Response to Add-on Inhaled Corticosteroids in COPD Based on Airway Hyperresponsiveness to Mannitol

Abstract

The use of inhaled corticosteroids in mild to moderate COPD is controversial. The aim of this study was to determine whether airway hyperresponsiveness to mannitol might identify patients who are likely to respond to add-on inhaled corticosteroids. Ninety subjects with mild to moderate COPD were recruited and 68 subsequently randomized in a double-blind manner to receive inhaled budesonide (1,600 μg/d, n = 31) or placebo (n = 37) for 3 months. Thirty-eight subjects had airway hyperresponsiveness to mannitol (17 received budesonide, 21 placebo). All subjects received tiotropium throughout the study, including 4 weeks before randomization. Spirometry, quality of life (St. George Respiratory Questionnaire), degree of dyspnea, airway responsiveness to mannitol, and exhaled nitric oxide were assessed at week 0 (recruitment), week 4 (baseline prior to randomization), and week 16 (posttreatment). Compared with placebo, budesonide was associated with improved quality of life in subjects showing airway hyperresponsiveness to mannitol (difference of changes in quality of life score between randomization and study completion, −9.1; 95% CI, −15.8 to −2.3; P < .01). Treatment with inhaled budesonide also led to a reduction in airway responsiveness to mannitol compared with placebo (difference in log10 response-dose ratio, −0.3; 95% CI, −0.6 to −0.04; P < .01). However, postrandomization changes in FEV1 % predicted, quality of life, and exhaled nitric oxide showed no difference between budesonide and placebo. In subjects with mild to moderate COPD and airway hyperresponsiveness to mannitol, quality of life and airway responsiveness improved after treatment with inhaled corticosteroids added to long-acting bronchodilator therapy.