title: Associated demographics of persistent exhaled nitric oxide elevation in treated asthmatics.
abstract: BACKGROUND
  The fraction of exhaled nitric oxide (FENO) is reduced by anti-inflammatory treatment in asthma. However, the FENO level is also regulated by individual demographics and there is considerable variation among clinically stable patients.
  
  
  OBJECTIVE
  We hypothesized that some demographics may be responsible for persistent FENO elevation despite inhaled corticosteroids (ICS) therapy in asthma.
  
  
  METHODS
  This was a prospective observational study. We initially screened 250 stable asthmatics and determined the FENO cut-off point for identifying poorly controlled asthma defined by one of the following criteria: Asthma control test <20, or forced expiratory volume in one-second % of predicted <80%, or peak expiratory flow variability <80% (Study 1). After 12-weeks, 229 patients who maintained high or low FENO were selected and the independent factors which might contribute to a high FENO were examined (Study 2).
  
  
  RESULTS
  A FENO level >39.5 p.p.b. yielded 67% sensitivity and 76% specificity for identifying the patients with poorly controlled asthma. The persistent high FENO group (≥ 40 p.p.b.) was more likely to be ex-smokers, to show evidence of atopy (positive specific IgE, higher serum IgE and blood eosinophils), and to have allergic comorbidities. Especially, past smoking history, blood eosinophils, and chronic rhinosinusitis were identified to be independent predictors of high FENO. Neither the dose of ICS nor other medication use showed any difference between the groups.
  
  
  CONCLUSIONS
  These results suggested that past smoking history, blood eosinophilia, and chronic rhinosinusitis are involved in the persistent airway inflammation detected by FENO. Although their relative contributions on FENO values should be further quantified, clarification of the features of the subjects with high FENO might provide clues for adjustment of the treatment approach in asthma.
authors.affiliation: Third Department of Internal Medicine, School of Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsunaga
authors.forename: S
authors.initials: S
authors.lastname: Yanagisawa
authors.forename: T
authors.initials: T
authors.lastname: Hirano
authors.forename: T
authors.initials: T
authors.lastname: Ichikawa
authors.forename: A
authors.initials: A
authors.lastname: Koarai
authors.forename: K
authors.initials: K
authors.lastname: Akamatsu
authors.forename: H
authors.initials: H
authors.lastname: Sugiura
authors.forename: Y
authors.initials: Y
authors.lastname: Minakata
authors.forename: K
authors.initials: K
authors.lastname: Matsunaga
authors.forename: T
authors.initials: T
authors.lastname: Kawayama
authors.forename: M
authors.initials: M
authors.lastname: Ichinose
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D003710:Demography; D045853:Exhalation; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis*; D012307:Risk Factors
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D009569:Nitric Oxide