A randomized controlled trial of inhaled flunisolide in the management of acute asthma in children. Early administration of corticosteroids in emergency room treatment of acute asthma. Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma. A randomized open-label comparative study of montelukast versus theophylline added to inhaled corticosteroid in asthmatic children. Controlled trial of intravenous corticosteroids in severe acute asthma. Efficacy of nebulized fluticasone propionate in adult patients admitted to the emergency department due to bronchial asthma attack. Hospital treatment of asthma: lack of benefit from theophylline given in addition to nebulized albuterol and intravenously administered corticosteroid. Early administration of hydrocortisone in the emergency room treatment of acute asthma: a controlled clinical trial. Outpatient management of childhood asthma by paediatrician or asthma nurse: randomised controlled study with one year follow up. Placebo controlled trial of systemic corticosteroids in acute childhood asthma. Efficacy of short-term corticosteroid therapy in outpatient treatment of acute bronchial asthma. High-dose and low-dose systemic corticosteroids are equally efficient in acute severe asthma. Inhaled budesonide in addition to oral corticosteroids to prevent asthma relapse following discharge from the emergency department: a randomized controlled trial. Corticosteroids in status asthmaticus. Potency ratio fluticasone propionate (Flixotide Diskus)/budesonide (Pulmicort Turbuhaler). Comparison of inhaled fluticasone with intravenous hydrocortisone in the treatment of adult acute 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. The efficacy of inhaled corticosteroids in the management of non asthmatic chronic airflow obstruction. Daily versus as-needed inhaled corticosteroid for mild persistent asthma (The Helsinki early intervention childhood asthma study). Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity. Endocrine and lung function in asthmatic children on inhaled corticosteroids.
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. To determine the effect of early administration of high-dose intravenous corticosteroids on duration of emergency room treatment and hospital admission rate in patients with acute asthma.
                Randomized, double-blind, placebo-controlled trial.
                The emergency room of a large, urban hospital with primary and referral care responsibilities.
                Eighty-one patients from 18 to 45 years of age with acute bronchial asthma and without pneumonitis or other serious underlying illnesses were studied on 91 occasions and were randomly assigned to control or experimental groups.
                The steroid group received 125 mg of intravenous methylprednisolone whereas the control group received intravenous normal saline 30 minutes after initial treatment. Additional treatment included aerosolized metaproterenol and oral theophylline therapy. Six hours after study entry, remaining patients were treated with 40 mg of intravenous methylprednisolone. Hospitalization was mandatory if total treatment time was greater than 12 hours.
                Age, sex, peak expiratory flow at entry, and prevalence of recent corticosteroids use were similar in both groups. Duration of emergency room treatment was 6.7 +/- 4.2 (SD) hours in the steroid group and 6.3 +/- 4.1 hours in the control group (P = 0.66). Hospitalization was necessary in 18% (95% CI, 7% to 30%) of the steroid group and in 13% (CI, 3% to 22%) of the control group. Frequency of return visits for acute asthma 2 days after emergency room discharge was 11% (CI, -1% to 22%) in the steroid group and 13% (CI, 2% to 23%) in the control group.
                These results fail to show any benefit for early administration of corticosteroids in patients with acute asthma. Routine administration of corticosteroids on initial presentation in such patients may not be warranted. 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 (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. The value of corticosteroids in severe acute asthma continues to be debated.
                Ninety consecutive patients admitted to the emergency room with severe acute asthma were studied in a randomised, double blind, controlled trial to determine the efficacy of corticosteroids. Eighty two patients completed the study. All received oxygen therapy and intensive bronchodilator treatment. The patients were divided into three groups for steroid treatment, receiving intravenous methylprednisolone 10 mg/kg every four hours for 48 hours (29 patients, group A); intravenous methylprednisolone 2 mg/kg every 4 hours for 48 hours (27 patients, group B); or no intravenous corticosteroids (26 patients, group C).
                There were no differences on admission among the three groups in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), or arterial oxygen or carbon dioxide tension; and the rates of recovery in FEV1, FVC, and PEF were similar.
                Corticosteroids given with bronchodilators have not shown a beneficial effect in the first 48 hours of recovery of severe acute asthma. Only in those patients who failed to respond by the third hour of treatment, and in those who were previously taking oral corticosteroids, does a favourable, though not statistically significant, effect appear to occur. Locally delivered steroids by inhalers or nebulizers have been shown in small trials to be effective in acute asthma attack, but evidence-based data are insufficient to establish their place as routine management of adult asthma attacks.
