Using fractional exhaled nitric oxide to guide step down treatment decisions in patients with asthma: a systematic review and individual patient data meta-analysis.
Wang K., Verbakel JY., Oke J., Fleming-Nouri A., Brewin J., Roberts N., Harada N., Atsuta R., Takahashi K., Mori K., Fujisawa T., Shirai T., Kawayama T., Inoue H., Lazarus S., Szefler S., Martinez F., Shaw D., Pavord ID., Thomas M.
BACKGROUND:High fractional exhaled nitric oxide (FeNO) levels are associated with greater risk of asthma exacerbations. However, it is not clear how FeNO can be used to guide safe reductions in inhaled corticosteroid (ICS) doses in asthma patients. This study assesses the ability of FeNO to guide ICS reductions. METHODS:Systematic searching of electronic databases identified prospective observational studies and randomised controlled trials which recruited participants with mild-to-moderate asthma aged ≥12 years and measured FeNO before reducing ICS. We performed multi-level mixed-effects logistic regression in relation to acute exacerbations and estimated each participant's exacerbation risk using our logistic regression model. RESULTS:We included data from seven out of eight eligible studies, representing 384 participants. ICS doses were halved in four studies and withdrawn in three studies. A baseline FeNO measurement of 50 ppb or higher was associated with increased risk of exacerbations (crude odds ratio [OR] 3.14, 95% confidence interval [CI] 1.41-7.00, p=0.005; adjusted OR 3.08, 95% CI 1.36-6.98, p=0.007) and corresponded to an estimated exacerbation risk cut-off of 15%. Reducing ICS when estimated exacerbation risk was below 15% versus 10% would result in fewer patients remaining on the same ICS dose (40/384, 10.4% versus 141/384, 36.7%) but similar proportions of patients avoiding exacerbations (222/243, 91.4%, 95% CI 87.1%-94.6% versus 311/344, 90.4%, 95% CI 86.8%-93.3%). CONCLUSION:In patients with mild-to-moderate asthma, gradual ICS reduction when FeNO is <50 ppb may help decrease ICS use without increasing exacerbations. Future research should aim to validate these findings in larger populations.