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Testing fractional exhaled nitric oxide (FeNO) is a convenient way to assess airway inflammation at the point-of-care.1,3 Performing a FeNO test with a device like the NIOX VERO® is simple, immediate, and non-invasive.5 Each test results in a single number, indicating the level of airway inflammation – and the likelihood of asthma – in one FeNO value.
Guidelines on interpreting FeNO
In the early 2000s, FeNO began to be used to diagnose and manage asthma. In 2005, the American Thoracic Society (ATS) and the European Respiratory Society (ERS) jointly published recommendations for standardised FeNO testing procedures.6 The ATS published its first FeNO guidelines in 2011, with clear direction on how to interpret FeNO levels with distinct cut-off points.7
The ATS-defined FeNO cut-off points are as follows:7
| FeNO levels and inflammation | |||
| FeNO (ppb) | LOW | INTERMEDIATE | HIGH |
| Adults | <25 | 25-50 | >50 |
| Children (<12 years) | <20 | 20-35 | >35 |
| Th2-driven inflammation | Unlikely | Likely | Significant |
Asthma diagnosis: interpreting FeNO using cut-off points
The ATS uses the cut-off points above to indicate the likelihood of responsiveness to anti-inflammatory treatment such as corticosteroids.7 Low FeNO is associated with a low likelihood of airway inflammation and therefore a reduced expectation of responsiveness.7 High FeNO, on the other hand, means airway inflammation is present and responsiveness to corticosteroids would be likely.7 Where FeNO values fall in between, the ATS recommends interpreting the patient's results within the clinical context for a fuller picture.7
A doctor explaining how the NIOX VERO® works before a test
Some countries have produced guidelines with a single cut-off point instead of a range.8 The UK's National Institute for Health and Care Excellence (NICE), for example, uses 40 ppb (35 ppb in children) as the unique cut-off to support an asthma diagnosis, although it also recommends monitoring peak flow variability if there is diagnostic uncertainty and a patient has a FeNO level between 25 and 39 ppb.8
Airway inflammation is a key characteristic of asthma and assessing its severity with FeNO testing can help to achieve more accurate diagnosis.1,2 When FeNO is 40 ppb or more, a patient could be seven times more likely to have asthma.9
Asthma management: interpreting FeNO using variation from baseline
It is important to note that the baseline can vary according to whether the patient is currently receiving inhaled corticosteroids (ICS) as ICS reduce FeNO levels.1,7 At follow-up appointments, the ATS guidelines recommend that an increase in FeNO greater than 20% for baseline values over 50 ppb or more than 10 ppb for values lower than 50 ppb should be considered a significant increase.7 A reduction of at least 20% in FeNO for values over 50 ppb or more than 10 ppb for values lower than 50 ppb indicate a significant response to anti-inflammatory therapy.7
Asthma affects a large number of people, many of whom may not be aware they have it, especially if their symptoms aren’t severe.10 High FeNO is associated with over three times greater risk of potentially severe asthma exacerbations.1 An elevated FeNO result can open up conversation with patients about inhaler technique and adherence or guide physicians in titrating corticosteroid dosage.4,11 Optimising treatment using FeNO has been shown to help reduce exacerbations by up to 50%.4,12,13
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FeNO-guided asthma management not only helps to improve outcomes for patients but is also associated with reduced costs as medication is optimised and unscheduled visits to the doctor or admissions to hospital are reduced or avoided.4,14-16
Factors influencing FeNO
Some factors can influence FeNO levels. Particularly, FeNO testing should always be performed prior to spirometry because of a potential and temporary reduction of FeNO.6 In addition, there are other influencing factors. Although they are not usually clinically significant, it is recommended that patients avoid food, drink, exercise and smoking before testing FeNO.6,7
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References
1.Busse WW et al. Baseline FeNO as a prognostic biomarker for subsequent severe asthma exacerbations in patients with uncontrolled, moderate-to-severe asthma receiving placebo in the LIBERTY ASTHMA QUEST study: a post-hoc analysis. Lancet Respir Med. 2021;9(10):1165-1173.
2.Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention, 2023. Available at; https://ginasthma.org/2023-gina-main-report/
3.Menzies-Gow A et al. Clinical utility of fractional exhaled nitric oxide in severe asthma management. Eur Respir J. 2020;55(3):1901633.
4.Hanania NA et al. Measurement of fractional exhaled nitric oxide in real-world clinical practice alters asthma treatment decisions. Ann Allergy Asthma Immunol. 2018;120(4):414-418.
5.Alving K et al. Validation of a new portable exhaled nitric oxide analyzer, NIOX VERO®: randomized studies in asthma. Pulm Ther. 2017;3:207-218.
6.American Thoracic Society; European Respiratory Society. ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am J Respir Crit Care Med. 2005;171(8):912-30.
7.Dweik RA et al. 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):602-15.
8.National Institute for Health and Care Excellence (NICE). NICE guideline. Asthma: diagnosis, monitoring and chronic asthma management. 2021.
9.Wang Z et al. Agency for Healthcare Research and Quality (AHRQ). The clinical utility of fractional exhaled nitric oxide (FeNO) in asthma management. Comparative Effectiveness Reviews, 197. 2017.
10.American College of Allergy, Asthma & Immunology (ACAAI). Asthma Symptoms. Available at; https://acaai.org/asthma/symptoms/. Accessed; November 2023.
11.Porsbjerg C et al. Asthma. The Lancet. 2023.
12.Price DB et al. Fractional exhaled nitric oxide as a predictor of response to inhaled corticosteroids in patients with non-specific respiratory symptoms and insignificant bronchodilator reversibility: a randomised controlled trial. Lancet Respir Med. 2017;6(1):29-39.
13.Petsky HL et al. Tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils): a systematic review and meta-analysis. Thorax. 2018;73(12):1110-9.
14.Barry LE et al. Cost-Effectiveness of Fractional Exhaled Nitric Oxide Suppression Testing as an Adherence Screening Tool Among Patients With Difficult-to-Control Asthma. The Journal of Allergy and Clinical Immunology: In Practice. 2023.
15.Ali H et al. The Potential of Fractional Exhaled Nitric Oxide as a Biomarker in Predicting and Optimizing Use of Treatment in Asthma. South East European Journal of Immunology. 2023;6(1):18-23.
16.Heaney LG et al. Medical Research Council UK Refractory Asthma Stratification Programme (RASP-UK). Remotely monitored therapy and nitric oxide suppression identifies nonadherence in severe asthma. Am J Respir Crit Care Med. 2019;199(4):454-464.
