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How FeNO and spirometry work in asthma care

FeNO (fractional exhaled nitric oxide) testing and spirometry can make a valuable pairing in asthma care. We’re looking at how these two pieces of the respiratory puzzle can help to complete the picture.

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Did you know asthma is an inflammatory disease? Research has shown that up to 90% of asthma patients have Type 2 airway inflammation, which is particularly associated with exacerbations.1,2

The use of biomarkers is becoming increasingly common to help assess the extent of airway inflammation, including FeNO, blood eosinophils and sputum analysis.3-5 FeNO correlates directly with the level of inflammation present in the lungs and helps to titrate inhaled corticosteroids (ICS) treatment.3,5 FeNO testing is also the only method of measuring airway inflammation which is simple, immediate and non-invasive, with the results available immediately at the point-of-care.3,5,6 Put simply, elevated FeNO of 40 ppb or more means a diagnosis of asthma is 7x more likely.7 At the same time, using FeNO testing to assess steroid-responsiveness and check adherence over time has been proven to reduce exacerbations by up to 50%.8,9

Where does FeNO fit?

Given the ease of FeNO testing, it is accepted as a biomarker that can be used to assess the extent of airway inflammation, and one that can assist in the management of asthma patients.3 “FeNO directly reflects the extent of airway inflammation, while spirometry measures airflow limitation. They both provide important information about different aspects of the disease,”3-5 says Charlene Mhangami, Senior Clinical Applications Specialist at respiratory diagnostics company Vitalograph.

“The UK’s National Institute for Health and Care Excellence (NICE) recommends the use of both tests to support asthma diagnosis.10 Concern has been expressed that diagnosing asthma based on clinical history alone results in both over- and under-diagnosis.5 In the diagnostic process, FeNO should be performed then spirometry.11 FeNO provides an objective measure of steroid responsiveness and provides an alert of persistent lung inflammation, even in the absence of evidence of airway obstruction.”12,13

How the tests work in practice

Consultant chest physician and the clinical director of respiratory medicine for NHS South-East England, Dr Richard Russell, describes his asthma care routine.14 He explains that elevated FeNO levels enhance the clinician’s ability to diagnose asthma and it’s used alongside other tests, such as spirometry. “High levels of FeNO are very predictive of response to ICS.” If a patient presents with typical asthma symptoms, such as cough, wheeze and breathlessness, and they have high FeNO, Dr Russell says it’s likely they have asthma. Further checks can then help with decision-making.14

FeNO testing changed the treatment pathway for Dr Russell’s primary care patients. Dr Russell highlights that it’s absolutely critical in helping make a diagnosis of steroid-responsive asthma. Spirometry results may or may not be normal with asthma but high FeNO levels mean airway inflammation, which is key because asthma is an inflammatory condition.14

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FeNO for patient education

It's not only clinicians who benefit from the increased certainty that FeNO brings. FeNO values are also important for patients, helping them understand that they should respond well to their treatment. Involving patients in tracking their FeNO score with their healthcare team also means they plainly see how their medication helps. “Patients really love FeNO testing,” Dr Russell reports. “They really want to know their number.”14

For example, Dr Russell says, if a patient has symptoms and they have “a FeNO value of 80 or 90, which is fairly typical of an early diagnosis of asthma, you treat them and the number comes right down. They get really excited about seeing that change. Because guess what! They’re feeling better too, so the things line up.” Dr Russell finds that, at follow-up appointments, patients are eager to test their FeNO and know that playing their part in managing their condition is worth it.14

Ms Mhangami agrees: “Changes in FeNO levels may be useful to guide the step up and step down of anti-inflammatory medication and may prompt an evaluation of adherence and inhaler technique.12,15 Having an objective test result may facilitate opening a conversation about adherence and inhaler technique that may be otherwise difficult to approach or forgotten. Overall FeNO and spirometry should be used alongside each other in the investigation of respiratory concerns.”10,16

Dr Russell performs FeNO testing at every consultation. He adds that, for any clinician considering implementing FeNO testing into their asthma diagnosis and management pathway, it’s an opportunity to establish a structured review of asthma. This could include FeNO, spirometry, symptom scores, peak flow and blood testing. A patient-centric approach may also include history, triggers, and adherence.14



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References

1. Maspero J et al. Type 2 inflammation in asthma and other airway diseases. ERJ Open Research. 2022;8(3).
2. 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.
3. 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.
4. Gao J et al. Association between fractional exhaled nitric oxide, sputum induction and peripheral blood eosinophil in uncontrolled asthma. Allergy, Asthma & Clinical Immunology. 2018;1
5. 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.
6. Czubaj-Kowal M et al. Relationship between air pollution and the concentration of nitric oxide in the exhaled air (feno) in 8–9-year-old school children in Krakow. International Journal of Environmental Research and Public Health. 2021 Jun 22;18(13):6690.
7. 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.
8. 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.
9. 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.
10. National Institute for Health and Care Excellence (NICE). NICE guideline. Asthma: diagnosis, monitoring and chronic asthma management. 2021.
11. 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.
12. Porsbjerg C et al. Asthma. The Lancet. 2023.
13. Price D et al. Using fractional exhaled nitric oxide (FeNO) to diagnose steroid-responsive disease and guide asthma management in routine care. Clinical and translational allergy. 2013;3(1):1-0.
14. Dr Richard Russell. A conversation with Dr Richard Russell, around the benefits of FeNO testing. 2021. Available at; https://youtu.be/0JMhqKFEOLA.
15. Menzies-Gow A et al. Clinical utility of fractional exhaled nitric oxide in severe asthma management. Eur Respir J. 2020;55(3):1901633.
16. Louis R et al. European Respiratory Society guidelines for the diagnosis of asthma in adults. European Respiratory Journal. 2022;60(3).