title: Central and peripheral airway sites of nitric oxide gas exchange in COPD.
abstract: 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.
authors.affiliation: Pulmonary Division, Department of Medicine, Lakewood Regional Medical Center, Lakewood, CA, USA. afgelb@msn.com
authors.forename: Arthur F
authors.initials: AF
authors.lastname: Gelb
authors.forename: Colleen
authors.initials: C
authors.lastname: Flynn Taylor
authors.forename: Anita
authors.initials: A
authors.lastname: Krishnan
authors.forename: Christine
authors.initials: C
authors.lastname: Fraser
authors.forename: Chris M
authors.initials: CM
authors.lastname: Shinar
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Schein
authors.forename: Kathryn
authors.initials: K
authors.lastname: Osann
mesh_terms: 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
chemical_list: D005938:Glucocorticoids; D020024:Leukotriene Antagonists; D009569:Nitric Oxide