FeNO as a Non-Invasive Biomarker of Type 2 Inflammation in Chronic Rhinosinusitis with Nasal Polyps: Correlation with Serum IgE and Eosinophils

Articles in Press

Document Type : Original

Authors

1 Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Sinus and Surgical Endoscopic Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

10.22038/ijorl.2025.88968.3979

Abstract

Introduction:
Chronic rhinosinusitis with nasal polyps is a heterogeneous inflammatory disorder often driven by type 2 inflammation. Identification of non-invasive biomarkers, such as fractional exhaled nitric oxide (FeNO), may support the assessment and personalized management.
Materials and Methods:
In this cross-sectional study, 141 patients with clinically and radiologically confirmed CRSwNP were assessed. FeNO levels, nasal eosinophilia, serum IgE, peripheral blood eosinophil counts, and skin prick test results were evaluated. Disease severity was measured using the SNOT-22 and Lund-Mackay CT scores.
Results:
FeNO showed a significant correlation with nasal eosinophilia (r = 0.53, p < 0.001), a moderate correlation with serum IgE (r = 0.40, p < 0.001), and a weak correlation with blood eosinophils (r = 0.17, p = 0.047). Serum IgE was significantly associated with both SNOT-22 and Lund-Mackay scores. FeNO did not show significant correlation with symptom severity or radiological extent, suggesting its use as a supportive marker rather than a stand-alone predictor.
 Conclusion:
FeNO may serve as a potential non-invasive marker for type 2 inflammation in CRSwNP, though it may not predict disease severity. Combining FeNO with other markers could improve clinical endotyping and management.

Keywords

Main Subjects

References

  1. Orlandi RR, Kingdom TT, Hwang PH, Smith TL, Alt JA, Baroody FM, et al. International consensus statement on allergy and rhinology: rhinosinusitis. Int Forum Allergy Rhinol. 2016; 6(Suppl 1):S22–S209.
  2. Benjamin MR, Stevens WW, Li N, Bose S, Grammer LC, Kern RC, et al. Clinical characteristics of patients with chronic rhinosinusitis without nasal polyps in an academic setting. J Allergy Clin Immunol Pract. 2019;7:1010–1016.
  3. Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, et al. Executive summary of EPOS 2020 including integrated care pathways. Rhinology. 2020;58(2):82–111.
  4. Khan A, Huynh TMT, Vandeplas G, Joos G, Bachert C, Fokkens WJ, et al. The GALEN rhinosinusitis cohort: chronic rhinosinusitis with nasal polyps affects health-related quality of life. Rhinology. 2019;57(5):343–351.
  5. Mormile M, Mormile I, Fuschillo S. Eosinophilic airway diseases: from pathophysiological mechanisms to clinical practice. Int J Mol Sci. 2023;24:7254.
  6. Calus L, Van Bruaene N, Bosteels C, De Ruyck N, Seys S, Van Zele T, et al. Twelve-year follow-up study after endoscopic sinus surgery in patients with chronic rhinosinusitis with nasal polyposis. Clin Transl Allergy. 2019;9:30.
  7. Staudacher AG, Peters AT, Kato A, Stevens WW. Use of endotypes, phenotypes, and inflammatory markers to guide treatment decisions in chronic rhinosinusitis. Ann Allergy Asthma Immunol. 2020;124(4):318–325.
  8. Laidlaw TM, Mullol J, Woessner KM, Amin N, Bachert C, Fokkens W. Chronic rhinosinusitis with nasal polyps and asthma. J Allergy Clin Immunol Pract. 2021;9(3):1133–1141.
  9. Yao Y, Zeng M, Liu Z, Wang F, Li Z, Huang Y. Revisiting Asian chronic rhinosinusitis in the era of type 2 biologics. Clin Exp Allergy. 2022;52(2):231–243.
  10. Shah SA, Ishinaga H, Takeuchi K. Pathogenesis of eosinophilic chronic rhinosinusitis. J Inflamm (Lond). 2016;13:9.
  11. Stevens WW, Schleimer RP, Kern RC. Chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol Pract. 2016;4(4):565–572.
  12. Murugesan N, Saxena D, Dileep A, Adrish M, Hanania NA. Update on the role of FeNO in asthma management. Diagnostics. 2023 Apr 15;13(8):1428.
  13. Park JA, Cha H, Yang SK, Lee J, Cho SH, Kim DW, et al. The role of fractional exhaled nitric oxide in diagnosing asthmatic type 2 chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy. 2023; 37(5): 524–530.
  14. Guida G, Rolla G, Badiu I, Bucca C, Caminati M, Heffler E, et al. Determinants of exhaled nitric oxide in chronic rhinosinusitis. Chest. 2010; 137(3): 658–664.
  15. Ferraro VA, Zanconato S, Baraldi E, Carraro S. Nitric oxide and biological mediators in pediatric chronic rhinosinusitis and asthma. J Clin Med. 2019; 8(11):1783.
  16. Lundberg JO, Farkas-Szallasi T, Weitzberg E, Rinder J, Lidholm J, Anggård A. High nitric oxide production in human paranasal sinuses. Nat Med. 1995;1(4):370–373.
  17. Zhang J, Sun Y, Liu M, Wang Y, Wang P, Lin X, et al. Predictive and diagnostic value of fractional exhaled nitric oxide in patients with chronic rhinosinusitis. Med Sci Monit. 2019;25:150–156.
  18. Jeong JH, Yoo HS, Lee SH, Kim SW, Dhong HJ, Chung SK. Nasal and exhaled nitric oxide in chronic rhinosinusitis with polyps. Am J Rhinol Allergy. 2014;28:e11–e16.
  19. Kobayashi Y, Asako M, Ooka H, Saito H, Tagaya E, Kikuchi Y. Residual exhaled nitric oxide elevation in asthmatics is associated with eosinophilic chronic rhinosinusitis. J Asthma. 2015; 52:1060–1064.
  20. Kambara R, Minami T, Akazawa H, Nakano Y, Nishimoto Y, Ueda T. Lower airway inflammation in eosinophilic chronic rhinosinusitis as determined by exhaled nitric oxide. Int Arch Allergy Immunol. 2017;173:225–232.
  21. Heffernan A, Phulka J, Thamboo A. Improving predictability of IgE-high type 2 chronic sinusitis with nasal polyps in the biologic era. J Otolaryngol Head Neck Surg. 2022;51(1):22.
  22. Mehta V, Campeau NG, Kita H, Hagan JB. Blood and sputum eosinophil levels in asthma and their relationship to sinus computed tomographic findings. Mayo Clin Proc. 2008;83(6):671–678.
  23. 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):912–930.
  24. Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO; American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. 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):602–615.
  25. Maniscalco M, Fuschillo S, Mormile I, Sanduzzi A, Pelaia G, Sofia M. Exhaled nitric oxide as biomarker of type 2 diseases. Cells. 2023; 12(21): 2518.
  26. Taruya T, Takeno S, Kubota K, Sasaki A, Ishino T, Hirakawa K. Comparison of arginase isoform expression in patients with different subtypes of chronic rhinosinusitis. J Laryngol Otol. 2015; 129(12): 1194–1200.
  27. Chan EY, Ng DK, Chan CH. Measuring FENO in asthma: coexisting allergic rhinitis and severity of atopy as confounding factors. Am J Respir Crit Care Med. 2009;180:281–282.
  28. Nabavi M, Arshi S, Bemanian M, Mahdavi M, Mirzaie A, Mesdaghi M. A prospective cross-sectional study on exhaled nitric oxide and sensitivity to indoor inhaled aeroallergens in patients with rhinosinusitis with nasal polyps. Jundishapur J Chronic Dis Care. 2020; 9(4): e104403.
  29. Al Ghobain MO, Alsubaie AS, Aljumah WA, Al-Harbi AS, Al-Ghamdi MA, Al-Saud SA. The correlation between fractional exhaled nitric oxide (FeNO), blood eosinophil count, immunoglobulin E levels, and spirometric values in patients with asthma. Cureus. 2023;15(2):e33914.
  30. Dabholkar YG, Saberwal AA, Velankar HK, Jadhav AG, Anap DB, Phadke RV. Correlation of nasal nitric oxide measurement with computed tomography findings in chronic rhinosinusitis. Indian J Otolaryngol Head Neck Surg. 2014; 66(1): 92–96.
  31. Hussien HA, Habieb MS, Hamdan AM. Evaluation of serum total immunoglobulin E, interleukin-17 and pentraxin-3 as biomarkers for chronic rhinosinusitis with nasal polyposis. Am J Rhinol Allergy. 2021;35(5):640–646.
  32. Greguric T, Trkulja V, Baudoin T, Demarin V, Hozo I, Vukovic D. Association between computed tomography findings and clinical symptoms in chronic rhinosinusitis with and without nasal polyps. Eur Arch Otorhinolaryngol. 2017;274(5):2165–2173.
  33. Green BJ, Beezhold DH, Gallinger ZR, Li Z, Khurana Hershey GK, Salo PM. Allergic sensitization in Canadian chronic rhinosinusitis patients. Allergy Asthma Clin Immunol. 2014; 10(1):15.
  34. Tomassen P, Vandeplas G, Van Zele T, Gevaert P, Holtappels G, Bachert C. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol. 2016;137(5):1449–1456.e4.
  35. Promsopa C, Kansara S, Citardi MJ, Mace JC, Soler ZM, Smith TL. Prevalence of confirmed asthma varies in chronic rhinosinusitis subtypes. Int Forum Allergy Rhinol. 2016;6(4):373–377.
  36. Song WJ, Lee JH, Won HK, Bachert C. Chronic rhinosinusitis with nasal polyps in older adults: clinical presentation, pathophysiology,and comorbi- dity.Curr Allergy Asthma Rep.2019;19:1–8.
  37. Won HK, Kim YC, Kang MG, Kim HJ, Lee CH, Kim SW. Age-related prevalence of chronic rhinosinusitis and nasal polyps and their relationships with asthma onset. Ann Allergy Asthma Immunol. 2018;120(4):389–394.
  38. Song WJ, Cho SH. Challenges in the management of asthma in the elderly. Allergy Asthma Immunol Res. 2015;7(5):431–9.
  39. Lin DC, Chandra RK, Tan BK, Zirkle W, Conley DB, Grammer LC, et al. Association between severity of asthma and degree of chronic rhinosinusitis. Am J Rhinol Allergy. 2011;25: 205–9.
  40. Singhvi P, Baisakhiya N, Singh G. Study the role of nasal scrap cytology in allergic rhinitis patients in rural population. Indian J Otolaryngol Head Neck Surg. 2019;71(Suppl 3):2057–64.

 

 

Iranian Journal of Otorhinolaryngology

Articles in Press, Corrected Proof
Available Online from 25 December 2025

Files

Share

How to cite

Statistics