{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:23:50Z","timestamp":1788740630001,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Biomarker-driven approaches have markedly improved the stratification and management of airway inflammatory diseases. However, in everyday clinical practice, these strategies still rely mainly on systemic indicators, which often provide only an indirect view of the inflammatory processes occurring within the airway mucosa. This limitation becomes particularly evident in chronic conditions such as chronic rhinosinusitis with nasal polyps (CRSwNP), where local inflammatory patterns may not relate to circulating biomarkers. Nasal cytology represents a simple, non-invasive, and reproducible technique that allows direct evaluation of the cellular components of the nasal mucosa. By identifying distinct inflammatory patterns, it offers a real-time snapshot of the local inflammatory microenvironment, bringing the clinician closer to the site of disease. In this hypothesis, we propose that airway inflammation is primarily driven by local cytological patterns. In particular, we suggest that the interaction between eosinophils and mast cells constitutes a key pathogenic axis underlying disease activity, severity, and progression. From a pathophysiological perspective, eosinophils may reflect a more chronic component of inflammation, whereas mast cells are more closely associated with active and dynamic phases of the disease. Their coexistence may therefore identify a state of amplified inflammatory activity, often associated with more severe clinical phenotypes. We further propose that integrating cytological findings into clinical\u2013cytological grading (CCG) systems could improve patient stratification and support more personalized therapeutic strategies. This model is readily testable in current clinical and research settings and may contribute to a progressive shift toward the use of local biomarkers in precision medicine.<\/jats:p>","DOI":"10.3390\/pathophysiology33020034","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:31:56Z","timestamp":1779885116000},"page":"34","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Nasal Cytology as a Local Biomarker of Airway Inflammation: A Paradigm Shift in Precision Medicine"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4406-0008","authenticated-orcid":false,"given":"Matteo","family":"Gelardi","sequence":"first","affiliation":[{"name":"Unit of Otolaryngology, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/S0140-6736(17)30879-6","article-title":"After asthma: Redefining airways diseases","volume":"391","author":"Pavord","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41572-020-00227-0","article-title":"Allergic rhinitis","volume":"6","author":"Bousquet","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1016\/j.jaip.2020.03.007","article-title":"Endotypes of chronic rhinosinusitis with nasal polyps: Pathology and possible therapeutic implications","volume":"8","author":"Bachert","year":"2020","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/j.jaip.2024.03.009","article-title":"Nonallergic rhinopathy: A comprehensive review of classification, diagnosis, and treatment","volume":"12","author":"Baroody","year":"2024","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1111\/cea.13207","article-title":"Nasal cytology: Methodology with application to clinical practice and research","volume":"48","author":"Heffler","year":"2018","journal-title":"Clin. Exp. Allergy"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Marcuccio, G., Raffio, G., Ambrosino, P., Candia, C., Cantone, E., Detoraki, A., Maniscalco, M., and Path2 Task-Force (2025). The Potential Role of Nasal Cytology in Respiratory Diseases: Clinical Research and Future Perspectives. J. Clin. Med., 14.","DOI":"10.3390\/jcm14030884"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1080\/1744666X.2025.2534060","article-title":"The role of nasal cytology in the diagnosis and treatment of Allergic rhinitis","volume":"21","author":"Song","year":"2025","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"245","DOI":"10.5415\/apallergy.0000000000000239","article-title":"Nasal cytology: Cornerstone and future directions in precision nasal disease management","volume":"15","author":"Zhang","year":"2025","journal-title":"Asia Pac. Allergy"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"14492","DOI":"10.1038\/s41598-022-18734-3","article-title":"Scraping nasal cytology in the diagnostics of rhinitis and the comorbidities","volume":"12","author":"Myszkowska","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s11882-026-01256-7","article-title":"Standardization of nasal cytology: An expert-based Delphi consensus","volume":"26","author":"Macchi","year":"2026","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/ni.3049","article-title":"The immunology of asthma","volume":"16","author":"Lambrecht","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mormile, M., Mormile, I., Fuschillo, S., Rossi, F.W., Lamagna, L., Ambrosino, P., De Paulis, A., and Maniscalco, M. (2023). Eosinophilic airway diseases: From pathophysiological mechanisms to clinical practice. