Corticosteroid treatment of eosinophilic meningitis. Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis. Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization. Topical corticosteroids in chronic rhinosinusitis: a randomized, double-blind, placebo-controlled trial using fluticasone propionate aqueous nasal spray. Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A double-blind, placebo-controlled trial. Early administration of corticosteroids in emergency room treatment of acute asthma. A multicenter randomized double-blind placebo-controlled trial of adjunctive corticosteroids in the treatment of Pneumocystis carinii pneumonia complicating the acquired immune deficiency syndrome. Corticosteroids in COPD. A clinical trial and reassessment of the literature. Strategy aimed at reduction of sputum eosinophils decreases exacerbation rate in patients with asthma.
The role of corticosteroids in the treatment of eosinophilic meningitis has not been definitely established. Patients given a 2-week course of prednisolone (treatment group), 60 mg/day, were compared with those given placebo (control group) in a randomized, double-blind trial. Fifty-five patients were enrolled in each group. There were significant differences between the treatment and control groups, with regard to the number of patients who still had headache after 14 days (5 vs. 25, respectively; P=.00004), the median length of time until complete disappearance of headache (5 vs. 13 days, respectively; P=.00000), and the number of patients who had repeat lumbar puncture (7 vs. 22, respectively; P=.002). Serious side effects were not detected. These results indicate that a 2-week course of prednisolone was beneficial in relieving headache in patients with eosinophilic meningitis. To study the effect of highdose prednisone on intracranial pressure (ICP), cranial computed tomographic (CT) findings, and clinical outcome in young children with moderate to severe tuberculous meningitis (TBM).
                Prospective, controlled, randomized study.
                Continuous lumbar, cerebrospinal fluid pressure monitoring and contrasted CT scanning were performed in 141 consecutive children with TBM at admission. All children were then randomly allocated to a nonsteroid group (71 children) or a steroid group (70 children) who received prednisone (first 16 children, 2 mg/kg per day; next 54 children, 4 mg/kg per day) for the first month of treatment. ICP monitoring and CT scanning were repeated regularly, and clinical outcome was assessed after 6 months of antituberculosis treatment.
                No statistically significant difference in ICP or the degree of hydrocephalus (as demonstrated by CT scan) was found between the steroid and nonsteroid groups after the first month of treatment. Basal ganglia infarcts developed in 16% of children in the steroid group and 24% in the nonsteroid group during the first month of treatment. Neither this incidence nor the eventual size of infarcts present at admission differed significantly between the two treatment groups. Single or multiple tuberculomas were seen on the first CT scans of 7 children (5%), whereas tuberculomas developed in 11 children (8%) at treatment. Both the response of the tuberculomas to treatment and the incidence of new tuberculomas were significantly improved by steroid therapy. Basal enhancement was also significantly less in the steroid group after 1 month of treatment. Steroids lowered mortality in stage III TBM significantly. Similarly, more surviving children in the steroid group had IQs of greater than 75 than did the those in the nonsteroid group. No significant difference was found in the incidence of motor deficit, blindness, or deafness.
                Corticosteroids significantly improved the survival rate and intellectual outcome of children with TBM. Enhanced resolution of the basal exudate and tuberculomas by steroids was shown by serial CT scanning. Corticosteroids did not affect ICP or the incidence of basal ganglia infarction significantly. Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia.
                The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia (CAP) requiring hospitalization.
                An open label, prospective, randomized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan.
                Thirty-one adult CAP patients who required hospitalization were enrolled.
                Fifteen patients received 40 mg of prednisolone intravenously for 3 days (steroid group). Sixteen patients did not receive prednisolone (control group). Both groups were also evaluated for their adrenal function. The primary endpoint was length of hospital stay. Secondary endpoints were duration of intravenous (IV) antibiotics and time required to stabilize vital signs. Both groups demonstrated similar baseline characteristics and length of hospital stay, and yet a shorter duration of IV antibiotics was observed in the steroid group (p < 0.05). In addition, vital signs were stabilized earlier in the steroid group (p < 0.05). These differences were more prominent in the moderate-severe subgroup but not as significant in the mild-moderate subgroup. The prevalence of relative adrenal insufficiency (RAI) in both groups was high (43%), yet there was no difference in baseline characteristics between patients, with or without RAI. In multiple regression models, RAI seemed to have no influence on clinical courses.
                In moderate-severe CAP, administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy. Chronic rhinosinusitis (CRS) is a recalcitrant inflammatory process which has a marked detrimental impact on quality of life. At the present there is no cure for this condition, measures are taken to stop progression, and provide symptomatic relief. Topical corticosteroids are commonly prescribed in the management of CRS, but few trials show effectiveness in clinical settings. We set up a randomized, double-blind, placebo-controlled trial to study the effectiveness of a topical corticosteroid agent--fluticasone propionate aqueous nasal spray (FPANS) in patients with CRS. We measured symptoms, diary card, and rigid endoscopy scores, acoustic rhinometry, middle meatal swabs, blood tests--CRP, ESR, WBC, and eosinophil count. Measurements were done at the start of the trial, at 8 weeks, and 16 weeks where possible. Twenty-two patients completed the trial, 9 received FPANS, and 13 had placebo. There was no difference between the 2 groups on all counts. When patients were considered as one group, there was an improvement in the diary card scores (p = 0.054), comparing baseline to 8 or 16 weeks. There was no evidence that the regular use of topical corticosteroid increased the risk of developing an infection. An important observation was that the topical corticosteroid did not precipitate acute sinusitis. There is compelling evidence that topical corticosteroids down-regulate cytokine expression, and it is likely that a larger, and longer multi-centre trial may prove their efficacy in CRS. Preliminary reports suggest that patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia may benefit from the addition of corticosteroid treatment to antibiotic therapy.
