Comparison of oral-steroid sparing by high-dose and low-dose inhaled steroid in maintenance treatment of severe asthma. Additive effects of prednisolone and beclomethasone dipropionate in patients with stable chronic obstructive pulmonary disease. Effect of a single oral dose of prednisolone in acute childhood asthma. Substitution of beclomethasone aerosol for oral prednisolone in the treatment of chronic asthma. High-dose beclomethasone: oral steroid-sparing effect in severe asthmatic patients. A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis. The response to inhaled and oral steroids in patients with stable chronic obstructive pulmonary disease. Methotrexate in the management of severe steroid dependent asthma. High-dose inhaled budesonide in treatment of severe steroid-dependent asthma. Steroid reversibility test followed by inhaled budesonide or placebo in outpatients with stable chronic obstructive pulmonary disease. The Danish Society of Respiratory Medicine. Randomised controlled trial comparing prednisolone alone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis. Prolonged versus standard prednisolone therapy for initial episode of nephrotic syndrome. A double-blind, randomized clinical trial of methylprednisolone in status asthmaticus. Randomised, double-blind, placebo-controlled trial of methotrexate in steroid-dependent asthma. A multicenter study of alternate-day prednisone therapy in patients with cystic fibrosis. Cystic Fibrosis Foundation Prednisone Trial Group. Intermittent versus long-term tapering prednisolone for initial therapy in children with idiopathic nephrotic syndrome. Severe nasal polyposis and its impact on quality of life. The effect of a short course of oral steroids followed by long-term intranasal steroid treatment. Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial. Corticosteroids in acute severe asthma: effectiveness of low doses. High-dose inhaled fluticasone does not replace oral prednisolone in children with mild to moderate acute asthma.
It is not clear whether high doses of inhaled steroids have a greater sparing effect than low doses on the requirement for systemic steroids. In a randomised, double-blind, multicentre study, we compared the effects of high-dose (1500 micrograms/day) and low-dose (300 micrograms/day) inhaled beclomethasone dipropionate (BDP) in patients with severe asthma requiring a daily oral prednisolone dose of 10-40 mg. During a 3-month run-in period, we tried to achieve optimum asthma control by means of oral steroid and inhaled BDP 300 micrograms/day. The patients were then allocated to high-dose (n = 71) or low-dose (n = 72) treatment by an independent observer who took into account various prognostic factors. BDP was administered by means of an aerosol inhaler with a spacer device. The dose of systemic steroid was reduced as much as possible during the 6-month study period while keeping the peak expiratory flow (PEF) constant and asthma clinically stable. There was no difference between the low-dose and high-dose treatment groups in the mean reduction in oral prednisolone dose achieved by the end of the study (5.2[ SD 7.9] vs 5.0 [9.4] mg/day). The maximum response to inhaled steroid was seen, however, only after several months' therapy in both groups. There were no differences between the groups in use of on-demand beta-agonist inhalations or in asthma symptoms, and PEF values were constant throughout the study. Both doses of BDP were well tolerated. High doses of inhaled steroid offer no further benefit over low doses in the maintenance treatment of severe steroid-dependent asthma when the inhaled steroid is administered with a spacer device. It remains unclear whether inhaled corticosteroids can produce the maximum benefits of corticosteroids in patients with chronic obstructive pulmonary disease (COPD). To assess the additive effects of 30 mg/day prednisolone to high-dose, inhaled beclomethasone dipropionate (BDP), we conducted a randomised double-blind, placebo-controlled cross-over trial. The study population consisted of 21 men with stable COPD. The mean age of the patients was 69.1 +/- 6.8 years, and FEV(1)was 0.86 +/- 0.28 l. Seventeen out of the 21 patients (81%) were considered susceptible to steroids in a previous trial (FEV(1)increased at least 15% from baseline after receiving 14 days of 30 mg/day prednisolone). All of the patients had been on 1600 microg/day BDP for more than 3 months. Spirometry was performed before the entry, and at the end of 3-week placebo and prednisolone periods. The peak expiratory flow (PEF), symptoms, and Guyatt's Chronic Respiratory Disease Questionnaire (CRQ) as a disease specific health-related quality of life over the last seven days of each period were also evaluated. Although a marginal increase in PEF was found during the prednisolone period, no significant differences in FEV(1), FVC, symptoms or CRQ scores were observed between the two treatment periods. We conclude that the therapeutic effects of steroid therapy may be achieved by the long-term use of high-dose, inhaled corticosteroid in some patients with stable COPD.
