{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:13:35Z","timestamp":1790363615988,"version":"4.1.0"},"reference-count":124,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Chronic rhinosinusitis (CRS) refers to an inflammatory disease of the sinonasal mucosa, with a significant economic burden and impact on quality of life. The diagnosis of CRS is conventionally made on careful history and physical examination, including nasoendoscopic assessment which requires technical expertise. There has been increasing interest in using biomarkers in the non-invasive diagnosis and prognostication of CRS, tailored to the disease inflammatory endotype. Potential biomarkers currently being studied can be isolated from peripheral blood, exhaled nasal gases or nasal secretions, as well as sinonasal tissue. In particular, various biomarkers have revolutionized the way in which CRS is managed, revealing new inflammatory pathways where novel therapeutic drugs are employed to curb the inflammatory process, which may be different from one patient to the next. Biomarkers that have been extensively studied in CRS, such as eosinophil count, IgE, and IL-5, have been associated with a TH2 inflammatory endotype which correlates with an eosinophilic CRSwNP phenotype that predicts a poorer prognosis, tends to recur after conventional surgical treatment, but responds to glucocorticoid treatment. Newer biomarkers that demonstrate potential, such as nasal nitric oxide, can support a diagnosis of CRS with or without nasal polyps, especially when invasive tests such as nasoendoscopy are unavailable. Other biomarkers such as periostin can be used to monitor disease course after treatment of CRS. With a personalized treatment plan, the management of CRS can be individualized, optimizing treatment efficiency and reducing adverse outcomes. As such, this review aims to compile and summarize the existing literature regarding the utility of biomarkers in CRS in terms of diagnosis and prognostication, and also makes recommendations for further studies to fill current knowledge gaps.<\/jats:p>","DOI":"10.3390\/diagnostics13040715","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T04:38:29Z","timestamp":1676349509000},"page":"715","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The Diagnostic and Prognostic Role of Biomarkers in Chronic Rhinosinusitis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4161-1804","authenticated-orcid":false,"given":"Jun Jie","family":"Seah","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Thong","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, National University Hospital, National University Health System, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0909-2963","authenticated-orcid":false,"given":"De Yun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"},{"name":"Infectious Diseases Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhin20.401","article-title":"European position paper on rhinosinusitis and nasal polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s11882-017-0690-5","article-title":"Economics of chronic rhinosinusitis","volume":"17","author":"Rudmik","year":"2017","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1111\/all.15074","article-title":"Endotypes of chronic rhinosinusitis: Relationships to disease phenotypes, pathogenesis, clinical findings, and treatment approaches","volume":"77","author":"Kato","year":"2022","journal-title":"Allergy"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.jaci.2008.07.008","article-title":"Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease","volume":"122","author":"Zhang","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1146\/annurev.immunol.24.021605.090720","article-title":"The eosinophil","volume":"24","author":"Rothenberg","year":"2006","journal-title":"Annu. Rev. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.cyto.2015.05.010","article-title":"T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production","volume":"75","author":"Zhu","year":"2015","journal-title":"Cytokine"},{"key":"ref_7","first-page":"e12314","article-title":"A Young Male With Anorexia, Abdominal Complaints and Marked Blood Eosinophilia","volume":"12","author":"Anyfantakis","year":"2020","journal-title":"Cureus"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1038\/s12276-020-0458-1","article-title":"Association between the sinus microbiota with eosinophilic inflammation and prognosis in chronic rhinosinusitis with nasal polyps","volume":"52","author":"Kim","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.jaci.2009.05.017","article-title":"Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese","volume":"124","author":"Cao","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.otohns.2007.07.036","article-title":"Histological and immunological features of non-eosinophilic nasal polyps","volume":"137","author":"Kim","year":"2007","journal-title":"Otolaryngol.