The clinical relevance of the clinical cytological grading in patients with chronic rhinosinusitis with nasal polyps.

To the Editor:

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. Notably, loss of smell has been proposed as one of the main criteria for an indication of and response to the new biological treatments. 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. 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. Nasal cytology is a well-standardized method that may be applied to all nasal inflammatory disorders. 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. 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.

Smell loss is a clinical marker of CRSwNP severity and is associated with type 2 inflammation: both conditions indicate a biological approach. 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. 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.

Fig 1

Distribution of the frequency concerning 791 patients with CRSwNP stratified according to CCG.