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Inhaled corticosteroid has been shown to be effective in the management of asthma. However, there is a lack of studies that assess the effect of cessation after long-term treatment with inhaled corticosteroid. This question was addressed in 28 children with stable asthma, aged 11 to 18 yr of age, who had completed 28 to 36 months of treatment with inhaled corticosteroid (budesonide 200 µg 3 times/day) and inhaled β-2-agonist (salbutamol 200 µg 3 times/day). The children were randomized in a 1:2 ratio in a double-blind study either to continue budesonide (n = 8) during a period of 6 months or to decrease the dose of budesonide (n = 20) within 2 months, followed by placebo for 4 months. Treatment with salbutamol 600 µg daily was continued in both groups. Eight children from the tapering-off group withdrew, mainly due to symptoms of asthma, compared with none in the continuous treatment group. Five patients in the tapering-off group experienced exacerbations for which prednisolone was given, compared with no...

We have investigated separate and interactive effects of corticosteroids and bronchodilators on airflow obstruction and airway hyperresponsiveness. Twelve allergic subjects with asthma were treated in a double-blind, crossover, randomized study with budesonide, 1.6 mg daily for 3 weeks, prednisone, 40 mg daily, for 8 days, and placebo. After each period, dose-response curves were measured on 4 study days with doubling doses of salbutamol, ipratropium, a combination of salbutamol and ipratropium, and placebo until a plateau in FEV1 was reached. A histamine challenge was then performed, and the provocation concentration causing a 20% fall in FEV1 (PC20) was calculated. The budesonide and prednisone regimens were equipotent. FEV1 was 81.2% of predicted after budesonide, 81.0% predicted after prednisone, and 67.5% predicted after placebo, bronchodilatation thus being 13.7% predicted (budesonide) and 13.5% predicted (prednisone). PC20 improved with 2.17 doubling concentrations (DCs) after budesonide, and 1.86 DCs after prednisone, compared with that of placebo. Salbutamol caused stronger bronchodilatation than ipratropium (26.2% versus 14.7% predicted) and a better protection against histamine challenge (3.95 versus 1.12 DC). The effects of corticosteroids and bronchodilators on FEV1 and PC20 were, in general, additive. This study emphasizes different modes of action on both airflow obstruction and airway hyperresponsiveness by corticosteroids and bronchodilators, and it demonstrates no enhancement of bronchodilator action by corticosteroids.

Background: The institution of inhaled corticosteroids is generally advocated for effective treatment of patients with asthma. It is yet unknown what is the best time to start inhaled corticosteroid therapy and especially whether delayed introduction is harmful. Phase 1: In a previous study in patients with asthma and COPD, we found that 2.5 years of treatment with a beta(2)-agonist plus inhaled corticosteroid (BA+CS) was more effective in improving the FEV(1) and the provocative concentration of histamine causing a 20% reduction in FEV(1) (PC20) than treatment with a beta(2)-agonist plus anticholinergic (BA+AC) or placebo (BA+PL). Phase 2: We extended this study with 6 months to investigate whether delayed introduction of inhaled CS therapy (800 mu g beclomethasone dipropionate) in the groups previously not treated with inhaled CS (BA+/-AC) could also improve FEV(1) and PC20 to the same degree, A distinction was made between patients with predominantly asthma (high baseline reversibility, Delta FEV(1) greater than or equal to 9% of predicted), and predominantly COPD (low baseline reversibility, Delta FEV(1) Results: Improvement of FEV(1) percent predicted by inhaled CS was comparable both in the asthmatics between phase 1 (13.8% predicted) and phase 2 (8.5% predicted; p=0.13) as well as in the patients with COPD (2.5% and 1.5% predicted, respectively), PC20, however, increased significantly more in the asthmatics in phase 1 (1.77 doubling concentration [DC]) than in phase 2 (0.79 DC; p=0.03). Improvement of PC20 in the patients with COPD was not significantly higher in phase 1 (0.74 DC) than in phase 2 (0.00 DC; p=0.19). Conclusions: Our study indicates that although delayed introduction of inhaled CS in asthmatics leads to similar improvements in FEV(1), improvements in PC20 are significantly less. These findings in patients with longer-existing asthma concur with other findings in newly detected asthma. We suggest that institution of inhaled CS therapy should not be postponed in asthmatics with documented airways obstruction and reversibility.

