Central and Peripheral Airway Sites of Nitric Oxide Gas Exchange in COPD

Background: This study investigated sites of nitric oxide (NO) gas exchange and response to inhaled corticosteroids (ICS) in patients with COPD and varying extents of emphysema. Methods: This was a prospective, randomized, single-blind, crossover study in treated, stable, ex-smoking patients with COPD who were ICS and leukotriene receptor antagonists naive. Lung function, high-resolution thin-section CT scan of the lung, and exhaled NO were measured at 50, 100, 150, and 200 mL/s. Airway NO was adjusted for NO axial backdiffusion. Results: In 39 (18 women), clinically stable ex-smokers with COPD aged 73 +/- 9 years (mean +/- SD) on salmeterol 50 mu g (S50) bid, after 180 mu g aerosolized albuterol, FEV1 (L) was 52% +/- 12% predicted and FEV1/FVC was 55% +/- 6%. Compared with 20 (12 men) age-matched controls, 39 patients with COPD had normal large airway NO flux and small airway/alveolar NO. Subsequently, 19 patients with COPD (Group A) were randomized and continued on S50, and 20 (Group B) were randomized to fluticasone propionate 250 mu g (F250)/S50 bid for 86 +/- 16 days. Group A (S50) patients were then switched to F250/S50, and 12 of 19 completed 77 +/- 15 days; there was significant (P < .001) reduction only in the exhaled fraction of NO (FENO) at 50 mL/s and large airway NO flux. In 20 patients with COPD initially randomized to F250/S50 (Group B), after 57 +/- 22 days of S50 in 16 of 20 patients there was a significant (P = .04) increase only in (FENO) at 50 mL/s and large airway NO flux, which was not reduced after 60 +/- 23 days of fluticasone propionate 100 mu g (F100)/S50(P = .07). There was no correlation between NO gas exchange and CT-scored emphysema. Conclusions: In COPD, there was; normal NO gas exchange in both large and small airways/alveoli and only large airway NO flux was suppressed with F250/S50 but not F100/S50, despite varying extents of emphysema. Peripheral NO must be corrected for axial NO backdiffusion to avoid spurious conclusions. CHEST 2010; 137(3):575-584