\u2013Head Neck Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.anl.2011.01.007","article-title":"New clinical diagnostic criteria for eosinophilic chronic rhinosinusitis","volume":"38","author":"Sakuma","year":"2011","journal-title":"Auris Nasus Larynx"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1007\/s00405-014-2910-0","article-title":"Clinical characteristics and surrogate markers of eosinophilic chronic rhinosinusitis in Southern China","volume":"271","author":"Zuo","year":"2014","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jaci.2010.04.011","article-title":"Practical approach to the patient with hypereosinophilia","volume":"126","author":"Roufosse","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1002\/lary.22507","article-title":"Diagnostic significance of blood eosinophil count in eosinophilic chronic rhinosinusitis with nasal polyps in Chinese adults","volume":"122","author":"Hu","year":"2012","journal-title":"Laryngoscope"},{"key":"ref_15","first-page":"59","article-title":"Systemic medication requirement in post-surgical patients with eosinophilic chronic rhinosinusitis","volume":"59","author":"Ho","year":"2021","journal-title":"Rhinology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1017\/S0022215116009324","article-title":"Reduction of blood eosinophil counts in eosinophilic chronic rhinosinusitis after surgery","volume":"130","author":"Honma","year":"2016","journal-title":"J. Laryngol. Otol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1002\/alr.21032","article-title":"Structured histopathology profiling of chronic rhinosinusitis in routine practice","volume":"2","author":"Snidvongs","year":"2012","journal-title":"Int. Forum Allergy Rhinology."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1016\/j.jaci.2012.01.079","article-title":"Increased neutrophilia in nasal polyps reduces the response to oral corticosteroid therapy","volume":"129","author":"Wen","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2332\/allergolint.10-RAI-0231","article-title":"Eosinophilic chronic rhinosinusitis in Japan","volume":"59","author":"Ishitoya","year":"2010","journal-title":"Allergol. Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1016\/j.jaci.2015.10.010","article-title":"Current and future treatment options for adult chronic rhinosinusitis: Focus on nasal polyposis","volume":"136","author":"Bachert","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/cea.12472","article-title":"Pathogenesis of nasal polyposis","volume":"45","author":"Hulse","year":"2015","journal-title":"Clin. Exp. Allergy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1097\/01.mlg.0000147917.43615.c0","article-title":"Molecular and cellular staging for the severity of chronic rhinosinusitis","volume":"114","author":"Kountakis","year":"2004","journal-title":"Laryngoscope"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.otohns.2009.10.005","article-title":"Impact of mucosal eosinophilia and nasal polyposis on quality-of-life outcomes after sinus surgery","volume":"142","author":"Soler","year":"2010","journal-title":"Otolaryngol.-Head Neck Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"350","DOI":"10.2500\/ajra.2015.29.4231","article-title":"Predictive significance of tissue eosinophilia for nasal polyp recurrence in the Chinese population","volume":"29","author":"Lou","year":"2015","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1111\/all.12644","article-title":"Novel scoring system and algorithm for classifying chronic rhinosinusitis: The JESREC Study","volume":"70","author":"Tokunaga","year":"2015","journal-title":"Allergy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/alr.22194","article-title":"High tissue eosinophilia as a marker to predict recurrence for eosinophilic chronic rhinosinusitis: A systematic review and meta-analysis","volume":"8","author":"McHugh","year":"2018","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"216","DOI":"10.4193\/Rhin17.240","article-title":"Multivariate analysis of inflammatory endotypes in recurrent nasal polyposis in a Chinese population","volume":"56","author":"Wei","year":"2018","journal-title":"Rhinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1177\/1945892418779451","article-title":"Systemic predictors of eosinophilic chronic rhinosinusitis","volume":"32","author":"Ho","year":"2018","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.anl.2012.12.005","article-title":"Risk factors for olfactory dysfunction in chronic rhinosinusitis","volume":"40","author":"Mori","year":"2013","journal-title":"Auris Nasus Larynx"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"110","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":"Gevaert","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1111\/cea.12287","article-title":"Local increase in IgE and class switch recombination to IgE in nasal polyps in chronic rhinosinusitis","volume":"44","author":"Baba","year":"2014","journal-title":"Clin. Exp. Allergy"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"AB238","DOI":"10.1016\/j.jaci.2014.12.1713","article-title":"Allergic sensitization, high local IL-5 and IgE predict surgical outcome 12 years after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis","volume":"135","author":"Gevaert","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"321","DOI":"10.4168\/aair.2015.7.4.321","article-title":"Local immunoglobulin E in the nasal mucosa: Clinical implications","volume":"7","author":"Devuyst","year":"2015","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1067\/mai.2001.112374","article-title":"Total and specific IgE in nasal polyps is related to local eosinophilic inflammation","volume":"107","author":"Bachert","year":"2001","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.jaci.2010.07.007","article-title":"Presence of IL-5 protein and IgE antibodies to staphylococcal enterotoxins in nasal polyps is associated with comorbid asthma","volume":"126","author":"Bachert","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.amsu.2014.09.001","article-title":"The history of monoclonal antibody development\u2014Progress, remaining challenges and future innovations","volume":"3","author":"Liu","year":"2014","journal-title":"Ann. Med. