title: Bronchial nitric oxide flux (J'aw) is sensitive to oral corticosteroids in smokers with asthma.
abstract: BACKGROUND
  Exhaled nitric oxide provides a convenient, non-invasive insight into airway inflammation. However it is suppressed by current smoking, reducing its potential as an endpoint in studies of smokers with asthma, a group with increased symptoms and poor clinical responses to corticosteroids. We examined extended nitric oxide analysis as some derived variables are thought to be unaffected. Therefore this approach could reveal hidden inflammation and enable its use as an exploratory endpoint in this group.
  
  
  METHODS
  Smokers (n = 22) and never smokers (n = 21) with asthma performed exhaled nitric oxide measurements and spirometry before and after two weeks of oral dexamethasone (6 mg/1.74 m(2)/day). Linear and non-linear nitric oxide analysis was performed to derive estimates for alveolar nitric oxide (C(alv)) and nitric oxide flux (J'(aw)) for each subject.
  
  
  RESULTS
  FE(NO50) was significantly lower in smokers with asthma and did not change significantly in response to dexamethasone. C(alv) derived by linear modelling was lower in smokers with asthma and did not change significantly in response in either group. J'(aw) was substantially lower in smokers with asthma (smokers (median (IQR)); 573 pl/s (217, 734), non-smoker; 1535 pl/s (785, 3496), p = 0.001) and was reduced in both groups following dexamethasone (non-smokers change (mean (95% CI)); -743.3 pl/s (-1710, -163), p = 0.005, smokers; -293 pl/s (-572, -60), p = 0.016). Correction for axial flow did not substantially change the derived results.
  
  
  CONCLUSIONS
  Bronchial NO flux appears to be sensitive to oral dexamethasone and may provide a useful exploratory endpoint for the analysis of novel anti-inflammatory therapies in smokers with asthma.
authors.affiliation: Respiratory Medicine Section, Institute of Infection, Immunity & Inflammation, University of Glasgow & Gartnavel General Hospital, Asthma Research Unit, Level 6, 1053 Gt Western Rd, Glasgow G12 OYN, United Kingdom. mark.spears@glasgow.ac.uk
authors.forename: Mark
authors.initials: M
authors.lastname: Spears
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Weir
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Smith
authors.forename: Charles
authors.initials: C
authors.lastname: McSharry
authors.forename: Rekha
authors.initials: R
authors.lastname: Chaudhuri
authors.forename: Martin
authors.initials: M
authors.lastname: Johnson
authors.forename: Euan
authors.initials: E
authors.lastname: Cameron
authors.forename: Neil C
authors.initials: NC
authors.lastname: Thomson
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D001944:Breath Tests; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D045853:Exhalation; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012129:Respiratory Function Tests; D012907:Smoking / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D009569:Nitric Oxide; D003907:Dexamethasone