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 (FENO) in populations. We evaluated the reproducibility of FENO in healthy subjects and determined the number of subjects necessary to carry out a longitudinal survey of FENO in a population containing smokers and non-smokers, based on the assessed reproducibility.

METHODS

The reproducibility of FENO was examined in 18 healthy smokers and 21 non-smokers. FENO 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 FENO and log-transformed FENO was described. The power of a longitudinal study based on a relative increase in FENO was estimated using a bilateral t-test of the log-transformed FENO using the between-session variance of the assay.

RESULTS

FENO measurements were highly reproducible throughout the study. FENO was significantly higher in males than females regardless of smoking status. FENO was positively associated with height (p < 0.001), gender (p < 0.034), smoking (p < 0.0001) and percent FEV1/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 FENO respectively.

CONCLUSION

The good reproducibility of FENO is not influenced by gender or smoking habits. In a well controlled, longitudinal study it should allow detecting even small increases in FENO with a reasonable population size.