title: Exhaled nitric oxide: a biomarker integrating both lung function and airway inflammation changes.
abstract: BACKGROUND
  The increased fraction of exhaled nitric oxide (Feno) values observed in asthmatic patients are thought to reflect increased airway inflammation. However, Feno values can be affected by airway caliber reduction, representing a bias when using Feno values to assess asthma control.
  
  
  OBJECTIVE
  We sought to determine the effect of changes in both airway caliber and inflammation on Feno values using the allergen challenge model.
  
  
  METHODS
  FEV1 and Feno values were measured during early airway responses (EARs) and late airway responses after challenge with house dust mite allergens in 15 patients with mild allergic asthma. Helium and sulfur hexafluoride (SF6) phase III expired concentration slopes (SHe and SSF6, respectively) from single-breath washout tests were measured to identify sites of airway constriction.
  
  
  RESULTS
  In EARs, FEV1 and Feno value decreases reached 36.8% and 22%, respectively (P < .001). ΔSHe was greater than ΔSSF6 (+189.4% vs +82.2%, P = .001). In late airway responses FEV1 and Feno value decreases reached 31.7% and 28.7%, respectively (P < .001), with the same ΔSHe and ΔSSF6 pattern (+155.8% vs +76%, P = .001). Eight hours after the EAR, FEV1 was still decreased (P < .001), whereas Feno values had returned to baseline. At 24 hours, FEV1 had returned to baseline, with Feno values increased by 38.7% (P = .04).
  
  
  CONCLUSIONS
  In patients with mild allergic asthma, airway caliber changes modulate changes in Feno values resulting from airway inflammation. Therefore Feno should no longer be considered solely an inflammation biomarker but rather a biomarker that integrates both airway inflammation and lung function changes. Furthermore, early and late phases resulting from allergen exposure were shown to involve similar lung regions.
authors: Chest Department, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium; Chest Department, Centre Hospitalier Régional de Namur, Namur, Belgium.
authors: Amaryllis
authors: A
authors: Haccuria
authors: Chest Department, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors: Alain
authors: A
authors: Michils
authors: Chest Department, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors: Sébastien
authors: S
authors: Michiels
authors: Chest Department, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: avmuylem@ulb.ac.be.
authors: Alain
authors: A
authors: Van Muylem
mesh_terms: D000328:Adult; D056151:Airway Remodeling; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000175:diagnosis* / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism*; D001944:Breath Tests / Q000379:methods*; D018450:Disease Progression; D045853:Exhalation; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011014:Pneumonia / Q000276:immunology; D011446:Prospective Studies; D039981:Pyroglyphidae; D012129:Respiratory Function Tests; D012137:Respiratory System / Q000276:immunology*
chemical_list: D039741:Antigens, Dermatophagoides; D015415:Biomarkers; D009569:Nitric Oxide
keywords: Allergen challenge; asthma; bronchoprovocation; fractional exhaled nitric oxide; house dust mite