Features of inflammatory endotypes and phenotypes in chronic rhinosinusitis

Chufistova A.V.; Shabaldina E.V.; Bedareva A.V.; Vakhrameev I.N.; Abramova N.A.; Shabaldin A.V.

doi:https://doi.org/10.17116/otorino20248904160

Close metadata

Recommended articles:

A Randomized Controlled Trial Comparing Budesonide and Mometasone Furoate Nasal Spray in the Treatment of Chronic Rhinosinusitis with Nasal Polyposis: Evaluating Symptom Scores and Quality of Life. Russian Rhinology. 2025;(1):12-17

Study of serum cytokine concentration in primary patients with gastric cancer. P.A. Herzen Journal of Oncology. 2025;(2):25-29

Cytokine status of patients with Alzheimer’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(4-2):5-12

Serum cytokines in patients with brain tumor undergoing uncomplicated and complicated postoperative period. Russian Journal of Anesthesiology and Reanimatology. 2025;(4):21-30

Influence of age and sex on values of SNOT-22 sinonasal test domains in children and adolescents with bronchial asthma. Russian Rhinology. 2025;(3):197-204

Sinonasal pathology in patients with primary ciliary dyskinesia. Russian Rhinology. 2025;(3):223-232

Search for informative predictors of the development and progression of multiple sclerosis. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(9):124-130

Optimization of chronic rhinosinusitis diagnosis using artificial intelligence. Russian Rhinology. 2025;(4):38-43

Molecular diagnostic biomarkers of subretinal fluid in assessing the severity and prognosis of rhegmatogenous retinal detachment. Russian Annals of Ophthalmology. 2025;(6):119-126

Abstract:

Recently, significant progress has been made in identifying the cellular and molecular mechanisms responsible for the pathogenesis of chronic rhinosinusitis (CRS). Cohort studies of CRS have led to advances in the clinical understanding of this disease. New therapeutic agents have been approved or are undergoing clinical trials to expand treatment options for this disease. One of the promising areas in medicine is the provision of personalized clinical care. From this perspective, CRS can be divided into three different endotypes depending on the type of underlying inflammatory response. In the United States, CRS with and without nasal polyps is predominantly characterized as the second inflammatory endotype. CRS with nasal polyps (about 17%) and without nasal polyps (up to 20%) belongs to the 1st and 3rd inflammatory endotypes, respectively. And if for the second inflammatory endotype the effectiveness of targeted biological therapy is beyond doubt, then for the first and third inflammatory endotypes the principles of such conservative therapy are under active development. Moreover, large validated studies to confirm associations between CRS phenotypes and endotypes, as well as to find effective biological markers of inflammatory endotypes, remain to be performed.

Keywords:

chronic rhinosinusitis

inflammatory endotypes

interleukins

Authors:

Chufistova A.V.

Kemerovo State Medical University

ORCID: 0000-0003-4714-328X

Shabaldina E.V.

Kemerovo State Medical University

ORCID: 0000-0002-0450-2767

Bedareva A.V.

Kemerovo State University

ORCID: 0000-0002-6068-5473

Vakhrameev I.N.

Podgorbunsky Kuzbass Clinical Hospital of Emergency Medical Care

ORCID: 0009-0004-6590-8252

Abramova N.A.

Belyaev Kuzbass Regional Clinical Hospital

ORCID: 0000-0001-9134-8309

Shabaldin A.V.

Kemerovo State Medical University;
Kemerovo State University

ORCID: 0000-0002-8785-7896

Received:

23.01.2024

Accepted:

30.05.2024

Close metadata

References:

