Comparative characteristics of different endotypes in chronic rhinosinusitis

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Abstract

Chronic rhinosinusitis (CRS) is the most common reason for consulting at the otolaryngologist. Although data on the prevalence of rhinosinusitis are inconsistent, the average global prevalence was 11.61±5.47%, ranging from 1.01% to a maximum of 57.6%. As based on the consensus document EPOS 2020 (European Position Paper on Rhinosinusitis and Nasal Polyposis), CRS is classified into polypous and polyp-free rhinosinusitis. Polypous rhinosinusitis is a special type characterized by inferior response to conservative therapy, and frequent relapses after surgical treatment. These serious medical and social issues are promoting the studies on pathogenesis and development of nasal polyps. This review provides information about immunological features and dysfunction leading to emergence of CRS with or without polyps. The purpose of this literature review is to evaluate the role of the first-line immune defense, congenital and acquired components of immunity in pathogenesis of polyposis versus nonpolypous CRS. The article provides a review of the research articles published worldwide. The authors conducted a search on the significance of immune response in development of CRS with and without polyps. We used appropriate keywords and filters in the PubMed and Google Scholar databases, in Scopus, Web of Science, MedLine, Cochrane Library, EMBASE, Global Health, and CyberLeninka databases. The detailed search has shown that all components of immune system do not fully perform their functions. E.g., the respiratory epithelium and mucociliary clearance present the first-line immune defense of nasal and sinus mucosa which form a mechanical barrier to infectious and other invading agents. At the next stage, the cells of innate immune response, along with complement system, take part in elimination of external pathogenic agents. Presentation of antigen epitopes to lymphocytes generates a specialized adaptive immune response. Tissue remodeling is among the most relevant aspects of the CRS pathogenesis. Production of periostin is found to be increased in polyposis rhinosinusitis, along with progressive tissue eosinophilia, higher production of cystatin SN, IL-25 and fibroblast contents, decreased TLR2, TLR4, TGF-β and collagen production as well as increased extracellular neutrophil traps and M1 macrophage levels. Further studies on the links in immune pathogenesis of CRS could allow us to develop a personalized algorithm for the diagnosis and treatment of such patients.

About the authors

Anna M. Lazareva

Research Institute of Medical Problems of the North, Krasnoyarsk Science Center, Siberian Branch, Russian Academy of Sciences

Author for correspondence.
Email: a.m.lazareva88@gmail.com
ORCID iD: 0000-0001-7972-3719

PhD (Medicine), Junior Researcher

Russian Federation, Krasnoyarsk

Olga V. Smirnova

Research Institute of Medical Problems of the North, Krasnoyarsk Science Center, Siberian Branch, Russian Academy of Sciences

Email: ovsmirnova71@mail.ru
ORCID iD: 0000-0003-3992-9207

PhD, MD (Medicine), Professor, Head, Laboratory of Molecular Cellular Pathophysiology

