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Indian Pediatr 2014;51: 101-102 |
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Exhaled Nitric Oxide Measurement in Pediatric
Asthma
PULMONOLOGIST’S PERSPECTIVE
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Ranjan Suri
Pediatric Respiratory Consultant, Respiratory Unit,
Great Ormond Street Hospital, and Portex Unit, UCL Institute of Child
Health, London, United Kingdom.
Email: [email protected]
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Nitric oxide (NO) is a biological mediator
produced by NO synthase (NOS) in airway epithelial cells, which diffuses
into the airway lumen. In the lungs, NO determines smooth muscle
relaxation, affects ciliary beat frequency, mucus secretion and plasma
exudation, and is involved in inflammation and cell-mediated immunity
processes [1]. Measurement of fractional exhaled NO (FENO) requires a
series of continuous expiratory manoeuvres using an incentive device.
However, the role of measuring FENO as a non-invasive biomarker to
optimize asthma management in children is hotly debated.
Chronic airway inflammation is an important feature
of asthma. FENO levels are increased in patients with asthma as a result
of induction of NOS-2 by pro-inflammatory cytokines. Elevated FENO
levels have been shown to correlate with increased eosinophils in blood,
bronchoalveolar lavage fluid and sputum, suggesting that FENO reflects
eosinophilic inflammation [2]. However, asthma is not a single disease
and at least three adult phenotypes of airway inflammation have been
identified on the basis of predominant eosinophilic, neutrophilic, or
pauci-granulocitic cellular pattern [3].
Even though FENO is increased in children with
allergic asthma [4], the obtained levels cannot discriminate among
school children with non-allergic asthma. Furthermore, FENO can be
elevated in patients who are atopic and not asthmatic. Levels of FENO
appear increased in asthmatics with pollen allergy during the season
even though there may be an absence of symptoms and normal lung function
[5].
It had been postulated that tracking FENO may be
helpful in managing asthma, as it improves after steroid treatment and
may predict exacerbations in pollen sensitive asthma. However, it has
been shown not to correlate with symptoms, and a meta-analysis [6] of
three pediatric studies showed that FENO-guided treatment did not
improve asthma outcomes.
The goal of long-term asthma treatment is to reduce
airway inflammation and control symptoms. In this month’s journal, Raj,
et al. [7] studied children with asthma to investigate whether
FENO could predict an acute exacerbation or its severity. This paper
addresses a very important issue in current asthma management, as FENO
has been proposed as a biomarker, correlating well with levels of
eosinophilic airway inflammation. Some papers have suggested its use for
guiding pharmacotherapy. In everyday practice, however, it seems to be
very helpful for some patients, while it does not correlate with
clinical symptoms and lung function in others.
The authors studied 243 asthmatic children (mean age
99 months), with an average duration of follow up of 434 days (range 84
to 825 days). Patients were reviewed every 3 months and underwent
spirometry, FENO, pulmonary symptom scores, skin prick tests to
aeroallergens and blood eosinophil counts were measured. Although FENO
levels increased during an exacerbation, the authors were unable to find
a particular cut-off which could help in either diagnosing an acute
asthma exacerbation or predicting its severity in children.
So, should the results of this and other recently
published studies [8,9] discourage the clinician from using FENO as a
routine marker for guiding management in this age group? If asthma
symptoms and inflammation were concordant, measuring FENO would not
likely be useful. It is only when they are discordant – that is
inflammation is disproportionately greater than symptoms, or vice-versa
– measuring FENO may prove beneficial. Clearly, measuring FENO or other
inflammatory biomarkers is no substitute for doing the basics of asthma
management correctly; as often, simple measures can improve symptoms and
avoid escalation of treatment. Adherence must be optimized,
co-morbidities treated, allergen load reduced to a minimum and inhaler
technique regularly checked.
Certainly more studies will need to be done in this
area of pediatric asthma. FENO may remain a useful marker for assessing
patients at the time of diagnosis and also to help monitor the level of
asthma control of individual patients in clinical practice.
References
1. Kharatonov SA, Barnes PJ. Exhaled markers of
pulmonary disease. Am J Respir Crit Care Med. 2001;163:1693-1722.
2. Jouaville LF, Annesi-Maesano I, Nguyen LT, Bocage
AS, Bedu M, Caillaud D. Interrelationship among asthma, atopy, rhinitis
and exhaled nitric oxide in a population-based sample of children. Clin
Exp Allergy. 2003;33: 1506-11.
3. Wenzel SE. Asthma: defining of the persistent
adult phenotypes. Lancet. 2006;368:804-13.
4. Frank TL, Adisesh A, Pickering AC, Morrison JF,
Wright T, Francis H, et al. Relationship between exhaled nitric
oxide and childhood asthma. Am J Respir Crit Care Med. 1998;158:1032-6.
5. Vahlkvist S, Sinding M, Skamstrup K, Bisgaard H.
Daily home measurements of exhaled nitric oxide in asthmatic children
during natural birch pollen exposure. J Allergy Clin Immunol.
2006;117:1272-6.
6. Petsky HL, Cates CJ, Lasserson TJ, Li AM, Turner
C, Kynaston JA, et al. A systematic review and meta-analysis:
tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide
or sputum eosinophils). Thorax. 2012;67:199-208.
7. Raj D, Lodha R, Mukherjee A, Sethi T, Agrawal A,
Kabra SK. Fractional exhaled nitric oxide in children with acute
exacerbation of asthma. Indian Pediatr. 2013;51:105-11.
8. de Jongste JC, Carraro S, Hop WC, the CHARISM
Study Group, Baraldi E. Daily telemonitoring of exhaled nitric oxide and
symptoms in the treatment of childhood asthma. Am J Respir Crit Care
Med. 2009;179:93-7.
9. Szefler SJ, Mitchell H, Sorkness CA, Gergen PT,
O’Connor GT, Morgan WJ, et al. Management of asthma based on
exhaled nitric oxide in addition to guideline-based treatment for
inner-city adolescents and young adults: a randomised controlled trial.
Lancet. 2008;372:1065-72.
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