Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial. Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. A randomized controlled trial of inhaled flunisolide in the management of acute asthma in children. A randomized open-label comparative study of montelukast versus theophylline added to inhaled corticosteroid in asthmatic children. Multicenter randomized controlled trial of withdrawal of inhaled corticosteroids in cystic fibrosis. Budesonide/formoterol maintenance plus reliever therapy: a new strategy in pediatric asthma. 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. Daily versus as-needed inhaled corticosteroid for mild persistent asthma (The Helsinki early intervention childhood asthma study).
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. 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. For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking.
                We randomly assigned 182 children (6 to 17 years of age), who had uncontrolled asthma while receiving 100 microg of fluticasone twice daily, to receive each of three blinded step-up therapies in random order for 16 weeks: 250 microg of fluticasone twice daily (ICS step-up), 100 microg of fluticasone plus 50 microg of a long-acting beta-agonist twice daily (LABA step-up), or 100 microg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up). We used a triple-crossover design and a composite of three outcomes (exacerbations, asthma-control days, and the forced expiratory volume in 1 second) to determine whether the frequency of a differential response to the step-up regimens was more than 25%.
                A differential response occurred in 161 of 165 patients who were evaluated (P<0.001). The response to LABA step-up therapy was most likely to be the best response, as compared with responses to LTRA step-up (relative probability, 1.6; 95% confidence interval [CI], 1.1 to 2.3; P=0.004) and ICS step-up (relative probability, 1.7; 95% CI, 1.2 to 2.4; P=0.002). Higher scores on the Asthma Control Test before randomization (indicating better control at baseline) predicted a better response to LABA step-up (P=0.009). White race predicted a better response to LABA step-up, whereas black patients were least likely to have a best response to LTRA step-up (P=0.005).
                Nearly all the children had a differential response to each step-up therapy. LABA step-up was significantly more likely to provide the best response than either ICS or LTRA step-up. However, many children had a best response to ICS or LTRA step-up therapy, highlighting the need to regularly monitor and appropriately adjust each child's asthma therapy. (ClinicalTrials.gov number, NCT00395304.)
                2010 Massachusetts Medical Society 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. Inhaled corticosteroids (ICSs) are widely used in combination with other classes of drugs for treatment of childhood asthma. The efficacy and the safety of montelukast added to low-dose ICS therapy were compared with those of sustained-release theophylline added to low-dose ICS therapy in asthmatic children in the present study.
                Following the 2-week run-in period, 6-to 14-year old patients receiving treatment with ICSs were randomized to treatment for 4 weeks with either montelukast 5 mg once daily or sustained release theophylline 5-8 mg/kg (dry syrup) or 100-200 mg (tablet) twice daily. Patients also received a fixed dose of ICS throughout the run-in and treatment periods. The primary efficacy endpoint was the change from baseline in peak expiratory flow (PEF) at Week 2.
                A significant increase in morning PEF was observed in the add-on montelukast group as compared with the add-on theophylline group at Week 2 (change from baseline of 22.8 L/minvs. 8.7 L/min; p = 0.041 for between-group difference) and at Week 4 (31.0 L/minvs. 9.8 L/min; p = 0.012). A significant increase in evening PEF was observed in the add-on montelukast group as compared with the add-on theophylline group at Week 4 (24.7 L/minvs. 8.7 L/min; p = 0.027). There were no significant differences between the treatment groups in incidences of clinical and laboratory adverse experiences.
                The results indicate that montelukast added to low-dose ICS is an effective and safe option for the treatment of asthma in children. Lung inflammation and injury is critical in cystic fibrosis. An ideal antiinflammatory agent has not been identified but inhaled corticosteroids are widely used despite lack of evidence.
                To test the safety of withdrawal of inhaled corticosteroids with the hypothesis this would not be associated with an earlier onset of acute chest exacerbations.
                Multicenter randomized double-blind placebo-controlled trial in 18 pediatric and adult UK centers. Eligibility criteria included age>6.0 yr, FEV1>or=40% predicted, and corticosteroid use>3 mo. During the 2-mo run-in period, all patients received fluticasone; they then took either fluticasone or placebo for 6 mo.
                Fluticasone group: n=84, median age 14.6 yr, mean (SD) FEV1 76% (18); placebo group: n=87, median age 15.8 yr, mean (SD) FEV1 76% (18). There was no difference in time to first exacerbation (primary outcome) with hazard ratio (95% confidence interval) of 1.07 (0.68 to 1.70) for fluticasone versus placebo. There was no effect of age, atopy, corticosteroid dose, FEV1, or Pseudomonas aeruginosa status. There was no change in lung function or differences in antibiotic or rescue bronchodilator use. Fewer patients in the fluticasone group withdrew from the study due to lung-related adverse events (9 vs. 15%); with a relative risk (95% confidence interval) of 0.59 (0.23-1.48) fluticasone versus placebo.
                In this study population (applicable to 40% of patients with cystic fibrosis in the UK), it appears safe to consider stopping inhaled corticosteroids. Potential advantages will be to reduce the drug burden on patients, reduce adverse effects, and make financial savings. A fixed combination of long-acting beta(2)-agonists (LABA) plus inhaled corticosteroids (ICS) has never been proven to reduce asthma exacerbations vs ICS alone in children. This 12-month, double-blind, randomized study in 341 children (age range, 4 to 11 years) with asthma uncontrolled on ICS investigated whether a novel regimen using budesonide/formoterol for maintenance and reliever therapy (Symbicort maintenance and relief therapy [SMART]) [Symbicort; AstraZeneca R&D, Lund, Sweden] could reduce exacerbations.
                Patients received SMART (budesonide/formoterol 80/4.5 microg qd maintenance plus additional inhalations for symptom relief), budesonide/formoterol 80/4.5 microg qd for maintenance (fixed combination), or higher-dose budesonide 320 microg qd (fixed-dose budesonide). Blinded as-needed medication (terbutaline 0.4 microg) was provided in both fixed-dose groups.
                SMART prolonged the time to first exacerbation vs fixed-dose budesonide (p = 0.02) and fixed-dose combination (p < 0.001). Rates of exacerbation requiring medical intervention were reduced by 70 to 79% with SMART vs fixed-dose budesonide and fixed-dose combination (0.08/patient vs 0.28/patient and 0.40/patient, respectively; both p < 0.001). Mild exacerbation days and awakenings were significantly lower with SMART; yearly growth improved by 1.0 cm vs fixed-dose budesonide (p < 0.01).
                The SMART regimen using budesonide/formoterol for both maintenance and as-needed symptom relief reduces the exacerbation rate compared with both fixed-dose combination and higher fixed-dose ICS alone in children with asthma. 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. 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.
In adolescents and adults with sub-optimal control on low dose ICS monotherapy, the combination of LABA and ICS is modestly more effective in reducing the risk of exacerbations requiring oral corticosteroids than a higher dose of ICS. Combination therapy also led to modestly greater improvement in lung function, symptoms and use of rescue ß2 agonists and to fewer withdrawals due to poor asthma control than with a higher dose of inhaled corticosteroids. Apart from an increased rate of tremor and less oral candidiasis with combination therapy, the two options appear relatively safe in adults although adverse effects associated with long-term ICS treatment were seldom monitored. In children, combination therapy did not lead to a significant reduction, but rather a trend towards an increased risk, of oral steroid-treated exacerbations and hospital admissions. These trends raised concern about the safety of combination therapy in view of modest improvement in children under the age of 12 years.