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Authors: Joaquim Mullol, Franklin Mariño, Meritxell Valls, Isam Alobid, Concepció Marin
Journal: Journal of Allergy and Clinical Immunology (2020)

In response to the correspondence reported by Gelardi et al,1Gelardi M. Cassano M. Ciprandi G. The clinical relevance of the clinical cytological grading in patients with chronic rhinosinusitis with nasal polyps.J Allergy Clin Immunol. 2020; 146: 462-463Abstract Full Text Full Text PDF Scopus (7) Google Scholar 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.2Mullol J. Mariño-Sánchez F. Valls M. Alobid I. Marin C. The sense of smell in chronic rhinosinusitis.J Allergy Clin Immunol. 2020; 145: 773-776Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar 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.3Fokkens 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 Among these criteria various methods have been accepted for both the diagnosis of loss of smell and the presence of type 2 inflammation. It is well known that loss of smell is frequently associated with viral (common cold) and postviral acute rhinosinusitis, the postviral origin being one of the main causes for permanent olfactory loss in the adult population.2Mullol J. Mariño-Sánchez F. Valls M. Alobid I. Marin C. The sense of smell in chronic rhinosinusitis.J Allergy Clin Immunol. 2020; 145: 773-776Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar Although the loss of smell and/or taste has been recently linked to coronavirus disease 2019, associated or not with local or systemic symptoms of the disease,1Gelardi M. Cassano M. Ciprandi G. The clinical relevance of the clinical cytological grading in patients with chronic rhinosinusitis with nasal polyps.J Allergy Clin Immunol. 2020; 146: 462-463Abstract Full Text Full Text PDF Scopus (7) Google Scholar more epidemiological and pathophysiological research is still needed to identify the potential role of the loss of smell and/or taste as a clinical marker of coronavirus disease 2019 (COVID-19) and its severity. The clinical cytological grading score, reported by Gelardi et al,1Gelardi M. Cassano M. Ciprandi G. The clinical relevance of the clinical cytological grading in patients with chronic rhinosinusitis with nasal polyps.J Allergy Clin Immunol. 2020; 146: 462-463Abstract Full Text Full Text PDF Scopus (7) Google Scholar which is based on clinical outcomes and nasal cytology, looks a reliable method to assess nasal inflammation and even its association with loss of smell in patients with CRSwNP. However, other methods such as the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis score4Tokunaga T. Sakashita M. Haruna T. Asaka D. Takeno S. Ikeda H. et al.Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC study.Allergy. 2015; 70: 995-1003Crossref PubMed Scopus (461) Google Scholar have also been reported as markers of eosinophilic CRS and predictors of refractoriness to endoscopic sinonasal surgery. The term eosinophilic CRS has been defined by different authors on the basis of different tissue eosinophil cutoff values going from 5 to 15 cells/hpf, whereas prediction of recurrence after endoscopic sinonasal surgery has been set at more than 55 cells/hpf for Chinese and greater than or equal to 70 cells/hpf for Japanese populations.4Tokunaga T. Sakashita M. Haruna T. Asaka D. Takeno S. Ikeda H. et al.Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC study.Allergy. 2015; 70: 995-1003Crossref PubMed Scopus (461) Google Scholar However, the role of eosinophils as primary biomarkers for the success of treatment in CRSwNP is still, like in asthma, into debate. For instance, dupilumab, a biological drug that has recently proved a fast and maintained potent effect on improving smell, symptoms, quality of life, and asthma control in patients with severe CRSwNP did not show an effect on depleting blood eosinophils.5Bachert C. Han J.K. Desrosiers M. Hellings P.W. Amin N. Lee S.E. et al.Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials.Lancet. 2019; 394: 1638-1650Abstract Full Text Full Text PDF PubMed Scopus (841) Google Scholar However, dexpramipexole, a drug with potent effect inducing eosinophil apoptosis, has not been proven to have a clinical effect on patients with CRSwNP.6Laidlaw T.M. Prussin C. Panettieri R.A. Lee S. Ferguson B.J. Adappa N.D. et al.Dexpramipexole depletes blood and tissue eosinophils in nasal polyps with no change in polyp size.Laryngoscope. 2019; 129: E61-E66Crossref PubMed Scopus (73) Google Scholar Taken together, all these studies show the complexity of the biological inflammatory networks involved in type 2 diseases, including CRSwNP and its multimorbidities, where not only eosinophils but also mast cells, innate lymphoid cells, epithelial cells, or platelets, assessed by different methods including clinical cytological grading, Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis, or others, may play an important role in the diagnosis and prognosis of the disease. However, a multidisciplinary approach and international consensus remain unmet needs to define proper biomarkers, both clinical and biological, for the diagnosis of type 2 upper airway inflammation as well as the prediction of the therapeutic success.7Mullol J. del Cuvillo A. Lockey R. Rhinitis phenotypes.J Clin Immunol Pract. 2020; 8: 1492-1503Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar The clinical relevance of the clinical cytological grading in patients with chronic rhinosinusitis with nasal polypsJournal of Allergy and Clinical ImmunologyVol. 146Issue 2PreviewSmell 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.1 Notably, loss of smell has been proposed as one of the main criteria for an indication of and response to the new biological treatments.2 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 ). 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