The role of Fraction Exhaled Nitric Oxide (FeNO) in asthma management: an Italian consensus statement on clinical and economic aspects

The role of Fraction Exhaled Nitric Oxide (FeNO) in asthma management: an Italian consensus statement on clinical and economic aspects

Authors

  • Matteo Bonini Department of Public Health and Infectious Diseases, Sapienza Università di Roma, Rome, Italy
  • Rosa Annibale Azienda Ospedaliera Universitaria Luigi Vanvitelli, Naples, Italy
  • Simona Barbaglia Associazione Nazionale pazienti "Respiriamo Insieme-APS", Italy
  • Marco Bo Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano (Turin), Italy
  • Federica Capano Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano (Turin), Italy
  • Mariagrazia Celeste Fondazione Policlinico Tor Vergata, Rome, Italy
  • Pasquale Di Girolamo Faraone Azienda Ospedaliera Universitaria Luigi Vanvitelli, Naples, Italy
  • Sabrina Ferri Fondazione Policlinico Tor Vergata, Rome, Italy
  • Carlotta Galeone Bicocca Applied Statistics Center (B-ASC), Università degli Studi di Milano-Bicocca, Milan, Italy
  • Mario Picozza Associazione FederAsma e Allergie, Italy
  • Umberto Restelli LIUC – Università Cattaneo, Castellanza (VA), Italy
  • Sofia Silvola LIUC – Università Cattaneo, Castellanza (VA), Italy
  • Fabio Luigi Massimo Ricciardolo Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Orbassano (Turin), Italy; Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Turin, Italy

Keywords:

Fraction Exhaled Nitric Oxide (FeNO), asthma, consensus, Italy

Abstract

Background: Chronic respiratory diseases cause significant global morbidity and mortality, with asthma being a major contributor. Globally, 461,000 asthma-related deaths and a prevalence of 262 million subjects were estimated in 2019. The objective of this paper is to summarize experts' opinions in the field of asthma to produce evidence on the clinical and economic impact of FeNO test in asthma management, as well as on its standard operational procedures.

Methods: The analysis conducted is based on a literature review of the FeNO test's role in asthma, focusing on its clinical and economic impact, strengths and limitations. Insights were gathered through interviews with ten Key Opinion Leaders in asthma management from various Italian regions. Their thoughts were summarized into key-messages and discussed in a joint meeting. A final document consolidating these discussions was outlined and approved by the experts involved.

Results: The FeNO test is crucial in the clinical management of asthma, aiding in phenotypic classification and guiding therapeutic decisions, particularly in severe cases. The value of FeNO assessment is supported by extensive literature evidence and recommended by international guidelines. Moreover, published economic analyses highlight the sustainability of the initial investment in FeNO technology thanks to a reduction of short-term medical costs for National Health Services by decreasing hospital admissions, specialist visits, and exacerbations related to asthma management. The test should be conducted at the first visit at the asthma centre and then regularly during follow-ups to monitor therapy adherence, adjust treatments, and predict response to drugs. FeNO testing facilitates early detection of bronchial inflammation, shortening the time for patients to access appropriate therapy. Despite its ease of use, interpreting the results requires specialist oversight due to potential confounding factors.

Conclusions: FeNO testing significantly improves asthma management by aiding in phenotyping, therapeutic strategy formulation, and monitoring. It enhances disease control, accelerates patient care, and offers economic benefits by reducing hospital admissions and treatment needs. However, practical and economic barriers can limit its adoption. Standardized test execution and result interpretation by specialists are essential for accurate patient management. The inclusion of FeNO assessment among exempt services for asthma patients would at last promote its equitable access.

References

1. Institute for Health Metrics and Evaluation. Findings from the Global Burden of Disease Study 2017. Seattle, WA: IHME 2018.

2. Viegi G, Maio S, Fasola S, Baldacci S. Global burden of chronic respiratory diseases. J Aerosol Med Pulm Drug Deliv 2020; 33: 171-7.

3. Shin YH, Hwang J, Kwon R, Lee SW, Kim MS, GBD 2019 Allergic Disorders Collaborators, et al. Global, regional, and national burden of allergic disorders and their risk factors in 204 countries and territories, from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019. Allergy 2023; 78: 2232-54.

4. Ministero della Salute, Alleanza contro le malattie respiratorie croniche GARD Italia. Asma grave. 2024. Available at: https://www.salute.gov.it/portale/gard/dettaglioContenutiGard.jsp?lingua=italiano&id=5822&area=gard&menu=attivita.

