Reference Ranges for Exhaled Nitric Oxide Fraction in Healthy Japanese Adult Population

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Abstract
The measurement of the exhaled nitric oxide fraction (FE(NO)) is proposed as a useful marker of airway inflammation. In healthy adults, there have been a few studies of the reference ranges for FE(NO) in Caucasians. A community study in other regions may reveal any possible ethnic differences in the FE(NO) levels. A total of 240 healthy adults aged between 18 to 74 years were recruited from four medical centers in Japan. Current smokers and subjects having a history of atopic disease were not included. FE(NO) was measured using an online electrochemical nitric oxide analyzer according to the current guidelines. The reference ranges for FE(NO) were estimated using two different statistical methods recommended by International Federation of Clinical Chemistry and Laboratory Medicine. The mean FE(NO) was 16.9 ppb (parts per billion) with a 95% prediction interval (2.5 to 97.5 percentiles) of 6.5 to 35.0 ppb in healthy Japanese adults. Normality assumptions were met for the logarithm-transformed FE(NO). The geometric mean FE(NO) was 15.4 ppb with a mean ± two standard deviations of 6.5 to 36.8 ppb. Age, gender, height, and past smoking history were not associated with the FE(NO) levels. The reference ranges for FE(NO) in healthy Japanese adults were similar to those of Caucasians. It seems reasonable that the upper limit of FE(NO) for healthy adults should be set at approximately 36.0 ppb irrespective of ethnic differences.