{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T02:02:01Z","timestamp":1780711321783,"version":"3.54.1"},"reference-count":55,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2018,12,7]],"date-time":"2018-12-07T00:00:00Z","timestamp":1544140800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["L30AI113795"],"award-info":[{"award-number":["L30AI113795"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000445"],"award-info":[{"award-number":["UL1TR000445"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute of Deafness and Communication Disorders","doi-asserted-by":"publisher","award":["RO3DC014809"],"award-info":[{"award-number":["RO3DC014809"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease with an as-yet-undefined etiology. The management of CRS has historically been phenotypically driven, and the presence or absence of nasal polyps has frequently guided diagnosis, prognosis, and treatment algorithms. Research over the last decade has begun to question the role of this distinction in disease management, and renewed attention has been placed on molecular and cellular endotyping and a more personalized approach to care. Current research exploring immunologic mechanisms, inflammatory endotypes, and molecular biomarkers has the potential to more effectively delineate distinct and clinically relevant subgroups of CRS. The focus of this review will be to discuss and summarize the endotypic characterization of CRS and the potential diagnostic and therapeutic implications of this approach to disease management.<\/ns4:p>","DOI":"10.12688\/f1000research.16222.1","type":"journal-article","created":{"date-parts":[[2018,12,7]],"date-time":"2018-12-07T10:30:07Z","timestamp":1544178607000},"page":"1909","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Recent advances in understanding chronic rhinosinusitis endotypes"],"prefix":"10.12688","volume":"7","author":[{"given":"Eric F.","family":"Succar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5501-9900","authenticated-orcid":false,"given":"Justin H.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2018,12,7]]},"reference":[{"key":"ref-1","first-page":"1-161","article-title":"Summary health statistics for U.S. adults: national health interview survey, 2012.","author":"D Blackwell","year":"2014","journal-title":"Vital Health Stat 10."},{"key":"ref-2","first-page":"1-218","article-title":"Summary health statistics for u.s. 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Ba","year":"2011","journal-title":"Allergy."},{"key":"ref-13","first-page":"554-61","article-title":"Antimicrobial peptides in nasal secretion and mucosa with respect to Staphylococcus aureus colonization in chronic rhinosinusitis with nasal polyps.","volume":"49","author":"M Thienhaus","year":"2011","journal-title":"Rhinology."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"1087-1096.e10","DOI":"10.1016\/j.jaci.2012.05.052","article-title":"Defective epithelial barrier in chronic rhinosinusitis: the regulation of tight junctions by IFN-\u03b3 and IL-4.","volume":"130","author":"M Soyka","year":"2012","journal-title":"J Allergy Clin Immunol."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"74-80.e1-8","DOI":"10.1016\/j.jaci.2009.04.019","article-title":"Dual nature of T cell-epithelium interaction in chronic rhinosinusitis.","volume":"124","author":"T Basinski","year":"2009","journal-title":"J Allergy Clin 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Zhang","year":"2011","journal-title":"Allergy."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"607-14","DOI":"10.1067\/mai.2001.112374","article-title":"Total and specific IgE in nasal polyps is related to local eosinophilic inflammation.","volume":"107","author":"C Bachert","year":"2001","journal-title":"J Allergy Clin Immunol."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"230-5","DOI":"10.1007\/s11882-011-0181-z","article-title":"The Role of IgE Production in the Pathophysiology of Rhinitis and Rhinosinusitis.","volume":"11","author":"E Hoddeson","year":"2011","journal-title":"Curr Allergy Asthma Rep."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"412","DOI":"10.12688\/f1000research.13170.1","article-title":"Recent advances in biologic therapy of asthma and the role in therapy of chronic rhinosinusitis [version 1; referees: 2 approved].","volume":"7","author":"R Divekar","year":"2018","journal-title":"F1000Res."