5. Global Initiative for Asthma. Global strategy for asthma management and prevention. 2024.

6. Kuo CR, Spears M, Haughney J, Smith A, Miller J, Bradshaw T, et al. Scottish consensus statement on the role of FeNO in adult asthma. Respir Med 2019; 155: 54-7.

7. Stonham C, Baxter N. FeNO testing for asthma diagnosis - a PCRS consensus. Prim Care Respir Update 2019: 1-5.

8. Alving K, Teague WG. Inflammatory markers to inform treatment of asthma with biologicals: FeNO versus blood eosinophils. J Allergy Clin Immunol Pract 2023; 11: 1221-3.

9. Bertolini F, Sprio AE, Baroso A, Riccardi E, Pizzimenti S, Carriero V, et al. Predictors of low and high exhaled nitric oxide values in asthma: a real-world study. Respiration 2022; 101: 746-56.

10. British Thoracic Society, Scottish Intercollegiate Guidelines Network. SIGN158, British guideline on the management of asthma: a national clinical guideline. 2003.

11. Busse WW, Wenzel SE, Casale TB, FitzGerald JM, Rice MS, Daizadeh N, 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: 1165-73.

12. Darbà J, Ascanio M, Syk J, Alving K. Economic evaluation of the use of FeNO for the diagnosis and management of asthma patients in primary care in Sweden. Clinicoecon Outcomes Res 2021; 13: 289-97.

13. Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, 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: 602-15.

14. Guida G, Bagnasco D, Carriero V, Bertolini F, Ricciardolo FLM, Nicola S, et al. Critical evaluation of asthma biomarkers in clinical practice. Front Med (Lausanne) 2022; 9: 969243.

15. Heffler E, Carpagnano GE, Favero E, Guida G, Maniscalco M, Motta A, et al. Fractional exhaled nitric oxide (FeNO) in the management of asthma: a position paper of the Italian Respiratory Society (SIP/IRS) and Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). Multidiscip Respir Med 2020; 15: 36.

16. Loewenthal L, Menzies-Gow A. FeNO in asthma. Semin Respir Crit Care Med 2022; 43: 635-45.

17. Louis R, Satia I, Ojanguren I, Schleich F, Bonini M, Tonia T, et al. European Respiratory Society guidelines for the diagnosis of asthma in adults. Eur Respir J 2022; 15: 2101585.

18. Marcos MC, Cisneros Serrano C. What is the added value of FeNO as T2 biomarker? Front Allergy 2022; 3: 957106.

19. Murugesan N, Saxena D, Dileep A, Adrish M, Hanania NA. Update on the role of FeNO in asthma management. Diagnostics (Basel) 2023; 13: 1428.

20. National Institute for Health and Care Excellence. Asthma: diagnosis, monitoring and chronic asthma management. 2017. Available at: www.nice.org.uk/guidance/ng80.

21. Ricciardolo FL, Sorbello V, Ciprandi G. FeNO as biomarker for asthma phenotyping and management. Allergy Asthma Proc 2015; 36: e1-8.

22. Ricciardolo FLM, Stufano S, Carriero V, Maniscalco M. Utilizzo della misura di ossido nitrico nell’aria espirata: un update. Rass Patol App Respir 2021; 36: 118-22.

23. Guida G, Carriero V, Bertolini F, Pizzimenti S, Heffler E, Paoletti G, et al. Exhaled nitric oxide in asthma: from diagnosis to management. Curr Opin Allergy Clin Immunol 2023; 23: 29-35.

24. Pavord ID, Deniz Y, Corren J, Casale TB, FitzGerald JM, Izuhara K, et al. Baseline FeNO independently predicts the dupilumab response in patients with moderate-to-severe asthma. J Allergy Clin Immunol Pract 2023; 11: 1213-20.

25. Holguin F, Comhair SA, Hazen SL, Powers RW, Khatri SS, Bleecker ER, et al. An association between L-arginine/asymmetric dimethyl arginine balance, obesity, and the age of asthma onset phenotype. Am J Respir Crit Care Med 2013; 187: 153-9.

26. Rognoni C, Milano C, Heffler E, Bonini M, Brussino L, Carpagnano GE, et al. Economic impact of a more extensive use of FeNO testing on the Italian population with asthma. Respir Res 2023; 24: 147.

