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 FENO 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.