Chronic obstructive pulmonary disease (COPD) is a progressive respiratory illness that results in an irreversible decrease in airflow. The leading risk factor for COPD is cigarette smoking. There is an inflammatory component in the pathophysiology of COPD, although the mechanism is felt to differ from that which occurs with asthma. Nonetheless, physicians often use inhaled corticosteroids to treat patients with COPD. Several studies to date have suggested a positive effect on respiratory function in patients who are given these medications. Other studies have shown little or no benefit. Pauwels and associates conducted a double-blind, placebo-controlled trial to see if inhaled corticosteroids would decrease the decline in lung function in patients with mild COPD who continue smoking.
Patients were enrolled at 39 study centers in Europe. Entry criteria included age of 30 to 65 years, current smoking history of at least five cigarettes per day for 10 years or more, or greater than five-pack-years. Forced expiratory volume in one second (FEV1) had to be 50 to 100 percent of predicted after the use of a bronchodilator and the ratio of pretreatment FEV1 to slow vital capacity had to be less than 70 percent. Exclusion criteria included a history of asthma, allergic rhinitis, allergic eczema and the use of more than four weeks of oral steroids during the previous six months.
The study began with a three-month smoking cessation program that used counseling and nicotine replacement gum. Patients who did not quit smoking were then given an inhaler that contained placebo to be used for three months. After this three-month period, patients who continued to smoke and were at least 75 percent compliant with the placebo inhaler were enrolled in the trial. These patients were randomly assigned to receive twice-daily inhaled therapy with either 400 mg of budesonide or placebo. All subjects were seen every three months for follow-up visits, at which time spirometry was performed. In addition, select patients had periodic bone mineral density studies and radiographs of the spine done to assess for fractures.
After exclusion criteria were applied, including cessation of smoking during the first three months, the remaining 1,277 patients were randomized. Baseline characteristics were essentially the same, the mean age being 52 years and 27 percent of the patients were women. The average number of years of smoking was 36, and the average number of cigarettes smoked per day was 18 ± 10.
By the end of the study, 9 percent of the budesonide group and 11 percent of the placebo group had quit smoking. The treated patients showed a 17 mL improvement in FEV1 during the first six months, compared with a decline of 81 mL in the placebo group. From month 9 until month 36, the decline in FEV1 was 57 mL per year in the budesonide patients and 69 mL in the placebo group—not a significant difference. Over the entire three years, the median decline in FEV1 was 140 mL in the budesonide group and 180 mL in the placebo group.
In a subset of patients who had more than a 36-pack-year smoking history, the decline in FEV1 was 160 mL for placebo and 150 mL for budesonide. Ten percent of treatment patients and 4 percent of the placebo group were noted to have skin bruising. There were no significant differences in the bone mineral densities or the number of vertebral fractures diagnosed among the patients during the three years of the study.
The authors conclude that for patients with mild COPD who continue to smoke, the benefits of inhaled corticosteroids are minimal. A small one-time improvement was noted that lasted only during the first six months of treatment with budesonide. Inhaled budesonide had no effect on the long-term decline of pulmonary function in these patients. In their discussion, the authors cite two smaller studies, one that used inhaled beclomethasone and a second with budesonide, that found a similar short-term improvement in pulmonary function but no long-term benefits.