title: Small airways function and molecular markers in exhaled air in mild asthma.
abstract: BACKGROUND
  Several studies suggest that the periphery of the lung is the major site of inflammation in asthma. Fractional exhaled nitric oxide (Feno) and 8-isoprostane have been proposed as biomarkers of inflammation and oxidative stress. We therefore hypothesised that small airway dysfunction in asthma is of inflammatory origin that can be detected by molecular markers in exhaled air. To test this hypothesis, we examined the relationship of Feno and 8-isoprostane in exhaled air with small airways function as assessed by the single breath nitrogen test.
  
  
  METHODS
  Sixteen patients (14 women) with mild atopic asthma (forced expiratory volume in 1 second >80% predicted) of mean (SD) age 23.0 (5.5) years participated in a cross sectional study. Feno was recorded by chemiluminescence and 8-isoprostane was measured by ELISA in concentrated exhaled breath condensate. The slope of phase III (deltaN2) and the closing volume (CV) were assessed from the single breath washout curve.
  
  
  RESULTS
  The median Feno level was 30.4 ppb (range 10.1-82.8), the median 8-isoprostane concentration in exhaled breath condensate was 2.2 pg/ml (range 1.6-2.7), and the mean (SD) deltaN2 value was 1.1 (0.4)% N2/l. Feno was positively associated with deltaN2 (r(s) = 0.54, p = 0.032) while 8-isoprostane was inversely correlated with FEV1% predicted (rs= -0.58; p = 0.017) and CV as a percentage of vital capacity (rs= 0.58; p = 0.019).
  
  
  CONCLUSIONS
  Feno and 8-isoprostane in exhaled air are associated with small airways function in mild asthma. This suggests that these markers reflect small airway inflammation and favours a role for them as disease markers that is complementary to spirometry in the monitoring of patients with asthma.
authors.affiliation: Lung Function Laboratory C2-P, Leiden University Medical Centre (LUMC), P O Box 9600, NL-2300 RC Leiden, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Battaglia
authors.forename: H
authors.initials: H
authors.lastname: den Hertog
authors.forename: M C
authors.initials: MC
authors.lastname: Timmers
authors.forename: S P G
authors.initials: SP
authors.lastname: Lazeroms
authors.forename: A M
authors.initials: AM
authors.lastname: Vignola
authors.forename: K F
authors.initials: KF
authors.lastname: Rabe
authors.forename: V
authors.initials: V
authors.lastname: Bellia
authors.forename: P S
authors.initials: PS
authors.lastname: Hiemstra
authors.forename: P J
authors.initials: PJ
authors.lastname: Sterk
mesh_terms: D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D015415:Biomarkers / Q000032:analysis; D001991:Bronchitis / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000032:analysis*; D014797:Vital Capacity / Q000502:physiology
chemical_list: D015415:Biomarkers; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D015237:Dinoprost