Asthma References ================= Engel, T., et al Glucocorticosteroid therapy in acute severe asthma: A critical review Eur Respir J 4(7):881, 1991 Background: The value of glucocorticosteroid therapy has not been clearly defined in the setting of acute severe exacerbations of asthma. Methods: The authors of this Scandinavian study reviewed the findings of 24 studies of steroid treatment in patients with acute severe asthma. Particular attention was paid to the methodological adequacy of the studies. Results: Many of the studies were considered to contain methodological flaws. However, most of the placebo-controlled studies conducted in adults and children with acute severe asthma have demonstrated a beneficial effect of steroid therapy on pulmonary function parameters, arterial oxygen tension, or reduction of the need for hospital admission. A dose-response relationship was observed in only two of ten studies that examined this parameter, and these studies examined only low doses of steroids. Few studies have examined the effects of steroids on the prevention of relapses. Only one of two studies in adults suggested a protective effect within 7-10 days after presentation, while all three studies conducted in children demonstrated a protective effect for up to four weeks. An overview of all studies examined failed to demonstrate an advantage of a particular route of administration (i.e., oral or IV). Conclusions: Based on their review, the authors suggest that steroid administration is a beneficial supplement to symptomatic treatment in patients with acute severe asthma, that a dose of 100-200mg of methylprednisolone in three or four divided doses over 24 hours is sufficient in adults (smaller doses may be sufficient in children), that higher doses may be associated with increased side effects, and that oral and IV administration appear to be equally effective. Jonsson, S., et al Comparison of the oral and intravenous routes for treating asthma with methylprednisolone and theophylline Chest 94(4):723, October 1988 This random, prospective study, from the University of Iceland, compared the effects of oral and IV steroid and theophylline therapy in 22 patients over the age of 20 presenting with acute exacerbations of asthma. In addition to inhaled beta-agonists, the patients were treated with either IV methylprednisolone (80mg/24 hr) plus IV aminophylline (600mg/day in patients weighing 55kg or less, 800mg/day in patients weighing 55-75kg, and 1000mg/day in patients weighing over 75kg), or with comparable doses of oral methylprednisolone (80mg/day in two divided doses) and a sustained-release oral theophylline preparation (200mg, 300mg, and 400mg daily in the three body weight groups). The degree of airway obstruction on admission was considered to be moderate based on initial spirometric testing (mean PaO2 on admission, 69.2 and 69.5mm Hg in the two groups). All of the study parameters improved in both treatment groups over the four-day study period. By day four, the mean FEV1 had reached the lower limits of normal. On days 3-4, patients receiving IV therapy exhibited a slight decline in FEV1. Both treatment regimens were associated with comparable improvement in spirometric parameters, dyspnea and wheezing, and arterial blood gas values. Side effects were more common with IV therapy (36% vs. 9% with oral therapy), but were minor and did not require discontinuation of treatment. The findings suggest that, in patients with acute asthma of moderate severity who are able to tolerate oral medications, oral methylprednisolone and theophylline in the doses listed in addition to inhaled beta-agonist therapy may be effective. Advantages of the oral regimen include lower cost, and reduced discomfort and immobility. Engel, T., et al Methylprednisolone pulse therapy in acute severe asthma: a randomized, double-blind study Allergy 45(3):15, April 1990 The authors of this random, double-blind, Danish study compared the effects of a single IV dose of methylprednisolone (1g given in 500ml of normal saline over 30 minutes) with a course of oral prednisolone (50mg initially, tapered until discontinuation of therapy over 18 days) in 18 episodes of acute severe asthma occurring in 15 patients. The study excluded patients receiving oral steroid maintenance therapy in doses above 10mg daily. The initial FEV1 was 33% of predicted in patients receiving IV methylprednisolone and 43% of predicted in those receiving oral prednisolone. There were no significant differences between the two groups in the peak expiratory flow (PEF) in the initial 24 hours after initiation of treatment, or in