Inhaled corticosteroids are used in the treatment of chronic obstructive pulmonary disease (COPD) to reduce cough, mucus secretion and airway inflammation. Although their benefit is well established in the management of asthma, long-term benefit has not been shown in the treatment of COPD. Vestbo and colleagues studied the long-term effects of inhaled budesonide on forced expiratory volume in one second (FEV1) in patients with mild to moderate COPD.
The double-blind, placebo-controlled study included 290 patients 30 to 70 years of age who had an FEV1-to-vital-capacity ratio of 0.7 and less than 15 percent reversibility in FEV1 in response to 1 mg of inhaled terbutaline and in response to 10 days of treatment with 37.5 mg of oral prednisolone daily. Three fourths of the patients entering the study were current smokers. Of the 203 patients completing the three-year study, 109 were in the budesonide treatment group and 94 were in the placebo group.
Inhaled budesonide was given in a dosage of 800 μg in the morning and 400 μg in the evening for six months, followed by a dosage of 400 μg twice daily for 30 months. During exacerbations, patients were allowed to use oral, inhaled or parenteral steroids for up to three periods of four weeks each year. At follow-up visits every three months, FEV1, vital capacity and forced vital capacity were measured 15 minutes after inhalation of 1 mg of terbutaline. Reversibility was evaluated every six months. Data on respiratory symptoms and smoking habits were also collected every six months.
Both groups reported improvement in symptoms, particularly breathlessness, during the study, but there were no statistically significant differences between the treated and placebo groups in reported alleviation of symptoms. No significant effect of budesonide was detected in the rate of FEV1 decline, which was the main outcome measure. The crude rate of loss of pulmonary function was 41.8 mL per year in the placebo group, compared with 45.1 mL per year in the budesonide group. The estimated rates of decline yearly in FEV1 were 49.6 mL per year in the placebo group and 46.0 mL per year in the budesonide group. No difference in the rate of FEV1 decline was noted when patients were stratified according to sex, smoking status and baseline FEV1.
Eleven patients in the budesonide group and eight patients in the placebo group withdrew from the study because of adverse effects. Temporary worsening of symptoms was reported by 36 budesonide-treated and 34 placebo-treated patients. None of the nine deaths (four in the budesonide group and five in the placebo group) was attributable to COPD or related to therapy.
The authors conclude that inhaled budesonide has no effect on the rate of decline in pulmonary function in COPD. The authors state that the criterion of steroid irreversibility in their study might have led to selection of patients who were less likely to respond to inhaled corticosteroids. They stress that this study included patients living in the community with relatively mild symptoms and a slower rate of decline in pulmonary function than that reported in studies of patients attending referral centers in other countries. Because steroids are of significant benefit in patients with asthma, the authors emphasize the need for differentiation between asthma and COPD in patients with pulmonary symptoms.