The role of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) is uncertain, although some beneficial effects have been demonstrated in recent studies. Van der Valk and colleagues performed a randomized, double-blind, placebo-controlled trial to assess the effect of discontinuation of high-dosage inhaled fluticasone propionate therapy on exacerbations and quality of life in patients with moderate to severe COPD.
Of 509 eligible patients from one outpatient pulmonary clinic, 269 patients were enrolled in the study, and 263 completed the four-month run-in period during which all participants received inhaled fluticasone propionate (500 mcg twice daily). The 244 patients who remained in the study after the run-in period were randomized to continue receiving the inhaled corticosteroid or to receive placebo. The majority of participants were men (84.4 percent) and former smokers (72.5 percent) and had used inhaled steroids at least six months before beginning the study (83.2 percent).
Outcomes assessed after randomization were time to first and second exacerbation, recurrent exacerbations, and health-related quality of life. An exacerbation of COPD was defined as worsening of respiratory symptoms that necessitated short-term treatment (10 days) with an oral corticosteroid or antibiotic.
The placebo group experienced a first exacerbation an average of 34.6 days sooner (adjusted for smoking status) than the fluticasone group. The hazard ratio (also adjusted for smoking status) was 1.5 for a first exacerbation and 2.4 for a second, both in favor of the fluticasone group. Measures of health-related quality of life were worse in the placebo group, with a statistically significant difference in total score. Rapid, recurrent exacerbations occurred in 21.5 percent of the placebo group; these patients were then given fluticasone unblinded. Only 4.9 percent of patients in the fluticasone group experienced rapid, recurrent exacerbations.
The authors conclude that cessation of inhaled corticosteroid therapy in patients with moderate to severe COPD results in an increased risk of recurrent exacerbations and shorter time to first and second exacerbations, as well as a decline in health-related quality of life. Because 40 percent of the study patients experienced no negative effects, the authors emphasize the need for further study to define the group of COPD patients that will benefit most from inhaled corticosteroid therapy. The authors acknowledge that because their study focused on patients in a pulmonary clinic, their results might not be representative of outcomes in primary care settings.