Russian Federation, Krasnoyarsk

References

  1. Bae C.H., Na H.G., Choi Y.S., Song S.Y., Kim Y.D. Clusterin Induces MUC5AC Expression via Activation of NF-kappaB in Human Airway Epithelial Cells. Clin. Exp. Otorhinolaryngol., 2018, Vol. 11, no. 2, pp. 124-132.
  2. Boita M., Bucca C., Riva G., Heffler E., Rolla G. Release of type 2 cytokines by epithelial cells of nasal polyps. J. Immunol. Res., 2016, Vol. 2016, 2643297. doi: 10.1155/2016/2643297.
  3. Boscke R., Vladar E.K., Konnecke M., Husing B., Linke R., Pries R., Reiling N., Axelrod J.D., Nayak J.V., Wollenberg B. Wnt Signaling in Chronic Rhinosinusitis with Nasal Polyps. Am. J. Respir Cell. Mol. Biol., 2017, Vol. 56, no. 5, pp. 575-584.
  4. Cho D.Y., Nayak J.V., Bravo D.T., Le W., Nguyen A., Edward J.A., Hwang P.H., Illek B., Fischer H. Expression of dual oxidases and secreted cytokines in chronic rhinosinusitis. Int. Forum Allergy Rhinol., 2013, Vol. 3, no. 5, pp. 376-383.
  5. Du K., Wang M., Zhang N., Yu P., Wang P., Li Y, Wang X., Zhang L., Bachert C. Involvement of the extracellular matrix proteins periostin and tenascin C in nasal polyp remodeling by regulating the expression of MMPs. Clin. Transl. Allergy., 2021, Vol. 11, no. 7, e12059. doi: 10.1002/clt2.12059.
  6. Ebenezer J.A., Christensen J.M., Oliver B.G., Oliver R.A., Tjin G., Ho J., Habib A.R., Rimmer J., Sacks R., Harvey R.J. Periostin as a marker of mucosal remodelling in chronic rhinosinusitis. Rhinology, 2017, Vol. 55, no. 3, pp. 234-241.
  7. Fokkens W.J., Lund V.J., Hopkins C., Hellings P.W., Kern R., Reitsma S., Toppila-Salmi S., Bernal-Sprekelsen M., Mullol J., Alobid I., Anselmo-Lima W.T., Bachert C., Baroody F., von Buchwald C., Cervin A., Cohen N., Constantinidis J., De Gabory L., Desrosiers M., Diamant Z., Douglas R.G., Gevaert P.H., Hafner A., Harvey R.J., Joos G.F., Kalogjera L., Knill A., Kocks J.H., Landis B.N., Limpens J., Lebeer S., Lourenco O., Meco C., Matricardi P.M., O'Mahony L., Philpott C.M., Ryan D., Schlosser R., Senior B., Smith T.L., Teeling T., Tomazic P.V., Wang D.Y., Wang D., Zhang L., Agius A.M., Ahlstrom-Emanuelsson C., Alabri R., Albu S., Alhabash S., Aleksic A., Aloulah M., Al-Qudah M., Alsaleh S., Baban M.A., Baudoin T., Balvers T., Battaglia P., Bedoya J.D., Beule A., Bofares K.M., Braverman I., Brozek-Madry E., Richard B., Callejas C., Carrie S., Caulley L., Chussi D., de Corso E., Coste A., El Hadi U., Elfarouk A., Eloy P.H., Farrokhi S., Felisati G., Ferrari M.D., Fishchuk R., Grayson W., Goncalves P.M., Grdinic B., Grgic V., Hamizan A.W., Heinichen J.V., Husain S., Ping T.I., Ivaska J., Jakimovska F., Jovancevic L., Kakande E., Kamel R., Karpischenko S., Kariyawasam H.H., Kawauchi H., Kjeldsen A., Klimek L., Krzeski A., Kopacheva Barsova G., Kim S.W., Lal D., Letort J.J., Lopatin A., Mahdjoubi A., Mesbahi A., Netkovski J., Tshipukane D.N., Obando-Valverde A., Okano M., Onerci M., Ong Y.K., Orlandi R., Otori N., Ouennoughy K., Ozkan M., Peric A., Plzak J., Prokopakis E., Prepageran N., Psaltis A., Pugin B., Raftopulos M., Rombaux P., Riechelmann H., Sahtout S., Sarafoleanu C. C., Searyoh K., Rhee C.