Nasal polyposis pathophysiology: Endotype and phenotype open issues.

PURPOSE: Endotyping chronic rhinosinusitis with nasal polyps (CRSwNP) poses a challenge for rhinologists nowadays. Phenotyping CRSwNP proved inappropriate as an approach to their classification because of their common clinical features. Endotyping, being based on the pathogenic mechanism, provides a precise picture more appropriate for use in clinical practice. Patients' treatment and follow-up can thus be tailored to cope with the degree of aggressiveness of a specific CRSwNP endotype. The aim of this study was to analyze the available information about the main currently accepted endotypes of CRSwNP; furthermore, we reported and commented evidence regarding some clinical conditions associated with nasal polyposis which could be related with new endotypes. MATERIALS AND METHODS: Pubmed and Scopus electronic database were searched. The main available studies about CRSwNP endotyping published predominantly in the last 5 years were critically analyzed. RESULTS: The pathophysiological features of some asthma-related CRSwNP (allergic fungal rhinosinusitis, aspirin-exacerbated respiratory disease) are quite well understood, including them among known endotypes of CRSwNP. On the other hand, because of their known pathophysiological mechanisms, some well-known diseases associated with aggressive forms of CRSwNP, such as eosinophilic granulomatosis with polyangiitis, primary ciliary dyskinesia and cystic fibrosis, should be investigated as potentially related with CRSwNP endotypes. CONCLUSIONS: CRSwNP comprises several inflammatory endotypes defined by different pathogenic mechanisms. These endotypes correlate with the disease's clinical manifestations and behavior. A thorough understanding of CRSwNP endotypes will enable targeted medical therapies and tailored follow-up protocols.