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<jats:sec><jats:title>Background</jats:title><jats:p>High exhaled nitric oxide fraction (<jats:italic>F</jats:italic><jats:sub>ENO</jats:sub>) levels are associated with greater risk of asthma exacerbation. However, it is not clear how <jats:italic>F</jats:italic><jats:sub>ENO</jats:sub> can be used to guide safe reductions in inhaled corticosteroid (ICS) doses in asthma patients. This study assesses the ability of <jats:italic>F</jats:italic><jats:sub>ENO</jats:sub> to guide ICS reductions.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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 <jats:italic>F</jats:italic><jats:sub>ENO</jats:sub> before reducing ICS. We performed multilevel mixed-effects logistic regression in relation to acute exacerbations and estimated each participant's exacerbation risk using our logistic regression model.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 ICS doses were halved in four studies and withdrawn in three studies.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 <jats:italic>F</jats:italic><jats:sub>ENO</jats:sub> measurement of ≥50 ppb was associated with increased risk of exacerbations (crude OR 3.14, 95% 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 &lt;15% <jats:italic>versus</jats:italic> &lt;10% would result in fewer patients remaining on the same ICS dose (40 (10.4%) out of 384 <jats:italic>versus</jats:italic> 141 (36.7%) out of 384), but similar proportions of patients avoiding exacerbations (222 (91.4%) out of 243, 95% CI 87.1–94.6% <jats:italic>versus</jats:italic> 311 (90.4%) out of 344, 95% CI 86.8–93.3%).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>In patients with mild-to-moderate asthma, gradual ICS reduction when <jats:italic>F</jats:italic><jats:sub>ENO</jats:sub> is &lt;50 ppb may help decrease ICS use without increasing exacerbations. Future research should aim to validate these findings in larger populations.</jats:p></jats:sec>

Original publication




Journal article


European Respiratory Journal


European Respiratory Society (ERS)

Publication Date





1902150 - 1902150