Dietz de Loos D, Lourijsen ES, Wildeman MAM, Freling NJM, Wolvers MDJ, Reitsma S, Fokkens WJ. Prevalence of chronic rhinosinusitis in the general population based on sinus radiology and symptomatology. Journal Allergy Clinical Immunology. 2019;143(3):1207-1214. https://doi.org/10.1016/j.jaci.2018.12.986
Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang de Y, Wormald PJ. European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Rhinology Supplement. 2012;23:3-298.
Mattos JL, Rudmik L, Schlosser RJ, Smith TL, Mace JC, Alt J, Soler ZM. Symptom importance, patient expectations, and satisfaction in chronic rhinosinusitis. International Forum of Allergy and Rhinology. 2019;9(6):593-600. https://doi.org/10.1002/alr.22309
Rudmik L, Smith TL, Schlosser RJ, Hwang PH, Mace JC, Soler ZM. Productivity costs in patients with refractory chronic rhinosinusitis. Laryngoscope. 2014;124(9):2007-2012. https://doi.org/10.1002/lary.24630
Rudmik L. Economics of chronic rhinosinusitis. Current Allergy and Asthma Reports. 2017;17(4):20. https://doi.org/10.1007/s11882-017-0690-5
Bhattacharyya N, Villeneuve S, Joish VN, Amand C, Mannent L, Amin N, Rowe P, Maroni J, Eckert L, Yang T, Khan A. Cost burden and resource utilization in patients with chronic rhinosinusitis and nasal polyps. Laryngoscope. 2019;129(9):1969-1975. https://doi.org/10.1002/lary.27852
Hamilos DL. Chronic rhinosinusitis in patients with cystic fibrosis. Journal of Allergy and Clinical Immunology. In Practice. 2016; 4(4):605e612. https://doi.org/10.1016/j.jaip.2016.04.013
Tyler MA, Luong AU. Current understanding of allergic fungal rhinosinusitis. World Journal of Otorhinolaryngology — Head and Neck Surgery. 2018;4(3):179-185. https://doi.org/10.1016/j.wjorl.2018.08.003
Laidlaw TM. Clinical updates in aspirin-exacerbated respiratory disease. Allergy and Asthma Proceedings. 2019;40(1):4e6. https://doi.org/10.2500/aap.2019.40.4188
White AA, Stevenson DD. Aspirin-exacerbated respiratory disease. New England Journal of Medicine. 2018;379(11):1060-1070. https://doi.org/10.1056/NEJMra1712125
Benjamin MR, Stevens WW, Li N, Bose S, Grammer LC, Kern RC, Tan BK, Conley DB, Smith SS, Welch KC, Schleimer RP, Peters AT. Clinical characteristics of patients with chronic rhinosinusitis without nasal polyps in an academic setting. Journal of Allergy and Clinical Immunology. In Practice. 2019;7(3):1010-1016. https://doi.org/10.1016/j.jaip.2018.10.014
Bachert C, Han JK, Desrosiers M, Hellings PW, Amin N, Lee SE, Mullol J, Greos LS, Bosso JV, Laidlaw TM, Cervin AU, Maspero JF, Hopkins C, Olze H, Canonica GW, Paggiaro P, Cho SH, Fokkens WJ, Fujieda S, Zhang M, Lu X, Fan C, Draikiwicz S, Kamat SA, Khan A, Pirozzi G, Patel N, Graham NMH, Ruddy M, Staudinger H, Weinreich D, Stahl N, Yancopoulos GD, Mannent LP. 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):1638-16504. https://doi.org/10.1016/S0140-6736(19)31881-1
Bachert C, Sousa AR, Lund VJ, Scadding GK, Gevaert P, Nasser S, Durham SR, Cornet ME, Kariyawasam HH, Gilbert J, Austin D, Maxwell AC, Marshall RP, Fokkens WJ. Reduced need for surgery in severe nasal polyposis with mepolizumab: randomized trial. Journal of Allergy and Clinical Immunology. 2017;140(4):1024-1031e14. https://doi.org/10.1016/j.jaci.2017.05.044
Gevaert P, Calus L, Van Zele T, Blomme K, De Ruyck N, Bauters W, Hellings P, Brusselle G, De Bacquer D, van Cauwenberge P, Bachert C. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. Journal of Allergy and Clinical Immunology. 2013;131(1):110-116e1. https://doi.org/10.1016/j.jaci.2012.07.047
