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 microg (S50) bid, after 180 microg aerosolized albuterol, FEV(1) (L) was 52% +/- 12% predicted and FEV(1)/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 microg (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 microg (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.


BACKGROUND
NCT #00568347.
Gelb
Arthur F
AF
Pulmonary Division, Department of Medicine, Lakewood Regional Medical Center, Lakewood, CA, USA. afgelb@msn.com
Flynn Taylor
Colleen
C
Krishnan
Anita
A
Fraser
Christine
C
Shinar
Chris M
CM
Schein
Mark J
MJ
Osann
Kathryn
K
D000280:Administration, Inhalation; D000368:Aged; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D045853:Exhalation / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D011659:Pulmonary Gas Exchange / Q000502:physiology*; D016037:Single-Blind Method; D014797:Vital Capacity
D005938:Glucocorticoids; D020024:Leukotriene Antagonists; D009569:Nitric Oxide