BACKGROUND: No pharmacologic intervention has been demonstrated to affect health deterioration or disease advancement of COPD. Use of inhaled steroids in moderate doses is common, but a controlled trial has shown that such treatment results in only a small benefit in changes in forced expiratory volume in 1 second (FEV1) and minimal improvement in clinical parameters.1
POPULATION STUDIED: Patients were current or former smokers aged between 40 and 75 years. All had nonasthmatic COPD defined as an FEV1 less than 85% of predicted, and an FEV1/forced vital capacity percentage less than 70% with less than 10% improvement from inhaled b-agonists. Previous use of inhaled or oral corticosteriods was permitted. Patients were excluded if they had a life expectancy of less than 5 years from concurrent diseases or if they used b-blockers. Concurrent use of theophyllines and bronchodilators was allowed during the study.
STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded study of 751 patients. There was no mention of allocation concealment. After an 8-week period of withdrawal from steroid use, patients received 14 days of oral prednisolone to determine whether a response to acute corticosteroids could predict a response to long-term inhaled corticosteroids. Patients then received either placebo or 500 mg fluticasone using a metered dose inhaler with a spacer twice daily. Patients were evaluated every 3 months for 3 years. Health status was measured by the St. George’s respiratory questionnaire; a 4-point change in this 100-point scale was judged to be clinically significant. An exacerbation was defined as worsening of respiratory symptoms requiring treatment with oral cortico- steroids or antibiotics.
OUTCOMES MEASURED: The primary end point was the annual decline in FEV1. Secondary end points were the frequencies of exacerbations, changes in health status, withdrawals because of respiratory disease, morning serum cortisol concentrations, and adverse events.
RESULTS: There was no difference in the decline of respiratory function as measured by FEV1 over the 3 years of the study in the fluticasone or placebo groups (59 mL/year vs 50 mL/year). The yearly exacerbation rate was lower in the fluticasone group than in the placebo group (0.99 vs 1.32 per year; P=.026). This resulted in 3 patients treated with high-dose fluticasone for a year (at a retail pharmacy cost in the United States of $1500 per patient) to prevent 1 exacerbation requiring steroids or antibiotics (number needed to treat=3). Health status measured by the increase in questionnaire score declined at a slower rate in the fluticasone group than in the placebo group (2.0 vs 3.2 units/year; P=.004). Although this was statistically significant, the difference is unlikely to be clinically relevant. Adverse effects were similar in each group. The response to oral prednisolone did not predict a subsequent response to inhaled corticosteroids.
High-dose inhaled corticosteroid use has a minimal clinical effect in patients with COPD. It did not affect the rate of decline of lung function and did not markedly affect health status. The only clinical benefit seen in this trial was a decrease in the frequency of exa- cerbations requiring oral steroid or antibiotic treatment. Since a trial of oral steroids was not useful in selecting patients more likely to benefit from this intervention, the decision to use inhaled steroids should be made on other clinical grounds and monitored periodically to determine effectiveness. The dose in this study is significantly higher than most dosages of inhaled steroids prescribed. Another study2 suggests that potent inhaled steroids may decrease bone mineral density. Given this risk and the small benefit demonstrated in this study, inhaled steroids should be used infrequently in patients with COPD.