Longitudinal Assessment of High Versus Low Levels of Fractional Exhaled Nitric Oxide Among Children with Asthma and Atopy

Abstract

Fractional exhaled nitric oxide (FeNO) has emerged as an important biomarker in asthma. Increasing evidence points to atopy as a confounding factor in the interpretation of elevated FeNO. We conducted a longitudinal study to understand the clinical significance of FeNO as an inflammatory biomarker. We identified 19 children aged 13-15years at baseline with a significant elevation in FeNO≥80 parts per billion (ppb) and randomly selected a group of children of similar age with a moderate elevation (40-79ppb) and normal-to-low FeNO (<40ppb). Between November 2010 and July 2011, three additional study visits were conducted. Ninety-three children participated in the study. There were 16, 24, and 53 participants in the high, mid, and low FeNO groups. During 1.5years of follow-up, mean FeNO levels were 82.6ppb (standard deviation [SD]=65.9) for atopic asthmatics, 50.6ppb (SD=42.6) for nonasthmatic atopics, 17.0ppb (SD=10.8) for nonatopic asthmatics, and 17.8ppb (SD=13.9) for nonatopic nonasthmatics (p<0.001). FeNO levels remained stable: 63% of the high FeNO group had a FeNO≥80 across all 4 measurements and 87 % of the normal-to-low FeNO group had a FeNO of <40 across all 4 measurements. The high FeNO group also was found to have an elevation in IL-5 (p=0.04), IL-6 (p=0.003), IL-10 (p=0.002), and total serum IgE (p<0.001), after adjustment by age, sex, height, body mass index, and atopy and asthma status. An elevation of FeNO appears to indicate an atopic phenotype regardless of an asthma diagnosis, clinical symptoms, or corticosteroid use. An elevation of FeNO also is associated with a systemic elevation in inflammatory cytokines.