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A sensitive issue: Why FeNO is measured in parts per billion

One part per billion. It’s difficult to picture it but this microscopic measure is an intrinsic element of the technology behind FeNO (fractional exhaled nitric oxide) testing and its practical application in asthma care. This article looks at the learning and explains why asthma diagnosis and management are in safe hands with FeNO.

Measuring the concentration of the composition of gas is an exact science. One part per billion (ppb) is of course very small – think one second in 32 years – but it’s crucial that FeNO testing achieves that kind of sensitivity so FeNO values are relayed in ppb.

“A small amount can have a large effect”

FeNO testing means measuring the level of fractional exhaled nitric oxide in a patient’s breath. Nitric oxide is a gas. As New Zealand’s National Institute of Water and Atmospheric Research neatly sums it up: “The reason gases are measured at these levels is that a small amount of some gases can have a very large effect, and if you want to study how these levels are changing over time, you need to make very sensitive measurements.”1

Using FeNO testing to detect airway inflammation – a key characteristic of asthma – is strongly recommended in national and international asthma guidelines.2,3 In fact, an asthma diagnosis is up to 7x more likely when a patient’s FeNO level is >40 ppb.4

For the longer term, FeNO-guided asthma management has been similarly defined. Changes in a patient’s FeNO level over time can be easily checked with desktop FeNO monitoring devices during a routine appointment. Significant increases in results between visits can indicate a loss of asthma control, while significant decreases can show that treatment is working.2 Optimising therapy and adherence with FeNO testing has been proven to reduce exacerbations in both adults and children by up to 50%.5

In short, knowing and tracking a patient’s FeNO level in parts per billion offers the kind of back-up that can really aid physicians in their efforts to identify and control asthma. Using FeNO and understanding that breath analysis is being conducted to such a degree of sensitivity can mean the difference between recognising cases of non-adherence, spotting when doses of medication are too high or too low and seeing instantly when a patient is at an increased risk of potentially life-threatening asthma attacks.6

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How does NIOX® achieve such sensitive measurements?

Devices like NIOX VERO®, which measure FeNO with electrochemical technology, have sensors that convert the gas concentration of exhaled breath into electrical signals. Unlike chemiluminescence and laser technology, they are small, convenient devices that are easy to use and give results right at the point-of-care. They are also relatively inexpensive.

However, although many studies have shown a high degree of correlation between the measurements of different devices, there are discrepancies between device readings, especially for higher levels of inflammation.7-9 Research has therefore concluded that FeNO devices are not interchangeable.9-12 This is where NIOX® technology really hits the mark. The most used cut-off points for the interpretation of FeNO levels are still those published by the American Thoracic Society (ATS) in 2011.2 These thresholds were derived from studies where 83% of patients performed FeNO testing on NIOX® devices.13 Based on studies comparing NIOX® readings with other devices, it seems that NIOX® better reflects the ATS cut-off points, offering a simple way to optimise asthma therapy on the spot.14

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References

1. New Zealand’s National Institute of Water and Atmospheric Research. What are ppm and ppb? Available at https://niwa.co.nz/atmosphere/faq/what-are-ppm-and-ppb. Last visited in August 2022.
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. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention, 2022. Available from ginaasthma.org.
4. 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.
5. 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.
6. Menzies-Gow A et al. Clinical utility of fractional exhaled nitric oxide in severe asthma management. Eur Respir J. 2020;55(3):1901633.
7. Silkoff PE et al. Clinical precision, accuracy, number and durations of exhalations for a novel electrochemical monitor for exhaled nitric oxide. J Breath Res. 2019;14(1):016011.
8. Korn S et al. Measurement of fractional exhaled nitric oxide: comparison of three different analysers. Respiration. 2020;99(1):1-8.
9. Huang T et al. Fractional exhaled nitric oxide measurement: Comparison between the Sunvou-CA2122 analyzer and the NIOX VERO analyzer. J Asthma. 2019:1-8.
10. Maniscalco M et al. Fractional exhaled nitric oxide-measuring devices: technology update. Med Devices (Auckl). 2016;9:151-60.
11. Saito J et al. Comparison of fractional exhaled nitric oxide levels measured by different analyzers produced by different manufacturers. J Asthma. 2020;57(11):1216-26.
12. Molino A et al. Comparison of three different exhaled nitric oxide analyzers in chronic respiratory disorders. J Breath Res. 2019;13(2):021002.
13. NIOX® data on file MKT-DOF-0001.
14. NIOX® data on file MKT-DOF-004.