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FeNO (Fractional Exhaled Nitric Oxide) testing is suitable for patients age 4 and above. As measurement requires patient cooperation, some children below the age of 7 may require additional coaching and encouragement. FeNO testing can play an important role in the diagnosis and management of their disease.1 In several recent studies, asthma therapy directed by FeNO testing has been shown to reduce asthma exacerbations in children when compared with symptom-based care or usual care.2-4
Use caution and clinical judgement when evaluating a single FeNO value without any previous measurements. Evaluate all clinical data (symptoms, spirometry, inhaled corticosteroid dosing, medication adherence and other information) before making any treatment decisions.
FeNO testing is not a replacement for spirometry. FeNO directly reflects the extent of airway inflammation, while spirometry measures airflow limitation. They both provide important information about different aspects of the disease. For example, FeNO can provide information on the level of underlying airway inflammation, but it cannot tell you the degree of airflow obstruction.
Measuring FeNO levels assists in the diagnosis of asthma and helps identify patients with Type 2 inflammation.5 For treatment optimisation, recent publications indicate that adjusting inhaled corticosteroids (ICS) dose according to FeNO value gives reductions in exacerbations up to 50%.2,6 FeNO measurement is recommended in addition to spirometry in national and international guidelines. 5,7
There are other causes of elevated exhaled nitric oxide (NO).8 After carefully excluding asthma with other tests, significant allergic rhinitis and other atopic disorders should be considered. Also, food allergies and bowel diseases have been reported to increase exhaled NO.9 A diet rich in nitrate-containing foods may also temporarily raise exhaled NO.7
A study done in 2012 showed that after starting a treatment with ICS, the FeNO levels follow an exponential decay curve. The t1/2 (half-life of exponential decay) for FeNO after starting treatment with ICS was 2.5 to 3 days. FeNO had reached a new plateau by 2 weeks.10 Thus, 10-14 days after starting ICS would be the earliest you may wish to consider rechecking FeNO levels.
This is unknown, as long-term studies specifically looking at variation in FeNO levels and its time course in relation to an exacerbation have not been performed.11
Results from spirometry poorly correlate with FeNO values since spirometry measures airway obstruction and FeNO testing measures airway inflammation.2,6 It is beneficial to measure inflammation, because if left untreated or uncontrolled, chronic inflammation in the lungs may lead to the progression of airflow limitation and reduction in airway reversibility over time.12
Generally, patients seen by asthma specialists should have a baseline FeNO measurement, particularly those who are not well controlled.5 Once treatment with ICS is started, FeNO levels should be monitored according to the patient’s symptoms while optimising the ICS dose.7 In studies that showed a reduction in exacerbations, measuring FeNO every 2 to 4 months and titrating ICS until FeNO value was in the low/normal range resulted in a 50% reduction in exacerbations when compared with protocols that used symptom-based treatments (ACQ – Asthma Control Questionnaire) or usual care.2,6
FeNO values in the intermediate range (25-50 ppb) should be interpreted cautiously and with reference to the clinical context (i.e. patient assessment, other asthma assessment tools, ICS dose, patient adherence, etc).7
References: 1. Malinovschi, A, Janson, C, Borres M. Simultaneously increased fraction of exhaled nitricoxide levels and blood eosinophil counts relate to increased asthma morbidity. J Allergy Clin Immunol. 2016 Nov; 138(5):1301-1308. 2. Peirsman EJ, Carvelli TJ, Hage PY, et al. Exhaled nitric oxide in childhood allergic asthma management: a randomised controlled trial. Pediatr Pulmonol. 2014;49(7):624-631. 3. Petsky H. Exhaled nitric oxide in children with asthma. Respiratory care nurse’s perspective. Indian Pediatr. 2014;51(2):102-103. 4. Mahr TA, Malka J, Spahn JD. Inflammometry in pediatric asthma: a review of fractional exhaled nitric oxide in clinical practice. Allergy Asthma Proc. 2013;34(3):210-219. 5. National Institute for Health and Clinical Excellence (NICE). Asthma: diagnosis, monitoring and chronic asthma management. NICE guideline [NG80]. 2017. 6. Syk J, Malinovschi A, Johansson G, et al. Anti-inflammatory treatment of atopic asthma guided by exhaled nitric oxide: a randomized, controlled trial. J Allergy Clin Immunol Pract. 2013;1(6):639-648. 7. Dweik RA, Boggs PB, Erzurum SC, et al; on behalf of the American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184(5):602-615. 8. Alving K, Malinovschi A. Basic aspects of exhaled nitric oxide. Eur Respir Mon. 2010;49:1-31. 9. Quenon L, Hindryckx P, De Vos M, et al. Hand-held fractional exhaled nitric oxide measurements as a non-invasive indicator of systemic inflammation in Crohn’s disease. J Crohn Colitis. 2013;7:644-648. 10. Anderson WJ, Short PM, Williamson PA, Lipworth BJ. Inhaled corticosteroid dose response using domiciliary exhaled nitric oxide in persistent asthma. Chest. 2012;142(6):1553-1561. 11. Beck-Ripp J, Griese M, Arenz S, Köring C, Pasqualoni B, Bufler P. Changes of exhaled nitric oxide during steroid treatment of childhood asthma. Eur Respir J. 2002;19(6):1015-1019. 12. Matsunaga K et al. Persistently high exhaled nitric oxide and loss of lung function in controlled asthma. Allergol Int. 2016 65(3):266-71.