Airways hyperresponsiveness is a hallmark of asthma, and many patients with COPD also demonstrate hyperresponsiveness. Inhaled corticosteroids improve hyperresponsiveness, but the extent of improvement may vary considerably between patients. This study was designed to determine which patient characteristics predict these differences in response. Patients with mild to moderately severe obstructive airways disease (asthma and COPD) were selected if PC20 less than or equal to 8 mg/ml and FEV(1)

Background - Despite effective treatments, the morbidity and mortality of obstructive airways disease (asthma and COPD) remains high. Home monitoring of peak expiratory dow (PEF) is increasingly being advocated as an aid to better management of obstructive airways disease. The few available studies describing effects of treatment on the level and variation of PEF have involved relatively small numbers of subjects and did not use control groups. Methods - Patients aged 18-60 years were selected with PC20 less than or equal to 8 mg/ml and FEV(1) Results - Improvements in PEF occurred within the first three months of treatment with BA + CS and was subsequently maintained: the mean (SE) increase in morning PEF was 51 (8) l/min in the BA + CS group compared with no change in the other two groups. Similarly, afternoon PEF increased by 22 (7) l/min. Diurnal variation in PEF (amplitude %mean) decreased from 18.0% to 10.2% in the first three months of treatment with BA + CS. Within-subject relations between changes in diurnal variation in PEF and changes in PC20 were found to be predominantly negative (median rho-0.40) but with a large scatter. Relations between diurnal variation ation in PEF and changes in symptom scores, FEV(1), and bronchodilator response were even weaker. Conclusions - In patients with moderately severe obstructive airways disease, PEF rates and variation are greatly improved by inhaled corticosteroids. Since the relation of diurnal PEF variation with PC20 symptoms, FEV(1), and bronchodilator response were all weak, these markers of disease severity may all provide different information on the actual disease state. PEF measurements should be used in addition to the other markers but not instead of them.

In a double-blind study of 2 parallel groups of 15 allergic asthmatic patients each, we investigated whether treatment with inhaled budesonide has a dose- and time-dependent effect on the degree of bronchial hyperreactivity. The patients were randomly allocated to treatment with either 200 or 800 micrograms budesonide per day for a period of 8 wk. The active treatment period was preceded by a selection period of 3 wk, and a single-blind placebo period of 2 wk. During these initial 5 wk the maintenance treatment of the patients, including cromolyn sodium and inhaled corticosteroids, was withheld. Spirometry and inhalation provocation tests with methacholine were carried out, and the symptom score was recorded every 2 wk. The methacholine provocation concentrations (geometric mean) causing a decrease in FEV1 of 20% (PC20) in the 200 and 800 micrograms/day treatment groups just before the active treatment period were 0.90 and 0.91 mg/ml, respectively. These values increased significantly to 1.21 and 1.84 mg/ml after 2 wk of treatment (p less than 0.05 and p less than 0.001, respectively) and to 1.55 and 2.74 mg/ml after 8 wk of treatment (p less than 0.01 and p less than 0.001). During the whole study period budesonide in a dosage of 800 micrograms/day induced a significantly larger change in PC20 than in a dosage of 200 micrograms/day. The FEV1 before treatment was 91 +/- 3% (SEM) and 84 +/- 2% of the predicted value in the 200 and 800 micrograms/day treatment groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

We wanted to compare the efficacy and safety of fluticasone propionate, a new topically active inhaled corticosteroid, to that of high dose beclomethasone dipropionate, in severe adult asthma. Patients currently receiving between 1.5-2.0 mg.day-1 of an inhaled corticosteroid were treated for six weeks in a double-blind, randomized, parallel group study with 1 mg.day-1 fluticasone propionate (n=82), or 2 mg.day-1 beclomethasone dipropionate (n=72). Mean morning peak expiratory flow rates (PEFR) increased from 303 to 321 l.min-1 with fluticasone propionate, and from 294 to 319 1.min-1 with beclomethasone dipropionate. There was an increase in evening PEFR, asthma symptoms improved, and rescue beta2-agonist use decreased for both treatment groups. None of these differences between treatments were statistically significant However, diurnal variation was significantly reduced with fluticasone propionate, when compared with beclomethasone dipropionate (difference = 7 l.min-1; p=0.038). Clinic lung function also improved with both treatments and, apart from % predicted PEFR, which showed no difference after beclomethasone dipropionate but increased from 73 to 78 % with fluticasone propionate, there were no differences between treatments. Forced expiratory volume in one second (FEV1) increased with both treatments. The geometric mean plasma cortisol concentration rose after treatment with fluticasone propionate (from 293 to 309 nmol.l-1) and fell after beclomethasone dipropionate (from 256 to 224 nmol.l-1); the difference between treatments was significant. The incidence of adverse events was low in both treatment groups. In conclusion, 1 mg-day-1 fluticasone propionate was as effective as 2 mg-day-1 beclomethasone dipropionate in the control of severe asthma. However, adrenal function was affected less by fluticasone propionate, which gives it a better overall safety profile. This study, therefore, demonstrates the increased therapeutic potential of fluticasone propionate over beclomethasone dipropionate in severe asthma.