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Interpreting FeNO test results to enhance asthma management

FeNO values are used to indicate the likelihood that a patient has airway inflammation, a key characteristic of asthma. Knowing a patient’s FeNO level can help diagnose asthma more accurately, as well as improve patient outcomes over time. This article looks at interpreting results into meaningful data for patient care and savings for healthcare budgets.

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Testing fractional exhaled nitric oxide (FeNO) is the most convenient way to assess airway inflammation at the point-of-care. Performing a FeNO test with a device like the NIOX VERO® is simple, immediate, and non-invasive. 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.1 The ATS published its first FeNO guidelines in 2011, with clear direction on how to interpret FeNO levels with distinct cut-off points.2

The ATS guidelines were based on a systematic review of numerous publications. 83% of subjects enrolled in the studies from which the ATS cut-off points were derived used NIOX technology to perform FeNO testing.3 As such, NIOX VERO® may be more reflective of the established ATS FeNO cut-off values, which remain the most used worldwide.4

The ATS-defined FeNO cut-off points are as follows:

FeNO levels and inflammation
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. Low FeNO is associated with a low likelihood of airway inflammation and therefore a reduced expectation of responsiveness. High FeNO, on the other hand, means airway inflammation is present and responsiveness to corticosteroids would be likely. Where FeNO values fall in between, the ATS recommends interpreting the patient's results within the clinical context for a fuller picture.

A General Practioner explaining how the NIOX VERO® works before a test.

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. 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 has statements about FeNO levels of 25-39 ppb.5

Airway inflammation is a key characteristic of asthma and assessing its severity with FeNO testing can help to achieve more accurate diagnosis. When FeNO is 40 ppb or more, a patient is seven times more likely to have asthma.6

Asthma management: interpreting FeNO using variation from baseline

Once a diagnosis has been confirmed, it is crucial to consider the variation in FeNO results between visits, instead of strict thresholds. This variation should be included as part of ongoing asthma management.

Each patient has an individual baseline FeNO value. 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. At follow-up tests, using the ATS guidelines, an increase in FeNO greater than 20% for baseline values over 50 ppb or more than 10 ppb for values lower than 50 ppb can be considered a significant increase. 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.

Even patients whose asthma appears to be controlled may have airway inflammation.7 High FeNO is associated with a four times greater risk of potentially severe asthma exacerbations.8 An elevated FeNO result can open up conversation with patients about inhaler technique and adherence or guide physicians in titrating corticosteroid dosage. Optimising medication adherence and therapy using FeNO has been shown to help reduce exacerbations by up to 50%.9

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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.10

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.1 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.2

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1. 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.
2. 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.
3. Data on file C-NIOX-0001. © Circassia Group PLC.
4. Data on file C-NIOX-0008. © Circassia Group PLC.
5. National Institute for Health and Care Excellence (NICE). NICE guideline. Asthma: diagnosis, monitoring and chronic asthma management. 2021.
6. 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.
7. Matsunaga K et al. Persistently high exhaled nitric oxide and loss of lung function in controlled asthma. Allergol Int. 2016;65(3):266-71.
8. 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.