Alveolar and Bronchial Nitric Oxide Output in Healthy Children

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Exhaled nitric oxide (NO) concentration is a marker of pulmonary inflammation. It is usually measured at a single exhalation flow rate. However, measuring exhaled NO at multiple flow rates allows assessment of the flow-independent NO parameters: alveolar NO concentration, bronchial NO flux, bronchial wall NO concentration, and bronchial diffusing capacity of NO. Our aim was to determine the flow-independent NO parameters in healthy schoolchildren and to compare two different mathematical approaches. Exhaled NO was measured at four flow rates (10, 50, 100, and 200 ml/sec) in 253 schoolchildren (7-13 years old). Flow-independent NO parameters were calculated with linear method (flows ≥50 ml/sec) and non-linear method (all flows). Sixty-six children (32 boys and 34 girls) with normal spirometry and no history or present symptoms of asthma, allergy, atopy or other diseases were included in the analysis. Median bronchial NO flux was 0.4 nl/sec (mean±SD: 0.5±0.3 nl/sec) and median alveolar NO concentration was 1.9 ppb (2.0±0.8 ppb) with the linear method. Bronchial NO flux correlated positively with height (r=0.423; P<0.001), FEV1 (r=0.358; P=0.003), and FVC (r=0.359; P=0.003). With the nonlinear method, median bronchial wall NO concentration was 49.6 ppb (68.0±53.3 ppb) and bronchial diffusing capacity of NO was 10.0 pl/sec/ppb (11.8±7.5 pl/sec/ppb). The non-linear method gave lower alveolar NO concentration (1.4 [1.5±0.7] ppb, P<0.001) and higher bronchial NO flux (0.5 [0.6±0.3] nl/sec, P<0.001) than the linear method, but the results were highly correlated between the two methods (r=0.854 and r=0.971, P<0.001). In conclusion, the multiple flow rate method is feasible in children but different mathematical methods give slightly different results. Reference values in healthy children are of value when applying bronchial and alveolar NO parameters in the diagnostics and follow-up of inflammatory lung diseases.

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