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Effect of airways constriction on exhaled nitric oxide

¹Respiratory Division, University Hospital UZ Brussel; ²Biomedical Physics Laboratory, Université Libre de Bruxelles; and ³Respiratory Division, University Hospital Erasme, Université Libre de Bruxelles, Brussels, Belgium

Submitted 25 September 2007 ; accepted in final form 11 January 2008

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 (FEV₁) 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 FEV₁ 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.

histamine challenge; small conductive airways

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				S. C. George How accurately should we estimate the anatomical source of exhaled nitric oxide? J Appl Physiol, April 1, 2008; 104(4): 909 - 911. [Full Text] [PDF]