Tidal breathing FENO measurements: a new algorithm

Fractional exhaled nitric oxide (FENO)
A large number of studies have shown that the fractional concentration of
nitric oxide in exhaled air (FENO) is a non-invasive marker of eosinophilic
airway inflammation. Elevated FENO in atopic asthma is attributed to the
induction of NO-synthase (iNOS) by proinflammatory cytokines and mediators
leading to the increased production of NO by the airway epithelium.

Methodology
Several factors are known to influence FENO measurements. Most important
factors are expiratory flow, ambient nitric oxide and nasal nitric oxide. FENO
is highly flow-dependent, with higher flows resulting in lower FENO.
In adults and older children international guidelines recommend to measure FENO
during a single slow exhalation from total lung capacity at a constant flow of
50 ml/s. Exhalation against a resistance ensures soft palate closure and avoids
nasal NO contamination. This method is unsuitable in uncooperative patients,
and the proportion of reliable measurements drops dramatically below the age of
5 to 6 years.
In preschool children tidal breathing (TB) methods with a mask or mouthpiece
have been used to measure FENO. These methods have been shown feasible,
reproducible and discrimination between groups with different respiratory
diseases has been possible with these techniques. However, with the TB method
it is especially hard to control for expiratory flow, and results are
insufficiently accurate for use in individual patients.

Clinical applications in pediatrics
FENO measurements are able to discriminate between children with and without
untreated asthma. In preschool children FENO might be a useful diagnostic tool
which can help to differentiate between children with transient wheeze (for
example due to respiratory infections) and children who wheeze due to asthma,
with underlying chronic eosinophilic airway inflammation.
Furthermore, several authors found lower FENO levels in patients with asthma
after treatment with inhaled or oral steroids. Pijnenburg et al. showed that
FENO may be an objective predictor of asthma relapse after discontinuation of
steroids in symptom free asthmatic children. Titration of inhaled steroids on
FENO and symptoms and/or lung function showed modest effects on bronchial hyper
responsiveness, lung function, and prednisone use. Therefore FENO measurements
seem to be useful not only as a diagnostic tool but also in the monitoring of
asthmatic children.

Primary objective: to assess the correlation and agreement between the new TB
technique and the conventional SB online technique with constant expiratory
flow.

Secondary objective: to investigate the reproducibility of this new technique.

Cross sectional design.

The data will be collected at the outpatient clinic of KinderHaven, a
specialized asthma clinic located at the Haven Hospital. At a routine visit
FENO will be measured with the new TB technique and with the conventional SB
online technique with constant expiratory flow of 50 ml/s. Furthermore, the
reproducibility of the new TB technique will be tested by performing the tidal
breathing FENO measurement twice. The study will be performed within 1 routine
visit for each study subject. We expect to need 3 months for including patients
and collecting all data.

When children and their parents agree to participate to this study the research
data will be collected during a routine visit and this will only take a couple
of minutes extra time. This new developed technique to measure FENO during
tidal breathing is particularly of value for children. The children who
participate in this study will not personally benefit from the results. If this
new technique proves to be reliable and comparative to the conventional
technique it will be possible to measure FENO also in younger children. In
preschool children, FENO measurements can possibly contribute to the early
diagnosis of asthma but also to the improvement of treatment and prevention of
exacerbations.