Gevaert P, Bachert C, Corren J, Mullol J, Han JK, Ow R, Islam L, Howard M, Owen R, Wong K, Kaufman D, Omachi T. Omalizumab efficacy and safety in nasal polyposis: results from two parallel double-blind placebo-controlled trials. Annals of Allergy, Asthma and Immunology. 2019;123(suppl):1-168. https://doi.org/10.1016/j.anai.2019.08.077
Pawlak M, Ho AW, Kuchroo VK. Cytokines and transcription factors in the differentiation of CD4+ T helper cell subsets and induction of tissue inflammation and autoimmunity. Current Opinion in Immunology. 2020;67:57-67. https://doi.org/10.1016/j.coi.2020.09.001
Fang D, Zhu J. Molecular switches for regulating the differentiation of inflammatory and IL-10-producing anti-inflammatory T-helper cells. Cellular and Molecular Life Sciences. 2020;77(2):289-303. Epub 2019 Aug 20. PMID: 31432236; PMCID: PMC11105075. https://doi.org/10.1007/s00018-019-03277-0
Immunoterapiya v praktike LOR-vracha i terapevta. Simbirtsev AS, Lavrenova GV, eds. 2-e izdanie. SPb: Dialog; 2022. (In Russ.).
Berghi NO, Dumitru M, Vrinceanu D, Ciuluvica RC, Simioniuc-Petrescu A, Caragheorgheopol R, Tucureanu C, Cornateanu RS, Giurcaneanu C. Relationship between chemokines and T lymphocytes in the context of respiratory allergies. Experimental and Therapeutic Medicine. 2020;20(3):2352-2360. https://doi.org/10.3892/etm.2020.8961
Gause WC, Rothlin C, Loke P. Heterogeneity in the initiation, development and function of type 2 immunity. Nature Reviews Immunology. 2020;20(10):603-614. https://doi.org/10.1038/s41577-020-0301-x
Cosmi L, Liotta F, Annunziato F. Th17 regulating lower airway disease. Current Opinion in Allergy and Clinical Immunology. 2016; 16(1):1-6. https://doi.org/10.1097/ACI.0000000000000227
Staudacher AG, Peters AT, Kato A, Stevens WW. Use of endotypes, phenotypes, and inflammatory markers to guide treatment decisions in chronic rhinosinusitis. Annals of Allergy, Asthma and Immunology. 2020;124(4):318-325. https://doi.org/10.1016/j.anai.2020.01.013
Bankova LG, Barrett NA. Epithelial cell function and remodeling in nasal polyposis. Annals of Allergy, Asthma and Immunology. 2020;124(4):333-341. https://doi.org/10.1016/j.anai.2020.01.018
Wang X, Sima Y, Zhao Y, Zhang N, Zheng M, Du K, Wang M, Wang Y, Hao Y, Li Y, Liu M, Piao Y, Liu C, Tomassen P, Zhang L, Bachert C. Endotypes of chronic rhinosinusitis based on inflammatory and remodeling factors. Journal of Allergy and Clinical Immunology. 2023;151(2):458-468. https://doi.org/10.1016/j.jaci.2022.10.010
Kato A, Peters AT, Stevens WW, Schleimer RP, Tan BK, Kern RC. Endotypes of chronic rhinosinusitis: relationships to disease phenotypes, pathogenesis, clinical findings, and treatment approaches. Allergy. 2022;77(3):812-826. https://doi.org/10.1111/all.15074
Pinu FR, Beale DJ, Paten AM, Kouremenos K, Swarup S, Schirra HJ, Wishart D. Systems biology and multi-omics integration: viewpoints from the metabolomics research community. Metabolites. 2019;9(4):76. https://doi.org/10.3390/metabo9040076
Veenstra TD. Omics in systems biology: current progress and future outlook. Proteomics. 2021;21(3-4):e2000235. https://doi.org/10.1002/pmic.202000235
Michalik M, Samet A, Dmowska-Koroblewska A, Podbielska-Kubera A, Waszczuk-Jankowska M, Struck-Lewicka W, Markuszewski MJ. An overview of the application of systems biology in an understanding of chronic rhinosinusitis (crs) development. Journal of Personalized Medicine. 2020;10(4):245. https://doi.org/10.3390/jpm10040245
Kao SS, Bassiouni A, Ramezanpour M, Chegeni N, Colella AD, Chataway TK, Wormald PJ, Vreugde S, Psaltis AJ. Scoping review of chronic rhinosinusitis proteomics. Rhinology. 2020;58(5):418-429. https://doi.org/10.4193/Rhin20.034
