title: Effect of airways constriction on exhaled nitric oxide.
abstract: While airway constriction has been shown to affect exhaled nitric oxide (NO), the mechanisms and location of constricted airways most likely to affect exhaled NO remain obscure. We studied the effects of histamine-induced airway constriction and ventilation heterogeneity on exhaled NO at 50 ml/s (Fe(NO,50)) and combined this with model simulations of Fe(NO,50) changes due to constriction of airways at various depths of the lung model. In 20 normal subjects, histamine induced a 26 +/- 15(SD)% Fe(NO,50) decrease, a 9 +/- 6% forced expiratory volume in 1 s (FEV(1)) decrease, a 19 +/- 9% mean forced midexpiratory flow between 25% and 75% forced vital capacity (FEF(25-75)) decrease, and a 94 +/- 119% increase in conductive ventilation heterogeneity. There was a significant correlation of Fe(NO,50) decrease with FEF(25-75) decrease (P = 0.006) but not with FEV(1) decrease or with increased ventilation heterogeneity. Simulations confirmed the negligible effect of ventilation heterogeneity on Fe(NO,50) and showed that the histamine-induced Fe(NO,50) decrease was due to constriction, with associated reduction in NO flux, of airways located proximal to generation 15. The model also indicated that the most marked effect of airways constriction on Fe(NO,50) is situated in generations 10-15 and that airway constriction beyond generation 15 markedly increases Fe(NO,50) due to interference with the NO backdiffusion effect. These mechanical factors should be considered when interpreting exhaled NO in lung disease.
authors.affiliation: Respiratory Division, Univ. Hospital UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. sylvia.verbanck@uzbrussel.be
authors.forename: Sylvia
authors.initials: S
authors.lastname: Verbanck
authors.forename: Yannick
authors.initials: Y
authors.lastname: Kerckx
authors.forename: Daniel
authors.initials: D
authors.lastname: Schuermans
authors.forename: Walter
authors.initials: W
authors.lastname: Vincken
authors.forename: Manuel
authors.initials: M
authors.lastname: Paiva
authors.forename: Alain
authors.initials: A
authors.lastname: Van Muylem
mesh_terms: D000328:Adult; D000465:Algorithms; D016084:Bronchoconstriction / Q000502:physiology*; D003198:Computer Simulation; D004058:Diffusion; D004242:Diving / Q000502:physiology; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006632:Histamine; D006801:Humans; D008168:Lung / Q000502:physiology; D008171:Lung Diseases / Q000503:physiopathology; D008297:Male; D008953:Models, Anatomic; D015233:Models, Statistical; D009569:Nitric Oxide / Q000378:metabolism*; D015656:Respiratory Mechanics / Q000502:physiology; D013147:Spirometry; D014797:Vital Capacity / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D006632:Histamine