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.