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Neutrophil infiltrates and eosinophil aggregates in chronic rhinosinusitis with nasal polyps and EGPA

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Abstract

Introduction/objectives

The histopathological study of inflammatory cells and their tendency to form aggregates in chronic rhinosinusitis with nasal polyps (CRSwNP) has shown promising results in determining the pathogenesis and predicting clinical outcome. Bilateral nasal polyps also occur in over 70% of patients with eosinophilic granulomatosis with polyangiitis (EGPA). The study aim was to investigate neutrophil infiltrates and eosinophil aggregates in CRSwNP and EGPA tissues of Caucasian patients.

Method

A histopathological study was performed on surgical specimens of nasal polyps from 144 adults (15 with allergic fungal rhinosinusitis; 19 with nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD); 16 with intrinsic asthma; 21 with extrinsic asthma; 21 with allergy; 22 with eosinophil CRSwNP (ECRSwNP); 17 with non-ECRSwNP; 13 with EGPA).

Results

Focusing on the presence of tissue eosinophil aggregates, NERD and ECRSwNP were the sub-cohorts with the highest rate. Neutrophil infiltrate rate was significantly higher in EGPA sub-cohort than in all CRSwNP sub-cohorts apart from non-ECRSwNP.

Conclusions

Structured histopathology is increasingly identifying the different histotypes of CRSwNP. This analysis can be used to better understand CRSwNP endotypes and develop targeted therapies. The response to therapy and therefore control of CRSwNP relapses definitely depends on our ability to act on the underlying inflammatory pattern.

Key points

Systematic analysis of how neutrophil infiltrates and eosinophilic aggregates are distributed in the different phenotypes of CRSwNP and EGPA.

Neutrophil infiltrates and eosinophil aggregates are strong risk factors for nasal polyps’ refractoriness.

NERD and ECRSwNP are the sub-cohorts of CRSwNP with the highest rate of tissue eosinophil aggregates.

Neutrophil infiltrates are significantly higher in EGPA.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsmaet S et al (2020) European position paper on rhinosinusitis and nasal polyps. Rhinology 58(Suppl S29):1–464

    PubMed  Google Scholar 

  2. Shi JB, Fu QL, Zhang H, Cheng L, Wang YJ, Zhu DD et al (2015) Epidemiology of chronic rhinosinusitis: results from a cross-sectional survey in seven Chinese cities. Allergy 70(5):533–539

    Article  CAS  Google Scholar 

  3. Hirsch AG, Stewart WF, Sundaresan AS, Young AJ, Kennedy TL, Scott Greene J et al (2017) Nasal and sinus symptoms and chronic rhinosinusitis in a population-based sample. Allergy 72(2):274–281

    Article  CAS  Google Scholar 

  4. Akdis CA, Bachert C, Cingi C, Dykewicz MS, Hellings PW, Naclerio RM et al (2013) Endotypes and phenotypes of chronic rhinosinusitis: a PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol 131(6):1479–1490

    Article  Google Scholar 

  5. Wang X, Zhang N, Bo M, Holtappels G, Zheng M, Lou H et al (2016) Diversity of TH cytokine profiles in patients with chronic rhinosinusitis: a multicenter study in Europe, Asia, and Oceania. J Allergy Clin Immunol 138(5):1344–1353

    Article  CAS  Google Scholar 

  6. Brescia G, Barion U, Zanotti C, Giacomelli L, Martini A, Marioni G (2017) The prognostic role of serum eosinophil and basophil levels in sinonasal polyposis. Int Forum Allergy Rhinol 7(3):261–267

    Article  Google Scholar 

  7. Cao PP, Wang ZC, Schleimer RP, Liu Z (2019) Pathophysiologic mechanisms of chronic rhinosinusitis and their roles in emerging disease endotypes. Ann Allergy Asthma Immunol 122(1):33–40

    Article  CAS  Google Scholar 

  8. Cho SH, Hamilos DL, Han DH, Laidlaw TM (2020) Phenotypes of chronic rhinosinusitis. J Allergy Clin Immunol Pract 8(5):1505–1511

    Article  Google Scholar 

  9. Brescia G, Marioni G, Franchella S, Ramacciotti G, Velardita C, Giacomelli L et al (2015) Can a panel of clinical, laboratory, and pathological variables pinpoint patients with sinonasal polyposis at higher risk of recurrence after surgery? Am J Otolaryngol 36(4):554–558

    Article  Google Scholar 

  10. Zhang N, Van Zele T, Perez-Novo C, Van Bruaene N, Holtappels G, DeRuyck N et al (2008) Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease. J Allergy Clin Immunol 122(5):961–968

