Effectiveness of montelukast versus budesonide on quality of life and bronchial reactivity in subjects with mild-persistent asthma. [Effectiveness and safety of montelukast versus budesonide at various doses on bronchial reactivity in subjects with mild persistent asthma]. Deterioration in asthma control when subjects receiving fluticasone propionate/salmeterol 100/50 mcg Diskus are "stepped-down". A randomized, double-blind trial of the effect of glucocorticoid, antileukotriene and beta-agonist treatment on IL-10 serum levels in children with asthma. Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial. [Effect of triamcinolone acetonide, montelukast, nedocromil sodium and formoterol on eosinophil blood counts, ECP serum levels and clinical progression of asthma in children]. Montelukast vs. inhaled low-dose budesonide as monotherapy in the treatment of mild persistent asthma: a randomized double blind controlled trial. Effects of pranlukast, a leukotriene receptor antagonist, on airway inflammation in mild asthmatics. Low-dose inhaled fluticasone propionate versus oral zafirlukast in the treatment of persistent asthma. The effect of montelukast on eosinophil apoptosis: induced sputum findings of patients with mild persistent asthma. Comparative efficacy and anti-inflammatory profile of once-daily therapy with leukotriene antagonist or low-dose inhaled corticosteroid in patients with mild persistent asthma. Daily versus as-needed corticosteroids for mild persistent asthma. Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma. Effect of montelukast compared with inhaled fluticasone on airway inflammation. Zafirlukast versus budesonide on bronchial reactivity in subjects with mild-persistent asthma. Comparison of montelukast and budesonide on bronchial reactivity in subjects with mild-moderate persistent asthma. Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma. Short-term and long-term asthma control in patients with mild persistent asthma receiving montelukast or fluticasone: a randomized controlled trial. The effect of montelukast and different doses of budesonide on IgE serum levels and clinical parameters in children with newly diagnosed asthma. Comparative effect of triamcinolone, nedocromil and montelukast on asthma control in children: A randomized pragmatic study. A randomized, double-blind trial of the effect of anti-asthma treatment on lung function in children with asthma. Effects of different anti-asthmatic agents on induced sputum and eosinophil cationic protein in mild asthmatics. Comparative efficacy and safety of low-dose fluticasone propionate and montelukast in children with persistent asthma. Randomized comparison of strategies for reducing treatment in mild persistent asthma. Efficacy and safety of low-dose fluticasone propionate compared with zafirlukast in patients with persistent asthma. Montelukast, compared with fluticasone, for control of asthma among 6- to 14-year-old patients with mild asthma: the MOSAIC study. Fluticasone propionate compared with zafirlukast in controlling persistent asthma: a randomized double-blind, placebo-controlled trial. Effect of budesonide and montelukast in asthmatic children exposed to relevant allergens. Montelukast added to inhaled beclomethasone in treatment of asthma. Montelukast/Beclomethasone Additivity Group. Roles of angiopoietin-1 and angiopoietin-2 on airway microvascular permeability in asthmatic patients. Fluticasone or montelukast for preschool children with asthma-like symptoms: Randomized controlled trial. Distribution of therapeutic response in asthma control between oral montelukast and inhaled beclomethasone. A comparison of short-term treatment with inhaled fluticasone propionate and zafirlukast for patients with persistent asthma. Montelukast versus fluticasone: effects on lung function, airway responsiveness and inflammation in moderate asthma. Traditional and patient-centred outcomes with three classes of asthma medication. Low-dose fluticasone propionate compared with montelukast for first-line treatment of persistent asthma: a randomized clinical trial. Steroid naive eosinophilic asthma: anti-inflammatory effects of fluticasone and montelukast. Effects of montelukast and beclomethasone on airway function and asthma control. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclomethasone Study Group. Comparative efficacy of once-daily therapy with inhaled corticosteroid, leukotriene antagonist or sustained-release theophylline in patients with mild persistent asthma. Comparative study of budesonide inhalation suspension and montelukast in young children with mild persistent asthma. Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. Predicting short term response to anti-inflammatory therapy in young children with asthma. Role of regular treatment with inhaled corticosteroid or leukotriene receptor antagonist in mild intermittent asthma. Oral montelukast versus inhaled beclomethasone in 6- to 11-year-old children with asthma: results of an open-label extension study evaluating long-term safety, satisfaction, and adherence with therapy. Fluticasone propionate versus zafirlukast: effect in patients previously receiving inhaled corticosteroid therapy. Effect of different antiasthmatic treatments on exercise-induced bronchoconstriction in children with asthma. A randomized study comparing the effect of loratadine added to montelukast with montelukast, loratadine, and beclomethasone monotherapies in patients with chronic asthma.
Insufficient data exist to evaluate the comparative effects of inhaled corticosteroids (ICS) versus leukotriene receptor antagonist (LTRA) on airway inflammation and quality of life (QoL). The aim of the study was to compare the effectiveness of montelukast compared to budesonide at different doses on QoL and bronchial reactivity in mild-asthmatic adult patients. 45 subjects with bronchial asthma were randomly assigned to a different treatment and divided in 3 treatment groups: A: 400 mg of budesonide twice a day; B: 10 mg of montelukast daily; C: 10 mg of montelukast daily plus 400 mg of budesonide twice a day. At the beginning of the study and at the end of the treatment period (16 weeks) all patients underwent complete clinical evaluation, pulmonary function testing and methacholine challenge test (MCHt). In group A the increase from baseline was 153.4&amp;#x0025;, in group C was 133.2&amp;#x0025;, and in group B 247.7&amp;#x0025;, the latter increase being statistically significant compared to that in the other 2 groups (p&amp;#x003C; 0.005 Wilcoxon test). In all domains the improvement in quality of life in the group treated with montelukast (group B) was significantly greater than that in the group treated with both medications (group C): in particular, the improvement was consistent in the symptoms (p&amp;#x003C; 0.01) and emotions (p&amp;#x003C; 0.01) domains, and weaker in the physical activity (p&amp;#x003C; 0.05). A similar difference was observed between group B and A, but only in the symptoms (p&amp;#x003C;0.01), emotions (p&amp;#x003C;0.01), and environmental stimuli domains (p&amp;#x003C;0.05). The personal perception of their own disease is important for a correct therapeutic management of asthma. In order to optimize the treatment, a complete adherence of the patient to the treatment itself is required, to be achieved through simplification of therapeutic schedule and easy administration of medications. Montelukast may be considered a valid alternative in the treatment of mild-persistent asthma, both for the clinical and functional benefits and for the great advantage of the once-daily dosage, which consistently improves the compliance with the chronic treatment of the disease. Insufficient data exist to evaluate the comparative effects of inhaled corticosteroids versus leukotriene receptor antagonists on airway inflammation and remodelling. The aim of the study was to evaluate the effectiveness and safety of montelukast versus budesonide at different doses on bronchial reactivity in mild-asthmatic adult patients.
                A total of 40 patients were randomly assigned to a different treatment and divided in 2 treatment groups (A, B) as follows: A-10 mg of montelukast daily; B-400 mg of budesonide twice a day.
                We studied 40 subjects (21 males, 19 females) divided in two groups of 20 subjects each: group A with mean age 25.16 +/- 7.68 years, group B with mean age 26.18 +/- 6.15 years. After 16 weeks of treatment in the group A the PC20 (provocative concentration of methacholine which cause a fall of FEV1 > or = 20%) was 620.12 +/- 140.54 micrograms/mL significantly highly compared to basal value of 315.75 +/- 100.16 micrograms/mL (p < 0.02). In the group B the PC20 was 795.67 +/- 312.76 micrograms/mL significantly highly compared to basal value of 342.87 +/- 132.38 micrograms/mL (p < 0.001). We not found differences in FEV1, FVC e PEF before and after the treatment.
                Montelukast may be considered a valid alternative in the treatment of mild-persistent asthma, both for the benefits on bronchial reactivity and for the great advantage of the once-daily dosage, which consistently improves the compliance with the chronic treatment of the disease. In this study, 647 subjects stable on fluticasone propionate/salmeterol Diskus 100/50 mcg BID (FSC) were randomized to continue FSC 100/50 mcg BID or "step down" to either fluticasone propionate (FP) 100 mcg BID, salmeterol (SAL) 50 mcg BID, or montelukast (MON) 10 mg once daily for 16 weeks. Overall asthma control significantly improved in the FSC group; whereas, "stepping down" to FP, SAL, or MON resulted in deterioration in asthma control, as determined by decreased measures of lung function and clinical features. This study provides support that treatment of both inflammation and smooth muscle dysfunction may be necessary to achieve and maintain asthma control in patients uncontrolled on ICS. Levels of an immunoregulatory and anti-inflammatory cytokine IL-10 are reduced in asthmatic airways, potentially contributing to more intense inflammation. Triamcinolone has anti-inflammatory properties and the anti-inflammatory effects of montelukast and formoterol have been discussed.
                The purpose of this study was to define the effect of treatment with triamcinolone, montelukast and formoterol on the serum level of IL-10, eosinophil blood counts, eosinophil cationic response (ECP) and clinical parameters (symptom score, FEV1 and PC20H) in children with moderate asthma.
                An 8-week, placebo-controlled and randomized, double-blind trial was carried out. The subjects were 91 children with moderate atopic asthma who were allergic to dust mite. Patients were randomly allocated to receive 400 microg triamcinolone (n = 19), 5 or 10 mg (according to age) montelukast (n = 18), 24 microg formoterol (n = 18) or placebo (n = 36).