                Copyright 2000 Academic Press. 140 children of 184 with acute asthma entered a randomised double-blind trial of oral prednisolone (n = 67) compared with placebo (n = 73) administered soon after admission. The dose of prednisolone was 30 mg in children under 5, otherwise 60 mg. All children also received salbutamol. All had moderate or severe dyspnoea. Initial evaluation was similar for both groups. On reassessment after a few hours 20 children in the prednisolone group were fit for discharge compared with only 2 in the placebo group. There were no early reattendances. Children remaining in hospital had a shorter median duration of stay and were less likely to require further steroid therapy if they had initially received prednisolone. In acute asthma the prompt use of a single dose of oral prednisolone can reduce morbidity and the need for hospital care. In a double-blind study 10 patients with chronic asthma received beclomethasone dipropionate 400 mug daily in a Freon propellant from a pressurized dispenser, and 10 patients received the Freon propellant alone. At the start of the trial each patient was receiving long-term maintenance treatment with oral prednisolone in a dose of 7.5 to 15 mg daily. The daily dose of prednisolone was reduced by 1 mg every four weeks and the patient's progress followed by regular clinical assessment and studies of pituitary-adrenal function. The trial was continued until the dose of prednisolone was reduced to zero or until asthmatic symptoms increased to an unacceptable level.In the 10 patients who received beclomethasone the mean maintenance dose of oral prednisolone was reduced by 5.6 mg/day but in only two cases could this drug be withdrawn completely. In the placebo group the mean reduction in dose was only 1.3 mg, thus there was a significant difference between the two groups (P <0.01). Studies of pituitary-adrenal function showed that a normal adrenal response to tetracosactrin stimulation returned only in the two patients from whom prednisolone was withdrawn.Hence the addition of beclomethasone dipropionate by inhalation to systemic corticosteroid therapy allows useful reductions to be made in the oral maintenance doses of corticosteroid. Reductions must be made with caution since there is wide individual variation in response to beclomethasone and in only a minority of patients can oral treatment by completely withdrawn. One hundred and twenty four patients with severe asthma requiring maintenance treatment with oral corticosteroids were included in a multicentre, double-blind, randomized study comparing the effects of inhaled beclomethasone dipropionate (BDP) (250 micrograms.puff-1), beginning with 1,000 micrograms daily, vs placebo (P). Pulmonary function was assessed and dosage of prednisone and BDP (or P) were adjusted every 15 days according to a clinical score. Our results showed, after 3 months: 1) A greater drop-out rate in the P group than in the BDP group (36 vs 6%, respectively, p less than 0.01); 2) A total weaning from prednisone in 76% of patients in the BDP group (mean BDP dosage = 1,270 +/- 340 micrograms.day-1, mean +/- SD), vs 34% in the P group (p less than 0.001). The mean daily dosage of prednisone was reduced from 17 +/- 7.5 mg to 3.1 +/- 7.4 mg in the BDP group vs 15.6 +/- 7.7 mg to 9.1 +/- 9.4 mg in the P group (p less than 0.001) without any relationship between the steroid-sparing effect and the initial dosage of prednisone; 3) Mean change in forced expiratory volume in one second (FEV1) was +7 +/- 21% from the initial value in the BDP group vs -6 +/- 20% in the P group; p less than 0.01. Thus, in patients with severe asthma requiring oral corticosteroids, high-dose BDP has an important oral steroid-sparing effect not related to the initial dosage of oral steroids and allows a better control of airway obstruction than oral corticosteroids alone. Patients with idiopathic pulmonary fibrosis have progressive scarring of the lung and usually die within four to five years after symptoms develop. Treatment with oral glucocorticoids is often ineffective. We conducted an open, randomized trial of treatment with a combination of interferon gamma-1b, which has antifibrotic properties, and an oral glucocorticoid. We studied 18 patients with idiopathic pulmonary fibrosis who had not had responses to glucocorticoids or other immunosuppressive agents. Nine patients were treated for 12 months with oral prednisolone alone (7.5 mg daily, which could be increased to 25 to 50 mg daily), and nine with a combination of 200 microg of interferon gamma-1b (given three times per week subcutaneously) and 7.5 mg of prednisolone (given once a day).
