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A one-week dose-ranging study of inhaled salmeterol in children with asthma. Impact of steroids on recovery after uvulopalatopharyngoplasty. Regulation of stromal cell-derived factor-1 and exhaled nitric oxide in asthmatic children following montelukast and ketotifen treatment. The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma. Multicenter study of bitolterol and isoproterenol nebulizer solutions in nonsteroid-using patients. Tolerability of indacaterol, a novel once-daily beta2-agonist, in patients with asthma: a randomized, placebo-controlled, 28-day safety study. High-Dose Inhaled Flunisolide versus Budesonide in the Treatment of Acute Asthma Exacerbations in Preschool-Age Children The Prevention of Early Asthma in Kids study: design, rationale and methods for the Childhood Asthma Research and Education network. 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Cromolyn versus triamcinolone acetonide for youngsters with moderate asthma. Daily or intermittent budesonide in preschool children with recurrent wheezing. Single centre open study to compare patient recording of PRN salbutamol use on a daily diary card with actual use as recorded by the MDI compliance monitor. Randomized controlled trial of fluticasone in preschool children with intermittent wheeze. Clinical comparability of ventolin formulated with hydrofluoroalkane or conventional chlorofluorocarbon propellants in children with asthma. A comparison of salmeterol with albuterol in the treatment of mild-to-moderate asthma. Zafirlukast for symptomatic mild-to-moderate asthma: a 13-week multicenter study. The Zafirlukast Trialists Group. Salmeterol powder compared with albuterol aerosol as maintenance therapy for asthma in adolescent and adult patients. A comparison of beclomethasone, salmeterol, and placebo in children with asthma. Canadian Beclomethasone Dipropionate-Salmeterol Xinafoate Study Group. Randomised trial comparing as-needed versus regular treatment with formoterol in patients with persistent asthma. Clinical Equivalence Trial on Budesonide Delivered either by the Novolizer® Multidose Dry Powder Inhaler or the Turbuhaler® in Asthmatic Patients Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing. Efficacy of salmeterol xinafoate powder in children with chronic persistent asthma. Tachyphylaxis following regular use of formoterol in exercise-induced bronchospasm. Haemodynamic responses to salbutamol and isometric exercise are altered in young adults with mild asthma Low-dose fluticasone propionate with and without salmeterol in steroid-naïve patients with mild, uncontrolled asthma. A controlled trial of twice daily triamcinolone oral inhaler in patients with mild-to-moderate asthma. 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Efficacy of salmeterol in the treatment of childhood asthma. Efficacy and Safety of Formoterol Delivered Via a New Multidose Dry Powder Inhaler (Certihaler™) in Adolescents and Adults with Persistent Asthma Maintenance plus reliever budesonide/formoterol compared with a higher maintenance dose of budesonide/formoterol plus formoterol as reliever in asthma:an efficacy and cost-effectiveness study Six‐year follow‐up of an intervention to improve the management of preschool children with asthma A comparison of celiprolol and chlorthalidone in hypertensive patients with reversible bronchial obstruction. Long-term effects of budesonide or nedocromil in children with asthma. Effect of clarithromycin on acute asthma exacerbations in children: an open randomized study. A twelve-week comparison of salmeterol and salbutamol in the treatment of mild-to-moderate asthma: a Canadian multicenter study. Effect of budesonide in combination with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study Fluticasone Propionate HFA-134a Pressurized Metered-Dose Inhaler in Adolescents and Adults with Moderate to Severe Asthma Inhaled beclomethasone dipropionate (BDP) prevents seasonal changes in atopic asthmatics. Effective control of asthma with hydrofluoroalkane flunisolide delivered as an extrafine aerosol in asthma patients. Intermittent or daily montelukast versus placebo for episodic asthma in children. Efficacy, safety, and impact on quality of life of salmeterol in patients with moderate persistent asthma. Tolerance to the protective effect of salmeterol in mild untreated asthmatics. Fluticasone propionate and salmeterol administered via Diskus compared with salmeterol or fluticasone propionate alone in patients suboptimally controlled with short-acting beta2-agonists. Asthma symptoms and airway hyperresponsiveness are lower during treatment with nedocromil sodium than during treatment with regular inhaled albuterol. Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma. Inflammatory cells and eosinophilic activity in asthmatics investigated by bronchoalveolar lavage. The effects of antiasthmatic treatment with budesonide or terbutaline. A placebo-controlled, dose-ranging study of montelukast, a cysteinyl leukotriene-receptor antagonist. Montelukast Asthma Study Group. Preemptive use of high-dose fluticasone for virus-induced wheezing in young children. A comparison of regular with intermittent bronchodilators in asthma patients on inhaled steroids Need for theophylline in severe steroid‐requiring asthmatics Safety of salmeterol in the maintenance treatment of asthma. [Comparative study of the effects of regular or on-demand salbutamol inhalation in the treatment of asthma]. A trial comparing nedocromil sodium (Tilade®) and placebo in the management of bronchial asthma Antibody response after varicella vaccination in children treated with budesonide inhalation suspension or non-steroidal conventional asthma therapy. Evaluation of montelukast in 8 to 14 year old children with mild persistent asthma and compared with inhaled corticosteroids. Efficacy of Uniphyl, salbutamol, and their combination in asthmatic patients on high-dose inhaled steroids. Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial Long-acting beta 2-agonist salmeterol compared with albuterol in maintenance asthma therapy. Does measuring BHR add to guideline derived clinical measures in determining treatment for patients with persistent asthma? The relationship among inspiratory muscle strength, the perception of dyspnea and inhaled beta2-agonist use in patients with asthma. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. [Salmeterol improves the control of disease in patients with moderate asthma. A comparative study of inhaled salmeterol 50 mg and salbutamol depot tablets 8 mg, both administered twice daily]. Cost Effectiveness of Budesonide/Formoterol for Maintenance and Reliever Therapy versus Salmeterol/ Fluticasone plus Salbutamol in the Treatment of Asthma No symptoms, no asthma: the acute episodic disease belief is associated with poor self-management among inner-city adults with persistent asthma. Asthma symptoms, morbidity, and antiinflammatory use in inner-city children. Long term treatment of severe asthma with subcutaneous terbutaline. Airway inflammation in patients with asthma with high-fixed or low-fixed plus as-needed budesonide/formoterol. Observations with tinset tablet in allergic respiratory tract diseases. A new index of prognostic severity for chronic asthma. Budesonide/formoterol maintenance and reliever therapy in primary care asthma management: effects on bronchial hyperresponsiveness and asthma control. Tachyphylaxis to systemic but not to airway responses during prolonged therapy with high dose inhaled salbutamol in asthmatics. The effect of sustained-release aminophylline on exercise-induced asthma. Budesonide/Formoterol Maintenance and Reliever Therapy in Asian Patients (Aged ≥16 Years) with Asthma A double-blinded, comparative study of the effects of short preseason specific immunotherapy and topical steroids in patients with allergic rhinoconjunctivitis and asthma. A Comparison of Budesonide/Formoterol Maintenance and Reliever Therapy Versus Conventional Best Practice in Asthma Management in Spain The clinical efficacy of fluticasone propionate (Fluvent) compared with beclomethasone dipropionates (Becotide) in patients with mild to moderate brochial asthma at the University College Hospital, Ibadan, Nigeria. Fluticasone propionate compared with theophylline for mild-to-moderate asthma. A randomized clinical trial of peak flow versus symptom monitoring in older adults with asthma. Effect of disease duration on dose-response of inhaled budesonide in asthma. Celiprolol--review of airways studies. Relationships between duration of asthma and asthma severity among children in the Childhood Asthma Management Program (CAMP) The Childhood Asthma Management Program (CAMP): design, rationale, and methods. Childhood Asthma Management Program Research Group. The effect of inhaled albuterol in moderate to severe asthma. No effect of inhaled budesonide on the response to inhaled ozone in normal subjects. Continuous and intermittent salbutamol tablet administration in asthmatic children. Efficacy of IV theophylline in children with severe status asthmaticus. Salmeterol xinafoate as maintenance therapy compared with albuterol in patients with asthma. Regular vs as-needed inhaled salbutamol in asthma control Comparison of 3 different doses of budesonide and placebo on the early asthmatic response to inhaled allergen. Improvements with tiotropium in COPD patients with concomitant asthma. The use of twice daily nedocromil sodium in the treatment of asthma. Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of chronic asthma: a multicenter, randomized, double-blind trial. Montelukast Clinical Research Study Group. Effectiveness and safety of salmeterol in nonspecialist practice settings. The therapeutic effects of inhaled long-acting beta2-adrenergics (LABA) and corticosteroids (ICS) are not affected by their inhalation sequence in moderate/persistent asthma. Aspirin intolerance in chronic childhood asthma: Detected by oral challenge. Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma. The effects of treatments with labetalol and hydrochlorothiazide on ventilatory function of asthmatic hypertensive patients with demonstrated bronchosensitivity to propranolol. Effectiveness of the Leukotriene Receptor Antagonist Zafirlukast for Mild-to-Moderate Asthma Tolerability of a salmeterol xinafoate/fluticasone propionate hydrofluoroalkane metered-dose inhaler in adolescent and adult patients with persistent asthma: a 52-week, open-label, stratified, parallel-group, multicenter study. Effect of montelukast and fluticasone propionate on airway mucosal blood flow in asthma. Nocturnal asthma: effect of salmeterol on quality of life and clinical outcomes. Pycnogenol® improvements in asthma management. [Salmeterol improves control in asthmatic patients treated in general practice. A comparative study of salmeterol (Serevent) and salbutamol (Ventoline) in patients with mild to moderate asthma]. Indacaterol, a novel inhaled β2-agonist, provides sustained 24-h bronchodilation in asthma Comparison of physician-, biomarker-, and symptom-based strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized controlled trial. Clinical effects of a Long-term Educational Program for children with asthma - Aironet. A 1-yr randomized controlled trial. Role of regular treatment with inhaled corticosteroid or leukotriene receptor antagonist in mild intermittent asthma.
BACKGROUND : A comparison of the effects of regular upsilon as needed inhaled beta agonist treatment on the control of asthma in the last 16 weeks of each of two 24 week treatment periods has been reported . This paper presents additional information on exacerbations of asthma and trends in lung function , airways hyperresponsiveness to methacholine , and bronchodilator responsiveness during the entire 24 week periods of regular or as needed beta agonist treatment . METHODS : Subjects undertook a year long r and omised , double blind crossover study of regular upsilon as needed inhaled beta agonist treatment . Fenoterol ( 400 micrograms ) or matching placebo was inhaled as a dry powder four times daily for 24 weeks , then subjects crossed over to the alternative regimen . Treatment with inhaled corticosteroids was used by 50 of the 64 subjects in constant doses throughout the study . Symptoms , peak expiratory flow rates , and drug use were recorded daily , spirometry was performed every four weeks , and methacholine and bronchodilator responsiveness were measured every eight weeks . RESULTS : Exacerbations of asthma symptoms occurred earlier and more often during regular treatment with fenoterol and four of five severe exacerbations requiring admission to hospital occurred during the period of regular treatment . Prebronchodilator forced expiratory volume in one second ( FEV1 ) was on average 0.15 litres lower ( 95 % confidence interval ( 95 % CI ) 0.11 - 0.19 ) and vital capacity ( VC ) 0.12 litres lower ( 95 % CI 0.08 - 0.16 ) than during the placebo period . Morning peak flow rates were significantly lower and evening peak flow rates significantly higher , with an increase in diurnal variation from 9.8 % ( 95 % CI 6.9 - 12.8 ) to 17.5 % ( 95 % CI 13.8 - 21.3 ) during regular treatment . Geometric mean concentration of methacholine causing a 20 % fall in FEV1 from the value after saline ( PC20 ) decreased significantly from 1.63 to 1.15 mg/ml , indicating increased bronchial hyperresponsiveness during regular treatment . Response to bronchodilator , as measured by the % increase in postbronchodilator FEV1 related to prebronchodilator FEV1 , was maintained with no evidence for tachyphylaxis . CONCLUSION : Chronic use of inhaled fenoterol result ed in more exacerbations , a significant decline in baseline lung function , and an increase in airway responsiveness to methacholine in asthmatic subjects , but did not alter bronchodilator responsiveness . These findings support the previous report that regular inhaled beta agonist treatment is deleterious in the long term control of asthma BACKGROUND The issue of whether regular use of an inhaled beta2-adrenergic agonist worsens airflow and clinical outcomes in asthma is controversial . Retrospective studies have suggested that adverse effects occur in patients with a genetic polymorphism that results in homozygosity for arginine ( Arg/Arg ) , rather than glycine ( Gly/Gly ) , at aminoacid residue 16 of the beta2-adrenergic receptor . However , the existence of any genotype-dependent difference has not been tested in a prospect i ve clinical trial . METHODS Patients with mild asthma , not using a controller medication , were enrolled in pairs matched for forced expiratory volume in 1 s ( FEV1 ) according to whether they had the Arg/Arg ( n=37 ; four of 41 matches withdrew before r and omisation ) or Gly/Gly ( n=41 ) genotype . Regularly scheduled treatment with albuterol or placebo was given in a masked , cross-over design , for 16-week periods . During the study , as-needed albuterol use was discontinued and ipratropium bromide was used as needed . Morning peak expiratory flow rate ( PEFR ) was the primary outcome variable . The primary comparisons were between treatment period for each genotype ; the secondary outcome was a treatment by genotype effect . Analyses were by intention to treat . FINDINGS During the run-in period , when albuterol use was kept to a minimum , patients with the Arg/Arg genotype had an increase in morning PEFR of 23 L/min ( p=0.0162 ) ; the change in patients with the Gly/Gly genotype was not significant ( 2 L/min ; p=0.8399 ) . During r and omised treatment , patients with the Gly/Gly genotype had an increase in morning PEFR during treatment with regularly scheduled albuterol compared with placebo ( 14 L/min [ 95 % CI 3 to 25 ] ; p=0.0175 ) . By contrast , patients with the Arg/Arg genotype had lower morning PEFR during treatment with albuterol than during the placebo period , when albuterol use was limited ( -10 L/min [ -19 to -2 ] ; p=0.0209 ) . The genotype-attributable treatment difference was therefore -24 L/min ( -37 to -12 ; p=0.0003 ) . There were similar genotype-specific effects in FEV1 , symptoms , and use of supplementary reliever medication . INTERPRETATION Genotype at the 16th aminoacid residue of the beta2-adrenergic receptor affects the long-term response to albuterol use . Bronchodilator treatments avoiding albuterol may be appropriate for patients with the Arg/Arg genotype AIMS Previous bronchoprovocation studies indicate that nifedipine attenuates airway responsiveness to several stimuli whereas diltiazem has no effect . The aim of this study was to determine whether such studies predict the efficacy of calcium channel blockers as maintenance therapy for persistent asthma . METHODS Twenty-one otherwise healthy adults with persistent asthma , mean age 25 years , completed treatment with maximum tolerated doses of placebo ( P ) , nifedipine ( N ) , and diltiazem ( D ) in a double-blind , r and omized , three-treatment , three-period , crossover manner , each for 4 weeks . Frequency and severity of asthmatic symptoms were recorded twice daily , as well as peak expiratory flow and frequency of ' prn ' use of inhaled  terbutaline .  Blood pressure , heart rate , P-R interval of the ECG and spirometry  were measured biweekly . At the end of each treatment , airway responsiveness to exercise was measured . RESULTS The mean ( s.e . mean)% of days with wheeze was 69plus minus7 % during P , 75plus minus6 % during N and 72plus minus6 % during D ( P=0.7 ) . FEV1 was 79plus minus2 % of predicted during P , 81plus minus2 % during N and 79plus minus2 % during D ( P=0.6 ) . The decrease in FEV1 after exercise was 32plus minus4 % during P , 32plus minus5 % during N and 27plus minus4 % during D ( P=0.5 ) . Heart rate was elevated during N ( P=0.0002 ) whereas P-R interval was prolonged during D ( P=0.0001 ) . CONCLUSIONS Maintenance therapy with calcium channel blockers , at doses that produce cardiovascular effects , do not suppress the signs and symptoms of persistent asthma . Previous bronchoprovocation studies did not predict these results We compared the efficacy of inhaled formoterol , a long-acting beta 2-agonist , with inhaled albuterol in 145 stable adult asthmatics in a 12-wk multicenter trial . Patients were allocated in r and omized double-blind fashion to maintenance therapy with either formoterol 12 micrograms twice a day or albuterol 200 micrograms four times a day in addition to their other asthma medications . Patients were allowed to use " rescue " 100-micrograms albuterol puffs on an as-needed basis . Mean baseline FEV , in the morning before bronchodilator was 2.14 + /- 0.76 L and 1.98 + /- 0.71 L for the formoterol and albuterol groups , respectively , these values being used as baseline covariates in subsequent analysis of predrug and postdrug FEV1 . Measured at each clinic visit , morning predrug FEV1 rose significantly with formoterol treatment and was significantly greater at all visits than in the albuterol group , the greatest difference being in Week 8 ( 2.40 + /- 0.77 versus 1.92 + /- 0.66 L , p less than 0.001 ) . Morning FEV1 30 min postdrug was significantly higher in the formoterol group at Weeks 2 and 8 , the trend not reaching statistical significance at other times . Diurnal variation in prebronchodilator peak flow rates was significantly reduced in the formoterol group throughout the trial ( 17 versus 42 L/min at Week 12 , p less than 0.0001 ) . The number of asthma episodes per week was significantly less in the formoterol group during Weeks 4 , 8 , and 12 as were the number of sleep disruptions during Weeks 2 , 4 , 6 , 8 , and 12 . Significantly more rescue albuterol was required in the albuterol group by Week 2 and throughout the remainder of the study . ( ABSTRACT TRUNCATED AT 250 WORDS Formaldehyde is an ubiquitous industrial and indoor air pollutant to which millions are daily exposed . Because of the paucity of scientific data concerning the inhalation toxicity of this compound in humans , we determined the symptoms and alterations in pulmonary function result ing from inhalation for 1 h of 3 parts per million formaldehyde in a controlled environmental chamber . The protocol consisted of r and omized exposure of each subject to clean air or 3.0 ppm HCHO on 2 separate days . Twenty-two healthy normal subjects engaged in intermittent heavy exercise ( VE = 65 L/min ) and 16 asthmatic subjects performed intermittent moderate exercise ( VE = 37 L/min ) .  Symptoms and pulmonary function were assessed during the time course of exposure ; nonspecific airway reactivity was assessed after exposure . Both groups exhibited similar , significant ( p less than 0.01 ) increases in perceived odor , nose/throat irritation , and eye irritation throughout the exposure . The normal group had the following statistically significant ( p less than 0.02 ) lower pulmonary functions after 55 min of exposure to formaldehyde as compared to clean air : 3.8 % in FEV1 , 2.6 % in FVC , and 2.8 % in FEV3 . The asthmatic group showed no statistically significant decrements in pulmonary function . Five of 38 subjects studied had decrements in FEV1 greater than 10 % . In conclusion , acute exposure to 3 ppm HCHO produced : consistent irritant symptoms in both normal and asthmatic subjects , small decreases in pulmonary function in normal subjects engaging in heavy exercise , and clinical ly significant responses ( defined here as decrements in FEU1 greater than 10 ) in 13 % of the study population . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of the present study was to compare the effectiveness , safety and health economics of budesonide/formoterol maintenance and a novel reliever therapy with conventional best practice in patients with persistent asthma in Canada . After 2 weeks of usual therapy , 1,538 patients were r and omised for 6 months to open-label budesonide/formoterol maintenance and reliever therapy 160/4.5 μg twice daily and as needed , or to guideline -based conventional best practice  . Severe asthma exacerbations , reliever medication use and total inhaled corticosteroid dose were analysed in all patients and airway inflammation was assessed in a sub- study of 115 patients . No differences were seen in time to first severe exacerbation and severe asthma exacerbation rate . There were numerically fewer emergency room visits or hospitalisations with budesonide/formoterol maintenance and reliever therapy ( 4.4 versus 7.5 events per 100 patients · yr−1 , 41 % reduction ) ; however , this did not reach statistical significance . Mean total inhaled corticosteroid dose , reliever use , asthma medication costs and total annual costs per patient were all significantly lower with budesonide/formoterol maintenance and reliever therapy . Mean sputum eosinophil cell counts remained in the range for controlled inflammation in both groups . In conclusion , budesonide/formoterol maintenance and reliever therapy achieved similar or improved clinical control compared with conventional best practice , with significantly lower total inhaled corticosteroid dose and lower cost , while maintaining similar control of eosinophilic inflammation SUMMARY Objective : The objective of this study was to evaluate montelukast 10 mg daily as treatment for allergic rhinitis in patients with symptomatic allergic rhinitis and active asthma during the allergy season . Methods : This was a multicenter study of 831 patients ( ages 15 years–85 years ) with seasonal allergen sensitivity , active symptoms of seasonal allergic rhinitis , and active asthma . Following a single-blind , placebo run-in period of 3 days–5 days , patients were r and omized to oral montelukast 10 mg ( n = 415 ) or placebo ( n = 416 ) daily during the 2-week , double-blind , active-treatment period . Main outcome measures : The primary endpoint was Daily Rhinitis Symptoms score , average of Daytime Nasal Symptoms and Nighttime Symptoms , as self-rated by patients on a 0–3 scale on daily diaries . Results : Montelukast  reduced the Daily Rhinitis Symptoms score : difference between montelukast and placebo in mean change from baseline was –0.12 [ 95 % CI –0.18 , –0.06 ; p ≤ 0.001 ] . Similar improvements were seen in Daytime Nasal Symptoms ( –0.14 [ –0.21 , –0.07 ; p ≤ 0.001 ] ) and Nighttime Symptoms ( –0.10 [ –0.16,–0.04 ; p ≤ 0.001 ] ) . Improvements ( p < 0.05 ) were seen in Daytime Eye Symptoms and in the secondary endpoints of Global Evaluations of AR by Patient and by Physician , and Rhinoconjunctivitis Quality of Life . In exploratory analyses , improvement in rhinitis symptoms was numerically ( though not statistically ) larger in patients with greater levels of asthma at study start . Montelukast provided benefit in the Global Evaluations of Asthma by Patient and by Physician : mean differences were –0.24 [ –0.41 , –0.06 ; p = 0.008 ] and –0.17 [ –0.33,–0.01 ; p = 0.037 ] . Similarly , as-needed β-agonist use ( puffs/day ) was reduced with montelukast ( p ≤ 0.005 ) . Conclusion : Montelukast provides significant relief from symptoms of seasonal allergic rhinitis , while also conferring a benefit for asthma , in patients with both allergic rhinitis and asthma BACKGROUND Although guidelines recommend daily therapy for patients with mild persistent asthma , prescription patterns suggest that most such patients use these so-called controller therapies intermittently . In patients with mild persistent asthma , we evaluated the efficacy of intermittent short-course corticosteroid treatment guided by a symptom-based action plan alone or in addition to daily treatment with either inhaled budesonide or oral zafirlukast over a one-year period . METHODS In a double-blind trial , 225 adults underwent r and omization . The primary outcome was morning peak expiratory flow ( PEF ) . Other outcomes included the forced expiratory volume in one second ( FEV1 ) before and after bronchodilator treatment , the frequency of exacerbations , the degree of asthma control , the number of symptom-free days , and the quality of life . RESULTS The three treatments produced similar increases in morning PEF ( 7.1 to 8.3 percent ; approximately 32 liters per minute ; P=0.90 ) and similar rates of asthma exacerbations ( P=0.24 ) , even though the intermittent-treatment group took budesonide , on average , for only 0.5 week of the year . As compared with intermittent therapy or daily zafirlukast therapy , daily budesonide therapy produced greater improvements in pre-bronchodilator FEV1 ( P=0.005 ) , bronchial reactivity ( P<0.001 ) , the percentage of eosinophils in sputum ( P=0.007 ) , exhaled nitric oxide levels ( P=0.006 ) , scores for asthma control ( P<0.001 ) , and the number of symptom-free days ( P=0.03 ) , but not in post-bronchodilator FEV1 ( P=0.29 ) or in the quality of life ( P=0.18 ) . Daily zafirlukast therapy did not differ significantly from intermittent treatment in any outcome measured . CONCLUSIONS It may be possible to treat mild persistent asthma with short , intermittent courses of inhaled or oral corticosteroids taken when symptoms worsen . Further studies are required to determine whether this novel approach to treatment should be recommended This r and omised , double-blind , 6-month study compared budesonide/formoterol for maintenance and relief with salmeterol/fluticasone and a fixed maintenance dose of budesonide/formoterol , both with terbutaline for relief . Following a 2-week run-in , 3335 symptomatic adults and adolescents ( mean FEV1 73 % predicted , mean inhaled corticosteroid dose 745 μg/day ) received budesonide/formoterol 160/4.5 μg one inhalation bid plus additional inhalations as needed , salmeterol/fluticasone 25/125 μg two inhalations bid plus as-needed terbutaline or budesonide/formoterol 320/9 μg one inhalation bid plus as-needed terbutaline . Budesonide/formoterol for maintenance and relief prolonged the time to first severe exacerbation requiring hospitalisation , emergency room treatment or oral steroids ( primary variable ) vs. fixed-dose salmeterol/fluticasone and budesonide/formoterol ( p = 0.0034 and p = 0.023 respectively ; log-rank test ) . Exacerbation rates were 19 , 16 and 12 events/100 patients /6 months for salmeterol/fluticasone , fixed-dose budesonide/formoterol and budesonide/formoterol for maintenance and relief , respectively , [ rate reduction vs. fixed-dose salmeterol/fluticasone ( 0.61 ; 95 % CI 0.49–0.76 , p < 0.001 ) and vs. fixed-dose budesonide/formoterol ( 0.72 ; 95 % CI 0.57–0.90 , p = 0.0048 ) ] . Budesonide/formoterol maintenance and relief patients used less inhaled corticosteroid vs. salmeterol/fluticasone and fixed-dose budesonide/formoterol patients . All treatments provided similar marked improvements in lung function , asthma control days and asthma-related quality of life  . Budesonide/formoterol for maintenance and relief reduces asthma exacerbations and maintains similar daily asthma control at a lower overall drug load compared with fixed-dose salmeterol/fluticasone and budesonide/formoterol A double-blind , r and omized , crossover chronic study was done to determine the efficacy of colchicine in 10 atopic patients with asthma . A constant dose of sustained-release theophylline and albuterol by inhalation , as needed , was administered . Compared to placebo , colchicine , 0.5 mg twice daily , significantly reduced the mean ( + /- SEM ) daily clinical score from 2.18 + /- 0.34 to 1.64 + /- 0.32 ( p less than 0.05 ) , and the daily number of inhalations of albuterol  from 5.89 + /- 1.48 to 4.01 + /- 1.26 ( p less than 0.02 ) . Colchicine significantly ( p less than 0.05 ) increased the concanavalin A-induced suppressor cell function from 16.2 + /- 4.6 % to 39.0 + /- 10.7 % , which was similar to healthy volunteers ( 41.1 + /- 3.5 % ) . Furthermore , colchicine significantly ( p less than 0.05 ) decreased serum IgE from 248 + /- 63 to 188 + /- 46 IU/ml . Colchicine had no significant effect on pulmonary function tests , the early phase reaction of antigen-induced bronchial inhalation challenge , and immediate skin test responses . Thus , colchicine has immunomodulatory effects that may perhaps have a mild benefit in the treatment of asthma BACKGROUND The association between genetic predisposition and environmental risk factors such as passive smoke in determining respiratory allergies is still uncertain ; even less is known about the role played by passive smoking in influencing the success of therapy for rhinitis and allergic asthma . OBJECTIVE The purpose of this prospect i ve , r and omised study was to determine whether passive smoking influences the outcome of therapies in paediatric patients with allergic respiratory diseases . METHODS The study included 68 children ( mean age 11.51 years ; range : 5 - 17 ) suffering from perennial rhinitis and intermittent asthma monosensitised to Dermatophagoides . Thirty-four subjects were exposed to daily passive smoking in their families , 34 were not . The two groups have been then r and omised to receive continuous treatment with cetirizine or SLIT for three years . RESULTS There were 3/34 ( 8.8 % ) dropouts in the SLIT arm and 4/34 ( 11.7 % ) in the cetirizine arm . After three years , the patients exposed to passive smoking showed higher nasal eosinophilia , a worse clinical -symptomatic and pharmacological score with a worsened bronchial reactivity and functional indices of persistent asthma , regardless of how they had been treated . Nevertheless , SLIT prevented the worsening of all the clinical parameters more than the antihistamine alone either among the children exposed to smoking or not . CONCLUSIONS Exposure to passive smoking in children suffering from respiratory allergies due to Dermatophagoides decreased the clinical response to both drug therapy and SLIT . Nonetheless , while the children su bmi tted to drug therapy worsened or did not show any significant improvement , the ones treated with SLIT improved For patients with persistent asthma , the National Asthma Education and Prevention Program recommends the regular use of controller medications to provide long-term control , together with as-needed use of rescue medications ( 1 ) . Inhaled corticosteroids are currently the most commonly used controller medications ( 1 ) . Although inhalation into the airway has advantages in terms of both safety and efficacy , problems with compliance with inhaled agents may limit their real-world effectiveness , especially in elderly and pediatric patients ( 2 , 3 ) . Cysteinyl leukotrienes are important pro-inflammatory mediators of asthma ( 4 ) . Recent clinical studies of leukotriene receptor antagonists ( 5 - 7 ) and a 5-lipoxygenase inhibitor ( 8) have shown these agents to have clinical benefit in patients with chronic asthma , and treatment guidelines now consider these agents alternative , first-line controller medications ( 1 ) . Recent studies showed that montelukast , a potent and specific leukotriene receptor antagonist ( 9 ) , had efficacy in adult ( over a 12-week period ) and pediatric ( over an 8-week period ) patient with chronic asthma and had a tolerability profile similar to that of placebo ( 10 - 12 ) . To date , no comparisons of leukotriene receptor antagonists and inhaled corticosteroids have been published . Our placebo-controlled , parallel-group study , which was primarily design ed to compare the effect of montelukast with that of placebo in a phase III clinical development trial , also compared montelukast and inhaled beclomethasone in patients with chronic asthma who require the daily use of a controller medication . Methods Patients Healthy , nonsmoking , male and female patients 15 years of age and older were eligible to participate if they had had asthma for at least 1 year before the initial study evaluation . Each patient also had to have 1 ) an FEV1 between 50 % and 85 % of predicted value , 2 ) an increase of at least 15 % in absolute FEV1 after the use of inhaled -agonist on at least two of three visits during period 1 [ see below ] , 3 ) a daytime asthma symptom score of at least 64 [ of a possible 336 ] , and 4 ) average daily use of at least one puff of as-needed , short-acting , inhaled -agonist ( salbutamol )  . Patients were excluded from the study if they had used inhaled and oral corticosteroids , cromolyn , or nedocromil within 4 weeks before the initial evaluation ; had used long-acting -agonists , antimuscarinics , and newly instituted theophylline within 2 weeks before the initial evaluation ; or had used long-acting antihistamines ( for example , they could not have used astemizole within 3 months of the initial evaluation , and they could not have used terfenadine or loratadine within 2 weeks of the initial evaluation ) . Intermittent use of short-acting antihistamines was allowed , and immunotherapy was permitted if it had been started at least 6 months before the initial study evaluation and if the monthly dose remained constant . Protocol Our r and omized , double-dummy , placebo-controlled , parallel-group trial had a 2-week , single-blind placebo run-in period ( period 1 ) ; a 12-week , double-blind treatment period ( period 2 ) ; and a 3-week , double-blind placebo washout period [ period 3 ] . Eligible patients were r and omly assigned to one of three treatment regimens : 1 ) montelukast , 10 mg once daily in the evening ; 2 ) inhaled beclomethasone , 200 g twice daily ; or 3 ) placebo . The ratio of montelukast recipients to beclomethasone recipients to placebo recipients was 3:2:2 , with a blocking factor of 7 , according to a single , computer-generated allocation schedule . Patients , investigators , and coordinating center staff were blinded to the treatment schedule until all corrections to the data base were completed . During period 3 , a subset of patients originally assigned to receive active treatment ( approximately 40 , as determined by the allocation schedule ) was switched to placebo in a blinded manner . The other patients originally assigned to receive active treatment continued to receive that treatment . This allowed us to assess withdrawal from therapy . The study was done at 36 clinical centers in 19 countries in Europe , Africa , Australia , Central America , and South America . The study protocol and informed consent were approved by local ethics review committees . All participants gave written informed consent before participation ; consent of parents or guardians was obtained for patients younger than 18 years of age . Patients were recruited from the patient pool of each clinical study center and through local newspaper advertisements . Medication The study medication consisted of 10-mg montelukast film-coated tablets , placebo tablets that were identical in appearance to the montelukast tablets , beclomethasone ( 100 g/puff ) in inhalers ( Allen & Hanburys , Stockley Park , United Kingdom ) , and placebo in inhalers identical to those used for beclomethasone . Patients were instructed to take one tablet at bedtime and to take two puffs from the inhaler ( using the AeroChamber spacer device [ Clement Clark , Columbus , Ohio ] ) at bedtime and in the morning . Short-acting , inhaled -agonist ( salbutamol , 100 g/puff ) ( Allen & Hanburys ) was to be used as needed . Patients with worsening episodes of asthma that required additional therapy were treated with oral corticosteroids according to a st and ard protocol . Patients who had more than two worsening episodes of asthma requiring corticosteroid therapy were dropped from the study . Measurements Central ized spirometry training was done according to st and ard American Thoracic Society criteria before the start of the study .  