                Seventy-nine children completed the study. After treatment with triamcinolone and montelukast the level of IL-10 in blood serum significantly increased, eosinophil blood counts and ECP levels significantly decreased and all clinical parameters improved; treatment with formoterol had no effect on IL-10 level, eosinophil blood counts in serum and bronchial hyper-reactivity; ECP level significantly decreased after treatment and asthma symptoms and FEV1 improved significantly. Mean IL-10 levels in serum before and after treatment with triamcinolone were 7.23 pg/mL with 95% CI, 6.74 -7.72% and 14.24 pg/mL with 95% CI, 11.6-16.88%, respectively (P < 0.001); with montelukast they were 6.59 pg/mL with 95% CI, 6.26-7.23% and 10.94 pg/mL with 95% CI, 8.24-12.65%, respectively (P < 0.002); with formoterol they were 7.06 pg/mL with 95% CI, 6.61-7.52% and 7.04 pg/mL with 95% CI, 6.15-7.93%. We found statistically significant correlations between serum level of IL-10 and serum level of ECP after treatment with triamcinolone and montelukast.
                This study demonstrates that one possible way by which triamcinolone and montelukast contribute to inhibition of inflammation is by increasing IL-10 levels. More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children.
                The Pediatric Asthma Controller Trial (PACT) compared the effectiveness of 3 regimens in achieving asthma control.
                A total of 285 children (ages 6-14 years) with mild-moderate persistent asthma on the basis of symptoms, and with FEV(1) >or= 80% predicted and methacholine FEV(1) PC(20) <or= 12.5 mg/mL, were randomized to 1 of 3 double-blind 48-week treatments: fluticasone 100 microg twice daily (fluticasone monotherapy), fluticasone 100 microg/salmeterol 50 microg in the morning and salmeterol 50 mug in the evening (PACT combination), and montelukast 5 mg in the evening. Outcomes included asthma control days (primary outcome), exacerbations, humanistic measurements, and pulmonary function measurements.
                Fluticasone monotherapy and PACT combination were comparable in many patient-measured outcomes, including percent of asthma control days, but fluticasone monotherapy was superior for clinic-measured FEV(1)/forced vital capacity (P = .015), maximum bronchodilator response (P = .009), exhaled nitric oxide (P < .001), and PC(20) (P < .001). Fluticasone monotherapy was superior to montelukast for asthma control days (64.2% vs 52.5%; P = .004) and for all other control outcomes. Growth over 48 weeks was not statistically different (fluticasone, 5.3 cm; PACT combination, 5.3 cm; montelukast, 5.7 cm).
                Both fluticasone monotherapy and PACT combination achieved greater improvements in asthma control days than montelukast. However, fluticasone monotherapy was superior to PACT combination in achieving other dimensions of asthma control. Growth was similar in all groups.
                Therefore, of the regimens tested, the PACT study findings favor fluticasone monotherapy in treating children with mild-moderate persistent asthma with FEV(1) >or= 80% predicted, confirming current guideline recommendations. Eosinophil-mediated damage to the respiratory epithelium is a major pathogenetic mechanism in asthma. Glucocorticoids have confirmed antiinflammatory properties and effect of formoterol, montelukast and nedocromil on markers of inflammation has been studied. Eosinophil blood counts and eosinophil cation protein (ECP) serum level are often use as markers of clinical monitoring of the disease activity. To evaluate the effect of treatment on allergic inflammation, we measured eosinophil blood counts and ECP serum level, and clinical parameters before and after 4 weeks treatment with triamcinolon, montelukast, nedocromil, formoterol. It was 8 week, placebo-controlled and randomized, double blind trial of 154 children with moderate atopic asthma. Patients were randomly allocated to receive 400 mg triamcinolon (n = 28), 5 or 10 mg (according to age) montelukast (n = 27), 16 mg nedocromil (n = 26), 24 micrograms formoterol (n = 28) or placebo (n = 45). 140 children completed the study. After treatment with triamcinolon and montelukast eosinophil blood counts significantly decreased, after treatment with triamcinolon, montelukast and nedocromil ECP serum level significantly decreased; all clinical parameters improved after treatment with each drug; treatment with triamcinolon had the strongest effect on most parameters (except of FEV1). Mean eosinophil blood counts before and after treatment with triamcinolon were 277.4 and 187.2 cells/mm3 respectively (p < 0.001); with montelukast were 279.6 and 250.7 cells/mm3 respectively (p = 0.002); with nedocromil were 181.7 and 170.1 cells/mm3 respectively (p < 0.183); with formoterol were 276.4 and 264.1 cells/mm3 respectively (p = 0.2). Mean ECP serum levels before and after treatment with triamcinolon were 94.3 and 63.5 micrograms/l respectively (p < 0.001); with montelukast were 85.1 micrograms/l and 71.2 micrograms/l respectively (p < 0.001); with nedocromil were 92.6 and 80.1 micrograms/l respectively (p < 0.001); with formoterol were 95.9 micrograms/l and 87.8 micrograms/l (p = 0.05). We found significant correlation between ECP and hyperresponsiveness after treatment with triamcinolon, montelukast. This study shows that triamcinolon, montelukast contribute to inhibition of allergic inflammation by decreasing eosinophil blood counts and ECP. The serum level of ECP seems to be a good clinical marker of monitoring the disease. Guidelines recommend daily controller therapy for mild persistent asthma. Montelukast has demonstrated consistent benefit in controlling symptoms of asthma and may be an alternative, orally administered, nonsteroidal agent for treating mild asthma. Aim: To determine whether montelukast is as effective as budesonide in controlling mild persistent asthma as determined by FEV(1).
                Between November 2003 to October 2005, participants aged 5-15 years with recently diagnosed mild persistent asthma (n = 62) were randomized to oral montelukast (5 mg daily) [N(1) = 30] or inhaled budesonide (400 microg per day in two doses) [N(2) = 32] in a single center, double-blind study.
                Baseline demographic and spirometric parameters were comparable. The median (95% confidence interval) percentage predicted FEV(1) was similar in the two groups after 12 weeks of treatment (budesonide: 76.70 (67.96-90.53%), montelukast: 75 (67.40-88.47)%; p = 0.44). There was similar improvement in spirometric parameters and clinical symptom scores in both the groups. There was no statistically significant difference between the groups in the need for rescue drugs as well as side effects reported by parents.
                Montelukast is as effective as inhaled budesonide in the treatment of mild persistent asthma in children aged 5-15 years. Montelukast may be used as an alternative to low dose inhaled corticosteroids for management of mild persistent asthma. To determine the anti-inflammatory actions of pranlukast, a cysteinyl leuklotriene receptor antagonist, we measured exhaled nitric oxide (NO) concentrations and eosinophil ratio in induced sputum of three groups of mild asthmatics (n = 30): treated with bronchodilators alone, with bronchodilators and inhaled steroid (beclomethasone dipropionate; 400 microg/day), and bronchodilators and pranlukast (450 mg/day). Pranlukast (450 mg/day) reduced the eosinophil ratio in the induced sputum significantly (p < 0.01) without a major effect on the concentration of exhaled NO. Pranlukast also increased values of peak expiratory flow significantly (p < 0.05). Pranlukast may be useful for mild asthmatics, in part through its ability to suppress eosinophilic airway infiltration. Few studies have compared the efficacy of inhaled corticosteroids and leukotriene modifiers for the treatment of persistent asthma.
                Our purpose was to compare the efficacy of a low dose of inhaled fluticasone propionate (FP) with that of oral zafirlukast in the treatment of persistent asthma previously treated with short-acting beta(2)-agonists alone.
                A 12-week, randomized, double-blind, double-dummy, multicenter study was conducted in 451 patients aged 12 years and older with asthma who were symptomatic on short-acting beta(2)-agonists alone. After an 8- to 14-day run-in period, patients were randomized to treatment with FP 88 microg twice daily or zafirlukast 20 mg twice daily.
                Treatment with FP was more effective than treatment with zafirlukast in increasing morning FEV(1) (by 0.42 L vs 0.20 L over baseline, P <.001), morning peak expiratory flow (by 49.94 L/min vs 11.68 L/min over baseline, P <. 001), and evening PEF (by 38.91 L/min vs 10.50 L/min over baseline, P <.001). Statistically significant differences between the two treatments in FEV(1) were noted after the first observation (week 4) and in morning and evening peak expiratory flow by week 2. Mean change in percentage of symptom-free days was greater with FP than with zafirlukast (28.5% of days vs 15.6% of days, P <.001) and FP significantly increased the percentage of rescue-free days by 40.4% of days compared with 24.2% of days with zafirlukast (P <.001). Treatment with FP significantly reduced albuterol use by 2.39 puffs per day compared with 1.45 puffs per day (P <.001) and increased the percentage of nights with no awakenings by 21.2% of nights compared with 8.0% of nights with zafirlukast (P <.001).
                The clinical effectiveness of a low dose of FP as first-line therapy in patients with persistent asthma who are symptomatic on beta(2)-agonists alone is superior to that of zafirlukast. Apoptosis may be important in limiting airway eosinophilia. Treatment with leukotriene antagonists decreases the number of eosinophils in both peripheral blood and sputum.
                To assess the effect of montelukast on eosinophil apoptosis in a group of patients with mild persistent asthma (MPA) and to compare this effect with the apoptotic effect of fluticasone propionate (FP).
                Randomly selected patients with MPA (n = 22) who had not taken anti-inflammatory therapy within the preceding 12 months were included in the study. The sputum induction procedure was performed and the patients were divided into two groups: group 1 (n = 10) received FP 250 microg/day and group 2 (n = 22) received montelukast 10 mg/day orally for 4 weeks. Sputum induction was repeated after the treatment period. The resulting cytospin slides were stained by Wright's stain and morphologic changes in apoptotic eosinophils were assessed by the use of light microscopy by two blinded expert pathologists. Serum soluble Fas ligand (sFasL) concentrations were measured by an ELISA method at baseline and after treatment in both groups, as well as in a group of healthy subjects.
