title: Both inflammation and remodeling influence nitric oxide output in children with refractory asthma.
abstract: BACKGROUND
  Exhaled nitric oxide can be used to monitor airway inflammation in asthma. We hypothesized that the strong link between nitric oxide and inflammation may obscure a weaker link with airway remodeling.
  
  
  OBJECTIVE
  The aim of this study was to determine whether airway remodeling influenced exhaled nitric oxide in 28 asthmatic children (median age [25th-75th], 11 [10-14] years old) with refractory asthma defined as airflow limitation and/or exacerbations despite high-dose inhaled steroids.
  
  
  METHODS
  Multiple-flow analysis of exhaled nitric oxide was used to correlate alveolar nitric oxide concentration and maximal conducting airway nitric oxide output to pulmonary function tests, bronchoalveolar lavage, and bronchial biopsy findings.
  
  
  RESULTS
  Nitric oxide measurements were related to inflammation and T(H)1/T(H)2 balance, that is, subepithelial eosinophilic infiltration and eosinophilic cationic protein and IFN-gamma/IL-4 ratio in bronchoalveolar lavage fluids. Nitric oxide measurements were also correlated with several parameters of airway remodeling: alveolar nitric oxide concentration with TGF-beta in bronchoalveolar lavage fluid (r = 0.42, P =.03) and maximal conducting airway nitric oxide output with reticular basement membrane thickness (r = 0.61, P =.0007) and tissue inhibitor of matrix metalloproteinases 1/matrix metalloproteinase 9 ratio in bronchoalveolar lavage fluid (r = 0.43, P =.04). Moreover, alveolar nitric oxide concentration was correlated with MEF(25-75) (r = 0.60, P =.02).
  
  
  CONCLUSIONS
  These findings suggest that both subacute inflammation and remodeling influence nitric oxide output in refractory asthma.
authors.affiliation: Service de Physiologie-Explorations Fonctionnelles, Hôpital Henri Mondor, AP-HP, Créteil, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Mahut
authors.forename: Christophe
authors.initials: C
authors.lastname: Delclaux
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tillie-Leblond
authors.forename: Philippe
authors.initials: P
authors.lastname: Gosset
authors.forename: Christophe
authors.initials: C
authors.lastname: Delacourt
authors.forename: Françoise
authors.initials: F
authors.lastname: Zerah-Lancner
authors.forename: Alain
authors.initials: A
authors.lastname: Harf
authors.forename: Jacques
authors.initials: J
authors.lastname: de Blic
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001485:Basement Membrane / Q000473:pathology*; D015415:Biomarkers; D001706:Biopsy; D001980:Bronchi / Q000276:immunology / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002648:Child; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D012129:Respiratory Function Tests
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide