The Role of Fractional Exhaled Nitric Oxide in Diagnosing Asthmatic Type 2 Chronic Rhinosinusitis With Nasal Polyps

Abstract

Background

Fractional exhaled nitric oxide (FeNO) is useful in the management of asthma and predicting the efficacy of standard corticosteroids and biologics. However, the diagnostic value of FeNO in asthmatic chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear.

Objective

We assessed FeNO levels in patients with CRSwNP and evaluated the diagnostic value of FeNO for screening type 2 CRSwNP (T2-CRSwNP) with asthma.

Methods

We enrolled 94 patients who were diagnosed with CRSwNP and underwent functional endoscopic sinus surgery. FeNO levels, the blood eosinophil percentage, total IgE, spirometry tests (FEV1/FVC), Lund–Mackay CT score, and percentage of patients with comorbid asthma were compared among CRSwNP subgroups. Spearman rank correlation test was used to assess the degree of association between variables. ROC curve analysis was conducted to evaluate the diagnostic capability to differentiate T2-CRSwNP based on clinical and histological classifications.

Results

FeNO levels and the blood eosinophil percentage were significantly higher in patients with T2-CRSwNP(h) based on histological data (P < .05). FeNO was correlated with the blood eosinophil percentage (r = 0.420, P < .001) and FEV1/FVC (r = −0.324, P = .001). A FeNO level of 27 ppb had a good ability to discriminate patients with asthmatic T2-CRSwNP(h) (AUC = 0.848; 95% CI = 0.7602-0.9361; sensitivity = 90.9%; specificity = 63.9%). The optimal cutoff values for FeNO and the blood eosinophil percentage for diagnosing asthmatic T2-CRSwNP(h) were 68 ppb and 5.6% (sensitivity = 95.5%; specificity = 86.1%; AUC = 0.931; 95% CI = 0.8832-0.9791). In the diagnosis of severe T2-CRSwNP(c) based on clinical data, a FeNO level of 36 ppb showed the highest AUC (0.816; 95% CI = 0.7173-0.914; sensitivity = 72.7%; specificity = 79.2%).

Conclusion

FeNO is a useful marker for screening asthmatic T2-CRSwNP even prior to biopsy or asthma evaluation and may assist in selecting a proper treatment.

Keywords

chronic rhinosinusitis nasal polyp fractional exhaled nitric oxide eosinophilic chronic rhinosinusitis endotype JESREC score

Get full access to this article

View all access options for this article.

References

Fokkens

Lund

Hopkins

, et al. European position paper on rhinosinusitis and nasal polyps 2020. Rhinology. 2020;58(Suppl S29):1–464.

Wang

Pan

Liu

. Neutrophils as a protagonist and target in chronic rhinosinusitis. Clin Exp Otorhinolaryngol. 2019;12(4):337–347.

Tomassen

Vandeplas

Van Zele

, et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol. 2016;137(5):1449–1456 e1444.

Tokunaga

Sakashita

Haruna

, et al. Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC study. Allergy. 2015;70(8):995–1003.

Lou

Zhang

Bachert

, et al. Highlights of eosinophilic chronic rhinosinusitis with nasal polyps in definition, prognosis, and advancement. Int Forum Allergy Rhinol. 2018;8(11):1218–1225.

Dweik

Boggs

Erzurum

, 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):602–615.

American Thoracic Society and 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.

Essat

Harnan

Gomersall

, et al. Fractional exhaled nitric oxide for the management of asthma in adults: a systematic review. Eur Respir J. 2016;47(3):751–768.

Gomersal

Harnan

Essat

, et al. A systematic review of fractional exhaled nitric oxide in the routine management of childhood asthma. Pediatr Pulmonol. 2016;51(3):316–328.

10.

Ricciardolo

Sorbello

Ciprandi

. A pathophysiological approach for FeNO: a biomarker for asthma. Allergol Immunopathol (Madr). 2015;43(6):609–616.

11.

Kim

Eun

Kim

, et al. Comparison between signature cytokines of nasal tissues in subtypes of chronic rhinosinusitis. Allergy Asthma Immunol Res. 2019;11(2):201–211.

