A Randomized Controlled Trial on the Effect of Inhaled Corticosteroids on Airways Inflammation in Adult Cigarette Smokers

STUDY OBJECTIVE: To determine whether inhaled corticosteroid treatment can reduce airways inflammation in adult cigarette smokers. DESIGN: This was a randomized, placebo-controlled, double-blinded clinical trial. SETTING: The subjects were recruited from the community by advertising. PARTICIPANTS: Seventy-one adults with a > or = 5 pack-year history who were current smokers, had a normal FEV1, and produced sputum daily. INTERVENTION: Sixty subjects were randomized to receive four puffs of placebo or beclomethasone dipropionate ([BDP]; total dosage, 1,000 microg/d) using a metered-dose aerosol inhaler with a valved holding chamber (AeroChamber; Trudell Medical; London, Ontario, Canada) for 28 days. MEASUREMENTS AND RESULTS: Eleven subjects were not randomized because of poor compliance. The primary outcome was fractional airway neutrophilia, as assessed by a differential cell count of sputum. Additional outcome measures were spirometry, measurement of airway responsiveness by methacholine challenge, and lung epithelial permeability measured by the clearance of radiolabeled diethylenetriamine pentaacetic acid. There were no significant differences between the two groups in any outcome measurement after 4 weeks of treatment. CONCLUSIONS: With normal spirometry, we found no benefit of treatment with inhaled BDP, 1,000 microg/d, on noninvasive measures of airways inflammation in adult smokers. This indicates that cigarette smoke-induced inflammation in its early stages (before a demonstrable airflow obstruction) is not steroid sensitive. This may occur because the site of involvement is not accessible to inhaled medications or because the inflammatory process is resistant to moderate doses of inhaled corticosteroids.