                In within-group comparisons, the apoptotic ratio (AR) increased at the end of the study period in group 1 (p = 0.05). In the group treated with FP the ratio of sputum eosinophils significantly decreased (p = 0.02), and the AR significantly increased (p < 0.005). No differences were found in the two study groups in serum sFasL levels at the end of the treatment period compared with baseline values (p > 0.05).
                Our findings demonstrate that 4 weeks' treatment with a CysLT receptor antagonist (montelukast) resulted in an increase in eosinophil apoptosis comparable to that produced by FP, suggesting that induction of apoptosis may be a potential mechanism for the mode of action of CysLT receptor antagonists in asthma. Current guidelines advocate the use of preventative anti-inflammatory therapy for mild persistent asthma.
                We compared the efficacy and anti-inflammatory profiles of a leukotriene receptor antagonist and a low dose of inhaled corticosteroid in patients with mild persistent asthma.
                Twenty-one adult patients with mild asthma received 4 weeks of either once-daily inhaled hydrofluoroalkane triamcinolone acetonide (450 microg/day ex-actuator dose) or oral montelukast (10 mg/day) in a randomized, placebo-controlled, single-blinded crossover study. Measurements were made before and after 2 and 4 weeks of each treatment.
                At the endpoint (after 4 weeks), triamcinolone and montelukast had improved the primary outcome (provocative dose of methacholine required to produce a 20% fall in FEV(1)) in comparison with placebo (P <.05), there being no difference between the treatments (1.09-fold; 95% CI 0.73 to 1.63). Triamcinolone was better than placebo or montelukast for effects on all other surrogate inflammatory markers (P <.05), including exhaled nitric oxide, blood eosinophils, serum eosinophil cationic protein, plasma intracellular circulating adhesion molecule 1, and plasma E-selectin. Both treatments improved (P <.05) morning and evening peak flow, nighttime beta2-agonist use, and symptoms in comparison with placebo, though triamcinolone was better than montelukast (P <.05) with regard to peak flow. Triamcinolone produced suppression (P <.05) of overnight urinary cortisol/creatinine and serum osteocalcin.
                Once-daily inhaled corticosteroid and leukotriene antagonist improved the primary outcome variable of bronchial hyperresponsiveness to a similar degree. 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.
                In a double-blind trial, 225 adults underwent randomization. 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.
                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.
                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.
                Copyright 2005 Massachusetts Medical Society. One-quarter to one-third of individuals with asthma smoke, which may affect response to therapy and contribute to poor asthma control.
                To determine if the response to an inhaled corticosteroid or a leukotriene receptor antagonist is attenuated in individuals with asthma who smoke.
                In a multicenter, placebo-controlled, double-blind, double-dummy, crossover trial, 44 nonsmokers and 39 light smokers with mild asthma were assigned randomly to treatment twice daily with inhaled beclomethasone and once daily with oral montelukast.
                Primary outcome was change in prebronchodilator FEV(1) in smokers versus nonsmokers. Secondary outcomes included peak flow, PC(20) methacholine, symptoms, quality of life, and markers of airway inflammation. Despite similar FEV(1), bronchodilator response, and sensitivity to methacholine at baseline, subjects with asthma who smoked had significantly more symptoms, worse quality of life, and lower daily peak flow than nonsmokers. Adherence to therapy did not differ significantly between smokers and nonsmokers, or between treatment arms. Beclomethasone significantly reduced sputum eosinophils and eosinophil cationic protein (ECP) in both smokers and nonsmokers, but increased FEV(1) (170 ml, p = 0.0003) only in nonsmokers. Montelukast significantly increased a.m. peak flow in smokers (12.6 L/min, p = 0.002), but not in nonsmokers.
                In subjects with mild asthma who smoke, the response to inhaled corticosteroids is attenuated, suggesting that adjustments to standard therapy may be required to attain asthma control. The greater improvement seen in some outcomes in smokers treated with montelukast suggests that leukotrienes may be important in this setting. Larger prospective studies are required to determine whether leukotriene modifiers can be recommended for managing asthma in patients who smoke. Inhaled corticosteroids are currently regarded as the gold standard in anti-inflammatory therapy, however, leukotriene receptor antagonists have been ascribed anti-inflammatory properties.
                We directly compared the anti-inflammatory effects of inhaled fluticasone propionate (FP, 100 microg Diskus, twice daily) and oral montelukast (MON 10 mg, nocte) in bronchial biopsies of patients with asthma in a double-blind, double-dummy, parallel-group design.
                Bronchial biopsies, serum and urine samples were collected from 36 atopic asthmatics before and after 8 weeks of treatment. Activated T cells (CD25+), eosinophils (MBP+) and mast cells (tryptase+) were analysed by immunohistochemistry. Serum eosinophil cationic protein (ECP) and IL-5 were analysed by radio and enzyme immunoassay (EIA), respectively. Urinary 9alpha-11beta-PGF2 and leukotriene E4 (LTE4) were measured by EIA.
                A comparison of changes from baseline [FP/MON ratio (95% confidence interval)] of activated T cells was not different when subjects were treated with FP compared to treatment with MON [1.00 (0.18-4.86); P=0.924]. Following treatment, mast cells in the FP group were significantly lower than in the group treated with MON [0.39 (0.16-0.97); P=0.041]. There was no difference in the number of eosinophils in the lamina propria following either treatment [0.54 (0.05-2.57); P=0.263]. However, treatment with FP resulted in a significantly greater decrease in serum ECP, compared to treatment with MON [0.37 (0.25-0.71); P=0.002].
                FP appears to be superior to MON as an anti-inflammatory therapy in mild asthmatics. Asthma is one of the most common chronic diseases in children and adults. Recent studies have shown that in asthmatic patients treated with inhaled corticosteroids there is a better diseases control when adding a second drug, than increasing the corticosteroids dose. The aim of this study has been to evaluate the effectiveness and tolerance of zafirlukast, a leukotriene receptor antagonist, versus budesonide in clinically steady patients with mild persistent bronchial asthma. We have enrolled 36 subjects non smokers, with mild persistent bronchial asthma and 12 healthy subjects as control group. At the beginning of this study and at the end of the treatment (8 weeks), all patients underwent complete clinical work-up, pulmonary function testing (FEV1, PEF and FVC) and methacholine challenge test. The patients were divided into 3 groups: group A) 20 mg of zafirlukast twice a day; group B) 400 mg of budesonide twice a day; group C) 20 mg of zafirlukast twice a day and 400 mg of budesonide twice a day. Basal FEV1 and PEF presented no significant statistical differences between control subjects and patients of group A, B and C. After eight weeks there were no significant changes for FEV1 and PEF among the three groups. After therapy a strong significant increase of PD20 was documented in group A (p&#x003C;0.005), group B (p&#x003C;0.001) and group C (p&#x003C;0.005), respect to baseline values. The antileukotriene drugs could be taken as an alternative drug, or in association with low-dose inhaled corticosteroids, in patients with mild persistent asthma, both for their clinical effectiveness and their easy ingestion, which is confirmed in compliance studies on inhaled steroids. We studied 51 atopic non-smoking subjects who were divided to four treatments groups: (A) montelukast 10mg daily, (B) budesonide 400 microg twice a day (bid), (C) montelukast 10 mg daily plus budesonide 400 microg bid and (D) budesonide 800 microg bid. Bronchial responsiveness was assessed before and after 12 weeks of treatment. The bronchial responsiveness, evaluated by means of PC(20) values, showed a strong significant increase in groups B, C and D, and a weak but significant rise in group A, when compared to basal data. Regarding other pulmonary parameters (FEV(1), PEF) there were no significant differences among the groups after 12 weeks of therapy. A statistical significance was founded after therapy between group A and C (p < 0.05), but not between the group B and D treated with only budesonide at different doses. No significant differences was observed in the side effect pattern among the various treatments. The study data demonstrated that administration of montelukast provided an important and additional effect on bronchial hyperresponsiveness. Oral administration represents a significant advantage over the majority of other anti-asthmatic drugs. Our results confirm the anti-inflammatory properties of both the inhaled corticosteroid (ICS) and montelukast and the possible role of these drugs can have on airway remodelling. While currently low dose ICS remains the reference drug as a controller in mild-moderate persistent asthma, montelukast may be viewed as a possible option, either in monotherapy or in association.
                Copyright 2003 Elsevier Science Ltd. Outcome data are needed to base recommendations for controller asthma medication use in school-aged children.
                We sought to determine intraindividual and interindividual response profiles and predictors of response to an inhaled corticosteroid (ICS) and a leukotriene receptor antagonist (LTRA).
                An ICS, fluticasone propionate (100 mug twice daily), and an LTRA, montelukast (5-10 mg nightly, age dependent), were administered to children ages 6 to 17 years with mild-to-moderate persistent asthma using only as-needed bronchodilators in a multicenter, double-masked, 2-sequence, 16-week crossover trial. Clinical, pulmonary, and inflammatory responses to these controllers were evaluated.
                Improvements in most clinical asthma control measures occurred with both controllers. However, clinical outcomes (asthma control days [ACDs], the validated Asthma Control Questionnaire, and albuterol use), pulmonary responses (FEV(1)/forced vital capacity, peak expiratory flow variability, morning peak expiratory flow, and measures of impedance), and inflammatory biomarkers (exhaled nitric oxide [eNO]) improved significantly more with fluticasone than with montelukast treatment. eNO was both a predictor of ACDs (P = .011) and a response indicator (P = .003) in discriminating the difference in ACD response between fluticasone and montelukast.
