Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial

Background Little is known about the long-term efficacy inhaled corticosteroids in chronic obstructive pulmonary disease (COPD). We investigated the efficacy of inhaled budesonide on decline in lung function and respiratory symptoms in a 3-year placebo-controlled study of patients with COPD. Methods We used a parallel-group, randomised, double-blind, placebo-controlled design in a single-centre study, nested in a continuing epidemiological survey (the Copenhagen City Heart Study). Inclusion criteria were as follows: no asthma; a ratio of forced expiratory volume in 1 s (FEV1) and vital capacity of 0·7 or less; FEV1 which showed no response (<15% change) to 1 mg inhaled terbutaline or prednisolone 37·5 mg orally once daily for 10 days. 290 patients were randomly assigned budesonide, 800 μg plus 400 μg daily for 6 months followed by 400 μg twice daily for 30 months, or placebo for 36 months. The mean age of the participants was 59 years and the mean FEV1 2·37 L or 86% of predicted. The main outcome measure was rate of FEV1 decline. Analyses were by intention to treat. Findings The crude rates of FEV1 decline were slightly smaller than expected (placebo group 41·8 mL per year, budesonide group 45·1 mL per year). The estimated rates of decline from the regression model did not differ significantly (49·1 mL vs 46·0 mL per year; difference 3·1 mL per year [95% CI −12·8 to 19·0]; p=0·7). Before the study, the minimum relevant difference was defined as 20 mL per year; this difference was outside the 95% CI. No effect of inhaled budesonide was seen on respiratory symptoms. 316 exacerbations occurred during the study period, 155 in the budesonide group and 161 in the placebo group. Treatment was well tolerated. Interpretation Inhaled budesonide was of no clinical benefit in COPD patients recruited from the general population by screening. We question the role of long-term inhaled corticosteroids in the treatment of mild to moderate COPD.