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

Abstract

PurposeExhaled 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.MethodsFor 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®. 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.ResultsA 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.ConclusionsThe current analysis presented reference ranges and the diagnostic utility of FeNO levels for asthma in Korean elderly adults.

Important non‐disease‐related determinants of exhaled nitric oxide levels in mild asthma – results from the Swedish GA2LEN study

“…The relation with height is thought to reflect a larger airway size, leading to a larger airway surface as a source of NO; in line with this, a clear relation with height can be found in children [38]. The association with weight is in line with results from univariate analysis from healthy adults, reported by Jo et al [39]. This could in theory be explained by Th1-polarisation [40] and lower levels of Th2-cytokines seen in obese patients with asthma [41] that could lead to lower FeNO levels.…”

“…This could in theory be explained by Th1-polarisation [40] and lower levels of Th2-cytokines seen in obese patients with asthma [41] that could lead to lower FeNO levels. However, this relation became statistically nonsignificant after adjustments in the present study, and it was mainly explained by gender differences in the report of Jo et al [39]. Allergic sensitization was related to higher levels of FeNO, especially when patients were sensitized to both perennial and pollen allergens.…”

Reference ranges for induced sputum eosinophil counts in Korean adult population

“…However, it should be noted that the reference values were obtained from relatively small numbers of studies conducted in Western populations [6, 7]. For FeNO analyses, the potential discrepancy between different ethnic or demographic groups have been suggested (frequently higher in Asians than Caucasians) [11, 14]. That was a motivation that we attempted to determine reference ranges in Korean adults in the present study.…”

“…However, currently available reference levels (defined as more than 3% of eosinophil count in total cell count) have been derived from Western population studies [6, 7, 8, 9, 10], but not have been examined in Korean adults yet. Considering the potential heterogeneity in fractional exhaled nitric oxide (FeNO) levels among ethnic groups [11], induced sputum profiles also need to be examined specifically for Korean populations. In this study, we aimed to determine reference ranges for induced sputum eosinophil in healthy Korean adults.…”

Repeated Measurement of Fractional Exhaled Nitric Oxide Is Not Essential for Asthma Screening

“…Spirometry was carried out on the first study day after the FeNO measurements. Lung function tests were performed with a spirometer (Vmax, SensorMedics) in accordance with ATS/ERS recommendations [10]. Forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), and the FEV 1 /FVC ratio were obtained from the best reproducible forced expiratory maneuvers.…”