                All the patients completed the study. Lung function deteriorated in all nine patients in the group given prednisolone alone: total lung capacity decreased from a mean (+/-SD) of 66+/-8 percent of the predicted value at base line to 62+/-6 percent at 12 months. In contrast, in the group receiving interferon gamma-1b plus prednisolone, total lung capacity increased (from 70+/-6 percent of the predicted value at base line to 79+/-12 percent at 12 months, P<0.001 for the difference between the groups). In the group that received interferon gamma-1b plus prednisolone, the partial pressure of arterial oxygen at rest increased from 65+/-9 mm Hg at base line to 76+/-8 mm Hg at 12 months, whereas in the group that received prednisolone alone it decreased from 65+/-6 to 62+/-4 mm Hg (P<0.001 for the difference in the change from baseline values between the two groups); on maximal exertion, the value increased from 55+/-6 to 65+/-8 mm Hg in the group that received combined treatment and decreased from 55+/-6 mm Hg to 52+/-5 mm Hg in the group given prednisolone alone (P<0.001). The side effects of interferon gamma-1b, such as fever, chills, and muscle pain, subsided within the first 9 to 12 weeks.
                In a preliminary study, 12 months of treatment with interferon gamma-1b plus prednisolone was associated with substantial improvements in the condition of patients with idiopathic pulmonary fibrosis who had had no response to glucocorticoids. A significant minority of patients with COPD have favourable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side-effects. Long-term administration of inhaled steroids is a safe means of treatment. However, only a few studies have addressed the role of inhaled steroids in patients with COPD, with conflicting results.
                Forty-four patients with stable COPD were defined as 'responders to bronchodilators' (increase in FEV1 > or = 20% following administration of beta 2-agonist) (group A), and 124 as 'non-responders to bronchodilators' (group B). All patients were randomized to receive a 6-week course of either a daily dose of 800 micrograms of inhaled budesonide or placebo, separated by 4 weeks when no medication was taken; were randomized again to receive a 6-week course of either 1600 micrograms day-1 of inhaled budesonide, or 800 micrograms day-1 of inhaled budesonide plus placebo; and were randomized once again to receive a 6-week course of either 40 mg day-1 of prednisone or placebo. All stages were performed in a double-blind cross-over design.
                Following administration of 800 micrograms day-1 of inhaled budesonide, there was an increase in the mean FEV1 from 1.40 +/- 0.20 to 1.92 +/- 0.22 L (P < 0.001) and a significant decrease in inhaled beta 2 agonist consumption in group A. These changes remained almost stable during the increased dose of inhaled budesonide or during prednisone treatment. The mean FEV1 did not change during the placebo period, or in group B in either treatments.
                Treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about one-quarter of patients with stable COPD, and this rate increased to about three-quarters in patients who responded to beta 2-agonist inhalation. There was no additional benefit in using a higher dose of inhaled budesonide or prednisone. This study was designed to assess the efficacy of low dose methotrexate, 15 mg weekly, as a steroid-sparing agent in asthmatic patients requiring long-term oral prednisone treatment.
                The study was a randomised, double blind, placebo controlled, cross over study of 48 weeks duration. Eleven patients with severe steroid-dependent asthma were included. A successful outcome was defined as a reduction in mean prednisone requirements of 7 mg daily compared to baseline requirements, during active treatment.
                Two patients were required to be withdrawn owing to methotrexate-related adverse effects. The mean prednisone dose for patients who completed the study was 14.4 mg per day (95% CI; 13.6, 15.1) during active treatment, and 12.9 mg per day (95% CI: 12.2, 13.6) during placebo treatment (NS). Only one patient reduced his individual dose requirements by more than 7 mg per day, whereas in three patients prednisone requirements actually increased during active treatment. There were no significant differences in symptom scores, pulmonary function data, and exacerbations between active and placebo treatments.