Kao SS, Bassiouni A, Ramezanpour M, Finnie J, Chegeni N, Colella AD, Chataway TK, Wormald PJ, Vreugde S, Psaltis AJ. Proteomic analysis of nasal mucus samples of healthy patients and patients with chronic rhinosinusitis. Journal of Allergy and Clinical Immunology. 2021;147(1):168-178. https://doi.org/10.1016/j.jaci.2020.06.037
Fazlollahi F, Kongmanas K, Tanphaichitr N, Mallen-St Clair J, Gopen Q, Faull KF, Suh JD. Lipidomic profiling of sinus mucosa from patients with chronic rhinosinusitis. Clinical and Translational Science. 2015;8(2):107-115. https://doi.org/10.1111/cts.12256
Miyata J, Fukunaga K, Kawashima Y, Watanabe T, Saitoh A, Hirosaki T, Araki Y, Kikawada T, Betsuyaku T, Ohara O, Arita M. Dysregulated fatty acid metabolism in nasal polyp-derived eosinophils from patients with chronic rhinosinusitis. Allergy. 2019;74(6):1113-1124. https://doi.org/10.1111/all.13726
Laidlaw TM, Mullol J, Woessner KM, Amin N, Mannent LP. Chronic rhinosinusitis with nasal polyps and asthma. The Journal of Allergy and Clinical Immunology. In Practice. 2021;9(3):1133-1141. https://doi.org/10.1016/j.jaip.2020.09.063
Turovskij AB. Chronic sinusitis. New possibilities of drug therapy. Poliklinika. 2013;2-1:66-68. (In Russ.).
Rumyantsev AG, Maschan AA, Shcherbina AYu. Federal’nye klinicheskie rekomendatsii po diagnostike i lecheniyu detej s tyazheloj kombinirovannoj immunnoj nedostatochnost’yu. Obshchestvennaya organizatsiya Natsional’noe obshchestvo detskikh gematologov, onkologov; FGBU «FNKTs DGOI im. Dmitriya Rogacheva» Minzdrava Rossii. M. 2015. (In Russ.). Accessed June 27, 2024. https://nodgo.org/sites/default/files/27%20%28%D0%93%29%D0%A2%D0%9A%D0%98%D0%9D.pdf
Hua HL, Deng YQ, Huang H, Tang YC, Han JB, Li F, Wang Y, Tao ZZ. Inflammatory endotypes of adenoidal hypertrophy based on a cluster analysis of biomarkers. International Immunopharmacology. 2024;127:111318. https://doi.org/10.1016/j.intimp.2023.111318
Stevens WW, Ocampo CJ, Berdnikovs S, Sakashita M, Mahdavinia M, Suh L, Takabayashi T, Norton JE, Hulse KE, Conley DB, Chandra RK, Tan BK, Peters AT, Grammer LC 3rd, Kato A, Harris KE, Carter RG, Fujieda S, Kern RC, Schleimer RP. Cytokines in chronic rhinosinusitis. role in eosinophilia and aspirin-exacerbated respiratory disease. American Journal of Respiratory Critical Care Medicine. 2015;192(6):682-694. https://doi.org/10.1164/rccm.201412-2278OC
Van Zele T, Claeys S, Gevaert P, Van Maele G, Holtappels G, Van Cauwenberge P, Bachert C. Differentiation of chronic sinus diseases by measurement of inflammatory mediators. Allergy. 2006;61(11):1280-1289. https://doi.org/10.1111/j.1398-9995.2006.01225.x
Perez-Novo CA, Watelet JB, Claeys C, Van Cauwenberge P, Bachert C. Prostaglandin, leukotriene, and lipoxin balance in chronic rhinosinusitis with and without nasal polyposis. Journal of Allergy and Clinical Immunology. 2005;115(6):1189-1196. https://doi.org/10.1016/j.jaci.2005.02.029
Tomassen P, Vandeplas G, Van Zele T, Cardell LO, Arebro J, Olze H, Förster-Ruhrmann U, Kowalski ML, Olszewska-Ziąber A, Holtappels G, De Ruyck N, Wang X, Van Drunen C, Mullol J, Hellings P, Hox V, Toskala E, Scadding G, Lund V, Zhang L, Fokkens W, Bachert C. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. Journal of Allergy and Clinical Immunology. 2016;137(5):1449-1456.e4. https://doi.org/10.1016/j.jaci.2015.12.1324
