A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis. Additive effects of prednisolone and beclomethasone dipropionate in patients with stable chronic obstructive pulmonary disease. A multicenter study of alternate-day prednisone therapy in patients with cystic fibrosis. Cystic Fibrosis Foundation Prednisone Trial Group. Corticosteroids in acute severe asthma: effectiveness of low doses. High doses of inhaled corticosteroids in unstable chronic asthma. A multicenter, double-blind, placebo-controlled study. Role of corticosteroids in the management of chronic obstructive lung disease: factors predicting response. High-dose inhaled fluticasone does not replace oral prednisolone in children with mild to moderate acute asthma. Doubling the dose of inhaled corticosteroid to prevent asthma exacerbations: randomised controlled trial. The response to inhaled and oral steroids in patients with stable chronic obstructive pulmonary disease.
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. 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. 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. 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. 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. A double-blind crossover trial of prednisolone was conducted in 70 patients of chronic obstructive lung disease (COLD). Emphysema dominated the clinical picture in 38, rest being chronic bronchitis with varying degrees of air trapping. None of the patients had clinical asthma. All the patients had obtained maximal benefit from an optimal dose of bronchodilators prior to entering the study. Prednisolone in a dose of 0.8 mg/kg was prescribed in a double blind crossover manner with identical appearing placebo tablets. Patients were evaluated on a weekly basis for an objective as well as a subjective response and side effects of therapy. Thirty-four patients demonstrated a statistically significant improvement in pulmonary functions. In 20 others only subjective response was observed. A good objective response was predicted by a pre-study variability in FEV1, disease duration of less than 10 years and a history of smoking less than 50 pack years. 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. 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. 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.
Oral corticosteroids at prednisolone-equivalent dose of 1 to 2 mg/kg alternate days appear to slow progression of lung disease in CF; benefit should be weighed against occurrence of adverse events. Risk-benefit analysis of low-dose alternate days corticosteroids is important and the short-term use of oral corticosteroids should be better evaluated.