                No significant steroid-sparing effect was obtained using low dose methotrexate in this study. This negative outcome may be attributable to the small population of patients studied, low baseline FEV1, and the omission of a steroid minimisation run-in period. Our results highlight the importance of careful patient selection and a painstaking approach in the management of patients with steroid-dependent asthma. Forty-five steroid-dependent asthmatic outpatients were treated twice daily for 51 weeks with a new inhalation steroid, budesonide (BUD), using a 750 ml spacer. During the initial 15 weeks the prednisone-sparing effects of a high daily dose (1600 micrograms) and a conventional dose (400 micrograms per day) were compared in a double-blind randomized trial including 50 patients. During the remaining 36 weeks 45 patients were treated openly with 1600 micrograms daily. All patients used other antiasthmatic drugs which were maintained throughout the study, except for inhalations of beta-2 agonists that could be used whenever needed. All patients but 2 were able to reduce the daily dose of oral prednisone. The mean daily dose decreased from 13.9 mg to 5.3 mg. Eighteen patients (40%) were able to discontinue oral prednisone. Adrenal gland function improved considerably as prednisone intake decreased. Oropharyngeal thrush frequency showed no change. No severe side effects were observed. The aim of this study was evaluate the predictive value of a 2 week course of prednisolone on the effect of 6 months treatment with inhaled budesonide in patients with stable chronic obstructive pulmonary disease (COPD). Forty patients with stable COPD entered the study, and received prednisolone (37.5 mg o.d.) for 2 weeks. They were subsequently divided into steroid-irreversible and steroid-irreversible, using 15% of baseline as a dividing point. In each group patients were randomized to receive budesonide 400 micrograms b.i.d. or placebo for 6 months. During treatment with prednisolone, three patients dropped out because of side effects. Of the remaining 37, only two patients (5%) were reversible with prednisolone forced expiratory volume in 1s [(FEV1) > 15% of baseline], and among the steroid-irreversible, 26 patients were evaluated after 6 months treatment with either placebo or budesonide. No significant differences in spirometry values, symptoms, or number of exacerbations were found between these two groups. Reversibility with prednisolone is rarely seen in COPD. In outpatients with stable COPD and no signs of asthma or atopy, 2 weeks treatment with prednisolone seems to be of no value in choosing subsequent long-term therapy. In a randomised, controlled study alternate day prednisolone with an initial high dose phase ("prednisolone only series") has been compared with cyclophosphamide plus alternate day low dose prednisolone ("cyclophosphamide-prednisolone series") in 43 patients with previously untreated fibrosing alveolitis (five patients had received prednisolone in minimal dosage). In the prednisolone only series prednisolone 60 mg daily was given for one month and then reduced by 5 mg a week to 20 mg on alternate days or the minimum dose to maintain early improvement. Patients in the cyclophosphamide-prednisolone series received 100, 110, or 120 mg cyclophosphamide daily (depending on body weight) plus 20 mg prednisolone on alternate days. Treatment was continued indefinitely, or changed to the alternative regimen if the patient deteriorated, failed to improve, or developed drug toxicity. For response to treatment (as judged by change in breathlessness score, radiographic appearance, and lung function) patients were classified as improved, stable, or deteriorating. Deaths from cryptogenic fibrosing alveolitis were also analysed. Improvement had occurred at one or more assessments in seven of the 22 patients in the prednisolone only series and in five of the 21 patients in the cyclophosphamide-prednisolone series. At three years, however, only two of the 22 patients in the prednisolone only series were still improved and three stable, compared with one and seven of the 21 patients in the cyclophosphamide-prednisolone series (three of the seven had stopped treatment because of toxicity). Life table analysis suggested better survival in patients in the cyclophosphamide-prednisolone series but this was not significant. At three years 10 of 22 patients in the prednisolone only series had died compared with three of 21 patients in the cyclophosphamide-prednisolone series. With death or failure of first treatment regimen as outcome there was a significant advantage to the patients having cyclophosphamide-prednisolone. This advantage was explained in part by the better lung volumes in this group on admission. After allowance had been made for total lung capacity (TLC), no other factor was predictive