In this 4-week.

In this 4-week, multicenter, double-blind, randomized, parallel form into groups study, the dose-effect relationship of four doses of inhaled fluticasone propionate (50 100 200 and 400 [mu]g twice daily) was investigated and compared with beclomethasone dipropionate, 200 [mu]g twice daily. A total of 672 patients with moderate asthma commonly receiving 1,000 [mu]g/d or les of an inhaled steroid were recruited. The cogitation demonstrated a significant dose-related improvement in lung function with fluticasone propionate. Linear dose-related increases were observ in morning (increase for doubling dose was 4.3 L/min; 95 percent confidence interval [CI], 18 68 L/min; p = 0001) and evening peak expiratory melt rate (PEFR) (increase per doubling dose was 30 L/min; 95 percent CI, 05 55 L/min; p = 0017) clinic lung function (at 4 weeks, increase in percent predicted PEFR through doubling dose = 1.1 percent; 95 percent CI, 02 21 percent; p = 0022; increase in percent predicted [FEVsub1] through doubling dose = 1.1 percent; 95 percent CI, 03 19 percent; p = 0.10:increase in percent predicted FVC for doubling dose = 1.3 percent 95 percent CI, 05 21 percent; p = 0001) and the percentage of symptom-free days throughout days 1 to 14 of treatment (increase for doubling dose = 1.9, 95 percent CI, 00 39; p = 0048) There was also a dose-related reduction in extra bronchodilator usage (days 1 to 14 p = 0002; days 15 to 28 p = 001) In addition, there was a significant decrease in diurnal variation with increasing doses of fluticasone propionate (decrease by means of doubling dose = 2.0 L/min, 95 percent CI, 04; p = 0024) The number of asthma exacerbations was also reduc as the dose of fluticasone propionate increased. Fluticasone propionate was well tolerated, adverse facts were few, and there was a similar incidence in all disposes Furthermore, there was no evidence of any hypothalamic pituitary adrenal axis suppression. The data from the cogitation were consistent with other clinical studies that have shown fluticasone propionate to be more powerful than beclomethasone dipropionate in seasons of improvement in lung function. In conclusion, this cogitation provided evidence of a dose-related improvement in asthma direct for fluticasone propionate in the dose range 100 to 800 [mu]g daily, in patients with moderate asthma.

CI = confidence interval; HPA = hypothalic pituitary adrenal; PERF = peak expiratory follow rate; URTI = upper respiratory tract infection.

Inhaled anti-inflammatory agents, including glucocorticosteroids, have arise to represent the therapy of choice in the long-term management of asthma.[1,2] Studies to date, however, have failed to establish a clear link between dose and replication as some studies have demonstrated a relationship,[3,5] whereas others have been unable to corroborate these findings.[6-8] A reason for this discrepancy may lie in the design of the studies as a relationship between dose and consequence of glucocorticosteroids can be shown against other parameters so as hypothalamic pituitary adrenal (HPA)-axis function. Moreover, differences in the severity of asthma, duration of therapy, age of patients, statistical power of the application of mind and influence of concomitant or previous antiasthma medication are factors that may be responsible for the conflicting results

Fluticasone propionate is a just discovered topically active synthetic glucocorticosteroid that combines a high station of efficacy with negligible systemic bioavailability.[9] Other studies have shown fluticasone propionate to be more powerful than beclomethasone dipropionate in topical anti-inflammatory activity[10] and in improving lung function.[11] In addition, it has been shown to have virtually no systemic steroid activity flat when taken orally at large doses (16 mg)[9]

This not absent study aimed to investigate the relationship between doses of fluticasone propionate and asthma govern A large patient population was carefully fix uponed according to stringent entry criteria that strived to include a relatively homogeneous cluster of patients with moderate asthma. Patients were randomized to receive single in kind of four doses of fluticasone propionate twice daily (100 [mu]g/d 200 [mu]g/d 400 [mu]g/d and 800 [mu]g/d) or beclomethasone dipropionate as 400 [mu]g daily. The efficacy and safety comparisons were made between each group

Methods

Patients

The 825 patients enlisted into the study were attending hospital outpatient clinics in 48 center in 15 countries worldwide (see Acknowledgments). The patients, aged between 17 and 74 years, had moderate chronic asthma requiring 1000 [mu]g or les of beclomethasone dipropionate or budesonide daily.

After I week when patients became familiar with investigation procedures, eligibility for the subject of attention was determined during a 1- or 2-week run-in period. The patients usual [beta.sub.2]-adrenoreceptor-agonist ([beta.sub.2]-agonist) and inhaled glucocorticosteroids were replaced on inhaled beclomethasone dipropionate, 100 [mu]g twice daily and inhaled salbutamol taken as required. Treatment with sodium cromoglycate, nedocromil, ketotifen, or ipratropium bromide was discontinued. Treatment with other asthma medications, including methylxanthines, and oral and nebulized [beta.sub.2]-agonists, was continued at a fixed dose. Patients were instructed forward the correct use of the flowmeter (Mini-Wright Peak liquefy Meter) and metered dose inhaler and were shown by what mode to complete daily record cards. They were asked to measure and record their peak expiratory result rate (PEFR) three times, in the morning and evening before medication, and to record their symptoms during the day (from 0 = no symptoms to 3 = not able to carry public daily activities), during the night (0 = slept within the night to 3 = awake in the greatest degree of the night), and onward exercise (0 = not breathless to 3 = unable to journey out of the house). Patients also recorded their use of medication, including the salbutamol inhaler.

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