title: Exhaled nitric oxide predicts persistence of wheezing, exacerbations, and decline in lung function in wheezy infants and toddlers.
abstract: BACKGROUND
  There are limited data assessing the predictive value of fraction of exhaled nitric oxide (FENO ) for persistence of wheezing, exacerbations, or lung function change over time in infants/toddlers with recurrent wheezing.
  
  
  OBJECTIVE
  In an ongoing longitudinal cohort of infants and toddlers with recurrent wheezing, we compared predictive values of single-breath FENO (SB-FENO ), tidal-breathing mixed expired FENO (tidal-FENO ), bronchodilator responsiveness (BDR) and the Castro-Rodriquez Asthma Predictive Index (API) for persistence of wheezing, exacerbations and lung function change through age 3 years.
  
  
  METHODS
  Enrolment forced expiratory flows and volumes infant pulmonary function tests (iPFTs) were measured in 44 infants/toddlers using the raised volume rapid thoracoabdominal compression method. SB-FENO was measured at 50 mL/s, and tidal-FENO was measured during awake tidal breathing. Clinical outcomes were assessed at age 3 years in 42 infants. Follow-up iPFTs were completed between ages 2.5-3 years in 32 subjects.
  
  
  RESULTS
  An enrolment SB-FENO concentration ≥ 30 p.p.b. predicted persistence of wheezing at age 3 years with a sensitivity of 77%, a specificity of 94%, and an area under the curve (AUC) of 0.86 (95% CI: 0.74-0.98). The sensitivity, specificity, positive predictive, and negative predictive values of SB-FENO for persistence of wheezing and exacerbations were superior to tidal-FENO , BDR, and the API. SB-FENO ≥ 30 p.p.b. and tidal-FENO ≥ 7 p.p.b. measured at enrolment was associated with a decline in both FEV0.5 and FEF25-75 between enrolment and age 3 years.
  
  
  CONCLUSIONS
  In wheezy infants/toddlers, SB-FENO was superior to tidal-FENO , BDR, and the API in predicting future exacerbations and persistence of wheezing at age 3 years. Both SB-FENO and tidal-FENO were associated with lung function decline over time.
authors.affiliation: Division of Pulmonary Medicine, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Elliott
authors.forename: S L
authors.initials: SL
authors.lastname: Heltshe
authors.forename: D C
authors.initials: DC
authors.lastname: Stamey
authors.forename: E S
authors.initials: ES
authors.lastname: Cochrane
authors.forename: G J
authors.initials: GJ
authors.lastname: Redding
authors.forename: J S
authors.initials: JS
authors.lastname: Debley
mesh_terms: D001249:Asthma / Q000175:diagnosis / Q000503:physiopathology; D002675:Child, Preschool; D045853:Exhalation; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D009569:Nitric Oxide; D011379:Prognosis; D012372:ROC Curve; D012129:Respiratory Function Tests; D012135:Respiratory Sounds / Q000175:diagnosis* / Q000503:physiopathology*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D009569:Nitric Oxide
keywords: FENO; exhaled nitric oxide; infants; pulmonary function; raised-volume rapid thoracic compression; recurrent wheezing