{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:00:41Z","timestamp":1785150041521,"version":"3.55.0"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cIuliu Hatiganu\u201d University of Medicine and Pharmacy","award":["646\/14\/11.01.2024"],"award-info":[{"award-number":["646\/14\/11.01.2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous type 2 inflammatory disease characterized by frequent postoperative recurrence despite endoscopic sinus surgery (ESS). Reliable biomarkers capable of predicting recurrence remain insufficiently validated. This study evaluates the prognostic utility of circulating biomarkers for recurrence prediction in CRSwNP, in addition to the predictive performance of the blood eosinophilia. Materials and Methods: A prospective cohort of 69 patients with CRSwNP undergoing primary ESS was followed for up to 3 years. Periostin, eotaxin-3, procalcitonin and IL-33 were taken from blood before surgery and analyzed by ELISA technique. Clinical outcomes were assessed using SNOT-22 and Perioperative Sinus Endoscopy (POSE) scores. Statistical analyses included Spearman\u2019s correlation, the Mann\u2013Whitney U test, the Kruskal\u2013Wallis test, Cox proportional hazards regression, multivariable binary logistic regression, ROC analysis, and longitudinal MANCOVA. Results: Blood eosinophilia remained the strongest clinical predictor of recurrence (OR = 4.55, p = 0.001). Serum periostin, eotaxin and procalcitonin significantly correlated with postoperative disease severity and recurrence, particularly with POSE scores at 1 and 3 years (p &lt; 0.05). Patients with recurrence demonstrated significantly higher serum levels of these biomarkers compared with controlled patients (all p &lt; 0.001). Multivariate Cox regression identified periostin (HR = 1.033, p = 0.010), eotaxin (HR = 1.554, p &lt; 0.001) and procalcitonin (HR = 1.183, p &lt; 0.001) as significant predictors of recurrence. Procalcitonin demonstrated the highest predictive performance in ROC analysis (AUC = 0.805). Longitudinal MANCOVA confirmed significant associations between periostin, eotaxin, procalcitonin, and persistent postoperative inflammatory burden over 3 years. Conclusions: Circulating periostin, eotaxin and procalcitonin are promising predictors of CRSwNP recurrence and appear to contribute to prognostic accuracy. Integration of serum biomarker profiling into clinical practice may improve personalized postoperative management and risk stratification in CRSwNP.<\/jats:p>","DOI":"10.3390\/medicina62081452","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:47:41Z","timestamp":1785145661000},"page":"1452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum Biomarkers as Predictors of Recurrence in Chronic Rhinosinusitis with Nasal Polyps"],"prefix":"10.3390","volume":"62","author":[{"given":"Maria-Delia","family":"Florean","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology and Head and Neck Surgery, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4920-7462","authenticated-orcid":false,"given":"Codru\u021ba","family":"Mare","sequence":"additional","affiliation":[{"name":"Statistics, Forecasting, Mathematics Department, Faculty of Economics and Business Administration, Babe\u015f-Bolyai University, 400591 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1089-8251","authenticated-orcid":false,"given":"Anda","family":"G\u00e2ta","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Head and Neck Surgery, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1498-312X","authenticated-orcid":false,"given":"Veronica Elena","family":"Trombita\u0219","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Head and Neck Surgery, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5725-662X","authenticated-orcid":false,"given":"Liviu\u021ba","family":"Budi\u0219an","sequence":"additional","affiliation":[{"name":"MedFuture Biomedical Research Institute, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana","family":"Zanoaga","sequence":"additional","affiliation":[{"name":"MedFuture Biomedical Research Institute, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5828-1325","authenticated-orcid":false,"given":"Ioana","family":"Berindan-Neagoe","sequence":"additional","affiliation":[{"name":"MedFuture Biomedical Research Institute, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen Gabriela","family":"Stelea","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, Faculty of Dental Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Roman","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Faculty of Dental Medicine, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2858-8470","authenticated-orcid":false,"given":"Silviu","family":"Albu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Head and Neck Surgery, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Albu, S. (2020). Chronic Rhinosinusitis-An Update on Epidemiology, Pathogenesis and Management. J. Clin. Med., 9.","DOI":"10.3390\/jcm9072285"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3390\/sinusitis7020003","article-title":"Central Compartment Atopic Disease as a Pathophysiologically Distinct Subtype of Chronic Rhinosinusitis: A Scoping Review","volume":"7","author":"Davies","year":"2023","journal-title":"Sinusitis"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1111\/all.15889","article-title":"Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper","volume":"78","author":"Jutel","year":"2023","journal-title":"Allergy"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/s41572-020-00218-1","article-title":"Adult