                The more favorable clinical, pulmonary, and inflammatory responses to an ICS than to an LTRA provide pediatric-based group evidence to support ICSs as the preferred first-line therapy for mild-to-moderate persistent asthma in children. eNO, as a predictor of response, might help to identify individual children not receiving controller medication who achieve a greater improvement in ACDs with an ICS compared with an LTRA. To determine whether montelukast is as effective as fluticasone in controlling mild persistent asthma as determined by rescue-free days.
                Participants aged 15 to 85 years with mild persistent asthma (n = 400) were randomized to oral montelukast (10 mg once nightly) or inhaled fluticasone (88 mug twice daily) in a year-long, parallel-group, multicenter study with a 12-week, double-blind period, followed by a 36-week, open-label period.
                The mean percentage of rescue-free days was similar between treatments after 12 weeks (fluticasone: 74.9%, montelukast: 73.1%; difference = 1.8%, 95% confidence interval [CI]: -3.2% to 6.8%) but not during the open-label period (fluticasone: 77.3%, montelukast: 71.1%; difference = 6.2%, 95% CI: 0.8% to 11.7%). Although both fluticasone and montelukast significantly improved symptoms, quality of life, and symptom-free days during both treatment periods, greater improvements occurred with fluticasone in lung function during both periods and in asthma control during open-label treatment. Post hoc analyses revealed a difference in rescue-free days favoring fluticasone in participants in the quartiles for lowest lung function and greatest albuterol use at baseline.
                In patients with mild persistent asthma, rescue-free days and most asthma control measures improved similarly with fluticasone or montelukast over the short term, but with prolonged open-label treatment, asthma control improved more with fluticasone. Improved asthma control with fluticasone appeared to occur in those with decreased lung function and greater albuterol use at baseline. In the remaining patients, the two treatments appeared to be comparable. These results suggest that classification criteria for mild persistent asthma may need to be re-evaluated. Since IgE is considered to play a crucial role in allergic immune responses, the reduction of free IgE level has been an attractive target in the treatment of allergic diseases. The present study was conducted to determine the effects of a 6-month treatment with different doses of inhaled budesonide and montelukast sodium in children with newly diagnosed atopic asthma.
                In this randomized, double-blind, double-dummy trial, 51 children with newly diagnosed asthma and sensitivity to house-dust mites were randomly allocated to receive budesonide (in two different doses 400 or 800 mcg) or montelukast for 6 months. The primary end point was the level of serum total and specific IgE before and after treatment. The secondary end points were clinical parameters and forced expiratory volume in 1s (FEV1).
                After 6 months of treatment, a high dose of inhaled corticosteroid and montelukast, significantly decreased levels of total and specific IgE. Medium dose of inhaled corticosteroid had no effect on total and specific IgE serum level. Clinical score and FEV1 significantly improved after 6 months of treatment with medium (P = 0.002) and high dose (P = 0.001) of inhaled budesonide and montelukast (P = 0.002). There were no differences between groups in changes of all clinical parameters after treatment.
                Only high doses of inhaled corticosteroids and montelukast decreased the serum IgE levels. Perhaps long-term treatment with montelukast will be beneficial to asthma patients by decreasing IgE levels. Asthma severity can be judged by measurements of symptoms, lung function, and medication requirements. The objective was to compare the effect of a 4-wk monotherapy with low-dose triamcinolone, montelukast and nedocromil on asthma control, lung function, eosinophil blood count, and bronchial hyper-reactivity in children with mild to moderate asthma allergic to dust mite. Two hundred fifty-six children, aged 6-18 yr, with mild to moderate asthma, participated in an 8-wk study. This was a three-arm, randomized no blinding or placebo pragmatic trial comparing the effect of triamcinolone acetonide (400 microg/day), inhaled nedocromil and montelukast sodium on clinical parameters of asthma [score, forced expiratory volume in 1 s (FEV(1))], PC20H, and eosinophil blood count. Two hundred forty-six children completed the study. After 4 wk of treatment with triamcinolone and montelukast, FEV(1) and PC20H significantly increased, and mean total symptoms score and mean number of eosinophil count in serum significantly decreased. Triamcinolone had a stronger effect on PC20H than montelukast. Nedocromil improved total asthma symptoms score and lung function. There was a reduction in the daytime and night-time symptom scores after treatment with all three drugs. Triamcinolone and montelukast had a stronger effect on asthma symptoms than nedocromil. There were statistically significant differences in reduction of nocturnal asthma symptoms between the triamcinolone and nedocromil groups (p < 0.001) and between montelukast and nedocromil (p = 0.001) groups, but not between the triamcinolone and montelukast groups. There was a reduction in beta-agonists use after treatment with all three drugs, with the strongest effect of triamcinolone. The study showed the strongest effect of low-dose inhaled steroids on clinical symptoms, lung function, bronchial hyper-reactivity and eosinophil blood count when compared to other asthma medications. Pulmonary function tests (PFTs) and especially spirometry measures are useful tools in evaluating early response to treatment of asthma in children mainly due to their worldwide availability. The aim of our study was to determine the effects of anti-asthma treatment in children, equally on FEV(1), FEF25-75%, R(int) and SR(aw) values.
                Children 6-18 years of age with moderate atopic asthma were randomized to 4-week, placebo-controlled, double-blind trial. Patients were randomly allocated to receive 200 microg budesonide (B) (n=29), 5 or 10 mg (according to age) montelukast (M) (n=29), 200 microg B + 5 or 10 mg M (n=29), 200 microg B + 9 microg formoterol (F) (n=29) or placebo (n=27). FEV(1,) FEF25-75%, R(int), SR(aw) were measured before and after treatment.
                R(int), SR(aw), FEV(1) improved significantly in all active treatment groups while FEF25-75% improved significantly only in BM group and M group. Combination therapy, showed significantly greater effects on R(int) than monotherapy: BM group compared to B group (P=0.01) and M group (P=0.03) and BF group compared to B group (P=0.01) and M group (P=0.04).
                This study shows that using single parameter for monitoring asthma can be misleading. Using combination of lung function techniques provides better assessment of treatment. Results of our study confirm this hypothesis. The best effect on large and small airways was achieved with combined anti-inflammatory therapy. Inhaled corticosteroids, leukotriene receptor antagonists, and theophylline are recommended for the treatment of mild persistent asthma. The aim of this study was to compare the changes in sputum total cell and eosinophil counts, and eosinophil cationic protein (ECP) levels in serum and sputum following treatment with leukotriene receptor antagonists, inhaled corticosteroids, and theophylline in patients with mild persistent asthma.
                Total cell counts, eosinophil percentage, and ECP levels in induced sputum and serum were determined both before and after treatment. Prior to sputum induction, FEV1 and PEF values and symptom scores were recorded at baseline and after 8 weeks of treatment. After baseline measurements, the asthmatic patients (n = 30) were randomized into three groups. A total of 10 patients were treated with zafirlukast, 20 mg bd, 10 with budesonide inhaler 200 microg bd, and 10 with theophylline 200 mg bd.
                There were significant decreases in sputum total cell counts and eosinophil percentage in all treatment groups. However, the decrease in sputum eosinophil counts was more significant in the corticosteroid-treated group. Although sputum ECP levels decreased significantly in the groups treated with zafirlukast and budesonide (zafirlukast group, 580-135 microg/L, P < 0.01; budesonide group, 683-268 microg/L, P < 0.01), the decrease was not statistically significant in the theophylline-treated group (498-361 microg/L, P > 0.05). In contrast, there were no significant changes in serum ECP levels in any of the treatment groups.
                All three treatments resulted in significant decreases in sputum total cell counts and eosinophil percentage, but the decrease in sputum ECP level was only seen in the groups treated with budesonide and zafirlukast. These results suggest that although all three treatments are considered as first-line treatments in most consensuses, theophylline seems to have less of an inhibitory effect on eosinophil activation. To evaluate efficacy, safety, health outcomes, and cost-effectiveness of fluticasone propionate (FP) versus montelukast (MON) in 342 children (6 to 12 years of age) with persistent asthma.
                Randomized, double-blind, 12-week study of treatment with FP inhalation powder 50 mug twice daily or MON chewable 5 mg once daily for 12 weeks.
                Compared with MON, FP significantly increased mean percent change from baseline FEV1 (forced expiratory volume in 1 second) (P=.002), morning PEF (peak expiratory flow) (P=.004), evening PEF (P=.020), and percent rescue-free days (P=.002) at end point, and it significantly reduced nighttime symptom scores (P <.001) and mean total (P=.018), and nighttime (P <.001) albuterol use. Withdrawals from the study were more frequent with MON (21%) than with FP (13%). Adverse events (69% vs 71%) and mean end point to baseline 12-hour urinary cortisol excretion ratios were similar. Parents and physicians were more satisfied with FP treatment than with MON (P=.006 and P=.016, respectively, at Week 12). Mean total daily asthma-related cost per patient in the FP group was approximately one-third of that in the MON group ($1.25 vs $3.49).
                FP was significantly more effective than MON in improving pulmonary function, asthma symptoms, and rescue albuterol use. Both therapies had similar safety profiles. Parent- and physician-reported satisfaction ratings were higher with FP treatment, and asthma-related costs were lower. Treatment guidelines recommend the use of inhaled corticosteroids in patients with asthma who have persistent symptoms and the "stepping down" of therapy to the minimum needed to maintain control of asthma. Whether patients with asthma that is well controlled with the use of inhaled corticosteroids twice daily can receive a step-down treatment with once-daily montelukast (our primary hypothesis) or once-daily fluticasone propionate plus salmeterol (our secondary hypothesis) has not yet been determined.
