title: Persistently high exhaled nitric oxide and loss of lung function in controlled asthma.
abstract: BACKGROUND
  It remains unclear whether a persistently high exhaled nitric oxide fraction (FeNO) in patients with controlled asthma is associated with the progressive loss of lung function.
  
  
  METHODS
  This was a 3-year prospective study. We examined the changes in pre- and post-bronchodilator forced expiratory volume in 1 s (FEV1) and FeNO in 140 patients with controlled asthma. We initially determined the FeNO cut-off point for identifying patients with a rapid decline in FEV1 (>40 mL/yr). Next, a total of 122 patients who maintained high or non-high FeNO were selected, and the associations between the FeNO trend and changes in FEV1 and bronchodilator response (BDR) were investigated.
  
  
  RESULTS
  A FeNO level >40.3 ppb yielded 43% sensitivity and 86% specificity for identifying patients with a rapid decline in FEV1. Patients with persistently high FeNO had higher rates of decline in FEV1 (42.7 ± 37.5 mL/yr) than patients with non-high FeNO (16.7 ± 31.5 mL/yr) (p < 0.0005). The changes in BDR from baseline to the end of the study, in patients who had high or non-high levels of FeNO were -0.8% and 0.1%, respectively (p < 0.01). In a multivariate analysis adjusted by age, body mass index, asthma control, blood eosinophil numbers, and FEV1% of predicted, a FeNO level of ≥40 ppb was independently associated with an accelerated decline in FEV1 (p < 0.05).
  
  
  CONCLUSIONS
  This study suggests that FeNO is potentially valuable tool for identifying individuals who are at risk of a progressive loss of lung function among patients with controlled asthma.
authors.affiliation: Division of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan. Electronic address: kazmatsu@yamaguchi-u.ac.jp.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Matsunaga
authors.affiliation: Division of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: Tsunahiko
authors.initials: T
authors.lastname: Hirano
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Oka
authors.affiliation: Division of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Ito
authors.affiliation: Division of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Edakuni
mesh_terms: D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology*; D018450:Disease Progression; D045853:Exhalation; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D011446:Prospective Studies; D012372:ROC Curve; D012129:Respiratory Function Tests; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D009569:Nitric Oxide
keywords: Adult asthma; Airflow limitation; Airway inflammation; Exhaled nitric oxide; Remodeling