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1080\/07853890802698842","article-title":"Challenges in monoclonal antibody-based therapies","volume":"41","author":"Samaranayake","year":"2009","journal-title":"Ann. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1111\/j.1365-2222.2005.02316.x","article-title":"Nasal biomarker profiles in acute and chronic rhinosinusitis","volume":"35","author":"Riechelmann","year":"2005","journal-title":"Clin. Exp. Allergy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"AB185","DOI":"10.1016\/j.jaci.2019.12.324","article-title":"Dupilumab reduces blood, urine, and nasal biomarkers of type 2 inflammation in patients with chronic rhinosinusitis with nasal polyps in the phase 3 SINUS-52 trial","volume":"145","author":"Bachert","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/S1357-2725(97)00127-1","article-title":"Molecules in focus eosinophil cationic protein (ECP)","volume":"30","author":"Venge","year":"1998","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.rmed.2006.08.012","article-title":"Eosinophil cationic protein: Is it useful in asthma? A systematic review","volume":"101","author":"Koh","year":"2007","journal-title":"Respir. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/j.1365-2133.1992.tb00677.x","article-title":"Serum eosinophil cationic protein (ECP) is a sensitive measure for disease activity in atopic dermatitis","volume":"126","author":"Czech","year":"1992","journal-title":"Br. J. Dermatol."},{"key":"ref_43","unstructured":"Rich, R.R., Fleisher, T.A., Shearer, W.T., Schroeder, H.W., Frew, A.J., and Weyand, C.M. (2012). Clinical Immunology E-Book: Principles and Practice, Elsevier Health Sciences."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1111\/j.1398-9995.2006.01225.x","article-title":"Differentiation of chronic sinus diseases by measurement of inflammatory mediators","volume":"61","author":"Claeys","year":"2006","journal-title":"Allergy"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/intimm\/dxy061","article-title":"Eosinophil-derived neurotoxin enhances airway remodeling in eosinophilic chronic rhinosinusitis and correlates with disease severity","volume":"31","author":"Tsuda","year":"2019","journal-title":"Int. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e75","DOI":"10.2500\/ajra.2013.27.3901","article-title":"Analyzing serum eosinophil cationic protein in the clinical assessment of chronic rhinosinusitis","volume":"27","author":"Kim","year":"2013","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_47","first-page":"245","article-title":"Eosinophil cationic protein in nasal secretion, serum and polyps tissue in patients with chronic rhinosinusitis","volume":"66","author":"Hamidova","year":"2011","journal-title":"Allergy"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"394","DOI":"10.4168\/aair.2019.11.3.394","article-title":"Serum levels of eosinophil-derived neurotoxin: A biomarker for asthma severity in adult asthmatics","volume":"11","author":"Lee","year":"2019","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_49","unstructured":"Lee, J.J., and Rosenberg, H.F. (2012). Eosinophils in Health and Disease, Academic Press."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0891-5849(90)90034-G","article-title":"Reactive oxygen species and airway inflammation","volume":"9","author":"Barnes","year":"1990","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"22118","DOI":"10.1074\/jbc.M116.750034","article-title":"Eosinophil peroxidase catalyzed protein carbamylation participates in asthma","volume":"291","author":"Wang","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1016\/j.jaci.2019.01.038","article-title":"Eosinophil peroxidase, GATA3, and T-bet as tissue biomarkers in chronic rhinosinusitis","volume":"143","author":"Lal","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_53","first-page":"679","article-title":"Biomarkers in chronic rhinosinusitis with nasal polyps","volume":"38","author":"Workman","year":"2018","journal-title":"Immunol. Allergy Clin."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1007\/s00405-017-4547-2","article-title":"Biomarkers in the evaluation and management of chronic rhinosinusitis with nasal polyposis","volume":"274","author":"Yao","year":"2017","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/j.jaci.2015.09.005","article-title":"Association of periostin expression with eosinophilic inflammation in nasal polyps","volume":"136","author":"Wang","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1705","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":"Jonstam","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2332\/allergolint.13-RAI-0673","article-title":"Expressions and roles of periostin in otolaryngological diseases","volume":"63","author":"Ohta","year":"2014","journal-title":"Allergol. Int."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1080\/00016489.2017.1388540","article-title":"Diagnostic significance of serum periostin in eosinophilic chronic sinusitis with nasal polyps","volume":"138","author":"Xu","year":"2018","journal-title":"Acta Oto-Laryngol."