12.

Rolla

Heffler

Bommarito

, et al. Exhaled nitric oxide in persistent rhinitis with or without lower airway involvement: a review of the literature. J Breath Res. 2007;1(2):024003.

13.

Jarvis

Newson

Lotvall

, et al. Asthma in adults and its association with chronic rhinosinusitis: the GA2LEN survey in Europe. Allergy. 2012;67(1):91–98.

14.

Philpott

Erskine

Hopkins

, et al. Prevalence of asthma, aspirin sensitivity and allergy in chronic rhinosinusitis: data from the UK National Chronic Rhinosinusitis Epidemiology Study. Respir Res. 2018;19(1):129.

15.

Stevens

Schleimer

Kern

. Chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol Pract. 2016;4(4):565–572.

16.

Bachert

Han

Desrosiers

, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019;394(10209):1638–1650.

17.

Fujieda

Matsune

Takeno

, et al. The effect of dupilumab on intractable chronic rhinosinusitis with nasal polyps in Japan. Laryngoscope. 2021;131(6):E1770–E1777.

18.

Frendo

Hakansson

Schwer

, et al. Asthma in ear, nose, and throat primary care patients with chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy. 2016;30(3):67–71.

19.

Kambara

Minami

Akazawa

, et al. Lower airway inflammation in eosinophilic chronic rhinosinusitis as determined by exhaled nitric oxide. Int Arch Allergy Immunol. 2017;173(4):225–232.

20.

Noda

Takeno

Fukuiri

, et al. Monitoring of oral and nasal exhaled nitric oxide in eosinophilic chronic rhinosinusitis: a prospective study. Am J Rhinol Allergy. 2012;26(4):255–259.

21.

Takeno

Taruya

Ueda

, et al. Increased exhaled nitric oxide and its oxidation metabolism in eosinophilic chronic rhinosinusitis. Auris Nasus Larynx. 2013;40(5):458–464.

22.

Yoshida

Takabayashi

Imoto

, et al. Reduced nasal nitric oxide levels in patients with eosinophilic chronic rhinosinusitis. Allergol Int. 2019;68(2):225–232.

23.

Ambrosino

Molino

Spedicato

, et al. Nasal nitric oxide in chronic rhinosinusitis with or without nasal polyps: a systematic review with meta-analysis. J Clin Med. 2020;9(1):200.

24.

Frendo

Hakansson

Schwer

, et al. Exhaled and nasal nitric oxide in chronic rhinosinusitis patients with nasal polyps in primary care. Rhinology. 2018;56(1):59–64.

25.

Wang

Lin

, et al. Role of pulmonary function and FeNO detection in early screening of patients with ACO. Exp Ther Med. 2020;20(2):830–837.

26.

Taylor

Pijnenburg

Smith

, et al. Exhaled nitric oxide measurements: clinical application and interpretation. Thorax. 2006;61(9):817–827.

27.

Maniscalco

Calabrese

D’Amato

, et al. Association between exhaled nitric oxide and nasal polyposis in severe asthma. Respir Med. 2019;152:20–24.

28.

Couillard

Shrimanker

Chaudhuri

, et al. Fractional exhaled nitric oxide nonsuppression identifies corticosteroid-resistant type 2 signaling in severe asthma. Am J Respir Crit Care Med. 2021;204(6):731–734.

29.

Workman

Kohanski

Cohen

. Biomarkers in chronic rhinosinusitis with nasal polyps. Immunol Allergy Clin North Am. 2018;38(4):679–692.

30.

Earls

Harvey

. Systemic biomarkers of eosinophilic chronic rhinosinusitis. Curr Opin Allergy Clin Immunol. 2020;20(1):23–29.

31.

Aslan

Altun

Paksoy

, et al.

Could eosinophilia predict clinical severity in nasal polyps?

Multidiscip Respir Med. 2017;12:21.

32.

Olonisakin

Moore

Barel

, et al. Fractional exhaled nitric oxide as a marker of mucosal inflammation in chronic rhinosinusitis. Am J Rhinol Allergy. 2022;36(4):473–473.