Dose Reduced

Abstract: We have demonstrated recently that 1 year of regular inhaled budesonide use can produce substantial improvements in airway responsiveness accompanied by significant improvements in clinical asthma severity. The present study was designed to evaluate whether these improvements are maintained when the dose of budesonide is reduced. At the end of the original study, 28 subjects with asthma, who had been in the active-treatment arm of the study were randomized either to continue taking the dose of budesonide taken in the original study or to have the dose reduced. Airway responsiveness to methacholine, bronchodilator requirements, symptoms, and spirometry were assessed after 6 weeks and 3 months. During the 3 months, no subject experienced an asthma exacerbation, and there was no evidence of change in airway responsiveness in subjects who had their steroids reduced (provocative concentration causing a 20% drop in FEV 1 : initial, 2.03 mg/ml; final, 1.91 mg/ml), and this change was not different from change in subjects maintained with a higher dose (initial, 3.02 mg/ml; final, 3.12 mg/ml) ( p = 0.39). Similarly, there was no evidence of any change in bronchodilator requirements ( p = 0.89). However, after 3 months of reduced steroid use, there was a small decline in spirometry (FEV 1 percent predicted: initial, 84.4%; final, 81.5%), and this change was significantly different from change in subjects in whom steroids were not reduced (initial, 90.2%; final, 90.2%) ( p = 0.002). At 3 months, symptoms (predominantly sputum production) were also beginning to redevelop in the reduced budesonide group ( p = 0.056). The results suggest that, when inhaled steroids are reduced after prolonged treatment, improvements in airway responsiveness can be maintained for at least 3 months and that a deterioration in spirometry and symptoms may precede an increase in responsiveness.

Abstract: Isolated rat hearts (n = 15 per group) were subjected to regional ischemia (10 min) and reperfusion. Superoxide dismutase (SOD; 8 X 10(3), 2 X 10(4), 4 X 10(4), 6 X 10(4), 8 X 10(4), 1.2 X 10(5), or 1.6 X 10(5) IU/l) given early (i.e., throughout the experiment) reduced the incidence of reperfusion-induced ventricular fibrillation (VF), the dose-response characteristics describing an asymmetric U-shaped curve. The optimal dose of SOD (8 X 10(4) IU/l) reduced VF incidence from its control value of 87 to 27% (P less than 0.05). Given late (i.e., 2 min before reperfusion), this dose of SOD exerted a reduced but nonetheless significant antifibrillatory effect. Early administration of catalase (1 X 10(3), 1 X 10(4), 2.5 X 10(4), 5 X 10(4), 1 X 10(5), 1.5 X 10(5), or 1 X 10(6) IU/l) reduced VF incidence in a linear dose-dependent manner, from its control value of 87 to 7% with 1 X 10(6) IU/l (P less than 0.05). Late administration of this dose reduced VF incidence from its control value of 87 to 27% (P less than 0.05). Allopurinol (0.07, 0.15, 0.37, 0.73, 1.10, or 1.47 mM added to the perfusate throughout the experiment) significantly reduced VF incidence over a wide range of doses, but low and high doses were ineffective. Pretreatment with allopurinol (0, 0.01, 0.02, 0.05, 0.10, 0.20, or 0.50 g.kg-1.day-1 per os 48, 24, and 1 h before study) reduced VF incidence from its control value of 93 to less than 50% at several doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: To assess whether the use of larger than usual doses of inhaled steroid to treat severe asthma may adversely affect bone turnover and whether such an effect may be mitigated by altering the dose schedule, we investigated the effects of budesonide (BUD) on serum osteocalcin and the urinary output of hydroxyproline and calcium. Healthy adults were administered 1.2 or 2.4 mg of BUD per day (N = 40) or placebo (N = 8) in a crossover, double-blind comparison of morning versus diurnal dosing schedules for 1 month each. Both BUD doses reduced the 24-hour urinary free-cortisol output (p less than 0.001) and serum osteocalcin (p less than 0.001). The larger dose reduced the morning serum cortisol levels (p = 0.002). Neither dose increased the 8 AM urinary calcium or hydroxyproline output. Osteocalcin and plasma cortisol levels were higher on morning than on diurnal dosing (p = 0.01). The 24-hour urinary free-cortisol output was the same with either schedule (p = 0.96). Additional study is required to assess the clinical importance of the inhibitory effect of BUD on bone formation, as evidenced by the reduction in osteocalcin levels. Of concern is the possibility of serious bone complications resulting from the long-term use of inhaled steroid, particularly in growing children or patients in whom other risk factors for osteoporosis are present. The clinical advantage, if any, of morning dosing remains questionable.