Spirometry  was done at each visit after inhaled -agonist therapy had been withheld for at least 6 hours , theophylline therapy had been withheld for at least 24 hours , and antihistamine therapy had been withheld for at least 48 hours . At least three spirometry maneuvers were done , and the largest FEV1 was reported . Spirometry data were transmitted electronically to a central data base and monitored continuously for quality , and feedback was given to the study centers ( 13 ) . If quality was not maintained , sites were visited by coordinating center personnel . Answers to four questions on daytime asthma symptoms and one question on nocturnal awakenings were collected on a daily diary card , as were morning and evening peak expiratory flow rate and daily use of as-needed salbutamol . With respect to daytime asthma symptoms , patients used a 7-point scale ( on which 0 means best and 6 means worst ) to rate the severity of symptoms , their frequency , the degree to which they were bothersome , and their impact on daily activities . These ratings were combined into a mean daily score . Nocturnal awakenings were evaluated by the patient 's response ( on a four-point scale ) to a single question ( 14 ) . The validation of these questions has been published elsewhere ( 14 ) . Peak expiratory flow was measured in the morning and in the evening immediately before study medication was taken . The best of three measurements was recorded . Prespecified end points other than peak expiratory flow included peripheral blood eosinophil counts , global evaluations by physicians and patients ( on a 7-point scale , on which 6 means very much worse and 0 means very much better ) ( 7 ) , and asthma-specific quality of life ( 15 ) . Asthma outcome end points , including asthma attacks ( defined as worsening asthma requiring oral corticosteroid treatment or an unscheduled visit to a physician , emergency department , or hospital ) , percentage of days with asthma exacerbations , and percentage of asthma-control days ( as defined elsewhere [ 11 , 16 ] ) , were also evaluated . The diary card , the Asthma Quality -of-Life Question naire ( 15 ) , and the global evaluation questions were translated from English into appropriate local language s and were vali date d for linguistic equivalence and cultural differences ( 17 ) . Patient compliance with study therapy was determined by weighing inhalers and counting tablets . The weight of a full canister was determined by averaging the weights of at least 50 canisters of beclomethasone and placebo . A st and ard puff weight was determined by repeatedly actuating and weighing 10 canisters . Laboratory safety tests , including hematologic tests , serum biochemistry analysis , and urinalysis , were done at prespecified visits , and the results were analyzed by a central laboratory . The central laboratory also determined eosinophil counts with an automated cell counter . Statistical Analysis Our primary objective was to compare montelukast with placebo with respect to two prespecified primary end points : FEV1 and daytime symptom score . Other objectives were to compare beclomethasone with placebo and to compare montelukast with beclomethasone in a stepwise manner in accordance with the Dunnet-Tamhane approach , with the comparison of montelukast and beclomethasone prespecified as an estimation of the difference using 95 % CIs ( 18 ) . No multiplicity adjustments were made for each of the secondary end points , which were prespecified as supportive . The analysis for each efficacy end point included all patients who had a measurement taken at baseline and at least one measurement taken after r and omization . Treatment responses were calculated as the average change or percentage change from baseline to period 2 ; the baseline value was the average value for period 1 . With SAS software ( SAS Institute , Inc. , Cary , North Carolina ) , we used an analysis of variance ( ANOVA ) model to estimate treatment group means and between-group differences and to construct 95 % CIs by using the least-square means and the differences in least-square means . The model contained factors for treatment , study center , and stratum ( theophylline use ) . The consistency of the treatment effect across study centers , strata , and subgroups ( which were formed according to sex , age , ethnicity , history of allergic rhinitis , and history of exercise-induced asthma ) was assessed by interaction testing done using the ANOVA model with an Previous results have demonstrated addition of long-acting beta2-adrenergic agonists to be beneficial in asthma patients already receiving inhaled corticosteroid . The purpose of this study was to determine , qualitatively as well as quantitatively , the steroid-sparing properties of salmeterol in stable asthma patients receiving maintenance inhaled corticosteroids ( 800 - 1600 microg day(-1 ) ) . In these patients , the daily dose of beclomethasone dipropionate was reduced by 200 microg each week until asthma deteriorated , with the minimal acceptable dose ( MAD ) being defined as the dose one step above deterioration ( sensitivity period ) . Following this , patients received three times the MAD for 2 weeks . Patients were r and omized to receive either salmeterol 50 microg twice daily or placebo and the MAD was again determined ( treatment period ) . Forced expiratory volume in 1 sec ( FEV1 ) was measured each week . Morning and evening peak expiratory flow ( PEF ) , symptom score and use of bronchodilator were recorded each day . Fifteen patients received salmeterol and 19 placebo .  The MAD was significantly lower in the salmeterol group compared with placebo during the treatment period ( P<0.01 ) . A 50 % reduction of the MAD was achieved by more patients treated with salmeterol than placebo ( P = 0.001 ) . Salmeterol caused a significantly greater reduction in daytime symptom score and use of as-needed beta2-agoinist therapy between sensitivity and treatment periods compared with placebo ( P<0.05 for both ) . The results demonstrate , that the addition of salmeterol to corticosteroid treatment offers a clinical ly relevant potential for reduction of inhaled corticosteroid dose in steroid sensitive asthmatics Background . It is often difficult to predict the timing and frequency of asthma attacks . In addition to interrupting the daily life of both the affected child and his/her family , asthma can also pose sudden danger to a child . Based on clinical observations , many asthma‐affected children and their parents must constantly adjust themselves to the uncertainty of the disease , which leads to increased stress on the family . The use of care maps has demonstrated increased efficiency and effectiveness in the care of asthma patients from a variety of setting s. Objective . We design ed this study to construct and evaluate a care map for asthmatic children in Taiwan . Specific attention was placed on comparing the study and control subjects by parental knowledge of asthma , medication used for asthma , hospital readmission , and health care re source usage . Subjects and Methods . The care map was constructed by in‐depth interviews with eight sets of parents of children with asthma . Forty‐four parents of 42 asthma children were r and omized into two groups in the Allergic Clinic of the Chang Gung Children 's Hospital . The experimental group of 22 parents received  individual instruction and training sessions in addition to the regular care provided to the control group of 22 parents . Results . Forty‐two children with asthma were surveyed in this study . To examine the reliability and validity of a care map for children with asthma , a quantitative survey was conducted with 42 outpatient parents with asthmatic children . There was less emergency room attending rate in experimental group ( 6/month ; p < 0.05 ) The underst and ing of the disease was much improved in parents of experimental group ( 13.85 ± 1.04 vs. 10.91 ± 2.14 ; p < 0.01 ) . Furthermore , parents acquired a more positive attitude to asthma , and almost all of the control group had irregular follow‐ups by a physician and had irregular use of medication . Conclusion . This study emphasizes that a  care map  in children with asthma ( CACM ) can be used to educate parents in how to provide the best treatment plan for their children . This study also shows how a CACM can help parents train their children in the best behaviors during asthma attacks . Empathetic assessment and elimination of cultural barriers , a well‐ design ed educational program , and a mutually developed treatment plan could significantly improve the quality of life for families and specific asthma outcomes The leukotrienes are known to be important mediators of bronchial asthma . The ability of montelukast , a potent and selective CysLT1 leukotriene receptor antagonist , to cause a dose-related improvement in chronic asthma  was investigated in a placebo-controlled , multicentre , parallel-group study . After a two week placebo run-in period , chronic asthmatic patients with a forced expiratory volume in one second ( FEV1 ) 40 - 80 % predicted with > or = 15 % increase ( absolute value ) after beta2-agonist were r and omly assigned to one of four treatment groups ( placebo or montelukast 2 , 10 , or 50 mg once daily in the evening ) for a three week , double-blind treatment period . For patient-reported end-points ( daytime symptom score , use of as needed inhaled beta2 agonist , asthma-specific quality of life ) and frequency of asthma exacerbations , montelukast 10 and 50 mg caused similar responses , superior to 2 mg and significantly ( p<0.05 ; linear trend test ) different from placebo . All three doses caused improvements in FEV1 and morning and evening peak expiratory flow rate ( PEFR ) that were significantly ( p<0.05 ) different from placebo . Differences ( least square mean ) between the pooled 10 and 50 mg montelukast treatment groups and placebo were : 7.1 % change from baseline in FEV1 , 19.23 L x min(-1 ) in morning PEFR , -0.29 in daytime asthma symptom score ( absolute value ) , and -0.82 in beta2-agonist use ( puff x day(-1 ) ) . The incidence of adverse experiences was neither dose-related nor different between montelukast and placebo treatments . We conclude that montelukast causes a dose-related improvement in patient-reported asthma end-points over the range 2 - 50 mg . Montelukast causes benefit to chronic asthmatic patients by improving asthma control end-points OBJECTIVE : In short term studies , asthma symptoms and pulmonary function have been reported to improve during and after medical treatment or surgical correction of gastroesophageal reflux ( GER ) . In this study , we aim ed to determine whether prolonged treatment of GER altered the long term natural history of asthma in asthmatics with GER . METHODS : A total of 62 patients with both GER and asthma entered a r and omized study of antireflux treatments for at least 2 yr : 24 controls ( antacids as needed ) ; 22 medical ( ranitidine 150 mg t.i.d . ) ; and 16 surgical ( Nissen fundoplication ) .  Asthma was defined as a previous diagnosis of asthma with discrete attacks of wheezing and 20 % reversibility in airway disease . GER was defined as an abnormal ambulatory 24-h esophageal pH test and macroscopic or microscopic evidence of GER disease . Overall clinical status , asthma symptom scores , and pulmonary medication requirements were recorded monthly . Peak expiratory flow rates were recorded up to seven times per day for 1 wk of each month throughout the years . Pulmonary function , esophageal manometry , and endoscopy with biopsy were repeated yearly . RESULTS : The 62 patients were followed for up to 19.1 yr . In the surgical group , but not in the medical or control groups , there was an immediate and sustained reduction in acute nocturnal exacerbations of wheezing , coughing , and dyspnea . By the end of 2 yr , improvement , marked improvement , or cure in the overall asthma status occurred in 74.9 % of the surgical group , 9.1 % of the medical group and 4.2 % of the control group , whereas the overall status worsened in 47.8 % of the control group , 36.4 % of the medical group , and 12.5 % of the surgical group ( p < 0.001 , surgical vs medical and control ) . The mean asthma symptom score of the surgical group improved 43 % , compared with less than 10 % in the medical and control groups ( p = 0.0009 ) . As determined by changes in peak expiratory flow rates , there was no statistically significant difference in pulmonary function during the 2-yr period or during regularly scheduled follow-up . There was no difference in medication requirements among the groups . There was no difference between the groups in overall survival . CONCLUSION : In patients with both GER and asthma , antireflux surgery ( but not medical therapy with ranitidine 150 mg t.i.d . ) has minimal effect on pulmonary function , pulmonary medication requirements , or survival , but significantly improves asthma symptoms and overall clinical status BACKGROUND The National Heart , Lung , and Blood Institute guideline recommends that dosing racemic albuterol be administered every 1 to 4 hours for treating patients with asthma or chronic obstructive pulmonary disease ( COPD ) in the hospital . Previously published preliminary and retrospective studies suggested that levalbuterol can be administered every 8 hours for the treatment of bronchoconstriction in hospitalized patients . However , it is unclear how the different dosing regimens affect the total number of nebulizations ( scheduled plus as-needed treatments ) and the costs of treatment of bronchoconstriction in a hospital setting . Moreover , it is not clear how the different dosing regimens affect symptom outcomes and health status in hospitalized patients with asthma or COPD . OBJECTIVE The aim of this study was to evaluate these issues in hospitalized patients with acute asthma or COPD . METHODS In this prospect i ve , multicenter , r and omized , open-label study , hospitalized patients aged > or = 18 years were r and omly assigned to receive 14-day treatment with levalbuterol 1.25 mg q6 - 8h or racemic albuterol 2.5 mg q1 - 4h , administered per routine hospital practice at each institution . The primary efficacy end point was total number of nebulizations during hospitalization . Pulmonary function , symptom evaluation ( subject general well-being score [ SGWB ] , disease symptom assessment [ DSA ] , and beta-mediated adverse effect scores ) , hospital costs ( excluding medication costs ) and hospital length of stay ( LOS ) were also evaluated . RESULTS In the intent-to-treat population ( n = 479 ; levalbuterol , 241;racemic albuterol , 238 ) , the mean ( SE ) age was 55.3 ( 16.9 ) years , the majority of patients were white ( 57.8 % ) , and the mean ( SE ) weight was 80.9 ( 24.5 ) kg . Demographic characteristics were similar between the 2 treatment groups , except that there were more females with COPD in the levalbuterol treatment group ( 63.88 % ) compared with the racemic albuterol treatment group ( 45.5 % ) ( P = 0.005 ) . Patients treated with levalbuterol required significantly fewer median total nebulizations ( 10 vs 12 ; P = 0.031 ) and scheduled nebulizations ( 9 vs 11 ; P = 0.009 ) compared with those in the racemic albuterol group . The 2 treatment groups required 0 rescue nebulizations . Mean ( SD ) forced expiratory volume in 1 second improved from baseline with both levalbuterol and racemic albuterol ( 0.06 [ 0.43 ] and 0.10 [ 0.37 ] L , respectively ) ; these improvements were maintained throughout the hospital stay ( 0.11 [ 0.48 ] and 0.16 [ 0.52 ] L ) . DSA and SGWB scores improved significantly from baseline in both treatment groups , and beta-mediated adverse effects mean scores were significantly greater with levalbuterol versus racemic albuterol ( P < 0.001 ) . In the levalbuterol and racemic albuterol treatment groups , hospital LOS ( 70.6 and 65.7 hours , respectively ) , time to discharge ( 66.0 and 62.8 hours ) , and total hospital costs ( least squares mean [ SE ] , US $ 4869.30 [ $ 343.58 ] and $ 4899.41 [ $ 343.20 ] ) were similar . CONCLUSIONS In these hospitalized patients with acute asthma or COPD treated with levalbuterol every 6 to 8 hours or racemic albuterol every 1 to 4 hours , significantly fewer total nebulizations were required with levalbuterol , without an increased need for rescue nebulizations during 14 days of hospitalization . Both treatments were associated with improvements from baseline in symptoms and health status . The costs of treating bronchoconstriction in hospitalized patients were similar between the levalbuterol and racemic albuterol groups Salbutamol diskus ( SD ) and formoterol turbuhaler ( FT ) are both fast-acting beta(2 ) agonists delivery systems used to relieve bronchoconstriction , such as that which accompanies acute exacerbations of asthma . Although SD ( which is used only on an as-needed basis ) is flow independent , the FT ( currently recommended for regular therapy ) requires a forceful deep inspiration . Thus , the efficacy of FT in children with bronchoconstriction may be inferior to that of SD . We have studied the bronchodilatation response induced by FT after a st and ard adenosine-5-monophosphate ( AMP ) bronchial challenge , and compared it to that induced by SD , and placebo .  Seventeen children ( mean age + /- SD 10.3 + /- 1.7 y ) with asthma underwent three AMP challenges , each time followed by inhalation of either placebo , SD ( 200 mug ) or FT ( 9 mug ) , in r and om order . Patterns of bronchodilatation ( forced expiratory volume in 1 second recovery ) to 90 % of baseline levels were compared . Both SD and FT were significantly better than placebo . FT was slightly better than SD , but this difference was not statistically significant . FT and SD are both effective bronchodilators and may be of comparable efficiency during acute bronchoconstriction in young children with asthma This was a 1-week study evaluating the safety and efficacy of two dosage regimens of salmeterol in children with asthma . A total of 243 children , aged 4 - 11 years , with mild-to-moderate asthma were enrolled in a r and omized , double-blind , placebo-controlled , parallel-group , multicenter study evaluating salmeterol xinafoate 21 micrograms and 42 micrograms administered via metered-dose inhaler ( MDI ) twice daily for 1 week . Patients were allowed to use albuterol MDI as needed for relief of acute symptoms . Inhaled corticosteroids and /or cromolyn at fixed dosages could be continued during the study , but theophylline and oral beta-agonists were not allowed . Twelve-hour serial spirometry ( for patients aged 6 - 11 years ) and serial peak expiratory flow rate ( PEFR ) ( all patients ) were performed on days 1 and 8 of treatment ; morning and evening PEFR were recorded each day prior to inhalation of the study drug . Safety was assessed by monitoring adverse events , clinical laboratory values , vital signs , electrocardiogram ( ECG ) , and 24-hr ECG ( Holter ) monitoring . Both the 21-micrograms and 42-micrograms doses of salmeterol produced significantly greater bronchodilation , as measured by 12-hr serial forced expiratory volume in 1 sec ( FEV1 ) ( p < or = 0.02 ) and PEFR ( p < or = 0.001 ) , than did placebo on days 1 and 8 . A small dose-response was observed , with the 42-micrograms dosage producing consistently higher serial FEV1 and PEFR than did the 21-micrograms dosage , although the differences were not statistically significant . Morning and evening PEFR increased significantly ( p < or = 0.008 ) with both dosages of salmeterol compared with placebo . Twelve patients ( 5 % ) experienced potentially drug-related adverse events , with headache ( 4 % in each salmeterol group ) being the most common . There were no clinical ly significant changes in heart rate as measured by Holter monitoring , ECGs , vital signs , or clinical laboratory values following treatment with either dose of salmeterol . Salmeterol 21 micrograms or 42 micrograms twice daily was effective in producing bronchodilation in children aged 4 - 11 years , and both dosages had good safety profiles . Patients treated with salmeterol 42 micrograms twice daily showed a trend toward greater improvement in asthma control compared with those who received salmeterol 21 micrograms OBJECTIVE To determine whether perioperative systemic corticosteroid administration can reduce uvulopalatopharyngoplasty ( UPPP ) postoperative morbidities ( e.g. , pain , anorexia , sleep disturbance , mouth odor , and fatigue ) or reduce narcotic analgesic usage . STUDY DESIGN A prospect i ve , double-blinded study with r and om assignment of treatment agent ( placebo or corticosteroid ) . METHODS From 1995 to 1998 , a consecutive sample of 48 adults presenting for elective UPPP surgery alone or in combination with tonsillectomy or septoplasty , or both , were enrolled . Twenty-eight subjects completed the protocol and were equally distributed by r and om assignment to intramuscular ( IM ) and intravenous ( IV ) doses of placebo ( saline ) or corticosteroid ( 60 mg methylprednisolone IM and 12 mg dexamethasone IV ) . Acetaminophen with codeine analgesic was available to both groups as needed . Subjects recorded a diary of symptom severity scores over the first postoperative week relating to eight commonly reported morbidities ( 1 - 4 points ) and the daily quantity of narcotic consumed . RESULTS Statistical comparison ( Wilcoxon 's rank sum test ) showed no significant differences between subjects treated with placebo or corticosteroid on postoperative day 1 or 7 . Three subjects ( 21 % ) in each treatment group reported no postoperative use of narcotic analgesic . CONCLUSIONS No statistically or clinical ly significant benefits were derived from perioperative systemic corticosteroid treatment in this sample of 28 adults treated with UPPP alone or in combination with tonsillectomy or septoplasty , or both . Some individuals tolerate post-UPPP discomfort without a narcotic analgesic BACKGROUND Montelukast and ketotifen are oral anti-allergy medications in asthmatic children . This study investigates the modulation effect of montelukast and ketotifen on children with intermittent to mild persistent asthma as demonstrated by the levels of peak expiratory flow ( PEF ) , asthma scores ( AS ) , exhaled nitric oxide ( eNO ) and plasma stromal cell-derived factor-1 ( SDF-1 ) concentration in a r and omized , prospect i ve study . METHODS Fifty asthmatic children were enrolled and received 8 weeks of treatment with oral montelukast sodium 5 mg chewable tablet administered once daily , or 1 mg ketotifen , and were followed for a 4-week post-treatment washout period .  ENO concentration , AS and PEF were measured before , 2 , 4 , 6 and 8 weeks after initial treatment , and 4 weeks after cessation of treatment . RESULTS Montelukast therapy was showed to improve AS , PEF and eNO within 2 weeks and remained the improvement during the treatment period . Montelukast also significantly decreased plasma SDF-1 levels after 8 weeks of treatment . In contrast , the ketotifen treatment revealed no significant effects in these clinical parameters until 4 and 6 weeks of the therapy , and did not suppress plasma SDF-1 levels after 8 weeks of treatment . To prove whether montelukast directly suppressed SDF-1 induction , we studied effects of montelukast on the LPS-induced SDF-1 expression and SDF-1-induced chemotaxis of monocytic ( THP-1 ) cells . Montelukast , but not ketotifen , could suppress SDF-1 expression and its related chemotaxis on THP-1 monocytic cells . CONCLUSIONS Leukotriene receptor antagonist , such as montelukast , may be a better non-steroid anti-inflammatory drug for mild childhood asthma in preventing airway inflammation Inhaled beta-adrenergic agonists are the most commonly used medications for the treatment of asthma although there is evidence that regular use may produce adverse effects in some patients . Polymorphisms of the beta(2)-adrenergic receptor ( beta(2)-AR ) can affect regulation of the receptor . Smaller studies examining the effects of such polymorphisms on the response to beta-agonist therapy have produced inconsistent results . We examined whether polymorphisms at codon 16 ( beta(2)-AR-16 ) and codon 27 ( beta(2)-AR-27 ) of the beta(2)-AR might affect the response to regular versus as-needed use of albuterol by genotyping the 190 asthmatics who had participated in a trial examining the effects of regular versus as needed albuterol use . During the 16-wk treatment period there was a small decline in morning peak expiratory flow in patients homozygous for arginine at B(2)-AR-16 ( Arg/Arg ) who used albuterol regularly . This effect was magnified during a 4-wk run out period , during which all patients returned to using as-needed albuterol , so that by the end of the study Arg Arg patients who had regularly used albuterol had a morning peak expiratory flow 30 . 5 + /- 12.1 L/min lower ( p = 0.012 ) than Arg/Arg patients who had used albuterol on an as needed basis . There was no decline in peak flow with regular use of albuterol in patients who were homozygous for glycine at beta(2)-AR-16 . Evening peak expiratory flow also declined in the Arg/Arg patients who used albuterol regularly but not in those who used albuterol on an as-needed basis . No significant differences in outcomes between regular and as-needed treatment were associated with polymorphisms at position 27 of the beta(2)-AR . No other differences in asthma outcomes that we investigated occurred in relation to these beta(2)-AR polymorphisms . Polymorphisms of the beta(2)-AR may influence airway responses to regular inhaled beta-agonist treatment Bitolterol mesylate , 1.0 mg , or isoproterenol hydrochloride , 1.5 mg , was administered three times daily for 3 months in a double-blind , multicenter study via closed-port , intermittent-flow , compressor-driven nebulizer system ( CPIF ) to 182 nonsteroid-using patients with asthma . Mean baseline FEV1 was approximately 60 % of predicted normal for both groups . Pulmonary function tests and vital signs were measured before and for up to 8 hours after treatments on test days 1 , 30 , 60 , and 90 . Mean maximum increases in FEV1 were 51 % , 54 % , 52 % , and 55 % for bitolterol versus 48 % , 46 % , 50 % , and 43 % for isoproterenol on these monthly test days . The mean FEV1 response remained greater than 15 % over zero time ( baseline ) for greater than or equal to 8 hours after medication with bitolterol on each of four monthly pulmonary function test days and 2 1/2 to 5 hours for isoproterenol .  Median duration s of bronchodilator activity for bitolterol were 7.3 , 6.5 , 6.5 , and 6.0 hours versus 4.0 , 1.7 , 3.7 , and 1.9 hours for isoproterenol on the monthly test days . On these test days , 37 % to 49 % of the patients treated with bitolterol had a duration of action of at least 8 hours compared with 16 % to 29 % after isoproterenol treatment . The onset of activity was within 5 minutes for both drugs . Bitolterol provided superior bronchodilator activity with fewer adverse effects compared with isoproterenol , and there was no evidence for drug tolerance during this 3-month study BACKGROUND Indacaterol is a novel , inhaled , once-daily beta2-agonist . OBJECTIVE To investigate the safety and tolerability of indacaterol at doses of 400 and 800 microg/d . METHODS R and omized , double-blind , placebo-controlled , parallel-group , multicenter , 28-day study . Patients with persistent asthma ( forced expiratory volume in 1 second [ FEV1 ] > or = -60 % predicted , < or = 1,600 microg of beclomethasone dipropionate or equivalent daily ) received indacaterol , 400 microg ( n = 59 ) or 800 microg ( n = 59 ) , or placebo ( n = 26 ) once daily via a single-dose dry powder inhaler . Safety assessment s were performed before and after dosing on days 1 , 14 , and 28 , with particular attention to key beta2-agonist safety variables . RESULTS A total of 144 patients were r and omized , with 135 ( 93.8 % ) completing the study .  Indacaterol was well tolerated : the incidence of adverse events ( AEs ) was similar between the active and placebo groups , and AEs , when they occurred , were mild or moderate for most ( 98.2 % ) . There was no dose-response relationship between indacaterol and the incidence of AEs ( 400 microg , 40.7 % ; 800 microg , 37.3 % ; and placebo , 38.5 % ) . Few AEs considered as beta2-agonist class effects occurred ( none leading to withdrawal ) . Small differences between indacaterol and placebo in mean serum potassium ( < or = -0.29 mmol/L ) and glucose ( < or = 0.93 mmol/L ) levels were occasionally statistically significant ( P < .05 ) but not regarded as clinical ly meaningful . As expected for a beta2-agonist , there was some indication of a trend in QTc prolongation with increasing exposure ( maximum mean change , 8.9 milliseconds ; P < .05 vs placebo ) . Significant increases in FEV1 ( P < .05 ) were seen at all postbaseline time points for both indacaterol doses vs placebo , with indacaterol-placebo differences 30 minutes after dosing of 0.21 to 0.25 L and before dosing on days 14 and 28 ( approximately 24 hours after the previous dose ) of 0.15 to 0.23 L. CONCLUSION Indacaterol had a good overall safety profile and was well tolerated at both doses , with predose FEV1 results on days 14 and 28 indicating 24-hour bronchodilator efficacy The role of inhaled corticosteroids in asthma exacerbation is debated . We compared high doses of nebulized budesonide versus high doses of nebulized flunisolide , in association with a short-acting beta-2-agonist , in the treatment of moderate asthma exacerbation in preschool children . In this r and omized , parallel group , simple blind study , 46 children aged between 3 and 5 years affected by an acute moderate asthma attack were treated with nebulized flunisolide ( Group 1 ) 40 μg/kg twice daily for 7 days and then 20 μg/kg twice daily for 14 days , or with nebulized budesonide ( Group 2 ) 0.5 mg twice daily for 7 days then 0.25 mg twice daily for 15 days . Inhaled salbutamol ( MDI+ spacer − 200 μg 4 times daily ) was administered during the first 3 days of the study and then as needed . At TO , T7 and T21 days , airway resistances were evaluated with the forced oscillation technique before and after inhalation of inhaled salbutamol ( 200 mcg ) . Parents recorded symptoms and drug use on a diary card . Forty children completed the study . Airway resistances were significantly reduced at T7 ( p < 0.01 flunisolide ; p < 0.05 budesonide ) and T21 ( p < 0.05 flunisolide ; p < 0.05 budesonide ) versus T0 in both groups , although at T7 the reduction occurred faster in group 1 than in group 2 ( p<0.01 ) . During the first 7 days of treatment , symptom scores decreased in both groups ; however , the decrease was greater in group 1 ( p < 0.05 ) . High doses of inhaled flunisolide and budesonide are both effective in the management of moderate asthma exacerbations in pre-school-age children , but the flunisolide  therapeutic effect was faster than budesonide Pediatric asthma remains an important public health concern as its prevalence and cost to the health care system is rising . In order to promote innovative research in asthma therapies , the National Heart , Lung and Blood Institute created the Childhood Asthma Research and Education Network in 1999 . As its first study , the steering committee of the Childhood Asthma Research and Education Network design ed a r and omized clinical trial to determine if persistent asthma could be prevented in children at a high risk to develop the disease . This communication presents the design of its first clinical trial , the Prevention of Asthma in Kids ( PEAK ) trial and the organization of the Childhood Asthma Research and Education Network that developed and implemented this trial . Studies of the natural history of asthma have shown that , in persistent asthma , the initial asthma-like symptoms and loss of lung function occur predominately during the first years of life . Therefore , in the Prevention of Asthma in Kids study , children 2 and 3 years old with a positive asthma predictive index were r and omized to twice daily treatment with fluticasone 88 microg or placebo via metered-dose inhaler and Aerochamber for 2 years . The double blind treatment period was followed by a 1-year observational period . Lung function was measured by spirometry and oscillometry technique at 4-month intervals throughout the study . Bronchodilator reversibility and exhaled nitric oxide ( ENO ) studies were performed at the end of the treatment and observation periods . The primary outcome measure was the number of asthma-free days . Other secondary outcomes included number of exacerbations , use of asthma medications and lung function . These measures were chosen to reflect the progression of the disease from intermittent wheezing to persistent asthma and measurement of the extent of airflow limitation and airway reactivity The aim of this study was to compare two budesonide/formoterol maintenance doses within the budesonide/formoterol maintenance and reliever therapy concept and to identify possible patient characteristics at baseline which would predict a better response to a higher than st and ard maintenance dose . A total of 8,424 patients with symptomatic asthma when using an inhaled corticosteroid ( ICS ) with or without a long-acting & bgr;2-agonist were r and omised to budesonide/formoterol 160/4.5 μg , one ( 1 × 2 ) or two ( 2 × 2 ) inhalations b.i.d . Patients used the same inhaler as needed for symptom relief . The primary outcome variable was time to first severe asthma exacerbation . In the total study population , the time to first severe asthma exacerbation was prolonged by 18 % with 2 × 2 versus 1 × 2 ( hazard ratio 0.82 ; p = 0.03 ) . Lung function ( peak expiratory flow ) was the only statistically significant predictor of a better response to 2 × 2 . The mean daily ICS doses were 737 and 463 μg in the 2 × 2 and 1 × 2 groups , respectively . In a real-life setting , budesonide/formoterol maintenance and reliever therapy at the 2 × 2 maintenance dose did prolong time to first severe exacerbation but at a higher medication load . Patients with low lung function benefited most from the higher maintenance dose In a double blind , controlled trial , the effect of high dose beclomethasone dipropionate ( 750 micrograms three times daily for five days ) administered by metered dose inhaler and valved spacer , was compared with placebo , during 70 paired episodes of acute asthma in 24 preschool children . Treatment commenced at home at the first sign of an attack . Parents ' blind preference for active treatment was significant . Data from 17 pairs of treatment , however , were affected by interventions such as hospital admission or oral corticosteroid treatment . These events occurred similarly in active and control periods . An intrasubject comparison was made of diary scores from the 18 pairs of episodes in which no intervention occurred in either the active or placebo treatment . Both daytime and night symptoms over the first week of the attack were significantly reduced by active treatment . Intermittent high dose inhaled beclomethasone dipropionate is beneficial in modifying the severity of acute episodic asthma in preschool children able to use a spacer device STUDY OBJECTIVES To determine the effect of long-term salmeterol aerosol therapy on  airway hyperresponsiveness  measured by methacholine challenge . DESIGN R and omized , double-blind , placebo-controlled , multicenter study . SETTING Thirty-one clinical centers in the United States . PATIENTS Four hundred eight asthmatic patients > or = 12 years of age with baseline FEV1 of > or = 70 % of predicted values . Patients were not using inhaled corticosteroids . INTERVENTIONS Twice-daily salmeterol aerosol , 42 microg , or placebo via metered-dose inhaler for 24 weeks . Backup albuterol was available . MEASUREMENTS AND RESULTS Pulmonary function tests were performed before , during , and after treatment . Subjects recorded asthma-related symptoms , morning and evening peak expiratory flow ( PEF ) levels , and use of supplemental albuterol daily on diary cards .  