Effect of airways constriction on exhaled nitric oxide

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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 (FeNO,50) and combined this with model simulations of FeNO,50 changes due to constriction of airways at various depths of the lung model. In 20 normal subjects, histamine induced a 26 ± 15(SD)% FeNO,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 (FEF25–75) decrease, and a 94 ± 119% increase in conductive ventilation heterogeneity. There was a significant correlation of FeNO,50 decrease with FEF25–75 decrease ( P = 0.006) but not with FEV1 decrease or with increased ventilation heterogeneity. Simulations confirmed the negligible effect of ventilation heterogeneity on FeNO,50 and showed that the histamine-induced FeNO,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 FeNO,50 is situated in generations 10–15 and that airway constriction beyond generation 15 markedly increases FeNO,50 due to interference with the NO backdiffusion effect. These mechanical factors should be considered when interpreting exhaled NO in lung disease.