                We conducted a double-blind, placebo-controlled trial to assess the efficacy of adjunctive corticosteroids in patients with AIDS and severe P. carinii pneumonia. Patients with marked abnormalities in gas exchange who had been treated with antibiotics for less than 72 hours were randomly assigned to receive either methylprednisolone (40 mg) or placebo every 6 hours for 7 days, in addition to treatment for 21 days with trimethoprim-sulfamethoxazole. The primary outcome measures were survival until hospital discharge and the development of respiratory failure.
                Twenty-three patients were enrolled in the study; there were no significant differences in base-line clinical or laboratory measures between the two treatment groups. Of 12 patients treated with corticosteroids, 9 (75 percent) survived until hospital discharge, as compared with only 2 of 11 placebo recipients (18 percent) (P less than 0.008). Respiratory failure developed in nine placebo recipients, as compared with only three patients treated with corticosteroids (P less than 0.008). No patient required the interruption or discontinuation of corticosteroid or antibiotic treatment because of toxicity or a complicating event. Because of the marked difference in survival, it was deemed unethical to continue the trial, and the study was terminated.
                Early adjunctive corticosteroid therapy can improve survival and decrease the occurrence of respiratory failure in patients with AIDS and severe P. carinii pneumonia. 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. A multicenter placebo-controlled trial of early short-term high-dose methylprednisolone enrolled 78 patients with moderate to severe Pneumocystis carinii pneumonia (PCP) complicating HIV infection. The mean pressure of oxygen (PO2) at study entry was 55 mm Hg for the 71 patients who had blood gases monitored while breathing room air. Patients were randomized to receive methylprednisolone (40 mg) or placebo parenterally twice daily for 10 days, and the first dose of study medication was given within 24 h of the first dose of antimicrobial therapy for PCP. The primary end point included death, need for mechanical ventilation for > 6 days, or a partial PO2 < 70 mm Hg while breathing room air 10 days after initiation of treatment. There was no statistically significant difference in the primary end point between patients randomized to corticosteroid (CS) or placebo (PL) (p = 0.522; 95% CI = -0.30, 0.16). The incidence of superinfections during therapy or of other HIV-associated infections or malignancies in the 6 months following treatment for PCP was not significantly different between the two groups. More patients randomized to placebo had to discontinue treatment with trimethoprim-sulfamethoxazole because of hypersensitivity than those randomized to corticosteroids (p = 0.039). We conclude that addition of corticosteroids does not significantly affect the outcome of PCP in patients with HIV and a PO2 < 70 mm Hg on room air at presentation but lowers the incidence of hypersensitivity reactions to trimethoprim-sulfamethoxazole. A placebo-controlled, double-blind cross-over trial was conducted to assess whether 16 men with chronic obstructive pulmonary disease (COPD) would benefit from orally taken corticosteroids. Two weeks of treatment with 40 mg of prednisone daily did not result in improvement of pulmonary symptoms or function in the group as a whole, although one patient had small improvement in airflow. The baseline spirometric data and beta-agonist responsiveness of the patients in the study were then compared to a reference population consisting of 264 men who fulfilled a criteria for chronic obstruction out of 730 men who comprised a systematic sample drawn from all patients referred for spirometry at three hospitals. Our study subjects and those of five similar trials of corticosteroids in COPD had more severe obstruction than this reference group. Furthermore, the proportion of steroid responders found in each study was inversely related to the baseline FEV1 of the patients examined. It appears that previous studies of corticosteroids in COPD may have overestimated the number of COPD patients who might benefit from corticosteroids, due to a bias resulting from the selection of severely obstructed subjects. Under Global Initiative for Asthma guidelines, the clinical control of disease activity and the adjustment of treatment in patients with asthma are based on symptoms, use of rescue medication, lung function and peak expiratory flow measurement (standard strategy). We investigated whether a strategy to reduce the number of sputum eosinophils (EOS strategy) gives better clinical control and a lower exacerbation rate compared with the standard strategy. Fifty-five patients with moderate to severe asthma entered this open, randomized, parallel-group study and visited the out-patient department every 3 months for 18 months. The dose of corticosteroids was adjusted according to the standard strategy or the percentage of sputum eosinophils (EOS strategy). During the study period, the EOS strategy led to a significantly lower incidence of asthma exacerbations compared with the standard strategy group (0.22 and 0.78 exacerbations per year per patient, respectively). There were significant differences between the strategies in time to first exacerbation.
Corticosteroids significantly help relieve headache in patients with eosinophilic meningitis. However, there is only one RCT supporting this benefit and this trial did not clearly mention allocation concealment and stratification. Future well-designed RCTs may be necessary.