Do changes in spirometric indices and FeNO predict asthma outcomes in children? An individual patient data analysis using results from seven FeNO trials

Introduction: Guidelines recommend spirometry and/or fractional exhaled nitric oxide (FeNO) as objective measurements to guide asthma management. Our hypothesis was that falling FEV1, FEV1/FVC ratio or FEF25-75 or rising FeNO measurements are associated with future adverse asthma outcomes. Methods: Data were obtained from 7 trials using FeNO to guide asthma treatment. Predictors were change in % FEV1, FEV1/FVC ratio or FEF25-75 and % change in FeNO between baseline and 3 months. Loss of asthma control and asthma attack between 3 and 6 months were the outcomes. A one-stage individual patient data meta-analysis was conducted using a mixed effects logistic model, including a random effect for study. Results: Data were available in 1112 children (58% male, mean age 12.6 years [SD 3.1]) from seven trials. A reduction of 10% FEV1 was associated with increased risk for future attack (OR 1.28 [1.02, 1.58]) and for loss of control (OR 1.21 [1, 1.45]), and a reduction of 10% FVC with increased risk for future attack (OR 1.40 [1.04, 1.88]). Changes in %FEF25-75 and %FEV1/FVC ratio were not linked to future outcomes. Each 20% increase in FeNO was associated with increased risk for future loss of control (OR 1.041 [1.000, 1.062]). Baseline %FEV1/FVC was associated with increased risk for attack over the next three months (OR per % predicted reduction 1.037 [1.007, 1.067]). Otherwise no measurement at baseline was associated with later outcome. Conclusions: Change in %FEV1 over a three month period may be useful as part of dynamic risk assessment. Whether a large change in FeNO may also be useful for dynamic risk assessment remains uncertain.