title: New method for single-breath fraction of exhaled nitric oxide measurement with improved feasibility in preschool children with asthma.
abstract: BACKGROUND
  Respiratory societies recommend use of standardized methodologies for fraction of exhaled nitric oxide (FeNO) measurements in adults and children, but in preschoolers, feasibility remains a problem. The exhalation time needed to obtain steady-state FeNO is unclear. Our primary aim was to study the feasibility of an adapted single-breath FeNO method with age-adjusted exhalation times. We also studied the association between time to steady-state NO level and height, as well as FeNO in relation to asthma and current treatment with inhaled corticosteroids (ICS).
  
  
  METHODS
  Sixty-three children aged 3-10 years performed FeNO measurements with a hand-held electrochemical device with a newly developed flow-control unit. Exhalation times were pre-adapted to age. Exhaled air was simultaneously sampled to a chemiluminescence analyzer to measure time to steady-state NO level.
  
  
  RESULTS
  Eighty-one percent of the children achieved at least one approved measurement. From 4 years upwards, success rate was high (96%). Time to steady-state [NO] (median and interquartile range) was 2.5 s (2.4-3.5) at the age of 3-4 years and 3.5 s (2.7-3.8) at the age of 5-6 years. Height was associated with time to steady state (r(2) = 0.13, p = 0.02). FeNO (geometric mean [95% CI]) was higher in ICS-naïve asthmatic children (n = 19): 15.9 p.p.b. (12.2-20.9), than in both healthy controls (n = 8) 9.1 p.p.b. (6.6-12.4) and asthmatic subjects on treatment (n = 24) 11.5 p.p.b. (9.7-13.6).
  
  
  CONCLUSIONS
  We found this adapted single-breath method with age-adjusted exhalation times highly feasible for children aged 4-10 years. ICS-naïve asthmatic children had FeNO levels under the current guideline cutoff level (20 p.p.b.), highlighting the importance of taking age into account when setting reference values.
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Heijkenskjöld-Rentzhog
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Pia
authors.initials: P
authors.lastname: Kalm-Stephens
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Nordvall
authors.affiliation: Department of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden.
authors.forename: Andrei
authors.initials: A
authors.lastname: Malinovschi
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Alving
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001944:Breath Tests / Q000379:methods*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D045853:Exhalation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D009569:Nitric Oxide
keywords: airway inflammation; asthma; biomarker; children; feasibility; fraction of exhaled nitric oxide; preschool