ArticlesMulticentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease
Introduction
Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of disorders, consisting of chronic bronchitis, emphysema, and small-airways disease, which lead to progressive, largely irreversible airflow obstruction that may be accompanied by airway hyper-responsiveness.1 COPD is characterised by cough, sputum production, and breathlessness associated with airflow obstruction. Patients generally have a progressive deterioration in lung function, which leads to substantial problems in their general health and quality of life, and eventual repiratory failure and early death.2 COPD is one of the leading causes of death worldwide, with an increasing prevalence and mortality rate.3
The major risk factor is cigarette smoking, but the pathogenesis of COPD is not clear. Airway inflammation seems to be involved, as it is in asthma.4 Corticosteroids have proved to be valuable in the treatment of asthma and may, therefore, be beneficial in patients with COPD, although their role in the management of COPD is less well established.5 Short-term inhaled corticosteroids in COPD have had little effect on airway hyper-responsiveness or forced expiratory volume in 1 s (FEV1), at doses that improve asthma.6, 7, 8, 9 Longer-term treatment has shown some benefit on lung function, but studies generally have not distinguished between COPD and asthma.10, 11 Exacerbations are an important clinical feature of asthma and COPD, and inhaled corticosteroids decrease their frequency and severity in asthma,10, 12 but this effect has not been proved in COPD.
Fluticasone propionate is effective and safe for patients with all grades of severity of asthma,12, 13, 14, 15 and has a therapeutic ratio superior to other inhaled corticosteroids.12, 16, 17 No clinical studies have assessed the effect of fluticasone propionate in COPD, although one study did show a reduction in neutrophil chemotactic activity and in the proteinase-antiproteinase ratio in the sputum of COPD patients treated for 8 weeks.18
We used a multicentre, double-blind, randomised, placebo-controlled design to investigate the efficacy and safety of fluticasone propionate in COPD patients.
Section snippets
Methods
We recruited 365 patients aged between 50 and 75 years with COPD. Our definition of COPD was consistent with the European Respiratory Society Consensus Statement,5 which defines COPD as a disorder characterised by decreased maximum expiratory flow and slow forced emptying of the lungs, which is slowly progressive, irreversible, and does not change markedly over several months. The patients were from 13 European countries, New Zealand, and South Africa, and recruited from hospital outpatient
Results
365 patients were initially enrolled into the study, but only 281 were assigned treatment (figure 1). 46 patients, 27 (19%) in the placebo group and 19 (13%) in the fluticasone proprionate group, withdrew, mostly because of adverse events, including exacerbations of COPD. One patient in the placebo group withdrew because of treatment failure, but had an exacerbation of COPD shortly before the withdrawal date. Patients were well-matched for age, sex, smoking history, baseline lung function, and
Discussion
We found no significant difference between treatments for the number of patients who experienced at least one exacerbation, but there was significant improvement in the other main clinical features in the patients on fluticasone propionate. There was also a numerical difference in favour of fluticasone propionate for total number of exacerbations.
Only about a third of patients in each group experienced an exacerbation, which was lower than our prediction when planning the size and power of the
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