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Introduction: Repeated measurements of fractional exhaled nitric oxide (FeNO) may be useful objective measurements in the management of asthma. There is uncertainty in what merits a clinically-relevant change in FeNO. Methods: Individual participant data were obtained from seven randomised controlled trials where FeNO was used to guide asthma treatment. The FeNO values at the start and end of a period of stable asthma were analysed. The median absolute and percentage change in paired FeNO measurements at the start and end of a stable period were determined for individuals with a baseline FeNO of Results: Data were available in 665 children (mean age 13.1, 59%male). When the initial FeNO was Conclusions: These findings support current recommendations for interpretation of what may be a clinically relevant change in a FeNO value of ≤20ppb but for higher values, greater absolute and percentage change in FeNO values should be tolerated before any alteration in treatment is considered.

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.

Background: Fractional exhaled nitric oxide (FeNO) may be a useful biomarker to guide asthma treatment. A study in children without asthma and with mild asthma suggested that FeNO may vary by up to 100% over 2 months. The aim of this study was to describe the change in FeNO over a 3 month period in children with moderate asthma who remained controlled and with stable inhaled corticosteroid (ICS) treatment. Methods: Data from 7 clinical trials were pooled. Each trial was broken down into three-month intervals. Individuals whose asthma was controlled and with stable ICS treatment over a particular 3-month interval were identified. The absolute and relative change in FeNO over this interval was described. Results: Data were available on 1115 children (58% male, mean age 12.6 years). FeNO values were similar in “FeNO” and “standard treatment” arms of the trials. There were 228 eligible children in the first three-month interval, 209 in the second, 294 in the third and 296 in the fourth interval. The median (interquartile range, IQR) change in FeNO during the first 3 months was +2 parts per billion, ppb (-6, +15) and values for the successive periods were +1 (-13, +10), 0 (-8, +10) and +1 (-6, +10). The median percentage change in FeNO (IQR) for the first 3 months was +10 (-28, 79) and for the next three periods were +2 (-35, 70), +1 (-24, 50) and +5 (-21, 46). Conclusions: FeNO values varied considerably in these eligible children. The 75th centile values suggest that absolute FeNO may rise by ≤15ppb and %FeNO by ≤80% without a change in the child’s clinical status. Similarly, the 25th centile values suggest that FeNO may fall by ≤15ppb or ≤40% without a change in clinical status.

Background: Meta-analysis shows FeNO guided treatment reduces the risk of asthma attacks compared to standard management. Here we test the hypothesis that there are sub groups of patients where FeNO guided treatment is associated with reduced risk for asthma attacks. Methods: Data from 7 clinical trials were pooled. Baseline characteristics included age, sex, ethnicity (white versus other), dose of inhaled corticosteroid (ICS), receipt of long acting beta agonist, receipt of leukotriene receptor antagonist (LTRA), %FEV1 and self-reported ICS adherence. The outcome was receipt of ≥1 course of oral corticosteroid (OCS) during the follow up period. Logistic regression related outcome to an interaction term between each characteristic and the trial arm (FeNO or standard treatment), including main effects and important covariates. Results: Data were available in 1115 children (58% male, mean age 12.6 years). The interaction term between LTRA treatment and trial group was significant (p=0.035): for those not treated with LTRA, 27% had ≥1 OCS course when treated by standard care and 20% with FeNO guided treatment; 38% treated with LTRA had ≥1 OCS course when treated by standard care and 43% when treated by FeNO guided management. There was a trend for outcomes to differ by ethnic group (p=0.070); for children other than white ≥1 OCS course was prescribed in 34% given standard treatment and 26% with FeNO guided treatment; and among white children the corresponding proportions were 19% and 23%. Conclusions: FeNO guided asthma treatment may be more effective in reducing the risk for asthma attacks among children who are non-white and not treated with LTRA.