days ( primary outcome ) , exacerbations , humanistic measurements , and pulmonary function measurements . RESULTS Fluticasone monotherapy and PACT combination were comparable in many patient-measured outcomes , including percent of asthma control days , but fluticasone monotherapy was superior for clinic-measured FEV(1)/forced vital capacity ( P = .015 ) , maximum bronchodilator response ( P = .009 ) , exhaled nitric oxide ( P < .001 ) , and PC(20 ) ( P < .001 ) . Fluticasone monotherapy was superior to montelukast for asthma control days ( 64.2 % vs 52.5 % ; P = .004 ) and for all other control outcomes . Growth over 48 weeks was not statistically different ( fluticasone , 5.3 cm ; PACT combination , 5.3 cm ; montelukast , 5.7 cm ) . CONCLUSION Both fluticasone monotherapy and PACT combination achieved greater improvements in asthma control days than montelukast . However , fluticasone monotherapy was superior to PACT combination in achieving other dimensions of asthma control . Growth was similar in all groups . CLINICAL IMPLICATION S Therefore , of the regimens tested , the PACT study findings favor fluticasone monotherapy in treating children with mild-moderate persistent asthma with FEV(1 ) > or= 80 % predicted , confirming current guideline recommendations
BACKGROUND Long-acting beta2-agonists ( LABA ) in combination with inhaled corticosteroids ( ICS ) are increasingly prescribed for children with asthma .
OBJECTIVES To assess the safety and efficacy of adding a LABA to an ICS in children and adolescents with asthma .
To determine whether the benefit of LABA was influenced by baseline severity of airway obstruction , the dose of ICS to which it was added or with which it was compared , the type of LABA used , the number of devices used to deliver combination therapy and trial duration .