Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial.

OBJECTIVES: To determine the effect of long term inhaled corticosteroids on lung function, exacerbations, and health status in patients with moderate to severe chronic obstructive pulmonary disease. DESIGN: Double blind, placebo controlled study. SETTING: Eighteen UK hospitals. PARTICIPANTS: 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second (FEV(1)) 50% of predicted normal. INTERVENTIONS: Inhaled fluticasone propionate 500 microgram twice daily from a metered dose inhaler or identical placebo. MAIN OUTCOME MEASURES: Efficacy measures: rate of decline in FEV(1) after the bronchodilator and in health status, frequency of exacerbations, respiratory withdrawals. Safety measures: morning serum cortisol concentration, incidence of adverse events. RESULTS: There was no significant difference in the annual rate of decline in FEV(1 )(P=0.16). Mean FEV(1) after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo (P<0.001). Median exacerbation rate was reduced by 25% from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate (P=0.026). Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate (P=0.0043). Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group (25% v 19%, P=0.034). CONCLUSIONS: Fluticasone propionate 500 microgram twice daily did not affect the rate of decline in FEV(1) but did produce a small increase in FEV(1). Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status. These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease.

Comparison of short courses of oral prednisolone and fluticasone propionate in the treatment of adults with acute exacerbations of asthma in primary care.

BACKGROUND: Oral corticosteroids used in short courses for acute asthma are regarded as safe, although the frequent use of these drugs may result in patients suffering from systemic side effects. It has become common practice for patients to increase their own inhaled corticosteroid intake when their asthma goes out of control, but it has never been established whether a high dose of inhaled corticosteroid can be as effective as a short course of oral corticosteroid in the treatment of acute exacerbations. METHODS: A multicentre, randomised, double blind, double dummy, parallel group study was undertaken to determine whether the introduction of a high dose of inhaled fluticasone propionate (2 mg daily) is as effective as a short reducing course of oral prednisolone (starting at 40 mg/day and reducing by 5 mg every other day) in the treatment of acute exacerbations of asthma not considered severe enough for admission to hospital but requiring treatment with oral corticosteroid. RESULTS: Four hundred and thirteen adult asthmatic subjects who presented to their general practitioner with an acute exacerbation of asthma were recruited in 47 general practices in the United Kingdom. Treatment failures, defined as a reduction in peak expiratory flow (PEF) to below 60% of the patient's best/predicted value on two consecutive occasions or persistent symptoms with no improvement on three consecutive days, occurred in 23% of patients who received oral prednisolone and 27% who received inhaled fluticasone propionate (difference in percentage of treatment failures 4.3, 95% CI -4.1 to 12.8, p = 0.31). In each group 48% were classified as treatment successes, defined as a 10% or greater increase in percentage best/predicted morning PEF. Both treatments were equally well tolerated. CONCLUSIONS: There is no evidence of a significant difference in efficacy between a reducing dose course of oral prednisolone and high dose inhaled fluticasone propionate in mild exacerbations of asthma which do not require admission to hospital.