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"1966-1978.e9","DOI":"10.1016\/j.jaci.2016.10.039","article-title":"Neutrophils are a major source of the epithelial barrier disrupting cytokine oncostatin M in patients with mucosal airways disease.","volume":"139","author":"K Pothoven","year":"2017","journal-title":"J Allergy Clin Immunol."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"1646-58","DOI":"10.1016\/j.jaci.2017.12.972","article-title":"The activation and function of IL-36\u03b3 in neutrophilic inflammation in chronic rhinosinusitis.","volume":"141","author":"H Wang","year":"2018","journal-title":"J Allergy Clin Immunol."},{"key":"ref-30","doi-asserted-by":"publisher","first-page":"1280-9","DOI":"10.1111\/j.1398-9995.2006.01225.x","article-title":"Differentiation of chronic sinus diseases by measurement of inflammatory mediators.","volume":"61","author":"T van 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Immunol."},{"key":"ref-34","doi-asserted-by":"publisher","first-page":"682-94","DOI":"10.1164\/rccm.201412-2278OC","article-title":"Cytokines in Chronic Rhinosinusitis. Role in Eosinophilia and Aspirin-exacerbated Respiratory Disease.","volume":"192","author":"W Stevens","year":"2015","journal-title":"Am J Respir Crit Care Med."},{"key":"ref-35","doi-asserted-by":"publisher","first-page":"130-4","DOI":"10.1002\/lio2.32","article-title":"A Review of Classification Schemes for Chronic Rhinosinusitis with Nasal Polyposis Endotypes.","volume":"1","author":"S Dennis","year":"2016","journal-title":"Laryngoscope Investig Otolaryngol."},{"key":"ref-36","doi-asserted-by":"publisher","first-page":"396-400","DOI":"10.2500\/ajra.2009.23.3334","article-title":"Efficacy of targeted medical therapy in chronic rhinosinusitis, and predictors of failure.","volume":"23","author":"D Lal","year":"2009","journal-title":"Am J Rhinol Allergy."},{"key":"ref-37","doi-asserted-by":"publisher","first-page":"1543-51","DOI":"10.1016\/j.jaci.2018.03.004","article-title":"Endotype-driven care pathways in patients with chronic rhinosinusitis.","volume":"141","author":"C Bachert","year":"2018","journal-title":"J Allergy Clin Immunol."},{"key":"ref-38","doi-asserted-by":"publisher","first-page":"359-74","DOI":"10.1111\/ppl.12117","article-title":"Bacteria isolated from roots and rhizosphere of Vitis vinifera retard water losses, induce abscisic acid accumulation and synthesis of defense-related terpenes in in vitro cultured grapevine.","volume":"151","author":"M Salomon","year":"2014","journal-title":"Physiol Plant."},{"key":"ref-39","doi-asserted-by":"publisher","first-page":"61-75","DOI":"10.1016\/j.jaci.2015.11.020","article-title":"Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3-like protein 1.","volume":"138","author":"T Hinks","year":"2016","journal-title":"J Allergy Clin Immunol."},{"key":"ref-40","doi-asserted-by":"publisher","first-page":"710-9","DOI":"10.1016\/j.jaci.2016.11.038","article-title":"Identification of airway mucosal type 2 inflammation by using clinical biomarkers in asthmatic patients.","volume":"140","author":"P Silkoff","year":"2017","journal-title":"J Allergy Clin Immunol."},{"key":"ref-41","doi-asserted-by":"publisher","first-page":"388-94","DOI":"10.1016\/j.jaci.2013.07.036","article-title":"Measures of gene expression in sputum cells can identify TH2-high and TH2-low subtypes of asthma.","volume":"133","author":"M Peters","year":"2014","journal-title":"J Allergy Clin Immunol."},{"key":"ref-42","doi-asserted-by":"publisher","first-page":"1390-1397.e6","DOI":"10.1016\/j.jaci.2015.09.058","article-title":"Gene expression profiling of asthma phenotypes demonstrates molecular signatures of atopy and asthma control.","volume":"137","author":"J Howrylak","year":"2016","journal-title":"J Allergy Clin Immunol."},{"key":"ref-43","doi-asserted-by":"publisher","first-page":"373-9","DOI":"10.1002\/alr.21904","article-title":"Unsupervised network mapping of commercially available immunoassay yields three distinct chronic rhinosinusitis endotypes.","volume":"7","author":"R Divekar","year":"2017","journal-title":"Int Forum Allergy Rhinol."},{"key":"ref-44","doi-asserted-by":"publisher","first-page":"1459-69","DOI":"10.1111\/all.13411","article-title":"Multidimensional endotypes of chronic rhinosinusitis and their association with treatment outcomes.","volume":"73","author":"B Liao","year":"2018","journal-title":"Allergy."