Reference Ranges and Determinant Factors for Exhaled Nitric Oxide in a Healthy Korean Elderly Population

Abstract

Purpose: Exhaled nitric oxide (NO) is a useful non-invasive biomarker for asthma diagnosis; however, the literature suggests that exhaled NO levels may be affected by demographic factors. The present analysis investigated determinant factors that present exhaled NO reference levels for Korean elderly adults. Methods: For reference levels, we analyzed the baseline data of healthy adult participants in the Ansung cohort. The fraction of exhaled NO (FeNO) was measured by NIOX MINO (R). The characterization of the subjects was performed through structured questionnaires, spirometry, and methacholine challenge tests. To validate the diagnostic utility of the determined reference levels, asthma patients were recruited from medical institutions for FeNO measurement. Results: A total of 570 healthy subjects were analyzed (mean age, 59.9 +/- 12.3; male, 37.0%) for reference levels. FeNO levels significantly correlated with weight height, body mass index, atopy, or forced expiratory volume in 1 second % predicted by simple linear regression analysis. Multiple linear regression analysis identified gender as an independent determinant for FeNO levels; subsequently, the reference values for FeNO were 18.2 +/- 10.6 ppb (5th to 95th percentile, 6.0 to 37.4 ppb) for males and 12.1 +/- 6.9 ppb (5th to 95th percentile, 2.5 to 27.0 ppb) for females. The diagnostic utility of FeNO reference levels was validated by receiver operating curve analysis (area under curve, 0.900 for males and 0.885 for females) for diagnosing asthma. The optimal cutoff values for the prediction of asthma were 30.5 ppb for males and 20.5 ppb for females. Conclusions: The current analysis presented reference ranges and the diagnostic utility of FeNO levels for asthma in Korean elderly adults.