                We randomly assigned 500 patients with asthma that was well controlled by inhaled fluticasone (100 microg twice daily) to receive continued fluticasone (100 microg twice daily) (169 patients), montelukast (5 or 10 mg each night) (166 patients), or fluticasone (100 microg) plus salmeterol (50 microg) each night (165 patients). Treatment was administered for 16 weeks in a double-blind manner. The primary outcome was the time to treatment failure.
                Approximately 20% of patients assigned to receive continued fluticasone or switched to treatment with fluticasone plus salmeterol had treatment failure, as compared with 30.3% of subjects switched to montelukast. The hazard ratio for both comparisons was 1.6 (95% confidence interval, 1.1 to 2.6; P=0.03). The percentage of days on which patients were free of asthma symptoms (78.7 to 85.8%) was similar across the three groups.
                Patients with asthma that is well controlled with the use of twice-daily inhaled fluticasone can be switched to once-daily fluticasone plus salmeterol without increased rates of treatment failure. A switch to montelukast results in an increased rate of treatment failure and decreased asthma control; however, patients taking montelukast remained free of symptoms on 78.7% of treatment days. (ClinicalTrials.gov number, NCT00156819 [ClinicalTrials.gov].).
                Copyright 2007 Massachusetts Medical Society. To compare the efficacy and safety of fluticasone propionate and zafirlukast in patients with relatively stable persistent asthma who were previously treated with inhaled corticosteroids and short-acting beta(2)-agonists.A total of 440 patients (> or =12 years of age) previously treated with inhaled corticosteroids (beclomethasone dipropionate or triamcinolone acetonide) and short-acting beta(2)-agonists were included in this randomized double-blind study. After an 8-day run-in period, patients were treated with fluticasone (88 microg) or zafirlukast (20 mg) twice daily for 6 weeks. Outcome measures included pulmonary function (forced expiratory volume in 1 second [FEV(1)], peak expiratory flow [peak flow]), albuterol use, asthma symptoms, withdrawals due to lack of efficacy, and asthma exacerbations. Patients treated with fluticasone (n = 224) experienced greater mean increases in FEV(1) (0.24 L vs. 0.08 L, P <0.001), morning peak flow (30 L/min vs. 6 L/min, P <0.001), and evening peak flow (23 L/min vs. 5 L/min, P <0.001) during the study than did those treated with zafirlukast (n = 216). Fluticasone-treated patients had significantly greater increases in the mean percentages of symptom-free days (22% vs. 8%, P <0.001), rescue-free days (23% vs. 10%, P = 0.002), nights with uninterrupted sleep (<1% vs. -5%, P = 0.006), and fewer asthma exacerbations (1% vs. 6%, P = 0.005). Fewer fluticasone-treated patients were withdrawn due to lack of efficacy (2% vs. 13%, P <0.001).Inhaled fluticasone was more effective than zafirlukast in maintaining or improving asthma control in patients with relatively stable asthma who were switched from low-dose inhaled corticosteroids. Guidelines recommend daily controller therapy for mild persistent asthma. Montelukast has demonstrated consistent benefit in controlling symptoms of asthma and may be an alternative, orally administered, nonsteroidal agent for treating mild asthma.
                The Montelukast Study of Asthma in Children (MOSAIC study) was a 12-month, multicenter, randomized, double-blind, noninferiority trial to determine the effect of once-daily, orally administered montelukast (5 mg) (n = 495), compared with twice-daily, inhaled fluticasone (100 microg) (n = 499), on the percentage of asthma rescue-free days (RFDs) (any day without asthma rescue medication and with no asthma-related resource use). Patients 6 to 14 years of age had mild persistent asthma (average percentage of predicted forced expiratory volume in 1 second: 87.2%; RFDs at baseline: 64%). Montelukast would be considered not inferior to fluticasone if the upper limit of the 95% confidence interval for the difference in mean percentages of RFDs (fluticasone minus montelukast) was above -7% (a difference of approximately 2 days/month).
                The mean percentage of RFDs was 84.0% in the montelukast group and 86.7% in the fluticasone group. The least-squares mean difference was -2.8% (95% confidence interval: -4.7% to -0.9%), within the noninferiority limit of -7%. The proportion of patients requiring systemic corticosteroids and the number of patients with an asthma attack were greater in the montelukast group. Both montelukast and fluticasone were well tolerated.
                Montelukast was demonstrated to be not inferior to fluticasone in increasing the percentage of RFDs among 6- to 14-year-old patients with mild asthma. Secondary end points, including percentage of predicted forced expiratory volume in 1 second value, days with beta-receptor agonist use, and quality of life, improved in both groups but were significantly better in the fluticasone treatment group. The objective of our study was to compare the efficacy and safety of fluticasone propionate (an inhaled corticosteroid) with zafirlukast (a leukotriene modifier) for persistent asthma.
                In this randomized placebo-controlled, parallel-group, double-blind, double-dummy trial, patients underwent an 8- to 14-day run-in period followed by 12 weeks of treatment with inhaled fluticasone propionate (88 mg twice daily by metered-dose inhaler), oral zafirlukast (20 mg twice daily), or placebo.
                We included a total of 338 persistent asthma patients, 12 years of age or older, using short-acting b2-agonists alone.
                measured Efficacy outcomes included changes in pulmonary function, asthma symptoms, rescue albuterol use, nighttime awakenings due to asthma, and quality of life. Safety outcomes included asthma exacerbations, adverse events, and clinically significant laboratory test results.
                After 12 weeks of treatment, patients taking fluticasone propionate experienced significantly greater improvements in all clinical parameters (symptom scores, percentages of symptom-free and albuterol-free days, albuterol use, and nighttime awakenings) compared with patients taking zafirlukast (P <.05) or placebo (P <.05). Treatment with fluticasone propionate resulted in significantly greater improvements in pulmonary function compared with zafirlukast (P <.05) or placebo (P <.05). Fewer fluticasone propionate patients (4%) had an exacerbation requiring oral corticosteroids compared with those taking zafirlukast (12%) or placebo (10%).
                Inhaled fluticasone propionate is more effective than zafirlukast in controlling asthma symptoms, improving pulmonary function, and improving quality of life for patients who are symptomatic with the use of short-acting b2-agonists alone. Montelukast has been shown to be effective in controlling the increase in exhaled NO in asthmatic children re-exposed to house dust mite (HDM). This study compared the effect of low dose inhaled budesonide and oral montelukast in preventing the expected relapse of airway inflammation and reactivity in a group of 24 mild asthmatic children allergic to HDM after a brief period of exposure to relevant allergens.
                Lung function, bronchial hyperresponsiveness (BHR) to methacholine (PC(20)), fractional exhaled nitric oxide (FeNO) levels and sputum eosinophilia were evaluated.
                Pulmonary function remained stable. The BHR was unchanged after exposure in the group treated with budesonide, whereas a significant increase (P = 0.028) was observed in the patients receiving montelukast. No significant difference was observed in FeNO levels after exposure to mite antigen in the two groups. In both the groups of asthmatic children we observed a significant increase in sputum eosinophil % after the exposure to mite antigen.
                The significant increase in BHR level observed in the group of children receiving montelukast suggests a more comprehensive effect as disease controller by inhaled steroids than by leukotriene antagonist in allergic asthmatic children re-exposed to relevant allergens. The primary objective of this study was to determine whether montelukast, an oral leukotriene receptor antagonist, provides additional clinical benefit to the effect of inhaled corticosteroids. A total of 642 patients with chronic asthma (FEV(1) 50 to 85% of predicted value and at least a predefined level of asthma symptoms) incompletely controlled with inhaled beclomethasone, 200 microg twice daily using a spacer device, during the 4-wk run-in period were randomly allocated, in a double-blind, double-dummy manner to one of four treatment groups: (1) montelukast 10 mg plus continuing inhaled beclomethasone; (2) placebo tablet plus continuing inhaled beclomethasone; (3) montelukast 10 mg and inhaled placebo (after blind beclomethasone removal); and (4) placebo tablet and inhaled placebo (after blind beclomethasone removal). The primary endpoints were FEV(1) and daytime asthma symptoms score. Montelukast provided significant (p < 0.05) clinical benefit in addition to inhaled beclomethasone by improving FEV(1), daytime asthma symptom scores, and nocturnal awakenings. Blind removal of beclomethasone in the presence of placebo tablets caused worsening of asthma control, demonstrating that patients received clinical benefit from inhaled corticosteroids. Blind removal of beclomethasone in the presence of montelukast resulted in less asthma control but not to the level of the placebo group. All treatments were well tolerated; clinical and laboratory adverse experiences were generally similar to placebo treatment in this study. In conclusion, montelukast provided additional asthma control to patients benefitting from, but incompletely controlled on, inhaled beclomethasone. Vascular endothelial growth factor (VEGF) increases microvascular permeability. Recently, considerable attention has been devoted to the physiologic roles of angiopoietin-1 and angiopoietin-2 as regulatory factors of VEGF. This study was designed to examine the roles of angiopoietin-1 and angiopoietin-2 in controlling airway microvascular permeability in asthma.
                Levels of these angiogenic factors and airway vascular permeability index were examined in 30 asthmatics and 12 control subjects. After 2-week run-in period, all asthmatics were randomly assigned to receive fluticasone propionate (400 mug/d) or montelukast (10 mg) for 12 weeks.
                VEGF, angiopoietin-1, and angiopoietin-2 levels in induced sputum were significantly higher in asthmatics than in control subjects. We found an inverse correlation between angiopoietin-1 level and vascular permeability index in asthmatics, while there was a positive correlation between angiopoietin-2 level and that index. VEGF and angiopoietin-1 levels were significantly decreased after fluticasone therapy, while VEGF and angiopoietin-2 levels were significantly decreased after montelukast therapy. Although VEGF levels after treatment were different between two groups, vascular permeability index in the montelukast group was the same level as that in the fluticasone group. Moreover, improvement in vascular permeability index after fluticasone therapy was inversely correlated with decrease in angiopoietin-1 level, while that after montelukast therapy was positively correlated with decrease in angiopoietin-2 level.