    Article  CAS  Google Scholar 

  11. Mahdavinia M, Suh LA, Carter RG, Stevens WW, Norton JE, Kato A et al (2015) Increased non eosinophilic nasal polyps in chronic rhinosinusitis in US second-generation Asians suggest genetic regulation of eosinophilia. J Allergy Clin Immunol 135(2):576–579

    Article  Google Scholar 

  12. Brescia G, Contro G, Giacomelli L, Barion U, Frigo AC, Marioni G (2020) Blood eosinophilic and basophilic trends in recurring and non-recurring eosinophilic rhinosinusitis with nasal polyps. Am J Rhinol Allergy:1945892420953960. https://doi.org/10.1177/1945892420953960

  13. Wang H, Li ZY, Jiang WX, Liao B, Zhai GT, Wang N et al (2018) The activation and function of IL-36γ in neutrophilic inflammation in chronic rhinosinusitis. J Allergy Clin Immunol 141:1646–1658

    Article  CAS  Google Scholar 

  14. Wen W, Liu W, Zhang L, Bai J, Fan Y, Xia W et al (2012) Increased neutrophilia in nasal polyps reduces the response to oral corticosteroid therapy. J Allergy Clin Immunol 129:1522–1528.e5

    Article  CAS  Google Scholar 

  15. Kim YS, Kim NH, Seong SY, Kim KR, Lee GB, Kim KS (2011) Prevalence and risk factors of chronic rhinosinusitis in Korea. Am J Rhinol Allergy 25:117–121

    Article  Google Scholar 

  16. Cottin V, Bel E, Bottero P, Dalhoff K, Humbert M, Lazor R et al (2016) Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Eur Respir J 48(5):1429–1441

    Article  CAS  Google Scholar 

  17. Suzuki M, Nakazono A, Morita S, Fukuda A, Honma A, Suzuki T et al (2020) Comparison of clinical characteristics of the nasal manifestations of eosinophilic granulomatosis with polyangiitis (EGPA) and eosinophilic chronic rhinosinusitis (ECRS). Allergol Int S1323-8930(20):30090–30093

    Google Scholar 

  18. Brescia G, Padoan R, Schiavon F, Contro G, Parrino D, Tealdo G et al (2020) Nasal polyps in eosinophilic granulomatosis with polyangiitis: structured histopathology and CD105 expression. Am J Otolaryngol 41(6):102661

    Article  CAS  Google Scholar 

  19. Brescia G, Alessandrini L, Giacomelli L, Parrino D, Zanotti C, Tealdo G et al (2020) A classification of chronic rhinosinusitis with nasal polyps based on structured histopathology. Histopathology 76(2):296–307

    Article  Google Scholar 

  20. Brescia G, Barion U, Zanotti C, Cinetto F, Giacomelli L, Martini A et al (2017) Blood eosinophil-to-basophil ratio in patients with sinonasal polyps: Does it have a clinical role? Ann Allergy Asthma Immunol 119(3):223–226

    Article  Google Scholar 

  21. Horak F, Doberer D, Eber E, Horak E, Pohl W, Riedler J et al (2016) Diagnosis and management of asthma - statement on the 2015 GINA Guidelines. Wien Klin Wochenschr 128(15–16):541–554

    Article  CAS  Google Scholar 

  22. Kowalski ML, Agache I, Bavbek S, Bakirtas A, Blanca M, Bochenek G et al (2019) Diagnosis and management of NSAID-exacerbated respiratory disease (N-ERD)-a EAACI position paper. Allergy 74(1):28–39

    Article  Google Scholar 

  23. Bent JP 3rd, Kuhn FA (1994) Diagnosis of allergic fungal sinusitis. Otolaryngol Head Neck Surg 111(5):580–588

    Article  Google Scholar 

  24. Brescia G, Sfriso P, Marioni G (2019) Role of blood inflammatory cells in chronic rhinosinusitis with nasal polyps. Acta Otolaryngol 139(1):48–51

    Article  Google Scholar 

  25. Dhong HJ, Kim HY, Cho DY (2005) Histopathologic characteristics of chronic sinusitis with bronchial asthma. Acta Otolaryngol 125(2):169–176

    Article  Google Scholar 

  26. Kuhar HN, Tajudeen BA, Mahdavinia M, Gattuso P, Ghai R, Batra PS (2017) Inflammatory infiltrate and mucosal remodelling in chronic rhinosinusitis with and without polyps: structured histopathologic analysis. Int Forum Allergy Rhinol 7:679–689

    Article  Google Scholar 

  27. Brescia G, Barion U, Zanotti C, Parrino D, Marioni G (2017) Pre- and postoperative blood neutrophil-to-lymphocyte and eosinophil-to-lymphocyte ratios in patients with sinonasal polyps: A preliminary investigation. Allergy and Asthma Proceedings 38 (5):64-69

