Correlation of tissue eosinophil count and chemosensory functions in patients with chronic rhinosinusitis with nasal polyps after endoscopic sinus surgery

  • Lichuan Zhang
  • Chunhua Hu
  • Zhifu Sun
  • Pengfei Han
  • Xingyu Han
  • Haili Sun
  • Dawei Wu
  • Qianwen Lv
  • Xiaoguang Yan
  • Wei Yu
  • Thomas Hummel
  • Yongxiang WeiEmail author



To investigate the correlation of tissue eosinophil count and chemosensory functions in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery (ESS).


This was a cross-sectional study including 40 patients with a history of ESS for CRSwNP recruited consecutively. Visual analog scale score and the Lund–Kennedy endoscopic score were recorded. Biopsies of the ethmoidal sinus mucosal were performed and evaluated. Chemosensory functions were measured by Sniffin’ Sticks and chemosensory event-related potentials (CSERP). The associations between chemosensory functions and tissue eosinophil count were analyzed using Spearman correlation and partial correlation after adjusting the confounding factors. Kendall’s tau-b correlation was performed between sneezing score and CSERP with ethyl alcohol (EAL) stimulation.


Olfactory and trigeminal nerve function was successfully evaluated using CSERP. Postoperative tissue eosinophil count was correlated with threshold (T) score (partial correlation coefficient r = − 0.460, p = 0.012) and CSERP peak latency for olfactory (N1: partial r = 0.471, p = 0.010; P2: partial r = 0.487, p = 0.007) and mixed olfactory–trigeminal (N1: partial r = − 0.516, p = 0.008; P2: partial r = − 0.590, p = 0.002). There were also correlations between T score and N1 latency with phenyl ethyl alcohol (PEA) (partial r = − 0.560, p < 0.001), between sneezing score and N1 latency with EAL (Kendall’s tau-b = − 0.40, p = 0.005).


Postoperative tissue eosinophilia is significantly associated with postoperative olfactory disorders as assessed by Sniffin’ Sticks and CSERP peak latency. Furthermore, olfaction as measured by T score correlates with olfactory ERP latency in inflammation-associated olfactory dysfunction. Trigeminal sensitivity also appears to relate to tissue eosinophilia, indicating mucosal inflammation can affect both sensory systems in the nose.


Rhinosinusitis Eosinophil Smell Trigeminal nerve Olfactory test Event-related potentials 


Author contribution

TH and LZ designed the study. CH analyzed the data. WY and YW performed histopathological analysis. LZ, PH and ZS wrote the manuscript. LZ, CH, XH, DW, HS and XY collected the clinical data and followed up with the patients. TH, YW read and revised the manuscript. All authors have read and approved the final manuscript.


This study was supported by the Natural Science Foundation of China (No. 81670903), the Beijing Key Laboratory of Upper Airway Dysfunction-related Cardiovascular Diseases (BZ0377), the Beijing Municipal Administration of Hospitals (No. DFL20150602), the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201605) and the Beijing Natural Science Foundation (No. 7152057).

Compliance with ethical standards

Financial disclosure

There are no financial disclosures of the authors.