Methacholine challenges were performed 10 to 14 h postdose at weeks 4 , 12 , and 24 , and 3 and 7 days posttreatment . Over 24 weeks of treatment , salmeterol provided significant ( p < 0.001 ) protection against methacholine-induced bronchoconstriction of approximately one doubling dose of methacholine when compared to placebo with no evidence for a progressive decrease in protection . A rebound increase in airway hyperresponsiveness was not observed 3 and 7 days after cessation of salmeterol therapy . Salmeterol treatment result ed in sustained improvements of 0.21 to 0.26 L in morning premedication FEV1 and an improvement of 26.2 L/min in morning PEF when compared to placebo ( p < 0.001 ) . The use of salmeterol significantly reduced combined daytime asthma symptoms by 20 % when compared to placebo ( p = 0.005 ) . A total of 34 and 48 exacerbations , respectively , were reported in the Salmeterol and placebo groups , and no evidence was present for a difference in the severity of asthma exacerbations between groups . Adverse event profiles were similar for the salmeterol and placebo groups . CONCLUSIONS Regular long-term use of salmeterol aerosol result ed in sustained improvements in pulmonary function and asthma symptom control over the 24-week treatment period . There was no increase in bronchial hyperresponsiveness or loss of bronchoprotection at 24 weeks from that seen following 4 weeks of therapy . There was no evidence of rebound airway hyperresponsiveness after cessation of salmeterol treatment . Regular treatment with the long-acting beta-agonist salmeterol does not lead to clinical instability or vulnerability to unpredictable asthma attacks BACKGROUND We hypothesized that asthma is preceded by a stage of recurrent episodes of wheezing during the first years of life and that inhaled corticosteroid therapy during symptomatic episodes in this early phase may delay progression to persistent wheezing . METHODS We assigned one-month-old infants to treatment with two-week courses of inhaled budesonide ( 400 mug per day ) or placebo , initiated after a three-day episode of wheezing , in this single-center , r and omized , double-blind , prospect i ve study of three years ' duration . The primary outcome was the number of symptom-free days ; key secondary outcomes were the time to discontinuation due to persistent wheezing and safety , as evaluated by height and bone mineral density at the end of the study . RESULTS We enrolled 411 infants and r and omly assigned 294 to receive budesonide at a first episode of wheezing . The proportion of symptom-free days was 83 percent in the budesonide group and 82 percent in the placebo group ( absolute difference , 1 percent ; 95 percent confidence interval , -4.8 to 6.9 percent ) . Twenty-four percent of children in the budesonide group had persistent wheezing , as compared with 21 percent in the placebo group ( hazard ratio , 1.22 ; 95 percent confidence interval , 0.71 to 2.13)--a finding that was unaffected by the presence or absence of atopic dermatitis . The mean duration of the acute episodes was 10 days in both groups and was independent of respiratory viral status . Height and bone mineral density were not affected by treatment . CONCLUSIONS Intermittent inhaled corticosteroid therapy had no effect on the progression from episodic to persistent wheezing and no short-term benefit during episodes of wheezing in the first three years of life . ( Clinical Trials.gov number , NCT00234390 . ) BACKGROUND Budesonide/formoterol maintenance and reliever therapy ( Symbicort SMART ) improves asthma control compared with fixed-dose inhaled corticosteroid/long-acting beta(2)-agonist ( ICS/LABA ) regimens , but its efficacy has not been assessed in comparison with sustained high-dose salmeterol/fluticasone ( Seretide ) plus a short-acting beta(2)-agonist ( SABA ) . METHODS Patients ( N=2309 ) with symptomatic asthma ( aged 12 years ; forced expiratory volume in 1s 50 % predicted ) , who had experienced an asthma exacerbation in the previous year , were r and omised to receive budesonide/formoterol 160/4.5 microg two inhalations twice daily and as needed , or one inhalation of salmeterol/fluticasone 50/500 microg twice daily plus terbutaline as needed , for 6 months . RESULTS Time to first severe exacerbation , the pre-specified primary outcome , was not significantly prolonged ( risk ratio 0.82 ; 95 % confidence interval 0.63 , 1.05 ) . Budesonide/formoterol maintenance and reliever therapy reduced total exacerbations from 31 to 25 events/100 patients /year ( P=0.039 ) , and exacerbations requiring hospitalisation/emergency room ( ER ) treatment from 13 to 9 events/100 patients /year ( P=0.046 ) . The treatments showed no difference in measures of lung function or asthma symptoms . The mean dose of ICS received was lower using budesonide/formoterol maintenance and reliever therapy ( 792 microg/day budesonide [ 1238 microg/day beclomethasone dipropionate ( BDP ) equivalent ] versus 1000 microg/day fluticasone [ 2000 microg/day BDP equivalent ] with salmeterol/fluticasone therapy ; P<0.0001 ) . Both treatments were well tolerated . CONCLUSION In the treatment of uncontrolled asthma , budesonide/formoterol maintenance and reliever therapy reduces the incidence of severe asthma exacerbations and hospitalisation/ER treatment with similar daily symptom control compared with sustained high-dose salmeterol/fluticasone plus SABA . This benefit is achieved with substantially less ICS exposure The efficacy , safety , tolerance , and bio-equivalence of albuterol ( a relatively selective beta 2-adrenergic drug ) was evaluated in 20 asthmatic children ( 6 to 14 years of age ) . The study was divided into two phases : a single-blind multiple-dose treatment with placebo and three separate weekly treatments with 2 , 4 , and 6 mg of albuterol ( tablets or syrup ) administered four times a day ; and a double-blind crossover period comparing 4-mg albuterol tablets to syrup and placebo . Patients recorded daily diaries and were seen weekly . Theophylline , isoproterenol , and /or epinephrine was administered as needed . In phase 1 , the 4- and 6-mg albuterol doses were superior with the latter causing more side effects . In phase 2 , a 4-mg dose of albuterol was superior to placebo . The syrup formulation was superior to tablets when extra medications ( P less than .01 ) and six-hour change in pulmonary function were evaluated ; the maximum effect of the 4-mg syrup dose was reached at four hours and lasted for six hours whereas the effect of the tablet peaked at two hours and was minimal after five hours . Heart rate changes from base line were greater with syrup . Four milligrams of albuterol syrup ( 2 mg/5 ml ) four times a day is the preferred dose for the asthmatic child 6 to 14 years of age BACKGROUND Exhaled nitric oxide ( eNO ) is a noninvasive test that measures airway inflammation . Insufficient information is available concerning correlations between eNO and biologic , physiologic , and clinical characteristics of asthma in children currently not taking controller medications . OBJECTIVE The aim of this study was to find correlations between eNO and other characteristics of children with mild to moderate asthma currently not taking medications . METHODS Children aged 6 to 17 years with mild to moderate persistent asthma , taking only albuterol as needed , were characterized during 2 visits 1 week apart before being r and omly assigned into a clinical trial . At the screening visit , online measurements of  eNO  ,  spirometry  before and after bronchodilator , and biomarkers of peripheral blood eosinophils , serum eosinophil cationic protein , total serum IgE , and urinary leukotriene E4 were obtained . During a week characterization period before r and omization , symptoms were recorded on a diary and peak expiratory flows were measured twice daily using an electronic device . At the r and omization visit , eNO was repeated followed by a methacholine challenge and aeroallergen skin testing . Correlations and rank regression analyses between eNO and clinical characteristics , pulmonary function , and biomarkers were evaluated . RESULTS eNO was significantly correlated with peripheral blood eosinophils ( r = .51 , P < .0001 ) , IgE ( r = .48 , P < .0001 ) , and serum eosinophil cationic protein ( r = .31 , P = .0003 ) but not with urinary leukotriene E4 ( r = .16 , P = .08 ) . A moderate correlation was found between eNO and the number of positive aeroallergen skin tests ( r = .45 , P < .0001 ) . eNO did not correlate with FEV1 % predicted but was weakly correlated with FEV1/forced vital capacity ( r = -.19 , P = .032 ) , bronchodilator response ( r = .20 , P = .023 ) , and FEV1 PC20 methacholine ( r = -.31 , P = .0005 ) . No significant correlations were found between eNO and clinical characteristics or morning or evening peak expiratory flow measurements . The rank regression analysis demonstrated that 5 variables accounted for an R square of.52 ( eosinophils [ P < .0001 ] , IgE [ P = .0023 ] , age [ P < .0001 ] , months of inhaled corticosteroid use in the year before study entry [ P = .01 ] , and FEV1 PC20 [ P = .0061 ] ) . CONCLUSIONS These findings suggest that eNO provides information about the asthmatic state consistent with information from other markers of inflammation . It is a noninvasive technique that could be used in decisional management of children with asthma STUDY OBJECTIVE To compare a novel asthma management strategy --budesonide/formoterol in a single inhaler for both maintenance therapy and symptom relief -- with a higher dose of budesonide plus as-needed terbutaline . METHODS This was a 6-month , r and omized , double-blind , parallel-group study in patients with mild-to-moderate asthma ( n = 697 ; mean age , 38 years [ range , 11 to 79 years ] ; mean baseline FEV1 , 75 % of predicted ; mean inhaled corticosteroid [ ICS ] dosage , 348 microg/d ) . Following a 2-week run-in period , all patients received two blinded , dry powder inhalers , one containing maintenance medication and one containing medication to be used as needed for the relief of symptoms . Patients were r and omized to receive either budesonide/formoterol ( 80 microg/4.5 microg , two inhalations qd ) for maintenance plus additional inhalations as needed for symptom relief , or budesonide ( 160 microg , two inhalations qd ) for maintenance medication plus terbutaline ( 0.4 mg ) as needed . The primary efficacy variable was morning peak expiratory flow ( PEF ) . RESULTS Patients receiving budesonide/formoterol showed greater improvements in morning PEF than patients receiving budesonide ( increases of 34.5 L/min vs 9.5 L/min , respectively ; p < 0.001 ) . The risk of having a severe exacerbation ( hospitalization/emergency department [ ED ] treatment , oral steroids for asthma , or a > or = 30 % decrease from baseline in morning PEF on 2 consecutive days ) was 54 % lower with budesonide/formoterol vs budesonide ( p = 0.0011 ) . Budesonide/formoterol patients experienced 90 % fewer hospitalizations/ED treatments due to asthma than budesonide patients ( 1 vs 10 , respectively ; p = 0.026 ) . The increased efficacy with budesonide/formoterol was achieved with less ICS than was used in the budesonide group ( mean dose , 240 microg/d vs 320 microg/d , respectively ) and with 77 % fewer oral steroid treatment days vs budesonide ( 114 days vs 498 days , respectively ) . Both treatments were well tolerated . CONCLUSIONS Budesonide/formoterol for both maintenance and relief improves asthma control with a lower steroid load compared with a higher dose of budesonide plus terbutaline BACKGROUND Asthma guidelines recommend that long-acting inhaled beta-agonists should be used as maintenance therapy for patients with asthma inadequately controlled on an inhaled corticosteroid . We studied the safety and efficacy of the long-acting beta-agonist formoterol compared with terbutaline , each taken as needed , in patients with moderate to severe asthma . METHODS Patients were taking an inhaled corticosteroid ( mean dose 870 microg daily ) and had a forced expiratory volume in 1 s ( FEV1 ) of at least 50 % predicted ( mean 74 % ) . Those requiring an inhaled beta-agonist three to eight times a day during the study run-in period ( 362 of 621 who started ) were r and omly assigned formoterol 4.5 microg or terbutaline 0.5 mg as needed by Turbuhaler in daily doses up to 54 microg and 6 mg , respectively , for 12 weeks in a double-blind , parallel-group study . Analyses were by intention to treat . FINDINGS The 362 r and omised patients ( 157 men , 205 women ) had a mean age of 47 years . Patients taking formoterol had a longer time to their first severe asthma exacerbation ( relative-risk ratio 0.55 [ 95 % CI 0.34 - 0.89 ] ) , took fewer inhalations of study drug , and had larger increases in FEV1 ( 5 % ) and morning and evening peak expiratory flow ( mean difference in increase 11 L/min and 8 L/min ) than those taking terbutaline . No safety issues were identified . INTERPRETATION When taken as needed , formoterol 4.5 microg provided better asthma control than terbutaline 0.5 mg in patients requiring moderate doses of relief medication despite inhaled corticosteroid treatment . Safety studies should be extended to a wider population of patients with asthma By morphometric investigation of the relative content of elastic and collagen fibres , we have tested the hypothesis that loss of elastic fibres in the conducting airways and lung parenchyma may reduce tissue elastic recoil , result ing in increased airway maximal closure and apparent increased responsiveness . The study groups comprised : Group A ( n = 11 ) with relatively mild atopic asthma using inhaled bronchodilators prn ( i.e. short-term corticosteroids users ) ; Group B ( n = 9 ) with more severe asthma requiring inhaled bronchodilators regularly , and daily inhaled glucocorticosteroids ( i.e. longterm corticosteroid users ) ; Group C ( n = 12 ) normal healthy workers . Bronchial biopsy sample s were taken from three sites from the left lung . Group A biopsy sample s were taken before and after a 4 wk treatment period with inhaled corticosteroids ( 200 micrograms b.i.d . ) and the relative elastic and collagen fibre content of a subepithelial zone was determined from electron micrographs . In a parallel study , the relative proportion of elastic fibre in post mortem lung tissue sample s ( inner aspect of the bronchial wall , alveolar wall , and points of attachment of surrounding alveoli to intrapulmonary bronchi ) from subjects suffering a fatal asthma attack ( n = 11 ) , and non-asthmatic suffering sudden death ( n = 9 ) , were determined using Miller 's elastic and eosin counterstain for light microscopy . In bronchial biopsies of normal subjects , 4.6 ( SEM 1.1)% of subepithelial connective tissue was elastic fibre , similar to mild asthmatic subjects , 1.9 ( SEM 0.48)% . Neither short-term ( 4 weeks ) inhaled corticosteroid ( 200 micrograms b.i.d . ) nor long-term ( < 6 months ) treatment with variable doses of inhaled steroids ( 100 - 1000 micrograms b.i.d . ) significantly altered the elastic or collagen content of the tissue . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Inhaled beta-agonists are the most commonly used treatment for asthma , but data suggest that regularly scheduled use of these agents may have deleterious effect on the control of asthma . We compared the effects of regularly scheduled use of inhaled albuterol with those of albuterol used only as needed in patients with mild chronic , stable asthma . METHODS In a multicenter , double-blind study , we r and omly assigned 255 patients with mild asthma to inhale albuterol either on a regular schedule ( 126 patients ) or only as needed ( 129 patients ) . The patients were followed for 16 weeks . RESULTS The primary outcome indicator , peak expiratory air flow measured in the morning , did not change significantly during the treatment period in the scheduled ( 416 liters per minute after the run-in period and 414 liters per minute after the treatment period ) or the as-needed ( 424 liters per minute at both times ) treatment groups ( P=0.71 ) . There were no significant differences between the two groups in peak flow variability , forced expiratory volume in one second , the number of puffs of supplemental albuterol needed , asthma symptoms , asthma quality -of-life score , or airway responsiveness to methacholine . The statistically significant differences between the groups in evening peak flow and in the short-term bronchodilator response to inhaled albuterol were small and judged to be clinical ly unimportant . CONCLUSIONS In patients with mild asthma , neither deleterious nor beneficial effects derived from the regular use of inhaled albuterol beyond those derived from use of the drug as needed . Inhaled albuterol should be prescribed for patients with mild asthma on an as-needed basis The aim of this study was to evaluate whether ozone exposure induces a similar airway inflammatory response in subjects with different degrees of asthma severity . Two groups of asthmatic subjects were studied : seven with intermittent mild asthma not requiring regular treatment ( group A ) ; and seven with persistent mild asthma requiring regular treatment with inhaled corticosteroids and long-acting beta2-agonists ( group B ) . All subjects were exposed , in a r and omized cross-over design , to air or O3 ( 0.26 parts per million ( ppm ) for 2 h with intermittent exercise ) ; subjects in group B withdrew from regular treatment 72 h before each exposure . Before the exposure , and 1 and 2 h after the beginning of the exposure they performed a pulmonary function test , and a question naire was completed to obtain a total symptom score ( TSS ) . Six hours after the end of the exposure , hypertonic saline ( HS ) sputum induction was conducted . Sputum cell percentages , eosinophil cationic protein ( ECP ) and interleukin (IL)-8 concentrations in the sputum supernatant were measured . TSS significantly increased and forced vital capacity ( FVC ) and forced expiratory volume in one second ( FEV1 ) significantly decreased after O3 exposure in comparison with air exposure in group A , whereas no changes were observed in group B except for a significant decrement of FEV1 2 h after the beginning of O3 exposure . Sputum neutrophil percentage was significantly higher after O3 exposure than after air exposure in both groups ( Group A : 70.2 % ( 28 - 87 ) versus 26.6 % ( 8.6 - 73.2 ) ; Group B : 62.1 % ( 25 - 82.4 ) versus 27.9 % ( 14.4 - 54 ) ) . IL-8 was higher in sputum supernatant collected 6 h after O3 exposure than after air , only in group A. No change due to O3 has been found in sputum eosinophil percentage and ECP concentration in both groups . In conclusion , the degree of airway response to a short-term exposure to ozone is different in subjects with asthma of different severity . The available data do not allow elucidation of whether this difference depends on the severity of the disease or on the regular anti-inflammatory treatment Objective : To compare the effect of inhaled budesonide given daily or as-needed on  mild persistent childhood asthma .  Patients , design and interventions : 176 children aged 5–10 years with newly detected asthma were r and omly assigned to three treatment groups : ( 1 ) continuous budesonide ( 400 μg twice daily for 1 month , 200 μg twice daily for months 2–6 , 100 μg twice daily for months 7–18 ) ; ( 2 ) budesonide , identical treatment to group 1 during months 1–6 , then budesonide for exacerbations as needed for months 7–18 ; and ( 3 ) disodium cromoglycate ( DSCG ) 10 mg three times daily for months 1–18 . Exacerbations were treated with budesonide 400 μg twice daily for 2 weeks . Main outcome measures : Lung function , the number of exacerbations and growth . Results : Compared with DSCG the initial regular budesonide treatment result ed in a significantly improved lung function , fewer exacerbations and a small but significant decline in growth velocity . After 18 months , however , the lung function improvements did not differ between the groups . During months 7–18 , patients receiving continuous budesonide treatment had significantly fewer exacerbations ( mean 0.97 ) , compared with 1.69 in group 2 and 1.58 in group 3 . The number of asthma-free days did not differ between regular and intermittent budesonide treatment . Growth velocity was normalised during continuous low-dose budesonide and budesonide therapy given as needed . The latter was associated with catch-up growth . Conclusions : Regular use of budesonide afforded better asthma control but had a more systemic effect than did use of budesonide as needed . The dose of ICS could be reduced as soon as asthma is controlled . Some children do not seem to need continuous ICS treatment Background : Previous studies have shown that breathing techniques reduce short acting β2 agonist use and improve quality of life ( QoL ) in asthma . The primary aim of this double blind study was to compare the effects of breathing exercises focusing on shallow nasal breathing with those of non-specific upper body exercises on asthma symptoms , QoL , other measures of disease control , and inhaled corticosteroid ( ICS ) dose . This study also assessed the effect of peak flow monitoring on outcomes in patients using breathing techniques . Methods : After a 2 week run in period , 57 subjects were r and omised to one of two breathing techniques learned from instructional videos . During the following 30 weeks subjects practised their exercises twice daily and as needed for relief of symptoms . After week 16 , two successive ICS downtitration steps were attempted . The primary outcome variables were QoL score and daily symptom score at week 12 . Results : Overall there were no clinical ly important differences between the groups in primary or secondary outcomes at weeks 12 or 28 . The QoL score remained unchanged ( 0.7 at baseline v 0.5 at week 28 , p = 0.11 both groups combined ) , as did lung function and airway responsiveness . However , across both groups , reliever use decreased by 86 % ( p<0.0001 ) and ICS dose was reduced by 50 % ( p<0.0001 ; p>0.10 between groups ) . Peak flow monitoring did not have a detrimental effect on asthma outcomes . Conclusion : Breathing techniques may be useful in the management of patients with mild asthma symptoms who use a reliever frequently , but there is no evidence to favour shallow nasal breathing over non-specific upper body exercises The aim of this study was to investigate whether budesonide , for 10 d , administered at the first sign of an upper respiratory tract infection , could reduce asthma symptoms in 1‐3‐y‐old children with asthma during infections . The primary efficacy variable was symptom scores . The study had a multicentre , r and omized , double‐blind , placebo‐controlled design with parallel groups . Fifty‐five children with a mean age of 26 months received either budesonide or placebo via a spacer with a facemask . Each child was monitored for 1 y. Budesonide was given 400 μg q.i.d . for the first 3 d and b.i.d . for 7 d. Symptoms ( cough , wheeze , noisy breathing and breathlessness ) were scored ( 0‐3 ) daily by the parents . Asthma symptom scores were lower in children treated with budesonide than in those given placebo . The effect was most pronounced for cough and noisy breathing , but it did not affect the need for hospital care . In conclusion , treatment with budesonide , started at the first sign of a respiratory infection , reduced asthma symptoms in toddlers with episodic asthma BACKGROUND Traditional clinical outcomes have demonstrated that salmeterol improves pulmonary function and reduces asthma symptoms . However , they do not evaluate how patients perceive the effect of therapeutic intervention on day-to-day functioning and well-being . OBJECTIVE We sought to evaluate the impact of salmeterol on disease-specific quality of life with the Asthma Quality -of-Life Question naire , as well as the efficacy and safety of salmeterol in patients with stable asthma who were symptomatic despite daily use of inhaled corticosteroids . METHODS This was a r and omized , double-blind , placebo-controlled , parallel-group study of 506 patients . Patients were treated with 42 microg salmeterol or placebo twice daily for 12 weeks delivered through a metered dose inhaler . RESULTS Mean change from baseline in asthma quality -of-life scores was significantly greater ( p < or = 0.006 ) after 12 weeks of treatment with salmeterol compared with placebo ( " as-needed " albuterol ) in global scores ( 1.08 vs 0.61 ) and individual domains ( activity limitations , 0.91 vs 0.54 ; asthma symptoms , 1.28 vs 0.71 ; emotional function , 1.17 vs 0.65 ; and environmental exposure , 0.84 vs 0.47 ) . Patients treated with salmeterol experienced significantly greater improvements from baseline to week 12 compared with placebo in FEV1 ( 0.42 L vs 0.15 L , p < 0.001 ) , morning peak expiratory flow ( 47 L/min vs 14 L/min , p < 0.001 ) , evening peak expiratory flow ( 29 L/min vs 11 L/min , p < 0.001 ) , and asthma symptom scores ( daytime scores reduced by 0.55 vs 0.30 , p < 0.001 ) . Patients treated with salmeterol used significantly less supplemental albuterol ( reduced by 3 puffs/day vs 1 puff/day , p < 0.001 ) . CONCLUSION Salmeterol provided significantly greater improvement in quality -of-life outcomes in patients whose asthma symptoms are not well controlled with inhaled corticosteroids . These results demonstrate that the benefits of salmeterol are not limited to conventional clinical measures of efficacy 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 In a multicenter , double-blind , group comparative trial , the efficacy of nedocromil sodium ( nedocromil , 4 mg , four times daily [ qid ] ) , cromolyn sodium ( 2 mg , qid ) , and placebo was compared in patients receiving inhaled beta 2-agonists and inhaled corticosteroids for the treatment of chronic reversible obstructive airway disease . After a 2-week baseline period , 132 patients ( 8 centers ) between the ages of 20 and 75 years entered a 4-week run-in period in which the dose of inhaled corticosteroid was reduced by 50 percent . During the run-in phase , deterioration of symptoms ( total symptom score ) by ten points qualified patients to enter the 6-week drug trial period . Patients in the nedocromil treatment group showed the most robust and consistent improvements over placebo and cromolyn sodium for all daily dairy variables . Statistically significant improvements over placebo were noted for both active treatment groups for daytime , nighttime , and total symptom score . Symptom scores for  nedocromil were statistically significantly improved over both cromolyn sodium and placebo for both daytime and nighttime asthma . Patients treated with nedocromil also demonstrated a significant reduction in the use of nighttime as needed ( prn ) beta 2-agonists as compared with either the placebo- or cromolyn sodium-treated groups . Only nedocromil-treated patients demonstrated a statistically significant improvement in morning peak expiratory flow rate ( PEFR ) as compared with placebo . Both nedocromil and cromolyn sodium groups demonstrated statistically significant improvements in afternoon and evening PEFRs . Collectively , the improvements in nighttime symptoms , decreased bronchodilator use , and improved morning PEFR show that patients treated with nedocromil had improved nocturnal symptoms . Pulmonary function tests ( FEV1 , FVC , PEFR ) demonstrated no statistically significant differences between the two active treatments , although trends favored nedocromil for both FEV1 and PEFR . Although symptoms improved in patients treated with cromolyn sodium , the level of symptom control was less than that achieved by nedocromil . As compared with baseline control ( regular dose of inhaled steroids ) , patients treated with nedocromil plus the 50 percent reduced dosage of inhaled corticosteroid consistently demonstrated comparable or better symptom control . Although both active drugs reduced symptoms , nedocromil proved to be more effective than cromolyn sodium for treatment of reversible obstructive airway disease in patients normally well maintained on regimens of low to moderate doses of inhaled corticosteroids Although both cromolyn ( C ) and inhaled corticosteroids are anti-inflammatory therapies for childhood asthma , there are few controlled comparisons of these medications for asthma therapy in children . None were conducted in the United States , and none specifically study triamcinolone acetonide ( T ) versus C. This 12-week evaluation followed 31 youths , aged 8 to 18 years , with moderate asthma who were assigned to receive C or T according to a prer and omized and blinded code . Patients were instructed to take two inhalations from the study metered-dose inhaler ( active T or placebo ) and to inhale the contents of one study -provided ampule ( C , 20 mg , or placebo ) from a compressor-driven home nebulizer three times per day . Patients also used albuterol , two inhalations from a metered-dose inhaler , three times a day ( before study medication ) and , additionally , if needed . Patients maintained a daily diary , recording extra medication use , adverse experiences , peak flow rates morning and night , and asthma symptom scores . Laboratory assessment of pulmonary function was done at 1 , 4 , 8 , and 12 weeks .  Cosyntropin challenge and methacholine bronchoprovocation challenge  were performed at the beginning and end of the study . C and T provided similar , adequate asthma control . Symptoms of wheezing , cough , and chest tightness decreased , and daily peak expiratory flow rate increased with both regimens compared to during a 2-week baseline when patients received medication only as needed . There was no significant change in methacholine sensitivity and no change in endocrine function , as measured with fasting plasma control before and after administration of cosyntropin . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Daily inhaled glucocorticoids are recommended for young children at risk for asthma exacerbations , as indicated by a positive value on the modified asthma predictive index ( API ) and an exacerbation in the preceding year , but concern remains about daily adherence and effects on growth . We compared daily therapy with intermittent therapy . METHODS We studied 278 children between the ages of 12 and 53 months who had positive values on the modified API , recurrent wheezing episodes , and at least one exacerbation in the previous year but a low degree of impairment . Children were r and omly assigned to receive a budesonide inhalation suspension for 1 year as either an intermittent high-dose regimen ( 1 mg twice daily for 7 days , starting early during a predefined respiratory tract illness ) or a daily low-dose regimen ( 0.5 mg nightly ) with corresponding placebos . The primary outcome was the frequency of exacerbations requiring oral glucocorticoid therapy .  RESULTS The daily regimen of budesonide did not differ significantly from the intermittent regimen with respect to the frequency of exacerbations , with a rate per patient-year for the daily regimen of 0.97 ( 95 % confidence interval [ CI ] , 0.76 to 1.22 ) versus a rate of 0.95 ( 95 % CI , 0.75 to 1.20 ) for the intermittent regimen ( relative rate in the intermittent-regimen group , 0.99 ; 95 % CI , 0.71 to 1.35 ; P=0.60 ) . There were also no significant between-group differences in several other measures of asthma severity , including the time to the first exacerbation , or adverse events . The mean exposure to budesonide was 104 mg less with the intermittent regimen than with the daily regimen . CONCLUSIONS A daily low-dose regimen of budesonide was not superior to an intermittent high-dose regimen in reducing asthma exacerbations . Daily administration led to greater exposure to the drug at 1 year . ( Funded by the National Heart , Lung , and Blood Institute and others ; MIST Clinical Trials.gov number , NCT00675584 . ) The aim of this study was to assess the patients '  use of inhaled short acting bronchodilators as rescue therapy during a 4-week study period . In this study an electronic metered-dose inhaler compliance monitor ( MDI-CM ) was used to measure the time and date of actuations of the device and this information was then compared with the patients ' self reporting diary card ( DC ) . Salbutamol canisters were used in the compliance monitor . The study was approved by the local ethics committee , and written informed consent was obtained from all patients . Patients aged 18 years and over who were either receiving , or in the investigators opinion required , inhaled salbutamol on a PRN basis were enrolled for a 4-week monitoring phase during which all rescue salbutamol used was obtained from the MDI-CM . Patients were recording their use of  salbutamol  in the DC each morning and evening . There was a 2-week follow-up period following completion of the monitoring phase or withdrawal from the study . Forty-four patients were enrolled and 35 patients completed the study . The mean age ( range ) was 43 ( 20 - 76 ) years and mean FEV1 2.32 ( 0.7 - 4.0 ) 1 , with male : female ratio of 19:25 . Comparison of MDI-CM and DC recordings showed patients fell into three categories : ( 1 ) patients who used rescue salbutamol appropriately and whose MDI-CM and DC recordings matched closely ; ( 2 ) patients who used rescue salbutamol for acute relief but whose MDI-CM and DC recordings did not correlate and ( 3 ) patients whose use of rescue salbutamol was inappropriate or erratic according to the MDI-CM but whose DC indicated good compliance . This category of patients include those who ' dumped ' all their salbutamol before attending clinic appointments . There was no significant difference in the demographic details or the severity of disease in the three groups . Recorded use of ' rescue ' bronchodilator  is frequently used as an indicator of efficacy for new anti-asthma therapies . This study comparing electronic data monitoring and remembered rescue salbutamol highlights the potential errors that can occur without accurate recording systems Preschool children with intermittent wheeze are often prescribed inhaled corticosteroids , although there is no proven benefit . Measurement of airway resistance by the interrupter technique can be used to objective ly assess response to treatment . If lung function improves , treatment may be justified . Children with intermittent wheeze aged 2 to < or= 5 years of age completed a 6-week r and omized controlled crossover trial of fluticasone propionate ( 100 micro g , twice daily ) , followed by a 10-week parallel extension . The relationships between changes in resistance , serum immunoglobulin E and sensitization measured by skin prick testing were investigated . Sixty-one children completed the crossover trial and 44 ( 72 % ) completed the extension . After 6 weeks , geometric mean change in resistance was -16.0 % ( 95 % confidence interval , -7.0 to -25.0 % , p = 0.003 ) in sensitized children and -3.5 % ( 95 % confidence interval , + 0.7 to -7.6 % , p = 0.1 ) in nonsensitized children . Changes in resistance were unrelated to immunoglobulin E. Sixteen weeks after stopping fluticasone , resistance returned to baseline . This is the first study of preschool children with intermittent wheeze that has related changes in lung function on treatment to aeroallergen sensitization . Lung function improved in sensitized children and deteriorated after stopping treatment . Treatment with inhaled steroids may be justified in sensitized children BACKGROUND Aerosolized asthma medications with chlorofluorocarbon ( CFC ) propellants are being phased out because of environmental concerns about the ozone layer . Medications are being reformulated with non-ozone-depleting propellants . OBJECTIVE To evaluate the clinical comparability of albuterol sulfate formulated in a new hydrofluoroalkane-134a ( HFA ) propellant ( Ventolin HFA Inhalation Aerosol ) , and conventional CFC-containing albuterol ( Ventolin Inhalation Aerosol ) in children with asthma . DESIGN R and omized , double-blind , placebo-controlled 2-week clinical trial with a 1- to 2-week run-in period . During the run-in , patients took Ventolin CFC as needed . Patients ( n = 135 ) aged 4 to 11 years with asthma then were assigned r and omly to treatment with Ventolin HFA , Ventolin CFC , or placebo administered 4 times daily via metered-dose inhaler for 2 weeks . All patients were allowed rescue albuterol use in matching propellant as needed for relief of breakthrough symptoms . The main outcome measure was the mean percentage of predicted peak expiratory flow ( PEF ) after the morning dose of study drug on day 1 and after 2 weeks as assessed by results of 6-hour serial tests . RESULTS At day 1 , the mean ( + /- SE ) percentage of predicted PEF increased postdose by 14 % ( + /- 1 % ) in the Ventolin HFA group and 13 % ( + /- 1 % ) in the Ventolin CFC group compared with 6 % ( + /- 2 % ) in the placebo group ( P</=.006 ) . At week 2 , mean postdose increases were 11 % ( + /- 1 % ) in the Ventolin HFA and CFC groups compared with 5 % ( + /- 1 % ) in the placebo group ( P<.001 ) . There were no significant differences between the Ventolin HFA and CFC groups in postdose increases in pulmonary function , time to onset of response , duration of response , or peak effects . Safety profiles were similar among the 3 groups . CONCLUSION Ventolin HFA is clinical ly comparable to Ventolin formulated with the conventional CFC-containing propellant when administered to children with asthma . Arch Pediatr Adolesc Med . 