Controlled clinical trial of methylprednisolone in patients with chronic bronchitis and acute respiratory insufficiency. Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease. Early corticosteroid use in acute exacerbations of chronic airflow obstruction. A randomized controlled trial of methylprednisolone in the emergency treatment of acute exacerbations of COPD.
To evaluate the role of corticosteroids as treatment for acute exacerbations of chronic obstructive pulmonary disease, we conducted a double-blind, randomized, placebo-controlled trial in 44 consecutive patients with chronic bronchitis and severe airflow obstruction. All were hospitalized with acute respiratory insufficiency from acute bronchitis. Patients with asthma, atopy, or pneumonia were excluded. Treatment consisted of intravenous aminophylline, inhaled isoproterenol, antibiotics, and either methylprednisolone, 0.5 mg/kg of body weight, or placebo every 6 h intravenously for 72 h. Bedside spirometry was done before and after bronchodilator inhalation three times daily. The methylprednisolone-treated group had a greater improvement in both prebronchodilator and postbronchodilator forced expiratory volume in 1 second (P less than 0.001). More patients with large improvements in their prebronchodilator or postbronchodilator flow rates, or both (greater than or equal to 40% by 72 h), received methylprednisolone (P less than 0.01). Methylprednisolone improved airflow more than placebo when added to standard therapy in patients with chronic bronchitis and acute respiratory insufficiency. Nebulized budesonide has been used successfully to treat acute asthma exacerbation, and we hypothesized that it could also be effective for exacerbations of chronic obstructive pulmonary disease (COPD). In this multicenter, double-blind, randomized, placebo-controlled trial, the efficacy of nebulized budesonide (Pulmicort Respules/Nebuamp), oral prednisolone, and placebo was compared in 199 patients with acute exacerbations of COPD requiring hospitalization. Patients received from randomization (H(0)) to 72 h (H(72)), 2 mg of budesonide every 6 h (n = 71), 30 mg of oral prednisolone every 12 h (n = 62), or placebo (n = 66). All received standard treatment, including nebulized beta(2)-agonists, ipratropium bromide, oral antibiotics, and supplemental oxygen. The mean change (95% confidence interval) in postbronchodilator FEV(1) from H(0) to H(72) was greater with active treatments than with placebo: budesonide versus placebo, 0.10 L (0.02 to 0.18 L); prednisolone versus placebo, 0.16 L (0.08 to 0.24 L). The difference in FEV(1) between budesonide and prednisolone was not significant, -0.06 L (-0.14 to 0.02 L). The occurrence of serious adverse events was similar for all groups. Budesonide had less systemic activity than prednisolone as indicated by a higher incidence of hyperglycemia observed with prednisolone. Both budesonide and prednisolone improved airflow in COPD patients with acute exacerbations when compared with placebo. Nebulized budesonide may be an alternative to oral prednisolone in the treatment of nonacidotic exacerbations of COPD but further studies should be done to evaluate its long-term impact on clinical outcomes after an initial episode of COPD exacerbation. Although their clinical efficacy is unclear and they may cause serious adverse effects, systemic glucocorticoids are a standard treatment for patients hospitalized with exacerbations of chronic obstructive pulmonary disease (COPD). We conducted a double-blind, randomized trial of systemic glucocorticoids (given for two or eight weeks) or placebo in addition to other therapies, for exacerbations of COPD. Most other care was standardized over the six-month period of follow-up. The primary end point was treatment failure, defined as death from any cause or the need for intubation and mechanical ventilation, readmission to the hospital for COPD, or intensification of drug therapy.
                Of 1840 potential study participants at 25 Veterans Affairs medical centers, 271 were eligible for participation and were enrolled; 80 received an eight-week course of glucocorticoid therapy, 80 received a two-week course, and 111 received placebo. About half the potential participants were ineligible because they had received systemic glucocorticoids in the previous 30 days. Rates of treatment failure were significantly higher in the placebo group than in the two glucocorticoid groups combined at 30 days (33 percent vs. 23 percent, P=0.04) and at 90 days (48 percent vs. 37 percent, P=0.04). Systemic glucocorticoids (in both groups combined) were associated with a shorter initial hospital stay (8.5 days, vs. 9.7 days for placebo, P=0.03) and with a forced expiratory volume in one second that was about 0.10 liter higher than that in the placebo group by the first day after enrollment. Significant treatment benefits were no longer evident at six months. The eight-week regimen of therapy was not superior to the two-week regimen. The patients who received glucocorticoid therapy were more likely to have hyperglycemia requiring therapy than those who received placebo (15 percent vs. 4 percent, P=0.002).