  28. Brescia G, Zanotti C, Parrino D, Barion U, Marioni G (2018) Nasal polyposis pathophysiology: Endotype and phenotype open issues. American Journal of Otolaryngology 39 (4):441-444

  29. Brescia G, Alessandrini L, Parrino D, Franz L, Barion U, Marioni G (2020) Emerging contribution of histopathology to our understanding of chronic rhinosinusitis endotypes: tissue eosinophil count and aggregates. American Journal of Rhinology & Allergy 34 (1):122-126

  30. Tajudeen BA, Ganti A, Kuhar HN, Mahdavinia M, Heilingoetter A, Gattuso P, et al, (2019) The presence of eosinophil aggregates correlates with increased postoperative prednisone requirement. The Laryngoscope 129 (4):794-799

  31. Wang H, Pan L, Liu Z (2019) Neutrophils as a protagonist and target in chronic rhinosinusitis. Clin Exp Otorhinolaryngol 12(4):337-347

  32. Kim DK, Kim JY, Han YE, Kim JK, Lim HS, Eun KM, et al. (2020) Elastase-positive neutrophils are associated with refractoriness of chronic rhinosinusitis with nasal polyps in an Asian population. Allergy Asthma Immunol Res 12(1):42-55

  33. Hwang JW, Kim JH, Kim HJ, et al. (2019) Neutrophil extracellular traps in nasal secretions of patients with stable and exacerbated chronic rhinosinusitis and their contribution to induce chemokine secretion and strengthen the epithelial barrier. Clin Exp Allergy 49(10):1306-1320

  34. Arebro J, Ekstedt S, Hjalmarsson E, Winqvist O, Kumlien Georén S, Cardell LO (2017) A possible role for neutrophils in allergic rhinitis revealed. Sci Rep 7:43568

  35. Dong Z, Lin E, Wechsler ME, Weller PF, Klion AD, Bochnwer BS, et al (2020) Pulmonary Eosinophilic Granulomatosis with polyangiitis has IgG4 plasma cels and immunoregulatory features. Am J Pathol 190: 1438-1448

  36. Mukherjee M, Thomas SR, Radford K, Dvorkin-Gheva A, Davydchenko S, Kjarsgaard M et al (2019) Sputum antineutrophil cytoplasmic antibodies in serum antineutrophil cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis. Am J Respir Crit Care Med 2: 158-170

  37. Jennette JC, Falk RJ, Hu P, Xiao H (2013) Pathogenesis of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis. Annu Rev Pathol 8:139-60

  38. Lyons PA, Peters JE, Alberici F, Liley J, Coulson RMR, Astle W, et al (2019) Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status. Nat Commun 10(1):5120

  39. Brescia G, Schiavon F, Nicolè L, Zanoletti E, Zanotti C, Padoan R et al. (2019) No differences in nasal tissue inflammatory cells and adhesion molecules (iCAM-1 and vCAM-1) based on the comparison of EGPA with eosinophilic chronic sinusitis with polyposis. Am J Rhinol Allergy 33(4):395-402

  40. Boyle JV, Lam KK, Han JK (2020) Dupilumab in the treatment of chronic rhinosinusitis with nasal polyposis. Immunotherapy 12(2):111-121

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Acknowledgments

The authors thank Alison Garside for correcting the English version of this paper.

Funding

This study was partly supported by grant no. DOR2090593/20 (G. Marioni) from the University of Padova, Italy.

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Authors and Affiliations

Authors

Contributions

GC: conceptualization, investigation, writing – review and editing; GB: conceptualization, investigation, writing – review and editing, supervision ENT topics; LA: investigation, writing – review and editing, supervision pathological topics; UB: review and editing, supervision ENT topics; RP: review and editing, supervision rheumatologic topics; ACF: statistical analysis, writing – review and editing; FS: review and editing, supervision rheumatologic topics; GM: conceptualization, investigation, writing – review and editing, supervision ENT topics, funding acquisition.

Corresponding author

Correspondence to Gino Marioni.

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Ethics approval

The study was conducted in accordance with the principles of the Helsinki Declaration. Data were examined in agreement with the Italian privacy and sensitive data laws and internal rules of Padova University’s Otolaryngology section.

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

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Patients signed informed consent regarding publishing their data and photographs.

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N/A.

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Contro, G., Brescia, G., Alessandrini, L. et al. Neutrophil infiltrates and eosinophil aggregates in chronic rhinosinusitis with nasal polyps and EGPA. Clin Rheumatol 40, 1949–1957 (2021). https://doi.org/10.1007/s10067-020-05474-w

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  • DOI: https://doi.org/10.1007/s10067-020-05474-w

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