-S., Shi J., Shkoukani M., Shukuryan A.K., Sicak M., Smyth D., Sindvongs K., Kosak T.S., Stjarne P., Sutikno B., Steinsvag S., Tantilipikorn P., Thanaviratananich S., Tran T., Urbancic J., Valiulius A., de Aparicio C.V., Vicheva D., Virkkula P.M., Vicente G., Voegels R., Wagenmann M.M., Wardani R.S., Welge-Lussen A., Witterick I., Wright E., Zabolotniy D., Zsolt B., Zwetsloot C.P. European position paper on rhinosinusitis and nasal polyps. Rhinology, 2020, Vol. 58, no. S9, pp. 1-464.
  8. Ito T., Ikeda S., Asamori T., Honda K., Kawashima Y., Kitamura K., Suzuki K., Tsutsumi T. Increased expression of pendrin in eosinophilic chronic rhinosinusitis with nasal polyps. Braz. J. Otorhinolaryngol., 2019, Vol. 85, no. 6, pp. 760-765.
  9. Jiao J., Duan S., Meng N., Li Y., Fan E., Zhang L. Role of IFN-gamma, IL-13, and IL-17 on mucociliary differentiation of nasal epithelial cells in chronic rhinosinusitis with nasal polyps. Clin. Exp. Allergy., 2016, Vol. 46, no. 3, pp. 449-460.
  10. Johnston L.K., Bryce P.J. Understanding interleukin 33 and its roles in eosinophil development. Front. Med., 2017, no. 4, 51. doi: 10.3389/fmed.2017.00051.
  11. Kaneko Y., Kohno T., Kakuki T., Takano K.I., Ogasawara N., Miyata R., Kikuchi S., Konno T., Ohkuni T., Yajima R., Kakiuchi A., Yokota S.-I., Himi T., Kojima T. The role of transcriptional factor p63 in regulation of epithelial barrier and ciliogenesis of human nasal epithelial cells. Sci. Rep., 2017, Vol. 7, no. 1, 10935. doi: 10.1038/s41598-017-11481-w.
  12. Kao S.S., Bassiouni A., Ramezanpour M., Finnie J., Chegeni N., Colella A.D., Chataway T.K., Wormald P.J., Vreugde S., Psaltis .AJ. Proteomic analysis of nasal mucus samples of healthy patients and patients with chronic rhinosinusitis. J. Allergy Clin. Immunol., 2021, Vol. 147, no. 1, pp. 168-178.
  13. Kato A., Peters A.T., Stevens W.W., Schleimer R.P., Tan B.K., Kern R.C. Endotypes of chronic rhinosinusitis: Relationships to disease phenotypes, pathogenesis, clinical findings, and treatment approaches. Allergy, 2022, Vol. 77, no. 3, pp. 812-826.
  14. Kato K., Chang E.H., Chen Y., Lu W., Kim M.M., Niihori M., Hecker L., Kim K.C. MUC1 contributes to goblet cell metaplasia and MUC5AC expression in response to cigarette smoke in vivo. Am. J. Physiol. Lung Cell. Mol. Physiol., 2020, Vol. 319, no. 1, pp. 82-90.
  15. Kim D.K., Jin H.R., Eun K.M., Mo J.H., Cho S.H., Oh S., Cho D., Kim D.W. The role of interleukin-33 in chronic rhinosinusitis. Thorax, 2017, Vol. 72, no. 7, pp. 635-645.
  16. Klingler A.I., Stevens W.W., Tan B.K., Peters A.T., Poposki J.A., Grammer L.C., Welch K.C., Smith S.S., Conley D.B., Kern R.C., Schleimer R.P., Kato A. Mechanisms and biomarkers of inflammatory endotypes in chronic rhinosinusitis without nasal polyps. J. Allergy Clin. Immunol., 2021, Vol. 147, no. 4, pp. 1306-1317.
  17. Liao B., Cao P.P., Zeng M., Zhen Z., Wang H., Zhang Y.-N., Hu C.-Y., Ma J., Li Z.-Y., Song J., Liu J.-X., Peng L.-Y., Liu Y., Ning Q., Liu Z. Interaction of thymic stromal lymphopoietin, IL-33, and their receptors in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps. Allergy, 2015, Vol. 70, no. 9, pp. 1169-1180.
