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Why is FeNO higher in asthma patients?

Several major guidelines recommend testing FeNO to accurately assess Type 2 airway inflammation, a key characteristic of asthma.1-7 In fact, a FeNO level greater than 40 parts per billion (ppb) means asthma is seven times more likely,8 making FeNO a useful biomarker in suspected cases.9 But why is FeNO higher in asthma patients? This article looks at the science.

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Type 2 inflammation is mainly driven by interleukins 4, 5 and 13, also known as IL-4, IL-5 and IL-13. These cytokines are involved in the recruitment and production of immunoglobulin E (IgE), eosinophils and nitric oxide (NO), which is then released in exhaled breath as FeNO (fractional exhaled nitric oxide).10

The body naturally produces an amount of NO and low levels of exhaled NO are normal.1 When Type 2 airway inflammation is present (the type of inflammation responsible for up to 93% of asthma cases11), IL-4 and IL-13 upregulate the activity of the iNOS enzyme, which produces NO in the airway.10 Levels of exhaled NO increase, giving healthcare professionals an objective measure of airway inflammation.1

FeNO has now become a common biomarker of Type 2 airway inflammation, along with sputum and blood eosinophils.12 Studies have shown that both FeNO and blood eosinophils have a significant positive relationship (p<0.0001), with both accurately predicting eosinophilic airway inflammation.13 Furthermore, Dr Reynaud Panettieri, Vice Chancellor for Clinical and Translational Science and Director of the Rutgers Institute for Translational and Medical Sciences in New Jersey, US, recently told the crowd at a NIOX® webinar that knowing a patient has either high FeNO or high eosinophils predicts a 25% increase in exacerbations. With both high FeNO and high eosinophils, the increase was almost four times greater.14

However, unlike sputum and blood eosinophil procedures, testing for FeNO is simple and non-invasive, making it a convenient starting point for assessing airway inflammation right there at the patient’s appointment.15

What is “high FeNO”?

The American Thoracic Society (ATS) defines high FeNO as a test result over 50 ppb in adults and 35 ppb in children. This kind of level indicates that airway inflammation is present, supports an asthma diagnosis in patients with variable cough, wheeze and shortness of breath, and suggests that the patient is likely to respond to treatment with corticosteroids.1

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FeNO is not only useful in the diagnosis of asthma but also in its ongoing management, offering a potentially precision-based approach to patient care.16 One of the additional benefits of FeNO testing is the fact that the test is reproducible: being able to track patients’ FeNO levels over time means physicians can check how the treatment plan is panning out.15 When medication is working, FeNO levels usually fall.17

Performing a FeNO test is straightforward17 and can be completed within a couple of minutes at the patient’s appointment. There is no need for onward referral before FeNO and physicians can take immediate action should they find a patient’s treatment is not working as expected.

To find out more about FeNO testing in asthma and how NIOX VERO® can help you assess airway inflammation at the point-of-care, book a demo or check out our videos to see NIOX® technology in action.

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References

1. 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.
2. Khatri SB et al. An official American Thoracic Society clinical practice guideline: use of fractional exhaled nitric oxide to guide the treatment of asthma. Am J Respir Crit Care Med. 2021;204(10):e97-e109.
3. Gaillard EA et al. European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5-16 years. Eur Respir J. 2021;58(5):2004173.
4. Louis R et al. European Respiratory Society Guidelines for the Diagnosis of Asthma in Adults. Eur Respir J 2022; in press
5. National Institute for Health and Care Excellence (NICE). NICE guideline. Asthma: diagnosis, monitoring and chronic asthma management. 2021.
6. Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and &Prevention Program Coordinating Committee (NAEPPCC) et al. 2020 Focused updates to the  asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020 Dec;146(6):1217-1270.
7. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2021 update.
8. 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.
9. Pavord ID, Afzalnia S, Menzies‐Gow A, Heaney LG. The current and future role of biomarkers in type 2 cytokine‐mediated asthma management. Clinical & Experimental Allergy. 2017 Feb;47(2):148-60.
10. Kuruvilla ME et al. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019;56(2):219-233.
11. Heaney LG et al. Eosinophilic and noneosinophilic asthma: an expert consensus framework to characterize phenotypes in a global real-life severe asthma cohort. Chest. 2021;160(3):814-830.
12. Loewenthal L et al. FeNO in asthma. Seminars in respiratory and critical care medicine. 2022. Thieme.
13. Gao J, Wu F. Association between fractional exhaled nitric oxide, sputum induction and peripheral blood eosinophil in uncontrolled asthma. Allergy, Asthma & Clinical Immunology. 2018 Dec;14:1-9.
14. Dr Reynold Panettieri. Utility of FeNO and Biomarkers in Asthma. Available at: https://www.niox.com/dr-reynold-panettier/
15. Alving K, Anolik R, Crater G, LaForce CF, Rickard K. Validation of a new portable exhaled nitric oxide analyzer, NIOX VERO®: randomized studies in asthma. Pulmonary Therapy. 2017 Jun;3:207-18.
16. Menzies-Gow A, Mansur AH, Brightling CE. Clinical utility of fractional exhaled nitric oxide in severe asthma management. European Respiratory Journal. 2020 Mar 1;55(3).
17. Heaney LG, Busby J, Bradding P, Chaudhuri R, Mansur AH, Niven R, Pavord ID, Lindsay JT, Costello RW. Remotely monitored therapy and nitric oxide suppression identifies nonadherence in severe asthma. American journal of respiratory and critical care medicine. 2019 Feb 15;199(4):454-64.