27. Wang R, Usmani OS, Chung KF, Sont J, Simpson A, Bonini M, et al. Domiciliary fractional exhaled nitric oxide and spirometry in monitoring asthma control and exacerbations. J Allergy Clin Immunol Pract 2023; 11: 1787-95.

28. Arnold RJG, Layton A, Massanari M. Cost impact of monitoring exhaled nitric oxide in asthma management. Allergy Asthma Proc 2018; 39: 338-44.

29. Beerthuizen T, Voorend-van Bergen S, van den Hout WB, Vaessen-Verberne AA, Brackel HJ, et al. Cost-effectiveness of FeNO-based and web-based monitoring in paediatric asthma management: a randomised controlled trial. Thorax 2017; 71: 607-13.

30. Berg J, Lindgren P. Economic evaluation of FeNO measurement in diagnosis and 1-year management of asthma in Germany. Respir Med 2008; 102: 219-31.

31. Brooks EA, Massanari M. Cost-effectiveness analysis of monitoring fractional exhaled nitric oxide (FeNO) in the management of asthma. Manag Care 2018; 27: 42-8.

32. Brooks EA, Massanari M, Hanania NA, Weiner DJ. Cost-effectiveness of fractional exhaled nitric oxide (FeNO) measurement in predicting response to omalizumab in asthma. Clinicoecon Outcomes Res 2019; 11: 301-7.

33. Buendía JA, Acuña-Cordero R, Rodriguez-Martinez CE. Cost utility of fractional exhaled nitric oxide monitoring for the management of children asthma. Cost Eff Resour Alloc 2021; 19: 33.

34. Buendía JA, Acuña-Cordero R, Rodriguez-Martinez CE. Analysis of the budget impact of fractional exhaled nitric oxide monitoring in the management of childhood asthma: the Colombian National Health System perspective. J Investig Allergol Clin Immunol 2022; 32: 200-5.

35. Bukstein D, Luskin AT, Brooks EA. Exhaled nitric oxide as a tool in managing and monitoring difficult-to-treat asthma. Allergy Asthma Proc 2011; 32: 185-92.

36. Honkoop PJ, Loijmans RJ, Termeer EH, Snoeck-Stroband JB, van den Hout WB, Bakker MJ, et al. Symptom- and fraction of exhaled nitric oxide-driven strategies for asthma control: a cluster-randomized trial in primary care. J Allergy Clin Immunol 2015; 135: 682-8.

37. LaForce C, Brooks E, Herje N, Dorinsky P, Rickard K. Impact of exhaled nitric oxide measurements on treatment decisions in an asthma specialty clinic. Ann Allergy Asthma Immunol 2014; 113: 619-23.

38. Massanari M, Brooks EA, Rickard KA, Roman AA. Investigation of the cost-effectiveness of FeNO measurement as a screening tool to detect omalizumab responsiveness in difficult-to-treat asthma patients. Value Health 2017; 20: A241.

39. Massanari M, Brooks EA, Rickard K, Roman AA. Cost-effectiveness of using FeNO in the management of asthma. Value Health 2017; 20: A241-A242.

40. Price D, Berg J, Lindgren P. An economic evaluation of NIOX MINO airway inflammation monitor in the United Kingdom. Allergy 2009; 64: 431-8.

41. Sabatelli L, Seppälä U, Sastre J, Crater G. Cost-effectiveness and budget impact of routine use of fractional exhaled nitric oxide monitoring for the management of adult asthma patients in Spain. J Investig Allergol Clin Immunol 2017; 27: 89-97.

42. Molino A, Fuschillo S, Mosella M, et al. Comparison of three different exhaled nitric oxide analyzers in chronic respiratory disorders. J Breath Res 2019; 13: 021002.

43. Maniscalco M, Vitale C, Vatrella A, Molino A, Bianco A, Mazzarella G. Fractional exhaled nitric oxide-measuring devices: technology update. Med Devices (Auckl) 2016; 9: 151-60.

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Published

11-04-2025

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Original Research Articles

How to Cite

1.
Bonini M, Annibale R, Barbaglia S, Bo M, Capano F, Celeste M, et al. The role of Fraction Exhaled Nitric Oxide (FeNO) in asthma management: an Italian consensus statement on clinical and economic aspects. Multidiscip Respir Med [Internet]. 2025 Apr. 11 [cited 2025 Apr. 19];20(1). Available from: https://mrmjournal.org/index.php/mrm/article/view/1006