of outcome. Analyses of subgroups according to TLC on admission showed that patients with a TLC below 60% predicted did badly and those with a TLC of 80% or more predicted did well with both regimens. Patients with an initial TLC of 60-79% predicted did better with the cyclophosphamide-prednisolone regimen. Side effects were uncommon in both series and those due to cyclophosphamide resolved when treatment was stopped. The combination of cyclophosphamide with prednisolone may be an alternative to prednisolone alone with an initial high dose phase. Many patients, however, failed to respond to either treatment. We have examined, in a prospective randomized controlled trial, the effect of 8- and 16-week initial steroid treatment on the course of idiopathic nephrotic syndrome (INS). Patients with a first episode of INS were randomized to receive standard 8-week prednisolone (2 mg/kg daily for 4 weeks, then 1.5 mg/kg on alternate days for 4 weeks) or prolonged 16-week prednisolone treatment (2 and 1.5 mg/kg daily each for 4 weeks, then 1.5 and 1 mg/kg on alternate days each for 4 weeks). Relapses were treated with prednisolone, 2 mg/kg daily for 2 weeks, then 1.5 mg/kg on alternate days for 4 weeks. Of 45 patients, 23 received standard therapy and 22 prolonged therapy. The mean duration of follow-up was 29.2 and 27.3 months in the standard and prolonged treatment groups, respectively. The time to first relapse was longer in the prolonged treatment (mean 222.2 days, median 120.0 days) than the standard group (mean 134.3 days, median 96.5 days). The percentage of patients with no relapse at 6 and 12 months after prednisolone withdrawal was 40.9% and 27.3% in the prolonged treatment and 21.7% and 8.7% in the standard groups, respectively. The inability to show statistically significant differences between the two groups was probably related to the small number of patients studied. Prolonged therapy did not affect the subsequent relapse rates and proportion of patients with frequent relapses and steroid dependence. The mean dose of prednisolone received, for the initial episode and relapses during the next year, was higher and associated with significant steroid toxicity in the prolonged treatment group. Our findings suggest that 16-week prednisolone treatment for the initial episode of INS may delay occurrence of the first relapse, but results in significant side effects. Prolongation of initial therapy may be useful in developing countries where frequent infections often induce early relapses. Twenty-five consecutive patients admitted with status asthmaticus were blindly randomized to receive intravenous (IV) methylprednisolone every six hours for three days at one of the following dosages: (1) low, 15 mg; (2) medium, 40 mg; or (3) high, 125 mg. All other therapy, including IV and inhaled bronchodilators, was kept constant. We measured forced expiratory volume in 1 s (FEV1) to quantitate response. The high-dose group improved significantly by the end of the first day, the medium-dose group improved by the middle of the second day, but the low-dose group did not improve significantly in three days. Together, the high- and medium-dose groups were significantly improved (FEV1 greater than 50% of predicted) compared with the low-dose group. No serious steroid side effects were encountered. We conclude that the greater benefit of higher doses of steroids, such as 125 mg of methylprednisolone every six hours, justifies their use in severe asthma. 69 patients with steroid-dependent asthma (mean daily prednisolone dose 14.2 [SD 6.1] mg) took part in a randomised, double-blind, placebo-controlled study of 24 weeks' treatment with methotrexate 15 mg weekly. The patients were seen every 4 weeks by the same physician, who reduced the daily prednisolone dose by 2.5 mg if the daily diary card variables and measurements of lung function were unchanged or improved. All other treatment remained unchanged. After 24 weeks of treatment the prednisolone dose had been reduced by a significantly greater proportion in the methotrexate than in the placebo group (50% vs 14%) and the reduction was not sustained after the study treatment stopped. There were substantial abnormalities in liver function tests in 5 of the 38 patients taking methotrexate. The purpose of this study was to evaluate the efficacy and safety of alternate-day prednisone therapy in treating patients with mild-to-moderate cystic fibrosis during a 4-year period. In 15 North American cystic fibrosis centers, we screened 320 patients and enrolled 285 patients from April 1986 to December 1987. Patients were randomly assigned to take prednisone, 1 mg/kg per dose or 2 mg/kg per dose, or a matching placebo given on alternate days. Lung function, clinical status, hospitalizations, growth, and steroid side effects were monitored. During the first 24 months the percentage