},{"key":"ref_59","doi-asserted-by":"crossref","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":"Ninomiya","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/alr.21056","article-title":"Expression of the extracellular matrix gene periostin is increased in chronic rhinosinusitis and decreases following successful endoscopic sinus surgery","volume":"2","author":"Zhang","year":"2012","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1016\/j.jaci.2016.09.026","article-title":"Cross-talk between human mast cells and epithelial cells by IgE-mediated periostin production in eosinophilic nasal polyps","volume":"139","author":"Kim","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/gt.2017.80","article-title":"Oligonucleotide-targeting periostin ameliorates pulmonary fibrosis","volume":"24","author":"Tomaru","year":"2017","journal-title":"Gene Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.anl.2013.02.001","article-title":"Increased exhaled nitric oxide and its oxidation metabolism in eosinophilic chronic rhinosinusitis","volume":"40","author":"Takeno","year":"2013","journal-title":"Auris Nasus Larynx"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s40463-017-0214-2","article-title":"IL-5 and IL-6 are increased in the frontal recess of eosinophilic chronic rhinosinusitis patients","volume":"46","author":"Kubota","year":"2017","journal-title":"J. Otolaryngol.-Head Neck Surg."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.jaci.2015.12.1324","article-title":"Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers","volume":"137","author":"Tomassen","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"192","DOI":"10.2500\/ajra.2014.28.4033","article-title":"Differences in initial immunoprofiles between recurrent and nonrecurrent chronic rhinosinusitis with nasal polyps","volume":"28","author":"Holtappels","year":"2014","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1001\/jamaoto.2016.0927","article-title":"Mucous cytokine levels in chronic rhinosinusitis-associated olfactory loss","volume":"142","author":"Schlosser","year":"2016","journal-title":"JAMA Otolaryngol.\u2013Head Neck Surg."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1034\/j.1398-9995.2003.00110.x","article-title":"Enhanced soluble interleukin-5 receptor alpha expression in nasal polyposis","volume":"58","author":"Gevaert","year":"2003","journal-title":"Allergy"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1046\/j.1365-2222.1998.00380.x","article-title":"GM-CSF, IL-5 and RANTES immunoreactivity and mRNA expression in chronic hyperplastic sinusitis with nasal polyposis (NP)","volume":"28","author":"Hamilos","year":"1998","journal-title":"Clin. Exp. Allergy"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/j.jaci.2006.05.031","article-title":"Nasal IL-5 levels determine the response to anti\u2013IL-5 treatment in patients with nasal polyps","volume":"118","author":"Gevaert","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.jaci.2011.07.056","article-title":"Mepolizumab, a humanized anti\u2013IL-5 mAb, as a treatment option for severe nasal polyposis","volume":"128","author":"Gevaert","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1024","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":"Bachert","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1016\/j.jaip.2017.05.007","article-title":"Nasal polyps and biomarkers","volume":"5","author":"Naclerio","year":"2017","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1084\/jem.20052448","article-title":"Type 2 immunity is controlled by IL-4\/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system","volume":"203","author":"Voehringer","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1002\/alr.22160","article-title":"Mucus T helper 2 biomarkers predict chronic rhinosinusitis disease severity and prior surgical intervention","volume":"8","author":"Turner","year":"2018","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"469","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":"Bachert","year":"2016","journal-title":"JAMA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/s00405-007-0300-6","article-title":"The role of interleukin-16 in eosinophilic chronic rhinosinusitis","volume":"264","author":"Lackner","year":"2007","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"175","DOI":"10.2500\/ajra.2015.29.4176","article-title":"Interleukin-25 and interleukin-33 as mediators of eosinophilic inflammation in chronic rhinosinusitis","volume":"29","author":"Lam","year":"2015","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/alr.21082","article-title":"Clinical severity and epithelial endotypes in chronic rhinosinusitis","volume":"3","author":"Lam","year":"2013","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"310","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":"Chen","year":"2017","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/j.jaci.2015.01.003","article-title":"IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis","volume":"135","author":"Shin","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s00405-016-4260-6","article-title":"The role of IL-25 and IL-33 in chronic rhinosinusitis with or without nasal polyps","volume":"274","author":"Ozturan","year":"2017","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"105","DOI":"10.2500\/ajra.2010.24.3446","article-title":"Treatment-recalcitrant chronic