Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma. Comparison of fluticasone propionate and sodium cromoglycate for the treatment of childhood asthma (an open parallel group study). A randomized controlled trial of inhaled flunisolide in the management of acute asthma in children. Outpatient management of childhood asthma by paediatrician or asthma nurse: randomised controlled study with one year follow up. EXCEL: A randomised trial comparing salmeterol/fluticasone propionate and formoterol/budesonide combinations in adults with persistent asthma. Steroid-sparing effects of fluticasone propionate 100 microg and salmeterol 50 microg administered twice daily in a single product in patients previously controlled with fluticasone propionate 250 microg administered twice daily. A placebo-controlled, crossover comparison of salmeterol and salbutamol in patients with asthma. Deterioration in asthma control when subjects receiving fluticasone propionate/salmeterol 100/50 mcg Diskus are "stepped-down". Combined salmeterol/fluticasone propionate versus fluticasone propionate alone in mild asthma : a placebo-controlled comparison.
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 are highly effective in the treatment of asthma at all ages and their use in younger children is increasing. As concerns exist about the long-term systemic side-effects of high dose inhaled corticosteroids, current guidelines continue to recommend sodium cromoglycate (SCG) as first line regular medication for children with frequent symptoms. Few published studies have compared the safety and efficacy of inhaled corticosteroids with SCG in children. This study compares SCG with the new inhaled corticosteroid, fluticasone propionate (FP), which has theoretical advantages over other currently available corticosteroids due to its negligible oral bioavailability. This was a randomized, open, multi-centre, parallel group comparison of 50 micrograms FP twice daily and 20 mg SCG four times daily over 8 weeks, preceded by a 2-week baseline period. Sixty-two general practices and two hospital centres enrolled 225 asthmatic children aged 4-12 years (110 received FP; 115 received SCG). Outcome measures improved in both groups, with a significant difference in favour of FP for the key variables of mean morning and evening % predicted PEFR and % of symptom-free days and nights. No significant difference was observed for FEV1, or relief medication use. Two children taking FP and 10 children taking SCG withdrew because of adverse events. This study showed that low dose FP was effective and superior to SCG in young children with mild-moderate asthma. Safety studies of longer duration are needed before changing the current recommendations for inhaled corticosteroid therapy. 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. Until now, care provided by asthma nurses has been additional to care provided by paediatricians. A study was undertaken to compare nurse led outpatient management of childhood asthma with follow up by a paediatrician.
                Seventy four children referred because of insufficient control of persistent asthma were randomly allocated to 1 year follow up by a paediatrician or asthma nurse. The main outcome measure was the percentage of symptom-free days. Additional outcome measures were airway hyperresponsiveness, lung function, daily dose of inhaled corticosteroids (ICS), number of exacerbations, number of additional visits to the general practitioner, absence from school, functional health status, and disease specific quality of life.
                There were no significant differences at the end of the 1 year study period between the two treatment groups in percentage of symptom-free days (mean difference 2.5%; 95% CI -8.8 to 13.8), airway hyperresponsiveness (log10 PD20 0.06; -0.19 to 0.32), functional health status (10.1; -0.3 to 19.8), disease specific quality of life of patients (0.08; -0.9 to 0.7), and disease specific quality of life of caregivers (0.09; -0.2 to 0.3), nor in any other outcome parameters. Most outcome parameters improved considerably over the 1 year study period. These improvements were achieved although the daily dose of ICS was reduced by a mean of 26% compared with the dose received by children at referral. All parents were satisfied with the asthma care received.
                After initial assessment in a multidisciplinary clinic, childhood asthma can be successfully managed by an asthma nurse in close cooperation with a paediatrician. During close follow up by paediatrician or asthma nurse, asthma control improved despite a reduction in ICS dose. This multicentre, parallel group, double-blind, double-dummy, randomised 24-week study was designed to compare the efficacy of salmeterol/fluticasone propionate combination (SFC) 50/250 microg one inhalation twice daily (bid) with formoterol/budesonide combination (FBC) 6/200 microg two inhalations bid in patients with persistent asthma, currently receiving 1000-2000 microg/day of inhaled corticosteroids.