                To determine the efficacy of nebulized compared to systemic steroids in adult asthmatics admitted to the emergency department following an acute attack.
                Adult asthmatics admitted to the ED were assigned in random consecutive case fashion to one of three protocol groups: group 1--nebulized steroid fluticasone (Flixotide Nebules), group 2--intravenous methylprednisolone, group 3--combined treatment by both routes. Objective and subjective parameters, such as peak expiratory flow, oxygen saturation, heart rate and dyspnea score, were registered before and 2 hours after ED treatment was initiated. Steroids were continued for 1 week following the ED visit according to the protocol arm. Data on hospital admission/discharge rate, ED readmissions in the week after enrollment and other major events related to asthma were registered.
                Altogether, 73 adult asthmatics were assigned to receive treatment: 24 patients in group 1, 23 in group 2 and 26 in group 3. Mean age was 44.4 +/- 16.8 years (range 17-75 years). Peak expiratory flow and dyspnea score significantly improved in group 1 patients compared with patients in the other groups after 2 hours of ED treatment (P = 0.021 and 0.009, respectively). The discharge rate after ED treatment was significantly higher in groups 1 and 3 than in group 2 (P = 0.05). All 73 patients were alive a week after enrollment. Five patients (20.8%) in the Flixotide treatment arm were hospitalized and required additional systemic steroids. Multivariate analysis of factors affecting hospitalization rate demonstrated that severity of asthma (odds ratio 8.11) and group 2 (OD 4.17) had a negative effect, whereas adherence to chronic anti-asthma therapy (OD 0.49) reduced the hospitalization rate.
                Our study cohort showed the advantage of nebulized steroid fluticasone versus systemic corticosteroids in adult asthmatics managed in the ED following an acute attack. Both these and previous results suggest that nebulized steroids should be used, either alone or in combination with systemic steroids, to treat adults suffering acute asthma attack. To determine the efficacy of theophylline when given in addition to nebulized albuterol and intravenously administered corticosteroid to children hospitalized with mild to moderate asthma.
                Randomized, prospective, placebo-controlled, double-blind trial.
                Tertiary-care children's hospital.
                Twenty-nine patients with asthma between the ages of 2 and 16 years completed the study. The treatment and placebo groups were similar in age, gender, race, illness severity, and emergency department treatment.
                All patients received intravenously administered methylprednisolone and nebulized albuterol. The treatment group received intravenous theophylline therapy and the placebo group dextrose in water. When intravenously administered medications were discontinued, therapy continued with oral administration of theophylline (or placebo) and of prednisone.
                Twice-daily assessments of clinical asthma symptoms were made by using a scoring system consisting of respiratory rate, inspiratory/expiratory ratio, wheeze, and accessory muscle use. Time required to reach study discharge criteria (asthma score < or = 2) (30.4 +/- 16.8 vs 27.0 +/- 10.3 hours; p = 0.51) and the rate of improvement of the clinical asthma score (-0.10 +/- 0.05 unit/hr vs -0.11 +/- 0.09 unit/hr; p = 0.88) were not significantly different between the theophylline and placebo groups. The number of albuterol aerosol treatments required and the adverse effects experienced were not significantly different between groups.
                When the combination of systemically administered corticosteroid and inhaled albuterol is used in the treatment of children hospitalized with mild to moderate asthma, addition of theophylline may not be justified. To determine whether early administration of a single dose of intravenous hydrocortisone (500 mg) modified the need for hospitalization and duration of treatment, and improve pulmonary function assessed by subjective and objective criteria of acute asthma patients.
                Randomized, double-blind, placebo-controlled trial.
                The emergency room (ER) of a large, urban hospital with primary and referral care responsibilities.
                Ninety-eight patients from 18 to 50 years of age with acute bronchial asthma, with a PEFR and FEV1 in the first second below 50% of predicted value (FEV1 mean % of predicted = 27.8 +/- 10.0) and without history of chronic cough or other medical disease.
                The corticosteroid group received 500 mg of intravenous hydrocortisone whereas the control group received intravenous normal saline immediately after arrival to the ER. Additional treatment included salbutamol delivered with metered-dose inhaler into a spacer device (Volumatic), in four puffs actuated in rapid succession (100 micrograms per actuation), at 10-min intervals. The final mean dose was 5.7 mg for the steroid group and 5.6 mg for the control one (P = 0.86). Hospitalization was mandatory if total treatment time was greater than 6 h.