Conflict of interest

All the authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Ethics Committee of Beijing An Zhen Hospital, Capital Medical University, and had been performed in accordance with the ethical standards as laid down in the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Cao PP, Li HB, Wang BF, Wang SB, You XJ et al (2009) Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese. J Allergy Clin Immunol 124:478–484. CrossRefGoogle Scholar
  2. 2.
    Tomassen P, Vandeplas G, Van Zele T et al (2016) Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol 137:1449–1456. CrossRefGoogle Scholar
  3. 3.
    Chung JH, Lee YJ, Kang TW, Kim KR, Jang DP, Kim IY, Cho SH (2015) Altered quality of life and psychological health (SCL-90-R) in patients with chronic rhinosinusitis with nasal polyps polyps. Ann Otol Rhinol Laryngol 124:663–670. CrossRefGoogle Scholar
  4. 4.
    Ishitoya J, Sakuma Y, Tsukuda M (2010) Eosinophilic chronic rhinosinusitis in Japan. Allergol Int 59:239–245. CrossRefGoogle Scholar
  5. 5.
    Wu D, Bleier BS, Li L, Zhan X, Zhang L, Lv Q, Wang J, Wei Y (2018) Clinical phenotypes of nasal polyps and comorbid asthma based on cluster analysis of disease history. J Allergy Clin Immunol Pract 6:1297–1305. CrossRefGoogle Scholar
  6. 6.
    Wu D, Bleier BS, Wei Y (2018) Temporary olfactory improvement in chronic rhinosinusitis with nasal polyps after treatment. Eur Arch Otorhinolaryngol 275:2193–2202. CrossRefGoogle Scholar
  7. 7.
    Oka H, Tsuzuki K, Takebayashi H, Kojima Y, Daimon T, Sakagami M (2013) Olfactory changes after endoscopic sinus surgery in patients with chronic rhinosinusitis. Auris Nasus Larynx 40:452–457. CrossRefGoogle Scholar
  8. 8.
    Haxel BR, Bertz-Duffy S, Fruth K, Letzel S, Mann WJ, Muttray A (2012) Comparison of subjective olfaction ratings in patients with and without olfactory disorders. J Laryngol Otol 126:692–697. CrossRefGoogle Scholar
  9. 9.
    Hummel T (2000) Assessment of intranasal trigeminal function. Int J Psychophysiol 36:147–155CrossRefGoogle Scholar
  10. 10.
    Doerfler H, Hummel T, Klimek L, Kobal G (2006) Intranasal trigeminal sensitivity in subjects with allergic rhinitis. Eur Arch Otorhinolaryngol 263:86–90CrossRefGoogle Scholar
  11. 11.
    Seidman MD, Gurgel RK, Lin SY et al (2015) Clinical practice guideline: allergic rhinitis. Otolaryngol Head Neck Surg 152:S1–S43. CrossRefGoogle Scholar
  12. 12.
    Bateman ED, Hurd SS, Barnes PJ et al (2008) Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 31:143–178. CrossRefGoogle Scholar
  13. 13.
    Liu Z, Lu X, Zhang XH, Bochner BS, Long XB, Zhang F, Wang H, Cui YH (2009) Clara cell 10-kDa protein expression in chronic rhinosinusitis and its cytokine-driven regulation in sinonasal mucosa. Allergy 64:149–157. CrossRefGoogle Scholar
  14. 14.
    Lund VJ, Kennedy DW (1995) Quantification for staging sinusitis. The staging and therapy group. Ann Otol Rhinol Laryngol Suppl 167:17–21CrossRefGoogle Scholar
  15. 15.
    Hummel T, Sekinger B, Wolf SR, Pauli E, Kobal G (1997) ‘Sniffin’ sticks’: olfactory performance assessed by the combined testing of odor identification, odor discrimination and olfactory threshold. Chem Senses 22:39–52CrossRefGoogle Scholar
  16. 16.
    Kobal G, Klimek L, Wolfensberger M et al (2000) Multicenter investigation of 1,036 subjects using a standardized method for the assessment of olfactory function combining tests of odor identification, odor discrimination, olfactory thresholds. Eur Arch Otorhinolaryngol 257:205–211CrossRefGoogle Scholar
  17. 17.
    Kobal G, Hummel T (1998) Olfactory and intranasal trigeminal event-related potentials in anosmic patients. Laryngoscope 108:1033–1035CrossRefGoogle Scholar
  18. 18.
    Rombaux P, Mouraux A, Bertrand B, Guerit JM, Hummel T (2006) Assessment of olfactory and trigeminal function using chemosensory event-related potentials. Neurophysiol Clin 36:53–62CrossRefGoogle Scholar
  19. 19.
    Olofsson JK, Nordin S (2004) Gender differences in chemosensory perception and event-related potentials. Chem Senses 29:629–637CrossRefGoogle Scholar
  20. 20.
    Beswick DM, Mace JC, Chowdhury NI, Alt JA, Hwang PH, DeConde AS, Smith TL (2017) Comparison of surgical outcomes between patients with unilateral and bilateral chronic rhinosinusitis. Int Forum Allergy Rhinol 7:1162–1169. CrossRefGoogle Scholar