                Angiopoietin-1 and angiopoietin-2 play complementary and coordinated roles in regulating microvascular permeability stimulated by VEGF in asthma. Combination of corticosteroids with leukotriene antagonists might effectively improve plasma leakage and provide a new strategy in treating bronchial asthma. Beneficial effects of anti-inflammatory therapy such as fluticasone propionate (FP) and montelukast (Mk) have been demonstrated in preschool children with asthma. However, comparative studies are lacking in this age group. Therefore, we conducted a study to evaluate and compare the effect of FP and Mk in preschool children with asthma-like symptoms.
                In this multicenter, randomized, placebo-controlled, double-blind, double-dummy trial, children aged 2-6 years with asthma-like symptoms were included. In total, 63 children were randomly allocated to receive FP (25), Mk (18) or placebo (20) for 3 months. The primary outcome was the daily symptom score (wheeze, cough, shortness of breath) as recorded by caregivers in a symptom diary card. Secondary endpoints were rescue medication free days, blood eosinophils and lung function (interrupter technique and forced oscillation technique (FOT)).
                During the 3 months study period, symptoms improved in all 3 groups, with a statistically significant difference between FP and placebo in favor of the FP group (p=0.021). A significant reduction in circulating eosinophils after 3 months of treatment was found in the Mk group only (p=0.008), which was significantly different from the change found in the placebo group (p=0.045). With the exception of frequency dependence (measured by FOT), which showed a difference between FP and Mk after 3 months of treatment in favor of the FP group (p=0.048), no differences in lung function within or between groups were found.
                In spite of a lack of power, our results suggest that FP has a beneficial effect on symptoms and Mk on blood eosinophil level as compared to placebo. Except for a difference in one lung function parameter after 3 months between FP and Mk in favor of the FP group, this study revealed no differences between FP and Mk. The distribution of responses in study populations provides a novel method of comparing the benefit of two treatments. This 6-week, randomised, placebo-controlled, double-blind study compared the effectiveness of oral montelukast with inhaled beclomethasone in chronic asthma by assessing the distribution and overlap of patient responses to therapy, as measured by a clinical outcome (asthma control days). A total of 730 adult patients with asthma, age 15-65 yrs, with a forced expiratory volume in one second (FEV1) at baseline of 50-85% of predicted and > or = 15% improvement in FEV1 after inhaled beta-agonist were enrolled. After a 2-week placebo run-in period, patients were randomly allocated to receive montelukast (10 mg once daily), inhaled beclomethasone (200 microg twice daily) or placebo. The primary end-point (per cent of asthma control days) was compared between treatments as the overlap in the response distributions. The overlap of the distribution of responses between the montelukast and beclomethasone groups was 89% for per cent asthma control days and 96% for change from baseline in FEV1. The mean (+/-SD) per cent asthma control days in the montelukast and beclomethasone groups was significantly higher than that in the placebo group (placebo 40.0+/-35.8, montelukast 50.7+/-37.1, beclomethasone 57.9+/-36.1). The mean differences between montelukast and placebo, beclomethasone and placebo, and montelukast and beclomethasone were significant. The mean per cent change (+/-SD) from baseline in FEV1 was 12.1+/-18.7 and 13.9+/-20.8 in the montelukast and beclomethasone groups, respectively, and significantly greater than that in the placebo group (6.4+/-20.1); there was no significant difference between the montelukast and beclomethasone groups in mean values or response distribution. There was also no difference among treatment groups in the frequency of adverse experiences. A comparison of the response distribution is an important approach to comparing therapies; montelukast and beclomethasone provided similar response distributions for the end-point of per cent asthma control days over a 6-week treatment period. To compare the short-term efficacy and safety of low-dose fluticasone propionate with that of oral zafirlukast therapy for patients previously treated with beta-2-agonists alone, and to evaluate the potential therapeutic benefit of switching from zafirlukast to a low-dose inhaled corticosteroid.
                This study consisted of a 4-week randomized, double-blind treatment period followed by a 4-week open-label period. Two hundred ninety-four patients > or =12 years old with asthma previously uncontrolled with beta-2-agonists alone were randomly assigned to treatment with low-dose inhaled fluticasone (88 microg twice daily) or oral zafirlukast (20 mg twice daily). After 4 weeks, all patients discontinued their double-blind therapy and received open-label fluticasone (88 microg twice daily). Outcomes included pulmonary function, asthma symptoms, albuterol use, asthma exacerbations, and adverse events.
                During the double-blind treatment period, fluticasone patients had significantly greater improvements in morning peak flow (29.3 L/min vs. 18.3 L/min), percentage of symptom-free days (19.8% vs. 11.6%), and daily albuterol use (-1.8 puffs per day vs. -1.1 puffs per day) compared with zafirlukast patients (P < or =0.025, each comparison). During the open-label treatment period, patients switched from zafirlukast to fluticasone experienced additional improvements in morning peak flow (17.2 L/min), evening peak flow (13.6 L/min), and FEV(1) (0.11 liter) and daily albuterol use (-0.9 puffs daily) compared with values obtained at the end of the double-blind treatment period (P < or =0.001, each comparison).
                Low-dose fluticasone was more effective than zafirlukast in improving pulmonary function and symptoms in patients with persistent asthma. In addition, switching patients from zafirlukast to fluticasone further improved clinical outcomes. Whether leukotriene receptor antagonists exhibit adequate anti-inflammatory effects in the treatment of asthma is still a controversial issue. The aim of the present study was to perform a direct comparison of the effects of a 4-week treatment with either montelukast (10 mg, once a day) or low-dose inhaled fluticasone (100 microg b.i.d.) on functional and inflammatory parameters in steroid-naïve patients with moderate asthma. Forty patients (forced expiratory volume in one second (FEV1), 60-80% predicted) were studied in a double-blind, randomised, crossover design. Treatment periods were separated by 3-8 weeks of washout. At the beginning and end of each period, FEV1, airway responsiveness to inhaled methacholine (provocative concentration causing a 20% fall in FEV1 (PC20)), the level of exhaled nitric oxide (NO) and sputum differential cell counts were determined. Only short-acting beta2-agonists were allowed for relief of symptoms. FEV1 increased by 0.50+/-0.07 L (mean+/-SEM) after fluticasone and by 0.37+/-0.07 L after montelukast (p<0.001, each), and PC20 by 1.33+/-0.13 (p<0.001) and 0.15+/-0.17 (NS) doubling doses, respectively. Correspondingly, percentages of sputum eosinophils were reduced by factor 2.7 (p<0.01) and 1.4 (nonsignificant (NS)), and the levels of exhaled NO (at 50 mL x s(-1)) by factor 2.1 (p<0.01) and 1.1 (NS). These data indicate a comparable bronchodilator action of montelukast and fluticasone in patients with moderate asthma, but additional attenuation of airway inflammation by fluticasone as detectable through noninvasive methods. Lung function is commonly used as the primary endpoint in asthma clinical trials, but it may not reflect changes which are important to patients. The present study compared changes in, and relationships between, traditional and patient-centred end-points during treatment with three classes of asthma medication. Subjects with mild-to-moderate asthma were randomised to double-blind, double-dummy crossover treatment with eformoterol 12 microg b.i.d. or montelukast 10 mg q.d., then single-blind treatment with fluticasone 250 microg b.i.d./placebo capsules, with 6-week treatment periods and 1-week washouts. Individual "traditional" end-points (symptoms, reliever use, forced expiratory volume in one second per cent predicted, morning peak expiratory flow, airway hyperresponsiveness) and "patient-centred" end-points (asthma control questionnaire, quality of life, patient global assessments) were assessed. Principal component analysis and linear modelling were used to explore overall rank orders for treatment, and relationships between outcomes. A total of 58 subjects were randomised. The rank order of benefit from eformoterol and fluticasone differed for three factors derived from principal component analysis (eformoterol>fluticasone for symptom/reliever use factor, fluticasone>eformoterol for lung function factor, eformoterol=fluticasone for patient-centred factor). Montelukast was ranked third for all three factors. A significant relationship between patient-based variables and lung function was found only for montelukast treatment. In asthma treatment, traditional end-points do not fully capture patient-centred benefits, and the relationship between end-points differs with medication class. Both inhaled corticosteroids and leukotriene modifiers are used in the maintenance treatment of persistent asthma.
                The goal was to compare the efficacy and safety of low-dose fluticasone propionate (FP) and montelukast as first-line maintenance therapy in symptomatic patients by using short-acting beta2-agonists alone to treat persistent asthma.
                In this multicenter, randomized, double-blind, double-dummy, parallel-group study, 533 patients (>15 years old) with persistent asthma who remained symptomatic while taking short-acting beta2-agonists alone were treated with FP (88 microg [2 puffs of 44 microg] twice daily) or montelukast (10 mg once daily) for 24 weeks.
                Compared with treatment with montelukast, treatment with FP resulted in significantly greater improvements at endpoint in morning predose FEV(1) (22.9% vs 14.5%, P <.001), forced midexpiratory flow (0.66 vs 0.41 L/sec, P <.001), forced vital capacity (0.42 vs 0.29 L, P =.002), morning peak expiratory flow (PEF) (68.5 vs 34.1 L/min, P <.001), and evening PEF (53.9 vs 28.7 L/min, P <.001). Similar improvements in PEF were observed in patients with milder asthma (>70%-80% predicted FEV(1)). At endpoint, FP was more effective than montelukast at decreasing rescue albuterol use (3.1 puffs/day vs 2.3 puffs/day, P <.001), asthma symptom scores (-0.85 [48.6% decrease] vs -0.60 [30.5%], P <.001), and nighttime awakenings due to asthma (-0.64 awakenings/night [62% decrease] vs -0.48 awakenings/night [47.5%], P =.023), and FP increased the percentage of symptom-free days (32.0% vs 18.4% of days, P <.001) compared with montelukast. The adverse event and asthma exacerbation profiles for FP and montelukast were similar.