                Age, sex, PEFR, FEV1, FVC, symptom index, and corticosteroids use were similar in both groups. FEV1 expressed as mean % of predicted was 54.6 +/- 17.3% in the control group and 54.6 +/- 17.4% in the steroid group (P = 0.75). Duration of ER treatment was 2.22 +/- 1.75 h in the corticosteroid group and 2.24 +/- 1.70 h in the control group (P = 0.81). The hospital admission rate was 10.2% for the corticosteroid group and 8.16% for the control group. There were no differences between the groups when patients admitted or discharged were examined separately.
                Early administration of corticosteroids does not modify outcome of ER treatment of asthma, and does not improve pulmonary function in the first 6 h of treatment. In accord with this, administration of corticosteroids to these patients could be delayed by several hours without modifying clinical outcome. When an aggressive beta-agonist bronchodilator regimen is used, it obviates the need for steroids in this early stage of treatment. 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. In a randomised controlled trial 38 asthmatic children aged 2-11 yr who had not received regular oral or inhaled steroids during the previous year, were treated with a standard regime of nebulised salbutamol and intravenous aminophylline plus either hydrocortisone and oral prednisolone for 5 days, or placebo. The children were observed throughout their hospital stay and for 3 months afterwards. There was a greater fall in heart rates in the steroid treated group on the second day of treatment (mean diff. 16 beats/min) and at discharge (mean diff. 13 beats/min); p less than 0.025. Peak Expiratory Flow Rates recorded in 26 children, 13 in each group, showed more improvement on day 2 in those given steroids (mean diff 16% predicted); p less than 0.05. This difference was not apparent at discharge but 9 children treated with steroids were clinically wheeze-free when they left hospital compared with 3 in the placebo group, p less than 0.05. There were no differences in respiratory rate, pulsus paradoxus and arterial oxygen saturation. Trends in duration of hospital stay and relapse rate during the succeeding 3 months favoured active treatment. These findings support the use of systemic corticosteroids in addition to high dose bronchodilators to treat 'non steroid dependent' children hospitalised with acute severe asthma. A group of adults with 76 episodes of acute asthma needing emergency therapy, but not requiring hospitalization, were discharged from an emergency department following standardized therapy with bronchodilators. Upon discharge, the patients were treated with a controlled regimen of oral theophylline, and were randomly assigned in double-blind manner to either a placebo treatment (42 patient episodes) or a corticosteroid treatment group (34 patient episodes). The latter were given an intravenous bolus of methylprednisolone followed by an eight-day tapering course of oral methylprednisolone, starting at 32 mg twice a day. Follow-up was carried out seven or 10 days after treatment in the emergency department. Relapse could not be predicted on the basis of peak expiratory flow rates measured during care in the emergency department. Those patients who received corticosteroids had a decrease in the need for repeated emergency care (5.9 percent versus 21 percent for placebo) and fewer respiratory symptoms (15.6 percent versus 36.4 percent for placebo). It is concluded that a short course of high-dose corticosteroids in outpatients reduces the relapse rate and symptoms following an acute asthmatic attack. The optimal amount of systemic corticosteroids to be used in acute severe asthma remains an unresolved issue. In this double-blind, randomized study we compared two doses of methylprednisolone (1 vs 6 mg.kg-1 q.d.) in asthmatics presenting with an acute severe asthma attack, unresponsive to an intensive beta 2-agonist regimen administered during a run-in period. Concurrent therapy, including oxygen, inhaled and intravenous salbutamol, and aminophylline was strictly standardized. The response was assessed by serial bedside spirometry. The primary outcome measurement was forced expiratory volume in one second (FEV1) (expressed as percentage of predicted values) at 24 and 44 h. The trial was designed in order to achieve a statistical power of 90%. Twenty three patients were included in the low-dose group and 24 in the high-dose group. Both groups were comparable in terms of demographic profiles, history of asthma, and severity of the current attack. Improvement in pulmonary function was similar in both groups. At 44 h, the mean (+/- SD) FEV1 values were 53 +/- 22 and 45 +/- 14% in the low and in the high-dose group respectively (NS). We conclude that high dose systemic corticosteroids offer no further benefit over low-doses in the treatment of severe acute asthma. Relapses of acute asthma following emergency department (ED) discharge can be reduced with systemic corticosteroid treatment. However, whether inhaled corticosteroids (ICSs) provide additional benefit is not known. Objective To determine whether the addition of ICSs to oral corticosteroid treatment would reduce relapses in patients with acute asthma discharged from the ED.