rhinosinusitis with polyps is associated with altered epithelial cell expression of interleukin-33","volume":"24","author":"Reh","year":"2010","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1136\/thoraxjnl-2016-208772","article-title":"The role of interleukin-33 in chronic rhinosinusitis","volume":"72","author":"Kim","year":"2017","journal-title":"Thorax"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"9739","DOI":"10.1073\/pnas.83.24.9739","article-title":"Oncostatin M: A growth regulator produced by differentiated histiocytic lymphoma cells","volume":"83","author":"Zarling","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jaci.2015.01.043","article-title":"Oncostatin M promotes mucosal epithelial barrier dysfunction, and its expression is increased in patients with eosinophilic mucosal disease","volume":"136","author":"Pothoven","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/ACI.0000000000000602","article-title":"Systemic biomarkers of eosinophilic chronic rhinosinusitis","volume":"20","author":"Ho","year":"2020","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1002\/lary.24154","article-title":"Subclassification of chronic rhinosinusitis with nasal polyp based on eosinophil and neutrophil","volume":"123","author":"Ikeda","year":"2013","journal-title":"Laryngoscope"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3389\/fimmu.2019.00074","article-title":"Eotaxin-3 as a plasma biomarker for mucosal eosinophil infiltration in chronic rhinosinusitis","volume":"10","author":"Yamada","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s40463-020-00465-y","article-title":"The roles of nasal nitric oxide in diagnosis and endotypes of chronic rhinosinusitis with nasal polyps","volume":"49","author":"Zhu","year":"2020","journal-title":"J. Otolaryngol.-Head Neck Surg."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.freeradbiomed.2006.01.037","article-title":"Role of epithelial nitric oxide in airway viral infection","volume":"41","author":"Xu","year":"2006","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1111\/j.1365-2222.2008.03006.x","article-title":"Nitric oxide evaluation in upper and lower respiratory tracts in nasal polyposis","volume":"38","author":"Delclaux","year":"2008","journal-title":"Clin. Exp. Allergy"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1046\/j.1365-2222.2002.01379.x","article-title":"Paradoxical low nasal nitric oxide in nasal polyposis","volume":"32","author":"Colantonio","year":"2002","journal-title":"Clin. Exp. Allergy"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"389","DOI":"10.2500\/ajra.2017.31.4480","article-title":"Role of exhaled nasal nitric oxide in distinguishing between chronic rhinosinusitis with and without nasal polyps","volume":"31","author":"Liu","year":"2017","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/S1081-1206(10)60310-9","article-title":"Nasal nitric oxide concentration in suspected chronic rhinosinusitis","volume":"101","author":"Bommarito","year":"2008","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.2500\/ajra.2014.28.3984","article-title":"Nasal and exhaled nitric oxide in chronic rhinosinusitis with polyps","volume":"28","author":"Jeong","year":"2014","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1002\/alr.21598","article-title":"Nasal nitric oxide as a marker of sinus mucosal health in patients with nasal polyposis","volume":"5","author":"Lee","year":"2015","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.anai.2010.08.017","article-title":"Effect of systemic steroids on humming nasal nitric oxide in chronic rhinosinusitis with nasal polyposis","volume":"105","author":"Vaidyanathan","year":"2010","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2500\/ajra.2009.23.3289","article-title":"Nitric oxide metabolites as biomarkers for follow-up after chronic rhinosinusitis surgery","volume":"23","author":"Deroee","year":"2009","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1161\/01.RES.0000070112.80711.3D","article-title":"Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function, and biochemistry","volume":"92","author":"Visse","year":"2003","journal-title":"Circ. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.jaci.2010.02.023","article-title":"Expression of TGF, matrix metalloproteinases, and tissue inhibitors in Chinese chronic rhinosinusitis","volume":"125","author":"Li","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1007\/s00405-012-2219-9","article-title":"Matrix metalloproteinases and their impact on sinusal extension in chronic rhinosinusitis with nasal polyps","volume":"270","author":"Malinsky","year":"2013","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.anai.2013.06.023","article-title":"Expression of matrix metalloproteinase 2 and 9 and tissue inhibitor of metalloproteinase 1 in nonrecurrent vs recurrent nasal polyps","volume":"111","author":"Yeo","year":"2013","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.2500\/ajra.2012.26.3724","article-title":"Corelationship between matrix metalloproteinase 2 and 9 expression and severity of chronic rhinosinusitis with nasal polyposis","volume":"26","author":"Wang","year":"2012","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1111\/j.1067-1927.2004.012411.x","article-title":"Predictive and monitoring value of matrix metalloproteinase-9 for healing quality after sinus surgery","volume":"12","author":"Watelet","year":"2004","journal-title":"Wound Repair Regen."