Short- and long-term efficacy of fluticasone propionate in subjects with early signs and symptoms of chronic obstructive pulmonary disease. Results of the DIMCA study

Background. Early treatment with inhaled corticosteroids may prevent progression of irreversible obstruction in COPD, especially in patients with bronchial hyperresponsiveness. We investigated the clinical effects of early introduction of inhaled steroids in subjects showing early signs and symptoms of COPD without a prior clinical diagnosis. Methods. Study subjects were detected in a general population screening and monitoring program. Those with a moderately accelerated annual FEV₁ decline and persistent respiratory symptoms were invited to participate in a 2-year randomized controlled trial comparing fluticasone propionate DPI 250 μg b.i.d. with placebo. Pre- and post-bronchodilator (BD) FEV₁, PC₂₀ histamine, functional status (COOP/WONCA charts) and occurrence of exacerbations were periodically assessed. Subjects recorded respiratory symptoms. Post-BD FEV₁ decline served as the main outcome. Multivariable repeated measurements analysis techniques were applied. Results. 48 subjects were randomized (24 fluticasone, 24 placebo). After 3 months, the post-BD FEV₁ had increased with 125 ml (SE = 68, P = 0.075) and the pre-BD FEV₁ with 174 ml (SE 90, P = 0.059) in the fluticasone relative to the placebo group. The subsequent post-BD and pre-BD FEV₁ decline were not beneficially modified by fluticasone treatment. There were no statistically significant differences in respiratory symptoms, functional status, or exacerbations favoring fluticasone. Subgroup analysis indicated that the presence of bronchial hyperresponsiveness modified the initial FEV₁ response on fluticasone, but not the subsequent annual FEV₁ decline. Conclusion. Early initiation of inhaled steroid treatment does not seem to affect the progressive deterioration of lung function or other respiratory health outcomes in subjects with early signs and symptoms of COPD. In subjects at risk for, or in an early stage of COPD, long-term inhaled steroid treatment should not be based on a single spirometric evaluation after 3 months.