Both inflammation and remodeling influence nitric oxide output in children with refractory asthma.
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.
Mahut
Bruno
B
Service de Physiologie-Explorations Fonctionnelles, Hôpital Henri Mondor, AP-HP, Créteil, France.
Delclaux
Christophe
C
Tillie-Leblond
Isabelle
I
Gosset
Philippe
P
Delacourt
Christophe
C
Zerah-Lancner
Françoise
F
Harf
Alain
A
de Blic
Jacques
J
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
D015415:Biomarkers; D009569:Nitric Oxide