Daily exhaled nitric oxide measurements and asthma exacerbations in children

Rationale

Fractional exhaled nitric oxide (FeNO) is a biomarker for eosinophilic airway inflammation and can be measured at home on a daily basis. Increase in airway inflammation assessed by FeNO may indicate a higher risk of asthma exacerbation.

Objective

To assess changes in FeNO before and after an exacerbation compared to a control period.

Methods

A post-hoc analysis of the CHARISM study (De Jongste, AJRCCM 2009) was performed on daily FeNO monitoring over 30 weeks in children with mild to moderate atopic asthma (n=77, mean age 11.6 years). Variability of daily FeNO was examined during 3-week periods before and after minor and major exacerbations and compared to reference periods of the same patients when stable. Minor exacerbations were defined by an increase in symptom scores, major exacerbations by prescription of a prednisone course. The percentage change in relation to the median of the reference period of FeNO before and after exacerbations was calculated. Individual mean and maximal FeNO values, their variability and cross-correlation with symptoms (strength of correlation between FeNO and symptoms), autocorrelation of FeNO (strength of correlation of FeNO with itself shifted by one day), as well as slopes of FeNO were quantified around exacerbations, and examined as predictors for exacerbations using logistic regression. In order to determine how frequently FeNO would have to be measured to predict an exacerbation, we randomly dropped data points from the 3-week FeNO blocks before exacerbations.

Main results

FeNO could be assessed in relation to 25 minor and 12 major exacerbations. Daily FeNO started to increase an average of 10 days before the onset of a minor exacerbation, but not before major exacerbations. The variability, cross-correlation, auto-correlation and slope of daily FeNO data were significantly increased well before minor exacerbations, but not before major exacerbations. Single FeNO values were not predictive for exacerbations. At least 3 to 5 random FeNO measurements in 3 weeks were needed to calculate a slope that predicted a minor exacerbation (for 3, 4 and 5 FeNO data points: OR 1.56 [0.97; 2.50], OR 1.92 [1.08; 3.41] and OR 1.79 [1.00; 3.20], respectively).

Conclusion

We observed a rise in FeNO starting 10 days before a minor asthma exacerbation, but not before major exacerbations. We speculate that the role of eosinophilic airway inflammation, as reflected by FeNO, differs between minor and major exacerbations. Further studies are warranted to examine if exacerbations could be prevented by acting upon frequent FeNO monitoring.