                Placebo-controlled, double-blind, randomized clinical trial conducted in a community teaching hospital ED in Canada between November 1995 and September 1997, with a 21-day follow-up.
                A total of 1006 consecutive patients aged 16 to 60 years presented to the ED with acute asthma; after excluding those using oral and/or inhaled corticosteroids as well as those meeting other exclusion criteria, 188 were included in the study.
                Patients were discharged with a nontapering course of oral prednisone (50 mg/d) for 7 days. In a double-blind fashion, patients were randomly assigned to 1600 microg/d of inhaled budesonide (n = 94) or identical placebo (n = 94) for 21 days.
                Incidence of relapse, defined as an unscheduled visit for worsening asthma symptoms, in budesonide vs placebo groups. Secondary outcomes included response to the Asthma Quality of Life Questionnaire, beta2-agonist use, symptom score, global asthma improvement assessment, and pulmonary function.
                Five patients in the budesonide group and 3 in the placebo group either dropped out or were lost to follow-up but were included in primary analyses. After 21 days, 12 (12.8%) of 94 patients in the budesonide group experienced a relapse compared with 23 (24.5%) of 94 in the placebo group, a 48% relapse reduction (P=.049). Asthma Quality of Life Questionnaire scores were higher (better quality) in the budesonide group (P=.001), as well as for all domain scores (P=.001 to .01). Fewer beta2-agonist activations were used at the end of the trial by patients receiving budesonide (2.4/d vs 4.2/d; P=.01). Symptom scores (P=.001 to .004) and self-assessed asthma improvement scores (based on a 7-point Likert scale) (6.2 vs 5.2; P<.001) were higher (indicating fewer symptoms) for budesonide vs placebo. There were no differences in pulmonary function between the groups (peak expiratory flow rate: budesonide, 437 vs placebo, 453 L/min; P= .39) at 21 days. Using this approach, as few as 9 patients would require budesonide to prevent 1 relapse.
                Patients discharged from the ED following treatment for acute asthma benefit from added treatment with high-dose inhaled budesonide for 21 days compared with oral corticosteroids alone. Nineteen children who were not steroid dependent and were hospitalized in status asthmaticus were studied to evaluate the effect of corticosteroids. They were randomized into two groups. Each group received salbutamol inhalations and intravenous aminophylline therapy. One group received 7 mg/kg hydrocortisone intravenously every six hours; the other group served as a control. Each group showed significant improvement in clinical score and peak expiratory flow rate after 36 hours; there was no statistical difference in the degree of improvement. Six of ten steroid-treated children and six of nine controls achieved a PEFR of 50% predicted by 36 hours. The response to inhaled salbutamol was similar in each group. The results show that in the first 36 hours of therapy, corticosteroids have no additive effect on the bronchodilator response of aminophylline and salbutamol and do not hasten the recovery of nonsteroid-dependent children in status asthmaticus. Although the results show that an inhaled sympathomimetic drug is beneficial in status asthmaticus, corticosteroid therapy does not increase the responsiveness of the airways to these agents. In the choice of, or switch between, various inhaled corticosteroids (ICS) it is important to know equipotent doses for clinical treatment effects of the alternatives. Various ICS do have different inherent potency. Further, the ICS are delivered from inhalers that may differ markedly in output characteristics and drug delivery to intrapulmonary airways. Therefore, clinical efficacy comparisons must include drug-inhaler comparisons. We estimated the therapeutic potency ratio of the Flixotide Diskus (fluticasone propionate, FP) and the Pulmicort Turbuhaler (budesonide, BUD) in steroid-naive asthma patients, using a dose-reduction technique (FP 500-0 mcg/day, BUD 800-0 mcg/day). The dose defining end point was loss of asthma control in this paper denoted as exacerbation. In total, 282 patients with proven asthma were enrolled in the study, and 103 in the FP group and 98 in the BUD group completed the study per protocol. In total, 80 patients in the FP-group and 79 in the BUD-group experienced a dose defining exacerbation. The exacerbation frequency increased in a dose-dependent way as the dose was titrated down. From these data the potency difference between the present drug inhaler combinations, Flixotide Diskus and Pulmicort Turbuhaler, was calculated to be between 1.50:1 (95% CI 1.10:1-2.05:1) and 1.75:1 (CI 1.26:1-2.43:1) depending on if patients with insufficient steroid-response were excluded from the calculations or not. In these steroid-naïve patients, the potency difference was evident only at low daily doses, below 200 mcg. Several studies published in the second half of the 1990s have shown a therapeutic early effect of inhaled corticosteroids in acute asthma. However, systemic corticosteroids are considered the standard of care.