                The intent-to-treat population comprised 694 patients in the SFC group and 697 patients in the FBC group.
                The primary endpoint, mean rate of all exacerbations over 24 weeks, was similar in both treatment groups (SFC: 2.69; FBC: 2.79; SFC/FBC ratio 0.96; 95% CL 0.84, 1.10; P=0.571). A reduction in the rate of exacerbations over time was observed in both treatment groups. Overall, there was a 30% lower annual rate of moderate/severe exacerbations in the SFC group compared with the FBC group (95% CI 0-49%, 52% reduction vs. 1% increase; P=0.059). This effect increased with time: in weeks 17-24 the moderate/severe exacerbation rate was 57% lower in the SFC group compared with the FBC group (95% CI 21-77% reduction; P=0.006). Similar improvements in lung function, asthma symptoms and rescue medication usage were seen with both treatments and both were well tolerated.
                Twice-daily treatment with SFC and FBC over 6 months significantly improved asthma symptoms and lung function in patients with persistent asthma. The rate of exacerbations was significantly reduced over time on both treatments but SFC was found to be significantly superior to FBC in reducing the rate of moderate/severe exacerbations with sustained treatment. Concurrent use of an inhaled corticosteroid (ICS) and an inhaled long-acting beta2-agonist provides better overall asthma control than the use of higher doses of ICS alone.
                The purpose of this investigation was to determine whether fluticasone propionate (FP) combined with salmeterol in the Diskus device can be used to reduce the dose of ICS in patients currently stable on medium-dose ICS while maintaining asthma control.
                This was a randomized, double-blind, parallel-group, 12- to 24-week trial consisting of a 3-part run-in period. The run-in period was designed to first establish FP 250 microg administered twice a day (bid) via Diskus as the minimum effective dose. During run-in period 1, patients received FP 220 microg bid or the equivalent for 10 to 14 days. Controlled patients moved to run-in period 2 (5-28 days), which assessed asthma stability on FP 100 microg bid administered via Diskus. Only patients who became unstable on FP 100 microg bid were eligible to enter run-in period 3 (26-30 days), during which they were placed on FP 250 microg bid and those regaining asthma control were eligible for randomization. The primary efficacy endpoint was the proportion of patients who remained in the study with no evidence of worsening asthma. Secondary efficacy measures included FEV1, morning peak expiratory flow, percent of symptom-free days, and daily albuterol use.
                Only 5% of patients treated with FP100/salmeterol withdrew because of worsening asthma in the first 12 weeks; this compared with 7% in the FP250 group. All patients from a subset of sites continued in the study for an additional 12 weeks; only an additional 1% of patients treated with either FP100/salmeterol or FP250 withdrew because of worsening asthma. Secondary efficacy measures confirmed primary efficacy results.
