Because airway inflammation is associated with chronic obstructive pulmonary disease (COPD), corticosteroids could provide effective therapy. However, short-term trials of inhaled corticosteroids in patients with COPD have shown little effect on airway hyperresponsiveness or forced expiratory volume in one second (FEV1). Longer-term corticosteroid therapy has shown some beneficial effects on pulmonary function. Paggiaro and colleagues conducted a randomized, placebo-controlled multicenter trial to study the efficacy and safety of inhaled fluticasone propionate in patients with COPD.
A total of 281 patients with COPD were enrolled in the study. Patients were included in the study if they were current or former smokers, had experienced cough and excess sputum production for at least three months' duration in at least two consecutive years, had at least one exacerbation annually for the previous three years and were likely to have an exacerbation during the six-month treatment period. After a run-in period during which baseline symptoms were recorded, patients were randomly assigned to treatment with either two puffs of fluticasone propionate twice daily (1,000 mg daily) or placebo. The two groups of patients were matched for age, sex, smoking history, pulmonary function and severity of COPD. Assessment of treatment efficacy was performed after four, eight, 16 and 24 weeks of therapy. Patients were allowed to take short-acting beta agonists as required for relief of symptoms, and other medications, such as anticholinergics and xanthine derivatives, throughout the study without dosage changes.
Of the 142 patients initially assigned to the treatment group, 19 (13 percent) subsequently withdrew from the study because of adverse events (nine patients), treatment failure (four patients) or other reasons (six patients). Twenty-seven of the 139 patients (19 percent) initially assigned to the placebo group withdrew because of adverse events (16 patients), noncompliance or failure to return (four patients), treatment failure (one patient) or other reasons (six patients).
During the study period, at least one exacerbation occurred in 51 patients (37 percent) in the placebo group and in 45 patients (32 percent) in the treatment group. Although the total number of exacerbations was not significantly different in the two groups, patients who received fluticasone had significantly fewer exacerbations of a moderate or severe degree. Of the 51 patients in the placebo group who had exacerbations, 44 (86 percent) had moderate or severe exacerbations. In contrast, exacerbations were moderate or severe in 27 (60 percent) of the 45 patients experiencing exacerbations in the treatment group.
Compared with the placebo group, patients who received fluticasone showed significantly greater improvement in symptoms, peak expiratory flow rate, forced vital capacity, FEV1 and mid-expiratory flow rate. The patients in the treatment group also showed a significant increase in the distance they could walk for six minutes. After six months of treatment, the mean change in distance was 27 m in the treatment group and 8 m in the placebo group.
Patients who responded to inhaled fluticasone tended to be those with a longer duration of COPD; however, no other variables appeared to predict which patients would respond. Adverse effects were reported by a comparable proportion of patients in each group and were predominantly associated with COPD and respiratory infections. Few patients reported side effects attributable to steroids, such as hoarseness, dysphonia and candidiasis.
The authors conclude that six months of treatment with inhaled fluticasone propionate appears to be safe and effective in patients with COPD. The findings suggest that this therapy may improve pulmonary function but may not necessarily reduce the number of exacerbations in patients with long-established disease.