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.
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.
In 39 (18 women), clinically stable ex-smokers with COPD aged 73 ± 9 years (mean ± SD) on salmeterol 50 μg (S50) bid, after 180 μg 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 μg (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 μg (F100)/S50(P = .07). There was no correlation between NO gas exchange and CT-scored emphysema.
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.