                Treatment with systemic glucocorticoids results in moderate improvement in clinical outcomes among patients hospitalized for exacerbations of COPD. The maximal benefit is obtained during the first two weeks of therapy. Hyperglycemia of sufficient severity to warrant treatment is the most frequent complication. In this randomized, double-blind, placebo-controlled trial, we studied the effectiveness of prednisone in reducing the risk of relapse after outpatient exacerbations of chronic obstructive pulmonary disease (COPD).
                We enrolled 147 patients who were being discharged from the emergency department after an exacerbation of COPD and randomly assigned them to 10 days of treatment with 40 mg of oral prednisone once daily or identical-appearing placebo. All patients received oral antibiotics for 10 days, plus inhaled bronchodilators. The primary end point was relapse, defined as an unscheduled visit to a physician's office or a return to the emergency department because of worsening dyspnea, within 30 days after randomization.
                The overall rate of relapse at 30 days was lower in the prednisone group than in the placebo group (27 percent vs. 43 percent, P=0.05), and the time to relapse was prolonged in those taking prednisone (P=0.04). After 10 days of therapy, patients in the prednisone group had greater improvements in forced expiratory volume in one second than did patients in the placebo group (mean [+/-SD] increase from base line, 34+/-42 percent vs. 15+/-31 percent; P=0.007). Patients in the prednisone group also had significant improvements in dyspnea, as measured by the transitional dyspnea index (P=0.04) and by the dyspnea domain of the Chronic Respiratory Disease Index Questionnaire (P=0.02), but not in health-related quality of life (P=0.14).
                Outpatient treatment with oral prednisone offers a small advantage over placebo in treating patients who are discharged from the emergency department with an exacerbation of COPD.
                Copyright 2003 Massachusetts Medical Society To determine the benefit of early steroid use in acute exacerbations of chronic airflow obstruction in the ED, 113 patients with an average age of 66 years, acute or chronic dyspnea, an FEV1 of < 60% and FEV1/FVC ratio of < 60% were included in a randomized, double-blinded, interventional clinical trial. All patients received the same bronchodilator treatment. At 6 hours the steroid- treated group showed a 21.71 L/min improvement in PEFR (P < .05) and 0.14 L improvement in FEV1 (P < .05), while the nonsteroid group showed insignificant improvements of 5.52 L/min and 0.02 L, respectively. Of those patients receiving steroids, 22 achieved > 40% improvements in PEFR by 6 hours and 17 achieved similar results in FEV1, whereas of those not receiving steroids, 13 and 8, respectively, achieved improvements. Within 24 hours of observation in the ED, 16 patients receiving steroids were discharged and none relapsed within 2 weeks. Of those not receiving steroids, only 10 were discharged and 3 returned with exacerbations. Although early response to steroids in chronic airflow obstruction is variable, the overall medical and cost benefits justify their early use in acute exacerbations. We conducted a randomized, controlled double-blind study to determine whether intravenous administration of methylprednisolone early in the therapy for acute exacerbations of COPD would improve pulmonary function in the Emergency Department and reduce the need for hospitalization. Ninety-six patients completed the study. All were at least 50 years of age and had no history of asthma. Patients received aminophylline and hourly administration of aerosolized isoetharine. Methylprednisolone (100 mg) or physiologic saline solution was given within one-half hour of arrival in the Emergency Department. Spirometry was performed initially and after the third and fifth aerosol treatments. We found no greater improvement in FEV1 in the group receiving the steroid (37 percent) than in the control group (43 percent; NS). There was also no difference in the rate of hospitalization (33 percent in the steroid-treated group vs 30 percent in the control group; NS). We conclude that early administration of methylprednisolone does not affect the emergency phase of treatment for acute exacerbations of COPD.
Treatment of an exacerbation of COPD with oral or parenteral corticosteroids significantly reduces treatment failure and the need for additional medical treatment and shortens hospital stay. It increases the rate of improvement in lung function and dyspnoea and the improvement continues during treatment, but there is a significantly increase in the risk of an adverse drug event occurring. The optimal dose and length of treatment regime needs to be better defined.