of the predicted forced vital capacity was greater in the 1 mg/kg group (p < 0.0001) and the 2 mg/kg group (p < 0.01) when each was compared with placebo. Patients in the 1 mg/kg group had a higher percentage of predicted forced vital capacity than placebo patients during the entire 48 months (p < 0.0025), but only in the group of patients who were colonized with Pseudomonas aeruginosa at baseline. For 48 months, the 1 mg/kg group had a higher percentage of predicted forced expiratory volume in 1 second than patients given placebo (p < 0.02). The prednisone-treated groups had a reduction in serum IgG concentrations (1 mg/kg vs placebo, p < 0.007; 2 mg/kg vs placebo, p < 0.003). From 6 months onward, height z scores fell in the 2 mg/kg group compared with those given placebo (p < 0.001). For the 1 mg/kg group, height z scores were lower from 24 months. An excess of abnormalities in glucose metabolism was seen in the 2 mg/kg group compared with the placebo group (p < 0.005). Our findings suggest a role for alternate-day prednisone therapy at a dose of 1 mg/kg in patients with mild to moderate cystic fibrosis. The benefit of improved lung function appears to outweigh the potential for adverse effects when the treatment period is less than 24 months. Forty-six children with steroid-responsive nephrotic syndrome were randomly allocated to receive two different prednisolone regimens for initial therapy. Twenty-nine children (group 1) received an intermittent regimen (60 mg/m2/day for 4 weeks, followed by 40/mg/m2/day on 3 days a week for 4 weeks); 17 children (group 2) had a long-term regimen (60 mg/m2/day for 4 weeks, followed by the same dose on alternate days for 4 weeks and the doses tapered by 10 mg/m2, given on alternate days every 4 weeks for 5 months). There was no difference between the two groups in the regimen used to treat relapses, steroid responsiveness, number of patients with relapses, and frequency of toxic reactions to steroids. However, the number of patients with a relapse within 6 months after initial therapy and the number of those with frequent relapses or steroid dependence were significantly higher in group 1 than in group 2 (P less than 0.05 for both). The data indicate that the long-term tapering regimen appears to be both safe and preferable to the intermittent regimen for initial therapy in children with idiopathic nephrotic syndrome. Nasal polyposis is not a life-threatening disorder but has a great impact on the quality of life. Steroids constitute the first line of treatment of nasal polyps. The aims of this study were to evaluate the quality of life in nasal polyp patients after: (1) a short course of oral steroids; and (2) a long-term treatment with intranasal steroids.
                Patients with severe nasal polyps received either oral prednisone (n = 60) or no steroid treatment (control group, n = 18) for 2 weeks. Patients treated with steroids were also followed-up and evaluated after 12, 24, and 48 additional weeks with intranasal budesonide treatment.
                Patients with nasal polyps showed worse scores on all SF-36 domains, except for physical functioning, compared to the Spanish general population. After two weeks, patients treated with oral prednisone demonstrated a significant improvement (p < 0.05) in all impaired QoL domains compared to both control group and baseline. The mental component summary (51.0 +/- 1.2, p < 0.05) and physical component summary (51.0 +/- 0.9, p < 0.05) were improved compared to both control group and baseline. The improvement of all SF-36 domains was sustained by intranasal budesonida (p < 0.05) after 12, 24, and 48 weeks. Nasal obstruction, sense of smell, and polyp size also improved after both the oral short course and the intranasal long-term steroids treatment (p < 0.05).
                These results suggest that the treatment with a short-course of oral steroids improves the quality of life of patients with severe nasal polyps and that this effect is maintained by a long-term treatment with intranasal steroids. Asthma self-management plans that include doubling the dose of inhaled corticosteroid when the condition deteriorates improve asthma control. Whether doubling the dose of corticosteroid in isolation is effective is unknown. We undertook a randomised controlled trial to investigate the effects of doubling the dose of inhaled corticosteriods when asthma deteriorates.
                390 individuals with asthma who were at risk of an exacerbation monitored their morning peak flow and asthma symptoms for up to 12 months. When peak flow or symptoms started to deteriorate, participants added an active or placebo corticosteroid inhaler to their usual corticosteroid for 14 days to produce a doubling or no change in dose. The primary outcome was the number of individuals starting oral prednisolone in each group.