Tan BK, Klingler AI, Poposki JA, Stevens WW, Peters AT, Suh LA, Norton J, Carter RG, Hulse KE, Harris KE, Grammer LC, Schleimer RP, Welch KC, Smith SS, Conley DB, Kern RC, Kato A. Heterogeneous inflammatory patterns in chronic rhinosinusitis without nasal polyps in Chicago, Illinois. Journal of Allergy and Clinical Immunology. 2017;139(2):699-703.e7. Epub 2016 Sept 14. PMID: 27639939; PMCID: PMC5303134. https://doi.org/10.1016/j.jaci.2016.06.063
Stevens WW, Peters AT, Tan BK, Klingler AI, Poposki JA, Hulse KE, Grammer LC, Welch KC, Smith SS, Conley DB, Kern RC, Schleimer RP, Kato A. Associations between inflammatory endotypes and clinical presentations in chronic rhinosinusitis. Journal of Allergy and Clinical Immunology. In Practice. 2019;7(8):2812-2820.e3. https://doi.org/10.1016/j.jaip.2019.05.009
Wang X, Zhang N, Bo M, Holtappels G, Zheng M, Lou H, Wang H, Zhang L, Bachert C. Diversity of TH cytokine profiles in patients with chronic rhinosinusitis: a multicenter study in Europe, Asia, and Oceania. Journal of Allergy and Clinical Immunology. 2016;138(5):1344-1353. https://doi.org/10.1016/j.jaci.2016.05.041
Zhang Y, Gevaert E, Lou H, Wang X, Zhang L, Bachert C, Zhang N. Chronic rhinosinusitis in Asia. Journal of Allergy and Clinical Immunology. 2017;140(5):1230-1239. https://doi.org/10.1016/j.jaci.2017.09.009
Pearlman AN, Chandra RK, Chang D, Conley DB, Tripathi-Peters A, Grammer LC, Schleimer RT, Kern RC. Relationships between severity of chronic rhinosinusitis and nasal polyposis, asthma, and atopy. American Journal of Rhinology and Allergy. 2009;23(2):145-148. https://doi.org/10.2500/ajra.2009.23.3284
Promsopa C, Kansara S, Citardi MJ, Fakhri S, Porter P, Luong A. Prevalence of confirmed asthma varies in chronic rhinosinusitis subtypes. International Forum of Allergy and Rhinology. 2016;6(4):373-377. https://doi.org/10.1002/alr.21674
Lin DC, Chandra RK, Tan BK, Zirkle W, Conley DB, Grammer LC, Kern RC, Schleimer RP, Peters AT. Association between severity of asthma and degree of chronic rhinosinusitis. American Journal of Rhinology and Allergy. 2011;25(4):205-208. https://doi.org/10.2500/ajra.2011.25.3613
Håkansson K, Bachert C, Konge L, Thomsen SF, Pedersen AE, Poulsen SS, Martin-Bertelsen T, Winther O, Backer V, von Buchwald C. Airway inflammation in chronic rhinosinusitis with nasal polyps and asthma: the united airways concept further supported. PLoS One. 2015;10(7):e0127228. https://doi.org/10.1371/journal.pone.0127228
Pal’chun VT, Karalkin AV, Petukhova PV. Assessment of mucociliary clearance of the maxillary sinus mucosa by radioisotope dynamic maxillary scintigraphy in various forms of sinusitis. Russian Bulletin of Otorhinolaryngology. 2004;4:4-6. (In Russ.).
Kowski R, Bouchoua F, Coffi net L, Vignaud JM. Clinical factors influencing the eosinophil infiltration of nasal polyps. Rhinology. 2002;40(4):173-178. https://pubmed.ncbi.nlm.nih.gov/12526243/
Hunsaker DH, Leid JG. The relationship of biofilms to chronic rhinosinusitis. Current Opinion in Otolaryngology and Head and Neck Surgery. 2008;16(3):237-241. https://doi.org/10.1097/MOO.0b013e3282fdc6d5
Savlevich EL, Mitrofanova ES, Kurbacheva OM, Dyneva ME, Shilovsky IP, Egorov VI, Pshennikov DS, Khaitov MR. The role of metalloproteinases in remodeling of the sinus mucosa in chronic rhinosinusitis. Immunologiya. 2023;44(3):379-390. (In Russ.). https://doi.org/10.33029/1816-2134-2023-44-3-379-390
Khronicheskij rinosinusit: patogenez, diagnostika i printsipy lecheniya (klinicheskie rekomendacii). Lopatin AS, ed. M. 2014. (In Russ.). Accessed June 27, 2024. https://rumedo.ru/uploads/sites/2/2018/09/chronsinus_14-1.pdf
Laidlaw TM, Buchheit KM. Biologics in chronic rhinosinusitis with nasal polyposis. Annals of Allergy, Asthma and Immunology. 2020;124(4),326-332. https://doi.org/10.1016/j.anai.2019.12.001