Airway responsiveness and inflammatory markers in non-asthmatic adolescents with elevated FeNO

Background: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation in the airways. Studies have reported correlations between FeNO, and eosinophilic inflammation and the degree of airway responsiveness. Recent studies suggest FeNO as a predictor of new-onset asthma. Objectives: To study airway responsiveness and other inflammatory markers in non-asthmatic adolescents with elevated FeNO. Methods: A total of 959 adolescents, aged 12-15 years from a general population, answered a standardized questionnaire and performed FeNO measurements at a baseline visit. Adolescents with elevated FeNO at baseline (FeNO100 >15 ppb) and negative in the clinical assessment of asthma, were invited to this follow-up study. Randomly selected subjects with low FeNO (FeNO100 < 5 ppb) and without reported symptoms of asthma or allergy at baseline, were selected as controls (n=28). Non-smoking, eligible subjects were invited to two study visits where FeNO50 and methacholine reactivity were measured. Human neutrophil lipocalin (HNL) and myeloperoxidase (MPO) were measured in serum. Results: The cases (n=19) had significantly lower cumulative methacholine dose causing a fall of 20% in FEV1 (p<0.05) than the controls. Blood eosinophil counts were significantly higher among the cases (p<0.001) and showed a correlation to FeNO (r=0.45; p= 0.002). Serum HNL and MPO were higher in the controls than cases (both p=0.03) and there was a negative correlation between HNL and FeNO (r=-0.30; p=0.04). Conclusions: Elevated FeNO in non-asthmatic adolescents was associated with eosinophilia, airway hyperresponsiveness and lower levels of neutrophil activation markers.