How can FeNO help optimise asthma treatment and improve ICS adherence?

Inhaled corticosteroids (ICS) are the cornerstone of asthma controller therapy. However, patients do not always adhere to their treatment or use good inhaler technique, and ICS doses are not always optimal.(1) In this article we’ll discuss how FeNO (fractional exhaled nitric oxide) testing can help optimise treatment decisions for ICS and check medication adherence.

Asthma is one of the most common chronic diseases worldwide. Airway inflammation is a central part of the condition and can lead to symptoms such as cough, wheezing, breathlessness and chest tightness.(2) The first asthma treatment guidelines from the 1990s focused on treating the inflammation that causes asthma.(3) ICS are anti-inflammatory and very effective in reducing airway inflammation.(2)

Why might patients remain symptomatic despite ICS?

It soon became clear that not all patients labelled as asthmatics responded to ICS as expected.(4) A prospective, multicentre cohort study by Aaron et al. in 2017 showed that about 33% of asthma diagnoses in adults may be incorrect.(5) Some asthma symptoms are common to other diseases, such as chronic obstructive pulmonary disease (COPD) and vocal cord dysfunction, so early and accurate asthma diagnosis is fundamental.(1)

Tools for diagnosing asthma include assessments of personal and family history, physical examination and lung function tests, such as spirometry.(2) However, while these are all important tools, they don’t directly reflect the extent of airway inflammation.(6) As a result, various international guidelines produced by the American Thoracic Society (ATS), European Respiratory Society (ERS) and the Global Initiative for Asthma (GINA) now recommend measuring a patient’s FeNO levels for a better idea of a patient’s condition.(1,2,7,8)

Asthma patients with a high FeNO level could be over three times more likely to experience an exacerbation.(9) With this in mind, considering FeNO as a modifiable risk factor and working to decrease a patient’s FeNO score through treatment optimisation will lower that risk.(6,10)

FeNO can help to optimise therapy

FeNO was discovered in the 1990s as a biomarker in exhaled breath.(11) Soon after, researchers understood that FeNO could help diagnose airway inflammation.(1,12) It is now well established that FeNO levels are elevated in asthma and reduced by steroids.(1) Thanks to simple and non-invasive testing devices like NIOX VERO?, clinicians can now easily measure FeNO at the point-of-care.(13) Studies have shown that clinicians who did not test FeNO levels were unable to recognise significant airway inflammation in up to 50% of patients.(6,14) It has also been shown that adding FeNO testing resulted in clinicians altering their asthma treatment plan in more than a third of cases.(6,14) Hanania et al. (2018) note that 90% of these cases involved changes to the prescription of ICS.(6) Treatment decisions based on regular FeNO testing also resulted in up to 50% fewer exacerbations and fewer hospital admissions, compared to traditional asthma management.(15-17) In essence, a FeNO level >50 ppb is considered a significant risk factor for uncontrolled asthma but by monitoring patients through FeNO testing, physicians can spot the issue as quickly as possible.(18)

FeNO as an indicator for ICS adherence

Non-adherence to medication is a major reason for poor asthma control.19 Up to 75% of the costs associated with asthma may be due to patients not taking their medication correctly.(20)

According to several studies, regular FeNO testing is a useful tool for checking whether patients are complying with their ICS treatment.(19,21-23) For example, compliance with ICS treatment was closely observed during an asthma camp for children. Improved adherence resulted in a significant reduction in FeNO levels.(24)

A study conducted by Heaney at al in 2019 showed FeNO levels were significantly reduced in non-adherent patients when daily ICS administration was observed.19 Typically, FeNO levels reduce by half in four days when patients comply with their medication.(19) The researchers recognised that non-adherence with ICS in asthma was common and consistently associated with poor clinical outcomes.(19) They noted that assessment of adherence to ICS is challenging, with physician estimates and patient self-report overestimating adherence when compared with objective measures.(19) However, the study found regular monitoring minimised the risk of committing a patient to unnecessary treatment when their disease could be readily controlled with ICS.(19) The researchers added that using FeNO testing to monitor adherence was straightforward for both the patient and the clinician.(19)

To find out more or to book a demonstration of the benefits of FeNO testing with NIOX VERO?, contact us today.

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. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention, 2023. Available at; https://ginasthma.org/2023-gina-main-report/

3. National Heart, Lung, and Blood Institute (NHLBI). National Asthma Education and Prevention Program Expert Report: Guidelines for the Diagnosis and Management of Asthma. 1991.

4. Szefler SJ et al. Asthma Clinical Research Network of the National Heart Lung, and Blood Institute. Significant variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol. 2002;109(3):410-8.

5. Aaron SD et al. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317(3):269-279.

6. 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.

7. Louis R et al. European Respiratory Society guidelines for the diagnosis of asthma in adults. European Respiratory Journal. 2022;60(3).

8. 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.

9. 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.

10. Petsky HL et al. Exhaled nitric oxide levels to guide treatment for adults with asthma. Cochrane Database Syst Rev. 2016;9(9) .

11. Gustafsson LE et al. Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans. Biochemical and biophysical research communications. 1991;181(2):852-7.

12. Silkoff PE et al. The Aerocrine exhaled nitric oxide monitoring system NIOX is cleared by the US Food and Drug Administration for monitoring therapy in asthma. J Allergy Clin Immunol. 2004;114(5):1241-56.

13. 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.

14. LaForce C et al. Impact of exhaled nitric oxide measurements on treatment decisions in an asthma specialty clinic. Ann Allergy Asthma Immunol. 2014;113(6):619-23.

15. Smith AD et al. Use of exhaled nitric oxide measurements to guide treatment in chronic asthma. N Engl J Med. 2005;352(21):2163-73.

16. Syk J et al. Anti-inflammatory treatment of atopic asthma guided by exhaled nitric oxide: a randomized, controlled trial. J Allergy Clin Immunol Pract. 2013;1(6):639-48.

17. 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.

18. Malinovschi A et al. Simultaneously increased fraction of exhaled nitric oxide levels and blood eosinophil counts relate to increased asthma morbidity. J Allergy Clin Immunol. 2016;138(5):1301-1308.e2.

19. 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.

20. Apter AJ. Enhancing patients’ adherence to asthma therapy. Up to Date. Last updated 2021.

21. Menzies-Gow A et al. Clinical utility of fractional exhaled nitric oxide in severe asthma management. Eur Respir J. 2020;55(3):1901633.

22. Porsbjerg C et al. Asthma. The Lancet. 2023.

23. McNicholl DM et al. The utility of fractional exhaled nitric oxide suppression in the identification of nonadherence in difficult asthma. Am J Respir Crit Care Med. 2012;186(11):1102-8.

24. Mallett LH et al. Role of asthma camp in improving the overall health of children with asthma. Proc (Bayl Univ Med Cent). 2019;32(1):54-57.

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