                During 12 months, 207 (53%) started their study inhaler and 46 (12%) started prednisolone--22 (11%) of 192 and 24 (12%) of 198 in the active and placebo groups, respectively. The risk ratio for starting prednisolone was therefore 0.95 (95% CI 0.55-1.64, p=0.8).
                We recorded little evidence to support the widely recommended intervention of doubling the dose of inhaled corticosteroid when asthma control starts to deteriorate. Although the need for corticosteroids in acute severe asthma is well established the appropriate dose is not known.
                The response to intravenous hydrocortisone 50 mg (low dose), 100 mg (medium dose), and 500 mg (high dose), administered every six hours for 48 hours and followed by oral prednisone, was compared in patients with acute asthma in a double blind randomised study. After initial emergency treatment with bronchodilators subjects received oral theophylline or intravenous aminophylline and nebulised salbutamol four hourly. Patients were given low, medium, or high doses of intravenous hydrocortisone and then 20, 40, or 60 mg/day respectively of oral prednisone with a reducing regimen over the following 12 days. Beclomethasone dipropionate, 400 micrograms twice daily by metered dose inhaler, was also started. Peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and visual analogue dyspnoea scores (VAS) were recorded daily in hospital and PEF and VAS twice daily after discharge for a total of 12 days.
                The 66 subjects (40 female) who completed the study had a mean (SD) age of 31(14) years. On presentation mean (SD) FEV1% predicted in the low (n = 22), medium (n = 20), and high dose (n = 24) groups was 17(13), 19(12), and 19(11) and after emergency bronchodilator treatment 32(20), 30(12), and 36(13). After 24 hours of treatment the respective post-bronchodilator FEV1% predicted values were 62(22), 62(23), and 65(28) compared with 71(24), 69(22), and 71(24) after 48 hours. No significant difference between the groups was detected. PEF and VAS improved with treatment over the 12 days but was not influenced by steroid dose.
                Hydrocortisone 50 mg intravenously four times a day for two days followed by low dose oral prednisone is as effective in resolving acute severe asthma as 200 or 500 mg of hydrocortisone followed by higher doses of prednisone. Inhaled corticosteroids are not as effective as oral corticosteroids in school-aged children with severe acute asthma. It is uncertain how inhaled corticosteroids compare with oral corticosteroids in mild to moderate exacerbations.
                The purpose of this work was to determine whether there is a significant difference in the percentage of predicted forced expiratory volume in 1 second in children with mild to moderate acute asthma treated with either inhaled fluticasone or oral prednisolone.
                This was a randomized, double-blind controlled trial conducted between 2001 and 2004 in a tertiary care pediatric emergency department. We studied a convenience sample of 69 previously healthy children 5 to 17 years of age with acute asthma and forced expiratory volume in 1 second at 50% to 79% predicted value; 41 families refused participation. Albuterol was given in the emergency department and salmeterol was given after discharge to all patients, as well as either 2 mg of fluticasone via metered dose inhaler and valved holding chamber in the emergency department plus 500 microg twice daily via Diskus for 10 doses after discharge (fluticasone group, N = 35) or 2 mg/kg of oral prednisolone in the emergency department plus 5 daily doses of 1 mg/kg of prednisolone after discharge (prednisolone group, N = 34). We measured a priori defined absolute change in percent predicted forced expiratory volume in 1 second from baseline to 4 and 48 hours in the 2 groups. RESULTS. At 240 minutes, the forced expiratory volume in 1 second increased by 19.1% +/- 12.7% in the fluticasone group and 29.8% +/- 15.5% in the prednisolone group. At 48 hours, this difference was no longer significant (estimated difference: 4.0 +/- 3.4; P = .14). The relapse rates by 48 hours were 12.5% and 0% in the fluticasone group and prednisolone group, respectively.
                Airway obstruction in children with mild to moderate acute asthma in the emergency department improves faster on oral than inhaled corticosteroids.
There is no evidence to support the long-term use of oral steroids at doses less than 10-15 mg prednisolone though some evidence that higher doses (≥ 30 mg prednisolone) improve lung function over a short period. Potentially harmful adverse effects e.g.. diabetes, hypertension, osteoporosis would prevent recommending long-term use at these high doses in most patients.