Exhaled nitric oxide concentrations: online versus offline values in healthy children

Exhaled nitric oxide (FE(NO)) is a noninvasive and practical method to assess airway inflammation. We conducted this investigation to determine the most appropriate flow rate to measure FE(NO) and to obtain reference values for FE(NO) in children. FE(NO) was measured in 112 healthy 6-18 year olds (60 males) at 4 expiratory flow rates (46, 31, 23, and 15 mL/sec) using a chemiluminescent nitric oxide analyzer. Offline and online analyses were done to determine FE(NO) intraclass correlation coefficients, the relationship between FE(NO) and expiratory flow rates, and the effects of age and gender on these measurements. The major findings were: 1) intraclass correlation coefficients for FE(NO) and flow rates ranged from 0.92-0.99 for offline values, and 0.99 for all online values; 2) variation at an expiratory flow rate of 46 mL/sec (SD, 9.39) was considerably less than at other flows, especially at 15 mL/sec (SD, 26.55); 3) FE(NO) increased as flow rates decreased for both offline and online values; 4) there were no significant differences and good agreement between offline bag and online FE(NO) values at 31 and 46 mL/sec expiratory flows; and 5) using multiple regression, significant predictors of FE(NO) were flow, body surface area, age, and FEF(25-75). We have provided FE(NO) values in healthy children and propose that the ideal expiratory flow rate for FE(NO) measurements in children using the single breath technique is between 30-50 mL/sec.