2000;154:1219 - 1225 BACKGROUND An effective , long-acting bronchodilator could benefit patients with asthma who have symptoms not controlled by antiinflammatory drugs . We compared a new long-acting , inhaled beta 2-adrenoceptor agonist , salmeterol , with a short-acting beta 2-agonist , albuterol , in the treatment of mild-to-moderate asthma . METHODS We r and omly assigned 234 patients ( 150 male and 84 female patients 12 to 73 years old ) to one of three treatment groups : one group received 42 micrograms of salmeterol twice daily , one received 180 micrograms of albuterol four times daily , and one received placebo . Treatment was assigned in a double-blind fashion , and all patients could use supplemental inhaled albuterol as needed during the 12-week treatment period . RESULTS Measurements of the forced expiratory volume in one second , performed hourly for 12 consecutive hours , showed that a single dose of salmeterol produced a greater mean area under the curve than two doses of albuterol taken 6 hours apart ( 6.3 vs. 4.9 liter.hr , P < 0.05 ) . The difference was significant on day 1 and at week 4 of the study , but not at week 8 or 12 . Salmeterol was also more effective than albuterol or placebo ( with albuterol taken as needed ) in increasing the morning peak expiratory flow rate : salmeterol induced a mean increase of 24 liters per minute over the pretreatment values , as compared with a decrease of 6 liters per minute with albuterol ( P < 0.001 ) and an increase of 1 liter per minute with placebo ( P = 0.002 ) . The mean overall symptom score was improved most by salmeterol treatment ( P < 0.05 ) , with the number of days with symptoms and of nights with awakenings decreasing by 22 percent and 52 percent , respectively ; there were no differences in results between albuterol treatment and placebo administration . We found no evidence of tolerance to the bronchodilating effects of salmeterol , and adverse reactions to all the treatments were infrequent and mild . CONCLUSIONS For the management of mild-to-moderate asthma , salmeterol given twice daily is superior to albuterol given either four times daily or as needed The efficacy of the oral leukotriene-receptor antagonist zafirlukast was assessed as maintenance therapy for patients with mild-to-moderate asthma . A total of 762 patients aged 12 to 76 years were enrolled in a 13-week , multicenter , double-masked , placebo-controlled , parallel-group trial and r and omly assigned to receive either zafirlukast ( 20 mg twice daily ) or placebo . Patients were maintained on as-needed beta-agonist therapy throughout the study and had to have a cumulative daytime asthma symptoms score > or = 8 ( on a daily scale of 0 to 3 ) over 7 consecutive days before r and omization . Efficacy was assessed by changes in symptoms , beta-agonist use , and pulmonary function . Safety was assessed by adverse experiences , laboratory test results , physical examination , and electrocardiography .  Zafirlukast significantly decreased daytime asthma symptoms scores ( -26.5 % ) , nighttime awakenings ( -19.8 % ) , mornings with asthma ( -29.0 % ) , and beta-agonist use ( -22.3 % ) and significantly increased morning peak expiratory flow rate ( 6.9 % ) and forced expiratory volume in 1 second ( 6.3 % ) compared with placebo .  Changes in symptoms , beta-agonist use , and pulmonary function occurred within 2 days of zafirlukast treatment and continued throughout the trial . Zafirlukast was well tolerated . Pharyngitis and headache were the most common adverse events , occurring with similar frequency in both the zafirlukast and placebo groups . No clinical ly significant changes were observed in laboratory test results , findings on physical examination , or electrocardiographic findings . We conclude that zafirlukast produces early and sustained effects in the treatment of mild-to-moderate asthma Two multicenter , r and omized , double-masked , placebo-controlled studies involving 451 adolescent and adult patients with mild-to-moderate asthma compared the efficacy and safety of salmeterol powder 50 micrograms twice daily with albuterol 180 micrograms four times daily or placebo ( with albuterol as needed ) for 12 weeks . Patients had forced expiratory volume in 1 second ( FEV1 ) of 50 % to 80 % . Throughout the 12-week treatment period , the mean change from baseline in percentage of predicted FEV1 was significantly greater with salmeterol than with placebo ;  mean area under the curve for FEV1 was significantly greater with salmeterol than with albuterol or placebo . Significant improvements in morning and evening peak expiratory flow , percentage of nights without awakening , and asthma symptoms were observed with salmeterol . Salmeterol was well tolerated , and no clinical ly significant changes in electrocardiographic activity were observed BACKGROUND An inhaled glucocorticoid is currently the medication of choice for long-term control of persistent asthma in children . The role of long-acting beta2-adrenergic-receptor agonists , such as salmeterol , needs to be defined . METHODS We conducted a r and omized , double-blind , placebo-controlled , parallel-group , one-year study of 241 children ( mean [ + /-SD ] age , 9.3+/-2.4 years ) with clinical ly stable asthma and less than one month of prior glucocorticoid use . We compared inhaled beclomethasone dipropionate ( 200 microg twice daily ) with salmeterol xinafoate ( 50 microg twice daily ) and placebo ( lactose ) . The primary outcome measure , airway responsiveness ( as assessed with a methacholine challenge ) was evaluated before treatment ; after 3 , 6 , 9 , and 12 months of treatment ( 12 and 36 hours after study medications had been withheld ) ; and 2 weeks after the end of treatment . Spirometry , symptoms , use of rescue medication ( 200 microg of albuterol inhaled as needed ) , and adverse effects were also assessed . RESULTS During months 1 through 12 overall , beclomethasone was associated with significantly less airway hyperresponsiveness than salmeterol ( P= 0.003 ) or placebo ( P<0.001 ) . This effect was lost two weeks after treatment had been stopped . As compared with placebo , beclomethasone was associated with less variability between morning and evening in the peak expiratory flow ( P=0.002 ) , as was salmeterol ( P=0.02 ) . Beclomethasone was also associated with a reduced need for albuterol as rescue therapy ( P<0.001 ) and fewer withdrawals because of asthma exacerbations ( P=0.03 ) , but salmeterol was not ( P=0.09 and 0.55 , respectively ) . During months 1 through 12 , linear growth was 3.96 cm in the children receiving beclomethasone , as compared with 5.40 cm in the salmeterol group ( P=0.004 ) and 5.04 cm in the placebo group ( P=0.018 ) . Height was not measured after treatment ended . CONCLUSIONS Beclomethasone was effective in reducing airway hyperresponsiveness and in controlling symptoms of asthma , but it was associated with decreased linear growth . Salmeterol was not as effective as beclomethasone in reducing airway hyperresponsiveness or in controlling symptoms ; however , it was an effective bronchodilator and was not associated with rebound airway hyperresponsiveness , masking of symptoms , or adverse effects PURPOSE The aim of this study was to demonstrate the equivalent efficacy of inhaled formoterol in asthmatic patients , either given as-needed or on a regular twice-daily schedule . METHODS R and omised , open 12-week study in patients with mild to moderate asthma not adequately controlled with inhaled glucocorticosteroids alone . Patients received inhaled formoterol as needed or on a regular schedule ( 2x2 puffs/day with 6 microg formoterol per puff ) . Patients in the twice-daily formoterol group could use salbutamol as a rescue medication . The primary endpoint was the number of patients with asthma exacerbations in each group . RESULTS Thirty-nine centres r and omised 359 patients . The number of patients with asthma exacerbations showed neither a clinical ly relevant nor a statistically significant difference between groups : formoterol as-needed : 3.95 % ( 7 of 177 ) ; twice daily : 3.45 % ( 6 of 174 ) . Patients in the formoterol as-needed group used significantly less formoterol ( -1.5 puffs per day ; P<0.0001 ) . Including the saved rescue medication ( up to one puff per day ) , total beta-2 agonist use in the formoterol as-needed group decreased by approximately 2 - 2.5 puffs per day . Both formoterol treatment schedules were well tolerated . Musculoskeletal pain and tremor were less frequent in the formoterol as-needed group : headaches were slightly more frequent . CONCLUSION Formoterol given as needed and without additional beta-2 agonist , and formoterol given on a regular basis twice daily , supplemented by salbutamol as a rescue medication , appeared equally effective in this clinical study . Drug consumption was markedly lower in the former group Background and Objectives : To investigate the therapeutic equivalence of the two formulations of the glucocorticosteroid budesonide delivered either by the budesonide Novolizer ® , i.e. a multidose dry powder inhaler , or by the Pulmicort ® Turbuhaler ® in asthmatic patients in terms of efficacy , safety and tolerability during a 12-week treatment . Methods : A total of 315 patients were r and omised in this open , multicentre study . Inclusion criteria comprised previously diagnosed bronchial asthma of mild to moderate persistent intensity ( ranging from 60 % to a maximum of 90 % predicted FEV1 ) , need for anti-inflammatory therapy , inhalation of β2-sympathomimetics on an as needed to regular basis , reversibility of airway obstruction of > 12 % after inhalation of 2 actuations of 100 µg salbutamol  . Primary variable was FEV1 , secondary were other pulmonary function test variables , PC20FEV1 for histamine challenge , morning and evening PEFR , salbutamol usage , asthma symptoms , reactions after inhalation , st and ard safety variables . Results : The comparison of the FEV1 at study endpoint indicated that the Novolizer ® was at least as efficacious as the Turbuhaler ® ( p < 0.001 ) . All other variables of the pulmonary function tests as well as the asthma symptoms , nocturnal awakenings , PEFR measurements , or salbutamol usage indicated no relevant difference . Only 1 patient ( Turbuhaler ® ) discontinued prematurely due to lack of efficacy . None of the other safety variables ( adverse events , laboratory variables , vital signs , etc . ) indicated any difference between the groups . Conclusions : The budesonide Novolizer ® is therapeutically equivalent to the Pulmicort ® Turbuhaler ® for the long-term treatment of patients with mild to moderate persistent asthma BACKGROUND Acute wheezing illnesses in preschoolers require better management strategies to reduce morbidity . OBJECTIVES We sought to examine the effectiveness of episodic use of an inhaled corticosteroid and a leukotriene receptor antagonist in preschoolers with intermittent wheezing . METHODS In a r and omized , double-blind , placebo-controlled 12-month trial , 238 children aged 12 to 59 months with moderate-to-severe intermittent wheezing received 7 days of either budesonide inhalation suspension ( 1 mg twice daily ) , montelukast ( 4 mg daily ) , or placebo in addition to albuterol with each identified respiratory tract illness ( RTI ) . Proportion of episode-free days ( EFDs ) during the 12-month trial was the primary outcome . RESULTS The 3 treatment groups did not differ in proportions of EFDs , with adjusted mean EFDs of 76 % ( 95 % CI , 70 % to 81 % ) for budesonide , 73 % ( 95 % CI , 66 % to 79 % ) for montelukast , and 74 % ( 95 % CI , 65 % to 81 % ) for conventional therapy ( P = .66 ) . The 3 groups did not differ in oral corticosteroid use , health care use , quality of life , or linear growth . However , during RTIs , budesonide and montelukast therapy led to modest reductions in trouble breathing ( 38 % [ P = .003 ] and 37 % [ P = .003 ] , respectively ) and interference with activity scores ( 32 % [ P = .01 ] and 40 % [ P = .001 ] , respectively ) that were most evident in those with positive asthma predictive indices . CONCLUSIONS In preschool children with moderate-to-severe intermittent wheezing , episodic use of either budesonide or montelukast early in RTIs , when added to albuterol , did not increase the proportion of EFDs or decrease oral corticosteroid use over a 12-month period . However , indicators of severity of acute illnesses were reduced , particularly in children with positive asthma predictive indices BACKGROUND The efficacy and safety of salmeterol powder have not previously been evaluated in children with asthma in the United States . OBJECTIVE The efficacy and safety of salmeterol powder versus placebo were compared in children between the ages of 4 and 11 years with chronic persistent asthma . METHODS A r and omized , double-blind , placebo-controlled , parallel group trial was performed at 11 clinical centers . Two hundred seven patients were r and omly assigned to receive 50 microg salmeterol powder or placebo ( and albuterol as needed ) twice daily via a breath-actuated device for 12 weeks . Twelve-hour serial pulmonary function assessment s were conducted on day 1 and at week 12 . Daily recordings of morning and evening peak expiratory flow ( PEF ) , supplemental albuterol use , asthma symptoms , and nocturnal awakenings were assessed . RESULTS On day 1 and at week 12 , weighted mean percent of predicted PEF ( P < .001 , day 1 and P=.008 , week 12 ) and weighted mean forced expiratory volume in one second ( P < .001 , day 1 and week 12 ) were significantly higher at all timepoints evaluated over the 12-hour postdosing period in patients treated with salmeterol powder compared with placebo . Overall reductions in supplemental albuterol use and mean asthma symptom scores were also significantly greater in children administered salmeterol compared with placebo ( P=.004 and P=.006 , respectively ) . The frequency of adverse events was similar in the two treatment groups . CONCLUSION Salmeterol powder ( 50 microg twice daily ) is effective and safe in producing bronchodilation and relieving symptoms in children with chronic persistent asthma during 12 weeks of treatment BACKGROUND Formoterol is a highly effective therapeutic agent in the prevention of exercise-induced bronchospasm ( EIB ) . Regular use of beta-adrenergic drugs may result in a reduction in the protective effect afforded by these bronchodilators against bronchoconstrictor stimuli . It is unknown whether this effect extends to formoterol and exercise . METHODS We performed a r and omized , double-blind , parallel clinical trial in 19 patients with EIB . Each patient received inhaled formoterol or placebo twice daily during 4 weeks . Patients performed two exercise tests in a cycle ergometer on the 1st , 14th , and 28th study days separated 3 hours from each other . A dose of formoterol was given 30 min prior to the 2nd test . RESULTS There were significant differences in bronchoprotection between days 1 and 14 ( p = .012 ) and between days 1 and 28 ( p = .012 ) in the formoterol group . No differences were found in the placebo group . The evolution of the bronchoprotection index was also significantly different between the formoterol and the placebo group ( p = .002 ) from day 1 to 28 . CONCLUSIONS Tachyphylaxis developed to the protective effect of formoterol against EIB after 4 weeks of regular dosing . Tolerance was already found on day 14 , though not progressive . Formoterol should be recommended only as needed in EIB Objectives : Tolerance to the haemodynamic effects of regularly inhaled β2 agonists has been reported in a research setting . It is unclear whether cardiovascular responses in adults with asthma are influenced by their use in routine clinical practice . This study aim ed to characterise the effects of acute salbutamol administration on systemic haemodynamics in adults with mild asthma who were receiving intermittent β2 agonist treatment . Methods : Ten patients with mild asthma and ten healthy age and sex-matched controls were recruited to a r and omised placebo-controlled double-blind two-way crossover study . Each received salbutamol 200 μg or placebo , then performed sustained isometric h and grip exercise as an adrenergic cardiovascular stimulus  . Heart rate and blood pressure responses were observed during rest and exercise , and cardiac index and systemic vascular resistance index were measured using non-invasive impedance cardiography . Results : Isometric exercise caused a greater increase in heart rate ( 12±3 vs. 8±3 bpm , P<0.01 ) and diastolic blood pressure ( 19±3 vs. 12±3 mmHg , P<0.01 ) in patients with asthma compared with healthy controls . Salbutamol administration significantly increased heart rate , blood pressure and cardiac index in healthy controls , but these responses were attenuated in patients with asthma . Conclusion : These findings indicate that adults with asthma , who are receiving intermittent β2 agonist treatment , have a greater cardiovascular responses to sympathetic stimulation , and haemodynamic tolerance to acute salbutamol administration 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 National and international guidelines recommend inhaled anti-inflammatory medications for patients with all but the mildest forms of asthma . Patients may also be more compliant with twice daily dosing . OBJECTIVE To evaluate the efficacy and safety of triamcinolone acetonide ( triamcinolone acetonide ) , 400 microg bid , in mild-to-moderate asthma patients . METHODS A multicenter , r and omized , double-blind , placebo-controlled study with a 7- to 21-day baseline and 6-week treatment period . Adult mild-to-moderate asthma patients poorly controlled by beta2-agonists alone were r and omized to receive placebo ( 48 ) or triamcinolone acetonide ( 53 ) . Patients recorded daytime and nighttime asthma symptoms , albuterol use , and morning and evening peak expiratory flow ( PEF ) rates on diary cards . Clinic spirometry measures included FEV1 , FEF25 - 75 % , FVC , FEV1/FVC , and PEF . RESULTS Triamcinolone acetonide treatment result ed in improvement from baseline of 17 % for FEV1 ( P < .0001 ) ; 44 % for albuterol use ( P = .0009 ) ; 9 % for FVC ( P = .0185 ) ; 19 % for PEF ( P = .0011 ) ; 42 % for FEF25 - 75 % ( P < .0001 ) ; 8 % for FEV1/FVC ( P = .0016 ) ; 36 % for daytime , 39 % for nighttime , and 38 % for total asthma symptoms ( P < or = .0001 ) ; and 12 % for morning , and 10 % for evening PEF ( P < or = .001 ) . These changes were highly significant when compared with placebo ( P < or = .0185 ) . Significant improvement for all variables was demonstrated within 1 to 2 weeks of active treatment , and maintained for most variables over the 6-week treatment phase . Both treatments were well tolerated . Respiratory adverse events occurred more frequently with placebo ;  pharyngitis was reported more frequently with triamcinolone acetonide . CONCLUSIONS Triamcinolone acetonide , administered twice daily , can effectively and safely treat patients with milder forms of asthma . In these patients , triamcinolone acetonide improves asthma symptoms and decreases the need for as-needed beta2-agonists 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 The present study compared the safety of 4.5 µg formoterol with 0.5 mg terbutaline , both by Turbuhaler ® and used as needed , in addition to regular formoterol in moderate asthma . In this double-blind parallel-group study , 357 patients taking a moderate-to-high dose of inhaled corticosteroids and additional terbutaline ( 2–5 inhalations·day−1 during run-in ) were r and omised to either formoterol or terbutaline as needed in addition to formoterol 9 µg b.i.d . over 12 weeks . Adverse events , serum potassium levels , electrocardiogram , vital signs and lung function were assessed monthly ; peak expiratory flow and severe asthma exacerbations were recorded daily . Patients used 2.16 ( range 0.0–6.3 ) formoterol and 2.34 ( range 0.1–7.5 ) terbutaline relief inhalations·day−1 . No clinical ly significant differences in safety variables were found between treatments . Statistically greater increases in cardiac frequency ( 2.6 beats·min−1 , p=0.03 ) were found on terbutaline . There were 44 and 52 severe asthma exacerbations with formoterol and terbutaline , respectively , with no significant difference in time to first exacerbation . There was also no difference between treatments for other efficacy measures ( peak expiratory flow , forced expiratory volume in one second and morning/evening symptom scores ) . Formoterol 4.5 µg as needed was at least as safe , well tolerated and effective as terbutaline 0.5 mg in stable patients ( requiring up to 6 relief inhalations·day−1 ) taking formoterol plus inhaled corticosteroids regularly over 12 weeks The aim of this study was to determine whether the effects of inhaled beclomethasone dipropionate and budesonide dry powder on pulmonary function correlate with those on measurement of serum eosinophil cationic protein ( sECP ) .  Thirty-two asthmatic adults in a stable phase , treated daily with 1,000 micrograms beclomethasone dipropionate metered-dose inhaler , completed a 2-week wash-out period and were then r and omized to receive a 200 micrograms/dose q.i.d . of either drug , over an 8-week period . Pulmonary function tests ( FEV1 , FVC , PEFR , FEF25 - 75 % and MEF50 ) were measured at study entry , before and after every 2 weeks of treatment , while PEFR ( morning and evening ) , symptom scores and salbutamol use PRN were recorded daily on a dairy card . sECP was measured at baseline and after 4 and 8 weeks of treatment . Safety variables included adverse reactions , morning serum cortisol and vital signs ( heart rate and blood pressure ) . FEV1 , FVC , PEFR , FEF25 - 75 % , MEF50 and morning PEFR significantly increased ( p < 0.05 ) over baseline in the beclomethasone group , while only FEV1 at week 6 and evening PEFR significantly increased ( p < 0.05 ) in the budesonide group ; no significant differences between groups were reported . sECP significantly decreased ( p < 0.01 ) in the beclomethasone group at week 4 and 8 ( p < 0.05 between groups ) . Evidence of statistically significant negative correlation between the FEV1 percent predicted and sECP was assessed at baseline ( correlation coefficient r = -0.60 , p < 0.05 ) in the total patient sample , and in the results , expressed as percent change over baseline , obtained at both week 4 and 8 ( p < 0.01 ) . A significant decrease in salbutamol use PRN , symptom score and number of daily bronchospasm attacks was also reported in the beclomethasone group ( p < 0.05 ) . No adverse reactions or relevant changes in morning cortisol and vital signs were reported in either group . It was concluded that sECP proved to be a reliable marker for monitoring inflammatory events in asthma ; inhaled beclomethasone dipropionate dry powder was at least as effective as budesonide in improving lung function and the underlying asthma inflammation BACKGROUND Asthma therapy is typically prescribed and titrated based on patient or parent self-report of symptoms . No longitudinal studies have assessed the relationship between symptoms and severe asthma exacerbations in children . The goal of our study was ( 1 ) to assess the association of asthma symptoms with severe asthma exacerbations and ( 2 ) to compare predictors of persistent asthma symptoms and predictors of severe asthma exacerbations . METHODS The Childhood Asthma Management Program was a multicenter clinical trial of 1,041 children r and omized to receive budesonide , nedocromil , or placebo ( as-needed β-agonist ) . We conducted a post hoc analysis of diary cards that were completed by subjects on a daily basis to categorize subjects as having persistent vs intermittent symptoms . We defined a severe asthma exacerbation as an episode requiring ≥ 3 days use of oral corticosteroids , hospitalization , or ED visit due to asthma based on self-report at study visits every 4 months . RESULTS While accounting for longitudinal measures , having persistent symptoms from asthma was significantly associated with having severe asthma exacerbations . Predictors of having persistent symptoms compared with intermittent symptoms included not being treated with inhaled corticosteroids , lower FEV(1)/FVC ratio , and a lower natural logarithm of provocative concentration of methacholine producing a 20 % decline in FEV(1 ) ( lnPC(20 ) ) . Predictors of having one or more severe asthma exacerbations included younger age , history of hospitalization or ED visit in the prior year , ≥ 3 days use of oral corticosteroids in the prior 3 months , lower FEV(1)/FVC ratio , lower lnPC(20 ) , and higher logarithm to the base 10 eosinophil count ; treatment with inhaled corticosteroids was predictive of having no severe asthma exacerbations . CONCLUSIONS Patients with persistent symptoms from asthma were more likely to experience severe asthma exacerbations . Nevertheless , demographic and laboratory predictors of having persistent symptoms are different from predictors of severe asthma exacerbations . Although symptoms and exacerbations are closely related , their predictors are different . The current focus of the National Asthma Education and Prevention Program guidelines on the two separate domains of asthma control , impairment and risk , are supported by our analysis Introduction In budesonide/formoterol ( Symbicort ® Turbuhaler ® , AstraZeneca , Lund , Sweden ) maintenance and reliever therapy ( SMART ) , patients with asthma take a daily maintenance dose of budesonide/formoterol , with the option of taking additional doses for symptom relief instead of a short-acting β2-agonist ( SABA ) . This study assesses the cost-effectiveness of SMART compared with usual care in patients with mild-to-moderate persistent asthma treated by general practitioners in the Netherl and s from a societal perspective . Methods The study was linked to a r and omized , active-controlled , open-label , multicenter , 12-month clinical trial , with a prospect i ve collection of re source use . One hundred and two patients ≥18 years with mild-to-moderate persistent asthma and daily inhaled corticosteroids ( ICS ) prior to the trial were included .  SMART was given as two inhalations of budesonide/formoterol ( 100/6 μg ) once daily , plus additional doses as needed . The control group was treated according to guidelines , which prescribe medium daily doses of ICS plus an SABA if needed . A long-acting β2-agonist ( LABA ) is added if necessary . Effectiveness was measured as the proportion of asthma-control days , Asthma Control Question naire ( ACQ ) scores , the net proportion of patients with relevant ACQ improvement , and the proportion of well-controlled patients . Costs included asthma medication , physician contacts , and absence from work . Results Mean total costs for SMART were € 134.81 lower ( 95 % CI : −€439.48 ; € 44.85 ) . Production losses were € 94.10 ( 95 % CI : −€300.60 ; € 0.29 ) lower for SMART ( € 10.77 vs. € 104.87 ) . No significant differences in health outcomes were seen , with 3.81 fewer asthma-control days per patient-year for SMART ( 95 % CI : −36.8 ; 30.8 ) , a 0.049 better ACQ score ( 95 % CI : −0.21 ; 0.29 ) , a 5.8 % larger net proportion of improved patients ( 95 % CI : t15.6 % ; 27.3 % ) , and a 2.1 % ( 95 % CI : −25.5 ; 20.8 % ) smaller increase in the proportion of well-controlled patients . Conclusions Treating primary care patients with mild-to-moderate persistent asthma with SMART instead of ICS plus bronchodilators does not affect health outcomes and does not increase costs ; therefore , is likely to be an alternative for guideline -directed treatment , from a health and economic perspective BACKGROUND Consensus asthma guidelines recommend antileukotriene agents as alternative therapy to existing anti-inflammatory medications ; however , the full therapeutic potential of these medications has not yet been determined . OBJECTIVE The purpose of this study was to assess the efficacy and safety of the oral leukotriene receptor antagonist zafirlukast ( 20 mg twice daily ) in subgroups of patients who have asthma with the use of integrated data from four 13-week trials . METHODS The trials had comparable design s , entry criteria , and clinical assessment s. Patient subgroups were characterized by demographic and baseline asthma characteristics . Analysis of covariance models were tested for overall treatment effect and for interactions between treatment and subgroup characteristics . RESULTS Patients with mild-to-moderate asthma ( 12 to 76 years old ) who were treated with albuterol alone were r and omized ( nZ = 879 ; nP = 605 ) and included in subset analyses . Significant overall treatment effects , favoring zafirlukast , were noted for measures of daytime and nighttime symptoms , beta2 -agonist use , and pulmonary function ( P < .05 ) . A significant , quantitative , treatment-by-age interaction was noted for beta2 -agonist use ( P < . 03 ) , suggesting greater reductions in rescue medication use with increasing patient age . Compared with placebo , similar size and /or direction of response was noted with zafirlukast in the various subgroups , indicating a benefit with zafirlukast regardless of subgroup . Significant treatment-by-strata interactions ( P < .05 ) , favoring zafirlukast , were noted for various outcome measures in subgroups with the greatest amount of baseline beta2 -agonist use ( > 8 puffs/day ) and with greater baseline peak flow variability ( > /=20 % ) and baseline airflow obstruction ( FEV1 /forced vital capacity ratio , < 0.70 ) . The overall treatment failure rate was significantly lower in the zafirlukast group compared with the placebo group ( P < .003 ) . No associations were observed between any adverse events and subgroups defined by demographic characteristics . CONCLUSIONS Exploratory subset analyses showed that zafirlukast is similarly efficacious in patients with asthma who have differing demographic characteristics and degrees of subjective symptoms . Additionally , zafirlukast appears to be incrementally beneficial in patients with more moderate disease , defined by a greater requirement for as-needed rescue medication and more abnormal pulmonary function at baseline . Over 13 weeks , zafirlukast was well tolerated and demonstrated a safety profile clinical ly indistinguishable from placebo The efficacy of nedocromil sodium ( 2 x 2 mg puffs twice a day ) was assessed in a multi-centre , double-blind parallel group placebo-controlled study of 159 adult patients with chronic reversible obstructive airways disease . Over two-thirds of the patients had been maintained on or used an inhaled bronchodilator prior to the study . During a 4-week baseline period , patients stopped using their current respiratory therapy , with the exception of oral bronchodilators , and were established on a maintenance regimen of inhaled salbutamol ( 2 puffs 4-times daily with additional doses as needed ) . Patients then received either nedocromil sodium or placebo in place of the maintenance salbutamol regimen and inhaled salbutamol was allowed only on an as needed basis during a 12-week double-blind period . Daily diary records were made by patients of symptom severity , morning and evening peak expiratory flow rate , and salbutamol usage . The doctor assessed overall severity of the patient 's condition at 4-weekly intervals , and both patients and doctor assessed treatment effectiveness at the end of the trial . Total symptom severity ( night-time symptoms , morning tightness and daytime symptoms ) was reduced and morning and evening PEFR improved throughout in the nedocromil sodium-treated patients , although evening PEFR returned nearly to the baseline in the final 4 weeks of the study . The reduction in combined day and night-time inhaled bronchodilator use from the baseline was significantly greater in the nedocromil sodium-treated patients and these patients were significantly ( p less than 0.05 ) improved compared to the placebo-treated patients on each of the three occasions that the physicians assessed disease severity . Of the 40 patients withdrawn during the double-blind period of the study ( 26 on nedocromil sodium , 14 on placebo ) , 9 and 7 patients , respectively , were withdrawn because of the onset of uncontrolled asthma , and 4 and 2 patients , respectively , because of suspected adverse reactions to treatment . A total of 21 patients treated with nedocromil sodium recorded unusual symptoms ( 9 commented on taste , 5 had nausea and vomiting ) compared with 16 patients on placebo . Overall , nedocromil sodium was considered to be moderately or very effective in at least 50 % of the patients , although no significant differences were seen between treatments in either the patients ' or physicians ' assessment OBJECTIVE To evaluate direct asthma-related costs in Swedish primary care in a real-life setting . DESIGN 12-month open-label study . SETTING Swedish primary care in a real-life setting . PARTICIPANTS 1776 patients with persistent asthma . INTERVENTIONS Patients with persistent asthma were r and omised to one of three treatments : a free adjustable combination of budesonide ( 100 - 400 microg/inhalation ) and formoterol ( 4.5 or 9 microg/inhalation ) via separate inhalers plus terbutaline as needed ; budesonide/formoterol ( 160/4.5 microg or 80/4.5 microg , two inhalations twice daily ) plus terbutaline as needed ; budesonide/formoterol ( 160/4.5 microg or 80/4.5 microg , one inhalation twice daily or two inhalations once daily ) , for maintenance plus additional inhalations as needed . Doses depended on previous inhaled corticosteroid dose . Patients attended the clinic at 0 , 1.5 , and 12 months . Telephone interviews were conducted at 4 , 6 , 8 , and 10 months . MAIN OUTCOME MEASURES The primary endpoint was direct asthma-related healthcare costs . RESULTS Statistically significant reductions in annual direct costs per patient were observed with budesonide/formoterol maintenance and reliever therapy compared with the free adjustable combination of budesonide and formoterol ( -13 % , P<0.001 ) and fixed-dose budesonide/formoterol plus terbutaline ( -20 % , P<0.001 ) . Time to first severe exacerbation did not differ significantly across treatment groups , with a mean reduction of 28 % versus the free adjustable combination of budesonide and formoterol ( P=0.076 ) . Patients receiving budesonide/formoterol maintenance and reliever therapy used a significantly lower daily dose of budesonide  compared with the conventional ( P<0.001 ) . CONCLUSIONS This study reports direct cost savings with budesonide/formoterol maintenance and reliever therapy compared with conventional treatment regimens with at least equivalent efficacy The aim of the clinical study reported here was to investigate the efficacy of salmeterol , a new long-acting selective beta 2-agonist , in patients with bronchial asthma . Twenty-four children with moderate asthma were enrolled in the longitudinal study , consisting of a run-in period of 2 weeks followed by a treatment period of 4 weeks . Maintenance treatment consisted of inhaled corticosteroid and disodium cromoglycate , or both , at the same daily dose throughout the study . During the run-in period , the patients continued to inhale salbutamol when needed and some of them ( 37 % ) also received theophylline . They were subsequently treated with salmeterol 50 micrograms twice daily and prn salbutamol for 4 weeks . Efficacy was evaluated using symptom scores and pulmonary function tests including forced vital capacity parameters , pulmonary volumes , airway resistance and specific airway conductance that were measured sensitively by a whole body plethysmograph . As a result , salmeterol produced significant improvement in morning and evening peak expiratory flow rates , vital capacity , airway resistance , conductance and asthma symptoms versus salbutamol and theophylline .  Adverse reactions were judged to be mild and few Our objective was to compare the efficacy and safety of formoterol ( Foradil ® ) delivered via a novel multidose dry powder inhaler ( Certihaler ™ ) with placebo and albuterol [ pressurized metered-dose inhaler ( pMDI ) ] , in patients with persistent asthma . After a 2-week run-in phase , 265 patients ( 13–81 years ) previously treated with regular/PRN bronchodilators for persistent asthma were r and omized to 12 weeks ' double-blind treatment with formoterol 10 µg BID via Certihaler ( n = 86 ) , albuterol 180 µg QID via pMDI ( n = 88 ) or placebo ( n = 91 ) . The primary efficacy variable was 12-hour AUC of FEV1 after 12 weeks ' treatment . Secondary efficacy variables included peak expiratory flow ( PEF ) , rescue bronchodilator medication use , asthma-related quality of life ( Juniper Mini Asthma Quality of Life Question naire ) , and asthma symptom scores . Formoterol via the Certihaler had an onset of action within 5 minutes and was associated with a clinical ly relevant and statistically significant increase in 12-hour AUC of FEV1 after 12 weeks ' treatment compared with placebo and albuterol ( p < 0.001 and p < 0.05 , respectively ) . Average PEF was significantly superior for formoterol compared with placebo and albuterol ( p < 0.001 and p < 0.05 , respectively ) . Compared with  placebo , rescue albuterol use during the study was significantly lower for formoterol ( p < 0.01 ) and was accompanied by a trend toward an improvement in asthma-related quality of life ( QoL ) . Asthma symptom scores improved to a similar extent for all treatment groups . Treatment with formoterol via Certihaler was well tolerated . Formoterol 10 µg BID , delivered via the novel Certihaler device , is well tolerated and provides rapid , long-lasting , and clinical ly superior bronchodilation to placebo and albuterol via pMDI in patients with persistent asthma ABSTRACT Objective : To evaluate efficacy and costeffectiveness of budesonide/formoterol ( Symbicort * ) maintenance ( one dose once or twice daily ) plus additional doses as needed ( Symbicort Maintenance And Reliever Therapy , SMART ) compared with a higher fixed dose of budesonide/ formoterol with formoterol as needed in patients with persistent asthma .  * Symbicort is a registered trade name of the AstraZeneca group of companies Study design and methods : 6‐month , open , r and omised study of 465 patients either not well controlled on an inhaled corticosteroid ( ICS ) , or well controlled on a combination of ICS and a long-acting β2‐agonist ( LABA ) . Treatments : budesonide/formoterol 160/4.5 µg , one inhalation , once or twice daily maintenance plus additional doses as-needed ( 1 × SMART or 2 × SMART ) , or budesonide/formoterol 160/4.5 µg two inhalations twice daily plus formoterol 4.5 µg as needed ( 2 × 2 FIX + F ) . Children 6–11 years old used an 80/4.5 µg dose strength . Primary variables of efficacy were the changes in the Asthma Control Question naire ( ACQ5 ) and morning peak expiratory flow ( PEF ) . Results : Mean age of patients 40 years ( range 6–82 years ) ; 53 % female . No differences between the groups were found in ACQ5 scores or asthma exacerbation rates . Morning PEF was higher in the 2 × 2 FIX + F group vs. the 1 × SMART and 2 × SMART groups ( differences 13 L/min and 9 L/min , respectively ; p < 0.002 ) . The 1 × SMART group showed a significant decrease in asthma controlled days compared with the two other groups . No difference was seen between the 2 × SMART group and the 2 × 2 FIX + F group . Treatment costs were significantly lower in the SMART groups compared with the 2 × 2 FIX + F group . Conclusion : Compared with the 2 × 2 FIX + F treatment the use of budesonide/formoterol was 30–40 % lower in the SMART groups while maintaining equal ACQ5 scores . Daily asthma control improved equally with 2 × SMART compared to 2 × 2 FIX + F with a reduction in asthma medication cost . The one dose once daily maintenance treatment ( 1 × SMART ) result ed in a low level of treatment failure ( exacerbations ) but led to more days with symptoms . Therefore , a daily dose of two inhalations seems to be the lowest appropriate dose in patients with moderate persistent asthma Aims : In a r and omized controlled study involving 60 preschool children with asthma , an intervention with extra information and support to parents in the form of group discussion s was performed . An earlier follow‐up after 18 months revealed an improved adherence and a reduction of exacerbation days . This is a 6‐year follow‐up The objective of this study was to evaluate the effects of celiprolol , a new beta-blocking drug , on the clinical condition and pulmonary function of hypertensive patients with reversible bronchial obstruction .  Celiprolol was compared with chlorthalidone , an antihypertensive drug without known effect on bronchial tone . The study consisted of a 4-week placebo run-in period and a 12-week titration period in which the dose of both drugs was increased at 4-week intervals if blood pressure was not reduced adequately . The doses of celiprolol were 200 , 400 , or 600 mg once daily ; those for chlorthalidone 12.5 , 25 , or 37.5 mg once daily . Entry criteria were a diastolic blood pressure between 90 and 115 mg Hg , and FEV-1 between 40 % and 80 % of predicted value , increasing by 15 % or more after salbutamol , and a need for occasional bronchodilator therapy . Prophylactic medication for asthma was given in constant dosage for a month before the study and throughout the study . Preliminary results on 66 patients demonstrate that neither drug had a clinical ly significant effect on FEV-1 , FEF 25 - 75 , or FVC . Clinical variables were not significantly changed by either drug : the average monthly asthma attacks fell from 18 to 13 with celiprolol and from 11 to 7 with chlorthalidone .  FEF was reduced by more than 50 % in two patients on celiprolol and three on chlorthalidone .  Monthly asthma attacks increased by more than 100 % in five patients on celiprolol and four on chlorthalidone . Thus , preliminary results are unable to demonstrate adverse effects from celiprolol in patients with asthma and hypertension BACKGROUND Antiinflammatory therapies , such as inhaled corticosteroids or nedocromil , are recommended for children with asthma , although there is limited information on their long-term use . METHODS We r and omly assigned 1041 children from 5 through 12 years of age with mild-to-moderate asthma to receive 200 microg of budesonide ( 311 children ) , 8 mg of nedocromil ( 312 children ) , or placebo ( 418 children ) twice daily . We treated the participants for four to six years . All children used albuterol for asthma symptoms . RESULTS There was no significant difference between either treatment and placebo in the primary outcome , the degree of change in the forced expiratory volume in one second ( FEV1 , expressed as a percentage of the predicted value ) after the administration of a bronchodilator . As compared with the children assigned to placebo , the children assigned to receive budesonide had a significantly smaller decline in the ratio of FEV1 to forced vital capacity ( FVC , expressed as a percentage ) before the administration of a bronchodilator ( decline in FEV1:FVC , 0.2 percent vs. 1.8 percent ) . The children given budesonide also had lower airway responsiveness to methacholine , fewer hospitalizations ( 2.5 vs. 4.4 per 100 person-years ) , fewer urgent visits to a caregiver ( 12 vs. 22 per 100 person-years ) , greater reduction in the need for albuterol for symptoms , fewer courses of prednisone , and a smaller percentage of days on which additional asthma medications were needed . As compared with placebo , nedocromil significantly reduced urgent care visits ( 16 vs. 22 per 100 person-years ) and courses of prednisone . The mean increase in height in the budesonide group was 1.1 cm less than in the placebo group ( 22.7 vs. 23.8 cm , P=0.005 ) ; this difference was evident mostly within the first year . The height increase was similar in the nedocromil and placebo groups . CONCLUSIONS In children with mild-to-moderate asthma , neither budesonide nor nedocromil is better than placebo in terms of lung function , but inhaled budesonide improves airway responsiveness and provides better control of asthma than placebo or nedocromil . The side effects of budesonide are limited to a small , transient reduction in growth velocity BACKGROUND Asthma exacerbations are major contributors to asthma morbidity and rather difficult to treat . There is inconclusive evidence that macrolide antibiotics may have an effect on asthma exacerbations through their antibacterial and /or anti-inflammatory properties . The aim of the study was to evaluate the efficacy of clarithromycin on medium-term asthma activity when given as an add-on therapy in children with acute asthma . METHODS This pilot , open-labeled , r and omized , prospect i ve study included 40 school-aged children , with intermittent or mild persistent asthma , presenting with an acute exacerbation . Children were r and omized to receive 15 mg/kg of clarithromycin for 3 wk , in addition to their regular ( GINA-guided ) exacerbation treatment . The microbial trigger of exacerbations was assessed by serology and PCR . Children were followed up with diary cards for 12 wk ; lung function was assessed at entry , 3 , and 12 wk after the exacerbation . RESULTS Children in the clarithromycin group had significantly more symptom-free days ( 78 ± 2 vs. 69 ± 6 days , p < 0.00001 ) and less total number of periods with loss of control ( 9 vs. 19 , respectively , p = 0.013 ) during the follow-up period , compared to controls . Moreover , treated children presented reduced duration of the index episode ( 5.0 ± 1 vs. 7.5 ± 1 days , p < 0.00001 ) . Lung function did not differ between groups . CONCLUSIONS When added to regular treatment , a 3-wk course of clarithromycin was associated with an increase in the number of symptom-free days , reductions in the number and severity of days with loss of control following index episode , and a decrease in the duration of the initial asthma exacerbation BACKGROUND A long-acting inhaled bronchodilator that is both well tolerated and effective could allow for improved control of both daytime and nighttime symptoms in patients with asthma who use frequent as-needed short-acting bronchodilators despite antiinflammatory treatment . OBJECTIVE AND METHODS We compared the efficacy and safety of inhaled salmeterol , 50 micrograms twice daily , with inhaled salbutamol , 200 micrograms four times daily , delivered through a metered-dose inhaler for 3 months in a multicenter , r and omized , double-blind , parallel-group study of 228 patients ( aged 12 to 76 years ) with mild-to-moderate asthma . RESULTS A single morning dose of salmeterol produced improvement in FEV1 that was significantly greater ( p < or = 0.012 ) than that produced by two doses of salbutamol ( taken 6 hours apart ) when patients were assessed 3 to 6 hours and 10 to 12 hours after the dose . This greater bronchodilation was present on day 1 of the study and after 4 , 8 , and 12 weeks of regular treatment . Over the 12 weeks , compared with salbutamol , salmeterol treatment was associated with a greater mean improvement in morning peak expiratory flow ( 35 L/min vs -3 L/min , p < 0.001 ) , a higher percentage of days with no symptoms ( 29 % vs 15 % ; p = 0.012 ) , and a higher percentage of nights with no awakenings ( 14 % vs -1 % ; p < 0.001 ) . Adverse events were similar for both treatments . CONCLUSIONS In this study salmeterol , 50 micrograms twice daily , was well tolerated and more effective than salbutamol , 200 micrograms four times daily , in improving symptoms and lung function in patients with mild-to-moderate asthma BACKGROUND The contributions of as-needed inhaled corticosteroids and long-acting beta2 agonists ( LABA ) to asthma control have not been fully established . We compared the efficacy and safety of three reliever strategies : a traditional short-acting beta2 agonist ; a rapid-onset LABA ( formoterol ) ; and a combination of LABA and an inhaled corticosteroid ( budesonide-formoterol ) in symptomatic patients receiving budesonide-formoterol maintenance therapy . METHODS We did a 12-month , double-blind , parallel-group study in 3394 patients ( aged 12 years or older ) , in 289 centres in 20 countries , who were using inhaled corticosteroids at study entry and symptomatic on budesonide-formoterol ( 160 microg and 4.5 microg , respectively ) , one inhalation twice daily , during a 2-week run-in . After run-in , patients were r and omly assigned budesonide-formoterol maintenance therapy plus one of three alternative as-needed medications-terbutaline ( 0.4 mg ) , formoterol ( 4.5 microg ) , or budesonide-formoterol ( 160 microg and 4.5 microg ) . The primary outcome was time to first severe exacerbation , defined as an event result ing in hospitalisation , emergency room treatment , or both , or the need for oral steroids for 3 days or more . FINDINGS Time to first severe exacerbation was longer with as-needed budesonide-formoterol versus formoterol ( p=0.0048 ; log-rank test ) and with as-needed formoterol versus terbutaline ( p=0.0051 ) . The rate of severe exacerbations was 37 , 29 , and 19 per 100 patients per year with as-needed terbutaline , formoterol , and budesonide-formoterol , respectively ( rate ratios budesonide-formoterol versus formoterol 0.67 [ 95 % CI 0.56 - 0.80 ; p<0.0001 ] ; budesonide-formoterol versus terbutaline 0.52 [ 0.44 - 0.62 ; p<0.0001 ] ; formoterol versus terbutaline 0.78 [ 0.67 - 0.91 ; p=0.0012 ] ) . Asthma control days increased to a similar extent in all treatment groups . As-needed formoterol did not significantly improve symptoms compared with as-needed terbutaline . All treatments were well tolerated . INTERPRETATION Both monocomponents of budesonide-formoterol given as needed contribute to enhanced protection from severe exacerbations in patients receiving combination therapy for maintenance In this r and omized , double-blind , placebo-controlled trial , 397 patients with moderate to severe asthma , previously treated with bronchodilators alone , received fluticasone propionate 88 , 220 , or 440 μg twice daily , or placebo via metered dose inhaler ( MDI ) for 12 weeks . Mean change from baseline to endpoint in pre-dose percent predicted forced expiratory volume in one second ( FEV1 ) was greater ( p < 0.001 ) in each fluticasone propionate group ( 9.0 % , 88 μg bid ; 9.8 % , 220 μg bid ; 11.2 % , 440 μg bid ) versus placebo ( 3.4 % ) . Morning and evening peak expiratory flow ( PEF ) , asthma symptoms , and supplemental albuterol use also improved in all fluticasone propionate groups versus placebo . The incidence of adverse events and 24-hour urine cortisol excretion rates were similar between active treatments and placebo Inhaled corticosteroids are most effective drugs currently available for the treatment of bronchial asthma . They have been shown to reduce airway inflammation and hyperresponsiveness . The aim of this study was to assess the preventive effect of inhaled steroid therapy in seasonal asthma . In a double-blind study , two groups of 10 allergic asthmatics were r and omly assigned to receive inhaled beclomethasone dipropionate ( BDP ) , 500 micrograms b.i.d . , or a matched placebo , two puffs b.i.d . The patients used inhaled salbutamol as needed . At the beginning of the study , and every month between February and June , the following parameters were assessed : lung function ( forced expiratory volume in one second ( FEV1 ) ; airway responsiveness ( provocative dose of methacholine producing a 20 % fall in forced expiratory volume in one second ( PD20 ) ) , serum eosinophil cationic protein ( ECP ) ; and blood eosinophil count . All subjects recorded daily asthma symptoms , beta 2-agonist consumption and peak expiratory flow ( PEF ) values . In the placebo group , all parameters except FEV1 worsened significantly during the pollen season compared with preseasonal values ( p < 0.001 ) . BDP produced complete protection , although a slight change from baseline was found for symptom score ( p < 0.01 ) , beta 2-agonist consumption ( p < 0.01 ) , and eosinophil number ( p < 0.05 ) in May , when the pollen load was highest . These data provide evidence that beclomethasone dipropionate treatment is able to inhibit the seasonal changes occurring during natural exposure in asthmatics . This preventive effect is probably due to the anti-inflammatory action of beclamethasone dipropionate , as documented by its effect on serum markers of airway inflammation BACKGROUND Inhaled corticosteroids are established as maintenance therapy for persistent asthma . A new aerosol formulation of flunisolide delivers a small particle size by using a hydrofluoroalkane ( HFA ) propellant with a built-in spacer . OBJECTIVE To compare efficacy and safety of two different flunisolide formulations , HFA and chlorofluorocarbon ( CFC ) , with placebo treatment over a range of doses . METHODS The multicenter , r and omized , double-blind , placebo-controlled trial consisted of a 2-week , active run-in phase with CFC flunisolide 500 microg , twice daily , followed by 12 weeks of double-blind treatment with placebo , HFA flunisolide ( 85 , 170 , or 340 microg , twice daily ) , or CFC flunisolide ( 250 , 500 , or 1,000 microg , twice daily ) . Patients ( N = 669 ) were nonsmokers , at least 12 years of age , with mild to moderate asthma who were being treated with inhaled corticosteroids . Outcome measures were change from baseline in forced expiratory volume in 1 second ( FEV1 ) , peak expiratory flow rate , as needed albuterol use , nocturnal awakenings , and asthma symptoms . RESULTS After 12 weeks of treatment , patients receiving 170 microg , twice daily , and 340 microg , twice daily , of HFA flunisolide showed a significant ( P < 0.01 ) improvement in percentage increase in FEV1 ( 12.22 % at 170 microg , twice daily , and 14.69 % at 340 microg , twice daily ) compared with the placebo group ( 5.35 % ) . At one-third the dose of CFC flunisolide , HFA flunisolide provided similar improvement in pulmonary function versus placebo . Both formulations demonstrated comparable linear dose dependency for the change from baseline in FEV1 without any evidence of cortisol suppression . Outcome values for all seven secondary efficacy measures were numerically superior in patients receiving HFA flunisolide compared with the CFC formulation . Both formulations seemed to be safe and well tolerated . CONCLUSIONS HFA flunisolide provides comparable efficacy and safety at one-third the dose of CFC flunisolide BACKGROUND No st and ard , optimal treatment exists for severe intermittent ( ie , episodic ) asthma in children . However , evidence suggests that both daily and episode-driven montelukast are effective for this phenotype . OBJECTIVE To assess the regimen-related efficacy of montelukast in treating pediatric episodic asthma . METHODS A multicenter , r and omized , double-blind , double-dummy , parallel-group , 52-week study was performed in children 6 months to 5 years of age comparing  placebo  with two regimens of montelukast 4 mg : ( 1 ) daily ; or ( 2 ) episode-driven for 12 days beginning with signs/symptoms consistent with imminent cold or breathing problem . The main outcome measure was the number of asthma episodes ( symptoms requiring treatment ) culminating in an asthma attack ( symptoms requiring physician visit , emergency room visit , corticosteroids , or hospitalization ) . RESULTS Five hundred eighty-nine patients were r and omized to daily montelukast , 591 to intermittent montelukast , and 591 to placebo . Compared with placebo , no significant difference was seen between daily montelukast ( P = .510 ) or intermittent montelukast ( P = .884 ) in the number of asthma episodes culminating in an asthma attack over 1 year . Daily montelukast reduced symptoms over the 12-day treatment period of asthma episodes compared with placebo ( P = .045 ) . Beta-agonist use was reduced with both daily ( P = .048 ) and intermittent montelukast ( P = .028 ) compared with placebo . However , because of prespecified rules for multiplicity adjustments ( requiring a positive primary endpoint ) , statistical significance for secondary endpoints can not be concluded . All treatments were well tolerated . CONCLUSIONS Montelukast did not reduce the number of asthma episodes culminating in an asthma attack over 1 year in children 6 months to 5 years of age , although numerical improvements occurred in some endpoints OBJECTIVE To evaluate the efficacy , safety , and impact on asthma-specific quality of life of salmeterol , a highly selective , long-acting beta 2-agonist , compared with that of placebo ( i.e. , " as-needed " albuterol ) . STUDY DESIGN R and omized , double-blind , placebo-controlled , parallel-group , multicenter study . PATIENTS AND METHODS Five hundred thirty-eight nonsmoking symptomatic patients 12 years of age and older meeting American Thoracic Society asthma criteria were enrolled at 55 outpatient clinics ; 443 patients completed the study . Patients were r and omly assigned to treatment with either salmeterol aerosol 42 micrograms twice daily or placebo ( as-needed albuterol ) for 12 weeks . We assessed changes in quality of life using the Asthma Quality of Life Question naire ( AQLQ ) . Efficacy measurements included daily peak expiratory flow ( PEF ) rate , daytime and nighttime asthma symptoms , results of pulmonary function tests , and supplemental albuterol use . Patients recorded their PEF rate , supplemental albuterol use , and asthma-related symptoms daily . Pulmonary function tests and AQLQ assessment s were performed at baseline and after 4 , 8 , and 12 weeks of treatment . Safety measurements included vital signs , physical examination , and reports of clinical adverse events at baseline and after 4 , 8 , and 12 weeks of treatment . RESULTS Mean changes from baseline in AQLQ global and domain scores were significantly greater in the salmeterol group compared with the placebo group ( P < 0.001 ) . Patients treated with salmeterol also had significant improvements in mean PEF rates , supplemental albuterol use , asthma symptom scores , and forced expiratory volume in 1 second compared with those given placebo . Both salmeterol and placebo were well tolerated and were not associated with any clinical ly significant changes in vital signs or physical examination findings . CONCLUSIONS Salmeterol 42 micrograms twice daily result ed in significantly greater improvements in asthma-specific quality of life , pulmonary function , and asthma symptoms compared with placebo ( as-needed albuterol ) in patients with moderate persistent asthma The aim of this study was to assess the distribution of the occurrence of tolerance to the protective effect of salmeterol on allergen challenge in a large sample of asthmatic subjects . We investigated 53 subjects ( 45 male and eight female ) , mean age 24+/-8.2 years , with mild intermittent asthma , in stable phase of the disease , never previously treated with regular beta2-agonists . All subjects with a previous positive early airway response ( EAR ) to a screening allergen challenge underwent , in double blind r and omized , cross-over manner , three further allergen challenges : after placebo ( T0 ) , after a single dose ( 50 microg ) of inhaled salmeterol ( T1 ) , and after regular treatment with inhaled salmeterol ( 50 microg bid ) for 1 week ( T2 ) . All subjects showed an EAR after placebo treatment ( T0 ) , and were completely protected against EAR by the single dose of salmeterol ( T1 ) . After 1-week regular treatment with salmeterol ( T2 ) . 24 out of 53 subjects ( 45 % ) were still protected , whereas 29 subjects ( 55 % ) showed a significant EAR . The distribution of the response to allergen challenge , which was quite homogeneous at T0 and T1 , showed considerable heterogeneity at T2 . Tolerance to the protective effect of salmeterol on allergen challenge can be observed in a large group of previously untreated mild asthmatic subjects . This phenomenon is heterogeneously distributed , with some subjects still showing a complete protection similar to that obtained after a single dose of salmeterol and others showing a response similar to that obtained after placebo . The reason of this heterogeneity needs to be eluci date 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 In a double-blind , double-dummy , multicenter study , 212 patients with asthma whose symptoms were not controlled by as-needed use of inhaled bronchodilators were r and omized to receive either 4 mg of nedocromil sodium or 180 micrograms of albuterol four times daily for 12 weeks . Asthma symptom scores ( daytime asthma , nighttime asthma , morning chest tightness , and cough ) and peak expiratory flow rate were recorded daily on diary cards . Bronchial hyperresponsiveness was assessed by changes in diurnal variation in peak expiratory flow rate and by methacholine inhalation challenge . Statistically significant differences were found between groups favoring nedocromil sodium for relief of day and nighttime asthma and morning chest tightness . Patients treated with nedocromil sodium also had significantly lower diurnal variation in peak expiratory flow rate compared with patients treated with albuterol . Compared with patients treated with albuterol , patients treated with nedocromil sodium showed a greater improvement in cough and a decreased sensitivity to methacholine challenge . Patients in both groups reduced their as-needed albuterol use . Regular treatment with nedocromil sodium therefore led to greater asthma symptom control and reduced bronchial responsiveness compared with regular treatment with albuterol . The study also showed that more frequent use of a beta 2-agonist ( for symptom relief or not ) did not improve asthma control . Both drugs were well tolerated 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 We investigated the constituents of bronchoalveolar lavage ( BAL ) regarding cell profiles and released eosinophilic cationic protein ( ECP ) in 11 patients treated occasionally with inhaled bronchodilators ( Group A ) and 11 patients treated regularly with inhaled corticosteroids ( Group B ) . A normal , healthy control group of 12 subjects was also recruited . Compared with Group A , Group B had a reduced recovery percentage of infused volume ( p less than 0.05 ) and total cell number ( p less than 0.01 ) . Compared with the control group , there was a significant increase in the percentage of eosinophils ( p less than 0.05 ) in both groups of asthmatics . In Group A there was also a significant increase in mast cells ( p less than 0.05 ) , serum-ECP ( p less than 0.05 ) , and BAL-ECP ( p less than 0.001 ) . No correlations between any of the cell variables and the level of airway responsiveness measured as PC20 histamine were found in any group . Group A patients were investigated twice -- before and after 4 wk of r and omly allocated treatment with either a regular beta-2-receptor agonist ( terbutaline 250 micrograms , two puffs four times a day ) or a regularly inhaled corticosteroid ( budesonide 200 micrograms twice a day ) . The BAL differential cell counts were similar and not significantly affected by either treatment . However , BAL-ECP levels were decreased by budesonide treatment ( p less than 0.05 ) . ECP levels in serum and BAL were significantly correlated ( p less than 0.05 to 0.001 ) . The eosinophilic cell involvement in asthma is further emphasized by this study but the increase in numbers of eosinophils seems less important than their activity , here measured as release of one degranulation product , ECP . To suppress disease activity , repeated long-term treatment is important , but clear preference for either treatment can not be given on the basis of our present results BACKGROUND The cysteinyl leukotrienes are important mediators of bronchial asthma . The clinical effect of montelukast , a potent cysteinyl leukotriene-receptor antagonist , was investigated in a r and omized , placebo-controlled , multicenter , parallel-group , dose-ranging study . METHODS After a 3-week , single-blind , placebo run-in period , 343 asthmatic patients ( FEV1 40 % to 80 % of the predicted value with an improvement in FEV1 of at least 15 % [ absolute value ] after receiving inhaled beta-agonists on at least two occasions ) were r and omly assigned to one of six treatment groups : placebo ; 10 , 100 , or 200 mg once daily montelukast in the evening ; or 10 or 50 mg twice daily montelukast for a 6-week , double-blind treatment period followed by a 1-week placebo washout period . All patients used inhaled , short-acting beta-agonists as needed . RESULTS All montelukast doses caused similar and significant differences compared with placebo in asthma control endpoints . The least-square mean difference between pooled montelukast groups and placebo in the percentage change from baseline in morning FEV1 ( 10.30 % ; 95 % CI : 5.56 to 15.04 ) , as-needed beta-agonist use ( -0.98 puffs ; 95 % CI : -1.53 to -0.44 ) , morning peak expiratory flow rate ( 18.80 L/min ; 95 % CI : 8.62 to 28.98 ) , physicians ' and patients ' global evaluations , and asthma-specific quality -of-life scores were all significant ( p < or = 0.050 ) . The incidence of adverse experiences was not dose related and was similar between placebo and montelukast treatment . CONCLUSION Montelukast caused a significant improvement in chronic asthma at an oral , once daily evening dose as low as 10 mg BACKGROUND Although virus-induced wheezing is common in preschool-age children , optimal management remains elusive . We examined the efficacy and safety of preemptive treatment with high-dose fluticasone in reducing the severity of recurrent virus-induced wheezing in children . METHODS We r and omly assigned 129 children who were 1 to 6 years of age to receive 750 microg of fluticasone propionate ( ex-valve [ manufacturer-measured ] dose ) or placebo twice daily , beginning at the onset of an upper respiratory tract infection and continuing for a maximum of 10 days , over a period of 6 to 12 months . The primary outcome was  rescue oral corticosteroid use . Secondary outcomes included symptoms , use of beta(2)-agonists , acute care visits , hospitalizations , discontinuation of the study drug , change in growth and bone mineral density , basal cortisol level , and adverse events . RESULTS Over a median period of 40 weeks , 8 % of upper respiratory tract infections in the fluticasone group led to treatment with  rescue systemic corticosteroids  , as compared with 18 % in the placebo group ( odds ratio , 0.49 ; 95 % confidence interval [ CI ] , 0.30 to 0.83 ) . Children who were treated with fluticasone , as compared with those who were given placebo , had smaller mean ( + /-SD ) gains from baseline in height ( 6.23+/-2.62 cm [ unadjusted value ] ; z score , -0.19 + /-0.42 vs. 6.56+/-2.90 cm [ unadjusted value ] ; z score , 0.00+/-0.48 ; difference between groups in z score from baseline to end point , -0.24 [ 95 % CI , -0.40 to -0.08 ] ) and in weight ( 1.53+/-1.17 kg [ unadjusted value ] ; z score , -0.15+/-0.48 vs. 2.17+/-1.79 kg [ unadjusted value ] ; z score , 0.11+/-0.43 ; difference between groups in z score from baseline to end point , -0.26 [ 95 % CI , -0.41 to -0.09 ] ) . There were no significant differences between the groups in basal cortisol level , bone mineral density , or adverse events . CONCLUSIONS In preschool-age children with moderate-to-severe virus-induced wheezing , preemptive treatment with high-dose fluticasone as compared with placebo reduced the use of rescue oral corticosteroids . Treatment with fluticasone was associated with a smaller gain in height and weight . Given the potential for overuse , this preventive approach should not be adopted in clinical practice until long-term adverse effects are clarified . ( Clinical Trials.gov number , NCT00238927 . The aim of this study was to compare the effect of regular versus intermittent ( p.r.n . ) bronchodilators on bronchial reactivity and asthma control in patients on concomitant inhaled corticosteroids . We studied 12 patients with asthma in a prospect i ve , r and omised , single-blind , single-dummy , three-period crossover trial comparing placebo ( 2 puffs t.d.s . ) , salbutamol ( 200μg t.d.s . ) and oxitropium bromide ( 200μg t.d.s . ) for 28 days each . Computerised spirometry and bronchial reactivity to histamine were obtained on entry and after each treatment period . Symptom scores , use of rescue bronchodilator and peak expiratory flow rates were recorded daily . There were no significant differences in bronchial hyperreactivity between the salbutamol , oxitropium and placebo treatment periods . There were no significant differences in baseline FEV1 , FEF25–75 % , symptom scores , use of rescue bronchodilator or morning and evening PEFR between treatment periods . Intermittent beta agonist therapy is as effective as regular therapy in terms of asthma control and bronchial hyperreactivity in patients on concomitant inhaled corticosteroid therapy . Since intermittent therapy achieves similar results with significantly lower beta agonist consumption , the data support current recommendations that beta agonists should be taken on a p.r.n . basis in asthma patients on inhaled steroids Concern about side‐effects of theophylline prompted us to investigate whether this drug could be eliminated from the multi‐medication regimen of severe asthmatics . We studied patients with a demonstrated requirement for systemic steroids who were taking most other available anti‐asthma medications in an attempt to reduce systemic steroids while maintaining clinical stability . Five in‐ patients , 12–15 years old , completed a double‐blind , cross‐over trial of theophylline vs placebo . All were stable for 4 weeks prior to the study with normal spirometry and mildly elevated lung volumes . Regular medications consisted of long‐acting theophylline with levels between 12 mcg/ml and 16 mcg/ml , and prednisone 10–30 mg on alternate days . In addition , they were all taking inhaled metaproterenol , cromolyn sodium , atropine sulphate , and beclomethasone dipropionate four times daily ( qid ) . Patients received either theophylline or placebo during two drug periods . All other medications were unchanged . Parameters measured were symptom score , number of extra respiratory treatments ( prn RTs ) , increase in steroid dosage , and daily spirometry . During the placebo period , all five patients required increased steroids , daily spirometry decreased and three patients developed severe exacerbations unrelated to viral infection . A marked increase in symptom score occurred within 48 hr of discontinuing theophylline in all . These findings emphasize that theophylline is beneficial in a subset of severe asthmatics who can not be controlled with all other available bronchodilators , cromolyn , and inhaled and systemic steroids BACKGROUND Salmeterol is the first long-acting inhaled beta 2-agonist available in the US for the maintenance treatment of asthma . OBJECTIVE To compare the safety of salmeterol with that of the short-acting beta 2-agonist albuterol . METHODS Two identically design ed , prospect i ve , r and omized , double-blind , parallel studies were conducted comparing salmeterol 42 micrograms twice daily , albuterol 180 micrograms four times daily , and placebo over 12 weeks in 556 patients ( 12 to 73 years old ) with mild-to-moderate chronic asthma . Patients in each treatment group could use albuterol as needed to control acute symptoms . RESULTS The incidence of potentially drug-related adverse events was similar among the treatment groups ( range : 22 % to 23 % ) , with headache being the most commonly reported ( range : 9 % to 10 % ) . No deaths occurred during the studies . Concomitant use of > 4 puffs of supplemental albuterol per day in the salmeterol group produced no increase in the incidence of adverse events either in general or of a cardiovascular nature . There were no statistically significant differences among treatment groups or clinical ly significant changes from pretreatment values in mean pulse rate , systolic/diastolic blood pressure , or clinical laboratory values after 12 weeks . There were no clinical ly significant differences among groups in heart rates nor were there differences in the frequency of supraventricular or ventricular ectopic beats during 24-hr Holter monitoring . The frequency of asthma exacerbations was lowest among patients receiving salmeterol ( and highest among those who received placebo ) , and this rate did not increase over the 12 weeks . Asthma exacerbations were treated successfully with nebulized albuterol ( 2.5 mg ) , with no evidence of any increased risk of cardiovascular events . CONCLUSIONS Salmeterol 42 micrograms twice daily is well-tolerated in patients with asthma , having a similar safety profile as that of albuterol 180 micrograms inhaled four times daily or placebo ( plus as-needed albuterol ) . Concomitant use of albuterol , either by MDI or nebulization , did not affect the safety of salmeterol . Extensive cardiovascular monitoring revealed no significant cardiovascular adverse effects or arrhythmogenic effects associated with salmeterol over 12 weeks 52 asthmatic patients aged 18 to 70 years took part in a double-blind crossover trial comparing the effects of regular treatment of asthma with inhaled salbutamol ( 400 micrograms qds ) versus irregular treatment ( 400 micrograms prn ) , each prescribed for 4 weeks . There were no differences between the two schedules regarding intensity of clinical symptoms , morning and evening values of peak expiratory flow rates and spirometric measurements . The mean daily consumption of salbutamol  was higher in the period of regular treatment ( 2148 + /- 548 micrograms ) than in the period of free treatment ( 800 + /- 700 micrograms ) . Patients expressed an obvious preference for the period of regular treatment ( 26 vs 13 ) . Salbutamol given prn or on a regular qds regimen was shown to be equally effective and safe in controlling the signs and symptoms of asthma . No tolerance or drug abuse was observed . In view of the patients ' preference for regular treatment , this schedule is a safe alternative in cases where low-dose symptomatic treatment given prn fails to alleviate symptoms Abstract . In a double‐blind group comparative trial nedocromil sodium ( Tilade ® ) at a dose of 4 mg four times daily was compared with placebo in the management of out‐ patients with bronchial asthma . Treatments were delivered by pressurized aerosol over a period of 28 days following a 2‐week base‐line during which patients continued on their usual therapy . Twenty‐one patients entered the nedocromil sodium group and twenty entered the placebo group . All were using beclomethasone dipropionate aerosol as maintenance steroid therapy plus intermittent use of a bronchodilator taken by inhalation . The dose of steroid was reduced for all patients after 2 weeks of treatment and again for approximately half the patients after 3 weeks trial treatment . Patients in the nedocromil sodium treatment group improved in respect of Diary Card symptom scores and peak expiratory flow rate ( PEFR ) , and in their requirements for inhaled bronchodilators . Patients in the placebo group were worse , particularly in respect of daytime asthma symptoms ( P < 0·01 ) , bronchodilator use ( P < 0·05 ) and morning PEFR during the third week of trial treatment ( P < 0·05 ) . More patients in the nedocromil sodium group than in the placebo group thought their treatment had been effective ( P < 0·05 ) .  