the time required to achieve a PEF above 70% of predicted. The mean improvement in FEV1 did not differ significantly in the two groups, although by 24 hours the mean FEV1 was higher in patients receiving oral prednisolone (65.8% vs. 50.8% in those receiving IV methylprednisolone). This trend continued to be observed one week after treatment, but disappeared over the remainder of the twelve-week study period. Oral prednisolone therapy was prescribed due to deterioration during the twelve-week period for 75% of patients initially receiving IV methylprednisolone, compared to 50% of those initially receiving oral prednisolone. Patients initially treated with IV methylprednisolone also exhibited a tendency to increased use of beta-2 agonists. There were no serious side effects of treatment. These findings suggest that, despite its long-lasting effects demonstrated in other inflammatory disorders, a single 1g dose of IV methylprednisolone does not appear to be superior to conventional courses of oral prednisolone in patients with acute severe asthma. Marquette, C.H., et al High-dose and low-dose systemic corticosteroids are equally efficient in acute severe asthma Eur Resp J 8(1):22, January 1995 BACKGROUND: Although it is generally accepted that corticosteroids are indicated in patients with acute asthma, opinions conflict regarding the optimal dose to be employed. Significant complications including acute myopathy and sudden death have been reported with high-dose steroids. METHODS: This randomized, double-blind French study compared the effects of low-dose and high-dose corticosteroids in 47 patients aged 18-65 presenting with acute severe asthma. The patients were treated with IV aminophylline (10mg/kg/day), nebulized albuterol (5mg every 4-6 hours), and IV albuterol (0.25mg/hour), in addition to IV methylprednisolone at a dose of either 1mg/kg/day or 6mg/kg/day. RESULTS: Both groups exhibited significant improvement in FEV1 by eight hours after study entry. By 24 hours, mean postbronchodilator FEV1 had increased from 32% (at baseline) to 59% of predicted in the low- dose steroid group, and from 27% to 51% of predicted in the high-dose group. There were no statistically significant differences between the groups in the degree of improvement in FEV1 throughout the 48-hour study period, the mean duration of hospitalization (7.1 and 8.2 days in the low- and high-dose steroid groups, respectively), or in the frequency of secondary worsening of bronchospasm (one patient in each group). No patient experienced adverse cardiovascular or gastrointestinal effects. Patients in the high-dose group exhibited a greater mean increase in blood sugar, and a higher mean white blood cell count than patients in the low-dose group. CONCLUSIONS: These findings fail to demonstrate an advantage of high- dose over low-dose corticosteroids in adults with severe acute asthma CORTICOSTEROIDS IN ACUTE SEVERE ASTHMA: EFFECTIVENESS OF LOW DOSES Bowler, S.D., et al, Thorax 47(8):584, August 1992 BACKGROUND: It has been established that corticosteroid therapy is beneficial in patients with acute severe asthma. However, the optimal steroid dose in these circumstances has not been established. METHODS: This random, double-blind British study compared the effects of three steroid doses in 66 adults presenting with acute severe asthma requiring hospital admission after ED treatment. The patients received 48-hour courses of IV hydrocortisone (50, 200, or 500mg every six hours) followed by tapered courses of oral prednisone (with initial doses of 20, 40, or 60mg daily). RESULTS: There were no significant differences between the three treatment groups in improvement in FEV1 after 24 and 48 hours of IV therapy. This finding was also observed in the subgroup with the most severe asthma (FEV1 less than 30% of predicted after ED treatment). Twelve-day outcome data were available for 40 patients. The mean morning prebronchodilator PEF tended to be higher in patients treated with high-dose steroids (95% of predicted, compared with 78% of predicted in patients treated with low- and intermediate-dose steroids). However, there were no differences between the groups in mean afternoon post-bronchodilator PEF (87-102% of predicted). The patients' subjective assessment of symptomatic improvement was not influenced by the steroid dose. CONCLUSIONS: Although some patients may require high-dose steroid therapy, recovery parameters do not appear to be affected by the dose of corticosteroids within the range employed in this study. The use of high doses is more costly, and may be more likely to produce adverse side effects.