Methodological issues related to exhaled nitric oxide measurement in children aged four to six years

This study was designed to test five methodological issues related to measurement of fractional exhaled nitric oxide (FE(NO)) in children aged 4-6 years using commercially available apparatus. Participants attended two randomly selected schools. A respiratory questionnaire was completed. Measurements of FE(NO) were made on successive days, using a NIOX analyzer employing standard or modified methodologies. Ninety-one children participated in the study (mean age, 5.3 years; 46 boys). Using a standard methodology (n = 61), FE(NO) was successfully measured in 28 (46%) children, 1/12 aged 4 years, 12/25 aged 5 years, and 15/24 aged 6 years (trend test P = 0.01). On the first assessment, FE(NO) could be determined in more boys than girls (64% vs. 30%, respectively, P = 0.008), but this gender difference was not apparent on the second assessment. Exhaled NO was reproducible over a 24-hr period; the mean difference between repeated measurements of natural log (ln) FE(NO) was 0.016 parts per billion (ppb) (95% confidence limits, -0.479, 0.511), n = 20. Data from 35 assessments showed that values of FE(NO) did not alter over nine individual, successive measurements. Use of a modified methodology in 30 children increased success in obtaining FE(NO), but these values were unreliable. In conclusion, measurements of FE(NO) can be obtained in the majority of 5- and 6-year-old but not 4-year-old children. Exhaled NO measurements were reproducible over a 24-hr interval, and did not change over up to nine expiratory maneuvers in these young children.