Daily versus as-needed inhaled corticosteroid for mild persistent asthma (The Helsinki early intervention childhood asthma study). Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma. A randomized controlled trial of inhaled flunisolide in the management of acute asthma in children. Daily or intermittent budesonide in preschool children with recurrent wheezing. A randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial of the minimal effective doses of budesonide and fluticasone dry-powder inhalers in adults with mild to moderate asthma. Endocrine and lung function in asthmatic children on inhaled corticosteroids. Comparative study of budesonide inhalation suspension and montelukast in young children with mild persistent asthma. Comparative efficacy of once-daily therapy with inhaled corticosteroid, leukotriene antagonist or sustained-release theophylline in patients with mild persistent asthma. Effectiveness and safety of inhaled corticosteroids in controlling acute asthma attacks in children who were treated in the emergency department: a controlled comparative study with oral prednisolone.
To compare the effect of inhaled budesonide given daily or as-needed on mild persistent childhood asthma. Patients, design and
                176 children aged 5-10 years with newly detected asthma were randomly assigned to three treatment groups: (1) continuous budesonide (400 microg twice daily for 1 month, 200 microg twice daily for months 2-6, 100 microg twice daily for months 7-18); (2) budesonide, identical treatment to group 1 during months 1-6, then budesonide for exacerbations as needed for months 7-18; and (3) disodium cromoglycate (DSCG) 10 mg three times daily for months 1-18. Exacerbations were treated with budesonide 400 microg twice daily for 2 weeks.
                Lung function, the number of exacerbations and growth.
                Compared with DSCG the initial regular budesonide treatment resulted in a significantly improved lung function, fewer exacerbations and a small but significant decline in growth velocity. After 18 months, however, the lung function improvements did not differ between the groups. During months 7-18, patients receiving continuous budesonide treatment had significantly fewer exacerbations (mean 0.97), compared with 1.69 in group 2 and 1.58 in group 3. The number of asthma-free days did not differ between regular and intermittent budesonide treatment. Growth velocity was normalised during continuous low-dose budesonide and budesonide therapy given as needed. The latter was associated with catch-up growth.
                Regular use of budesonide afforded better asthma control but had a more systemic effect than did use of budesonide as needed. The dose of ICS could be reduced as soon as asthma is controlled. Some children do not seem to need continuous ICS treatment. 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. Inhaled corticosteroids (ICS) may provide benefit in the therapy of acute asthma. The purpose of this study was to test the hypothesis that ICS are as effective as oral corticosteroids (OCS) in the management of acute childhood asthma.
                A randomized, masked, placebo-controlled study was conducted in children aged 6 to 16 years seeking emergent care for an acute exacerbation of asthma. Patients were randomized into one of two groups: group 1 (OCS), oral prednisone, 2 mg/kg (maximum of 60 mg/d) for 7 days, and placebo pressurized metered-dose inhaler with valved holding chamber, four inhalations bid; and group 2 (ICS), flunisolide, four inhalations (1 mg) bid for 7 days, and daily placebo tablets. Spirometry (FEV(1)) was performed at baseline, day 3, and day 7 of the study. A symptom diary and twice-daily peak expiratory flow were recorded.
                A total of 58 subjects receiving ICS (n = 27) or OCS (n = 28) were enrolled. Baseline asthma severity, race, gender, and age were balanced between the two groups. chi(2) showed no significant difference in symptom severity between the two groups at any time during the study. FEV(1) percentage of predicted was lower in the ICS group on day 3 (65% vs 78%, p = 0.03) and on day 7 (77% vs 95%, p = 0.002).
                ICS were found to be useful in the management of acute asthma in children; however, spirometry data suggested a more rapid resolution of asthma with OCS. Daily inhaled glucocorticoids are recommended for young children at risk for asthma exacerbations, as indicated by a positive value on the modified asthma predictive index (API) and an exacerbation in the preceding year, but concern remains about daily adherence and effects on growth. We compared daily therapy with intermittent therapy.
                We studied 278 children between the ages of 12 and 53 months who had positive values on the modified API, recurrent wheezing episodes, and at least one exacerbation in the previous year but a low degree of impairment. Children were randomly assigned to receive a budesonide inhalation suspension for 1 year as either an intermittent high-dose regimen (1 mg twice daily for 7 days, starting early during a predefined respiratory tract illness) or a daily low-dose regimen (0.5 mg nightly) with corresponding placebos. The primary outcome was the frequency of exacerbations requiring oral glucocorticoid therapy.
                The daily regimen of budesonide did not differ significantly from the intermittent regimen with respect to the frequency of exacerbations, with a rate per patient-year for the daily regimen of 0.97 (95% confidence interval [CI], 0.76 to 1.22) versus a rate of 0.95 (95% CI, 0.75 to 1.20) for the intermittent regimen (relative rate in the intermittent-regimen group, 0.99; 95% CI, 0.71 to 1.35; P=0.60). There were also no significant between-group differences in several other measures of asthma severity, including the time to the first exacerbation, or adverse events. The mean exposure to budesonide was 104 mg less with the intermittent regimen than with the daily regimen.
                A daily low-dose regimen of budesonide was not superior to an intermittent high-dose regimen in reducing asthma exacerbations. Daily administration led to greater exposure to the drug at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; MIST ClinicalTrials.gov number, NCT00675584.). Inhaled corticosteroids are established first-line anti-inflammatory treatment for asthma. Clinical trials comparing inhaled corticosteroids must take into consideration that because of their excellent effect at low doses, they typically induce a near-maximal response in asthma patients.
                The aim of the present dose-response study was to estimate the minimal effective doses (MEDs) of budesonide and of fluticasone propionate via dry-powder inhaler in adults with mild to moderate asthma.
                This was a randomized, double-blind, double-dummy, parallel-group, multicenter, dose-reduction trial performed in adults to compare these 2 inhaled corticosteroids. After a 4- to 6-week run-in period with beclomethasone dipropionate 2000 pg/d, patients fulfilling defined criteria for asthma control were randomly allocated to treatment with budesonide or fluticasone, both administered BID at a total of 800 pg/d. At 5-week intervals, the dose was reduced to 400 and then 200 pg/d (200 and 100 pg BID) if asthma control was maintained according to further defined criteria. The MED was defined as the last dose level before deterioration of asthma control.
                Subjects were 197 asthmatic patients with a mean age of 40.6 years in the budesonide group and 41.5 years in the fluticasone group. In both groups, baseline mean forced expiratory volume in 1 second (FEV(1)) was 79.4% of the predicted normal volume and baseline mean FEV(1) reversibility was 22.3%. The median MED for both groups was 400 microg/d, with no detectable difference in dis-tributions. The budesonide-to-fluticasone ratio for the geometric mean MED was 123% (95% CI, 99-153 [not significant]). No statistically significant differences regarding lung function, symptom scores, or rescue medication usage were found between the treatment groups during the first treatment period. Adverse-event profiles were similar in both groups, and no unexpected adverse events were considered to be caused by the study drugs.
                This effect-controlled study did not detect a statistically significant difference between the MEDs for budesonide and fluticasone via dry-powder inhaler in adults with mild to moderate asthma. The safety of inhaled corticosteroids in the treatment of chronic asthma has been questioned. In a prospective crossover study asthmatic children not controlled on other medications were commenced on beclomethasone dipropionate (BDP) or budesonide (BUD), both administered at the dose of 200 micrograms twice per day for 2 wk each in randomized order. Recordings at home included twice daily symptom scores, peak expiratory flow readings, and the use of additional antiasthma medications. Before and after each treatment period the patients were admitted for overnight blood sampling for cortisol, ACTH, and growth hormone, 24-h urine collections for cortisol, and detailed lung function tests. A total of 12 children completed the study. The nocturnal serum cortisol production was significantly reduced by 27 and 35% after 2 and 4 wk of treatment (p = 0.005, p = 0.004; Wilcoxon test), and the urinary free cortisol showed a similar reduction of 33 and 48% (p = 0.023, p = 0.005). Such suppression could be shown on both drugs, BDP and BUD, and there was no significant difference between them. The ACTH and growth hormone values were not significantly changed on any treatment. Lung function tests showed an impressive improvement in FVC, FEV1, FEF50, and FEF25 after 2 wk of treatment regardless of the medication. Differences in lung function improvements between the two drugs were very small and not of clinical relevance. The observations indicate that even low-dose inhaled corticosteroids in the form of BDP or BUD have a systemic effect, which emphasizes the importance of using the minimum dose compatible with good control of 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. 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. Inhaled corticosteroids have a greater antiinflammatory potency and fewer systemic effects than intravenous, intramuscular, or oral corticosteroids. However, their role in acute asthma has not been established. We prospectively investigated the efficacy and safety of inhaled corticosteroids in controlling moderately severe acute asthma attacks in children who were treated in the emergency department.
                Children who were treated in the emergency department with moderately severe asthma attacks after receiving treatment with inhaled terbutaline were allocated by double-blind design to receive 1 dose of either 1600 micro(g) budesonide turbohaler or 2 mg/kg prednisolone. The pulmonary index score and peak expiratory flow rate were measured hourly for the first 4 hours. After discharge the children were treated with the same initial doses given 4 times daily, followed by a 25% reduction in dose every second day for 1 week. Parents recorded asthma symptoms and use of beta-2 agonists on a daily diary card. Serum cortisol concentration was measured at the end of weeks 1 and 3.
                Twenty-two children (11 in each group) with similar baseline parameters completed the study. There was a similar improvement in pulmonary index score and peak expiratory flow rate in the 2 groups. Children treated with budesonide showed an earlier clinical response than those given prednisolone, who also showed a decrease in serum cortisol concentration.
                In children with moderately severe asthma attacks who were treated in the emergency department, a short-term dose schedule of inhaled budesonide turbohaler, starting with a high dose and followed by a decrease over 1 week, is at least as effective as oral prednisolone, without suppressing serum cortisol concentration.
In children and adults with persistent asthma and in preschool children suspected of persistent asthma, there was low quality evidence that intermittent and daily ICS strategies were similarly effective in the use of rescue oral corticosteroids and the rate of severe adverse health events. The strength of the evidence means that we cannot currently assume equivalence between the two options.. Daily ICS was superior to intermittent ICS in several indicators of lung function, airway inflammation, asthma control and reliever use. Both treatments appeared safe, but a modest growth suppression was associated with daily, compared to intermittent, inhaled budesonide and beclomethasone. Clinicians should carefully weigh the potential benefits and harm of each treatment option, taking into account the unknown long-term (> one year) impact of intermittent therapy on lung growth and lung function decline.