chronic rhinosinusitis","volume":"6","author":"Bachert","year":"2020","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"BSR20193101","DOI":"10.1042\/BSR20193101","article-title":"Comparative analysis of inflammatory signature profiles in eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyposis","volume":"40","author":"Yao","year":"2020","journal-title":"Biosci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"234","DOI":"10.4193\/Rhino16.215","article-title":"Periostin as a marker of mucosal remodelling in chronic rhinosinusitis","volume":"55","author":"Ebenezer","year":"2017","journal-title":"Rhinology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1093\/cid\/cir050","article-title":"Procalcitonin as a biomarker in respiratory tract infection","volume":"52","author":"Gilbert","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1084\/jem.190.7.895","article-title":"Crucial role of the interleukin 1 receptor family member T1\/ST2 in T helper cell type 2-mediated lung mucosal immune responses","volume":"190","author":"Coyle","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1016\/j.jaci.2015.10.019","article-title":"IL-25\/IL-33-responsive TH2 cells characterize nasal polyps with a default TH17 signature in nasal mucosa","volume":"137","author":"Lam","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","unstructured":"Zieli\u0144ska-Bli\u017aniewska, H., Paprocka-Zjawiona, M., Merecz-Sadowska, A., Zajdel, R., Bli\u017aniewska-Kowalska, K., and Malinowska, K. (2022). Serum IL-5, POSTN and IL-33 levels in chronic rhinosinusitis with nasal polyposis correlate with clinical severity. BMC Immunol., 23.","DOI":"10.1186\/s12865-022-00507-2"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1002\/lary.20191","article-title":"Eotaxin-1, -2, and -3 immunoreactivity and protein concentration in the nasal polyps of eosinophilic chronic rhinosinusitis patients","volume":"119","author":"Yao","year":"2009","journal-title":"Laryngoscope"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Yamada, T., Miyabe, Y., Ueki, S., Fujieda, S., Tokunaga, T., Sakashita, M., Kato, Y., Ninomiya, T., Kawasaki, Y., and Suzuki, S. (2019). Eotaxin-3 as a plasma biomarker for mucosal eosinophil infiltration in chronic rhinosinusitis. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00074"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.14639\/0392-100X-suppl.1-43-2023-01","article-title":"How to manage recurrences after surgery in CRSwNP patients in the biologic era: A narrative review","volume":"43","author":"Settimi","year":"2023","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref_16","first-page":"183","article-title":"Staging in Rhinosinusitus","volume":"31","author":"Lund","year":"1993","journal-title":"Rhinology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/j.1365-2273.1995.tb00007.x","article-title":"Efficacy of Topical Corticosteroid Powder for Nasal Polyps: A Double-Blind, Placebo-Controlled Study of Budesonide","volume":"20","author":"Lildholdt","year":"1995","journal-title":"Clin. Otolaryngol. Allied Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1177\/19458924231224343","article-title":"MicroRNA-125b Is a Potential Predictor of Surgical Outcomes in Chronic Rhinosinusitis with Nasal Polyps","volume":"38","author":"Gata","year":"2024","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/MLG.0b013e31814842f8","article-title":"Impact of Perioperative Systemic Steroids on Surgical Outcomes in Patients With Chronic Rhinosinusitis With Polyposis: Evaluation With the Novel Perioperative Sinus Endoscopy (POSE) Scoring System","volume":"117","author":"Wright","year":"2007","journal-title":"Laryngoscope"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1111\/coa.14208","article-title":"Machine Learning Model Predicts Postoperative Outcomes in Chronic Rhinosinusitis with Nasal Polyps","volume":"49","author":"Gata","year":"2024","journal-title":"Clin. Otolaryngol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1080\/00016489.2020.1844288","article-title":"Blood eosinophil count combined with asthma history could predict chronic rhinosinusitis with nasal polyp recurrence","volume":"141","author":"Wang","year":"2021","journal-title":"Acta Otolaryngol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.1016\/j.jaip.2021.06.013","article-title":"Defining the Allergic Endotype of Chronic Rhinosinusitis by Structured Histopathology and Clinical Variables","volume":"9","author":"Brown","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"230","DOI":"10.21053\/ceo.2022.00052","article-title":"Clinical and Laboratory Features of Various Criteria of Eosinophilic Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis","volume":"15","author":"Kim","year":"2022","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1061658","DOI":"10.1155\/2022\/1061658","article-title":"Exploration of Predictive Biomarkers for Postoperative Recurrence in Chronic Rhinosinusitis with Nasal Polyps Based on Serum Multiple-Cytokine Profiling","volume":"2022","author":"Wang","year":"2022","journal-title":"Mediat. Inflamm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5707","DOI":"10.1007\/s00405-022-07492-7","article-title":"The