Controlled trial of intravenous corticosteroids in severe acute asthma. High doses of inhaled corticosteroids in unstable chronic asthma. A multicenter, double-blind, placebo-controlled study. Corticosteroids in status asthmaticus. Early administration of corticosteroids in emergency room treatment of 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. Early parenteral corticosteroid administration in acute asthma. Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease. A randomized controlled trial of inhaled flunisolide in the management of acute asthma in children. 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.
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. In a multicenter, randomized, double-blind study, inhaled beclomethasone dipropionate (BDP) 1,500 micrograms/day was compared to placebo in 43 chronic asthmatic patients uncontrolled by inhaled salbutamol and oral theophylline. During the prestudy period, a test of maximal steroid reversibility with oral prednisolone 0.5 mg/kg/day for 14 days was performed. The therapeutic response was measured over an 8-wk period as the ability to maintain the clinical improvement and the optimal pulmonary function induced by prednisolone. During the study, severe asthma exacerbation occurred in one (5%) of the 21 patients who received BDP and in 15 (78%) of the 22 patients who received placebo (p less than 0.001). In patients who received BDP, FEV1 and peak expiratory flow (PEF) remained above the optimal postprednisolone value, with a trend to improvement during the 8-wk study period. In patients who received placebo, FEV1 and PEF decreased and remained below the optimal value. We conclude that, in chronic asthma, inhaled BDP 1,500 micrograms/day maintains the optimal pulmonary function in addition to the clinical benefit induced by a short course of oral corticosteroids. 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. 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. 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. To test the hypothesis that early parenteral corticosteroid administration may be associated with a rapid improvement in airflow obstruction in adult asthmatic patients, a randomized, double-blind placebo-controlled study was carried out. Forty-five adult asthmatic patients, with initial peak expiratory flow rates (PEFRs) of < 200 L/sec received an intravenous bolus of either 125 mg methylprednisolone (MP) or normal saline before any other emergency department treatments. This was immediately followed by 3 aerosol treatments of 2.5 mg of albuterol separated by 20-minute intervals. PEFRs and heart rates were measured over a 1-hour time frame. There was not a significantly higher rate of increase of PEFR in the MP group compared with the saline group. Similarly, the rate of increase in percent PEFR showed a trend to being higher in the saline group (P = .061). There was no significant difference in the proportion of hospitalizations and side effects between the two groups. Adjustment for other variables did not result in a model showing an enhanced PEFR improvement with MP treatment. This study does not support the concept that corticosteroid treatment effects are beneficial within the first hour after administration. Further studies of rapid-acting modalities to enhance bronchodilation are needed in treating acute asthmatics. Inhaled corticosteroids are known to be beneficial for patients with asthma, but their role in treating patients with stable chronic obstructive pulmonary disease (COPD) remains controversial. A study was undertaken to determine whether inhaled corticosteroids are of functional benefit in patients who did not show improvement with a trial of oral corticosteroids.
                In phase I patients with stable COPD were given a two week course of oral placebo followed by two weeks of prednisone 40 mg per day in a single blind manner to distinguish between responders and non-responders to oral corticosteroids. In phase II a double blind, randomised, parallel group trial of inhaled budesonide 1600 micrograms per day versus placebo was carried out in 79 nonresponders to oral corticosteroids. The primary outcome measure was forced expiratory volume in one second (FEV1), and secondary outcome measures were exercise capacity, dyspnoea with exertion, quality of life, peak expiration flow rate, and respiratory symptoms.
                Randomisation allocated 39 subjects to inhaled corticosteroids and 40 to placebo. There was no difference in the change in FEV1 from baseline between the treatment and placebo groups; mean difference -12 ml (95% CI -88 to 63) at three months and -4 ml (95% CI -95 to 87) at six months. The proportion of patients with a 15% or greater improvement was no higher among those receiving inhaled corticosteroids than in the placebo group at any of the follow up visits. Changes in secondary outcomes were also no different.
                Inhaled corticosteroids, even at high doses, were of no physiological or functional benefit in these patients with advanced COPD. 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 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.
Intranasal corticosteroids were well tolerated. While INCS tended to improve asthma symptoms and forced expiratory volume in one second, the results did not reach significance. The combination of intranasal plus intrabronchial corticosteroids should remain the current clinical practice until more research is done.