Towards better treatment of childhood asthma: inflammometry with exhaled nitric oxide

Eosinophilic airway inflammation is a hallmark of asthma. The fractional concentration of nitric oxide in exhaled breath (FENO) is elevated in patients with steroid-naive atopic asthma and correlates with eosinophilic infiltration of the airway wall. This makes FENO the first non-invasive, valid marker of asthmatic airway inflammation. This thesis consists of two parts. The first part deals with methodological issues of measuring FENO in children, including the collection of normal values. The second part of this thesis presents clinical applications of FENO measurements in asthmatic children. Anti-inflammatory treatment with inhaled corticosteroids (ICS) is the cornerstone of asthma treatment. Decisions to start ICS or to change the dose are now mainly based on symptoms, which however, are not closely related to airway inflammation. We showed that ICS dose titration on inflammation by using FENO improved important objective endpoints in children with moderate to severe allergic asthma. Then, in asymptomatic asthmatic children on a low dose of ICS FENO measured 2 and 4 weeks after discontinuation of steroids appeared an objective predictor of asthma relapse. In asthmatic children with persistently elevated FENO values, we showed that faulty inhaler technique or an inadequate dose of ICS were not the main explanations for these elevated values. Finally we found that home measurements of FENO with a newly developed hand-held NO-analyzer are feasible, although there was a marked individual fluctuation. We conclude that FENO measurements provide useful information that may guide the treatment of asthmatic children, in addition to symptoms and lung function tests. They allow for ICS to be used more rationally and efficiently. We feel that the time has come to incorporate FENO in the routine assessment of asthmatic children and in treatment guidelines.

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