                To compare the effect of repeated doses of inhaled fluticasone with the standard treatment of systemic corticosteroids in adult patients with severe acute asthma.
                One hundred six patients (mean age, 33.5 +/- 8.8 years) were randomly assigned to receive fluticasone (3,000 microg/hour) administered through a metered-dose inhaler and spacer at 10-minute intervals for 3 hours, or 500 mg of intravenous hydrocortisone. In addition, all patients received inhaled albuterol and ipratropium bromide.
                Subjects treated with fluticasone showed 30.5 and 46.4% greater improvements in PEF and FEV1, respectively, compared with the hydrocortisone group. The fluticasone group had better PEF and FEV1 at 120, 150, and 180 minutes (p < 0.05). Also, the fluticasone group showed higher rates of patients who obtained the discharge threshold at 90, 120, and 150 minutes. This therapeutic benefit was particularly evident in those patients with the most severe obstruction. Subjects with a baseline FEV1 of less than 1 L treated with fluticasone showed a significant increase in pulmonary function (p = 0.001) and a significant decrease in hospitalization rate (p = 0.05).
                The use of repeated doses of inhaled fluticasone was more effective than intravenous hydrocortisone and was associated with an early improvement. This therapeutic benefit was particularly evident in those patients with the most severe obstruction. 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. The aims of this investigation were to evaluate the efficacy of regular inhaled beclomethasone in the control of symptoms and lung function with non-asthmatic smoking related obstructive pulmonary disease and to evaluate the relationship between clinical responses to a short course of oral prednisone and longer term outcomes using inhaled steroid.
                The study was a randomised, double blind, placebo controlled, crossover investigation in 18 patients. The active treatment was inhaled beclomethasone 1000 micrograms given twice daily for three months by metered dose inhaler. At the end of each treatment period, patients received oral prednisone 30 mg/day for ten days. The two treatment phases were separated by a one month washout interval. Peak flow rates, symptom scores and "rescue" bronchodilator use were recorded twice daily. Lung function (FEV1, FVC and lung volumes) and bronchial hyperresponsiveness (PC20 methacholine) were measured at monthly visits. The number of exacerbations requiring intervention therapy were also recorded.
                There were no consistent benefits attributable to beclomethasone. Lung function was not significantly better as a result of active treatment. Sputum production improved but other symptom scores were similar during active and placebo therapy. Three patients exhibited an increase in FEV1 of 15% or more during active treatment but did not do so when oral prednisone was administered immediately after the period of placebo treatment. A further three patients showed an improvement in FEV1 of 15% or more with oral prednisone but failed to improve during treatment with inhaled beclomethasone. The predictive value of the "trial of steroid" was 0% and 81.3% for positive and negative outcomes respectively.
                Our results indicate that in non-asthmatic chronic obstructive pulmonary disease inhaled corticosteroid fails to achieve significant improvements in either lung function or symptoms. The response to a "trial of steroid" using oral prednisone is not clinically helpful in selecting the small number of patients who may subsequently benefit from this form of therapy. 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 order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD. 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.
ICS therapy reduces hospital admissions in patients with acute asthma who are not treated with oral or intravenous corticosteroids. They may also reduce admissions when they are used in addition to systemic corticosteroids; however, the most recent evidence is conflicting. There is insufficient evidence that ICS therapy results in clinically important changes in pulmonary function or clinical scores when used in acute asthma in addition to systemic corticosteroids. Also, there is insufficient evidence that ICS therapy can be used in place of systemic corticosteroid therapy when treating acute asthma. Further research is needed to clarify the most appropriate drug dosage and delivery device, and to define which patients are most likely to benefit from ICS therapy. Use of similar measures and reporting methods of lung function, and a common, validated, clinical score would be helpful in future versions of this meta-analysis.