  18. Meng J., Zhou P., Liu Y., Liu F., Yi X., Liu S., Holtappels G., Bachert C., Zhang N. The Development of nasal polyp disease involves early nasal mucosal inflammation and remodelling. PLoS ONE, 2013, Vol. 8, no. 12, e82373. doi: 10.1371/journal.pone.0082373.
  19. Mueller S.K., Wendler O., Nocera A., Grundtner P., Schlegel P., Agaimy A., Iro H., Bleier B.S. Escalation in mucus cystatin 2, pappalysin-A, and periostin levels over time predict need for recurrent surgery in chronic rhinosinusitis with nasal polyps. Int. Forum Allergy Rhinol., 2019, Vol. 9, no. 10, pp. 1212-1219.
  20. Nagarkar D.R., Poposki J.A., Tan B.K., Comeau M.R., Peters A.T., Hulse K.E., Suh L.A., Norton J., Harris K.E., Grammer L.C., Chandra R.K., Conley D.B., Kern R.C., Schleimer R.P., Kato A. Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis. J. Allergy Clin. Immunol., 2013, Vol. 132, no. 3, pp. 593-600.e12.
  21. Park S.K., Jin Y.D., Park Y.K., Yeon S.H., Xu J., Han R.N., Rha K.S. IL-25-induced activation of nasal fibroblast and its association with the remodeling of chronic rhinosinusitis with nasal polyposis. PLoS ONE, 2017, Vol. 12, no. 8, e0181806. doi: 10.1371/journal.pone.0181806.
  22. Shin H.W., Kim D.K., Park M.H., Eun K.M., Lee M., So D., Kong I.G., Mo J.-H., Yang M.-S., Jin H.R., Park J.W., Kim D.W. IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis. J. Allergy Clin. Immunol., 2015, Vol. 135, no. 6, pp. 1476-1485.e7.
  23. Soler Z.M., Yoo F., Schlosser R.J., Mulligan J., Ramakrishnan V.R., Beswick D.M., Alt J.A., Mattos J.L., Payne S.C., Storck K.A., Smith T.L. Correlation of mucus inflammatory proteins and olfaction in chronic rhinosinusitis. Int. Forum Allergy Rhinol., 2020, Vol. 10, no. 3, pp. 343-355.
  24. Soyka M.B., Wawrzyniak P., Eiwegger T., Holzmann D., Treis A., Wanke K., Kast J.I., Akdis C.A. Defective epithelial barrier in chronic rhinosinusitis: The regulation of tight junctions by IFN-gamma and IL-4. J. Allergy Clin. Immunol., 2012, Vol. 130, no. 5, pp. 1087-1096.e10.
  25. Wise S.K., Laury A.M., Katz E.H., Den Beste K.A., Parkos C.A., Nusrat A. Interleukin-4 and interleukin-13 compromise the sinonasal epithelial barrier and perturb intercellular junction protein expression. Int. Forum Allergy Rhinol., 2014, Vol. 4, no. 5, pp. 361-370.
  26. Wu D., Yan B., Wang Y., Wang C., Zhang L. Prognostic and pharmacologic value of cystatin SN for chronic rhinosinusitis with nasal polyps. J. Allergy Clin. Immunol., 2021, Vol. 148, no. 2, pp. 450-460.
  27. Xu X., Luo S., Li B., Dai H., Zhang J. IL-25 contributes to lung fibrosis by directly acting on alveolar epithelial cells and fibroblasts. Exp. Biol. Med., 2019, Vol. 244, no. 9, pp. 770-780.
  28. Yan B., Lou H., Wang Y., Li Y., Meng Y., Qi S., Wang M., Xiao L., Wang C., Zhang L. Epithelium-derived cystatin SN enhances eosinophil activation and infiltration through IL-5 in patients with chronic rhinosinusitis with nasal polyps. J. Allergy Clin. Immunol., 2019, Vol. 144, no. 2, pp. 455-469.

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