  21. 21.
    Knížek Z, Vodička J, Brothánková P, Shejbalová H (2017) Olfactory function in patients undergoing FESS for chronic rhinosinusitis. Cas Lek Cesk 156:187–191Google Scholar
  22. 22.
    Prasad S, Fong E, Ooi EH (2017) Systematic review of patient-reported outcomes after revision endoscopic sinus surgery. Am J Rhinol Allergy 31:248–255. CrossRefGoogle Scholar
  23. 23.
    Pause BM, Krauel K (2000) Chemosensory event-related potentials (CSERP) as a key to the psychology of odors. Int J Psychophysiol 36:105–122CrossRefGoogle Scholar
  24. 24.
    Wu J, Chandra RK, Li P, Hull BP, Turner JH (2018) Olfactory and middle meatal cytokine levels correlate with olfactory function in chronic rhinosinusitis. Laryngoscope 128:E304–E310. CrossRefGoogle Scholar
  25. 25.
    Bachert C, Sousa AR, Lund VJ, Scadding GK, Gevaert P (2017) Reduced need for surgery in severe nasal polyposis with mepolizumab: randomised trial. J Allergy Clin Immunol 140:1024–1031. CrossRefGoogle Scholar
  26. 26.
    Pause BM, Sojka B, Ferstl R (1997) Central processing of odor concentration is a temporal phenomenon as revealed by chemosensory event-related potentials (CSERP). Chem Senses 22:9–26CrossRefGoogle Scholar
  27. 27.
    Kohli P, Naik AN, Farhood Z, Ong AA, Nguyen SA, Soler ZM, Schlosser RJ (2016) Olfactory outcomes after endoscopic sinus surgery for chronic rhinosinusitis: a meta-analysis. Otolaryngol Head Neck Surg 155:936–948CrossRefGoogle Scholar
  28. 28.
    Banglawala SM, Oyer SL, Lohia S, Psaltis AJ, Soler ZM, Schlosser RJ (2014) Olfactory outcomes in chronic rhinosinusitis with nasal polyposis after medical treatments: a systematic review and meta-analysis. Int Forum Allergy Rhinol 4:986–994. CrossRefGoogle Scholar
  29. 29.
    Levy JM, Mace JC, Sansoni ER, Soler ZM, Smith TL (2016) Longitudinal improvement and stability of olfactory function in the evaluation of surgical management for chronic rhinosinusitis. Int Forum Allergy Rhinol 6:1188–1195. CrossRefGoogle Scholar
  30. 30.
    Poetker DM, Jakubowski LA, Lai D, Hwang PH, Wright ED, Smith TL (2013) Oral corticosteroids in the management of adult chronic rhinosinusitis with and without nasal polyps: an evidence-based review with recommendations. Int Forum Allergy Rhinol 3:104–120. CrossRefGoogle Scholar
  31. 31.
    Daiber P, Genovese F, Schriever VA, Hummel T, Möhrlen F, Frings S (2013) Neuropeptide receptors provide a signalling pathway for trigeminal modulation of olfactorytransduction. Eur J Neurosci 37:572–582. CrossRefGoogle Scholar
  32. 32.
    Kobal G, Hummel C (1988) Cerebral chemosensory evoked potentials elicited by chemical stimulation of the human olfactory and respiratory nasal mucosa. Electroencephalogr Clin Neurophysiol 71:241–250CrossRefGoogle Scholar
  33. 33.
    Livermore A, Hummel T (2004) The influence of training on chemosensory event-related potentials and interactions between the olfactory and trigeminal systems. Chem Senses 29:41–51CrossRefGoogle Scholar
  34. 34.
    Yu S, Ouyang A (2011) Effect of synthetic cationic protein on mechanoexcitability of vagal afferent nerve subtypes in guinea pigesophagus. Am J Physiol Gastrointest Liver Physiol 301:G1052–G1058. CrossRefGoogle Scholar
  35. 35.
    Drake MG, Scott GD, Blum ED, Lebold KM, Nie Z, Lee JJ, Fryer AD, Costello RW, Jacoby DB (2018) Eosinophils increase airway sensory nerve density in mice and in human asthma. Sci Transl Med. Google Scholar
  36. 36.
    Durack DT, Ackerman SJ, Loegering DA, Gleich GJ (1981) Purification of human eosinophil-derived neurotoxin. Proc Natl Acad Sci USA 78:5165–5169CrossRefGoogle Scholar
  37. 37.
    Fredens K, Dahl R, Venge P (1982) The Gordon phenomenon induced by the eosinophil cationic protein and eosinophil protein X. J Allergy Clin Immunol 70:361–366CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Otolaryngology–Head and Neck Surgery, Beijing An Zhen HospitalCapital Medical UniversityBeijingPeople’s Republic of China
  2. 2.Department of OtorhinolaryngologyTechnische Universitat DresdenDresdenGermany
  3. 3.Beijing An Zhen Hospital, Beijing Institute of Heart, Lung and Blood Vessel DiseasesCapital Medical UniversityBeijingPeople’s Republic of China
  4. 4.Department of Pathology, Beijing An Zhen HospitalCapital Medical UniversityBeijingPeople’s Republic of China

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