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1097\/01.mlg.0000150674.30237.3f","article-title":"Neutrophil-derived metalloproteinase-9 predicts healing quality after sinus surgery","volume":"115","author":"Watelet","year":"2005","journal-title":"Laryngoscope"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1016\/j.jaci.2010.02.020","article-title":"Oral steroids and doxycycline: Two different approaches to treat nasal polyps","volume":"125","author":"Gevaert","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1111\/j.1524-475X.2008.00429.x","article-title":"Pilot study using doxycycline-releasing stents to ameliorate postoperative healing quality after sinus surgery","volume":"16","author":"Huvenne","year":"2008","journal-title":"Wound Repair Regen."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"175","DOI":"10.4193\/Rhino15.291","article-title":"Prospective open-label evaluation of long-term low-dose doxycycline for difficult-to-treat chronic rhinosinusitis with nasal polyps","volume":"55","author":"Bezerra","year":"2017","journal-title":"Rhinology"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/alr.21004","article-title":"Regional expression of epithelial MDR1\/P-glycoprotein in chronic rhinosinusitis with and without nasal polyposis","volume":"2","author":"Bleier","year":"2012","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1002\/alr.21176","article-title":"P-glycoprotein is a marker of tissue eosinophilia and radiographic inflammation in chronic rhinosinusitis without nasal polyps","volume":"3","author":"Feldman","year":"2013","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1002\/lary.26249","article-title":"Secreted P-glycoprotein is a noninvasive biomarker of chronic rhinosinusitis","volume":"127","author":"Nocera","year":"2017","journal-title":"Laryngoscope"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.jaci.2016.11.014","article-title":"Double-blind placebo-controlled randomized clinical trial of verapamil for chronic rhinosinusitis with nasal polyps","volume":"140","author":"Miyake","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"789","DOI":"10.2741\/3646","article-title":"Importance of glucocorticoid receptors in upper and lower airways","volume":"15","author":"Pujols","year":"2010","journal-title":"Front. Biosci.-Landmark"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1067\/mai.2001.116428","article-title":"GR\u03b2 expression in nasal polyp inflammatory cells and its relationship to the anti-inflammatory effects of intranasal fluticasone","volume":"108","author":"Hamilos","year":"2001","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1365-2222.2008.03144.x","article-title":"Evaluating budesonide efficacy in nasal polyposis and predicting the resistance to treatment","volume":"39","author":"Valera","year":"2009","journal-title":"Clin. Exp. Allergy"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1046\/j.1524-4741.2001.007001040.x","article-title":"Expression of epithelial mucins Muc1, Muc2, and Muc3 in ductal carcinoma in situ of the breast","volume":"7","author":"Diaz","year":"2001","journal-title":"Breast J."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1091\/mbc.7.4.565","article-title":"A mechanism for inhibition of E-cadherin-mediated cell-cell adhesion by the membrane-associated mucin episialin\/MUC1","volume":"7","author":"Wesseling","year":"1996","journal-title":"Mol. Biol. Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.jaci.2014.07.011","article-title":"Mucin 1 downregulation associates with corticosteroid resistance in chronic rhinosinusitis with nasal polyps","volume":"135","author":"Milara","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.jaci.2016.06.064","article-title":"MUC4 impairs the anti-inflammatory effects of corticosteroids in patients with chronic rhinosinusitis with nasal polyps","volume":"139","author":"Milara","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/alr.21253","article-title":"The bitter taste receptor T2R38 is an independent risk factor for chronic rhinosinusitis requiring sinus surgery","volume":"4","author":"Adappa","year":"2014","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/alr.21803","article-title":"Correlation of T2R38 taste phenotype and in vitro biofilm formation from nonpolypoid chronic rhinosinusitis patients","volume":"6","author":"Adappa","year":"2016","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.jaip.2017.09.014","article-title":"Bitter and sweet taste tests are reflective of disease status in chronic rhinosinusitis","volume":"6","author":"Workman","year":"2018","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3593","DOI":"10.1111\/all.15507","article-title":"Updates in biologic therapy for chronic rhinosinusitis with nasal polyps and NSAID-exacerbated respiratory disease","volume":"77","author":"Xu","year":"2022","journal-title":"Allergy"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/4\/715\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:34:47Z","timestamp":1760121287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/4\/715"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,14]]},"references-count":124,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["diagnostics13040715"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics13040715","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,14]]}}}