Alveolar, but not bronchial nitric oxide production is elevated in cystic fibrosis

Exhaled nitric oxide (NO) remains a promising non-invasive marker for measuring inflammation in lung diseases. In cystic fibrosis (CF), exhaled NO measured at a single expiratory flow has been found to be normal or low. However, this measure cannot localize the anatomical site of NO production. The aims of this study were to apply a multiple-flow NO analysis to compare alveolar NO concentration and bronchial NO flux in CF children with healthy controls. Twenty-two children with CF and 17 healthy controls had exhaled NO measured at four different expiratory flows to calculate bronchial NO flux and alveolar NO concentration. Median (range) alveolar NO concentration was 2.2 (0.6-5.6) ppb for children with CF and 1.5 (0.4-2.6) ppb for healthy controls. Median (range) bronchial NO flux was 445 (64-1,256) pL/sec for children with CF and 509 (197-1,913) pL/sec for healthy controls. Children with CF had a significantly higher alveolar NO concentration, but no significant difference in bronchial NO flux compared to healthy children. In conclusion, children with CF have increased alveolar NO production, but not bronchial NO flux compared to healthy controls. The distal airway is a major site of inflammation in CF, and measuring alveolar NO may be a marker of distal inflammation in this disease.