                Low-dose FP is more effective than montelukast as first-line maintenance therapy for patients with persistent asthma who are undertreated and remain symptomatic while taking short-acting beta2-agonists alone. Inhaled corticosteroids and leukotriene receptor antagonists reduce airway eosinophilia and have been used as first line anti-inflammatory therapy for mild persistent asthma.
                A multicentre, randomised, placebo controlled, parallel group study was performed to compare the anti-inflammatory effects of fluticasone propionate and montelukast as measured by sputum eosinophils in 50 adults with symptomatic steroid naive asthma and sputum eosinophilia of > or =3.5%.
                Eighteen patients received low dose fluticasone (250 mug/day), 19 received montelukast (10 mg/day), and 13 were given placebo for 8 weeks. Fluticasone treatment resulted in a greater reduction in sputum eosinophils (geometric mean (SD) 11.9 (2.3)% to 1.7 (5.1)%) than montelukast (10.7 (2.3)% to 6.9 (3.8)%; p = 0.04) or placebo (15.4 (2.4)% to 7.8 (4.2)%; p = 0.002), and improvement in FEV(1) (mean (SD) 2.6 (0.9) l to 3.0 (0.9) l) than montelukast (2.8 (0.7) l to 2.8 (0.9) l; p = 0.02) or placebo (2.4 (0.8) l to 2.4 (0.9) l; p = 0.01). Treatment with fluticasone suppressed sputum eosinophilia within a week while montelukast only attenuated it. The effect of montelukast was maximal at 1 week and was maintained over 4 weeks. The effect of fluticasone was maintained over 8 weeks while that of montelukast was not.
                Montelukast is not as effective as low dose fluticasone in reducing or maintaining an anti-inflammatory effect in steroid naive eosinophilic asthma. Maintaining asthma control is a major objective of therapy. Traditionally, the effectiveness of asthma therapy has been judged primarily by its effect on airway function rather than on multiaspect asthma control.
                An inhaled corticosteroid and a leukotriene receptor antagonist were compared to determine whether they provided equivalent effects, as judged by days of asthma control.
                In a randomized, multicenter, double-blind, placebo-controlled, parallel-group study, asthmatic patients (n = 782) with FEV(1) percent predicted values of between 50% and 85% and a weekly average beta-agonist use of more than 2 puffs per day were randomized to receive montelukast (10 mg daily), beclomethasone (200 microg twice daily), or placebo treatment for 6 weeks in a double-dummy fashion. We examined the distribution of the primary end point: percentage of days of asthma control. Secondary end points included FEV(1), albuterol use, occurrence of an asthma attack, asthma flare-up, rescue corticosteroid use, sustained asthma control, and adverse experiences.
                The percentage of days of asthma control was almost identical between the montelukast and beclomethasone groups (98% overlap in the distribution). Montelukast was at least equal to beclomethasone, and both were greater than placebo on the basis of frequency of asthma attacks, asthma flare-ups, and rescue corticosteroid use. Beclomethasone had a greater effect than montelukast and both treatments were better than placebo at improving FEV(1).
                Montelukast was as effective as beclomethasone, as judged by indices of clinical control other than FEV(1). When evaluating the outcome of montelukast therapy, FEV(1) might underestimate clinical effectiveness. Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma.
                To compare the clinical benefit of montelukast, a once-daily oral leukotriene receptor antagonist; placebo; and inhaled beclomethasone.
                Randomized, double-blind, double-dummy, placebo-controlled, parallel-group, 12-week study.
                36 sites worldwide.
                895 patients 15 to 85 years of age with chronic asthma and an FEV1 50% to 85% of predicted.
                Montelukast, 10 mg once daily at bedtime; inhaled beclomethasone, 200 microg twice daily, administered with a spacer device; or placebo.
                Primary end points were daytime asthma symptom score and FEV1. Secondary end points were peak expiratory flow rates in the morning and evening, as-needed beta-agonist use, nocturnal awakenings, asthma-specific quality of life, and worsening asthma episodes.
                Over the 12-week treatment period, the average percentage change from baseline in FEV1 was 13.1% with beclomethasone, 7.4% with montelukast, and 0.7% with placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). The average change from baseline in daytime symptom score was -0.62 for beclomethasone, -0.41 for montelukast, and -0.17 for placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). Each agent improved peak expiratory flow rates and quality of life, reduced nocturnal awakenings and asthma attacks, increased the number of asthma-control days, and decreased the number of days with asthma exacerbations (P < 0.001 for each active treatment compared with placebo for each end point; P < 0.01 for beclomethasone compared with montelukast for each end point). Although beclomethasone had a greater mean clinical benefit than montelukast, montelukast had a faster onset of action and a greater initial effect. The two agents caused similar decreases in peripheral blood eosinophil counts (P < 0.05 for each agent compared with placebo). Both agents had tolerability profiles similar to that of placebo over the 12-week study.
                Although beclomethasone had a larger mean effect than montelukast, both drugs provided clinical benefit to patients with chronic asthma. This finding is consistent with the use of these agents as controller medications for chronic asthma. The purpose of this study was to compare the efficacy and safety of the inhaled budesonide, sustained-release theophylline and montelukast, a leukotriene receptor antagonist, in patients with mild persistent asthma. In this single-center, randomized, parallel-group study that not designed blindly and placebo-controlled manner, 74 patients with mild persistent asthma were treated with either inhaled budesonide 400 microg once daily, oral montelukast 10 mg once daily, or sustained-release theophylline 400 mg once daily for 3 months. In all three treatment groups, improvements were attained in overall asthma control. Asthma symptom scores and supplemental beta2-agonist use were quite the same in all three treatment groups (P>0.05). Although inhaled budesonide group resulted in significantly greater improvements compared with the other two groups in the lung functions (P<0.05), the changes in FEV1 and PEF are within the baseline variability and there was no statistically significant difference among the groups when analyzed by treatment month (P>0.05). Exacerbations of asthma were experienced by 16% of the patients in the montekulast group, by 12.5% of the patients in the theophylline group, and by none of the patients in the budesonide group. The adverse event in each of the three groups was 12%, 16% and 16.7%, respectively. It is concluded that the most important clinical parameters do not point that one of the treatments is more effective than others. Treatment with inhaled corticosteroid is preferred, but sustained-release theophylline and leukotriene antagonists are alternative controller medications in mild persistent asthma. Budesonide inhalation suspension and the leukotriene receptor antagonist montelukast have demonstrated efficacy in children with mild persistent asthma, but comparative long-term studies in young children are needed.
                To compare the long-term efficacy and safety of budesonide inhalation suspension and montelukast.
                After a run-in period, children 2 to 8 years old with mild asthma or recurrent wheezing were randomized to once-daily budesonide inhalation suspension 0.5 mg or once-daily oral montelukast 4 or 5 mg for 52 weeks. Subjects were stepped up to twice-daily budesonide inhalation suspension or oral corticosteroids for mild or severe asthma worsening, respectively. The primary outcome was time to first additional medication for asthma worsening at 52 weeks. Secondary variables included times to the first additional asthma medication measured at 12 and 26 weeks; times to the first asthma exacerbation (mild and severe) measured at 12, 26, and 52 weeks; exacerbation rates (mild and severe) over a period of 52 weeks; diary variables (eg, peak expiratory flow [PEF]); patient-reported outcomes; and Global Physician and Caregiver Assessments.
                No significant between-group differences were observed for time to first additional asthma medication at 52 weeks; however, time to first additional asthma medication was longer (unadjusted P = .050) at 12 weeks and exacerbation rates were lower over a period of 52 weeks (unadjusted P = .034) for budesonide versus montelukast. Time to first severe exacerbation (requiring oral corticosteroids) was similar in both groups, but the percentage of subjects requiring oral corticosteroids over a period of 52 weeks was lower with budesonide (25.5% vs 32.0%). Peak flow and Caregiver and Physician Global Assessments favored budesonide.
                Both treatments provided acceptable asthma control; however, overall measures favored budesonide inhalation suspension over montelukast.
                These findings are consistent with studies in older children demonstrating better outcomes with inhaled corticosteroids versus montelukast. Responses to inhaled corticosteroids (ICSs) and leukotriene receptor antagonists (LTRAs) vary among asthmatic patients.
                We sought to determine whether responses to ICSs and LTRAs are concordant for individuals or whether asthmatic patients who do not respond to one medication respond to the other.
                Children 6 to 17 years of age with mild-to-moderate persistent asthma were randomized to one of 2 crossover sequences, including 8 weeks of an ICS, fluticasone propionate (100 microg twice daily), and 8 weeks of an LTRA, montelukast (5-10 mg nightly depending on age), in a multicenter, double-masked, 18-week trial. Response was assessed on the basis of improvement in FEV 1 and assessed for relationships to baseline asthma phenotype-associated biomarkers.
