title: A novel approach to partition central and peripheral airway nitric oxide.
abstract: BACKGROUND
  Determining the site of airways inflammation may lead to the targeting of therapy. Nitric oxide (NO) is a biomarker of airway inflammation and can be measured at multiple exhalation flow rates to allow partitioning into bronchial (large/central airway maximal nitric oxide flux [J'awno]) and peripheral (peripheral/small airway/alveolar nitric oxide concentration [Cano]) airway contributions by linear regression. This requires a minimum of three exhalations. We developed a simple and practical method to partition NO.
  
  
  METHODS
  In 29 healthy subjects (FEV1, 97% ± 3% predicted), 13 patients with asthma (FEV1, 90% ± 4% predicted), 14 patients with COPD (FEV1, 59% ± 3% predicted), and 12 patients with cystic fibrosis (CF) (FEV1, 60% ± 3% predicted), we measured the area under the curve of the NO concentration/exhalation time plot (AUC-NO) at exhalation flow rates of 50, 100, 200, and 300 mL/s. We determined the change of the total AUC-NO production (ΔAUC-NO) among the four different exhalation flow rates and compared these levels to Cano and J'awno indices measured conventionally by linear regression.
  
  
  RESULTS
  The change in AUC-NO between increasing exhalation flow rates of 50 to 200 mL/s (ΔAUC-NO50-200) was strongly correlated with J'awno in all patient groups as follows: healthy subjects (r = 0.94, P &lt; .001), patients with asthma (r = 0.98, P &lt; .001), patients with COPD (r = 0.93, P &lt; .001), and patients with CF (r = 0.74, P &lt; .05). In all subjects, AUC-NO at an exhalation flow rate of 200 mL/s (AUC-NO200) correlated with Cano (r = 0.69, P &lt; .01).
  
  
  CONCLUSIONS
  The bronchial production of NO can be determined by measuring ΔAUC-NO50-200, whereas AUC-NO200 measures its peripheral concentration. This approach is simple, quick, and does not require sophisticated equipment or mathematical models.
authors.affiliation: Airways Disease Section, National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, London, England. Electronic address: p.paredi@imperial.ac.uk.
authors.forename: Paolo
authors.initials: P
authors.lastname: Paredi
authors.affiliation: Airways Disease Section, National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, London, England.
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Kharitonov
authors.affiliation: Airways Disease Section, National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, London, England.
authors.forename: Sally
authors.initials: S
authors.lastname: Meah
authors.affiliation: Airways Disease Section, National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, London, England.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
authors.affiliation: Airways Disease Section, National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, London, England.
authors.forename: Omar S
authors.initials: OS
authors.lastname: Usmani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001249:Asthma / Q000175:diagnosis* / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests / Q000379:methods*; D001980:Bronchi / Q000276:immunology; D055745:Bronchioles / Q000276:immunology; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000276:immunology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000276:immunology; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000276:immunology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide