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

Abstract

Purpose 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. Methods We identified 19 children aged 13–15 years 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 (40–79 ppb) and normal-to-low FeNO (<40 ppb). Between November 2010 and July 2011, three additional study visits were conducted. Results Ninety-three children participated in the study. There were 16, 24, and 53 participants in the high, mid, and low FeNO groups. During 1.5 years of follow-up, mean FeNO levels were 82.6 ppb (standard deviation [SD] = 65.9) for atopic asthmatics, 50.6 ppb (SD = 42.6) for nonasthmatic atopics, 17.0 ppb (SD = 10.8) for nonatopic asthmatics, and 17.8 ppb (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. Conclusions 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.

High prevalence of house dust mite sensitization in children with severe asthma living at high altitude in a tropical country

“…This increase has been associated with the severe asthma atopic phenotype. In our study, we find a weak, marginal, but non‐significant correlation between FE NO values and the FEV 1 /FVC ratio (the higher the FE NO value the lower the FEV 1 /FVC ratio); this result is similar to that found by Elmasri in his study on FE NO levels in children with asthma and atopy . We do not have reference values for FE NO at the altitude of Bogotá (located at 2640 meters).…”

An Overview of Fractional Exhaled Nitric Oxide and Children with Asthma

“…One study of 52 children aged 5–36 months demonstrated significantly higher FeNO levels in children with a positive asthma predictive index (API) compared to those with a negative API, although the median levels in both groups were low at 12.5 and 5.6 ppb, respectively [34]. FeNO levels have been described to be higher in allergic or atopic asthma compared to nonallergic asthma [45], but are also elevated in children who have allergic sensitization as demonstrated by positive skin-prick testing or aeroallergen-specific IgE [32,35,43]. FeNO levels have been shown to be higher in children with allergic sensitization or atopy and no asthma compared to nonallergic asthma [32,35,45], and have been found to be higher in children both with treated and untreated asthma than in healthy nonatopic children [54].…”

S2k-Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma

“…Die Bestimmung des FeNO kann bei Erwachsenen und bei Kindern hilfreich sein bei der Sicherung der Asthmadiagnose, insbesondere, wenn die Messung beim Patienten ohne regelmäßige ICS-Therapie und im obstruktionsfreien Intervall durch-geführt wird [160]. Bei allergischem Asthma wurden höhere FeNO-Werte als bei nicht allergischem Asthma gefunden [161]. Niedrige FeNO-Werte allein erlauben dagegen nicht den differenzialdiagnostischen Ausschluss von Asthma bronchiale [162].…”