Nedocromil was well tolerated . Despite the short duration of treatment imposed at this stage in the clinical evaluation of a new compound , our results were sufficiently encouraging to prompt further evaluation of nedocromil sodium over the longer period required ( 3–12 months ) for the clinical assessment of a new treatment for chronic asthma We evaluated if budesonide inhalation suspension ( BIS ) reduces the immunogenicity of the varicella vaccine in paediatric patients with asthma . This open-label , parallel-group , cohort study included varicella-naïve ( disease and vaccine ) children aged 12 months to 8 years with asthma requiring therapy . Patients who received > or = 4 weeks of asthma treatment with BIS 0.25 - 1 mg daily or non-steroidal conventional asthma therapy ( NSCAT ) daily or as needed and met eligibility requirements received the varicella vaccine ( Varivax ) and continued the same asthma treatment for > or = 8 weeks postvaccination . Varicella-zoster virus ( VZV ) antibody levels were assessed before and 6 weeks after vaccination using a glycoprotein enzyme-linked immunosorbent assay ( gpELISA ) . Adverse events ( AEs ) were assessed throughout the study . Antibody levels were analysed in 243 of 274 patients who were vaccinated and received treatment . After immunisation , the percentage of patients in each group achieving a ' protective ' level of VZV antibody ( > or = 5 gpELISA units/ml ) was similar : 85 % ( 129/151 ) in the BIS group and 90 % ( 83/92 ) in the NSCAT group ( relative risk = 0.95 ; 95 % confidence interval 0.86 - 1.04 ) . Eight patients in each group reported AEs related to varicella vaccination ( primarily pyrexia , agitation and injection-site reactions ) . There were no cases of severe varicella in either group ; one case of mild varicella-like rash was reported in a 12-month-old child in the NSCAT group 11 days after vaccination . VZV antibody responses and tolerability to the live varicella vaccine in paediatric asthma patients treated with BIS vs. NSCAT were comparable , demonstrating that young children with asthma receiving nebulised BIS can be immunised effectively with Varivax OBJECTIVES To determine the clinical effectiveness , tolerability and reliability of montelukast and to compare this drug with inhaled corticosteroids . METHODS We performed a r and omized , 14-week , 2-period , prospect i ve parallel group study . After a 2-week run-in period , patients received treatment for 12 weeks . Sixty-three clinical ly stable out patients aged 8 to 14 years with a history of mild persistent asthma for at least 1 year and a forced expiratory volume in one second ( FEV1 ) greater than 80 % of the predicted value were evaluated . RESULTS Montelukast produced improvement in airway obstruction , daily symptom scores , total daily as-needed beta-agonist use , nocturnal awakenings , percentage of days and percentage of patients with asthma exacerbations , and urinary leukotriene E4 levels . These beneficial effects were similar to those produced by inhaled corticosteroids . There were no significant adverse effects requiring treatment discontinuation . CONCLUSIONS Montelukast may be a well-tolerated and effective therapeutic option in 8 to 14-year-old patients with mild persistent asthma A group of 32 patients with moderately severe , chronic asthma ( mean FEV1 55 % of predicted ) , maintained on moderately high doses of inhaled corticosteroids ( mean dose 1,100 micrograms/d ) , participated in this double-blind , placebo-controlled crossover study . The effect on pulmonary function of adding theophylline ( U , once daily Uniphyl ) , inhaled salbutamol ( S , 200 micrograms four times per day ) , and their combination ( C ) or placebo ( P ) was assessed on Day 14 of each treatment phase . Patients recorded peak expiratory flow , asthma symptom severity ( morning and evening ) , and use of rescue salbutamol inhaler in daily diaries . Mean FEV1 between 0730 and 1800 h and maximum FEV1 between 0730 and 1300 h were significantly higher on U , S , and C compared with P ( p < 0.006 ) . Morning peak flow and FEV1 ( 0730 h ) were significantly higher on U and C compared with S and P ( p < 0.01 ) . Evening peak flow was higher on U than P ( p < 0.001 ) , and C was higher than S and P ( p < 0.01 ) . Rescue salbutamol inhaler use was significantly higher on P than on U , C , or S ( p = 0.0001 ) . Patient rating of asthma symptoms during C was significantly better than on S or P ( p < 0.05 ) . Patient rating of asthma control and study phase preference was significantly higher on combination and Uniphyl alone than on placebo , the combination also being superior to salbutamol alone . Addition of Uniphyl or a combination of Uniphyl and salbutamol significantly improves pulmonary function and asthma symptoms in patients treated with high doses of inhaled corticosteroids and as-needed beta agonists . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Daily inhaled corticosteroids are an effective treatment for mild persistent asthma , but some children have exacerbations even with good day-to-day control , and many discontinue treatment after becoming asymptomatic . We assessed the effectiveness of an inhaled corticosteroid ( beclomethasone dipropionate ) used as rescue treatment . METHODS In this 44-week , r and omised , double-blind , placebo-controlled trial we enrolled children and adolescents with mild persistent asthma aged 5 - 18 years from five clinical centres in the USA . A computer-generated r and omisation sequence , stratified by clinical centre and age group , was used to r and omly assign participants to one of four treatment groups : twice daily beclomethasone with beclomethasone plus albuterol as rescue ( combined group ) ; twice daily beclomethasone with placebo plus albuterol as rescue ( daily beclomethasone group ) ; twice daily placebo with beclomethasone plus albuterol as rescue ( rescue beclomethasone group ) ; and twice daily placebo with placebo plus albuterol as rescue ( placebo group ) . Twice daily beclomethasone treatment was one puff of beclomethasone ( 40 μg per puff ) or placebo given in the morning and evening . Rescue beclomethasone treatment was two puffs of beclomethasone or placebo for each two puffs of albuterol ( 180 μg ) needed for symptom relief . The primary outcome was time to first exacerbation that required oral corticosteroids . A secondary outcome measured linear growth . Analysis was by intention to treat . This study is registered with clinical trials.gov , number NCT00394329 . RESULTS 843 children and adolescents were enrolled into this trial , of whom 288 were assigned to one of four treatment groups ; combined ( n=71 ) , daily beclomethasone ( n=72 ) , rescue beclomethasone ( n=71 ) , and placebo (n=74)-555 individuals were excluded during the run-in , according to predefined criteria . Compared with the placebo group ( 49 % , 95 % CI 37 - 61 ) , the frequency of exacerbations was lower in the daily ( 28 % , 18 - 40 , p=0·03 ) , combined ( 31 % , 21 - 43 , p=0·07 ) , and rescue ( 35 % , 24 - 47 , p=0·07 ) groups . Frequency of treatment failure was 23 % ( 95 % CI 14 - 43 ) in the placebo group , compared with 5·6 % ( 1·6 - 14 ) in the combined ( p=0·012 ) , 2·8 % ( 0 - 10 ) in the daily ( p=0·009 ) , and 8·5 % ( 2 - 15 ) in the rescue ( p=0·024 ) groups . Compared with the placebo group , linear growth was 1·1 cm ( SD 0·3 ) less in the combined and daily arms ( p<0·0001 ) , but not the rescue group ( p=0·26 ) . Only two individuals had severe adverse events ; one in the daily beclomethasone group had viral meningitis and one in the combined group had bronchitis . INTERPRETATION Children with mild persistent asthma should not be treated with rescue albuterol alone and the most effective treatment to prevent exacerbations is daily inhaled corticosteroids . Inhaled corticosteroids as rescue medication with albuterol might be an effective step-down strategy for children with well controlled , mild asthma because it is more effective at reducing exacerbations than is use of rescue albuterol alone . Use of daily inhaled corticosteroid treatment and related side-effects such as growth impairment can therefore be avoided . FUNDING National Heart , Lung and Blood Institute BACKGROUND Salmeterol is the first long-acting inhaled bronchodilator available in the United States . This paper summarizes the combined results of the two pivotal US studies evaluating the efficacy of this beta 2-agonist in the maintenance treatment of asthma . METHODS Salmeterol ( 42 micrograms twice daily ) was compared with the short-acting beta 2-agonist albuterol ( 180 micrograms four times daily ) in two double-blind , r and omized studies involving 556 patients with mild-to-moderate asthma . All patients could use supplemental inhaled albuterol as needed for breakthrough symptoms , and patients were allowed to continue to use inhaled corticosteroids during the study . RESULTS Salmeterol , 42 micrograms bid , was more effective than albuterol , 180 micrograms qid , or placebo in maintaining bronchodilation , as measured by FEV1 over 12-hour periods and morning and evening peak expiratory flow rates . Patients who received salmeterol also experienced significantly greater increases in the number of days without asthma symptoms and the percentage of nights without awakenings compared with either the albuterol or placebo group . There was no difference between patients who received concomitant inhaled corticosteroids and those who did not with respect to pulmonary-function measurements or improvements in symptoms . There was no loss of asthma control with salmeterol over the 12-week period . CONCLUSIONS Salmeterol , 42 micrograms twice daily , was more effective than albuterol , 180 micrograms four times daily , or placebo ( plus as-needed albuterol ) in improving pulmonary function and controlling asthma symptoms RATIONALE Little is known about the use of biomarkers in guiding treatment decisions in routine asthma management . The objective of this study was to determine whether adding a LABA to an ICS would control bronchial hyperresponsiveness ( BHR ) at an overall lower dose of ICS when titration of medication was based upon the assessment of routine clinical measures with or without the measurement of BHR . METHODS After a 2-week run-in period , subjects ( > or = 12 years ) were r and omized to one of three treatment groups . Two groups followed a BHR treatment strategy ( based on clinical parameters [ lung function , asthma symptoms , and bronchodilator use ] and BHR ) and were treated with either fluticasone propionate/salmeterol ( FSC(BHR ) group ) or fluticasone propionate ( FP(BHR ) group ) ( n=156 each ) . The third group followed a clinical treatment algorithm ( based on clinical parameters alone ) and were treated with fluticasone propionate ( FP(REF ) group ; n=154 ) . All treatments were administered via Diskus . Treatment doses were adjusted as needed every 8 weeks for 40 weeks according to the subject 's derived severity class , which was based on clinical measures of asthma control with or without BHR . RESULTS The mean total daily inhaled corticosteroids ( ICS ) dose during the double-blind treatment period was lower , although not statistically significant , in the FSC(BHR ) group compared with the FP(BHR ) group ( a difference of -42.9 mcg ; p=0.07 ) . Compared with the FP(REF ) group , the mean total daily ICS dose was higher in the FSC(BHR ) group ( a difference of 85.2 mcg ) and was significantly higher in the FP(BHR ) group ( a difference of 131.2 mcg , p=0.037 ) . CONCLUSION This study demonstrated that for most subjects , control of BHR was maintained when treatment was directed toward control of clinical parameters . In addition , there was a trend towards control of BHR and clinical measures at a lower dose of ICS when used concurrently with salmeterol BACKGROUND It is well documented that the perception of dyspnea ( POD ) , subjectively reported by patients , is related to the activity and strength of the inspiratory muscles , and influences the use of ' as needed ' beta2-agonists . STUDY OBJECTIVE To investigate the relationship among the increase in inspiratory muscle strength after specific inspiratory muscle training , beta2-agonist consumption and the POD in patients with persistent , mild to moderate asthma . METHODS Inspiratory muscle strength , daily beta2-agonist consumption and the POD were measured in 30 patients with mild to moderate asthma . Patients were then r and omly assigned to two groups : one group received specific inspiratory muscle training until an increase of more than 20 cm H2O was reached , and one group was a control group and received sham training .  Inspiratory muscle strength , the POD and daily beta2-agonist consumption were assessed during and after the training period . RESULTS There was no good correlation between the baseline maximal inspiratory pressure and the POD , or between the baseline maximal inspiratory pressure and the mean daily beta2-agonist consumption . However , there was a significant correlation between the POD and the mean daily beta2-agonist consumption . The increase in inspiratory muscle strength after the inspiratory muscle training was closely correlated with the decrease in the POD ( P<0.001 ) and the decrease in beta2-agonist consumption ( P<0.001 ) . CONCLUSIONS The present study shows that , in patients with mild to moderate , persistent asthma , there is a correlation between the POD and the mean daily beta2-agonist consumption . When the inspiratory muscles are strengthened , there is a significant decrease in the POD and in beta2-agonist consumption BACKGROUND The role of long-acting , inhaled beta2-agonists in treating asthma is uncertain . In a double-blind study , we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide . METHODS After a four-week run-in period of treatment with budesonide ( 800 microg twice daily ) , 852 patients being treated with glucocorticoids  were r and omly assigned to one of four treatments given twice daily by means of a dry-powder inhaler ( Turbuhaler ) : 100 microg of budesonide plus placebo , 100 microg of budesonide plus 12 microg of formoterol , 400 microg of budesonide plus placebo , or 400 microg of budesonide plus 12 microg of formoterol . Terbutaline was permitted as needed . Treatment continued for one year ; we compared the frequency of exacerbations of asthma , symptoms , and lung function in the four groups . A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days . RESULTS The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent , respectively , when formoterol was added to the lower dose of budesonide . The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent , respectively . Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent , respectively . Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide , but the improvements with formoterol were greater . CONCLUSIONS In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids , the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial . The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma In a r and omized , double-blind , double-dummy , cross-over study the efficacy and safety of inhaled salmeterol 50 mcg ( b.i.d . ) was compared with oral salbutamol controlled release 8 mg ( b.i.d . ) . Fifty-nine patients with moderate asthma were r and omized to two four-week periods of treatment with a two-week washout period . During the study period the patients were allowed to use inhaled Salbutamol on a prn . basis . Inhaled steroids , if any , were continued . On diary cards patients recorded peak expiratory flow rate ( PEFR ) morning and evening before medication , asthma symptom score , and use of inhaled salbutamol .  Salmeterol was more effective than salbutamol CR in decreasing daily symptoms ( p = 0.001 ) and increasing morning-PEFR ( p = 0.004 ) . Salmeterol result ed in significantly more days without symptoms ( p = 0.0004 ) and days and nights without need for rescue medication ( p = 0.01 and p = 0.01 ) . Salmeterol was better tolerated than salbutamol CR Abstract Introduction : Budesonide/formoterol ( Symbicort ® ) Maintenance And Reliever Therapy ( SMART ) is an effective and well tolerated treatment option for patients with asthma . We compared the cost effectiveness from a societal perspective of this one-inhaler regimen with that of maintenance salmeterol/fluticasone propionate ( Seretide ® ) plus salbutamol ( albuterol ) as needed ( Seretide ® Fixed Combination [ SFC ] ) . Study design : A cost-effectiveness analysis was performed based on effectiveness and re source -utilisation data collected prospect ively in a r and omised , 12-month study performed in 2143 patients in 16 countries . Re source utilisation data were pooled and unit costs ( € , year 2003 values ) from Italy , France , the UK and Germany were used to generate estimates of direct and total costs per patient per year and cost per severe exacerbation avoided . Methods : Adolescents and adults with asthma ( n = 2143 ; mean forced expiratory volume in 1 second [ FEV1 ] 73 % predicted ; mean inhaled corticosteroid [ ICS ] dose 884 µg/day ) were r and omised to SMART or SFC . The effectiveness measure used was the number of severe exacerbations per patient per year . Direct costs included medication use ( budesonide/formoterol 160µg/4.5 µg or salmeterol/fluticasone 50µg/100 µg , 50µg/250 µg or 50µg/500 µg plus salbutamol ) and nonmedication-related re source use , including days in hospital , emergency room visits , specialist or primary care physician visits and other healthcare provider contacts . Indirect costs , including the number of days when the patient or their carer was unable to attend to their normal daily activities , were also assessed . The study assumed a European societal perspective ( i.e. including direct and indirect costs ) . Results : Treatment with SMART result ed in significantly fewer severe exacerbations per patient per year compared with SFC ( 0.24 vs 0.31 events per patient per year ; p = 0.0025 ) . Re source use was low in both groups . Medication costs accounted for the majority of the total costs . The increased  effectiveness of SMART was achieved at a reduced or similar cost compared with SFC . SMART dominated when German unit costs were applied ( i.e. there was a statistically significant reduction in both costs and number of exacerbations ) . In all other countries , the incremental cost-effectiveness ratios showed that there was a reduction in mean total cost per exacerbation avoided ; however , this difference was not statistically significant . Conclusion : This analysis demonstrates that , compared with SFC , SMART may be cost effective from a societal perspective for the treatment of patients with asthma in Italy , Germany , France and the UK . SMART provided a reduction in the number of severe exacerbations per patient per year , at no statistically significant increase in cost — or even at a lower cost — compared with SFC plus as-needed reliever salbutamol OBJECTIVE Asthma morbidity and mortality is highest among inner-city population s. Suboptimal beliefs about the chronicity of asthma may perpetuate poor asthma control among inner-city asthmatics . This study sought to characterize beliefs about the chronicity of disease and its correlates in a cohort of inner-city adults with persistent asthma . DESIGN Prospect i ve , longitudinal , observational cohort study . PATIENTS One hundred ninety-eight adults hospitalized with asthma over a 12-month period at an inner-city teaching hospital . MEASUREMENTS Sociodemographics , clinical history , disease beliefs , and self-management behaviors were collected by interview . Information on self-reported use of inhaled corticosteroids ( ICS ) , peak flowmeters , and regular asthma visits was collected during hospitalization , and 1 month and 6 months after discharge . RESULTS This cohort was predominantly low income and nonwhite , with high rates of prior intubation , oral steroid use , and emergency department visits and hospitalizations . Overall , 53 % of patients believed they only had asthma when they were having symptoms , what we call the no symptoms , no asthma belief . Men patients , those > or = 65 years old , and those with no usual place of care had greater odds of having the no symptoms , no asthma belief , and those receiving oral steroids all or most of the time or with symptoms most days had half the odds of having this belief ( p < 0.05 for all ) . The no symptoms , no asthma belief was negatively associated with beliefs about always having asthma , having lung inflammation , or the importance of using ICS , and was positively associated with expecting to be cured . The acute disease belief was associated with one-third lower odds of adherence to ICS when asymptomatic at all three time periods ( p < 0.02 for all ) . CONCLUSION The single question , " Do you think you have asthma all of the time , or only when you are having symptoms ? " can efficiently identify patients who do not think about or manage their asthma as a chronic disease BACKGROUND Asthma is a major cause of morbidity that disproportionately affects inner-city children . For children with persistent asthma , defined as having asthma symptoms 3 or more days per week or 3 or more nights per month , national guidelines recommend the use of daily antiinflammatory agents . Despite these recommendations , antiinflammatory agents remain underused , particularly in inner-city children with high asthma morbidity . OBJECTIVES The objectives of our study were to determine : 1 ) whether persistent asthma symptoms in inner-city children are related to acute care utilization and to the frequency of acute exacerbations ; 2 ) whether children with persistent asthma are receiving recommended daily antiinflammatory agents ; and 3 ) whether antiinflammatory medication use relates to sociodemographic factors , caretaker self-efficacy , the frequency of primary care visits , and /or measures of quality asthma care . DESIGN AND METHODS A 64-item telephone survey was administered between July 1996 and June 1997 to 219 parental caretakers of 2- to 12-year-old children who had been hospitalized with asthma at an inner-city medical center between January 1995 and February 1996 . Persistent asthma symptoms were assessed by inquiring about the frequency of daily and nocturnal asthma symptoms over the last 4 weeks . Children 's asthma severity was classified by applying the 1997 National Asthma Education and Prevention Program ( NAEPP ) Asthma Guidelines ' severity classification scheme based on the frequency of asthma symptoms . Asthma morbidity was defined as the frequency of acute asthma exacerbations , emergency department visits and hospitalizations . Daily antiinflammatory medication use was compared by sociodemographic factors , caretaker self-efficacy , frequency of primary care visits , and measures of quality asthma home management . RESULTS In this sample , quantifying persistent asthma symptoms and applying the NAEPP symptom criteria identified 17 % of the children with mild intermittent asthma , 27 % with mild persistent asthma and 56 % with moderate to severe persistent asthma . There were no differences in the age of the children in the 3 groups ( mean age : 6 years ) . Asthma morbidity , as measured by the number of asthma exacerbations in the last 6 months , was significantly higher in the children with moderate to severe persistent asthma compared with children with mild intermittent asthma ( 9.8 vs 3.5 ) or mild persistent asthma ( 9.8 vs 4.5 ) . In addition , there were significantly more emergency department visits in the moderate to severe group than in the mild persistent ( 3.05 vs 1.69 ) or mild intermittent group ( 3.05 vs 1.76 ) . Lastly , as asthma symptom frequency increased , there were trends toward more hospitalizations and more days hospitalized . Overall , 35 % of the 219 families reported giving daily antiinflammatory medications to their child ( mostly cromolyn sodium ) . Of the 181 children ( 83 % ) who met NAEPP symptom criteria for persistent asthma , only 39 % were receiving daily antiinflammatory treatment . Of the children with symptoms of moderate to severe asthma , only 15 % were receiving inhaled steroids in contrast to the guidelines ' recommendations . Use of antiinflammatory agents was not related to caretaker sociodemographic factors or self-efficacy scores . Measures of quality asthma home management , which included use of mattress covers , written plans , and peak flow meters , correlated positively with use of antiinflammatory agents . Children whose families reported using daily antiinflammatory medications had more primary care visits in the last 6 months than those children not receiving antiinflammatory medications . CONCLUSION Question ing parents about the frequency of their child 's asthma symptoms is an important , inexpensive , and readily accessible bedside and office tool that may aid in the detection of persistent symptoms and help direct therapy . Our study suggests that classifying asthma severity by quantifying persistent asthma symptoms , as defined in the NAEPP Guidelines , is a clinical ly useful tool that relates to asthma morbidity . In our sample of previously hospitalized children with asthma , 83 % met 1997 NAEPP symptom criteria for persistent asthma , and yet only 35 % were receiving daily antiinflammatory agents . Use of antiinflammatory agents correlated positively with other indicators of quality asthma home management . Additional work is necessary to increase appropriate use of antiinflammatory agents in this population , and in particular , to increase  inhaled steroid use for children with moderate or severe symptoms We have investigated the use of subcutaneous terbutaline in 17 patients with brittle asthma and five patients with chronic severe asthma . Twelve of the 17 patients with brittle asthma improved both subjectively and objective ly ( mean lowest daily PEF rising from 142 litres/min to 297 litres/min ) , with reduction in oral steroid dose , nebulized beta-agonist dose and number of hospital admissions . Both continuous infusion and 6-hourly divided dose regimens were equally effective . Only one of the five with chronic severe asthma showed any lasting response . Eighteen patients have continued to use subcutaneous terbutaline over long periods ( 2 - 40 months ) . Overall 11 patients suffered side-effects of usually minor degree , although one patient had to withdraw because of the development of painful subcutaneous nodules . We conclude that subcutaneous terbutaline delivered by infusion or by intermittent injections is a useful addition to the therapy of some patients with brittle asthma BACKGROUND Budesonide/formoterol maintenance and reliever therapy maintains asthma control and reduces exacerbation frequency compared with higher fixed-dose combination regimens . Its effects on eosinophilic airway inflammation and structure are unknown . OBJECTIVE We sought to compare the effects of budesonide/formoterol 200/6 microg twice daily plus as-needed with budesonide/formoterol 800/12 microg twice daily on airway eosinophils and remodeling . METHODS This 52-week , parallel-group , r and omized , double-blind study of 127 asthma patients who were symptomatic despite therapy compared ( 1 ) the change between induced sputum percent eosinophils at baseline and the geometric mean of 4 on-treatment values and ( 2 ) the change in endobronchial biopsy eosinophil counts pre- and post-treatment . RESULTS Mean daily doses of budesonide/formoterol were 604/18 microg in the maintenance and reliever therapy group and 1,600/24 microg in the high fixed-dose group . In the former , the geometric mean percent sputum eosinophils remained unchanged ( 1.6 % to 1.9 % ) , whereas biopsy specimen subepithelial eosinophils increased ( 6.2 to 12.3 cells/mm(2 ) ) . Sputum and biopsy eosinophil counts decreased with high fixed-dose treatment ( 2.2 % to 1.2 % and 7.7 to 4.8 cells/mm(2 ) , respectively ) , result ing in significant treatment differences of 0.7 % ( ratio , 1.8 ; 95 % CI , 1.2 - 2.8 ; P = .0038 ) and 7.5 cells/mm(2 ) ( ratio , 2.9 ; 95 % CI , 1.6 - 5.3 ; P < .001 ) , respectively . There were no between-treatment differences in reticular basement membrane thickness , exhaled nitric oxide , exacerbation frequency , or FEV(1 ) . CONCLUSION Compared with fixed-dose combination treatment containing a 4-fold higher maintenance dose of budesonide , budesonide/formoterol maintenance and reliever therapy is associated with higher eosinophil counts , but these remain within the range associated with stable clinical control The effect of Tinset tablet ( 30 mg oxatomide ) has been examined in 68 patients suffering from allergic diseases of the upper respiratory tract or from allergic diseases accidentally accompanying different pulmonary diseases . In general the daily doses were 2 x 1 tab . , occasionally 2 x 2 tab . , a number of 12 - 16-year old patients received only 1 tab . daily . On the basis of the clinical symptoms , spirometric examinations , and global evaluation it has been concluded that the drug may be used most successfully in seasonal rhinitis , allergodermatosis , and allergic conjunctivitis cases and in extrinsic allergic asthma of children . The therapeutic effectiveness of the drug is insignificant in perennial rhinitis and adult extrinsic asthma cases . The somnolence-inducing effect of the drug is notable ( it developed in 50 % of the patients ) . In 23 of the 68 patients weight-gain , in 3 cases each gastric complaint or dryness of mouth developed OBJECTIVE To develop a prognostic clinical index for adults with chronic stable asthma . DESIGN Analysis of data from a 48-week r and omized , crossover trial of regular vs as-needed inhaled beta-agonist therapy . PATIENTS Eligible patients included 70 men and women between the ages of 15 and 64 years with asthma for > 1 year . OUTCOME MEASURE Asthma deterioration within 20 weeks , defined as either a marked decline in FEV1 ( > or = 1.0 L or > or = 30 % from baseline ) or initiation of systemic corticosteroid therapy  for asthma exacerbation . RESULTS Three baseline factors independently predicted asthma deterioration : frequent symptoms on waking in the 4 weeks before baseline , past hospitalization for asthma , and age 35 years or older . Based on cross-stratification and consolidation of these prognostic factors , an index was developed that stratified subjects into four risk groups with distinctive deterioration rates of 9 % , 21 % , 39 % , and 67 % ( p<0.001 ) . CONCLUSION For adults with chronic stable asthma , three simple clinical factors can be combined to stratify effectively for risk of subsequent asthma deterioration BACKGROUND The management of asthma has changed since the introduction of budesonide/formoterol ( Symbicort ® ) as both maintenance and reliever therapy ( SMART ) . SMART and its effects on bronchial hyperresponsiveness ( BHR ) have not been studied in primary care . AIMS To compare the effects of SMART and guideline -driven usual care ( UC ) on BHR and clinical asthma severity in primary care practice . METHODS Patients with mild-to-moderate stable asthma were r and omised to receive SMART treatment ( n=54 ) ( budesonide/formoterol 80/4.5 μg Turbuhaler ® , two puffs once daily and extra inhalations as needed ) or UC treatment ( n=48 ) for 12 months . Diary data , Asthma Control Question naire scores , forced expiratory volume in 1 second ( FEV1 ) , and peak expiratory flow ( PEF ) measurements were collected during run-in and after 1 , 3 , 6 , and 12 months of treatment . BHR , measured as the dose of histamine provoking a fall in FEV1 of 20 % ( PD20-histamine ) , was determined at r and omisation and after 12 months . RESULTS One hundred and two patients with asthma participated in the study .  The change in PD20-histamine during the study was not significantly different between the SMART and UC groups ( p=0.26 ) . The mean inhaled corticosteroid ( ICS ) dose was 326 μg beclomethasone dipropionate ( BDP ) equivalents/day ( 95 % CI 254 to 399 ) with SMART , which was significantly lower ( p<0.0001 ) than the mean ICS dose with UC treatment ( 798 μg BDP equivalents/day ( 95 % CI 721 to 875 ) . Morning and evening PEF values increased significantly with SMART treatment compared with UC ; FEV1 , symptoms and asthma control did not differ . CONCLUSIONS Despite a 59 % lower dose of ICS , BHR and other clinical outcomes remained stable during SMART treatment while PEF values improved High doses of inhaled salbutamol produce substantial improvements in airway response in patients with asthma , and are associated with dose-dependent systemic beta-adrenoceptor responses . The purpose of the present study was to investigate whether tachyphylaxis occurs during prolonged treatment with high dose inhaled salbutamol .  Twelve asthmatic patients ( FEV1 , 81 + /- 4 % predicted ) , requiring only occasional inhaled beta-agonists as their sole therapy , were given a 14-day treatment with high dose inhaled salbutamol ( HDS ) , 4,000 micrograms daily , low dose inhaled salbutamol ( LDS ) , 800 micrograms daily , or placebo ( PI ) by metered-dose inhaler in a double-blind , r and omized crossover design . During the 14-day run-in and during washout periods , inhaled beta-agonists were withheld and ipratropium bromide was substituted for rescue purpose s. At the end of each 14-day treatment , a dose-response curve ( DRC ) was performed , and airway ( FEV1 , FEF25 - 75 ) chronotropic ( HR ) , tremor , and metabolic ( K , Glu ) responses were measured at each step ( from 100 to 4,000 micrograms ) . Treatment had no significant effect on baseline values . There were dose-dependent increases in FEV1 and FEF25 - 75 ( p less than 0.001 ) , and pretreatment with HDS did not displace the DRC to the right . DRC for HR ( p less than 0.001 ) , K ( p less than 0.001 ) , and Glu ( p less than 0.005 ) were attenuated after treatment with HDS compared with PI . There were also differences between HDS and LDS for HR ( p less than 0.001 ) and Glu ( p less than 0.05 ) responses . Frequency and severity of subjective adverse effects were also reduced after HDS : tremor ( p less than 0.001 ) , palpitations ( p less than 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract The effect of a sustained-release aminophylline on exercise-induced asthma ( EIA ) has been studied in nine young adult asthmatic patients , whose asthma was mild enough to be controlled with intermittent inhaled β-adrenoceptor agonists only . Exercise testing consisted of running for six minutes on a treadmill at a workload that was held constant for each individual and was sufficient to result in a pulse rate of greater than 160 beats/minute . Placebo or sustained-release aminophylline tablets were each given twice daily for one week periods in double blind r and om order . At the end of each week , morning and afternoon exercise tests were performed four and eight hours after the last dose of tablets , and plasma theophylline levels at these times were measured . The maximum falls in peak expiratory flow rate ( PEFR ) in the 20-minute period following the exercise tests were compared . On placebo the maximum fall in PEFR for the group after exercise testing was 29.6 ± 5.6 % ( mean ± se ) in the morning and 28.5 ± 5.6 % in the afternoon . On sustained-release aminophylline all subjects were found to have plasma theophylline levels greater than 7 μg/ml ( range 7–17 μg/ml ) with a mean of 10.8 μg/ml in the morning and 11.2 μg/ml in the afternoon . The maximum fall in PEFR following exercise was 13.3 ± 3.6 % ( mean ± se ) in the morning and 18.6 ± 2.5 % in the afternoon . The difference between the percentage falls in PEFR for the group on placebo compared to sustained-release aminophylline was significant at the 1 % level for the morning tests and the 5 % level for the afternoon tests . These results demonstrate that slow-release aminophylline  is effective in inhibiting EIA over a prolonged period and that therapeutic levels of theophylline were present four and eight hours after the last dose of drug Abstract Background : The combination of an inhaled corticosteroid ( ICS ) , budesonide , and a rapid long-acting β2-agonist ( LABA ) , formoterol , in a single inhaler for use as maintenance and reliever therapy ( Symbicort Turbuhaler SMART ™ ) effectively achieves a high level of asthma control and reduces exacerbations and asthma-related hospitalizations . The COSMOS study , a multinational , 12-month study ( N = 2143 ) , compared budesonide/formoterol maintenance and reliever therapy with salmeterol/fluticasone propionate plus as-needed salbutamol , allowing physicians to modify maintenance doses of both combinations according to routine clinical practice . Objective : The aim of this post hoc sub-group analysis of the COSMOS study is to provide focused data on budesonide/formoterol maintenance and reliever therapy compared with salmeterol/fluticasone propionate plus as-needed salbutamol in patients ( aged ≥16 years ) enrolled across Asian countries , specifically China , Korea , Taiwan and Thail and . Methods : This sub- analysis of the COSMOS study concerns all 404 r and omized patients ≥16 years of age ( mean forced expiratory volume in 1 second [ FEV1 ] 69.1 % ) who were recruited from Asian countries . Patients received either budesonide/formoterol ( Symbicort Turbuhaler SMART ™ , n=198 ) , starting dose 160 mg/4.5 mg two inhalations twice daily ( bid ) [ plus additional as-needed inhalations ] , or salmeterol/fluticasone propionate ( Seretide ® Diskus ® , n = 206 ) , starting dose 50 mg/250 mg bid ( plus salbutamol [ Ventolin ® ] as needed ) . Maintenance doses could be titrated by clinicians after the first 4 weeks ( budesonide/formoterol maintenance plus as needed , n= 198 ; salmeterol/fluticasone propionate plus salbutamol , n = 206 ) . To allow for free adjustment in maintenance doses in both arms , the trial was performed open-label ; maintenance doses could be titrated by clinicians after the first 4 weeks . The time to first severe exacerbation ( defined as deterioration in asthma result ing in hospitalization/emergency room treatment , oral corticosteroids for ≥3 days or unscheduled visit leading to treatment change ) was the primary variable . Results : The time to first severe exacerbation was prolonged in patients using maintenance plus as-needed budesonide/formoterol compared with salmeterol/fluticasone propionate plus salbutamol ( log-rank p = 0.024 ) . The risk of a first exacerbation was reduced by 44 % ( hazard ratio 0.56 ; 95 % confidence interval [ CI ] 0.32 , 0.95 ; p = 0.033 ) in patients using the adjusted budesonide/formoterol regimen versus titrated salmeterol/fluticasone propionate .  