Relationships of online exhaled, offline exhaled, and ambient nitric oxide in an epidemiologic survey of schoolchildren

Field measurements of exhaled nitric oxide (FeNO) and ambient nitric oxide (NO) are useful to assess both respiratory health and short-term air pollution exposure. Online real-time measurement maximizes data quality and comparability with clinical studies, but offline delayed measurement may be more practical for large epidemiological studies. To facilitate cross-comparison in larger studies, we measured FeNO and concurrent ambient NO both online and offline in 362 children at 14 schools in 8 Southern California communities. Offline breath samples were collected in bags at 100 ml/s expiratory flow with deadspace discard; online FeNO was measured at 50 ml/s. Scrubbing of ambient NO from inhaled air appeared to be nearly 100% effective online, but 50–75% effective offline. Offline samples were stored at 2–8°C and analyzed 2–26 h later at a central laboratory. Offline and online FeNO showed a nearly (but not completely) linear relationship (R2=0.90); unadjusted means (ranges) were 10 (4–94) and 15 (3–181) p.p.b., respectively. Ambient NO concentration range was 0–212 p.p.b. Offline FeNO was positively related to ambient NO (r=0.30, P<0.0001), unlike online FeNO (r=0.09, P=0.08), indicating that ambient NO artifactually influenced offline measurements. Offline FeNO differed between schools (P<0.001); online FeNO did not (P=0.26), suggesting artifacts related to offline bag storage and transport. Artifact effects were small in comparison with between-subject variance of FeNO. An empirical statistical model predicting individual online FeNO from offline FeNO, ambient NO, and lag time before offline analysis gave R2=0.94. Analyses of school or age differences yielded similar results from measured or model-predicted online FeNO. Conclusions: Either online or offline measurement of exhaled NO and concurrent ambient NO can be useful in field epidemiology. Influence of ambient NO on exhaled NO should be examined carefully, particularly for offline measurements.