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087254"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.jaip.2016.05.004","article-title":"Phenotypes and emerging endotypes of chronic rhinosinusitis","volume":"4","author":"Bachert","year":"2016","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","unstructured":"Costanzo, G., Costanzo, G.A.M.L., Del Moro, L., Nappi, E., Pelaia, C., Puggioni, F., Canonica, G.W., Heffler, E., and Paoletti, G. (2023). Mast cells in upper and lower airway diseases: Sentinels in the front line. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119771"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"AlBloushi, S., and Al-Ahmad, M. (2024). Exploring the immunopathology of type 2 inflammatory airway diseases. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1285598"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"324","DOI":"10.14639\/0392-100X-N2422","article-title":"Practical recommendations for managing severe chronic rhinosinusitis with nasal polyps in the era of biologics","volume":"43","author":"Pipolo","year":"2023","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/nri3690","article-title":"Mast cell secretory granules: Armed for battle","volume":"14","author":"Wernersson","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","first-page":"181","article-title":"Nasal-sinus polyposis: Clinical-cytological grading and prognostic index of relapse","volume":"23","author":"Gelardi","year":"2009","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12421","DOI":"10.2147\/JIR.S521238","article-title":"Targeting eosinophils in asthmatic inflammation: Benefits and drawbacks","volume":"18","author":"Broide","year":"2025","journal-title":"J. Inflamm. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1159\/000539309","article-title":"Eosinophil\u2013epithelial cell interactions in asthma","volume":"185","author":"Steffan","year":"2024","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_23","first-page":"e85","article-title":"Airway remodelling in asthma: From benchside to clinical practice","volume":"17","author":"Bergeron","year":"2010","journal-title":"Can. Respir. J."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hussain, M., and Liu, G. (2024). Eosinophilic asthma: Pathophysiology and therapeutic horizons. Cells, 13.","DOI":"10.3390\/cells13050384"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Galdiero, M.R., Varricchi, G., Seaf, M., Marone, G., Levi-Schaffer, F., and Marone, G. (2017). Bidirectional mast cell\u2013eosinophil interactions in inflammatory disorders and cancer. Front. Med., 4.","DOI":"10.3389\/fmed.2017.00103"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e70018","DOI":"10.1111\/imr.70018","article-title":"Pathobiology and regulation of eosinophils, mast cells, and basophils in allergic asthma","volume":"331","author":"Whetstone","year":"2025","journal-title":"Immunol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e20221212","DOI":"10.1084\/jem.20221212","article-title":"Type 2 inflammation and biological therapies in asthma: Targeted medicine taking flight","volume":"220","author":"Howell","year":"2023","journal-title":"J. Exp. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Locatello, L.G., Tonon, S., Mele, V., Santini, S., Miani, C., and Pucillo, C.E.M. (2024). Update on the Biological and Clinical Relevance of Mast Cells in Chronic Rhinosinusitis with Nasal Polyps. Biomedicines, 12.","DOI":"10.3390\/biomedicines12112647"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12101","DOI":"10.1038\/s41598-023-39149-8","article-title":"Eosinophil-mast cell pattern of intraepithelial infiltration as a marker of severity in CRSwNP","volume":"13","author":"Gelardi","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"39","DOI":"10.14639\/0392-100X-N2877","article-title":"Blood and local nasal eosinophilia in chronic rhinosinusitis with nasal polyps: Prevalence and correlation with severity of disease","volume":"45","author":"Montuori","year":"2025","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"104275","DOI":"10.1016\/j.amjoto.2024.104275","article-title":"Dupilumab\u2019s impact on nasal citology: Real life experience after 1 year of treatment","volume":"45","author":"Gelardi","year":"2024","journal-title":"Am. J. Otolaryngol."}],"container-title":["Pathophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1873-149X\/33\/2\/34\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:38:18Z","timestamp":1779889098000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1873-149X\/33\/2\/34"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":31,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["pathophysiology33020034"],"URL":"https:\/\/doi.org\/10.3390\/pathophysiology33020034","relation":{},"ISSN":["1873-149X"],"issn-type":[{"value":"1873-149X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]}}}