The overall exacerbation rates were 0.16 versus 0.26 events/patient-year , respectively , with a 38 % reduction ( rate ratio 0.62/patient/year ; 95 % CI 0.41 , 0.94 ; p = 0.024 ) in favour of the budesonide/formoterol regimen . Compared with baseline , both regimens provided clinical ly relevant improvements in asthma control , quality of life and FEV1 ; no statistically significant differences between the treatment groups were observed . Mean adjusted ( st and ard deviation ) ICS dose ( expressed as beclomethasone dose equivalents ) during treatment , including as-needed budesonide doses , was 944 ( 281 ) and 1034 ( 394 ) mg/day , respectively , in patients using maintenance plus as-needed budesonide/formoterol compared with salmeterol/fluticasone propionate . Conclusion : In patients ( aged ≥16 years ) enrolled from Asian countries as part of the COSMOS study , the budesonide/formoterol maintenance and reliever regimen was associated with a lower future risk of exacerbations versus the physicians ’ free choice of salmeterol/fluticasone propionate dose plus salbutamol . Single inhaler combination treatment with maintenance plus as-needed budesonide/formoterol was also at least as efficacious as salmeterol/fluticasone propionate dose plus salbutamol in improving current asthma control BACKGROUND Both specific immunotherapy ( SIT ) and nasal steroid ( NS ) have been shown to effectively reduce symptoms of  allergic rhinitis .  Although a number of investigators have convincingly shown anti-inflammatory effects of both treatments in separate studies , few comparative studies have been performed . OBJECTIVE The purpose of this study was to compare the effects of preseason SIT with a st and ardized allergen extract and NS in seasonal allergic disease ( rhinoconjunctivitis and asthma ) . METHODS We examined 41 patients allergic to birch pollen , 21 with rhinoconjunctivitis and 20 with both rhinoconjunctivitis and asthma ; they were treated in a r and omized , double-blinded comparative study with birch SIT and NS ( budesonide 400 microg daily ) . Bronchial hyperresponsiveness was measured before and during the season . Changes in eosinophil number , eosinophil cationic protein , and eosinophil chemotactic activity ( ECA ) in peripheral blood were investigated . RESULTS Symptoms of rhinoconjunctivitis increased significantly less in the NS-treated patients than in the SIT-treated patients during the final 2 weeks of the season ( P = .03 and P = .04 , respectively ) . Seasonal peak expiratory flow values decreased significantly only in the NS-treated patients ( P = .01 ) . In the NS-treated patients , bronchial hyperresponsiveness increased significantly during the season ( P = .0001 ) ; however , SIT treatment prevented seasonal PC(20 ) increase in the asthmatic patients . Measurement of blood eosinophils , eosinophil cationic protein , and eosinophil chemotactic activity demonstrated significant seasonal increase only in the NS-treated asthmatic patients . CONCLUSION Treatment with NS was more effective than short-course preseason SIT in reducing symptoms of rhinoconjunctivitis ; however , the 2 therapies were equivalent in terms of the need for rescue medication . SIT prevented seasonal increase in bronchial hyperresponsiveness , eosinophil number , eosinophil cationic protein , and eosinophil chemotactic activity only in asthmatic patients . The mechanisms underlying bronchial hyperresponsiveness developing during allergen exposure in rhinitis might be different from those operating in asthma 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 This open , r and omized trial was conducted at the Medical Out patient Department of University College Hospital , Nigeria to compare the clinical efficacy of Beclomethasome dipropionate ( Becotide ) with Fluticasone propionate ( Fluvent ) in patients with mild to moderate bronchial asthma . The study was performed as a week screening , 8-weeks open comparative clinical trial involving Fluticasone propionate ( Fluvent ) at a daily dose of 22 microg and Beclomethasone Dipropionate ( Becotide ) at a dose of 400 microg daily delivered through pressurized metered-dose inhaler ( pMDI ) . The main objective of this study is to assess the efficacy of Fluvent in patients with mild to moderate asthma compared to Becotide . At the second visit ( end of 1 week ) , 10 patients were given either Becotide of Fluvent but all were maintained on as needed beta2agonist ( Salbutamol inhaler ) therapy throughout the study . Efficacy was assessed by changes in symptoms , number of times beta2-agonist was used and results of pulmonary function tests ( PEFR and FEV1 ) while safety was assessed by adverse event experiences . The baseline characteristics of the patients r and omized into the two drug groups were comparable and of no statistical significance . The changes in the pulmonary function tests as well as the reduction in the asthma symptoms suggest a statistically significant improvement in the asthma status of the patients . However , these changes were more rapid among the patients using Fluvent . Also , there was higher percentage decline in the episodes of asthma symptoms either in the morning , day or night in the Fluvent group than Becotide group . The drugs were well tolerated and no adverse event was noticed on any of the patients . We therefore concluded that Fluvent would be more efficacious than Becotide in the treatment of Asthma BACKGROUND The inhaled corticosteroid , fluticasone propionate , was compared with the oral bronchodilator theophylline in the maintenance treatment of asthma . OBJECTIVE The objective of the present study was to compare the efficacy and safety of twice-daily inhaled fluticasone propionate , 50 micrograms , and fluticasone propionate , 100 micrograms , with that of theophylline in the maintenance treatment of mild-to-moderate asthma . METHODS In this r and omized , double-blind , placebo-controlled , parallel-group study , 353 adult and adolescent patients with asthma inadequately controlled with inhaled beta-agonist therapy alone received fluticasone propionate , 50 micrograms , or fluticasone propionate , 100 micrograms , by metered-dose inhaler ; theophylline capsules ; or placebo twice daily for 12 weeks . Only inhaled albuterol was permitted as needed for acute symptoms . RESULTS Both fluticasone propionate groups had a significantly greater probability of remaining in the study ( ie , meeting asthma stability criteria ) than did either the theophylline or placebo group ( P < or = .008 ) ; 39 % and 51 % in the theophylline and placebo groups , respectively , were withdrawn due to lack of treatment efficacy compared with 14 % and 21 % in the fluticasone propionate , 50 micrograms , and fluticasone propionate , 100 micrograms , groups . Both fluticasone propionate groups experienced significantly greater improvement in FEV1 and PEF compared with patients in the theophylline or placebo group ( P < or = .004 ) . The incidence of potentially drug-related adverse events was significantly greater in the theophylline group ( 25 % ) than in the placebo group ( 11 % ) ( P = .031 ) , while there were no differences between placebo and fluticasone propionate , 50 micrograms , ( 18 % ) or fluticasone propionate 100 micrograms , ( 22 % ) . CONCLUSION Twice daily treatment with inhaled fluticasone propionate 50 micrograms or 100 micrograms was significantly more effective than theophylline in the treatment of mild-to-moderate asthma OBJECTIVE To determine whether peak flow monitoring has value above and beyond symptom monitoring when used as part of an asthma management plan . METHODS From a large managed-care organization , 296 adults , aged 50 - 92 yr , were recruited and r and omly assigned in equal numbers to either use of symptoms or peak flow rate ( twice daily or " as needed " ) for asthma monitoring , and monitored every 6 mo for 2 yr . Interventions were delivered in four 90-min small-group classes and included a personalized action plan and coaching in proper use of asthma inhalers . RESULTS We found no significant differences between peak flow rate and symptom monitoring , or between twice-daily and as-needed peak flow monitoring in the primary or secondary study outcomes : health care utilization ( acute , nonacute , or total asthma visits ) , Asthma Quality -of-Life Question naire ( AQLQ ) scores , and lung function . AQLQ scores and prebronchodilator FEV1 increased significantly for both groups between baseline and 6 mo ( AQLQ : mean , 0.4 units ; 95 % confidence interval , 0.3 , 0.5 ; p < 0.0001 ; FEV1 % predicted : mean , 4 % ) . Inhaler technique improved substantially in both groups . CONCLUSIONS Peak flow monitoring has no advantage over symptom monitoring as an asthma management strategy for older adults with moderate-severe asthma when used in a comprehensive asthma management program . Improved outcomes in both groups suggest that underst and ing proper medication use , regular monitoring of asthma status , and underst and ing how to respond to changes are of primary importance BACKGROUND Inhaled corticosteroids ( ICS ) represent first-line treatment in persistent asthma with clinical studies showing benefits of initiating therapy early . Whether treatment should be started with a high or low dose remains controversial . We investigated the importance of disease duration on the response to the starting dose of the ICS , budesonide , in asthma patients not previously treated with ICS . METHODS Forty patients with newly detected asthma ( symptoms for < 12 months ) and 41 patients with established asthma ( mean duration 5.2 years , range 2 - 11 ) were r and omized ( double-blind , parallel-group ) to treatment with budesonide Turbuhaler 100 or 400microg twice daily or placebo for 12 weeks . RESULTS For morning peak expiratory flow ( mPEF ) , all four budesonide treatments result ed in statistically significant improvements from baseline and , after 12 weeks , the changes in all four groups were statistically significantly greater than placebo . In patients receiving early treatment , no significant differences were seen between budesonide doses . In patients with established symptoms , 800 mg/day [ corrected ] improved mPEF significantly more than 200 mg/day [ corrected ] The 200 mg/day [ corrected ] dose in the early treatment group improved mPEF significantly more than in the delayed treatment group . Changes in forced expiratory volume in 1s ( FEV(1 ) ) , the concentration of inhaled histamine causing a 20 % drop in FEV(1 ) , and use of as-needed medication behaved in very similar ways to mPEF . Asthma symptoms were reduced in all budesonide groups without a difference between doses . CONCLUSION In patients with newly detected asthma treated early the initial ICS dose is not important . In contrast , in patients with symptoms for a longer duration a high starting dose improves airway function and hyperresponsiveness significantly better than a low dose Celiprolol was compared with chlorthalidone in a double-blind r and omized placebo-controlled study of 30 hypertensive or anginal patients with reversible bronchial obstruction . The study consisted of a 4-week placebo run-in period and a 12-week titration period during which the dose of both drugs was increased at 4-week intervals if blood pressure was not reduced adequately . The doses of celiprolol were 200 , 400 or 600 mg once daily , whereas those for chlorthalidone were 12.5 , 25 or 37.5 mg once daily . Entry criteria were a diastolic blood pressure between 90 to 115 mm Hg , forced expiratory volume in 1 second between 40 and 80 % of predicted value , increasing by 15 % or more after salbutamol inhalation and the need for occasional bronchodilator therapy . Prophylactic medication for asthma was given at a constant dosage for 1 month before the study and throughout the study . Clinical variables were not significantly changed by either drug , and neither celiprolol nor chlorthalidone had any significant effect on forced expiratory volume in 1 second BACKGROUND Many factors , including heredity , atopic status , and environment , have been implicated in the determination of asthma severity . Relatively little is known about the degree to which asthma duration influences asthma severity . OBJECTIVE The  Childhood Asthma Management Program ( CAMP  ) , consisting of 1041 children ( age 8 . 9 + /- 2.1 years at enrollment ) with mild-to-moderate asthma , offers an opportunity to examine the relationship between asthma duration and asthma severity . METHODS By using the extensive CAMP baseline cross-sectional data on asthma duration , spirometry , bronchial responsiveness , symptomatology , and markers of atopy , univariate and multivariate regression models were used to evaluate whether asthma duration is associated with asthma severity . RESULTS Duration of asthma in the study cohort from time of diagnosis until r and omization into CAMP ranged from 0.3 to 12.1 years ( mean , 5.0 ; SD , 2.7 ; median , 4.8 ) . Asthma duration is associated in univariate analyses both with lower levels of several lung functions ( P < .001 ) , including methacholine bronchial reactivity ( natural log [ ln ] FEV1 PC20 , mg/mL ; r = -0.112 ) , prebronchodilator and postbronchodilator percent predicted FEV1 ( r = -0.176 and r = -0.130 , respectively ) , and prebronchodilator and postbronchodilator FEV1 /forced vital capacity ( FVC ) ( % ) ( r = -0.237 and r = -0.211 , respectively ) , as well as higher levels of symptoms ( symptom score : r = 0.147 , P < . 001 ) and borderline greater use of albuterol for symptoms ( r = 0.058 , P = .064 ) during a 28-day screening period before r and omization . Simple linear regression detected the following differences in lung functions per year of asthma duration : ln FEV1 PC20 , -0.050 mg/mL/y ; prebronchodilator FEV1 , -0.907 percent predicted/y ; and prebronchodilator FEV1 /FVC , -0.729 percent predicted/y . After controlling for potential explanatory variables ( atopy , inflammatory markers , household Der p 1 levels , anti-inflammatory medication use , and clinical center ) , regression models revealed that the duration of asthma remained significantly and independently associated with ln FEV1 PC20 ( P = .004 ) , prebronchodilator percent predicted FEV1 ( P = .043 ) , and prebronchodilator and postbronchodilator FEV1 /FVC ( % ) ( P < .001 ) , as well as being positively associated with mean daily symptom score ( P < .001 ) and albuterol use for symptoms ( P = .003 ) during a 28-day screening period . Duration was also found to be significantly associated with physician/nurse assessment of asthma severity and other historical measures of medication use . CONCLUSIONS These data demonstrate that asthma duration is associated with lower lung function , greater methacholine responsiveness , more asthma symptomatology , and greater use of as-needed albuterol , which are all measures of asthma severity . As such , early diagnosis and intervention may be necessary to ameliorate these adverse effects of persistent asthma The Childhood Asthma Management Program ( CAMP ) is a multicenter , r and omized , double-masked clinical trial design ed to determine the long-term effects of three inhaled treatments for mild to moderate childhood asthma : budesonide ( a glucocorticoid used daily ) and albuterol ( a short-acting beta-agonist bronchodilator used as needed ) ; nedocromil ( a nonsteroid anti-inflammatory agent used daily ) and albuterol ; and placebo and albuterol .  One thous and forty-one children ( 32 % from ethnic minority groups ) , aged 5 to 12 years at screening , are currently participating . The primary outcome measure is lung growth as indicated by postbronchodilator forced expiratory volume in 1 second ( FEV1 ) percent of predicted , observed over 5- to 6-year period . The trial also assesses differences between treatment groups with respect to airway responsiveness , morbidity , physical growth and development , and psychological growth and development . This report describes the design of the trial , the rationale for the design choices made , and the methods used to carry out the trial BACKGROUND Some recent clinical investigations suggest that regular use of inhaled bronchodilators may lead to deterioration in asthma control . OBJECTIVE The purpose of this study was to evaluate the effect of albuterol dosing schedule on clinical outcome in subjects with moderate to severe stable asthma . METHODS Seventeen adults were r and omized to two 15-week treatment periods in a double-blind crossover design . Throughout the study , subjects were instructed to take two inhalations four times daily from an unlabeled " test " canister . In the four times daily and as-needed ( QID + PRN ) period , this canister contained albuterol ; in the as-needed ( PRN ) period , it contained placebo . A " rescue " albuterol canister was available for as-needed use at all times . Inhaler actuations from both the test and rescue canisters were electronically recorded . Outcome measures included prednisone requirements , morning and evening symptoms and peak expiratory flow rates , total and nighttime rescue albuterol use , and asthma-specific quality of life . RESULTS The two treatment periods did not differ in symptoms , nighttime albuterol use , or asthma quality of life . During the QID+PRN period both morning and evening peak expiratory flow rates were significantly higher ( p < 0.01 and 0.001 , respectively ) and total rescue use of albuterol  was significantly less ( p < 0.05 ) than the PRN period . Days on prednisone tended to be lower in the regular dosing period ( p = 0.08 ) . CONCLUSION In our sample of patients with moderate to severe asthma , four times daily dosing of albuterol did not lead to deterioration of asthma control Inhalation of ozone in normal subjects causes a neutrophilic inflammatory response in the airways . Pretreatment with inhaled corticosteroids reduces the inflammatory response to inhaled ozone in dogs . We undertook a double-blind , r and omized , placebo-controlled , crossover study to investigate the effects of 2 wk of treatment with inhaled budesonide 800 microg twice daily or placebo prior to ozone exposure in humans . Fifteen ( six male ; mean age , 31.1 + /- 2.1 yr ) healthy nonsmokers were exposed to 400 parts per billion ( ppb ) ozone for 2 h with intermittent exercise .  Spirometry , exhaled carbon monoxide ( CO ) and nitric oxide ( NO ) levels , measurement of methacholine reactivity , and collection of exhaled air condensate and induced sputum sample s were performed at baseline , preexposure , and at intervals up to 24 h postexposure . Ozone exposure led to significant decreases in spirometry and increased methacholine reactivity and sputum neutrophils and myeloperoxidase ( MPO ) . There were no changes in exhaled NO and CO levels , or exhaled breath nitrite after ozone exposure . There were no differences in any of the parameters after treatment with budesonide compared with placebo , and no differences in the response to ozone between treatment groups . We conclude that a high dose of inhaled corticosteroid does not protect against the effects of ozone exposure in normal subjects We studied 22 asthmatic children aged seven years two months to thirteen years eight months over a four-month period . Each child received two months continuous and two months intermittent salbutamol tablets using a double-blind cross-over technique . No significant clinical differences were found between the two treatment regimens as judged by daily diary card scores . Daily PEFRs ( both a.m. and p.m. ) were significantly higher ( P < 0.05 ) when the children were receiving continuous salbutamol and this was more obvious in the eleven children under ten years old . Lung function tests performed monthly in hospital showed no significant differences between the two treatment regimens STUDY OBJECTIVE To determine whether adding IV theophylline to an aggressive regimen of inhaled and IV beta-agonists , inhaled ipratropium , and IV methylprednisolone would enhance the recovery of children with severe status asthmaticus admitted to the pediatric ICU ( PICU ) . DESIGN A prospect i ve , r and omized , controlled trial . Asthma scoring was performed by investigators not involved in treatment decisions and blinded to group assignment . SETTING The PICU of an urban , university-affiliated , tertiary-care children 's hospital . PATIENTS Children with a diagnosis of status asthmaticus who were admitted to the PICU for < or = 2 h and who were in severe distress , as indicated by a modified Wood-Downes clinical asthma score ( CAS ) of > or = 5 . INTERVENTIONS All subjects initially received continuous albuterol nebulizations ; intermittent , inhaled ipratropium ; and IV methylprednisolone . The theophylline group was also administered infusions of IV theophylline to achieve serum concentrations of 12 to 17 microg/mL. A CAS was tabulated twice daily . MEASUREMENTS AND RESULTS Forty-seven children ( median age , 8.3 years ; range , 13 months to 17 years ) completed the study . Twenty-three children received theophylline  . The baseline CASs of both groups were similar and included three subjects receiving mechanical ventilation in each group . All subjects receiving mechanical ventilation and theophylline were intubated before drug infusion . Among the 41 subjects who were not receiving mechanical ventilation , those receiving theophylline achieved a CAS of < or = 3 sooner than control subjects ( 18.6 + /- 2.7 h vs 31.1 + /- 4.5 h ; p < 0.05 ) . Theophylline had no effect on the length of PICU stay or the total incidence of side effects . Subjects receiving theophylline had more emesis ( p < 0.05 ) , and control patients had more tremor ( p < 0.05 ) . CONCLUSIONS Theophylline safely hastened the recovery of children in severe status asthmaticus who were also receiving albuterol , ipratropium , and methylprednisolone . The role of theophylline in the management of asthmatic children in impending respiratory failure should be reexamined OBJECTIVE To compare the efficacy and safety of inhaled salmeterol xinafoate , a long-acting beta 2-adrenoceptor agonist , with that of albuterol , a short-acting inhaled beta 2-agonist , in the treatment of asthma . DESIGN R and omized , double-blind , placebo-controlled , parallel-group study . SETTING Eleven outpatient clinical centers . SUBJECTS A total of 322 male and female patients at least 12 years of age with chronic symptomatic asthma requiring daily therapy . INTERVENTION Patients were treated with salmeterol xinafoate ( 42 micrograms inhaled twice daily ) , albuterol ( 180 micrograms inhaled four times daily ) , or placebo ( four times a day ) for 12 weeks ; patients in all three groups could use inhaled albuterol as backup medication for breakthrough symptoms . MAIN OUTCOME MEASURES Serial 12-hour forced expiratory flow in 1 second ( FEV1 ) , peak expiratory flow ( PEF ) , asthma symptoms , nocturnal awakenings due to asthma , episodes of asthma exacerbations , and electrocardiography . RESULTS The mean area under the curve for FEV1 throughout each 12-hour period was consistently greater after a single dose of salmeterol than after two doses of albuterol administered 6 hours apart ( P < .001 ) , with the difference ranging from 3.1 to 4.3 L.h . Salmeterol produced an average increase in morning and evening PEF of 26 and 29 L/min , respectively , over pretreatment values compared with decreases of -13 and -3 L/min , respectively , in the albuterol group and -2 L/min both in the morning and evening in the placebo group ( P < .001 ) . Patients in the salmeterol group had significantly fewer days and nights with symptoms than did either the albuterol or placebo group ( P < .001 ) . Responses to salmeterol were similar at day 1 and at week 12 . Adverse events in all treatment groups were equally infrequent , and no clinical ly significant change in cardiac rhythm was observed with salmeterol treatment . CONCLUSION Salmeterol inhaled twice daily is more effective than albuterol inhaled four times a day ( or as needed ) in patients with asthma requiring maintenance therapy . No deterioration of asthma control was observed with the use of salmeterol over a 3-month period Recent studies have suggested that regular use of inhaled beta 2 agonists cause loss of asthma control as measured by worsening peak-flow rates , increased asthma symptoms , and more frequent need for supplementary bronchodilators .  However , the magnitude of this effect and the reliability of investigator-originated definitions of control is unknown . We studied 341 people with asthma in a four-week , r and omised , crossover trial of regular salbutamol ( 2 puffs--200 micrograms -- four times daily ) for two weeks and as needed for two weeks . There were no significant differences in morning and evening peak-flow rates between treatments but asthma symptoms and supplementary bronchodilator use were significantly less frequent when salbutamol was given regularly . Asthma episodes occurred 1.39 ( 1.52 ) times per day during regular treatment and 2.44 ( 1.75 ) times per day during as-needed treatment ( p < 0.0001 ) and 0.50 ( 0.56 ) vs 0.65 ( 0.66 ) times per night ( p < 0.0001 ) . Daytime use of supplementary salbutamol was 1.14 ( 1.40 ) vs 2.35 ( 1.71 ) puffs per day , ( p < 0.0001 ) ; night-time use was 0.45 ( 0.55 ) vs 0.64 ( 0.66 ) puffs per night ( p < 0.0001 ) . When control endpoints were compared between treatment periods for each individual by two blinded investigators and control judged by six different sets of criteria , in 70 asthmatics there was no difference in symptom control between periods but in the remainder , control was achieved more often by regular than by as-needed salbutamol ( 166 vs 69 , p < 0.0001 ) . In asthma of moderate severity , regularly administered salbutamol does not produce lower peak flow rates than as-needed salbutamol and is associated with less frequent asthma symptoms BACKGROUND A simple laboratory method to evaluate relative potency of inhaled corticosteroids in asthma would be valuable . Single-dose studies with the allergen-induced late asthmatic response have failed to show a useful dose-response relationship . Treatment for several days with inhaled corticosteroids will also inhibit the allergen-induced early asthmatic response . METHODS Twelve atopic asthmatic subjects were studied during a season when no medications were required except ipratropium  bromide  as needed . These subjects had positive allergen and methacholine inhalation tests and FEV1 greater than 70 % of predicted value . A double-blind , r and omized , cross-over study compared placebo and budesonide 100 , 200 , and 400 microg administered by means of Turbuhaler twice daily for 7 days with 6-day washout periods . Methacholine PC20  was measured before and after 6 days of treatment , and allergen PC15 was measured after 7 days of treatment . RESULTS The allergen PC15 ( n = 11 ) was significantly larger ( P = .0001 ) for all doses of budesonide compared with placebo , but there was no significant difference between the 3 doses of budesonide , and no dose response was demonstrated . The methacholine PC20 was significantly larger after all budesonide treatments compared with placebo ( P = .024 ) , but there was no difference between the 3 doses . There was a progressive increase in the allergen PC15 chronologically ( sequence effect ) that was not explained by improvement in FEV1 or airway responsiveness ; sequence effects were not seen for FEV1 or for pretreatment or posttreatment methacholine PC20 . Statistical adjustment for sequence effect did not alter allergen PC15 statistics . CONCLUSION A 7-day course of budesonide administered by means of Turbuhaler at 200 , 400 , or 800 microg per day provided marked and significant inhibition of the allergen-induced early asthmatic response compared with placebo . There was , however , no difference between the 3 doses . Therefore this method with these doses is not useful for providing assessment of relative potency BACKGROUND Chronic obstructive pulmonary disease ( COPD ) and asthma have different diagnostic criteria and treatment paradigms . Both are common and can occur in the same patient . We sought to determine the spirometric effects of tiotropium in COPD patients with concomitant asthma . METHODS A 12-week r and omized , double-blind , placebo-controlled , parallel group trial with tiotropium 18 mcg daily was performed . Patients continued usual respiratory medications except for inhaled anticholinergics . INCLUSION CRITERIA Physician diagnosis of COPD and asthma , age > or= 40 years , smoking > 10 pack years , post-bronchodilator forced expiratory volume in 1s ( FEV(1))<80 % predicted , FEV(1)/forced vital capacity (FVC)<70 % , > or= 12 % , and > or= 200 ml increase in FEV(1 ) following inhaled bronchodilator , treatment with inhaled steroids > or= 1 year . Spirometry was measured serially for 6h on days 1 , 29 and 85 . RESULTS Four hundred and seventy-two patients were r and omized . Baseline characteristics were balanced . Mean age=59.6 years , 61.4 % were men , and FEV(1)=1.55l ( 53.0 % predicted ) . Improvements at 12 weeks with tiotropium were observed for the primary endpoint FEV(1 ) area under the curve ( AUC ) from 0 to 6h ( difference=186+/-24 ml , p<0.001 ) and for morning pre-dose FEV(1 ) ( difference=98+/-23 ml , p<0.001 ) . Significant differences in favor of tiotropium were observed for pre-dose FVC ( difference=128+/-34 ml , p<0.001 ) and FVC AUC 0 - 6h ( difference=232+/-35 ml , p<0.001 ) . Compared to baseline , the mean weekly number of daily puffs of prn salbutamol was reduced by 0.05+/-0.12 puffs/day in the placebo group and by 0.50+/-0.12 puffs/day in the tiotropium group at week 12 ( p<0.05 ) . CONCLUSIONS Patients with COPD and concomitant asthma achieve spirometric improvements with tiotropium along with symptomatic benefit as seen by reduced need for rescue medication The efficacy and safety of nedocromil sodium inhalation aerosol ( 4 mg of Tilade administered by metered-dose inhaler ) given twice daily was compared with placebo in 112 patients with mild-to-moderate asthma who had been receiving maintenance therapy with oral or inhaled bronchodilators or both . After a 2-week run-in period and a subsequent 2-week baseline period , patients were r and omized to active treatment ( n = 56 ) or placebo ( n = 56 ) for 8 weeks . All maintenance bronchodilators were withdrawn before the baseline period , and patients entered the treatment period only after demonstrating a specified level of asthma symptoms . Twice daily administration of nedocromil sodium improved all asthma symptoms in these patients who had symptoms as a result of the withdrawal of their maintenance theophylline and /or oral and inhaled beta 2-agonist bronchodilators . During the primary time period ( treatment weeks 5 to 8) , statistically significant between-group differences favored nedocromil sodium for the asthma summary score ( primary variable , p = 0.001 ) , daytime asthma ( p = 0.001 ) , and sleep difficulty caused by asthma ( p = 0.006 ) . Furthermore , significant reductions in the use of as-needed rescue medications were reported in the nedocromil sodium group ( p = 0.003 ) compared with the placebo group . Final overall opinions of treatment effectiveness expressed by physicians ( p = 0.016 ) and patients ( p = 0.002 ) strongly favored nedocromil sodium OBJECTIVES To determine the clinical effect of oral montelukast sodium , a leukotriene receptor antagonist , in asthmatic patients aged 15 years or more . DESIGN R and omized , multicenter , double-blind , placebo-controlled , parallel-group study . A 2-week , single-blind , placebo run-in period was followed by a 12-week , double-blind treatment period ( montelukast sodium , 10 mg , or matching placebo , once daily at bedtime ) and a 3-week , double-blind , washout period . SETTING / PATIENTS Fifty clinical centers r and omly allocated 681 patients with chronic , stable asthma to receive placebo or montelukast after demonstrating a forced expiratory volume in 1 second 50 % to 85 % of the predicted value , at least a 15 % improvement in forced expiratory volume in 1 second ( absolute value ) after inhaled beta-agonist administration , a minimal predefined level of daytime asthma symptoms , and inhaled beta-agonist use . Twenty-three percent of the patients used concomitant inhaled corticosteroids . PRIMARY END POINTS : Forced expiratory volume in 1 second and daytime asthma symptoms . RESULTS Montelukast improved airway obstruction ( forced expiratory volume in 1 second , morning and evening peak expiratory flow rate ) and patient-reported end points ( daytime asthma symptoms , " as-needed " beta-agonist use , nocturnal awakenings ) ( P<.001 compared with placebo ) . Montelukast provided near-maximal effect in these end points within the first day of treatment . Tolerance and rebound worsening of asthma did not occur . Montelukast improved outcome end points , including asthma exacerbations , asthma control days ( P<.001 compared with placebo ) , and decreased peripheral blood eosinophil counts ( P<.001 compared with placebo ) . The incidence of adverse events and discontinuations from therapy were similar in the montelukast and placebo groups . CONCLUSIONS Montelukast , compared with placebo , significantly improved asthma control during a 12-week treatment period . Montelukast was generally well tolerated , with an adverse event profile comparable with that of placebo STUDY OBJECTIVES To evaluate the effectiveness and safety of inhaled salmeterol in patients managed in nonspecialist practice setting s. DESIGN A r and omized , double-blind , 6-month , parallel-group study involving 253 centers . SETTING Primarily nonspecialist practice s ( n = 232 ) . PATIENTS A total of 911 subjects ( 417 men ; 494 women ) who met American Thoracic Society asthma criteria were enrolled and r and omized to treatment with either twice-daily salmeterol aerosol ( 50 microg ; n = 455 ) or matching placebo twice daily ( n = 456 ) . Both groups were allowed to take salbutamol as needed . All subjects were previously treated with anti-inflammatory maintenance therapy that was continued throughout the study . MEASUREMENTS AND RESULTS The primary outcome variable was the proportion of subjects with serious asthma exacerbations defined as an exacerbation requiring hospitalization , emergency department visit , or use of prednisone during the treatment period . A total of 712 subjects competed the study . There was no significant difference in the proportion of subjects experiencing serious exacerbations between the salmeterol and placebo groups ( 20.8 % vs 20.9 % , respectively ; p = 0.935 ; power > 88 % ) . Peak expiratory flow was significantly higher in the salmeterol group ( 398 L/min vs 386 L/min for placebo ; p < 0.01 ) . Median daily use of salbutamol was two inhalations for the salmeterol group and three inhalations for placebo ( p < 0.001 ) . The proportion of subjects sleeping through the night was significantly higher in the salmeterol group ( 74 % ) as compared to placebo ( 68 % ; p = 0.028 ) . CONCLUSIONS Salmeterol treatment is effective in subjects typically cared for in the primary -care setting and does not increase the frequency of severe exacerbations UNLABELLED Bronchial asthma is defined as " a chronic inflammatory disease of the airways involving many cells " and inhaled corticosteroids have therefore become the fundamental drugs for the long-term management of the disease . In moderate and severe persistent asthma the use of a long-acting bronchodilator is recommended in order to control symptoms and to enhance the efficacy of corticosteroids . Although not based on scientific evidence , it has been assumed that the , 2 adrenergic and the inhaled steroid should be administered in a strict inhalation sequence : the bronchodilatator first and then the steroid . The aim of the study was to assess the effects of this assumption experimentally , common indeed since long ago . MATERIAL S AND METHODS Twelve subjects with moderate-persistent asthma ( 7 males , aged 18 - 64 , basal FEV1 = 65.59 % pred . + /- 7.59 ds ; reversibility = + 14.8 % + /- 8.3 ds from baseline after Salbutamol 200 mg ) , symptomatic despite the regular home treatment with Fluticasone p. 250 mg bid and beta 2 short-acting prn for over 6 weeks , were initially treated with combined SM/FP 50/250 mg bid from an unique Diskus " device , for 6 weeks . After this initial phase , the treatment continued according to a r and omised , double-blind , cross-over design : all subjects received the same drugs , from two different Diskus " inhalers , and according to two different sequences of administration : 1 ) SM first and FP 20 ' later for 4 weeks , and then FP first and SM 20 ' later for a further 4 weeks ; 2 ) vice versa . No wash-out period was included between these two phases of cross-over treatment . FEV1 ( % pred . ) ; morning PEF ( L/min ) , the use of short-acting beta 2 as required ( n/week ) ; the number of awakenings at night ( n/week ) , and the daytime asthma symptom score were measured . STATISTICS The t paired test and anova ( Duncan test ) were used for statistical comparisons : a p<0.05 was accepted as the minimum level of significance . RESULTS After the first six weeks of treatment with combined Salmeterol/Fluticasone , 50/250 mg FEV1 changed from 69.6 % pred . + /- 7.59 ds to 79.8 % pred . + /- 10.1 ds ( p>0.005 ) , whilst the morning PEF changed from 282.2 l/min : 64.1 ds to 333.4 l/min + /- 55.5 ds ( p<0.02 ) . Furthermore , the consumption of beta 2 adrenergic prn dropped from 4.4 ( no./week ) + /- 7.3 ds to 1.2 + /- 0.9 ds ( p<0.001 ) ; the number of night-time awakenings decreased from 1.6 ( no./week ) + /- 0.2 ds to 0.2 + /- 0.3 ds ( p<0.001 ) , and the daytime symptom score changed from 3.4 + /- ds 0.8 to 1.9 + /- 0.7 ds ( p<0.001 ) . This therapeutic performance was maintained over the two subsequent 4-week periods of treatment from two distinct devices independently of the inhalation sequence . In particular , by both using salmeterol first or using fluticasone first , the therapeutic effects proved quite identical : FEV1 : 80.7 % pred . + /- 9.5 ds and 80.3 + /- 7.4 ds ; morning PEF : 336.5 l/min + /- 55.4 ds and 338.6 l/min + /- 67.1 ds ; consumption of beta 2 adrenergic as required : 0.9 ( no./week ) + /- 0.6 ds and 0.9 ( no./week ) + /- 0.8 ds ; number of awakenings : 0.3 ( no./week ) + /- 0.3 and 0.2 ( no./week ) + /- 0.3 ds ; day-time/night-time symptom score : 1.7 + /- 0.5 ds and 1.8 + /- 0.6 ds , respectively ( anova = ns ) . CONCLUSIONS Both in terms of lung function and of clinical outcomes the efficacy of SM and FP administration proved completely independent of the particular sequence for their separate inhalation and quite superimposable to thatachieved b y their combined inhalation from an unique device Most previously reported individuals with acetylsalicylic acid ( aspirin , ASA)-induced asthma have been adults . This study was undertaken to define the prevalence of ASA intolerance among children with intractable asthma . Fifty children ( 34 boys and 16 girls ) ranging in age from 6 to 18 years with extrinsic ( atopic ) asthma were studied . None had a history of ASA sensitivity or nasal polyps ; all required continuous medication including cromolyn sodium and daily or intermittent steroids . Anti-asthmatic medications were stopped 12 hours prior to testing . At the same time of day , each subject , in a doubleblind manner , on two separate days , ingested either 300 mg of ASA or 100 mg of lactose ( placebo ) . Measurements of FVC , FEV1 , and FEF25 - 75 were obtained prior to challenge and one half , one , two , three , and four hours after . ASA intolerance required a decrease of 30 % in lung function with ASA as compared to placebo . Fourteen of 50 ( 28 % ) were ASA-intolerant ; a greater number were girls , and they had more sinusitis and an onset of disease prior to 2 years of age . Steroid dependency , frequency of eczema , nasal eosinophilia , serum IgE levels , and peripheral eosinophil counts did not differ between the two groups . The use of aspirin in childhood asthma should be limited BACKGROUND Treatment guidelines recommend the regular use of inhaled corticosteroids for patients with mild persistent asthma . We investigated whether the symptom-driven use of a combination of beclomethasone dipropionate and albuterol ( also known as salbutamol ) in a single inhaler would be as effective as the regular use of inhaled beclomethasone and superior to the as-needed use of inhaled albuterol . METHODS We conducted a 6-month , double-blind , double-dummy , r and omized , parallel-group trial . After a 4-week run-in , patients with mild asthma were r and omly assigned to receive one of four inhaled treatments : placebo twice daily plus 250 microg of beclomethasone and 100 microg of albuterol in a single inhaler as needed ( as-needed combination therapy ) ; placebo twice daily plus 100 microg of albuterol as needed ( as-needed albuterol therapy ) ; 250 microg of beclomethasone twice daily and 100 microg of albuterol as needed ( regular beclomethasone therapy ) ; or 250 microg of beclomethasone and 100 microg of albuterol in a single inhaler twice daily plus 100 microg of albuterol as needed ( regular combination therapy ) . The primary outcome was the morning peak expiratory flow rate . RESULTS In 455 patients with mild asthma who had a forced expiratory volume in 1 second of 2.96 liters ( 88.36 % of the predicted value ) , the morning peak expiratory flow rate during the last 2 weeks of the 6-month treatment was higher ( P=0.04 ) and the number of exacerbations during the 6-month treatment was lower ( P=0.002 ) in the as-needed combination therapy group than in the as-needed albuterol therapy group , but the values in the as-needed combination therapy group were not significantly different from those in the groups receiving regular beclomethasone therapy or regular combination therapy . The cumulative dose of inhaled beclomethasone  was lower in the as-needed combination therapy group than in the groups receiving regular beclomethasone therapy or regular combination therapy ( P<0.001 for both comparisons ) . CONCLUSIONS In patients with mild asthma , the symptom-driven use of inhaled beclomethasone ( 250 microg ) and albuterol ( 100 microg ) in a single inhaler is as effective as regular use of inhaled beclomethasone ( 250 microg twice daily ) and is associated with a lower 6-month cumulative dose of the inhaled corticosteroid . ( Clinical Trials.gov number , NCT00382889 [ Clinical Trials.gov ] . ) Fifty-two asthmatic patients with mild to moderate hypertension were screened for bronchosensitivity to propranolol in a double-blind r and omized fashion after a 2-week minimum placebo run-in period . Thirty-five patients qualified on the basis of a decrease in 1-second forced expiratory volume FEV1 by greater than or equal to 20 % after 80 mg of propranolol with no more than a + /- 15 % change after placebo .  Of these patients , 18 were then r and omly assigned to antihypertensive treatment with labetalol at doses that were increased at weekly intervals ( 100 , 200 , 400 , 600 mg BID ) and 17 , with hydrochlorothiazide ( HCTZ ) ( 25 or 50 mg BID ) as needed for control of hypertension . At each placebo washout visit and at each of the four active drug-treatment phase visits , spirometric measurements were obtained just prior to the morning dose of medication and again 2 hours later on the initial visit ( i.e. , following the initial dose of active treatment ) and on each visit when the dosage was increased . Neither HCTZ nor labetalol ( average daily doses at the end of the study were 88 and 555 mg , respectively ) caused bronchoconstriction : Mean FEV1 did not change from the baseline neither prior to the morning dose ( evaluation of the " chronic " treatment effect ) nor 2 hours after dosing ( evaluation of " acute " treatment effect ) . Three patients in each treatment group reported increased dyspnea and two on labetalol and one on HCTZ had increased wheezing ; the mean weekly isoproterenol usage per patients was similar for the two treatments ( 1.3 times/week/pt for labetalol and 1.6 times/week/pt for HCTZ ) . ( ABSTRACT TRUNCATED AT 250 WORDS In 1990 , the total cost of asthma in the United States was estimated to be more than $ 6 billion per year , of which some $ 1.1 billion , or almost 20 % , was spent on drug therapy [ 1 ] . Moreover , the overall cost of drugs for the treatment of asthma is expected to increase substantially as a result of a greater emphasis on expensive anti-inflammatory agents , such as inhaled corticosteroids and cromolyn [ 2 - 4 ] , and the introduction of new drugs , such as long-acting -agonists . It is hoped , however , that the higher initial costs will be offset by the reduction in morbidity and absence from work that may result from the use of these newer , more effective medications . The effect of a new drug on relevant and costly outcomes now needs to be shown during the introduction of that drug . As of 1992 , no studies of the economic effectiveness of either existing or new drugs for the treatment of asthma had been done [ 5 ] . Recently , studies assessing the effect of inhaled corticosteroids in patients with asthma and chronic obstructive pulmonary disease have shown that the higher initial costs of these drugs may be offset by the savings generated by reduced use of health care [ 6 , 7 ] . Leukotriene receptor antagonists , a new generation of asthma medications , are being developed because they interfere with the action of leukotrienes . Leukotrienes are implicated in bronchoconstriction and the formation of airway edema , which result from the inflammatory process in patients with asthma . Several leukotriene receptor antagonists are currently at different stages of development and testing [ 8 ] . Zafirlukast ( ICI-204 , 219 , or ACCOLATE [ Zeneca Pharmaceuticals , Wilmington , Delaware ] ) is one such compound ; it acts through selective leukotriene receptor antagonism . It has been shown to block both early and late asthmatic responses to inhaled allergens [ 9 ] . In phase II dose-ranging studies , it was found to decrease the use of concurrent asthma medication , improve FEV1 and the morning peak expiratory flow rate , and decrease the incidence of asthma symptoms [ 10 ] . The effect of zafirlukast on clinical and economic outcomes has yet to be examined . We studied the clinical and economic effectiveness of zafirlukast among patients with mild-to-moderate asthma who were receiving only -agonists as needed ( the need was frequent ) and who therefore might have obtained benefit from additional regular medication . We focus particularly on clinical effectiveness outcomes ( such as symptoms , limitation of activity , and sleep disturbance ) and economic effectiveness outcomes ( such as health care use , the need for other medications , and absence from work or school ) . Methods The data for this effectiveness study originated from a large , r and omized , double-blind , multicenter trial design ed to assess the efficacy of zafirlukast in 762 patients with mild-to-moderate asthma who were followed for 13 weeks [ 11 ] . Of the 63 centers participating in that trial , 28 agreed to collect the additional outcome data needed for our study . Of the 335 patients from those 28 centers , 150 agreed to participate ; these 150 patients are the subject of our analysis . Clinical Protocol The trial from which this study arose was design ed to compare zafirlukast plus as-needed -agonist therapy with placebo plus as-needed -agonist therapy in patients with mild-to-moderate asthma who needed additional treatment but would not have been unduly put at risk if such treatment were to be delayed for 3 months . After an initial 1-week observation period ( visits 1 and 2 ) and a 7- to 14-day placebo run-in period ( visit 3 ) , the patients were r and omly assigned in a 2 to 1 ratio to receive either zafirlukast and -agonists ( albuterol from a metered-dose inhaler , 100 g per inhalation ) or placebo and -agonists . Patients were then followed every 2 weeks for visits 4 and 5 and every 3 weeks thereafter ( visits 6 through 8) , for a total of 13 weeks . The initial 1-week period was devoted to observation , screening , eligibility testing , and instruction about question naires and the general structure of the trial . The run-in period , during which both groups received placebo , was used to assess final eligibility criteria and compliance with study procedures . After r and omization , patients received zafirlukast , 20 mg , or placebo orally in a double-blind manner twice daily . With the exception of -agonists , no concurrent medications for asthma were permitted . Patients were eligible for the study if they were 12 years of age or older , had not smoked cigarettes in the previous 6 months , had a smoking history of less than 10 pack-years , and had an FEV1 at least 55 % of the predicted value . They had to 1 ) have a 15 % or greater improvement in FEV1 after inhalation of a bronchodilator within the previous 6 months or 2 ) show bronchial hyperresponsiveness ( a decrease in FEV1 20 % at an inhaled concentration 8.0 mg/mL of histamine or methacholine ) . Patients also had to be symptomatic ( defined as a 7-day asthma symptom score 8) during the run-in period . The asthma symptom score was the sum over 7 days of an overall assessment of asthma symptoms , which were rated daily by the patient as 0 = none , 1 = mild ( no interference with activities ) , 2 = moderate ( interference with some activities ) , or 3 = severe ( interference with many activities ) . The occurrence of more than one visit to an emergency department , one hospitalization for asthma , or the worsening of asthma necessitating therapy with agents other than -agonists result ed in the termination of follow-up for treatment failure . Follow-up was also terminated for severe adverse reactions , development of concurrent severe disease unrelated to asthma , voluntary withdrawal , and noncompliance with study procedures . Information on pulmonary function , daytime symptoms ( classified as none , mild , moderate , or severe ) , nighttime awakenings , symptoms on arising , the occurrence and duration of adverse events , the use of other medications ( type and duration ) , and the use of -agonist inhalers ( number of puffs per day ) was collected daily using patient report forms . Physical and physiologic data were obtained at each visit . Outcomes Sub protocol We obtained data through an extended patient report form , which was given to each participant for the purpose of collecting daily information on major clinical and economic effectiveness outcomes , such as activity limitation due to asthma ; absence from work or school due to asthma ; and additional clinic visits , hospital visits , and contacts with health care personnel outside of the scheduled protocol structure . All procedures done and medications given outside of the trial structure were also described on the form . Data on quality of life were obtained but are not presented here ; they will be combined with data from an ongoing study of patient preferences in a separate quality -of-life and costutility analysis . Clinical and Economic Effectiveness Outcomes Days without symptoms , days without limitation of activity , days without use of -agonists , days without sleep disturbance , and days without episodes of asthma were selected as measures of clinical effectiveness because they were simple and clinical ly relevant . We obtained information on the daily occurrence of asthma symptoms , asthma-related limitation of activity , use of -agonists , and sleep disturbance due to asthma directly from the daily patient report forms to compute the number of days per month that were free of each outcome . A composite outcome variable , episode-free days , was defined as the number of days without an asthma attack ( severe symptoms ) , without the use of -agonists , without sleep disturbance due to asthma , and without an adverse event [ 12 ] . The economic effectiveness outcomes included the use of health services and re sources as well as the extent of absenteeism . Only the health services that varied between arms of the trial were considered ; thus , the protocol -driven re sources incurred by each patient ( which were theoretically equal between the arms of the trial ) were ignored . These re sources were the frequency of unscheduled health care visits and contacts , the total number of -agonist inhalers used , and the number of prescriptions for all nonasthma medications consumed . Absenteeism was quantified as the number of days of absence from work or school due to asthma . Statistical Analysis Measures were computed across patient-days . Patient-days for which data were missing during follow-up were not directly included in the calculations , but estimates derived from nonmissing data were extrapolated to the totality of all follow-up days for a given patient . This was done by imputing the average for the days that were not missing data to the days that were missing data . For all outcome variables , the individual approach to data analysis was used , with the patient as the unit of analysis . For the clinical effectiveness outcomes , for which the patient either had or did not have a clinical event reported daily , the measure was based on the proportion of relevant days ( for example , days without symptoms ) of all of the patient 's follow-up days of treatment . These were st and ardized into mean days per month by multiplying by 30 . For these clinical effectiveness measures , multiple linear regression was used to estimate the mean differences between the two groups and to assess the statistical significance of those differences [ 13 ] . These estimates were adjusted for baseline differences and for baseline values of the effectiveness measures to increase precision . In addition , a generalized linear regression model with a logarithmic link was used for these outcomes to estimate the percentage change for each mean outcome [ 14 ] . For the economic effectiveness outcomes , which were based on infrequent events , a Poisson regression model with a logarithmic link and with variances adjusted for between-subject overdispersion by the deviance was used to estimate the percentage change in the outcome rate between groups [ 14 ] . To i BACKGROUND Many patients with asthma require an inhaled long-acting beta(2)-agonist ( LABA ) in addition to an inhaled corticosteroid to adequately control their disease . OBJECTIVE The purpose of this study was to assess the long-term tolerability of a salmeterol xinafoate/ fluticasone propionate ( SFC ) hydrofluoroalkane metered-dose inhaler ( MDI ) at 3 different doses BID . METHODS This 52-week , open-label , stratified , parallel-group study assessed SFC in patients with persistent asthma . Patients , aged > or = 12 years , with a diagnosis of asthma for > or = 6 months , and a percent predicted forced expiratory volume in 1 second ( FEV(1 ) ) or peak expiratory flow ( PEF ) between 40 % and 90 % were enrolled between January 1999 and June 1999 . The last patient completed the 12-month study in June 2000 . Patients were allowed to continue their current asthma treatment during run-in , with the exception that short-acting beta(2)-agonists ( SABAs ) , LABAs , and oral bronchodilators were not to be used 6 , 12 , and 24 hours , respectively , prior to the r and omization visit . During the open-label r and omized treatment period , patients were instructed to discontinue all other asthma medications with the exception of the albuterol MDI to use on an as-needed basis . Patients were assigned to treatment based on their existing asthma regimen : SABA monotherapy or LABA with or without fluticasone propionate ( FP ) < 250 microg/d or equivalent ( group 1 ) ; FP 250 to 500 microg/d or equivalent with or without LABA ( group 2 ) ; and FP > 500 to 1000 microg/d or equivalent with or without LABA ( group 3 ) . Patients administered 2 inhalations BID of SFC hydrofluoroalkane at doses of 25/50 microg/actuation ( group 1 ) , 25/125 microg/actuation ( group 2 ) , or 25/250 pg/actuation ( group 3 ) . The primary end point was tolerability as assessed by adverse events ( AEs ) . AEs were determined via diary cards and investigator inquiry at visits . Serious AEs were defined as death , any life-threatening event , hospitalization , disability , congenital anomaly in the patient 's offspring , or other important medical events judged by the investigator to be serious . Other outcomes included clinical laboratory tests ( hematology , chemistry , electrolytes ) , 24-hour urinary-free cortisol excretion , 12-lead  electrocardiograms , oropharyngeal examinations , vital signs , clinic visit lung function tests ( FEV(1 ) and PEF ) , daily diary card entries of morning PEF , and rescue medication usage . RESULTS Of the 372 patients assessed for eligibility , 325 from 22 centers across Canada were enrolled and r and omized to treatment . Group 1 consisted of 98 patients ( 55 % women ; 86 % white ; mean age , 37 years ; mean [ SD ] weight , 79 [ 20 ] kg ) . Group 2 consisted of 109 patients ( 46 % women ; 94 % white ; mean age , 44 years ; mean [ SD ] weight , 80 [ 17 ] kg ) . Group 3 consisted of 118 patients ( 47 % women ; 90 % white ; mean age , 45 years ; mean [ SD ] weight , 80 [ 18 ] kg ) . A total of 15 adolescents ( aged 12 - 17 years ) comprised 11 % , 2 % , and 2 % of groups 1 , 2 , and 3 , respectively . Treatments were well tolerated , and 274 ( 84 % ) of the 325 patients enrolled completed the study . Upper respiratory tract infection was the most common AE reported : 52 % , 37 % , and 49 % of patients in groups 1 , 2 , and 3 , respectively . Twenty ( 6 % ) patients withdrew because of an AE , with worsening asthma being the most frequent reason ( n = 9 ) . None of the serious AEs ( 11 [ 3 % ] ) were considered drug related by the investigators . Improvements in FEV(1 ) and PEF and re- duction in symptomatic albuterol use occurred during the first 4 weeks and were maintained in all groups throughout the 52-week study . CONCLUSIONS BID doses of SFC hydrofluoroalkane 50/100 pg , 50/250 pg , and 50/500 pg administered via MDI for 52 weeks were well tolerated in this population of adolescents and adults with persistent asthma Asthma is associated with an increase in airway blood flow ( Qaw ) , presumably as a manifestation of airway inflammation . We therefore determined the effect of the antiinflammatory agents montelukast ( ML ) and fluticasone propionate ( FP ) on Qaw in 12 patients with mild intermittent asthma . Using a double-blind approach , Qaw along with FEV(1 ) and Vmax(50 ) were determined before and after a 2-week treatment period with either ML ( 10 mg/day ) , FP ( 440 microg/day ) , or 10 mg of ML plus 440 microg of FP daily , separated by 2-week washout periods . Mean ( + /- SEM ) Qaw ranged from 68 + /- 4.2 to 71.8 + /- 5.9 microl x minute(-1 ) x ml(-1 ) anatomic dead space before the treatment periods . ML , FP , and ML plus FP decreased mean Qaw by 21.5 , 20.8 , and 26.9 % , respectively ( p < 0.05 for all ) . No significant difference was observed among the three regimens . FEV(1 ) and Vmax(50 ) were not changed by any of the treatments . We conclude that at the dosages used , ML and FP are equipotent in reducing Qaw in patients with mild asthma , and that the magnitude of the response is not greater if the two drugs are combined . The results also suggest that the vascular effects of these agents can be assessed independent of their effects on airway function OBJECTIVE To evaluate the effect of salmeterol on asthma-specific quality of life in patients experiencing significant nocturnal symptoms . DESIGN R and omized , double-blind , placebo-controlled , multicenter clinical trial . SETTING Allergy/respiratory care clinics . PATIENTS Nonsmokers > or = 12 years of age with nocturnal asthma symptoms on at least 6 of 14 days during screening and > or = 15 % decrease in peak expiratory flow ( PEF ) from baseline on nocturnal awakening at least once during screening . INTERVENTIONS Salmeterol , 42 microg , or placebo twice daily . Patients were allowed to continue theophylline , inhaled corticosteroids , and " as-needed " albuterol . MEASUREMENTS AND RESULTS Outcome measures included Asthma Quality of Life Question naire ( AQLQ ) global and individual domain scores , FEV1 , PEF , nighttime awakenings , asthma symptoms , and supplemental albuterol use . Mean change from baseline for the global and domain AQLQ scores was significantly greater ( p < or = 0.005 ) with salmeterol compared with placebo . At week 12 , salmeterol significantly ( p < 0.001 compared with placebo ) increased mean change from baseline in FEV1 , morning and evening PEF , percentage of symptom-free days , percentage of nights with no awakenings due to asthma , and the percentage of days and nights with no supplemental albuterol use . Significant improvements in PEF were observed after treatment with salmeterol regardless of concomitant treatment with theophylline ( p < 0.05 ) . CONCLUSIONS These results provide evidence that vali date s the role of salmeterol in improving quality of life in patients with moderate persistent asthma who exhibited nocturnal asthma symptoms and supports the efficacy of salmeterol compared with that of placebo ( ie , " as-needed " albuterol ) AIM The simplification of the management of asthma in the different clinical phases of this common chronic inflammatory disorder is the main goal of therapy . Pycnogenol ® , a st and ardized extract of French maritime pine bark , inhibits expression of 5-lipoxygenase and consequently decreases leukotriene levels in asthmatic patients .  Pycnogenol ® anti-inflammatory activities may be supportive when taken in addition to inhalation corticosteroid ( ICS ) , putatively allowing for a reduction in dosage and frequency of ICS administration . METHODS This study evaluated the efficacy of Pycnogenol ® during a period of six months for improving allergic ( mite in house dust ) asthma management in patients with stable , controlled conditions .  Pycnogenol ® was used at a daily dosage of 100 mg , distributed as 50 mg in the morning at 9 am and again in the evening at 9 pm ) . An individual patient 's asthma condition was grade d in five steps based on the daily dosage of inhaled fluticasone propionate with step 1 indicating 0 µg and step 5 the maximum dose of 500 µg ICS twice daily . RESULTS A total 76 patients were enrolled for this study . The group taking Pycnogenol ® in addition to ICS and the group taking only ICS were comparable for age , gender and clinical characteristics including FEV1 . The analysis of therapeutic ranking steps showed that 55 % of patients taking Pycnogenol ® improved as judged by passing to a lower ICS dose step . In comparison , only 6 % of patients depending exclusively on ICS progressed to a lower ( ICS dose ) therapeutic step . No deterioration ( passage to a higher ICS therapeutic step ) was observed in the Pycnogenol ® group , whereas in 18.8 % of patients depending exclusively on corticosteroids a deterioration requiring a higher dosage step was observed . The passage to different therapeutic steps was statistical significant between groups ( P<0.05 ) . Drop-outs were associated entirely to irregularities in follow-up and not due to medical reasons . No serious adverse events were observed in both groups and tolerability of Pycnogenol ® was very good . The levels of asthma control in the 6 interventional months as compared to the same period in the previous year were compared . In the Pycnogenol ®  group , night-awakenings were less frequent , the number of days with PEF<80 % were decreased , days with asthma score > 1 were lower , requirement for salbutamol and additional asthma medication less frequent , and consultation of general practitioner and specialist required less commonly . All these parameters were statistical significantly improved in Pycnogenol ® + ICS group versus the ICS control group where no considerable changes were observed . Various common signs and symptoms were evaluated by visual analog scale , ( dry ) cough , severity of chest symptoms , wheezing , dyspnea and daytime symptoms . In the ICS-only group values did not improve while they did improve significantly in the ICS + Pycnogenol ® group ( P<0.05 vs. ICS only group ) . A decrease by 15.2 % of the specific IgE titer was found in the Pycnogenol ® + ICS group , whereas the titer increased by 13.4 % in the ICS-only group , while IgG1 and IgG4 remained unchanged in both groups . CONCLUSION Pycnogenol ® administration was effective for better control of signs and symptoms of allergic asthma and reduced the need for medication This r and omised , double-blind , double-dummy , cross-over study was conducted at 29 general practitioners ' offices . Ninety-two patients with stable asthma were r and omised to treatment with either Salmeterol 50 micrograms ( b.i.d . ) or Salbutamol 400 micrograms ( q.i.d . ) . After four weeks treatment the patients continued another four weeks with the alternative treatment . During the study period the patients were allowed to use Salbutamol on a prn . basis . Inhaled steroids , if any , were continued . On diary cards patients recorded peak expiratory flow rate ( PEFR ) morning and evening before medication , asthma symptomscore , and use of additional doses of prn . beta 2-agonist . After the end of the last treatment period patients were asked which period they had preferred . Judged from all effect parameters , Salmeterol gave a better asthma control than Salbutamol . All improvements -except evening peak-flow and daily use of prn . salbutamol -were statistically significant . Most patients preferred Salmeterol treatment . Finally , the effect of Salmeterol was independent of any concurrent inhaled steroid treatment The present study examined the bronchodilator and safety profiles of single-dose indacaterol in intermittent or persistent asthma . In the present double-blind crossover study , 42 patients were r and omised to receive single doses of indacaterol ( 50 , 100 , 200 and 400 µg ) or placebo via a hydrofluoroalkane pressurised metered-dose inhaler . The primary efficacy comparisons were the per cent changes in forced expiratory volume in one second ( FEV1 ) between indacaterol and placebo 30 min and 21 h post-dose . All doses result ed in prolonged bronchodilation , with indacaterol 200 and 400 µg meeting pre-specified efficacy criteria . The mean percentage increases in FEV1 from placebo with indacaterol 200 and 400 µg were 7.6 and 14.9 % , respectively , at 30 min , and 7.5 and 10.4 % , respectively , at 21 h post-dose . At these doses , changes in mean FEV1 relative to placebo were statistically significant from 5 min to 25 h , inclusive . At 5 min , the geometric least squares mean values for FEV1 were 3.08 and 3.22 L for the 200 and 400 µg doses , respectively , compared with 2.99 L for placebo . At 24 h after dosing , the baseline-adjusted geometric least square mean FEV1 was 3.13 , 3.11 , 3.24 and 3.30 L for indacaterol 50 , 100 , 200 and 400 µg , respectively , and 2.98 L for placebo . All treatments were well tolerated . Once-daily indacaterol at doses of 200 and 400 µg provided sustained 24-h bronchodilation , with a rapid onset and a good tolerability and safety profile CONTEXT No consensus exists for adjusting inhaled corticosteroid therapy in patients with asthma . Approaches include adjustment at outpatient visits guided by physician assessment of asthma control ( symptoms , rescue therapy , pulmonary function ) , based on exhaled nitric oxide , or on a day-to-day basis guided by symptoms . OBJECTIVE To determine if adjustment of inhaled corticosteroid therapy based on exhaled nitric oxide or day-to-day symptoms is superior to guideline -informed , physician assessment -based adjustment in preventing treatment failure in adults with mild to moderate asthma . DESIGN , SETTING , AND PARTICIPANTS A r and omized , parallel , 3-group , placebo-controlled , multiply-blinded trial of 342 adults with mild to moderate asthma controlled by low-dose inhaled corticosteroid therapy  ( n = 114 assigned to physician assessment -based adjustment [ 101 completed ] , n = 115 to biomarker-based [ exhaled nitric oxide ] adjustment [ 92 completed ] , and n = 113 to symptom-based adjustment [ 97 completed ] ) , the Best Adjustment Strategy for Asthma in the Long Term ( BASALT ) trial was conducted by the Asthma Clinical Research Network at 10 academic medical centers in the United States for 9 months between June 2007 and July 2010 . INTERVENTIONS For physician assessment -based adjustment and biomarker-based ( exhaled nitric oxide ) adjustment , the dose of inhaled corticosteroids was adjusted every 6 weeks ; for symptom-based adjustment , inhaled corticosteroids were taken with each albuterol rescue use . MAIN OUTCOME MEASURE The primary outcome was time to treatment failure . RESULTS There were no significant differences in time to treatment failure . The 9-month Kaplan-Meier failure rates were 22 % ( 97.5 % CI , 14%-33 % ; 24 events ) for physician assessment -based adjustment , 20 % ( 97.5 % CI , 13%-30 % ; 21 events ) for biomarker-based adjustment , and 15 % ( 97.5 % CI , 9%-25 % ; 16 events ) for symptom-based adjustment . The hazard ratio for physician assessment -based adjustment vs biomarker-based adjustment was 1.2 ( 97.5 % CI , 0.6 - 2.3 ) . The hazard ratio for physician assessment -based adjustment vs symptom-based adjustment was 1.6 ( 97.5 % CI , 0.8 - 3.3 ) . CONCLUSION Among adults with mild to moderate persistent asthma controlled with low-dose inhaled corticosteroid therapy , the use of either biomarker-based or symptom-based adjustment of inhaled corticosteroids was not superior to physician assessment -based adjustment of inhaled corticosteroids in time to treatment failure . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00495157 Educational self-management programs for children with asthma have now become a routine feature in the management of the disease , as international guidelines underline . We design ed this trial to find out whether Aironet , an educational program developed for children with asthma , influenced asthma severity and improved parents ' knowledge of the disease . In a multicenter , prospect i ve , r and omized controlled trial we enrolled 123 children , 72 boys , mean age 8.78 yr ( + /-2.33 s.d . ) , with intermittent or mild persistent asthma . Participants were r and omly assigned to an education group , who received Aironet at baseline and 2 months later ( 60 children ) , or to a control group who did not ( 63 children ) . Follow-up lasted 12 months and included out-patient clinic visits and spirometry at 2 , 4 and 12 months . At baseline and at 12 months follow-up , parents were question ed about their knowledge of asthma , and their children 's asthmatic attacks , use of systemic corticosteroids , family physician or hospital emergency room visits , hospitalizations and asthma-related school absences . Question naire replies at 12-month follow-up reported significantly fewer asthma attacks in patients who received the program than in those who did not ( 1.65 + /- 1.21 vs. 2.34 + /- 1.73 ; p < 0.05 ) . For the subgroup of children who had > or =3 asthma attacks at baseline , parents ' knowledge improved significantly more in the educational group than in the control group . The out-patient educational program Aironet reduces the number of asthma attacks in children with intermittent or mild persistent asthma and improves knowledge of the disease Current guidelines for asthma treatment do not recommend daily maintenance therapy in patients with mild intermittent ( step 1 ) asthma . However , because there is increasing evidence that airway inflammation is present even in this patient group , maintenance anti-inflammatory therapy may be considered . We investigated the clinical impact of regular treatment with the inhaled corticosteroid beclomethasone dipropionate and the leukotriene receptor antagonist pranlukast in the patients concerned . The study was a r and omized , controlled , parallel-group , multicenter trial . Eighty-five symptomatic patients with newly diagnosed mild intermittent asthma having normal pulmonary function were assigned beclomethasone or pranlukast for 8 weeks . Then , these medications were stopped for the next 16 weeks . Main outcome measures were asthma symptoms , pulmonary function , and airway inflammation . Treatment with beclomethasone and pranlukast significantly increased forced expiratory volume in 1 second and peak expiratory flow from baseline and decreased asthma symptom scores and sputum eosinophil counts and eosinophil cationic protein contents . After discontinuation of the treatment , symptom scores remained unchanged , but pulmonary function and airway inflammation were aggravated and then returned to the baseline levels . Therefore , maintenance therapy with inhaled corticosteroid or leukotriene receptor antagonist can provide further improvements in asthma symptoms , pulmonary function , and airway inflammation , and discontinuation of the therapy causes worsening of asthma , indicating that stopping or interrupting anti-inflammatory therapy may not be advisable in patients with symptomatic mild intermittent asthma
BACKGROUND Daily inhaled corticosteroids ( ICS ) are the recommended mainstay of treatment in children and adults with persistent asthma .
However , often , ICS are used intermittently by patients or recommended by physicians to be used only at the onset of exacerbations .
OBJECTIVES The aim of this review was to compare the efficacy and safety of intermittent versus daily ICS in the management of children and adults with persistent asthma and preschool-aged children suspected of persistent asthma .