Central and peripheral airway sites of nitric oxide gas exchange in COPD

Chest. 2010 Mar;137(3):575-84. doi: 10.1378/chest.09-1522. Epub 2009 Oct 9.


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.

Trial registration: NCT #00568347.

Trial registration: ClinicalTrials.gov NCT00568347.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Aged
  • Cross-Over Studies
  • Drug Therapy, Combination
  • Exhalation / physiology*
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume
  • Glucocorticoids / administration & dosage*
  • Humans
  • Leukotriene Antagonists / administration & dosage*
  • Male
  • Nitric Oxide / metabolism*
  • Prognosis
  • Prospective Studies
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pulmonary Gas Exchange / physiology*
  • Single-Blind Method
  • Vital Capacity


  • Glucocorticoids
  • Leukotriene Antagonists
  • Nitric Oxide

Associated data

  • ClinicalTrials.gov/NCT00568347