diagnostic importance of periostin as a biomarker in chronic rhinosinusitis with nasal polyp","volume":"279","author":"Yilmaz","year":"2022","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_26","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_27","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_28","first-page":"305","article-title":"Periostin: A novel biomarker for chronic rhinosinusitis","volume":"12","author":"Qin","year":"2016","journal-title":"B-ENT"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1002\/alr.22407","article-title":"Escalation in mucus cystatin 2, pappalysin-A, and periostin levels over time predict need for recurrent surgery in chronic rhinosinusitis with nasal polyps","volume":"9","author":"Mueller","year":"2019","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1177\/0194599819838782","article-title":"Periostin and inflammatory disease: Implications for chronic rhinosinusitis","volume":"160","author":"Lehmann","year":"2019","journal-title":"Otolaryngol. Head. Neck Surg."},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1159\/000509253","article-title":"Increased serum periostin levels and eosinophils in nasal polyps are associated with the preventive effect of endoscopic sinus surgery for asthma exacerbations in chronic rhinosinusitis patients","volume":"181","author":"Kanemitsu","year":"2020","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.alit.2019.12.004","article-title":"Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis","volume":"69","author":"Oka","year":"2020","journal-title":"Allergol. Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6585","DOI":"10.21037\/jtd.2018.11.12","article-title":"Excessive periostin expression and Th2 response in patients with nasal polyps: Association with asthma","volume":"10","author":"Wei","year":"2018","journal-title":"J. Thorac. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1007\/s00405-019-05326-7","article-title":"Does procalcitonin have a role in the pathogenesis of nasal polyp?","volume":"276","author":"Bilici","year":"2019","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9155080","DOI":"10.1155\/2022\/9155080","article-title":"Predictive Values of Serum IL-33 and sST2 in Endotypes and Postoperative Recurrence of Chronic Rhinosinusitis with Nasal Polyps","volume":"2022","author":"Zhang","year":"2022","journal-title":"Mediat. Inflamm."},{"key":"ref_37","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. Otorhinolaryngol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Porfire Irimia, I.M., Berindan-Neagoe, I., Budisan, L., Leucuta, D.C., Gata, A., Minoiu, A.C., Georgescu, B.A., Covaliu, B.F., and Albu, S. (2023). Tissue Interleukin-33: A Novel Potential Regulator of Innate Immunity and Biomarker of Disease Severity in Chronic Rhinosinusitis with Nasal Polyps. J. Clin. Med., 12.","DOI":"10.3390\/jcm12247537"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s00005-019-00547-4","article-title":"MicroRNAs: Potential Biomarkers and Targets of Therapy in Allergic Diseases?","volume":"67","author":"Specjalski","year":"2019","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Seah, J.J., Thong, M., and Wang, Y. (2023). The Diagnostic and Prognostic Role of Biomarkers in Chronic Rhinosinusitis. Diagnostics, 13.","DOI":"10.3390\/diagnostics13040715"},{"key":"ref_41","first-page":"81","article-title":"Predicting difficult-to-treat chronic rhinosinusitis by noninvasive biological markers","volume":"59","author":"Guo","year":"2021","journal-title":"Rhinology"},{"key":"ref_42","first-page":"386","article-title":"Evaluating inflammatory markers in sudden sensorineural hearing loss: The neutrophil-to-lymphocyte ratio, the systemic immune inflammation index, and the pan immune inflammation value as prognostic tools","volume":"47","author":"Aliyeva","year":"2025","journal-title":"Osman. T\u0131p Derg."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Aliyeva, A., Hashimli, R., and Y\u0131lmaz, B. (2025). Hematological Biomarkers of the Obstructive Sleep Apnea Syndrome: A Machine Learning-Based Diagnostic and Prognostic Model. J. Clin. Med., 14.","DOI":"10.3390\/jcm14238437"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4661","DOI":"10.1007\/s00405-025-09529-z","article-title":"Long-term clinical control in chronic rhinosinusitis: Outcomes more than five years after surgery","volume":"282","author":"Joustra","year":"2025","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_45","first-page":"38","article-title":"Development and psychometric validation of the Chronic Rhinosinusitis Control Test","volume":"64","author":"Cotter","year":"2026","journal-title":"Rhinology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s11882-023-01118-6","article-title":"Remission in Type 2 Inflammatory Diseases: Current Evidence, Unmet Needs, and Suggestions for Defining Remission in Chronic Rhinosinusitis with Nasal Polyps","volume":"24","author":"Caminati","year":"2024","journal-title":"Curr. Allergy Asthma Rep."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/8\/1452\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:17:55Z","timestamp":1785147475000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/8\/1452"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["medicina62081452"],"URL":"https:\/\/doi.org\/10.3390\/medicina62081452","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]}}}