Exhaled nitric oxide and the management of childhood asthma: yet another promising biomarker "has been" or a misunderstood gem

Childhood asthma is a common chronic condition. Approximately five percent of all children in western countries are prescribed treatment with inhaled corticosteroids (ICS) to prevent asthma symptoms. Current guidelines advocate titrating ICS dose to symptoms but this approach is not without problem, e.g. how to discern asthmatic from non-asthmatic symptoms? And when to reduce ICS dose? This review describes the strengths and weaknesses of fractional exhaled nitric oxide (FENO) as an objective index for individualising asthma control in children. Epidemiological and mechanistic evidence suggest that FENO should be a promising biomarker for eosinophilic airway inflammation (a hall mark for asthma) but somewhat surprisingly, clinical trials in children have not consistently found benefit from adding FENO to a symptom-based approach to ICS treatment in children. There are a number of reasons why FENO has apparently failed to translate from promising biomarker to clinically useful tool, and one reason may be a lack of understanding of what merits a significant intrasubject change in FENO. This review describes the rise and apparent fall of FENO as biomarker for asthma and then focuses on more recent evidence which suggest that FENO may prove to have a role in the management of childhood asthma, and in particular preventing exacerbations.