The clinical relevance of the clinical cytological grading in patients with chronic rhinosinusitis with nasal polyps
Authors: Matteo Gelardi, Michele Cassano, Giorgio Ciprandi
Journal: Journal of Allergy and Clinical Immunology (2020)

Smell dysfunction is a common symptom and has a diagnostic value in the workup of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) as recently outlined by Mullol et al.1Mullol J. Marino-Sanchez F. Valls M. Alobid I.A. Marin C. The sense of smell in chronic rhinosinusitis.J Allergy Clin Immunol. 2020; 145: 773-776Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Notably, loss of smell has been proposed as one of the main criteria for an indication of and response to the new biological treatments.2Fokkens W. Lund V. Hopkins C. Hellings P. Kern R. Reitsma S. et al.EPOS2020: European Position Paper on Rhinosinusitis and Nasal Polyps 2020.Rhinology. 2020; 58: 1-464Crossref Scopus (4) Google Scholar Of note, it has been very recently reported that a significant part (20%-60%) of the patients with coronavirus disease 2019 (COVID-19) experienced the loss of smell; anosmia can be the first presenting symptom and so the European Rhinologic Society advised that patients with sudden-onset loss of smell should be considered to be COVID-19 positive (www.europeanrhinologicsociety.org). CRSwNP is characterized by a type 2 inflammation and is frequently associated with some comorbidity, including asthma, aspirin sensitivity, and allergy.3Fokkens W.J. Lund V. Bachert C. Mullol J. Bjermer L. Bousquet J. et al.EUFOREA consensus on biologics for CRSwNP with or without asthma.Allergy. 2019; 74: 2312-2319Crossref PubMed Scopus (251) Google Scholar Type 2 inflammation leads to eosinophils and mast cells recruitment and activation in upper airways. Therefore, to document the presence of inflammatory cells in the nose by nasal cytology is a simple and fruitful way to assess the severity of disease and evaluate the response to treatments.4Gelardi M. Fiorella M.L. Russo C. Fiorella R. Ciprandi G. Role of nasal cytology.Int J Immunopathol Pharm. 2010; 23: 45-49PubMed Google Scholar Nasal cytology is a well-standardized method that may be applied to all nasal inflammatory disorders.5Ciprandi G. Silvestri M. Standardization of the nasal cytology in the work-up of allergic rhinitis.Ann Allergy Asthma Immunol. 2019; 123: 213-216Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar Therefore, nasal cytology may be performed as a useful step in the workup of patients with CRSwNP. As a consequence, a clinical cytological grading (CCG), including the documentation of possible asthma, allergy, or aspirin sensitivity comorbidity, and the presence of eosinophils and/or mast cells in the nose, has been proposed as a precision medicine–based approach in the management of patients with CRSwNP.6Gelardi M. Iannuzzi L. De Giosa M. Taliente S. De Candia N. Quaranta N. et al.Non-surgical management of chronic rhinosinusitis with nasal polyps based on clinical cytological grading: a precision medicine-based approach.Acta ORL Ital. 2017; 37: 38-45Crossref PubMed Scopus (36) Google Scholar In particular, 3 CCG grades were defined on the basis of the score: low (1-3), medium (4-6), and high (≥7). A recent study provided evidence that a CCG value of more than 4 was a reliable (area under the curve, 0.83, and adjusted odds ratio, 7.46) cutoff to identify patients with CRSwNP with olfactory dysfunction.7Gelardi M. Piccininni K. Quaranta N. Quaranta V. Silvestri M. Ciprandi G. Olfactory dysfunction in patients with chronic rhinosinusitis with nasal polyps is associated with clinical-cytological grading severity.Acta ORL Italica. 2019; 39: 329-335PubMed Google Scholar Smell loss is a clinical marker of CRSwNP severity and is associated with type 2 inflammation: both conditions indicate a biological approach.1Mullol J. Marino-Sanchez F. Valls M. Alobid I.A. Marin C. The sense of smell in chronic rhinosinusitis.J Allergy Clin Immunol. 2020; 145: 773-776Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar The CRSwNP overall prevalence has been approximately estimated to be 2% to 4% of the general population and approximately 30% of these patients also have asthma.2Fokkens W. Lund V. Hopkins C. Hellings P. Kern R. Reitsma S. et al.EPOS2020: European Position Paper on Rhinosinusitis and Nasal Polyps 2020.Rhinology. 2020; 58: 1-464Crossref Scopus (4) Google Scholar On the basis of these epidemiological considerations, a large group of Italian outpatients with CRSwNP (791; 424 males, mean age, 48.8 years) was recruited in a real-world study to define the distribution of the CCG grades. The preliminary results showed that 210 (26.5%) outpatients had low-grade CCG, 366 (46.3%) medium, and 215 (27.2%) high (Fig 1). High-grade CCG was frequently characterized by mixed cytological phenotype and severe progress. Patients with CRSwNP deserve adequate management and optimal identification of the best-tailored therapy; in this regard, CCG could be a fruitful tool. In particular, considering the estimated prevalence of CRSwNP and the current findings, it could be reasonably expected that at least 5 million Europeans have CRSwNP with high-grade CCG. Therefore, intercepting the most severe patients and launching an early and tailored treatment, including the new biologics, could positively modify the natural history and improve the quality of life. ReplyJournal of Allergy and Clinical ImmunologyVol. 146Issue 2PreviewIn response to the correspondence reported by Gelardi et al,1 we would like to say that the sense of smell has recently become relevant because a number of studies have shown that olfactory dysfunction may be considered a relevant clinical marker of severity not only in chronic rhinosinusitis with nasal polyps (CRSwNP) but also in other type 2 inflammatory diseases such as allergic rhinitis, asthma, and nonsteroidal anti-inflammatory drug–exacerbated respiratory disease.2 In consequence, the loss of smell and its recovery have been adapted by Education, Innovation and Research in Allergy and Airway Diseases and European Position Paper on Rhinosinusitis and Nasal Polyps international consensus as 1 of the 5 main criteria to define both the indication for and the response to biological treatment in severe CRSwNP. Full-Text PDF