Effects of extra-fine inhaled and oral corticosteroids on alveolar nitric oxide in COPD

Abstract

Purpose Alveolar nitric oxide (CANO) has been suggested as a surrogate marker of distal airway inflammation in COPD. Coarse particle-inhaled corticosteroids (ICS) have been shown not to suppress CANO. We evaluated whether extra-fine particle size ICS (HFA-BDP) or systemic oral corticosteroids could suppress CANO in COPD. Methods Chronic obstructive pulmonary disease (COPD) patients with a FEV1/FVC ratio \0.7, FEV1 \80% predicted with CANO[2 ppb underwent a double-blind randomized, controlled, crossover trial with an open-label systemic steroid comparator. After a 2 week steroid washout period, participants were randomized to 3 weeks of 100 mcg of HFA-BDP twice daily and then 3 weeks of 400 mcg of HFA-BDP twice daily, or matched placebos with subsequent crossover. All patients then received 1 week open-label, 25 mg/day of prednisolone. Exhaled nitric oxide, plasma cortisol, and lung function were recorded. CANO was corrected for axial diffusion. Results In 16 participants, there were no significant differences seen with either dose of HFA-BDP compared with placebo. Oral prednisolone significantly reduced FENO and J'aw NO but not CANO. Plasma cortisol was significantly suppressed by oral prednisolone only. Conclusions Whilst CANO remains a biomarker of interest in COPD, it is not suppressed by systemic or extra-fine particle ICS. CANO is not a useful marker for monitoring response of small airway disease to therapies in COPD. The study was approved by the local Committee on Medical Research Ethics and registered on Clinical Trials. Gov (NCT 00921921). © 2012 Springer Science+Business Media, LLC.