Reproducibility of exhaled nitric oxide in smokers and non-smokers: relevance for longitudinal studies

BACKGROUND: Currently, there is much interest in measuring fractional exhaled nitric oxide (FE(NO)) in populations. We evaluated the reproducibility of FE(NO )in healthy subjects and determined the number of subjects necessary to carry out a longitudinal survey of FE(NO )in a population containing smokers and non-smokers, based on the assessed reproducibility. METHODS: The reproducibility of FE(NO )was examined in 18 healthy smokers and 21 non-smokers. FE(NO )was assessed once at 9 AM on five consecutive days; in the last day this measurement was repeated at 2 PM. Respiratory symptoms and medical history were assessed by questionnaire. The within- and between-session repeatability of FE(NO )and log-transformed FE(NO )was described. The power of a longitudinal study based on a relative increase in FE(NO )was estimated using a bilateral t-test of the log-transformed FE(NO )using the between-session variance of the assay. RESULTS: FE(NO )measurements were highly reproducible throughout the study. FE(NO )was significantly higher in males than females regardless of smoking status. FE(NO )was positively associated with height (p < 0.001), gender (p < 0.034), smoking (p < 0.0001) and percent FEV(1)/FVC (p < 0.001) but not with age (p = 0.987). The between-session standard deviation was roughly constant on the log scale. Assuming the between-session standard deviation is equal to its longitudinal equivalent, either 111 or 29 subjects would be necessary to achieve an 80% power in detecting a 3% or a 10% increase in FE(NO )respectively. CONCLUSION: The good reproducibility of FE(NO )is not influenced by gender or smoking habits. In a well controlled, longitudinal study it should allow detecting even small increases in FE(NO )with a reasonable population size.