Fractional exhaled nitric oxide as a determinant for the clinical course of asthma: a systematic review

Background: Precision medicine means linking the right patient to the right management strategy including best possible pharmacological therapy, considering the individual variability of the disease characteristics, type of inflammation, genes, environment, and lifestyle. For heterogenous diseases such as asthma, reliable biomarkers are needed to facilitate the best possible disease control and reduce the risk of side effects. The present review examines fractional exhaled nitric oxide (FeNO) as a guide for the management strategy of asthma and predictor of its clinical course. Method: The literature included was identified by searching the PubMed database using specific key words and MeSH terms. Studies were not excluded based on their design alone. The search resulted in 212 hits, of which 35 articles were included in this review. Results: Several studies support a potential role for high FeNO levels as a prognostic biomarker for accelerated lung function decline in adults with newly diagnosed asthma. Furthermore, studies report an association between high FeNO levels and excess decline in FEV(1) in adults with long-standing moderate to severe asthma despite optimised therapy, whereas the findings for patients with less severe disease are conflicting. Applying a FeNO-based management algorithm reduces the exacerbation rate in adults with asthma. Similar observations are seen in children, though based on fewer studies. The available studies provide evidence that the level of FeNO may be useful as a predictor of subsequent loss of asthma control in adults, though the evidence is somewhat conflicting in children and young adults. Conclusion: The present review provides evidence of the prognostic value of FeNO as a surrogate biomarker for type 2 inflammation in the airways. FeNO is likely to emerge as an important biomarker in monitoring and tailoring modern asthma treatment, either alone or in combination with other biomarkers.