title: Effects of extra-fine inhaled and oral corticosteroids on alveolar nitric oxide in COPD.
abstract: OBJECTIVE
  Alveolar nitric oxide (CA(NO)) has been suggested as a surrogate marker of distal airway inflammation in COPD. Coarse particle-inhaled corticosteroids (ICS) have been shown not to suppress CA(NO). We evaluated whether extra-fine particle size ICS (HFA-BDP) or systemic oral corticosteroids could suppress CA(NO) in COPD.
  
  
  METHODS
  Chronic obstructive pulmonary disease (COPD) patients with a FEV1/FVC ratio <0.7, FEV1 <80% predicted with CA(NO) > 2 ppb underwent a double-blind randomized, controlled, crossover trial with an open-label systemic steroid comparator. After a 2 week steroid washout period, participants were randomized to 3 weeks of 100 mcg of HFA-BDP twice daily and then 3 weeks of 400 mcg of HFA-BDP twice daily, or matched placebos with subsequent crossover. All patients then received 1 week open-label, 25 mg/day of prednisolone. Exhaled nitric oxide, plasma cortisol, and lung function were recorded. CA(NO) was corrected for axial diffusion.
  
  
  RESULTS
  In 16 participants, there were no significant differences seen with either dose of HFA-BDP compared with placebo. Oral prednisolone significantly reduced FE(NO) and J'aw(NO) but not CA(NO). Plasma cortisol was significantly suppressed by oral prednisolone only.
  
  
  CONCLUSIONS
  Whilst CA(NO) remains a biomarker of interest in COPD, it is not suppressed by systemic or extra-fine particle ICS. CA(NO) is not a useful marker for monitoring response of small airway disease to therapies in COPD. The study was approved by the local Committee on Medical Research Ethics and registered on ClinicalTrials.Gov (NCT 00921921).
authors.affiliation: Asthma and Allergy Research Group, Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, University of Dundee, Dundee DD1 9SY, Scotland.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Short
authors.forename: Peter A
authors.initials: PA
authors.lastname: Williamson
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000627:therapeutic use*; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D011650:Pulmonary Alveoli / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D009569:Nitric Oxide; D011239:Prednisolone