Exhaled nitric oxide and airway hyperresponsiveness to adenosine 5′-monophosphate and methacholine in children with asthma

Background: There is increasing interest in the role of indirect bronchial challenges because clinical studies have shown that indirect airway hyperresponsiveness (AHR) reflects underlying airway inflammation better than direct AHR. Fractional exhaled nitric oxide (FeNO) appears to be a useful clinical tool for assessing airway inflammation noninvasively. We examined whether FeNO is more closely related to AHR to indirect stimuli than AHR to direct stimuli in children with mild to moderate asthma. Methods: Fifty-nine asthmatic children aged 6-16 years without rhinitis, underwent spirometry, FeNO measurement and blood tests for serum total IgE, blood eosinophil count and serum eosinophil cationic protein (ECP). All subjects underwent methacholine and adenosine 5-monophosphate (AMP) challenge tests at intervals of 3 days. Results: In a univariate linear regression analysis, FeNO was significantly associated with both PC₂₀ AMP (R² = 0.341, p < 0.001) and PC₂₀ methacholine (R² = 0.188, p = 0.001). After adjustment for age, sex, serum total IgE and blood eosinophil count, the association between FeNO and PC₂₀ AMP (β = -1.98, p = 0.001) was more robust than that between FeNO and PC₂₀ methacholine (β = -0.87, p = 0.081). The significant correlation between FeNO and PC₂₀ AMP was observed in the steroid-naïve group (β = -2.48, p = 0.001), but not in the steroid-treated group (β = 0.88, p = 0.463). Conclusions: FeNO levels were more closely associated with PC₂₀ AMP than with PC₂₀ methacholine. This relationship could only be seen in the steroid-naïve subjects. These results suggest that FeNO levels in children with asthma may be more closely related to indirect AHR than to direct AHR.