Factors affecting exhaled nitric oxide measurements: the effect of sex

BACKGROUND: Exhaled nitric oxide (F(E)NO) measurements are used as a surrogate marker for eosinophilic airway inflammation. However, many constitutional and environmental factors affect F(E)NO, making it difficult to devise reference values. Our aim was to evaluate the relative importance of factors affecting F(E)NO in a well characterised adult population. METHODS: Data were obtained from 895 members of the Dunedin Multidisciplinary Health and Development Study at age 32. The effects of sex, height, weight, lung function indices, smoking, atopy, asthma and rhinitis on F(E)NO were explored by unadjusted and adjusted linear regression analyses. RESULTS: The effect of sex on F(E)NO was both statistically and clinically significant, with F(E)NO levels approximately 25% less in females. Overall, current smoking reduced F(E)NO up to 50%, but this effect occurred predominantly in those who smoked on the day of the F(E)NO measurement. Atopy increased F(E)NO by 60%. The sex-related differences in F(E)NO remained significant (p < 0.001) after controlling for all other significant factors affecting F(E)NO. CONCLUSION: Even after adjustment, F(E)NO values are significantly different in males and females. The derivation of reference values and the interpretation of F(E)NO in the clinical setting should be stratified by sex. Other common factors such as current smoking and atopy also require to be taken into account.