},{"key":"ref-45","doi-asserted-by":"publisher","first-page":"1175-83","DOI":"10.1002\/alr.22160","article-title":"Mucus T helper 2 biomarkers predict chronic rhinosinusitis disease severity and prior surgical intervention.","volume":"8","author":"J Turner","year":"2018","journal-title":"Int Forum Allergy Rhinol."},{"key":"ref-46","doi-asserted-by":"publisher","first-page":"11450","DOI":"10.1038\/s41598-018-29612-2","article-title":"Periostin as a novel biomarker for postoperative recurrence of chronic rhinosinitis with nasal polyps.","volume":"8","author":"T Ninomiya","year":"2018","journal-title":"Sci Rep."},{"key":"ref-47","doi-asserted-by":"publisher","first-page":"181-6","DOI":"10.1177\/0194599817737967","article-title":"Periostin as a Biomarker for Nasal Polyps in Chronic Rhinosinusitis.","volume":"158","author":"A Maxfield","year":"2018","journal-title":"Otolaryngol Head Neck Surg."},{"key":"ref-48","doi-asserted-by":"publisher","first-page":"1705-1708.e3","DOI":"10.1016\/j.jaci.2017.07.031","article-title":"Serum periostin, IgE, and SE-IgE can be used as biomarkers to identify moderate to severe chronic rhinosinusitis with nasal polyps.","volume":"140","author":"K Jonstam","year":"2017","journal-title":"J Allergy Clin Immunol."},{"key":"ref-49","doi-asserted-by":"publisher","first-page":"310-316.e2","DOI":"10.1016\/j.anai.2017.07.012","article-title":"Nasal interleukin 25 as a novel biomarker for patients with chronic rhinosinusitis with nasal polyps and airway hypersensitiveness: A pilot study.","volume":"119","author":"F Chen","year":"2017","journal-title":"Ann Allergy Asthma Immunol."},{"key":"ref-50","doi-asserted-by":"publisher","first-page":"472-7","DOI":"10.1002\/alr.21685","article-title":"Impact of omalizumab therapy on medication requirements for chronic rhinosinusitis.","volume":"6","author":"R Chandra","year":"2016","journal-title":"Int Forum Allergy Rhinol."},{"key":"ref-51","doi-asserted-by":"publisher","first-page":"110-6.e1","DOI":"10.1016\/j.jaci.2012.07.047","article-title":"Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma.","volume":"131","author":"P Gevaert","year":"2013","journal-title":"J Allergy Clin Immunol."},{"key":"ref-52","doi-asserted-by":"publisher","first-page":"1024-1031.e14","DOI":"10.1016\/j.jaci.2017.05.044","article-title":"Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial.","volume":"140","author":"C Bachert","year":"2017","journal-title":"J Allergy Clin Immunol."},{"key":"ref-53","doi-asserted-by":"publisher","first-page":"469-79","DOI":"10.1001\/jama.2015.19330","article-title":"Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial.","volume":"315","author":"C Bachert","year":"2016","journal-title":"JAMA."},{"key":"ref-54","doi-asserted-by":"publisher","first-page":"1133-41","DOI":"10.1016\/j.jaci.2006.05.031","article-title":"Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps.","volume":"118","author":"P Gevaert","year":"2006","journal-title":"J Allergy Clin Immunol."},{"key":"ref-55","doi-asserted-by":"publisher","first-page":"23-6","DOI":"10.2500\/aap.2016.37.3923","article-title":"Differential effect of omalizumab on pulmonary function in patients with allergic asthma with and without chronic rhinosinusitis.","volume":"37","author":"M Clavenna","year":"2016","journal-title":"Allergy Asthma 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.17716.r41268, Murugappan Ramanathan Jr, Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA, 07 Dec 2018, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/7-1909\/v1#referee-response-41268","order":0,"name":"referee-response-41268","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.17716.r41267, Zheng Liu, Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, 07 Dec 2018, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/7-1909\/v1#referee-response-41267","order":1,"name":"referee-response-41267","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"JHT has received grant support from the National Institutes of Health (NIH)\/National Institute of Deafness and Communication Disorders and additional support from the NIH\/National Institute of Allergy and Infectious Diseases. He receives salary and other support through NIH RO3 DC014809, L30 AI113795, and CTSA award UL1TR000445 from the National Center for Advancing Translational Sciences (NCATS). The manuscript contents are solely the responsibility of the authors and do not necessarily represent official views of the NCATS or the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}