Indian Pediatr 2014;51: 102-103
Exhaled Nitric Oxide in Children with Asthma
RESPIRATORY CARE NURSE’S PERSPECTIVE
Queensland Children’s Medical Research Institute,
Queensland University of Technology, Royal Children’s Hospital, Herston,
sthma is one of the most common chronic diseases
in children. Acute exacerbations are not uncommon in children with
asthma and many are hospitalized. Not surprisingly, hospitalizations for
asthma are very common, accounting for 12-21% of hospitalizations
worldwide . Thus prevention of exacerbations, particularly severe
ones, is one goal of good asthma management. The second component in
asthma management is monitoring of asthma control, by both subjective
and objective measures [2-4]. Subjective measures usually involve a
series of questions used for clinical assessment, diary cards and
quality of life (QoL) questionnaires. Traditional objective methods
include peak flow meters, spirometry and degree of airway
hyperresponsiveness (AHR). Newer and arguably more sensitive methods
include measurement of airway inflammation such as airway cellularity in
induced sputum or fractional exhaled nitric oxide (FENO). In asthma,
inflammation can be eosinophilic or non-eosinophilic. In patients with
eosinophilic inflammation, the use of inhaled corticosteroids (ICS)
reduces exacerbations and improves symptoms and asthma control. FENO
correlates with other markers of asthma eg. eosinophilia in induced
sputum  and bronchial reactivity in non-steroid treated subjects .
The first study to use FENO as a biomarker was
published by Dupont and colleagues  in 1998. They measured FENO in
steroid treated and untreated adults with mild asthma. These levels
correlated with the degree of AHR as measured by the dose of histamine
required to produce a 20% decrease in forced expiratory volume in first
second (FEV1). The authors
concluded that FENO levels reflect AHR in patients with mild asthma who
were steroid naïve. The adults who were treated with ICS had similar
FENO levels as the healthy controls
As asthma in adults is not identical to that in
children, data relating FENO and asthma control specific to children is
important. There are many studies that have related FENO with various
clinical aspects of asthma in children. Byrnes, et al. 
recruited 39 children as controls from local school and 31 children with
a clinical diagnosis of asthma. The aims of the study were to determine
if FENO could be measured in children, and whether the pattern seen in
adults with asthma versus adult controls is observed in children with
asthma on bronchodilators only, had the highest FENO level. The FENO
levels for children with asthma on regular ICS was not statistically
different from the control children . As FENO relates to airway
eosinophilic inflammation, FENO as a biomarker can be potentially used
in children with asthma to monitor the response to (and hence adjust)
asthma medications, verify the adherence to ICS, and predict upcoming
asthma exacerbations. Based on data above that showed the potential
value of using FENO in improving asthma outcomes, the research
undertaken by Raj, et al.  has provided further evidence that
FENO levels increase during an asthma exacerbation but may not provide
any clinical significance.
A Cochrane review  assessing the efficacy of
tailoring asthma interventions based on FENO levels versus clinical
symptoms for improving asthma related outcomes has been undertaken. The
review includes 6 studies (2 adult studies and 4 involving children or
adolescents). These studies differed in definition of asthma
exacerbations, FENO cut-off levels used to determine adjustment of
medications, type of therapy adjustment and the duration of studies. In
the meta-analysis, there was no significant difference between groups
for the primary outcome of asthma exacerbations, or for other outcomes
(clinical symptoms, FENO level and spirometry). In post-hoc analysis, a
significant reduction in mean final daily dose inhaled corticosteroid
per adult was found in the group where treatment was based on FENO in
comparison to clinical symptoms, (mean difference -450 mcg; 95% CI -677
to -223 mcg budesonide equivalent/day). However, the total amount of
inhaled corticosteroid used in one of the adult studies was 11% greater
in the FENO arm. In contrast, in the pediatric studies, there was a
significant increase in inhaled corticosteroid dose in the FENO strategy
arm (mean difference of 140 mcg; 95% CI 29 to 251 mcg budesonide
equivalent/day). These results have limited applicability, the most
significant issue was that none of the six included studies considered
presence or severity of atopy in their algorithm of management although
some but not all subjects were atopic. This is important because atopy
influences FENO levels regardless of the presence of asthma.
Funding: None; Competing interest: None
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