title: Different patterns of exhaled nitric oxide response to β2-agonists in asthmatic patients according to the site of bronchodilation.
abstract: BACKGROUND
  In asthmatic patients undergoing airway challenge, fraction of exhaled nitric oxide (FENO) levels decrease after bronchoconstriction. In contrast, model simulations have predicted both decreased and increased FENO levels after bronchodilation, depending on the site of airway obstruction relief.
  
  
  OBJECTIVE
  We sought to investigate whether β2-agonists might induce divergent effects on FENO values in asthmatic patients as a result of airway obstruction relief occurring at different lung depths.
  
  
  METHODS
  FENO, FEV1, and the slope of phase III of the single-breath washout test (S) of He (S(He)) and sulfur hexafluoride (S(SF6)) were measured in 68 asthmatic patients before and after salbutamol inhalation. S(He) and S(SF6) decreases reflected preacinar and intra-acinar obstruction relief, respectively. Changes (Δ) were expressed as a percentage from the baseline.
  
  
  RESULTS
  No FENO change (|ΔFENO| ≤ 10%) was found in 16 patients (mean [SD]: 2.5% [5.2%]; ie, FENO= group); a ΔFENO value of greater than 10% was found in 23 patients (31.7% [20.3%]; ie, the FENO+ group); and a ΔFENO value of less than -10% was found in 29 patients (-31.5% [17.3%]; ie, the FENO- group). All groups had similar ΔFEV1 values. In the FENO= group neither S(He) nor S(SF6) changed, in the FENO+ group only S(He) decreased significantly (-21.8% [SD 28.5%], P = .03), and in the FENO- group both S(He) (-29.8% [24.0%], P < .001) and S(SF6) (-27.2% [23.3%], P < .001) decreased.
  
  
  CONCLUSIONS
  Three FENO behaviors were observed in response to β2-agonists: a decrease likely caused by relief of an intra-acinar airway obstruction that we propose reflects amplification of nitric oxide back-diffusion, an increase likely associated with a predominant dilation up to the preacinar airways, and FENO stability when obstruction relief involved predominantly the central airways. In combination, these results suggest a new role for FENO in identifying the site of airway obstruction in asthmatic patients.
authors.affiliation: Chest Department, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Alain
authors.initials: A
authors.lastname: Michils
authors.affiliation: Department of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden.
authors.forename: Andrei
authors.initials: A
authors.lastname: Malinovschi
authors.affiliation: Chest Department, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Amaryllis
authors.initials: A
authors.lastname: Haccuria
authors.affiliation: Chest Department, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Michiels
authors.affiliation: Chest Department, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: avmuylem@ulb.ac.be.
authors.forename: Alain
authors.initials: A
authors.lastname: Van Muylem
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use; D045853:Exhalation; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D015203:Reproducibility of Results; D012129:Respiratory Function Tests; D012680:Sensitivity and Specificity; D014797:Vital Capacity
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents; D015415:Biomarkers; D001993:Bronchodilator Agents; D009569:Nitric Oxide
keywords: Asthma; bronchodilation; fraction of exhaled nitric oxide; ventilation distribution