                In patients requiring FP250 bid for asthma stability, FP100/salmeterol bid was steroid-sparing, allowing a 60% reduction in the FP dose while maintaining overall asthma control. We compared the effects of salmeterol (Sm) (50 micrograms twice daily) with that of salbutamol (Sb) (200 micrograms four times daily) and placebo (P) in patients with mild-to-moderate asthma with asthma symptoms and related the effectiveness of these therapies between patients who used concurrent inhaled corticosteroids (ICS) and those who did not. The study was a 12-wk, multicenter, double-blind, placebo-controlled crossover trial with 367 adult asthmatics randomized to each trial medication for 4 wk. Inhaled Sb was provided as rescue medication to all patients throughout the trial. Only 80% of patients, albeit the majority, were receiving maintenance treatment with ICS throughout this trial; this reflects practice current in early 1990. Each study day, patients recorded their morning and evening peak expiratory flows (PEF), assessment of asthma symptoms, and use of rescue medication. Both morning and evening PEF were greater during treatment with Sm than with Sb (mean differences between the treatments of 29.8 and 14.3 L/min, respectively) or P (27.7 and 20.3 L/min, respectively) (p < 0.0001). Sm was also more effective than Sb or P in lowering diurnal variation in PEF and increasing the percentage of symptom-free days and rescue-free days and nights with no sleep disturbance (p < or = 0.0004). Sb was more effective than P in increasing evening PEF and the percentage of symptom-free days (p < 0.05) and rescue-free days (p < 0.0001). The same clinical superiority of Sm compared with Sb and P was observed in those patients using ICS (p < 0.001 for all treatment comparisons), and to a greater extent than in those patients not using ICS (i.e., Sm was more effective than Sb and P in just six of the 20 treatment comparisons; p < 0.05). In conclusion, Sm 50 micrograms twice daily is effective in the management of mild-to-moderate asthma and it further improves asthma control in patients already using ICS. 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. Combined therapy with inhaled corticosteroids (ICSs) and long-acting beta(2)-adrenoceptor agonists (LABAs) is the recommended approach for the treatment of patients with asthma that is uncontrolled on ICSs alone. Additional studies are needed to assess the safety and efficacy of combination treatment with ICSs and LABAs in patients with mild asthma. The aim of this study was to compare the efficacy and tolerability of once-daily salmeterol/fluticasone propionate combination (SFC) with once-daily fluticasone propionate (FP) over a 12-week treatment period in patients with mild persistent asthma.
                This was a randomized, double-blind, placebo-controlled, parallel-group, multicentre study carried out in primary care or at a hospital outpatient department and included patients 12-79 years of age with mild persistent asthma (n = 458). After a 2-week run-in period, patients were randomized to receive SFC 50 microg/100 microg (n = 149), FP 100 microg (n = 154) or placebo (n = 155) once daily in the morning for 12 weeks. The primary efficacy endpoint was patient-recorded pre-dose mean morning peak expiratory flow (PEF). Other assessments included asthma symptom scores, use of rescue medication and investigator-recorded exacerbations. Lung function was measured and assessed during clinic visits.
                For the primary efficacy endpoint of mean change in morning PEF, SFC achieved significantly greater increases from baseline than both placebo (difference in adjusted means 23 L/min; 95% CI 15.0, 30.3; p < 0.001) and FP (difference in adjusted means 14 L/min; 95% CI 6.3, 21.7; p < 0.001). Compared with those who received FP, patients in the SFC group demonstrated significantly greater improvements in mean evening PEF (95% CI 11.7, 28.1; p < 0.001), forced expiratory volume in 1 second (95% CI 0.093, 0.257; p < 0.001), forced expiratory flow between 25% and 75% of forced vital capacity (95% CI 0.242, 0.617; p < 0.001), the percentage of symptom-free days (95% CI 0.34, 0.87; p = 0.011), and the percentage of rescue medication-free days (95% CI 0.34, 0.90; p = 0.018). During weeks 5-12, 52% of patients in the SFC group achieved 'well controlled' asthma, compared with 42% and 26% of patients in the FP and placebo groups, respectively. Only one patient (receiving placebo) had a severe asthma exacerbation during the study; the frequency of adverse events was similar across the three treatment groups.
                Once-daily SFC 50 microg/100 microg provided significantly greater improvements in lung function and in asthma symptoms than once-daily FP 100 microg alone in patients with mild persistent asthma. However, twice-daily treatment with either SFC or ICSs plus short acting beta(2)-adrenoceptor agonists could be required to achieve guideline-defined asthma control in some patients.
ICS were superior to SCG on measures of lung function and asthma control for both adults and children with chronic asthma. There were few studies reporting on quality of life and health care utilization, which limited our ability to adequately evaluate the relative effects of these medications on a broader range of outcomes. Although there were no differences in adverse effects between ICS and SCG, most trials were short and may not have been of sufficient duration to identify long-term effects. Our results support recent consensus statements in the U.S. and elsewhere that favour the use of ICS over SCG for control of persistent asthma.