                Defining response as improvement in FEV 1 of 7.5% or greater, 17% of 126 participants responded to both medications, 23% responded to fluticasone alone, 5% responded to montelukast alone, and 55% responded to neither medication. Compared with those who responded to neither medication, favorable response to fluticasone alone was associated with higher levels of exhaled nitric oxide, total eosinophil counts, levels of serum IgE, and levels of serum eosinophil cationic protein and lower levels of methacholine PC(20) and pulmonary function; favorable response to montelukast alone was associated with younger age and shorter disease duration. Greater differential response to fluticasone over montelukast was associated with higher bronchodilator use, bronchodilator response, exhaled nitric oxide levels, and eosinophil cationic protein levels and lower methacholine PC(20) and pulmonary function values.
                Response to fluticasone and montelukast vary considerably. Children with low pulmonary function or high levels of markers associated with allergic inflammation should receive ICS therapy. Other children could receive either ICSs or LTRAs. Currently available anti-inflammatory treatment for young children with asthma includes inhaled corticosteroids (ICS) and the leukotriene receptor antagonist (LTRA) montelukast.
                To evaluate potential biomarkers of predicting short-term (6-week) response to ICS and LTRAs in children with asthma.
                A total of 102 children aged 4 to 7 years with episodic asthma were enrolled in an open labelled single-centre study. Biomarkers and asthma characteristics were evaluated as predictors of treatment. Of 102 patients 45 became symptomatic during observation and were randomised to treatment either to montelukast or fluticasone for 6 weeks.
                Forced Expiratory Volume in one second (FEV1) increased with both treatments: FEV1 at randomisation was 90.2% and after therapy 106.8% with fluticasone vs. 90.8% and 103.7% for montelukast, respectively, showing that montelukast and fluticasone were equally effective in this age group (p = 0.44). Strong correlations to a favourable treatment response were pre-bronchodilatory FEV1 (p < 0.001) and airway reversibility (p = 0.04) at time of randomisation. None of the other biomarkers (methacholine testing, exhaled nitric oxide [eNO], presence of allergy, total Immunoglobulin E [IgE], cumulative specific IgE, eosinophils and parental smoking) were predictive.
                Despite the small sample size and the open-label design, the study suggests that the use of pre-bronchodilatory FEV1 and airway reversibility appears to be a good indicator of short-term anti-inflammatory therapy in young children with asthma. 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 randomized, 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. This 6-month, open-label extension study of a previously described base study compared oral montelukast with inhaled beclomethasone in terms of safety, forced expiratory volume in one second (FEV1) measurements, parent and patient satisfaction with treatment, asthma-related medical resource utilization, school absenteeism, and parental work loss in children with asthma. A total of 124 of 266 asthmatic children, 6 to 11 years of age, who enrolled in the base study entered a 6-month open-label extension study (74 boys, 50 girls) and were re-randomized (2:1 ratio) to receive once-daily oral montelukast (n = 83) or inhaled beclomethasone 100 mcg three times daily (n = 41). Children were evaluated in the clinic prior to re-randomization (Month 0) and at regular visits at 1, 3, and 6 months. Children and their parents showed a significantly higher overall satisfaction for montelukast at 6 months than for inhaled beclomethasone (p = 0.001 and p < 0.05, respectively). According to parents, montelukast was more convenient (p < 0.001), less difficult to use (p = 0.005), and was used as instructed more of the time (p = 0.006) compared with beclomethasone. Oral corticosteroid use was similar in the montelukast (13% of patients) and beclomethasone (17%) treatment groups. The montelukast treatment group was more adherent with their regimen than the inhaled beclomethasone treatment group; almost twice as many children on montelukast compared with inhaled beclomethasone were highly compliant (82% versus 45%). The two study groups were similar with respect to overall safety, change in FEV1, asthma-related medical resource utilization, school absenteeism, and parental work loss. Montelukast represents a safe and effective asthma treatment regimen to which children with asthma are more likely to adhere. The use of inhaled corticosteroids compared with leukotriene modifying drugs in the treatment of persistent asthma has not been extensively studied.
                To compare the efficacy and safety of a low dose of fluticasone propionate (FP) and zafirlukast in patients previously maintained on inhaled corticosteroids.
                Patients (> or = 12 years old; FEV1 = 60% to 85% of predicted) with persistent asthma who were previously treated with low doses of triamcinolone acetonide (TAA) 400 to 800 microg/day or beclomethasone dipropionate (BDP) 168 to 336 microg/day were randomized to treatment with FP aerosol 88 microg BID (FP, n = 221) or zafirlukast 20 mg BID (n = 216) over 6 weeks.
                Treatment with FP significantly increased the mean change at endpoint (the last post-baseline observation) in FEV1 (0.22 L versus 0.03 L, P < .001), morning PEF (17.8 versus 3.1 L/min, P = .004), evening PEF (16.7 versus 2.6 L/min, P = .002), the percentage of symptom-free days (16.2 versus 7.1%, P = .007), and the percentage of rescue-free days (23.4 versus 9.3%, P < .001), and significantly decreased rescue albuterol use (-0.66 puffs/day versus an increase of 0.27 puffs/day, P < .001) and combined symptom scores (-0.13 versus an increase of 0.08, P < .001) compared with zafirlukast. Treatment with FP maintained the percentage of awakening-free nights (-1.0 +/- 1.0); in contrast, treatment with zafirlukast reduced the percentage of awakening-free nights (-9.0 +/- 1.6, P < .001). A clinically meaningful difference (change of > or = 0.5; P < .001) was observed between FP and zafirlukast in the Asthma Quality of Life Questionnaire (AQLQ) global score and for each domain score except activity limitation (change of 0.3, P < .001). Significantly more patients in the zafirlukast group experienced an asthma exacerbation (n = 14) compared with FP-treated patients (n = 5, P = .035). Patients in the zafirlukast group were significantly more likely to be withdrawn due to lack of efficacy (P < .001).
                Switching patients from low doses of inhaled corticosteroids to a lower total microgram dose of FP improves pulmonary function, asthma symptoms, and quality of life, while switching to the leukotriene receptor antagonist zafirlukast may result in worsening of asthma control. This was indicated by the significant number of zafirlukast-treated patients who were dropped from the study due to lack of efficacy within 6 weeks of discontinuing inhaled corticosteroids. Exercise-induced bronchoconstriction occurs in a large proportion of children with asthma, limiting everyday activities important for their physical and social development.
                The purpose of this randomized, double-blind, placebo-controlled study was to compare the ability of different patterns of antiasthmatic treatment, recommended in childhood asthma, to protect patients from exercise-induced bronchoconstriction.
                Children 6 to 18 years of age with atopic asthma were randomized to a 4-week, placebo-controlled, double-blind trial. Patients were randomly allocated to receive daily 200 microg budesonide (twice daily, 100 microg per dose) + 9 microg formoterol (twice daily, 4.5 microg per dose; n = 20); 200 microg budesonide + 5 or 10 mg montelukast (once daily at bedtime; n = 20); 5 or 10 mg montelukast (n = 20); 200 microg budesonide (n = 20); or placebo (n = 20). A standardized treadmill exercise challenge was performed before and after treatment.
                Exercise-induced bronchoconstriction, reflected by area under the curve for the FEV1 values from exercise over the 20-minute period and by maximum percent fall in FEV1 after exercise, was significantly diminished after 4 weeks in all active treatment groups, and compared with placebo. Exercise-induced bronchoconstriction protection improved more significantly in the budesonide + montelukast and montelukast groups compared with other therapeutic options.
                These data indicate differences in effects on exercise-induced bronchoconstriction between therapeutic options recommended in childhood asthma. Control of childhood asthma with exercise-induced bronchoconstriction can be obtained by using regular controller treatment. Loratadine added to montelukast has been suggested to improve endpoints of asthma.
                This study investigated the additive effects of concomitant montelukast and loratadine when compared with montelukast, loratadine, and inhaled beclomethasone monotherapies in asthma. Methods. Patients (N = 406) were 15 to 65 years of age with a forced expiratory volume in 1 second (FEV(1))-predicted of 50% to 85%, FEV(1) reversibility > or = 15%, and a minimal level of daytime symptoms and beta -agonist use. This three-part 2X2 crossover-study consisted of two double-blind 6-week treatment periods where patients were administered once daily oral montelukast 10 mg, loratadine 10 mg, montelukast 10 mg + loratadine 10 mg, or twice daily inhaled beclomethasone 200 mu g. A subsequent 48-week extension study compared montelukast + loratadine with beclomethasone. The primary endpoint was the percentage change from baseline in FEV(1).
                Over 6 weeks of double-blind treatment, significant improvements (p < 0.05) in the primary endpoint of FEV(1) were seen for montelukast + loratadine versus loratadine (least-square mean percentage-point difference of 5.8%), beclomethasone versus montelukast + loratadine (2.35%), montelukast versus loratadine (5.94%), and beclomethasone versus montelukast (4.65%); a numerical improvement (p = 0.054) was seen for montelukast + loratadine versus montelukast (1.60%). Significant improvements for montelukast + loratadine versus montelukast were seen in some secondary endpoints (evening peak expiratory flow, nocturnal asthma symptom score, nocturnal awakenings, and asthma-specific quality of life) but not others. Significant improvements in most endpoints except daytime asthma symptoms score were seen for montelukast + loratadine versus loratadine. In the extension study, both montelukast + loratadine and beclomethasone improved several endpoints. All treatments were generally comparable in the percentage of patients with clinical and laboratory adverse experiences.
                In this study, the addition of loratadine to montelukast produced a small numerical, but not statistically significant, improvement in FEV(1) and, in general, no consistent improvement in other asthma endpoints. No improvement of montelukast + loratadine versus beclomethasone was seen in any endpoint.
As monotherapy, inhaled corticosteroids display superior efficacy to anti-leukotrienes in adults and children with persistent asthma; the superiority is particularly marked in patients with moderate airway obstruction. On the basis of efficacy, the results support the current guidelines' recommendation that inhaled corticosteroids remain the preferred monotherapy.